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.     

Valproate versus diazepam for generalized convulsive status epilepticus: a pilot study

Background and purpose: Evidence‐based data to guide the management of status epilepticus (SE) after failure of primary treatment are still scarce and the alternate needs to be found when phenytoin (PHT) is not available or contraindicated. Comparison of intravenous (IV) valproate (VPA) and diazepam (DZP) infusion has not been conducted in adults with SE. This prospective randomized controlled trial is thus designed to evaluate the relative efficacy and safety of IV VPA and continuous DZP infusion as second‐line anticonvulsants. Methods: After failure of first‐line anticonvulsants treatment, patients with generalized convulsive status epilepticus (GCSE) were randomized to receive either IV VPA or continuous DZP infusion. Primary outcome was the proportion of patients with effective control. Side effects were also evaluated. Results: There were 66 cases enrolled, with the mean age of 41 ± 21 years. Seizure was controlled in 56% (20/36) of the DZP group and 50% (15/30) of the VPA group (P = 0.652). No patient in the VPA group developed respiratory depression, hypotension, or hepatic dysfunction, whereas in the DZP group, 5.5% required ventilation and 5.5% developed hypotension. Time (hour) for regaining consciousness after control was near‐significantly longer in the DZP group [13(3.15–21.5)] than in the VPA group [3(0.75–11)] (P = 0.057). Virus encephalitis and long duration of GCSE were independent risk factors of drug resistance. Conclusions: Both IV VPA and continuous DZP infusion are effective second‐line anticonvulsants for GCSE. IV VPA was well tolerated and free of respiratory depression and hypotension, which may develop in the DZP group. Outcome parameters were not significantly different between groups.     

惊厥性癫痫持续状态并发急性胰腺炎二例分析

目的探讨惊厥性癫痫持续状态（GCSE）并发急性胰腺炎的临床特点和治疗方法。方法 资料完整的GCSE住院患者二例，强直阵挛发作病史11、13年。急性胰腺炎诊断根据血尿淀粉酶化验和腹部超声波、CT检查。结果二例GCSE患者强直阵挛发作持续状态24h后出现继发性急性胰腺炎，经静脉应用地西泮癫痫状态停止，保守和支持治疗胰腺炎痊愈后出院。随访3个月未出现GCSE和腹痛。结论GCSE可以引起急性胰腺炎．GCSE后腹痛应进行急性胰腺炎有关指标的检查，明确诊断后避免使用具有胰腺毒性的抗癫痫药物。     

全身强直-阵挛性癫持续状态的临床与预后分析

目的 分析全身强直-阵挛性癫(?)持续状态(GCSE)的临床与预后。方法 采用回顾性调查的方法结合Logistic回归分析,对近30年来GCSE患者的临床资料进行分析。结果 GCSE可造成多脏器功能损害。血糖高于正常、乳酸脱氢酶(LDH)及乳酸脱氢酶同功酶(LDH-MB)同时异常升高、EKG异常等三项临床因素与死亡密切相关。结论 临床工作中,如发现患者出现血糖高于正常、LDH及LDH-MB同时异常升高、EKG异常等情况,应予以高度重视。     

难治性癫痫持续状态患者的脑电图特征

目的 探究难治性癫痫持续状态(RSE)患者的脑电图(EEG)特征.方法 将60例全面惊厥性癫痫持续状态(GCSE)患者根据抗癫痫药物(AEDs)疗效分为RSE和非难治性癫痫持续状态(NRSE),比较两组患者EEG模式的差异.结果 所有患者中,与NRSE组比较,RSE组患者发作期EEG呈持续性放电比例更高,差异具有统计学意义(OR=5.44,95%CI=1.24~23.96,P=0.04).50例EGG呈间歇性演变的患者中,与NRSE组比较,RSE组患者发作间歇期EEG呈周期性放电与痫样放电的比例较高,差异有统计学意义(OR=29.75,4.12;95%CI=3.19~277.32,1.09~15.58;P<0.05);而RSE组患者发作后EEG为正常模式的比例较低,差异具有统计学意义(OR=0.11,95%CI=0.01~0.91,P=0.04).结论 GCSE患者如EEG出现持续性放电、周期性放电、发作间期痫样放电,应引起临床的高度重视,给以强化抗惊厥治疗.     

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.     

Ictal generalized rhythmic alpha activity during non-convulsive status epilepticus

We investigated the repetitive manifestation of non-convulsive status epilepticus with an uncommon ictal electroencephalographic pattern observed in two patients suffering from epilepsy (aged 29 and 55 years). The patients had suffered from epilepsy since the age of 1 and 40 years, respectively. Interictal and ictal neurological, neuropsychological and electroencephalographic investigations were carried out. Non-convulsive status started and ended abruptly, clinically as well as electroencephalographically. The ictal electroencephalographic pattern was a monomorphic alpha activity with a generalized bilateral distribution. Altered responsiveness, sometimes eyelid myoclonia (in one patient) and amnesia were the most characteristic clinical findings during non-convulsive status. Intellectual development was delayed in the patient with early onset of epilepsy. However, this was not the case in the other patient, who developed memory impairment during the course of the disease. In both patients, lamotrigine added to valproate reduced the frequency of status epileptici significantly. Obviously, these patients suffer(ed) from a type of generalized non-convulsive status epilepticus with an uncommon electroencephalographic pattern.     

Orphenadrine induces secondarily generalized convulsive status epilepticus in rats

The current study was aimed to assess the convulsant potency of orphenadrine (ORPH) in rats together with a screen of different conventional antiepileptic drugs (AEDs) on their efficacy to suppress it. ORPH was administered intraperitoneally (i.p.) in doses of 50-80 mg/kg in male Wistar rats. The latency to first seizure, the number of seizure episodes and the duration of overt status epilepticus (SE) as well as the incidence of deaths was scored with simultaneous electroencephalographic (EEG) recordings. Subsequently, the effects of conventional AEDs on ORPH-evoked (80 mg/kg) seizure incidence were studied. ORPH dose-dependently induced seizures in increasing number of animals, reaching 100% at a dose of 80 mg/kg, associated with low mortality and no drug-related neurotoxicity. Epileptic attacks started as complex partial fits consisting of stereotyped behavior, limb movements, head shaking and myoclonic twitches of the body. Subsequently, an overt generalized convulsive SE appeared, lasting for approximately 2 h. Among conventional AEDs: carbamazepine, ethosuximide and phenytoin had no effect while valproate (p < 0.001), diazepam (p < 0.01), and phenobarbital (p < 0.001) dose-dependently suppressed seizure activity. All the above characteristics make the new model, a useful, easy to perform experimental tool to study the pathophysiology of SE as well as the effects of new AEDs.     

Aphasic or amnesic status epilepticus detected on PET but not EEG

Purpose:   To describe five patients with ictal aphasia and one patient with ictal amnesia, who had focal positron emission tomography (PET) hypermetabolism but no clear ictal activity on electroencephalography (EEG).
Methods:   ¹⁸F-Fluorodeoxyglucose (FDG)–PET scans with concomitant EEG were obtained in five patients with suspected ictal aphasia or ictal amnesia without ictal activity on EEG. We reviewed medical history, EEG, imaging data, and treatment outcome.
Results:   Brain magnetic resonance imaging (MRI) showed no structural abnormalities in any of the patients. EEG showed left temporal irregular delta activity in three patients, with aphasia and nonspecific abnormalities in two other patients, all without clear ictal pattern. All patients demonstrated focal hypermetabolism on PET scan. The hypermetabolism was in the left frontotemporal region in patients with ictal aphasia and in the bilateral hippocampal region in the patient with amnesia. Three patients who received intravenous benzodiazepines during their episodes had transient clinical improvement. With antiepileptic drug (AED) treatment, symptoms gradually resolved in all patients. Concomitant resolution of PET hypermetabolism was documented in three patients who had follow up scans. One patient with ictal aphasia later developed recurrent episodes, each with recurrent PET hypermetabolism. This patient and one other patient required immune-modulating therapy in addition to AEDs.
Discussion:   FDG-PET imaging should be considered as a diagnostic tool in patients with suspected ictal aphasia or amnesia, who fail to show clear evidence of ictal activity on EEG.     

Aborted and refractory status epilepticus in children: a comparative analysis

PURPOSE: The aims of this retrospective study were: (1) to compare the demographics, clinical characteristics, etiology, and EEG findings of status epilepticus aborted with medication (ASE) and refractory status epilepticus (RSE), (2) to describe the treatment response of status epilepticus (SE), and (3) to determine predictors of long-term outcome in children with SE. METHODS: Medical records and EEG lab logs with ICD-9 diagnostic codes related to SE were reviewed. Patients younger than 18 years of age, hospitalized in 1994-2004 at the Mayo Clinic, Rochester, were included. RESULTS: One hundred fifty-four children had SE; 94 (61%) had ASE, and 60 (39.0%) had RSE. Family history of seizures, higher seizure frequency score, higher number of maintenance antiepileptic drugs (AEDs), nonconvulsive SE, and focal or electrographic seizures on initial EEG were associated with RSE by univariate analysis. In-hospital mortality was significantly higher in RSE (13.3%) than in ASE (2.1%). In the long term, survivors with RSE developed more new neurological deficits (p < 0.001) and more epilepsy (p < 0.004) than children with ASE. Children treated in a more aggressive fashion appeared to have better treatment responses (p < 0.001) and outcomes (p = 0.03). Predictors of poor outcome were long seizure duration (p < 0.001), acute symptomatic etiology (p = 0.04), nonconvulsive SE (NCSE) (p = 0.01), and age at admission <5 years (p = 0.05). DISCUSSION: Several patient and clinical characteristics are associated with development of RSE and poor outcome. Prospective, randomized trials that assess different treatment protocols in children with SE are needed to determine the optimal sequence and timing of medications.     

Panayiotopoulos syndrome with convulsive status epilepticus at the onset: A long-term study

PurposeTo better define the convulsive status epilepticus (CSE) as a possible manifestation at the onset of Panayiotopoulos syndrome (PS) and to assess its prognostic value in these children.MethodsChildren with CSE and diagnostic criteria of PS were identified, followed clinically and compared with a group of patients with PS without CSE from 1993 to 2012.ResultsWe identified 37 patients with CSE at the onset of PS. During the same period we identified 72 children with autonomic symptoms of PS without CSE. The first episode of CSE occurred at a mean age of 6.5 years. Generalized clonic seizures were the most common ictal event and one-third of the patients required admission to Intensive Care Units. Interictal EEGs showed occipital spike activity in 31 (83.7%) subjects. Only 14 (37.8%) patients were treated with valproic acid and for two of them (5.40%) it was necessary to administer other drugs. There were no intractable cases. The overall prognosis was excellent. After the first event, 15 subjects (40.54%) experienced at least another typical PS seizure, but all patients were seizure free at the last follow-up.ConclusionCSE is not uncommon in PS and it may occur at the onset of benign childhood epilepsy, without leading to a poor prognosis.     

EFNS guideline on the management of status epilepticus in adults

The objective of the current article was to review the literature and discuss the degree of evidence for various treatment strategies for status epilepticus (SE) in adults. We searched MEDLINE and EMBASE for relevant literature from 1966 to January 2005 and in the current updated version all pertinent publications from January 2005 to January 2009. Furthermore, the Cochrane Central Register of Controlled Trials (CENTRAL) was sought. Recommendations are based on this literature and on our judgement of the relevance of the references to the subject. Recommendations were reached by informative consensus approach. Where there was a lack of evidence but consensus was clear, we have stated our opinion as good practice points. The preferred treatment pathway for generalised convulsive status epilepticus (GCSE) is intravenous (i.v.) administration of 4–8 mg lorazepam or 10 mg diazepam directly followed by 18 mg/kg phenytoin. If seizures continue more than 10 min after first injection, another 4 mg lorazepam or 10 mg diazepam is recommended. Refractory GCSE is treated by anaesthetic doses of barbiturates, midazolam or propofol; the anaesthetics are titrated against an electroencephalogram burst suppression pattern for at least 24 h. The initial therapy of non‐convulsive SE depends on type and cause. Complex partial SE is initially treated in the same manner as GCSE. However, if it turns out to be refractory, further non‐anaesthetising i.v. substances such levetiracetam, phenobarbital or valproic acid should be given instead of anaesthetics. In subtle SE, in most patients, i.v. anaesthesia is required.     

EFNS guideline on the management of status epilepticus

The objective of the current paper was to review the literature and discuss the degree of evidence for various treatment strategies for status epilepticus (SE) in adults. We searched MEDLINE and EMBASE for relevant literature from 1966 to January 2005. Furthermore, the Cochrane Central Register of Controlled Trials (CENTRAL) was sought. Recommendations are based on this literature and on our judgement of the relevance of the references to the subject. Recommendations were reached by informative consensus approach. Where there was a lack of evidence but consensus was clear we have stated our opinion as good practice points. The preferred treatment pathway for generalised convulsive status epilepticus (GCSE) is intravenous (i.v.) administration of 4 mg of lorazepam or 10 mg of diazepam directly followed by 15-18 mg/kg of phenytoin or equivalent fosphenytoin. If seizures continue for more than 10 min after first injection another 4 mg of lorazepam or 10 mg of diazepam is recommended. Refractory GCSE is treated by anaesthetic doses of midazolam, propofol or barbiturates; the anaesthetics are titrated against an electroencephalogram burst suppression pattern for at least 24 h. The initial therapy of non-convulsive SE depends on the type and the cause. In most cases of absence SE, a small i.v. dose of lorazepam or diazepam will terminate the attack. Complex partial SE is initially treated such as GCSE, however, when refractory further non-anaesthetising substances should be given instead of anaesthetics. In subtle SE i.v. anaesthesia is required.     

Outcome of severe refractory status epilepticus in children

PURPOSE: Refractory status epilepticus (RSE) is the persistence of seizure activity despite appropriate therapy; it is treated with high-dose suppressive anesthetic agents. We report here the outcome of RSE in a large series of children. METHODS: We retrospectively reviewed cases of RSE treated at Children's Hospital, Boston, between 1992 and 2000. Factors evaluated included age, history of seizures or neurologic impairment, etiology, outcome, including mortality or return to baseline, and initial EEG findings. RESULTS: Twenty-two patients ages 4.5 months to 18 years were admitted to the intensive care unit for RSE. All were treated with high-dose suppressive therapy consisting of pentobarbital, midazolam, propofol infusion, or high-dose phenobarbital, either alone, or in combination, for < or =146 days. The overall mortality was seven of 22. Mortality was related to etiology, age, and EEG findings. No death occurred in the remote symptomatic group, and three of four younger than 3 years died, whereas only four of 18 older than 3 years died. The mortality rate among patients with focal abnormalities on the EEG was lower than that among those with multifocal or generalized abnormalities. None of the children with normal premorbid neurologic status returned to baseline. CONCLUSIONS: Our data demonstrate a high mortality and morbidity for childhood RSE. Mortality is related to etiology and is higher in younger children and with multifocal or generalized abnormalities on the initial EEG.     

脑炎后癫痫持续状态进展为难治性癫痫持续状态及超级难治性癫痫持续状态的早期预测因素

目的 探讨脑炎后癫痫持续状态(SE)进展为难治性SE(RSE)及超级RSE(SRSE)的早期预测因素.方法 根据疾病进展情况将89例脑炎后SE患者分为非RSE组、RSE组及SRSE组.比较各组临床资料.结果 非RSE组、RSE组及SRSE组年龄、SE严重程度评分量表(STESS)评分、基于流行病学SE病死率评分(EMS...     

An MRI and neuropathological study of a case of fatal status epilepticus

We report a case of fatal status epilepticus of unknown origin resulting in acute neuropathological changes in the hippocampus and claustrum.The case history, brain magnetic resonance images, and results of neuropathological study of the whole brain were obtained.The subject was a 35 year old male with no significant previous medical history who presented with generalized epileptic seizures progressing to status epilepticus. He died 6 days after developing status epilepticus. Magnetic resonance imaging (MRI) brain scans were performed before and four days after developing status epilepticus. The first scan was normal and the second showed high signal lesions on T2 weighted images in the medial aspects of both temporal lobes and in the right claustrum. Neuropathological studies showed severe neuronal loss in the Sommer section of both hippocampi with early glial reactive changes. Similar changes were seen in the claustrum on both sides. There was no evidence of other causes of brain injury such as infectious encephalitis or global hypoxic-ischaemic change.The patient died of status epilepticus for which no underlying cause was found despite extensive investigation. In this case the radiological and pathological changes found bilaterally in the claustrum and hippocampus appear to be the direct result of the status epilepticus.     

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.     

Propofol treatment of refractory status epilepticus: a study of 31 episodes

PURPOSE: Refractory status epilepticus (RSE) is a critical medical condition with high mortality. Although propofol (PRO) is considered an alternative treatment to barbiturates for the management of RSE, only limited data are available. The aim of this study was to assess PRO effectiveness in patients with RSE. METHODS: We retrospectively considered all consecutive patients with RSE admitted to the medical intensive care unit (ICU) between 1997 and 2002 treated with PRO for induction of EEG-monitored burst suppression. Subjects with anoxic encephalopathy showing pathological N20 on somatosensory evoked potentials were excluded. RESULTS: We studied 31 RSE episodes in 27 adults (16 men, 11 women; median age, 41.5 years). All patients received PRO, and six also subsequently thiopental (THP). Clonazepam (CZP) was administered with PRO, and other antiepileptic drugs (AEDs) concomitant with PRO and THP. RSE was successfully treated with PRO in 21 (67%) episodes and with THP after PRO in three (10%). Median PRO injection rate was 4.8 mg/kg/h (range, 2.1-13), median duration of PRO treatment was 3 days (range, 1-9), and median duration of ICU stay was 7 days (range, 2-42). In 24 episodes in which the patient survived, shivering after general anesthesia was seen in 10 episodes, transient dystonia and hyperlipemia in one each, and mild neuropsychological impairment in five. The seven deaths were not directly related to PRO use. CONCLUSIONS: PRO administered with CZP was effective in controlling most of RSE episodes, without major adverse effects. In this setting, PRO may therefore represent a valuable alternative to barbiturates. A randomized trial with these drug classes could definitively assess their respective role in RSE treatment.