Partial status epilepticus related to independent occipital foci in posterior reversible encephalopathy syndrome (PRES)

Posterior reversible encephalopathy syndrome (PRES) is an acute disorder characterised by a variable association of neurologic symptoms with potentially reversible oedematous abnormalities mainly in the parieto-occipital regions of the brain. Despite the significant incidence of seizures, the EEG characteristics of epileptic disorders related to PRES have rarely been investigated. We report the case of an 85-year-old man who presented with generalised tonic-clonic seizures and prolonged disturbances of consciousness as clinical manifestations of PRES due to moderate exacerbation of chronic hypertension. An EEG performed during an alteration of mental function displayed a pattern of partial status epilepticus (SE) in both temporo-parieto-occipital regions. The seizure activity originated from two independent epileptic foci located in the occipital area of each hemisphere and could be related to the parenchymal abnormalities of PRES. The EEG pattern of partial SE related to independent occipital foci illustrates a distinctive seizure disorder that could be characteristic of PRES in adult patients.

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Sommario  La sindrome della encefalopatia posteriore reversibile (PRES) è caratterizzata da una associazione di sintomi neurologici acuti (principalmente cefalea, vomito, alterazione della coscienza, crisi epilettiche e cecità corticale) e lesioni edematose potenzialmente reversibili delle regioni cerebrali parieto-occipitali. Descriviamo il caso di un soggetto maschile di 85 anni che ha manifestato crisi tonico-cloniche generalizzate ed un prolungato disturbo della coscienza come manifestazione di PRES secondaria a moderato incremento della pressione arteriosa. L’EEG ha evidenziato uno stato di male epilettico parziale legato a localizzazioni epilettogene occipitali bilaterali ed indipendenti. L’attività epilettica era correlabile alle alterazioni parenchimali della PRES. Il quadro EEGrafico osservato configura un disturbo epilettico raramente descritto nella letteratura, che potrebbe essere caratteristico della PRES in pazienti adulti.

     

Effectiveness of lidocaine infusion for status epilepticus in childhood: a retrospective multi-institutional study in Japan

We evaluated the usefulness of intravenous lidocaine therapy for managing of status epilepticus (SE) during childhood in a retrospective multi-institutional study. Questionnaires were sent to 28 hospitals concerning patients admitted for SE who were managed with lidocaine, assessing patient characteristics, treatment protocols and efficacy. In 279 treated patients, 261 SE occurrences at ages between 1 month and 15 years were analyzed. SE was classified as showing continuous, clustered, or frequently repeated seizures. Considering efficacy and side effects in combination, the usefulness of lidocaine was classified into six categories: extremely useful, useful, slightly useful, not useful, associated with deterioration, or unevaluated. In 148 SE cases (56.7%), lidocaine was rated as useful or extremely useful. Multivariate analysis indicated lidocaine was to be useful in SE with clustered and frequently repeated seizures, and SE attributable to certain acute illnesses, such as convulsions with mild gastroenteritis. Efficacy was poor when SE caused by central nervous system (CNS) infectious disease. Standard doses (approximately 2mg/kg as a bolus, 2mg/kg/h as maintenance) produced better outcomes than lower or higher doses. Poor responders to the initial bolus injection of lidocaine were less likely to respond to subsequent continuous infusion than good initial responders. We recommend lidocaine for use in SE with clustered or frequently repeated seizures, and in SE associated with benign infantile convulsion and convulsions with mild gastroenteritis. Lidocaine should be initiated with a bolus of 2mg/kg. If SE is arrested by the bolus, continuous maintenance infusion should follow; treatment should proceed to different measures when SE shows a poor response to the initial bolus of lidocaine.     

The association between seizure clustering and convulsive status epilepticus in patients with intractable complex partial seizures

PURPOSE: We examined the association between seizure clustering and convulsive status epilepticus (SE) in patients with intractable complex partial seizures, to identify whether patients whose seizures typically cluster are at high risk for convulsive SE (CSE). METHODS: Seventy-six patients with intractable complex partial epilepsy who underwent presurgical evaluation in the Montefiore Epilepsy Management Unit from 1993 to 1997 were contacted and interviewed about typical seizure frequency and distribution and history of CSE. Seizure clustering was defined as three or more complex partial seizures within a 24-h period, with return to baseline between seizures. RESULTS: Of the 76 patients contacted, 21 (28%) had experienced at least one episode of CSE, and 36 (47%) typically experienced clustered seizures. SE occurred in 16 (44%) of 36 patients with clustered seizures, and in five (12.5%) of 40 patients with nonclustered seizures (p < 0.002). Of 53 patients with temporal lobe epilepsy, CSE occurred in 13 (50%) of 26 patients with clustered seizures, and four (14.8%) of 27 patients with nonclustered seizures (p < 0.006). CONCLUSIONS: Patients with intractable complex partial or localization-related epilepsy who typically experience seizure clustering are at a significantly higher risk for CSE than are patients with nonclustered seizures.     

Anticonvulsive effect of a selective mGluR8 agonist (S)-3,4-dicarboxyphenylglycine (S-3,4-DCPG) in the mouse pilocarpine model of status epilepticus

Summary:  Purpose: We sought to investigate the anticonvulsive and neuroprotective effect of a selective metabotropic glutamate receptor 8 (mGluR8) agonist ( S )-3,4-dicarboxyphenylglycines ( S -3,4-DCPG) on pilocarpine-induced status epilepticus (PISE) and subsequent loss of hilar neurons in the dentate gyrus after systemic (intravenous) or local (intracerebroventricular) administration. We compared the difference in granular cell responses after paired-pulse stimulation of the perforant pathway and the sensitivity to local injection of S -3,4-DCPG into the stratum granulosum in the control and mice at 2 months after PISE.
Methods: We used intravenous, intracerebroventricular, or intrahippocampal administration of S -3,4-DCPG to mice with status epilepticus or temporal lobe epilepsy and neurophysiologic recording of somatic field excitatory postsynaptic potential (sfEPSP) and population spike (PS) of granular cells in response to perforant-pathway stimulation or S -3,4-DCPG treatment.
Results: Intracerebroventricular (1.91 μmol) but not systemic administration of S -3,4-DCPG (at doses of 12.5, 50, 100, 200, 400, 800, and 1,200 mg/kg) could control PISE with no neuroprotective effect. In epileptic mice, mGluR8-mediated inhibition of fEPSPs was reduced significantly in granular cell bodies.
Conclusions: At doses ranging from 12.5 to 1,200 mg/kg, intravenous administration of S -3,4-DCPG may not be effective in controlling status epilepticus. Down-regulation of mGluR8 may be related to reduced S -3,4-DCPG–mediated inhibition and the subsequent occurrence of spontaneously recurrent seizures.     

Misdiagnosis due to gastrointestinal symptoms in an adolescent with probable autonomic status epilepticus and Panayiotopoulos syndrome

Panayiotopoulos syndrome is a common benign epilepsy affecting otherwise healthy children that present with autonomic seizures, in which nausea, retching, and vomiting are particularly common and prominent. Because of the unusual ictal symptoms and lengthy manifestations, misdiagnosis is a common major problem. We describe a young girl with intractable and lengthy vomiting attacks, several admissions to hospitals, and extensive gastroenterological workup for several years from early childhood. On all previous occasions the diagnosis varied from psychosomatic disease, to functional dyspepsia, to cyclic vomiting syndrome. The possibility of autonomic epileptic seizures and Panayiotopoulos syndrome, though likely, was not considered.     

不同类型小儿癫痫持续状态的临床及脑电图分析

目的 分析不同类型儿童癫痫持续状态（ＳＥ）的临床和脑电图（ＥＥＧ）特征,以期对ＳＥ作出早期诊断及处理。方法 用录像脑电图监测的方法对１９９６年３月至１９９９年３月北京医科大学第一医院儿科（２４例）和香港大学儿科部（３例）收治的２７例癫饿按发作类型进行分类,分析不同为临床发作特征及年龄、病因、脑发育水平、诱发因素和药物反应等对ＳＥＲ 影响。结果 本组２７例ＳＥ患儿强直＝阵挛性ＳＥ１例,强直性ＳＥ２例     

中老年复杂部分性发作癫痫持续状态的临床特征及误诊分析

目的 分析中老年复杂部分性发作癫痫持续状态(CPSE)的临床特点及误诊原因.方法 收集广州医学院第二附属医院神经内科自2008年1月至12月收治、曾被外院误诊的中老年CPSE患者的临床资料,进行视频脑电图(EEG)、头颅MR、生化检查,根据国际抗癫痫联盟的CPSE诊断标准进行诊断,并随访3个月以上. 结果 本组患者7例,均为女性,其中额叶癫痫(FLE)2例,颞叶癫痫(TLE)5例;CPSE患者临床症状和视频EEG表现多样化;经抗癫痫药物(AEDs)治疗后3例至少3个月无发作,3例仍有CPSE发作,1例仍有反复CPSE. 结论 由于CPSE患者临床症状和EEG表现欠典型,常合并其他系统疾病和社会因素的影响易被误诊,应及早做视频EEG检查以明确诊断;口服AEDs治疗可取得良好效果.     

Strain differences in seizure-induced cell death following pilocarpine-induced status epilepticus

Mouse strains differ from one another in their susceptibility to seizure-induced excitotoxic cell death. Previously, we have demonstrated that mature inbred strains of mice show remarkable genetic differences in susceptibility to the neuropathological consequences of seizures in the kainate model of status epilepticus. At present, while the cellular mechanisms underlying strain-dependent differences in susceptibility remain unclear, some of this variation is assumed to have a genetic basis. However, it remains unclear whether strain differences in susceptibility to seizure-induced cell death observed following kainate administration are observed following systemic administration of other chemoconvulsants. In rodents, the cholinomimetic convulsant pilocarpine is widely used to induce status epilepticus (SE), followed by hippocampal damage and spontaneous recurrent seizures, resembling temporal lobe epilepsy. This model has initially been described in rats, but is increasingly used in mice. We characterized neuronal pathologies after pilocarpine-induced status epilepticus (SE) in eight inbred strains of mice focusing on the hippocampus. A ramping-up dose protocol for pilocarpine was used and behavior was monitored for 4-5 h. While we did not observe any significant differences in seizure latency or duration to pilocarpine among the inbred strains, we did observe a significant difference in susceptibility to the neuropathological consequences of pilocarpine-induced SE. Of the eight genetically diverse mouse strains screened for pilocarpine-induced status, BALB/cJ and BALB/cByJ were the only two strains that were resistant to the neuropathological consequences of seizure-induced cell death. Additional studies of these murine strains may be useful for investigating genetic influences on pilocarpine-induced status epilepticus.     

A multicenter study on the prevalence of psychiatric disorders among new referrals for epilepsy in Japan

PURPOSE: To investigate the prevalence rate and risk factors of psychiatric disorders among new referrals for epilepsy, a multicenter study was conducted by using the International League Against Epilepsy (ILAE) criteria for epilepsy and the ICD-10 criteria for psychiatric disorders. METHODS: From April 2000 to March 2001, 398 patients with epilepsy, who were referred to nine neuropsychiatric outpatient clinics specialized for epilepsy in the Tokyo metropolitan area, were evaluated by using a newly developed five-axis classification scheme. RESULTS: Forty-two percent of the subjects showed a psychiatric disorder. Twenty-four percent of the total showed psychiatric disorders, including neurotic disorders in 8%, psychotic disorders in 7%, and affective disorders in 1%. In addition, 23% of the total showed mental retardation, and 18% showed personality disorders. A logistic regression analysis revealed that the three risk factors for a psychiatric disorder were mental retardation, temporal lobe epilepsy (as opposed to other subtypes), and a high seizure frequency. CONCLUSIONS: The presence of mental retardation was the primary risk factor for developing a psychiatric disorder, especially a schizophrenia-spectrum disorder. The type of epilepsy alone is not a strong predictor of psychiatric illness, and intractable temporal lobe epilepsy with a high seizure frequency is accountable for the link between the epilepsy and the psychiatric illness.     

Nitric oxide synthase immunoreactivity in the rat hippocampus after status epilepticus induced by perforant pathway stimulation

Nitric oxide has recently been implicated in mediation of neuronal excitotoxicity and damage. This study aimed at elucidating the changes in the expression of neuronal isoform of nitric oxide synthase (nNOS) in the hippocampus after status epilepticus induced by perforant pathway stimulation. nNOS-immunoreactivity (nNOS-ir) and neuronal damage, assessed by silver staining, were evaluated separately in different hippocampal subfields 2 weeks after induction of status epilepticus. Perforant pathway stimulation resulted in an increase in the number of nNOS-immunoreactive neurons in the stratum radiatum of the CA1 and CA3 subfields of the hippocampus proper, and the hilus of the dentate gyrus. The morphology and distribution of the nNOS-ir neurons resembled that of interneurons. No correlation of the number of nNOS-ir neurons to the neuronal damage score was observed. Our results suggest that status epilepticus provokes a de novo expression of nNOS protein, and the nNOS expressing neurons may be selectively resistant to epileptic brain injury.     

Management of and prophylaxis against status epilepticus in children with severe myoclonic epilepsy in infancy (SMEI; Dravet syndrome)--a nationwide questionnaire survey in Japan

The aim of this study was to establish strategies for prophylaxis against status epilepticus (SE) associated with high fever and for management of ongoing SE in children with severe myoclonic epilepsy in infancy (SMEI). Methods: The investigation was performed retrospectively using a questionnaire, asking about medications, which was distributed to epilepsy specialists throughout Japan. All respondents were members of the Japan Epilepsy Society (JES) and/or the Japanese Society of Child Neurology (JSCN). Data from 109 SMEI patients (51 males and 58 females), 1–37 (M ± SD, 10.7 ± 6.53) years old, were used for this study. Of these 109 patients, 10 were excluded because they had not experienced SE, such that data from 99 patients were analyzed. Results: Among the anti-epileptic drugs (AEDs) used daily, excellent efficacy against SE evolution was obtained with the following: potassium bromide (KBr) (41.7%), zonisamide (ZNS) (13.5%), clobazam (CLB) (10.0%), valproate (VPA) (8.0%), phenobarbital (PB) (6.7%), and phenytoin (PHT) (2.6%). Excellent efficacy was not obtained with either clonazepam (CZP) or carbamazepine (CBZ). The diazepam (DZP) suppository was the most frequently given drug for prophylaxis against SE triggered by fever, but only 2 (2.4%) cases showed excellent results. Excellent efficacy in terminating ongoing SE was obtained with the following medications; intravenous barbiturates (75–100%), intravenous midazolam (MDZ) (68.8%), intravenous DZP (54.3%), intravenous lidocaine (Lid) (21.4%), and intravenous PHT (15.4%). Conclusions: Daily KBr was most efficacious for controlling seizures in SMEI patients. Early use of intravenous barbiturates is the most effective strategy in stopping SE in a subset of patients. Reliable efficacy in SE was not obtained with prophylactic DZP, intravenous benzodiazepines (BZPs), PHT and Lid.     

Panayiotopoulos syndrome and symptomatic occipital lobe epilepsy of childhood: a clinical and EEG study

Aim. Panayiotopoulos syndrome (PS) is an age‐related seizure susceptibility syndrome that affects the central autonomic system. Although the majority of the few ictal recordings obtained so far suggest an occipital origin, semiological and interictal EEG data appear to favour more extensive involvement. In this study, the characteristics (including those based on semiology and EEG) of children with Panayiotopoulos syndrome (n=24) and those with lesion‐related, symptomatic occipital lobe epilepsy (SOLE) (n=23) were compared. Methods. Detailed semiological information and EEG parameters including the localisation, distribution, density (n/sec), reactivity, and morphological characteristics of spike‐wave foci and their relationship with different states of vigilance were compared between the two groups. Results. The age at seizure onset was significantly younger in patients with symptomatic occipital lobe epilepsy than in those with PS (mean age at onset: 3.4 versus 5.6 years, respectively; p=0.044). Autonomic seizures (p=0.001) and ictal syncope (p=0.055) were more frequent in PS than in symptomatic occipital lobe epilepsy (87.5% and 37.5% versus 43.5% and 13%, respectively). The interictal spike‐wave activity increased significantly during non‐rapid eye movement (non‐REM) sleep in both groups. The spike waves in non‐REM seen in PS tended to spread mainly to central and centro‐temporal regions. Conclusions. The results indicate that although common features do exist, Panayiotopoulos syndrome differs from symptomatic occipital lobe epilepsy and has a unique low epileptogenic threshold related to particular brain circuits.     

Incidence and short-term prognosis of status epilepticus in adults in Bologna,Italy

PURPOSE: To determine the incidence and the 30-day case fatality of status epilepticus (SE) in the adult resident population of the city of Bologna, Italy. METHODS: Over a 1-year period (March 1, 1999 to February 29, 2000), all patients older than 20 years with SE were included. The case-finding method was based on (a) a prospective surveillance of all public general hospitals in the city by neurologic units, and (b) a review of all discharge codes concerning epilepsy. RESULTS: The crude and standardized annual incidence rate of SE was 13.1 per 100,000 [95% confidence interval (CI), 9.5-17.5] and 10.7 (95% CI, 7.5-13.8). It was higher in the elderly (older than 60 years) than in young adults (26.2 vs. 5.2) and in women than in men (14.9 vs. 11.0). Acute symptomatic SE accounted for 48%, and a cerebrovascular pathology was the most frequently associated etiologic condition (41%). A history of seizures was reported in 39% of patients. The 30-day case fatality was 39% (33% excluding postanoxic patients). CONCLUSIONS: This study reports the first data on the epidemiology of SE in Italy. The incidence rate found in the population of Bologna is in the same range as that of the other European countries. The 30-day case fatality is higher than all the other population studies (both European and American), despite the broadly similar clinical features of patients. Indirect evidence suggests that some inaccurate patient management could have negatively influenced the outcome of SE.     

In vivo diffusion tensor imaging and ex vivo histologic characterization of white matter pathology in a post-status epilepticus model of temporal lobe epilepsy

Although epilepsy is historically considered a disease of gray matter, recent diffusion tensor imaging (DTI) studies have shown white matter abnormalities in patients with epilepsy. The histopathologic correlate of these findings, and whether they are a cause or consequence of epilepsy, remains unclear. To characterize these changes and their underlying histopathology, DTI was performed in juvenile rats, 4 and 8 weeks after pilocarpine‐induced status epilepticus (SE). In the medial corpus callosum (CC), mean diffusivity and axial diffusivity (MD and λ₁) as well as a myelin staining were significantly reduced at 4 weeks. Only the λ₁ decrease persisted at 8 weeks. In the fornix fimbriae (FF), λ₁ and myelin staining were decreased at both time points, whereas fractional anisotropy (FA) and MD were significantly reduced at 8 weeks only. We conclude that SE induces both transient and chronic white matter changes in the medial CC and FF that are to some degree related to myelin pathology.     

Autonomic status epilepticus in Panayiotopoulos syndrome and other childhood and adult epilepsies: a consensus view

PURPOSE: To discuss and propose a definition of autonomic status epilepticus (SE), describe its clinical and EEG features, and review what is known about its epidemiology, pathophysiology, differential diagnosis, and management. METHODS: An international consortium of established researchers in the field was identified from their published work, agreed the purpose of the project, searched the literature, and, by use of e-mail communication, agreed the consensus document. RESULTS: Autonomic SE is a condition lasting at least 30 min and characterized by epileptic activity causing altered autonomic function of any type at seizure onset or in which manifestations consistent with altered autonomic function are prominent (quantitatively dominant or clinically important) even if not present at seizure onset. It is best described, and probably most commonly encountered in children, with Panayiotopoulos syndrome. However, it also occurs in children with symptomatic epilepsies and, exceptionally, in adults. Its pathogenesis and most appropriate management are poorly understood. CONCLUSIONS: It is hoped that this document will help clinical recognition of Autonomic SE, reduce misdiagnosis, and promote further interest and studies into what has been a relatively neglected area.     

Early-life status epilepticus induces ectopic granule cells in adult mice dentate gyrus

A large number of aberrant hilar granule cells (GCs) are found in the patients and animal models of adult temporal lobe epilepsy (TLE), and these “ectopic” GCs have synchronous epileptiform bursting with other hippocampal neurons. In this study, we investigated whether early-life status epilepticus (SE) induces hilar ectopic GCs that remain in the adulthood because TLE patients frequently experience seizures in the early childhood when a large number of postnatally born GCs migrate in the hilus. To label newborn GCs, bromodeoxyuridine (BrdU) was injected daily for three consecutive days to C57BL/6J mice at different postnatal days starting at postnatal-0-day-old (P0) (Group1), P7 (Group2), or P35 (Group3). Mice in each group underwent pilocarpine-induced SE at P14. Six months later, to determine whether SE induces ectopic GCs, we plotted the distribution of postnatally born GCs which were immunohistochemically defined as BrdU- and the GC marker Prox1-colabeled cells. We also examined whether SE causes the granule cell layer (GCL) dispersion and/or the mossy fiber (MF) sprouting, other representative pathologies of TLE hippocampus. Only SE-experiencing mice in Group1 had significantly more neonatally born ectopic GCs compared with control mice. Neither control nor SE mice had dispersed GCL. All mice that underwent SE had sprouted MFs in CA3. We conclude that early-life SE disrupts a normal incorporation of GCs born pre-SE but not post-SE, inducing ectopic GCs in the adult hilus. Interestingly, the results also indicate that developmentally earlier born GCs are more responsive to early-life SE in terms of the emergence of ectopic GCs.     

Long-term decrease in calbindin-D28K expression in the hippocampus of epileptic rats following pilocarpine-induced status epilepticus

Acquired epilepsy (AE) is characterized by spontaneous recurrent seizures and long-term changes that occur in surviving neurons following an injury such as status epilepticus (SE). Long-lasting alterations in hippocampal Ca²⁺ homeostasis have been observed in both in vivo and in vitro models of AE. One major regulator of Ca²⁺ homeostasis is the neuronal calcium binding protein, calbindin-D28k that serves to buffer and transport Ca²⁺ ions. This study evaluated the expression of hippocampal calbindin levels in the rat pilocarpine model of AE. Calbindin protein expression was reduced over 50% in the hippocampus in epileptic animals. This decrease was observed in the pyramidal layer of CA1, stratum lucidum of CA3, hilus, and stratum granulosum and stratum moleculare of the dentate gyrus when corrected for cell loss. Furthermore, calbindin levels in individual neurons were also significantly reduced. In addition, the expression of calbindin mRNA was decreased in epileptic animals. Time course studies demonstrated that decreased calbindin expression was initially present 1 month following pilocarpine-induced SE and lasted for up to 2 years after the initial episode of SE. The results indicate that calbindin is essentially permanently decreased in the hippocampus in AE. This decrease in hippocampal calbindin may be a major contributing factor underlying some of the plasticity changes that occur in epileptogenesis and contribute to the alterations in Ca²⁺ homeostasis associated with AE.     

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.