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.     

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.     

Nonconvulsive status epilepticus and coma

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

Non-convulsive status epilepticus: usefulness of clinical features in selecting patients for urgent EEG

BACKGROUND: Non-convulsive status epilepticus (NCSE) is status epilepticus without obvious tonic-clonic activity. Patients with NCSE have altered mental state. An EEG is needed to confirm the diagnosis, but obtaining an EEG on every patient with altered mental state is not practical. OBJECTIVE: To determine whether clinical features could be used to predict which patients were more likely to be in NCSE and thus in need of an urgent EEG. METHODS: Over a six month period, all patients for whom an urgent EEG was ordered to identify NCSE were enrolled. Neurology residents examined the patients and filled out a questionnaire without knowledge of the EEG results. The patients were divided into two groups, NCSE and non-NCSE, depending on the EEG result. The clinical features were compared between the two groups. The sensitivity and specificity of the features were calculated. RESULTS: 48 patients were enrolled, 12 in NCSE and 36 not in NCSE. Remote risk factors for seizures, severely impaired mental state, and ocular movement abnormalities were seen significantly more often in the NCSE group. The combined sensitivity of remote risk factors for seizures and ocular movement abnormalities was 100%. CONCLUSIONS: There are certain clinical features that are more likely to be present in patients in NCSE compared with other types of encephalopathy. Either remote risk factors for seizures or ocular movement abnormalities were seen in all patients in NCSE. These features may be used to select which patients should have an urgent EEG.     

Tiagabine-induced generalised non convulsive status epilepticus in patients with lesional focal epilepsy.

PURPOSE: To report 3 cases with focal lesional epilepsy that had non-convulsive status epilepticus (NCSE) induced by treatment with tiagabine (TGB) and review the previously published cases. Drugs that enhance GABAnergic transmission are recognised to promote absence seizures in patients with generalised epilepsy syndromes and may on occasions even induce NCSE. However, that TGB can also induce NCSE in focal lesional epilepsy is not widely recognised in clinical practice. METHOD: The clinical history, EEG and MRI findings were reviewed in 3 patients with lesional focal epilepsy who presented to our epilepsy programs over a 12 month period with TGB-induced NCSE. All previously reported cases in the English medical literature were reviewed. RESULTS: The three patients had longstanding complex partial and secondarily generalised seizures refractory to multiple different anti-epileptic drugs. In two cases, MRI demonstrated a focal malformation of cortical development in the left parieto-occipital region and in the third left mesial temporal sclerosis. Following commencement of TGB in one patient and dose escalation in two, prolonged episodes of confusion and poor responsiveness were noted. Prolonged EEG monitoring demonstrated continuous high amplitude, generalised, 2-4 Hz delta activity with intermingled spikes during the episodes of unresponsiveness, consistent with NCSE. The clinical and EEG activity normalised following the administration of IV clonazepam followed by dose reduction or withdrawal of the TGB. Eleven previously reported cases of patients with partial epilepsy and a focal underlying lesion on MRI were identified, all of whom had similar features to that seen in our cases. CONCLUSIONS: These cases illustrate that TGB may induce generalised NCSE in patients with focal lesional epilepsy, in addition to those with generalised syndromes. We hypothesise that patients may have developed an acquired alteration in the sensitivity of their thalamocortical circuitry that renders them more sensitive to the effects of drugs that enhance GABAnergic activity.     

Clinical characteristics of status epilepticus in an emergency hospital: importance of nonconvulsive status epilepticus]

Although nonconvulsive status epilepticus (NCSE) is a major neurological emergency, its frequency and clinical course are not well clarified. We investigated the clinical characteristics of status epilepticus focusing on the significance of NCSE. One thousand seven hundred twenty-three patients were admitted as neurological emergency cases in our hospital between October 2003 and September 2006. Of these cases, 94 (5.5%) were diagnosed as status epilepticus of which, 24 (25.5%) were diagnosed with NCSE on admission. Moreover, 8 patients who presented with convulsive status epilepticus on admission had episodes of NCSE during hospitalization. Thus, 32 patients (34.0%) suffered from NCSE during their clinical course. We analyzed the prognostic factors of status epilepticus using the Glasgow Outcome Scale. Poor outcome was significantly correlated with NCSE (p = 0.003) and acute cerebrovascular disease (p = 0.010), independent of age, sex, history of epilepsy, and other etiologies. Our study revealed that NCSE is not a rare condition and results in a poor outcome. Careful EEG evaluation of patients with consciousness disturbance might increase the diagnostic accuracy of NCSE, and aggressive treatment of patients with NCSE should be necessary to improve the prognosis of NCSE.     

Clinical and EEG findings in six patients with altered mental status receiving tiagabine therapy

Tiagabine (TGB), a novel GABA reuptake inhibitor antiepileptic drug, has been reported to induce nonconvulsive status epilepticus (NCSE) in patients with generalized or partial onset seizures. We describe six patients with refractory partial epilepsy treated with add-on TGB. They developed acute intermittent or progressive chronic confusion associated with diffuse slowing of the electroencephalogram (EEG), shortly after an increase in dose of TGB. This remitted in each situation after reduction of the daily dose. The possibility of nonconvulsive status epilepticus or toxic encephalopathy is discussed.     

Non-convulsive status epilepticus of frontal origin as the first manifestation of Hashimoto's encephalopathy

Hashimoto's encephalopathy is an often misdiagnosed, life threatening, condition which improves promptly with steroid therapy. Since clinical manifestations are heterogeneous and non-specific, the diagnosis is often difficult. Several case reports of Hashimoto's encephalopathy presenting with partial or generalised seizures are described, but only a few have focused on status epilepticus as the first clinical manifestation. We report two patients presenting with repetitive and prolonged seizures characterised by progressive reduction in contact and reactivity associated with frontal/diffuse polyspike-and-wave activities. This condition, which can be interpreted as a form of non-convulsive status epilepticus (NCSE) of frontal origin, was refractory to antiepileptic drugs but responded promptly to high doses of intravenous steroid treatment. In cases of unexplained encephalopathy with EEG documentation of NCSE, the early recognition and treatment of Hashimoto's encephalopathy may lead to a favourable prognosis. [Published with video sequences].     

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.     

Absence status epilepticus in monozygotic twins with Jeavons syndrome

As a generalized form of nonconvulsive status epilepticus (NCSE), absence status epilepticus is the most common form. It manifests as prolonged, confusional states of varying severity, and continuous or repetitive generalized discharges of spikes, multiple spikes, and slow waves on EEG. Jeavons syndrome (JS) is a new type of epilepsy syndrome. Hitherto, only four sets of monozygotic twin with JS have been reported. Absence status epilepticus occurring in monozygotic twins with JS have not been reported. Here we report on monozygotic male twins of Chinese origin with JS. Both of them presented with status epilepticus with eyelid myoclonia and absences. [Published with video sequences].     

Sporadic Creutzfeldt–Jakob disease presenting as nonconvulsive status epilepticus case report and review of the literature

Creutzfeldt–Jakob disease (CJD) is the most common transmissible human spongiform encephalopathy. Seizures and status epilepticus (SE) are an uncommon finding in CJD. We report a 64-year-old woman with rapid cognitive decline who had electroencephalographic (EEG) changes suggestive of nonconvulsive status epilepticus (NCSE). She was later diagnosed with sporadic CJD (sCJD). We also reviewed the literature for published cases on this topic. MEDLINE was employed to identify all published reports of CJD and SE. We identified 8 references with a total of 12 cases with CJD and NCSE. sCJD should be considered in the differential diagnosis of any patient who presents with rapid cognitive decline and EEG changes consistent with status epilepticus.     

Diagnosis of nonconvulsive status epilepticus (NCSE) in adults with altered mental status: clinico-electroencephalographic considerations

The high incidence of nonconvulsive status epilepticus (NCSE) and difficulties encountered in rapid diagnosis have only recently become apparent and most neurophysiology textbooks have yet to fully address this topic. There is an immediate need to provide neurologists, neurology residents, and electroneurodiagnostic technologists with information to assist them in achieving early, accurate diagnosis of NCSE in patients they encounter on a daily basis. Instead of attempting to write a comprehensive review of the topic, we examined over 90 NCSE publications since 1972 and focused our efforts on extracting and summarizing those EEG and clinical considerations we found most useful for accurate diagnosis of NCSE in an adult population. The wide overlap between the clinical symptoms of NCSE and many other disorders causing change in mental status limits the usefulness of clinical measures for diagnosis. Those clinical parameters which have some utility are outlined. EEG testing and accurate interpretation is needed to identify NCSE in most instances. EEG patterns of NCSE are detailed and examples provided in order of progressive complexity. Timely treatment reduces patient risk for morbidity attributed to NCSE. Electroneurodiagnostic technologists who learn to recognize the entire spectrum of NCSE EEG patterns are better able to alert electroencephalographers to EEGs likely needing expedited review. This may facilitate early diagnosis if electroencephalographers determine that NCSE is indeed present. Electroencephalographers correlate the EEG pattern, clinical activity, and other diagnostic information to provide the treating medical doctors with an interpretation and recommendation in a timely manner. Lastly, EEG and clinical checklists and an algorithm which uses benzodiazepine response in conjunction with continuous EEG monitoring are provided to help reduce uncertainty in interpretation of equivocal EEG patterns of NCSE.     

Nonconvulsive status epilepticus due to a de novo contralateral focus during tiagabine adjunctive therapy.

We describe a 30-year-old woman with an infantile-onset epilepsy due to a left temporal gliotic area who developed a nonconvulsive status epilepticus (NCSE) during tiagabine (TGB) adjunctive therapy. The ictal EEG recording showed a de novo right temporal focus not previously evident. After the i.v. administration of 4 mg lorazepam, the NCSE episode rapidly resolved and her usual left temporal EEG abnormalities reappeared. To our knowledge this is the first case of paradoxical seizure exacerbation associated with TGB therapy in which the clinical and EEG features are congruous with a new contralateral focus.     

Utilidad del electroencefalograma en el manejo de la epilepsia en el Servicio de Urgencias

IntroductionElectroencephalography (EEG) is an essential diagnostic tool in epilepsy. Its use in emergency departments (ED) is usually restricted to the diagnosis and management of non-convulsive status epilepticus (NCSE). However, EDs may also benefit from EEG in the context of other situations in epilepsy.MethodsWe conducted a retrospective observational study using the clinical histories of patients treated at our hospital's ED for epileptic seizures and suspicion of NCSE and undergoing EEG studies in 2015 and 2016. We collected a series of demographic and clinical variables.ResultsOur sample included 87 patients (mean age of 44 years). Epileptic seizures constituted the most common reason for consultation: 59.8% due to the first episode of epileptic seizures (FES), 27.6% due to recurrence, and 12.6% due to suspected NCSE. Interictal epileptiform discharges (IED) were observed in 38.4% of patients reporting FES and in 33.3% of those with a known diagnosis of epilepsy. NCSE was confirmed by EEG in 36.4% of all cases of suspected NCSE. Presence of IED led to administration of or changes in long-term treatment in 59.8% of the patients.ConclusionsEEG is a useful tool for seizure management in EDs, not only for severe, sudden-onset clinical situations such as NCSE but also for diagnosis in cases of non-affiliated epilepsy and in patients experiencing the first episode of epilepsy.     

Non convulsive status epilepticus after replacement of valproate with lamotrigine

Purpose: Lamotrigine (LTG) and valproate (VPA) are widely used in the treatment of generalized epilepsies. Nevertheless seizure aggravation with LTG has been reported in juvenile myoclonic epilepsy and epilepsy with myoclonic absences. The aim of this study was to describe clinical features and EEG findings in patients with non convulsive status epilepticus (NCSE) after replacement of VPA with LTG. Method: Retrospective analysis of three identified patients in a large university hospital. Results: We describe three adult patients aged 39, 50 and 75 years, who developed non-convulsive status epilepticus (NCSE) after replacement of VPA with LTG. The episodes of NCSE presented as an acute confusional state with mild myoclonus. Ictal EEG showed generalized spike-wave or polyspike wave activity. The clinical symptoms and the EEG responded promptly to IV benzodiazepines and patients remained well controlled with dose reduction of LTG (in one patient) or discontinuation of LTG (in two patients). Conclusion: The reported episodes of NCSE in these patients with generalized epilepsy may be either due to a possible paradoxical reaction to LTG or due to a withdrawal effect of VPA. Received: 5 November 2001, Received in revised form: 8 April 2002, Accepted: 23 April 2002 Correspondence to Eugen Trinka, MD     

非惊厥性癫痫持续状态临床及脑电图表现四例

目的由于非惊厥性癫痫持续状态(NCSE)的临床表现及脑电图的变化在儿童和成人很难被识别,容易被误诊,本研究主要是探讨NCSE的临床特点及脑电图表现。方法收集我院诊治过的4例NCSE患者的临床资料及脑电图资料,分析其特点。结果 4例患者既往均有癫痫发作。例1患者停药后出现NCSE发作,例3、例4患者由于药物控制不佳,例2患者的NCSE均发生在惊厥发作后,每次发作持续时间从0.5h至3d不等。例2、例3及例4患者反复多次出现NCSE。4例患者均表现为行为异常,例1、例2及例4患者发作时不讲话,不能和外界进行交流,例3患者发作时构音不清。随访后发现例2、例3患者记忆力下降,例1、例4患者智能基本正常。从脑电图来看,均表现为持续性棘慢波发放。例1为失神发作癫痫持续状态,例2、例3及例4为部分性发作癫痫持续状态。结论 NCSE在早期易漏诊,反复NCSE可导致患者记忆力下降,如癫痫患者出现持续半小时以上的行为异常等表现,应急行脑电图检查明确是否NCSE,使用苯二氮卓类及抗癫痫药物可终止NCSE。     

Diagnosis and management of nonconvulsive status epilepticus in children

Nonconvulsive status epilepticus (NCSE) encompasses a wide range of diagnoses with variable outcomes and treatment recommendations. In children, NCSE can be observed in various conditions, including acute neurological injuries, specific childhood epilepsy syndromes and other neurological conditions, and can also be observed in individuals with learning difficulties. NCSE in children is thought to be under-recognized, and further studies examining the electrographic characteristics of very young children in NCSE would aid the prompt recognition of additional patients. Some subtypes of NCSE are probably more harmful than others, and long-term prospective studies are needed to evaluate the damaging potential of NCSE itself as opposed to that of the underlying circumstances in which it occurs. Specific data in childhood are clearly lacking, but extrapolation from adult studies indicates that aggressive treatment is most warranted in comatose patients. By contrast, a cautious approach seems to be indicated for absence status epilepticus, complex partial status epilepticus and electrical status epilepticus during sleep.     

Real‐time differentiation of nonconvulsive status epilepticus from other encephalopathies using quantitative EEG analysis: A pilot study

Purpose: Distinguishing nonconvulsive status epilepticus (NCSE) from some nonepileptic encephalopathies is a challenging problem. In many situations, NCSE and nonepileptic encephalopathies are indistinguishable by clinical symptoms and can produce very similar electroencephalography (EEG) patterns. Misdiagnosis or delay to diagnosis of NCSE may increase the rate of morbidity and mortality. Methods: We developed a fast‐differentiating algorithm using quantitative EEG analysis to distinguish NCSE patients from patients with toxic/metabolic encephalopathy (TME). EEG recordings were collected from 11 patients, including 6 with NCSE and 5 with TME. Three nonlinear dynamic measures were used in the proposed algorithm: the maximum short‐term Lyapunov exponent (STLmax), phase of attractor (phase/angular frequency), and approximate entropy (ApEn). A further refined metric derived from STLmax and phase of attractor (the mean distance to EEG epoch samples from their centroid in the feature space) was also utilized as a criterion. Paired t tests were carried out to further clarify the separation between the EEG patterns of NCSE and TME. Results: Computational results showed that the performance of the proposed algorithm was sufficient to distinguish NCSE from TME. The results were consistent in all subjects in our study. Conclusions: The study presents evidence that the maximum short‐term Lyapunov exponents (STLmax) and phase of attractors (phase/angular frequency) can be useful in assisting clinical diagnosis of NCSE. Findings presented in this article provide a promising indication that the proposed algorithm may correctly distinguish NCSE from TME. Although the exact mechanism of this association remains unknown, the authors suggest that epileptic activity is highly associated with and can be modeled by dynamic systems.     

Tiagabine-induced non-convulsive status epilepticus in a patient without history of epilepsy

Cases of non-convulsive status epilepticus (NCSE) induced by tiagabine (TGB) were occasionally reported. Almost all had a prior history of epilepsy. We describe here, the clinical and EEG findings in a patient, without history of seizures, who after the start of TGB developed NCSE. A 53-year-old man with history of paranoid schizophrenia, presented with "alteration of his mental state." Three weeks early, TGB was added to his psychiatric regimen. On the second day of admission, he became unresponsive with a blank stare. Concomitant EEG showed abundant sharp and slow wave complexes. The episode lasted for 4 hours and was aborted by the intravenous administration of lorazepam. The TGB was discontinued without recurrence of subsequent seizure activity. This case supports the contention that TGB can induce NCSE in subjects not previously known to have seizures.