Classification of hydrocephalus .
In the pathophysiology of pediatric hydrocephalus, a significant role is played by the negative influence of cerebral circulation with the emergence of cerebral hypoperfusion. Transcranial Doppler sonography is a noninvasive method that can be used for indirect measurement of intracranial pressure and decrease of intracranial compliance by assessment of changes of cerebral circulation. The goal of this work was to assess the cerebral circulation and intracranial dynamics in pediatric hydrocephalus. The work is also focused on evaluation of impact of various intracranial factors on Doppler parameters of cerebral circulation, especially in neonates with hydrocephalus. The ambition of this work is to improve indication and timing of drainage procedure in children with hydrocephalus by application of the scientific results and clinical experience.
- transcranial Doppler sonography
- pediatric hydrocephalus
1. Physiology of the cerebrospinal fluid, cerebrospinal fluid pathways, and intracranial space
In physiological conditions, the cerebrospinal fluid is a clear, colorless liquid with a volumetric weight of 1007 kg/m3 and pH value of 7.33–7.35. The list of functions of the cerebrospinal fluid is shown in Figure 1 .
According to Archimedes’ principle, the cerebrospinal fluid unweights and protects the central nervous system against a shock. This function is of great importance, especially regarding the fact that the brain, which weighs 1500 g, pushes on the base of the cranium by power of 50 g .
1.1 Production of the cerebrospinal fluid
In physiological conditions, 80% of the cerebrospinal fluid is produced in the choroid plexus in the lateral cerebral ventricles and in the fourth cerebral ventricle. The ultrastructure of epithelial cells in the choroid plexus corresponds with secretion elements. Cerebrospinal fluid production is an active process. Sodium-potassium adenosine triphosphatase (Na-K ATPase), which takes place in the atypical membrane of choroid epithelial cells, plays a key role in the cerebrospinal fluid production . The choroid plexus produces the hemato-liquor barrier. Even in extreme conditions, the concentration of natrium, potassium, calcium, and chlorides in the cerebrospinal fluid remains the same [3, 4].
The cerebrospinal fluid secretion velocity is stable in physiological conditions. It depends on the weight of the choroid plexus. In adults, the liquor secretion velocity is approximately 21 ml/h  or 0.3–0.35 ml/min . Daily, 450–600 ml of cerebrospinal fluid is produced, which means that the cerebrospinal fluid will change 3–4 times in 24 h.
The liquor production is not influenced by rapid changes of intracranial pressure in physiological range of values. Chronic increase of intracranial pressure, which occurs also in hydrocephalus, leads to atrophy of the choroid plexus and decrease of cerebrospinal fluid production .
Cerebrospinal fluid production can be influenced also by medication. The experimental studies confirmed that inhibition of carboanhydrase by acetazolamide decreases cerebrospinal fluid production to 50% . The same effect was achieved when furosemide was administered .
The cerebrospinal fluid is produced also in other parts of the central nervous system. Most of the extrachoroidal cerebrospinal fluid is produced in the interstitial space and in the ependyma [5, 9]. The fluid gets into the liquor space via ependyma in the brain ventricles. Water and other substances penetrate in the subarachnoid space located in the cerebral convexity from the meningeal arteries and directly from the brain.
1.2 Cerebrospinal fluid circulation
Cerebrospinal fluid produced in the lateral cerebral ventricles flows through the foramina interventriculares (Monroi) into the third cerebral ventricle and through aqueductus mesencephali (Sylvii) into the fourth cerebral ventricle ( Figure 2 ). From the fourth cerebral ventricle, it flows through apertura mediana ventriculi quarti (foramen Magendie) and apertura lateralis ventriculi quarti (foramina Luschka) into the subarachnoid space. Approximately, 80% of the cerebrospinal fluid flows through basal cisterns into the subarachnoid space of the cerebral convexity, and 20% flows into the spinal subarachnoid space . From sinus venosus (superior sagittal sinus), the cerebrospinal fluid is absorbed into the venous system.
The circulation of cerebrospinal fluid is influenced by pressure of liquor secretion, ciliary activity, ependymal cells, arterial pulse waves, breathing, body movements, and pressure gradient between arachnoid villi and sinus venosus.
1.3 Absorption of the cerebrospinal fluid
Most of the cerebrospinal fluid is absorbed in arachnoid villi (villi arachnoidales). The villi protrude into dural sinuses and meningeal veins, at most parasagitally in cerebral convexity; a small number can be found in the cranial base and around spinal nerves roots. The arachnoid villi are one-way valves which enable cerebrospinal fluid to be absorbed into the venous circulation .
Inflow of the cerebrospinal fluid into the vascular system is a passive process based on pressure gradient between the subarachnoid space and the dural sinus. The accurate mechanism of cerebrospinal fluid absorption into the sinuses remains still disputable. Two contradictory theories about cerebrospinal fluid resorption (the process of filtration through membrane and direct flow of liquor in the arachnoid villi) were substituted by the hypothesis of vacuole transport system [12, 13, 14, 15]. Rate resorption of the cerebrospinal fluid is pressure-based .
The cerebrospinal fluid is primarily absorbed in the arachnoid villi to superior sagittal sinus. However, there are also alternative ways for it to be absorbed. The results of some studies highlight the meaning of resorption through the lymphatic system . The cerebrospinal fluid can be absorbed also along the cranial nerves and spinal nerve roots and in the plexus choroideus . The exact meaning of the alternative ways of liquor resorption under physiological and pathological conditions is not still fully clarified. Some clinical results highlight a potential role of the central channel in the spinal cord in the cerebrospinal fluid resorption, especially in children .
1.4 The intracranial pressure
The intracranial pressure (ICP), defined as a hydrostatic pressure of the cerebrospinal fluid, is a result of active secretion, flow resistance, and passive liquor resorption into the venous system .
In the physiological range of values of intracranial pressure, the degree of cerebrospinal fluid resorption is the same as its production. The intracranial pressure is directly dependent on the venous pressure in venous sinus and then just follows its changes [17, 18].
In lying position in children and adults, the normal value of ICP is 12 ± 2 cm H2O. In newborns and infants, the normal value of the intracranial pressure is lower. The intracranial hypertension in preterm newborns is defined as ICP ≥ 6 cm H2O and in term neonates and infants as ICP ≥ 10 cm H2O. The value of intracranial pressure gradually increases and stabilizes at the value of the adults when calvas ossificate and the cranial sutures and fontanelles close up.
1.5 The intracranial space
Monro  and Kellie  described the intracranial space as a closed compartment, known as the Monro-Kellie hypothesis. According to the hypothesis, the intracranial volume is constant, and the intracranial cavity is completely full. When the volume of any of the intracranial compartment increases, then the volume of another compartment has to decrease in order to keep the intracranial pressure stable. The Monro-Kellie hypothesis cannot be applied in all cases.
The exception is the cranium of neonates and infants before completion of ossification and closure of the cranial sutures and fontanelles. When volume of the cerebrospinal fluid and intracranial pressure rise (the cases of active hydrocephalus), then the volume of the cranium and the size of the skull increase, which leads to diastasis of cerebral sutures and bulging of fontanelles as a compensatory mechanism of intracranial hypertension (obr. 3–7). In any age group, the intracranial space cannot be considered a completely closed system because in the pressure-volume regulation, the cranial space communicates with the extracranial space through the carotid and vertebral arteries, jugular veins, and spinal cerebrospinal fluid compartment.
In physiological conditions, the intracranial volume is made up of 80% of brain tissue, 10% of cerebrospinal fluid, and 10% of intravascular blood. Volume of the brain tissue can vary because of the change in volume of cells and the change of volume of the intracellular fluid. The vascular system is connected to the extracranial space, compressible, and sensitive to fast changes of the intracranial volume. Extracellular fluid of the central nervous system is made up of the cerebrospinal fluid and extracellular (interstitial) fluid. They communicate with each other through ependymal lining of the cerebral ventricles and perivascular space.
The cranium of a newborn (preterm and term births), the cranium of an infant before and after the cranial suture closure and fontanelle closure, and the cranium of the children and adults have to be differentiated with respect to the intracranial dynamics. The dynamic characteristics of the cranium among newborns vary as well. The biomechanics of cranium is influenced by the size of fontanelles and distance between cranial sutures (in preterm neonates and hypotrophic neonates, the enlarged fontanelle and small cranial suture distention can occur). In infants, the fontanelles diminish gradually. Compensational distance of the cranial sutures in intracranial hypertension is limited, even impossible with higher age of an infant. After fontanelle and cranial suture closure, the child´s skull gradually gets biomechanical characteristics of the skull of the adults .
Impact of volume changes in the cranial cavity on intracranial pressure depends on the condition of compensatory mechanisms (flow of cerebrospinal fluid to spinal compartment, decrease of blood volume in the brain, biomechanic characteristics of the skull and brain tissue). Tolerance of the intracranial space to accept higher volume without changes of the intracranial pressure is called compliance. Compliance (C) is defined by the relations ∆V/∆P (∆V, change of volume; ∆P, change of pressure). According to the pressure-volume curve, when compensatory mechanisms are depleted, the value of intracranial pressure rises exponentially ( Figure 3 ). When compliance is high, increase of relatively high volume may lead to only low increase of intracranial pressure. When compliance is low, small increase of volume is sufficient for significant rise of ICP. Elasticity is indirectly propositional to compliance (∆P/∆V). Elasticity is defined by the so-called pressure-volume index, which shows steepness of the pressure-volume curve .
Biomechanics of the intracranial space is influenced also by changes of biomechanical characteristics of the cerebrospinal fluid. Especially in the cases of infectious and posthemorrhagic hydrocephalus, the changes of rheological characteristics and liquor viscosity occur, which changes mechanical characteristics of the cerebrospinal fluid [24, 25].
2. Cerebral circulation
The vascular system of the brain is composed of the carotid and vertebrobasilar circulations. Both are interconnected by posterior communicating arteries (arteriae communicantes posteriores cerebri). The anterior communicating artery (arteria communicans anterior cerebri) connects both anterior cerebral arteries (arteriae cerebri anteriores). Despite the fact that blood flow in communicating arteries in physiological conditions is low, the arteries represent the main collateral connection between the intracranial cerebral arteries (circulus Willisi). The connection between the external and internal carotid systems is ensured by ophthalmic arteries. The connection between external carotid system and spinal arteries is ensured by occipital arteries. The external carotid arteries supply also the leptomeningeal arteries which may penetrate to the cerebral cortex. Symon  demonstrated effectivity of collateral circulation in the cerebral circulation in a monkey. In his work, he found out that complete occlusion of internal carotid artery resulted in 14% decrease of perfusion pressure in ipsilateral middle cerebral artery. When both carotid arteries were closed, the perfusion pressure in middle cerebral arteries dropped down to 50%.
2.1 Development of cerebral blood flow
Disruption of cerebral blood flow plays a key role in etiopathogenesis of perinatal and neonatal brain damage. Cerebral ischemia is considered as the main factor of damage of the cerebral cortex, deep gray matter structures, and periventricular white matter in preterm neonates [27, 28, 29]. Frequent consequence of the brain damage is disorder of psychomotor development and onset of spasticity .
From the 32nd to 42nd week of gestation, blood flow in the brain rises gradually. This is caused by simultaneous increase of weight of the brain and cerebral circulation. The cerebral perfusion reflects increased metabolic demand of the brain tissue when functional activity of the brain rises during fast growth and organization of the brain structures . The rise of the metabolic demand of the brain during gestational age of the fetus was also confirmed in observation of glucose metabolism by positron emission tomography  and observation of the use of oxygen in the brain tissue by near-infrared spectroscopy .
A significant rise of cerebral blood flow (CBF) is related to increase of blood flow in the cerebral cortex in the next gestational weeks. Hüppi et al.  used 3D nuclear magnetic resonance and found out that proportional intracranial volume in the gray matter increased from about 39% in the 32nd week of gestation to the value of 52% in the 41st week of gestation. It is well known that perfusion of the brain gray matter is significantly higher than perfusion of the white matter of the brain. Blood flow in the cerebral cortex in neonates is about 10 times higher than blood flow in the subcortical white matter .
In neonates between 32nd and 42nd week of gestation, the relative involvement of the vertebrobasilar system in total cerebral blood flow is 26 ± 8%. It remains constant in this period . Studies of various authors confirmed decrease of relative involvement of the posterior cerebral circulation in total cerebral blood flow from the value of 31% in 3-year-old children to the values of 24% in 18-year-old adolescents. The value of 24% has remained constant in adulthood [36, 37]. During observation of the cerebral blood flow circulation in neonatal period, childhood, and adulthood, no differences were found between genders neither in total CBF nor in relative involvement of the anterior and posterior cerebral circulation to total cerebral blood flow [31, 36, 38, 39, 40].
2.2 Blood flow dynamics of the vascular system
Particles moving in the lumen require force to transport themselves from one place to another. This force depends on pressure gradient between two points. Blood flow in the vessels depends on this phenomenon. Blood flow velocity is determined by two factors: pressure gradient between two points (force given by myocardial contractility and cardiac output) and the vascular wall resistance.
Blood flow velocity is directly dependent on a pressure gradient and indirectly dependent on the vascular wall resistance. Other factors, which have impact on blood flow velocity, are hydrostatic component (associated with gravitation), static component (associated with blood volume), blood viscosity, and diameter of the vessel.
In physiological conditions, blood flow in the vessels is laminar in its character. It means that layers of the blood flow move by constant velocity increasing from zero velocity value of the layer at the vascular wall up to maximum velocity in the middle of the lumen in the vessel. But the layers do not mix with each other.
When velocity of blood flow is high or the vascular lumen is narrow, laminar character of blood flow becomes turbulent. Critical velocity for onset turbulent circulation is defined by the Reynolds number, Re = v.d.ρ/τ, in which v means blood flow velocity, d is the diameter of the vessel, ρ is the density of blood, and τ is the viscosity of blood. If the Reynolds number is higher than 2000, laminar blood flow becomes turbulent, in which the concentric and parallel layers of blood flow start to mix. This results in a number of separate flows with different velocity and direction to occur in the lumen of the vessel .
The blood vessels divide into smaller ones in various angles. In the site of division of the vessel, laminar blood flow becomes slightly turbulent. However, it usually is not important in terms of changing blood flow. Walls of the intracranial vessels differ from the walls of the vessels in the rest of the body in compliance and tension. The compliance of the intracranial vessels enables blood to flow in the vessels also during diastole. The cerebral vessels narrow toward peripheral circulation. If the cerebral vessel is narrowed significantly, velocity of blood flow increases in this place of the vessel.
3. Regulation of cerebral circulation
The brain has high metabolism of energy, approximately 20% of total usage of oxygen in the body. There is not any storage of oxygen in the brain. The brain cannot create its structural and functional integrity by anaerobic metabolism. It is an anaerobic organ. In these terms, it is necessary to ensure constant blood flow in the brain, which represents 15% of the myocardial output. Knowledge about regulation of cerebral circulation is needed for understanding of pathogenesis of various conditions (including hydrocephalus) and effect of medication to the central nervous system.
3.1 Humoral and metabolic regulation of cerebral circulation
Besides brain perfusion, it is also necessary to ensure relationship between blood flow through the brain (transport of nutrients and oxygen) and metabolic demands of the brain tissue. This relationship has not been fully described yet. However, when metabolism rises, in a couple of minutes, also blood flow in the brain rises . Many chemical compounds, some of which are also metabolic products, play a key role in blood flow regulation in the brain ( Figure 4 ).
3.1.1 Nitric oxide (NO)
Nitric oxide is catalyzed from
Both in in vitro and in vivo conditions, nitric oxide has a vasodilatational effect . In the smooth muscle tissue of the vascular wall, it stimulates guanyl cyclase and increases the concentration of cGMP, which leads to relaxation of the vascular wall.
Decrease of blood flow in the brain during NOS inhibition is not related to changes in cerebral metabolism. However, it can be assumed that the release of NO during activation of neurons plays a crucial role in elevation of blood flow in the brain (Wang et al., 1993) .
Endogenous production of nitric oxide is related to the development and degree of intraventricular bleeding in preterm neonates. Increased concentration of NO with vasodilatation effects leads to increase of blood flow in the brain as well as to higher risk of bleeding in the germinal matrix, especially in sudden increase of arterial blood pressure .
Corticosteroids decrease production of nitric oxide . It has been found out that in the antenatal use of corticosteroids, the preterm neonates have higher values of arterial blood pressure, need less vasoactive substances to support blood circulation, and are at a significantly lower risk of intraventricular bleeding [47, 48].
3.1.2 Hydrogen ions, pH
Hydrogen ions (H+) are products of metabolism. Increased extracellular concentration of hydrogen ions decreases vascular resistance. The effect of pH change to cerebral circulation is of importance for response of cerebral vessels to carbon dioxide penetrating through hematoencephalic barrier into perivascular space, where it produces H+ and thus changes pH value [49, 50]. However, in metabolic acidosis, hydrogen ions and other fixed acids cannot penetrate through the hematoencephalic barrier, so the resistance of cerebral vessels does not change.
Increased concentration of potassium cations (K+) in the perivascular space is caused by function of cell membranes. It results in dilatation of the arterioles with relatively low onset. In the cerebral vessels, there are several types of potassium channels such as ATP-sensitive channels and Ca2+-dependent channels. When the channels open, potassium cations are released from the cell, and there is closure of tension-regulated calcium channels, resulting in decrease of intracellular concentration of calcium and vascular wall relaxation [51, 52].
Adenosine is a metabolic product with potential vasodilatation effect on the cerebral and the pial arteries. The velocity of changes of the arterial lumen influenced by adenosine is most likely too slow to cause fast changes in cerebral blood flow .
In the cerebral vessels, two isoforms of cyclooxygenase (COX-1 and COX-2) have been identified. Prostacyclin causes endothelium-independent relaxation of the cerebral vessels due to the activation of cAMP and K+ channels. Indomethacin, an inhibitor of cyclooxygenase, decreases cerebral blood flow and reactivity to CO2 and ICP, which may be accompanied by ischemic changes of the brain .
There are three isoforms: ET-1, ET-2, and ET-3. Under the normal conditions, ET-1 is produced in the endothelium of cerebral vessels. Endothelin causes significant and long-term vasoconstriction dependent on extracellular calcium concentration. In conditions when tension of the vascular wall was increased, decreased transcription of ET-1 gene was discovered [55, 56].
3.1.7 Reactivity and carbon dioxide
Carbon dioxide (CO2) has significant impact on cerebral blood flow; the change in paCO2 of 1 mmHg leads to change of CBF about 3–5%. Hypercapnia causes dilatation of the cerebral arteries, while hypocapnia leads to vasoconstriction. The relationship between paCO2 and CBF is S-shaped with plateau below 25 mmHg and above 75 mmHg. Carbon dioxide has impact on the lumen of cerebral vessels by change of pH.
Many studies confirmed that carbon dioxide influences mainly the diameter of arterioles. When arterial blood pressure decreases, the autoregulation-related vasodilatation develops as a result of gradual decrease of reactivity to CO2. In severe arterial hypotension (e.g., in neonates in critical conditions), vasoconstriction reaction to CO2 may diminish completely [57, 58].
3.2 Neural regulation of cerebral circulation
Cerebral circulation, especially frontal circulation, is highly innervated by the sympathetic, parasympathetic, and sensitive nerve fibers [42, 59]. Sympathetic nerve fibers come out from the superior cervical ganglion, parasympathetic fibers from the sphenopalatine and otic ganglion, and sensitive fibers from the trigeminal ganglion.
The role of autonomous nerve control of cerebral circulation remains still controversial. Experimental studies on animals did not show constant change of cerebral blood flow under the condition of electric stimulation nor in autonomous denervation .
At the same time, impact of the innervations on relationship between CPP and CBF or response of the cerebral vessels to metabolic stimuli remained unclear . New knowledge on regulation of cerebral circulation has allowed using transcranial Doppler sonography (Grubb et al., 1991; Diamant et al., 2002) [62, 63, 64, 65, 66]. Observation of blood flow velocity in the middle cerebral artery showed that vasoconstriction of cerebral arteries is connected to raised sympathetic activity during ortostase .
A study by Zhang et al.  confirmed that blockage of nerve ganglia leads to the alteration of dynamic and static autoregulation of cerebral circulation, which is accompanied by moderate but significant decrease of the cerebral blood flow. The authors assume that the autonomous nerve control of cerebral circulation is a tonic activity, which plays a key role in regulation of cerebral blood flow in beat-to-beat regulation.
It was confirmed that increased cerebral blood flow is due to stimulation of the ganglion sphenopalatinum. Despite this fact, the parasympathetic nerve control of cerebral circulation is not as clear as the sympathetic [67, 68].
3.3 Cerebral autoregulation
Cerebral autoregulation is a sensitive homeostatic mechanism, which is necessary for control of cerebral blood flow. In , it was defined by Lassen as an ability to sustain constant cerebral blood flow when perfusion pressure of the brain changes. This is called classic definition of cerebral autoregulation.
Experimental and clinical studies confirmed that the system of autoregulation allows to keep relatively constant CBF ranging from 50 to 170 mmHg ( Figure 5 ) of the perfusion pressure [70, 71]. Mechanism of the autoregulation varies from relationship between blood flow and metabolism (coupling) and reactivity of the cerebral vessels to CO2 .
The cerebral autoregulation is a complex of various physiological mechanisms, which differ in rate of onset and length of response. It can be assumed that restoration of CBF after an immediate change of CPP is due to change of vascular resistance in the cerebral arterioles . In the restoration, two components play a role: fast response, which is sensitive to blood pulsation, and slow response, which is sensitive to changes of the mean arterial pressure [73, 74]. The responses are changing by activity of the sympathetic nervous system and vasomotor reactivity to CO2. While increased sympathetic tonus and hypocapnia shift the range of the autoregulation to upper and lower limits, hypercapnia and vasodilatation substances decrease the autoregulatory limits . In patients with chronic arterial hypertension, the autoregulation range is shifted toward upper limits of CPP [75, 76].
Alteration of the cerebral autoregulation occurs in various pathological conditions (brain injuries, subarachnoid hemorrhage, acute cerebral ischemia, intracerebral hemorrhage, and hydrocephalus) or is influenced by medication. In general, the cerebral autoregulation in the intravenous anesthesia is regarded to be intact. However, when inhalation anesthetics are used, the cerebral autoregulation is impaired [74, 77, 78, 79]. In the cases of the cerebral autoregulation impairment, even the small changes in the arterial blood pressure or CPP, if not controlled early and correctly, may lead to the cerebral hypoperfusion, development of cerebral ischemia, and edema . The cerebral autoregulation impairment may be a sign of compensatory storage depletion of the cerebral circulation. It can be a sign of bad prognosis of the patient´s condition [80, 81, 82, 83, 84, 85].
When advantages of early detection of the cerebral autoregulation impairment were detected, there was a need for methods allowing repeated noninvasive bedside treatment of the cerebral circulation and autoregulation [86, 87]. Examination of the cerebral blood flow using xenon-133 clearance , positron emission tomography , and near-infrared spectroscopy  (Adcock et al., 1999) was technically and economically demanding and invasive. In general, it was clinically unusable, based on radionuclide methods including methodical and ethical limitations .
To observe the cerebral circulation, the transcranial Doppler sonography has been used successfully because it allows noninvasive bedside examination of the cerebral autoregulation by measuring the blood flow velocity in the cerebral vessels. Even though the use of the transcranial Doppler sonography doesn´t measure the value of the cerebral blood flow directly, currently, it is widely accepted that the changes of blood flow velocity in the cerebral vessels in the fixed insonation angle reflect the change in the cerebral blood flow accurately . Implementation of Doppler sonography into multimodal monitoring of patients with neurological impairment allows fast detection of hemodynamic changes in the brain and provides an opportunity for adequate and early change of the treatment [72, 92, 93, 94, 95, 96, 97, 98, 99].
The cerebral autoregulation can be divided into static and dynamic. The static autoregulation describes a level of CBF change responding to CPP change in the stationary condition. It can be calculated by measuring change of blood flow before and after CPP change was induced. Normal static autoregulation response was described as a CBF change of 0.5–4.0% when CPP changed about 1 mmHg . The next option is to calculate index of regulation (IOR) as a proportional change of CVR when CPP changes: IOR = %∆CVR/%∆CPP. Cerebral circulation resistance can be calculated using the following formula: CVR = CPP/CBF. If the proportional CVR change equals the CPP proportional change, CBF does not change. IOR value of 1.0 shows that autoregulation works well in comparison with IOR value of 0, denoting complete autoregulation failure . Transcranial Doppler sonography has facilitated assessment of the static autoregulation by observation of blood flow velocity in the cerebral vessels [74, 79]. Then cerebral vessel resistance could be calculated using the following formula: CVR = MAP/CBF velocity .
The dynamic autoregulation defines velocity of CVR change when CPP changes in a certain period of time. The following formula is being used: %∆CVR/%∆CPP/time . Most assessment methods of dynamic cerebral autoregulation are based on transcranial Doppler sonography [80, 100, 101, 102, 103, 104, 105].
Dynamic cerebral autoregulation describes the speed of restoration of the velocity of blood flow (%/s) with respect to MAP change. The normal value of the dynamic cerebral autoregulation is 20% in the time to 5 s [64, 106].
Static cerebral autoregulation and dynamic cerebral autoregulation describe CBF change as a response to slow or fast CPP changes. Tiecks and Lam  described direct correlation between both mechanisms in patients with intact or pharmacologically impaired cerebral autoregulation.
Results of research confirmed that both types of autoregulation may be controlled by different mechanisms. Dynamic autoregulation is more sensitive to negative effects and can be impaired earlier than static autoregulation. Dawson and Panerai  confirmed that in acute cerebral ischemia, dynamic cerebral autoregulation was impaired, whereas static was intact.
Especially, neonates with the need of intensive care are sensitive to impairment of cerebral autoregulation . Impaired dynamic cerebral autoregulation was detected in preterm neonates without signs of neurological disorders and in term neonates with neurological disorder. Both groups needed intensive medical care .
In , Lou was the first who described impaired cerebral autoregulation in preterm neonates detected by the xenon-133 clearance. Later Panerai et al.  confirmed impaired cerebral autoregulation under the dynamic conditions.
In normotensive preterm neonates, the intact cerebral autoregulation without reactivity to paCO2 was detected. In hypotensive preterm neonates, the alteration or even failure of the cerebral autoregulation with decreased or no reactivity of CBF to paCO2 was detected . Some authors found out that in preterm neonates, the cerebral blood flow is present even though there are low values of the arterial blood pressure. However, only static cerebral autoregulation was studied in these works .
3.4 The cerebral venous system
Approximately 15% of intracranial blood volume is contained in cerebral arteries and 15% in the dural sinuses. The largest volume of blood within the intracranial space can be found in the cerebral venous system .
The factors having impact on venous blood volume are as follows:
The vasoconstriction and vasodilatation factors
Chemical and metabolic factors
Compression of cerebral veins
Volume of cerebrospinal fluid
Cerebral tissue (edema)
Resistance of venous blood flow
Rotation of the neck
Obstruction of the jugular system
The head down position
Increased intrathoracic pressure
Cerebral perfusion pressure
Arterial blood pressure
Closure of the arteries
4. Definition and classification of hydrocephalus
4.1 Definition of hydrocephalus
Hydrocephalus is a pathological condition of excessive accumulation of cerebrospinal fluid in the intracranial space due to disorder of production and flow or absorption of cerebrospinal fluid. Dilatation of the cerebral ventricles develops. In active hydrocephalus, it is accompanied by increased intracranial pressure ( Figure 6 ).
In general, hydrocephalus is defined as a hydrodynamic disorder of cerebrospinal fluid, excluding hydrocephalus ex vacuo, in which the space developed due to atrophy of the cerebral tissue is filled with cerebrospinal fluid passively.
Prevalence of hydrocephalus is 1–1.5%, and incidence of congenital hydrocephalus is 0.9–1.8% cases per 1000 labors . Incidence of neonatal hydrocephalus is dropping down because of decreased occurrence of congenital anomalies of the brain and spinal cord, which are related to hydrocephalus, and improvement of prenatal screening and postnatal intensive care.
4.2 Classification of hydrocephalus
Classification of hydrocephalus is shown in Table 1 . Hydrocephalus can be divided into two functional types:
Obstructive (noncommunicating) hydrocephalus
A disorder of flow of cerebrospinal fluid proximal to villi arachnoidales (Pacchioni).
Dilatation of cerebral ventricles proximal to the blockage of flow of cerebrospinal fluid.
The obstruction can be intraventricular (internal hydrocephalus) or extraventricular (external hydrocephalus).
Communicating (nonobstructive) hydrocephalus
It can be caused by increased production of cerebrospinal fluid, decreased cerebrospinal fluid absorption (most of the cases), or insufficient venous drainage.
|Functional classification||Obstructive (noncommunicating) hydrocephalus|
|Communicating (nonobstructive) hydrocephalus|
|Types of hydrocephalus according to etiopathogenesis||Hyperproductive|
|Types of hydrocephalus according to the course||Acute (days)|
|Chronic (months, years)|
|Types of hydrocephalus according to value of ICP||Hypertensive|
|Types of hydrocephalus according to the origin||Congenital|
|• Acquired in the uterus|
According to etiopathogenesis, hydrocephalus can be classified as:
Overproduction of cerebrospinal fluid (in sporadic papilloma or hypertrophy of plexus choroideus)
Obstruction of cerebrospinal fluid pathways
A disorder of absorption of cerebrospinal fluid
According to the course, hydrocephalus can be divided into:
Chronic (months, years)
According to the relationship to intracranial pressure, we can distinguish:
Intracranial pressure is increased.
Temporal increase of ICP values was observed in direct measurement of intracranial pressure. The value of intracranial pressure can vary and may be dependent on the relation to arterial or respiration cerebrospinal fluid pulsation .
Hydrocephalus can be divided into:
For example, X chromosome-linked recessive hereditary hydrocephalus.
Acquired during intrauterine development
Often called idiopathic because it is difficult to detect the cause clearly. In most of the cases, overcoming intrauterine infection is presumed but rarely confirmed.
Hydrocephalus acquired after birth, during postnatal development.
Hydrocephalus ex vacuo. Dilatation of cerebrospinal fluid pathways is caused by atrophy of the brain tissue. Intracranial pressure is not increased. It usually occurs in adults because it is linked to higher age and neurodegenerative diseases (Alzheimer´s disease, Creutzfeldt-Jakob disease, Binswanger´s disease). It also occurs in children with neurodegenerative diseases and hypoxic-ischemic encephalopathy (e.g., perinatal asphyxia, posttraumatic conditions).
Hydrancephalus is a complete or significant loss of brain tissue. Occurrence of the small bundles of brain tissue corresponds with this diagnosis. Calva and meninges are intact, and intracranial cavity is filled with cerebrospinal fluid ( Figure 7 ). The most common cause is bilateral hypoperfusion in the internal carotid arteries, which results in loss of brain tissue in the space supplied by ACA and MCA, while brain tissue in PCA is present. The other causes of hydrancephalus are congenital or neonatal herpetic infection or toxoplasmosis. Progressive dilatation of cerebral ventricles may imitate significant maximal hydrocephalus. These two types of hydrocephalus must be distinguished because re-expansion of brain tissue after drainage procedure may be expected only in maximal hydrocephalus.
External hydrocephalus is the enlargement of subarachnoid space in convexities of the cerebral hemispheres and basal cisterns in childhood. It is often accompanied with abnormal increase of head circumference, which is manifested with normal or slightly enlarged cerebral ventricles. Idiopathic external hydrocephalus ( Figure 8 ) must be distinguished from symptomatic chronic extra-axial cerebrospinal fluid collections. Itis sometimes equated with benign subdural (extra-axial) collections in childhood. Idiopathic external hydrocephalus may be a variant of communicating hydrocephalus . The cause is not clear. External hydrocephalus can also occur after intraventricular hemorrhage or obstruction of the superior vena cava.
The isolated fourth cerebral ventricle. The fourth cerebral ventricle does not communicate with the third cerebral ventricle through the aqueductus (Sylvii) or with the basal cisterns through the foramina Luschka and Magendie. It occurs in hydrocephalus with long-term insertion of drainage system in the lateral cerebral ventricle, especially in postinfectious hydrocephalus (mainly fungal) and in recurrent shunt infections. Plexus choroideus in the fourth cerebral ventricle carries on in production of cerebrospinal fluid. This leads to dilatation and increase of pressure in the fourth ventricle.
Arrested hydrocephalus is a term that has not been well defined and widely accepted yet. Some authors use the term compensated hydrocephalus. Most authors use this term to describe the condition, in which progression of dilatation of the cerebral ventricles or negative consequences of hydrocephalus do not occur. The criteria for arrested hydrocephalus without a drainage system are as follows :
Almost normal size of the cerebral ventricles
Normal growth curve of head circumference
Appropriate psychomotor development
Stability of size of cerebral ventricles is determined by the use of alternative ways of cerebrospinal fluid absorption. The fragile stationary condition may be disrupted by various factors (fever, infection, mild brain injury), which leads to immediate decompensation of hydrocephalus with increasing intracranial pressure and need for a drainage procedure .
5. Etiology of hydrocephalus
Etiology of pediatric hydrocephalus is heterogeneous. Several etiological factors can determine development and course of hydrocephalus in a patient ( Table 2 ). The causes of hydrocephalus are:
Increased production of cerebrospinal fluid
Disorder of flow of cerebrospinal fluid through CSF pathways
Decreased absorption of cerebrospinal fluid
5.1 Congenital hydrocephalus
Idiopathic congenital hydrocephalus means that the cause is not clear.
Congenital stenosis of aqueductus mesencephali (Sylvii) causes 66% of congenital hydrocephalus. It represents 10% of all cases of neonatal hydrocephalus ( Figure 9 ). In 75% of cases, the exact etiology of stenosis of aqueduct is not known. Stenosis of aqueduct can be primary or secondary. Atresia of aqueduct and division into several small channels, membrane composed of ependymal cells going through aqueduct, and aqueduct consisting of two blind-ended channels may be present. In a few cases, stenosis of aqueduct is present in hereditary X-linked hydrocephalus. In most cases, secondary congenital stenosis of aqueduct occurs due to gliosis after intrauterine neural infection or intraventricular hemorrhage.
Chromosome X-linked hydrocephalus (Bickers-Adams syndrome) is a gonosomal recessive hereditary form of hydrocephalus. Incidence is 17–36 cases per 1 million men. It is characterized by stenosis of aqueduct, severe mental retardation, and adduction-flection deformity of the thumbs, which occurs in 50% of the cases. Agenesis of the corpus callosum may occur as well.
Arnold-Chiari malformation. There are four types of them. Currently, only two of them are taken into consideration:
Type I—a lower tentorial insertion; decreased volume of the posterior cranial fossa; a tongue-like extension of the cerebellar tonsils, which are moved to the upper part of the spinal channel; and attachment to the spinal cord. Hydromyelia and syringomyelia occur. But there is no meningomyelocele.
Type II—the fourth cerebral ventricle is long and narrow, the cerebellar tonsils extend deeply into the spinal channel, and the medulla and the cranial part of the spine cord are extended and caudal.
Dandy-Walker malformation (DWM), also known as Dandy-Walker syndrome (DWS), is a maldevelopment of the vermis cerebelli, extension of the fourth cerebral ventricle, and enlargement of the posterior cranial fossa. DWM represents 5–10% of all cases of congenital hydrocephalus and 2–4% cases of pediatric hydrocephalus. The incidence is 1:25–30,000 born-alive babies. Girls are at a higher risk than boys. The exact etiology of DWS is not clear. The risk factors include chromosomal anomalies (3q+, 5p+, 6p+, 8p+, 8q+, 9p+, 17q+, triploidy), impact of isotretinoin in the first trimester of gestation, marriage between close family members (1.5%), and familial occurrence of autosomal recessive hereditary disease. DWM is characterized by six main signs: hydrocephalus, maldevelopment of the vermis cerebelli, cystic enlargement of the fourth cerebral ventricle, elevation of the transverse venous sinuses and their confluens sinuum and tentorium, increased volume of the posterior cranial fossa, and blockage of one or all orifices in the fourth cerebral ventricle . In more than 70% of the cases, another anomaly of the CNS is present (agenesis of corpus callosum, stenosis of aqueductus (Sylvii), lymphoma in the posterior cranial fossa, syringomyelia, agyria, microgyria, heterotopy of the gray matter of the brain, defects of the neural tube, prosencephalon, colpo-encephalon, infundibular hamartomas, occipital encephalocele or meningocele, hemangiomas, dermoid cysts, anomalies of the cores, and pathways of the brain stem). In 20–30% of cases, anomalies of other organs (macrocephaly, blepharoptosis, dysgenesis of the retina, choroidal coloboma, cleft lip and cleft palate, congenital heart defects, polycystic kidneys, polydactyly, syndactyly, anomalies of the lumbar vertebrae) are present.
|Congenital hydrocephalus||Idiopathic congenital hydrocephalus|
|Congenital stenosis of aqueductus (Sylvii)|
|Chromosome X-linked hydrocephalus|
|Postinfectious (intrauterine infection)|
|Posthemorrhagic (intrauterine bleeding in germinal matrix)|
|Caudal neural tube defects|
|Acquired postnatal hydrocephalus||Postinfectious hydrocephalus|
|Expansive intracranial processes|
|Hydrocephalus related to spinal tumors|
|Aneurysm vena Galeni|
|Thrombosis of venous sinuses of the brain|
5.2 Acquired postnatal hydrocephalus
Postinfectious hydrocephalus is mostly caused by purulent ventriculitis, meningitis, or meningoencephalitis. There is obstruction of basal cisterns and moderate dilatation of the cerebral ventricles, which may diminish spontaneously or prograde to active hydrocephalus, in which a drainage is necessary. Hydrocephalus ex vacuo may develop, too. Basilar meningitis may be caused by tuberculous infection. Blockage of the pores of Pacchionian granulations by proteins in neural infection may lead to hyporesorptive hydrocephalus. Neurocysticercosis is a common cause of postinfectious hydrocephalus in Asian countries.
Posthemorrhagic hydrocephalus is one of the most common causes of pediatric hydrocephalus ( Figures 13 and 14 ). It may occur due to subarachnoidal hemorrhage or intraventricular hemorrhage. Hydrocephalus may result from obstruction of CSF pathways by blood clots or decreased cerebrospinal fluid absorption in Pacchionian granulations due to their blockage by erythrocytes and waste products after erythrocytolysis. Germinal matrix hemorrhage and intraventricular hemorrhage develop in 50–60% of preterm neonates who weigh less than 1500 g. Hydrocephalus may occur temporarily after intraventricular hemorrhage. Chronic hydrocephalus dependent on a drainage system develops in 20–50% of neonates with severe intraventricular hemorrhage .
Expansive intracranial processes can be benign or malignant. The most common causes of obstruction of CSF pathways are:
Obstructive hydrocephalus in children develops due to tumors located in the midline of the posterior cranial fossa, the suprasellar area, the third cerebral ventricle, and the area of pineal gland. The suprasellar expansion of tumors of the pituitary gland or the expansion due to pituitary apoplexy may result in hydrocephalus as well.
Postsurgical hydrocephalus develops in 20% of children after tumor removal in the posterior cranial fossa. A drainage is necessary. Hydrocephalus may occur even 1 year after surgery.
Posttraumatic hydrocephalus may be caused by obstruction of CSF pathways in intraventricular hemorrhage, by negative impact on subarachnoid CSF pathways, and by resorption of cerebrospinal fluid in posttraumatic subarachnoid hemorrhage. Hydrocephalus ex vacuo may develop due to atrophy of the brain tissue resulting from a severe brain injury.
The cause of hydrocephalus associated with spinal tumors is not clear. It is assumed that increased concentration of proteins, increased venous pressure, or bleeding plays a role.
Aneurysm vena magna Galeni. Pathophysiology of hydrocephalus includes compression of aqueductus (Sylvii) by aneurysmal sac of vena magna Galeni and increase of venous pressure resulting from the arteriovenous shunt. This leads to decreased absorption of cerebrospinal fluid. Signs of heart failure are common in clinical findings in neonates. Hydrocephalus manifests later.
Thrombosis of venous sinuses of the brain may lead to the development of hydrocephalus. Optic hydrocephalus is an infection in the middle ear, resulting in the development of sigmoid or petrous sinus thrombosis. Thrombosis of superior sagittal sinus may develop if infection spreads directly to the sinus, in cases of severe hypernatremic dehydration and other thrombophilic conditions. Progressive communicating hydrocephalus may be caused by thrombosis of superior vena cava due to compression by tumors of mediastinum or long-term insertion of the central venous catheter.
Increased venous pressure in the venous sinuses of the brain may also occur in achondroplasia or craniostenosis.
Hypervitaminosis A may lead to hydrocephalus because of increased production of cerebrospinal fluid and increased permeability of hematoencephalic barrier.
Constitutional ventriculomegaly is asymptomatic and treatment is not necessary.
6. Pathophysiology of hydrocephalus
Currently, the main interest in pathophysiology of pediatric hydrocephalus is hydrodynamic, vascular, biochemical, and metabolic changes of the brain ( Table 3 ). Deeper knowledge on multifactorial-dependent brain damage in hydrocephalus allows to change treatment procedures and improves functional result of treatment in children with hydrocephalus [120, 121, 122, 123, 124, 125] (Williams et al., 2007).
|Pathologic changes||Flattening and damage of ciliary apparatus of ependymal cells of the cerebral ventricles, disruption of ependymal basal membrane, diminishing and stretching of the cortical mantel, edema of the periventricular white matter, axon degeneration (demyelination), decrease of neurons, cerebral atrophy, perforation of septum pellucidum, compression of cerebellum hemispheres, and erosion on their surface|
|Vascular changes||Distortion of the cerebral vessels, collapse of capillaries, disorder of regulation of the cerebral circulation, hypoperfusion, ischemic brain injury|
|Biochemical changes||The role of neuronal death, Ca2+-activated proteolytic processes, lipid peroxidation, alteration of neurotransmitter systems|
|Changes of cerebral metabolism||Alteration of energetic metabolism, acidosis, increased lactate concentration, changes in total volume of water, free and bound water in the brain tissue|
The international congress National Institutes of Health (NIH)-sponsored workshop Hydrocephalus: Myths, New Facts, and Clear Directions, in which well-known experts on pediatric and adult hydrocephalus participated, was held from September 29 to October 1, 2005, in Bethesda, Maryland. The goal was to define current state and make strategy for further research of hydrocephalus ( Figures 15 and 16 ) (Williams et al., 2007). Research focused on pediatric hydrocephalus at our workplace follows the outcomes of this scientific event.
6.1 Pathophysiological mechanisms of onset and development of hydrocephalus
Mechanism of dilatation of the cerebral ventricles in hydrocephalus development has not been fully described yet. Dilatation of the cerebral ventricles is more than just a result of excessive accumulation of CSF due to imbalance between production and absorption of cerebrospinal fluid [126, 127]. The mechanism of dilatation of cerebral vessels is complex. Various factors play a significant role in different stages of its development.
The following factors are responsible for onset and progress of dilatation of the cerebral ventricles in hydrocephalus :
Compression of vascular system, which can be compressed.
Redistribution of cerebrospinal fluid and extracellular fluid in CNS.
Changes of biomechanical properties of the brain (compliance of the brain tissue, disruption of viscoelastic properties of the brain).
Effect of pulse pressure of cerebrospinal fluid.
Loss of brain tissue accompanied by enlargement of the cerebral ventricles.
Increase of total volume of the skull resulting from effects of abnormal pressure on functional sutures in the skull of small children. In this age, additive cranial volume is the main factor of increase of volume of cerebrospinal fluid and enlargement of the cerebral ventricles .
Generally, in obstructive hydrocephalus, it is assumed that there is a significant pressure gradient between the cerebral ventricles, which is proximal to the site of obstruction of the CSF pathways and the subarachnoid space on convexity. However, the results of measurements confirmed that the pressure gradient is very low or zero. Even the low gradient between the cerebral ventricles and the subarachnoid space on convexity can cause onset and development of dilatation of the cerebral ventricles. The final value of intracranial pressure depends on transmission of the intraventricular pressure through the cerebral tissue toward the surface of the brain, which is influenced mainly by elastic properties of the brain tissue. If the brain tissue is less compressible (low compliance of the brain tissue), then transmission of pressure is significant, which leads to tension hydrocephalus. If the brain tissue is more compressible (higher compliance of the brain tissue), then transmission of pressure from the intraventricular compartment toward the brain surface is lower, which results in normotensive hydrocephalus . The important role of viscoelastic properties of the brain and changes of CSF absorption in the development of the cerebral ventricle dilatation has been confirmed also by other researchers [130, 131].
Klarica et al.  performed the experiment with cats, which confirmed that obstruction of aqueduct is not the single cause of development of hypertensive acute hydrocephalus (induced by obstruction of aqueduct). Instillation of fluid into the cerebral ventricles, which are proximal to the site of obstruction, leads to development of pressure gradient between the cerebral ventricles and cisterna magna. After instillation of fluid, the pressure gradient diminished. However, pressure in the subarachnoid space, which acted on cerebrospinal fluid in the cerebral ventricles through the brain tissue, had increased during instillation of fluid into cisterna magna.
Peña et al.  also confirmed that in acute obstructive hydrocephalus, the degree of dilatation of cerebral ventricles depends on pressure gradient between the cerebral ventricles and the subarachnoid space. Development of periventricular edema was dependent on expansive (tension) forces acting on the brain tissue near the frontal and occipital horns of lateral cerebral ventricles. On the other hand, a concave shape of the lateral cerebral ventricle resulted in the development of compressive forces in the adjacent brain tissue. The results of the research confirmed that distribution of periventricular edema in acute hydrocephalus is independent on the intraventricular pressure as well as on geometrics of the cerebral ventricles.
Examination of cerebrospinal fluid by nuclear magnetic resonance showed that almost every movement of CSF is pulse in its nature. This provides evidence that hyperdynamic pulsations of the choroid plexus in communicating hydrocephalus are not only necessary but also sufficient for induction of dilatation of the cerebral ventricles. Communicating hydrocephalus can be developed also due to redistribution of CSF pulsations in the intracranial space .
Beside other factors, dilatation of cerebral ventricles also depends on the age of a child. Mechanic properties of the brain of a preterm neonate lead to preferential dilatation of posterior parts of lateral cerebral ventricles. This phenomenon can be defined by two mechanisms: increased compliance of the posterior part of the skull before cranial suture closure and decreased distensibility of the anterior part of the cerebral ventricles, which is surrounded by compact gray matter of the basal ganglia .
Increased production of cerebrospinal fluid is almost always present in tumors or villous hypertrophy of plexus choroideus, especially in papilloma or carcinoma of choroidal plexus [135, 136]. The increase of CSF production itself leads to increase of intracranial pressure and dilatation of the cerebral ventricles . It must be emphasized that factors such as compression of CSF pathways, fibrosis of subarachnoid spaces, or villi arachnoidales due to microbleeding, which may increase CSF flow resistance, occur in patients with tumor of the choroid plexus. Even though the patients underwent resection of tumor, increased production persists. Increased production of cerebrospinal fluid was confirmed also in hypervitaminosis A .
Obstruction of CSF pathways is a common cause of hydrocephalus. The obstruction can be either intraventricular (mainly in narrow inner CSF pathways) or extraventricular (obliteration of outer CSF pathways such as basal cisterns and subarachnoid spaces on convexity). Dilatation of cerebral ventricles depends on a site of obstruction. According to this, we can distinguish hydrocephalus of one, two, three, or four ventricles.
The obstruction of the CSF flow may develop due to various pathological conditions:
Malformations, which lead to local constriction of CSF pathways (e.g., stenosis of aqueductus (Sylvii))
Expansive processes leading to compression of CSF pathways (tumors, arachnoid cysts, hematomas)
Inflammatory processes—infections, fibrous changes after bleeding and inflammation, diseases (e.g., mucopolysaccharidosis), which induce ependymal reaction, leptomeningeal fibrosis, and obliteration of arachnoid villi
Increase of venous pressure in dural sinus results in two consequences:
Increase of venous pressure in the cerebral cortex leads to increase of intracranial venous volume.
Increase of intracranial pressure above the level, which is needed to ensure CSF flow in contrast to increase of venous pressure in the sinus.
Increase of venous pressure in the sinus may be of organic (thrombosis in the sinus, jugular vessels, or superior vena cava, spread of tumor to the sinus, achondroplasia) or functional (high-flow arteriovenous malformations) origin [18, 138].
6.2 Pathologic changes in hydrocephalus
Dilatation of the cerebral ventricles and increase of intracranial pressure in active hydrocephalus result in various pathological changes .
Ependyma of the cerebral ventricles is highly vulnerable. In the acute phase, ependymal cells are flattened, and ciliary apparatus is damaged. In the advanced phase, disruption of ependymal basal membrane can be seen. Eventually, the ependymal membrane is seriously damaged, and the surface of cerebral ventricles is covered by glial tissue. Ependymal cells have atypical surface. They are distorted, and desmosomes are damaged . Nakamura and Sato  emphasized that ciliary dyskinesis in aqueductus (Sylvii) might be one of the factors, which have impact on the development of hydrocephalus.
The cortical mantle is diminished and stretched due to dilatation of cerebral ventricles and increased intracranial pressure. Character and distribution of pathological changes depend on age, in which hydrocephalus has developed, development rate, size of cerebral ventricle dilatation, and duration of hydrocephalus. In the acute phase, edema of periventricular white matter is present. And neurons are not damaged too much. In the advanced stage, edema of white matter diminished and is substituted by fibrotic changes and axon degeneration (demyelination), which is responsible for brain atrophy and focal decrease of neurons [142, 143]. Brain damage results from the combination of mechanic distortion and cerebral blood flow disorder (distortion of cerebral vessels, compression of cerebral capillaries). Cortical dysgenesis may occur in the early onset of dilatation of cerebral ventricles .
Changes in cerebral cortex after drainage procedure include major regeneration of myelin of residual axons and astroglial proliferation with mesenchymal reaction, especially in capillaries. Increase of neuron fibers was not confirmed. The extent of damage of the cerebral cortex is a critical moment for regeneration of cortical mantle in chronic hydrocephalus . Drainage procedure provides only partial regeneration of the brain tissue. Damage of dendrites persists. This has negative impact on the development of connections between neurons during postsurgical recovery [144, 146].
Among other pathological changes in the development of hydrocephalus, there are perforations of septum pellucidum, ventrolateral compression of nucleus caudatus, and compression of cerebellum hemispheres with erosion on their surface .
Azzi et al.  emphasize causal relationship between increased intracranial pressure, dilatation of cerebral ventricles, and cerebral edema, which is responsible for hydrocephalus. Alteration of the parameters occurs rather in sequences than simultaneously, and the course of manifestations of hydrocephalus is different.
The difference between total volume of free water and bound water, which is contained in the cerebral cortex, was not found in any stage of hydrocephalus. Any evidence of change was found in total volume of water in periventricular white matter. But in acute and subacute stages of hydrocephalus, total volume of free water was increased, while volume of bound water was decreased. In the chronic stage, values of free and bound water were in standard range. In acute and subacute stages of hydrocephalus, free water flows through ependymal lining of cerebral ventricles into the periventricular white matter, which results in decrease of volume of free water. In chronic hydrocephalus, employment of alternative drainage pathways enables drainage of free water from the periventricular white matter, so volume of free water is back in standard values . When volume of free water in the periventricular white matter is increased, alteration of energetic metabolism is present. Employment of alternative drainage pathways decreases edema of the white matter and improves energetic state of the white matter of the brain .
Increase of intracranial pressure in pediatric hydrocephalus may cause disorders of the autonomous nervous system and regulation of body temperature . When it is accompanied by dysfunction of the autonomous nervous system, then dysfunction of cerebral cortex, subcortical structures, and cerebral stem develops. When drainage procedure was performed in neonates with active hydrocephalus, dysfunction of cardiac regulation has improved [152, 153].
6.3 Vascular changes in hydrocephalus
Changes in nerve tissue are accompanied by alteration of the vascular system, which may improve if hydrocephalus is treated early and appropriately . Distortion of cerebral vessels, compression and collapse of capillaries, and disorder of cerebral circulation occur. The vascular system of periventricular white matter and cerebral cortex is usually most damaged. Damage of the cerebral system involves development and worsening of ischemic damage and alteration of energetic cerebral metabolism ( Figure 17 ).
The degree and type of changes of cerebral circulation depend on the development and course of hydrocephalus. Compression of capillaries, also called cerebrovascular compression, plays a significant role in the acute stage. Various research studies have confirmed collapse of cerebral capillaries in the periventricular white matter and cortical and subcortical gray matter [154, 155, 156, 157, 158]. Changes of cerebral circulation, which are adaptive in their nature, also known as cerebrovascular adaptation, occur in the chronic stage of hydrocephalus. Their role is to ensure appropriate cerebral perfusion and metabolic demands of the brain. Development and employment of adaptive processes require time, so they are preferred mainly in slowly progressive hydrocephalus.
In the experimental study with dogs, Luciano et al.  confirmed that adaptive changes of cerebral circulation appeared 10–12 weeks after induction of hydrocephalus. After initial decrease of vascular supply of the cerebral tissue (collapse of cerebral capillaries), they found out that cerebral circulation in the periventricular white matter, nucleus caudatus, and cerebral cortex can be restored in chronic hydrocephalus. An increased number of cerebral capillaries, confirmed by histological examination, may be caused by continuous blood flow in capillaries as well as capillary angiogenesis in chronic hypoxic condition.
In chronic hydrocephalus, the protective effect of nimodipine has been proven in experimental studies. It improved blood flow in periventricular white matter but did not affect proteolytic processes in axons due to Ca2+ influx .
da Silva et al.  observed changes of cerebral blood flow in cats with kaolin-induced hydrocephalus. They found out that ICBF in the cerebral cortex, white matter, and subcortical structures of the gray matter was decreased 1 week after hydrocephalus induction.
The biggest decrease of ICBF was confirmed in the white matter of the parietal lobe. Three weeks after hydrocephalus induction, decrease of ICBF persisted only in the white matter (in the parietal lobe, occipital lobe, and corpus callosum), while perfusion of cerebral cortex and deep subcortical structures had returned to normal values.
6.4 Biochemical changes in hydrocephalus
Studies on potential prognostic markers of brain damage in hydrocephalus have shown an increased amount of proteins in cerebrospinal fluid and change of electrophoretic spectrum of proteins in various conditions of hydrocephalus . Concentration of fatty acids, xanthine, hypoxanthine, ganglioside GM1, and lactate in cerebrospinal fluid seems to be an interesting prognostic factor [166, 167, 168, 169].
A role of neuronal death in pathophysiology is not clear. Ding et al.  found out that neuronal death did not play a main role in experimental hydrocephalus. However, when acute ischemia was induced in the frontal lobe of the brain in rats with hydrocephalus, increased tolerance of neurons to ischemia has been confirmed.
Shinoda et al.  proved increased expression of neurotrophins and their receptors in damaged structures of the brain in rats.
Experiments have shown that besides other mechanisms, also Ca2+ -activated proteolytic processes cause damage of periventricular white matter in hydrocephalus .
Caner et al.  in their study revealed an increased level of lipid peroxidation of the cerebral vessels. It might be a result of ischemia caused by stretching of cerebral vessels in hydrocephalus.
Onset and development of hydrocephalus leads to alteration of neurotransmitter systems in the brain. Tashiro et al.  confirmed that mechanic distortion in progressive hydrocephalus causes functional damage of cholinergic and GABAergic neurons in neostriatum and dopaminergic neurons in the substantia nigra compacta. Disorders of neurotransmitter signals in the basal ganglia may explain some of the functional motoric disorders in hydrocephalus. Chovanes et al.  found out that the level of noradrenaline (71%), dopamine (73%), and serotonin (50%) was decreased in the cerebral cortex, neostriatum, and cerebellum. The level of noradrenaline and serotonin was increased in the brain stem. This might be a sign of axonal transport deficit from the locus ceruleus to the raphe area.
Hydrocephalus is associated with progressive malfunction and destruction of axons and neurons. Growth-associated protein 43 is responsible for neuroaxonal regeneration and synaptic remodelation. In the early stage of hydrocephalus, the level of growth-associated protein 43 increases in periventricular axons. This shows how important early intervention in prevention and restoration of axonal damage in hydrocephalus is. Increased expression of growth-associated protein 43 in the cerebral cortex is a sign of alteration of cortical synaptogenesis . Suda et al.  observed the level of synaptic vesicle-associated protein 38 (SVP-38) and developmentally regulated brain proteins (drebrins) in rats with congenital hydrocephalus. Their study confirmed alteration of synaptogenesis in prenatal period, which had been restored after early drainage procedure.
The glutamate/aspartate transporter (GLAST) system plays a significant role in maintaining the extracellular concentration of glutamate below neurotoxic level. Masago et al.  confirmed GLAST expression in the reactive astrocytes in the periventricular white matter and regulation of glutamate concentration in hydrocephalus.
Increased concentration of vascular endothelial growth factor (VEGF) and erythropoietin (EPO) in cerebrospinal fluid was confirmed in neonates and children with active hydrocephalus. The levels increased due to brain tissue hypoxia, which stimulates expression of genes for EPO and VEGF .
6.5 Changes of cerebral metabolism in hydrocephalus
Changes of energetic and membrane metabolism of the brain tissue play a significant role in pathogenesis of hydrocephalus. The changes can be described in detail by in vitro and in vivo nuclear magnetic spectroscopy.
Tamaki et al.  performed an experiment using in vivo 31P-MR spectroscopy. The experiment revealed decreased the ratio between organic creatine phosphate and inorganic phosphate, which is an indicator of bioenergetic state (energetic index) in acute and subacute stages of hydrocephalus. Restoration of the ratio between organic creatine phosphate and inorganic phosphate was found in the chronic stage of hydrocephalus. Decrease of adenosine triphosphate was not confirmed in any of these stages.
da Silva et al.  observed changes of energetic metabolism in hydrocephalus and impact of drainage procedure (VP shunt insertion) on energetic condition of the brain tissue. The experiment revealed decrease of the ratio between organic creatine phosphate and inorganic phosphate and increase of the ratio between inorganic phosphate and ATP. Direct correlation between energetic index and size of cerebral ventricles was confirmed. When drainage procedure was performed, periventricular edema diminished, cerebral ventricles decreased, and the ratio of organic creatine phosphate/inorganic phosphate and the ratio of inorganic phosphate/ATP return to normal values. The results show that hypoxic-ischemic encephalopathy accompanied by malfunction of energetic metabolism, which can be reversible if drainage procedure is performed early, occurs in active hydrocephalus.
Braun et al.  used 1H MR spectroscopy to observe changes in the brain tissue in adult rats. Malfunction and structural damage of neurons and membrane systems can be detected when the level of neurometabolites is examined. The results showed increase of lactate and decrease of pH. Moreover, decrease of ratio N-acetylaspartate/choline and ratio of creatine/choline was found out in the acute as well as chronic stage of hydrocephalus. This is a sign of neural dysfunction, neural destruction, changes of phospholipid metabolism in membranes, and myelin damage.
Harris et al.  observed changes of neurometabolites in the cerebral cortex. The experiment showed decrease of myoinositol, creatine, choline, N-acetylaspartate, taurine, glutamine, glutamate, aspartate, alanine, glycine, GABA, and phosphocreatine.
7. Clinical manifestations of pediatric hydrocephalus
Signs of dilatation of the frontal horns of lateral cerebral ventricles (apathy) and dilatation of aqueduct and the third cerebral ventricle (oculomotor dysfunction) and signs of intracranial hypertension are clinical manifestations of active hydrocephalus in children. Clinical signs of intracranial hypertension can be divided into anatomic (the biomechanical properties of calva—diastasis of cerebral sutures, enlarged and bulged fontanelles, bigger size of the head) and signs associated with the homeostasis of intracranial space such as vomiting, quantitative disturbance of consciousness, breathing pattern disorders, bradycardia, and oculomotor dysfunction [184, 185]. Other clinical manifestations of pediatric hydrocephalus are noticeable and enlarged veins of calva caused by reverse blood flow from cerebral veins due to increased intracranial pressure and a cracked pot sign.
Manifestation of clinical signs of intracranial hypertension depends on course of hydrocephalus, age of a child, fibroelastic and biomechanical properties of the cranium, and employment of compensation mechanisms. Clinical signs of intracranial hypertension vary widely mainly in babies (neonates and infants). After cerebral suture closure and ossification of the calva, the skull gets biomechanical properties of the skulls of an adult. This is the cause of uniform clinical manifestation of increased intracranial pressure in older child age categories. In older children, hydrocephalus may manifest with headache, worse school results, or changes in behavior [186, 187].
According to course of hydrocephalus, we can distinguish acute hydrocephalus with need of immediate drainage procedure, progressive hydrocephalus, and chronic compensated hydrocephalus either with subcompensation of intermittent episodes or immediate decompensation. Severe decompensation of hydrocephalus with rapid deterioration of neurological condition is rare in children (unconsciousness, low values at Glasgow coma scale, development of bilateral mydriasis accompanied by defects of photoreaction, breathing pattern disorders, bradycardia). If the anterior fontanelle is not closed, puncture of the lateral cerebral ventricle through the anterior fontanelle is immediately performed. It is an urgent procedure performed during cerebral resuscitation. The Chiraflex needle can be used for the urgent puncture of the lateral cerebral ventricle. It can be combined with intravenous cannula, which helps to measure intracranial pressure. Then cerebrospinal fluid derivation is done by aspiration. The amount of derived CSF depends on an individual (age of a child, CSF production, size of CSF pathways). The amount of aspired cerebrospinal fluid should decrease ICP to the values of 10–12 cm H2O. This will lead to temporary compensation of the condition, in which detailed diagnosis (if it was not done before the ventricular puncture due to lack of time) and immediate surgery can be performed. If the anterior fontanelle is closed, trepanation is performed in the frontal part of the skull at the right side with insertion of external ventricular drainage. If cerebrospinal fluid derivation is not done quickly and effectively in a child with severe decompensated hydrocephalus, there is only a low chance for a good neurological effect of the drainage procedure .
Some signs of intracranial hypertension (apathy, somnolence, vomiting, irritability, and breathing pattern disorders) are nonspecific and may occur also in other illnesses. Usually they occur in infections of the upper and lower airways, gastroenteritis, or in infection of the uropoetic system. They may imitate activity of hydrocephalus or failure of the internal drainage system, especially in neonates and young children with hydrocephalus. On the other hand, infection, which occurs in compensated hydrocephalus without need of drainage, may lead to decompensation of the stationary state, in which a drainage procedure is necessary .
In active hydrocephalus, the head size of neonates and infants increases due to diastasis of cranial sutures and fontanelles ( Figures 18 – 23 ). There is high variability of biomechanical properties of the skull in a particular age group; therefore, manifestation of the signs will be different. It is important to take measures of three dimensions: circumference of the head, lateral and ventrodorsal. While a child is staying in hospital, the same nurse should measure his head. Then the measures are being compared with the referential values in relation to the gestation age of a child. The percentile graph with assessment scale of head circumference is usually used in clinical practice ( Figure 24 ) . Before a child is discharged from a hospital, his parents are informed about clinical manifestations of increased intracranial pressure and drainage system failure and how to measure head circumference. Parents should be given the child’s identity card, which contains information about insertion of the drainage system and contact details of the department where the shunt procedure was performed. After discharge, the parents should measure the circumference of child´s head at least once a week and take records of the measures [186, 191].
The diastasis of sagittal and lambdoid suture is examined by palpation of a child´s head. Enlargement of the lambdoid suture is considered pathognomonic. Enlargement of the cranial sutures can be seen at X-ray or CT scan of the skull ( Figures 21 and 22 ). The anterior fontanelle is usually bulged over niveau, enlarged and hard when palpated. However, palpation examination of the anterior fontanelle might be ambiguous even though the intracranial pressure is increased. If compliance of the brain tissue is increased (in hypoxic-ischemic encephalopathy, in inflammatory processes in the brain), the cerebral ventricles may enlarge significantly during the initial stage of increase of intracranial pressure, and clinical manifestations of intracranial hypertension don´t have to be manifested clearly, without any change in the anterior fontanelle and cranial sutures. On the contrary, hypoxic-ischemic encephalopathy or brain damage caused by inflammation may result in reduction of cerebral tissue and hydrocephalus ex vacuo without increase of intracranial pressure .
Variability of clinical manifestations of intracranial hypertension, especially in young children, may be a complication for indication of drainage procedure in children with hydrocephalus. Despite the dysfunction of cerebrospinal fluid dynamics and increased intracranial pressure, the clinical signs of intracranial hypertension might be manifested only partially or not at all [192, 193, 194].
For this reason, in assessment of pediatric hydrocephalus, we have also focused on the analysis of clinical signs of intracranial hypertension in neonates and infants. The statistical methods were used to describe significance of chosen clinical signs, which are linked to urgent indication of drainage procedure. The results showed that the drainage procedure was indicated early and appropriately, without waiting for further progression in the clinical findings of a child. The clinical signs, which have the highest sensitivity in relation to indication of the drainage procedure, in neonates and infants with hydrocephalus, are increased head circumference (72%), progression of head circumference (61%), tense anterior fontanelle in palpation (56%), and diastasis of cranial sutures (56%). The clinical signs of intracranial hypertension with the highest specificity are bulged anterior fontanelle (99%), progression of head circumference (98%), tense anterior fontanelle in palpation (91%), and diastasis of lambdoid suture (88%). The most positive value of the Youden index was found in progression of head circumference. The value of the Youden index for nonspecific signs of intracranial hypertension (apathy, somnolence, vomiting, sundown syndrome, and irritability) was very low ( Table 4 ) .
|Clinical signs||Sensitivity (%)||Specificity (%)||False-positive result (%)||False-negative result (%)||Youden index|
|Diastasis of cranial sutures||56||65||35||45||0.205|
|Diastasis of sagittal suture||56||65||35||45||0.205|
|Diastasis of lambdoid suture||42||88||12||58||0.297|
|Tense fontanelle in palpation||56||91||9||44||0.461|
|Increased head circumference||72||72||28||28||0.44|
|Progression of head Circumference||61||98||2||39||0.593|
|Breathing pattern disorders||0||92||8||100||−0.077|
Besides common clinical signs, less common or rare manifestations, such as torticollis, opisthotonus, dilatation of vessels in the face, episodes of whistling and screaming, hothead syndrome, occur in children with hydrocephalus . In some cases, hydrocephalus may manifest with spasms and epileptic seizures. Especially in preterm neonates with posthemorrhagic or postinfectious hydrocephalus, subclinical seizures may be detected bedside by aEEG ( Figure 25 ).
The results of the studies confirmed that clinical signs might not show the real value of intracranial pressure [197, 198, 199]. Indirect measuring of ICP by a tonometer or Ladd ICP monitor, which can be used to examine ICP values, is limited by a wide range of findings and high subjectivity of examination .
Direct measurement of intracranial pressure is not routinely performed when assessing indication of the drainage procedure, because it is invasive and may cause complications in children with hydrocephalus. If diagnosis is not clear and clinical symptomatology indicates dysfunction of cerebrospinal fluid dynamics and increased intracranial pressure, invasive methods, for example, ICP screening followed by ICP monitoring and infusion tests, are being used . In neonates and infants with hydrocephalus, ICP value is usually measured during ventricular or lumbar puncture, which was performed to take a sample of cerebrospinal fluid for biochemical and microbiological examination. The value of intracranial pressure may be measured during surgery, which will confirm intracranial hypertension and appropriate indication of drainage procedure. Moreover, a neurosurgeon may use the intraoperative ICP values to setting the opening pressure in programmable valves of the drainage system ( Figure 26 ).
Regarding various measurement methods, normal and abnormal ICP values will differ among neonates with low birth weight. For noninvasive methods of ICP measurement, which employ optic fibers  and pneumatic-tonometric sensors , the normal value in healthy neonates ranges from 4.5 to 7.0 cm H2O. The normal values of ICP measured during lumbar puncture range from 3 to 7 cm H2O . The accurate value, which determines development of progressive dilatation of the cerebral ventricles in neonates, is not clear. Generally, the ICP value must be higher than the normal ICP value. Regarding high volume of water, low level of myelin, increase in cerebral compliance, and enlarged subarachnoid space of the brain in preterm neonates, the ICP value, which determines onset and development of progressive dilatation of cerebral ventricles, might be lower [28, 202]. Generally, in lying children, the normal ICP value is 12 ± 2 cm H2O. In neonates and infants, the normal values of intracranial pressure are lower (ICP ≤ 6 cm H2O for preterm neonates and ICP ≤ 10 cm H2O for term neonates and infants).
The use of drainage systems (shunts) plays an important role in the treatment of pediatric hydrocephalus ( Figure 27 ). In the survey of 1791 patients, up to 56% of them had experienced at least one episode of dysfunction of the drainage system during 12 years since the shunt had been inserted . Similarly, Lazareff et al.  confirmed that 44% out of 224 children had experienced a dysfunction of the drainage system during 6 years since the shunt had been inserted. The highest risk of dysfunction is in the first year of a shunt insertion. Some authors observed malfunction of VP shunt in the first year of insertion in 40% of cases [205, 206, 207]. The overview of the most common complications of the drainage systems is shown in Table 5 .
|Noninfectious complications||Hyperdrainage condition||Slit ventricles syndrome, subdural collections|
|Proximal part of drainage system||Dislocation and obstruction of ventricular catheter, subcutaneous CSF collection, CSF fistula and leak, wound dehiscence|
|Valve||Dysfunction of valve, obstruction of valve, change of permeability in programmed valves, decubitus above valve, breakdown of the system|
|Distal part of drainage system||Obstruction and dislocation of a distal catheter; VP shunt, migration of a catheter into the peritoneal cavity; CSF pseudocyst; VA shunt, migration of a catheter into the right cavities of the heart; thrombus; embolism in pulmonary artery; shunt nephritis; lung hypertension|
|Infectious complications (shunt infections)||Local infection in the wound and along the drainage system, ventriculitis, meningitis, meningoencephalitis, endocarditis, septicemia, lung abscesses, peritonitis|
Regarding a high risk of complications associated with the drainage systems [208, 209], the endoscopic surgery is currently preferred in pediatric hydrocephalus . Endoscopic procedures in children with hydrocephalus usually include ventriculostomy of the third cerebral ventricle ( Figure 28 ), aqueductoplasty, septoplasty, and removal of the intraventricular tumors and cysts . The results of various studies show that ETV is successful in 49–100% cases [212, 213, 214, 215, 216, 217, 218, 219]. Increased risk of ETV failure has been found in posthemorrhagic and postinfectious hydrocephalus in infants under 1 year of age [220, 221, 222]. According to some authors , success of ETV is determined rather by etiology of hydrocephalus than by age of the child.
The value of intracranial pressure is often used in children with active hydrocephalus as an indicator of dysfunction of the ventriculoperitoneal shunt [224, 225]. Gilkes et al.  dealt with changes of the intracranial pressure and cerebral perfusion pressure in shunt-dependent children with hydrocephalus with VP shunt dysfunction linked to employment of compensation mechanisms. They found out that ICP was significantly lower in cases with the use of compensation mechanism than cases in which the compensation mechanisms were not employed at all. Even though ICP value is normal, dysfunction of the drainage system may be present anyway. The insufficient use of compensation mechanisms leads to ICP increase. When compensation mechanisms have been employed, the level of cerebral perfusion pressure was normal in 60% of cases compared to 30% if they have not been used.
In most cases dysfunction of drainage system in shunt-dependent children with hydrocephalus manifests with clinical signs of intracranial hypertension [227, 228]. Clinical manifestation of acute blockage of the drainage system is heterogeneous. High morbidity and mortality are common if it is not diagnosed and treated early. Clinical signs of intracranial hypertension might be very low or none. The common signs of dysfunction of drainage system are headache, vomiting, and drowsiness. The atypical signs are seizures, abdominal pseudocyst, syringomyelia, neural dysfunction, and hemiparesis . Rigidity, visual impairment, and delay of psychomotor development of a child may occur as well.
Presence of disease, which may manifest with similar clinical symptoms, e.g., respiratory infection, virosis, gastroenteritis, and infection of the uropoetic system, must be taken into consideration during examination of a child with hydrocephalus if dysfunction of the drainage system is suspected.
Regarding the age of a child and the fact that 60% of children with hydrocephalus attend special schools, lack of information in medical history provided by a child often causes problems in examination [120, 230, 231].
According to Barnes et al. , if headache, vomiting, and drowsiness occur together in a child with hydrocephalus who has the drainage system, there is a high risk of drainage system dysfunction, mostly acute blockage. Less common is shunt infection, especially in children without manifestation of increased body temperature. Strong positive correlation between drowsiness and acute blockage of drainage system has been found in statistical analysis of the clinical signs linked to drainage system dysfunction. There is weak predictive value of isolated headache or vomiting related to acute blockage drainage system. Therefore a child should be examined for the presence of other diseases. According to some authors [229, 233], the range of clinical signs in children with hydrocephalus with drainage system dysfunction (including infection) is as follows: headache (47–55%), vomiting (40–90%), and drowsiness (30–60%).
Arnell et al.  emphasize the role of ophthalmologic examination in drainage system dysfunction in shunt-dependent children with hydrocephalus. Loss of vision due to increased intracranial pressure and drainage system dysfunction has been described in literature, but the occurrence is not clear . Loss of vision may be caused either by damage of the anterior optic tract, especially edema of the optic disc ( Figure 29 ), atrophy of the optic disc, and slowed or missing reaction to light exposure, or by damage of the posterior optic tract resulting in cortical blindness [237, 238, 239]. In young children with hydrocephalus, increased intracranial pressure may occur independently on the presence of the optic disc edema [239, 240]. However, in older children, a regular ophthalmologic examination focused on the optic disc is recommended. This may help early detection of dysfunction of drainage system with some or only discretely manifested clinical signs of intracranial hypertension as well as in cases when CT image is not clear enough .
The parents play a significant role in clinical examination of a child. The parent´s experience with episode of drainage system dysfunction must be taken into consideration when examining the child with hydrocephalus. A neurosurgeon examines the child once a year, or even less, if he relies on a general pediatrician. The parents know the child´s daily routines the best so they can assess changes in his behavior. Therefore, close cooperation between a doctor and the parents is a basic requirement for early detection of drainage system dysfunction .
8. Basic properties of ultrasound
Definition of ultrasound. The ultrasound waves are mechanical-elastic oscillations, which move in the matter. Their movement is enabled by elasticity and compactness of the matter. The frequency of oscillation of ultrasound is above the upper level, i.e., 20,000 Hz. The frequency of 2–10 MHz is used in medicine .
The ultrasound is a mechanic oscillation, which transits the area of hard particles and makes vibrations. Properties of vibrations depend on density and structure of the tissue. Instead of movement of the matter, energy spreads around. This kind of oscillation is called longitudinal . Other types of oscillation (transversal, etc.) cannot spread around in the environment sufficiently.
The basic properties of the ultrasound are:
Frequency is measured in hertz (Hz) or in cycles per second.
Wavelength is a distance between compression of the same place of a medium in two successive cycles; it is measured in meters or corresponding subunits.
Movement velocity is determined by properties of environment, in which oscillation spreads around.
Pressure of waves depends on pressure oscillations related to counteractive static pressure (atmospheric, tissue).
Oscillation intensity is the spread of energy described by a unit of surface in a unit of time; it is measured in W/cm2.
When applying ultrasound to the human body, two limitations need to be taken into consideration—distinguishing property and absorption of ultrasound in tissues. The shorter the wave distance is, the better the distinguishing property of an ultrasound is. But at the same time, ultrasound is more absorbed in tissues . The human tissue is not a homogenous environment for spread of oscillation, so the oscillation is modified in various ways. It can be reflected off, refracted, broken apart, or absorbed.
If an ultrasound beam crosses the boundary of two environments, one part of the beam goes through it, while the other part reflects off. If the beam reflects off, the angle of reflection depends on the angle of incidence and acoustic impedance of two different environments. If the acoustic resistance of boundary environments differs significantly (e.g., tissue and gas), all energy can be reflected. Oscillation, which has not been reflected, subordinates to scattering. Then it interferes and part of it goes back through the boundary of the environments. This part may play a crucial role in the final interpretation of a sonographic image. The ability of the tissue to reflect echoes is called echogenicity (or echogeneity). The strongest reflections (echogenous and hyperechogenous) make large surfaces with high amount of collagen (the diaphragm, vessels, and sacs of the organs). The small surfaces containing low amount of collagen, which reflect narrow beams, are called hypoechogenous (parenchymal organs) .
9. Biological effects of ultrasound
Biological effects of ultrasound include all processes in the living tissue, which are caused by oscillation. It may induce them directly, or it serves as a trigger and facilitator factor for their onset and development .
Assessment of the ultrasound-induced biological effects and safety of ultrasound diagnostic method has become more complex because of advances in research and capacity regulation of the equipment. The modern sonographic equipment is more effective in diagnostic processes, but it produces higher acoustic intensity than the simple B-mode device .
Ultrasound examination is an inevitable part of diagnostic methods applied in neurological disorders not only in neonates and infants but also in adults. However, an increase of number and duration of examinations leads to higher exposure of the brain tissue to ultrasound oscillations. The harmful biological effects on patients and healthcare professionals exposed to ultrasound within the diagnostic power range have not been confirmed yet. However, types of damage caused by mechanisms, which have been already recognized, or by the new ones must be taken into consideration. The harmful effects of ultrasound examinations are still a disputed topic in literature .
The biological effect depends on properties of ultrasound oscillation and environment. Ultrasound is a mechanical form of energy, in which pressure wave goes through the tissue. In general, physical effects of ultrasound are classified as follows:
Thermal effects—overheating of the tissue after ultrasound transition; heat is also produced on the surface of a probe.
Cavitation—production of gas bubbles at high negative pressure.
Other mechanic effects—radiation power causing streaming in fluids and tension on the contact point of the tissue.
9.1 Thermal effects
When ultrasound beam is transmitted into the tissue, friction power in the tissue makes the ultrasound-induced molecules move, and some energy is absorbed and transformed into heat. Production or loss of heat depends on factors which modify heat production and diffusion. Increased heat production is influenced by pressure amplitude of ultrasound, acoustic impedance of tissue, and absorption coefficient of a medium. Diffusion and loss of heat are determined by local tissue perfusion and conduction.
Thermal effect is influenced also by thermal toleration. The human body deals with changes of temperature in various physiological processes. To some extent, the body can tolerate them without any further damage. Transformation of absorbed ultrasound into heat depends on the absorption coefficient of the tissue. The highest degree of transformation is typical for the tissues with high absorption coefficient (mainly the bones). On the contrary, the lowest degree of energy transformation takes place in the tissues with low coefficient (e.g., amniotic fluid).
Previous observations have shown that oscillation intensity of 100 mW/cm2 with frequency of 1 MHz during longitudinal exposure may be the threshold intensity for biological effect of ultrasound. The surface layers are heated in high frequencies, while the deep layers are heated in low frequencies. Focusation is considered the most significant factor determining the thermal effects in various oscillation intensities. Focusation controls width of the beam by increase of lateral distribution. As a result, heat production of a medium decreases, and heat distribution becomes more efficient. Finally, it is manifested by decrease of thermal effect .
Any adverse effects of the ultrasound have not been described in clinical practice yet. However, this fact cannot be neglected, especially because of increased interest in continual longitudinal monitoring by the transcranial Doppler sonography as well as the more frequent use of color duplex devices in prenatal screening .
The bubbles in body fluids are produced and moved by the ultrasound. There are two types of cavitation: long-term (stable, inert) and temporary (noninert).
Stable cavitation is of great potential to damage the tissue. Bubble are compressing and enlarging continuously. Their size remains the same when shifts of compressions and enlargement are regular. The inert bubble absorbs part of oscillation energy, which will be transformed into heat or circular oscillation. It enables flow of fluids around the bubble, which is followed by pressure effect. Pressure effect may manifest by fragmentation of the cell membranes and biomacromolecules.
Temporary cavitation occurs in bubble oscillation, when the effect of expansion is greater than compression. This increases size of a bubble. Exceeding critical size leads to sudden collapse and occurrence of critical pressure, the so-called shock waves. Intensive increase of pressure and temperature during collapse of bubbles may result from various biological effects such as lysis of the cells, production of free oxygen radicals, and vaporization. Production of free radicals may lead to cell damage. Furthermore, the mutagenous effect is also possible to happen . The Bioeffect Committee of the American Institute of Ultrasound in Medicine  states that temporary cavitation may occur in the soft tissues when there are extremely short pulses with power of 3300 W/cm2. However, it is not reached in the common ultrasound diagnostic process. In recent years, requirements on sonography devices have been increasing as well as power output of the device. Therefore, this effect needs to be taken into consideration in the future.
Results of some studies on animals claim that ultrasound-induced cavitation causes hemorrhage in the lungs and the intestines. These effects have been found in the tissues which were in contact with gas [248, 249, 250, 251, 252]. The use of a contrast substance leads to production of microbubbles which provides gas cores for onset of cavitation. This means that the contrast substance decreases the threshold for onset of cavitation.
9.3 Other mechanic effects
The course of ultrasound oscillation causes low-frequency radiation in the tissue. Radiation produces pressure in the direction of a bundle of rays from the probe. It should not be confused with oscillation pressure of the ultrasound as such. Pressure and pressure gradient, which are produced in a bundle of rays, are very low, even at higher intensities of a diagnostic range of ultrasound oscillations . The effect of radiation manifests when liquids are present. Oscillation, which may manifest with liquid flow, is produced. The velocity of liquid flow is low, and usually it does not cause any harm.
10. Doppler sonography
In 1842, Austrian physicist Johann Christian Doppler (1803–1853) in his work called Über das farbige Licht der Doppelsterne und einiger andere Gestirne des Himmels described the principle that says that frequency of oscillation changes if the source moves against the observer ( Figure 30 ). Doppler´s discovery of change of oscillation from a movable source was far ahead of his time. It was applied in practice for the first time in the 1920s. According to the frequency moves recorded in spectral lines of radiation, which come from distant galaxies, for the first time, the astronomers could claim that the universe is enlarging. This discovery, made by Edwin P. Hubble in 1929, has changed significantly the approach of a modern astronomy to nature of the universe .
Doppler’s effect enabled construction of navigation systems and radars during World War II.
In medicine, Doppler ultrasonography has been applied just a few decades ago. It was used later than the ultrasound monitoring devices, which were more difficult to construct. In the 1970s, the use of duplex technique has enabled imaging blood flow in the vessel which could be seen in the tomographic B-image. This improved the use of Doppler sonography. Later, modernization of the ultrasound devices has allowed the use of color Doppler imaging in clinical practice. The imaging method based on the Doppler effect is accurate, noninvasive, and accessible. The Doppler effect is a basic principle of the ultrasound diagnostic procedure. It measures velocity of moving particles in vivo. Evaluation of selected hemodynamic parameters of blood flow in vessels is the most common use of Doppler ultrasound. When Doppler sonography is used, the morphologic information gained by traditional ultrasound imaging is enriched with important information, which is functional in its nature .
10.1 The role of Doppler principle in ultrasonography
The Doppler effect occurs when the ultrasound frequency changes due to ultrasound oscillation, which is reflected from a moving obstacle (e.g., blood elements in vessels) ( Figure 31 ).
When ultrasound oscillation is reflected from moving blood elements in the vessel, the frequency will change in relation to the angle of beam reflection and velocity and direction of blood flow. According to the direction of the blood element movement, whether it goes toward or away from the source of ultrasound oscillation (a probe), the frequency range can be described as positive or negative ( Figure 32 ).
The difference between frequency of transmitted and absorbed oscillation is called the frequency Doppler shift (∆F). It is defined by the following formula:
where ∆F is the frequency Doppler shift, v is the velocity of erythrocytes flow, Fe is the emission frequency wave, α is the angle between the ultrasound beam and the vector of erythrocyte flow, and C is the velocity of ultrasound in tissue (it is relatively constant in most tissues of the human body; therefore, the value ∆F is not significantly influenced).
In practice, frequency of ultrasound and velocity of ultrasound wave in tissue is constant. If a constant angle between ultrasound beam and vessel is maintained, velocity of blood flow in the vessel is a determining factor of Doppler frequency shift. The angle of the ultrasound beam and long axis of the vessel is known as the angle of insonation. If the angle of insonation is 0°, then frequency shift equals the velocity of blood flow (cos 0° = 1). On the contrary, if the angle of insonation is 90°, then there is no frequency shift. The relation between measured and real velocity of particles can be expressed as v measured = v real × cos α3 . In theory, the angle of insonation should be as small as possible, but in practice, the beam smaller than 30° is being used. Cos 30° = 0.87 means that measured velocity is 13% smaller than the real velocity.
Two basic types of Doppler record can be distinguished:
The spectral record describes dependence of velocity of blood flow on time and enables determination of flow parameters in the vessel.
The color Doppler record enables to determine direction of blood flow in the vessel and rough range of velocity of blood flow in the vessel.
In the spectral Doppler record, the positive Doppler frequency shifts (flow toward a probe) are drawn above the zero line by red, while the negative frequency shifts (from a probe) are drawn below it by blue ( Figure 32 ).
The following basic Doppler systems are applied in diagnostic sonography:
The systems of continuous emission
The pulsatility systems
The colorful system of Doppler tomography
The procedure of color imaging of Doppler power
10.2 The Doppler systems with continuous wave (CW)
The Doppler systems with continuous wave represent the simplest form of Doppler devices. The probes use two piezoelectric elements. One probe transmits ultrasound waves, and the other absorbs reflections of waves continuously. The biggest disadvantage of the system is a lack of axial differentiation. It means that venous structures, which are located in various depths along the axis of the Doppler bundle, are insonated simultaneously and altogether influence the results in the Doppler record. Therefore, it is not possible to determine which part of the total spectrum represents the particular vessel .
10.3 The pulsatility Doppler systems (the pulsed waves, PW)
The pulsatility Doppler systems use one piezoelectric element, which transmits and absorbs ultrasound waves alternatively. The probe functions in the alternating regime, which means that after transmitting a short ultrasound impulse, the probe absorbs delayed reflections created in moving blood elements in the vessel.
In the PW method, setting the location and size of sampling volume allows to direct an ultrasound beam to the vessel. The selected size of sampling volume should correspond with the width of transparency in the vessel. If the volume in the middle of the vessel is too low, then the lower frequencies occurring near the vascular wall, where the erythrocytes move slowly, will not be recorded. Therefore, the values of velocity will be significantly increased. On the other hand, when the sampling volume is oversized, measurement takes place in the vessel and its surrounding, the average values will be lower, and high artifact disturbance (noise) will be present .
Transmission frequency of oscillation series is called the pulse repetition frequency (PRF). The PRF must be at least two times greater than the frequency of detected Doppler shift (the Nyquist’s limit) (PRF = 2fdmax). The depth of ultrasound intersection into the tissue decreases due to increasing emission frequency, and thus the PRF has to be the lower, the greater distance between the vessel and the probe is. The PRF values, which are determined by the required depth of intersection, delimit the highest velocity (the Doppler shift), which can be measured .
If low PRF is chosen for measuring the velocities, the disturbance artifact, so-called aliasing, occurs. It is manifested by Doppler frequencies lower than ½ PRF in the negative spectrum of values  ( Figure 33 ).
This phenomenon is responsible for misinformation on frequency shift and causes lower or reverse frequency shift. It is manifested by the signal cutoff and its occurrence on the opposite side of the scale. Therefore, high pulse repetition frequency is necessary for detection of fast moving blood elements caused by high Doppler shift. On the contrary, high frequency controls maximum depth at which the signal can be accepted. It has to be noted that the Doppler shift depends on the transmitter frequency. The relationship between these quantities is as follows :
where Vmax is the maximum velocity of the moving object (blood elements), c is velocity of ultrasound transmission in the tissue, D is depth at which it is measured, and Fo is frequency of the transmitted signal from the probe.
This relationship shows that the greater the depth for measuring velocity of moving blood cells is, the lower is the maximum detected velocity. That is why blood flow of higher velocity is measured by the low-frequency probes [58, 256].
10.4 The color flow Doppler tomography (CFD, real-time two-dimensional Doppler)
The system of the color Doppler sonography can analyze all Doppler shifts in the selected area. After assessment of the amplitude, frequency, and properties, the CFD transmits echo into the black and color spectra. The B-image is created from the indifferent, nonmoving points. The moving structures, which make the Doppler shift, are drawn by colors. Red color represents the flow toward the probe, blue stands for the flow from the probe, and green is assigned to the turbulent blood flow. The light shades represent fast flow, while the darker ones show slow flow [11, 257].
In neurosonology, the color Doppler sonography is mainly used for accurate detection of strains in the vessel, assessment of blood flow in the sections of vessel, making diagnosis of vascular malformations, and differentiation of the avascular lesions from the vascularized lesions [258, 259, 260]. Despite the disadvantages, the color Doppler sonography can in some cases substitute angiography and provides accurate information about vascular structures in the CNS in neonates and infants .
10.5 The technique of the color Doppler power mapping (color Doppler energy, CDE; color power angio, CPA; Doppler power mode; power mapping)
The principle of Doppler power mapping is based on determination of the amplitude of Doppler signals created in the moving structures. The color Doppler energy enables better imaging of the tiny vessels with slow blood flow. However, information about the direction and velocity of blood flow is missing here . The advantages of the CDE method are the sensitivity to slow blood flow and independence on the angle of insonation (except of 90°). The three-dimensional reconstructions of anatomy of the blood vessels are more visible in the unified color mapping than in traditional color imagining.
11. The transcranial color-coded Doppler ultrasonography
Transcranial color-coded Doppler ultrasonography (TCCD) enables insonation of the cerebral arteries through the standard acoustic windows. In 1967, Fox was the first to perform the Doppler recording of cerebral arteries [262, 263]. The publication by H. Bada from Springfield, Illinois , has been of a great importance for further development. The transcranial Doppler ultrasonography was introduced to clinical medicine by Aaslid .
Thanks to the pulse mode, the spectral image is obtained from accurately set distances and simultaneously by color coding from precisely defined segments of the cerebral vessels in two-dimensional imaging and color imaging.
11.1 The transcranial color-coded Doppler ultrasonographic examination
In order to avoid waking or upsetting the child, the examination has to be performed as carefully as possible. The patient should be calm. The lumen of cerebral vessels should be stable, and the position of sample volume in the vessel should be constant. The venous outflow might be decreased, and the real values of the Doppler curve might be changed if the baby´s head is rotated inappropriately. During examination, it is important to perform the selected method precisely. The double screen for the B real-time image with color-coded flow and the PW image is used. Color coding is used to localize a particular segment of the cerebral vessel and detect direction of blood flow. Appropriate correction of the angle of insonation is of a great importance. The best Doppler signal image containing at least three up to seven cardiac cycles is used for assessment. The measurements are performed by the software equipment. The linear and convex sonographic probes are applied during examination ( Figure 34 ) [58, 266].
The following ultrasound approaches can be applied:
The approach through the anterior fontanelle is applied in neonates and infants with the unclosed fontanelle. The probe is placed on the anterior fontanelle in the midline area ( Figure 35 ). This approach is mainly used for blood flow imaging in the ACA, ICA, and BA.
The transtemporal approach is used to assess blood flow in the MCA and PCA. The probe is introduced into the darkest place on the temporal bone above the zygomatic arch, 1–2 cm from the external auditory canal ( Figures 36 and 37 ) .
The suboccipital approach—the distal segments of vertebral arteries and basilar artery can be easily visualized through the foramen occipitale magnum ( Figure 37 ).
The transorbital and submandibular approach are used occasionally ( Figure 37 ).
The approach through the defects of calva (posttraumatic, postsurgical).
During examination, firstly, the basal Doppler parameters are assessed by a sonographic probe, which touches the skin gently through the layer of a gel. Then the compressive test on the anterior fontanelle is carried out. The Doppler parameters are assessed, while the anterior fontanelle is compressed by the sonographic probe or ophthalmodynamometer. The pressure is stated in g/cm2 ( Figure 38 ). Measurement is performed through the anterior fontanelle or the temporal acoustic window [269, 270, 271]. The compressive test on the anterior fontanelle is considered positive if the basal RI value of cerebral vessels increases more than 25% or the value of compressive RI is higher than 0.90 .
12. The Doppler curve, measured and calculated parameters
12.1 The Doppler curve
The cerebral circulation is a low-resistance vascular system, which is typical for organs requiring constant high minute blood flow. The Doppler curve of low-resistance vascular circulation is characterized by positive blood flow during systole but also during diastole ( Figures 39 and 40 ). In contrast, the physiological process of a high-resistance vascular system Doppler curve, for example, in the extremities, has three phases and is characterized by short-term reverse flow during early diastole and short positive flow during end-diastole ( Figure 41 ) .
In physiologic conditions, blood flow is laminar in its nature. The highest velocity is in the middle, while the lowest is near the vascular wall. When pressure gradient rapidly increases during systole, blood flow in the arterial network increases, too. Therefore, systolic segment of the Doppler curve is characterized by rapid increase. During diastole, blood flow decreases, and thus erythrocytes near the vascular wall move slower than erythrocytes which are in the middle of the vessel. Therefore, the diastolic phase of the spectrum is lower; its profile is nonhomogeneous and rich in various frequency shifts.
The shape of the arterial Doppler curve is influenced by various factors. Myocardial contraction creates pressure gradient in the arterial network. Rapid increase of systolic segment of the curve depends on a range of pressure gradients, vascular wall elasticities, and blood viscosities. The pressure wave diminishes in distal direction, and thus velocity of blood flow decreases. Myocardial contraction transfers energy into the elastic vascular wall of the great arteries. Their gradual compression during diastolic phase of the pulse wave ensures continuous prograde blood flow. Blood flow decreases during diastole. The shape and properties of diastolic phase of the Doppler curve are characterized primarily by resistance of the distal vascular network and secondarily by systemic, venous, and intrathoracic pressure. When peripheral vascular resistance is high, velocity of diastolic blood flow decreases. Sometimes it can even drop down to negative values. In physiological conditions, diastolic blood flow in cerebral arteries has always the same direction as the systolic .
12.2 Measured and assessed parameters of the Doppler curve
The following parameters can be assessed by the Doppler curve of blood flow in cerebral arteries:
Peak systolic blood flow velocity (Vsyst)—the maximal velocity pulse wave. The value is expressed by maximal height of the curve during systole.
End-diastolic blood flow velocity (Ved)—the value of end-diastole is assessed instead of the minimal blood flow velocity during diastole.
Mean blood flow velocity (Vmean)—it expresses the value of mean blood flow velocity between the beginning of systole and end of diastole during one cardiac cycle. Blood flow velocity is stated in cm/s or m/s.
From the aspect of cerebral perfusion assessment, the assessment of systolic and diastolic velocities from blood flow is not sufficient, because the values are very variable. Concerning change in vessel caliber, the change in blood flow velocity does not have to correspond with the change in degree of perfusion . This deficit can be substituted by qualitative analysis of the Doppler curve, which compares systolic and diastolic blood flow velocities in the vessel .
The advantage of qualitative analysis of the Doppler curve is the fact that the results are less influenced by the nonstandard angle α and local turbulences in the arterial lumen. The angle of insonation has impact on systolic and diastolic velocities, but the ratio of velocities remains stable.
The most common indices of the Doppler curve are as follows:
The resistance index (RI, Pourcelot index) has been used in 1974. It is a parameter showing resistance of the vascular network. It is defined as:
The pulsatility index (PI, Gösling index) is defined by Gösling in 1969:
Regarding the mean blood flow velocity, the PI values in a place of a denominator are higher than the RI values. PI is very important especially in zero or retrograde diastolic blood flow when RI or S/D index cannot be calculated .
The systolic-diastolic ratio (S/D index) is defined as:
Another parameter of the Doppler curve is the acceleration time (AT), which is measured from the beginning of systole until it reaches the maximal velocity . It is determined by the factors such as myocardial contractibility, cardiac output, arterial blood pressure, and vessel compliance.
12.3 Development of Doppler parameters of cerebral circulation: physiological values
The normal values of blood flow velocity in cerebral vessels, which can be assessed by transcranial Doppler ultrasonography in adults [276, 277, 278, 279, 280, 281, 282] and children [37, 278, 283, 284, 285, 286, 287], have been published repeatedly.
In order to differentiate of pathological values, knowledge of the physiological range of values is an inevitable background of an examining method. Although the parameters of cerebral circulation examined by Doppler technique have been published repeatedly, there are no unified and generally accepted reference values. The issue of normal values is caused by several reasons:
Use of various ultrasonographical equipment
Developmental changes in quality of Doppler equipment
Unknown technical parameters and methodology
Nonunified documentation and presentation of results
The reference values published by the authors stated above are not generally applicable. In the Clinic of Neurosurgery at the University Hospital Martin, we use physiological values proposed by Minárik  with precisely defined methodology and examination technique. The values of selected parameters of the Doppler curve of cerebral arteries are shown in Tables 6 – 8 . The critical RI values are those which are increased at a maximum of about 0.05 in comparison with the utmost value of a normal range.
|The standard values of the basal RI-ACA in the segment before genu corporis callosi in preterm neonates|
|<33rd gestation week||0.77 ± 0.09|
|>34th gestation week||0.70 ± 0.07|
During the first three weeks of life, the linear correlation between age and blood flow velocity in cerebral arteries is being observed. As they are getting older, the blood flow velocity increases in all cerebral arteries. The degree of blood flow increase throughout cerebral arteries does not depend on weight and gaining weight. The most significant changes occur in the first hours and days after birth because increase of blood flow velocity in cerebral arteries and decrease of resistance index are very rapid. Generally, preterm neonates have lower blood flow velocity reflected in higher value of resistance index ( Table 9 ). Higher degree of immaturity and lower weight at birth are linked with higher percentage of changes in Ved. In hypotrophic neonates, decreased Vsyst and Vmean were observed in the anterior cerebral artery, but blood flow velocity in the middle cerebral artery did not change. The Doppler parameters of cerebral arteries in hypotrophic neonates are influenced by weight at birth, gestational age, and mother´s smoking during pregnancy due to intrauterine growth retardation .
After the third week of age, increase of blood flow velocity in cerebral arteries slows down. The maximal values are reached before the age of 9 years. Since then blood flow velocity gradually decreases in an average of about 1–1.5 cm/s/year. The values for adults are reached in the age of 18 years. The resistance index gradually decreases during 12 months of age from the value of 0.70 to the value of 0.55 and then remains the same. In physiological conditions, blood flow velocity measured in the right and left parts of the brain does not change significantly .
12.4 The factors influencing the value of qualitative indices of the Doppler curve
The values of qualitative indices of the Doppler curve of blood flow are influenced mainly by the factors which change the diastolic segment of the curve. An overview of extra- and intracranial factors, which have impact on the Doppler parameters of the cerebral arteries, is shown in Table 10 . During examination, the factors described below need to be taken into consideration as well:
Interindividual norms. Methodology applied in measurement and technical parameters of ultrasound equipment have to be taken in account. When the results are ambiguous, it is recommended to observe dynamic intraindividual trends instead of comparing measured values with the norm [11, 58].
Physical and mental activity can also influence cerebral perfusion. During increased mental and physical activity of infants and older children, systolic, diastolic, and mean blood flow velocities in the proximal and distal segments of arteries have been significantly increased in the observed cerebral arteries. However, the resistance index did not change significantly if activity was changed .
Manipulation with the neonate, moving him from the incubator to a bed, and endotracheal suction from cannula may increase blood flow velocity in cerebral arteries as well.
Taking higher amount of blood sample, bradycardia, and apneic pauses may lead to decreased cerebral blood circulation, too.
|Extracranial factors||Intracranial factors|
|Increased resistance index||Hypocapnia, hyperoxia, congenital heart disease with left-to-right short circuit (ductus arteriosus Botalli persistens, truncus arteriosus), polyglobulia, blood hyperviscosity, increased hematocrit, indomethacin, severe arterial hypotension, decreased cardiac output, neuronal death||Acute intracranial hypertension (brain injury, cerebral edema, active hydrocephalus), brain infarction, intracerebral and intraventricular hemorrhage|
|Decreased resistance index||Hypercapnia, hypoxemia, hypoxia, seizures, asphyxia, hyaline membrane disease, increased cardiac output, hypervolemia, increased central venous pressure (right-sided heart failure, pneumothorax)||Inflammatory congestion, arteriovenous malformations of the brain, seizures|
12.4.1 The factors increasing the resistance index of cerebral arteries
Acute intracranial hypertension accompanies brain injuries, brain edema, and active hydrocephalus. It is manifested by increased RI and decreased, zero, or even reverse blood flow during diastole. The Vsyst values do not change significantly.
Hypocapnia—decrease of paCO2 causes vasoconstriction of cerebral arteries, and thus cerebral blood flow decreases. Decrease of paCO2 results in decrease of Ved and increase of RI. Rapid decrease of paCO2 leads to decrease of Vsyst . Loss of vascular reactivity to change of paCO2 is in relatively good correlation with severity and prognosis of child´s clinical condition .
Hyperoxia—increased paO2 causes mild vasoconstriction of cerebral arteries and is linked to decreased cerebral blood flow. The cerebrovascular response to change of paO2 is more uniform than the response to paCO2.
Congenital heart disease with left-to-right short circuit, for example, ductus arteriosus Botalli persistens truncus arteriosus, can have negative impact on cerebral perfusion. The range of changes in cerebral circulation depends on hemodynamic severity of left-to-right short circuit. No changes in the Doppler curve can be observed in small-signal short circuit [292, 293].
Indomethacin induces vasoconstrictions of cerebral arteries. The use of indomethacin increases resistance index of cerebral arteries. Inadequately high doses of indomethacin may cause ischemic damage of cerebral tissue.
Blood hyperviscosity—in polyglobulia, it is accompanied by decrease of absolute values of blood flow velocity in cerebral arteries and just mild increase of resistance index. Changes can occur in proximal and distal segments of cerebral arteries. Changes of the Doppler curve parameters during change of hematocrit are influenced by changes of viscosity and rheological properties of blood.
In intraventricular hemorrhage in neonates, increase of RI and decrease of Ved occur in cerebral arteries on the site of hemorrhage. But change is mild or none in arteries, in which branches do not protrude into the site of hemorrhage or do so only partially. The range of changes of parameters of the Doppler blood flow curve depends on severity of IVH and accompanying factors. In IVH of grades 3 and 4, changes can be detected in all main cerebral vessels [58, 264].
In severe systemic arterial hypotension, resistance index of cerebral arteries increases due to significant decrease of blood flow velocity during diastole in low cardiac output.
In determination of neuronal death, prograde diastolic blood flow in cerebral arteries cannot be seen.
Brain infarction—usually after acute brain infarction, blood flow is not initially detectable in a particular segment, and decreased Ved with increased RI is detected in proximal segment of the vessel. Arterial recanalization can be detected by gradual return of the Doppler signal to the standard curve followed by temporary increase of velocity, probably a sign of hyperemia [58, 278].
12.4.2 Factors decreasing the resistance index of cerebral arteries
Hypercapnia causes vasodilatation of cerebral arteries and increases blood flow in the brain. When paCO2 increases, Ved increases but RI decreases. When increase of paCO2 is more rapid, Vsyst increases, too.
Seizures decrease resistance index of cerebral arteries. Increased metabolic demands of the brain give rise to vasodilatation.
Inflammatory congestion decreases the resistance index. But the index increases during progression of hyperemia and development of intracranial hypertension.
Asphyxia—immediately after asphyxia, the values of resistance index of cerebral arteries can be abnormal, determined by moderate redistribution of blood circulation, cardiac output, and cerebral autoregulation. Afterward, postasphyctic cerebral hyperemia, characterized by the so-called soft flow with high values of blood flow velocity during diastole and low resistance index, occurs .
Hyaline membrane disease (idiopathic respiratory distress syndrome, IRDS) is a combination of hypoxia, hypercapnia, and systemic arterial hypotension. If autoregulatory mechanisms of cerebral circulation are functional, the resistance index of cerebral arteries can get back to normal by adequate ventilation regime [11, 297].
In increased cardiac output or in hypervolemia, the resistance index usually decreases.
Conditions with increased central venous pressure, for example, pneumothorax, endotracheal suction from cannula, and right-sided heart failure, result in decrease of resistance index of cerebral vessels.
In venous anomalies of the brain, bidirectional flows are often present, but also steal phenomenon may occur.
13. Morphology of the cerebral ventricles in pediatric hydrocephalus
For the reason of difficult accessibility, assessment of volume of the cerebral ventricles by computed analysis is not commonly used in children with hydrocephalus in clinical practice. Linear morphometric parameters, which can precisely detect intracranial structures, are preferred instead. Assessment of morphology of CSF pathways by USG, CT, or MRI examination plays a crucial role in assessment of dynamics of pediatric hydrocephalus.
Considering detection of onset of the cerebral ventricle dilatation and further observation of its dynamics in neonates and infants with hydrocephalus (before closure of the anterior fontanelle), transcranial ultrasonography plays the most important role [298, 299]. Gyrification of the brain, shift of midline structures, the CSF pathways (the cerebral ventricles and subarachnoid space), and pathological lesions are assessed by ultrasonography. Transcranial ultrasonography enables assessment of dynamics of intracranial bleeding in preterm neonates. In acute hydrocephalus, dilatation and roundness of the occipital and temporal horns of the lateral cerebral ventricles and the trigonum area develop at first. Especially the frontal horns and bodies of the lateral cerebral ventricles are enlarged in ventriculomegaly due to cerebral atrophy .
In a child with hydrocephalus, morphometry of the cerebral ventricles and subarachnoid space is an important part of the ultrasonographic examination. Accurate size of the CSF pathways enables comparison with standard values as well as observation of intraindividual dynamics. Subjective assessment of the CSF pathways should be done together with size measurement. The most common morphologic parameters of the brain measured in children with hydrocephalus are as follows:
Wdx.—width of the right lateral cerebral ventricle (usually width of the frontal horn in the coronal plane going through the foramen of Monro)
Wsin.—width of the left lateral cerebral ventricle
VIdx.—ventricular index of the right lateral cerebral ventricle (the ventricular index, the greatest distance of the lateral wall of the anterior horn of the lateral cerebral ventricle from midline)
VIsin—ventricular index of the left lateral cerebral ventricle, size of the third and fourth cerebral ventricles, width of the interhemispheric fissure, and width of the subarachnoid spaces on convexity
IV—interventricular distance (distance between the lateral corners of the lateral cerebral ventricles)
TC—transcerebral size (width of both hemispheres)
Thickness of the cortical mantle ( Figure 42 )
The frontal and temporal horn ratio (the ratio of interventricular distance between the frontal and temporal horns of the lateral cerebral ventricles) is probably the new ultrasonographic index, which can be easily measured on the coronal sonographic section of the brain. The statistical comparison between new frontal and temporal horn ratio and commonly used frontal and occipital horn ratio shows strong linear correlation between both coefficients .
Many researchers have dealt with determination of the reference values for assessment of size of the cerebral ventricles in neonates by transcranial ultrasonography. Davies et al.  measured the reference values of linear size of the cerebral ventricles in preterm neonates between 23rd and 33rd gestation week ( Table 11 ). The size of the frontal horn of the lateral cerebral ventricle corresponded with results of the research by Perry et al. . They determined the value of 3 mm as the upper limit for the 26th–42nd gestational week. The values of thalamo-occipital distance were similar to the fetal values in this gestation age . The position of the head during examination and gender of a child did not have impact on the value of parameters measured. The highest variability, but in acceptable low values, was found in the size of the fourth cerebral ventricle. Perry et al.  confirmed that width of the frontal horn of the lateral cerebral ventricle does not change between 26th and 42nd gestation week. Similarly, Sauerbrei et al.  found out that ventricular index does not change between 25th and 35th gestation week.
|The linear parameters of cerebral ventricles||Mean||SD||Referential scale|
|Width of the frontal horn of the lateral cerebral ventricle||1.27||0.81||0–2.9|
|Width of the third cerebral ventricle||1.07||0.74||0–2.6|
|Width of the fourth cerebral ventricle||5.37||1.03||3.3–7.4|
|Length of the fourth cerebral ventricle||4.74||1.09||2.6–6.9|
On the other side, results of other research on assessment of size of the cerebral ventricles in a wide range of gestational ages confirmed that ventricular index of the frontal horn of the lateral cerebral ventricle slightly increases regarding gestational age of the infant ( Figures 43 and 44 ) [305, 306]. Sondhi et al.  also confirmed a slight increase of size of the cerebral ventricles (size of the frontal horn of the lateral cerebral ventricle, thalamo-occipital distance, and width of the third and fourth cerebral ventricle) in relation to gestational age of the infant. But it was proportional to change of the brain tissue.
The computed tomography (CT) or nuclear magnetic resonance (MRI) is used for a more precise assessment of the intracranial morphology. Beam radiation, which has a negative effect on a child´s organism, is the main disadvantage of CT examination. When these examination techniques are indicated, transport of the child, especially in nonstable preterm neonates, and necessity of sedation have to be taken into consideration. Active hydrocephalus can be detected by the presence of typical periventricular hypodensity or increased intensity of the signal in T2-weighted MRI image due to transependymal diffusion of cerebrospinal fluid ( Figure 6 ). In pathological lesions, MRI technique enables accurate measurement of degree and relation to the surrounding structures. Degree of hypoxic-ischemic brain damage can be also clearly seen in an MRI image. Flow of cerebrospinal fluid through CSF pathways can be shown by cine-phase MRI sequence. It is also used in postsurgical assessment of the function of endoscopic ventriculostomy of the third cerebral ventricle ( Figure 45 ). The combination of CT or MRI examination with neuronavigation enables to plan trajectory and depth of ventricular catheter insertion of drainage systems and precise insertion of neuroendoscope into the cerebral ventricles ( Figure 46 ) .
Width of the frontal horn of the lateral cerebral ventricle in the coronal plane; sonographic section through the foramen of Monro; thalamo-occipital distance in the parasagittal section, in which whole lateral cerebral ventricle is presented; distance between the thalamus and the most dorsal segment of the occipital horn of the lateral cerebral ventricle; width of the third cerebral ventricle in the axial plane near the foramen of Monro; width and length of the fourth cerebral ventricle between the right and left side of the lateral recess; width and length of the fourth cerebral ventricle in the transverse axis through the posterior aperture, through asterion used as an acoustic window. Width of the fourth cerebral ventricle represents the distance between the base and peak of a triangle. SD, standard deviation.
When morphometry of the CSF pathways is assessed on CT and MRI image, the following linear parameters of the brain are taken into consideration ( Figures 47 and 48 ): Evans´ index, the ratio between maximum width of the frontal horns of the lateral cerebral ventricles and maximal internal diameter with of the calva ; the ratio between the frontal horns of the lateral cerebral ventricles (FHR, frontal horn ratio); the ratio between maximum width of the frontal horns of the lateral cerebral ventricles and maximal internal diameter of the calva at the same level; the bicaudate ratio, the ratio between width of the lateral cerebral ventricles between the caudate nuclei and maximal internal diameter width of the calva at the same level; the ratio between the frontal and occipital horns of the lateral cerebral ventricles (FOR, frontal/occipital horn ratio); and the ratio between sum of maximum width of the frontal and occipital horns of the lateral cerebral ventricles and twice the amount of maximal internal diameter width of the calva . Ventriculomegaly is defined by Evans´ index ≥ 0.30. The standard value of FOR equals 0.37, and it is independent on child´s age .
Interesting results can be found in the research by Eide  who assessed the relationship between intracranial pressure and size of the cerebral ventricles in hydrocephalus, craniosynostosis, and dysfunction of drainage systems. To measure intracranial pressure, he used the continual ICP monitoring with quantitative analysis of the data. The size of the intracranial ventricles was assessed by selected linear morphometric parameters. Significant correlation was not confirmed between current size of the cerebral ventricles and value of intracranial pressure in the sample of 184 patients. The relationship between measured parameters was not influenced by age of patients nor etiology of intracranial hypertension. In addition, statistically significant correlation between long-term change of size of the cerebral ventricles and change of intracranial pressure was not observed either. Statistically significant correlation between change of size of the cerebral ventricles and change of mean of ICP or number of peaks of ICP was not found in 31 cases of simultaneous measurement of ICP and size of the cerebral ventricles. The results show that assessment of current size and long-term change of size of the cerebral ventricles by CT examination, in craniostenosis and dysfunction of the drainage systems, is not a reliable indicator of current value and change of value of intracranial pressure.
Low correlation between size of the cerebral ventricles and pressure of the anterior fontanelle was also confirmed in 19 cases of asymptomatic pediatric hydrocephalus . Statistically significant correlation between size of the cerebral ventricles and change of ICP values was not observed in the sample of 12 cases of asymptomatic intracranial hypertension . Statistically significant correlation between mean of intracranial pressure measured during lumbar puncture and size of the cerebral ventricles measured by CT examination was not found in a bigger sample of 181 children with communicating hydrocephalus .
In experimental conditions, a decreased number of structural proteins and enzymes bound to myelin followed by demyelination and axonal loss were measured in the white matter in cases of progressive hydrocephalus . Assessment of changes in the white and gray matter of the brain before and after drainage procedure showed that early drainage of cerebrospinal fluid in progressive pediatric hydrocephalus is the basic requirement for positive neurological outcome of treatment .
Volume of the cerebral ventricles in children with hydrocephalus before insertion of drainage system can be up to 14 times the standard value. Gradual decrease of size of the cerebral ventricles can last 6 months after insertion of the drainage system (shunt). Change in amount of volume of the cerebral ventricles can be also influenced by a type of drainage system, especially a valve used. Xenos et al.  confirmed a significant postsurgical decrease of volume of the cerebral ventricles in children with hydrocephalus after insertion of the medium pressure cylindrical valve shunt compared with insertion of the Delta 1.5 valve (Medtronic PS Medical, Goleta, California). However, difference was not confirmed in statistical analysis. Despite that fact, the authors of the study suppose that the medium pressure cylindrical valve shunt can cause hyperdrainage in comparison with the Delta 1.5 valve, especially within first months after operation. Jain et al.  confirmed that the first insertion of the medium pressure cylindrical valve shunt decreased size of the cerebral ventricles in comparison to cases with initial insertion of the Delta 1.5 valve. No difference in postsurgical change of size of the cerebral ventricles between these two types of shunts was found when revision of dysfunctional drainage systems had been performed. In children with drainage system, change of size of the cerebral ventricles can change intracranial dynamics, viscoelastic properties, compliance of the brain tissue, and reaction to shunt functioning. The effect of change of biomechanical properties of the brain might be greater than impact of a different valve used. The results of both studies revealed importance of individual analysis of intracranial dynamics in pediatric hydrocephalus before drainage system insertion and shunt optimization according to the type and opening valve pressure.
Location and adjacent tissue of the intraventricular end of ventricular catheter are an important prediction factor in relation to risk of shunt dysfunction. Location of ventricular catheter in the frontal and occipital horn of the lateral cerebral ventricle as well as a condition, in which the end of the catheter is surrounded by cerebrospinal fluid or touches the brain, can decrease risk of drainage system failure. Therefore, adequate design of a drainage system and appropriate location of the ventricular catheter are necessary for good control of size of the cerebral ventricles .
The analysis of sonographic morphometric parameters of the cerebral ventricles after successful drainage procedure in 40 neonates with hydrocephalus revealed a significant decrease of size of the cerebral ventricles. The drainage procedure had led to significant decrease of width of both lateral cerebral ventricles, bidirectional ventricular index, and width of the third cerebral ventricle. Before drainage procedure, progressive dilatation of the cerebral ventricles was observed in 36 (90%) cases and stable dilatation in 4 (10%) cases. During the early postsurgical stage after drainage procedure, regressive dilatation of the cerebral ventricles was observed in 31 (77.5%) cases and stable dilatation in 9 (22.5%) cases. Although drainage procedure (with increased ICP value measured before the surgery) had been performed, stable dilatation of the cerebral ventricles was observed in 10% of neonates with hydrocephalus. After drainage procedure, the clinical signs of intracranial hypertension had disappeared in the early postsurgical period. However, in 22.5% of cases, stable dilatation of the cerebral ventricles had been present after the surgery . Also, other studies on pediatric hydrocephalus [28, 320, 321] confirmed decrease of size of the cerebral ventricles due to cerebrospinal fluid derivation when it was assessed by ultrasonography.
It is generally known that the use of CT examination is limited in suspicion of dysfunction of drainage system in children with hydrocephalus. It may be helpful to compare current CT image with the previous one when assessing dynamics of the intracranial lesion or size of CSF pathways. The previous CT images cannot be often accessed (entering the archive in the night, performing CT examination in a different hospital), which decreases validity of the examination. When CT examination shows progression of dilatation of the cerebral ventricles, it is usually a sign of blockage of drainage system. On the contrary, the stabilized size of the cerebral ventricles doesn´t exclude acute blockage of the drainage system, in which an urgent neurosurgical intervention is needed . Studies of various researchers refer to occurrence of dysfunction of drainage systems without change of size of the cerebral ventricles found in the CT image [227, 228, 322, 323].
The degree of dilatation of the cerebral ventricles depends on viscoelastic properties of the wall of the brain tissue . Firstly, dilatation develops in the lateral cerebral ventricles. Then it spreads to the third cerebral ventricle, to the aqueduct, and finally to the fourth cerebral ventricle. This order is given by resistance of the brain tissue around the CSF pathways . Slit ventricle syndrome may develop in children with chronic hyperdrainage of the cerebral ventricles [325, 326, 327]. In children with narrow cerebral ventricles, if obstruction of the shunt occurs, enlargement of the cerebral ventricles might not be seen in the CT image regardless of increased intracranial pressure . Decreased re-expansibility of the cerebral ventricles can be caused by subependymal gliosis and decreased compliance of the wall of the cerebral ventricles and the brain tissue. At the same time, Laplace´s law can play a role. According to it, to enlarge a compartment with low volume, greater pressure is necessary than for enlargement of a compartment of larger volume [224, 324, 329].
In cases of long-term inserted drainage system, changed biomechanical properties of the brain may be also responsible for different clinical manifestations of shunt dysfunction. In relation to drainage system obstruction, faster deterioration of neurological manifestations was observed in children with narrow lateral cerebral ventricles (Evans’ index ≤ 0.35) than in children with large cerebral ventricles (Evans’ index > 0.35). The predictive factors of decreased re-expansibility of the cerebral ventricles in shunt obstruction in children with hydrocephalus with indwelling drainage system are as follows: decreased size of the cerebral ventricles (Evans’ index < 0.33), children over 3 years of age (if initial insertion of the shunt was performed in the first year of age), or period of 5 years after the first shunt insertion .
Nowadays, ventriculostomy of the third cerebral ventricle plays a significant role in the treatment of pediatric hydrocephalus. However, the long-term changes in intracranial dynamics after successful ETV have not been clearly described [215, 217, 318, 331, 332, 333]. The definition of successful ventriculostomy of the third cerebral ventricle also includes radiological criteria, emphasizing the clinical criteria . Some studies revealed that successful performance of ETV did not decrease size of the cerebral ventricles [335, 336]. Results of the studies indicate that decrease of intracranial pressure does not have to be accompanied by change of size of the cerebral ventricles.
George et al.  studied changes of volume of the cerebral ventricles in children with hydrocephalus after successful performance of ETV. During longitudinal observation (24 months after surgery), they assessed volume of the cerebral ventricles as well as dynamics of the cerebral ventricles. If presurgical volume of the cerebral ventricles was greater than fivefold of the normal value, statistically significant decrease of volume of the cerebral ventricles appeared 3 up to 6 months after ETV. Even later the volume of the cerebral ventricles was the same. In the group of children with medium volume of the cerebral ventricles, which was measured before the surgery (less than fivefold of the normal value), less significant decrease of volume in the cerebral ventricles was observed 3–6 months after ETV. In the next period, volume of the cerebral ventricles was stable or slightly increased. In all cases, especially in the group of children with significant dilatation of the cerebral ventricles, volume of the cerebral ventricles after ETV was increased when compared to normal values. It can be caused by decreased absorption of cerebrospinal fluid. Based on the results mentioned above, the authors believe that successful ETV helps to create conditions for compensated communicating hydrocephalus. Impact of persistent dilatation of the cerebral ventricles on psychomotor development of a child is still the topic of the debate. Research of other authors confirmed that size of the cerebral ventricles did not change to the standard range after ETV [335, 338].
After successful ETV, clinical manifestations of intracranial hypertension can diminish in early postsurgical period. Despite the improvement of clinical condition of the child in the early postsurgical period, size of the cerebral ventricles did not change significantly [215, 335]. Indirect correlation between chronic hydrocephalus and decrease of size of the cerebral ventricles after ETV was observed. The longer hydrocephalus develops, the lower the decrease of volume of the cerebral ventricles after ETV was detected . On the other hand, ETV does not always help to eliminate clinical manifestations of intracranial hypertension. Therefore, follow-up checkups of the cerebral ventricles may be helpful when assessing the effect of ETV .
Considering the type of drainage procedure applied (shunt or ETV) in children with chronic hydrocephalus, significant differences in effect on decrease of diameter of the head and size of the cerebral ventricles in postsurgical period were found. Decrease of diameter of the head and size of the cerebral ventricles in neonates and infants with obstructive hydrocephalus was more significant after shunt insertion than after the use of ETV .
In daily clinical practice, it may be difficult to perform visual assessment of change of volume of the cerebral ventricles, especially in cases with low decrease of volume of the cerebral ventricles and irregular-shaped cerebral ventricles . Xenos et al.  found out that change of volume of the cerebral ventricles can be seen only if volume of the cerebral ventricles changed at least about 20%. Despite the fact that change of the cerebral ventricles is not visible 1 month after ETV, Schwarz et al.  found out that detailed measurement of parameters of the cerebral ventricles by CT can prove decrease of size of the third cerebral ventricle as well as both lateral cerebral ventricles.
In postsurgical period, successful ETV can change distribution of cerebrospinal fluid between the cerebral ventricles and subarachnoid space. Di Rocco et al.  confirmed progressive decrease of volume of the cerebral ventricles after ETV due to increase of liquor in the subarachnoid space. When stomy closed, distribution of cerebrospinal fluid regained properties typical for presurgical stage. Based on the results, assessment of change of CSF distribution between the cerebral ventricles and subarachnoid space is an appropriate indicator of ETV dysfunction.
Progressive dilatation of the cerebral ventricles occurred approximately in 25% of neonates with mild or moderate intraventricular hemorrhage and in 50–80% of neonates with the third stage of IVH and periventricular hemorrhagic brain infarction . The stage of intraventricular hemorrhage in neonates can be diagnosed by the grading scale of Papile ( Table 12 ) . Recent data showed that only 15% of preterm neonates with severe intraventricular hemorrhage need permanent CSF drainage by drainage system . Considering high morbidity and mortality, management of posthemorrhagic hydrocephalus in preterm neonates with low birth weight is a topic of a great importance.
|1st degree||Isolated subependymal hemorrhage in germinal matrix|
|2nd degree||Hemorrhage in the lateral cerebral ventricle without dilatation|
|3rd degree||Hemorrhage in the lateral cerebral ventricle with acute dilatation|
|4th degree||Hemorrhage spread into the periventricular cerebral tissue|
Drainage procedures in this age group are characterized by high risk of infectious and noninfectious conditions [346, 347, 348]. The list of drainage procedures includes repetitive lumbar puncture with CSF derivation (it is not preferred because of high risk of infections and insufficient amount of aspired CSF), external ventricular drainage, insertion of a subcutaneous reservoir followed by CSF derivation by repetitive aspirations, ventriculosubgaleal shunt, insertion of long-term internal drainage system (shunt), and endoscopic methods . In relation to higher incidence of infectious and noninfectious conditions, subcutaneous reservoir insertion followed by intermittent aspiration of cerebrospinal fluid is applied more often than external ventricular drainage [350, 351, 352]. In preterm neonates with extremely low birth weight (<1000 g), implantation of subcutaneous reservoir is associated with high risk of complications .
Accurate value of volume of aspired cerebrospinal fluid and frequency of CSF derivation in neonates with posthemorrhagic hydrocephalus are often based on subjective assessment of clinical manifestations (degree of tension of the anterior fontanelle) and small changes of the cerebral ventricles detected by sonographic examination. In some extent, assessment of small changes of size of the cerebral ventricles by sonographic examination is subjective, and size of the cerebral ventricles does not often correlate with measured values of intracranial pressure .
Heep et al.  found out that volume of cerebrospinal fluid, which is necessary for prevention of progressive dilatation of the cerebral ventricles in cases with posthemorrhagic hydrocephalus, is not determined by child´s weight but clinical manifestation. On the contrary, Bass et al.  performed direct continual measurement of intracranial pressure and found out that aspiration of 10 ml/kg volume of cerebrospinal fluid per day returns intracranial pressure to the normal values. In addition, they confirmed that regime of CSF derivation from subcutaneous reservoir leads to fluctuation of values of intracranial pressure. Volve (2001) also recommends volume of CSF derivation of 10–15 ml/kg per day in neonates with posthemorrhagic hydrocephalus.
Hunt et al.  analyzed the impact of derivation of cerebrospinal fluid on regional volume of the brain tissue in preterm neonates with progressive posthemorrhagic hydrocephalus. They performed volumetric examination by means of magnetic resonance. Derivation of sufficient volume of cerebrospinal fluid during puncture into the Rickham reservoir revealed increased volume of the gray matter about 39% and also increased volume of the myelin white matter about 61%. However, there was only minimum change in volume of demyelinated white matter and basal ganglia. Changes of the regional volumes after aspiration of cerebrospinal fluid provide new perspective on development of the brain in preterm neonates due to progressive posthemorrhagic dilatation of the cerebral ventricles.
Experimental studies on hydrocephalus confirmed morphological and biochemical changes in the cerebral cortex including impaired synaptogenesis and neuronal degeneration [356, 357]. Dilatation of the cerebral ventricles in progressive posthemorrhagic hydrocephalus has negative impact on differentiation of neurons in the gray matter due to axonal destruction . Development of neuronal fibers plays a crucial role in development of cerebral gyrification . Decrease of volume of the gray matter may provide an explanation for neurocognitive disorders in preterm neonates with posthemorrhagic hydrocephalus . Based on confirmation of significant increase of volume of the gray matter in preterm neonates with posthemorrhagic hydrocephalus after derivation of cerebrospinal fluid, it can be assumed that early ventricular drainage has positive effect on psychomotor development of the child . Besides the amount of extra- and intracranial factors resulting from child´s immaturity, the final neurological condition is influenced also by the degree of intracranial hemorrhage and degree of destruction of the brain tissue [361, 362].
Even though neurosurgical procedures are usually performed after birth, prenatal assessment of ventriculomegaly is very important for prognosis of child´s development, early termination of pregnancy, or early postnatal management of the child . Ultrasonography plays a key role in investigation of ventriculomegaly in prenatal screening ( Figure 49 ). In case of doubts in diagnosis or need of detailed assessment of the brain including the structures of the posterior cerebral fissure, fetal MRI examination can be performed. However, screening of the neural tube caudal defects by fetal MRI is not more effective than prenatal ultrasonography . Ventriculomegaly is the most common developmental anomaly of the brain, which can occur during fetal period, approximately in 1 case per 1000 live-born children [366, 367]. Child´s prognosis is mainly determined by occurrence of associated intra- and extracranial anomalies (2/3 of cases) and aneuploid lesions (9% of cases) [108, 368].
The term isolated ventriculomegaly describes dilation of the cerebral ventricles (width, diameter of the lateral cerebral ventricle in the level of glomus plexus choroideus >10 mm) without the presence of another developmental anomaly. The lateral cerebral ventricle in mild ventriculomegaly is 11–14 mm wide but ≥15 mm wide in severe ventriculomegaly.
Prognosis for development of the child, who is diagnosed ventriculomegaly by prenatal screening, is influenced by several factors:
Width of the lateral cerebral ventricles—a prognostic factor is width of the lateral cerebral ventricles ≥12 mm measured during sonographic examination of ventriculomegaly [364, 369, 370, 371, 372]. The other studies revealed that prognosis is better in children with mild ventriculomegaly than in children with severe ventriculomegaly [108, 373].
The presence of bilateral asymmetric ventriculomegaly characterized by difference between width of the right and left lateral cerebral ventricle >2 mm is considered to be a negative prognostic factor . Many studies confirmed good prognosis for children with unilateral ventriculomegaly [375, 376, 377].
Dynamics of ventriculomegaly—approximately in 85% of cases with isolated mild ventriculomegaly, size of the cerebral ventricles during intrauterine development returns to normal range of values, decreases, or stabilizes. Progression of size of the cerebral ventricles is a sign of unfavorable prognosis [364, 373].
During prenatal sonographic examination, not only width and asymmetry of the cerebral ventricles are measured but also morphological factors. It helps to predict etiology of ventriculomegaly and prognosis of the child, such as predilection sites of dilatation and shape of the cerebral ventricles, ependymal fissures, irregularity of walls of the cerebral ventricles, and destruction of the periventricular cerebral tissue .
14. Assessment of Doppler parameters of the cerebral arteries in children with hydrocephalus
Increased accumulation of cerebrospinal fluid in pediatric hydrocephalus leads to increased intracranial pressure, dilatation of the cerebral ventricles, decrease of intracranial compliance, and reduction of the brain tissue with negative impact on neurological condition of the child and his neurological development in the future. Alteration of cerebral circulation includes compression of the cerebral capillaries, stretching of the cerebral arteries, dysregulation of cerebral circulation, increase of cerebrospinal resistance, and decrease of cerebral blood flow. Progression of damage of the brain tissue results from decrease of cerebral blood flow and cerebral ischemia accompanied by changes in energetic metabolism ( Figure 17 ). To measure reversibility of acute pathophysiological changes, and thus improve indication and timing of drainage procedure in a noninvasive way, there is a need for examination technique, which could be used in daily clinical practice. This is the potential of transcranial Doppler ultrasonography. It can analyze blood flow in the cerebral vessels and thus enables to perform noninvasive assessment of hemodynamic parameters of cerebral circulation.
Interpretation of changes in the Doppler curve of the cerebral arteries in pediatric hydrocephalus remains to be a discussed issue. Increase of cerebrovascular resistance of the cerebral arteries due to increased intracranial pressure is reflected in change of blood flow velocity and increased values of qualitative indices in the Doppler curve. Generally, there is good correlation between resistance index and pulsatility index of the cerebral arteries and intracranial pressure. Relationship between intracranial pressure, clinical manifestations of intracranial hypertension, dilatation of the cerebral ventricles, and Doppler parameters of the cerebral arteries is defined by biomechanical properties of the skull and the brain in various age groups. It may be also influenced by the amount of intra- and extracranial factors, which affect cerebral circulation [266, 289]. In critically ill children, several factors are usually combined, which may, but do not have to, affect changes in the Doppler curve of the cerebral arteries. Therefore, cerebral blood flow in this type of patients has to be assessed carefully .
Bada et al.  were the first who described the relationship between Doppler parameters of cerebral circulation and intracranial pressure in preterm neonates with posthemorrhagic hydrocephalus. The results showed increased resistance index of the cerebral arteries due to increased intracranial pressure. In the same year, Hill and Volpe  presented results of their research on changes of RI-ACA in neonates with hydrocephalus. In 9 out of 10 cases, dilatation of the cerebral ventricles was accompanied by increase of intracranial pressure. In all cases, RI-ACA was increased. It was affected mainly by decrease of Ved. But after drainage procedure, RI-ACA decreased due to increase of Ved. According to the authors, ventriculomegaly was considered a more significant factor influencing hemodynamic parameters of ACA than increased intracranial pressure. Because, in most of the cases, dilatation of the cerebral ventricles was accompanied by increased intracranial pressure, it is difficult to differentiate impact of dilatation of the cerebral ventricles from impact of increased intracranial pressure on cerebral circulation.
Fisher and Livingstone  observed change of parameters of blood flow in the Doppler curve of MCA, ACA, and ICA. The research revealed increase of PI, significant decrease of Ved, and slight decrease of Vsyst before drainage procedure. After drainage procedure, which is the functional internal drainage system, return of hemodynamic parameters to normal range of values was confirmed. However, this change was not accompanied by return of size of the cerebral ventricles to normal values, excluding width of the third cerebral ventricle. Correlation between size of the cerebral ventricles and Vsyst was not proven. Relationship between Ved and size of the cerebral ventricle was intraindividual in its nature. The strongest correlation was found between size of the cerebral ventricles and pulsatility index. Regarding morphological parameters, width of the third cerebral ventricle showed to be a precise indicator of changes of intracranial volume. It was found out that ACA and MCA have the highest predisposition to early reaction to change of intracranial dynamics [382, 383]. During observation of RI-ACA, RI-MCA, and RI-ICA in children with hydrocephalus before drainage procedure as well as in the early and later postsurgical periods, the biggest changes of blood flow Doppler parameters were found in the anterior cerebral artery . In children with hydrocephalus, Nishimaki et al.  measured RI-ACA and RI-BA. They found out that both indices were significantly increased before drainage procedure, but RI-ACA was more increased than RI-BA. However, indices of both cerebral arteries were significantly increased after drainage procedure, and decrease of RI-ACA was more significant than RI-BA. Significant change of RI-ACA comparing with change of RI-BA before and after drainage procedure is probably determined by the anatomical location of the arteries. The anterior cerebral artery lies closely to the lateral cerebral ventricles, and the third cerebral ventricle and the basilar artery are located in the basal cistern in front of the pons. In most of the cases of hydrocephalus, the lateral cerebral ventricles are dilated more significantly than the third and the fourth cerebral ventricles. Therefore, the authors of the study assume that dilatation of cerebral ventricles has greater effect on the anterior cerebral arteries than on the basilar artery.
Although the basilar artery does not belong to the arteries with the highest predisposition to early reaction to volume-pressure changes in the intracranial space, assessment of increased RI-BA value and size of the cerebral ventricles, which had been performed in dogs with hydrocephalus, helped to distinguish cases, in which drainage procedure is necessary—with sensitivity of 77% and specificity of 94%. The value of neurological manifestations of symptomatic hydrocephalus correlated with RI-BA value and size of the cerebral ventricles. During measurement of individual dynamics, changes in clinical symptomatology had been accompanied by changes of RI-BA and size of the cerebral ventricles .
When observing changes of pulsatility index and cerebral artery resistance in children with hydrocephalus before and after drainage procedure, various studies revealed significant increase of PI and RI values of the cerebral arteries before drainage procedure and significant decrease of PI and RI in functional internal drainage system after surgery. Change of qualitative indices of the Doppler curve was affected by change of Ved. The results of studies showed that increased cerebrovascular resistance before drainage procedure was determined by increased intracranial pressure, which is reversible after drainage procedure. Positive impact of drainage procedure on Doppler parameters of the cerebral arteries is based on postsurgical change of cerebrovascular resistance and regulation of cerebral circulation due to decrease of intracranial pressure [319, 320, 384, 387, 388, 389, 390].
The assessment of Doppler parameters of cerebral circulation and heart rate variability in preterm neonates with posthemorrhagic hydrocephalus showed that hemodynamic parameters as well as chronotropic regulation of cardiac function changed after drainage procedure . A significant relationship between RI-MCA and PI-MCA was observed in the presurgical period in infants with congenital hydrocephalus .
On the contrary, van Bel et al. , who investigated 10 preterm neonates with posthemorrhagic hydrocephalus before drainage procedure, proved significant increase of PI-ACA resulting from significant increase of Vsyst. After successful drainage procedure, PI-ACA and Vsyst significantly decreased. The values of PI-ACA after drainage of cerebrospinal fluid were within standard range. When van Bel et al.  compared values of Ved and Vmean before and after drainage procedure, they did not find any significant changes. The authors of this study concluded that increase of PI-ACA before drainage procedure was determined only by increase of Vsyst. The same results were confirmed by Alvisi et al. . Many researchers claim that increase of Vsyst before drainage procedure is caused by movement and compression of the anterior cerebral arteries through enlarged cerebral ventricles and flow of cerebrospinal fluid into the white matter, which results in decrease of transmural pressure gradient [393, 394, 395].
In neonates, infants, and older children, Goh et al. [396, 397] studied the relationship between intracranial pressure and resistance index of ACA and MCA. They found good intraindividual correlation between ICP and RI-ACA and RI-MCA in neonates and general good correlation between ICP and RI-ACA and RI-ACM in infants and older children. The difference between the age groups is probably caused by individual pressure-volume compensation of the intracranial pressure in neonates with hydrocephalus in various stages of hydrocephalus and various degrees of compliance of the skull and cranial sutures. Intracranial dynamics is more uniform in infants and older children. This corresponds with general good correlation between intracranial pressure and resistance index of the cerebral arteries. Significant decrease of RI-ACA and RI-MCA, determined by increase of Ved, was observed after drainage procedure in all age categories. Only in neonates, increase of Ved was accompanied by moderate increase of Vsyst and Vmean.
During continuous observation of blood flow in MCA by transcranial Doppler ultrasonography, positive impact of drainage of cerebrospinal fluid on Doppler parameters of MCA had been observed in children with hydrocephalus in the presurgical period while inserting ventriculoperitoneal shunt. Insertion of ventricular catheter into the lateral cerebral ventricle with CSF derivation led to obvious and immediate 30% increase of blood flow in MCA. When drainage procedure had been performed, values of PI-MCA, which were increased before the surgery, returned to standard range. The results of presurgical changes of Doppler parameters of MCA confirmed positive impact of CSF derivation on hemodynamic parameters of cerebral circulation in children with hydrocephalus .
Results of various studies emphasize the importance of data from assessment of changes of Doppler parameters of cerebral circulation to the record of dilatation of cerebral ventricles. Experiment on newborn rats with progressive communicating hydrocephalus showed that onset of dilatation of cerebral ventricles was not accompanied by alteration of parameters of the Doppler curve of the cerebral arteries. Pulsatility index of the cerebral arteries had been increased during development of hydrocephalus and followed by progression of ventricular dilatation. This means that dilatation of cerebral ventricles did not change pulsatility index of the cerebral arteries. Instead, the change occurred due to progression of hydrocephalus and increase of intracranial pressure. It can be concluded that in this developmental stage of hydrocephalus, cerebral circulation was more influenced by increased intracranial pressure than by ventricular dilatation . In chronic stage, changes of cerebral hemodynamics and advanced dilatation of cerebral ventricles were accompanied by other structural pathological changes .
Relation between dynamics of dilatation of cerebral ventricles (progressive, stable, or regressive) and basal and compressive values of RI-ACA was not found in neonates with hydrocephalus in the presurgical period. It means that dynamics of ventricular dilatation is not the only parameter influencing Doppler parameters of the cerebral arteries. In all cases of neonates with hydrocephalus, intracranial pressure was increased during drainage procedure, and clinical manifestations of intracranial hypertension had diminished after the surgery. Therefore, the authors of the study assume that Doppler parameters of the cerebral arteries are influenced by combination of increased intracranial pressure and dilatation of cerebral ventricles. Additionally, the results of the study confirmed that not only progressive but also stable dilatation of cerebral ventricles with increased intracranial pressure has a negative effect on cerebral circulation . On the contrary, in neonates with stable dilatation of cerebral ventricles, in which drainage procedure was not necessary, basal Doppler parameters of blood flow in ACA reached normal values . Similarly, Quinn and Pople  confirmed increase of PI-MCA in children with hydrocephalus who experienced dysfunction of drainage system. CT examination, however, revealed change of size of the lateral ventricles only in 10 out of 32 patients. Comparing with stable dilatation of cerebral ventricles, results showed increased value of PI-MCA and presence of clinical manifestations of dysfunction drainage system, in which surgical procedure is needed. When the procedure had been performed, PI-MCA significantly decreased. However, if intracranial pressure was not increased in stable dilatation of cerebral ventricles, resistance index of the cerebral arteries did not change either .
Not only increase of intracranial pressure and development of dilatation of cerebral ventricles but also changes of the cerebral arteries, such as distortion, compression, and stretching, may occur in pediatric hydrocephalus, especially in asymptomatic hydrocephalus .
The results of the study  targeted at children with hydrocephalus confirmed that asymmetric dilatation of cerebral ventricles had significantly influenced values of basal RI-ACA before drainage procedure and compressive RI-ACA after it. Statistical analysis showed that values of basal RI-ACA after drainage procedure and compressive RI-ACA before drainage procedure was not influenced by asymmetric dilatation of cerebral ventricles. Asymmetric dilatation of cerebral ventricles before drainage procedure may lead to stretching of the anterior cerebral arteries. When accompanied by increased intracranial pressure, it results in increase of cerebrovascular resistance and RI-ACA value. The presumption that asymmetry of the cerebral ventricles has significant impact on presurgical values of compressive RI-ACA was not confirmed. The authors of this study believe that it was caused by distribution of range of compressive RI-ACA before drainage procedure. In 36 neonates out of 40 (90%), compressive RI-ACA before drainage procedure reached maximal value of 1.0 regardless of asymmetric ventricular dilatation. In normal values of intracranial pressure after drainage procedure, the values of basal RI-ACA were not influenced by asymmetric dilatation of cerebral ventricles. In cases with standard values of intracranial pressure in asymmetric ventricular dilatation, dislocation of the anterior cerebral ventricles may occur without significant stretching and change of cerebrovascular resistance of anterior cerebral arteries. Compression of the anterior fontanelle in asymmetric ventricular dilatation, which is related to intracranial normotension, may worsen dislocation of the anterior cerebral ventricles if it is accompanied by increase of cerebrovascular resistance, resulting in values of compressive RI-ACA. Based on this study and clinical experience, the authors emphasize the fact that interpretation of Doppler parameters of the cerebral arteries in pediatric hydrocephalus with asymmetry of cerebral ventricles has to be done carefully .
In neonates with hydrocephalus, besides hydrocephalus itself, the following pathological changes of the periventricular cerebral tissue may also have negative impact on cerebral circulation: periventricular leukomalacia and peri- and intraventricular hemorrhage.
Impact of these changes on cerebral circulation and Doppler parameters of the cerebral arteries should be taken into consideration when assessing hemodynamic parameters of cerebral circulation in neonates with hydrocephalus in relation to observation of intracranial dynamics and indication of drainage procedure.
The most common cause of periventricular leukomalacia is perinatal infection (e.g., chorioamnionitis) and hypoxic-ischemic damage of the brain tissue. Considering various degrees of maturity of the brain tissue, consequences of hypoxic-ischemic brain injury differ in preterm neonates and in term neonates .
In preterm neonates, the periventricular white matter is at higher risk of hypoxia, which leads to focal or diffuse type of periventricular leukomalacia, while in term neonates, it is the white matter near the cerebral cortex, in which cortical and subcortical lesions of white matter can be detected .
The cystic leukomalacia lesions do not occur from the moment of insult of the brain tissue, but they develop continuously. At first, hyperechogenicity of the periventricular brain tissue is confirmed by a sonography. Then cystic lesions are formed during 10–14 days . Pathological changes of structure of the periventricular brain tissue are accompanied by hemodynamic changes. Dysfunction of cerebral autoregulation was confirmed in preterm neonates with periventricular leukomalacia . Many researchers also confirmed alteration of cerebral circulation in neonates with periventricular leukomalacia. By means of transcranial Doppler ultrasonography, Fukuda et al.  observed long-term decrease of blood flow velocity within all major cerebral arteries. In another research on periventricular leukomalacia in neonates with low birth weight, Fukuda et al.  confirmed that blood volume in ICA and VA had decreased a few days after birth and then between the 21st and 42nd day. Research by Ilves et al.  revealed that mean velocity of blood flow in ACA, MCA, ICA, and BA was increased in 83 asphystic term neonates due to severe hypoxic-ischemic encephalopathy during first days after asphyxia. However, increased mean blood flow velocity in the cerebral arteries was only short term. During the period of 21–59 days, it dropped below standard values of healthy term neonates. Changes of Doppler parameters of MCA in neonates with hypoxic-ischemic encephalopathy were also proven by Liu et al. . In children with severe encephalopathy, the values of RI-MCA were <0.50 or RI-MCA >0.90 as a result of change of blood flow velocity in MCA.
To classify intracranial hemorrhage in neonates, the grading scale of Papile, which was created in 1978 ( Table 12 ), is still being used . In the past, it was assumed that grade IV denotes spread of subependymal bleeding into the surrounding brain tissue. Nowadays, decrease of venous drainage and development of venous hemorrhagic infarction are regarded to be the main triggers of intracerebral hemorrhage in neonates (Taylor, 1997) . Subsequently, porencephalic cysts may develop in the site of periventricular venous infarction. In general, higher grades of intracranial hemorrhage lead to increased risk of severe neurological disorders in children. If grades III and IV of intracranial hemorrhage occur in active hydrocephalus, the brain tissue and cerebral circulation of a neonate are negatively affected by bleeding itself as well as changes related to increased intracranial pressure and progressive dilatation of cerebral ventricles. Moreover, there are many extracranial factors, which impact negatively on cerebral circulation, especially in preterm neonates [410, 411, 412]
Peri- and intracranial hemorrhage in neonates leads to dysfunction of regulation of cerebral circulation including autoregulation. Increased values of resistance index of the cerebral arteries, which were found out in the site of bleeding, are a sign of increased cerebrovascular resistance and presence of vasoconstriction near hemorrhagic lesions [264, 413]. Various research studies on neonates with posthemorrhagic hydrocephalus showed positive effect of drainage procedures and decrease of intracranial pressure on cerebral circulation.
The issue of frequency and appropriate time management of cerebrospinal fluid derivation during intermittent drainage in children with posthemorrhagic hydrocephalus remains open to debate. Large multicentric studies confirmed very low effect of frequent and early performed drainage, based on the assessment of size of the cerebral ventricles, in comparison with a conservative approach . Since one of the prospective goals of intermittent drainage of cerebrospinal fluid is to prevent dysfunction of cerebral circulation due to increased intracranial pressure, changes of Doppler parameters of cerebral circulation in neonates with posthemorrhagic hydrocephalus have become a center of attention.
Nishimaki et al.  found out that values of RI-ACA in children with posthemorrhagic hydrocephalus were significantly increased before lumbar puncture or puncture of subcutaneous reservoir. But after aspiration of 5–10 ml/kg, they significantly decreased. Similarly, Kempley and Gamsu  confirmed decrease of intracranial pressure accompanied by significant increase of Vmean and decrease of PI-ACA, when CSF derivation had been performed in children with posthemorrhagic hydrocephalus. Quinn et al.  compared impact of increased intracranial pressure and CSF derivation on blood flow in ACA and internal cerebral vein (ICV) in neonates with posthemorrhagic hydrocephalus. RI-ACA was significantly increased before drainage procedure. But afterward, it decreased significantly. Changes of blood flow velocity in ACA weren´t accompanied by change of blood flow velocity in ICV.
Maertzdorf et al.  observed hemodynamic parameters of ACA and MCA in the Doppler curve of preterm neonates with IVH and PHH during early gestation weeks. Aspirations of cerebrospinal fluid from subcutaneous reservoir of the ventricular catheter (type Ommaya) had been performed repetitively. When ICP before drainage procedure was ≥6 cm H2O, then Ved and Vmean had increased significantly after performing aspiration. After derivation of CSF, when ICP was <6 cm H2O, RI-ACA and RI-MCA had decreased. The value of Vsyst was not significantly changing after cerebrospinal fluid aspiration. The results confirmed good intraindividual correlation between RI-ACA, RI-MCA, and ICP in neonates with posthemorrhagic hydrocephalus. The use of infrared spectroscopy revealed that CSF derivation from subcutaneous reservoir leads not only to change of Doppler parameters of cerebral circulation, especially significant decrease of pulsatility index, but also to improvement of intravascular oxygenation of cerebral circulation [419, 420].
During assessment of effect of periventricular posthemorrhagic lesions on Doppler parameters of blood flow in ACA of neonates with hydrocephalus, significant correlation had been found between periventricular posthemorrhagic lesions and basal RI-ACA and compressive RI-ACA after drainage procedure. Before drainage procedure, Doppler parameters in ACA were influenced by increased intracranial pressure and also by posthemorrhagic lesions .
Based on the research, it can be concluded that derivation of cerebrospinal fluid in neonates with posthemorrhagic hydrocephalus leads to improvement of cerebral blood flow ( Figure 50 ). While indicating and planning derivation of cerebrospinal fluid, changes of Doppler parameters of cerebral circulation should be taken into account [289, 421].
Doppler ultrasonography enables assessment of hemodynamic parameters of cerebral circulation of a fetus during prenatal sonographic screening. Comparison of findings with referential values may detect changes of cerebral circulation in various pathological conditions including fetal hydrocephalus . During examination, a sonographic probe should touch the body gently because strong pressure can significantly increase RI, PI, and Vsyst and decrease Ved in MCA. But the Valsalva maneuver by mother doesn´t affect Doppler parameters of blood flow in MCA . Regarding prognosis and child management, the role of Doppler parameters of cerebral circulation as a complementary measurement in prenatal screening in fetal ventriculomegaly remains questionable.
Zalel et al.  did not find any correlation between widths of the lateral cerebral ventricles and RI-MCA in fetuses with normal size of the cerebral ventricles nor in six cases of ventriculomegaly. In the case of unilateral or bilateral mild fetal ventriculomegaly, no changes of Doppler parameters of blood flow in MCA were found in comparison to severe stage of ventriculomegaly . Mai et al.  presuppose that examination of blood flow in MCA by Doppler ultrasonography does not provide new information regarding diagnosis and prognosis of fetal ventriculomegaly.
On the contrary, Voigt et al.  studied 143 cases of fetal hydrocephalus and confirmed that progressive dilatation of the cerebral ventricles results in increased cerebrovascular resistance and decreased cerebral blood flow. They concluded that assessment of changes of cerebral blood flow using Doppler ultrasonography helps to detect risk of brain tissue damage due to increased intracranial pressure and cerebral ischemia. To decrease secondary brain damage, drainage procedure should be performed early either in utero or postnatal after induced labor. Cavalheiro et al. [428, 429] confirmed that drainage procedure in utero between 24th and 32nd gestation week is of great importance in cases with isolated progressive infectious ventriculomegaly without signs of brain tissue destruction and chromosomal anomalies. Labor induction per C-section followed by postnatal drainage procedure is preferred from 32nd gestation week. Interdisciplinary collaboration, especially between a gynecologist, neonatologist, neurosurgeon, and anesthesiologist, is necessary when applying this procedure in clinical practice.
Changes of Doppler parameters of the cerebral arteries were found also in cases with dysfunction of drainage system after surgical revision.
Pople  focused on identification of referential values of PI-MCA in children with hydrocephalus with functional internal drainage system ( Table 13 ). The sample included 248 asymptomatic children with hydrocephalus with functional shunt. They were 1 week to 16 years old. It is known that blood flow velocity in the cerebral arteries increases during aging. Changes of blood flow velocity in the cerebral arteries are more variable in children, especially in younger age groups, than in adults. The highest blood flow velocity was measured between the 3rd and 4th year of age. Since then it had been gradually decreasing to the level of values in adults. Pulsatility index had been significantly decreasing during the first 6 months of age. The lowest value was measured between 2nd and 6th year of age. Since then it had been gradually increasing up to the value of 0.9 in the age of 16. In addition to identification of referential values of PI-MCA in children with hydrocephalus with functional internal drainage system, Pople emphasized significant interindividual differences of Doppler parameters and importance of following the intraindividual trend . In 63 children with hydrocephalus with dysfunction of drainage system, values of PI-MCA were compared with referential values. It was found out that increase of PI-MCA determines shunt malfunction with sensitivity of 56% and specificity of 97%. The values of PI-MCA correlated with intracranial pressure of children with shunt obstruction . Increased resistance index of the cerebral arteries was also confirmed in children with dysfunction of drainage systems [319, 320, 432].
|Pulsatility index (mean)||Number (n=248)|
In addition to increased resistance index of the cerebral arteries, vascular reactivity malfunction to paCO2 change was detected in children with active hydrocephalus before drainage system insertion and in dysfunction of drainage system. When drainage system was inserted and dysfunctional shunt revised, resistance index decreased significantly. Then cerebrovascular reactivity to paCO2 change had been improved, and that also led to functional cerebral circulation and regulation change .
Assessment of cerebral circulation by transcranial Doppler ultrasonography can be used not only to observed function of shunt but also ventriculostomy of the third cerebral ventricle. Vajda et al.  found out that PI-MCA significantly decreased in children with obstructive hydrocephalus after successful ETV. The difference was not statistically significant when they compared PI-MCA measured immediately after ETV with value measured in the 5th day after surgery. Effect of ventriculostomy was confirmed by assessment of cerebrospinal fluid flow using cine-phase MRI examination.
Clinical symptomatology improved immediately after the procedure in 17 out of 22 patients. Any correlation between PI-MCA and age or gender of children in the sample of patients was not found. The results showed importance of Doppler ultrasonography for observation of ETV function in the early postsurgical period.
Taylor et al.  used compressive test on the anterior fontanelle during TCCD examination in children with abnormal intracranial compliance. They studied basal values of RI-ACA and change of RI-ACA during the compressive test. The change was expressed as percentage difference in contrast to basal value. The basal values of RI-ACA of preterm neonates and neonates with abnormal intracranial compliance were significantly increased when compared to basal values of healthy term neonates. Only slight change of RI-MCA was observed in healthy preterm neonates and healthy term neonates during compression on the anterior fontanelle. However, RI-MCA was significantly increased in neonates with abnormal intracranial compliance. Basal values of RI-MCA were increased in neonates with increased intracranial pressure. Hemodynamic reaction of the cerebral arteries to compression of the anterior fontanelle had improved after drainage of cerebrospinal fluid. Compression test on the anterior fontanelle during TCCD examination can help to detect alteration of intracranial compliance before increase of intracranial pressure. The increase of ICP is manifested by increased basal values of RI. The study showed possibility of indirect noninvasive measurement of intracranial compliance and intracranial pressure by transcranial Doppler ultrasonography. In another study, Taylor et al.  assessed hemodynamic reaction of the anterior cerebral artery during compressive test on the anterior fontanelle in neonates with hydrocephalus. It revealed a significant increase of RI-ACA in neonates who were indicated for drainage procedure and in which increased intracranial pressure was confirmed by direct measurement.
Westra et al.  also dealt with the use of compressive test on the anterior fontanelle in children with hydrocephalus. They confirmed significantly increased basal and also compressive values of RI-ACA in pediatric hydrocephalus with increased intracranial pressure. A significant decrease of basal and compressive values of RI-ACA was found out when drainage procedure had been performed. Based on the results, they defined the boundary value of 0.70 for basal RI-ACA and 0.90 for compressive RI-ACA.
Gera et al.  focused on assessment of Doppler parameters of the anterior cerebral artery in relation to drainage procedure indication and change of measured Doppler parameters after drainage procedure. In children indicated for drainage procedure, they found out significantly increased value of basal RI-ACA and RI-ACA during compressive test. But after drainage procedure, the value of basal RI-ACA and compressive RI-ACA significantly decreased.
Change of Doppler parameters indicates increase of intracranial compliance after drainage procedure. However, any correlation between ICP and RI-ACA (both basal and compressive) was not found. The researchers believe that it is caused by complexity of the relationship between ICP and RI and potential nonlinearity of the relationship. During observation of RI-ACA in children with hydrocephalus in relation to indication of drainage procedure, the following values of basal RI-ACA were found out: sensitivity of 72.5%, specificity of 80%, and diagnostic accuracy of 75%. Assessment of RI-ACA by compressive test on the anterior fontanelle showed sensitivity of 75%, specificity of 100%, and diagnostic accuracy of 83.3%. False negativity in assessment of basal and compressive RI-ACA was the same (25%). Table 14 presents comparison of the role of assessment of hemodynamic parameters of the cerebral arteries by Doppler ultrasonography during compressive test in children with hydrocephalus and indication of drainage system.
The compressive test on the anterior fontanelle increases sensitivity and specificity of resistance index and pulsatility index in regard to indirect measurement of increased intracranial pressure and decreased intracranial compliance in children with hydrocephalus. On the other hand, results of the compressive test require more careful assessment of effect of intra- and extracranial factors on cerebral circulation because their influence on compressive values is more significant than effect on basal values. Pressure applied to the anterior fontanelle during compressive test is defined within the range 0–200 g/cm2. The pressure can gradually increase when using an ophthalmodynamometer . When using a sonographic probe, shape (linear or convex) and size of a probe and pressure, which will be created by a doctor, need to be taken into consideration. Therefore, if a child was indicated for sonographic examination, it should be performed by the same doctor and the same probe. Regarding indirect measurement of intracranial hypertension and intracranial compliance, false positivity of compressive test can be found in preterm neonates who require intensive care (instability of extracranial factors), in severe stages of intra- and periventricular hemorrhage and dilatation of cerebral ventricles. False negativity of compressive test can be caused by CSF leak, subcutaneous CSF fistula, or small size of the anterior fontanelle [266, 319, 436].
Although transcranial Doppler sonography has been used for more than 30 years to assess Doppler parameters of cerebral circulation, interpretation of parameters in the Doppler curve of the cerebral arteries, intracranial pressure, intracranial compliance, and cerebral hemodynamics in pediatric hydrocephalus remains to be an open topic. On the one side, results of various studies showed possibility of indirect noninvasive assessment of intracranial pressure and compliance by means of transcranial Doppler sonography. On the other hand, results showed limitations and difficulties when assessing Doppler parameters of cerebral circulation in children with hydrocephalus. When assessing relation between intracranial pressure, resistance index, and pulsatility index of the cerebral arteries, wide range of factors, which can change shape and properties of the Doppler curve, need to be taken into consideration. Behrens et al.  used a mathematical model of cerebrospinal fluid circulation, which confirmed that relation between ICP and PI-MCA is significantly influenced by vascular compliance, autoregulation, and arterial pressure. They believe that individual variability of these physiological parameters is responsible for inaccurate reference of ICP value. Similarly, Hanlo et al.  confirmed decreased resistance index and pulsatility index of the cerebral vessels measured in children with progressive hydrocephalus after drainage procedure. However, during longitudinal simultaneous ICP/TCCD monitoring, correlation between ICP, RI, and PI was very weak. Based on the results, which showed a wide range of referential Doppler parameters of cerebral circulation and impact of extracranial factors, authors of this study believe that pulsatility index and resistance index of the cerebral vessels do not help in assessment of intracranial dynamics in patients with increased intracranial pressure.
This inconsistency of results on assessment of relationship between RI and PI of the cerebral vessels and intracranial pressure has led to research of more accurate noninvasive parameters of intracranial pressure. Hanlo et al.  presented new Doppler index known as trans-systolic time. The results confirmed that trans-systolic time of the cerebral arteries in the Doppler curve is less influenced by other factors (e.g., heart rate) and is more accurate for comparison of ICP, RI, and PI changes. Also, Leliefeld et al.  confirmed significant correlation between trans-systolic time and ICP. Despite these positive results, assessments of trans-systolic time of the cerebral arteries are not used for noninvasive measurement of intracranial pressure. It might be caused by a lack of referential range in children population and lack of experience with use in clinical practice. In another study, Leliefeld et al.  dealt with the possibility to use MR examination of cerebral circulation for indirect measurement of intracranial pressure. They found out that standard values of blood flow velocity in the brain and low values in ADC map were referred to compensated hydrocephalus without a need of drainage procedure. They claim that noninvasive changes of cerebral circulation by MR examination enable to distinguish the cases of compensated pediatric hydrocephalus with normal intracranial pressure without a need of drainage procedure from the cases of gradually progressive hydrocephalus with a need of drainage surgery.
Galarza and Lazareff  focused on clinical validity of transcranial Doppler ultrasonography in children with various types of hydrocephalus. The study showed that values of PI-MCA and RI-MCA were significantly higher in progressive hydrocephalus with a need of drainage procedure. On the other hand, RI-MCA and PI-MCA were not increased, and blood flow velocity in MCA was not decreased in the cases with compensated hydrocephalus (also known as arrested hydrocephalus) and ventriculomegaly (or essential ventriculomegaly). The results showed importance of transcranial Doppler sonography for indication of drainage procedure in children with hydrocephalus. However, the authors emphasize the importance of individual and careful assessment of Doppler parameters of cerebral circulation regarding pediatric hydrocephalus in clinical practice.
Rodríguez-Nuñez et al.  confirmed the role of clinical manifestations of intracranial hypertension, radiological morphometric parameters of the brain (Evans´ index), biochemical parameters of cerebrospinal fluid (level of hypoxanthine, xanthine, and urea acid), and Doppler parameters of the cerebral circulation during assessment of pediatric hydrocephalus and indication of drainage procedure.
15. Case reports
15.1 Assessment of intracranial dynamics in the preterm neonate with hydrocephalus before and after insertion of external ventricular drainage
The preterm neonate (33rd gestation week) suffering from idiopathic hydrops with development of progressive hydrocephalus of four ventricles (posthemorrhagic, postinfectious) was indicated for insertion of external ventricular drainage. The mechanical ventilation in the child was used. Extracranial factors such as anemia, bronchopneumonia, and hepatopathy were presented. The neonate was 36 weeks old when drainage procedure was performed. Signs of intracranial hypertension were not clear in clinical manifestation before EVD insertion. Total body hydrops and edema of soft tissues caused difficulties in physical examination of the head. Enlargement of the cranial sutures was present, and the anterior fontanelle was opened, quite tense when palpated. The diameter of the head was not increased; it was stable regarding dynamics. Progressive dilatation of the cerebral ventricles with roundness of the horns of the lateral cerebral ventricles was confirmed by sonography. It was a sign of activity of hydrocephalus. Alteration of basal and compressive parameters of the Doppler curve of blood flow in ACA was found by transcranial Doppler ultrasonography ( Figures 51 and 52 ). Drainage procedure confirmed increased value of ICP +13 cm of CSF column by direct measurement. After insertion of external ventricular drainage, palpable finding on the anterior fontanelle (soft) changed, the diameter of the head decreased, and the distance between the cranial sutures diminished. Sonography showed significant decrease of size of the cerebral ventricles, which was accompanied by improvement of basal and compressive Doppler parameters of blood flow in ACA ( Figures 53 and 54 ).
15.2 Observation of intraindividual dynamics in the preterm neonate with asphyxia and development of progressive hydrocephalus regarding indication of drainage procedure
The preterm neonate in 33rd gestation week. Immediately after birth, failure of respiration and the need of cardiopulmonary resuscitation were presented. In the first day after birth, ultrasonography of the brain revealed periventricular hyperechogenic lesions and moderate asymmetry of dilatation of the lateral cerebral ventricles with the asphyctic type of the Doppler curve of blood flow in ACA (low value of RI) ( Figure 55 ).
The child was connected to mechanic ventilation. Slight increase of the head circumference, enlargement of the lambdoid suture, and tense anterior fontanelle were presented in the clinical picture. In the eighth day after birth, a checkup by sonographic examination of the brain confirmed progression of dilatation of the lateral cerebral ventricles and the third cerebral ventricle. Hemorrhage occurred in the third cerebral ventricle. Cystic periventricular leukomalacia had been developing when asphyxia had been eliminated. The change of the type of the Doppler curve of the blood flow in ACA was confirmed. The value of RI-ACA was in the normal range regarding age of the child. Compressive test on the anterior fontanelle was negative ( Figure 56 ).
Physical signs on the child´s head changed 11 days after birth. Increased diameter of the head was accompanied by significant diastasis of the cranial sutures and tense anterior fontanelle when palpated. The child had been still connected to mechanical ventilation. Sonography showed progressive dilatation of the lateral cerebral ventricles, without change of the size of the third cerebral ventricle. Doppler parameters of blood flow in ACA had changed—basal value of RI-ACA was slightly increased, and compressive test on the frontal fontanelle was positive with end-diastolic block of blood flow ( Figure 57 ). Regarding dynamics in the clinical manifestations of intracranial hypertension and sonographic image, ventricular puncture was performed. The value of directly measured ICP was 16 cm of CSF column. After derivation of 34 ml of cerebrospinal fluid, ICP decreased to the value of 6 cm of CSF column.
Ventricular puncture with cerebrospinal fluid derivation had led to short-term stabilization of intracranial hypertension. However, signs of activity of hydrocephalus were found in clinical manifestations again (tense anterior fontanelle, without bulging, diastasis of lambdoid suture, and increased head circumference). By means of one-time cerebrospinal fluid derivation, extracranial factors of the child had been stabilized for 10 days. Then, 21 days after birth, sonographic examination of the brain confirmed progression of dilatation of the lateral cerebral ventricles, communication of the right lateral cerebral ventricle, and cystic periventricular leukomalacia. The value of basal RI-ACA was slightly increased. While the anterior fontanelle had been compressed, reverse blood flow in ACA was presented ( Figure 58 ). When assessment of dynamics of clinical and sonographic image had been done, the insertion of ventriculoperitoneal shunt was indicated.
15.3 Impact of tachycardia on Doppler parameters of blood flow in ACA in the infant with active hydrocephalus
Polystigmatized infant with hydrocephalus presenting with multiple congenital developmental anomalies such as congenital four-ventricular hydrocephalus, agenesis of corpus callosum, cavum septi pellucidi, ductus arteriosus Botalli apertus (condition after clipping), duodenal atresia (postsurgical condition), Meckel diverticulum (postsurgical condition), hypospadia glandis, and hypoplasia of the 12th pair of ribs. The child was born prematurely in 32nd gestation week. In the age of 1 year, signs of intracranial hypertension appeared. The clinical picture indicated activity of four-ventricular hydrocephalus, which had been stabilized up to that time. In clinical manifestation, increased head circumference with progressive dynamics of growth, tense and bulged anterior fontanelle, sunset eyes syndrome, and somnolence were presented. Transcranial sonography confirmed dilatation of cerebral ventricles. Low quality of the sonographic image disabled precise assessment of morphology of the brain and intracranial space ( Figure 59 ). However, CT of the brain showed significant dilatation of cerebral ventricles and all the developmental anomalies of CNS mentioned above in the text.
Transcranial Doppler ultrasonography did not show increased values of RI-ACA and PI-ACA, while impact of severe tachycardia on the shape of the Doppler curve of blood flow in ACA had been assessed by Doppler parameters. Considering signs of intracranial hypertension, insertion of ventriculoperitoneal shunt was indicated. Increased ICP value of CSF column of 14.5 cm was found out by direct measurement during surgery. The case study revealed a false-negative result of RI-ACA and PI-ACA assessment in regard to prediction of increased ICP in the infant with active hydrocephalus accompanied by tachycardia ( Figure 60 ).
15.4 Assessment of intracranial dynamics of the infant with schizencephaly
In the child with schizencephaly, diagnosed by CT ( Figure 61 ), clinical signs of intracranial hypertension (increased head circumference, tense and bulged anterior fontanelle, somnolence) appeared in the 11th month of age. Up to that time, the child was stabilized, dispensarized by the pediatric neurologist. Examination of blood flow in ACA by transcranial Doppler ultrasonography showed alteration of hemodynamic parameters of blood flow in ACA (decreased Ved, increased RI): Vsyst 84 cm/s, Ved 20 cm/s, and RI 0.76 ( Figure 62 ). The ventriculoperitoneal shunt was inserted. After surgery, the child was more active, the anterior fontanelle was soft when palpated, and head circumference was stable. Also Doppler parameters of blood flow in ACA had improved when drainage procedure was performed (increased Ved, decreased RI): the basal parameters Vsyst 90 cm/s, Ved 34.8 cm/s, and RI 0.61; the compressive test on the anterior fontanelle was negative: Vsyst 85 cm/s, Ved 32 cm/s, and RI 0.613.
15.5 Assessment of intracranial dynamics in the term neonate with congenital hydrocephalus, Arnold-Chiari malformation type II, and lumbosacral myelomeningocele
The term neonate was born in 40th gestation week with open lumbosacral myelomeningocele. The neonate underwent the surgery up to 8 hours after birth closure of the caudal neural tube defect ( Figure 63 ). Congenital hydrocephalus was detected by ultrasonography. Then MRI of the brain was performed. It revealed Arnold-Chiari malformation type II. Monitoring of intracranial dynamics was focused on the assessment of clinical picture and a sonographic image of the brain (USG, TCCD). The surgical wound was without CSF leak. The circumference of the head had been gradually increasing, the cranial sutures enlarged, and palpation examination on the anterior fontanelle changed (from soft it changed to tense fontanelle). No signs of deterioration were presented in the neurological status of the child. Checkup sonographic examination of the brain confirmed progressive dilatation of cerebral ventricles, which was accompanied by increase of basal RI-ACA and positive compressive test on the anterior fontanelle with end-diastolic blockage of blood flow ( Figure 64 ). Ventriculoperitoneal shunt insertion was indicated because of the progression in the clinical and sonographic picture.
15.6 Assessment of intracranial dynamics in the preterm neonate with posthemorrhagic hydrocephalus
The preterm neonate was born in 28th gestation week. He was connected to mechanical ventilation after birth, blood circulation had to be supported by vasoconstrictors, and thrombocytopenia and bronchopulmonary dysplasia were presented. Hemorrhage into the germinal matrix and intraventricular hemorrhage with dilatation of the lateral cerebral ventricles (the third degree of the grading scale of Papile) was presented. No clinical signs of intracranial hypertension were presented in the child nor activity of posthemorrhagic hydrocephalus examined by transcranial sonography. Therefore the drainage procedure was not indicated. Surgery for retinopathy and PDA was performed. Later clinical signs of intracranial hypertension had appeared, confirming the activity of hydrocephalus—diastasis of the cranial sutures, increase of head circumference, and tense anterior fontanelle. The child was connected to mechanical ventilation, and apathy combined with irritability of the child occurred. Sonographic examination showed progression of the dilatation of the lateral cerebral ventricles and the third cerebral ventricle with alteration of Doppler parameters of blood flow in ACA ( Figures 65 and 66 ).
Puncture of the right lateral cerebral ventricle was performed. The value of directly measured ICP was of 15 cm of CSF column; after derivation of 14 ml of cerebrospinal fluid (sent to laboratory for biochemical and microbiological examination), ICP dropped to 5 ml of CSF column. After drainage procedure, it was found that the anterior fontanelle was soft when palpated. Derivation of sufficient amount of cerebrospinal fluid led to decrease of ICP to normal range accompanied by slight decrease of width of the lateral cerebral ventricles (width of the third cerebral ventricle remained the same) and improvement of Doppler parameters of blood flow in ACA (decreased RI-ACA and PI-ACA) ( Figures 67 and 68 ). Overview of morphometric parameters of the cerebral ventricles and Doppler parameters of blood flow in ACA before and after cerebrospinal fluid derivation is presented in Table 15 . Biochemical examination of cerebrospinal fluid confirmed increased concentration of proteins and increased amount of erythrocytes. Therefore, Rickham subcutaneous reservoir was inserted. Ventriculoperitoneal shunt insertion was performed after three-week-long period of cerebrospinal fluid derivations from reservoir.
|Parameters||Before CSF derivation||After CSF derivation|
|Width of right lateral cerebral ventricle (mm)||16||13.1|
|Width of left lateral cerebral ventricle (mm)||14||11.4|
|Ventricular index of right lateral cerebral ventricle (mm)||20||17.1|
|Ventricular index of left lateral cerebral ventricle (mm)||15||13.1|
|Width of the third cerebral ventricle (mm)||6||6.1|
|Basal Doppler parameters|
|Resistance index (RI)||0.860||0.722|
|Pulsatility index (PI)||1.750||1.230|
|Compressive Doppler parameters|
|Resistance index (RI)||1.00||0.778|
|Pulsatility index (PI)||2.104||1.387|
|ICP value (cm of CSF column)||15||5|
15.7 Assessment of intracranial dynamics in the neonate with occipital encephalocele and congenital hydrocephalus
The term neonate was born in 23rd gestation week suffering from occipital encephalocele and congenital hydrocephalus ( Figure 69 ). CT examination was performed in the day of birth. It showed three-ventricular obstructive hydrocephalus and occipital encephalocele. Dilatation of the lateral cerebral ventricles was dominant on the CT image ( Figures 70 and 71 ). Examination of blood flow in ACA by transcranial Doppler ultrasonography confirmed alteration of basal parameters: increased RI-ACA ( Figure 72 ).
The following signs of intracranial hypertension were found in clinical manifestation: widely enlarged and tense anterior fontanelle, diastasis of cranial sutures, and enlarged head circumference. Compression of the anterior fontanelle caused bradycardia. Occipital encephalocele resection and ventriculoperitoneal shunt insertion during one operation were performed.
After surgery, the anterior fontanelle was soft when palpated, head circumference did not change in the early postoperative period, and diastasis of the sagittal suture and anterior fontanelle was presented. CT checkup examination was performed 14 days after surgery. It showed significant decrease of the size of right lateral cerebral ventricle, asymmetry width of the lateral cerebral ventricles, and movement of the septum pellucidum to the right by 4 mm ( Figure 73 ).
The parameters of the Doppler curve in ACA were as follows: basal, Vsyst 48.3 cm/s, Ved 14 cm/s, and RI 0.711 (boundary value RI); compressive, Vsyst 55.3 cm/s, Ved 5.12 cm/s, and RI 0.91 (positive compressive test). The clinical signs of intracranial hypertension were not presented after surgery. Impact of asymmetry of the lateral cerebral ventricles and midline shift on Doppler parameters of blood flow in ACA might cause the alteration of Doppler parameters, especially during compressive test on the anterior fontanelle. The impact of asymmetry of the lateral cerebral ventricles on Doppler parameters of the anterior cerebral arteries was described in the study by Kolarovszki et al. .
15.8 Assessment of intracranial dynamics in the term neonate with birth trauma, intracerebral hemorrhage, and hemocephalus
The term neonate born in 38th gestation week was in the first day after birth transported to the Clinic of Neonatology of the Jessenius Faculty of Medicine and the University Hospital Martin from a regional hospital. According to the medical record, the child was born by occiput. But instrumental labor was not mentioned in the medical record. On admission, blue mask syndrome (stagnation cyanosis of the face), large cephalhematoma, and swelling of soft tissues of the head were presented ( Figure 74 ). Signs of intracranial hypertension were not presented. The frontal fontanelle was in niveau, soft when palpated, pupils were isocoric, and symmetric movement of the extremities was presented. The subclinical seizure activity was shown on the continual aEEG image.
Severe hemorrhage in right cerebral hemisphere and blood in the lateral cerebral ventricles and in the third cerebral ventricle were shown by sonography ( Figure 75 ). Basal parameters of the Doppler curve in ACA were altered and Vsyst, Ved, and Vmean decreased. Regarding significant decrease of Ved, the value of RI was increased ( Figure 76 ).
CT examination was done on the day of admission because of the finding in the sonographic image. It confirmed severe intracerebral hemorrhage (parieto-occipital right), which spread into the ventricular system, hemocephalus without development of acute obstructive hydrocephalus, subdural hematoma above the tentorium on the right, and shift of the septum pellucidum by 7 mm to the left. Also, graphic image of cephalhematoma, swelling of the soft brain tissue, and impression of the occipital bone into the intracranial space around the lambdoid suture ( Figures 77 and 78 ) were presented. Clinical finding on the head and result of CT examination pointed out the diagnosis of birth trauma. MRI of the brain did not show cerebral anomalies or brain tumor.
The second day after birth, the neonate´s condition was stabilized, without signs of intracranial hypertension, subclinical spasm activity was shown by aEEG, and in neurological status the hyperreflexia was presented. Checkup sonography of the brain confirmed stable finding of intracranial hemorrhage, without development of obstructive hydrocephalus ( Figure 79 ). For the increased blood flow velocity in ACA, value of RI-ACA was only slightly increased ( Figure 80 ). Because of the risk of effect of the midline shift to Doppler parameters of blood flow in ACA, parameters of the Doppler curve of blood flow in BA were assessed as well. Blood flow velocity in BA was greater than blood flow velocity in the ACA. The value of RI-BA was within normal range. During examination, the characteristic of blood flow in the deep venous system of the brain was not negatively influenced ( Figures 80 and 81 ).
Clinical condition of the neonate was stabilized. Seven days after birth, MRI examination of the brain was performed. It did not show any cerebral anomalies or brain tumor. Size of the cerebral ventricles was stabilized. Elimination of midline shift, stability of intracerebral hemorrhage (parieto-occipital right) and subdural hematoma in the tentorium on the right ( Figure 82 ) were confirmed. Follow-up treatment in the hospital was without significant changes in the intracranial finding.
15.9 Assessment of intracranial dynamics in the neonate with congenital hydrocephalus and VP shunt revision
The neonate was born in 38th gestation week by cesarean section, with the suspicion to gestational infection of the mother. The postnatal adaptation of the neonate was appropriate. In the first day after birth, the head circumference of the child was slightly larger, but the intracranial sutures were not enlarged significantly, and the anterior fontanelle was soft when palpated. Significant dilatation of the temporal and occipital horns of the lateral cerebral ventricles occurred: WI dx. 13 mm, WI sin. 15.3 mm, VI dx. 20.1 mm, VI sin. 17.9 mm, and width of the third cerebral ventricle 3.8 mm. Doppler parameters of blood flow in ACA were as follows: basal, Vsyst 21.23 cm/s, Ved 6.13 cm/s, RI 0.71, and PI 1.33 (increased RI and PI), and compressive, Vsyst 21.86 cm/s, Ved 0 cm/s, RI 1.0, and PI 2.20 (end-diastolic blockage, positive compressive test).
Thirteen days after birth, MRI of the brain showed three-ventricular hydrocephalus accompanied by stenosis of aqueduct. Significant dilatation of the occipital and temporal horns of the lateral cerebral ventricles was presented. The size of third cerebral ventricle was increased only very slightly. Significant reduction of the cerebral cortex mantle in the occipital region was confirmed ( Figure 83 ).
Eighteen days after birth, sonographic examination showed progressive dilatation of the lateral cerebral ventricles, and the width of the third cerebral ventricle had not changed: WI dx. 17.1 mm, WI sin. 17.1 mm, VI dx. 19.9 mm, VI sin. 19.9 mm, and width of the third cerebral ventricle 3.9 mm. Doppler parameters of blood flow in ACA were as follows: basal, Vsyst 30.2 cm/s, Ved 6.4 cm/s, Vmean 15.5 cm/s, RI 0.789, and PI 1.543 (increased RI and PI), and compressive, Vsyst 37.4 cm/s, Ved 0 cm/s, Vmean 18.7 cm/s, RI 0, and PI 2.004 (end-diastolic blockage of blood flow, increased PI, positive compressive test).
Although both MRI and ultrasonography examination of the brain confirmed activity of hydrocephalus (progressive dilatation of the lateral cerebral ventricles, alteration of basal and compressive Doppler parameters, periventricular halo, dominant dilatation in the trigonum, the occipital and temporal horns of the lateral cerebral ventricles), the clinical manifestations were not clear. The cranial sutures were only slightly enlarged as well as diameters of the head. The anterior fontanelle was in niveau, boundary finding when palpated. Based on the signs of the activity of hydrocephalus on MRI and sonographic image, the insertion of ventriculoperitoneal shunt was indicated.
Increased value of ICP of 14 cm of CSF column was confirmed by direct measurement during surgery. We can conclude that in this case, excessive accumulation of cerebrospinal fluid due to stenosis of aqueduct and increased ICP led mainly to progressive dilatation of the lateral cerebral ventricles and alteration of Doppler parameters of blood flow in ACA than to clear clinical manifestations of intracranial hypertension. The most likely cause was increased compliance of the brain tissue, which enabled development of significant dilatation of lateral cerebral ventricles. Three days after ventriculoperitoneal shunt insertion, sonographic examination showed enlarged lateral cerebral ventricles and the third cerebral ventricle: WI dx. 11.5 mm, WI sin. 11.4 mm, VI dx. 20.3 mm, VI sin. 19.1 mm, and width of the third cerebral ventricle 2 mm. Also, changes in Doppler parameters of blood flow in ACA were measured: basal, Vsyst 42.63 cm/s, Ved 16.52 cm/s, RI 0.61, and PI 0.90 (decreased RI due to increased Ved), and compressive, Vsyst 49.74 cm/s, Ved 15.93 cm/s, RI 0.68, and PI 1.1 (negative compressive test).
Retroauricular subcutaneous CSF accumulation occurred after 3 weeks. It enlarged when baby was crying and diminished at the rest. As retroauricular subcutaneous CSF accumulation has been growing ( Figure 84 ), whole-body X-ray focused on drainage system function, X-ray of the skull ( Figure 85 ), and CT examination of the brain were performed. The examinations showed dislocation of the ventricular catheter from intracranial space beyond the calva ( Figure 86 ).
Basal Doppler parameters of blood flow in ACA were within the standard range: Vsyst 64 cm/s, Ved 21.2 cm/s, and RI 0.67. Compressive test was not performed because of the small size of the anterior fontanelle. CT examination of the brain showed decrease of the lateral cerebral ventricles and thickening of the cerebral cortex mantle. There were not any clinical manifestations of intracranial hypertension nor diastasis of the cranial sutures. The anterior fontanelle was small and soft when palpated. Regarding compensation of the intracranial space, cerebrospinal fluid drainage through a small trepanation whole in the calva to the subcutaneous space was effective. This resulted in decreased size of the cerebral ventricles and normal range of Doppler parameters of blood flow in ACA. Blockage of the valve was confirmed during revision surgery ( Figure 87 ). Obstruction of the valve of drainage system disabled drainage of cerebrospinal fluid through the shunt. It resulted in the rise of intracranial pressure, which was followed by pushing the ventricular catheter out of the intracranial space beyond the calva. When cerebrospinal fluid drainage had been performed through the small trepanation whole in the calva, intracranial pressure dropped down.
This case study shows that dynamics of dilatation of cerebral ventricles and Doppler parameters of blood flow in ACA represent the state of compensation of the intracranial space in respect to pressure-volume changes but not the drainage system dysfunction itself. After surgery, the child´s condition was stable without relapse of subcutaneous CSF accumulation, and wound was healing well. Basal Doppler parameters of blood flow in ACA were within the normal range: Vsyst 63.8 cm/s, Ved 21.0 cm/s, and RI 0.671.
15.10 Assessment of intracranial dynamics of congenital hydrocephalus in prenatal and postnatal period
Dilatation of cerebral ventricles was detected by prenatal sonographic examination in the fetus in 33rd gestation week. Up to then, gestation was without complications and without any signs of maternal infection. Prenatal sonographic examination performed 1 week later, in 34th gestation week, confirmed significant progression of dilatation of the lateral cerebral ventricles and reduction of the cerebral mantle, especially in the occipital region of the brain. Because progression was rapid, prenatal interdisciplinary consultation between the gynecologist-obstetrician, neonatologist, and neurosurgeon and then appointment with parents were arranged. Preterm labor was indicated so that early drainage procedure could be performed. Cesarean section was performed without any complications. Neurosurgeon examined the child 1 hour after birth. The first postnatal sonographic examination of the brain was performed. Increased head circumference, diastasis of cranial sutures, and tense anterior fontanelle were presented in the clinical picture. Sonographic examination of the brain showed significant dilatation of the lateral cerebral ventricles and the third cerebral ventricle, hyperechogenicity of the choroidal plexus, and hemorrhage in the lateral cerebral ventricles. High echogenicity of the wall of the cerebral ventricles indicated ventriculitis. Also, alteration of basal and compressive Doppler parameters of blood flow in ACA was confirmed ( Figure 88 ). Ventricular puncture was performed because clinical and sonographic signs indicated activity of hydrocephalus. The value of ICP was 11.5 of CSF column (macroscopically brown-green); after derivation of 20 ml of cerebrospinal fluid, ICP dropped to 3 cm of CSF column. Also, the anterior fontanelle changed to soft when palpated. Biochemical examination of cerebrospinal fluid confirmed increased concentration of proteins and number of erythrocytes. The values of C-reactive protein and procalcitonin in serum of the neonate were in normal range. In the mother´s blood, positive IgG antibodies against toxoplasmosis were found, which indicated overcoming of toxoplasmosis during gestation. From an etiological perspective, the condition was diagnosed as congenital postinfectious hydrocephalus with hemorrhage in the lateral cerebral ventricles due to overcoming intrauterine toxoplasmic neuroinfection.
Dynamics of hydrocephalus was assessed daily by clinical examination and transcranial sonography of the brain as well as by assessing Doppler parameters of blood flow in ACA ( Figure 89 ). One-time early postnatal puncture of the cerebral ventricle with cerebrospinal fluid derivation maintained compensation of hydrocephalus during 4 days and so enabled biochemical and microbiological assessment of cerebrospinal fluid as well as stabilizing of extracranial factors.
Five days after birth, head circumference had increased, and finding on the anterior fontanelle had changed (bulged, tense when palpated); the cranial sutures had been enlarged. The sonographic image did not show progression of dilatation of the cerebral ventricles. Despite the stable dilatation of the cerebral ventricles, alteration of Doppler parameters of blood flow in ACA was found ( Figure 90 ). Subcutaneous reservoir insertion and regular cerebrospinal fluid derivation were indicated. The regime of daily liquor derivation of 24 ml from subcutaneous reservoir ensured compensation of hydrocephalus and positive change of Doppler parameters of blood flow in ACA ( Figure 91 ). Ventriculoperitoneal shunt insertion was performed on the 27th day after birth.
16. Report of assessment of intracranial dynamics in neonate and infant with hydrocephalus
Date of birth:
Etiology of hydrocephalus:
Date of examination:
Time relation to drainage procedure:
General condition of a patient on examination: _sleeping _calm _crying
Analgesics sedation: No Yes: ___________________________
I. Clinical manifestations
• Diastasis of cranial sutures Yes No
• Diastasis of sagittal suture Yes No
• Diastasis of lambdoid suture Yes No
• Palpated finding on the anterior fontanelle
◦ Soft Yes No
◦ Boundary tense Yes No
◦ Tense, bulged Yes No
• Head circumference increased the same progression regression stable
• Sunset eyes syndrome Yes No
• Vomiting Yes No
• Breathing pattern disorders, apneic pauses Yes No
• Bradycardia Yes No
• Apathy, somnolence Yes No
• Hypersensitivity Yes No
• Drainage system: Yes No
◦ Type of drainage procedure
◦ Palpable functional valve Yes No Not clear
• Drainage functioning Functional Dysfunctional
• Cause of drainage dysfunction
• Subcutaneous CSF accumulation, CSF fistula, CSF leak Yes No
• Associated disorders, pathological conditions
• Examination of ocular background Yes No
• Presence of edema in the optic disc Yes No
• Presence of atrophy in the optic disc Yes No
• Other ophthalmologic findings
Extracranial factors Stable Nonstable
• Hematocrit Hemoglobin Heart rate Blood pressure
• Acidobasis SaO2 paO2 paCO2 pH
• Pulse oximeter SpO2
• Body temperature
• Mechanical ventilation Yes No Type of ventilation
USG examination of the brain
• Dilatation of cerebral ventricles Yes No
• Dynamics of dilatation of cerebral ventricles Stable Progression Regression
• Asymmetric dilatation of the lateral cerebral ventricles Yes No
• Shift of midlines structures Yes No
• Type of hydrocephalus
• Width (WI) of the frontal horn of the lateral cerebral ventricle Left: Right:
• Ventricular index (VI) of the frontal horn of the lateral ventricle Left: Right:
• Width (WI) of the third cerebral ventricle
• Width (WI) of the fourth cerebral ventricle
• Periventricular leukomalacia, cysts Yes No
• Other pathological findings:
TCCD examination of the brain: the segment of ACA before the genu corporis callosi in the sagittal section
• Vsyst Ved Vmean
• RI (Pourcelot) PI (Gösling)
• Vsyst Ved Vmean
• RI (Pourcelot) PI (Gösling)
CT and MRI examination of the brain
• Type of hydrocephalus
• Periventricular edema Yes No
• Width (WI) of the frontal horn of the lateral cerebral ventricle Left: Right:
• Ventricular index (VI) of the frontal horn of the lateral ventricle Left: Right:
• Width (WI) of the third cerebral ventricle
• Width (WI) of the fourth cerebral ventricle
• Evans’ index
• Frontal-occipital horn ratio (FOR)
• Other pathological findings:
Assessment of the condition, notes, and conclusion
Healthcare about the child with hydrocephalus gradually develops using the latest knowledge and its application in clinical practice. Milestone in treatment of pediatric hydrocephalus in the middle of last century was determined by the use of drainage systems with a valve mechanism which enabled regulated internal cerebrospinal drainage. Since then, new and modern valves have been developed to ensure physiological alternative drainage of cerebrospinal fluid as much as possible. Despite that, shunt insertion is related to infectious and noninfectious conditions, which have a negative effect on psychomotor development of the child. The second milestone has been more frequent implementation of endoscopic methods in treatment of children with hydrocephalus since the end of last century.
Assessment of a child with hydrocephalus should be based on understanding pathophysiology and biomechanics of hydrocephalus. Therefore, the research is focused on assessment of intracranial dynamics and analysis of pressure-volume relationships, which are combined with assessment of intracranial pressure and compliance. Transcranial Doppler ultrasonography has been used as a noninvasive technique for indirect measurement of intracranial pressure and effect of drainage surgery because it enables to assess values of blood flow velocity in the cerebral arteries and cerebrovascular resistance. In general, increased intracranial pressure leads to increased cerebrovascular resistance of the cerebral arteries. This results in increased resistance index and pulsatility index of the Doppler curve of blood flow in the cerebral arteries. Initial discrepancy in methodology of the use of transcranial Doppler ultrasonography and interpretation of data resulted in various conclusions. Since then, various research studies have brought precisely defined methodology and analysis of Doppler parameters of cerebral circulation. Complex relationship between size of cerebral ventricles, intracranial pressure, intracranial compliance, and Doppler parameters of cerebral circulation, accompanied by impact of multiple intra- and extracranial factors on cerebral circulation, is responsible for the condition that not in each case the values of measured Doppler parameters reflect automatically the increased value of intracranial pressure. This fact is one of the causes why assessment of cerebral circulation by transcranial Doppler ultrasonography in children with hydrocephalus remains to be open for discussion.
Based on our (the author of this monography) 17-year-long clinical experience and scientific research on pediatric hydrocephalus, we can summarize the results of research and a role of transcranial Doppler ultrasonography in assessment of intracranial dynamics of pediatric hydrocephalus as follows:
Assessment of Doppler parameters of cerebral circulation before drainage procedure in children with hydrocephalus revealed alteration of basal and compressive parameters of the Doppler curve of blood flow in ACA. Increased RI-ACA was caused by decreased Ved [389, 436]. After drainage procedure, RI-ACA values dropped down to the normal range because of increased values of Ved. Change of Doppler parameters before and after drainage procedure confirmed positive effect of the drainage procedure to cerebral circulation in children with hydrocephalus [319, 320, 387].
Realization of compressive test on the anterior fontanelle during sonographic examination increases validity of assessment of cerebral circulation by transcranial Doppler ultrasonography and enables indirect assessment of decrease of intracranial compliance. Increase of basal Doppler parameters reflects increase of intracranial pressure .
While interpreting Doppler parameters of cerebral circulation measured in a child with hydrocephalus, it is important to assess impact of both intra- and extracranial factors on cerebral circulation. Then it is possible to say to which extent Doppler parameters show the real value of intracranial pressure and intracranial compliance. The fact is that extracranial factors affect cerebral circulation. Our research was focused on detailed analysis of impact of the intracranial morphologic factors on Doppler parameters of blood flow in ACA. The results showed that asymmetric dilatation of the lateral cerebral ventricles and posthemorrhagic periventricular lesions influenced the RI-ACA values both in intracranial hypertension and intracranial normotension .
While assessing relation between dynamics of dilatation of the cerebral ventricles and value of RI-ACA, we found out that the values of RI-ACA were increased in those cases in which stable dilatation of the cerebral ventricles was accompanied by increased intracranial pressure and drainage procedure was necessary. On the contrary, the values of RI-ACA were within the normal range in children in which intracranial pressure wasn´t increased. The results show that the values of RI-ACA in active hydrocephalus aren´t increased due to dilatation of cerebral ventricles but increased intracranial pressure [319, 400].
Assessment of Doppler parameters of blood flow in ACA in children with hydrocephalus with functional drainage system or ETV revealed normal range of RI-ACA values. On the other hand, the values of RI-ACA increased in the shunt-dependent children with dysfunctional drainage system and ETV, even though the cerebral ventricles enlarged slightly or maintained the same size. After successful revision surgery, the value of RI-ACA dropped down to normal range [319, 320, 387].
Assessment of cerebral circulation by transcranial Doppler ultrasonography in children with hydrocephalus allows an accessible, indirect, noninvasive, bedside, and repetitive measurement of intracranial pressure and intracranial compliance. Regarding complexity of intracranial dynamics, the relationship between intracranial pressure and Doppler parameters of the cerebral arteries, individual assessment of measured Doppler parameters, as well as assessment of effect of extra- and intracranial factors to cerebral circulation should be performed in each case of pediatric hydrocephalus. If the results are not clear, examination should be repeated, and intraindividual tendency should be observed in the child. It is important to design and follow detailed methodology of sonographic examination and include it into the report of assessment of intracranial dynamics in the child with hydrocephalus [186, 266, 289].
Clinical applications of transcranial Doppler ultrasonography in children with hydrocephalus are as follows :
Indication and timing of drainage procedure
Observation of effectivity of drainage procedure—internal drainage systems (shunts), ventriculostomy of the third cerebral ventricle, external ventricular drainage, cerebrospinal fluid derivation from subcutaneous Rickham reservoir (determination of frequency and amount of aspired cerebrospinal fluid)
Observation of function and detection of malfunction of external and internal drainage systems and ventriculostomy of the third cerebral ventricle
Assessment of dependence of the child on drainage system (shunt dependence)—important for indication of external ventricular drainage conversion, Rickham reservoir conversion on internal drainage system (shunt), and ETV, need for a revision of dysfunctional drainage system.
To sum up, it can be said that including assessment of cerebral circulation by transcranial Doppler ultrasonography into management of children with hydrocephalus provides additional information to clinical manifestation and morphological results of imaging techniques. This helps better understand intracranial dynamics and activity of hydrocephalus in regard to indication and timing of drainage procedure.
|ACA||anterior cerebral artery|
|ATP||adenosine triphosphate, adenosine triphosphate acid|
|cAMP||cyclic adenosine triphosphate|
|CBF||cerebral blood flow|
|CDE||color Doppler energy|
|CFD||color flow Doppler|
|cGMP||cyclic guanosine monophosphate|
|cm/s||centimeter per second|
|CNS||central nervous system|
|CPA||color power angio|
|CPP||cerebral perfusion pressure|
|eNOS||endothelial synthetase of nitric oxide|
|ETV||endoscopic third ventriculostomy|
|EVD||external ventricular drainage|
|FHR||frontal horn ratio|
|FOR||frontal/occipital horn ratio|
|g/cm2||gram per square centimeter|
|GLAST||glutamate/aspartate transport system|
|Hz||hertz, unit of frequency|
|ICA||internal carotid artery|
|ICV||internal cerebral vein|
|iNOS||induced synthetase of nitric oxide|
|IOR||index of regulation|
|IRDS||idiopathic respiratory distress syndrome|
|lCBF||local cerebral blood flow|
|m/s||meter per second|
|MAP||mean arterial pressure|
|MCA||middle cerebral artery|
|MR spectroscopy||magnetic resonance spectroscopy|
|MRI||magnetic resonance imaging|
|mW/cm2||milliwatt per square centimeter|
|NGF||nerve growth factor|
|nNOS||neural synthetase of nitric oxide|
|NOS||synthetase of nitric oxide|
|paCO2||partial arterial blood pressure of carbon dioxide|
|paO2||partial arterial blood pressure of oxygen|
|PCA||posterior cerebral artery|
|PDA||ductus arteriosus Botalli apertus|
|PI||index of pulsatility, Gösling´s index|
|PRF||pulsed repetitive frequency|
|RI||index of resistance, Pourcelot´s index|
|S/D index||systolic/diastolic index|
|SVP||synaptic vesicle protein|
|TCCD||transcranial color-coded Doppler sonography|
|tRNA||transcription ribonucleic acid|
|Ved||end-diastolic blood flow velocity|
|VEGF||vascular endothelial growth factor|
|VIdx.||ventricular index of right lateral cerebral ventricle|
|VIsin.||ventricular index of left lateral cerebral ventricle|
|Vmean||mean blood flow velocity|
|VP shunt||ventriculoperitoneal shunt|
|Vsyst||peak systolic blood flow velocity|
|W/cm2||watt per square centimeter|
|Wdx.||width of the right lateral cerebral ventricle|
|Wsin.||width of the left lateral cerebral ventricle|