Kas epilepsia ravis on arenguruumi?

Epilepsia on üks sagedasemaid kroonilisi närvihaigusi, mis tihti põhjustab väljendunud stigmatisatsiooni. Epilepsia ravi tõhustamiseks tuleb kasutada vana ja uue põlvkonna ravimeid vastavalt epilepsia käsitlusjuhendile. Eesti Arst 2004; 83 (1): 54-5

Epilepsia kirurgiline ravi – alakasutatud võimalus ravimrefraktaarse epilepsia raviks

Ravimrefraktaarne epilepsia on tõsine probleem, kuna epilepsiaravimitele mittealluv haigus esineb ligi kolmandikul patsientidest ja on seotud eluaegse puude ning 5–10 korda suurema suremusega. Sellistel patsientidel hinnatakse epilepsia kirurgilise ravi võimalikkust, kuna eduka ravi korral saab vabaneda epileptilistest hoogudest ja seeläbi vähendada ka epilepsiaga seotud suremust ning puuet. Kahjuks jõuab vähem kui 1% ravimrefraktaarse epilepsiaga patsientidest epilepsia kirurgilise ravi võimalikkuse hindamisele ja viivitus on pikk, epilepsia on selleks ajaks kestnud enamasti aastakümneid. Patsientidele, kes ei ole kirurgilise ravi kandidaadid, on võimalik pakkuda teisi ravimeetodeid, näiteks uitnärvi stimulatsiooni. Artikli eesmärk on anda ülevaade epilepsia kirurgilise ravi olemusest ja operatsioonieelsest hindamisest

Qualitative study of hippocampal formation in hypertensive rats with epilepsy

The aim of our study was to investigate the hippocampus and dentate gyrus neuropathological features of spontaneous hypertensive rats (SHR) with epilepsy. METHOD: Animals were randomly divided into 4 groups: control Wistar, Wistar with epilepsy, control SHR and SHR with epilepsy. The pilocarpine model of epilepsy was used in this experiement. After spontaneous recurrent seizures, all animals were perfused and their brains processed for histological analysis through Nissl and neo-Timm methods. RESULTS: In the Wistar rats with epilepsy we observed cell loss in hippocampal subfields CA1, CA3 and hilus of the dentate gyrus when compared with control animals. In the SHR with epilepsy we observed hippocampal formation atrophy with ventricular dilatation. No morphological alterations were observed in SHR and Wistar control rats. The neo-Timm staining of hippocampal formation has shown supragranular sprouting in Wistar and SHR with epilepsy. CONCLUSION: We found neuropathological alterations in hippocampal formation in Wistar with epilepsy and SHR with epilepsy, suggesting that epilepsy per se or associated to hypertention are able to cause neuronal damage.O objetivo deste estudo foi avaliar qualitativamente o hipocampo e o giro dentado de ratos espontaneamente hipertensos (SHR) com epilepsia. MÉTODO: Os animais foram divididos em 4 grupos: Wistar controle, Wistar com epilepsia, SHR controle e SHR com epilepsia. Para indução da epilepsia, utilizamos o modelo da pilocarpina. Após os animais apresentarem crises espontâneas e recorrentes, o tecido cerebral dos animais foi encaminhado para análise histológica através dos métodos de Nissl e neo-Timm. RESULTADOS: Nos animais Wistar e SHR controle submetidos à coloração de Nissl observamos a manutenção das camadas celulares da formação hipocampal. Nos animais Wistar com epilepsia verificamos intensa morte neuronal na região CA1 e CA3 do hipocampo e no hilo do giro dentado. Nos animais SHR com epilepsia verificou-se a presença de atrofia hipocampal com dilatação do sistema ventricular. A coloração de neo-Timm revelou a presença de brotamento supragranular em todos os animais com epilepsia. CONCLUSÃO: Foram encontradas alterações neuropatológicas na citoarquitetura hipocampal nos animais Wistar com epilepsia e SHR com epilepsia, demonstrando que a epilepsia isoladamente ou associadamente à hipertensão são capazes de causar destruição neuronal.UNIFESP-EPMUniversidade de Mogi das Cruzes Universidade de Mogi das Cruzes Laboratório de NeurociênciasCentro Universitário São CamiloUNIFESP, EPMSciEL

Nonictal EEG biomarkers for diagnosis and treatment.

There are no reliable nonictal biomarkers for epilepsy, electroencephalography (EEG) or otherwise, but efforts to identify biomarkers that would predict the development of epilepsy after a potential epileptogenic insult, diagnose the existence of epilepsy, or assess the effects of antiseizure or antiepileptogenic interventions are relying heavily on electrophysiology. The most promising EEG biomarkers to date are pathologic high-frequency oscillations (pHFOs), brief EEG events in the range of 100 to 600 Hz, which are believed to reflect summated action potentials from synchronously bursting neurons. Studies of patients with epilepsy, and experimental animal models, have been based primarily on direct brain recording, which makes pHFOs potentially useful for localizing the epileptogenic zone for surgical resection, but application for other diagnostic and therapeutic purposes is limited. Consequently, recent efforts have involved identification of HFOs recorded with scalp electrodes, and with magnetoencephalography, which may reflect the same pathophysiologic mechanisms as pHFOs recorded directly from the brain. The search is also on for other EEG changes that might serve as epilepsy biomarkers, and candidates include arcuate rhythms, which may reflect repetitive pHFOs, reduction in theta rhythm, which correlates with epileptogenesis in several rodent models of epilepsy, and shortened sleep spindles that correlate with ictogenesis

Timing matters: impact of anticonvulsant drug treatment and spikes on seizure risk in benign epilepsy with centrotemporal spikes

OBJECTIVE: Benign epilepsy with centrotemporal spikes (BECTS) is a common, self-limited epilepsy syndrome affecting school-age children. Classic interictal epileptiform discharges (IEDs) confirm diagnosis, and BECTS is presumed to be pharmacoresponsive. As seizure risk decreases in time with this disease, we hypothesize that the impact of IEDs and anticonvulsive drug (ACD) treatment on the risk of subsequent seizure will differ based on disease duration. METHODS: We calculate subsequent seizure risk following diagnosis in a large retrospective cohort of children with BECTS (n = 130), evaluating the impact of IEDs and ACD treatment in the first, second, third, and fourth years of disease. We use a Kaplan-Meier survival analysis and logistic regression models. Patients were censored if they were lost to follow-up or if they changed group status. RESULTS: Two-thirds of children had a subsequent seizure within 2 years of diagnosis. The majority of children had a subsequent seizure within 3 years despite treatment. The presence of IEDs on electroencephalography (EEG) did not impact subsequent seizure risk early in the disease. By the fourth year of disease, all children without IEDs remained seizure free, whereas one-third of children with IEDs at this stage had a subsequent seizure. Conversely, ACD treatment corresponded with lower risk of seizure early in the disease but did not impact seizure risk in later years. SIGNIFICANCE: In this cohort, the majority of children with BECTS had a subsequent seizure despite treatment. In addition, ACD treatment and IEDs predicted seizure risk at specific points of disease duration. Future prospective studies are needed to validate these exploratory findings.Published versio

Clinically indicated electrical stimulation strategies to treat patients with medically refractory epilepsy.

Focal epilepsies represent approximately half of all diagnoses, and more than one-third of these patients are refractory to pharmacologic treatment. Although resection can result in seizure freedom, many patients do not meet surgical criteria, as seizures may be multifocal in origin or have a focus in an eloquent region of the brain. For these individuals, several U.S. Food and Drug Administration (FDA)-approved electrical stimulation paradigms serve as alternative options, including vagus nerve stimulation, responsive neurostimulation, and stimulation of the anterior nucleus of the thalamus. All of these are safe, flexible, and lead to progressive seizure control over time when used as an adjunctive therapy to antiepileptic drugs. Focal epilepsies frequently involve significant comorbidities such as cognitive decline. Similar to antiepilepsy medications and surgical resection, current stimulation targets and parameters have yet to address cognitive impairments directly, with patients reporting persistent comorbidities associated with focal epilepsy despite a significant reduction in the number of their seizures. Although low-frequency theta oscillations of the septohippocampal network are critical for modulating cellular activity and, in turn, cognitive processing, the coordination of neural excitability is also imperative for preventing seizures. In this review, we summarize current FDA-approved electrical stimulation paradigms and propose that theta oscillations of the medial septal nucleus represent a novel neuromodulation target for concurrent seizure reduction and cognitive improvement in epilepsy. Ultimately, further advancements in clinical neurostimulation strategies will allow for the efficient treatment of both seizures and comorbidities, thereby improving overall quality of life for patients with epilepsy

Perfil neuropsicológico em doentes com epilepsia do lobo temporal

A epilepsia do lobo temporal (ELT) é o tipo de epilepsia refractária mais comum nos adultos. O compromisso da memória verbal nos doentes com ELT à esquerda é relativamente consensual. No entanto, no que concerne a outras funções como é o caso da atenção, funções executivas, rendimento intelectual e linguagem, o consenso não é tão generalizado. Nesta investigação fomos estudar o perfil neuropsicológico dos défices cognitivos apresentados por doentes com epilepsia do lobo temporal e clarificar o impacto da cronicidade da doença na cognição. Para esta investigação analisámos retrospectivamente um grupo de 76 doentes com epilepsia refractária, 48 doentes com epilepsia do lobo temporal (23 com foco à direita e 25 com foco à esquerda) e 28 doentes com epilepsia extratemporal. Aplicámos uma bateria de provas utilizada no âmbito do programa da Cirurgia da Epilepsia do Hospital de Egas Moniz, em Lisboa. Os resultados mostram que a bateria aplicada apresenta consistência interna no âmbito da avaliação dos doentes com ELT. Encontrámos que os doentes com ELT à direita e à esquerda apresentam um padrão generalizado de défices, sobreponíveis aos apresentados pelos doentes com epilepsia extratemporal, o que pode ser indicador de compromisso noutras áreas cerebrais para além do hipocampo. Um achado que consideramos pertinente foi o facto da memória verbal com interferência (memória a longo termo) não mostrar alterações nos doentes com ELT tanto à direita como à esquerda, sugerindo que esta função não está comprometida na ELT. Os nossos resultados mostram ainda que os doentes com ELT lateralizada à esquerda apresentam maior compromisso cognitivo do que os doentes com lateralização à direita. Por último, para além do padrão generalizado de défices cognitivos, também conseguimos observar o impacto da doença ao nível das variáveis sócio-demográficas

Demonstration project on epilepsy in Brazil - WHO/ILAE/IBE Global Campaign Against Epilepsy - A foreword

In 2002, ASPE (Assistência à Saúde de Pacientes com Epilepsia)* initiated an Epilepsy Demonstration Project (DP) in Brazil as part of the Global Campaign Against Epilepsy "Epilepsy out of the Shadows", led by the World Health Organization (WHO), the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE)1-4. Demonstration Projects have been carried out in several countries and their main aim is to develop treatment models for people with epilepsy in primary health care settings, improving the quality of life of people with epilepsy and their families5-9. The project in Brazil has targeted areas in Campinas and São José do Rio Preto municipalities, both in São Paulo State, in Southeastern region8. A task force has been established to assess strategies to expand this nationwide. The DP was carried out in six phases as shown in Figure 1. The Brazilian DP was officially closed during the IV Workshop of the WHO/ILAE/IBE Global Campaign Against Epilepsy "Epilepsy out of the Shadows", held on May 4-5th 2006, in Campinas. The workshop reviewed the results of the project and discussed the establishment of a National Epilepsy Policy. This supplement presents some results from all phases of the Brazilian DP which were discussed during the Workshop. In brief, we believe that the DP had an impact in our society and brought a new perspective on epilepsy. Awareness campaigns are now carried out on September 9th (Epilepsy Awareness Day) annually in many sites around the country. Regulations and Bills related to epilepsy have been proposed in several regions. Epilepsy has been officially adopted as a theme to be considered in elementary education by the Ministry of Education. Currently, a National Epilepsy Programme, endorsed by the main Brazilian non-governmental organizations in the field of epilepsy, is under review at the Ministry of Health. We hope that this will benefit some of the many people with epilepsy in the country and will eventually bring epilepsy out of the shadows in Brazil

Acute and long-term effects of brivaracetam and brivaracetam-diazepam combinations in an experimental model of status epilepticus.

ObjectiveTo evaluate acute and long-term effects of intravenous brivaracetam (BRV) and BRV + diazepam (DZP) combination treatment in a rat model of self-sustaining status epilepticus (SSSE).MethodsRats were treated with BRV (10 mg/kg) 10 min after initiation of perforant path stimulation (PPS) as early treatment; or BRV (10-300 mg/kg), DZP (1 mg/kg), or BRV (0.3-10 mg/kg) + DZP (1 mg/kg) 10 min after the end of PPS (established SSSE). Seizure activity was recorded electrographically for 24 h posttreatment (acute effects), and for 1 week at 6-8 weeks or 12 months' posttreatment (long-term effects). All treatments were compared with control rats using one-way analysis of variance (ANOVA) and Bonferroni's test, or Kruskal--Wallis and Dunn's multiple comparison tests, when appropriate.ResultsTreatment of established SSSE with BRV (10-300 mg/kg) resulted in dose-dependent reduction in SSSE duration and cumulative seizure time, achieving statistical significance at doses ≥100 mg/kg. Lower doses of BRV (0.3-10 mg/kg) + low-dose DZP (1 mg/kg) significantly reduced SSSE duration and number of seizures. All control rats developed spontaneous recurrent seizures (SRS) 6-8 weeks after SSSE, whereas seizure freedom was noted in 2/10, 5/10, and 6/10 rats treated with BRV 200 mg/kg, 300 mg/kg, and BRV 10 mg/kg + DZP, respectively. BRV (10-300 mg/kg) showed a dose-dependent trend toward reduction of SRS frequency, cumulative seizure time, and spike frequency, achieving statistical significance at 300 mg/kg. Combination of BRV (10 mg/kg) + DZP significantly reduced SRS frequency, cumulative seizure time, and spike frequency. In the 12-month follow-up study, BRV (0.3-10 mg/kg) + low-dose DZP markedly reduced SRS frequency, cumulative seizure time, and spike frequency, achieving statistical significance at some doses. Early treatment of SSSE with BRV 10 mg/kg significantly reduced long-term SRS frequency.SignificanceThese findings support clinical evaluation of BRV for treatment of status epilepticus or acute repetitive seizures

Getting the best outcomes from epilepsy surgery.

Neurosurgery is an underutilized treatment that can potentially cure drug-refractory epilepsy. Careful, multidisciplinary presurgical evaluation is vital for selecting patients and to ensure optimal outcomes. Advances in neuroimaging have improved diagnosis and guided surgical intervention. Invasive electroencephalography allows the evaluation of complex patients who would otherwise not be candidates for neurosurgery. We review the current state of the assessment and selection of patients and consider established and novel surgical procedures and associated outcome data. We aim to dispel myths that may inhibit physicians from referring and patients from considering neurosurgical intervention for drug-refractory focal epilepsies. Ann Neurol 2018;83:676-690