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.

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.

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.

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.

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.

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.

Immunological mechanisms in the aetiology of epilepsy: implications for treatment.

About 30 years ago, an autoimmune reaction was hypothesised in animal models of epilepsy and for the genesis of the 'mirror focus' in some patients with refractory epilepsy. However, this hypothesis did not attract attention among clinicians. During the 1950s, cortisone and corticotropin appeared to be efficacious in some epileptic syndromes, but the link with the immune system was not made. Furthermore, controlled studies were not rigorously planned and the best dosage and schedule still remain unknown. Later, immune deficits were described in patients with epilepsy, but the origin (disease-related or treatment-related) of these deficits is still open. An immunogenetic predisposition was also described in these patients, but results were often contradictory. During the 1980s, the successful use of intravenous immunoglobulin (IVIg) in childhood epilepsies again suggested a possible autoimmune process in some patients. During the last few years, specific autoantibodies have been found in Rasmussen disease and other epileptic syndromes. Immunomodulatory treatments (IVIg, plasmapheresis) have been used with significant success in refractory epilepsies, and IVIg is considered by most epileptologists as the first-choice treatment in Rasmussen syndrome. Recent work has shown that autoantibodies directed against some brain components might interact with ion-gated channels or neurotransmitters and therefore affect the stability of neuronal membranes. Autoimmune mechanisms are considered possible in the process of epileptogenesis. Taking this hypothesis further, immunomodulatory treatment at the time of brain injury (such as by trauma, prolonged seizures or stroke) could offer a preventive approach against epileptogenesis and therefore prevent recurrent seizures.

Bradycardia, an epileptic ictal manifestation.

Two patients with recurrent paroxysmal cardio-vascular symptoms are described. The first, an adult, suffered from syncopal events which did not respond to carbamazepine treatment and had a normal interictal EEG and ECG. The second, a child, presented with attacks of cyanosis, apnoea, and non-responsiveness in clusters, with normal interictal examinations. In both patients, prolonged simultaneous EEG and ECG monitoring demonstrated ictal bradycardia accompanied by paroxysmal discharges in the left temporal area.

Effect of levetiracetam in patients with epilepsy and interictal epileptiform discharges.

The effect of acute treatment with the new antiepileptic drug (AED) levetiracetam (Keppra) on the frequency of interictal epileptiform discharges (IEDs) was evaluated in a double-blind, placebo-controlled, crossover study with therapeutic drug monitoring and serial electroencephalographic (EEG) observations. Acute (500 mg twice daily) and chronic (individualized, 500-1000 mg twice daily) doses of levetiracetam were administered as an add-on to current AED treatment. Efficacy was tested by measuring the frequency of IEDs in EEG recordings and the number of seizures. A single acute dose of levetiracetam induced a reduction of IEDs in eight out of ten patients. During the acute phase, an insufficient number of seizures occurred for analysis. During chronic treatment over 8 weeks, seven patients showed a reduction in seizure frequency (responder rate), and one patient remained seizure free. No correlation was seen between levetiracetam levels and IED frequency. Doses of levetiracetam of up to 2000 mg/day were well tolerated, and no interactions were seen with concomitant AEDs.

Non-epileptic seizures: delayed diagnosis in patients presenting with electroencephalographic (EEG) or clinical signs of epileptic seizures.

The clinical differentiation between epileptic seizures (ES) and non-epileptic seizures (NES) is often difficult and mostly based on the presence or absence of widely recognized features of ES such as tongue biting, falling, incontinence or concomitant epileptic abnormalities in the electroencephalogram (EEG). We retrospectively analysed the records of all patients referred to our Epilepsy Centre for refractory epilepsy and finally diagnosed with NES between 1980 and 1999 ( n= 103), half of them also exhibiting ES. The mean time-lapse between first attack and NES diagnosis was 8.7 +/- 1.3 years and 16.5 +/- 1.4 years for the NES and NES + ES groups respectively. At least one of the usual signs associated with generalized tonic-clonic seizures (tongue biting, falling or incontinence) was reported by 66% and 60% of patients with NES or NES + ES respectively. Interictal EEG abnormalities were recorded in 16% of NES patients vs. 80% of NES + ES patients. In the NES group, delay before establishing the correct diagnosis was significantly longer when the patients exhibited > or =1 symptom(s) of generalized seizures, or when patients exhibited interictal EEG abnormalities. Upon admission, 72% of NES patients and all NES + ES patients were being treated with antiepileptic drugs (AEDs).We conclude that EEG or clinical abnormalities suggestive of epileptic seizures are common in undiagnosed NES patients. Such diagnostic pitfalls, besides considerably delaying NES diagnosis, also considerably delay appropriate treatment implementation.

Medical treatment of newly diagnosed epilepsy.

The first step in the treatment of epilepsy is the confirmation of the diagnosis. A correct diagnosis not only includes the epileptic origin of the event, but also the diagnosis of the seizure type and the epileptic syndrome. The second step is to try to find the aetiology of the seizures. Some papers have shown that the prognosis of epilepsy is better if the seizures are treated earlier, but other papers did not find any difference in the long-term prognosis between patients treated after the first seizure or after several seizures. Therefore, one of the most difficult points, after confirmation of the diagnosis, with a first or few seizures will be to identify the risks of relapse in some patients and to immediately treat them and to avoid treating the others who will have only one or rare seizures during their lives without any damage. In most cases, the first treatment will be the prescription of an antiepileptic drug (AED) in monotherapy. If the cause is treatable, it will be treated concomitantly. In generalised epilepsies, especially in idiopathic syndromes, valproate will be the first choice, most of the classic AEDs may worsen some seizure types in these syndromes. In partial epilepsies, there are no statistically significant differences in efficacy between the 4 classic major AEDs (carbamazepine, phenytoin, phenobarbitone and valproate) in pooled data. The choice of the drug should be more influenced by considerations of safety profile, dosing frequency, and costs for equivalent advantages. Accordingly, valproate is a good first choice in patients in whom the epilepsy syndrome is not clearly defined. Efficacy of newer AEDs is similar to old AEDs but most are better tolerated. However, some studies including seizure control, side effects, medical consultation, inpatient, accidental injuries, and laboratory investigations showed that newer AEDs are more expensive in newly diagnosed patients, compared to classic major AEDs and this notion should be taken into account for the prescription.

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.

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.

[Bradycardia: an unrecognized complication of some epileptic crises]. / La bradycardie: une complication méconnue de certaines crises épileptiques.

A 36-year-old man, treated for epilepsy since early childhood, was hospitalized for nocturnal paroxysmal disorders. The EEG-EKG-video monitoring revealed complex partial seizures with bradycardia secondary to a sino-auricular block. The occurrence of autonomic disturbances during seizures is well known, mostly described in temporal epilepsy. Ictal bradycardia, with asystole, has been unfrequently reported, while tachycardia appears more common. A systematic investigation of cardiac data synchronized with EEG recordings, especially in case of aspecific fainting, could give a more accurate diagnosis and treatment, and so reducing sudden unexplained death in epileptic patients.

[External and internal hydrocephalus caused by an arteriovenous malformation in an infant]. / Hydrocéphalie externe et interne par malformation artério-veineuse chez un nourrisson.

In a 9 month-old infant, who displayed an epileptic seizure, the Brain CT-Scan shows a ventricular enlargement and a bilateral pericerebral effusion, associated with a left parieto-temporal arterio-venous malformation. Angiogram reveals a small angioma shunting the blood flow from the left middle cerebral artery into the lateral sinus. Intracranial pressure, recorded with a fontanellar transducer, is borderline. The angioma is excised and the operation, during which the subarachnoid location of the pericerebral effusion is confirmed, is followed by gradual subsiding of the internal and external hydrocephalus, that was caused by enhancement of the pressure in the venous sinuses. This case belongs to an infantile form of Benign Intracranial Hypertension, in which CT-Scan has to be interpreted cautiously, to avoid the pitfall of a wrong diagnosis of brain atrophy.