The interpretation of the EEG in stupor and coma

This review discusses a variety of causes of stupor and coma and associated electroencephalographic (EEG) findings. These include metabolic disturbances such as hepatic or renal dysfunction, which are often characterized by slowing of background rhythms and triphasic waves. Hypoxia and drug intoxications can produce a number of abnormal EEG patterns such as burst suppression, alpha coma, and spindle coma. Structural lesions, either supra- or infratentorial, are reviewed. EEGs in the former may show focal disturbances such as delta and theta activity, epileptiform abnormalities, and attenuation of faster frequencies. In infratentorial lesions, the EEG may appear normal, particularly with a pontine lesion. Some patients may be encephalopathic because of ongoing epileptic activity with minimal or no motor movements. This entity, nonconvulsive status epilepticus (NCSE), is difficult to diagnose in obtunded/comatose patients, and an EEG is required to verify the diagnosis and to monitor treatment. Several EEG patterns and their interpretation in suspected cases of NCSE such as periodic lateralized epileptiform discharges (PLEDs), bilateral independent periodic lateralized epileptiform discharges (BIPLEDs), generalized periodic epileptiform discharges (GPEDs), and triphasic waves are reviewed. Other entities discussed include the locked-in syndrome, neocortical death, persistent vegetative state, brainstem death, and brain death.     

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”.     

Nonconvulsive status epilepticus in children: clinical and EEG characteristics

BACKGROUND: Nonconvulsive status epilepticus (NCSE) is a highly heterogeneous clinical condition that is understudied in the pediatric population. OBJECTIVE: To analyze the epidemiological, clinical, and electroencephalograpic features in pediatric patients with NCSE. METHODS: We identified 19 pediatric patients with NCSE from the epilepsy database of the Comprehensive Epilepsy Center at, Columbia University between June 2000 and December 2003. Continuous electroencephalographic (EEG) monitoring was analyzed and chart review was performed. RESULTS: The patients ranged from 1 month old to 17 years of age. Five patients developed NCSE following convulsive status epilepticus (CSE), and a further 12 patients developed NCSE after brief convulsions. Two developed NCSE as the first manifestation during a comatose state following hypoxic events. Acute hypoxic-ischemic injury was the most frequent etiology of NCSE in our population (5 of 19; 26%), followed by exacerbation of underlying neurometabolic disease (4 of 19; 21%), acute infection (3 of 19; 16%), change in antiepileptic drug regimen (3 of 19;16%), refractory epilepsy (2 of 19; 11%) and intracranial hemorrhage (2 of 19; 11%). Six patients had associated periodic lateralized epileptiform discharges (PLEDs), one had generalized periodic epileptiform discharges (GPEDs). Five (5 of 19; 26%) patients died of the underlying acute medical illness. Periodic discharges were associated with worse outcome. CONCLUSION: The majority of our patients with NCSE had preceding seizures in the acute setting prior to the diagnosis of NCSE, though most of these seizures were brief, isolated convulsions (12 patients) rather than CSE (five patients). Prolonged EEG monitoring to exclude NCSE may be warranted in pediatric patients even after brief convulsive seizures. Prompt recognition and treatment may be necessary to improve neurological outcome.     

Presentation,evaluation, and treatment of nonconvulsive status epilepticus

Nonconvulsive status epilepticus (NCSE) is much more common than is generally appreciated. It is certainly underdiagnosed, but its presentation is protean. Diagnostic criteria and treatment are controversial. Absence status is characterized by confusion or diminished responsiveness, with occasional blinking or twitching, lasting hours to days, with generalized spike and slow wave discharges on the EEG. Complex partial status consists of prolonged or repetitive complex partial seizures (with a presumed focal onset) and produces an "epileptic twilight state" with fluctuating lack of responsiveness or confusion. There is a clear overlapping of syndromes. Other confused, stuporous, or comatose patients with rapid, rhythmic, epileptiform discharges on the EEG may have "electrographic" status and should be considered in the same diagnostic category. NCSE typically occurs following supposedly controlled convulsions or other seizures, but with persistent neurologic dysfunction despite apparently adequate treatment. Confusion in the elderly or among emergency room patients is also a typical setting. The diagnosis of NCSE usually involves an abnormal mental status with diminished responsiveness, a supportive EEG, and often a response to anticonvulsant medication. All patients have clinical neurologic deficits, but the EEG findings and response to seizure medication are variable and are more controversial criteria. The response to drugs can be delayed for up to days. Experimental models and pathologic studies showing neuronal damage from status epilepticus pertain primarily to generalized convulsive status. Most morbidity from NCSE appears due to the underlying illness rather than to the NCSE itself. Some cases of prolonged NCSE or those with concomitant systemic illness, focal lesions, or very rapid epileptiform discharges may suffer more long-lasting damage. Although clinical studies show little evidence of permanent neurologic injury, the prolonged memory dysfunction in several cases and the similarities to convulsive status suggest that NCSE should be treated expeditiously. The diagnosis is important to make because NCSE impairs the patient's health significantly, and it is often a treatable and completely reversible condition.     

No, some types of nonconvulsive status epilepticus cause little permanent neurologic sequelae (or: « The cure may be worse than the disease »)

Nonconvulsive status epilepticus (NCSE) is characterized by a cognitive or behavioral change which lasts for at least 30 minutes, with EEG evidence of seizures. Although there is little argument that generalized nonconvulsive status epilepticus (GNSE) does not cause lasting deficits, there is still debate regarding the morbidity of complex partial status epilepticus (CPSE). Because the EEG is used for diagnosis, a strong argument can be made that NCSE is significantly under-recognized and diagnosed. Furthermore, since the documented cases of permanent neurologic sequelae are few, the potential permanent morbidity from CPSE may be significantly exaggerated. The literature indicates that comatose patients have a poor prognosis largely as a result of comorbid conditions and coma, whereas lightly obtunded or slightly confused patients with NCSE have little or no sequelae. Patients with NCSE may suffer (hypotension and respiratory suppression) from iatrogenic 'aggressive' treatment with intravenous anti-epileptic drugs (IV-AEDs), and the findings in the literature indicate that subjects treated with benzodiazepines may have a worse prognosis. The clinician must balance the potential but rare neurologic morbidity associated with NCSE against the not infrequent morbidity caused by IV-AEDs. Better stratification of the level of consciousness and comorbid conditions is needed when evaluating outcomes so as to clearly distinguish among the deficits due to: comorbid conditions; the effects of treatment and the effects of status epilepticus (SE) proper.     

Prevalence of nonconvulsive status epilepticus in comatose patients

BACKGROUND: Nonconvulsive status epilepticus (NCSE) is a form of status epilepticus (SE) that is an often unrecognized cause of coma. OBJECTIVE: To evaluate the presence of NCSE in comatose patients with no clinical signs of seizure activity. METHODS: A total of 236 patients with coma and no overt clinical seizure activity were monitored with EEG as part of their coma evaluation. This study was conducted during our prospective evaluation of SE, where it has been validated that we identify over 95% of all SE cases at the Medical College of Virginia Hospitals. Only cases that were found to have no clinical signs of SE were included in this study. RESULTS: EEG demonstrated that 8% of these patients met the criteria for the diagnosis of NCSE. The study included an age range from 1 month to 87 years. CONCLUSION: This large-scale EEG evaluation of comatose patients without clinical signs of seizure activity found that NCSE is an underrecognized cause of coma, occurring in 8% of all comatose patients without signs of seizure activity. EEG should be included in the routine evaluation of comatose patients even if clinical seizure activity is not apparent.     

Nonconvulsive status epilepticus

Nonconvulsive status epilepticus (NCSE) is a heterogeneous disorder with multiple subtypes. Although attempts have been made to define and classify this disorder, there is yet no universally accepted definition or classification that encompasses all subtypes or electroclinical scenarios. Developing such a classification scheme is becoming increasingly important, because NCSE is more common than previously thought, with a bimodal peak, in children and the elderly. Recent studies have also shown a high incidence of NCSE in the critically ill. Although strong epidemiological data are lacking, NCSE constitutes about 25-50% of all cases of status epilepticus. For the purposes of this review, we propose an etiological classification for NCSE including NCSE in metabolic disorders, NCSE in coma, NCSE in acute cerebral lesions, and NCSE in those with preexisting epilepsy with or without epileptic encephalopathy. NCSE is still underrecognized, yet potentially fatal if untreated. Diagnosis can be established using an electroencephalogram (EEG) in most cases, sometimes requiring continuous monitoring. However, in comatose patients, diagnosis can be difficult, and the EEG can show a variety of rhythmic or periodic patterns, some of which are of unclear significance. Although some subtypes of NCSE are easily treatable, such as absence status epilepticus, others do not respond well to treatment, and debate exists over how aggressively clinicians should treat NCSE. In particular, the appropriate treatment of NCSE in patients who are critically ill and/or comatose is not well established, and large-scale trials are needed. Overall, further work is needed to better define NCSE, to determine which EEG patterns represent NCSE, and to establish treatment paradigms for different subtypes of NCSE.     

Rhythmic diffuse delta frequency activity presenting as an unusual EEG correlate of nonconvulsive status epilepticus: three case studies

We report three cases of nonconvulsive status epilepticus (NCSE) in which electroencephalograms (EEGs) were dominated by rhythmic or semirhythmic, high-voltage, diffuse, delta activity. These recordings initially contained little or no clear epileptiform activity. Two of these patients had prolonged episodes of NCSE, which were recorded with continuous long-term EEGs. These recordings revealed focal epileptiform discharges as well as persistent generalized epileptiform patterns. Rhythmic or semirhythmic, diffuse, delta activity with little or no clear epileptiform components has only rarely been reported with NCSE. Diffuse delta slowing is commonly seen in many toxic-metabolic encephalopathies, and this activity may occasionally appear rhythmic. EEG and clinical characteristics that may help distinguish these conditions are discussed.     

Falsely pessimistic prognosis by EEG in post-anoxic coma after cardiac arrest: the borderland of nonconvulsive status epilepticus

Background. Prognostication following anoxic coma relies on clinical assessment and is assisted by neurophysiology. A non-evolving EEG spike burst/isoelectric suppression pattern after the first 24 hours almost invariably indicates poor outcome, while an evolving pattern implies nonconvulsive status epilepticus (NCSE) that may "hide" surviving brain activity and is amenable to treatment. Case study. We present the case of a 53-year-old woman who had a witnessed out-of-hospital ventricular fibrillation cardiac arrest, was resuscitated by paramedics, but remained comatose. An EEG, performed 36 hours post-insult, showed an unremitting, non-evolving, unresponsive 2-6?Hz high-voltage spike burst/isoelectric suppression pattern, which remained unchanged at 96 hours post-insult, following therapeutic hypothermia. During this period, she was completely off sedation and taking triple antiepileptic treatment, without systemic confounding disorders. Although the initial pattern was indicative of poor neurological outcome, she eventually made meaningful functional recovery; the last EEG showed satisfactory background rhythms and stimulus-induced epileptiform discharges without seizures. Conclusion. In post-anoxic coma, non-evolving >2?Hz spike burst/isoelectric suppression pattern may still reflect NCSE and therefore should be considered in the diagnostic EEG criteria for NCSE. Such borderline patterns should not dissuade physicians from intensifying treatment until more confident prognostication can be made.     

“Paradoxical” EEG response to propofol may differentiate post‐cardiac arrest non‐convulsive status epilepticus from diffuse irreversible cerebral anoxia

Current EEG criteria for the diagnosis of non‐convulsive status epilepticus in critically ill patients with repetitive generalised or focal epileptiform discharges primarily rely on a widely accepted low cut‐off frequency limit of 2.5–3 Hz for non‐evolving patterns, or on discharge evolution of frequency, location or mophology. The secondary criterion is a significant clinical or EEG improvement following acute administration of a rapidly acting antiepileptic drug, such as lorazepam. We describe a comatose patient after out‐of‐hospital cardiac arrest, in whom very slow (1‐Hz), non‐evolving generalised periodic epileptiform discharges against an almost completely depressed background would suggest substantial anoxic damage and poor neurological outcome. Yet, reloading with propofol for diagnostic purposes completely dispersed generalised periodic epileptiform discharges and revealed previously absent biological activity, raising the possibility of non‐convulsive status epilepticus that was subsequently confirmed. Brain MRI showed no significant anoxic brain damage and EEG improved, but the patient died from severe cardiopulmonary complications. These observations suggest that in rare cases, slow, non‐evolving generalised periodic epileptiform discharges may reflect non‐convulsive status epilepticus rather than diffuse irreversible cerebral anoxia, while reloading with propofol can be used as an additional secondary diagnostic criterion.     

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.     

Continuous EEG predictors of outcome in patients with altered sensorium

PurposeTo evaluate EEG predictors of outcome in patients with altered sensorium suspected to have seizure and to assess whether short term EEG is as effective as long term continuous EEG (cEEG) in predicting the outcome of patients with altered sensorium due to neurological causes.MethodsWe identified 99 consecutive critically ill patients with altered sensorium in whom nonconvulsive seizures were suspected. They underwent cEEG. Functional outcome was assessed with the modified Rankin Scale (mRS) at 4 weeks, discharge or death. We compared efficacy of short term EEG and long term continuous EEG in recording the abnormal patterns on EEG. Logistic regression analysis was performed to identify EEG findings associated with poor outcome, defined as mRS 4–6 (dead or moderately to severely disabled).ResultsPoor outcome was associated with nonconvulsive seizures (NCS), nonconvulsive status epilepticus (NCSE), periodic lateralized epileptiform discharges (PLEDS), PLEDS plus, generalized periodic epileptiform discharges (GPEDS) and abnormal EEG background. Short term EEG can detect seizure activity and other electrographic markers of poor outcome but the values are statistically insignificant.ConclusioncEEG monitoring provides independent prognostic information in patients with altered sensorium and suspected seizures. Unfavorable findings include nonconvulsive seizures, periodic epileptiform discharges and abnormal background. Short term EEG is ineffective in detecting seizures on EEG in patients with altered sensorium and should not be used as substitute for Long term EEG     

EEG im Status epilepticus und bei Enzephalopathie

Status elepiticus is a medical emergency and requires immediate treatment. Clinically pragmatic reasons argue for a division into convulsive status (CSE) and nonconvulsive status (NCSE). The EEG is essential for diagnosis of NCSE. If distinct clinical symptoms are lacking, the EEG can assist in the diagnosis of status epilepticus. A special challenge is the presentation of comatose patients. The spectrum of the EEG in encephalopathies is very broad and can be divided into slow and rhythmic EEG coma patterns. Typical patterns depending on the severity of the encephalopathy are presented.     

Topiramate and status epilepticus: report of three cases

OBJECTIVE: The goal of this study was to report the effectiveness of topiramate in treating status epilepticus. METHODS: Three patients with status epilepticus were treated with topiramate 500 mg twice daily for 2-5 days, with the dose gradually tapered thereafter to 200 mg twice daily. The patients' clinical status and EEG recordings were followed. RESULTS: Patient 1 was admitted for subacute encephalopathy that was complicated by secondarily generalized status epilepticus resistant to lorazepam, fosphenytoin, and pentobarbital coma. Topiramate was added and, 2 days later, pentobarbital was tapered with no recurrence of ictal discharges as the patient improved clinically. Patient 2 had end-stage liver disease and was hospitalized for peritonitis, and his course was complicated by partial status epilepticus. Topiramate was started and, 2 days later, his mental status improved as repeat EEG showed no further ictal discharges although periodic epileptiform discharges were seen in the left centroparietal area. The patient later died from complications of variceal bleeding. Patient 3 suffered cardiopulmonary arrest, and developed postanoxic seizures, which did not respond to lorazepam, fosphenytoin, valproate, and propofol coma as continuous EEG recordings showed recurrent generalized ictal discharges. Two days after topiramate was started, propofol was tapered and discontinued and EEG showed generalized slow wave activity and no ictal discharges. The patient was discharged to another facility 12 days later. CONCLUSIONS: Topiramate was effective in treating two patients with refractory generalized status epilepticus and one with complex partial status epilepticus. It should therefore be considered as an option in these situations, especially when other medications cannot be used.     

Two Cases of Nonconvulsive Status Epilepticus in Association with Tiagabine Therapy

We report two patients with intractable partial seizures who developed generalized nonconvulsive status epilepticus (NCSE) after receiving tiagabine (TGB). Neither had a history of absence seizures or generalized epileptic discharges on prior EEG monitoring. Clinicians need to be aware of a possible association between TGB and NCSE.     

Focal nonconvulsive status epilepticus associated to PLEDs and intense focal hyperemia in an AIDS patient.

PURPOSE: Periodic lateralised epileptiform discharges (PLEDs) can be seen associated to nonconvulsive status epilepticus (NCSE), although their pathophysiological meaning remains questionable. Functional neuroimaging has suggested that, in this setting, PLEDs may indeed be an ictal pattern. In this report we describe perfusional changes in a patient with AIDS, PLEDs and NCSE. METHODS: A 37-year-old man with AIDS, cryptococcosis and recurrent epileptic seizures was admitted. After initial treatment, he remained comatose, and had MRI and serial EEG recordings performed. Technetium-99m-ethyl cysteinate dimer (99mTc-ECD) SPECT scans were also obtained, before and after continuous benzodiazepine infusion. RESULTS: EEG disclosed PLEDs over the right fronto-polar region while MRI revealed meningeal thickening and scattered unspecific findings. SPECT revealed marked focal hyperperfusion overlapping the areas with PLEDs, both resolved after continuous midazolam infusion and clinical improvement. CONCLUSIONS: This report demonstrates association of PLEDs, NCSE, and focal hyperperfusion on SPECT, additionally supporting the concept of PLEDs as an ictal pattern. Considering that status epilepticus may eventually not be detected by conventional approaches alone, we advocate the use of functional neuroimaging to assess suspected patients with impaired consciousness.     

Nonconvulsive status epilepticus with frontal features: quantitating severity of subclinical epileptiform discharges provides a marker for treatment efficacy,recurrence and outcome

Nonconvulsive status epilepticus (NCSE) is difficult to diagnose but is an important cause of cognitive impairment. Electroencephalogram (EEG) monitoring is required for diagnosis and treatment. Little is known regarding the stability of subclinical epileptiform discharges (SEDs) preceding NCSE nor what strategies may optimize patient outcomes. We report extended follow-up of patients with recurrent frontal SEDs, integrating EEG and cognitive findings before and following treatment of NCSE, and show that quantitating SED severity provides an objective marker of treatment efficacy and recurrence.     

Nonconvulsive Status Epilepticus: EEG Analysis in a Large Series

Summary: We analyzed EEG characteristics comprehensively in a large series of nonconvulsive status epilepticus (NCSE) cases. Eighty-five ictal episodes in 78 patients were analyzed. The ictal discharges were generalized (group G) in 59 episodes (69%), diffuse with focal predominance (group GF) in 15 (18%), and focal (group F) in 11 (13%). The morphologies and patterns of persistence varied greatly. Frequency of ictal discharge was also variable and was almost always <3 Hz. Demonstration of focal epileptic features in response to intravenous (i.v.) diazepam (DZP) and the presence of interictal focal epileptiform discharges in some cases in groups G and GF suggested possible focal onset secondarily generalized in these cases. This study suggests that electrographically NCSE is a highly heterogeneous epileptic state, and i.v. DZP may serve as a valuable diagnostic tool in differentiating generalized from focal onset NCSE.     

Can absence status epilepticus be of frontal lobe origin?

Five women with an unclassifiable nonconvulsive status epilepticus (NCSE) characterized by young age at onset, prolonged confusions, focal motor seizures, and both generalized spike-and-wave discharges and focal epileptic discharges on the EEG were studied with video-EEG monitoring. Electrographically, the NCSE originated from the left frontal lobe in 4 patients, and the left hemisphere with multifocal seizure discharges in 1 patient. Focal motor seizures seemed to originate from the left hemisphere in all 5 patients, particularly from its anterior part in 3 of them. Results show that the NCSE is complex partial status epilepticus of frontal lobe origin electroclinically mimicking absence status epilepticus once it reaches a full-blown phase.     

Treatment of refractory status epilepticus with hemispherectomy

A 7-year-old boy with left hemiparesis secondary to right hemispheric cortical dysplasia was admitted to the hospital with increasing numbers of seizures. Magnetic resonance imaging showed a small dysplastic right hemisphere with abnormally thickened gyri and an apparently normal left hemisphere. Previous video-electroencephalogram (EEG) monitoring showed bilateral independent spikes and generalized slow spike-and-wave episodes on EEG and [18F]fluorodeoxyglucose (FDG) positron emission tomography scan demonstrated scattered areas of regional hypometabolism bilaterally; therefore hemispherectomy was not undertaken at that time. During this hospital stay, nonconvulsive status epilepticus developed and was refractory to multiple medical therapies including pentobarbital (PTB) coma. Burst-suppression pattern during PTB coma appeared to be generalized spike and wave, but when EEG was reviewed with increased time resolution spikes suggested a right hemisphere origin. The patient underwent bilateral intracarotid amobarbital spike-suppression test that showed only minimal suppression of epileptiform discharges with injection of the left carotid, but complete suppression of spike activity after right-sided carotid injection. A right hemispherectomy was performed with complete cessation of status epilepticus. Postoperative EEG showed no epileptiform discharges. Patient follow-up was limited to 12 months after surgery. The patient had regained the ability to walk unaided and was seizure free with a single antiepileptic medication. This case illustrates a potentially life-saving procedure for refractory status epilepticus and several techniques including a spike-suppression test to aid in prediction of cessation of seizures after hemispherectomy.