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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; intermittent; theta; triphasic wave.
1. FOCAL SLOWING
Focal slowing in the EEG suggests an underlying abnormality but is of nonspecific etiology. 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 slowing. This EEG is from a 36-yr-old man with a right frontal
brain tumor. Note the continuous polymorphic theta and delta activities involving the right hemispheric channels with
relatively preserved normal rhythms over the left.
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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 hyperventilation is a normal finding in children, adolescents, and young adults. Finally, some special 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 pattern 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 frequently 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 background 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 background 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 rhythmicity 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 function, 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 cerebral 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 activity. This tracing is from an 83-yr-old woman with dementia, normal
pressure hydrocephalus, and syncope. Note the bursts of rhythmic delta activity with bi-anterior predominance. There
is also slowing of posterior background rhythms.
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Fig. 3. Continuous generalized slowing. This is from a 73-yr-old man with a several year history of memory loss
and recently increased confusion. Note the slightly irregular, continuous, 5- to 6-Hz activity evident biposteriorly as
well as more diffusely in this tracing.
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neoplastic processes, dementing illnesses, and even in multifocal conditions, such as multifocal, bihemispheric vascular insults. Indeed, because EEG offers relatively poor spatial resolution, 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 symmetric, 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 consciousness 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 assessment 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. Triphasic waves. This is derived from the EEG of a 46-yr-old man with hepatic encephalopathy. Note the
bi-anteriorly predominant waveforms with triphasic morphology. There are no clear phase reversals or embedded
sharp elements, and a subtle phase lag is evident along the anterior–posterior axis of the tracing.
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Fig. 5. Nonconvulsive status epilepticus. This tracing is from a 13-yr-old boy with absence epilepsy and a new prolonged
confusional state. Note the incessant, bisynchronous, very high amplitude 3-Hz spike-and-wave pattern. The patient was
quite confused, but could repeat if reminded to do so. This indicates absence status epilepticus.
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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 cerebral 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 precipitants 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 unreactive 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 clinical 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 woman was recorded while undergoing induction with general anesthesia for
vascular surgery. Bursts of bilaterally synchronous, higher amplitude mixed frequencies occur lasting 1 to 2 s, punctuated
by periods of relative 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 intensive care unit, partly sedated,
in coma. He was unreactive to noxious stimulation. Note the diffuse and fairly continuous 9- to 9.5-Hz activities, with reversal of the usual anterior–posterior voltage gradient. This activity failed to vary with attempts to arouse the patient.
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Fig. 8. Electrocerebral inactivity. This record is from a 66-yr-old man after a cardiopulmonary arrest. Note that the
sensitivity is at 2 µV/mm and “double distance” electrode comparisons are in use. The record is dominated by amplified ECG-derived artifact. No convincing brain-derived rhythms are seen.
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Table 1
EEG Criteria for Electrocerebral Inactivity
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
A minimum of eight scalp electrodes should be used
Interelectrode impedances should be less than 10,000 Ω but more than 100 Ω
The integrity of the entire recording system must be verified
Interelectrode distances should be at least 10 cm
The sensitivity should be at least 2 µV/mm for at least 30 min of recording
Appropriate filter settings should be used
Additional monitoring techniques should be used when necessary
There should be no EEG reactivity to afferent stimulation
The recording should be made by a qualified technician
A repeat EEG should be performed if there is doubt regarding the presence of electrocerebral
inactivity
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.
Lüders 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.
2.
3.
4.
5.
6.
What are the two main characteristics of slowing? What is their significance?
What is the significance of focal, arrhythmic polymorphic slowing?
What is the significance of focal, rhythmic monomorphic slowing?
What is IRDA and when is it encountered?
What are triphasic waves and when are they most commonly encountered?
How does the reactivity of an EEG in coma speak to the depth of coma?
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7.
8.
9.
10.
Donnelly and Blum
How is the EEG beneficial in epileptic stupor, that is, nonconvulsive status epilepticus?
What do burst suppression patterns signify?
When is alpha coma encountered and what is its significance?
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 posteriorly 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 environmental 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 invaluable 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 anesthesia or in barbiturate coma for status epilepticus, among others. Thus, it may have a good prognosis 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.