interpretación del EEG en estupor y coma.

ORIGINAL ARTICLE

The Interpretation of the EEG in Stupor and Coma

Richard P. Brenner, MD

Abstract: This review discusses a variety of causes of stupor andcoma and associated electroencephalographic (EEG) findings. Theseinclude metabolic disturbances such as hepatic or renal dysfunction,which are often characterized by slowing of background rhythmsand triphasic waves. Hypoxia and drug intoxications can produce anumber of abnormal EEG patterns such as burst suppression, alphacoma, and spindle coma. Structural lesions, either supra- or infrat-entorial, are reviewed. EEGs in the former may show focal distur-bances such as delta and theta activity, epileptiform abnormalities,and attenuation of faster frequencies. In infratentorial lesions, theEEG may appear normal, particularly with a pontine lesion. Somepatients may be encephalopathic because of ongoing epileptic ac-tivity with minimal or no motor movements. This entity, noncon-vulsive status epilepticus (NCSE), is difficult to diagnose in ob-tunded/comatose patients, and an EEG is required to verify thediagnosis and to monitor treatment. Several EEG patterns and theirinterpretation in suspected cases of NCSE such as periodic lateral-ized epileptiform discharges (PLEDs), bilateral independent peri-odic lateralized epileptiform discharges (BIPLEDs), generalizedperiodic epileptiform discharges (GPEDs), and triphasic waves arereviewed. Other entities discussed include the locked-in syndrome,neocortical death, persistent vegetative state, brainstem death, andbrain death.

Key Words: coma, EEG, encephalopathy, nonconvulsive statusepilepticus

(The Neurologist 2005;11: 271–284)

Despite advances in neuroimaging, the electroencephalo-gram (EEG) remains a valuable tool in the evaluation of

stuporous and comatose patients. These recordings are usu-ally performed in the intensive care unit and are oftencontaminated by artifacts arising from monitoring equipment,life support systems, and personnel. The use of additionalelectrodes, monitoring the electrocardiogram, body move-ments (eg, body, tongue, and eye) and respiration, and tem-porary disconnection of other equipment may be needed toidentify the noncerebral origin of such activity (Fig. 1).

When recording comatose patients, it is important totest for reactivity, which is defined as a change in EEG

activity after stimulation. The recording should be continuedfor sufficient time without stimulation so that the ongoingEEG activity can be studied and the presence or absence ofspontaneous variability determined. Painful or auditory stim-uli should be applied when both the patient and surroundingsare relatively quiet. If reactivity is present, the EEG mayshow an attenuation of ongoing activity or an increase inamplitude, which is usually accompanied by the appearanceof slower-frequency activity (Fig. 2). Reactivity indicates alighter level of coma, and because the prognosis in most casesof coma is related to severity more than etiology, this isgenerally a good sign. However, with patients in comasecondary to a drug intoxication in which recovery willusually occur if appropriate treatment is instituted, the pres-ence or absence of reactivity on the EEG is of less valueregarding prognosis.

The EEG may indicate that the alteration of conscious-ness is the result of: 1) diffuse physiological brain dysfunc-tion, particularly hepatic, renal, or some drug intoxications;2) a focal brain lesion, supratentorial mass lesions compress-ing the diencephalic and mesencephalic reticular formation,diffuse bihemispheric structural lesions, or infratentorialmass or destructive lesions; or 3) continued epileptic activitywithout convulsive movements.

One of the limitations of the EEG is its lack of speci-ficity. For example, focal continuous polymorphic delta ac-tivity (PDA) is usually indicative of a focal structural cerebrallesion. However, the variety of pathologic disturbances ca-pable of producing this EEG abnormality is diverse andincludes an infarct, tumor, hemorrhage, and other focal le-sions. Diffuse slowing of background rhythms is seen invarious encephalopathies regardless of etiology. The EEGmay be of prognostic value if the etiology of the coma isknown. If not, then serial EEGs are needed to indicate theprogression of the encephalopathy.

This review emphasizes the role of conventional visualEEG analysis in the evaluation of adults with alteration ofconsciousness. Several recent studies have reviewed contin-uous digital-video EEG monitoring in the intensive care unit,including the use of quantified EEG analysis.1–5 It is expectedthat this area will grow considerably in the future.

METABOLIC ENCEPHALOPATHYA leading cause of coma is diffuse or metabolic brain

dysfunction. With progression from lethargy to coma, there isdiffuse slowing of background rhythms from alpha to thetaand, subsequently, delta activity.6 The degree of slowingusually parallels the degree of alteration of consciousness and

From the University of Pittsburgh, Pittsburgh, Pennsylvania.Reprints: Richard P. Brenner, MD, WPIC, Room 111, 3811 O’Hara Street,

Pittsburgh, PA 15213. E-mail: [email protected] © 2005 by Lippincott Williams & WilkinsISSN: 1074-7931/05/1105-0271DOI: 10.1097/01.nrl.0000178756.44055.f6

The Neurologist • Volume 11, Number 5, September 2005 271

indicates its severity, although there are exceptions. The EEGmay also show intermittent bursts of rhythmic delta activityin a generalized distribution. In adults, this is usually maxi-mal anteriorly and is referred to as frontal intermittent rhyth-mic delta activity (FIRDA). Although a diffusely slow recordindicates cerebral dysfunction, it is not specific for a singleetiology. Possibilities would include a host of metabolic–toxic disturbances, inflammatory processes, and head trauma.Several of these entities are discussed in further detail in thefollowing sections.

HepaticSome patterns in metabolic encephalopathies, although

not pathognomonic, are often suggestive of a specific etiol-

ogy. Foley et al7 described blunt spike-and-slow wave com-plexes in patients with liver disease. These waveforms weresubsequently termed triphasic waves by Bickford and Butt8

and consist of bursts of moderate to high amplitude (100–300uV) activity, usually of 1.5 to 2.5 Hz, and often occurring inclusters (Fig. 3). Although frequently predominant in thefrontal regions, occasionally they are maximal posteriorly. Afronto-occipital lag may be present. The initial negativecomponent is the sharpest, whereas the following positiveportion of the complex is the largest and is subsequentlyfollowed by another negative wave. They are bisynchronousbut may show shifting asymmetries. A persistent asymmetry(not related to technical factors or a skull defect) wouldsuggest an underlying structural lesion on the side of loweramplitude.

Triphasic waves were initially believed to be highlyspecific for hepatic dysfunction. Karnaze and Bickford,9

however, in a study of 50 patients whose EEGs showedtriphasic waves, found etiologies to be: hepatic (28), azotemia(10), hypoxia (9), hyperosmolarity (2), and hypoglycemia (1).Bahamon-Dussan et al10 found multiple metabolic derange-ments to be the most common cause of triphasic waves, beingpresent in 12 of 30 patients. Patients were either very lethar-gic or comatose and the mortality was 77%. Periodic sharpcomplexes, most often triphasic or biphasic, and occurringapproximately every second, can also be seen in patients withdegenerative disorders such as Creutzfeldt-Jakob disease

FIGURE 1. Respirator artifact in a 65-year-old woman. Thederivation in the bottom channel consists of electrodesplaced above and below the lips. The sensitivity of this chan-nel is one tenth of the other channels.

FIGURE 2. Reactivity in a 19-year-old woman with an intra-ventricular hemorrhage. There is attenuation of faster fre-quencies and bursts of delta activity when the patient iscalled.

FIGURE 3. Triphasic waves in a 74-year-old man with renalfailure.

Despite advances in neuroimaging, the

electroencephalogram (EEG) remains a valuable

tool in the evaluation of stuporous and

comatose patients.

Brenner The Neurologist • Volume 11, Number 5, September 2005

© 2005 Lippincott Williams & Wilkins272

(CJD). In addition, Sundaram and Blume11 found that seniledementia of the Alzheimer type was the most commondiagnosis among 37 patients with triphasic waves who did nothave a metabolic encephalopathy. Clearly, the causes of thisEEG pattern will depend on the patient population at theinstitution where the study is performed.

In a study of the diagnostic specificity of triphasicwaves, those occurring in hepatic encephalopathy were morelikely to be associated with severe EEG background slowingthan other encephalopathies with these waveforms.12 How-ever, none of the morphologic features of triphasic waves,which included longitudinal topography, phase lag, symme-try, and longitudinal bipolar phase reversal sites, reliablydistinguished hepatic encephalopathy from other forms ofmetabolic encephalopathy. Sundaram and Blume11 found thatthe etiology of triphasic waves was more closely related tothe level of consciousness at the time of recording than onany of their morphologic aspects, distributional features, ornature of EEG background activity. Awake but confusedpatients all had nonmetabolic encephalopathies, particularlyAlzheimer disease, whereas all unarousable patients hadmetabolic encephalopathies.

RenalRenal disease shows abnormalities similar to other

metabolic encephalopathies with progressive slowing ofbackground rhythms and superimposed bursts of slow activ-ity. Triphasic waves are also seen, the incidence being similarto that in hepatic disease (approximately 20%). Seizures andepileptiform abnormalities are more common in uremic thanhepatic encephalopathy. Occasionally, with photic stimulation,there may be a photoparoxysmal or photomyogenic response.

Hughes13 reviewed the correlation between multipleEEGs (362) and chemical changes in 23 uremic patientsundergoing chronic hemodialysis over long periods of time(up to 18 months). Seventy percent of patients had at leastone abnormal EEG. The one single serum index that corre-lated best with the EEG was the blood urea nitrogen, espe-cially if the record showed a worsening. Other syndromesdescribed in patients with renal disease undergoing dialysisinclude dialysis disequilibrium syndrome and progressivedialysis encephalopathy. In patients who develop dialysisdisequilibrium syndrome, there is a worsening of the clinicalstate and EEG after dialysis. In dialysis encephalopathysyndrome, Hughes and Schreeder14 found bilateral spike-and-wave complexes in 77% of patients with dialysis encepha-lopathy compared with only 2% in chronic renal patients

without dialysis encephalopathy. Bursts of diffuse slowwaves, usually maximal in the frontal area, were also morefrequent in patients with dialysis encephalopathy, althoughcommon in both groups. In a review of EEG and clinicalfeatures in 14 patients with dialysis encephalopathy, the mostcharacteristic EEG feature (12 patients) was paroxysmal high-voltage delta activity, usually maximal anteriorly.15 Spike-and-wave activity occurred in 5; 2 patients had triphasic waves.

SEPSISNeurologic complications often occur in patients in the

intensive care unit initially admitted with nonneurologic dis-orders. In one study, metabolic encephalopathy was the mostfrequently encountered neurologic complication; most oftenthis was the result of sepsis.16 Young et al17 found that inpatients with septic encephalopathy (an encephalopathy as-sociated with an infection outside the nervous system, posi-tive blood cultures, and without evidence for hepatic or renaldysfunction or hypoxemia), the EEG was a more sensitiveindex of brain function than the clinical criteria and wasuseful in monitoring patients.

DRUG INTOXICATIONGeneralized fast activity on an EEG of a comatose patient

should arouse the suspicion of drug intoxication, particularlywith drugs that are known to increase beta activity on the EEGsuch as barbiturates or benzodiazepines. Usually, this activity issomewhat slower (10–16 Hz) than the 20- to 25-Hz beta activityseen in patients who are awake and taking these medications,and it is superimposed on a diffusely slow background (Fig. 4).With deeper levels of coma, intermittent episodes of suppres-sion, a burst-suppression pattern, and ultimately electrocerebralinactivity (ECI) can be seen. An unusual pattern consisting ofsinusoidal theta activity interrupted every few seconds by peri-odic slow-wave complexes has been described in phencyclidine(“angel dust,” “PCP”) intoxication.18

Generalized, bisynchronous sharp complexes, at timesperiodic and often with a triphasic configuration, have beendescribed in a variety of drug-related disorders, as well as afterhypoxia–ischemia19,20 and in metabolic encephalopathies.21

These include baclofen,22,23 levodopa,24 lithium,25 ifosf-amide,26,27 and metrizamide.28–32 Some have felt that thesepatterns may represent nonconvulsive status epilepticus,whereas others view it as an encephalopathy that resolves whenthe offending agent is discontinued. Drug intoxication can alsoresult in other interesting EEG patterns such as an alpha comaand spindle coma, which are described in subsequent sections.

Most anesthetic agents produce similar EEG changes.Barbiturates and most of the nonbarbiturate induction agents,

The EEG may be of prognostic value if the

etiology of the coma is known. If not, then

serial EEGs are needed to indicate the

progression of the encephalopathy.

The EEG is often normal in alcohol withdrawal

or may contain excessive low-amplitude

fast activity.

The Neurologist • Volume 11, Number 5, September 2005 EEG in Stupor and Coma

© 2005 Lippincott Williams & Wilkins 273

including propofol, a short-acting intravenous agent oftenused in the intensive care unit, can initially cause an increasein beta activity with a loss of the alpha rhythm. As the dosageincreases, the frequency of EEG activity decreases, whereasamplitude increases. A burst-suppression pattern occurs athigh doses. If titrated further, electrocerebral inactivity (ECI)may result. Another drug commonly used in the intensivecare unit is midazolam, which has EEG effects similar toother benzodiazepines.33 Like propofol, it may result in analpha or spindle coma pattern, or burst suppression.

In delirium resulting from drug withdrawal such asfrom barbiturates, spontaneous epileptiform abnormalitiesmay occur, and there may be a photomyogenic or photopar-oxysmal response. The EEG is often normal in alcoholwithdrawal or may contain excessive low-amplitude fastactivity. Two studies found that photomyogenic responseswere extremely rare and that photoparoxysmal responses didnot occur in either untreated alcohol withdrawal34 or aftertreatment of alcohol-related seizures.35 Kelly and Reilly36 feltthat a normal or near-normal EEG in patients with grossimpairment of sensorium and other signs of delirium shouldraise the possibility of alcohol withdrawal. Furthermore, thepresence of marked abnormalities suggests other complica-tions as being responsible for the alteration in consciousnessrather than only delirium tremens.36,37

Idiopathic recurring stupor has been described with anEEG pattern of diffuse alpha activity, maximal anteriorly38 orfast (14–16 Hz), unreactive background activity.39 Flumaze-nil, a benzodiazepine receptor antagonist, promptly reversedthe EEG changes and clinical state in these patients. Initially,it was felt that the 20 reported cases represented recurringstupor linked to endozepine-4 accumulation.40 All presentedwith the same clinical picture and EEG pattern (low-ampli-tude, 13–14 Hz unreactive background activity) during stuporand transient awakening and normalization of the EEG afterflumazenil administration. Development of a newer, morespecific toxicologic assay, however, led to a reanalysis of theblood samples that had been obtained in 9 of the 20 patients,

and lorazepam was detected. The authors concluded that theendozepine origin of the stupor episodes of the patients, espe-cially those in whom the diagnosis was based on clinical criteriaalone, should be considered unproven.41 In another poorly de-fined entity, several elderly patients experienced unexplainedtransient unresponsiveness, sometimes recurrent, with the EEGshowing slight slowing of background rhythms.42,43

HYPOXIALike drugs, hypoxia can produce a wide variety of

abnormal EEG patterns.19,44 Of these, a burst-suppressionpattern is associated with an extremely poor prognosis (Fig.5). Kuroiwa and Celesia45 reviewed 11 cases of their own andpreviously published reports of 105 other patients with aburst-suppression pattern who were comatose after a cardio-respiratory arrest and not under the effects of central nervoussystem depressants. Of the 116 patients, 111 (96%) died. Insome patients with a burst-suppression pattern, spontaneousmovements can occur. These are usually orofacial–lingualmovements such as eye opening or chewing and may bemisleading regarding the patient’s level of consciousness.46,47

In comatose patients having repetitive myoclonic jerksafter an arrest, the EEG often shows the jerks to be associatedwith repetitive spikes, sharp waves, or triphasic waves occur-

FIGURE 4. Anesthetic pattern in a 65-year-old man undergo-ing a carotid endarterectomy.

Another type of alpha coma has been described

with brainstem lesions and is discussed in a

subsequent section, as is the

spindle coma pattern.

FIGURE 5. A burst-suppression pattern in an 84-year-oldwoman after a cardiorespiratory arrest. The bursts were asso-ciated with eye opening.



ring at approximately 1-second intervals with periods ofsuppression between the intervals or a burst-suppressionpattern (Fig. 6). This entity, which has gone under a varietyof terms, including myoclonic status epilepticus,48 statusmyoclonus,49 generalized status myoclonicus,50 and general-ized myoclonic status epilepticus,51 is usually associated witha fatal outcome.52,53 Some patients described as subtle gen-eralized convulsive status epilepticus by Treiman et al54 havehad similar clinical and EEG findings.

A generalized periodic pattern after a cardiorespiratoryarrest carries a poor prognosis.20,55,56 Often there are noassociated clinical changes other than a decreased level ofconsciousness. Another pattern that occurs in hypoxia, aswell as in metabolic encephalopathies, consists of brief (up toseveral seconds) intermittent periods of generalized suppres-sion without associated bursts.57,58 This pattern is oftenassociated with a poor prognosis.

Several EEG grading systems have been proposed toaid in prognosis.55,59,60 The ratings are similar with EEGsshowing normal or near-normal frequency activity beingassigned low grades, whereas those with predominantly deltaactivity, intermittent suppression, burst suppression, and ul-timately electrocerebral silence (ECS) having higher gradesthat reflects a poorer prognosis. Synek61 classified patternsinto benign, uncertain, and malignant. Benign patterns were:near-normal; rhythmic theta, reactive; frontal rhythmic delta,reactive or nonreactive; and spindle coma. Uncertain pat-terns were: mixed theta and delta, nonreactive; dominantdelta, reactive or nonreactive; alpha-coma, reactive; andepileptiform discharges on a base of diffuse delta. Malig-nant categories were: low-amplitude delta (�50 uV), non-reactive; burst suppression; suppression (�20 uV), alpha/theta coma, nonreactive; and epileptiform discharges withburst suppression. Further modification of the classifica-tion system resulted in greater interrater reliability.62 Sev-eral studies have reviewed early prediction of poor out-

come in hypoxic–ischemic coma using clinical findingsand electrophysiological studies (EEG and somatosensoryevoked potential).63– 66

An alpha coma pattern (Fig. 7) has been described afterhypoxia67 as well as with drug intoxications. Although thefrequency of the activity is in the alpha range, it is wide-spread, often of greatest amplitude anteriorly, and does notshow the usual reactivity to passive eye opening and eyeclosure. Thus, it does not represent the normal physiologicalalpha rhythm, but rather is an abnormal pattern. In a reviewof 94 posthypoxic cases, only 10 of 86 patients survivedwhen the pattern was secondary to cardiopulmonary arrest.68

In contrast, when resulting from a respiratory arrest (8 pa-tients), 7 survived.

Unfortunately, there have been few studies comparingthe outcome of patients with coma associated with alphafrequency activity in the EEG with a clinically similar groupof individuals who have other EEG findings after cerebralhypoxia from cardiac arrest. One such study69 suggested thatthe prognosis in patients with alpha pattern coma was noworse than in other patients who had been comatose for morethan 24 hours after cardiac arrest. Austin et al70 reached asimilar conclusion and felt that alpha coma is a descriptiveterm, lacking prognostic significance. Young et al71 reviewedalpha coma, theta coma, and alpha–theta coma patterns. Theyfelt that these patterns represented transient clinical EEGphenomena that did not differ from each other in etiology oroutcome and indicated severe disturbance in thalamocorticalphysiology. Using serial recordings, the authors found thatthese patterns usually changed to a more definitive patternwithin 5 days and that EEG reactivity in subsequent tracingswas relatively favorable.

A study of 14 comatose patients with an alpha–thetacoma (ATC) after cardiac arrest and a review of 283 reportedcases of posthypoxic ATC suggested the existence of incom-plete and complete variants of ATC.72 Incomplete ATC (thealpha/theta EEG activity was not monotonous, partially reac-tive, or posteriorly dominant) was associated with a full

FIGURE 6. Myoclonic status epilepticus in a 65-year-old co-matose man who experienced an anoxic event 48 hours be-fore the recording. The EEG shows generalized polyspikesoccurring approximately every second.

FIGURE 7. An alpha coma pattern in a 68-year-old manpostcardiorespiratory arrest.



recovery, whereas complete ATC was invariably associatedwith a poor outcome. Kaplan et al73 retrospectively reviewed36 patients with alpha coma pattern and performed a meta-analysis of 335 cases of alpha coma in the world literature.They stressed the importance of etiology as well as reactivity.For example, there was a very high mortality with patientswith a cardiorespiratory arrest, whereas approximately 90%with drug-induced coma and this EEG pattern survived. Theyalso found that EEG reactivity to noxious stimuli favoredsurvival; without it, most patients died. This was independentof etiology.

Another type of alpha coma has been described withbrainstem lesions and is discussed in a subsequent section, asis the spindle coma pattern. The latter may be seen withhypoxia, drug intoxications, diffuse encephalopathies, as wellas subtentorial or supratentorial lesions.

STRUCTURAL LESIONS

SupratentorialThe EEG is usually markedly abnormal when coma is

the result of a supratentorial lesion. The abnormalities aregreater with acute and rapidly expanding lesions rather thanwith chronic, slow-growing processes. The EEG, however, isof limited value in the precise localization of the lesion withinthe affected hemisphere. Several types of abnormalities maybe seen (Fig. 8). Often, there is continual focal PDA over theinvolved side or increased focal delta and theta activity. Withdisturbances of deeper structures, FIRDA usually appears.Other EEG abnormalities may include focal attenuation ofactivity, a decrease of faster frequencies over the affectedside, and focal epileptiform abnormalities. Such findings arenot specific for a single etiology.

A pattern often seen with acute or subacute unilaterallesions is periodic lateralized epileptiform discharges(PLEDs) (Fig. 9). Chatrian et al74 described PLEDs as con-sisting of lateralized complexes usually recurring every 1 to

2 seconds. The complexes often consist of sharp waves orspikes that may be followed by a slow wave. Reiher et al75

proposed a classification of PLEDs that included PLEDs Plusand PLEDs Proper. PLEDs Plus consists of a brief, low-amplitude focal rhythmic activity that occurs in associationwith PLEDs, whereas PLEDs Proper consisted of repetitiveand stereotyped PLEDs without the rhythmic discharges.PLEDs Plus is more likely to be associated with clinicalseizures and seizure discharges than is PLEDs Proper.

PLEDs occur in a variety of disorders, most ofteninfarcts or tumors. They may also be seen in patients withchronic seizure disorders or old static lesions, especiallywhen associated with recent seizures, alcohol withdrawal, ora toxic–metabolic disorder.76 The clinical picture associatedwith PLEDs is usually obtundation, focal seizures, and focalneurologic signs. In a review of 586 cases of PLEDs reportedin the literature, Snodgrass et al77 found the etiologies to becerebrovascular accident (35%), mass lesion (26%), infection(6%), hypoxia (2%), and other (22%). The majority of pa-tients with herpes simplex encephalitis (HSE) have PLEDs,particularly when serial recordings are obtained. The pres-ence of PLEDs in the EEG in a patient with suspected viralencephalitis should raise the suspicion of HSE; however, it isnot pathognomonic.78 Regardless of etiology, PLEDs are atransient phenomenon. With time, the discharges usuallydecrease in amplitude, the repetition rate decreases, andultimately the discharges cease.

PLEDs are lateralized; however, they are often re-flected synchronously to a lesser degree over homologousareas in the contralateral hemisphere. In contrast, in patientswith bilateral independent periodic lateralized epileptiformdischarges (BIPLEDs), the complexes are asynchronous, usu-ally differing in morphology, amplitude, rate of repetition,and site of maximal involvement (Fig. 10) De la Paz andBrenner79 reported clinical findings in 18 patients whoseEEGs showed this pattern. The most common cause ofBIPLEDs was hypoxic encephalopathy (5), central nervous

FIGURE 8. There is suppression of background rhythms overthe left hemisphere in this 19-year-old woman with a trau-matic left middle cerebral artery infarct after a motor vehicleaccident. There is also rightsided slowing.

FIGURE 9. Periodic lateralized epileptiform discharges in a74-year-old-woman after removal of a left subdural hema-toma 4 days earlier.



system infection (encephalitis or meningitis–5), and chronicseizure disorders (4). When compared with patients withPLEDs, those with BIPLEDs were more likely to be coma-tose (72% vs. 24%) and had a higher mortality rate (61% vs.29%), but focal neurologic deficits and focal seizures wereless common.

SubtentorialThe EEG is of less value in the evaluation and prog-

nosis of comatose patients when the lesion is subtentorialrather than supratentorial or as a result of a diffuse metabolicprocess. The EEG is better in assessing hemispheric function,which determines quality of survival, rather than brainstemfunction, which is needed for survival. However, the EEGmay still be of value. As indicated earlier, an alpha patterncoma has been described in patients with brainstem lesions.This is the result of involvement of the upper pons and caudalmidbrain, usually secondary to a vascular insult. With bilat-eral involvement of the pontine tegmentum, the patient iscomatose with an EEG showing alpha activity.80 In contrastto the posthypoxic alpha pattern coma, the alpha frequencyactivity seen with a brainstem lesion is more posterior andshows more variability. In addition, there may be reactivitywith sensory stimulation such as passive eye opening and eyeclosure or painful stimuli.67 Although the EEG resemblesnormal wakefulness, few patients survive. Patients with thistype of alpha pattern coma need to be distinguished clinicallyfrom patients with a “locked-in” syndrome.81–83 The latterare conscious, although paralyzed and mute, and can oftencommunicate with eye blinks. Here the lesion affects theventral pons but does not involve the pontine tegmentum, andconsciousness is not affected. Higher involvement of themidbrain and diencephalon result in coma and produce gener-alized slow (delta) waves that may be continuous orintermittent. Another condition that may simulate coma ispsychogenic unresponsiveness. The EEG is usually normaland the alpha rhythm, if present, shows reactivity to passiveeye opening and eye closure. Neurologic findings, particu-

larly the presence of nystagmus with oculovestibular testing,will help identify the cause of this apparently altered state ofconsciousness. A normal-appearing EEG in a truly comatosepatient (not psychogenic coma) is indicative of a brain-stem lesion.

A spindle coma pattern (Fig. 11) is thought to be theresult of altered function caudal to the thalamus but rostral tothe pontomesencephalic junction.84 Chatrian et al85 first de-scribed the pattern in 11 patients with head injury andconcluded that the presence of slow-wave sleep activity suchas spindles indicated a good prognosis. Britt et al84 reported36 patients with nontraumatic alteration of consciousness ofdiverse etiologies, whose EEG activity resembled slow-wavesleep. In those patients who were comatose,21 only 4 sur-vived, whereas the prognosis was good in patients who werestuporous or semicomatose (14 of 15 patients survived). In astudy of 370 comatose patients, among whom 5.9% (22patients) showed a spindle coma pattern, approximately onethird was the result of a head injury, whereas another thirdwas secondary to cerebral hemorrhage or cerebral hypoxia.86

The authors concluded that EEGs with spindle patterns are ofdubious value in indicating the prognosis of coma, becausethe outcome for patients with this EEG pattern was no betterthan those without it. Hulihan and Syna87 reviewed EEGsleep patterns in posthypoxic stupor and coma in 14 patients.They found that the presence of spindles did not indicate afavorable prognosis but that the absence of spindles or reac-tivity was associated with a poor outcome (death or persistentvegetative state). Like other EEG patterns, spindle coma isnot specific for a single etiology, and the prognosis is depen-dent on several factors, including severity of insult, type ofinjury, neurologic findings, patient age, and time of recordingin relation to insult. Kaplan88 studied 15 patients with spindlecoma resulting from various causes and found that the out-come was favorable. EEG reactivity to noxious stimuli bestpredicted outcome. In reviewing the literature, they con-cluded that spindle coma was an EEG pattern conferring a

FIGURE 10. Bilateral independent periodic lateralized epilep-tiform discharges in an 82-year-old man status postresectionof a right subdural hematoma.

FIGURE 11. The EEG shows sleep spindles in this comatose25-year-old man status postmotor vehicle accident with ahead injury and receiving propofol.



good prognosis, particularly if associated with reactivity toexternal stimuli. However, this was most likely the result ofits respective benign or reversible underlying etiologies.

NONCONVULSIVE STATUS EPILEPTICUSConvulsive status epilepticus (SE) is the most serious,

as well as the most easily recognized type of SE, and ischaracterized by a loss of consciousness, recurrent or contin-uous convulsions, and generalized ictal activity on EEG. It isnonconvulsive status epilepticus (NCSE) that is more heter-ogeneous and controversial. Within this group, the termsabsence status or petit mal status are usually used for thosepatients with generalized EEG findings who may be ambu-latory and often appear confused with repetitive automatisms,whereas those with a partial EEG onset have been termedcomplex partial SE (CPSE). The term NCSE is more oftenapplied to patients who are severely obtunded or comatosewith minimal or no motor movements, often with seriousmedical conditions. However, some investigators have usedNCSE to include all the patients described, ranging fromthose with barely detectable mental status changes to thosein coma.

I prefer to subdivide NCSE based on clinical featuressuch as degree of impairment of consciousness.89 In a recentstudy of 100 consecutive cases of NCSE, mortality wasassociated with an acute medical cause as the underlyingetiology, severe mental status impairment, and developmentof acute complications.90 For example, in patients with anacute medical cause of NCSE, 14 of 52 patients (27%) died,whereas only one of 31 patients with epilepsy died. If therewas severe mental status impairment, the mortality was 39%compared with 7% in mildly obtunded patients. Clearly, theprognosis is very different and is related to the etiology,clinical findings such as level of consciousness, and associ-ated comorbidities.91 Initially, ambulatory forms of NCSEare reviewed.

NCSE is defined as an epileptic state lasting more than30 minutes with some clinically evident change in mentalstatus or behavior from baseline and ictal activity on EEG.There are 2 major categories of NCSE: generalized andpartial. Numerous terms have been used to describe general-ized NCSE in patients who are often confused but ambula-tory92,93; absence status is the most widely used. A variety ofEEG patterns have been described in generalized NCSE.Most commonly, the EEG shows more or less continuous, orfrequently recurring, generalized, bilaterally synchronous,symmetric spike and wave, which may be at a frequency of 3Hz but is often less,90,94–97 or generalized polyspike andwave discharges (Fig. 12).

The EEG is extremely useful in the identification ofNCSE, particularly when the cause of this acute confusionalstate is not clinically apparent. The behavioral alterations ingeneralized NCSE have sometimes resulted in an incorrectinitial diagnosis of a primary psychiatric disorder98,99 such asdepression, psychosis, or hysteria. There are often clues tohelp identify the underlying epileptic nature of this acutedisturbance. Most commonly, the episodes occur in knownepileptic patients (90–95%),96 although they can occur without

a history of seizures, particularly in the elderly,96,98 In this lattergroup, benzodiazepine withdrawal has been implicated.100,101

The presence of associated myoclonic movements such aseyelid flutter and rhythmic facial or upper extremity move-ments is also suggestive of absence status. However, an EEGis the only means of verifying the diagnosis.

Other entities in the differential diagnosis include apostictal state,102,103 drug intoxication, metabolic encepha-lopathy, transient global amnesia, psychiatric disorders, andcomplex partial status epilepticus (CPSE). In contrast toabsence status, in CPSE, the EEG abnormalities usually arefocal, most often affecting the temporal area, although theycan become generalized. The focal EEG abnormalities maynot be appreciated, particularly if the recording begins afterthe onset of the status. The rhythmic focal discharge that maycharacterize complex partial seizures can range from the deltato beta frequency. The EEG findings may show recurrentfocal seizures or a more continuous cycling with alterationsof unresponsiveness and partially responsive phases.

NCSE can be difficult to classify (generalized vs. par-tial) at times, even with ictal EEG recordings. In particular,frontal seizures may show a generalized pattern on EEG.104

Guberman et al99 felt that transitional cases of NCSE existwith lateralizing EEG features and that some cases are prob-ably the result of secondary generalization from a temporal orfrontal focus. Tomson and colleagues105 felt that most casesof NCSE represent CPSE. However, Granner and Lee,97 in alarge series of patients with NCSE (85 ictal episodes in 78patients), found that 69% of the episodes were generalized onEEG, 18% were generalized with focal predominance, and13% were focal. The difficulty in distinguishing NCSE fromCPSE may, in part, explain the differences in EEG interpre-tation after metrizamide myelography, which has been de-scribed as either generalized31 or partial status epilepticus.29

Porter and Penry92 believed that the clinical differencesbetween generalized and partial NCSE could help to differ-entiate between these 2 disorders. The former ends abruptlywithout postictal abnormality, whereas the latter is associated

FIGURE 12. The EEG of a 20-year-old man in absence statusepilepticus, ambulatory but confused. He had absence sei-zures beginning in childhood.



with postictal confusion, depression, or general malaise. Oth-ers emphasized cyclic clinical phases in patients with CPSE,alternating between total unresponsiveness with stereotypedautomatisms and partial responsiveness with reactive auto-matisms.106 Tomson et al107 did not feel that this clinicalcharacteristic allowed unequivocal differentiation between ab-sence status and the continuous form of complex partial status.

NCSE is difficult to diagnose in obtunded/comatose pa-tients.108–110 A variety of terms have been used to describe thesepatients: subtle generalized SE,54 electrographic SE,111 SE incomatose patients,112 generalized electrographic SE,113 non-tonic–clonic SE,114 subclinical SE,115 and NCSE.89,116–118

Sometimes the same term has been used when describingdifferent disorders, whereas different terms are often appliedto the same clinical entity. Because these patients are oftendifficult to diagnose, the diagnosis is usually delayed. Theymay display subtle, intermittent, focal, or multifocal rhythmicmovements suggestive of seizures.119 Husain et al120 felt thatcertain clinical features were more likely to be present inpatients with NCSE compared with other types of encepha-lopathy. These included either a remote history of seizures orocular movement abnormalities. NCSE can occur in a variety ofdisorders, including hypoxia, metabolic disturbances,111–113 andafter convulsive seizures.121

There are a number of EEG patterns that have beendescribed in NCSE and some are controversial, particularlyas to whether they are ictal. These include PLEDs, BIPLEDs,periodic epileptiform discharges (PEDs), which can be eitherfocal or generalized, and generalized triphasic waves.

The majority of patients with PLEDs will have seizuresduring the acute stage of illness. During the recording of theEEG, PLEDs usually will be transiently replaced by a newpattern if a seizure occurs, often consisting of faster rhythmicactivity (Fig. 13). For this reason, PLEDs are usually consid-ered an interictal pattern, although not all agree.122–124 Inseveral studies of NCSE, PLEDs alone were not considered anictal pattern.125–127 Pohlmann-Eden et al128 viewed PLEDs as anelectrographic signature of a dynamic pathophysiological statein which unstable neurobiologic processes create an ictal–inter-ictal continuum. BIPLEDs are much less common than PLEDs.Like PLEDs, the complexes are often replaced by a lateralizedrhythmic pattern during a seizure (Fig. 14).

Generalized, periodic, bisynchronous, sharp com-plexes, often with a triphasic configuration, have beendescribed in a variety of drug-related disorders, metabolicencephalopathies,21 following anoxia–ischemia,19 and inconvulsive status epilepticus.121 Treiman et al121 describeda progressive sequence of EEG changes during generalizedCSE; however, others have not found this sequence ofchanges.112,115,123,129 Whether the final pattern of thisproposed sequence, namely generalized periodic epilepti-form discharges (GPEDs) with a “flat” background (Fig.15), should be considered ictal is debatable.19,56,123,129 Likein patients with PLEDs or BIPLEDs, a longer recording (1hour instead of 25 minutes) may demonstrate discrete sei-zures. Furthermore, although some authors have felt thatPEDs may represent NCSE, others view it as an epilepticencephalopathy in which spikes and sharp waves may not

impair clinical function, but rather reflect damage from se-vere brain injury.130,131

Another pattern described by some as consistent withNCSE is triphasic waves. When EEGers use the term tripha-sic waves, they are usually implying a pattern seen with avariety of metabolic encephalopathies, particularly hepatic orrenal dysfunction. However, the term triphasic can also beused to describe the morphology of the waveform in thatsharp-and-slow wave complexes usually have 3 phases;hence, they are triphasic waves. Difficulties in distinguishingtriphasic waves from epileptiform sharp-and-slow wave com-plexes were initially noted by Foley et al,7 and recommen-dations are provided by several investigators.132–134 Kaplan89

felt that triphasic waves may straddle the borders betweenepilepsy and encephalopathy and that the distinction betweenNCSE and encephalopathy can be difficult, whereas Litt etal117 felt that monorhythmic triphasic waves could be distin-guished from ictal patterns. Clearly, there are times when thisdistinction can be difficult; hence, the terms “triphasic-likewaves” and nonepileptiform “true triphasic waves.”56 Tripha-sic waves may increase with stimulation; this is also true ofPLEDs, BIPLEDs, and GPEDs.2 In a study of 150 criticallyill patients undergoing continuous EEG monitoring (with orwithout video), 33 patients exhibited stimulus-induced, rhyth-mic, periodic, or ictal discharges, which the authors termedSIRPIDs. They concluded that further research is necessaryto determine the pathophysiological, prognostic, and thera-peutic significance of SIRPIDS.

NCSE consists of EEG ictal episodes that are continu-ous or recurrent for greater than 30 minutes without improve-ment in clinical state or return to preictal EEG patternbetween seizures. There are no agreed-on criteria to diagnoseNCSE in obtunded/comatose patients. Litt et al117 described3 EEG patterns of electrographic SE: focal, generalized, andbihemispheric (Fig. 16A–C). It is relatively easy to diagnoseNCSE when there are frequent focal electrographic seizures.The problem is greater with generalized spike and wave andsharp-and-slow wave complexes. The latter should not be

FIGURE 13. Left-sided electrographic discharge in the pa-tient shown in Figure 9.



invariant. There should be a waxing and waning of thesepatterns for inclusion; however, this can often be a verysubjective interpretation. Furthermore, changes in the pattern,if present, usually should not be only state-related. Forproposed criteria of nonconvulsive seizures (NCS), whichhelps define NCSE, see Young et al.135

Medications such as benzodiazepines, their effects onthe EEG, and their role in diagnosis are also debated. Forexample, a test dose of lorazepam may complicate matters,because most EEG patterns may resolve if the patient is givenan adequate dose, including triphasic waves resulting from ametabolic encephalopathy.136 Sometimes this can be shownto be the result of a state change, because the pattern recursafter painful stimulation. Improvement in the EEG after treat-ment does not prove that the discharges were ictal and respon-sible for the patients’ decreased responsiveness; clearly, markedclinical improvement is the preferred response.

The incidence of NCSE in obtunded/comatose patientsis uncertain. Towne and colleagues118 found that 8% of

comatose patients, excluding those with clinical evidence orhistory of seizures, were in NCSE, whereas Claassen et al1

reported that 59 of 570 critically ill patients were in NCSE. Ina prospective study of 198 cases with alteration of conscious-ness but without convulsions, 74 (37%) showed clinical orEEG evidence of definite or probable nontonic–clonic SE.114

NCSE should be considered in patients with an apparentlyprolonged “postictal state” after convulsive seizures. Jaitly etal127 studied 180 patients, ages 17 to 96 years, who weremonitored after clinical SE. Of these, 96 had ictal dischargesthat included both CSE and NCSE. Others116 found that afterCSE was controlled, EEG monitoring demonstrated that 48%had persistent electrographic seizures and 14% manifestedNCSE, which was predominantly partial rather than general-ized. NCSE should also be considered with unexplainedalteration of mental status or coma, with or without subtlemotor activity, such as facial myoclonus or nystagmoid eyemovements. An EEG is the only way to verify the diagnosis,although, as has been emphasized, interpretation can bedifficult. An EEG is also helpful in monitoring patients whoare being treated for SE, particularly because the neurologicexamination is affected by the administration of drugs such aslorazepam, midazolam, propofol, pentobarbital, or neuromus-cular-blocking agents.

The diagnostic criteria for NCSE are controversial, andthere are no agreed-on criteria to diagnose NCSE in ob-tunded/comatose patients, and there is no consensus on howit should it be treated.91 Furthermore, outcome is poor andseveral studies113,117 suggest that treatment may not be helpful.

ELECTROCEREBRAL INACTIVITYThe end stage of coma is electrocerebral inactivity

(ECI), previously called electrocerebral silence (ECS), de-fined as “no cerebral activity over 2 uV when recording fromscalp or referential electrode pairs, 10 or more cm apart withinterelectrode resistances under 10,000 ohms (or impedancesunder 6000 ohms) but over 100 ohms”137 (Fig. 17).

FIGURE 14. (A and B) (A) A left-sided electrographic seizureand (B) a right-sided seizure in the patient shown in Figure 10.

FIGURE 15. Periodic epileptiform discharges in a 75-year-old-woman.



EEG is an optional confirmatory test in the evaluationof brain death in adults. The American EEG Society Guide-lines137 discuss in detail technical standards to be used inrecording patients with suspected cerebral death. These in-clude considerations such as recording time, number of elec-trodes, interelectrode impedances, appropriate sensitivity andtime constant, tests of reactivity, and monitoring techniques.In cases in which ECI is present and the patient is beingevaluated for brain death, both hypothermia and drug intox-ication, which are potentially reversible, must be excluded.137

Regarding the former, Walker et al138 state that unless thetemperature is less than 32°C, it does not seem to depress theEEG appreciably, whereas arterial hypotension (at or belowshock levels) is a more potent depressor of EEG activity andshould be considered when interpreting the EEG. They alsofelt that the record usually should not be performed untilclinical evidence of brain death has been present for 12 hours,although this time might be shortened if the cause of coma iswell established as irreversible. In practice, 6 hours is oftenthe minimum.

Occasionally, patients with a persistent vegetative state(PVS) may have ECI, although the majority show EEGactivity. PVS implies permanent and total loss of forebrainfunction; however, many brainstem functions such as breath-ing, chewing, swallowing, and cranial nerve reflexes arelargely preserved. Similarities and contrasts between braindeath and PVS have been reviewed by Young et al.135 Otherpatients may clinically appear brain-dead yet the EEG dem-onstrates cerebral activity. Such examples include brainstemdeath139–142 or severe polyradiculoneuropathy.143,144 Cha-trian and Turella145 have critically reviewed the concept ofbrain death, including definition, clinical criteria, and differ-ences between the United Kingdom and the United States, aswell as other states of altered responsiveness such as selectivefailure of brainstem function and vegetative states.

FIGURE 16. (A) A focal right posterior head region electro-graphic seizure in this 83-year-old-man in partial nonconvulsivestatus epilepticus (NCSE). (B) Bihemispheric NCSE in a 72-year-old woman status postresection of a bifrontal–parietal meningi-oma. (C) Generalized NCSE in a 64-year-old-man after anoxia.

FIGURE 17. A 44-year-old man in a persistent vegetativestate. There is no definite cerebral activity. Eye blink artifactis present.



ACKNOWLEDGMENTSMuch of this material appeared in Brenner RP. The

EEG in encephalopathy and coma. Am J End Technol 2003;43:164–184. Reproduced with permission of the publisher.

REFERENCES1. Claassen J, Mayer SA, Kowalski RG, et al. Detection of electrographic

seizures with continuous EEG monitoring in critically ill patients.Neurology. 2004;62:1743–1748.

2. Hirsch LJ, Claassen J, Mayer SA, et al. Stimulus-induced rhythmic,periodic, or ictal discharges (SIRPIDs): a common EEG phenomenonin the critically ill. Epilepsia. 2004a;45:109–123.

3. Hirsch LJ, Kull LL. Continuous EEG monitoring in the intensive careunit. Am J Electroneurodiagnostic Technol. 2004b;44:137–158.

4. Pandian JD, Cascino GD, So EL, et al. Digital video-electroencepha-lographic monitoring in the neurological–neurosurgical intensive careunit: clinical features and outcome. Arch Neurol. 2004;61:1090–1094.

5. Scheuer ML, Wilson SB. Data analysis for continuous EEG monitoringin the ICU: seeing the forest and the trees. J Clin Neurophysiol. 2004.

6. Young GB. The EEG in coma. J Clin Neurophysiol. 2000;17:473–485.7. Foley JM, Watson CW, Adams RD. Significance of the electroencepha-

lographic changes in hepatic coma. Trans Am Neurol Assoc. 1950;75:161–164.

8. Bickford RG, Butt HR. Hepatic coma: the electroencephalographicpattern. J Clin Invest. 1955;34:790–799.

9. Karnaze DS, Bickford RG. Triphasic waves: a reassessment of theirsignificance. Electroencephalogr Clin Neurophysiol. 1984;57:193–198.

10. Bahamon-Dussan JE, Celesia GG, Grigg-Damberger MM. Prognosticsignificance of EEG triphasic waves in patients with altered state ofconsciousness. J Clin Neurophysiol. 1989;6:313–319.

11. Sundaram MB, Blume WT. Triphasic waves: clinical correlates andmorphology. Can J Neurol Sci. 1987;14:136–140.

12. Fisch BJ, Klass DW. The diagnostic specificity of triphasic wavepatterns. Electroencephalogr Clin Neurophysiol. 1988;70:1–8.

13. Hughes JR. Correlations between EEG and chemical changes in ure-mia. Electroencephalogr Clin Neurophysiol. 1980;48:583–594.

14. Hughes JR, Schreeder MT. EEG in dialysis encephalopathy. Neurol-ogy. 1980;30:1148–1154.

15. O’Hare JA, Callaghan NM, Murnaghan DJ. Dialysis encephalopathy.Clinical, electroencephalographic and interventional aspects. Medicine.1983;62:129–141.

16. Bleck TP, Smith MC, Pierre-Louis SJ, et al. Neurologic complicationsof critical medical illnesses. Crit Care Med. 1993;21:98–103.

17. Young G, Leung L, Campbell V, et al. The electroencephalogram inmetabolic/toxic coma. Am J EEG Technol. 1992a;32:243–259.

18. Stockard JJ, Werner SS, Aalbers JA, et al. Electroencephalographicfindings in phencyclidine intoxication. Arch Neurol. 1976;33:200–203.

19. Brenner RP, Schaul N. Periodic EEG patterns: classification, clin-ical correlation, and pathophysiology. J Clin Neurophysiol. 1990;7:249 –267.

20. Yamashita S, Morinaga T, Ohgo S, et al. Prognostic value of electro-encephalogram (EEG) in anoxic encephalopathy after cardiopulmonaryresuscitation: relationship among anoxic period, EEG grading andoutcome. Intern Med. 1995;34:71–76.

21. Yemisci M, Gurer G, Saygi S, et al. Generalised periodic epileptiformdischarges: clinical features, neuroradiological evaluation and progno-sis in 37 adult patients. Seizure. 2003;12:465–472.

22. Hormes JT, Benarroch EE, Rodriguez M, et al. Periodic sharp waves inbaclofen-induced encephalopathy. Arch Neurol. 1988;45:814–815.

23. Zak R, Solomon G, Petito F, et al. Baclofen-induced generalizednonconvulsive status epilepticus. Ann Neurol. 1994;36:113–114.

24. Neufeld MY. Periodic triphasic waves in levodopa-induced encepha-lopathy. Neurology. 1992;42:444–446.

25. Smith SJ, Kocen RS. A Creutzfeldt-Jakob like syndrome due to lithiumtoxicity. J Neurol Neurosurg Psychiatry. 1988;51:120–123.

26. Simonian NA, Gilliam FG, Chiappa KH. Ifosfamide causes a diaze-pam-sensitive encephalopathy. Neurology. 1993;43:2700–2702.

27. Wengs WJ, Talwar D, Bernard J. Ifosfamide-induced nonconvulsivestatus epilepticus. Arch Neurol. 1993;50:1104–1105.

28. Drake ME, Erwin CW. Triphasic EEG discharges in metrizamideencephalopathy. J Neurol Neurosurg Psychiatry. 1984;47:324–325.

29. Elian M, Fenwick P. Metrizamide and the EEG: three case reports anda review. J Neurol. 1985;232:341–345.

30. Levin R, Lee SI. Nonconvulsive status epilepticus following metriz-amide myelogram. Ann Neurol. 1985;17:518–519.

31. Obeid T, Yaqub B, Panayiotopoulos C, et al. Absence status epilepticuswith computed tomographic brain changes following metrizamidemyelography. Ann Neurol. 1988;24:582–584.

32. Potts K. Seizures and encephalopathies following metrizamide myelog-raphy and cisternography. Am J EEG Technol. 1990;30:45–57.

33. Herkes GK, Wszolek ZK, Westmoreland BF, et al. Effects of midazo-lam on electroencephalograms of seriously ill patients. Mayo ClinProc. 1992;67:334–338.

34. Fisch BJ, Hauser WA, Brust JC, et al. The EEG response to diffuse andpatterned photic stimulation during acute untreated alcohol withdrawal.Neurology. 1989;39:434–436.

35. Vossler DG, Browne TR. Rarity of EEG photo-paroxysmal and photo-myogenic responses following treated alcohol-related seizures. Neurol-ogy. 1990;40:723–724.

36. Kelly JT, Reilly EL. EEG, alcohol and alcoholism. In: Hughes JR,Wilson WP, eds. EEG and Evoked Potentials in Psychiatry andBehavioral Neurology. Boston: Butterworths; 1983:55–78.

37. Allahyari H, Deisenhammer E, Weiser G. EEG examination duringdelirium tremens. Psychiatr Clin (Basel). 1976;9:21–31.

38. Lotz BP, Schutte CM, Bartel PR, et al. Recurrent attacks of uncon-sciousness with diffuse EEG alpha activity. Sleep. 1993;16:671–677.

39. Tinuper P, Montagna P, Plazzi G, et al. Idiopathic recurring stupor.Neurology. 1994;44:621–625.

40. Lugaresi E, Montagna P, Tinuper P, et al. Endozepine stupor. Recurringstupor linked to endozepine-4 accumulation. Brain. 1998a;121:127–133.

41. Lugaresi E, Montagna P, Tinuper P, et al. Suspected covert lorazepamadministration misdiagnosed as recurrent endozepine stupor. Brain.1998b;121:2201.

42. Haimovic IC, Beresford HR. Transient unresponsiveness in the elderly.Report of five cases. Arch Neurol. 1992;49:35–37.

43. Rao TH, Schneider LB, Lupyan Y. Transient unresponsiveness in theelderly. Arch Neurol. 1994;51:644.

44. Drury I. The EEG in hypoxic–ischemic encephalopathy. Am J EEGTechnol. 1988;70:1–8.

45. Kuroiwa Y, Celesia GG. Clinical significance of periodic EEG patterns.Arch Neurol. 1980;37:15–20.

46. Pourmand R. Burst-suppression pattern with unusual clinical corre-lates. Clin Electroencephalogr. 1994;25:160–163.

47. Reeves AL, Westmoreland BF, Klass DW. Clinical accompanimentsof the burst-suppression EEG pattern. J Clin Neurophysiol. 1997;14:150–153.

48. Jumao-as A, Brenner RP. Myoclonic status epilepticus: a clinical andelectroencephalographic study. Neurology. 1990;40:1199–1202.

49. Krumholz A, Stern BJ, Weiss HD. Outcome from coma after cardio-pulmonary resuscitation: relation to seizures and myoclonus. Neurol-ogy. 1988;38:401–405.

50. Celesia GG, Grigg MM, Ross E. Generalized status myoclonicus inacute anoxic and toxic–metabolic encephalopathies. Arch Neurol.1988;45:781–784.

51. Rothner A, Morris H. Generalized status epilepticus. In: Luders H LR,ed. Epilepsy: Electroclinical Syndromes. London: Springer-Verlag;1988:207–222.

52. Young GB, Gilbert JJ, Zochodne DW. The significance of myoclonicstatus epilepticus in postanoxic coma. Neurology. 1990;40:1843–1848.

53. Wijdicks EF, Parisi JE, Sharbrough FW. Prognostic value of myoclo-nus status in comatose survivors of cardiac arrest. Ann Neurol. 1994;35:239–243.

54. Treiman D, DeGirgio C, Salisbury S, et al. Subtle generalized statusepilepticus. Epilepsia. 1984;25:653.

55. Scollo-Lavizzari G, Bassetti C. Prognostic value of EEG in post-anoxiccoma after cardiac arrest. Eur Neurol. 1987;26:161–170.

56. Husain AM, Mebust KA, Radtke RA. Generalized periodic epilepti-form discharges: etiologies, relationship to status epilepticus, andprognosis. J Clin Neurophysiol. 1999;16:51–58.

57. Brenner RP, Schwartzman RJ, Richey ET. Prognostic significance of



episodic low amplitude or relatively isoelectric EEG patterns. Dis NervSyst. 1975;36:582–587.

58. Rae-Grant AD, Strapple C, Barbour PJ. Episodic low-amplitude events:an under-recognized phenomenon in clinical electroencephalography.J Clin Neurophysiol. 1991;8:203–211.

59. Hockaday JM, Potts F, Epstein E, et al. Electroencephalographicchanges in acute cerebral anoxia from cardiac or respiratory arrest.Electroencephalogr Clin Neurophysiol. 1965;18:575–586.

60. Markand ON. Electroencephalography in diffuse encephalopathies.J Clin Neurophysiol. 1984;1:357–407.

61. Synek VM. Prognostically important EEG coma patterns in diffuseanoxic and traumatic encephalopathies in adults. J Clin Neurophysiol.1988;5:161–174.

62. Young GB, McLachlan RS, Kreeft JH, et al. An electroencephalo-graphic classification for coma. Can J Neurol Sci. 1997;24:320–325.

63. Bassetti C, Bomio F, Mathis J, et al. Early prognosis in coma aftercardiac arrest: a prospective clinical, electrophysiological, and bio-chemical study of 60 patients. J Neurol Neurosurg Psychiatry. 1996;61:610–615.

64. Chen R, Bolton CF, Young B. Prediction of outcome in patients withanoxic coma: a clinical and electrophysiologic study. Crit Care Med.1996;24:672–678.

65. Chiappa KH, Hill RA. Evaluation and prognostication in coma. Elec-troencephalogr Clin Neurophysiol. 1998;106:149–155.

66. Zandbergen EG, de Haan RJ, Stoutenbeek CP, et al. Systematic reviewof early prediction of poor outcome in anoxic–ischaemic coma. Lancet.1998;352:1808–1812.

67. Westmoreland BF, Klass DW, Sharbrough FW, et al. Alpha-coma.Electroencephalographic, clinical, pathologic, and etiologic correla-tions. Arch Neurol. 1975;32:713–718.

68. Iragui VJ, McCutchen CB. Physiologic and prognostic significance of‘alpha coma’. J Neurol Neurosurg Psychiatry. 1983;46:632–638.

69. Sorensen K, Thomassen A, Wernberg M. Prognostic significance ofalpha frequency EEG rhythm in coma after cardiac arrest. J NeurolNeurosurg Psychiatry. 1978;41:840–842.

70. Austin EJ, Wilkus RJ, Longstreth WT Jr. Etiology and prognosis ofalpha coma. Neurology. 1988;38:773–777.

71. Young GB, Blume WT, Campbell VM, et al. Alpha, theta and alpha-theta coma: a clinical outcome study utilizing serial recordings. Elec-troencephalogr Clin Neurophysiol. 1994;91:93–99.

72. Berkhoff M, Donati F, Bassetti C. Postanoxic alpha (theta) coma: areappraisal of its prognostic significance. Clin Neurophysiol. 2000;111:297–304.

73. Kaplan PW, Genoud D, Ho TW, et al. Etiology, neurologic correlations,and prognosis in alpha coma. Clin Neurophysiol. 1999b;110:205–213.

74. Chatrian GE, Shaw CM, Leffman H. The significance of periodiclateralized epileptiform discharges in EEG: an electrographic, clinicaland pathological study. Electroencephalogr Clin Neurophysiol. 1964;17:177–193.

75. Reiher J, Rivest J, Grand’Maison F, et al. Periodic lateralized epilep-tiform discharges with transitional rhythmic discharges: associationwith seizures. Electroencephalogr Clin Neurophysiol. 1991;78:12–17.

76. Garcia-Morales I, Garcia MT, Galan-Davila L, et al. Periodic lateral-ized epileptiform discharges: etiology, clinical aspects, seizures, andevolution in 130 patients. J Clin Neurophysiol. 2002;19:172–177.

77. Snodgrass SM, Tsuburaya K, Ajmone-Marsan C. Clinical significanceof periodic lateralized epileptiform discharges: relationship with statusepilepticus. J Clin Neurophysiol. 1989;6:159–172.

78. Brick JF, Brick JE, Morgan JJ, et al. EEG and pathologic findings inpatients undergoing brain biopsy for suspected encephalitis. Electro-encephalogr Clin Neurophysiol. 1990;76:86–89.

79. de la Paz D, Brenner RP. Bilateral independent periodic lateralizedepileptiform discharges. Clinical significance. Arch Neurol. 1981;38:713–715.

80. Chase TN, Moretti L, Prensky AL. Clinical and electroencephalo-graphic manifestations of vascular lesions of the pons. Neurology.1968;18:357–368.

81. Markand ON. Electroencephalogram in ‘locked-in’ syndrome. Electro-encephalogr Clin Neurophysiol. 1976;40:529–534.

82. Gutling E, Isenmann S, Wichmann W. Electrophysiology in the locked-in-syndrome. Neurology. 1996;46:1092–1101.

83. Bassetti C, Hess CW. Electrophysiology in locked-in syndrome. Neu-rology. 1997;49:309.

84. Britt CW Jr. Nontraumatic ‘spindle coma’: clinical, EEG, and prog-nostic features. Neurology. 1981;31:393–397.

85. Chatrian GE, White LE Jr, Daly D. Electroencephalographic patternsresembling those of sleep in certain comatose states after injuries to thehead. Electroencephalogr Clin Neurophysiol. 1963;15:272–280.

86. Hansotia P, Gottschalk P, Green P, et al. Spindle coma: incidence,clinicopathologic correlates, and prognostic value. Neurology. 1981;31:83–87.

87. Hulihan JF Jr, Syna DR. Electroencephalographic sleep patterns inpost-anoxic stupor and coma. Neurology. 1994;44:758–760.

88. Kaplan PW, Genoud D, Ho TW, et al. Clinical correlates and prognosisin early spindle coma. Clin Neurophysiol. 2000;111:584–590.

89. Kaplan PW. Assessing the outcomes in patients with nonconvulsivestatus epilepticus: nonconvulsive status epilepticus is underdiagnosed,potentially overtreated, and confounded by comorbidity. J Clin Neu-rophysiol. 1999a;16:341–352.

90. Shneker BF, Fountain NB. Assessment of acute morbidity and mortal-ity in nonconvulsive status epilepticus. Neurology. 2003;61:1066–1073.

91. Kaplan PW. Nonconvulsive status epilepticus. 2003;61:1035–1036.92. Porter RJ, Penry JK. Petit mal status. In: Delgado-Escueta AV, Was-

terlain CG, Treiman DM, et al., eds. Advances in Neurology StatusEpilepticus: Mechanisms of Brain Damage and Treatment. New York:Raven Press; 1983:61–68.

93. Shorvon S. Status Epilepticus: Its Clinical Features and Treatment inChildren and Adults. Cambridge: Cambridge University Press; 1994.

94. Agathonikou A, Panayiotopoulos CP, Giannakodimos S, et al. Typicalabsence status in adults: diagnostic and syndromic considerations.Epilepsia. 1998;39:1265–1276.

95. Baykan B, Gokyigit A, Gurses C, et al. Recurrent absence status epilep-ticus: clinical and EEG characteristics. Seizure. 2002;11:310–319.

96. Gastaut H, Tassineri C. Epilepsies. In: Remond A, ed. Handbook ofElectroencephalography and Clinical Neurophysiology. Amsterdam:Elsevier; 1975:39–45.

97. Granner MA, Lee SI. Nonconvulsive status epilepticus: EEG analysisin a large series. Epilepsia. 1994;35:42–47.

98. Lee SI. Nonconvulsive status epilepticus. Ictal confusion in later life.Arch Neurol. 1985;42:778–781.

99. Guberman A, Cantu-Reyna G, Stuss D, et al. Nonconvulsive general-ized status epilepticus: clinical features, neuropsychological testing,and long-term follow-up. Neurology. 1986;36:1284–1291.

100. Thomas P, Beaumanoir A, Genton P, et al. De novo absence status oflate onset: report of 11 cases withdrawal syndrome. Neurology. 1992;42:104–110.

101. Thomas P, Lebrun C, Chatel M. De novo absence status epilepticus asa benzodiazepine withdrawal syndrome. Epilepsia. 1993;34:355–358.

102. Fagan KJ, Lee SI. Prolonged confusion following convulsions due togeneralized nonconvulsive status epilepticus. Neurology. 1990;40:1689–1694.

103. Varma NK, Lee SI. Nonconvulsive status epilepticus following elec-troconvulsive therapy. Neurology. 1992;42:263–264.

104. Thomas P, Zifkin B, Migneco O, et al. Nonconvulsive status epilepti-cus of frontal origin. Neurology. 1999;52:1174–1183.

105. Tomson T, Lindbom U, Nilsson BY. Nonconvulsive status epilepticusin adults: thirty-two consecutive patients from a general hospitalpopulation. Epilepsia. 1992;33:829–835.

106. Treiman DM, Delgado-Escueta AV. Complex partial status epilepticus.In: Delgado-Escueta AV, Wasterlain CG, Treiman DM, et al., eds.Advances in Neurology. Status Epilepticus: Mechanisms of BrainDamage and Treatment. New York: Raven Press; 1983:69–81.

107. Tomson T, Svanborg E, Wedlund JE. Nonconvulsive status epilep-ticus: high incidence of complex partial status. Epilepsia. 1986;27:276 –285.

108. Brenner RP. Is it status? Epilepsia. 2002;43(suppl 3):103–113.109. Lawn ND, Wijdicks EF. Progress in clinical neurosciences: status

epilepticus: a critical review of management options. Can J Neurol Sci.2002;29:206–215.

110. Walker MC. Diagnosis and treatment of nonconvulsive status epilep-ticus. CNS Drugs. 2001;15:931–939.



111. Simon RP, Aminoff MJ. Electrographic status epilepticus in fatalanoxic coma. Ann Neurol. 1986;20:351–355.

112. Lowenstein DH, Aminoff MJ. Clinical and EEG features ofstatus epilepticus in comatose patients. Neurology. 1992;42:100 –104.

113. Drislane FW, Schomer DL. Clinical implications of generalized elec-trographic status epilepticus. Epilepsy Res. 1994;19:111–121.

114. Privitera M, Hoffman M, Moore JL, et al. EEG detection of nontonic–clonic status epilepticus in patients with altered consciousness. Epi-lepsy Res. 1994;18:155–166.

115. So E, Ruggles K, Ahmann P, et al. Clinical significance and outcomeof subclinical status epilepticus in adults. Epilepsy. 1995;8:11–15.

116. DeLorenzo RJ, Waterhouse EJ, Towne AR, et al. Persistent noncon-vulsive status epilepticus after the control of convulsive status epilep-ticus. Epilepsia. 1998;39:833–840.

117. Litt B, Wityk RJ, Hertz SH, et al. Nonconvulsive status epilepticus inthe critically ill elderly. Epilepsia. 1998;39:1194–1202.

118. Towne AR, Waterhouse EJ, Boggs JG, et al. Prevalence of nonconvulsivestatus epilepticus in comatose patients. Neurology. 2000;54:340–345.

119. Treiman DM. Electroclinical features of status epilepticus. J ClinNeurophysiol. 1995;12:343–362.

120. Husain AM, Horn GJ, Jacobson MP. Non-convulsive status epilepticus:usefulness of clinical features in selecting patients for urgent EEG.J Neurol Neurosurg Psychiatry. 2003;74:189–191.

121. Treiman DM, Walton NY, Kendrick C. A progressive sequence ofelectroencephalographic changes during generalized convulsive statusepilepticus. Epilepsy Res. 1990;5:49–60.

122. Handforth A, Cheng JT, Mandelkern MA, et al. Markedly increasedmesiotemporal lobe metabolism in a case with PLEDs: further evidencethat PLEDs are a manifestation of partial status epilepticus. Epilepsia.1994;35:876–881.

123. Garzon E, Fernandes RM, Sakamoto AC. Serial EEG during humanstatus epilepticus: evidence for PLED as an ictal pattern. Neurology.2001;57:1175–1183.

124. Assal F, Papazyan JP, Slosman DO, et al. SPECT in periodic lateral-ized epileptiform discharges (PLEDs): a form of partial status epilep-ticus? Seizure. 2001;10:260–265.

125. Claassen J, Hirsch LJ, Emerson RG, et al. Continuous EEG monitoringand midazolam infusion for refractory nonconvulsive status epilepti-cus. Neurology. 2001;57:1036–1042.

126. Jordan KG. Nonconvulsive status epilepticus in acute brain injury.J Clin Neurophysiol. 1999;16:332–340; discussion 353.

127. Jaitly R, Sgro JA, Towne AR, et al. Prognostic value of EEG moni-toring after status epilepticus: a prospective adult study. J Clin Neuro-physiol. 1997;14:326–334.

128. Pohlmann-Eden B, Hoch DB, Cochius JI, et al. Periodic lateralized epilepti-form discharges—a critical review. J Clin Neurophysiol. 1996;13:519–530.

129. Nei M, Lee JM, Shanker VL, et al. The EEG and prognosis in statusepilepticus. Epilepsia. 1999;40:157–163.

130. Krumholz A. Epidemiology and evidence for morbidity of nonconvulsivestatus epilepticus. J Clin Neurophysiol. 1999;16:314–322; discussion 353.

131. Niedermeyer E, Ribeiro M. Considerations of nonconvulsive statusepilepticus. Clin Electroencephalogr. 2000;31:192–195.

132. Klass DW. Principles in the differentiation of atypical spike-wavesand triphasic waves. Am J EEG Technol. 1990;30:313–314.

133. Hughes J. Principles in the differentiation of atypical spike-waves andtriphasic waves. Am J EEG Technol. 1990;30:309–312.

134. Ghigo J. Principles in the differentiation of atypical spike-waves andtriphasic waves: a technologist’s view. Am J EEG Technol. 1990;30:315–316.

135. Young GB, Jordan KG, Doig GS. An assessment of nonconvulsiveseizures in the intensive care unit using continuous EEG monitoring: aninvestigation of variables associated with mortality. Neurology. 1996;47:83–89.

136. Fountain NB, Waldman WA. Effects of benzodiazepines on triphasicwaves: implications for nonconvulsive status epilepticus. J Clin Neu-rophysiol. 2001;18:345–352.

137. American EEG Society. Guideline 3: Minimum technical standards forEEG recording in suspected cerebral death. J Clin Neurophysiol.1994;11:10–13.

138. Walker AE, Bennett DR, Bricolo A, et al. Report on the cessation ofcerebral function. In: Cobb WA, ed. Recommendations for the Practiceof Clinical Neurophysiology. Amsterdam: Elsevier; 1983:41–43.

139. Ferbert A, Buchner H, Ringelstein EB, et al. Isolated brain-stem death.Case report with demonstration of preserved visual evoked potentials(VEPs). Electroencephalogr Clin Neurophysiol. 1986;65:157–160.

140. Darby J, Yonas H, Brenner RP. Brainstem death with persistent EEGactivity: evaluation by xenon-enhanced computed tomography. CritCare Med. 1987;15:519–521.

141. Grigg MM, Kelly MA, Celesia GG, et al. Electroencephalographicactivity after brain death. Arch Neurol. 1987;44:948–954.

142. Kaukinen S, Makela K, Hakkinen VK, et al. Significance of electricalbrain activity in brain-stem death. Intensive Care Med. 1995;21:76–78.

143. Drury I, Westmoreland BF, Sharbrough FW. Fulminant demyelinatingpolyradiculoneuropathy resembling brain death. ElectroencephalogrClin Neurophysiol. 1987;67:42–43.

144. Vargas F, Hilbert G, Gruson D, et al. Fulminant Guillain-Barre syn-drome mimicking cerebral death: case report and literature review.Intensive Care Med. 2000;26:623–627.

145. Chatrian GE, Turella GS. Electrophysiological evaluation of coma,other states of diminished responsiveness, and brain death. In: EbersoleJS, Pedley TA, eds. Current Practice of Clinical Electroencephalog-raphy, 3rd ed. Philadelphia: Lippincott Williams & Wilkins; 2003:405–462.



interpretación del EEG en estupor y coma.

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