J. Helen Cross

Rasmussen's encephalitis: clinical features, pathobiology, and treatment advances

Rasmussens encephalitis is a rare chronic neurological disorder, characterised by unilateral inflammation of the cerebral cortex, drug-resistant epilepsy, and progressive neurological and cognitive deterioration. Neuropathological and immunological studies support the notion that Rasmussens encephalitis is probably driven by a T-cell response to one or more antigenic epitopes, with potential additional contribution by autoantibodies. Careful analysis of the association between histopathology and clinical presentation suggests that initial damage to the brain is mediated by T cells and microglia, suggesting a window for treatment if Rasmussens encephalitis can be diagnosed early. Advances in neuroimaging suggest that progression of the inflammatory process seen with MRI might be a good biomarker in Rasmussens encephalitis. For many patients, families, and doctors, choosing the right time to move from medical management to surgery is a real therapeutic dilemma. Cerebral hemispherectomy remains the only cure for seizures, but there are inevitable functional compromises. Decisions of whether or when surgery should be undertaken are challenging in the absence of a dense neurological deficit, and vary by institutional experience. Further, the optimum time for surgery, to give the best language and cognitive outcome, is not yet well understood. Immunomodulatory treatments seem to slow rather than halt disease progression in Rasmussens encephalitis, without changing the eventual outcome.

Timing of antiepileptic drug withdrawal and long-term seizure outcome after paediatric epilepsy surgery (TimeToStop): a retrospective observational study

BACKGROUNDnPostoperative antiepileptic drug (AED) withdrawal practices remain debatable and little is known about the optimum timing. We hypothesised that early AED withdrawal does not affect long-term seizure outcome but allows identification of incomplete surgical success earlier than late withdrawal. We aimed to assess the relation between timing of AED withdrawal and subsequent seizure recurrence and long-term seizure outcome.nnnMETHODSnTimeToStop included patients aged under 18 years from 15 centres in Europe who underwent surgery between Jan 1, 2000, and Oct 1, 2008, had at least 1 year of postoperative follow-up, and who started AED reduction after having reached postoperative seizure freedom. Time intervals from surgery to start of AED reduction (TTR) and complete discontinuation (TTD) were studied in relation to seizure recurrence during or after AED withdrawal, seizure freedom for at least 1 year, and cure (defined as being seizure free and off AEDs for at least 1 year) at latest follow-up. Cox proportional hazards regression models were adjusted for identified predictors of timing intervals.nnnFINDINGSnTimeToStop included 766 children. Median TTR and TTD were 12·5 months (95% CI 11·9-13·2) and 28·8 months (27·4-30·2), respectively. 95 children had seizure recurrence during or after AED withdrawal. Shorter time intervals predicted seizure recurrence (hazard ratio [HR] 0·94, 95% CI 0·89-1·00, p=0·05 for TTR; and 0·90, 0·83-0·98, p=0·02 for TTD). After a mean postoperative follow-up of 61·6 months (SD 29·7), 728 patients were seizure free for at least 1 year. TTR and TTD were not related to regain of seizure freedom after restart of drug treatment (HR 0·98, 95% CI 0·92-1·05, p=0·62; and 0·93, 0·83-1·05, p=0·26, respectively), or to seizure freedom (0·97, 0·89-1·07, p=0·55; and 1·03, 0·93-1·14, p=0·55, respectively) or cure (0·97, 0·97-1·03, p=0·84; and 0·98, 0·94-1·02, p=0·31, respectively) at final follow-up.nnnINTERPRETATIONnEarly AED withdrawal does not affect long-term seizure outcome or cure. It might unmask incomplete surgical success sooner, identifying children who need continuous drug treatment and preventing unnecessary continuation of AEDs in others. A prospective randomised trial is needed to study the possible cognitive effects and confirm the safety of early AED withdrawal after epilepsy surgery in children.nnnFUNDINGnDutch National Epilepsy Fund.

Psychopathology in children before and after surgery for extratemporal lobe epilepsy

Aimu2002 To establish the rates and types of psychiatric disorder in children before and after surgery for extratemporal epilepsy. Relationships between psychiatric morbidity and demographic/clinical variables were examined.

Fever and fever-related epilepsies

Febrile seizures are a common emergency faced by general pediatricians. They are mostly self‐limiting, isolated events with no sequelae in later life. A minority are more complex. In the acute stage, there are a small number of underlying etiologies that are important to recognize in order to determine the prognosis accurately and to optimize management. There has been a long‐standing debate about the relationship of early febrile seizures to the later development of epilepsy. It is now clear that this risk differs for simple and complex febrile seizures: complex febrile seizures may herald the presentation of a number of epilepsy syndromes of which febrile and illness‐related seizures are part of the phenotype. This review examines the existing knowledge on febrile seizures and the various clinical phenotypes to which they are linked.

Advancing the management of childhood epilepsies.

Childhood epilepsies comprise a heterogeneous group of disorders and syndromes that vary in terms of severity, prognosis and treatment requirements. Effective management requires early, accurate recognition and diagnosis, and a holistic approach that addresses each individuals medical and psychosocial needs within the context of their overall health status and quality of life. With increasing understanding of underlying aetiologies, new approaches to management and treatment are emerging. For example, genetic testing is beginning to provide a tool to aid differential diagnosis and a means of predicting predisposition to particular types of epilepsy. Despite the availability of an increasing number of antiepileptic drugs (AEDs)--due not only to the development of new AEDs, but also to changes in regulatory requirements that have facilitated clinical development--seizure control and tolerability continue to be suboptimal in many patients, and there is therefore a continuing need for new treatment strategies. Surgery and other non-pharmacological treatments (e.g. vagus nerve stimulation, ketogenic diet) are already relatively well established in paediatric epilepsy. New pharmacological treatments include generational advances on existing AEDs and AEDs with novel modes of action, and non-AED pharmacological interventions, such as immunomodulation. Emerging technologies include novel approaches allowing the delivery of medicinal agents to specific areas of the brain, and closed-loop experimental devices employing algorithms that allow treatment (e.g., electrical stimulation) to be targeted both spatially and temporally. Although in early stages of development, cell-based approaches (e.g., focal targeting of adenosine augmentation) and gene therapy may also provide new treatment choices in the future.

Current use of imaging and electromagnetic source localization procedures in epilepsy surgery centers across Europe

In 2014 the European Union–funded E‐PILEPSY project was launched to improve awareness of, and accessibility to, epilepsy surgery across Europe. We aimed to investigate the current use of neuroimaging, electromagnetic source localization, and imaging postprocessing procedures in participating centers.

Faulty cardiac repolarization reserve in alternating hemiplegia of childhood broadens the phenotype

Alternating hemiplegia of childhood is rare and usually results from mutations in cardiac- and brain-expressed ATP1A3. In an ECG study of 52 cases, Jaffer et al. reveal dynamic cardiac repolarisation or conduction abnormalities in over 50%. Abnormalities are more common in those ≥16 years, and suggest impaired cardiac repolarisation reserve.

Current practices in long-term video-EEG monitoring services: A survey among partners of the E-PILEPSY pilot network of reference for refractory epilepsy and epilepsy surgery.

PURPOSEnThe European Union-funded E-PILEPSY network aims to improve awareness of, and accessibility to, epilepsy surgery across Europe. In this study we assessed current clinical practices in epilepsy monitoring units (EMUs) in the participating centers.nnnMETHODnA 60-item web-based survey was distributed to 25 centers (27 EMUs) of the E-PILEPSY network across 22 European countries. The questionnaire was designed to evaluate the characteristics of EMUs, including organizational aspects, admission, and observation of patients, procedures performed, safety issues, cost, and reimbursement.nnnRESULTSnComplete responses were received from all (100%) EMUs surveyed. Continuous observation of patients was performed in 22 (81%) EMUs during regular working hours, and in 17 EMUs (63%) outside of regular working hours. Fifteen (56%) EMUs requested a signed informed consent before admission. All EMUs performed tapering/withdrawal of antiepileptic drugs, 14 (52%) prior to admission to an EMU. Specific protocols on antiepileptic drugs (AED) tapering were available in four (15%) EMUs. Standardized Operating Procedures (SOP) for the treatment of seizure clusters and status epilepticus were available in 16 (59%). Safety measures implemented by EMUs were: alarm seizure buttons in 21 (78%), restricted patients ambulation in 19 (70%), guard rails in 16 (59%), and specially designated bathrooms in 7 (26%). Average costs for one inpatient day in EMU ranged between 100 and 2200 Euros.nnnCONCLUSIONnThis study shows a considerable diversity in the organization and practice patterns across European epilepsy monitoring units. The collected data may contribute to the development and implementation of evidence-based recommended practices in LTM services across Europe.

Children with epilepsy in Africa: recommendations from the International Child Neurology Association/African Child Neurology Association Workshop.

This article presents key findings from the International Child Neurology Association/African Child Neurology Association Workshop. The viability of international guidelines for the management of children with epilepsy should be reviewed within each African country, and adapted to comply with the regional capacity. Such recommendations can be used to lobby for resources. More training centers should be developed in Africa, so that specialists can be trained within Africa, in skills relevant to the continent, in collaboration with “out of Africa” visiting-specialists to develop the concept of “train the trainers.” At least 1 child neurology specialist per 100 000 of the population is required. Specific to Africa are the challenges from stigma, prejudice, and misconceptions. “Epilepsy teams,” inclusive of the traditional healers, would enable management of increased numbers of children, and challenge policy such that it is the right of the child with epilepsy to have reliable access to appropriate antiepileptic drugs, support, and health care equity between the rural and urban settings.

Ketogenic dietary therapies for adults with epilepsy: Feasibility and classification of response

Ketogenic dietary therapies are an effective treatment for children with drug-resistant epilepsy. There is currently no high-quality evidence regarding ketogenic dietary therapies in adults, and further research has been recommended. This audit aimed to provide further evidence for the feasibility of dietary treatment for adults and to consider factors that may aid response classification in this population. We evaluated the effectiveness and tolerability of ketogenic dietary therapies in 23 adults with epilepsy attending specialist clinics. Medical notes were used to obtain seizure frequency information and other effects associated with dietary treatment. Individuals who achieved ≥50% seizure reduction at all follow-up points were classified as responders. Response rates, in terms of seizure frequency, were similar to those commonly reported in pediatric cohorts: 9/23 (39%) adults were classified as responders. These responders remained on the diet for at least one year (follow-up: 1-10 years). Other benefits reported by patients, but not quantified, included a reduction in seizure severity and increased alertness and concentration. Such factors often favor continuation of ketogenic dietary therapies despite a <50% seizure reduction. One individual experienced psychosis while following dietary treatment; most commonly reported adverse events were gastrointestinal. Adverse events did not lead to discontinuation of treatment in any cases. Our findings suggest that adults with epilepsy are able to follow ketogenic dietary therapies long-term, and such treatment can lead to seizure reduction. Other aspects besides seizure frequency may be relevant when classifying response in adults, and appropriate ways to quantify these factors should be considered for use in future studies.