Over recent years, the importance of sleep physiology and pathology has been better understood in terms of correct diagnosis, treatment, prognosis and innovative research of diseases. Sleep disorders are often confused with clinical symptoms of adult and pediatric medical conditions. In medicine, electrophysiological signal recording methods are very important for establishing a correct diagnosis especially in neurological sciences. Polysomnography (PSG) is a golden standard diagnostic method that records electrophysiological signals used for sleep physiology and diseases. When the medical disciplines and diseases that make use of this diagnostic method are considered, its significance becomes clearer. For example, medical disciplines benefiting from PSG are as follows: “Clinical Physiology, Neurology, Ear Nose and Throat, Dentistry, Psychiatry, Pulmonology, Cardiology, Pediatric Neurology, Pediatric Cardiology, Internal Medicine, Neurosurgery, Endocrinology, etc.” The patient groups diagnosed with PSG are as follows: “Sleep Disordered Breathing (Central Sleep Apnea Syndrome, Obstructive Sleep Apnea Syndrome), Obesity, Morbid Obesity, REM Behavior Disorder, Restless Leg Syndrome, Rhythm Disorders, Epileptic Disorders, Insomnia, Insomnia and Headache, Hypersomnia, Narcolepsy, Secondary Hypertension, etc.” Interpretation and understanding electrophysiological signals correctly show us interactions of body systems with sleep physiology and integrated therapeutic approaches to sleep disorders. In conclusion; new approaches to sleep pathophysiology depend on a better understanding and further advancement of polysomnography.
- correct diagnosis
Electrophysiological signal recordings are used in medicine for research, clinical diagnosis and follow-up of diseases as well as for providing guidance to their treatment. For example; “Electrocardiogram (ECG)” is used daily as inpatient and as outpatient, it is the most basic electrophysiological signal recording in which five waves (P, Q, R, S, and T) are interpreted. When all monitorization activities performed at the bedside of the patient are taken into consideration, recording electrophysiological signals with well-calibrated equipment and correct interpretation of the obtained results by doctors and healthcare staff seems to be at the crossroads of correct diagnosis, follow-up and treatment. In sleep monitorization, electrophysiological signal recordings are performed by multiple electrodes and provide us with important clinical information. In fact, monitoring wakefulness as much as sleep is quite important in clinical practice; it helps to establish a correct diagnosis in clinical practice and sometimes provides the opportunity to have access to unsuspected information. If PSG could be used as frequently as ECG by well-trained medical doctors and healthcare personnel in sleep medicine, sleep health and sleep disorders of the individuals in the society could be understood much better. Therefore, health could be evaluated not only in wakefulness but also in sleep leading to a continuum. During its preliminary years, sleep related studies attracted the attention of physiologists and as time passed clinical information regarding sleep disorders increased significantly and the possibility to treat all these diseases brought the attention of clinicians into this field. For human physiology and especially for the central nervous system to continue its functioning; there needs to be a healthy interaction and an organism specific balance between wakefulness and sleep cycles. Sleep is a physiological need; a state where the response of the brain to environmental stimuli has stopped reversibly. The insufficiency or absence of this need negatively influences the interactions in the neuronal circuits and pathways that are responsible for the wakefulness of the brain. It is very well known that many functions of the organism change during sleep and different physiological mechanisms come into play during NREM and REM sleep. Diseases also show changes during sleep and during NREM and REM phases. Electrophysiological studies could assist in the understanding of basic mechanisms in neurological sciences. Electrophysiological methods and PSG that are geared to understand the nights as well as the days aim at not only establishing correct diagnosis and delineating pathophysiological mechanisms but also engaging in innovation and developing novel diagnostic and therapeutic methods.
2. Sleep physiology and polysomnogram, physiopathology and symptomatology in sleep medicine
2.1 Sleep physiology and polysomnogram in sleep medicine
Sleep is a physiological and behavioral process that an individual requires to carry out his daily functions. This process is completed in a regular and continuous manner every night. As a part of biological rhythm, human brain has a healthy functioning by differentiating dark and day hours of the day. From controlling hormone levels to muscle tone, from regulating pace of breathing to contents of our thought; sleep influences all bodily and mental functions. It is not surprising that sleep can make these changes happen in the body because sleep causes significant changes in the electrical activity of the brain as a whole . Sleep characterizes itself by not responding to one’s surroundings and by drifting away from perception; yet it is a reversible behavior. During 1940–1950, physiologists believed that sleep was initiated as a result of tiredness that developed during the day and by a slowing down in the activation of the fore brain from weakening in the activation of the reticular activating system. Later, based on transection studies, brain stem was shown to be responsible for generating sleep especially studies in cats; where total sections performed on pontine tegmentum induce sleeplessness. Physiologist Nathaniel Kleitman was working at Chicago University and he discovered REM sleep together with his colleague Dement in 1959 leading to a revolution in the field of sleep medicine. Two colleagues demonstrated the nature of sleep and the relation of eye movements with sleep by recording spontaneous whole night sleep. During their observations, it was understood for the first time that sleep consisted of 90–120 minutes cycles, it first got deep and then became superficial, and that during this superficial stage rapid eye movements appeared and then sleep deepened once again. Through the same series of observations it was found that, during the first half of the night deep sleep was more frequent and that REM sleep constituted 20–25% of the total length of the sleep [2, 3]. Sleep has an important function in an individual and sleep deprivation for a couple of days can hinder an individual’s cognitive and physical performance, general productivity and health. The vital role of sleep on homeostasis can be clearly demonstrated by the possible death of rats who suffer from sleep deprivation for 2–3 weeks. Despite the obvious importance of sleep, we still have limited information about why it is an obligatory part of life. Sleep has two main types of physiological effects: First, its effect on the nervous system itself and second its effects on other functional systems of the body. There is no doubt that the effects on the nervous system are important. Long lasting wakefulness generally leads to progressive impairments of thought processes and even to abnormal behavioral activities (thoughts are blurred, as the duration of wakefulness lengthens irritability and psychosis ensues). Therefore, sleep is considered to protect the normal order of brain activity by different means and to preserve the normal “balance” between the different functions of the central nervous system [4, 14].
2.1.1 Mechanisms of wakefulness and sleep
In the regulation of wakefulness and sleep brain stem, hypothalamus, basal fore brain and their neurotransmitters all play a role. When we analyze
2.1.2 Normal sleep
Sleep is a complex mix of physiological and behavioral processes. Typically, sleep takes place while the individual is in a horizontal position, immobile with closed eyes and when all other indicators point out to sleep. There are two distinct stages of sleep: The one with non-rapid eye movements (NREM) and the one with rapid eye movements (REM). These stages are differentiated from one another and from wakefulness with clear margins. NREM sleep is classically divided into three stages based on EEG. EEG patterns usually consist of a mixture of synchronous sleep spindles, regular waves like K-complexes and high voltage slow waves. Based on the depth of sleep, there are three NREM stages, during the first two stages, wake-up thresholds are generally low and during the third stage it is at its highest or a body that can move and for a brain that can regulate, NREM sleep is a relatively inactive state going together with minimal and fragmental activity. On the other hand, during REM stage, the body is immobile because of muscular atonia, in EEG shows activation and episodic rapid eye movements can be observed. Sleep cycle starts with NREM (calm, synchronized sleep, deep wave sleep); nearly every 90 minutes NREM and REM (mobile, desynchronized, paradoxical sleep) follow one another. Slow wave sleep dominates the first one third of the night and is related to the duration of wakefulness before sleep. REM sleep dominates the last one-third portion of the night and is related to the circadian rhythm. First stage of sleep, namely NREM-1 lasts only for a couple of minutes after the initiation of sleep and it goes together with low wake-up threshold and provides the transition from wakefulness to sleep. NREM-2 stage of sleep is identified by the presence of sleep spindles and K-complexes on EEG. To wake-up, there needs to be a more intense stimulus during NREM-2 compared to NREM-1. If stimuli given during NREM-1 are administered during NREM-2, there is no arousal; but K-complexes will appear. NREM-2 gradually progresses to high voltage slow activity and transforms into NREM-3 stage. In a young healthy individual, the percentage of slow waves in sleep pattern should be 20–50%. NREM-REM cycles of sleep follow throughout the night by repetitions. First NREM-REM cycle lasts about 70–100 minutes, the second and further cycles last around 90–120 minutes. In young adults, during the first one third of the night deep sleep is predominantly seen during NREM stage, whereas during the last one-third portion of the night REM sleep dominates. Short wake-up periods usually happen when shifting to REM sleep [10, 11].
2.1.3 Electrophysiological signal recordings of wakefulness and sleep
During wakefulness electroencephalogram (EEG) reflects an active cerebral cortex engaged in perception and cognitive functions that shows relatively low voltage, high frequency and rapid activity. The discharge by a single neuron or a single nerve fiber can never be recorded from the scalp surface. Only when thousands even millions of neurons or fibers are simultaneously fired, electrical potentials pertaining to a single neuron or a single fiber can be recorded as this much of an electrical potential would suffice to make such a measurement from scalp surface . When eyes are closed, several neurons show synchronous discharges at a frequency of 12 per second constituting alpha waves. When the eyes are opened afterwards, the activity of the brain increases to a greater degree; but the synchronicity of the signals decrease which leads to the canceling out of the brain waves. As a result of this, weak waves of higher but irregular frequency which are called beta waves appear. If the cortex does not have any connection with the thalamus, then alpha waves are not generated. Stimulation of non-specific reticular nuclei that surround thalamus and stimulation of diffuse nuclei that are located inside the thalamus result in the generation of waves in the thalamocortical system with a frequency of 8–13 per second which is the natural frequency for alpha waves. That is why it is possible that alpha waves appear from the spontaneous negative feedback impulses in the diffuse thalamocortical system that also includes brain stem activating system. Delta waves include all the waves in EEG that have a frequency of less than 3–5 per second. They appear during very deep sleep, they also appear in the experimental animal studies where cortex has been separated from the thalamus with a subcortical section. Therefore, delta waves can appear in the cortex independent of the activities in the lower parts of the brain. Sleep spindles are produced by the thalamus. They appear as 12–15 Hz oscillations in between slow waves during NREM sleep in human EEGs. The production mechanism of these oscillations is related to the degree of hyperpolarization in thalamocortical cells. While shifting from wakefulness to sleep, the membrane potentials of thalamocortical cells are exposed to a progressive hyperpolarization, thus synaptic responsiveness decreases and sensory information transfer is prevented. When a sufficient level of hyperpolarization is achieved, we start seeing rhythmic bursting in nucleus reticularis neurons belonging to thalamus at a frequency interval which is in correlation with sleep spindle. Furthermore, slow wave oscillations due to membrane hyperpolarization also take place. It is accepted that sleep homeostasis is significantly affected by the size and characteristics of the sleep spindles that are formed [11, 12, 13, 14].
2.1.4 Polysomnogram and polysomnography
“Polysomnography” “PSG” is the recording of sleep via electrophysiological signals. Sleep recordings that appear on a sheet of paper or on a computer screen are called “Polysomnogram”. Throughout one night electrophysiological signals recorded during wakefulness and sleep are as follows: “Electroencephalogram (EEG), electromyogram (EMG; jaw, arm and leg), electrooculogram (EOG), electrocardiogram (ECG), snoring, oro-nasal air flow (L/s) (liter/second) chest and abdomen movements (respiratory effort recordings), O2 saturation, and body position and real time-video-image recordings”. “Penile tumescence, gastroesophageal reflux and blood pressure” are other electrophysiological signals that are recorded, despite not being performed for all patients. Polysomnography is the procedure where different physiological or pathophysiological parameters are recorded during sleep for six or more hours, evaluation of these by a medical doctor and generation of a report (Figure 1).
Polysomnography is performed for two main purposes: (1) Understanding physiological (normal) sleep and meanwhile demonstrating the changes that take place in the organism (for example heart rate changes can be analyzed) (2) Identification of abnormal events that take place during sleep; diagnosis of different sleep disturbances, guide in their treatments. PSG starts by explaining the procedure to the patient in great detail. The patient should understand that there would not be any pain involved with the procedure, that no medications would be used. The patients are informed that their natural sleep will be recorded through superficial electrodes to be placed on their bodies. The patients should be reminded that they would not be spending the night by themselves, and that a technician would be present to follow the process from a monitor. After the patient puts on his sleepwear, electrodes are placed for an overnight sleep test and calibration process is initiated. First, the calibration of PSG equipment is made. This is performed before the electrodes are placed. Afterwards the electrodes are calibrated. This is done after the electrodes are placed in the electrode box. Lastly, physiological calibration is performed. This calibration is performed via the electrodes that transmit physiological changes through EEG, EOG, and EMG, leg movements, chest and abdomen movements. The PSG records of electrophysiological signals features are as follows (Figure 2):
2.1.5 Recording and scoring of sleep
Scoring of sleep corresponds to staging of sleep. For the staging of sleep polysomnography recordings are separated into 30 second-long intervals (epoch); each epoch is scored with a sleep stage. Sleep stages are as follows: “Stage N1 (or NREM1), Stage N2 (or nREM2), Stage N3 (or NREM3), Stage R (REM), Stage W (wakefulness)”. Each 30 second interval needs to match with one of these stages. Three main electrophysiological signals are used when sleep stages are identified: “EEG, EMG, EOG”. There three parameters are evaluated for each epoch and one sleep stage is matched with each 30 second interval. There are certain rules to be respected when staging of sleep is performed:
2.1.6 Recording and scoring of breathing during sleep
American Academy of Sleep Medicine (AASM) has published the rules for scoring sleep, sleep associated events as well as respiratory events. Based on these rules, abnormal respiratory occurrences that are observed during sleep are “apnea, hypopnea, arousal associated with respiratory effort, hypoventilation and Cheyne-Stokes breathing”. Electrophysiological signal recordings that are required for interpreting respiratory problems in PSG are: “O2 saturation, nasal/oronasal air flow (nasal cannula, thermistor), thoracic, abdominal respiratory effort, EEG recordings (absolutely required to identify arousal), body position, tracheal microphone, ECG, leg EMG recordings”. To detect respiratory effort the following methods are used: (1)
2.2 Physiopathology and symptomatology in sleep medicine
2.2.1 Relationship of sleep with body systems and diseases
2.2.2 Basic signs in sleep disorders and pathophysiological causes (semiology, propedeutics, preliminary instruction, introduction to further study)
The first step in the evaluation of a patient with a sleep disorder is to identify the main symptom. A detailed history of the sleep and wakefulness cycle constitutes the second step. This is followed by the medical history of the patient, a list of previously used medications, family history, detailed information about school, work, family and social life and a physical exam of bodily systems. Relevant laboratory tests are performed for differential diagnosis. PSG establishes the definitive diagnosis. Despite developments in the field of sleep medicine, we see that neither the society nor the physicians are adequately informed about sleep and sleep disturbances. However, diseases associated with sleep are frequent in the population and can have significant consequences: they can negatively influence the individual’s “work or school success, social life, marriage and other relationships as well as leading to occupational and traffic accidents. Sleep disturbances can hinder the cognitive functions of an individual and can increase the risk of having psychiatric and other system related diseases. Sleep apnea syndrome has a role in the etiology of severe diseases namely hypertension, myocardial infarction, heart failure, stroke and diabetes. Sleep deprivation can result in an increase in the number of seizures in a patient with epilepsy. Complaints of patients with diseases of other systems can be related to sleep disorders: in a patient having a follow-up with a Holter recording for hypertension, the reason behind an increase in blood pressure during sleep can be sleep apnea syndrome. Frequent arousals during the night, chest pain, not being able to climb the stairs during the day, tiredness, complaints about sleepiness are evaluated as angina by cardiologists and angiograms are performed. However, a PSG to be performed on this patient can establish the correct diagnosis of central apnea syndrome. In a patient with goiter disease, during an overnight sleep test, it is possible to diagnose sinusal bradycardia. Likewise, patients having severe OSAS can have predominant depression symptoms and can therefore admit to psychiatry outpatient departments. Children admitting to pediatric neurology outpatient departments with sleep episodes are valuated multidimensionally and then treated for epilepsy. However, if these children were to undergo PSG and MSLT (multiple sleep latency test), correct diagnoses of underlying sleep apnea syndrome, central hypersomnia and narcolepsy could have been established.