The EEG in metabolic encephalopathy and coma.

Excellent early work on stupor and coma can be found (particularly with regard to anoxia) in the work of Fischgold and Mathis (1959) in France, and Pamela Prior in England (1973a). These workers correlated deepening levels of coma with particular EEG patterns, and the suppression of EEG reactivity. Alpha frequency patterns in coma (alpha coma), spindle-like sleep patterns in coma (spindle coma) and "triphasic waves" are among the wide variety of endocrine disorders discussed in case reports and series leading to identification of particular EEG patterns. EEG correlations with prognosis are most reliable with cardiorespiratory arrest (CRA) with its consequent anoxic-ischemic insult. If etiology is known, EEG can often be a reliable predictor of outcome. EEG usually has little specificity with regards to etiology, but some patterns do favor particular diagnoses: for example, triphasic waves (TWs) are frequently seen with hepatic and renal insufficiency in young adults; spindle coma patterns are believed to indicate dysfunction at the brainstem level (Chatrian, 1990). EEG is most useful in differentiating organic from psychiatric conditions, in excluding nonconvulsive status epilepticus (NCSE), and in providing a rough guide as to the degree of cortical and subcortical dysfunction.     

Short- and long-term prognostic value of the electroencephalogram in children with severe head injury

To determine the prognostic value of the EEG in severely head-injured children, 24 patients were studied for 8-36 months. During coma, 4 EEG patterns were found: borderline, sleep-like, changeable and slow monotonous (SM). For the short-term prognosis, we conclude that the SM pattern (12/24 patients) indicates a bad prognosis because it was associated with a longer coma and awakening period than that of other EEG patterns and because it was observed in the 3 patients who died from brain injury. In contrast, we describe a 'prewake' pattern (11/22 survivors) which, when it occurs, always announces the onset of a complete awakening. For the long-term prognosis, only 50% of the survivors who had an SM pattern during coma have as good an intellectual and motor outcome as the survivors who displayed other EEG patterns. No other EEG features recorded during coma have short- or long-term prognostic significance.     

"Theta pattern coma" occurring in younger adults

Since our previous report, where "theta pattern coma" was described in 2 elderly patients as an EEG pattern with a grave prognosis, we have had the opportunity to see another 9 affected patients. In this article, 3 men with a mean age of 36 years who died after cardiorespiratory arrest presented a "theta coma pattern." The EEG activity was initially reactive to and attenuated by external stimulation in 2, but prior to death the pattern became arreactive. This article shows that "theta pattern coma" is not an age related phenomenon as previously considered. So far, 11 patients with this type of EEG abnormality have been seen in our department; all have died, and all were over 30 years of age. An expanded definition of "theta pattern coma" is given in the discussion. The pathophysiological mechanisms involved in generation of this abnormality are not known. This abnormality, when seen in the unconscious patient, should be classified as a grade 4 abnormality on the EEG coma scale and should be differentiated from rather diffuse theta activity in coma. The prognostic significance of "theta pattern coma" appears to be similar to that of "alpha pattern coma."     

The clinical significance of EEG cyclic alternating pattern during coma.

To define the clinical significance of EEG "cyclic alternating pattern" (ECAP). ECAP is the periodic presence of a high-voltage slow waves alternating with low voltage irregular faster activity. This term was first described in comatose patients in 1944. It has been less recognized and may be underreported since then. The clinical significance of ECAP in the state of coma remains unknown. We reviewed our prospective EEG database for consecutive patients studied over a period of 4 years (n = 4,819) looking for patterns consistent with ECAP. We reviewed the charts of the patients with the above EEG pattern to define the clinical setting and the eventual outcome. Eleven patients were identified. All patients identified were found to be in the coma state at the time of the EEG. The majority of patients (n = 10) survived the coma, and half returned to the community in good functional status. ECAP is seen rarely in comatose patients. Regardless of the cause of the coma, the presence of ECAP carries an overall good prognosis for both survival and recovery.     

Physiologic and prognostic significance of "alpha coma".

A patient with posthypoxic "alpha coma" is described whose EEGs were recorded before coma, within two hours following the onset of coma and after recovery. The differences observed between the alpha activity during coma and that seen before and after suggest that the alpha activity during coma and the physiologic alpha rhythm are different phenomena. This case, as well as others reported, also suggests that "alpha coma" resolving in the first 24 hours following hypoxia may have a better prognosis than "alpha coma" detected after the first day, and stresses the need for EEG monitoring begun in the immediate period following hypoxia in order to assess accurately the prognostic significance of this EEG pattern in the early stages of postanoxic encephalopathy. The aetiology of "alpha coma" also affects outcome. The survival rate appears higher in patients with respiratory arrest than in those with combined cardiopulmonary arrest.     

Prognostically important EEG coma patterns in diffuse anoxic and traumatic encephalopathies in adults

Because of the paucity in the English literature of a detailed and universally accepted EEG grading scale relating to survival after diffuse traumatic and anoxic brain insults, prognostically oriented EEG patterns including recently described abnormalities are presented and discussed. The significance of these patterns may also apply in cases of coma of other etiologies, which can present morphologically similar features. EEG patterns have been classified into five major grades based on an internationally accepted scale. Individual patterns have been more clearly defined on the basis of the morphology of dominant activities, their distribution, persistence, and reactivity to external stimulation. Favorable outcome with survival seems to occur with both grade 1 and the "reactive type" of grade 2 abnormalities, with preservation of normal sleep features, and with frontal monorhythmic delta activity. Prognostically uncertain patterns are "nonreactive" grade 2 abnormalities, diffuse delta activity with grade 3 abnormality, and the "reactive type of alpha pattern coma." The following patterns are suggested to be prognostically malignant if persistent: grade 3 abnormality with small amplitude, diffuse, irregular delta activity; grade 4 ("burst suppression pattern"), in particular when epileptiform discharges are present and with "low-output EEG"; and grade 5 ("isoelectric EEG"). Fatal outcome is also common with the "nonreactive type of alpha pattern coma" and the recently reported "theta pattern coma." These patterns are presented in the illustrations. It is intended that this more detailed subdivision will promote understanding between electroencephalographers using visual EEG assessment in cases of coma.     

Electroencephalographic findings in coma caused by fatal chloroquine poisoning

A 19-year-old patient in deep anoxic coma after cardiopulmonary arrest due to suicidal acute overdosage of chloroquine was resuscitated at the intensive care unit. An EEG starting about 12 hours later and lasting for 93 minutes showed a rapid succession of diffuse ectopic rhythms, diffuse slow output, generalized periodic slow waves in paroxysmal episodes which preceded burst suppression patterns and definite establishment of electrocerebral silence. All these EEG patterns indicating a poor prognosis were registered about three hours before the patient died during irreversible ventricular fibrillation.     

The electroencephalogram in altered states of consciousness

The EEG can be very helpful in the evaluation of patients with altered states of consciousness. Diffuse slowing of background rhythms and the presence of triphasic waves suggests metabolic dysfunction, particularly hepatic. Generalized fast activity may be seen in patients with a drug intoxication. Abnormalities, such as PLEDs or focal continual PDA, support a diagnosis of supratentorial lesion, whereas a normal appearing EEG in a comatose patient suggests a brain-stem lesion. In addition, the EEG may reveal that the alteration in consciousness is due to continual epileptic activity without motor manifestations (nonconvulsive status) that had not been suspected. As indicated, certain patterns have prognostic implications. However, as these patterns are not specific for a single etiology, the EEG is of most help when the cause is known. For example, burst suppression or a diffuse alpha pattern coma can be seen in either hypoxia or a drug intoxication. With hypoxia, these patterns carry an extremely poor prognosis for useful recovery, whereas complete recovery is often seen in cases secondary to drug ingestion. As a more extreme example, a patient whose EEG shows ECS secondary to drug intoxication may recover but will not if the ECS is due to hypoxia or severe head trauma. If the etiology of the encephalopathy is unknown, then sequential records are needed for prognosis.     

EEG in the prognosis of toxic coma: reflections apropos of unusual data

During acute intoxications, the first EEG may show persistence or abolition of cerebral activity, but the possibility of recovery after isoelectric tracing in toxic comas must be emphasized. EEG patterns frequently suggest the probability of hypnotic tranquilizer poisoning; 4 types of EEG are encountered corresponding to different grades of toxic coma. Recurrent periods of electrical silence alternating with bursts of activity are habitually recorded in carus comas with hypothermia due to acute barbiturate intoxication, with good prognosis. The possibility of a neurological disturbance associated with drug overdose must be raised whenever an asymmetric tracing is encountered. Serial recordings may detect complications such as: a localized lesion, anoxia or, very rarely, typical paroxysmal abnormalities reappearing in comitial patients before emergence from a toxic coma. Paradoxical monomorphic delta activity corresponding to improvement must not be considered as an aggravation. Peculiar EEG findings occur after oral trichlorethylene poisoning, with temporary clinical deterioration and intermittent periods of electrical silence; recovery is possible. An alpha-like pattern after cardiac arrest of toxic origin has a poor prognosis. The appearance of alternating patterns suggests the development of irreversible brain damage.     

Nonconvulsive status epilepticus and coma

Nonconvulsive status epilepticus (NCSE) in a comatose patient cannot be diagnosed without electroencephalography (EEG). In many advanced coma stages, the EEG exhibits continuous or periodic EEG abnormalities, but their causal role in coma remains unclear in many cases. To date there is no consensus on whether to treat NCSE in a comatose patient in order to improve the outcome or to retract from treatment, as these EEG patterns might reflect the end stages of a dying brain. On the basis of EEG, NCSE in comatose patients may be classified as generalized or lateralized. This review aims to summarize the ongoing debate of NCSE and coma and to critically reassess the available literature on coma with epileptiform EEG pattern and its prognostic and therapeutic implications. The authors suggest distinguishing NCSE proper and comatose NCSE, which includes coma with continuous lateralized discharges or generalized epileptiform discharges (coma‐LED, coma‐GED). Although NCSE proper is accompanied by clinical symptoms suggestive of status epilepticus and mild impairment of consciousness, such as in absence status or complex focal status epilepticus, coma‐LED and coma‐GED represent deep coma of various etiology without any clinical motor signs of status epilepticus but with characteristic epileptiform EEG pattern. Hence coma‐LED and coma‐GED can be diagnosed with EEG only. Subtle or stuporous status epilepticus and epilepsia partialis continua–like symptoms in severe acute central nervous system (CNS) disorders represent the borderland in this biologic continuum between NCSE proper and comatose NCSE (coma‐LED/GED). This pragmatic differentiation could act as a starting point to solve terminologic and factual confusion.     

Clinical neurophysiologic monitoring and brain injury from cardiac arrest

Electrophysiologic testing continues to play an important role in injury stratification and prognostication in patients who are comatose after cardiac arrest. As discussed previously, however, the adage about treating whole patients, not just the numbers, is relevant in this situation. EEG and SSEP can offer high specificity for discerning poor prognosis as long as they are applied to appropriate patient populations. As discussed previously, EEG and SSEP patterns change during the first hours to days after cardiac arrest and negative prognostic information should not be based solely on studies performed during the first 24 hours. Both electrophysiologic techniques also are susceptible to artifacts that may worsen the electrical patterns artificially and suggest a falsely poor prognosis. EEG is suppressed by anesthetic agents and hypothermia, both of which may produce ECS and burst suppression. Patients who experience respiratory arrest from a toxic ingestion of narcotics or barbiturates, in particular, may present with high-grade EEG patterns initially. Many patients also receive anesthetic medications at the time of tracheal intubation, which may linger beyond their normal half-life in patients who have hepatic or renal insufficiency or concurrent use of interacting medications. SSEP is much less susceptible to sedative anesthetic agents, but hypothermia is demonstrated to prolong evoked potential latencies. As therapeutic hypothermia becomes more common after cardiac arrest, the effect of temperature on electrophysiologic testing needs to be taken into account. The publications discussed previously also emphasize the need to adjust the prognostic value of electro-physiologic tests to the pretest probability of meaningful neurologic recovery in individual patients. Clearly, grade I EEG patterns and normal N20 potentials indicate a much better prognosis in patients who have a short du-ration of cardiac arrest, short duration of coma after resuscitation, and when the studies are performed within the first few days. In patients who remain in coma days after resuscitation and lack appropriate brainstem reflexes, however, even the most normal appearing electrophysiologic patterns do little to change the overall prognosis. Aside from prognostication, electrophysiologic testing holds great promise in defining the basic anatomy and physiology of coma emergence after cardiac arrest. In addition, quantitative EEG and automated evoked potentials have the potential to render these tools less subjective and arcane and more applicable for monitoring patients in the period during and immediately after resuscitation. Quantitative EEG also has great potential asa tool to define the time window for neuroprotective intervention and the means to track the response to such therapies in real time.     

Unusual EEG patterns in coma, and their evolution.

A 23-year-old chronic asthmatic patient is reported who showed successively four different EEG patterns within a 7 day period of unconsciousness following cardio-respiratory arrest. The initial record was dominated by alpha activity, then beta activity supervened, to be followed by spindle components. Finally an isoelectric tracing occurred before death. A computer file search for all cases of unusual EEG coma patterns was carried out. It failed to reveal any other patient with a similar sequence, but various types of evolution were noted. Such features are seen in only a very small percentage of comatose patients, and in the context of cardio-respiratory arrest are almost invariably fatal.     

EEG monitoring in the intensive care unit

EEG recording in the intensive care setting presents a number of technical challenges. It is essential to differentiate artifact from pathophysiologic EEG changes that would suggest encephalopathy, epileptiform activity, or seizures. There are particular patterns typical of deepening encephalopathy, as well as, coma patterns that have diagnostic and prognostic significance (e.g., spindle coma, alpha coma, burst suppression activity, and triphasic waves). Epileptiform patterns, including periodic lateralized epileptiform discharges (PLEDs), bilateral independent periodic lateralized epileptiform discharges (BIPLEDs), and generalized periodic epileptiform discharges (GPEDs), present particular challenges as there is a gray-zone between interictal patterns and the evolving (usually faster) patterns of nonconvulsive seizures. Accurate use of EEG in the intensive care unit requires optimal EEG technical expertise in performing the study, and appropriate interpretation by a trained electrophysiologist.     

Which EEG patterns in coma are nonconvulsive status epilepticus?

Nonconvulsive status epilepticus (NCSE) is common in patients with coma with a prevalence between 5% and 48%. Patients in deep coma may exhibit epileptiform EEG patterns, such as generalized periodic spikes, and there is an ongoing debate about the relationship of these patterns and NCSE. The purposes of this review are (i) to discuss the various EEG patterns found in coma, its fluctuations, and transitions and (ii) to propose modified criteria for NCSE in coma.Classical coma patterns such as diffuse polymorphic delta activity, spindle coma, alpha/theta coma, low output voltage, or burst suppression do not reflect NCSE. Any ictal patterns with a typical spatiotemporal evolution or epileptiform discharges faster than 2.5 Hz in a comatose patient reflect nonconvulsive seizures or NCSE and should be treated. Generalized periodic diacharges or lateralized periodic discharges (GPDs/LPDs) with a frequency of less than 2.5 Hz or rhythmic discharges (RDs) faster than 0.5 Hz are the borderland of NCSE in coma. In these cases, at least one of the additional criteria is needed to diagnose NCSE (a) subtle clinical ictal phenomena, (b) typical spatiotemporal evolution, or (c) response to antiepileptic drug treatment. There is currently no consensus about how long these patterns must be present to qualify for NCSE, and the distinction from nonconvulsive seizures in patients with critical illness or in comatose patients seems arbitrary.The Salzburg Consensus Criteria for NCSE [1] have been modified according to the Standardized Terminology of the American Clinical Neurophysiology Society [2] and validated in three different cohorts, with a sensitivity of 97.2%, a specificity of 95.9%, and a diagnostic accuracy of 96.3% in patients with clinical signs of NCSE. Their diagnostic utility in different cohorts with patients in deep coma has to be studied in the future.This article is part of a Special Issue entitled “Status Epilepticus”.     

Pearls,perils, and pitfalls in the use of the electroencephalogram

Despite advances in neuroimaging techniques over the past three decades that have helped in identifying structural lesions of the central nervous system, electroencephalography (EEG) continues to provide valuable insight into brain function by demonstrating focal or diffuse background abnormalities and epileptiform abnormalities. It is an extremely valuable test in patients suspected of epilepsy and in patients with altered mental status and coma. Patterns in the EEG make it possible to clarify the seizure type; it is indispensable for the diagnosis of nonconvulsive status epilepticus and for separating epileptic from other paroxysmal (nonepileptic) episodes. There are EEG patterns predictive of the cause of the encephalopathy (i.e., triphasic waves in metabolic encephalopathy) or the location of the lesion (i.e., focal polymorphic delta activity in lesions of the subcortical white matter). The various EEG characteristics of infantile, childhood, and adult epilepsies are described as well as the EEG patterns that are morphologically similar to interictal/ictal epileptiform discharges but unrelated to epilepsy. An EEG is most helpful in determining the severity and, hence, the prognosis of cerebral dysfunction. Lastly, EEG is extremely helpful in assessing normal or abnormal brain functioning in a newborn because of the serious limitation in performing an adequate neurologic examination on the neonate who is intubated or paralyzed for ventilatory control. Under such circumstances, the EEG may be the only available tool to detect an encephalopathic process or the occurrence of epileptic seizures.     

"Alpha-pattern coma" in high voltage electrical injury.

Two cases are reported in which reversible deep coma subsequent to high voltage electrical injury occurred in association with alpha frequencies in the EEG. The EEG pattern differs from the alpha rhythm of the normal awake patient by its diffuse distribution and unresponsiveness to a variety of stimulation. The term "alpha-pattern coma" is introduced to designate the occurrence of this pattern in comatose patients. The EEG in the cases described initially demonstrated activity in the alpha frequency which occurred in a generalized distribution and was unresponsive to stimulation. During the early stages of recovery an increased incidence of theta and delta activity was observed. The recovery records contained a low voltage alpha rhythm and responded to photic stimulation. The literature on this subject is reviewed and the possible modes of pathogenesis are discussed. The authors conclude that such examples of alpha-pattern coma are the result of diffuse cerebral damage and might be detected more frequently in comatose patients who survive if these patients are studied earlier in their clinical course with EEGs.     

The usefulness of EEG, exogenous evoked potentials, and cognitive evoked potentials in the acute stage of post-anoxic and post-traumatic coma

Three-modality evoked potentials (TMEPs) have been used for several years in association with the EEG as a diagnostic and prognostic tool in acute anoxic or traumatic coma. Cognitive EPs have been recently introduced. EEG and cognitive EPs provide functional assessment of the cerebral cortex. TMEP parameters can be described by two indices: the index of global cortical function (IGCF) and the index of brainstem conduction (IBSC). Although it remains a unique tool for epilepsy assessment, the value of EEG is largely limited by its high sensitivity to the electrical environmental noise, its dependence on sedative drugs, and its inability to test the brainstem. Major TMEP alterations (absence of cortical activities more than 24 hours after the onset of post-anoxic coma, major pontine involvement in head trauma) are associated in all cases with an ominous prognosis (death or vegetative state). However, even if mild TMEP changes are associated with a good prognosis in 65% (post-anoxic coma) to 90% (head trauma) of cases, some patients never recover despite exogenous TMEPs that are only mildly altered in the acute stage. Thus, cognitive EPs can usefully complement exogenous EPs as a prognostic tool in coma. Indeed, even if the absence of cognitive EPs in comatose patients does not have any prognostic value, their presence implies a very high (more than 90%) probability of consciousness recovery. The major technical challenge for the future will be the development of reliable tools for continuous EEG and TMEP monitoring.     

EEG abnormality grades and subdivisions of prognostic importance in traumatic and anoxic coma in adults

The EEG has long been established as an important laboratory test when assessing cerebral function in comatose states. During the last three decades, several grading scales regarding severity of the EEG abnormality in coma have been suggested to increase the prognostic power of the EEG for survival. Their main limitation was, that the majority of EEG abnormalities in coma fell in the middle of the five point scaling systems, i.e. Grade 3 abnormality on the five grade abnormality scales. In addition, it was considered that non-reactivity of EEG pattern in coma is confined only to the most advanced grades. The purpose of the present article is to define precisely the main five abnormality grades and their subdivisions, and to allocate them in five principal categories regarding their significance for survival. The five categories are: 1 = optimal, 2 = benign if persistent, 3 = uncertain, 4 = malignant if persistent, and 5 = fatal unless caused by drug effect or hypothermia. After the inclusion of more recently described coma patterns, it was possible to outline prognostic significance for survival in eleven types of abnormalities with assurance. Only four remain of uncertain prognostic significance. The EEG abnormalities as discussed in this article are generally applicable only to coma after diffuse brain trauma and cerebral hypoxia. However, they may also be found in some other diffuse encephalopathies associated with coma.     

Ictal EEG patterns in band heterotopia

Band heterotopia (BH) or "double cortex" syndrome is a neuronal migration disorder resulting in a diffuse band of subcortical grey matter and variable abnormality of the overlying cortex. Patients with BH have a spectrum of psychomotor delay and seizures. Associated epileptic syndromes and interictal EEG findings have been described, but ictal EEG patterns are lacking. METHODS: We describe the clinical, interictal, and ictal EEG findings in two girls with BH and intractable seizures. RESULTS: Ictal EEG patterns correlated well with clinical seizure types, and did not have features unique to BH. Similarly, seizure behaviors and interictal EEG findings were typical of those seen in symptomatic generalized epilepsies. CONCLUSIONS: Despite evidence implicating the ectopic grey matter in seizure discharges, we conclude that seizure semiology and associated ictal EEG patterns in BH are no different from those seen in other causes of symptomatic generalized epilepsies.     

Differentiation of alpha coma from awake alpha by nonlinear dynamics of electroencephalography

The electroencephalogram, as a probe of scalp-recorded electrical activity arising from the human cortex, provides useful information because of its temporal and spatial organization. Recent developments in nonlinear dynamics suggest that an object can be constructed in an n-dimensional space out of a temporal sequence of data such as an EEG signal and that its organization is characterized by the dimensionality of the object (in this case, human brain activity). We have carried out an analysis of a set of alpha coma EEG patterns in comparison to the awake alpha EEG patterns of normal volunteers and patients. Alpha coma recorded from a single channel is visually indistinguishable from normal resting alpha due to its similar frequency spectrum (a broad-band spectrum with 1/f characteristics). Our results show that alpha coma dimensionality, however, differs from that of normal alpha in that it has a greater variability over different temporal segments of EEG. Single channel recordings in 7 patients with alpha coma were differentiable from those of 10 subjects with “normal” EEGs. Through dynamic analysis of the EEG, novel methods of signal extraction from EEG may become evident and applicable to clinical practice.