Racial disparities in the utilization of invasive neuromodulation devices for the treatment of drug-resistant focal epilepsy.

Racial disparities affect multiple dimensions of epilepsy care including epilepsy surgery. This study aims to further explore these disparities by determining the utilization of invasive neuromodulation devices according to race and ethnicity in a multicenter study of patients living with focal drug-resistant epilepsy (DRE). We performed a post hoc analysis of the Human Epilepsy Project 2 (HEP2) data. HEP2 is a prospective study of patients living with focal DRE involving 10 sites distributed across the United States. There were no statistical differences in the racial distribution of the study population compared to the US population using census data except for patients reporting more than one race. Of 154 patients enrolled in HEP2, 55 (36%) underwent invasive neuromodulation for DRE management at some point in the course of their epilepsy. Of those, 36 (71%) were patients who identified as White. Patients were significantly less likely to have a device if they identified solely as Black/African American than if they did not (odds ratio = .21, 95% confidence interval = .05-.96, p = .03). Invasive neuromodulation for management of DRE is underutilized in the Black/African American population, indicating a new facet of racial disparities in epilepsy care.

Levetiracetam em monoterapia para epilepsia focal em pacientes com falha no tratamento com carbamazepina / Levetiracetam monotherapy for focal epilepsy in patients failing treatment with carbamazepine

Contexto: A epilepsia é uma doença cerebral crônica causada por diversas etiologias e caracterizada pela recorrência de crises epilépticas não provocadas. O tratamento disponível no Sistema Único de Saúde (SUS) atualmente inclui as drogas antiepiléticas fenobarbital, fenitoína, primidona, topiramato, lamotrigina, carbamazepina e valproato de sódio, indicadas no Protocolo Clínico do Ministério da Saúde (MS). Pergunta: O uso do levetiracetam em monoterapia é tão eficaz e seguro quanto as demais drogas antiepilépticas (lamotrigina) e topiramato) disponíveis no SUS, por meio do Componente Especializado da Assistência Farmacêutica - CEAF, para o tratamento de pacientes com epilepsia focal após a falha no tratamento com carbamazepina? Evidências científicas: Não há evidências clínicas para o uso do levetiracetam em monoterapia em crises epiléticas focais para a pergunta de pesquisa estabelecida na presente solicitação de avaliação. Avaliação econômica: Foi apresentada uma análise de custo-minimização seguindo a premissa de que o levetiracetam não possui superioridade clínica sobre os medicamentos oferecidos pelo SUS. Porém o custo de tratamento do levetiracetam é maior do que os tratamentos disponíveis no sistema público. Deliberação final: A análise do conteúdo de todas a contribuições da consulta pública não trouxe elementos que pudessem alterar a recomendação de não incorporação. Assim, os membros da CONITEC recomendaram por unanimidade a não incorporação no SUS do levetiracetam em monoterapia para epilepsia focal em pacientes com falha no tratamento com carbamazepina. Decisão: Não incorporar o levetiracetam em monoterapia para epilepsia focal em pacientes com falha no tratamento com carbamazepina, no âmbito do Sistema Único de Saúde - SUS. A decisão foi dada pela Portaria SCTIE-MS nº 9 publicada no Diário Oficial da União (DOU) nº 38, de 22 de fevereiro de 2017.

The RNS System: responsive cortical stimulation for the treatment of refractory partial epilepsy.

The RNS(®) System is the first commercially available device to provide closed-loop responsive brain stimulation. The system includes a cranially implanted neurostimulator that continually monitors the electrocorticogram through one or two depth and/or subdural cortical strip leads that are placed at the seizure focus. When abnormal electrographic activity is detected, the neurostimulator delivers brief pulses of electrical stimulation to the seizure focus through the implanted leads. In November 2013, the US FDA approved the RNS System as an adjunctive therapy for patients with drug resistant, partial onset seizures who have undergone diagnostic testing that localized no more than 2 epileptogenic foci. Safety and effectiveness of the RNS System for the indicated patient population was demonstrated in a multicenter, randomized, sham-stimulation controlled 2-year pivotal study. An ongoing, prospective, long-term treatment study is currently gathering an additional 7 years of prospective safety and effectiveness data of the RNS System.

[Clinical and economical effectiveness of the treatment of focal epilepsies].

One hundred and seventy-three patients with symptomatic and probable symptomatic epilepsies, mean age 31.2 years, were studied. The study included evaluation of anamnesis, clinical and neurological examination, routine EEG and/or video-EEG-monitoring, X-ray CT and/or MRI of the brain. The antiepileptic therapy was corrected. The duration of follow-up study was 2 years. General neurologist therapy (initial therapy) and epileptologist therapy (final therapy) were compared using cost-effectiveness analysis, frequency of using different drugs, ABC- and VEN-analysis. The final therapy was effective in 93.1% of cases, a remission was achieved in 53.2%. The ineffective therapy decreased from 56.6 to 6.9%. The ineffective expenses for the initial therapy were 82.8%. The final therapy was significantly effective (p = 0.001) and expensive (p = 0.004) but the cost difference was low (3420 roubles/year).

[Vagus nerve stimulation and refractory partial epilepsies]. / La stimulation du nerf vague dans le traitement des épilepsies partielles pharmaco-résistantes.

Since 1988, intermittent electric stimulation of the cervical portion of the left vagus nerve is proposed as additive treatment of epilepsy. The effects of vagus nerve stimulation (VNS) on the modulation of cerebral activity, shown in animals and confirmed by the data of functional imagery in human beings, can be apprehended by the anatomic and functional characteristics of this nerve, whereas the anti-epileptic mode of action remains unknown. Following five controlled multicentric studies, including 440 patients presenting refractory epilepsy, 20,000 patients worldwide have been treated by VNS for this indication. Proposed as additive symptomatic treatment of refractory epilepsies, VNS has proven effective and well tolerated by both children and adults with refractory partial epilepsy. After 2 years of treatment, patients achieve an overall average of 40 p. 100 reduction of seizure frequency. In 40 to 50 p. 100 of the patients, the frequency of seizure can even be decreased by 50 p. 100. Moreover, even in the absence of a significant reduction of seizure, patients subjected to this treatment have reported an improvement in their quality of life. The economic surveys also show a favorable impact of VNS on the management of refractory partial epilepsies.

[Specific medico-social supports for drug-resistant partial epilepsies]. / Prise en charge médico-sociale spécifique des épilepsies partielles pharmaco-résistantes.

While employment appears to be among major concerns for epileptic patients, these are confronted with a very high rate of unemployment, especially when epilepsy is pharmacoresistant. However, the persistence of seizures is not the only factor bearing on vocational training or employment; other factors may intervene as well: cognitive dysfunctions, psychological/behavioral disturbances, impact of AEDs, education, vocational training, family members and relatives' attitude, school teams' attitude, employers' attitude, occupational physicians' attitude. Educational level is lower when epilepsy started at school-age; persisting seizures together with other problems may lead the epileptic child or teenager to attend specialized schools. In France, there are few institutions dedicated to children or teenagers with severe epilepsy, and these are very unevenly distributed over the French territory. The main social measures regarding children with epilepsy in France are mentioned. Besides being seizure-free and able to drive, work is one major expectation of patients from epilepsy surgery. The results of epilepsy surgery regarding employment are somewhat controversial; in some studies, temporal lobe surgery may not raise the employment rate; other studies point out that operated-on patients need a long time (up to 6 years) to find a job after surgery. The vocational level or the previous work experiences appear to be as important factors for further employment as being seizure-free, a condition which may not be met in all favourable work outcomes. The medico-social support to patients with pharmacoresistant partial epilepsies has to deal with all the factors mentioned previously; the opportunity for epilepsy surgery may have to be considered early in order to try and prevent the detrimental impact of pharmacoresistant epilepsy on school achievement and vocational training; adult patients with pharmacoresistant epilepsy often cumulate a low qualification level, an absence of a solid work experience, a lack of motivation and a social deprivation. Neurologists may have an insufficient knowledge of social and work regulations: in this paper we describe the main possibilities for epileptic patients to obtain social supports in France. Likewise, occupational physicians seldom know much about epilepsies. We have a positive experience of a multidisciplinary approach combining neurologists, occupational physicians and insertion teams. We are convinced that a personalized follow-up of the epileptic person is useful and often

[Drug-resistant partial epilepsy: medico-social aspects of adults in France]. / Epilepsies partielles pharmaco-résistantes: prise en charge médico-sociale spécifique de l'adulte.

In this article, we describe the social and economic aspects of adult epileptic patients in France. The different measures to facilitate their reintegration and employment are presented. The missions of the COTOREP (Technical Commission for Professional Orientation and Reclassification) include the identification of a disability rate, the recognition of status as a disabled worker, and orientation to an individually adapted job, e.g. in a specialized center. The COTOREP provides information and training. For patients with major disabilities, the commission can decide on admission in a specialized institution. The COTOREP but also the French national Social Security propose allocations and financial assistance for patients with low income or who have a work inaptitude. In this text, we also describe the general French laws for the protection of adult patients which include measures not specific for epileptic patients.

[Medical and medico-social case management of drug-resistant partial epilepsy. Specific implementation of long-term antiepileptic treatment in the adult]. / Prise en charge médicale et médico-sociale des EPPR. Conduite spécifique du traitement antiépileptique au long cours chez l'adulte.

Medical treatment of refractory localisation-related epilepsies in adults should always be considered with regard to surgical possibilities. When long-term therapy with antiepileptic drugs is necessary, the treatment tries to achieve maximal efficacy with the lowest unavoidable toxicity. Until an evidence-based choice can be made, the management is currently based on empirical knowledge. In this article, the available literature on effectiveness and monitoring of long term antiepileptic therapy is reviewed.

Analysis of direct hospital costs before and 18 months after treatment with vagus nerve stimulation therapy in 43 patients.

Vagus nerve stimulation (VNS) therapy is an established method for treating patients with refractory seizures. Although the initial cost of the device is about 10,000 US dollars, the battery life of the model 100 implanted in the patients in this analysis can exceed 5 years at standard settings. It is important to understand what type of cost-benefit can be expected after implantation. Our aim was to assess unplanned hospital costs 18 months before and 18 months after VNS implantation in 43 patients. The VNS therapy system was implanted according to standard procedures and stimulation of 0.75 to 2.0 mA was delivered either as 30 seconds on and 5 minutes off or 7 seconds on and 14 seconds off. Seizure frequency was calculated before and after 18 months of treatment. During this time no changes were made with other therapies for epilepsy. Hospitalization for emergency room (ER) visits, ward stays, and intensive care days were calculated according to the costs at Sahlgrenska University Hospital in Sweden. Therapy response was defined as 25% or greater reduction in seizure frequency. For all patients, intensive care unit (ICU) costs were reduced from 46,875 to 0 US dollars, ER visits from 13,000 to 9,000 US dollars, and ward stays from 151,125 to 21,375 US dollars. Total hospital costs for the 43 patients studied before VNS therapy were 211,000 US dollars and after 18 months of treatment were reduced to 30,375 US dollars, an average annual cost savings of approximately 3,000 US dollars per patient. The cost savings applied to all patients, irrespective of whether they responded to VNS therapy. VNS therapy resulted in annual reductions of approximately 3000 US dollars in unplanned hospital costs per study patient. Such direct savings sustained over the battery life of the VNS therapy system can equal or exceed the purchase price of the device.

Rasmussen's encephalitis: the relevance of neuropsychological assessment in patient's treatment and follow up.

Rasmussen's encephalitis is characterized by refractory epilepsy, neurological deterioration and progressive atrophy of one cerebral hemisphere. The objective of this study is to describe the importance of neuropsychological evaluation in the treatment decision and follow-up of patients with Rasmussens encephalitis. Neuropsychological assessment was performed in two steps. Firstly, the clinical history was obtained and the Vineland adaptative behavior scale (VABS) was applied. After this first step, the patients with social maturity level equal or higher than the inferior limit underwent a battery of neuropsychological assessment. We evaluated three patients before any specific treatment was started, and six months after the intervention (surgery or plasmapheresis). Patient 1 underwent left hemispherectomy and had global improvement on second neuropsychological assessment. This suggests that the decision of performing surgery was adequate. Patients 2 and 3 underwent plasmapheresis. They did not present cognitive decline between both evaluations which suggest that our decision of postponing surgery was adequate as well. We conclude that neuropsychological assessment is important when evaluating patients with Rasmussens encephalitis. That is especially true for patients in whom disease progression is slow, and surgery timing has to be carefully planned.

Transcutaneous vagus nerve stimulation for partial onset seizure therapy. A new concept.

A new concept for transcutaneous vagus nerve stimulation for control of partial onset seizures is described. The rationale for the application of this innovative noninvasive method is discussed.

Cost analysis of epilepsy surgery and of vigabatrin treatment in patients with refractory partial epilepsy.

In this study the direct actual costs associated with epilepsy-related health care, treatment with the novel antiepileptic drug vigabatrin (gamma-vinyl GABA, GVG), epilepsy surgery evaluation (ESE) and epilepsy surgery were analysed in 52 patients with intractable partial epilepsy who were on a waiting-list for ESE while trying GVG. Sixty percent of the 52 patients obtained a reduction in seizure frequency of 50% or more with GVG. Of the twenty-one operated patients 57% became seizure free, 10% had more than 75%, 5% had 50-75% and 29% had less than 50% reduction of seizure frequency. Of the 17 patients who did not go through ESE (the "GVG responders"), the corresponding outcome was 6%, 59%, 29% and 6%. For the 14 patients who were neither operated nor GVG responders, the outcome was 0%, 0%, 36% and 64%. The mean yearly costs (expressed in 1991 prices) of epilepsy-related health care including antiepileptic drug treatment was US $1,594 the year before starting GVG therapy, and US $2959 the first year of GVG treatment including a mean yearly cost of GVG of US $1,572. The mean total cost for ESE and surgery was US $46,778 (N = 21), while the mean cost of ESE in patients evaluated but not accepted for surgery (N = 14) was US $24,054. Considering the costs for ESE and surgery in the whole patient series, the mean total cost of rendering one patient seizure free with surgery was US $110,000. Surgery is the most effective treatment option in selected cases of severe partial epilepsy. If its costs are distributed over the patient's expected lifetime, the yearly cost is comparable to the present yearly cost of medication with GVG. However, since many patients achieve satisfactory seizure control with GVG, and considering the risks of surgery, we consider it a rational policy to let patients try this drug (or another of the new generation of antiepileptic drugs) before entering ESE.