9 Focal and Generalized Slowing, Coma, and Brain Death

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Focal and Generalized Slowing, Coma, and Brain Death

Edward M. Donnelly and Andrew S. Blum

Summary

This chapter addresses the related topics of focal and generalized slowing, coma, and brain death.

These EEG abnormalities are encountered in a wide range of clinical situations of variable severity.

Focal and generalized slowing are both common and highly nonspecific findings in the EEG laboratory.

Despite their lack of etiological specificity, EEG slowing and related patterns often bear important implications for both the location of CNS abnormalities and/or the prognosis for neurological recovery.

Key Words: Burst suppression; continuous; delta; diffuse; electrocerebral inactivity; focal; intermit- tent; theta; triphasic wave.

1. FOCAL SLOWING

Focal slowing in the EEG suggests an underlying abnormality but is of nonspecific etiol- ogy. It may reflect structural (i.e., tumor or infarct) or functional (i.e., postictal or migraine) abnormalities. There exist two spectra of severity, one pertaining to frequency, with slower rhythms representing more severe lesions, and one pertaining to persistence, with continuous slowing a more significant abnormality than intermittent slowing. An interhemispheric frequency difference of less than 1 Hz is not considered significant.

Continuous slowing in the EEG, whether focal or generalized, tends to take the appearance of either rhythmic monomorphic or arrhythmic polymorphic waveforms. These patterns often have differing significance. Continuous focal arrhythmic polymorphic slowing (Fig. 1) usually suggests some type of structural lesion in the underlying subcortical white matter. Abscesses, ischemic strokes, tumors, contusions, and so on, all may produce this pattern. The mechanism for this form of slowing may reflect disordered intracortical connectivity. Even transient functional disturbances, such as migraine and the postictal state, can be responsible. This illustrates the value of follow-up EEGs looking for evolution or resolution of any focal slowing that may be present. Rarely, focal slowing (and even focal seizures) can suggest toxic–metabolic disturbances, especially in hypoglycemic and hyperglycemic states. Continuous focal rhythmic monomorphic slowing, by contrast, is more commonly associated with underlying gray matter lesions. Note that focal cortical lesions are more likely to produce focal voltage attenuation or epileptiform abnormalities rather than focal slowing. Focal rhythmic monomorphic slow activity can also be intermittent. This is a less common pattern. The manner of appearance should be considered. Recurrent bursts of paroxysmal focal slowing may raise

From: The Clinical Neurophysiology Primer

Edited by: A. S. Blum and S. B. Rutkove © Humana Press Inc., Totowa, NJ

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Fig . 1. Continuous focal arrhythmic polymorphic slo wing. This EEG is from a 36-yr -old man with a right frontal brain tumor . Note the continuous polymorphic theta and delta acti vities in v olving the right hemispheric channels with relati v ely preserv ed normal rhythms o v er the left.

a suspicion for an underlying epileptogenic focus. A seizure focus is also suggested when the focal slowing shows exceptional rhythmicity or frequency evolution, that is, rhythmic slow waves that speed up and slow down. The location of focal intermittent rhythmic slowing may be significant. For example, if observed in the temporal regions, that is, temporal intermittent rhythmic delta, an underlying epileptogenic focus is more likely.

2. GENERALIZED SLOWING

In discussing generalized slowing of the EEG, several qualifiers must be mentioned. Is the slowing intermittent or continuous? Is it rhythmic–monomorphic or arrhythmic–polymorphic?

In what context does it occur? For example, a buildup of generalized slowing during hyper- ventilation is a normal finding in children, adolescents, and young adults. Finally, some spe- cial examples will be considered.

Intermittent rhythmic delta activity (IRDA) tends to be monomorphic and is a commonly observed EEG abnormality. It is usually diffuse, bisynchronous, monomorphic, and reactive to eye opening. Hyperventilation may activate the pattern and sleep may attenuate it.

Commonly, there is bianterior predominance to the slowing, hence, the term frontal IRDA (FIRDA) (Fig. 2). Note that children and adolescents often show a biposterior predominant IRDA and, thus, the term occipital IRDA activity has been applied.

IRDA is thought to be a projected rhythm and may reflect diffuse gray matter dysfunction, either cortical or subcortical. Acute or subacute disturbances are more likely to produce this pattern than chronic encephalopathies. FIRDA suggests a changing or evolving underlying disturbance— an encephalopathy that is either worsening or improving. Toxic–metabolic encephalopathies or electrolyte disturbances are typical underlying etiologies. Rarely, this pat- tern may accompany a postictal state. Eye blink or glossokinetic artifact should be excluded because they are common FIRDA imitators.

Continuous generalized slowing (Fig. 3) is an extremely common pattern, distinct from the intermittent rhythmic pattern described in the preceding paragraphs, although they may fre- quently appear together within the same tracing. Continuous slow patterns may refer solely to slowing of the posterior waking background rhythm. This observation usually implies a type of diffuse encephalopathy. In adults, a commonly used lower limit of normal for the waking back- ground rhythm is 8 Hz. Varying degrees of background slowing may be encountered, including delta and theta frequencies. The degree of slowing of the posterior waking background rhythm is thought to correlate with the degree of clinical cerebral disturbance. As the encephalopathy deepens, other features may accrue in addition to progressive slowing of the posterior back- ground rhythm. These include slowing of anterior rhythms; the normal frontal beta activity may slow to reveal varying degrees of frontal alpha or theta frequencies. In addition, the overall rhyth- micity of the tracing wanes in conjunction with progressive deepening of encephalopathic states.

In more marked encephalopathies, the entire tracing may become dominated by polymorphic slow forms, particularly delta activities, with much less of the reactivity and organization observed in the normal tracing. Owing to its fidelity as a surrogate marker of current CNS func- tion, serial EEGs may be valuable to monitor the course of an acute or subacute encephalopathy.

Despite the helpful correlation between the degree of EEG slowing and the degree of cere- bral dysfunction, there is no specificity to the observation of continuous slowing. It may be observed equally in static encephalopathies or in those of acute or subacute natures.

Continuous diffuse slowing may arise in the setting of any diffuse CNS insult, including head

trauma, hypoxic–ischemic injury, toxic or metabolic derangement, diffuse CNS infectious or

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Fig . 2. Frontal intermittent rhythmic delta acti vity . This tracing is from an 83-yr -old w oman with dementia, normal pressure hydrocephalus, and syncope. Note the b ursts of rhythmic delta acti vity with bi-anterior predominance. There is also slo w ing of posterior background rhythms.

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Fig . 3. Continuous generalized slo wing. This is from a 73-yr -old man with a se v eral year history of memory loss and recently increased confusion. Note the slightly irre gular , continuous, 5- to 6-Hz acti vity e vident biposteriorly as well as more dif fusely in this tracing.

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neoplastic processes, dementing illnesses, and even in multifocal conditions, such as multifo- cal, bihemispheric vascular insults. Indeed, because EEG offers relatively poor spatial resolu- tion, as vascular events accrue in the CNS, the tracing may lose its focal/multifocal quality and may appear diffusely slow. Likewise, focal abnormalities may have less distinctive EEG signatures amid the diffuse slowing caused by an encephalopathy; focal details are lost. It is also important to remember that generalized slowing is a normal feature of the drowsy or sleep tracing. One must take stock of the patient’s state when interpreting whether the observed slowing is pathological or merely reflective of state.

Triphasic waves (Fig. 4) represent a special type of generalized continuous slowing. The key features that distinguish triphasic waves from other forms of slowing include their typical triphasic morphology and a phase lag. The waves themselves are usually medium- to high-voltage slow waves occurring at a frequency of 1.5 to 2.5 Hz. They typically occur in a bilaterally sym- metric, bisynchronous fashion. Although they may wax and wane somewhat in amplitude and frequency during the recording, they tend to exhibit a somewhat monotonous appearance.

Triphasic waves usually show a phase lag of 25 to 140 ms across the anterior–posterior axis. This phase lag is more commonly observed in an anterior-to-posterior direction than vice versa.

Triphasic waves suggest a toxic–metabolic encephalopathy, most commonly a hepatic encephalopathy. However, this pattern is not specific for hepatic encephalopathy. Triphasic waves can also be observed in other metabolic disorders, such as uremia, hyperthyroidism, hypercalcemia, hypoglycemia, hyponatremia, and lithium intoxication. Alzheimer’s disease and other dementias; prion diseases; structural pathologies, such as stroke and subdural hematoma; and cerebral carcinomatosis can also demonstrate this pattern. Triphasic waves may be quite difficult to differentiate from triphasic-appearing epileptiform morphologies, blunted sharp and slow wave complexes. This is even more problematic because both may equally occur in similar clinical settings, such as in uremic encephalopathy.

3. COMA

Coma refers to a clinical state in which a person exhibits a decreased level of conscious- ness with eyes closed and no purposeful responses to applied stimuli. Just as in milder encephalopathic conditions, the depth of the coma is paralleled by helpful EEG findings. In lighter forms of coma, the EEG may show some responsivity to stimuli with higher voltage and more prominent slowing. As the coma deepens, a blocking type response ensues, in which stimuli produce a voltage drop and attenuation of background activity. Finally, in deeper coma, the EEG becomes unreactive to patient stimulation.

Causes of coma are many and may include toxic–metabolic or hypoxic–ischemic encephalopathies as well as supratentorial or infratentorial structural pathologies. The EEG in coma may show several possible patterns, some of which can help identify etiology and some of which may have prognostic implications.

When coma is caused by nonconvulsive status epilepticus (Fig. 5), the EEG can be

extremely helpful because it not only quickly establishes etiology, but may also permit assess-

ment of subsequent anticonvulsant treatment efficacy. In no other instance is the specificity of

the EEG in coma higher than in nonconvulsive status epilepticus. Keep in mind, however, that

although the EEG may identify the cause of coma as an epileptic encephalopathy, there may

be an as yet unidentified disturbance acting as a precipitant, for instance, hypoxic–ischemic

encephalopathy, uremia, stroke, and so on. The EEG provides an immediate assessment of

treatment efficacy in abolishing the epileptiform activity.

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Fig . 4. T riphasic w av es. This is deri v ed from the EEG of a 46-yr -old man with hepatic encephalopathy . Note the bi-anteriorly predominant w av eforms with triphasic morphology . There are no clear phase re v ersals or embedded sharp elements, and a subtle phase lag is e vident along the anterior–posterior axis of the tracing.

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Fig . 5. Noncon vulsi v e status epilepticus. This tracing is from a 13-yr -old bo y with absence epilepsy and a ne w prolonged confusional state. Note the incessant, bisynchronous, v ery high amplitude 3-Hz spik e-and-w av e pattern. The patient w as quite confused, b ut could repeat if reminded to do so. This indicates absence status epilepticus.

Focal slowing in the EEG of a comatose patient may suggest a structural cause, such as a supratentorial structural lesion. Such lesions often produce coma in the setting of various cere- bral herniation syndromes via mechanical compression of pontomesencephalic tegmental zones important in “alerting” the cortex and permitting wakefulness.

Generalized burst suppression (Fig. 6) is another common EEG pattern observed in coma.

The bursts occur in a quasi-periodic fashion and may contain admixed sharp and/or spike and slow waves. Myoclonic jerks can accompany the bursting. Asynchronous bursting may reflect disordered interhemispheric cortical connectivity. Asymmetric burst voltage often signifies asymmetric cortical injury and/or raises the suspicion of a breach effect or an overlying fluid collection. The quasi-periodic bursts and suppressive intervals vary in duration with the depth of the coma. As the coma deepens, the bursts of activity become shorter and more infrequent and the suppressive intervals widen. This pattern reflects an exceptionally profound level of depressed consciousness. It is often observed during induction of general anesthesia. It is also the desired EEG pattern during administration of barbiturate therapy for refractory status epilepticus or to help control increased intracranial pressure after traumatic brain injury.

Burst suppression suggests a poor prognosis, depending on the etiology. In the setting of a toxin- or medication-induced coma, the prognosis may be far better than in hypoxic–ischemic injury or trauma, in which burst suppression patterns may suggest a poor outcome.

Monotonous monorhythmic patterns can also be observed in the EEG of a comatose patient.

Persistent, diffuse 8- to 12-Hz activity in a comatose patient is known as alpha coma (Fig. 7).

This pattern, at first glance, may resemble normal background activity. However, the 8- to 12-Hz activity appears diffusely, not over posterior head regions, as in the normal waking background rhythm. Additionally, the pattern is completely unreactive to exogenous stimuli. Typical precip- itants of alpha coma include brainstem lesions and hypoxic–ischemic mechanisms. It may also be observed as an ante mortem pattern as the patient progresses from burst suppression to electrocerebral inactivity (ECI). Alpha coma is, thus, thought to imply a very poor prognosis, particularly in the setting of anoxic injury. However, rare case reports have shown neurological recovery from this EEG pattern. Beta coma, theta coma, and delta coma are less common unre- active monomorphic EEG patterns whose prognostic significance is less clear.

Comatose patients can exhibit an EEG that seems to show features of normal sleep.

Spindles, vertex waves, and K-complexes can be observed with cyclic variability. The EEG is distinguishable from normal sleep, however, because the patient is unarousable and the EEG does not react to applied stimuli. This pattern is sometimes referred to as spindle coma.

These features associated with the EEG of sleep may disappear as the coma deepens.

Cheyne–Stokes respirations in a comatose patient may have a specific EEG correlate. An alternating pattern consisting of low-voltage irregular periods followed by higher-voltage slowing mirrors the respiratory rhythm changes. The cyclic alternating pattern may represent the effects of a cortical release phenomenon on the pacemaker function of the brainstem arousal system.

4. BRAIN DEATH

Brain death is a clinical diagnosis made when there is no evidence of brainstem function on

successive neurological exams. Protocols for declaring brain death vary among institutions and

according to the age of the patient. The EEG is one of several tests that can help confirm the

diagnosis. Complete absence of brain-derived rhythms, ECI (Fig. 8), can help confirm the clin-

ical diagnosis of brain death. Electrocardiogram and respirator derived artifacts are often all that

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Fig . 6. Burst suppression. This 49-yr -old w oman w as recorded while under going induction with general anesthesia for v ascular sur gery . Bursts of bilaterally synchronous, higher amplitude mix ed frequencies occur lasting 1 to 2 s, punctuated by periods of relati v e attenuation lasting 3 to 4 s.

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Fig . 7. Alpha coma. This recording is of a 59-yr -old man on a respirator in the medical intensi v e care unit, partly sedated, in coma. He w as unreacti v e to noxious stimulation. Note the dif fuse and f airly continuous 9- to 9.5-Hz acti vities, with re v er- sal of the usual anterior–posterior v oltage gradient. This acti vity f ailed to v ary with attempts to arouse the patient.

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Fig . 8. Electrocerebral inacti vity . This record is from a 66-yr -old man after a cardiopulmonary arrest. Note that the sensiti vity is at 2 µ V/mm and “double distance” electrode comparisons are in use. The record is dominated by ampli- fied ECG-deri v ed artif act. No con vincing brain-deri v ed rhythms are seen.

are observed in ECI. Several technical requirements must be met to ensure the validity of the finding. The American Electroencephalographic Society has published technical criteria that must be met before an EEG can be considered to fulfill ECI (Table 1).

One technicality deserving special mention is the diagnosis of brain death in infants and children. Persistence of the EEG ECI pattern must be documented in these age groups. For infants younger than 2 mo of age, two EEGs showing ECI must be obtained, separated by 48 h. For infants between 2 and 12 mo of age, the two EEGs showing ECI must be separated by 24 h.

Of course, administration of sedative–hypnotic medications, for instance, barbiturates and benzodiazepines, negates the ability of the EEG to speak to brain death because the observed findings could be attributed to reversible, medication-induced effects. Variable requirements exist for the duration of time necessary since the last administration of sedative medication before the EEG can support the diagnosis of brain death. Other potential confounders of ECI must be excluded, such as hypothermia, hypotension, and severe electrolyte and glucose abnormalities, among others.

SUGGESTED READING

Bennett DR, Hughes JR, Korein J, Merlis JK, Suter C. Atlas of Electroencephalography in Coma and Cerebral Death: EEG at the Bedside or in the Intensive Care Unit. Raven, New York, NY, 1976.

Daly DD, Pedley TA. Current Practice of Clinical Electroencephalography, 2nd ed. Raven, New York, NY, 1990.

Lü ders HO, Noachtar S. Atlas and Classification of Electroencephalography, 1st ed. WB Saunders, Philadelphia, PA, 2000.

Niedermeyer E. Electroencephalography: Basic Principles, Clinical Applications and Related Fields, 5th ed. Williams and Wilkins, Baltimore, MD, 2004.

Spehlman R. EEG Primer, 2nd ed. Elsevier, Amsterdam, Holland, 1991.

REVIEW QUESTIONS

1. What are the two main characteristics of slowing? What is their significance?

2. What is the significance of focal, arrhythmic polymorphic slowing?

3. What is the significance of focal, rhythmic monomorphic slowing?

4. What is IRDA and when is it encountered?

5. What are triphasic waves and when are they most commonly encountered?

6. How does the reactivity of an EEG in coma speak to the depth of coma?

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Table 1

EEG Criteria for Electrocerebral Inactivity

1. A minimum of eight scalp electrodes should be used

2. Interelectrode impedances should be less than 10,000 Ω but more than 100 Ω 3. The integrity of the entire recording system must be verified

4. Interelectrode distances should be at least 10 cm

5. The sensitivity should be at least 2 µV/mm for at least 30 min of recording 6. Appropriate filter settings should be used

7. Additional monitoring techniques should be used when necessary 8. There should be no EEG reactivity to afferent stimulation 9. The recording should be made by a qualified technician

10. A repeat EEG should be performed if there is doubt regarding the presence of electrocerebral

inactivity

7. How is the EEG beneficial in epileptic stupor, that is, nonconvulsive status epilepticus?

8. What do burst suppression patterns signify?

9. When is alpha coma encountered and what is its significance?

10. What are some technical criteria for recording ECI?

REVIEW ANSWERS

1. The frequency of the observed slowing and its persistence are two important characteristics. In general, the slower the recorded rhythms, the more severe the lesion. Additionally, in general, the more persistent the slowing, the more severe the process.

2. Focal, arrhythmic polymorphic slowing usually implies a focal subcortical white matter lesion.

However, it is nonspecific to etiology.

3. Focal, rhythmic monomorphic slowing usually suggests a lesion of the underlying gray matter.

However, when such a pattern becomes notably repetitively paroxysmal and burst-like, one should also entertain the possibility of a focal epileptic process.

4. IRDA usually signifies an acute or subacute process leading to diffuse cortical or subcortical gray matter dysfunction. It is usually bianteriorly predominant, that is, FIRDA, but may be pos- teriorly maximal in childhood and adolescence, that is, occipital IRDA.

5. Triphasic waves are broad waveforms with characteristic triphasic morphology. They are usually diffusely represented and bilaterally synchronous, at 1.5 to 2.5 Hz. Often, they exhibit a helpful phase lag across the anterior–posterior axis. They mainly occur in metabolic encephalopathies, usually in hepatic insufficiency, but are not exclusive to hepatic disease states.

6. As comatose states become deeper, the EEG becomes progressively less reactive to environmen- tal stimuli. Lighter comas may still show some reactivity, even when this is clinically unapparent.

7. The EEG is critical to making the diagnosis of nonconvulsive status epilepticus. It is also invalu- able in assessing the progress of therapeutic interventions in this setting.

8. Burst suppression is observed in many comatose states. As the periods of voltage suppression become longer, the coma becomes deeper. This pattern may be iatrogenic as in general anesthe- sia or in barbiturate coma for status epilepticus, among others. Thus, it may have a good prog- nosis in intoxications, but may carry a poor prognosis in other etiologies, for instance, hypoxic–ischemic insults.

9. Alpha coma is denoted by widespread alpha activity that is unreactive to applied stimuli. It implies a poor prognosis in most instances, although when associated with medication related coma, recovery may occur.

10. The criteria for ECI include a minimum of eight leads, 10-cm interelectrode distances or greater, sensitivity set to 2 µV/mm for at least 30 min of recording, among others (Table 1). In children, a repeat tracing may be necessary.

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