Hippocampus and epilepsy: Findings from human tissues.

Surgical removal of the epileptogenic zone provides an effective therapy for several focal epileptic syndromes. This surgery offers the opportunity to study pathological activity in living human tissue for pharmacoresistant partial epilepsy syndromes including temporal lobe epilepsies with hippocampal sclerosis, cortical dysplasias, epilepsies associated with tumors and developmental malformations. Slices of tissue from patients with these syndromes retain functional neuronal networks and may generate epileptic activities. The properties of cells in this tissue may not be greatly changed, but excitatory synaptic transmission is often enhanced and GABAergic inhibition is preserved. Typically epileptic activity is not generated spontaneously by the neocortex, whether dysplastic or not, but can be induced by convulsants. The initiation of ictal discharges in the neocortex depends on both GABAergic signaling and increased extracellular potassium. In contrast, a spontaneous interictal-like activity is generated by tissues from patients with temporal lobe epilepsies associated with hippocampal sclerosis. This activity is initiated, not in the hippocampus but in the subiculum, an output region, which projects to the entorhinal cortex. Interictal events seem to be triggered by GABAergic cells, which paradoxically excite about 20% of subicular pyramidal cells while simultaneously inhibiting the majority. Interictal discharges thus depend on both GABAergic and glutamatergic signaling. The depolarizing effects of GABA depend on a pathological elevation in levels of chloride in some subicular cells, similar to those of developmentally immature cells. Such defect is caused by a perturbed expression of the cotransporters regulating intracellular chloride concentration, the importer NKCC1 and the extruder KCC2. Blockade of NKCC1 actions by the diuretic bumetanide restores intracellular chloride and thus hyperpolarizing GABAergic actions and consequently suppressing interictal activity.

First genetic evidence of GABA(A) receptor dysfunction in epilepsy: a mutation in the gamma2-subunit gene.

Major advances in the identification of genes implicated in idiopathic epilepsy have been made. Generalized epilepsy with febrile seizures plus (GEFS+), benign familial neonatal convulsions and nocturnal frontal lobe epilepsy, three autosomal dominant idiopathic epilepsies, result from mutations affecting voltage-gated sodium and potassium channels, and nicotinic acetylcholine receptors, respectively. Disruption of GABAergic neurotransmission mediated by gamma-aminobutyric acid (GABA) has been implicated in epilepsy for many decades. We now report a K289M mutation in the GABA(A) receptor gamma2-subunit gene (GABRG2) that segregates in a family with a phenotype closely related to GEFS+ (ref. 8), an autosomal dominant disorder associating febrile seizures and generalized epilepsy previously linked to mutations in sodium channel genes. The K289M mutation affects a highly conserved residue located in the extracellular loop between transmembrane segments M2 and M3. Analysis of the mutated and wild-type alleles in Xenopus laevis oocytes confirmed the predicted effect of the mutation, a decrease in the amplitude of GABA-activated currents. We thus provide the first genetic evidence that a GABA(A) receptor is directly involved in human idiopathic epilepsy.

[Management of tumoral epilepsy in meningioma surgery: Review of the literature and survey of French national practices]. / Gestion de l'épilepsie tumorale dans la chirurgie des méningiomes : revue de la littérature et enquête sur les pratiques nationales.

Prophylaxis or treatment of tumor-associated seizures is adaily concern in neurosurgical practice but is often guided by the surgeon's habits rather than evidence from clinical trials, which is lacking. The present study reviews the literature on the incidence, clinical aspects and treatment of epilepsy and epileptic seizures in patients undergoing surgery for meningioma. Based on the published data, we then performed a French nationwide survey of neurosurgeons' practices regarding perioperative management of meningioma-related epilepsy and epileptic seizures.

[Ictal single photon computed tomography and SISCOM: methods and utility]. / Tomographie d'émission monophotonique ictale et Siscom: technique et utilité

Ictal single photon emission computed tomography (SPECT) reflects epileptic activity through hyperperfusion associated with ictal discharge. It provides valuable spatial information on ictal activity, but its temporal resolution is limited. Therefore, information provided by SPECT is not restricted to the epileptogenic zone, but demonstrates a larger epileptogenic network, related to the spatiotemporal dynamics of ictal processes. This review includes a description of the technique, followed by a description of the different parameters likely to influence the ictal perfusion images. SPECT gives contributes original diagnostic data to the decision-making process which will complete, the other evaluation parameters.

[Epileptiform activities generated in vitro by human temporal lobe tissue]. / Activités épileptiques produites in vitro par le tissu temporal humain.

Drug-resistant partial epilepsies, including temporal lobe epilepsies with hippocampal sclerosis and cortical dysplasias, offer the opportunity to study human epileptic activity in vitro since the preferred therapy often consists of the surgical removal of the epileptogenic zone. Slices of this tissue retain functional neuronal networks and may generate epileptic activity. The properties of cells in this tissue do not seem to be significantly changed, but excitatory synaptic characteristics are enhanced and GABAergic inhibition is preserved. Typically, epileptic activity is not generated spontaneously by the neocortex, whether dysplastic or not, but can be induced by convulsants. The initiation of ictal discharges in neocortex depends on both GABAergic signaling and increased extracellular potassium. In contrast, a spontaneous interictal-like activity is generated by tissues from patients with temporal lobe epilepsies associated with hippocampal sclerosis. This activity is initiated not in the hippocampus but in the subiculum, an output region that projects to the entorhinal cortex. Interictal events seem to be triggered by GABAergic cells, which paradoxically excite approximately 20% of subicular pyramidal cells, while simultaneously inhibiting the majority. Interictal discharges are therefore sustained by both GABAergic and glutamatergic signaling. The atypical depolarizing effects of GABA depend on a pathological elevation in the basal levels of chloride in some subicular cells, similar to those of developmentally immature cells. This defect is caused by the perturbation of the expression of the cotransporters regulating the intracellular chloride concentration, the importer NKCC1, and the extruder KCC2. Blockade of excessive NKCC1 by the diuretic bumetanide restores intracellular chloride and thus hyperpolarizing GABAergic actions, suppressing interictal activity.

Preoperative and intraoperative neurophysiological investigations for surgical resections in functional areas.

Brain regions are removed to treat lesions, but great care must be taken not to disturb or remove functional areas in the lesion and in surrounding tissue where healthy and diseased cells may be intermingled, especially for infiltrating tumors. Cortical functional areas and fiber tracts can be localized preoperatively by probabilistic anatomical tools, but mapping of functional integrity by neurophysiology is essential. Identification of the primary motor cortex seems to be more effectively performed with transcranial magnetic stimulation (TMS) than functional magnetic resonance imaging (fMRI). Language area localization requires auditory evoked potentials or TMS, as well as fMRI and diffusion tensor imaging for fiber tracts. Somatosensory cortex is most effectively mapped by somatosensory evoked potentials. Crucial eloquent areas, such as the central sulcus, primary somatomotor areas, corticospinal tract must be defined and for some areas that must be removed, potential compensations may be identified. Oncological/functional ratio must be optimized, resecting the tumor maximally but also sparingly, as far as possible, the areas that mediate indispensable functions. In some cases, a transient postoperative deficit may be inevitable. In this article, we review intraoperative exploration of motricity, language, somatosensory, visual and vestibular function, calculation, memory and components of consciousness.

Validity and reliability of two muscle strength scores commonly used as endpoints in assessing treatment of myasthenia gravis.

Valid and reliable measurements of muscle impairment are needed to assess therapeutic efficacy in patients with generalized myasthenia gravis (MG). In 22 patients we compared the validity and interobserver reliability of two scoring methods commonly used as main endpoints in clinical trials, i.e., the Myasthenic Muscle Score (MMS) ranging from 0 to 100 (normal) and the Quantified Myasthenia Gravis Strength Score (QMGSS) ranging from 0 (normal) to 39. Each score is correlated more with functional scale and less with the patient's self-evaluation. Using intraclass correlation we found strong agreement between observers for both the MMS (r = 0.906) and the QMGSS (r = 0.905). The correlation between MMS and QGMSS was high (r = 0.87). The reliability of neither score depended on any specific item, since the removal of individual items did not significantly alter the intraclass correlation coefficient (ranging from 0.86 to 0.93).

[Recurrent idiopathic stupor in a patient: responsibility of exogenous or endogenous benzodiazepines?]. / Stupeur récurrente idiopathique chez un patient: imputabilité des benzodiazépines endogènes ou exogènes?

Recurrent transitory consciousness loss represents a neurological diagnostic difficulty. A 56 year old man was hospitalised for recurrent stupor episodes. Explorations allowed to exclude hepatic, renal or respiratory failures, epilepsy or sleep disorder. During a stuporous state, since the patient was clearly awakened by flumazenil administration, the retained diagnosis was idiopathic recurrent stupor, a rare and not well-known disease. The authors discuss the possible effect of a treatment with zolpidem, though its pharmacokinetic characteristics did not correspond to the patient manifestations, and the possible responsibility of endogenous benzodiazepines in the genesis of this trouble.