Focal Arrhythmic (Polymorphic) Slow Activity

Polymorphic slow activity is irregular activity in the delta (1 to 4 Hz) or theta (4 to 7 Hz) range, which when continuous has a strong correlation with a localized cerebral lesion such as infarction, hemorrhage, tumor, or abscess. Intermittent focal slow activity also may indicate localized parenchymal dysfunction but is less predictive than polymorphic slow activity.

Intermittent Rhythmic Slow Waves

Paroxysmal bursts of generalized bisynchronous rhythmic theta or delta waves usually indicate thalamocortical dysfunction and may be seen with metabolic or toxic disorders, obstructive hydrocephalus, deep midline or posterior fossa lesions, and also as a nonspecific functional disturbance in patients with generalized epilepsy. Focal bursts of rhythmic waves lateralized to one hemisphere usually indicate deep (typically thalamic or periventricular) abnormalities, often of a structural nature.

Generalized Arrhythmic (Polymorphic) Slow Activity

Diffuse disturbances in background rhythms marked by excessive slow activity and disorganization of waking EEG patterns arise in encephalopathies of metabolic, toxic, or infectious origin and with brain damage caused by a static encephalopathy.

Voltage Attenuation

Cortical disease causes voltage attenuation. Generalized voltage attenuation is usually associated with diffuse depression of function such as after anoxia or with certain degenerative diseases (e.g., Huntington disease). The most severe form of generalized voltage attenuation is electrocerebral inactivity, which is corroborative evidence of brain death in the appropriate clinical setting. Focal voltage attenuation reliably indicates localized cortical disease such as porencephaly, atrophy, or contusion, or an extra-axial lesion such as a meningioma or subdural hematoma.

Epileptiform Discharges

Epileptiform discharges are spikes or sharp waves that occur interictally in patients with epilepsy and sometimes in persons who do not experience seizures but have a genetic predisposition to epilepsy. Epileptiform discharges may be focal or generalized, depending on the seizure type.

Epilepsy

The EEG usually is the most helpful laboratory test when a diagnosis of epilepsy is considered. Because the onset of seizures is unpredictable, and their occurrence is relatively infrequent in most patients, EEG recordings usually are obtained when the patient is not having a seizure. Fortunately, electrical abnormalities in the EEG occur in most patients with epilepsy even between attacks.

The only EEG finding that has a strong correlation with epilepsy is epileptiform activity, a term used to describe spikes and sharp waves that are clearly distinct from ongoing background activity. Clinical and experimental evidence supports a specific association between epileptiform discharges and seizure susceptibility. Only about 2% of nonepileptic patients have epileptiform EEGs, whereas as many as 90% of patients with epilepsy show epileptiform activity, depending on the circumstances of the recording and the number of studies obtained.

Nonetheless, interpretation of interictal findings always requires caution. Correlating most epileptiform discharges with the frequency and likelihood of recurrence of epileptic seizures is poor (Selvitelli et al., 2010). Furthermore, a substantial number of patients with unquestionable epilepsy have consistently normal interictal EEGs. The most convincing proof that a patient’s episodic symptoms are epileptic is obtained by recording an electrographical seizure discharge during a typical behavioral attack. Although ictal EEG tracings greatly increase the sensitivity of the study in assessing the pathophysiology of specific behavioral episodes, the clinician must still be aware of limitations inherent in such recordings. (Videos showing actual EEG recordings obtained during seizures [Videos 32A.1 to 32A.3] are available at www.expertconsult.com.)

In addition to epileptiform patterns, EEGs in patients with epilepsy often show excessive focal or generalized slow-wave activity. Less often, asymmetries of frequency or voltage may be noted. These findings are not unique to epilepsy and are featured in other conditions such as static encephalopathies, brain tumors, migraine, and trauma. In patients with unusual spells, nonspecific changes on EEG should be weighed cautiously and are not to be considered direct evidence for a diagnosis of epilepsy. On the other hand, when clinical data are unequivocal, or when epileptiform discharges occur as well, the degree and extent of background EEG changes may provide information important for judging the likelihood of an underlying focal cerebral lesion, a more diffuse encephalopathy, or a progressive neurological syndrome. Additionally, EEG findings may help determine prognosis and aid in the decision to discontinue antiepileptic medication.

The type of epileptiform activity on EEG is helpful in classifying a patient’s seizure type correctly and sometimes in identifying a specific epileptic syndrome (see Chapter 67). Clinically, generalized tonic-clonic seizures may be generalized from the outset or may be secondary to spread from a focus. Lapses of awareness with automatisms may be a manifestation either of a generalized nonconvulsive form of epilepsy (absence seizures) or of focal epileptogenic dysfunction (temporal lobe epilepsy). The initial clinical features of a seizure may be uncertain because of postictal amnesia or nocturnal occurrence. In these and similar situations, the EEG can provide information crucial to the correct diagnosis and appropriate therapy.

In generalized seizures of nonfocal origin, the EEG typically shows bilaterally synchronous diffuse bursts of spikes and spike-and-wave discharges (Fig. 32A.5). All generalized EEG epileptiform patterns share certain common features, although the exact expression of the spike-wave activity varies depending on whether the patient has pure absence, tonic-clonic, myoclonic, or atonic-astatic seizures. The EEG also may distinguish between primary and secondary generalized epilepsy. In the former instance, no cerebral disease is demonstrable, whereas in the latter, evidence can be found for diffuse brain damage. Typically, primary (idiopathic) generalized epilepsy is associated with normal or near-normal EEG background rhythms, whereas secondary (symptomatic) epilepsy is associated with some degree of generalized slow-wave activity.

Fig. 32A.5 Examples of generalized spike-wave patterns from different patients with primary generalized (idiopathic) epilepsy. The patient in A had mainly tonic-clonic seizures, with occasional absence attacks. The patient in B had juvenile myoclonic epilepsy.

Consistently focal epileptiform activity is the signature of partial (focal) epilepsy (Fig. 32A.6). With the exception of the benign focal epilepsies of childhood, focal epileptiform activity results from neuronal dysfunction caused by demonstrable brain disease. The waveform of focal epileptiform discharges is largely independent of localization, but a reasonable correlation exists between spike location and the type of ictal behavior. Anterior temporal spikes usually are associated with complex partial seizures, rolandic spikes with simple motor or sensory seizures, and occipital spikes with primitive visual hallucinations or diminished visual function as an initial feature.

Fig. 32A.6 Focal right anterior temporal spikes occurring on the electroencephalogram of a 69-year-old woman with complex partial seizures after a stroke involving branches of the right middle cerebral artery.

In addition to distinguishing epileptiform from nonepileptiform abnormalities, EEG analysis sometimes identifies specific electroclinical syndromes. Such syndromes include hypsarrhythmia associated with infantile spasms (West syndrome) (Fig. 32A.7); 3-Hz spike-and-wave activity associated with typical absence attacks (petit mal epilepsy) (Fig. 32A.8); generalized multiple spikes and waves (polyspike-wave pattern) associated with myoclonic epilepsy, including so-called juvenile myoclonic epilepsy of Janz (see Fig. 32A.5, B); generalized sharp and slow waves (slow spike-and-wave pattern) associated with Lennox-Gastaut syndrome (Fig. 32A.9); central-midtemporal spikes associated with benign rolandic epilepsy (Fig. 32A.10); and periodic lateralized epileptiform discharges (PLEDs) associated with acute destructive cerebral lesions such as hemorrhagic cerebral infarction, a rapidly growing malignancy, or herpes simplex encephalitis (Fig. 32A.11) (Pohlmann-Eden et al., 1996). PLEDs may also reappear in patients with chronic structural lesions in the context of new metabolic derangements.

Fig. 32A.7 Electroencephalographic pattern termed hypsarrhythmia in a recording obtained in an 8-month-old boy with infantile spasms. Background activity is high-voltage and unorganized, with abundant multifocal spikes.

Fig. 32A.8 A 3-Hz spike-and-wave paroxysm on the electroencephalogram of a 9-year-old boy with absence seizures (petit mal epilepsy). During this 12-second discharge, the child was unresponsive and demonstrated rhythmic eye blinking.

Fig. 32A.9 Generalized sharp-wave and slow-wave discharges on the electroencephalogram (EEG) of a 9-year-old child with mental retardation and uncontrolled typical absence, tonic, and atonic generalized seizures. This constellation of clinical and EEG features constitutes the Lennox-Gastaut syndrome.

Fig. 32A.10 Electroencephalogram obtained during drowsiness in a 10-year-old boy with benign rolandic epilepsy. Stereotypical diphasic or triphasic sharp waves occur in the right central-parietal and midtemporal regions.

Fig. 32A.11 Two examples of periodic lateralized epileptiform discharges (PLEDs) on the electroencephalogram. A, Right parasagittal PLEDs in a 69-year-old man with severe brain damage caused by meningitis with multiple cerebral infarctions. B, A 65-year-old woman with herpes simplex encephalitis. PLEDs are bilateral but have a right-sided predominance.

The increased availability of special monitoring facilities for simultaneous video and EEG recording and of ambulatory EEG recorders has improved diagnostic accuracy and the reliability of seizure classification. Prolonged continuous recordings through one or more complete sleep/wake cycles constitute the best way to document ictal episodes and should be considered in patients whose interictal EEGs are normal or nondiagnostic and in clinical dilemmas that are resolvable only by recording actual behavioral events. Although EEG documentation of an ictal discharge establishes the epileptic nature of a corresponding behavioral change, the converse is not necessarily true. Sometimes muscle or movement artifacts so obscure the EEG recording that it is impossible to know whether any EEG change has occurred. In these circumstances, postictal slowing usually is indicative of an epileptic event if similar slow waves are not present elsewhere in the recording and if the EEG recording subsequently returns to baseline. In addition, focal seizures not accompanied by alteration in consciousness occasionally have no detectable scalp correlate. On the other hand, persistence of alpha activity and absence of slowing during and after an apparent convulsive episode are inconsistent with an epileptic generalized tonic-clonic seizure.

Focal Cerebral Lesions

The use of electroencephalography to detect focal cerebral disturbances has declined because of the development and widespread availability of computerized anatomical imaging techniques. Nonetheless, the EEG has a role in documenting focal physiological dysfunction in the absence of discernible structural pathology and in evaluating the functional disturbance produced by known lesions.

Focal delta activity is the usual EEG sign of a local disturbance. A structural lesion is likely if the delta activity is (1) present continuously; (2) shows variability in waveform, amplitude, duration, and morphology (so-called arrhythmic or polymorphic activity); and (3) persists during changes in wake/sleep states (Fig. 32A.12). The localizing value of focal delta activity increases when it is topographically discrete or associated with depression or loss of superimposed faster background frequencies. Superficial lesions tend to produce restricted EEG changes, whereas deep cerebral lesions produce hemispherical or even bilateral delta activity.

Fig. 32A.12 The patient was a 46-year-old man with a glioblastoma involving the right temporal and parietal lobes. A, Lesion is well demonstrated on this computed tomography scan of the brain. B, Electroencephalogram demonstrates continuous arrhythmic slowing over the right temporal and parieto-occipital areas. In addition, loss of the alpha rhythm and overriding faster frequencies are seen in corresponding areas of the left cerebral hemisphere.

Bilateral paroxysmal bursts of rhythmic delta waves (Fig. 32A.13) with frontal predominance—once attributed to subfrontal, deep midline, or posterior fossa lesions—are actually nonspecific and seen more often with diffuse encephalopathies. Focal or lateralized intermittent bursts of rhythmic delta waves as the prominent EEG abnormality suggest a deep supratentorial (periventricular or diencephalic) lesion.

Fig. 32A.13 Bursts of intermittent rhythmic delta waves on the electroencephalogram (EEG) of a 36-year-old man with primary generalized epilepsy and tonic-clonic seizures. Generalized spike-wave activity occurred elsewhere in the EEG. Intermittent rhythmic delta waves are a nonspecific manifestation of the patient’s generalized epileptic disorder.

(Courtesy Dr. Bruce J. Fisch.)

The character and distribution of the EEG changes caused by a focal lesion depend on its size, its distance from the cortical surface, the specific structures involved, and its acuity. A small stroke critically located in the thalamus may produce widespread hemispherical slowing and alteration in sleep spindles and alpha rhythm regulation. A lesion of the same size located at the cortical surface produces few if any EEG findings.

Single lacunae usually produce little or no change in the EEG. Similarly, transient ischemic attacks not associated with chronic cerebral hypoperfusion or imminent occlusion of a major vessel do not significantly affect the EEG outside the symptomatic period. Superficial cortical or large, deep hemispherical infarctions are usually associated with localized EEG abnormalities.

Focal EEG changes (and other nonepileptiform abnormalities) are common in migraine. The likelihood of an abnormal EEG and the severity of the abnormality relate to the timing and character of the migraine attack. EEGs are more likely to be focally abnormal, with complicated rather than common migraine and during rather than between headaches. EEG changes seen with brain tumors are caused by disturbances in bordering brain parenchyma; tumor tissue is electrically silent. Focal EEG changes are caused by interference with patterns of normal neuronal synaptic activity, by destruction or alteration of the cortical neurons, and by metabolic effects caused by changes in blood flow, cellular metabolism, or the neuronal environment. Diffuse EEG changes are the consequence of increased intracranial pressure, shift of midline structures, or hydrocephalus. Electroencephalography is especially helpful in following the extent of cerebral dysfunction over time, in distinguishing between direct effects of the neoplasm and superimposed metabolic or toxic encephalopathies, and in differentiating among epileptic, ischemic, and noncerebral causes for episodic symptoms.

The role of electroencephalography in the management of patients with head injuries is limited. Transient generalized slowing is common after concussion. A persistent area of continuous localized slow-wave activity suggests cerebral contusion even in the absence of a focal clinical or CT abnormality, and unilateral voltage depression suggests subdural hematoma. Electroencephalography performed in the first 3 months after injury does not predict posttraumatic epilepsy.

Altered States of Consciousness

The EEG has a major role in evaluating patients with altered levels of consciousness. Because this study permits a reasonably critical assessment of supratentorial brain function, it complements the clinical examination in patients with significant depression of consciousness. Abnormalities typically are nonspecific with regard to etiology. In general, however, a correlation with the clinical state is good. Some findings are more suggestive of particular causes than of others and occasionally are prognostically useful as well. Specific questions the EEG may help to answer (depending on the clinical presentation) are the following:

Metabolic Encephalopathies

Metabolic derangements affecting the brain diffusely constitute one of the most common causes of altered mental function in a general hospital. Generalized slow-wave activity is the main indication of decreased consciousness. The degree of EEG slowing closely parallels the patient’s mental status and ranges from only minor slowing of alpha-rhythm frequency (slight inattentiveness and decreased alertness) to continuous delta activity (coma). Slow-wave activity sometimes becomes bisynchronous and assumes a high-voltage, sharply contoured triphasic morphology, especially over the frontal head regions (Fig. 32A.14). These triphasic waves, originally considered diagnostic of hepatic failure, occur with equal frequency in other metabolic disorders such as uremia, hyponatremia, hyperthyroidism, anoxia, and hyperosmolarity. The value of triphasic waves is that they suggest a metabolic cause in an unresponsive patient.

Fig. 32A.14 Triphasic waves on the electroencephalogram of a 61-year-old man with hepatic failure.

(Courtesy Dr. Bruce J. Fisch.)

Some EEG features increase the likelihood of a specific metabolic disorder. Prominent generalized rhythmic beta activity raises the suspicion of drug intoxication in a comatose patient. Severe generalized voltage depression indicates impaired energy metabolism and suggests hypothyroidism if anoxia and hypothermia can be excluded. A photoconvulsive response is seen more often with uremia than with other causes of metabolic encephalopathy. Focal seizure activity is common in patients with hyperosmolar coma.

Hypoxia

Hypoxia, with or without circulatory arrest, produces a wide range of EEG abnormalities depending on the severity and reversibility of the brain damage. EEGs obtained 6 hours or more after the hypoxic insult may show patterns that have prognostic value. Sequential EEGs strengthen the validity of such findings. EEG abnormalities associated with poor neurological outcome are alpha coma, burst suppression, and periodic patterns.

The term alpha coma refers to the apparent paradoxical appearance of monorhythmic alpha frequency activity in the EEG of a comatose patient; the EEG recording may appear normal to the inexperienced observer (Fig. 32A.15). In contrast with normal alpha activity, that seen with alpha coma is generalized, often maximal frontally, and unreactive to external stimuli.

Fig. 32A.15 Alpha coma in a 34-year-old man with severe hypoxic-ischemic brain damage from subarachnoid hemorrhage with diffuse prolonged cerebral vasospasm. Unlike the normal alpha rhythm, the alpha range activity on the electroencephalogram of this comatose patient is widespread but maximal frontally, unreactive, and superimposed on low-voltage arrhythmic delta frequencies.

The burst suppression pattern consists of occasional generalized bursts of medium- to high-voltage, mixed-frequency, slow-wave activity, sometimes with intermixed spikes, with intervening periods of severe voltage depression or cerebral inactivity (Fig. 32A.16). Massive myoclonic body jerks may accompany the bursts.

Fig. 32A.16 Burst suppression pattern on the electroencephalogram of a 53-year-old woman with anoxic encephalopathy following cardiorespiratory arrest. The patient died several days later.

(Courtesy Dr. Barbara S. Koppel.)

The periodic pattern consists of generalized spikes or sharp waves that recur with a relatively fixed interval, typically 1 or 2 per second (Fig. 32A.17). Sometimes the periodic sharp waves occur independently over each hemisphere. Myoclonic jerks of the limbs or whole body usually accompany a postanoxic periodic pattern.

Fig. 32A.17 Periodic pattern on the electroencephalogram of a patient with anoxic encephalopathy following cardiorespiratory arrest. The patient was paralyzed with pancuronium because of bilateral myoclonus.

The prognostic value of these patterns relates exclusively to the cause. Similar features are recognized with potentially reversible causes of coma including deep anesthesia, drug overdose, and severe liver or kidney failure.

Infectious Diseases

Of all infectious diseases affecting the brain, herpes simplex encephalitis is the one for which electroencephalography is most useful in initial assessment. Early and accurate diagnosis is important because the response to acyclovir is best when treatment is started early. Although establishing a definitive diagnosis requires brain biopsy, characteristic EEG changes in the clinical setting of encephalitis are helpful in selecting patients for early treatment and biopsy. The EEG result usually is abnormal and suggestive of herpes infection before CT lesions are recognized.

Viral encephalitis is expected to cause diffuse polymorphic slow-wave activity, and a normal EEG result raises doubt about the diagnosis. With herpes simplex encephalitis, a majority of patients show focal temporal or frontotemporal slowing that may be unilateral or, if bilateral, asymmetrical. Periodic sharp-wave complexes over one or both frontotemporal regions (occasionally in other locations and sometimes generalized) add additional specificity to the EEG findings (see Fig. 32A.11, B). These diagnostic features usually appear between days 2 and 15 of illness and sometimes are detectable only with serial tracings.

Bacterial meningitis causes severe and widespread EEG abnormalities, typically profound slowing and voltage depression, but viral meningitis produces little in the way of significant changes. Although CT has replaced electroencephalography in evaluating patients with suspected brain abscess, focal EEG changes may occur in the early stage of cerebritis before an encapsulated lesion is demonstrable on CT images.

EEG abnormalities usually resolve as the patient recovers, but the rate of resolution of clinical deficits and that of the electrographical findings may be different. It is not possible to predict either residual neurological morbidity or postencephalitic seizures by EEG criteria. An early return of normal EEG activity does not exclude the possibility of persistent neurological impairment.

Brain Death

The diagnosis of brain death rests on strict clinical criteria that, when satisfied unambiguously, permit a conclusive determination of irreversible loss of brain function. In the United States, the usual definition of brain death is irreversible cessation of all functions of the entire brain, including the brainstem. Because the EEG is a measure of cerebral—especially cortical—function, it has been widely used in association with clinical evaluation to provide objective evidence that brain function is lost. Several studies have demonstrated that enduring loss of cerebral electrical activity, termed electrocerebral inactivity or electrocerebral silence, accompanies clinical brain death and is never associated with recovery of neurological function. The determination of electrocerebral inactivity is technically demanding, requiring a special recording protocol. Specific criteria have been established by the American Clinical Neurophysiology Society.

Temporary and reversible loss of cerebral electrical activity is observable immediately after cardiorespiratory resuscitation, drug overdose from CNS depressants, and severe hypothermia. Therefore, accurate interpretation of an EEG demonstrating electrocerebral inactivity must take into account these exceptional circumstances. Chapter 48 summarizes the clinical criteria for establishing the diagnosis of brain death.

Aging and Dementia

Because the EEG is a measure of cortical function, theoretically it should be useful in the diagnosis and classification of dementia. The utility of single EEG examinations in evaluating patients with known or suspected dementing illnesses, however, is often disappointing. Two important reasons for this limitation are (1) problems in distinguishing the effects on cerebral electrical activity of normal aging from those caused by disease processes and (2) the absence of generally accepted quantifiable methods of analysis and statistically valid comparison measures.

With increasing age beyond 65 years, a slight reduction in alpha rhythm frequency and in the total amount of alpha activity is normal. Normal elderly persons also show slightly increased amounts of theta and delta activity, especially over the temporal and frontotemporal regions, as well as changes in sleep patterns. Early in the course of some dementing illnesses, no EEG abnormality may be apparent (this is the rule with Alzheimer disease), or the normal age-related changes may become exaggerated, differing more in degree than in kind.

In practice, the EEG can assist in the evaluation of suspected dementia by confirming abnormal cerebral function in patients with a possible psychogenic disorder and by delineating whether the process is focal or diffuse. Sequential EEGs usually are more helpful than a single tracing, and a test early in the course of the illness may provide more specific information than can be obtained later on. Overall, the degree of EEG abnormality shows good correlation with the degree of dementia.

EEG findings in Alzheimer disease are highly dependent on timing. The EEG initially is normal or shows an alpha rhythm at or just below the lower limits of normal. Generalized slowing ensues as the disease progresses. In patients with focal cognitive deficits, accentuation of slow frequency activity over the corresponding brain area may be a feature. Continuous focal slowing is sufficiently unusual to suggest the possibility of another diagnosis. Prominent focal or bilateral independent slow-wave activity, especially if seen in company with a normal alpha rhythm, favors multifocal disease such as multiple cerebral infarcts. Sometimes a specific cause may be suggested. For example, an EEG showing generalized typical periodic sharp-wave complexes in a patient with dementia is virtually diagnostic of Creutzfeldt-Jakob disease (Fig. 32A.18).

Fig. 32A.18 Periodic sharp-wave pattern on the electroencephalogram of a 67-year-old woman with Creutzfeldt-Jakob disease. Generalized bisynchronous diphasic sharp waves occur approximately 1.5 to 2.0 per second.

Event-related evoked potentials have application in the study of dementia. These long-latency events (i.e., potentials occurring more than 150 msec after the stimulus) are heavily dependent on psychic and cognitive factors. Ideally, they measure the brain’s intrinsic mechanisms for processing certain types of information and are potentially valuable in the electrophysiological assessment of dementia. The best known of the event-related potentials is the P300, or P3, wave. The place of these long-latency evoked potentials in the evaluation of dementia is still under investigation, but the pattern of electrophysiological abnormality may be helpful in distinguishing among types of dementia (Comi and Leocani, 2000).

Normal Visual Evoked Potential

More sensitive and reliable responses are obtained using a pattern-reversal stimulus. The subject focuses on a high-contrast checkerboard of black and white squares displayed on a video or optical projection screen. The stimulus is the change of black squares to white and of white squares to black (pattern reversal). When appropriate check sizes are used (15 to 40 minutes of arc at the subject’s eye), the VEP is generated primarily by foveal and parafoveal elements. Monocular full-field stimulation almost always is used, so the test is most sensitive to lesions of the optic nerve anterior to the chiasm. It is possible, however, to modify the stimulus presentation so that only selected portions of the visual field are stimulated, thereby permitting detection of postchiasmatic abnormalities as well. VEPs elicited by pattern-reversal stimuli show less intersubject variability than flash VEPs and are much more sensitive to lesions affecting the visual pathways.

A few investigators have further refined the pattern-shift stimulus by using a black-and-white sinusoidal grating rather than a checkerboard pattern. This adaptation appears to enhance test sensitivity by permitting selective stimulation of retinal elements responsive to specific spatial frequencies and of cortical elements sensitive to both spatial frequency and orientation.

A normal pattern-reversal VEP to full-field monocular stimulation is illustrated in Fig. 32A.20. The VEP waveform is deceptively simple. It is the sum of many waveforms generated simultaneously by various areas of the retinotopically organized occipital cortex. By selectively stimulating portions of the visual field, it is possible to dissect the full-field VEP wave into its component waveforms. For example, Fig. 32A.21, recorded from the same patient as in Fig. 32A.20, illustrates VEPs to right and left hemifield stimulation. It is apparent that the full-field VEP is the sum of the two hemifield responses. In principle, it is possible to divide the visual fields into progressively smaller and smaller components and to record the VEP to each independently.

Fig. 32A.20 Normal pattern-reversal visual evoked potentials to full-field monocular stimulation. The MO electrode is in the posterior midline over the occiput. RO and RT are 5 and 10 cm, respectively, to the right of MO, and LO and LT are 5 and 10 cm, respectively, to the left of MO. All electrodes are referred to Fpz (a midline frontopolar electrode). The response is largest at MO and symmetrically distributed left and right of midline.

Fig. 32A.21 Normal pattern-shift visual evoked potentials to right and left hemifield stimulation of one eye. Same subject as in Fig. 35A.20. Partial-field responses are asymmetrical about the midline, with the largest positivities ipsilateral to the stimulated field.

The primary basis for interpretation of the VEP is measurement of the latency of the P100 component (the major positive wave having a nominal latency of approximately 100 msec in normal persons) after stimulation of each eye separately. After the absolute P100 latency for each eye is measured, the intereye P100 latency difference is determined. Comparison of these values with normative laboratory data will indicate the normal or abnormal nature of the response. Whenever possible, the clinical significance of the findings is interpreted in the context of other relevant clinical data.

Because optic nerve fibers from the temporal retina decussate at the chiasm, unilateral prolongation of P100 latency after full-field monocular stimulation implies an abnormality anterior to the optic chiasm on that side. Bilateral lesions either anterior or posterior to the optic chiasm or a chiasmal lesion will cause bilateral delay of the P100, demonstrated by separate stimulation of each eye. Unilateral hemispherical lesions do not alter the latency of the full-field P100 (because of the contribution from the intact hemifield) but do alter the scalp topography of the response.

Visual Evoked Potentials in Neurological Disease

Acute optic neuritis is accompanied by marked attenuation or loss of P100 wave amplitude following pattern-reversal stimulation of the affected eye. After the acute attack, the VEP shows some recovery, but P100 latency usually remains prolonged, even with restoration of functionally normal vision. In patients with a history of optic neuritis, P100 latency typically is prolonged, but waveform amplitude and morphology often are relatively well preserved (Fig. 32A.22). Factors contributing to changes in P100 probably include the combined effects of patchy conduction block, areas of variably slowed conduction, temporal dispersion of the afferent volley in the optic nerve, loss of some components of the normal VEP, and the appearance of previously masked components.

Fig. 32A.22 Pattern-shift visual evoked potentials recorded in a patient with right optic neuritis, illustrating marked delay of the P100 component from the right eye. As is typical with demyelinating optic neuropathies, the waveform is relatively preserved.

Pattern-shift VEPs are abnormal in nearly all patients with a definite history of optic neuritis. More important, the pattern-shift VEP is a sufficiently sensitive indicator of optic nerve demyelination that it can reveal asymptomatic and clinically undetectable lesions. Thus, 70% to 80% of patients with definite multiple sclerosis (MS) but no history of optic neuritis or visual symptoms have abnormal VEPs. Many patients with abnormal VEPs have normal neuro-ophthalmological examination results.

Pattern-reversal VEPs are highly sensitive to demyelinating lesions but are not specific for MS. Box 32A.1 provides a partial list of other causes of abnormal VEPs. VEPs may be helpful in distinguishing hysteria or malingering from blindness. A normal pattern-reversal VEP is strong evidence in favor of psychogenic illness. Rare cases have been reported, however, in which essentially normal VEPs were present in cortical blindness because of bilateral destruction of Brodmann area 17, with preservation of areas 18 and 19, or bilateral occipital infarcts with preservation of area 17 (Epstein, 2000).

Normal Brainstem Auditory Evoked Potentials

Unlike VEPs, which are cortical responses, BAEPs are generated in or caudal to the mesencephalon. BAEPs are characteristically quite resistant to the effects of metabolic disturbances and pharmacological agents. Indeed, in the absence of anatomical lesions, BAEPs persist essentially unchanged into deep coma or in the presence of general anesthesia.

Fig. 32A.23 illustrates a normal BAEP recording. Summated neuronal activities in anatomical structures activated sequentially by the afferent sensory volley produce the components designated by roman numerals. Uncertainty exists regarding the relative contributions to the scalp-recorded BAEP of synaptic potentials occurring in nuclear structures and compound action potentials in fiber tracts. Although the following electroanatomical relationships may be somewhat oversimplified, they are useful for purposes of clinical localization. Wave I, corresponding to N1 of the electrocochleogram, represents the auditory nerve compound action potential, which arises in the distalmost portion of the nerve. The potential represented by wave II is generated mainly in the proximal eighth nerve but probably also includes a contribution from the intraaxial portion of the nerve and perhaps the cochlear nucleus as well. The wave III potential is generated in the lower pons in the region of the superior olive and trapezoid body. The generators of waves IV and V lie in the upper pons and the midbrain, as high as the inferior colliculus. Waves II and IV are inconsistently identified in some normal persons, so clinical interpretation of BAEPs is based primarily on latency measurements of waves I, III, and V. Despite decussation of brainstem auditory pathways at multiple levels, clinical experience indicates that unilateral BAEP abnormalities usually reflect lesions ipsilateral to the stimulated ear.

Fig. 32A.23 Normal brainstem auditory evoked potentials. Major waveform components are labeled with roman numerals and are discussed more fully in the text. M2 is an electrode over the mastoid process ipsilateral to the stimulated ear, in this case the right. Left and right mastoid electrodes are connected to an electrode at the vertex (Cz).

Brainstem Auditory Evoked Potentials in Neurological Disease

Auditory nerve pathology has several effects on the BAEP, related in part to the nature and size of the lesion. Findings range from prolongation of the I-III interpeak interval, to preservation of wave I with distortion or loss of later components, to loss of all BAEP components. Any of these abnormalities occur with acoustic neurinomas and other cerebellopontine angle tumors (Fig. 32A.24). In fact, the BAEP is perhaps the most sensitive screening test for acoustic neurinoma, detecting abnormalities in greater than 90% of the patients. The sensitivity of the test can be extended further by using a range of stimulus intensities and evaluating the effect on components of the BAEP (the latency intensity) (Fig. 32A.25).

Fig. 32A.24 Brainstem auditory evoked potentials recorded in a patient with a left acoustic neurinoma. The I-III interval on that side is prolonged, and the overall response is not as well formed as that from the normal ear.

Fig. 32A.25 Brainstem auditory evoked potential wave V latency plots as a function of increasing stimulus intensity from 20 to 70 dBSL (decibel sound level) in a woman with a left intracanalicular acoustic neurinoma. Brainstem auditory evoked potentials at 70 dBSL are normal bilaterally, but responses at lower intensities are quite asymmetrical, and the response threshold is elevated on the left. Hearing thresholds are expressed in dBnHL, or dB hearing threshold. AD, Auris dextra (right ear); AS, auris sinistra (left ear).

In patients with focal brainstem lesions that impinge on the auditory pathways, the BAEP is abnormal and the type of abnormality reflects the lesion’s location and extent. For example, Fig. 32A.26 illustrates a BAEP recorded in a patient with a brainstem hemorrhage that involved the rostral two-thirds of the pons but spared the caudal third. Waves IV and V are absent, but waves I, II, and III are relatively normal. BAEPs are normal when brainstem lesions do not involve auditory pathways, as is often the case in the locked-in syndrome produced by ventral pontine infarction, or with Wallenberg lateral medullary syndrome. By contrast, pontine gliomas nearly always produce abnormal BAEPs.

Fig. 32A.26 A, Brainstem auditory evoked potentials recorded in a patient with a brainstem hemorrhage sparing the lower third of the pons. Waves I, II, and III are preserved, but later components are lost. B, Coronal section through the pons; A is at the pontomesencephalic border, and B is at the pontomedullary border.

(Reprinted with permission from Chiappa, K.H., 1985. Evoked potentials in clinical medicine, in: Baker, A.B., Baker, L.H. (Eds.), Clinical Neurology. Harper & Row, New York.)

Nearly 50% of patients with definite MS have abnormal BAEP results. Of greater clinical importance, approximately 20% of patients with possible or probable MS have abnormal BAEPs even in the absence of clinical signs or symptoms referable to the brainstem. In such cases, abnormalities usually consist of absence or decreased amplitude of BAEP component waves, most often of waves IV and V, or increased III-V interpeak latency. Occasionally, prolongation of the I-III interpeak interval occurs, probably reflecting involvement of the central myelin that covers the proximal and immediately intraaxial portion of the auditory nerve.

BAEPs may document brainstem involvement in patients with nonfocal neurological disease, especially those affecting myelin, such as metachromatic leukodystrophy and adrenoleukodystrophy. In such diseases, BAEP testing also may show electrophysiological abnormalities in clinically asymptomatic heterozygotes.

BAEPs are useful to assess hearing in young children and in patients otherwise unable to cooperate with standard audiological testing. A latency intensity study, discussed previously, permits characterization of the response threshold for wave V as well as the relationship between wave V latency and stimulus intensity. Such testing allows estimation of hearing threshold and may distinguish between conductive and sensorineural types of hearing impairment. Brainstem audiometry, however, is not really a hearing test per se but rather a measure of the brainstem’s sensitivity to auditory input. The BAEP is normal in the rare patient with deafness due to bilateral cortical lesions. On the other hand, patients with MS or a pontine glioma often have abnormal BAEP results but normal hearing (although their ability to localize sound accurately in space may diminish). One limitation to use of BAEPs to test hearing is that the brainstem must be intact, so that BAEP alterations reflect dysfunction in the peripheral hearing apparatus (Lueders and Terada, 2000).

Normal Median Nerve Somatosensory Evoked Potentials

Fig. 32A.27 shows a normal SEP elicited by median nerve stimulation. The accompanying diagram indicates presumed generator sources for the various components of the SEP. An electrode at the Erb point ipsilateral to the stimulated arm registers the afferent volley as it passes through the brachial plexus. The Erb point potential serves as a reference point against which the latencies of subsequent components are measured. Electrodes over the midcervical dorsal spine record two potentials with independent but partially overlapping waveforms that reflect local activity in the spinal cord. The first of these, designated DCV (for dorsal column volley), is the afferent volley in the cuneate tract. The second, N13, reflects postsynaptic activity in the central gray matter of the cervical cord, generated by input from axon collaterals off the primary large-fiber afferents. A simultaneous potential of opposite polarity (P13) over the anterior neck accompanies the N13. Lesions that disrupt the central gray matter, such as syringomyelia, may selectively affect the N13/P13.

Fig. 32A.27 Presumed generator sources of median nerve somatosensory evoked potentials. Cc and Ci are central-parietal scalp locations contralateral (Cc) and ipsilateral (Ci) to the stimulated nerve. They are 2 cm posterior to the C3 and C4 placements of the International Ten-Twenty System. EP and SC5 are electrodes located over the Erb point and the spinous process of the fifth cervical vertebra, respectively. NC is a noncephalic (such as elbow) reference.

An electrode placed on the scalp away from the primary sensory area best records the SEP components generated in the brainstem. This electrode “sees” subcortical activity that is volume-conducted to the scalp surface. Generation of the P14 is in the cervicomedullary region, probably by the caudal medial lemniscus. Following the P14 is the N18, seen as a long-duration negative wave whose origin is uncertain but probably includes postsynaptic activity from multiple generators in the brainstem. Fig. 32A.28 illustrates preservation of the P14 but loss of the N18 and all later waves in a patient with an arteriovenous malformation of the right pons. This pattern probably is the electrophysiological equivalent of functional transection of the medial lemniscus at a pontine level.

Fig. 32A.28 Left median nerve somatosensory evoked potentials recorded in a patient with a right pontine arteriovenous malformation. All components after P14 (cervicomedullary potential) are absent. Unless otherwise labeled, a right elbow reference was used.

The initial cortical response to the afferent sensory volley is designated N20 and is best recorded by a scalp electrode placed directly over the primary sensory cortex contralateral to the stimulated side. The N20 waveform is a composite made up of signals from multiple generators within or close to the primary cortical receiving area. This can be demonstrated by selective stimulation of cutaneous and muscle-spindle afferent fibers in the median nerve, which are known to project to adjacent but distinct cortical regions, or by observation of state-dependent changes in the N20 (Fig. 32A.29). Sleep, for example, attenuates small inflections that are often present on the waking N20 wave, a phenomenon probably caused by downward modulation of some generators contributing to N20 and to alterations in thalamic input to cortex during sleep.

Fig. 32A.29 Right median nerve somatosensory evoked potentials recorded in a normal subject awake and then asleep after sedation with diazepam. Note the state-dependent change in morphology of the N20. Multiple small inflections present on the rising limb of N20 during wakefulness disappear during sleep.

Normal Posterior Tibial Nerve Somatosensory Evoked Potentials

Somatosensory evoked potentials to posterior tibial nerve stimulation are in many ways analogous to median nerve SEPs. When the posterior tibial nerve is stimulated, recordings from electrodes over the lumbar spine show two distinct potentials (Fig. 32A.30). One of these, PV, is produced by the afferent volley in the lumbar nerve roots and gracile tract, and the other, N22, is a summated synaptic potential generated in the gray matter of the lumbar cord. Because of its stability, fixed latency, and relatively high voltage, the clinical use of the N22 lumbar potential is as a reference point against which latencies of subsequent components are measured. Additionally, determination of the spinal level where N22 voltage is maximal provides an approximate indication of the position of the lumbar cord enlargement. This capability sometimes is clinically useful with suspected spinal cord tethering (Fig. 32A.31).

Fig. 32A.30 Recordings over the lumbar and lower thoracic spinal segments obtained after posterior tibial nerve stimulation. Recording electrodes are referenced to the iliac crest. Note increasing latency of the propagated volley (PV) and the appearance at T12 of a second stationary potential (N22). See text for further details.

Fig. 32A.31 Posterior tibial nerve somatosensory evoked potentials recorded in a patient with a tethered spinal cord. The maximal amplitude of the lumbar potential, normally between T10 and T12, is caudally displaced. The cortical response also is absent. Unless labeled otherwise, an iliac crest reference was used.

Subcortical activity from posterior tibial nerve stimulation consists of P31, seen on the EEG as a positive wave, followed by N34, seen as a long-duration negative wave (Fig. 32A.32). These components are analogous to the P14 and N18 occurring after median nerve stimulation and probably are generated by the afferent volley in the caudal medial lemniscus and by postsynaptic activity in the rostral brainstem, respectively.

Fig. 32A.32 Normal posterior tibial somatosensory evoked potentials. The lower channel is a bipolar recording between two electrodes over the popliteal fossa.

The initial cortical response to posterior tibial nerve stimulation is a prominent positivity (P38) that is recorded from scalp electrodes placed at the vertex and central parasagittal regions, close to the cortical areas representing the leg (see Fig. 32A.32). This positive potential usually is maximal just lateral to the vertex, ipsilateral to the stimulated nerve. This apparently paradoxical localization of the P38 reflects the mesial location of the primary sensory area for the leg and foot within the interhemispherical fissure.

Somatosensory Evoked Potentials in Neurological Disease

Several different conditions that disturb conduction within the somatosensory system produce SEP abnormalities. These include focal lesions (tumors, strokes, cervical spondylosis) and diseases that affect the nervous system more diffusely (hereditary ataxias, subacute combined degeneration, vitamin E deficiency). Up to 90% of patients with definite MS have either upper- or lower-limb SEP abnormalities. Furthermore, an abnormal SEP occurs in 50% to 60% of patients with MS even in the absence of symptoms or signs referable to the large-fiber sensory system. Other diseases that affect myelin (e.g., Pelizaeus-Merzbacher disease, metachromatic leukodystrophy, adrenoleukodystrophy, adrenomyeloneuropathy) also produce SEP abnormalities. With adrenoleukodystrophy and adrenomyeloneuropathy, SEP abnormalities are demonstrable in heterozygotes.

Many lesions alter the SEP by producing a conduction delay or block. This results in prolonged interpeak latencies or in attenuation or even loss of one or more SEP components. Abnormally large SEPs involving exaggeration of cortical components occurring after N20 (from the median nerve) are characteristic of patients with progressive myoclonus epilepsy, some patients with photosensitive epilepsy, and children with late infantile ceroid lipofuscinosis (Fig. 32A.33) (Emerson and Pedley, 2003).

Fig. 32A.33 Recording from central-parietal scalp electrodes obtained after median nerve stimulation in a patient with cortical myoclonus. Marked exaggeration of later cortical components is evident. A noncephalic reference was used in the upper two tracings.

An important application of SEP is as an aid to prognosis in patients resuscitated following cardiopulmonary arrest. In that setting, bilateral absence of the N20 is accurately predictive of a poor neurological outcome (Wijdicks et al., 2006) (Fig. 32A.34).

Fig. 32A.34 Left (A) and right (B) median nerve sensory evoked potentials (SEPs) recorded in a 45-year-old man with a history of a cardiomyopathy, 2 days following cardiopulmonary arrest and resuscitation. Erb point and subcortical (P14, N18) waves are present, but N20 is absent bilaterally (top channel).