Bioavailability of Rectally Administered Carbamazepine Suspension in Dogs

The relative bioavailability of an investigational carbamazepine suspension was studied following rectal administration in dogs. Doses of carbamazepine, 20 mg/kg, were given to six dogs. The routes of administration were oral tablet, oral suspension, and rectal suspension. There was no significant difference (p greater than 0.05) in total absorption, as indicated by the area under the serum concentration-time curve between the oral and rectal suspensions. The notable differences between the oral suspension and the rectal suspension were in the maximum serum concentration achieved and the time to achieve this maximum serum concentration. This is due to a prolonged absorption of carbamazepine given rectally, which may limit the ability to achieve therapeutic serum concentrations rapidly. Carbamazepine suspension given rectally may be a satisfactory alternative when administration by the oral route is not possible.     

Relative Bioavailability of Rectally Administered Carbamazepine Suspension in Humans

The relative bioavailability of an investigational carbamazepine suspension was studied following rectal administration in human volunteers. Carbamazepine, in doses of approximately 6 mg/kg, was given to nine men. The routes of administration were oral tablet, oral suspension, and rectal suspension. There was no significant difference (p greater than 0.05) in total absorption, maximum serum concentration, and time to achieve maximum serum concentration between the orally-administered tablet and the rectally administered suspension. Orally administered suspension was absorbed more quickly and completely. All volunteers complained of a strong defecatory urge after the suspension was given rectally. The slow absorption after rectal administration precludes the use of this route in status epilepticus; however, it may be a satisfactory alternative for maintenance therapy when administration by the oral route is not possible.     

De Novo Absence Status Epilepticus as a Benzodiazepine Withdrawal Syndrome

Summary: A 67-year-old woman with a history of psychotropic drug abuse developed confusion. EEG was consistent with absence status epilepticus (AS). Intravenous (i.v.) flumazenil 1 mg, a benzodiazepine antagonist with anticonvulsant properties, increased both confusion and paroxysmal activity. Complete resolution was obtained after diazepam was administered i.v., and the patient then admitted that she had abruptly discontinued long-standing treatment with carpipramine, amitryptiline, bromazepam, and flunitrazepam. The aggravating effect of flumazenil indicates that benzodiazepine withdrawal was probably the elective triggering factor of this de novo absence status epilepticus.     

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.     

The Use of Althesin in Drug-Resistant Status Epilepticus

The properties of Althesin (anticonvulsant activity, depression of oxygen consumption, lowering of ICP, rapid excretion) led us to use this steroid combination to treat 11 patients in status epilepticus resistant to the standard drugs (benzodiazepines and barbiturates). The administration of Althesin by slow intravenous injection was ineffective in 2 of the 3 patients thus treated. The doses used (2--10 ml) were probably too small. One only administration of a 10% solution of Althesin in 10% fructose by intravenous drip (the rate was calculated so as to obtain the burst suppression stage at the EEG) stopped status epilepticus in 7 of the 9 patients thus treated. In this group the doses used varied from 25 to 50 ml. The 2 patients in whom it was necessary to repeat Althesin administration and combine it with other drugs had both been operated on for severe brain injuries involving marked cerebral edema. In spite of the very small number of cases, the definitive arrest of status epilepticus obtained in 8 out of 11 patients first treated with other drugs is encouraging: Althesin probably may be regarded as an adjunct in the treatment of status epilepticus.     

Myocardial Infarction Complicating Status Epilepticus

No documentation is available for myocardial infarction complicating status epilepticus. A 31-year-old man developed an acute inferolateral myocardial infarction during repetitive epileptic seizures. A cineangiographic study performed 6 months later revealed normal coronary arteries and an apical aneurysm in the left ventricle. The main pathogenetic mechanisms involved and a therapeutic possibility are discussed.     

癫痫持续状态预后评分进展

癫痫持续状态具有较高的死亡率,是神经内科常见的危急重症。对患者预后风险进行评 估,对其病情严重程度进行准确分级将有助于临床医师制定个体化的治疗方案,最大限度地使癫痫 持续状态患者获益。目前国际上共有4个癫痫持续状态预后风险的评分：癫痫持续状态严重程度评 分（status epilepticus severity score,STESS）、基于流行病学死亡率的癫痫持续状态评分（epidemiology based mortality score in SE,EMSE）、改良癫痫持续状态严重程度评分（modified STESS,mSTESS）以 及END-IT评分[包括脑炎与否（Encephalitis）、是否合并非惊厥性癫痫持续状态（Nonconvulsive status epilepticus,NCSE）、是否有地西泮抵抗（Diazepam resistance）、神经影像学特征（Image）以及是否进行 气管插管（Tracheal intubation）]。本文回顾了癫痫持续状态预后评分的进展,简述了每个评分的建立 过程及其优势和局限性,以期增强临床医师对癫痫持续状态预后评分的认识、裨益临床研究。     

How I Treat Status Epilepticus in the Neuro-ICU

Status epilepticus still remains a formidable adversary to neurointensivists. Although the majority of cases admitted to the Neuro-ICU are easily controlled with one or two antiepileptic drug defense lines, several cases become refractory and end up receiving general anesthetics for days or weeks with significant morbidity. Treatment algorithms have been published and should be followed, but in many cases they are inadequate because, especially in the distal branches of the treatment tree, are based on anecdotal data or small series of patients. In addition, a double-blind, randomized-controlled study in status has not been done for many years and solid data are lacking for the newer antiepileptics. Therefore, in the moderately to severely refractory cases, status treatment is based on personal previous experience and becomes an art more than a science. In this review of a difficult case, we discuss some fine details of the treatment provided and emphasize the multidisciplinary approach that should be followed including involvement of neurointensivists, epileptologists, electroencephalographers, and neurosurgeons.

Prolonged Refractory Status Epilepticus Related to Thrombotic Thrombocytopenic Purpura

Background  Thrombotic thrombocytopenic purpura (TTP) is an extremely rare cause of status epilepticus. Review of literature demonstrated only four cases of brief status epilepticus (SE) associated with TTP. Case  We describe a young woman with yet incomplete neurological recovery after prolonged refractory status epilepticus. Management required pentobarbital-induced coma for 60 days. Five months after onset, she was conversant and oriented with continued neuromuscular deficits. Conclusions  This is an unusual presentation of severe refractory SE associated with TTP. With aggressive life support and prolonged pentobarbital infusion, however, survival and the chance of meaningful recovery appear to be possible.     

Physiologic Consequences of Status Epilepticus

Summary: Prolonged seizures produce central nervous system damage. Physiologic consequences of status epilepticus may exacerbate this damage or may mislead the physician into making inappropriate therapeutic decisions. Status results in an elevation of body temperature, an increase in the peripheral white cell count, and often a transient pleocytosis in the spinal fluid. A marked metabolic acidosis occurs routinely. Prominent elevations in plasma hormonal concentrations occur as well. Epinephrine levels are in the arrhythmogenic range and could play a role in sudden death. Transient but marked pressure responses occur in the systemic and pulmonary circulations. Pulmonary edema may result from these pressure transients.     

癫痫持续状态的定义演变

癫痫持续状态是神经内科常见的急危重症。对癫痫持续状态概念的界定是进行临床诊疗 和科学研究的基础,随着癫痫持续状态病理生理机制研究的深入,其定义也在不断地修订与完善, 由抽象到具体,由惊厥到非惊厥,癫痫发作持续时间逐渐严谨且更加强调难治性的概念。本文着重 回顾癫痫持续状态的定义演变历程。     

Oculoclonic Status Epilepticus

Continuous oculoclonic status epilepticus occurred for 90 min in a 4-year-old girl. The seizure consisted of continuous contralateral horizontal nystagmus concurrent with left occipital spike discharges, occasional vomiting and no loss of consciousness. Oculoclonic status epilepticus may be a variant form of versive status epilepticus.     

Hippocampal Pyramidal Cell Loss in Human Status Epilepticus

A pilot case-control quantitative study of the hippocampus in patients with severe status epilepticus was performed to identify specific patterns of pyramidal cell loss. Pyramidal cell densities from five patients who died following status epilepticus were compared with five normal controls and five controls matched for age, hypoxia/ischemia, previous epilepsy, and alcohol abuse. Neuronal densities were greatest in the normal control group and least in patients with status epilepticus. Significant reductions were identified in Sommer's sector (prosubiculum and CA1) as well as in CA3 when compared to normal controls.     

De Novo Aphasic Status Epilepticus

: The literature contains only a handful of reports of patients with aphasia as the principal or only obvious manifestation of partial status epilepticus. Even fewer patients of this type have been well documented both clinically and by ictal EEG monitoring. We studied an otherwise healthy woman with abrupt onset of aphasia initially thought to be the result of an infarct of the left temporoparietal area. We were able to document partial status epilepticus involving the left temporoparieta1 area with EEG/video monitoring and showed rapid reversal of the aphasic disorder with antiepileptic drug (AED) treatment. The case is presented with a review of previous reports to underscore the importance of considering this diagnosis in patients with abrupt onset of aphasia.     

Programmed Neuronal Necrosis and Status Epilepticus

Summary:  We examined the mechanism of neuronal necrosis induced by hypoxia in dentate gyrus cultures or by status epilepticus (SE) in adult mice. Our observations showed that hypoxic necrosis can be an active process starting with early mitochondrial swelling and loss of the mitochondrial membrane potential, followed by cytochrome c release and caspase-9–dependent activation of caspase-3. This sequence of events (or program) was independent of protein synthesis and may be induced by energy failure and/or calcium overloading of mitochondria. We called this form of necrosis "programmed necrosis." After SE in adult mice, CA1 and CA3 pyramidal neurons displayed a necrotic morphology, associated with caspase-3 immunoreactivity and with double-stranded DNA breaks, suggesting that "programmed necrosis" may be involved in SE-induced neuronal loss.     

Propofol in Prehospital Treatment of Convulsive Status Epilepticus

Summary: We studied the safety and efficacy of intravenous propofol in the out–of–hospital treatment of convulsive status epilepticus (SE) in 8 patients (age 29–70 years), 4 of them with posttraumatic epilepsy. Four patients had no history of seizures. Convulsions ceased promptly after patients received a bolus of 100–200 mg propofol administered before hospital admission by staff of a mobile intensive care unit (ICU). The median duration of coma was 3 h 15 min (range 2–41 h), and the median duration of hospital treatment was 3 1/2 days (range 12 h to 23 days). Only 1 patient was admitted to the hospital's ICU. No adverse effects were observed except for a transient decrease in systolic blood pressure (SBP). Propofol may be a useful drug for the prehospital treatment of recurrent seizures not responding to intravenous diazepam (DZP).