Electroencephalography (EEG) is a non-invasive neurophysiological study that monitors electrical activity of the brain. EEG is an essential investigational tool to analyze and record electrical impulses of the brain and considered to be the gold standard electrophysiological test which can be used to help diagnose epilepsy. EEG can also be used to diagnose and evaluate other conditions such as sleep disorders, neurometabolic diseases with encephalopathy and neuropsychiatric disorders. It is also an essential ancillary test in other conditions such as brain death assessment. However, it is essential not to entirely rely on EEG for an absolute diagnosis of epilepsy as the main indication of EEG in general and in Pediatric age group in particular is to categorize different types of seizure and epilepsy syndromes for further evaluation and management.
EEG is a common, non-invasive and essential electrophysiological technique used to evaluate and study the brain function. EEG measures and investigates the cerebral electrical impulses by direct application of electrodes to the patient’s scalp. EEG is considered the main neurophysiological study used in Pediatric population especially in children with epilepsy [1, 2] and remains the primary test used to study and assess other clinical conditions such as parasomnia and encephalopathy associated with neurometabolic disorders and post traumatic brain injury . EEG study has been used in the evaluation and assessment of organic brain pathology in patients presented with psychiatric and behavioral disorders and has been also an essential tool to confirm absence of cerebral electrical activity in patients with brain death [4, 5]. Epilepsy diagnosis is primarily made based on the clinical history of the patient and hence it is necessary not to rely completely on the EEG study to confirm the diagnosis of epilepsy , however EEG is the major neurophysiological test used in the classification and evaluation of seizures and epilepsy syndrome in Pediatric patients .
In 1875, Richard Caton an English physician reported a spontaneous electrical variation from exposed cortical brain hemispheres of rabbits and monkeys . Early in the twentieth century, specifically in 1912, Vladimir Vladimirovich Pravdich-Neminsky a Russian Physiologist reported the first electrical brain impulse and evoked response in animals (dog) . However, in 1924 German Neurologist and Psychiatrist Hans Berger recorded the first human EEG in a graph paper which later named an electroencephalogram (EEG) device. Berger subsequently characterized different rhythmic nature and wave patterns of the brain activity based on the different physiological state of the subjects (Figure 1) . The initial description of clinical encephalography was first reported by an American neurologist Frederic Andrews Gibbs in 1935 who initially documented the classical interictal spikes associated with epilepsy and first to demonstrate the typical 3 per second spike and wave discharges associated with absence epilepsy. He also described EEG pattern during impaired consciousness level (Figure 2) [8, 9, 10].
2. Analysis and understanding the complex brain network
The human brain consists of a complete and comprehensive network map of neuronal connections called human connectome. The normal maturation of these interconnected neurons associated with normal development of high cortical functions and motor skill consolidation. The failure of this network maturation can lead to some serious neurodevelopmental disabilities .
The connectivity of this complex brain network can be classified into three types: structural connectivity, functional connectivity and effective connectivity . Structural connectivity can be further subdivided into two types. First the anatomical connections that links a bundle of neural elements and second is the interregional fibers linking cortical to subcortical gray matter areas .
Functional connectivity is obtained from time series analysis and reflects the statistical dependence within neural units. This time sense date can be defined by different methods which include EEG, Functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG) .
Effective connectivity (EC) defines the casual effects that one neural system exerts over another. EC cannot be assessed directly so several techniques have been used to study the EC. The Dynamic Casual Modeling (DCM) is the main method for evaluating EC by analyzing data from neuroimaging studies such as Functional Magnetic Resonance Imaging (fMRI) .
3. Preparing pediatric patients for EEG study
Performing electroencephalography (EEG) in children can be quite challenging as most of these children are not cooperative during this study due to the great fear and restlessness during the EEG procedure. It is vitally important to prepare a Pediatric patient for EEG study in order to have better interpretation of the EEG results. The application of psychological technique prior to the study and the availability of the parents during the procedure can be helpful to conduct the study smoothly and minimize the need for premedication drugs. However, the behavioral and psychological techniques are not always successful in a small proportion of children. Different premedication protocols have been proposed in order to alleviate the great distress and anxiety during the study. The ideal pharmacological agents for such procedure should have a minor impact on the EEG tracing with fast onset and few side effects. Benzodiazepine is the most common premedication agent used with Midazolam being the most popular drug to induce sedation for EEG study in children .
Chloralhydrate is another medication which has been used to induce sedation in the Pediatric population during different neurological studies including EEG. Chloralhydrate is a safe, cheap hypnotic non-opiate drug with no major side effects with the exception of vomiting in few cases. Chloralhydrate has been also shown to be effective and more time saving during EEG procedure .
4. Technical aspects of electroencephalography
Electroencephalography EEG, since it’s first introduction early in the 20th century, has been an essential and the most common neurophysiological device to monitor and study the electrical and functional activity of the brain . EEG is a commonly used non-invasive tool to track and record the electrical field potentials captured by electrodes placed on the patient scalp. These electric field potentials created by dipoles as a result of excitation of the epical dendritic postsynaptic potential at the cortical pyramidal cells [18, 19]. The measurement and assessment of the electric field potentials can be made by attaching conductive electrodes to the human scalp. At the present time the wet electrodes are the gold standard used for EEG study . A conductive paste or gel need to be used during the application of wet electrodes to minimize electrode-skin impedance in order to achieve good conductivity of the electrical impulse. The typical value of skin impedance should be kept between 5 and 20 KΩ. This skin impedance should be continuously monitored during the EEG study to ensure proper and high-quality conductivity between the skin and the EEG electrode. Performing an EEG study is a time consuming process which require an expert EEG technician or neurophysiologist in order to obtain good quality EEG results for proper interpretation and reporting as the reading and analyzing EEG data is a hard task and must be interpreted by expert neurophysiologists. The location site and description of the scalp electrodes is well recognized by the international 10–20 system (Figure 3) [19, 20].
During the first EEG only 20–50% of patients with seizure disorder show interictal epileptiform discharges (IED) so the yield of the EEG study can be enhanced by many activation methods in order to capture the interictal epileptiform discharges which help confirming the diagnosis of epilepsy and seizure disorder . The common activation procedure used in EEG laboratories includes Hyperventilation, intermittent photic stimulation (IPS), sleep and sleep deprived techniques. Hyperventilation (HV) is considered to be the first and oldest activation method used to trigger the interictal epileptiform discharges (IED) especially the one associated with absence epilepsy. HV is more effective in Pediatric population than in adult. A proper effective HV should be carried out for full 3 minutes with continuous recording and monitoring for one-minute post hyperventilation. HV is more efficient in diagnosing generalized seizures than focal epilepsy. The mechanism of HV to trigger interictal epileptiform discharges can be explained by hypocapnia induction which also manifest as background slowing or focal slowing in the EEG . HV is a major provocation technique used to trigger the typical 3-Hz spike-and-wave discharge (SWD) which is characteristic for absence epilepsy as more than 90% of patients who have absence epilepsy show SWD during HV. The non-specific thalamic projection system (NSTPS) which is a part of the thalamocortical networks triggered by respiratory alkalosis and considered to be the major induction of SWD associated with absence epilepsy during the process of HV . HV is an efficient and safe activation method for epilepsy and seizure disorder provocation however there are certain contraindication to perform HV during EEG study which includes patients with cardiopulmonary disease, sickle cell anemia, Moy-Moya disease, subarachnoid and intracerebral bleeding and severe carotid stenosis .
A standard activation procedure used during the routine EEG study is the intermittent photic stimulation. This procedure done in a dimmed light room and application of different light frequencies between 1 and 30 Hz for 5 to 10 seconds during eye closure. The flashing light device should be kept 30 cm form the patient eyes. The response to intermittent photic stimulation (IPS) can be seen as an evoked potentials at frequencies less than 5 Hz seen posteriorly or drive response at the occipital regions or in the form of photoparoxysmal response (PPR) which was previously named photoconvulsive response. The most common types seizure disorder seen with IPS are absence epilepsy, myoclonic and tonic–clonic seizures .
Among the activation techniques used during routine EEG study is the sleep and sleep deprived approach which produce the maximum yield of interictal epileptiform discharges (IED) as compared to the hyperventilation and intermittent photic stimulation procedure. The young age patients tend to have better yield of IED with each activation technique than older patients .
5. Brain computer interface
A Brain Computer Interface (BCI) which also named as Brain –machine Interface (BMI) is a computer- build network system that allow direct communication between cerebral brain activity and external recordable machine without using human muscles or peripheral nervous system. BCI utilize and analyzes the brain signals to collect information and send them to output system. BCI network consists of five phases: Signal Acquisition, Signal Magnification, Feature Extraction, Categorization and Control Interface. BCI assesses and analyze brain activity through mainly electrophysiological and hemodynamic studies. The electrophysiological study consists mainly of EEG, electrocorticography and magnetoencephalography. The hemodynamic study measures glucose uptake by an active neurons and this can be evaluated by procedures like functional magnetic resonance and infrared spectroscopy. BCIs commonly used EEG to gain details from brain activity. The design of BCI is complex due to restricted resolution and data reliability detected by the brain [25, 26].
6. Different types of EEG study
The American Clinical Neurophysiology Society suggest at least 20 minutes’ time duration for routine outpatient study. However, the International League against Epilepsy suggests a minimum 30 minute for routine EEG recording. Currently most routine EEG studies are done with an average time between 20 and 30 minutes. The abnormal epileptiform discharges found in 29–55% in patients with epilepsy on their first routine EEG study. Ambulatory prolonged EEG study is considered to be helpful diagnostic technique to capture interictal epileptiform discharges (IEDs) in epilepsy patients whom their first routine EEG studies reported normal. Prolonged ambulatory EEG study is considered to be superior to routine EEG in identifying IEDs specially during the natural sleep state. This procedure is also helpful to differentiate epileptic from non-epileptic psychogenic events. The duration of the ambulatory EEG study usually between 24 to 96 hours [27, 28].
Epilepsy Monitoring Unit (EMU) is an important and crucial part of the neurophysiological work up for the diagnosis and classification of epilepsy and evaluation of psychogenic non-epileptic seizures (PNES). EMU is also essential for patients with intractable epilepsy resistant to antiepileptic medications and for evaluating candidates for possible epilepsy surgery .
EMU is strongly recommended for children with unclear history of paroxysmal episodes in order to differentiate between epileptic and non-epileptic events as this can be quite challenging in pediatric population. EMU is also important in evaluating different types of epilepsy syndromes in children. One of the vital advantages of the video-EEG telemetry is the monitoring and recording the ictal events especially in patients with partial epilepsy. EMU is a highly selective study should be done for carefully selected patients as this is an expensive and time consuming procedure . The process of monitoring and recording video-EEG telemetry can range from 24 hours to 7 days. In some situation antiepileptic drugs need to be tapered in order to induce seizure activity for better evaluation of seizure semiology and localization of the epileptogenic zone .
The Amplitude-Integrated EEG (aEEG) is another continuous electrophysiological modality used in both term and preterm newborns in the neonatal intensive care units (NICUs). Since it’s first introduction late in 1980s. the aEEG considered to be the gold standard to monitor and assess neonatal brain background activity, diagnose and manage newborn seizure disorders and help in selecting newborns who might be benefit from cooling therapy. The aEEG also plays a major role in predicting the neurodevelopmental outcomes for term and preterm newborn babies. The application and recording of the aEEG is done by using two or four scalp electrodes applied to C3, P3, C4 and P4 positions of the newborn head according to the international 10–20 system. aEEG is a safe procedure which has a major limitation as it covers only small area of the head surface and hence focal epileptiform activity cannot be monitored during the aEEG recording [32, 33, 34].
EEG is considered to be the commonest procedure used for intraoperative neurophysiological and cerebral perfusion monitoring . EEG is also considered to be the gold standard modality for evaluating patients for possible epilepsy surgery to localize and define different epileptogenic foci. EEG also plays an important role in understanding the nature and pathophysiology of epilepsy and presurgical evaluation of functional cortical mapping. However, routine EEG monitoring might not be always sufficient to evaluate certain types of epilepsy such as non-lesional temporal lobe epilepsy which necessitate the need of more interventional procedure such as the invasive electroencephalography (iEEG) [36, 37].
7. Basic EEG interpretation
A proper and detailed history taking is more reliable and important in diagnosing epilepsy and seizure disorders than EEG study. A solid and classical history of seizure even with the presence of normal EEG finding make the diagnosis of epilepsy is more likely as the sensitivity of single routine EEG study is only about 50% in diagnosing seizure disorders .
A single EEG study provides extensive data for interpretation. The main initial description of the EEG recording includes the amplitude, frequency and wave morphology. Hans Berger described two characteristic EEG wave frequencies during awake state: The alpha rhythm (8–12 Hz) which is more prominent in the arousable stage with eye closure and beta rhythm (13–30 Hz) commonly seen with mind focus state. In most people eye closure will result in frequency transfer from beta to alpha rhythms. Subsequent wave frequencies were identified the theta rhythm (4–7 Hz) and the delta rhythm (0.5–3 Hz) which are predominant during sleep in adults, and the gamma rhythm (> 30 Hz) which is associated with memory, information processing and cognitive skill (Figure 4) .
It is vitally important to ensure proper education and gain enough experience to read and interpret EEG recording in order to avoid misdiagnosis of epilepsy and to provide better care to the patient. It is also essential to appreciate the common benign variations of normal EEG study [40, 41].
A common normal patterns seen in EEG study which can be falsely interpreted as abnormal epileptiform discharges include multifocal sharp waves and spikes, generalized slowing with hyperventilation, hypnagogic hypersynchrony and most commonly is the background alteration at the temporal area (Figures 5 and 6) .
Over interpretation of normal EEG tracing is the main factor for misdiagnosis of epilepsy and seizure disorders. Improper neurophysiological training and inadequate experience is the major reason for over interpretation of normal EEG study. Conservative EEG interpretation and avoiding biased history are strongly recommended by all epileptologists .
8. Common clinical applications of EEG in children
Although the diagnosis of epilepsy is primarily made by clinical history, EEG remains an essential investigational tool to differentiate between epileptic and non-epileptic events, it’s also important in the classification of different types of epilepsy and epilepsy syndromes [44, 45, 46]. Frequent classical epileptiform abnormalities seen in Pediatric population are hypsarrhythmia associated with infantile spasm, 3 Hz spike and wave discharges in absence epilepsy and burst suppression (Figures 7 and 8) .
According to the American Academy of Neurology and Child Neurology Society, EEG is recommended in children presented with their first attack of unprovoked seizure . EEG is indicated in children with atypical febrile convulsion or prolonged febrile seizure and it is an essential investigational study in patients with newly diagnosed epilepsy and in classification of common childhood epilepsy syndromes such as centrotemporal spikes associated with benign rolandic epilepsy and Panayiotopoulos syndrome (idiopathic childhood epilepsy). EEG is also important in recording continuous spike-waves during slow-wave sleep (CSWS) in epileptic encephalopathies (Figures 9 and 10) .
Pediatric patients diagnosed with autistic spectrum disorder (ASD) with positive history of epilepsy and abnormal findings in the neurological examination, EEG study is indicated as a part of their screening tests. EEG is also recommended in monitoring antiepileptic medication in patients with confirmed diagnosis of epilepsy .
The background EEG monitoring has been also used in children with traumatic brain injury which is helpful in evaluating prognosis in these patients [50, 53]. EEG study with poor reactivity, prolonged discontinuity and burst suppression associated with poor prognosis, whereas EEG with good reactivity and normal sleep rhythm favor a good prognosis . A prolonged EEG recording is also essential in children admitted to the PICU (Pediatric Intensive Care Unit) with suspected non-convulsive seizures (NCS). It has been also important in monitoring Pediatric patients underwent surgery for congenital cardiac anomalies as they are at risk to have seizure post-surgery .
Viral encephalitis is an inflammatory infectious neurological disease that affects the central nervous system (CNS) which triggers an immune response by the viral antigen causing damage to the brain parenchyma and associated with electrical disturbance of the brain activity . Viral encephalitis is common in children with Herpes Simplex Virus (HSV) being the commonest agent for encephalitis in Pediatric population [54, 55]. EEG study is considered to be a part in the investigational work up in patients with viral encephalitis . Patients with Herpes Simplex Encephalitis (HSE) found to have significant EEG changes in the early stage of the diagnosis. Unilateral Periodic Lateralized Epileptiform Discharges (PLED) is considered to be the most typical EEG finding which correlate with diagnosis of HSE  and found to have a good outcome as compared to bilateral periodic lateralized epileptiform discharges which associated with unfavorable prognosis (Figure 11) .
EEG study can be also used as an ancillary test to support the diagnosis of brain death. Although positive diagnosis of brain death can be made by two separate settings of clinical examination, The American Neurological Association strongly suggest the use of EEG study to confirm the diagnosis of brain death. Hypothermia and hypotension should be avoided when applying EEG for brain death assessment . Isoelectric encephalogram is confirmed when 30 minutes of EEG recording reveals complete absence of cerebral activity with sensitivity over 2 μV/mm in the absence of electrolyte disturbance and sedative medications (Figure 12) .
EEG is considered to be save non-invasive procedure since its first application early in the 20th century. This procedure is done by trained EEG technicians and it should be interpreted by Neurologist or expert Neurophysiologists in order to obtain a high quality report to reach a proper diagnosis and provide optimal management to the patient.
Performing EEG study in children can be a difficult task because of the great fear and anxiety in this age group patients, so its vitally important to properly prepare these patients to minimize EEG artifacts for better interpretation of the EEG report.
EEG is an essential neurophysiological study especially in Pediatric patients to differentiate epileptic form and non-epileptic events as the differential diagnosis for paroxysmal episodes in children is wide and varies according to certain age group.
Although the diagnosis of brain death is primarily made on clinical basis, EEG remains an important ancillary test for diagnostic confirmation of brain death.
Conflict of interest
The author declares no conflict of interest.
|fMRI||functional magnetic resonance imaging|
|IED||interictal epileptiform discharges|
|IPS||intermittent photic stimulation|
|BCI||brain computer interface|
|EMU||epilepsy monitoring unit|
|ASD||autistic Spectrum disorder|