Periictal diffusion abnormalities of the thalamus in partial status epilepticus

Purpose:   To identify and describe thalamic dysfunction in patients with temporal as well as extratemporal status epilepticus (SE) and to also analyze the specific clinical, radiological, and electroencephalography (EEG) characteristics of patients with acute thalamic involvement.
Methods:   We retrospectively identified patients who presented with clinical and electrographic evidence of partial SE and had thalamic abnormalities on diffusion-weighted imaging (DWI) within 5  days of documentation of lateralized epileptiform discharges (group 1). The spatial and temporal characteristics of the periodic lateralized epileptiform discharges (PLEDs) and the recorded electrographic seizures were analyzed and correlated with magnetic resonance imaging (MRI)-DWI hyperintense lesions. The findings of group 1 patients were compared with those of patients with partial SE without thalamic abnormalities on DWI (group 2).
Results:   The two groups were similar with regard to clinical presentation and morphology of epileptiform discharges. Group 1 patients had thalamic hyperintense lesions on DWI that appeared in the region of the pulvinar nucleus, ipsilateral to the epileptiform activity. Statistically significant relationship was noted between the presence of thalamic lesions and ipsilateral cortical laminar involvement (p = 0.039) as well as seizure origin in the posterior quadrants (p = 0.038). A trend towards PLEDs originating in the posterior quadrants was also noted (p = 0.077).
Discussion:   Thalamic DWI hyperintense lesions may be observed after prolonged partial SE and are likely the result of excessive activity in thalamic nuclei having reciprocal connections with the involved cortex. The thalamus likely participates in the evolution and propagation of partial seizures in SE.     

Transient abnormalities on magnetic resonance imaging after partial status epilepticus

We report two patients who developed focal abnormalities on MRI after partial status epilepticus.Maximum radiological modification occurred in the area of maximal epileptic discharge. Subsequent MRI failed to demonstrate persistent abnormalities.These transient abnormalities on MRI could be an expression of cerebral edema caused by focal epileptic status.

---

Sommario Riportiamo due casi che hanno sviluppato anomalie transitorie alla RMN dopo stato di male parziale non convulsivo. La massima modificazione radiologica si è verificata in corrispondenza della zona di maggior attività critica. Le RMN eseguite successivamente sono risultate negative. La transitorietà delle alterazioni è probabilmente da interpretare sulla base di un edema critico. Alterazioni di neuroimaging possono essere quindi una conseguenza piuttosto che una lesione causale dello stato di male.

     

MRI findings in aphasic status epilepticus

Ictal-MRI studies including diffusion-weighted imaging (DWI), perfusion-weighted imaging (PWI), and MR-angiography (MRA) in patients with aphasic status epilepticus (ASE) are lacking. In this report, we aim to describe the consequences of the ASE on DWIs and its impact on cerebral circulation. We retrospectively studied eight patients with ASE confirmed by ictal-EEG, who underwent ictal-MRI shortly after well-documented onset (mean time delay 3 h). ASE consisted in fluctuating aphasia, mostly associated with other subtle contralateral neurological signs such as hemiparesia, hemianopia, or slight clonic jerks. In MRI, six patients showed cortical temporoparietal hyperintensity in DWI and four of them had also ipsilateral pulvinar lesions. Five patients showed close spatial hyperperfusion areas matching the DWI lesions and an enhanced blow flow in the middle cerebral artery. Parenchymal lesions and hemodynamic abnormalities were not associated with seizure duration or severity in any case. The resolution of DWI lesions at follow-up MRI depended on the length of the MRIs interval. In patients with ASE, lesions on DWI in the temporo-parietal cortex and pulvinar nucleus combined with local hyperperfusion can be observed, even when they appear distant from the epileptic focus or the language areas.     

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.     

Diffusion-weighted magnetic resonance imaging in nonconvulsive status epilepticus

BACKGROUND: In human and experimental models, diffusion-weighted magnetic resonance imaging (DWI) findings in status epilepticus (SE) have been reported to show that apparent diffusion coefficients are reduced during the initial phase and normalized or increased in the later phase of prolonged SE. This effect is caused by cytotoxic edema induced by excitotoxicity. In humans, only focal DWI abnormalities have been reported in partial SE. OBJECTIVES: To report and discuss the DWI findings suggesting diffuse neuronal injury in a patient with nonconvulsive SE. DESIGN AND METHODS: A 56-year-old man was admitted because of changing levels of consciousness over 3 days. On admission he was comatose. He had nystagmoid eye movement, forced eye blinking, and oroalimentary automatism. The results of a search for possible infectious and metabolic etiologies were negative, and electroencephalographic findings showed continuous, semirhythmic, bifrontal sharp waves of 2 Hz. Phenytoin and midazolam hydrochloride were infused to alleviate the seizure activities. He underwent DWI initially (3 days after the onset of seizure) and at the 5-month follow-up. SETTING: The neurology department of a tertiary referral center. RESULTS: During SE, DWI findings showed marked, diffuse gyriform cortical hyperintensity throughout the brain. The apparent diffusion coefficient decreased in the corresponding areas, especially in the occipital lobes. Findings from T2-weighted magnetic resonance imaging showed the intense cortical hyperintensity with gyral swelling and no involvement of brainstem, basal ganglia, thalamus, and white matter. The follow-up DWI findings showed marked atrophy and hypointensity in the corresponding regions. The apparent diffusion coefficient increased in the corresponding regions. CONCLUSIONS: Diffusion-weighted imaging in our patient indicated that the magnetic resonance imaging abnormalities of the affected cortex were due to cytotoxic edema caused by neuronal excitotoxicity during prolonged SE. Diffusion-weighted imaging can be used in the localization of seizure focus for predicting the prognosis of the affected tissue and for researching the basic pathophysiology of SE.     

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.     

Short-term outcomes of children with febrile status epilepticus

Febrile status epilepticus (SE) represents the extreme end of the complex febrile seizure spectrum. If there are significant sequelae to febrile seizures, they should be more common in this group. We have prospectively identified 180 children aged 1 month to 10 years who presented with febrile SE over a 10-year period in Bronx, New York, and Richmond, Virginia. They were compared with 244 children who presented with their first febrile seizure (not SE) in a prospective study done in the Bronx. The mean age of the children with febrile SE was 1.92 years, and of the comparison group, 1.85 years. Duration of SE was 30-59 min in 103 (58%), 60-119 min in 43 (24%), and > or =120 min in 34 (18%). Focal features were present in 64 (35%) of cases. There were no deaths and no cases of new cognitive or motor handicap. Children with febrile SE were more likely to be neurologically abnormal (20% vs. 5%; p < 0.001), to have a history of neonatal seizures (3% vs. 0; p = 0.006) and a family history of epilepsy (11% vs. 5%; p = 0.05) and less likely to have a family history of febrile seizures (15% vs. 27%; p = 0.01) than were children in the comparison group. The short-term morbidity and mortality of febrile SE are low. There are differences in the types of children who have febrile SE compared with those who experience briefer febrile seizures. Long-term follow-up of this cohort may provide insight into the relationship of prolonged febrile seizures and subsequent mesial temporal sclerosis.     

Simple partial status epilepticus in Chinese adults

Simple partial status epilepticus (SPSE) is uncommon compared with generalized tonic-clonic status epilepticus. We evaluated the clinical profile and predictors of poor outcome in a group of Chinese patients with this condition. We identified 32 patients above the age of 14 years with SPSE from a large urban hospital over an eleven-year period. Factors for poor outcome, defined as death or morbidity, were analyzed. The most common underlying causes were due to cerebrovascular disease (46.9%), CNS infection (15.6%), metabolic derangement (12.5%) and tumor (12.5%). At 30 days from the onset of seizures, 13(40.5%) patients had recovered fully and seven (21.9%) had died. Poor outcome was associated with the presence of an acute symptomatic injury.     

Inpatient treatment costs of status epilepticus in adults in Germany

PurposeStatus epilepticus (SE) is an important neurological emergency and a significant source of direct costs related to hospitalization; however, no cost-of-illness (COI) studies have been performed in Europe. The objective of this study was to determine and characterize hospital costs related to the acute inpatient treatment of SE and to provide national estimates of SE hospitalization costs.MethodsAdult inpatient treatment costs related to SE and costs attributable to epilepsy-related hospital admissions were derived from billing data of participating hospitals.ResultsDuring the 4-month study period a total of 96 patients (59.5 ± 21.6 years; 52 male) received inpatient treatment for epilepsy-related reasons, 10 of these (10.4%) were treated for SE. Epilepsy was newly diagnosed in 30/96 patients (31.3%), of whom five presented with SE. The admission costs related to SE (€8347 ± 10,773 per patient per admission) were significantly higher than those related to admissions of patients with newly diagnosed (€1998 ± 1089; p = 0.014) or established epilepsy (€3475 ± 4413; p = 0.026). Of the total inpatient costs (€346,319) 24.4% were attributable to SE, 14.4% to newly diagnosed epilepsy without SE (n = 25) and 61.2% to complications of established epilepsy (n = 61). Extrapolation to the whole of Germany (population 82 million) indicates that SE causes hospital costs of more than €83 million per year while the total of epilepsy-related inpatient treatment costs amounts to €342 million.ConclusionAcute treatment of SE is responsible for a high proportion of hospital costs associated with epilepsy. With a high incidence of SE in the elderly population, the health care systems will face an increasing number of presentations with SE and its associated costs, underlining the necessity to further evaluate the burden and optimize the treatment of SE.     

Pentobarbital and EEG burst suppression in treatment of status epilepticus refractory to benzodiazepines and phenytoin

Seven patients with complex partial or secondarily generalized tonic-clonic status epilepticus (SE) refractory to benzodiazepines (BZDs) and phenytoin (PHT) were treated with pentobarbital (PTB) coma with an EEG burst suppression (BSP) pattern. PTB administered by continuous intravenous (i.v.) infusion pump at a loading dose of 6-8 mg/kg in 40-60 min was usually sufficient to produce BSP activity and seizure control. PTB was continued 0-24 h at 1-4 mg/kg/h, adjusted to maintain blood pressure (BP) and BSP. Infusion rate was decreased if systolic BP (SBP) was less than 90 mm Hg. Normal saline fluid challenge was occasionally used to elevate BP, but in no case was it necessary to discontinue PTB infusion or use pressors. Other antiepileptic drugs (AEDs) were maintained at therapeutic levels for chronic seizure protection. Seizures were stopped in all cases. Four patients attained premorbid neurologic status, two patients briefly survived in vegetative states with recurring seizures after PTB withdrawal, and one patient died of asystole after receiving PTB for 7 h. Patients who had poor outcomes had prolonged seizures (16 h to 3 weeks) before institution of PTB anesthesia, and all had significant underlying central nervous system (CNS) pathology. PTB-induced BSP appears to be safe and effective for refractory SE if it is started soon after failure of a BZD and PHT. Ultimate prognosis depends on SE etiology.     

Intellectual prognosis of status epilepticus in adult epilepsy patients: analysis with Wechsler Adult Intelligence Scale-revised

PURPOSE: Status epilepticus (SE) appears to cause cognitive dysfunction as well as other serious neurologic sequelae. To confirm whether SE produces a subsequent intellectual decline, we evaluated intellectual function prospectively in adult epilepsy patients with and without SE. METHODS: Of 1,685 patients with epilepsy who underwent comprehensive neuropsychological testing in two national hospitals in Japan, 15 patients experienced an episode of SE afterward and underwent the second neuropsychological examination after the SE episode. Forty clinically matched patients with epilepsy, but without an episode of SE since their initial neuropsychological examination, were also reevaluated. We compared IQs and subscores from the Wechsler Adult Intelligence Scale-Revised between the two groups by repeated measures analysis of variance. In the patients who experienced an SE episode, SE-related variables (i.e., age at the SE episode and type and duration of SE) and epilepsy-related variables such as epilepsy type, lateralization of EEG abnormalities, the presence of mesial temporal sclerosis, and previous history of SE, were evaluated in relation to intellectual outcome. RESULTS: Patients with SE, in comparison to those without SE, failed to show any significant post-SE intellectual decline. Furthermore, neither the SE-related variables nor the clinical characteristics were correlated with intellectual outcome. CONCLUSIONS: Our findings suggest that SE does not lead to a significant intellectual decline in adult patients receiving treatment for epilepsy.     

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 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.     

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.     

Transient magnetic resonance imaging abnormalities during partial status epilepticus

Magnetic resonance imaging is an important tool in the evaluation of patients with seizures. Frequently, abnormalities are found that lead to further, invasive testing. The first child with transient abnormal findings on magnetic resonance imaging during a time of frequent partial seizures is presented. This lesion disappeared with seizure control. The imaging literature is reviewed concerning transient findings on any imaging modality during frequent seizures. Caution in recommending invasive procedures is suggested when abnormalities are found on magnetic resonance imaging during frequent seizures.     

Propofol-associated fatal myocardial failure and rhabdomyolysis in an adult with status epilepticus

Propofol is increasingly used for the treatment of status epilepticus due to the ease of use and tolerability, even if safety data from randomized clinical trials are lacking. An association of high infusion rates of propofol (>5 mg/kg/h) for more than 48 h and constellation of acidosis, rhabdomyolysis, and cardiovascular collapse has been reported in children, but has only been described in a few adult cases. We report a case and autopsy findings of an adult who developed rhabdomyolysis and cardiac failure after receiving propofol for status epilepticus. The patient became symptomatic within 55 h after initiation of propofol infusion. The maximal infusion rate did not exceed 7.2 mg/kg/h, and propofol in excess of 5mg/kg/h was infused for less than 20 h. Preexisting antiepileptic medication may have exacerbated acidosis. Propofol infusion for the treatment of status epilepticus should be carefully weighted against its real risk to develop propofol infusion syndrome, and alternative agents such as benzodiazepines or barbiturates should be considered for first line therapy. If necessary, prolonged propofol infusion at high doses for the treatment of status epilepticus should be used with caution, and in all cases careful monitoring for rhabdomyolysis and acidosis must be performed.     

Intravenous midazolam in convulsive status epilepticus in children with pharmacoresistant epilepsy

Although the efficacy of midazolam in refractory status epilepticus and as a first-line agent in children with established status epilepticus has been reported, differences in starting doses, continuation method, timing of efficacy assessment, and discontinuation pose limitations in deriving a specific protocol for midazolam use. An audit of clinical experience with a protocol of midazolam as first-line agent for impending status epilepticus (defined as a continuous, generalized, convulsive seizure lasting >5 minutes) in 76 episodes of unprovoked convulsive status epilepticus in children 1–15 years old with treatment-refractory epilepsy demonstrated that: (1) repeated bolus midazolam 0.1 mg/kg (every 5 minutes, maximum 5) controlled 91% of events; (2) three bolus doses controlled 89% of the episodes, with minimal chance of response beyond that; (3) treating impending status resulted in lower doses (mean 0.17 mg/kg) than reported and infrequent utilization of additional anticonvulsants (9%); and (4) adverse events were infrequent (respiratory depression 13%, assisted ventilation 3%).