Clinical aspects

Indications

The American Clinical Neurophysiology Society has established guidelines for conducting EEG in adults and children (www.acns.org/practice/guidelines). Guidelines for video EEG monitoring and continuous EEG monitoring for seizures in the intensive care unity are available. The American Board of Registration of Technologists in EEG and Evoked Potentials has devised standards for performing EEG (www.abret.org). The American Board of Clinical Neurophysiology and the American Board of Psychiatry and Neurology have set minimal competency examinations for physicians interpreting EEG. Clinical uses have been further detailed by the American Clinical Neurophysiology Society (ACNS), American Epilepsy Society (AES), and American Academy of Neurology (AAN) to detail the clinical usefulness of EEG in adult and pediatric populations.

EEG may be useful in the following clinical scenarios by leading to an alteration in management or prognosis.

Contraindications

The EEG alone should not be used to exclude a diagnosis of epilepsy or to support the presence of a structural lesion of the brain. MRI or CT brain neuroimaging are more reliable, especially for subcortical locations in the brain.

Generally, recording a standard scalp EEG is safe. It is a noninvasive test, and rarely, patients have reported allergy and reactions to the electrodes or paste/gel. Activating procedures may precipitate lightheadedness, tingling, and rarely, syncope during hyperventilation. There are no contraindications to EEG recording in pregnancy; however, activation procedures are sometimes avoided because of the small risk of inducing a complication such as seizure or inducing preterm labor during pregnancy with adverse influence on the developing fetus. Hyperventilation is breathing deeply at a rate of 18 to 24 breaths per minute for 2 to 3 minutes. Relative contraindications to hyperventilation include the following (46):

Intermittent photic stimulation is routinely performed during EEG. The patient is presented with a series of photic flashes delivered by a strobe light at a measured distance of 20 to 30 cm from the patient’s head. A series of stimulus trains of flashing light are presented for 4 to 10 seconds, with at least 4 seconds between each train successively up to 30 Hz. Intermittent photic stimulation should be performed at a separate time from hyperventilation. Significant ophthalmologic conditions, migraine, and recent surgeries are a relative contraindication. Neither a diagnosis of epilepsy nor a historical report of seizures is a contraindication to photic stimulation. However, persistent photic stimulation, when a photoparoxysmal response has been demonstrated, should be avoided. The photoparoxysmal response (formerly known as photoconvulsive response) occurs when photic stimulation produces bilaterally synchronous epileptiform discharges, which may outlast the stimulus by several seconds and even precipitate a seizure. Patients with genetic generalized epilepsy should be made aware of the possibility of a breakthrough seizure and the implications of reproducing a seizure.

Results

Interictal EEG. EEG features are divided into the following phases:

The utility of interictal EEG has been the foundation for evaluating patients with epilepsy (51; 76). It is rare to capture a seizure during a routine outpatient EEG in adults; however, interictal epileptiform discharges are very specific and are highly correlated with epilepsy in the proper clinical setting, though they are not diagnostic for epilepsy (44).

The prevalence of interictal epileptiform discharges depends in part on the age of the subject and the presence of intracranial disease. It has been reported that 29% to 55% of adults with epilepsy will show one or more interictal epileptiform discharge on a single EEG (97; 56; 57). With repeated testing, including sleep recording, an interictal epileptiform discharge is seen in the EEG of 59% to 92% of epilepsy patients with the fourth recording, but there is minimal additional yield thereafter (97; 56; 10).

The sensitivity of EEG to detect interictal epileptiform discharges varies considerably depending on seizure frequency, epilepsy syndrome, and the site of seizure onset. Diagnostic yield of the EEG can be increased by sleep deprivation, recording sleep, serial studies, and early post-seizure recording.

Interictal epileptiform discharges can infrequently be found in asymptomatic and healthy individuals. The sample sizes of asymptomatic adults with interictal epileptiform discharges who have follow-up data are small, but it appears that less than 3% go on to have seizures (97; 27; 60). One study of 13,658 adult males aged 17 to 25 without a previous history of significant illness who were medically screened for training in the Royal Air Force of England yielded 69 (0.5%) military personnel with unequivocal interictal epileptiform discharges (27).

Common types of interictal epileptiform discharges seen in asymptomatic individuals include centrotemporal spikes, occipital spikes, and a self-limited photoparoxysmal response (14; 27).

About 2% to 3% of asymptomatic school-age children have centrotemporal spikes, but only a small fraction of these, possibly as low as 10%, will develop rolandic seizures (14). The presence of interictal epileptiform discharges in the EEG of asymptomatic individuals is associated with an increased likelihood of developing epilepsy. In patients with a pathological condition of the brain, the incidence of interictal epileptiform discharges is increased. Patients with interictal epileptiform discharges and congenital brain malformations, brain tumors, prior craniotomy, and intellectual disability are at high risk for subsequently manifesting clinical seizures (97). Some medications may also cause interictal epileptiform discharges. In a series of 3,143 nonepileptic psychiatric patients, interictal epileptiform discharges were found in 3.0% to 3.8% of patients taking major tranquillizers, antidepressants, or lithium compared with 0.8% of patients taking benzodiazepines (60).

Ictal EEG. The ictal EEG reflects an electrographic pattern that is characteristic of patients with epilepsy. It is identified by recurrent epileptiform activity that begins abruptly and continues to evolve in frequency and spatial distribution following a paroxysmal occurrence. The onset and termination are usually abrupt, with changes that take place over seconds to a couple of minutes. Seizures that occur for more than 5 minutes are “prolonged” and are commonly associated with status epilepticus.

The ictal EEG is generally composed of a rhythmic pattern that increases and decreases in frequency. Temporal evolution occurs, and the ictal activity displays increasing amplitude and often crescendo-decrescendo (focal) or decrescendo (generalized) changes in frequency. There is also spatial evolution that occurs due to seizure propagation as new regions of the brain become involved and a broad field of spread becomes evident. The morphologic characteristics of the ictal EEG can vary by the seizure type. For example, frontal lobe seizures may be marked by a nonlocalized diffuse attenuation or generalized theta/delta but may also occur with lateralized, low-voltage, ictal fast activity. The site of seizure onset and the frequency and topographic distribution of the ictal EEG is usually a better marker. In temporal lobe epilepsy, mesial temporal lobe epilepsy is characterized by a rhythmic theta frequency (5 to 9 Hz), whereas in lateral temporal lobe epilepsy a rhythmic delta frequency (lower than 4 Hz) at seizure onset often predominates. In genetic generalized epilepsy, generalized interictal epileptiform discharges may increase, become repetitive, and evolve into bilateral, faster (alpha/beta) frequencies that are bilaterally synchronous and symmetrical, unlike the lateralized interictal epileptiform discharges of localization-related (focal) epilepsy. The characteristics of a focal "ictal" pattern in focal seizures consist of:

Irrefutable evidence for epilepsy is present when a seizure occurs and is simultaneously associated with an ictal discharge in the EEG. Detection of seizures without awareness is not an uncommon finding during video epilepsy monitoring (38). EEG may also serve to quantify subtle focal seizures without self-awareness and subclinical seizures. However, one must exercise caution when stereotyped events that are consistent with clinical seizures do not demonstrate an ictal pattern on EEG, particularly focal aware seizures/auras (69).

EEG mimics. Approximately 30% of patients admitted to epilepsy monitoring units (representing over 250,000 people in the United States) are misdiagnosed with epilepsy (05). The clinical impact of EEG is supported by the large number of patients with recurrent “spells” that are misdiagnosed as epilepsy. The misinterpretation of normal electrophysiological activity and artifact is not uncommon and can lead to misdiagnosis and mismanagement (07). The diagnostic significance of the EEG depends on the clinical context and the nature of the EEG abnormality. Learning the common traps and pitfalls to misinterpretation of the EEG, such as variations of normal, benign variants, and common artifacts, is essential to avoid gaps in diagnosis and treatment (74).

Normal variations in EEG. Normal background rhythms and their variations may provide fluctuation and an “apiculate” morphology (ie, alpha rhythm), mimicking pathological interictal epileptiform discharges, and leading to misinterpretation of the EEG (81).

Normal waveforms that may be confused with interictal epileptiform discharges include:

In one series of patients undergoing video EEG monitoring for newly diagnosed psychogenic nonepileptic attacks, up to 32% had epileptiform “abnormalities” identified on a previous EEG report, but on review by a board-certified electroencephalographer, these were found to reflect normal fluctuation of the background instead (07). A breach rhythm occurs on the EEG due to the presence of a skull defect. At the site where the EEG is “breached,” higher amplitudes and faster frequencies make the rhythms appear “spiky,” potentially leading to misinterpretation due to the inherent qualitative visual analysis used during standard interpretation of the EEG. Sleep may enhance normal physiological waveforms and give a spiky appearance to mimic interictal epileptiform discharges in asymptomatic subjects (09). Another common source of confusion is the mu rhythm. This is a centrally located arciform alpha frequency (8 to 10 Hz) that can appear abnormal due to the spiky appearance. However, these bursts are reactive and can be attenuated with contralateral extremity movement. Lambda waves are electropositive “sharp waves” located in the occipital region and are usually bilateral and evoked when visually scanning a picture.

Benign variants. The principal importance of benign variants lies with the ability to mimic interictal epileptiform discharges (74). Distinguishing benign EEG variants of unknown significance from a true interictal epileptiform discharge can be challenging. The high prevalence of temporal lobe epilepsy in patients with localization-related epilepsy coupled with the predisposition for benign variants to occupy the temporal lobe can lead to a bias with a propensity to “overall-call” and misidentify normal waveforms as interictal epileptiform discharges (74). Common benign variants include the following:

These benign variants are often susceptible to overinterpretation, leading to misdiagnosis and erroneous diagnosis of epilepsy (02; 07; 33).

Perhaps the most challenging of these are wicket spikes (71). These are bursts or trains of sharply contoured, monophasic, arciform waveforms that appear in the temporal regions during drowsiness. They phase-reverse in the mid-temporal derivations but do not have an after-going slow wave nor do they distort the background activity. They occur within the 6- to 11-Hz band often obtaining amplitudes of up to 200 µV in the temporal regions during drowsiness and light sleep. When they appear in isolation, they occur as a single, high-amplitude waveform that can be mistaken for an interictal epileptiform discharge. Rarely noted benign waveforms (eg, “third rhythm”) may surface using invasive EEG to underscore the uniqueness of EEG depending on the conditions of the recording.

Artifact. Potentials without a cortically generated electrophysiological field reflect an artifact of extracerebral origin (80). Artifacts are present in virtually every EEG recording. Artifacts from over-filtering, electrode pops, and myogenic discharges may beguile the interpreter to misidentify the artifact as a pathological waveform. Artifacts may be generated from a wide variety of sources. However, artifacts are also an essential part of the record to identify levels of wakefulness and sleep.

Some artifacts may lure the interpreter into misidentifying waveforms that falsely mimic epileptiform discharges. The EEG can be misinterpreted as abnormal and subsequently incorrectly viewed as pathological interictal epileptiform discharges (73). During nonepileptic convulsions, movement artifacts may impair the ability to observe the underlying cerebral activity.

A properly trained technologist is invaluable to ensure that a “contaminated” record does not occur. The responsibility of the technologist during the recording is to prove whether a waveform is artifact or not and to identify or eliminate it from the recording (83). The American Board of Registration for EEG Technologists and Evoked Potentials has examinations to certify competency for performing EEG.

Computer-based algorithms exist for epileptiform discharge detection, though none are perfect. Frequent false positive detections occur during detection and can limit practical use of spike (and seizure) detection during extended EEG recording to facilitate accurate EEG interpretation. Essential criteria are available to EEG interpreters to help proper identification of epileptiform activity and provide value in differentiating between pathological interictal epileptiform discharges and similar nonepileptiform transients (45; 37). Newer algorithms using a novel automated source space method to identify interictal epileptiform discharges found a high specificity (greater than 95%) and sensitivity (81% to 85%) for identification of epileptiform discharges based on 100 consecutive patients receiving a definitive diagnosis following video-EEG monitoring (37).

EEG and video. At present, most proprietary EEG recording systems have the capability of video recording in addition to standard EEG recording. EEG coupled with video provides a greater diagnostic yield and the added benefit of visualization of events for more accurate classification (13; 89). When compared, video alone versus EEG alone had similar sensitivities (93% vs. 89%, respectively) and specificities (both 94%) (15). Short-term EEG with video recording has been used to differentiate a seizure from a nonseizure event (06). The International Federation of Clinical Neurophysiology guidelines recommend that video-EEG monitoring is a useful tool in establishing diagnosis of epilepsy and can aid in surgical evaluation (88; 84).

Diagnosis and EEG. The initial EEG recorded in patients with epilepsy is “positive” in only 29% to 55% of patients; this increases to 80% to 90% with repeated recordings (51). Long-term EEG monitoring increases the yield of detecting epileptiform discharges in evaluating patients with concern for epilepsy (53; 77). Interictal EEG helps to classify whether seizures have a focal or generalized mechanism in addition to helping to define the specific epilepsy syndrome. Generalized interictal epileptiform discharges that are bilaterally synchronous and symmetrical are associated with generalized epilepsies. Focal or lateralized discharges are associated with those that are localization-related epilepsies.

The International Federation of Clinical Neurophysiology (IFCN) has established evidence-based guidelines for clinical utility of EEG in diagnosing and monitoring epilepsy in adults. The following are the guidelines (84):

Focal epilepsy. Focal epilepsy is location specific and represents the condition of recurrent seizures that originate within networks confined to one hemisphere of the brain. The most common site for focal interictal epileptiform discharges is the temporal lobe. The finding of persistent epileptiform discharges on a standard EEG provides supportive evidence of a focal epilepsy syndrome. Ictal scalp EEG is a standard neurophysiological technique used to localize seizure onset during presurgical evaluation of patients with drug-resistant focal epilepsies. Scalp EEG and matched stereo-EEG recordings in 75 patients (greater than 3000 seizures) found a localized scalp ictal EEG, independent of location, predicted a favorable outcome after surgery (70).

Adult focal epilepsy syndromes

Temporal lobe epilepsy. Temporal lobe epilepsy represents a group of syndromes arising from different areas within the temporal lobe. The most common syndromes are mesial temporal lobe epilepsy and neocortical or lateral temporal lobe epilepsy.

Frontal lobe epilepsy. Frontal lobe epilepsy is the second most common site of epileptic seizures and may present as a diagnostic challenge. The semiology can be bizarre and mistaken for psychogenic attacks or other neurologic events (eg, parasomnias). Focal seizures of frontal lobe epilepsy are generally associated with cephalic or somatosensory auras, head or eye version, vocalization, and complex or hypermotor activity with a minimal postictal state. They are brief in duration and activated by sleep or arousal from sleep.

Parietal-occipital lobe epilepsy. The semiology of seizures that begin in the posterior quadrant of the brain involving the parietal lobe epilepsy is variable. Like frontal lobe epilepsy, the seizures may appear bizarre and manifest falsely lateralizing semiology or EEG epileptiform activity. Sensory symptoms may be contralateral or bilateral and predominate when present. Visual auras accompany occipital lobe epilepsy with greater specificity than parietal lobe epilepsy, though both positive (phosphenes) and negative (ictal blindness) may occur. Symptoms are mainly visual hallucinations contralateral to the occipital focus.

Autosomal dominant partial epilepsy with auditory features. Occurring in early adulthood, this is an autosomal dominantly inherited, non-ion channel epilepsy with a missense gene mutation in the leucine-rich, glioma-inactivated 1 (LGI-1) area on chromosome 10q22-24. Focal seizures are typically responsive to antiseizure drugs. Simple auditory hallucinations are the hallmark of autosomal dominant partial epilepsy, though other visual, autonomic, psychic, and olfactory auras can also be encountered.

Autosomal dominant nocturnal frontal lobe epilepsy. This is an uncommon form of familial nonlesional focal epilepsy characterized by hypermotor seizures arising from the frontal lobe, typically during sleep. Although the age range for first seizures is between 1 and 30 years old, the mean age is about 12 years old, during the early adolescent period. The first gene identified was a missense mutation in the alpha 4 subunit of the neuronal nicotinic acetylcholine receptor (CHRNA4) on chromosome 20 (20q13.2-13.3), through others have also been described. The seizures are brief, often complex, and usually occur in clusters during non-REM sleep; this can lead to misinterpretation as a parasomnia. Seizures may lead to simple arousals, wandering behavior, or more intense hypermotor movements involving bimanual-bipedal automatism with kicking, bicycling, flailing, or flinging movements. Vocalizations of moaning, crying, or gasping may also occur, simulating nocturnal panic attacks.

Generalized epilepsy. Generalized seizures encompass seizures and interictal epileptiform discharges that arise from networks originating in both cerebral hemispheres simultaneously. Most generalized interictal epileptiform discharges are bilaterally distributed and are maximal in the anterior derivations of the EEG. The prototypic interictal feature in the EEG of patients with generalized epilepsies is the generalized spike-and-slow wave discharge. Some interictal EEG findings may be suggestive of a particular epilepsy syndrome (ie, childhood absence epilepsy with 3 Hz generalized spike-and-waves), though none are 100% specific (58).

The morphologic characteristics of the generalized interictal epileptiform discharges have little correlation with a single type of seizure. The presence of generalized spike-and-waves and generalized polyspike-and-wave discharges may be associated with absence, myoclonus, or generalized tonic-clonic seizures without specificity. Lateralized interictal epileptiform discharges (and semiologies) are commonly seen in many patients with the genetic generalized epilepsies. This can create confusion for the EEG interpreter regarding selection of the correct classification. Confusion exists primarily between genetic generalized epilepsy and frontal lobe epilepsy when frontal or parasagittal interictal epileptiform discharges are encountered. In addition, the semiologies may both appear as a generalized motor seizure (34). Likewise, seizure onset during the adult years following adolescence (usually seen in localization-related epilepsy) may occur in some patients with genetic generalized epilepsy. Often focal motor signs and focal interictal EEG findings are seen in patients with generalized epilepsy, which can be misconstrued as a focal syndrome. Correlation of EEG with video and semiology may help clarify such cases (22). The EEG, therefore, becomes very important in classifying abnormalities for a correct syndromic diagnosis in epilepsy.

Genetic generalized epilepsy. Genetic generalized epilepsy consists of several syndromes diagnosed and classified on the basis of clinical features and EEG abnormalities. The hallmark of genetic generalized epilepsy seen on interictal EEG may be either or both generalized spike-and-wave or generalized polyspike-and-wave at greater than 2.5 Hz, arising from a normal background.

The classic features of generalized spike-and-wave and generalized polyspike-and-wave are synchronous bilateral paroxysmal regular generalized discharges that characteristically have a “typical” (3 Hz) or “fast” (> 3 Hz) interspike burst frequency. Voltage asymmetries between the hemispheres or any regional (anterior, posterior, or lateral, lateralized or not) lead-in are not uncommon. Though there are several typical EEG features of genetic generalized epilepsy, the presence of atypical features (in particular, focal changes) should be kept in mind to avoid mistaking genetic generalized epilepsy for a focal epilepsy. The use of activation techniques, such as sleep deprivation, intermittent photic stimulation, and hyperventilation, during EEG recording can help increase the diagnostic yield.

During non-REM sleep, generalized spike-and-waves tend to increase in frequency and may acquire a polyspike component. Bursts may become shorter, incomplete, or fragmented and tend to lateralize during light sleep. Occasionally, focal spikes may appear independently but are often in the frontal region. Normally, the interictal epileptiform discharges are inhibited during REM sleep. The generalized spike-and-wave or generalized polyspike-and-wave discharges may be subclinical or occur in association with measurable behavioral change, such as impaired response or cognition. They may also affect motor and autonomic manifestations. Most genetic generalized epilepsy is responsive to antiepileptic drugs. The syndromes of juvenile myoclonic epilepsy, juvenile absence epilepsy, and generalized tonic-conic seizures alone that occur on awakening (GTCS-A) typically require long-term antiseizure drug treatment.

Adult generalized epilepsy syndromes

Juvenile myoclonic epilepsy. Juvenile myoclonic epilepsy is the most common genetic generalized epilepsy, representing about 10% of all epilepsies with onset in adolescence (90). Myoclonic seizures are the hallmark of this syndrome, which is associated with generalized tonic-clonic seizures in more than 90% of patients.

Juvenile absence epilepsy. Juvenile absence epilepsy is responsible for 8% to 10% of all genetic generalized epilepsy. Juvenile absence epilepsy typically begins in early adolescence, between the ages of 9 and 13 years (range 5 to 20 years) (86). The majority of patients begin with recurrent absence seizures.

Epilepsy with generalized tonic-clonic seizures alone. The syndrome of epilepsy with generalized tonic-clonic seizures alone (eg, grand mal seizures on awakening and epilepsy with generalized tonic-clonic seizures on awakening (GTCS-A)) was first described by Dr. Dieter Janz. This form of genetic generalized epilepsy may be challenging to distinguish from epilepsy with sporadic generalized tonic-clonic seizures. The age of onset is typically about 16 years (range 6 to 28 years), with frequency estimates accounting for 20% to 30% of genetic generalized epilepsy. GTCS-A is characterized by generalized tonic-clonic seizures occurring within 1 to 2 hours of awakening from sleep without myoclonic or absence seizures.

Developmental and epileptic encephalopathies. In patients with seizures associated with severe epilepsies and encephalopathy, markedly abnormal background activity is present. It may be difficult to identify a superimposed acute encephalopathy and nonconvulsive status epilepticus when limitations in cognition or speech exist at baseline, even with the benefit of previously recorded EEGs (04). Epileptic encephalopathy is used to describe pediatric epilepsy syndromes and implies that interictal epileptiform discharges seen on EEG contribute to the patient’s encephalopathy and cognitive dysfunction.

Lennox-Gastaut syndrome. Lennox-Gastaut syndrome is a severe epileptic encephalopathy that is often acquired during development. Lennox-Gastaut syndrome is associated with a high rate of morbidity and mortality (04). Lennox Gastaut syndrome is composed of a triad of intellectual disability, mixed seizure types, and an EEG demonstrating slow spike-and-waves. Drop attacks composed of tonic and atonic seizures are the most debilitating seizures, predisposing patients to recurrent injury. Lennox-Gastaut syndrome usually occurs de novo but may also evolve from other severe infantile epilepsies in 30% of cases; most notably, West syndrome with epileptic spasms (04). Treatment with antiseizure medication is usually ineffective, and neuromodulation, ketogenic diet, or disconnection surgery often become management considerations.

Other special syndromes. Epilepsy with myoclonic absences is a rare subtype of genetic generalized epilepsy with onset in late childhood, but it may occur in adolescence and persist into adulthood, mimicking juvenile absence epilepsy. Myoclonic absences are seizures that occur with tonic stiffening of the arms with repetitive myoclonic jerks that involve the arms and legs. Most patients also have generalized tonic-clonic seizures. The interictal EEG typically has a normal background with 3-Hz generalized spike-and-wave and generalized polyspike-and-wave discharges during myoclonic-absence seizures.

EEG in epilepsy management

When primary care physicians were surveyed regarding neurologic reasons for electronic consulting, seizures were found to be 1 of the top 5 reasons to obtain an e-consult with a neurologist, with diagnostic tests including EEG as one of the main reasons to request reevaluation (11). This has been true for both medical and surgical patients undergoing EEG evaluation.

Medical treatment. The decision to start antiseizure drugs is challenging after the first unprovoked seizure. Approximately 21% to 45% of patients with a first unprovoked seizure will experience a recurrence in the following 2 years (35). The risk of seizure recurrence compared to the general population is doubled when interictal epileptiform discharges were present in the EEG (84), and treatment is usually warranted. It is important to remember that some interictal epileptiform discharges may be present without seizures and may not need treatment independent of clinical events. The conditions below may yield interictal epileptiform discharges without manifesting seizures:

In the case of genetic generalized epilepsy with generalized spike-and-waves on EEG, prolonged recordings may be warranted to quantify the frequency of absences intermittently during treatment to determine the efficacy of therapy. When selecting an antiseizure drug, the characteristics of the interictal epileptiform discharges help to classify the seizure type and syndromes. The importance of classification resides in the potential for inefficacy or aggravation of seizure frequency. Some drugs, such as valproate and ethosuximide, may suppress generalized spike-and-waves and reflect the effectiveness of therapy (19). Lamotrigine may reduce photosensitivity. Benzodiazepines and barbiturates may acutely reduce interictal epileptiform discharges. Most antiseizure drugs used for focal epilepsy do not substantially alter the frequency. Many of the newer antiseizure drugs remain to be evaluated (75); this may be important when considering valproate taper in genetic generalized epilepsy after achieving seizure freedom. The finding of interictal epileptiform discharges prior to discontinuation of antiseizure drugs increases the risk of relapse in many studies (03; 95).

Nonmedical treatment. Between 30% and 40% of patients with focal epilepsy are resistant to antiseizure drugs (21). Epilepsy surgery candidates include those who are drug-resistant, those disabled by seizures, those who are healthy and motivated to undergo surgery, and those who have a localized and surgically accessible lesion. Ictal EEG recordings are often obtained in an epilepsy-monitoring unit during video-EEG monitoring designed to characterize the electroclinical features of the focal seizures for localization of the epileptogenic zone prior to neurosurgical resection or ablation.

The presurgical evaluation includes an initial comprehensive noninvasive assessment with video-EEG interictal and ictal recordings, providing the foundation for concordance between neuropsychometric testing, radiologic evaluations (eg, MRI, PET, SPECT), and Wada testing. Wada testing occurs in a conscious patient in which one hemisphere of the brain is independently anesthetized by intracarotid administration of a barbiturate drug to examine language and memory lateralization. EEG is used during the procedure to ensure appropriate cerebral hemianesthesia.

When comprehensive, noninvasive evaluation shows discordant information, magnetoencephalography brain mapping recording magnetic fields produced by electrical currents occurring in the brain may provide information on tangential dipolar sources not readily identified by EEG. Intracranial EEG is considered when a noninvasive evaluation fails to identify a solitary seizure-onset zone (61; 79). Invasive recordings may be necessary using subdural strips, grids, or intracortical electrodes alone or in combination when nonlocalized or discordant information is obtained from the noninvasive evaluation. Stereoelectroencephalography is becoming a mainstay for invasive EEG evaluation in the United States using multiple (12 to 15) intracortical (stereo-EEG) electrodes for better 3-dimensional spatial-temporal resolution.

When epilepsy surgery is not possible, neuromodulation and low glycemic dietary management is also considered. Three forms of neurostimulation are now approved for clinical use by the U.S. Food and Drug Administration: vagus nerve stimulation, responsive neurostimulation targeting deep or superficial neocortical generators, and deep brain stimulation targeting the anterior nucleus of the thalamus. The responsive neurostimulator is unique in that it is based on the electrocorticographic recording seizures during chronic invasive ambulatory EEG, providing a preprogrammed set of stimulation parameters in response to a detection.

Critical care EEG and status epilepticus

EEG monitoring is an important diagnostic tool with specific indications in the critically ill patient and unique terminology for describing abnormal patterns (31). Seizures are a common occurrence in patients with neurologic impairments admitted to an intensive care unit. Innovation in technology now allows continuous digital EEG monitoring of multiple critically ill patients simultaneously. With greater use of EEG in the intensive care unit, our experience with “sicker” brains is advancing rapidly (43; 16). The use of cEEG monitoring has been useful to enhance the sensitivity of clinical seizure detection and guide management of nonconvulsive seizures, including nonconvulsive status epilepticus (66). In addition, cEEG can provide dynamic information about cerebral function, such as brain ischemia, to allow early detection of changes in the neurologic status independent of seizures. This is especially useful when the clinical examination is limited, such as during stupor or coma.

Paroxysmal and periodic patterns are common occurrences in the neurocritical care setting using cEEG. These patterns encompass a spectrum of interictal and ictal rhythms that lie on a continuum relative to interictal and ictal EEG. Though the current knowledge of their precise specificity relative to outcome is imperfect, several studies have indicated that periodic discharges have predictive value in subclinical seizures, clinical seizures, and nonconvulsive status epilepticus (24; 48; 54; 66; 84). Unexplained persistent altered cognition in patients with epilepsy can result from drug intoxication or frequent unrecognized seizures.

Undoubtedly, the most significant impact of the EEG in seizure disorders rests in the diagnosis of nonconvulsive status epilepticus (29). In this condition, the EEG is the sole instrument of diagnosis. Emergent EEG or stat EEG is performed to rule out nonconvulsive status and seizures and guide management (42; 26). Continuous EEG is also used to guide management. When nonconvulsive seizures or status epilepticus occurs, pharmacological coma inducing a suppression-burst pattern with anesthetic drugs may be required when seizures are refractory to therapy. Furthermore, the EEG may help in predicting a higher likelihood of a potentially poor prognosis (47).

Stimulus-induced rhythmic, periodic, or ictal discharges (SIRPIDs) were recognized less than 15 years ago (30). This new waveform may provide additional prognostic information and may be repeated to status epilepticus when encountered, though the relationship remains to be further elucidated (01). Greater specificity of certain waveforms, such as the periodic discharges in epilepsy and other neurologic conditions such as dementia and herpes encephalitis, amplifies the need for continued research with EEG. Greater specificity of certain waveforms, such as the periodic discharges and rhythmic slow wave patterns, amplifies the need for continued research with EEG, with clinical management algorithms being developed using these EEG features (66). The impact of the EEG in these situations cannot be overstated.

The greatest limitation to EEG in the intensive care unit is the subjective interpretation with suboptimal inter-rater reliability. Quantitative EEG can be used to review large amounts of information generated by cEEG monitoring. Quantitative EEG is able to analyze long-term trends, allowing a more effective visual analysis that may clarify slowly evolving patterns, such as seizures encountered on cEEG that may be subtle (76).

Quantitative EEG applies the Fourier transformation to identify objective measure of waveform frequency, power, amplitude, asymmetry, and degree of rhythmicity generating numerical values, ratios, or percentages. These are monitored and graphically displayed over long periods of time in a series of trends. Alerting signal may be sent to staff and physicians wirelessly to provide continuous information of the patient’s condition. Their utility in seizure detection is seen regardless of level of training with a sensitivity of at least 80% (68).

Adverse effects

There are no anticipated adverse effects when patients undergo a standard scalp EEG. Patients may be uncomfortable during the procedure with the limitations imposed by sustained positioning, provocation techniques, and the time involved performing the study. Rarely, skin irritation from the disc electrodes may be evident following the procedure. This is usually noticeable within the first few days and clears without intervention. Prolonged monitoring may lead to frank skin breakdown at the electrode site. When skin breakdown is severe, ensuring adequate wound care is required, but rarely is a topical antibiotic necessary.

In general, hyperventilation is safe but carries a small risk of inducing potentially adverse effects including seizures or cardiac, respiratory, and cerebrovascular problems. Adverse effects from hyperventilation are expected to be seen in fewer than 3% of patients. Ischemic stroke is a concern in patients with severe cerebrovascular disease and recent stroke (within 3 months) given the risk of hyperventilation-induced vasoconstriction from hypocarbia. Because activating procedures may induce a seizure, patients must provide informed consent prior to performance. In the unlikely event that a seizure occurs, routine seizure management and precautions are instituted.

Invasive electrodes used during intracranial EEG performed as part of a presurgical evaluation carry a risk. In general, for strip electrodes the morbidity is low; infection occurs in 1% of patients. Bleeding is more likely with depth electrodes and stereo-EEG and with larger subdural grids. A greater number of electrodes, longer recording sessions, and more than 1 cable exit site carry a higher risk that has improved over the years to about 10%. Overall, any complication either immediate or delayed from invasive procedures employing intracranial EEG is low but center-dependent. Therefore, invasive EEG is best handled by a level 4 center (National Association of Epilepsy Centers) with 24-hour neurosurgical support and an on-site intensive care unit in case complications arise.

Special considerations

Special considerations should be observed when performing EEG in certain groups of patients. Pregnant females may require an EEG, and although there is no contraindication to undergoing an EEG, activating procedures should be avoided due to the potential ramifications of an activated seizure on the fetus. Hyperventilation should also be avoided in patients with severe or recent coronary artery and cerebrovascular disease as well as in patients with severe pulmonary disease due to the potential for hyperventilation-induced hypocarbia, leading to vasoconstriction or bronchospasm. Similarly, patients with sickle cell anemia, moyamoya disease, large vessel stenosis supplying the brain, and vasospasm should not undergo hyperventilation procedures given the risk of accentuating ischemia to the point of producing a stroke.

EEG lead placement can change in patients with open traumatic head injuries or craniotomy, and the location should be noted if altered from the 10-20 or 10-10 international system of electrode placement.

Children may have a particularly difficult time tolerating the procedure. Those with an intellectual or neurodevelopmental disability may have any combination of language or communication limitations, high levels of anxiety, or behavioral disorders or may manifest sensory hypersensitivities that create barriers and challenges that make it difficult for even the most seasoned technologist to complete a successful EEG. It is essential to provide a soothing and calming influence to comfort a distressed child. Modifications might be made during activating procedures to accommodate the child, including blowing a pinwheel to induce hyperventilation. Photic stimulation is useful in the pediatric population due to potential for provoking generalized spike-and-waves in the form of a photoparoxysmal response that is important not only for diagnosis but also for treatment.

The procedural technique in patients with suspected (or diagnosed) psychogenic nonepileptic attacks should be a standard scalp EEG recording. Care in documenting any events as typical of the outpatient habitual event is important. Video recording is available on most modern proprietary EEG machines and should be used. Activating procedures should be performed unless otherwise contraindicated as they have proven useful for reproducing nonepileptic events in some patients.

Once nonconvulsive seizures or nonconvulsive status epilepticus has been diagnosed, prolonged EEG monitoring is required. Similarly, generalized or lateralized periodic discharges identified on scalp EEG are special considerations for requiring cEEG. In addition to the prognostic value, the benefits of cEEG include both diagnosis and quantification of nonconvulsive seizures, avoidance of over- and undertreatment of status, and maintenance of suppression-burst on EEG in refractory and super-refractory status.

EEG recording parameters are modified when evaluating brain death. A full set of scalp electrodes are used (except in areas superficial to recent cranial surgery or trauma), and impedance is adjusted to 100 to 10,000 Ohms; the integrity of each electrode is tested, interelectrode distance should be at least 10cm, sensitivity must be increased to at least 2uV/mm, and the test should proceed for at least 30 minutes without blood pressure, temperature, and sedation issues that could interfere with recording (64).

Clinical vignette

Case history. A 26-year-old man from Kuwait was in good health until he sustained a “grand mal” seizure at 20 years of age. No early risk factors for epilepsy were present. His general and neurologic examinations were normal. An MRI of the brain demonstrated a right temporal lesion consistent with a meningioma. An initial standard scalp EEG was normal, but a repeat sleep-deprived EEG demonstrated intermittent right regional temporal delta slowing. He was treated with phenytoin 400 mg daily though adverse effects led to variable compliance and poor control of convulsions. A trial of carbamazepine led to improved compliance, but seizures continued every other month. Lamotrigine was added to carbamazepine, which led to improvement of convulsions though resulted in adverse effects including dizziness and “tics.” He was subsequently referred for epilepsy surgery and was admitted to the epilepsy monitoring unit for video-EEG monitoring to characterize his seizures as part of a presurgical evaluation. A single seizure was captured following a series of stronger “tics” after antiseizure drug taper.

Conclusion. The interictal EEG demonstrates 4 Hz generalized spike-and-wave and generalized polyspike-and-wave. On video review, there were several myoclonic jerks prior to the convulsion. He was diagnosed with juvenile myoclonic epilepsy on the basis of his interictal and ictal video-EEG monitoring and subsequently began valproate.

Discussion. This case illustrates several important points. First, it illustrates the importance of the EEG in evaluating patients with drug-resistant epilepsy. Next, it demonstrates the intermittency of findings that in this person were two-fold because both focal slowing and generalized spike-and-wave and generalized polyspike-and-wave were present. Additionally, it underscores the importance of the EEG in selecting antiepileptic drugs, which in this case aggravated the symptoms. And lastly, despite the power of recovering a structural lesion in predicting the localization and response to epilepsy surgery, ictal recordings with EEG are important in confirming the mechanism and localization prior to surgery. After he was given a definitive diagnosis of juvenile myoclonic epilepsy as his epilepsy syndrome, he was informed that he was not a candidate for epilepsy surgery. He was followed up by neurosurgery, who recommended conservative management of the lesion. He ultimately became seizure-free on carbamazepine and valproate and was later simplified to valproate monotherapy. Serial brain MRIs at 1-year interviews remained stable.

Scientific basis

Electrical signals are transmitted down a nerve through depolarization of the neuronal axon. When depolarization occurs at the nerve terminus, a synaptic potential occurs, depolarizing the adjacent nerve dendrite. Excitatory and inhibitory postsynaptic potential are summed and are responsible for EEG waveforms (76). When electroactive volumes are large enough (at least 10 cm2), interictal epileptiform discharges can appear on scalp EEG. Electroactive generators have both positive and negative poles, creating a dipole (49). The EEG essentially shows continuous changing voltage fields over different geographic areas across time.

The essential components of an EEG include electrodes, amplifiers, a computer control module, and a display device. Electrocardiogram leads, eye movement monitors, electromyogram, and respiratory monitors are frequently used polygraphic leads that are used in conjunction with EEG commonly during sleep studies. Electrodes are placed on the scalp using the standard international 10-20 system of electrode placement. More detailed coverage of the scalp when performing EEG includes the 10-10 system, which modifies the original 10-20 system and implements a newer alphanumeric nomenclature. More closely spaced scalp electrodes (eg, high-density EEG) have an even higher yield (39). At least 21 electrodes are recommended for a clinical study.

The A-P (anterior-posterior) longitudinal bipolar montage is most commonly used as a screening montage and identifies maximal electronegativity based on the presence of “phase reversals,” whereas a reference montage identifies it by the highest amplitude or voltage. A minimum of 3 montages are utilized during an EEG recording using referential and bipolar recordings according to the American Clinical Neurophysiology Society (62).

The input provided by the EEG technologists is critical at the time of EEG recording. An electrolytic paste is placed between the electrode and the skin and is held in place by adhesive (Collodion), suction, or a cap that conducts the electrical potentials to the amplifiers. Minimal technical requirements for performing EEG have been developed (62). The most common recording setting includes sensitivity (adult = 5 to 15 µV/mm, child = 10 to 20 µV/mm, infant = 15 to 30 µV/mm); standard filter settings of 1 Hz to 70 Hz (notched filter used with 60 Hz artifact) and a time base of 30 mm/second.

Montages follow a common system where left over right derivations are displayed. The ability to integrate software applications (eg, spike and seizure detection algorithms) and obtain quantitative EEG (compressed spectral arrays) with multimodal trending has extended this capability to the critically ill population (67). Computer-assisted source modeling of dipolar and distributed EEG sources has been helpful for identification of abnormalities in parallel with greater computational ability seen with digital system technology (52).

The utility of EEG in clinical practice relies on an accurate interpretation of the recording. Oftentimes, the interpreter is not the treating clinician, and, therefore, optimal reporting is essential to translate the results of the EEG into clinical management of the patient. The moderate interobserver reliability of EEG interpretation may be partly explained by the different reporting styles utilized, and there is significant variability in the observation of guidelines for EEG reporting that couples the science of electrophysiology with clinical practice (08).