Behavioural changes in patients with intellectual disability treated with brivaracetam.

OBJECTIVE: The purpose of this study was to evaluate the tolerability and efficacy of brivaracetam (BRV) in residential patients at our epilepsy centre. PATIENTS AND METHODS: We assessed retrospectively 33 patients (14 females; mean age 38.2 years, with range 17-63 years) with intellectual disability (ID) and drug-resistant epilepsy using an industry-independent, non-interventional study design based on standardized daily seizure records. Mean seizure frequency was compared between the 3-month baseline period and subsequent 3-month treatment period. Evaluation, including calculation of retention rate, was carried out for the intervals 3-6 and 9-12 months after brivaracetam initiation. Responders were defined as having a 50% reduction in seizure frequency. The Clinical Global Impression scale (CGI) was applied to allow assessment of qualitative changes in seizure severity, and the Aggressive Behaviour Scale (ABS) gave further insights into challenging behaviour. RESULTS: The responder rate was 19%, and one non-responder attained an improvement in CGI score. The retention rate after 12 months was 37%. Brivaracetam treatment was stopped because of adverse events (n = 3), lack of efficacy (n = 8) or both (n = 6). Thirteen patients experienced behavioural changes, with aggressive behaviour being the commonest effect. We also observed ataxia (n = 2), gastrointestinal disorder (n = 3) and sedation (n = 2). The ABS showed deterioration, or new occurrence, of aggressive behaviour in 13 patients. CONCLUSIONS: Brivaracetam seems to be effective in a small number of patients suffering from difficult-to-treat epilepsy and intellectual disability. Challenging behaviour was documented in a relevant number of patients, with psychiatric illness being a risk factor for this.

Behavioural changes in patients with intellectual disability treated with perampanel.

OBJECTIVES: The aim of this cross-sectional retrospective study was to assess the tolerability and efficacy of perampanel in patients with drug-resistant epilepsy who also suffered from intellectual disability (ID). PATIENTS AND METHODS: We used an industry-independent, non-interventional retrospective evaluation based on standardized, daily seizure records. Twenty-seven patients with ID and drug-resistant epilepsy were started on perampanel between September 2012 and November 2015 after a 3-month observation period without perampanel treatment. Perampanel was given at a maximum dosage of 4-12 mg daily. Evaluation was carried out after 6, 12 and 24 months, including calculation of the retention rate. Mean seizure frequency was compared between the 3-month baseline period and subsequent 3-month treatment periods. The Clinical Global Impression scale was applied to assess qualitative changes in seizure severity, and the Aggressive Behaviour Scale (ABS) gave further insights into challenging behaviour. RESULTS: Perampanel was efficacious and well tolerated in five of 25 patients. In 18 patients, perampanel treatment was stopped, mainly because of adverse events (n=6), lack of efficacy (n=3) or both (n=9). Behavioural changes were documented in 15 of 27 patients, with aggressive behaviour being the commonest effect; we observed ataxia (n=6) and sedation (n=8) in further patients. The ABS showed worsening of aggressive behaviour in six patients. CONCLUSIONS: Perampanel was well tolerated and efficacious in one-fifth of our patients. We observed challenging behaviour, ataxia and sedation in a relevant number of patients with ID under perampanel treatment. Further studies are warranted to explore the tolerability of perampanel in patients with ID.

Adjunctive retigabine in refractory focal epilepsy: Postmarketing experience at four tertiary epilepsy care centers in Germany.

PURPOSE: Retigabine (RTG, ezogabine) is the first potassium channel-opening anticonvulsant drug approved for adjunctive treatment of focal epilepsies. We report on the postmarketing clinical efficacy, adverse events, and retention rates of RTG in adult patients with refractory focal epilepsy. METHODS: Clinical features before and during RTG treatment were retrospectively collected from patients treated at four German epilepsy centers in 2011 and 2012. RESULTS: A total of 195 patients were included. Daily RTG doses ranged from 100 to 1500 mg. Retigabine reduced seizure frequency or severity for 24.6% and led to seizure-freedom in 2.1% of the patients but had no apparent effect in 43.1% of the patients. Seizure aggravation occurred in 14.9%. The one-, two-, and three-year retention rates amounted to 32.6%, 7.2%, and 5.7%, respectively. Adverse events were reported by 76% of the patients and were mostly CNS-related. Blue discolorations were noted in three long-term responders. Three possible SUDEP cases occurred during the observation period, equalling an incidence rate of about 20 per 1000 patient years. CONCLUSIONS: Our results are similar to other pivotal trials with respect to the long-term, open-label extensions and recent postmarketing studies. Despite the limitations of the retrospective design, our observational study suggests that RTG leads to good seizure control in a small number of patients with treatment-refractory seizures. However, because of the rather high percentage of patients who experienced significant adverse events, we consider RTG as a drug of reserve.

[Impact of early benefit assessment on patients with epilepsy in Germany: Current healthcare provision and therapeutic needs]. / Auswirkungen der frühen Nutzenbewertung auf Patienten mit Epilepsie in Deutschland : Aktuelle Versorgungsrealität und therapeutischer Bedarf.

Epilepsy is one of the most common chronic neurological diseases and represents a significant burden for patients, their families and society. In more than 75 % of patients anticonvulsant therapy consists of valproate, carbamazepine, lamotrigine or levetiracetam. There is a need for polytherapy in drug-refractory patients and they suffer from negative effects on quality of life and employment that is associated with high indirect costs. To allow a comprehensive treatment in this patient group, access to new anticonvulsants with novel modes of action is needed; however, all applications for new antiepileptic drugs failed to prove added benefits during the Pharmaceutical Market Restructuring Act (AMNOG) in Germany. One of the main reasons is the mandatory definition of a standard comparative therapy. It remains unclear whether there will be studies in the future which will fulfill the requirements of the current version of AMNOG. Observational studies after approval and marketing of new antiepileptic drugs could be better alternatives to prove added benefits for individual patients in the current German healthcare system.

[Invasive stimulation procedures and EEG diagnostics in epilepsy]. / Invasive Stimulationsverfahren und EEG-Diagnostik bei Epilepsien.

Stimulation has been performed experimentally and in small case series to treat epilepsy since the 1970s. Since the introduction of vagus nerve stimulation in 1997 and intracranial stimulation methods in 2011 into patient care, invasive stimulation has become a rapidly developing but infrequently used therapeutic option in Europe. Whereas vagus nerve stimulation is frequently used, particularly in the USA, intracranial stimulation differs in its regional availability. In order to improve the efficacy of stimulation, develop criteria for its use and assure low complication rates, a concentration on experienced centers and multicenter data acquisition and sharing are needed.Invasive electroencephalographic (EEG) monitoring with subdural electrodes and especially with stereotactically implanted depth electrodes have been used increasingly more often for presurgical evaluation in recent years. They are applied when non-invasive diagnostics show insufficient results to exactly identify the location and extent of the epileptogenic zone or cannot be adequately distinguished from eloquent cortex areas. Complications include intracranial hemorrhage, infections and increased intracranial pressure but lasting deficits or even death are rare (≤2 %). The outcome of invasive monitoring is inferior to non-invasive monitoring because of the higher degree of complexity of the cases; however, it is far superior to the seizure-free rates achieved by anticonvulsant drug treatment alone.

[New aspects in the field of epilepsy]. / Neues auf dem Gebiet der Epilepsien.

Regarding epilepsy several new developments can be reported. The International League Against Epilepsy (ILAE) has suggested a new definition of epilepsy, for the first time including a definition of epilepsy resolution. Progress in the diagnosis relates to new genetic findings, improvements in magnetic resonance imaging (MRI) and the increasing use of stereo electroencephalograms (sEEG). Regarding treatment there are new clinically relevant data on the pathophysiology and prevention of sudden unexpected death in epilepsy (SUDEP). Zonisamide has been approved by the European Medicines Agency (EMA) for monotherapy in adults with focal seizures and combination therapy in children aged ≥ 6 years. Retigabin and perampanel have been approved but are currently taken off the market in Germany (only) because the Gemeinsamer Bundesausschuss (GBA, Joint Federal Committee) did not find any additional therapeutic value as compared to lamotrigine due to a lack of data. A decision regarding a new application for perampanel is pending. Regarding surgical treatment novel ablation techniques (e.g. stereotactic radiofrequency and laser ablation as well as focussed ultrasound ablation) and brain stimulation paradigms are under investigation. Experimental studies, generously supported by the European Union (EU) and the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) are focusing on (opto-)genetic (e.g. using lentoviral transfection), epigenetic (e.g. micro-RNA-related) approaches and on the investigation of neuronal micronetworks.

Predicting return to work following treatment of chronic pain disorder.

BACKGROUND: The care of injured workers with chronic pain remains an important public health issue given its increasing prevalence. The consequences often include loss of self-esteem and stress in family relationships. AIMS: To report our interdisciplinary approach to the care of chronic pain disorder (CPD) and describe the predictors associated with a successful return to work (RTW). METHODS: Relevant covariates, including demographic data, time from injury, and functional scores were recorded for clients injured at work in Ontario, Canada. Our primary outcome, RTW, was assessed at 3 months post-discharge. Descriptive statistics and logistic regression were used to identify those factors predicting a successful RTW. RESULTS: Of the injured workers who participated in the interdisciplinary CPD treatment programme, 1002 clients met our inclusion criteria and were included in the study. Fifty-five per cent were male with a mean age of 46 years. Median time from injury to treatment was 720 days. At 3 months post-treatment, 136 (14%) of the participants were working. Multivariable logistic regression revealed that earlier time since injury (OR = 0.71, 95% CI 0.55-0.92) and presence of an RTW coordinator (RTWC) (OR = 3.42, 95% CI 2.08-5.63) were significant predictors of successful RTW. There was also a significant interaction between RTWC involvement and time since injury. The latter did not appear to influence the likelihood of RTW when an RTWC was present. CONCLUSIONS: Workers compensation boards should refer injured workers with CPD to treatment programmes as early as possible to achieve a successful RTW. Additionally, RTWCs play an important role in improving work outcomes.

A single-center observational study on long-term neurodevelopmental outcomes in children with tuberous sclerosis complex.

BACKGROUND: Tuberous sclerosis complex (TSC) is a rare multisystem disorder caused by mutations in the TSC1 or TSC2 gene. More than 90% of patients with TSC develop neurological and/or neuropsychiatric manifestations. The aim of the present study was to determine the developmental and cognitive long-term outcomes of pediatric TSC patients. METHODS: This cross-sectional, monocenter study included pediatric TSC patients who received multidisciplinary long-term care with a last visit between 2005 and 2019. Neurological manifestations and cognitive development (BSID, K-ABC) were analyzed in relation to age and type of mutation. RESULTS: Thirty-five patients aged 13.5 ± 7.8 years were included in the study. Diagnosis was confirmed genetically in 65.7% of patients (TSC1, 26.1%; TSC2, 65.2%; NMI, 8.7%). Mean age at diagnosis was 1.3 ± 3.5 years; 74.3% of the patients had been diagnosed within the first year of life due to seizures (62.9%) or/and cardiac rhabdomyomas (28.6%). The most common TSC manifestations included structural brain lesions (cortical tubers, 91.4%; subependymal nodules, 82.9%), epilepsy (85.7%), and cardiac rhabdomyomas (62.9%). Mean age at seizure onset was 1.5 ± 2.3 years, with onset in 80.0% of patients within the first two years of life. Infantile spasms, which were the first seizure type in 23.3% of the patients, developed earlier (0.6 ± 0.4 years) than focal seizures (1.8 ± 2.5 years). Refractory epilepsy was present in 21 (70.0%) patients, mild or severe intellectual impairment in 66.6%, and autism spectrum disorders in 11.4%. Severe cognitive impairment (33.3%) was significantly associated with epilepsy type and age at seizure onset (p < 0.05). CONCLUSIONS: The results emphasized the phenotypic variability of pediatric-onset TSC and the high rate of neurological and neuropsychiatric morbidity. Early-onset refractory epilepsy was associated with impaired cognitive development. Children of all ages with TSC require multidisciplinary long-term care and individual early-intervention programs.

[Neuropathology and etiology of focal epilepsy]. / Neuropathologie und Ätiologie fokaler Epilepsien.

In 2010 the International League against Epilepsy published a new classification of epilepsies. A major advance of this classification system is the acknowledgment of a genetic or pathologic-anatomic basis of epilepsy as important predictors of outcome (cause matters). This applies in particular to structural-metabolic lesions, which were frequently recognized in surgical specimens obtained from patients with drug-resistant focal epilepsy, i.e. hippocampal sclerosis, glioneuronal tumors, focal cortical dysplasias, vascular malformations, ischemia, intracerebral hemorrhage, glial scars or inflammation. A better understanding and classification of the etiopathology as well as the underlying molecular mechanisms will help to anticipate and appreciate the clinical course of a disease as well as to develop new and targeted drug treatment. Surgically available human brain tissue will be most helpful to support this approach but will also need careful neuropathological evaluation with accurate classification systems and use of terminology.

[Non-convulsive status epilepticus: temporary fad or reality in need of treatment?]. / Nonkonvulsiver Status epilepticus : Modeerscheinung oder behandlungspflichtige Realität?

The term non-convulsive status epilepticus (NCSE) refers to a heterogeneous group of diseases with different etiology, prognosis and treatment. The different forms of NCSE comprise about 25-50% of all status epilepticus cases. The most frequent form encountered in clinical practice is complex-partial SE but the rarer conditions of absence status, aura status and subtle SE are also included under this category. A diagnosis of NCSE should be considered in all patients with otherwise unexplained changes in consciousness or behavior and this diagnosis demands rapid further diagnostic work up including clinical examination, a detailed clinical history from the patient or an accompanying person, cranial computed tomography (CCT) and an electroencephalogram (EEG). If signs of an infectious or inflammatory disorder are present, a spinal tap is indicated. The EEG is of high relevance although interpretation can be challenging in NCSE.Absence status is usually treated by benzodiazepines and if necessary a broad spectrum anticonvulsive drug (ACD) such as valproic acid (VPA) can be added. The treatment of complex-partial SE follows the same scheme as that of generalized tonic-clonic SE and an initial benzodiazepine (i.v. lorazepam or intramuscular midazolam) followed by a bolus of one of the ACDs available as i.v. solution (e.g. VPA, phenytoin, phenobarbitol or levetiracetam). The third treatment step is general anesthesia if NCSE fails to be controlled. The aggressiveness of the applied therapy depends on the severity of the NCSE and the general condition of the patient. The prognosis is determined by the subtype of NCSE and the underlying etiology.

Men and women are different: diffusion tensor imaging reveals sexual dimorphism in the microstructure of the thalamus, corpus callosum and cingulum.

INTRODUCTION: Numerous magnetic resonance imaging (MRI) studies have addressed the question of morphological differences of the brain of men and women, reporting conflicting results regarding brain size and the ratio of gray and white matter. In the present study, we used diffusion tensor imaging (DTI) to delineate sex differences of brain white matter. METHODS: We investigated brain microstructure in 25 male and 25 female healthy subjects using a 3T MRI scanner. Whole-head DTI scans were analyzed without a-priori hypothesis using Tract-Based Spatial Statistics (TBSS) calculating maps of fractional anisotropy (FA), radial diffusivity (RD, a potential marker of glial alteration and changes in myelination) and axial diffusivity (AD, a potential marker of axonal changes). RESULTS: DTI revealed regional microstructural differences between the brains of male and female subjects. Those were prominent in the thalamus, corpus callosum and cingulum. Men showed significantly (p<0.0001) higher values of fractional anisotropy and lower radial diffusivity in these areas, suggesting that the observed differences are mainly due to differences in myelination. DISCUSSION: As a novel finding we showed widespread differences in thalamic microstructure that have not been described previously. Additionally, the present study confirmed earlier DTI studies focusing on sexual dimorphism in the corpus callosum and cingulum. All changes appear to be based on differences in myelination. The sex differences in thalamic microstructure call for further studies on the underlying cause and the behavioral correlates of this sexual dimorphism. Future DTI group studies may carefully control for gender to avoid confounding.

Quality of life and employment status are correlated with antiepileptic monotherapy versus polytherapy and not with use of "newer" versus "classic" drugs: results of the "Compliant 2006" survey in 907 patients.

"Classic" and "newer" antiepileptic drugs (AEDs) were compared in an epidemiological survey regarding patient's acceptance of AEDs, quality of life (QoL), and employment. Data from 907 outpatients, 45.9% female (mean age: 44.8 ± 17.9 years), were evaluated by 90 neurologists in private practices, who were also involved in a non-interventional study by Sanofi-Aventis Deutschland GmbH, regarding medication, seizure type, illness duration, employment, patients' acceptance of AEDs (4-point scale where 1=very good), and QoL (6-point scale where 1=very good). Among the patients, 69.7% were on monotherapy, 25.4% were taking two AEDs, and 4.9% were taking more than two AEDs. Patient's acceptance of AEDs (mean ± SD=1.65 ± 0.62) and QoL (2.34 ± 0.89) were "good." Among patients aged 18-65 years, 68.6% were employed. QoL and acceptance were lower with polytherapy. Older age and polytherapy were associated with lower probability of employment. No differences emerged between "classic" and "newer" AED monotherapy. Polytherapy-associated lower QoL could be due to severity of illness or adverse effects of treatment.

[Primary brain tumors and brain metastases. Symptomatic epilepsy and driving ability - systematic review and expert opinion]. / Primäre Hirntumoren und Hirnmetastasen. Symptomatische Epilepsie und Fahreignung - Expertenumfrage und systematisches Review.

PURPOSE: Primary brain tumors and metastases are common causes of symptomatic epilepsy. Seizures, neurological and neuropsychological deficits can interfere with driving ability. The present paper aims to systematically review the incidence of epileptic seizures in brain tumor patients and to discuss driving ability in the context of the current German guidelines and expert opinions. METHODS: To evaluate the incidence of epileptic seizures which occur at the beginning and in the course of the disease, we performed a systematic literature research in PubMed from 1960 to 2007. Additionally on the basis of this data we performed a survey collecting expert opinions regarding the driving ability of brain tumor patients from members of the German working groups "Arbeitsgemeinschaft für prächirurgische Epilepsiediagnostik und operative Epilepsietherapie" (Working Group for Presurgical Epilepsy Diagnostics and Operative Epileptic Therapy) and "Neuroonkologische Arbeitsgemeinschaft" (Neuro-oncological Working Group). RESULTS: The incidence of epileptic seizures depends on the entity, dignity and localization of the tumor. The driving ability of brain tumor patients is not explicitly regulated in Germany. Of the interviewed experts 72% judged the guidelines to be precise enough and 44% did not want to deprive the patients of their driving ability without a first seizure, independent of the individual risk. DISCUSSION: The available studies are methodologically insufficient and show that a further evaluation is necessary to assess the driving ability. Possible restrictions of the driving ability in patients with a high risk of seizures in the course of the disease have to take into account the balance between individual rights and the interests of the general public.

Alterations of intracerebral connectivity in epilepsy patients with secondary bilateral synchrony.

INTRODUCTION: The aim of our study was to evaluate intracerebral network changes in epilepsy patients demonstrating secondary bilateral synchrony (SBS) in EEG by applying a new Diffusion Tensor Imaging (DTI) method using an energy-based global tracking algorithm. MATERIALS AND METHODS: 10 MRI negative epilepsy patients demonstrating SBS in 10-20 surface EEG were included. EEG findings were analyzed for irritative zones characterized by focal interictal epileptiform discharges (IEDs) triggering SBS. In addition, DTI including an energy-based global tracking algorithm was applied to analyze fiber tract alterations in irritative zones. To measure the deviation of a certain cortical connection in comparison to healthy controls, normalized differences of fiber tract streamline counts (SC) and their p-values were evaluated in comparison to corresponding fibers of the control group. RESULTS: In 6 patients the irritative zone initiating SBS was located in the frontal lobe, in 3 patients in the temporal lobe and in 1 patient in the region surrounding the right central sulcus. All patients demonstrated significantly altered SC in brain lobes where the irritative zone triggering SBS was located (p ≤ 0.05). Seven out of 10 patients demonstrated SC alterations in tracts connecting brain lobes between the ipsilateral and the contralateral hemisphere (p ≤ 0.05). CONCLUSION: Our data demonstrate that alterations in fiber tracts in irritative zones triggering SBS are not necessarily associated with intracerebral lesions visible in high resolution MRI. Our study gives evidence that diffusion tensor imaging is a promising non-invasive additive tool for intracerebral network analyses even in MRI-negative epilepsy patients.

Bias in request for medical care and impact on outcome during office and non-office hours in stroke patients.

BACKGROUND AND PURPOSE: We compared characteristics and treatment success of ischaemic stroke patients admitted during daytime on working days (office hours) with patients admitted on weekend or nighttime (non-office hours) to test if differences in presentation or restraints of medical care during non-office hours determine outcome in stroke patients. METHODS: We analyzed a prospective stroke registry and grouped patients according to admission on office hours and non-office hours. Clinical state on admission, risk factors, sociodemographic items, complications, place of discharge, and clinical state on discharge were recorded. RESULTS: A total of 37,396 stroke patients were evaluated. Onset-admission time on Monday was significantly elevated and on weekend significantly reduced. Number of patients with treatment success did not differ between patient groups whilst mortality within 7 days, proportion of embolic stroke, overall mortality and rate of complications where higher in patients admitted during non-office hours, rate of thrombolytic treatment was significantly higher during non-office hours. After adjustment for clinical state and admission latency, risk for severe outcome or death was independent from time of admission. CONCLUSION: Considering the fact that stroke patients admitted during non-office hours were in more severe clinical condition we found no differences in outcome. Fear of impaired access to sophisticated treatment options during non-office hours could be dispelled by the fact, that rate of thrombolytic treatment was even higher during night and weekend. Therefore, our data do not confirm a weekend effect or night effect on stroke treatment. Delay in request of medical care of mildly affected patients that suffer from stroke on weekends confirms need for educational efforts.

[Seizures and epilepsies after stroke]. / Epileptische Anfälle und Epilepsien nach "Schlaganfall"

Epilepsies after stroke represent 20% of all adult-onset epilepsies and exhibit special characteristics with respect to diagnosis, treatment, and prognosis. Patients are frequently amnestic for their seizures the signs of which can be very subtle. Postictal pareses and confusional states can last for days, which further complicate diagnosis. Single seizures after stroke were reported in 2% to 10% of cases, and community-based studies found epilepsies in 3% to 4% of stroke patients. Analyses of subgroups identified epilepsy risks of 3% after ischemic infarction, 6% to 10% after intracerebral hemorrhage, and 9% after subarachnoid hemorrhage. Status epilepticus developed in less than 1% of stroke patients. Besides etiology, further risk factors for epilepsy comprise: remote seizures (latency >2 weeks, risk of recurrence >50%) more than early seizures (latency <2 weeks, risk of recurrence <50%), extent of stroke, cortical involvement, and degree of neurological deficit. The first appearance of seizures in patients older than 60 years represents a risk factor for future stroke with a hazard ratio of 2.89.There is currently no sufficient evidence for starting AED treatment before seizures occur. The benefit is still unclear of starting AED after a single early post-stroke seizure. Most authors recommend AED treatment after the second seizure but also after a first remote seizure because of the high risk of seizure recurrence in these situations. Possible pharmacokinetic interactions should be considered when choosing AED. Especially the first-generation AED carry the potential to interact with comedication, which is usually seen in stroke patients receiving substances such warfarin and salicylates. Only very few studies investigate specific AED exclusively in stroke patients. Lamotrigine and gabapentin have been successfully tested in these patients.

Topiramate, nutrition and weight change: a prospective study.

PURPOSE: To evaluate prospectively the relationship between appetite, food composition, nutritional habits and weight loss following administration of topiramate (TPM) and to identify predictors for TPM induced weight loss. METHODS: 22 patients with epilepsy who were started on TPM were prospectively followed for 6 months and contacted again after a mean follow-up time of 37.1 months. RESULTS: Body mass index (BMI) loss occurred in 59% of patients, with a mean weight loss of 9.5 kg after 6 months while receiving TPM without further weight loss at the long term follow-up. Weight loss was associated with reduction in appetite without affecting food composition. Predictors for BMI loss after 6 months were high initial BMI and body fat. After 3 weeks of treatment with TPM, the recorded parameters did not predict BMI loss but at 3 months, weight loss, reduction of appetite and amount of food intake were predictive for the amount of BMI loss after 6 months.

Intravenous levetiracetam in the treatment of benzodiazepine refractory status epilepticus.

In 2006, levetiracetam was approved as the first of the newer anticonvulsive drugs as an intravenous formulation (ivLEV) for patients with epileptic seizures who are unable to take oral medication. We report our experience with the use of ivLEV for the treatment of 18 episodes of benzodiazepine refractory focal status epilepticus (SE) in 16 patients, including four patients with secondary generalised SE. SE was controlled in all patients by the given combination of drugs; application of further antiepileptic medications after ivLEV was necessary in two episodes. No severe side effects occurred. Our data suggest that ivLEV may be an alternative for the treatment of SE in the future, even in patients that did not respond to benzodiazepines. A large prospective, randomised, controlled study is warranted to investigate the efficacy and safety of ivLEV for the treatment of SE.