Arielle Crespel

Increased number of neural progenitors in human temporal lobe epilepsy

An increased neurogenesis is reported in animal models of mesial temporal lobe epilepsy (MTLE) but the fate of newborn cells is unknown. Here, we attempted to demonstrate neurogenesis in adult epileptic tissue obtained after hippocampectomy. MTLE hippocampi showed increased expression of division markers and of Musashi-1, a marker of neural progenitors, compared to control hippocampi. Large quantities of Musashi-1+ cells were obvious in the subgranular layer and the subventricular zone, both known neurogenic areas, and in the fissura hippocampi. Musashi-1 was expressed by small cells that were mainly vimentin+ or nestin+, rarely Dcx+ or PSA-NCAM+ and negative for markers of mature neurons or astrocytes. Some of them are present in the granular layer, the hilus, and CA1 area resembling the ectopic positions described in rodents. These findings demonstrate that neural progenitors proliferate in chronic epilepsy and suggest that the fissura hippocampi behaves like another neurogenic area.

IgG Leakage May Contribute to Neuronal Dysfunction in Drug-Refractory Epilepsies With Blood-Brain Barrier Disruption

Abstract Focal epilepsies are often associated with blood-brain barrier disruption. In 4 entorhinal cortex tissue samples and 13 hippocampal samples from patients with pharmacoresistent temporal lobe epilepsy, we observed immunoglobulin G (IgG) leakage in the parenchyma and IgG-positive neurons that had evidence of neurodegeneration, such as shrinkage and eosinophilia. These findings were not present in samples from 12 nonepileptic control subjects. To complement these findings, we used a rat in vivo model that mimics the development of limbic epilepsy with blood-brain barrier disruption. During epileptogenesis, IgG leakage and neuronal IgG uptake increased concomitantly with the occurrence of seizures. Immunoglobulin G accumulation in neurons was selective, particularly for interneurons and pyramidal neurons. Immunohistochemistry and electron microscopy showed that IgG uptake in the rat neurons was associated with eosinophilia, shrinkage, and ultrastructural degenerative changes. Moreover, IgG-positive neurons lost their NeuN immunohistochemical staining. Together, these observations suggest that IgG leakage is related to neuronal impairment and may be a pathogenic mechanism in epileptogenesis and chronic epilepsy.

Management of juvenile myoclonic epilepsy

Juvenile myoclonic epilepsy (JME) is a common form of epilepsy and a fairly lifelong disorder that may significantly lower a patients expectations and potential for a full life. Luckily, it is also a highly treatable disorder, and up to 85% of patients with JME will enjoy satisfactory seizure control. Among anticonvulsants, valproate still stands out as the most efficacious drug, but may be poorly tolerated by some, and is considered unsafe for the fetuses of pregnant women. Alternatives have emerged in recent years, especially levetiracetam, but also topiramate, zonisamide or lamotrigine. In some cases, combination therapy may be useful or even required. One should not forget the potential aggravation induced not only by some commonly used anticonvulsants, especially carbamazepine and oxcarbazepine, but also, in some patients, by lamotrigine. In special settings, older drugs like benzodiazepines and barbiturates may be useful. But the management of JME should also include intervention in lifestyle, with strict avoidance of sleep deprivation and the management of copathologies, including the cognitive and psychiatric problems that are often encountered. With adequate management, there will only remain a small proportion of patients with uncontrolled epilepsy and all of its related problems. Juvenile myoclonic epilepsy is a condition in which the clinician has a fair chance of significantly helping the patient with medication and counseling.

Idiopathic generalized epilepsy of late onset

Most idiopathic generalized epilepsies have an onset in childhood or adolescence, with a moderate second incidence peak in the presenium predominantly in women. This study addressed the question of a later onset. The available literature and the records of four personal data sets (two prospective incidence surveys of epileptic seizures, one prevalence study of epilepsy, and one clinical series of individuals with epilepsy) were screened for patients who had experienced a first generalized convulsive seizure with bilateral spike-wave complexes on EEG after 60 years of age. Reports of first idiopathic generalized tonic-clonic seizures occurring after age 60 were extremely rare and none was found in our four cohorts regardless of the methodology involved. Only five case reports were found, all involving a woman. Two had a family history of seizure disorders and two had had at least one seizure earlier in life. Idiopathic generalized epilepsy of late onset, if this condition actually exists, is likely to be the consequence of a genetic predisposition triggered by acquired epileptogenic factors.

Dramatic Weight Loss with Levetiracetam

Background: Levetiracetam is considered a “weight‐neutral” drug. We report 19 cases of significant weight loss associated with levetiracetam at a dose ranging from 500 to 2000 mg/day.

Senile myoclonic epilepsy of Genton: Two cases in Down syndrome with dementia and late onset epilepsy

Senile myoclonic epilepsy of Genton is a newer epileptic syndrome of the older patients with Down syndrome associated with an Alzheimer-type dementia. We report two observations in whom the clinical and electroencephalographic features are consistent with the description of this syndrome. Both experienced a progressive deterioration of cognitive functions few years before the onset of the epilepsy. The EEG was characteristic with generalized fast spike-waves or polyspikes or polyspike-waves with or without bilateral myoclonic jerks especially at awakenings. One patient had a photoparoxysmal response (11-21Hz) with bilateral myoclonic jerks. Hence, the senile myoclonic epilepsy of Genton is an easily recognizable newer epileptic syndrome of the older Down syndrome patient.

Sleep before and after temporal lobe epilepsy surgery

PURPOSE Patients with epilepsy often complain of non-restorative sleep. This is the consequence of the acute effect of seizures and the chronic effect of epilepsy responsible for disrupting sleep architecture. Other factors such as antiepileptic drugs (AEDs), also play a role in the alteration of sleep organization. The aim of this study was to evaluate the specific effect of seizures and interictal epileptiform abnormalities (IEAs) on sleep, in particular to see whether reducing seizure frequency by epilepsy surgery might improve sleep organization in these patients. METHODS Eleven patients with refractory mesial temporal lobe epilepsy, who underwent surgical treatment and who were seizure free at the follow-up, were included in the study. Treatment with AEDs was not significantly modified before the second year of follow-up. Patients were evaluated before surgery, at 1-year and 2-year follow-up visits with a videoEEG monitoring (24h/24). At each follow-up visit, interictal epileptiform abnormalities and sleep macrostructure parameters were assessed. RESULTS All patients showed a reduction of their IEAs. At 1-year follow-up, total sleep time and REM sleep increased significantly (p=0.032 and p=0.006, respectively). At 2-year follow-up, an important increase of REM sleep was observed (p=0.028). Most significant variations were noted 1 year after surgery. No significant variations were observed between the first and the second year after surgery. CONCLUSIONS Surgical treatment of temporal lobe epilepsy may improve sleep macrostructure by reducing the number of seizures and of IEAs. These results indirectly confirm the role of epilepsy in disrupting sleep organization chronically.

Cardiac asystole during a cluster of right temporo-parietal seizures

Ictal bradycardia and asystole can appear during an epileptic seizure. They must be promptly recognized and treated due to their potential life threatening consequences. Indeed, they have been implicated in the pathogenesis of sudden unexpected death in epilepsy (SUDEP). We report the case of a 33 year-old woman with a right temporo-parietal lobe epilepsy who presented a 19 s asystole during a cluster of seizures. Careful interview revealed appearance of numerous episodes of fall in the previous years. The patient underwent cardiological investigations including echocardiography and His bundle electrography that resulted to be normal. A pacemaker was immediately implanted and, although she continued presenting seizures, no more episodes of falls occurred. In order to better preview ictal asystole several risk factors need to be searched. Attention should be paid to an accurate medical history (ask for episodes of falls) and a simultaneous ECG/EEG recording. The occurrence of bradycardia during a seizure should lead to further cardiological investigations. This could help preventing the occurrence of dramatic consequences such as traumatic falls or SUDEP.

Carbamazépine et clarithromycine : une interaction médicamenteuse cliniquement significative

Resume Introduction La carbamazepine est soumise a de nombreuses interactions medicamenteuses dont la troleandromycine et l’erythromycine qui inhibent son metabolisme. La clarithromycine est un macrolide de 3 e generation derivee de l’erytromycine. Elle est indiquee dans les infections des voies respiratoires, dans les infections a mycobacteries atypiques et dans l’eradication d’ Helicobacter jejuni . Methodes Afin de rapporter une interaction entre la carbamazepine et la clarithromycine, nous presentons une etude comprenant 3 patients regulierement suivis au niveau du service d’Epileptologie de Montpellier ainsi que 7 cas issus de la pharmacovigilance francaise. Resultats Chez ces patients traites au long cours par carbamazepine, seule ou en association a d’autres molecules, l’ajout de la clarithromycine a ete responsable d’un surdosage transitoire (ataxie, vertiges, diplopie, nausees, vomissements, somnolence). Un bilan sanguin a ete effectue chez 8 patients revelant une concentration plasmatique en carbamazepine allant de 13,3 a 28,5 mg/l. Conclusion La carbamazepine est metabolisee en grande partie par les enzymes du cytochrome P450 dont l’isoenzyme CYP3A4. Comme la clarithromycine est aussi metabolisee par l’isoenzyme CYP3A4, elle a la propriete d’inhiber le metabolisme de la carbamazepine. La clarithromycine doit etre ainsi evitee chez les patients traites par carbamazepine.

Dramatic weight loss with rufinamide

Rufinamide (RUF) is a novel antiepileptic drug considered as second‐line therapy in the treatment of Lennox‐Gastaut syndrome. Treatment‐emergent adverse events (AEs) have consisted mainly of drowsiness, irritability, vomiting, and loss of appetite. RUF is considered as a “weight‐neutral” drug. We found clinically significant weight loss in 7 of 15 consecutive adult patients (47%; 3 male, 4 female, aged 18–31 years) treated with RUF as add‐on therapy (800–2,400 mg/day: 23.5–57.1 mg/kg/day). The body mass index (BMI) decreased by 7.3–18.7%. Two patients were obese class I before RUF. Five patients (71%) were underweight before RUF (mild in one case, moderate in two cases, and severe in two cases). Four of these patients stopped RUF because of this adverse effect. RUF was recommenced in two patients using a lower and slower dosing strategy; one patient showed improvement in seizure control and no weight loss but RUF was re‐stopped in the second patient because of continued weight loss. Despite of weight loss, RUF was continued in two other patients because it reduced seizure activity. We primarily related weight loss to reduced food intake, that is, loss of appetite and nausea, although in two patients no obvious loss of appetite was reported. RUF can cause clinically significant weight loss in adult patients, even at low dose. This AE can affect patients who are already underweight. There is a possibility that lower starting doses and slower escalation might minimize weight loss, but further information is required to determine whether this is the case.