Barbara C. Jobst

Two‐year seizure reduction in adults with medically intractable partial onset epilepsy treated with responsive neurostimulation: Final results of the RNS System Pivotal trial

To demonstrate the safety and effectiveness of responsive stimulation at the seizure focus as an adjunctive therapy to reduce the frequency of seizures in adults with medically intractable partial onset seizures arising from one or two seizure foci.

Medically intractable, localization-related epilepsy with normal MRI: presurgical evaluation and surgical outcome in 43 patients.

Summary:  Purpose: High‐resolution magnetic resonance imaging (MRI) plays a crucial role in the presurgical evaluation of patients with medically refractory partial epilepsy. Although MRI detects a morphologic abnormality as the cause of the epilepsy in the majority of patients, some patients have a normal MRI. This study was undertaken to explore the hypothesis that in patients with normal MRI, invasive monitoring can lead to localization of the seizure‐onset zone and successful epilepsy surgery.

Long-term treatment with responsive brain stimulation in adults with refractory partial seizures.

Objective: The long-term efficacy and safety of responsive direct neurostimulation was assessed in adults with medically refractory partial onset seizures. Methods: All participants were treated with a cranially implanted responsive neurostimulator that delivers stimulation to 1 or 2 seizure foci via chronically implanted electrodes when specific electrocorticographic patterns are detected (RNS System). Participants had completed a 2-year primarily open-label safety study (n = 65) or a 2-year randomized blinded controlled safety and efficacy study (n = 191); 230 participants transitioned into an ongoing 7-year study to assess safety and efficacy. Results: The average participant was 34 (±11.4) years old with epilepsy for 19.6 (±11.4) years. The median preimplant frequency of disabling partial or generalized tonic-clonic seizures was 10.2 seizures a month. The median percent seizure reduction in the randomized blinded controlled trial was 44% at 1 year and 53% at 2 years (p < 0.0001, generalized estimating equation) and ranged from 48% to 66% over postimplant years 3 through 6 in the long-term study. Improvements in quality of life were maintained (p < 0.05). The most common serious device-related adverse events over the mean 5.4 years of follow-up were implant site infection (9.0%) involving soft tissue and neurostimulator explantation (4.7%). Conclusions: The RNS System is the first direct brain responsive neurostimulator. Acute and sustained efficacy and safety were demonstrated in adults with medically refractory partial onset seizures arising from 1 or 2 foci over a mean follow-up of 5.4 years. This experience supports the RNS System as a treatment option for refractory partial seizures. Classification of evidence: This study provides Class IV evidence that for adults with medically refractory partial onset seizures, responsive direct cortical stimulation reduces seizures and improves quality of life over a mean follow-up of 5.4 years.

Intractable seizures of frontal lobe origin: clinical characteristics, localizing signs, and results of surgery.

Summary: Purpose: We analyzed the clinical characteristics of seizures of frontal lobe (FL) origin with particular emphasis on establishing different categories and determining if these categories had any localizing or lateralizing value. In addition, results of surgery are reported.

Resective Epilepsy Surgery for Drug-Resistant Focal Epilepsy: A Review

IMPORTANCE Epilepsy surgery is indicated for patients with focal seizures who do not respond to appropriate antiepileptic drug therapy consisting of 2 or more medications. OBJECTIVES To review resective surgery outcomes for focal epilepsy, to identify which patients benefit the most, and to discuss why epilepsy surgery may not be universally accepted. EVIDENCE REVIEW Medline and Cochrane databases were searched between January 1993 and June 2014 for randomized clinical trials, meta-analyses, systematic reviews, and large retrospective case series (>300 patients) using Medical Subject Headings and indexed text terms. Fifty-five articles were included. Subpopulations and prognostic factors were identified. Systematic reviews for cognitive, psychiatric, quality-of-life, and psychosocial outcomes were included. FINDINGS Two randomized clinical trials enrolling 118 patients with temporal lobe epilepsy found greater freedom from seizures with surgery when compared with continued medical treatment (58% vs 8% [n = 80] and 73% vs 0% [n = 38], P < .001). Nine systematic reviews and 2 large case series of medically refractory patients treated with surgery reported seizure-free outcomes in 34% to 74% of patients (median, 62.4%). The remainder of systematic reviews and meta-analyses examined subpopulations. Epilepsy surgery was less effective when there were extratemporal lesions, the epilepsy was not associated with a structural lesion, or both. Seizure-free outcomes were similar between children and adults. Hippocampal sclerosis and benign tumors were associated with better outcomes relative to other pathologies. Similar procedures such as selective amygdalohippocampectomy and temporal lobectomy for temporal lobe epilepsy were associated with subtle differences in seizure and neuropsychological outcome. There is low perioperative mortality (0.1%-0.5%) from epilepsy surgery. The most frequent neurologic complication is visual field defect occurring from temporal lobe resection. Quality of life improved after surgery but improved the most in patients who were seizure-free after surgery. CONCLUSIONS AND RELEVANCE Epilepsy surgery reduced seizure activity in randomized clinical trials when compared with continued medical therapy. Long-term cognitive, psychiatric, psychosocial, and quality-of-life outcomes were less well defined. Despite good outcomes from high-quality clinical trials, referrals of patients with seizures refractory to medical treatment remain infrequent.

Hippocampal interictal epileptiform activity disrupts cognition in humans

Objective: We investigated whether interictal epileptiform discharges (IED) in the human hippocampus are related to impairment of specific memory processes, and which characteristics of hippocampal IED are most associated with memory dysfunction. Methods: Ten patients had depth electrodes implanted into their hippocampi for preoperative seizure localization. EEG was recorded during 2,070 total trials of a short-term memory task, with memory processing categorized into encoding, maintenance, and retrieval. The influence of hippocampal IED on these processes was analyzed and adjusted to account for individual differences between patients. Results: Hippocampal IED occurring in the memory retrieval period decreased the likelihood of a correct response when they were contralateral to the seizure focus (p < 0.05) or bilateral (p < 0.001). Bilateral IED during the memory maintenance period had a similar effect (p < 0.01), particularly with spike-wave complexes of longer duration (p < 0.01). IED during encoding had no effect, and reaction time was also unaffected by IED. Conclusions: Hippocampal IED in humans may disrupt memory maintenance and retrieval, but not encoding. The particular effects of bilateral IED and those contralateral to the seizure focus may relate to neural compensation in the more functional hemisphere. This study provides biological validity to animal models in the study of IED-related transient cognitive impairment. Moreover, it strengthens the argument that IED may contribute to cognitive impairment in epilepsy depending upon when and where they occur.

Prescribing antiepileptic drugs: should patients be switched on the basis of cost?

To assess the costs of switching from one antiepileptic drug (AED) to another, all associated direct and indirect costs, not only drug acquisition costs, must be considered. The perspective of the healthcare system evaluated in cost-effectiveness analysis is of crucial importance. Multiple clinical factors can influence clinical decisions regarding switching AEDs. The economic cost of poorly controlled epilepsy is enormous and the most cost-effective intervention is an AED that provides total seizure control. Cost-minimisation studies have evaluated costs associated with various medications. If only efficacy and adverse events were considered, then the ‘older’ AEDs were generally more cost effective than the ‘newer’ AEDs. Most studies only examine very specific clinical situations and are not suitable for establishing general clinical recommendations. The pharmacoeconomics of AED choice is highly country specific. While switching to generic formulations is, in general, cost effective, some changes may be detrimental and more costly than remaining on the trade name preparation. For example, as a result of differences in bioavailability and possible loss of seizure control, changing patients to generic phenytoin and carbamazepine can be problematic. Fosphenytoin may only be cost effective in certain clinical situations compared with intravenous phenytoin. Seizure control should not be sacrificed on the basis of costs alone, as the major endpoint in treating epilepsy with AEDs is seizure control without adverse effects. Switching AEDs in clinical practice still depends on the individual clinical situation and choosing AED therapy solely on the basis of initial acquisition costs is unlikely to be cost effective in the long-term care of patients with epilepsy.

Interictal PET and ictal subtraction SPECT: Sensitivity in the detection of seizure foci in patients with medically intractable epilepsy

Purpose:  Interictal positron emission tomography (PET) and ictal subtraction single photon emission computed tomography (SPECT) of the brain have been shown to be valuable tests in the presurgical evaluation of epilepsy. To determine the relative utility of these methods in the localization of seizure foci, we compared interictal PET and ictal subtraction SPECT to subdural and depth electrode recordings in patients with medically intractable epilepsy.

Secondarily Generalized Seizures in Mesial Temporal Epilepsy: Clinical Characteristics, Lateralizing Signs, and Association With Sleep–Wake Cycle

Summary:  Purpose: Secondarily generalized seizures (SGSs) are often considered to be stereotyped, presumably sharing a common electrical pathway. We examined whether SGSs are uniform in a homogeneous group of patients with mesial temporal epilepsy, and whether certain clinical signs associated with generalization are lateralizing with regard to seizure origin.

The role of intracranial electrode reevaluation in epilepsy patients after failed initial invasive monitoring.

Summary: Purpose: Intracranial electrode recording often provides localization of the site of seizure onset to allow epilepsy surgery. In patients whose invasive evaluation fails to localize seizure origin, the utility of further invasive monitoring is unknown. This study was undertaken to explore the hypothesis that a second intracranial investigation is selected patients warrants consideration and can lead to successful epilepsy surgery.