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Drug-resistant Epilepsy (drug-resistant + epilepsy)

Distribution by Scientific Domains

Medical Sciences	94%

Selected Abstracts

Slow Repetitive TMS for Drug-resistant Epilepsy: Clinical and EEG Findings of a Placebo-controlled Trial

EPILEPSIA, Issue 2 2007
Roberto Cantello
Summary:,Purpose: To assess the effectiveness of slow repetitive transcranial magnetic stimulation (rTMS) as an adjunctive treatment for drug-resistant epilepsy. Methods: Forty-three patients with drug-resistant epilepsy from eight Italian Centers underwent a randomized, double-blind, sham-controlled, crossover study on the clinical and EEG effects of slow rTMS. The stimulus frequency was 0.3 Hz. One thousand stimuli per day were given at the resting motor threshold intensity for 5 consecutive days, with a round coil at the vertex. Results:"Active" rTMS was no better than placebo for seizure reduction. However, it decreased interictal EEG epileptiform abnormalities significantly (p < 0.05) in one-third of the patients, which supports a detectable biologic effect. No correlation linked the rTMS effects on seizure frequency to syndrome or anatomic classification, seizure type, EEG changes, or resting motor threshold (an index of motor cortex excitability). Conclusions: Although the antiepileptic action was not significant (p > 0.05), the individual EEG reactivity to "active" rTMS may be encouraging for the development of more-powerful, noninvasive neuromodulatory strategies. [source]

Drug Resistance in Epilepsy: Putative Neurobiologic and Clinical Mechanisms

EPILEPSIA, Issue 6 2005
Dieter Schmidt
Summary:, Drug-resistant epilepsy with uncontrolled severe seizures despite state-of-the-art medical treatment continues to be a major clinical problem for up to one in three patients with epilepsy. Although drug resistance may emerge or remit in the course of epilepsy or its treatment, in most patients, drug resistance seems to be continuous and to occur de novo. Unfortunately, current antiepileptic drugs (AEDs) do not seem to prevent or to reverse drug resistance in most patients, but add-on therapy with novel AEDs is able to exert a modest seizure reduction in as many as 50% of patients in short-term clinical trials, and a few become seizure free during the trial. It is not known why and how epilepsy becomes drug resistant, while other patients with seemingly identical seizure types can achieve seizure control with medication. Several putative mechanisms underlying drug resistance in epilepsy have been identified in recent years. Based on experimental and clinical studies, two major neurobiologic theories have been put forward: (a) removal of AEDs from the epileptogenic tissue through excessive expression of multidrug transporters, and (b) reduced drug-target sensitivity in epileptogenic brain tissue. On the clinical side, genetic and clinical features and structural brain lesions have been associated with drug resistance in epilepsy. In this article, we review the laboratory and clinical evidence to date supporting the drug-transport and the drug-target hypotheses and provide directions for future research, to define more clearly the role of these hypotheses in the clinical spectrum of drug-resistant epilepsy. [source]

The Costs of Childhood Epilepsy in Italy: Comparative Findings from Three Health Care Settings

EPILEPSIA, Issue 5 2001
R. Guerrini
Summary: ,Purpose: To determine the direct costs of epilepsy in a child neurology referral population, stratified by disease, duration, and severity, comparing three different health care settings [i.e., teaching or clinical research (CR) hospitals, general hospitals, and outpatient services]. Methods: Patients were accepted if they had confirmed epilepsy and were resident in the center catchment area. Eligible subjects were grouped in the following categories: (a) newly diagnosed patients; (b) patients with epilepsy in remission; (c) patients with active non,drug-resistant epilepsy; and (d) those with drug-resistant epilepsy. Over a 12-month period, data regarding the consuming of all resources (i.e., consultations, tests, hospital admissions, drugs), were collected for each patient. Using the Italian National Health Service tariffs, the unit cost of each resource was calculated and indicated in Euros, the European currency. Results: A total of 189 patients was enrolled by two teaching-CR hospitals, two general hospitals, and two outpatient services. The patients were evenly distributed across the four categories of epilepsy. The mean annual cost per person with epilepsy was 1,767 Euros. Drug-resistant epilepsy was the most expensive category (3,268 Euros) followed by newly diagnosed epilepsy (1,907 Euros), active non,drug-resistant epilepsy (1,112 Euros), and epilepsy in remission (844 Euros). Costs were generally highest in teaching-CR hospitals and lowest in outpatient services. Hospital services were the major cost in all epilepsy groups, followed by drugs. Conclusions: The cost of epilepsy in children and adolescents in Italy tends to vary significantly depending on the severity and duration of the disease Hospitals services and drugs are the major sources of costs. The setting of health care plays a significant role in the variation of the costs, even for patients in the same category of epilepsy. [source]

Revisiting the role of the insula in refractory partial epilepsy

EPILEPSIA, Issue 3 2009
Dang Khoa Nguyen
Summary Purpose:, Recent evidence suggesting that some epilepsy surgery failures could be related to unrecognized insular epilepsy have led us to lower our threshold to sample the insula with intracerebral electrodes. In this study, we report our experience resulting from this change in strategy. Methods:, During the period extending from October 2004 to June 2007, 18 patients had an intracranial study including 10 with insular coverage. The decision to sample the insula with intracerebral electrodes was made in the context of (1) nonlesional parietal lobe-like epilepsy; (2) nonlesional frontal lobe-like epilepsy; (3) nonlesional temporal lobe-like epilepsy; and (4) atypical temporal lobe-like epilepsy. Results:, Intracerebral recordings confirmed the presence of insular lobe seizures in four patients. Cortical stimulation performed in 9 of 10 patients with insular electrodes elicited, in decreasing order of frequency, somatosensory, viscerosensory, motor, auditory, vestibular, and speech symptoms. Discussion:, Our results suggest that insular cortex epilepsy may mimic temporal, frontal, and parietal lobe epilepsies and that a nonnegligeable proportion of surgical candidates with drug-resistant epilepsy have an epileptogenic zone that involves the insula. [source]

Slow Repetitive TMS for Drug-resistant Epilepsy: Clinical and EEG Findings of a Placebo-controlled Trial

Transient Athetosis Induced by Tiagabine

EPILEPSIA, Issue 4 2006
Mario Tombini
Summary:, Movement disorders have been reported with use of different antiepileptic drugs (AEDs). We report a 32-year-old woman, affected by a symptomatic focal drug-resistant epilepsy and a mild hemiparesis, with acute athetoid movements, transiently linked to increasing tiagabine (TGB) therapy. To our knowledge, no other cases of acute athetosis related to TGB have been reported to date. However, we cannot rule out the possibility that involuntary movements were induced by an interaction between TGB and concomitant AEDs, in particular phenobarbital (PB), possibly by increasing GABAergic transmission. We hypothesize that the presence of a static encephalopathy may have influenced the kind of extrapyramidal side effect induced by TGB in our patient, leading to athetosis. [source]

Drug Resistance in Epilepsy: Putative Neurobiologic and Clinical Mechanisms

Functional MRI Predicts Memory Performance after Right Mesiotemporal Epilepsy Surgery

EPILEPSIA, Issue 2 2005
Jozsef Janszky
Summary:,Purpose: Anterior temporal lobe resection (ATR) is a treatment option in drug-resistant epilepsy. An important risk of ATR is loss of memory because mesiotemporal structures contribute substantially to memory function. We investigated whether memory-activated functional MRI (fMRI) can predict postoperative memory loss after anterior temporal lobectomy in right-sided medial temporal lobe epilepsy (MTLE). Methods: We included 16 patients (10 women) aged 16,54 years. The mean age at epilepsy onset was 12.5 years (range, 1,26 years). The patients' mean Wechsler IQ score was 95.2 (range, 62,125). The activation condition of fMRI consisted of retrieval from long-term memory induced by self-paced performance of an imaginative walk. All but one patient had left-sided speech dominance according to speech-activated fMRI. Outside the scanner, we evaluated the pre- and postoperative visual memory retention by using Rey Visual Design Learning Test. Results: We found a correlation between the preoperative asymmetry index of memory- fMRI and the change between pre- and postsurgical measures of memory retention. Reduced activation of the mesiotemporal region ipsilateral to the epileptogenic region correlated with a favorable memory outcome after right-sided ATR. Conclusions: In light of the postoperative results, the theoretical implication of our study is that fMRI based on a simple introspective retrieval task measures memory functions. The main clinical implication of our study is that memory- fMRI might replace the invasive Wada test in MTLE by using a simple fMRI paradigm. Predictive power, however, will be studied in larger patient samples. Other studies are required for left-sided MTLE and neocortical epilepsies to assess the clinical usefulness of memory- fMRI. [source]

Seizure Suppression by Adenosine A1 Receptor Activation in a Mouse Model of Pharmacoresistant Epilepsy

EPILEPSIA, Issue 7 2003
Nicolette Gouder
Summary: Purpose: Because of the high incidence of pharmacoresistance in the treatment of epilepsy (20,30%), alternative treatment strategies are needed. Recently a proof-of-principle for a new therapeutic approach was established by the intraventricular delivery of adenosine released from implants of engineered cells. Adenosine-releasing implants were found to be effective in seizure suppression in a rat model of temporal lobe epilepsy. In the present study, activation of the adenosine system was applied as a possible treatment for pharmacoresistant epilepsy. Methods: A mouse model for drug-resistant mesial temporal lobe epilepsy was used, in which recurrent spontaneous seizure activity was induced by a single intrahippocampal injection of kainic acid (KA; 200 ng in 50 nl). Results: After injection of the selective adenosine A1 -receptor agonist, 2-chloro- N6 -cyclopentyladenosine (CCPA; either 1.5 or 3 mg/kg, i.p.), epileptic discharges determined in EEG recordings were completely suppressed for a period of ,3.5 h after the injections. Seizure suppression was maintained when 8-sulfophenyltheophylline (8-SPT), a non,brain-permeable adenosine-receptor antagonist, was coinjected systemically with CCPA. In contrast, systemic injection of carbamazepine or vehicle alone did not alter the seizure pattern. Conclusions: This study demonstrates that activation of central adenosine A1 receptors leads to the suppression of seizure activity in a mouse model of drug-resistant epilepsy. We conclude that the local delivery of adenosine into the brain is likely to be effective in the control of intractable seizures. [source]

The Costs of Childhood Epilepsy in Italy: Comparative Findings from Three Health Care Settings

Word imageability affects the hippocampus in recognition memory

HIPPOCAMPUS, Issue 6 2005
Peter Klaver
Abstract Concrete words, whose meanings are readily imagined, are better remembered than abstract words. However, the neural correlates of this effect are poorly understood. Here, we investigated the effect of imageability on brain activity in the medial temporal lobe (MTL) processes underlying recognition memory. We recorded event-related potentials (ERPs) via depth electrodes from within the MTL in 14 patients with drug-resistant epilepsy. Patients performed a continuous word recognition task with words of high and low imageability (controlled for word frequency). Behaviorally, recognition performance was better for high, compared to low, imageable words. Two ERP components associated with recognition memory, the AMTL-N400 and the hippocampal late negative component, showed an old/new effect, but only the hippocampal P600 showed a main effect of imageability. We suggest that the hippocampal effect of imageability in recognition memory may be associated with conceptual or pictorial information processing of concrete words. © 2005 Wiley-Liss, Inc. [source]

Ketones: Metabolism's Ugly Duckling

NUTRITION REVIEWS, Issue 10 2003
Theodore B. Vanitallie MD
Ketones were first discovered in the urine of diabetic patients in the mid-19th century; for almost 50 years thereafter, they were thought to be abnormal and undesirable by-products of incomplete fat oxidation. In the early 20th century, however, they were recognized as normal circulating metabolites produced by liver and readily utilized by extrahepatic tissues. In the 1920s, a drastic "hyperketogenic" diet was found remarkably effective for treatment of drug-resistant epilepsy in children. In 1967, circulating ketones were discovered to replace glucose as the brain's major fuel during the marked hyperketonemia of prolonged fasting. Until then, the adult human brain was thought to be entirely dependent upon glucose. During the 1990s, dietinduced hyperketonemia was found therapeutically effective for treatment of several rare genetic disorders involving impaired neuronal utilization of glucose or its metabolic products. Finally, growing evidence suggests that mitochondrial dysfunction and reduced bioenergetic efficiency occur in brains of patients with Parkinson's disease (PD) and Alzheimer's disease (AD). Because ketones are efficiently used by mitochondria for ATP generation and may also help protect vulnerable neurons from free radical damage, hyperketogenic diets should be evaluated for ability to benefit patients with PD, AD, and certain other neurodegenerative disorders. [source]

Valproic acid and phenobarbital blood levels during the first month of treatment with the ketogenic diet

ACTA NEUROLOGICA SCANDINAVICA, Issue 4 2010
G. Coppola
Coppola G, Verrotti A, D'Aniello A, Arcieri S, Operto FF, Della Corte R, Ammendola E, Pascotto A. Valproic acid and phenobarbital blood levels during the first month of treatment with the ketogenic diet. Acta Neurol Scand: 2010: 122: 303,307. © 2010 John Wiley & Sons A/S. Objective,,, The aim of this study was to assess how the ketogenic diet influences the blood levels of antiepileptic drugs in the first month of treatment in a pediatric population with drug-resistant epilepsy. Methods,,, The plasma concentrations of antiepileptic drugs were investigated in an open study on 36 consecutive children and adolescents (20 males), aged between 6 months and 16 years (mean age 4.7 years), who were put on the ketogenic diet because of medically refractory epilepsy. The plasma levels of antiepileptic drugs were determined 30 days and immediately before the diet and on days 8, 15, 22 and 29 after the start of the diet. The daily dose of each drug was not changed during the first month of treatment, while the daily dose of benzodiazepines was reduced by up to 30% if excessive sedation or drowsiness occurred. Results,,, While plasma concentrations of phenobarbital did not change in the first month on the ketogenic diet (mean increase of 2.3 mg/l ± 1.0), valproic acid showed a slight but not significant decrease (mean decresase of 6.7 mg/l ± 3.2), 2 weeks after the start of the diet. Conclusions,,, Adjustments in the daily dose of either drug before the start of the diet do not however appear to be justified. [source]

Uncontrolled epilepsy following discontinuation of antiepileptic drugs in seizure-free patients: a review of current clinical experience

ACTA NEUROLOGICA SCANDINAVICA, Issue 5 2005
D. Schmidt
Purpose,,, We reviewed the impact of planned discontinuation of antiepileptic drugs (AEDs) in seizure-free patients on seizure recurrence and the seizure outcome of reinstituted treatment. Methods,,, A literature review was performed yielding 14 clinical observations of seizure recurrence after discontinuation and its treatment outcome. Results,,, Seizure recurrence rate after AED discontinuation ranged between 12 and 66% (mean 34%, 95%CI: 27,43) in the 13 reviewed studies (no data in one study). Reinstitution of AEDs after recurrence was efficacious between 64,91% (mean of 14 studies, 80%, 95%CI: 75,85%) at follow-up. Mean follow-up ranged from 1,9 years. Seizure outcome of resumed treatment was not different for series in children and adolescents (84%, mean of 4 studies, 95%CI: 75,93) or in adults only (80%, mean of 9 studies, 95%CI: 74,86). Although seizure control was regained within approximately one year in half of the cases becoming seizure free, it took some patients as many as 5,12 years. In addition, in 19% (mean of 14 studies, 95%CI: 15,24%), resuming medication did not control the epilepsy as before, and chronic drug-resistant epilepsy with many seizures over as many as five years was seen in up to 23% of patients with a recurrence. Factors associated with poor treatment outcome of treating recurrences were symptomatic etiology, partial epilepsy and cognitive deficits. Conclusions,,, These serious and substantial risks weigh against discontinuation of AEDs in seizure-free patients, except perhaps for selected patients with idiopathic epilepsy syndromes of childhood or patients with rare seizures. [source]

Coeliac disease, unilateral occipital calcifications, and drug-resistant epilepsy: successful lesionectomy

ACTA NEUROLOGICA SCANDINAVICA, Issue 3 2005
K. O. Nakken
Purpose , To draw attention to the triad of coeliac disease (CD), occipital calcifications, and drug-resistant epilepsy, with focus on the outcome of epilepsy surgery. Methods , We describe a male patient who despite a diagnosis of CD from the age of 9 did not comply with the gluten-free diet. At the age of 11 he developed simple and complex partial seizures with visual symptoms, anxiety, and ambulatory automatisms. His epilepsy appeared to be drug resistant, and after having tried nine antiepileptic drugs (AEDs), alone or in combinations, he underwent a presurgical evaluation at the age of 30. Interictal standard electroencephalograms (EEGs) disclosed frequent biparieto-occipital epileptiform discharges. Computed tomography showed cortical,subcortical punctate calcifications in the right parieto-occipital region, where his seizures seemed to start, according to ictal EEG registrations from intracranial strip electrodes. Results , At the age of 31 he underwent epilepsy surgery. A 5 × 6 cm large area of the right parieto-occipital region was resected, including the area with calcifications. Except for a few short-lasting episodes of anxiety (simple partial seizures?) he has now been seizure-free for 12 years. AEDs were withdrawn 5 years ago. Postoperatively he was left with an upper left-sided quadrant anopsia, which is not bothering him. Conclusions , In patients with CD, unilateral occipital calcifications, and drug-resistant epilepsy, epilepsy surgery should be considered, as a lesionectomy might be very successful. [source]

Prognostic factors in the surgical treatment of medically intractable epilepsy associated with mesial temporal sclerosis

ACTA NEUROLOGICA SCANDINAVICA, Issue 6 2001
M. J. Hennessy
Objectives, To assess the prognostic factors determining seizure remission after temporal lobectomy for intractable epilepsy associated with mesial temporal sclerosis (MTS) at pathology. Methods, The clinical and investigative features of 116 consecutive patients who had temporal lobe surgery for drug-resistant epilepsy and MTS at pathology were assessed using actuarial statistics and logistic regression analysis. Results, At a median follow-up of 63 months the probability of achieving at least a 1-year period of continuous seizure freedom was 67%. Factors contributing to a favourable outcome were interictal EEG localization to the operated lobe and the absence of secondarily generalized seizures. These were also selected in the multivariate analysis, although at lower statistical significance (P=0.08 and 0.09, respectively). Perinatal complications were associated with a significantly worse outcome but overall, complicated febrile convulsions and congruent neuropsychological deficits were not significantly predictive variables. Conclusions, The present findings may aid in the non-invasive presurgical assessment of patients with intractable TLE and clinical and neuroimaging evidence of MTS. [source]