Kenou van Rijckevorsel

Deep EEG Recordings of the Mammillary Body in Epilepsy Patients

Summary:  Purpose: To our knowledge, the epileptic and nonepileptic electroencephalographic (EEG) discharges recorded within the human mammillary body (MB) and mammillothalamic tract (MTT) areas have never been published. Herein, we present the EEG recordings from these structures in patients with refractory epilepsy (RE).

A prospective, multicenter study of cardiac-based seizure detection to activate vagus nerve stimulation.

PURPOSE This study investigates the performance of a cardiac-based seizure detection algorithm (CBSDA) that automatically triggers VNS (NCT01325623). METHODS Thirty-one patients with drug resistant epilepsy were evaluated in an epilepsy monitoring unit (EMU) to assess algorithm performance and near-term clinical benefit. Long-term efficacy and safety were evaluated with combined open and closed-loop VNS. RESULTS Sixty-six seizures (n=16 patients) were available from the EMU for analysis. In 37 seizures (n=14 patients) a ≥ 20% heart rate increase was found and 11 (n=5 patients) were associated with ictal tachycardia (iTC, 55% or 35 bpm heart rate increase, minimum of 100 bpm). Multiple CBSDA settings achieved a sensitivity of ≥ 80%. False positives ranged from 0.5 to 7.2/h. 27/66 seizures were stimulated within ± 2 min of seizure onset. In 10/17 of these seizures, where triggered VNS overlapped with ongoing seizure activity, seizure activity stopped during stimulation. Physician-scored seizure severity (NHS3-scale) showed significant improvement for complex partial seizures (CPS) at EMU discharge and through 12 months (p<0.05). Patient-scored seizure severity (total SSQ score) showed significant improvement at 3 and 6 months. Quality of life (total QOLIE-31-P score) showed significant improvement at 12 months. The responder rate (≥ 50% reduction in seizure frequency) at 12 months was 29.6% (n=8/27). Safety profiles were comparable to prior VNS trials. CONCLUSIONS The investigated CBSDA has a high sensitivity and an acceptable specificity for triggering VNS. Despite the moderate effects on seizure frequency, combined open- and closed-loop VNS may provide valuable improvements in seizure severity and QOL in refractory epilepsy patients.

Impact of early hemispherotomy in a case of Ohtahara syndrome with left parieto-occipital megalencephaly.

This report illustrates the usefulness and safety of very early hemispherotomy in an infant with Ohtahara syndrome (OS) secondary to left parieto-occipital megalencephaly. It provides evidence that surgical intervention might provide promising results in selected cases, and that young age is not a contraindication for this type of surgery.

Recommendations for the treatment of epilepsy in adult patients in general practice in Belgium: an update

In 2008, a group of Belgian epilepsy experts published recommendations for antiepileptic drug (AED) treatment of epilepsies in adults and children. Selection of compounds was based on the registration and reimbursement status in Belgium, the level of evidence for efficacy, common daily practice and the personal views and experiences of the authors. In November 2011 the validity of these recommendations was reviewed by the same group of Belgian epilepsy experts who contributed to the preparation of the original paper. The recommendations made in 2008 for initial monotherapy in paediatric patients were still considered to be valid, except for the first choice treatment for childhood absence epilepsy. This update therefore focuses on the treatment recommendations for initial monotherapy and add-on treatment in adult patients. Several other relevant aspects of treatment with AEDs are addressed, including considerations for optimal combination of AEDs (rational polytherapy), pharmacokinetic properties, pharmacodynamic and pharmacokinetic interaction profile, adverse effects, comorbidity, treatment of elderly patients, AED treatment during pregnancy, and generic substitution of AEDs.

Epileptic discharges in a mammillary body of a patient with refractory epilepsy

Objectives.  To document epileptiform discharges recorded within a mammillary body (MB) of a patient with chronic refractory epilepsy (CRE).

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.

Perioral myoclonia with absences and myoclonic status aggravated by oxcarbazepine

Perioral myoclonia with absences belongs to the “idiopathic generalised epilepsy syndromes in development”, currently not yet cited in the ILAE classification. This epilepsy syndrome is associated with a seizure type that appears to be specific. Here, we report polygraphic recordings of this seizure type in a young boy, previously misdiagnosed with focal epilepsy. EEG and clinical features were useful to differentiate diagnosis of his seizures from other absence or myoclonic seizures. Interestingly, some seizures were associated with neck myoclonia. Home video recording of myoclonic status aggravated by inappropriate treatment is also presented.

Post-resection electrocorticography has no added value in epilepsy surgery.

Intra-operative electrocorticography (ECoG) has been traditionally used in the surgical management of medically refractory partial epilepsies to identify the limits of the epileptogenic zone. This retrospective study had as goal to evaluate whether tailored surgery based on the presurgical evaluation completed by intra-operative post-resection ECoG improves outcome. We reviewed 94 cases of epilepsy surgery with intra-operative ECoG and determined how many had an ECoG-guided surgical procedure in addition to the initial planned surgery. We also reviewed the presence of specific recurrent ECoG patterns of interictal epileptiform discharges (IED) in the exposed cortical surface, such as: electrographic seizures, bursts, intermittent spike waves, polyspikes or fast rhythms and continuous or quasi-continuous spiking. When performing a post-resection ECoG-tailored surgery, outcome did not improve in lesional or non-lesional epilepsy. Postoperative residual IED did not correlate with a poorer outcome. In our study, the persistence of post-resection IED on ECoG is not correlated with outcome in patients with lesional or non-lesional epilepsy.

Development of an electronic decision tool to support appropriate treatment choice in adult patients with epilepsy – Epi-Scope®

BACKGROUND Given the continuous knowledge progression and the growing number of available antiepileptic drugs (AEDs), making appropriate treatment choices for patients with epilepsy is increasingly difficult. While published guidelines help for separate clinical aspects, patients with a combination of specific characteristics may escape proper guidance. This study aimed to determine the appropriateness of AEDs for particular clinical variables and to offer treatment recommendations for adult patients with epilepsy in a user-friendly format for practicing neurologists. METHODS Using the RAND/UCLA Appropriateness Method, the appropriateness of AEDs as initial/second mono-therapy and combination therapy was assessed in relation to selected clinical variables by a Belgian panel of 13 experts in epilepsy. Panel recommendations for particular patient profiles were determined by the outcome of these separate ratings. RESULTS The appropriateness outcome of individual AEDs was not substantially different between first and second mono-therapy; valproate was considered appropriate for all types of generalised and partial seizures. The outcome for combination therapy was highly dependent on the type of AED and seizures. With respect to co-morbidities and co-treatments, levetiracetam and pregabalin proved to have the least contra-indications. For the elderly and with respect to factors related to the female reproductive system the appropriateness of AEDs showed a more diffuse pattern. Although caution was deemed necessary for some combinations, the AEDs were never considered inappropriate regarding their drug interaction profile. CONCLUSIONS The Epi-Scope(®) tool that displays appropriateness recommendations for highly specific, possibly complex cases, supports optimal treatment choices for adult patients with epilepsy in daily practice.

Impact of reimbursement restrictions on the choice of antiepileptic drugs: Belgian Study on Epilepsy Treatment (BESET).

BACKGROUND In Belgium, new and costly antiepileptic drugs (AEDs) are only reimbursed as second-line treatment, after documented treatment with conventional and cheaper AEDs has failed. The objective of this study was to describe the treatment of epilepsy in Belgium and to analyze the impact of the reimbursement restrictions on the choice of AEDs. METHODS Between May and June 2003, a sample of 100 neurologists, representative of the entire neurological community in teaching, academic, and regional hospitals in Belgium, were personally interviewed on the basis of a structured questionnaire (modified Rand method). The questionnaire contained questions on treatment choices and strategies in adult epilepsy. RESULTS Unanimously, initial monotherapy was the preferred treatment strategy in all types of epilepsy. In the opinion of most neurologists, valproate was the first choice for idiopathic generalized and focal epilepsy with/without secondary generalization. Carbamazepine as their first choice for the treatment of focal epilepsy. New AEDs were most often prescribed as second-line therapy. Lamotrigine was the most frequently prescribed new AED and used for both generalized and focal epilepsy. It was followed by levetiracetam, topiramate and oxcarbazepine for focal epilepsy. In the absence of reimbursement restrictions, two new AEDs would be significantly more often prescribed as a first-line therapy: lamotrigine for idiopathic generalized epilepsy and oxcarbazepine for focal epilepsy. CONCLUSIONS The neurologists reached a high level of consensus on many of the key treatment questions. Monotherapy with valproate and carbamazepine was the standard treatment strategy in Belgium. Lamotrigine and less so levetiracetam, topiramate and oxcarbazepine were commonly prescribed as second-line AEDs. In the absence of reimbursement restrictions, lamotrigine and oxcarbazepine would be more frequently prescribed.