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.     

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.     

Nonconvulsive status epilepticus in a neurological intensive care unit: profile in a developing country

PURPOSE: Nonconvulsive status epilepticus (NCSE) is an under-recognized cause of altered mental status. There are hardly any reported data on NCSE in developing countries. MATERIAL AND METHODS: Prospectively 210 consecutive patients with altered mental status admitted to neurological intensive care unit (NICU) of a tertiary care center in south India were studied for the frequency of NCSE. All patients were evaluated initially with 60-min emergent EEG (EmEEG) and subsequently by continuous EEG (cEEG) monitoring. RESULTS: Of the 210 with altered mental status admitted to NICU, the diagnosis of NCSE was established in 22 (10.5%) patients, in 12 (55%) patients with 60-min EmEEG and in 10 (45%) after cEEG monitoring for 12 to 48 hours. Of the 22 patients with NCSE, 32% had subtle motor phenomena, these were not an initial presenting features, but were apparent during cEEG recording. Acute medical or neurologic etiology was the risk factor in 68% of patients. Central nervous system (CNS) infections and cortical sino-venous thrombosis (CSVT), respectively, accounted for 23% and 14% of the etiologies. Intravenous midazolam terminated NCSE in 19 patients and valproate in 2. Of the 15 patients with acute symptomatic NCSE, 4 (18%) had poor prognosis (3 deaths and one persistent vegetative state). The etiological risk factors in the 9 (41%) patients with excellent outcome included epilepsy (3), remote symptomatic (2), cryptogenic (1), and metabolic and drugs (3). CONCLUSIONS: The frequency of NCSE in the current study was comparable with those in prior reports from developed countries. CNS infections accounted for about a fifth of the etiology. Outcome was excellent in patients with nonacute symptomatic NCSE. Initial 60-min EmEEG may be performed in establishing the diagnosis of NCSE, but almost half of patients with NCSE will be missed with this approach.     

Nonconvulsive status epilepticus in the elderly: a case-control study

BACKGROUND: Nonconvulsive status epilepticus (NCSE) is a usually underdiagnosed and potentially treatable cause of altered awareness in the elderly. To assess etiologies, associations with other medical problems, and prognosis of NCSE in a population aged >75 years we performed a nested case-control study. METHODS: We retrospectively evaluated the clinical manifestations and EEG findings in 19 consecutive elderly patients (mean age 83.3 years) presenting with NCSE and compared them with 34 elderly patients (mean age 83.3 years) with altered mental status but without EEG evidence of NCSE. The variables compared included brain lesions on CT or MRI, number of concomitant chronic active diseases, previous neurological disorders, acute medical problems, the use and withdrawal of medications, and outcome. Statistical analysis was performed using chi-square test, t-test, Fisher's exact two-tailed test, and Wilcoxon rank sum test. RESULTS: The etiology of NCSE was epilepsy in 2, acute medical disorders in 14, and a cryptogenic cause in 4. The NCSE group had a more frequent history of epilepsy, 35% versus 8.8% (p = 0.028); tramadol use, 31% versus 0% (p = 0.00151); longer hospitalization, 25 days versus 7 days (p = 0.0004); and unfavorable outcome, 50% versus 5.8% (p = 0.00031). No significant differences were found in the other variables. Unfavorable outcome was associated with a higher number of comorbidities (>2) and to a severely altered mental status. CONCLUSIONS: NCSE is a serious cause of altered mental status in the elderly. Although its direct role in brain damage is controversial, elderly patients with NCSE have higher morbidity and worst prognosis than those with altered mental status without NCSE.     

Complex partial status epilepticus in children with epilepsy

Purpose: Complex partial status epilepticus (CPSE) is often under-diagnosed, especially in children. The aim of this study was to clarify the characteristics and pathophysiology of CPSE in children with epilepsy. Subjects and methods: We retrospectively reviewed the medical records and EEGs of 17 children with epilepsy who were diagnosed as having CPSE by ictal or postictal EEGs to investigate clinical and EEG features. Results: The ages at diagnosis of CPSE ranged from 3 months to 17 years. At the time of diagnosis of CPSE, 13 patients had symptomatic localization-related epilepsy, two had epilepsy with continuous spike-waves during slow wave sleep, and each patient had cryptogenic localization-related epilepsy and idiopathic localization-related epilepsy. Only subtle symptoms including autonomic ones associated with disturbance of consciousness were the main clinical features in 12 of 44 CPSE episodes. Another 22 episodes showed minor focal motor elements, and the other 10 had major convulsive phase during or immediately before CPSE. Ictal EEGs of CPSE were divided into three types according to the degree of high-voltage slow waves (HVS) and spike components. Ictal EEGs could show spike-dominant or spike and HVS mixed patterns even if patients showed only subtle symptoms. The epileptogenic areas estimated by the ictal or postictal EEGs showed variability with only two cases of temporal origin. Conclusion: The close observation of clinical symptoms such as various subtle symptoms and/or mild convulsive elements and ictal EEGs are absolutely needed for the diagnosis of CPSE in children.     

Nonconvulsive status epilepticus in patients with cancer

Patients with systemic cancer may have altered mental status without evidence of metastases, strokes, or metabolic encephalopathies. Six such patients are described whose EEGs showed continuous generalized epileptiform discharges in the absence of clinical signs of seizures. Two patients had never had any clinical evidence of seizures and four had seizures that were thought to have stopped before the EEG. Three patients were confused and three were stuporous or comatose. In some patients the nonconvulsive epileptic activity may have been directly related to the cancer; three had findings suggestive of possible paraneoplastic encephalopathies. Anticonvulsants led to an improved mental status in four patients, but all except one died. Nonconvulsive generalized status epilepticus may explain altered mental status in some patients with cancer and anticonvulsant medication treatment can be beneficial.     

Nonconvulsive status epilepticus after temporal lobectomy

Acute brain injury can cause nonconvulsive status epilepticus (NCSE). However, this condition has not been reported immediately after brain surgery. We describe a patient who had NCSE in the recovery room after an otherwise successful right temporal lobectomy and emphasize the usefulness of electroencephalography in this situation.     

2例非惊厥癫痫持续状态患者的临床特征及脑电图分析

非惊厥性癫痫持续状态（Nonconvulsive Status Epilepticus,NCSE）年发病率为5.6～18.3/10万[1],约占癫痫持续状态的一半,并非罕见,以往由于对其认识不足和诊断标准不一致[2],常被误诊或漏诊,得不到及时有效的治疗.不同类型的NCSE,临床表现和脑电图特点各不相同[3].现将首都医科大学宣武医院神经内科2012年7～10月收治的2例NCSE患者的临床特征及脑电图结果报道如下.     

Assessment of hairline EEG as a screening tool for nonconvulsive status epilepticus

PURPOSE: Because of the high incidence of nonconvulsive status epilepticus (NCSE), the attraction of a "quick and easy" screening electroencephalogram (EEG) is obvious. Previous studies have shown utility of hairline EEG in diagnosing epilepsy. However, this technique has not been evaluated as a screening tool for NCSE. We wanted to provide proof of principle that a screening hairline EEG has sufficient sensitivity to use as a screening tool for diagnosing NCSE. METHODS: A total of 120, 2- to 3-min EEG samples of normal and various abnormal digital EEG studies were reformatted in three six-channel montages (A, longitudinal bipolar; B, referential to ipsilateral ear; C, referential to contralateral ear) that mimicked a hairline recording and were interpreted by five neurophysiologists. The test data interpretation was compared with the original EEG interpretation. RESULTS: Performance was best with montages A and B; 71% and 70.5% of the samples were interpreted correctly by using these montages. Only 65% of the samples were correctly interpreted by using montage C. With the best montage (A), the sensitivities ranged from 91% for normal EEG to 54% for periodic lateralized epileptiform discharges (PLEDs). The sensitivity for seizures was only 72%. Seizures were frequently misinterpreted as more benign patterns such as normal and diffuse slowing. CONCLUSIONS: EEG data reformatted to resemble a hairline EEG had low sensitivity for detecting seizures. As a result, we do not recommend further pursuit of hairline EEG as a "quick and easy" screening tool for NCSE.     

Nonconvulsive status epilepticus on treatment with levetiracetam

In several studies the efficacy and tolerability of levetiracetam (LEV) have been demonstrated. We report two patients who developed nonconvulsive status epilepticus on treatment with LEV. Both patients never experienced status epilepticus before. One patient had a symptomatic epilepsy with complex partial seizures following radiotherapy of astrocytoma in 1985; the second patient had complex partial seizures due to mesial temporal sclerosis. Both patients received LEV 2000 mg/day. We postulate a correlation between occurrence of nonconvulsive status and treatment with LEV. This has not been described before apart from a single report of mentally retarded patients with status epilepticus on high dosages of LEV.     

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。     

Epileptic prodromes: Are they nonconvulsive status epilepticus?

PurposeThe aim of this study was to assess how frequently prodromes occur in an adult patient group from a tertiary referral epilepsy centre and to investigate the EEG changes during the prodromes.Methods578 consecutive patients were interviewed on subjective phenomena, experiences heralding the seizures, for at least 30 min before the start of the seizure. EEGs were recorded during the prodromes.ResultsTen out of 490 included patients had prodromes (2%). We were able to record EEG during prodromes in 6 patients. Three patients had EEG changes corresponding to nonconvulsive status epilepticus. Three patients had unrevealing EEG recordings during prodromes.ConclusionOur results suggest that at least in a part of the patients, the prodromes are actually ictal phenomena, and should be treated as nonconvulsive status epilepticus.     

Nonconvulsive status epilepticus due to drug induced neurotoxicity in chronically ill children

Nonconvulsive status epilepticus (NCSE) is a specific form of status epilepticus and is defined as epileptic activity on an EEG without seizures and as an alteration in mental status lasting more than 30 min. NCSE may be caused by drugs, cerebrovascular events, metabolic disorders or toxins. Herein, we present four cases of patients with drug-induced NCSE who were chronically ill due to renal failure or childhood leukemia. NCSE should be suspected in patients with an altered mental status without clinical seizures who are being treated with multiple drugs.     

Nonconvulsive status epilepticus following rotavirus gastroenteritis in two pediatric patients

BackgroundNonconvulsive status epilepticus (NCSE) comprises a range of conditions in which prolonged electrographic seizures result in nonconvulsive clinical symptoms. An understanding of NCSE is especially important in emergency care. Among the various causes of NCSE, an infectious etiology has been rarely reported to date.Case reportsWe report two pediatric cases of rotavirus gastroenteritis complicated by NCSE. In both cases, bilateral rhythmic delta activity (2.5–3 Hz) with occipital predominance fluctuated with the patient’s consciousness level. The paroxysmal waves disappeared completely and consciousness immediately and remarkably improved after intravenous midazolam infusion. The patients remained alive 10 and 2 years, respectively, after short-term oral anticonvulsant administration, with no epileptic seizures.ConclusionThe etiology of NCSE was identical and the clinical presentations were analogous in the two patients. The seizure semiology differed from that in benign convulsion with gastroenteritis. NCSE was considered the prominent cause of neurological symptoms; however, the pathogenic mechanism remains unclear, including the coexistence of acute encephalopathy.     

Nonconvulsive status epilepticus manifesting as pure alexia (alexia without agraphia)

Pure alexia is a rare disorder usually caused by an ischemic or hemorrhagic stroke. We describe a case of pure alexia due to nonconvulsive status epilepticus (NCSE). This 57-year-old man presented in a hyperosmolar, nonketotic state with fluctuations in mental status and an inability to read. His EEG was diagnostic of NCSE originating from the left temporo-occipital region. MRI of the brain revealed increased FLAIR signal over the left occipitotemporal region. Following initiation of antiepileptic treatment, his neurological examination normalized concomitantly with resolution of the NCSE. A follow-up MRI scan of the brain obtained 1 month later was normal. NCSE can have unusual clinical manifestations, and a high index of suspicion is necessary to correctly diagnose these patients.     

Nonconvulsive status epilepticus in patients with brain tumors

PurposeThe prevalence of nonconvulsive status epilepticus (NCSE) in brain tumor patients is unknown. Since NCSE has been associated with significant mortality and morbidity, early identification is essential. This study describes the clinical and EEG characteristics, treatment, and outcome in brain tumor patients with NCSE.MethodAll patients admitted to Mount Sinai Hospital from 2009 to 2012 with an ICD-9 brain tumor code were cross-referenced with the epilepsy department's database. EEGs from matching patients were reviewed for NCSE. Relevant information from the medical records of the patients with NCSE was extracted.Results1101 brain tumor patients were identified, of which 259 (24%) had an EEG and 24 (2%) had NCSE. The vast majority of seizures captured were subclinical with 13 patients (54%) having only subclinical seizures. Treatment resolved the NCSE in 22 patients (92%) with accompanying clinical improvement in 18 (75%) of those patients. Tumor recurrence or progression on MRI was associated with decreased 2-month survival (75% mortality, p = 0.035) compared to stable tumors (20% mortality). Patients with metastatic disease had median survival from tumor diagnosis of 1.2 months.ConclusionNCSE in brain tumor patients may be under diagnosed due to the frequent lack of outward manifestations and highly treatable with improvement in the majority of patients. NCSE patients with progressing brain lesions, tumor recurrence, or metastatic disease are at serious risk of mortality within 2 months. Continuous EEG monitoring in brain tumor patients with recent clinical seizures and/or a depressed level of consciousness may be critical in providing appropriate care.     

Continuous video-EEG monitoring increases detection rate of nonconvulsive status epilepticus in the ICU

Purpose: Status epilepticus (SE) is an important neurologic emergency requiring treatment on an intensive care unit (ICU). Although convulsive SE is self‐evident, the diagnosis of nonconvulsive SE (NCSE) depends on electroencephalography (EEG) confirmation. Previous work showed that 82% of patients with SE had NCSE in our ICU. We hypothesize that continuous video‐EEG monitoring (CVEM) may increase the diagnostic yield in patients with SE, especially NCSE, and leave fewer patients undiagnosed. Methods: We retrospectively assessed the EEG reports of 537 patients with suspected SE during three comparable 9‐month periods, two groups before (groups 1 and 2) and one (group 3) after CVEM introduction. Differences in monthly rates of SE between groups were assessed using the Mann‐Whitney U‐test. Key Findings: The rates of diagnosis increased significantly after implementation of CVEM (p = 0.0546). There was no significant difference in monthly rates of NCSE diagnosis between groups 2 and 1 (difference = 0.78 new diagnosis/month; p = 0.374). Differences between groups 3 and 2 (2.89; p = 0.0173), between groups 3 and 1 (3.67; p = 0.006) and between group 3 and pooled groups 1 and 2 (3.28; p = 0.002) were statistically significant. Significance: Frequency of NCSE diagnosis increased significantly after implementation of CVEM and was higher than the increment of performed investigations alone. Such an effect may result from the combination of longer observation periods during CVEM, greater and permanent availability of EEG recordings, and heightened awareness of NCSE. Future studies may corroborate improvement of diagnosis and outcomes in patients with disorders of consciousness by CVEM.     

Oral ketamine controlled refractory nonconvulsive status epilepticus in an elderly patient

Nonconvulsive status epilepticus (NCSE) is a heterogeneous disorder with different seizure types and diverse etiologies, and is mainly characterized by altered consciousness. The recognition of NCSE is more challenging than generalized convulsive SE, and diagnosis and treatment are often delayed. Therefore, some cases can evolve into refractory SE and become pharmacoresistant even with GABAergic anesthetics. Herein we report the successful clinical experience of pharmacoresistant complex partial SE treated with ketamine. An elderly woman was profoundly stuporous and had relentless clonic movements of the right hand and forearm. Electroencephalography revealed repetitive periodic lateralized epileptiform discharges (PLEDs). There was a poor clinical response to standard anticonvulsants and GABAergic anesthetics. Both the clinical and electroencephalographic SE were controlled after intravenous ketamine therapy. Rebound refractory NCSE occurred about six days after discontinuing the intravenous ketamine, which was successfully terminated by oral ketamine treatment. There were no adverse effects observed.     

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.     

Treatment of electrographic seizures and status epilepticus in critically ill children: A single center experience

PurposeElectrographic seizures (ES) and electrographic status epilepticus (ESE) are common in encephalopathic children in the pediatric intensive care unit (PICU) and associated with worse short-term outcome. Survey data indicate most physicians treat ES and ESE with antiepileptic drugs (AEDs), but few data are available regarding AED usage patterns. We aimed to describe AED usage for ES and ESE in critically ill children.MethodsWe performed an observational study of patients who underwent continuous electroencephalographic (cEEG) monitoring in the PICU of a single quaternary care children's hospital. We collected data regarding age, clinical diagnoses, ES and ESE occurrence, and AEDs utilized.Results200 subjects underwent cEEG. ES occurred in 21% (41/200) and ESE occurred in 22% (43/200). Of the 84 patients with ES or ESE, 80 received non-benzodiazepine AEDs including 48% (38 of 80) with ES and 52% (42 of 80) with ESE. The most commonly administered first AEDs were levetiracetam in 38% (30/80), phenobarbital in 31% (25/80), phenytoin–fosphenytoin in 28% (22/80), and valproate in 4% (3/80). Seizures terminated after administration of the first AED in 74% (28/38) with ES and 22% (9/41) with ESE.ConclusionsLevetiracetam, phenobarbital, and phenytoin–fosphenytoin are commonly used to manage ES and ESE at our center. Over half of subjects received multiple AEDs.