Significant Seizure Reduction Research Articles

Levetiracetam Extended Release as Adjuvant Therapy for the Control of Partial-onset Seizures

Extended release (XR) formulation of levetiracetam (LEV) is approved by the Food and Drug Administration as an add-on to other antiepileptic drugs (AEDs) for adults with partial onset seizures. This is based on class-I evidence demonstrating significant seizure reduction in once daily dosing. Keppra-XR is marketed with the brand name of Keppra XR since 2008 (UCB Pharma). Its original immediate release (IR) formulation has been in the market since 2000. LEV has a unique molecular structure which is chemically unrelated to existing AEDs. The precise mechanism of action is unknown. Animal studies showed binding to synaptic vesicle protein SV2A, thought to be involved in modulating synaptic neurotransmitter release. LEV-IR is proven effective as adjunctive therapy for partial-onset seizures, primary generalized tonic-clonic seizures and myoclonic seizures. It was shown to be equivalent to carbamazepine as first-line treatment for partial-onset seizures. The extended release formulation added advantages such as better tolerance and increased compliance.

A Pooled Analysis of Lacosamide Clinical Trial Data Grouped by Mechanism of Action of Concomitant Antiepileptic Drugs

Lacosamide, a new antiepileptic drug (AED) with a different pharmacological action that enhances sodium channel slow inactivation, is approved for the adjunctive treatment of partial-onset seizures in adults. Previous analyses of pooled phase II/III trials have demonstrated that lacosamide provides additional efficacy when added to a broad range of AEDs. To further evaluate the efficacy and safety of lacosamide by grouping patients based upon the sodium channel-blocking properties of their concomitant AEDs. Post hoc exploratory analyses were performed on pooled data in which patients were grouped based upon inclusion or non-inclusion of at least one 'traditional' sodium channel-blocking AED (defined as carbamazepine, lamotrigine, oxcarbazepine and phenytoin derivatives) as part of their concomitant AED regimen. Data pooled from previously conducted phase II/III clinical trials of lacosamide. Adult patients with partial-onset seizures with or without secondary generalization (N = 1308). Four- to six-week Titration Phase followed by 12-week maintenance treatment with adjunctive lacosamide (Vimpat®) [200, 400 or 600 mg/day] or placebo. Efficacy variables included change in seizure frequency per 28 days and the proportion of patients experiencing a ≥50% reduction in seizure frequency (50% responder rate) from Baseline to the Maintenance Phase. The proportion of patients experiencing a ≥75% reduction in seizure frequency from Baseline to the Maintenance Phase (75% responder rate) was also assessed. Safety parameters assessed were treatment-emergent adverse events (TEAEs) and discontinuation due to TEAEs. Additional safety assessments were changes in ECG and laboratory parameters as well as vital signs (including bodyweight). Of 1308 patients in the pooled phase II/III population, the majority (82%) were using at least one 'traditional' sodium channel-blocking concomitant AED. In this subgroup of patients, adjunctive lacosamide showed significant reductions in seizure frequency (p < 0.01, all dosages) and significantly greater 50% and 75% responder rates (p < 0.01 for 400 mg/day; p < 0.01 [50% responder rate] and p < 0.05 [75% responder rate] for 600 mg/day) compared with placebo; these effects were similar to the results seen in the pooled phase II/III population. TEAEs and discontinuations due to TEAEs in this subgroup were dose related and similar to the pooled phase II/III population. In the remaining subgroup of patients, i.e. those not taking 'traditional' sodium channel-blocking AEDs as part of their concomitant AED regimen (n = 231; 18%), a pronounced, dose-related seizure reduction was observed with lacosamide (p < 0.01, 400 and 600 mg/day for median percent seizure reduction and 50% or 75% responder rates). Also in this group, incidences of TEAEs were low, and discontinuations due to TEAEs did not appear to increase with dose. Analyses of ECG, laboratory and vital signs (including bodyweight) assessments did not identify abnormalities in either subgroup that were outside of the known safety profile of lacosamide observed in the pooled phase II/III population. In this post hoc exploratory analysis, adjunctive lacosamide demonstrated significant seizure reduction over placebo regardless of the inclusion of 'traditional' sodium channel blockers in the concomitant AED regimen. Future prospective studies evaluating single AED combinations (e.g. lacosamide plus one other drug) are needed to better evaluate the potential for additive or synergistic effects of lacosamide in combination with AEDs not considered 'traditional' sodium channel blockers.

Predicting the Unpredictable: Stereotactic Radiosurgery and Temporal Lobe Epilepsy

Predictors of Efficacy After Stereotactic Radiosurgery for Medial Temporal Lobe Epilepsy. Chang EF, Quigg M, Oh MC, Dillon WP, Ward MM, Laxer KD, Broshek DK, Barbaro NM; Epilepsy Radiosurgery Study Group. Neurology 2010;74(2):165–172. BACKGROUND: Stereotactic radiosurgery (RS) is a promising treatment for intractable medial temporal lobe epilepsy (MTLE). However, the basis of its efficacy is not well understood. METHODS: Thirty patients with MTLE were prospectively randomized to receive 20 or 24 Gy 50% isodose RS centered at the amygdala, 2 cm of the anterior hippocampus, and the parahippocampal gyrus. Posttreatment MRI was evaluated quantitatively for abnormal T2 hyperintensity and contrast enhancement, mass effect, and qualitatively for spectroscopic and diffusion changes. MRI findings were analyzed for potential association with radiation dose and seizure remission (Engel Ib or better outcome). RESULTS: Despite highly standardized dose targeting, RS produced variable MRI alterations. In patients with multiple serial imaging, the appearance of vasogenic edema occurred approximately 9–12 months after RS and correlated with onset of seizure remission. Diffusion and spectroscopy-detected alterations were consistent with a mechanism of temporal lobe radiation injury mediated by local vascular insult and neuronal loss. The degree of these early alterations at the peak of radiographic response was dose-dependent and predicted long-term seizure remission in the third year of follow-up. Radiographic changes were not associated with neurocognitive impairments. CONCLUSIONS: Temporal lobe stereotactic radiosurgery resulted in significant seizure reduction in a delayed fashion which appeared to be well-correlated with structural and biochemical alterations observed on neuroimaging. Early detected changes may offer prognostic information for guiding management.

Cerebellar stimulation in the management of medically intractable epilepsy: a systematic and critical review

The wide application of deep brain stimulation in the management of movement as well as other degenerative neurological and psychiatric disorders has renewed the interest in using deep brain stimulation in the management of medically intractable epilepsy. Various stimulation targets have been used with significantly varying results in aborting seizure activity. Electrical cerebellar stimulation (CS) has been used for more than 50 years in the management of epilepsy, with conflicting results. In the current study, the authors review the pertinent literature to outline the role of CS in the management of medically refractory epilepsy. The PubMed medical database was systematically searched for the following terms: "cerebellar," "epilepsy," "stimulation," and "treatment," and all their combinations. Case reports were excluded from this study. The pertinent articles were categorized into 2 large groups: animal experimental and human clinical studies. Particular emphasis on the following aspects was given when reviewing the human clinical studies: their methodological characteristics, the number of participants, their seizure types, the implantation technique and its associated complications, the exact stimulation target, the stimulation technique, the seizure outcome, and the patients' psychological and social poststimulation status. Three clinical double-blind studies were found, with similar implantation surgical technique, stimulation target, and stimulation parameters, but quite contradictory results. Two of these studies failed to demonstrate any significant seizure reduction, whereas the third one showed a significant poststimulation decrease in seizure frequency. All possible factors responsible for these differences in the findings are analyzed in the present study. Cerebellar stimulation seems to remain a stimulation target worth exploring for defining its potential in the treatment of medically intractable epilepsy, although the data from the double-blind clinical studies that were performed failed to establish a clear benefit in regard to seizure frequency. A large-scale, double-blind clinical study is required for accurately defining the efficacy of CS in epilepsy treatment.

Brain stimulation for the treatment of epilepsy

Direct brain stimulation is an emerging treatment of epilepsy. Scheduled or responsive stimulation has been applied. The most explored targets for scheduled stimulation are the anterior nucleus of the thalamus and the hippocampus. The anterior nucleus of the thalamus was studied in a large multicenter trial. There was a significant seizure reduction with the stimulator "on" versus "off" during several months after stimulator implantation. The hippocampus as stimulation target has not yet been studied in a large randomized trial. Responsive stimulation applies a stimulus whenever epileptiform activity occurs. It requires on-line detection of epileptiform activity. This concept is based on the observation that epileptiform activity during functional mapping can be aborted by brief pulses of cortical stimulation. Current technology is able to detect seizure activity intracranially on-line and delivers a high frequency stimulus if epileptiform activity is detected. A large randomized multicenter trial has been conducted testing this system for focal epilepsy.

Lacosamide: new adjunctive treatment option for partial-onset seizures

Importance of the field: Epilepsy is one of the most common neurological disorders, affecting up to 2% of the population worldwide. Studies show that patients with refractory seizures have higher morbidity and mortality rates, as well as a poorer quality of life, than those with controlled seizures. Therefore, treatment that reduces the frequency of seizures may improve patients' quality of life. Lacosamide (LCM) is a recently approved anticonvulsant in Europe and the USA which offers new mechanisms of action and favorable safety profiles. Efficacy data have shown fast onset of anticonvulsant effects and significant reduction of partial-onset seizures as adjunctive therapy at LCM 200 and 400 mg/day, even in a severely refractory population.Areas covered in this review: This article reviews three pivotal clinical trials of LCM, including its efficacy and tolerability over 7 years. In addition, LCM's key pharmacodynamics and pharmacokinetics from a search of the literature are reviewed in detail. This article also includes recent publications on the safety and use of intravenous LCM solution for patients with epilepsy.What the reader will gain: This article provides comprehensive review of efficacy and safety information of LCM along with comprehensive pharmacokinetic information, which includes absolute bioavailability, low protein binding, lack of hepatic enzyme induction or inhibition, and low potential for drug-drug interactions.Take home message: Considering the fact that more than 30% of epilepsy patients remain refractory despite various antiepileptic drugs, LCM may provide added benefit to patients with refractory seizures.

Anticonvulsant effects and behavioural outcomes of rAAV serotype 1 vector-mediated neuropeptide Y overexpression in rat hippocampus

Neuropeptide Y (NPY) is an endogenous peptide with powerful anticonvulsant properties. Its overexpression in the rat hippocampus, mediated by the local application of recombinant adeno-associated viral (rAAV) vectors carrying the human NPY gene, results in significant reduction of seizures in acute and chronic seizure models. In this study, we characterized a more efficient rAAV-NPY vector to improve cell transfection in the injected area. The changes included pseudotyping with the AAV vector serotype 1 (rAAV1), and using the strong constitutive hybrid CBA promoter, which contains a cytomegalovirus enhancer and chicken beta-actin promoter sequences. We compared NPY expression and the associated anticonvulsant effects of this new vector, with those mediated by the former rAAV vector with chimeric serotype 1/2 (rAAV1/2). In addition, we investigated whether rAAV serotype 1 vector-mediated chronic NPY overexpression causes behavioural deficits that may detract from the clinical utility of this therapeutic approach. We report that rAAV-NPY serotype 1 vector has significantly improved anticonvulsant activity when compared with serotype 1/2 vector, as assessed by measuring EEG seizure activity in kainic acid treated rats. rAAV1-mediated NPY overexpression in naive rats did not result in alterations of physiological functions such as learning and memory, anxiety and locomotor activity. In addition, we did not observe glia activation, or humoral immune responses against serotype 1 vector, which could inactivate gene expression. Our findings show that rAAV1-NPY vector with the CBA promoter mediates powerful anticonvulsant effects and seems to be safe in rodents, thus it may be considered a vector of choice for possible clinical applications.

Role of eslicarbazepine in the treatment of epilepsy in adult patients with partial-onset seizures

Eslicarbazepine is a new dibenzazepine antiepileptic agent. It is a high affinity antagonist of the voltage-gated sodium channel. It is closely related to both carbamazepine and oxcarbazepine. Eslicarbazepine has similar affinity to inactivated sodium channels (channels in just activated neurons) as carbamazepine, and greater efficacy in animal models of seizure than oxcarbazepine. In human placebo-controlled trials of a single daily dose of eslicarbazepine added to other anti-epileptic agents, significant seizure reductions occurred with 800 and 1200 mg daily, with nearly half of the patients experiencing a greater than 50% reduction in seizure frequency. Adverse events (AEs) occurred in over 50% of patients receiving therapeutic doses of eslicarbazepine (compared to 31.4%-44.7% of placebo-treated subjects), but were generally mild or moderate. Eight to 19.6% of eslicarbazepine treated patients discontinued due to AEs (compared to 3.9%-8.5% of placebo-treated subjects). In these patients receiving combination anticonvulsant therapy, the most common AEs were dizziness, nausea and vomiting, somnolence, and diplopia. Eslicarbazepine is an effective and reasonably well-tolerated adjunct in patients with suboptimal control of their partial seizures.

Predictors of efficacy after stereotactic radiosurgery for medial temporal lobe epilepsy

Stereotactic radiosurgery (RS) is a promising treatment for intractable medial temporal lobe epilepsy (MTLE). However, the basis of its efficacy is not well understood. Thirty patients with MTLE were prospectively randomized to receive 20 or 24 Gy 50% isodose RS centered at the amygdala, 2 cm of the anterior hippocampus, and the parahippocampal gyrus. Posttreatment MRI was evaluated quantitatively for abnormal T2 hyperintensity and contrast enhancement, mass effect, and qualitatively for spectroscopic and diffusion changes. MRI findings were analyzed for potential association with radiation dose and seizure remission (Engel Ib or better outcome). Despite highly standardized dose targeting, RS produced variable MRI alterations. In patients with multiple serial imaging, the appearance of vasogenic edema occurred approximately 9-12 months after RS and correlated with onset of seizure remission. Diffusion and spectroscopy-detected alterations were consistent with a mechanism of temporal lobe radiation injury mediated by local vascular insult and neuronal loss. The degree of these early alterations at the peak of radiographic response was dose-dependent and predicted long-term seizure remission in the third year of follow-up. Radiographic changes were not associated with neurocognitive impairments. Temporal lobe stereotactic radiosurgery resulted in significant seizure reduction in a delayed fashion which appeared to be well-correlated with structural and biochemical alterations observed on neuroimaging. Early detected changes may offer prognostic information for guiding management.

Adrenocorticotropic Hormone versus Pulsatile Dexamethasone in the Treatment of Infantile Epilepsy Syndromes

For treatment of intractable epilepsies, there are no data comparing conventional adrenocorticotropic hormone and pulsatile corticoid therapy with dexamethasone. A retrospective comparison of efficacy was therefore conducted for both forms of application. Between 1989 and 2001, a series of 11 children with West syndrome and 3 with Lennox-Gastaut syndrome were treated with adrenocorticotropic hormone (group 1); between 2003 and 2006, 7 children with West syndrome, 5 with electrical status epilepticus during slow sleep, and 2 with Lennox-Gastaut syndrome were treated with pulsatile corticoid therapy (group 2). In group 1 (n = 14), 9/11 West syndrome patients became seizure free, but none with Lennox-Gastaut syndrome (0/3). In group 2 (n = 14), 4/7 West syndrome patients became seizure-free, 1/2 with Lennox-Gastaut syndrome exhibited seizure-frequency reduction, and 2/5 patients with electrical status epilepticus during slow-wave sleep exhibited significant improvement according to electroencephalograms. In West syndrome, pulsatile corticoid therapy was an effective alternative treatment to adrenocorticotropic hormone, whereas in Lennox-Gastaut syndrome in general steroids did not lead to a significant seizure reduction. In electrical status epilepticus during slow-wave sleep, treatment with pulsatile corticoid therapy seems to be effective and should be investigated in a larger group of patients.

Gamma knife radiosurgery for the treatment of recurrent seizures after incomplete anterior temporal lobectomy

To evaluate the efficacy and safety of gamma knife radiosurgery (GKS) in treating temporal lobe epilepsy, GKS was performed in four adult patients with recurrent complex partial seizures who underwent incomplete anterior temporal lobectomy (ATL) but were reluctant to undergo a second resective surgery. A marginal dose of 24.5–25 Gy, corresponding to 65–70% isodose curve, was delivered to the treatment target that included the residual amygdala and the head and anterior body of the hippocampus. None of the patients had severe acute side effects but three patients had radiation-induced MRI signal changes around the target volume 13, 20, and 24 months after GKS, respectively. All four patients had significant seizure reduction during the first 6-month period and clinical efficacy persisted throughout the 2-year follow-up period. All of the patients also had improved neuropsychological profiles, including memory function and quality-of-life, compared to their pre-GKS conditions. In conclusion, the safety and clinical efficacy of GKS make it a reasonable and suitable therapeutic alternative for patients with recurrent seizures after incomplete ATL. A higher marginal dose of >25 Gy and wider coverage may be more clinically beneficial but warrant further investigation.

Neuropeptide Y Overexpression Using Recombinant Adenoassociated Viral Vectors

Gene therapy may represent a promising alternative treatment of epileptic patients who are resistant to conventional anti-epileptic drugs. Among the various approaches for the application of gene therapy in the treatment of CNS disorders, recombinant adeno-associated viral (AAV) vectors have been most widely used. Preclinical studies using a selection of "therapeutic" genes injected into the rodent brain to correct the compromised balance between inhibitory and excitatory transmission in epilepsy, showed significant reduction of seizures and inhibition of epileptogenesis. In particular, transduction of neuropeptide genes, such as galanin and neuropeptide Y (NPY) in specific brain areas in experimental models of seizures resulted in significant anticonvulsant effects. Recent findings showed a long-lasting NPY over-expression in the rat hippocampus by local application of recombinant AAV vectors associated with reduced generalization of seizures, delayed kindling epileptogenesis, and strong reduction of chronic spontaneous seizures. These results establish a proof-of-principle evidence of the efficacy of gene therapy as anticonvulsant treatment. Additional investigations are required to address safety concerns and possible side effects in more detail.

Cavernous angiomas: An uncontrolled clinical study of 87 surgically treated patients

Cerebral cavernous angiomas remain as one of the most negotiable and controversial topics in neurological and neurosurgical practice. We present statistical evaluation of initial presentation, preoperative neurological findings, surgical complications, and outcome of surgically treated patients with intracerebral cavernous angiomas. During 1997 to 2004, 87 patients (41 men, 46 women) with intracerebral cavernous angiomas underwent surgical treatment in the tertiary referral center, and these were included into the present uncontrolled clinical study. The mean age of the patients at the time of operation was 42.4 years, and the mean duration of illness was 120.5 days. All patients underwent preoperative magnetic resonance imaging, and pre- and postoperative clinical examination. The clinical course was documented using the Karnofski performance scale. A simplified version of Engel's classification of the outcome of the patients with chronic seizures was applied. The most common clinical presentation of cavernous angiomas was seizures, significant part of which was chronic. No association was found between lesion location by cerebral lobes and clinical presentation by seizures. No significant differences in the likelihood of presenting with hemorrhage between supratentorial and subtentorial lesions were detected. In addition, no associations were found between size of cavernoma and the initial presentation of cavernoma by an extralesional hemorrhage or chronic seizures. In the group of patients presenting with headache, sporadic seizures, or intracerebral hemorrhage, good postoperative outcome was achieved in 83% of the patients. Of the patients who underwent operation for seizure control, significant seizure reduction or elimination after surgery was observed in 79% of the patients. Microsurgical removal of cavernous angiomas and surrounding hemosiderin plate tends to significant reduction or elimination of epileptic seizures and improved postoperative neurological status.

INTRACRANIAL ELECTROENCEPHALOGRAPHY WITH SUBDURAL GRID ELECTRODES

Intracranial subdural grid monitoring is a useful diagnostic technique for surgical localization in patients with intractable partial epilepsy. The rationale for the present study was to assess the morbidity of intracranial recordings and the surgical outcomes. We retrospectively reviewed the clinical data for 189 unique patients undergoing 198 intracranial subdural grid monitoring sessions between 1996 and 2004 at a tertiary epilepsy center. The mean age of patients undergoing monitoring was 28 +/- 14 years. An average of 63 +/- 23 electrodes were inserted. The mean duration of monitoring was 8 +/- 4 days. Localization of an epileptogenic zone occurred in 156 sessions (79%) resulting in 136 resections (69%). There were 13 major complications (6.6%), including five infections and six hematomas. Three patients (1.5%) developed permanent deficits related to implantation. Sixty-two (47%) of 136 patients undergoing resection were seizure-free after resection. An additional 38 patients (28%) had a significant reduction in seizures. The mean follow-up was 51 +/- 30 months. The duration of monitoring, bone flap replacement, number of electrodes, and perioperative corticosteroids were not associated with infection or complication. Subdural grid monitoring for identification an epileptogenic focus is high yield, revealing a focus in 79% of monitoring sessions. Complications rarely result in permanent morbidity (1.5%). Surgical outcome indicated that 74% of patients experienced a favorable reduction in seizure tendency.

Reduction of secondarily generalized tonic–clonic (SGTC) seizures with pregabalin

To determine whether pregabalin reduces SGTC seizures in clinically refractory epilepsy. Post hoc analysis performed on pooled data from three double-blind, placebo-controlled trials of similar design. Patients with partial seizures who failed > or =2 antiepileptic drugs at maximally tolerated doses. This analysis excluded those who did not have an SGTC seizure during baseline or treatment periods. Absolute and conditional reduction analyses examined change from baseline in SGTC seizure rates. The absolute reduction analysis used response ratio (RRatio) to compare reduction in seizure-frequency from baseline (B) during a 12-week treatment (T) period [RRatio=((T-B)/(T+B))x100]. The conditional analysis examined proportional risk of having SGTC seizure if a partial seizure had occurred. Of 1052 intent-to-treat patients, 409 were included. Sixteen were seizure-free during treatment and not included in the conditional analysis. A significant reduction in absolute SGTC seizures from baseline was observed in patients receiving pregabalin 600 mg/day (treatment RRatio, -33 versus placebo, -3.7; P=0.0005). A lower dose of pregabalin (300mg/day), administered in one study, demonstrated a trend (nonsignificant) toward reduced SGTC seizures (treatment, -24.7 versus placebo, -10.0; P=0.2493). As adjunctive therapy, pregabalin 600 mg/day is effective in reducing the absolute frequency of SGTC seizures in patients with refractory partial epilepsy, but not secondary generalization.

Outcomes of epilepsy surgery in adults and children

Surgery is widely accepted as an effective therapy for selected individuals with medically refractory epilepsy. Numerous studies in the past 20 years have reported seizure freedom for at least 1 year in 53-84% of patients after anteromesial temporal lobe resections for mesial temporal lobe sclerosis, in 66-100% of patients with dual pathology, in 36-76% of patients with localised neocortical epilepsy, and in 43-79% of patients after hemispherectomies. Reported rates for non-resective surgery have been less impressive in terms of seizure freedom; however, the benefit is more apparent when reported in terms of significant seizure reductions. In this Review, we consider the outcomes of surgery in adults and children with epilepsy and review studies of neurological and cognitive sequelae, psychiatric and behavioural outcomes, and overall health-related quality of life.

Déconnexion chirurgicale des hamartomes hypothalamiques

Surgical resection of hypothalamic hamartomas (HHs) associated with drug-resistant gelastic epilepsy carries a considerable risk of neurological and endocrine morbidity. Alternative surgical routes and techniques have therefore been proposed, especially for broadly attached lesions and for those with a third ventricular location. We present an updated series of 43 patients (aged nine months to 34 years), operated on from 1998 through 2005 at our institution. The hamartoma was disconnected using a microsurgical pterional approach of those lesions extending from the hypothalamic floor downward into the interpeduncular cistern. When the HH presented as a paramedian mass, partly or exclusively bulging into the third ventricle, with a rather vertical plane of attachment, we chose a frameless stereotactic endoscopic technique to disconnect the lesion. In several of our patients, both methods were applied subsequently. Surgery-related morbidity was lower with the ventricular endoscopic technique. Twenty-one patients (50%) are seizure-free and two patients (5%) almost seizure-free, while in 17 patients (40%), there was a significant seizure reduction. Two patients (5%) had no postoperative improvement. According to the different topographic features of the HHs, for which we have recently proposed a classification into four subtypes, the intraventricularly located hamartoma had the best prognosis following endoscopic disconnection. Ten of the 12 patients (83%) with this HH location became seizure-free. Resection of epilepsy-related HHs can be replaced by disconnective procedures. Our results confirm their feasibility and acceptable morbidity, with particularly good seizure outcome in patients with intraventricularly located HHs.

Stimulation chronique du nerf vague dans le traitement del’épilepsie pharmacorésistante

Proposed as an additive symptomatic treatment of refractory epilepsy, vagus nerve stimulation (VNS) has proven to be effective and well-tolerated in patients presenting with refractory epilepsy for whom cortical resection is not indicated. After two years of treatment, the overall reduction of seizure frequency averaged 40%. In 50% of the patients, the frequency of seizures decreased by at least 50%. Moreover, even in absence of a significant reduction of seizures, patients who undergo this treatment reported an improvement in their quality of life. Economic surveys also demonstrate a favorable impact of VNS on the management of refractory epilepsy. Since 1988, 65,000 patients with refractory epilepsy throughout the world have been treated by VNS for this indication (1000 in France). The surgical implantation technique used in our department, the effects of vagus nerve stimulation reported in the literature, and our experience with a cohort of 70 patients with refractory epilepsy who received implants over the last 10 years are described.

Sécurité et efficacité des trans-sections sous-piales multiples : analyse d’une série consécutive de 30 patients

PurposeTo present our results using multiple subpial transections (MST) for the treatment of pharmacologically refractory epilepsy (PRE) with epileptogenic foci in eloquent areas. MethodBetween January 2003 and March 2006, we treated 33 patients with PRE with epileptogenic foci in eloquent areas by MST “in rays”, either isolated (MSTs group) or completing resection or disconnection of other cortical areas (MST+ group). Our first 30 patients had a follow-up of at least 24 months: eight in the MSTs group and 22 in the MST+ group. Four postoperative grades were distinguished based on a modified Engel classification: seizure-free (100% seizure reduction equals to Grade I), substantial significant seizure reduction (75% to 99% seizure reduction equals to Grade II), moderate significant reduction (50% to 74% seizure reduction equals to Grade III) and finally no significant reduction (seizure reduction less than 50% equals to Grade IV). ResultsIn the MSTs group, two patients (25%) were in grade I and five (62%) in grade II or III. In the MST+ group, six patients (27%) were in grade I and 13 (59%) in grade II or III. All patients showed some seizure reduction and some improvement in behavior or cognitive function with no permanent neurological deficit. ConclusionThis series supports the notion that multiple subpial transections are associated with a significant seizure reduction (in 86.6% of the cases reported herein) and that the risk of permanent neurological deficit can be very low.

The promise of gene therapy for the treatment of epilepsy

Gene therapy involves the transfer and expression of a therapeutic gene into a target tissue, and essentially represents an intervention that alters the instruction set of a cell having a dominant effect on the cell phenotype. Gene therapy techniques may provide a realistic therapeutic option for CNS disorders that are difficult to treat with conventional drugs, such as for drug-resistant focal epilepsies. Preclinical studies using a selection of ‘therapeutic’ genes delivered into the rodent brain showed significant reduction of seizures and inhibition of epileptogenesis, thus establishing the proof-of-principle evidence of the potential applicability of this technology to human epilepsy. The promising potential of gene therapy for the treatment of CNS pathologies still requires further investigation to improve the efficacy and the safety of this approach using clinically relevant experimental models. The recent advances in refining gene therapy tools and in methods of gene delivery make this innovative approach a definite possibility for therapeutic intervention.