Pearls, Perils, and Pitfalls In the Use of the Electroencephalogram

Omkar N. Markand, MD, FRCPC

Disclosures

Semin Neurol. 2003;23(1) 

In This Article

EEG in Patients with Altered Mental Status or Diffuse Encephalopathies

The term encephalopathy is usually applied to patients displaying altered mental status as a result of a diffuse disturbance of brain function. Common encephalopathies are divided into metabolic, toxic, inflammatory (encephalitis), anoxic, and degenerative types. The EEG in most encephalopathies shows an alteration of background activities and emergence of varying degrees of theta-delta slowing. Remember that the EEG findings are generally nonspecific from a differential standpoint. The EEG is unable to distinguish between different etiologies. The main contribution of the EEG is in providing an objective measure of severity of encephalopathy, prognosis, and effectiveness of therapy.[10]

There is a good correlation between the severity of the EEG changes, the severity of the encephalopathy, and the clinical state of the patient. In mild encephalopathy associated with mild clouding of consciousness and confusion, there is at first slowing of the posterior dominant rhythm, which decreases from a higher to a lower alpha frequency and then into the theta frequency range. More severe encephalopathy is associated with deeper levels of coma, and the background consists mainly of high-amplitude irregular delta activity. With further deterioration in the encephalopathy, the amplitude of all activities drop below 20 µV and the EEG may consist of relatively low-amplitude, invariant delta activity. Some tracings reveal suppression-burst pattern where there is regular alternation of very-low-amplitude EEG with relatively higher-amplitude EEG segments. The most extreme type of abnormality is, of course, lack of any cerebral activity (i.e., electrocerebral inactivity). Presence of the later three types of EEG patterns (invariant low-amplitude delta, suppression-burst, and electrocerebral inactivity) carry a grave prognosis, if drug intoxication can be excluded as the cause of encephalopathy. If due to drug intoxication, these severely abnormal patterns are quite reversible with treatment, with a high potential for complete recovery of neurologic functioning.

Besides the degree of background slowing, there are two other features in the EEG that must be evaluated to determine the severity of encephalopathy. These are spontaneous variability of the EEG over several seconds to minutes, and reactivity to painful stimulation. In milder encephalopathies, the EEG shows spontaneous variability during the recording period and evidence of EEG reactivity to painful stimulation. When the EEG shows reactivity, painful stimulation commonly results in reduction of the amplitude, increase in frequency of the background activity, and reduction in the slow activity. There is often a "paradoxical activation," which is a period of more severe delta slowing following painful stimulation (Fig. 3). The presence of any type of reactivity (reduction in slow activity or increase in the degree of slowing) on painful stimulation suggests a lower grade of encephalopathy, whereas the EEG lacking spontaneous variability (invariant EEG) and total lack of any reactivity to intense and prolonged stimulation suggests a severe degree of encephalopathy.

Figure 3.

EEG of an 8-year-old child with hemolytic anemia and uremia, showing paradoxical activation characterized by increased delta slowing induced by painful stimulation. (Reprinted from Markand ON. Electroencephalogram in metabolic encephalopathies. Electroencephalogr Clin Neurophysiol Suppl 1999;50:301-310; with permission from Elsevier.)

A grading system of EEG abnormalities in adults is shown in Table 1 , similar to other rating systems.[11,12] It is helpful in prognosis, evaluation of effectiveness of therapy, and comparing serial EEG studies. The slow activities associated with an encephalopathy are usually widespread and symmetrical over the two hemispheres. In children, the slowing may predominate over the posterior hemisphere, and in adults, usually over the frontal areas. These are simply maturation-related spatial EEG features, which do not signify that the encephalopathy is more severe posteriorly in children and anteriorly in adults.

It is unusual to see prominent focal or lateralized EEG findings with a diffuse encephalopathy unless there is an associated focal process, such as an old infarct or tumor. An exception is nonketotic hyperosmolar coma, a form of metabolic encephalopathy, which is very often associated with focal clinical (e.g., focal seizures) and focal EEG findings. Herpes simplex encephalitis and Creutzfeldt-Jakob disease (in the early stages) may also produce lateralized EEG slowing related to unilateral emphasis of the associated pathologic process (see below).

Another EEG pattern associated with a mild form of encephalopathy is the presence of bursts of intermittent rhythmic delta activity (IRDA) superimposed on a more or less normal background activity. Depending on the area of predominance, the IRDA is further divided into frontal or occipital types. IRDA has been traditionally considered a "projected rhythm" and a hallmark of EEG findings in patients with deep midline lesions of diencephalic, upper brain stem, or posterior fossa locations.[13] Critical evaluations subsequently have cast serious doubts on this classic concept because this EEG pattern has been found in a large variety of pathological conditions and is often absent in deep midline lesions. As a matter of fact, the most common etiology of IRDA is a mild to moderate encephalopathy associated with some disturbance in consciousness (Fig. 4).[14]

Figure 4.

EEG of an 82-year-old patient with recent history of lethargy and confusion, showing frontal intermittent rhythmic delta activity. (Reprinted from Markand,[10] with permission from Lippincott Williams & Wilkins.)

Are there any unique or specific EEG features that help narrow the differential diagnosis of diffuse encephalopathy and point toward a more specific etiology? There are a few EEG patterns (e.g., triphasic waves, positive spikes, and periodic complexes) that, although not commonly encountered in encephalopathic patients, when present suggest a specific etiology for the encephalopathy. Periodic patterns are specifically encountered in anoxic encephalopathy and certain encephalitides, whereas triphasic waves and positive spikes characteristically occur in metabolic encephalopathies.

Metabolic Encephalopathy

An EEG showing diffuse slowing of the background and presence of triphasic waves is highly suggestive of a metabolic encephalopathy. Triphasic waves are high amplitude (200 to 300 µV), usually bilaterally synchronous, symmetrical, and maximum in amplitude over the frontocentral regions (Fig. 5). The most prominent component is a positive sharp wave that is preceded by a short-duration negative sharp wave and followed by a long-duration negative slow wave.[15] However, variations are quite common and the waveform may be monophasic or biphasic.

Figure 5.

EEG of a 69-year-old patient with hepatic encephalopathy, showing triphasic waves. (Reprinted from Markand ON. Electroencephalogram in metabolic encephalopathies. Electroencephalogr Clin Neurophysiol Suppl 1999;50:301-310; with permission from Elsevier.)

Although earlier authors[15] emphasized that the triphasic waves were highly specific for hepatic encephalopathy, this EEG pattern has been found to correlate best with any metabolic type of encephalopathy; hepatic, renal, and anoxic etiologies account for over 75% of EEGs with triphasic waves.[16,17,18] A feature of triphasic waves often stressed is the progressive time lag (25 to 140 milliseconds) of the positive component of the triphasic wave from the anterior to the posterior region. This feature was considered to be most specific for hepatic etiology.[17,19] Recent studies[18] demonstrated that the time lag is neither a consistent feature of triphasic waves, nor has any specificity with regard to the type of metabolic encephalopathy. The "peril" is that no single feature or group of features regarding triphasic waves distinguish hepatic from nonhepatic cases.

There are a few other "pearls" regarding triphasic waves. Patients with metabolic encephalopathies showing prominent triphasic wave activity in their EEG have an overall poor prognosis; in one series, over two thirds died in a matter of a few months.[20] Furthermore, triphasic waves occur essentially in adults; this pattern has been rarely reported below the age of 20 years.[21] This is particularly true with Reyes disease, an acute childhood encephalopathy with hepatic fatty infiltration, where triphasic waves are absent.[22] The EEG pattern of 14 to 6 per second, positive spikes are a well-known maturational EEG pattern normally seen in children in adolescence during NREM sleep. The presence of positive spike bursts in comatose patients with continuous delta activity is a unique, albeit rare, EEG pattern associated with hepatic or anoxic encephalopathy in children (Fig. 6).[23,24]

Toxic Encephalopathy

Overdose of hypnotic-sedative drugs is a common cause of coma encountered in the emergency room; excessive beta activity is a prominent feature in the EEG over the anterior head regions. What is less well recognized is that with more severe intoxication, the fast activity assumes a slower frequency (usually 10 to 13 Hz), which is widespread but with anterior predominance. The presence of generalized theta-delta activity with superimposed alpha frequency activity is a unique encephalographic pattern highly characteristic of sedative drug intoxication (Fig. 7). In the absence of prominent slow activity, the anterior dominant generalized fast activity produces alpha or spindle coma pattern in the EEG indistinguishable from that seen with severe anoxic encephalopathy.[25,26]

Figure 7.

EEG of an 18-year-old patient with phenobarbital intoxication, showing generalized theta-delta activity with superimposed beta frequencies (A) followed in 3 days by normalization of the EEG (B). (Reprinted from Markand,[10] with permission from Lippincott Williams & Wilkins.)

Very severe drug intoxication results in suppression-burst pattern or electrocerebral inactivity. Even though these patterns signify advanced intoxication, they do not carry as ominous a prognosis as when they occur in the setting of cardiopulmonary arrest. It has been repeatedly demonstrated that patients with drug-induced coma may have electrocerebral inactivity lasting over a day and may still make a full neurologic recovery.

Phencyclidine hydrochloride ("angel dust," "PCP pills") is associated with a distinctive EEG pattern similar to that of subacute sclerosing panencephalitis (SSPE). The EEG shows generalized sinusoidal 6.0 cps theta activity that is interrupted approximately every 4 seconds by generalized slow wave discharges.[27] A similar periodic EEG pattern is described transiently during ketamine (a phencyclidine derivative) anesthesia.

Anoxic Encephalopathy

EEG is commonly performed in patients with anoxic encephalopathy due to cardiopulmonary arrest for assessing the severity of cerebral insult and for prognosis. Patients with normal or almost normal EEG tracings (grade I encephalopathy) following an episode of cerebral anoxia have an excellent prognosis for full neurologic recovery. On the other hand, patients with grade IV or V EEG abnormalities have a uniformly fatal prognosis; most of these patients die without regaining consciousness. An EEG should be obtained at least 5 or 6 hours after successful resuscitation since it takes an hour or more for the EEG to stabilize after an anoxic episode.[12]

Besides electrocerebral inactivity, there are three other unique EEG patterns, encountered in association with anoxic encephalopathy, that carry a poor prognosis for neurologic recovery.

  1. Periodic discharges in anoxic encephalopathy may be either bilaterally synchronous periodic epileptiform discharges (BiPLEDs)[28] or independently occurring periodic lateralized epileptiform discharges (bilateral PLEDs).[29] Both periodic EEG patterns are often associated with myoclonic seizures (or even myoclonic status) and carry an extremely poor prognosis and uniform mortality (Fig. 8). Vigorous antiepileptic medication treatment of myoclonic seizures related to the two EEG patterns do not affect the ultimate prognosis.

  2. Suppression-burst EEG pattern due to anoxic encephalopathy is at times associated with interesting clinical phenomena; during periods of activity both eyes may open or there are other brief body movements (Fig. 9).[30,31] Whether this is an epileptic event (a brief myoclonic seizure) or a brain stem release phenomena remains unknown. At times these movements may cause confusion in the minds of relatives and even treating physicians about the patient's state of consciousness, as they may mimic volitional motor activity.

  3. A rare EEG pattern seen in severe anoxic encephalopathy is the alpha coma pattern, denoting the conjunction of clinical coma associated with alpha frequency activity.[32,33,34] Because in such tracings the dominant frequency is alpha frequency activity without significant slower frequencies, the EEG superficially resembles that of an "awake" person, but there are major differences. The alpha frequency activity in alpha pattern coma is widespread in distribution and is often prominent over the anterior head regions (Fig. 10). Reactivity to any type of sensory stimulation is usually absent. The prognosis of alpha pattern coma is extremely poor; all patients have either died or survived in chronic vegetative state.

Figure 8.

EEG of a 49-year-old comatose patient following severe anoxic encephalopathy, showing bisynchronous periodic epileptiform discharges synchronous with jerks of the left lower extremity monitored on a separate channel.

Figure 9.

EEG of a 75-year-old patient with severe anoxic encephalopathy, showing suppression-burst pattern. During the burst activity there is opening of the eyes; eye movements monitored in the last channel.

Figure 10.

EEG of a 77-year-old comatose patient following cardiopulmonary arrest 4 days previously, showing "alpha coma pattern." Patient died after 2 days. (Reprinted from Markand,[10] with permission from Lippincott Williams & Wilkins.)

Remember that EEG findings of alpha pattern coma are also seen in the setting of sedative/hypnotic drug intoxication[25,35] and in association with intrinsic brain stem lesions[36] with a much more favorable prognosis.

Cerebral Death

The EEG is being employed with increasing frequency for the determination of cerebral death in patients with irreversible coma, particularly when organs have to be salvaged for transplantation. It cannot be overemphasized that the absence of cerebral activity on the EEG is only one of the criteria, and should always be considered along with the clinical findings and blood flow studies for brain death. To properly identify very-low-voltage cerebral activity, to distinguish physiological or instrumental artifacts, and to eliminate the possibility of errors through malfunctioning equipment or inadequate techniques, the American EEG Society[37] has a number of recommendations that must be followed during EEG recordings in all cases of suspected brain death. In such "flat" tracings, EEG activity may be obscured by very-low-amplitude fast activity due to sustained contraction of scalp muscles, which can be eliminated by giving a short-acting neuromuscular blocking agent (succinylcholine, 20 to 40 mg IV). This step, which is very easy to undertake, is often overlooked to obtain a satisfactory recording in such patients.

A single EEG and a 6- to 12-hour clinical observation after an unequivocal acute cerebral insult are minimum requirements for brain death evaluation in an adult. In young children, the guidelines are slightly different because of the more difficult task of confirming brain death in this age group. A special task force[38] recommended the following:

  1. Brain death should not be determined until at least 7 days of age.

  2. Seven days to 2 months: two examinations and two EEGs separated by at least 48 hours are required.

  3. Two months to 1 year: two examinations and two EEGs separated by at least 24 hours are required.

  4. Older than 1 year: similar criteria as an adult (i.e., one EEG and at least 12 hours of observation).

Encephalitides

In viral encephalitis the severity of the EEG abnormalities generally parallel the clinical picture, but at times the EEG may be more disorganized and slow than the mental state of the patient may suggest. With a few exceptions, the EEG changes in different viral encephalitides are generally nonspecific and not helpful to distinguish one etiologic agent from another.[39]

The EEG pattern and its evolution in herpes simplex encephalitis are rather characteristic so that the diagnosis can often be suspected by EEG findings when considered in the proper clinical setting. The EEG in herpes simplex encephalitis may show a prominent focal abnormality, usually a focus of polymorphic delta activity over a temporal region, corresponding to the initial localization of pathology to the temporal lobe of the brain.[40,41,42] The most characteristic EEG feature of herpes simplex encephalitis is the occurrence of pseudo-periodic, focal or unilateral, large amplitude, sharp wave complexes that repeat at regular intervals of 1 to 3 seconds.[40,41,42,43] These periodic lateralized epileptiform discharges are usually expressed maximally over the involved temporal lobe (Fig. 11). This characteristic periodic pattern is usually seen between 2 and 15 days after the onset of illness. As the disease progresses and the other hemisphere becomes involved, the periodic complexes may disappear on the side of initial involvement before appearing on the side more recently involved. With bilateral involvement of the brain, periodic complexes may occur over both hemispheres; they may then occur either synchronously or independently over the two sides.

Figure 11.

EEG of a 65-year-old patient with Herpes simplex encephalitis, showing periodic epileptiform discharges occurring over the right temporal region every 1 to 2 seconds.

The presence of unilateral or focal periodic complexes (PLEDs) is not unique for herpes simplex encephalitis. PLEDs may occur with acute focal cerebral hemispheric processes (e.g. infarction, brain abscess, or neoplasm).[44] Nevertheless, the presence of unilateral periodic complexes in association with an acute febrile illness, focal seizures, and spinal fluid pleocytosis is strongly suggestive of herpes simplex encephalitis.

SSPE, a childhood disorder that is a slow virus infection of the central nervous system due to measles, has virtually disappeared from the United States since the introduction of measles vaccination. The EEG in SSPE is highly specific and characterized by the presence of high-amplitude periodic complexes that are bilateral, usually synchronous, and symmetrical.[45,46,47] They are remarkably stereotyped and consist of two or more delta waves with or without sharp wave components intermixed with them. The periodic complexes repeat with a fair regularity every 4 to 10 seconds and there is a 1:1 relationship of the EEG periodic complexes to the clinical myoclonic jerks, when present (Fig. 12). In the early stages of the disease, the periodic complexes may occur at irregular and long intervals, and sleep may activate them. A sleep recording, therefore, is recommended in a suspected case of SSPE in which the awake tracing has failed to reveal periodic complexes.[48] Also, in the early stages there is asymmetry of the periodic complexes, which may be associated with asymmetry of the myoclonic jerks that occur contralateral to the periodic complexes.[47] Later in the disease, the periodic complexes are bilaterally symmetrical and synchronous.

Figure 12.

EEG of a 16-year-old patient with subacute sclerosing panencephalitis, showing high-amplitude generalized periodic complexes repeating at intervals of 8 to 10 seconds and accompanied by eye jerks and myoclonic jerks of the upper extremities monitored on the last two channels. (Reprinted from Markand,[10] with permission from Lippincott Williams & Wilkins.)

Creutzfeldt-Jakob disease, a prion disorder of the central nervous system (CNS), is also characterized by a very specific EEG pattern, which consists of periodic, bilaterally synchronous wave forms.[49] The periodic discharges take the form of diphasic or triphasic sharp waves, which repeat regularly at a frequency close to one per second. There is a fairly close relationship between the periodic complexes and myoclonic jerks; the latter may occur a few milliseconds before or after the electrical event.

What is less well known is the fact that in the early stages of Creutzfeldt-Jakob disease, focal or lateralized periodic sharp waves (PLEDs) may occur,[50,51] which later evolve into bilaterally symmetrical and synchronous periodic discharges superimposed on a "flat" background (Fig. 13). Although the periodic EEG pattern is not pathognomonic, the presence of periodic sharp waves occurring regularly around one per second, in association with clinical findings of progressive dementia and myoclonus in elderly individuals, provides strong support to the diagnosis of Creutzfeldt-Jakob disease. This characteristic periodic pattern is reported in more than 75% of patients with histologically verified Creutzfeldt-Jakob disease, and the pattern becomes fully established within the first 3 months of the onset of symptoms.[52,53]

Degenerative Encephalopathies

In degenerative encephalopathies, a common denominator is a disturbance in the regulation and frequency of the background activity, but the EEG features do differ with regard to whether the pathologic process involves predominantly cortical and/or subcortical gray matter or cerebral white matter.[54] In disorders that primarily involve the cerebral white matter, the EEG is characterized predominantly by the presence of high-amplitude continuous generalized polymorphic delta activity associated with a markedly disordered background and virtual absence of epileptiform activity or paroxysmal discharges. Such changes are characteristically seen in all types of leukodystrophies, Schilder's disease, and multifocal leukoencephalopathy. In diffuse cortical gray matter encephalopathies, the EEG is characterized by abnormal background activity that is slow, irregular, and low in amplitude. There is minimal continuous generalized polymorphic delta activity, and paroxysmal findings are usually absent or minimal. Examples include Alzheimer's or Pick's disease. In diffuse cortical and subcortical gray matter encephalopathies, the EEG shows generalized bilaterally synchronous paroxysmal discharges in the form of bursts of monorhythmic delta waves or paroxysms of slow spike wave activity superimposed on an abnormal background. Pathological conditions include cerebromacular degeneration (e.g., Batten's disease).

Degenerative disorders with lesions predominantly below the cerebrum produce only minimal alterations in the EEG. This is usually the case in spinocerebellar degeneration, Parkinson's disease, progressive supranuclear palsy, and so on, where the EEG either remains normal or shows mild nonspecific slowing of the background activity. There are virtually no other EEG features associated with degenerative encephalopathies that have a high correlation to a specific etiologic process. The exception is the occurrence of large-amplitude spikes in response to single flashes or at flickering rates below three per second, which is a highly characteristic feature of Batten's disease.[55] These large potentials may reach 50 to 500 µV, maximum over the occipital region, and sometimes associated with myoclonic jerks of the limbs and face (Fig. 14). With advancing retinal disease and blindness, the characteristic photic response is lost.

Figure 14.

EEG of a 6-year-old patient with Batten's disease, showing high-amplitude spikes induced by photic stimulation at one per second. (Reprinted from Markand,[10] with permission from Lippincott Williams & Wilkins.)

In patients with senile or presenile dementia, the EEG background shows varying degrees of slowing and disorganization[56,57,58] but may remain within normal limits in individuals with obvious intellectual impairment. A slowing of the alpha rhythm from 11 to 12 Hz to 8 to 9 Hz may represent a significant deterioration of the EEG, but in the absence of serial studies this would remain unrecognized. Furthermore, the rate of progression of dementia is important because patients with very slowly progressing dementia are likely to show minimal EEG changes. Epileptiform discharges are rare in the Alzheimer's type of presenile or senile dementia except in very advanced disease. Sharp or triphasic waves over the posterior head regions in severely demented patients have been reported.[59] At times these EEG waveforms may raise a suspicion of Creutzfeldt-Jakob disease; however, unlike Creutzfeldt-Jakob disease, these discharges occur irregularly with little or no tendency toward periodic occurrence.

Huntington's disease has a very characteristic clinical picture, and the diagnosis is confirmed by genetic testing. There is a high incidence of abnormal EEG tracing in Huntington's disease; the characteristic feature is the presence of a "flat tracing" with virtual absence of rhythmic activity. Such features are reported in as high as two thirds of the patients with Huntington's disease.[60] There is absence of any EEG activity in excess of 10 µV. In addition, the EEG is practically devoid of any rhythmic activity, not merely a paucity of recognizable rhythms. Such "flat" EEGs in Huntington's disease need to be differentiated from a normal variant, low-amplitude tracings in adults, which have activity less than 20 µV and a paucity of recognizable rhythms. Hyperventilation would increase the amount and amplitude of rhythmic activity with normal variant, whereas in patients with Huntington's disease hyperventilation remains ineffective.[2]

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