Zonisamide for the treatment of myoclonic seizures in progressive myoclonic epilepsy: an open-label study.

PURPOSE: To examine the safety and efficacy of zonisamide in treating myoclonic seizures associated with progressive myoclonic epilepsy (PME), in an open-label setting. METHODS: Thirty patients with refractory PME (aged > or = 5 years), who were taking up to three antiepileptic drugs, received adjunctive zonisamide (< or = 6 mg/kg/day) therapy for 16 weeks. Myoclonic seizures were recorded daily over a 24-hour period or in 10-minute epochs in the morning, afternoon, and evening. Safety was assessed via adverse events (AEs); efficacy was measured by the percentage of patients experiencing a > or = 50% decrease in myoclonic seizure frequency from baseline. RESULTS: Treatment-related AEs, experienced by 53% (n = 16/30) of patients, led to five patients discontinuing zonisamide. The most common AEs were decreased appetite, somnolence, and asthenia. Overall, 36% of patients (n = 10/28) had a > or = 50% reduction in myoclonic seizure frequency. CONCLUSIONS: These results suggest that zonisamide may be useful in the treatment of patients with PME. However, due to the size and open-label character of this study, further research is required.

Estimulación del sistema nervioso para el control de la epilepsia refractaria / Stimulating the nervous system to control refractory epilepsy

Vagal nerve stimulation (VNS), an indirect stimulation of the brain, proved effective in animal models of epilepsy, and then in open, as well as double-blinded trials, in over 450 patients. The benefit, seizure reduction, improved for at least 1 1/2 years with almost 50% of treated patients achieving about a 50% reduction in seizure frequency. Other benefits are: seizure termination and improved mood. Benefits have been shown in children and adults with partial and generalized epilepsies, and in specific epilepsy syndromes. Implantation is easy. The method of action is largely unknown, although VNS appears to alter metabolic activity in specific brain nuclei. The improvement in mood has led to its approved use in patients with severe depression. Deep brain stimulation (DBS) is under investigation as an alternate method for controlling medically refractory seizures. It is based on the observation that thalamic stimulation can influence the EEG over a wide area. Several thalamic nuclei, as well as the amygdalahippocampus complex, caudate nucleus, and substantia nigra, have been the object of stimulation, all holding promise in the treatment of medically refractory epilepsy. Intraoperative brain imaging is essential and the procedure is done under local anesthesia. Experience with DBS is limited, but growing

La estimulación del nervio vago (ENV), una estimulación indirecta del cerebro, demostró ser efectiva en modelos de epilepsia con animales y, posteriormente, en un estudio de tipo abierto y en ensayos a doble ciego con más de 450 pacientes. El beneficio, valorado por la disminución en el número de episodios convulsivos, se mantuvo por al menos un año y medio; aproximadamente el 50% de los pacientes tratados logró una reducción de casi el 50% en la frecuencia de las convulsiones. Otros beneficios fueron: la terminación de las convulsiones y la mejoría en el estado de ánimo. Los beneficios se demostraron en niños y adultos con epilepsias generalizadas y parciales y en síndromes epilépticos específicos. El procedimiento de implante es sencillo. El mecanismo de acción es desconocido, aunque la ENV parece alterar la actividad metabólica en núcleos cerebrales específicos. La mejoría en el estado de ánimo llevó a que su uso fuese aprobado en pacientes con depresión grave. La estimulación cerebral profunda (ECP) está en investigación como método alternativo para el control de las convulsiones refractarias a la medicación. Se basa en que la estimulación talámica puede influir sobre el EEG en un área extensa. Diversos núcleos talámicos, así como el complejo amígdala-hipocampo, el núcleo caudado y la sustancia negra fueron objeto de la estimulación, con resultados promisorios en el tratamiento de la epilepsia refractaria al tratamiento médico. El procedimiento se realiza bajo anestesia local y es esencial la obtención de imágenes cerebrales intraoperatorias. La experiencia con la ECP es limitada, pero creciente

Improving the lives of patients with medically refractory epilepsy by electrical stimulation of the nervous system.

Vagal nerve stimulation proved effective in animal models of epilepsy, and in open and double-blinded trials, in over 450 patients. Seizure reduction improved for at least 2 years. Almost 50% of treated patients achieve at least a 50% reduction in seizure frequency. Other advantages include termination of a seizure and improved alertness. Benefits were demonstrated in children, partial and generalized epilepsies, and in specific neurologic syndromes.

Vagal nerve stimulation in refractory epilepsy: the first 100 patients receiving vagal nerve stimulation at a pediatric epilepsy center.

OBJECTIVE: To determine the outcome of intermittent left vagal nerve stimulation on the first 100 consecutive patients treated at our pediatric epilepsy center. METHODS: Patients were identified by means of operating room records. Data collected described the patient's epilepsy, previous and subsequent therapies, adverse events, nonepileptic changes, and outcomes. RESULTS: Average age was 10.4 years; years of epilepsy, 8.5; total number of antiepileptic therapies, 8.4; and median monthly seizure frequency, 120. Data on seizure frequency at follow-up were available for 96 of the 100 patients. Forty-five percent of patients achieved greater than 50% reduction; and 18% had had no seizures for the last 6 months. Response was similar in patients with more than 7 years of refractory epilepsy as compared with patients with a shorter history. Magnet-generated, on-demand current reduced seizure intensity in almost half of the patients with available data. Generator infections occurred in 3 patients. Twenty-four patients had their generators removed. Subsequently, 2 of these patients died. CONCLUSIONS: Seizure reduction was the same in patients younger than 12 years and 12 years or older and in patients with shorter and longer histories of refractory epilepsy. Adverse effects were few in this population, particularly in those younger than 12 years. Vagal nerve stimulation appears to be a relatively safe and potentially effective treatment for children with severely intractable epilepsy.

Observations on the use of vagus nerve stimulation earlier in the course of pharmacoresistant epilepsy: patients with seizures for six years or less.

BACKGROUND: This study retrospectively compared the effectiveness of vagus nerve stimulation (VNS) therapy among a constant cohort of patients in the patient outcome registry, which systematically monitors outcomes of patients receiving VNS therapy. Patients in the study had pharmacoresistant seizures for 6 years or less (early treatment group) or more than 6 years (late treatment group) before initiation of VNS therapy, and results are provided after both 3 and 12 months. REVIEW SUMMARY: Of 405 patients, 51 were in the early and 354 in the late treatment groups. Median age at onset of seizures was 7 years in the early and 4.5 years in the late treatment group. Seizure reduction of 100% was reported in 7.8% (early) and 3.7% (late) patients at 3 months and 11.8% (early) and 4.5% (late) at 12 months (P = 0.033). Reductions in seizure frequency greater than or equal to 90% for early and late treatment groups were similar: 11.8% (early) and 11.0% (late) at 3 months and 23.5% (early) and 17.0% (late) at 12 months. CONCLUSIONS: Patients treated earlier with VNS therapy were twice as likely to report no seizures as patients who had seizures for more than 6 years before they received VNS therapy. The effectiveness of VNS therapy should be assessed among other patients with pharmacoresistant seizures and lesser cumulative seizure loads.

Stimulation of the nervous system for the management of seizures: current and future developments.

Vagal nerve stimulation (VNS) for the treatment of refractory epilepsy appears to have started from the theory that since VNS can alter the EEG, it may influence epilepsy. It proved effective in several models of epilepsy and was then tried in short-term, open-label and double-blind trials, leading to approval in Canada, Europe and the US. Follow-up observations in these patients demonstrated continued improvement in seizure control for up to 2 years. Close to 50% of treated patients have achieved at least a 50% reduction in seizure frequency. This therapy was also useful as rescue therapy for ongoing seizures in some patients; many patients are more alert. The initial trials were completed in patients >/=12 years of age with refractory partial seizures. Subsequently, similar benefits were shown in patients with tuberous sclerosis complex, Lennox-Gastaut syndrome, hypothalamic hamartomas and primary generalised seizures. Implanting the generator and leads is technically easy, and complications are few. The method of action is largely unknown, although VNS appears to alter metabolic activity in specific brain nuclei. Considering that improvement in mood is frequently found in patients using VNS, it has undergone trials in patients with depression. Other illnesses deserving exploration with this unusual therapy are Alzheimer's disease and autism. Some aspects of VNS have proven disappointing. Although patients have fewer seizures, the number of antiepileptic drugs they take is not significantly reduced. In addition, there is no way to accurately predict the end of life of the generator. Optimal stimulation parameters, if they exist, are unknown. Deep brain stimulation is a new method for controlling medically refractory seizures. It is based on the observation that thalamic stimulation can influence the EEG over a wide area. Several thalamic nuclei have been the object of stimulation in different groups of patients. Intraoperative brain imaging is essential for electrode placement. The procedure is done under local anaesthesia. Experience with this therapy is currently limited, but growing.

Vagus nerve stimulator implantation in children.

BACKGROUND: Vagus nerve stimulation was approved in 1997 as an adjunctive treatment of partial-onset seizures refractory to medical therapy. Subsequent to the initial clinical trials, few studies have been published specifically addressing perioperative management issues. OBJECTIVES: To review the operative technique and perioperative management of patients undergoing vagus nerve stimulator implantation and to analyze complications and their management. DESIGN: Retrospective medical record review and survey of patients who underwent implantation. SETTING: A tertiary care pediatric hospital in Kansas City, Mo. PATIENTS: One hundred two patients aged 21 months to 40 years. INTERVENTION: Vagus nerve stimulator implantation and lead placement. MAIN OUTCOME MEASURES: The surgical technique of vagus nerve stimulator implantation is presented in detail. Perioperative complications are enumerated, and strategies for their management are described. A subjective patient survey addresses some quality-of-life issues and the effect on swallowing and voice. RESULTS: One hundred two patients successfully underwent vagus nerve stimulator implantation. Three patients experienced infection of the chest wound holding the generator and required explantation. These 3 patients underwent reimplantation within 2 months after the infection had cleared. Most patients experience some degree of hoarseness when the generator is activated, but this symptom usually does not significantly affect the ability to communicate. Responses to questions regarding quality of life are positive. CONCLUSIONS: Vagus nerve stimulator implantation has a low incidence of serious complications. Quality of life seems to be improved for most patients. Modifications to the surgical procedure must be considered when performing the implantation on a young patient.