Multiple subpial transections and magnetic resonance imaging.

INTRODUCTION: Multiple subpial transection (MST) has been applied to the treatment of refractory epilepsy when epileptogenic zone involves eloquent areas since 1989. However, there is a lack of data evaluating the effect of this surgical technique on the cortex as measured by Magnetic Resonance Imaging (MRI). PATIENTS AND METHODS: Ten consecutive patients (3F/7M, average age: 18.5 years) were operated on using radiating MST (average: 39; min: 19, max: 61) alone (n=3) or associated with another technique (n=7). Seven patients underwent a post-operative 3.0T MRI while 3 had a 1.5T MRI. Three patients had an early post-operative MRI and 7 a late MRI, among which 3 previously had an intraoperative MRI. RESULTS: The MR sequences that allowed the best assessment of MST-induced changes were T2 and T2*. The traces of MST are more visible on late MRI. These discrete non-complicated stigmas of MST were observed in all 10 studied patients: on the intraoperative MRI they are seen as micro-hemorrhagic spots (hypo-T2), on the early postoperative MRI as a discreet and limited cortical edema whether associated or not with micro-hemorrhagic spots and on the late MRI as liquid micro-cavities (hyper-T2) surrounded with a fine border of hemosiderin. CONCLUSIONS: MST-induced cerebral lesions are best visualized in T2-sequences, mainly on the late postoperatively MRIs. On all the MRI examinations in this study, the MST are only associated with limited modifications of the treated cortical regions.

Topiramate in childhood epileptic encephalopathy with continuous spike-waves during sleep: A retrospective study of 21 cases.

OBJECTIVE: Encephalopathy with continuous spike-wave during sleep (CSWS) is a particularly difficult-to-treat childhood epileptic syndrome. This study sought to present the EEG improvement and clinical efficacy of topiramate (TPM), a broad spectrum antiepileptic drug (AED), in a series of 21 children with CSWS encephalopathy. METHODS: We retrospectively reviewed the EEG results and clinical data of children with CSWS followed-up in our institution and treated with TPM. Sleep EEGs were performed 0-3 months prior to TPM introduction and then at 3 and 12 months. The exclusion criteria were (1) introduction of another AED and (2) withdrawal of a potentially aggravating AED during the first 3 months of treatment. In addition to spike index (SI), the severity of EEG abnormalities was rated using an original scale that also considered the spatial extent of interictal epileptiform discharges. RESULTS: 21 patients were included (18 males, 4-14y, three symptomatic cases). At 3 months, sleep EEG was improved in 14 and normalized in four (TPM doses: 2-5.5 mg/kg/day). Among these 18 patients, 16 manifested cognitive or behavioural improvement. In a subgroup of seven patients with frequent seizures, five became seizure-free and one had over 75% decrease in seizure frequency. At the one-year follow-up, 20 children were still on TPM and 10 exhibited persistent EEG improvement without any other AED being introduced, most of them with clinical benefits. CONCLUSION: TPM can decrease EEG abnormalities in epileptic encephalopathy with CSWS, achieving clinical improvement in the majority of patients. However, relapse may occur in the long-term in nearly half of cases. Otherwise, TPM has proven particularly useful in reducing seizure frequency in refractory cases.

Invasive EEG in refractory epilepsy: insertion of subdural grids through linear craniectomy reduces complications and remains effective.

OBJECTIVE: To evaluate our technique of implanting subdural grids by linear craniectomy under computer-assisted navigation for invasive electroencephalography in medically refractory epilepsy. MATERIAL AND METHOD: We report results from our first 38 consecutive patients with medically refractory epilepsy who underwent subdural grids implantation by linear craniectomy. For each case, a preoperative MRI was performed for navigation followed by a postoperative MRI for localization control of the intracranial electrode contacts. A linear skin incision, adapted to the depth and type of subdural electrode (strip or grid) and compatible with possible subsequent therapeutic surgery, was carried out. One or two linear craniectomies (maximal length 6cm, width 1cm) were then drilled with a bevel. The dura mater was incised under microscopic guidance to avoid opening the arachnoid. The required subdural electrodes were then slipped subdurally through each linear craniectomy (letter-box technique). RESULTS: Forty-one invasive electroencephalographies were performed with 28 (68%) bilateral. For all invasive electroencephalographies, at least one subdural grid was implanted. Sixty-one subdural grids were implanted in total, 52 with 20 contacts and nine with 32 contacts. No cerebrospinal fluid leakage, no infection, no neurological deficit and no permanent complications were observed. Three subdural grids (5%) were not positioned exactly as planned but this had no consequence for the invasive electroencephalography analysis. CONCLUSION: The implantation of 61 consecutive subdural grids for invasive electroencephalography through linear craniectomies was associated with no transient or permanent complications in this population. This letter-box technique appears to be practical and safe without limiting explorative efficacy.

Takotsubo syndrome (TKS): a possible mechanism of sudden unexplained death in epilepsy (SUDEP).

We report a case of Takotsubo syndrome after epilepsy, and review the literature. We identified 59 cases of Takotsubo syndrome after focal or generalised epilepsy. As in Takotsubo syndrome in general, the patients were mostly female (84%), with a mean age of 63 years, and the evolution was generally favourable. There was one death and one stroke, and 4 cases were of relapsing Takotsubo after a new seizure. Takotsubo syndrome may induce cardiac arrhythmias. A near-SUDEP (sudden unexplained death in epilepsy) was reported in one patient. Animal models of SUDEP have shown similar cardiac lesions to those seen in Takotsubo syndrome, and strengthen the hypothesis of a link between these conditions. Takotsubo syndrome after epilepsy may be relatively common; we suggest measurement of serum troponin levels in high-risk patients and cardiac follow-up.

Epileptic syndromes: differential treatment in infants, children, and adolescents.

This paper proposes therapeutic guidelines for the management of some epileptic syndromes in infants, children, and adolescents, based on available medical literature and clinical practice in the French Community of Belgium. The guidelines address both epileptic encephalopathies (West syndrome, Lennox-Gastaut syndrome, and Dravet syndrome) and idiopathic epilepsies (typical absence seizures, epilepsy with centro-temporal spikes and juvenile myoclonic epilepsy).

Opinion of Belgian neurologists on antiepileptic drug treatment in 2006: Belgian study on epilepsy treatment (BESET-2).

OBJECTIVES: (i) To describe the medical treatment of epilepsy in Belgium in 2006, (ii) to detect the presence or absence of consensus in epilepsy treatment and (iii) to analyze the evolution of the neurologists' opinion between 2003 and 2006. MATERIALS AND METHODS: In December 2006, 100 neurologists were interviewed with a structured questionnaire, based on ordinal four-point scales. The questionnaire contained questions on treatment choices in adult patients with epilepsy. The results of this survey were compared with results of a previous one done in 2003. RESULTS: Initial monotherapy was the preferred treatment strategy. Valproate was first choice in idiopathic generalized epilepsy. Carbamazepine and oxcarbazepine were first choice in focal epilepsy with partial seizures. Valproate was also first choice in focal epilepsy with secondarily generalized seizures. New antiepileptic drugs were recommended in second line. However, in special treatment situations, they were considered first-line, e.g. lamotrigine in case of women in childbearing age. In comparison with 2003, there was a trend of using earlier the new antiepileptic drugs. CONCLUSIONS: In end 2006, carbamazepine, valproate and oxcarbazepine were considered to be first choice drugs, whereas other newer drugs, like lamotrigine, levetiracetam and topiramate were predominantly prescribed in second line.

[Safety and efficacy of multiple subpial transections: report of a consecutive series of 30 cases]. / Sécurité et efficacité des trans-sections sous-piales multiples: analyse d'une série consécutive de 30 patients.

PURPOSE: To present our results using multiple subpial transections (MST) for the treatment of pharmacologically refractory epilepsy (PRE) with epileptogenic foci in eloquent areas. METHOD: Between 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). RESULTS: In 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. CONCLUSION: This 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.

Current approaches to the use of generic antiepileptic drugs.

Generic substitution is encouraged as a cost containment strategy for the management of health care resources. However, in epilepsy, the consequences of loss of symptom control are important, and antiepileptic drugs have narrow therapeutic indices. For this reason, generic substitution may be problematic, and certain health authorities have excluded antiepileptic drugs from overall policy recommendations on generic prescribing. The absence of bioequivalence data among generic forms and the relatively broad criteria for bioequivalence with the branded drug allow differences in drug exposure to arise that may be clinically relevant and necessitate monitoring of plasma levels when switching formulations to avoid loss of seizure control or emergence of side effects. Management of these issues carries a significant cost, which should be weighed carefully against the cost savings acquired when purchasing the drug. Both physicians and patients have a right to be informed and approve before pharmacists make a generic substitution or switch between generics.

Opinion of Belgian neurologists on antiepileptic drugs: Belgian Study on Epilepsy Treatment (BESET).

OBJECTIVES: To describe the choice of treatment in adult patients with epilepsy in Belgium, to detect the presence or absence of consensus among neurologists in epilepsy treatment, and to analyze the gaps between current guidelines and prescriptions. MATERIALS AND METHODS: Hundred Belgian neurologists were systematically interviewed between May and June 2003 using a structured questionnaire (modified Rand method). RESULTS: Initial monotherapy was the preferred treatment strategy. Valproate was the first choice in idiopathic generalized epilepsy (IGE) and carbamazepine in focal epilepsy (FE). The new antiepileptic drugs (AED) were usually recommended in second-line. However, in special treatment situations, they were considered first-line, e.g., lamotrigine in case of women of childbearing age. CONCLUSIONS: Neurologists reached consensus for most questions on epilepsy treatment. In 2003, monotherapy with valproate and carbamazepine was the common treatment strategy in Belgium, whereas lamotrigine and to a lesser extent levetiracetam, topiramate, and oxcarbazepine were predominantly prescribed in second-line. This is in agreement with the recently published UK epilepsy guidelines but not in agreement, however, with the US guidelines, that for new onset epilepsy, new and old drugs are equally effective. Belgian neurologists, except for some special situations still prefer old drugs as first line.

Guidelines for the management of epilepsy in the elderly.

Seizures starting in patients over 60 years old are frequent. Diagnosis is sometimes difficult and frequently under- or overrated. Cerebrovascular disorders are the main cause of a first seizure. Because of more frequent comorbidities, physiologic changes, and a higher sensitivity to drugs, treatment has some specificity in elderly people. The aim of this paper is to present the result of a consensus meeting held in October 2004 by a Belgian French-speaking group of epileptologists and to propose guidelines for the management and the treatment of epilepsy in elderly people.

The epileptic syndromes with continuous spikes and waves during slow sleep: definition and management guidelines.

The authors propose to define the epileptic syndromes with continuous spikes and waves during slow sleep (CSWS) as a cognitive or behavioral impairment acquired during childhood, associated with a strong activation of the interictal epileptiform discharges during NREM sleep--whatever focal or generalized--and not related to another factor than the presence of CSWS. The type of syndrome will be defined according to the neurological and neuropsychological deficit. These syndromes have to be classified among the localization-related epileptic syndromes. Some cases are idiopathic and others are symptomatic. Guidelines for work-up and treatment are proposed.

Cognitive problems related to epilepsy syndromes, especially malignant epilepsies.

Neurocognitive impairment is frequent in epilepsy patients. Causes are multiple, and may be influenced by several factors including the epilepsy syndrome. Most cognitive complaints in adult patients are mental slowness, memory difficulties and attention deficits. In children, cognitive problems are more diffuse, responsible for language troubles, learning difficulties, poor academic outcome, behavior problems and finally unfortunate socio-professional prognosis. The most devastating epilepsy syndromes such as epileptic encephalopathies are nearly exclusively described in infancy and childhood. This paper will review the major cognitive complaints in relation to the epilepsy syndrome, with a more detailed interest for the malignant epilepsies in infancy and childhood such as Ohtahara and West syndrome, Lennox-Gastaut syndrome and epileptic encephalopathis with continuous spike-and-wase during slow wave sleep. The impact of surgery on cognition will be briefly discussed in adults and youger patients.

Clinical, electrophysiological and brain imaging features during recurrent ictal cortical blindness associated with chronic liver failure.

Transient neuroimaging features indicating primary cortical and secondary subcortical white matter cytotoxic oedema have been described in association with prolonged or intense seizures. We describe the unusual condition of recurrent ictal cortical blindness due to focal occipital status epilepticus, in the context of chronic hepatic failure. There was a close association between the onset and disappearance of clinical, electrophysiological and magnetic resonance imaging abnormalities.

Prophylaxis of the epilepsies: should anti-epileptic drugs be used for preventing seizures after acute brain injury?

In many circumstances antiepileptic drugs are used in patients who have never presented any clinical epileptic seizures. These substances are administered on the assumption of a potential risk for the patients of developing acute or delayed chronic seizures after brain injuries such as trauma, stroke, hemorrages or even neurosurgical interventions. The aim of this paper is to propose therapeutic guidelines for the management of this prophylactic attitude in epilepsy based on basic research and clinical practice in the French community in Belgium. We will distinguish between the prevention of acute (early onset-provoked) seizures and a delayed truly post-lesional (unprovoked) epilepsy. Some therapeutic goals can be achieved under the former circumstances whereas in the latter situation we all agree for the absence of any coherent antiepileptic prophylactic behaviour.

Therapeutic issues in women with epilepsy.

Approximately 20% of people with epilepsy are of childbearing potential and about 3 to 5 births per thousand will be to women with epilepsy. Both epilepsy and antiepileptic drugs can cause specific problems in women and embryos (less than 8 weeks of gestational age) or foetuses (more than 8 weeks of gestational age). The aim of this paper is to discuss therapeutic issues for the management of women with epilepsy: initiation of antiepileptic therapy, contraception, pregnancy, breast feeding and menopause. Some fertility issues are also discussed.

Quantification of human brain benzodiazepine receptors using [18F]fluoroethylflumazenil: a first report in volunteers and epileptic patients.

Fluorine-18 fluoroethylflumazenil ([18F]FEF) is a tracer for central benzodiazepine (BZ) receptors which is proposed as an alternative to carbon-11 flumazenil for in vivo imaging using positron emission tomography (PET) in humans. In this study, [18F]FEF kinetic data were acquired using a 60-min two-injection protocol on three normal subjects and two patients suffering from mesiotemporal epilepsy as demonstrated by abnormal magnetic resonance imaging and [18F]fluorodeoxyglucose positron emission tomography. First, a tracer bolus injection was performed and [18F]FEF rapidly distributed in the brain according to the known BZ receptor distribution. Thirty minutes later a displacement injection of 0.01 mg/kg of unlabelled flumazenil was performed. Activity was rapidly displaced from all BZ receptor regions demonstrating the specific binding of [18F]FEF. No displacement was observed in the pons. Plasma input function was obtained from arterial blood sampling, and metabolite analysis was performed by high-performance liquid chromatography. Metabolite quantification revealed a fast decrease in tracer plasma concentration, such that at 5 min post injection about 70% of the total radioactivity in plasma corresponded to [18F]FEF, reaching 24% at 30 min post injection. The interactions between [18F]FEF and BZ receptors were described using linear compartmental models with plasma input and reference tissue approaches. Binding potential values were in agreement with the known distribution of BZ receptors in human brain. Finally, in two patients with mesiotemporal sclerosis, reduced uptake of [18F]FEF was clearly observed in the implicated left hippocampus.

Clinical and EEG findings in six patients with altered mental status receiving tiagabine therapy.

Tiagabine (TGB), a novel GABA reuptake inhibitor antiepileptic drug, has been reported to induce nonconvulsive status epilepticus (NCSE) in patients with generalized or partial onset seizures. We describe six patients with refractory partial epilepsy treated with add-on TGB. They developed acute intermittent or progressive chronic confusion associated with diffuse slowing of the electroencephalogram (EEG), shortly after an increase in dose of TGB. This remitted in each situation after reduction of the daily dose. The possibility of nonconvulsive status epilepticus or toxic encephalopathy is discussed.

Therapeutic strategies in the choice of antiepileptic drugs.

The choice of treatment of newly diagnosed epilepsy involves many factors such as age, sex, life style, general health and concomitant medication. The seizure type, syndrome, and the pharmacology, efficacy and safety of the antiepileptic drugs (AEDs) should also be considered. Some of the new AEDs appear to provide at least equivalent efficacy with better tolerability. Some of these drugs have the potential to become drugs of first choice in newly diagnosed epilepsy. At the present time, we also must consider the criteria of reimbursement of these drugs. In this paper, we try to describe common and practical strategies to start a treatment of newly diagnosed epilepsy.