Frontal nonconvulsive status epilepticus associated with high-dose tiagabine therapy in a child with familial bilateral perisylvian polymicrogyria

PURPOSE: Antiepileptic drugs are known to exacerbate absence and myoclonic seizures, especially in patients with idiopathic generalized epilepsies. Exacerbation of nonconvulsive generalized seizures in patients with partial epilepsy is less common. Recently, however, a number of cases of putative generalized nonconvulsive status epilepticus (NCSE) or NCSE without further specification have been reported in patients with chronic partial epilepsy treated with the gamma-aminobutyric acid reuptake inhibitor tiagabine. Although complex partial status epilepticus during tiagabine therapy has also been reported, possible precipitation of NCSE specifically associated with frontal lobe discharges does not appear to have been recognized. In this communication, we describe the case of a boy with familial bilateral perisylvian polymicrogyria who developed frontal NCSE after being stabilized on high-dose tiagabine METHODS: A 12-year-old boy with familial bilateral perisylvian polymicrogyria, mental retardation, and refractory partial seizures was administered tiagabine in addition to sodium valproate. The tiagabine dosage was increased gradually up to 10 mg t.i.d. (1 mg/kg per day), resulting in complete seizure control. RESULTS: After 1 week on maintenance treatment, seizures were completely controlled, but the child developed hypoactivity, decreased reactivity, and affective detachment. An EEG recording revealed subcontinuous sharp-wave discharges with irregular runs of atypical spike-wave complexes over the anterior regions of both hemispheres, consistent with a diagnosis of frontal NCSE. A reduction in tiagabine dosage to 15 mg/day led to complete regression of the behavioral and affective changes and to disappearance of the subcontinuous EEG discharges. CONCLUSIONS: Although tiagabine-induced NCSE has been described previously, particularly in patients with preexisting spike-wave abnormalities, this is the first report that identifies its potential role in the precipitation of frontal NCSE.     

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.     

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.     

Non-convulsive status epilepticus in two patients receiving tiagabine add-on treatment

We report two patients with epileptic syndromes who developed non-convulsive status epilepticus under adjunctive antiepileptic therapy with tiagabine. The paradoxical effect may be the result of a difference in effects between GABA_A and GABA_B receptors, or between GABA receptors in different regions of the brain. Received: 18 February 2000 / Received in revised form: 29 June 2000 / Accepted: 1 August 2000     

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.     

Non-convulsive status epilepticus associated with tiagabine therapy in children

A case of a 7-year-old male with epilepsy who developed non-convulsive status epilepticus (NCSE) with electroclinical features consistent with those of atypical absence seizures after adjunctive antiepileptic therapy of tiagabine (TGB) is reported. The patient had frequent generalised and rare partial seizures with generalised epileptic discharges on prior electroencephalogram (EEG) recordings. NCSE was developed when rapid dosage increase and high dose of TGB was given. This case emphasises the need for close monitoring of children with epilepsy taking TGB for exacerbation of seizures or development of NCSE.     

Two Patients with Juvenile Myoclonic Epilepsy and Nonconvulsive Status Epilepticus

We report 2 girls, aged 10 and 13 years, with juvenile myoclonic epilepsy (JME) who had episodes of nonconvulsive status epilepticus (NCSE). Symptoms included only mild lethargy, slow responses, and trembling of the eyelids. There was no ataxia or myoclonus of the limbs or body, and they were always able to respond. Electroencephalograms during these episodes showed almost continuous generalized polyspike-waves in both patients. Patients with JME can develop NCSE, which may be overlooked because of the subtle clinical symptoms.     

Persistent Nonconvulsive Status Epilepticus After the Control of Convulsive Status Epilepticus

Summary: Purpose: Convulsive status epilepticus (CSE) is a major medical and neurological emergency that is associated with significant morbidity and mortality. Despite this high morbidity and mortality, most acute care facilities in the United States cannot evaluate patients with EEG monitoring during or immediately after SE. The present study was initiated to determine whether control of CSE by standard treatment protocols was sufficient to terminate electrographic seizures. Methods: One hundred sixty-four prospective patients were evaluated at the Medical College of Virginia/VCU Status Epilepticus Program. Continuous EEG monitoring was performed for a minimum of 24 h after clinical control of CSE. SE and seizure types were defined as described previously. A standardized data form entry system was compiled for each patient and used to evaluate the data collected. Results: After CSE was controlled, continuous EEG monitoring demonstrated that 52% of the patients had no after-SE ictal discharges (ASIDS) and manifested EEG patterns of generalized slowing, attenuation, periodic lateralizing epileptiform discharges (PLEDS), focal slowing, and/or burst suppression. The remaining 48% demonstrated persistent electrographic seizures. More than 14% of the patients manifested nonconvulsive SE (NCSE) predominantly of the complex partial NCSE seizure (CPS) type (2). These patients were comatose and showed no overt clinical signs of convulsive activity. Clinical detection of NCSE in these patients would not have been possible with routine neurological evaluations without use of EEG monitoring. The clinical presentation, mortality, morbidity, and demographic information on this population are reported. Conclusions: Our results demonstrate that EEG monitoring after treatment of CSE is essential to recognition of persistent electrographic seizures and NCSE unresponsive to routine therapeutic management of CSE. These findings also suggest that EEG monitoring immediately after control of CSE is an important diagnostic test to guide treatment plans and to evaluate prognosis in the management of SE.     

In Nonconvulsive Status Epilepticus (NCSE), Treat to Burst-Suppression: Pro and Con

Summary:  When refractory NCSE is combined with acute brain injury, it produces synergistically compounded brain damage that is time dependent. Treating to EEG burst-suppression is the most rapid and effective method for stopping NCSE. The risks of burst-suppression are common to many intensive care interventions and can be minimized with expert management.     

Predictors of refractoriness in a Turkish status epilepticus data bank

Refractory status epilepticus (RSE) is known to constitute approximately 10–50% of all cases of status epilepticus (SE) and is associated with significant morbidity and mortality. In the present study, data from a prospectively collected SE database were analyzed. Patients with RSE (defined as a SE episode requiring a second line of intravenous treatment following intravenous phenytoin) were compared with patients with nonrefractory SE (NRSE); 290 episodes of SE were identified, of which 108 (38%) were defined as RSE. Univariate analysis revealed that age, female gender, SE type, SE duration, and acute etiology were associated with refractoriness, whereas electroencephalographic patterns were not. Nonconvulsive SE, which is probably associated with delays in treatment initiation, was a predictor of RSE, although it was not retained as a predictor in multivariate analysis. In the latter analysis, female gender (odds ratio: 1.815, 95% CI: 1.053–3.126) and acute etiology (odds ratio: 0.619, 95% CI: 0.429–0.894) were shown to be the only significant independent predictors of refractoriness.     

Nonconvulsive Status Epilepticus in Two Patients Receiving Tiagabine Treatment

Summary: In the course of an open study on the add-on treatment of tiagabine (TGB) in patients with localization-related epilepsy syndromes, 2 of 9 patients developed nonconvulsive status epilepticus (NCSE) with electroclinical features consistent with those of atypical absence seizures. One patient had never had atypical absence seizures before. In both cases, immediate discontinuation of TGB was followed by complete and sustained electroclinical remission; we suggest a possible causative role of TGB. This observation may be consistent with a paradoxical effect of TGB in selected cases. Possible risk factors and a pathophysiological hypothesis are discussed.     

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.     

Nonconvulsive Status Epilepticus in Adults: Thirty-Two Consecutive Patients from a General Hospital Population

We studied all adult patients who between 1984 and 1989 were initially diagnosed at our hospital as having nonconvulsive status epilepticus. Thirty-two patients fulfilled the criteria, which included ictal EEG recordings. The annual incidence was 1.5 in 100,000 inhabitants. The median age at onset of status was 51 years. Ten patients had status as their first epileptic manifestation, but most patients had a previous history of epilepsy. Median duration of epilepsy at onset of status was 4 years. Fourteen patients had focal ictal seizure activity on EEG and thus met the criteria for complex partial status. Eighteen patients had generalized seizure activity on EEG, but only 6 of these had a history of absence epilepsy or juvenile myoclonic epilepsy. None had Lennox-Gastaut syndrome. The clinical features of status in the remaining 12 patients were in some respects similar to those of the patients with complex partial status. We hypothesize that the EEG seizure activity in these patients may have been generalized from an initial focus.     

Status epilepticus in the elderly

Children and the elderly (≥60 years of age) have the highest incidence of status epilepticus (SE). Because of their general health, elderly individuals are much more likely than younger (<60 years of age) persons to have more severe consequences from seizures. The incidence of SE is 15.5/100 000 in the 60‐69 age group, 21.5/100 000 in the 70‐79 age group and 25.9/100 000 in persons 80 and older. The most common cause in the elderly is acute symptomatic, with stroke and hypoxia the most frequent. The overall mortality of SE is quite high and occurs early, often within the first few days, and is related to the cause, with mortality of more than 80% in persons with anoxia. Although the cause of SE is an important factor in mortality, the aging body and brain may contribute to an unfavorable outcome. Treatment in the elderly is essentially the same as in younger adults with benzodiazepines (lorazepam, diazepam, clonazepam) and longer acting antiseizure drugs (phenytoin, fosphenytoin, valproate, levetiracetam, and lacosamide. At this time there are no evidence‐based studies regarding Axis 2 (etiology) and Axis 4 (age). All current interventions for SE involve antiseizure drugs that were developed for treatment of chronic epilepsy. Treatments should be developed that are more specific for the various etiologies and involve drugs that work on the underlying cause of the SE.     

Status Epilepticus: Risk Factors and Complications

Summary: Status epilepticus is common and associated with significant mortality and complications. It affects approximately 50 patients per 100,000 population annually and recurs in >13%. History of epilepsy is the strongest single risk factor for generalized convulsive status epilepticus. More than 15% of patients with epilepsy have at least one episode of status epilepticus and low antiepileptic drug levels are a potentially modifiable risk factor. Other risks include young age, genetic predisposition, and acquired brain insults. Fever is a very common risk in children, as is stroke in adults. Mortality rates are 15% to 20% in adults and 3% to 15% in children. Acute complications result from hyperthermia, pulmonary edema, cardiac arrhythmias, and cardiovascular collapse. Long-term complications include epilepsy (20% to 40%), encephalopathy (6% to 15%), and focal neurologic deficits (9% to 11%). Neuronal injury leading to temporal lobe epilepsy is probably mediated by excess excitation via activation of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors and consequent elevated intracellular calcium that causes acute necrosis and delayed apoptotic cell death. Some forms of nonconvulsive status epilepticus may also lead to neuronal injury by this mechanism, but others may not. Based on clinical and experimental observations, complex partial status epilepticus is more likely to result in neuronal injury similar to generalized convulsive status epilepticus. Absence status epilepticus is much less likely to result in neuronal injury, and complications because it may be mediated primarily through excess inhibition. Future research strategies to prevent complications of status epilepticus include the study of new drugs (including NMDA antagonists, new drug delivery systems, and drug combinations) to stop seizure activity and prevent acute and delayed neuronal injury that leads to the development of epilepsy.     

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.     

Treatment of refractory complex-partial status epilepticus with propofol: case report

PURPOSE: We report a case of a 65-year-old woman who had a subarachnoid and intraventricular hemorrhage secondary to rupture of an anterior communicating artery aneurysm and developed nonconvulsive status epilepticus of the complex-partial type, refractory to phenytoin (PHT), phenobarbital (PB), valproate (VPA), and lorazepam (LZP). METHODS: Three weeks after diagnosis of nonconvulsive status epilepticus, general anesthesia was induced with propofol and titrated to burst suppression on the electroencephalogram (EEG). RESULTS: During propofol infusion, the serum VPA level declined markedly, and despite >3 g daily doses, did not return to the therapeutic range, until several days after propofol was discontinued. Continuous propofol infusion was stopped after 7 days, and the patient recovered consciousness. Despite further complications, she gradually regained normal function and was discharged home 4 months after surgery. CONCLUSIONS: This is the first case of nonconvulsive status epilepticus successfully treated with propofol.     

Nonconvulsive Status Epilepticus: High Incidence of Complex Partial Status

Nonconvulsive status epilepticus may be subdivided into generalized (absence) status and complex partial status. The latter is regarded as a rarity, whereas the former constitutes the dominant part of the hitherto reported cases. We report 10 consecutive cases of adult patients with nonconvulsive status epilepticus, all documented by ictal electroencephalographic (EEG) recordings. Five had a complex partial status; the origin of the complex partial status appeared to be frontal in four of these patients. Three had recurrent complex partial seizures with incomplete recovery between seizures, and two had more continuous symptoms. One of the latter exhibited neither motor phenomena nor automatisms. The effect of diazepam or clonazepam was immediate in all 10 cases though transient in eight. A lasting control of the status was not achieved in six patients until i.v. phenytoin was added. The difficulties in the differentiation between complex partial status and absence status despite ictal EEG recordings are discussed, illustrated by a case with seizure discharges of a focal onset which rapidly generalized. The study indicates that complex partial status may be more common and the clinical expressions of absence status more variable than hitherto recognized.     

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.     

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.