levetiracetam and Sclerosis

Mesial temporal lobe epilepsy associated with hippocampal sclerosis (MTLE-HS) is a syndrome that is often refractory to drug treatment. The effects on specific syndromes are not currently available from the pre-marketing clinical development of new AEDs; this does not allow the prediction of whether new drugs will be more effective in the treatment of some patients.. We have reviewed all the existing literature relevant to the understanding of a potential effectiveness in MTLE-HS patients for the latest AEDs, namely brivaracetam, eslicarbazepine, lacosamide, perampanel and retigabine also including the most relevant clinical data and a brief description of their pharmacological profile. Records were identified using predefined search criteria using electronic databases (e.g., PubMed, Cochrane Library Database of Systematic Reviews). Primary peer-reviewed articles published up to the 15 June 2015 were included.. All the drugs considered have the potential to be effective in the treatment of MTLE-HS; in fact, they possess proven efficacy in animal models; currently considered valuable tools for predicting drug efficacy in TLE. Furthermore, for some of these (e.g., lacosamide and eslicarbazepine) data are already available from post-marketing studies while brivaracetam acting on SV2A like levetiracetam might have the same potential effectiveness with the possibility to be more efficacious considering its ability to inhibit voltage gated sodium channels; finally, perampanel and retigabine are very effective drugs in animal models of TLE.

Topics: Acetamides; Anticonvulsants; Carbamates; Clinical Trials as Topic; Dibenzazepines; Epilepsy, Temporal Lobe; Hippocampus; Humans; Lacosamide; Levetiracetam; Nitriles; Phenylenediamines; Piracetam; Pyridones; Sclerosis; Syndrome

Parosmia has been described in neurological disorders, including temporal epilepsy. We reported a case of parosmia associated with unilateral hyposmia and mesial temporal sclerosis. We assessed the olfactory function by using Sniffin' sticks test and olfactory event-related potentials (OERPs). The findings of unilateral deficit of identification associated with parosmia only in the side ipsilateral to mesial temporal sclerosis area, that involves temporal olfactory regions responsible for higher level of smell processing, suggest a central genesis of olfactory disorders. The administration of levetiracetam restored olfactory function, OERP N1-P2 amplitude, and mesial temporal sclerosis-related electroencephalographic findings.

Topics: Anticonvulsants; Electroencephalography; Evoked Potentials; Female; Hippocampus; Humans; Levetiracetam; Magnetic Resonance Imaging; Middle Aged; Olfaction Disorders; Piracetam; Sclerosis; Temporal Lobe

The spontaneously epileptic rat (SER) begins to exhibit both tonic convulsions and absence seizures from 6 weeks of age and SERs have stable seizures after 10 weeks of age. Low-dose administrations of levetiracetam (LEV) for 4- to 5-weeks-old SERs which did not show spontaneous seizures reduced both seizures 5 weeks after termination of administration. The hippocampus of SER exhibited decreased CA3 neurons, sprouting of mossy fibers, and hyperexpression of the brain-derived neurotrophic factor (BDNF). We attempted prophylactic LEV administrations in preseizure-manifesting SERs to evaluate if such a treatment regimen would protect the hippocampal sclerosis-like changes observed in SERs. The osmotic mini-pump administered LEV dissolved in saline to 4-weeks-old SERs for 4 weeks at 2.5 μl/h. LEV was administered at 420 mg/ml for 4 weeks in Group A. In Group B, LEV was given at 420 mg/ml for the first 2 weeks followed by doubling the dosage (840 mg/ml) in the following 2 weeks. LEV administrations in preseizure-manifesting SERs reduced the decrease of CA3 neurons and mossy fibers sprouting at 10-11 weeks of age in both group A and B. LEV attenuated BDNF expression in inner molecular layers of the dentate gyrus, striatum radiatum, and CA3 in 10- to 11- and 14- to 15-weeks-old SERs. In group B, LEV decreased BDNF expression in hilus and CA1 of 10- to 11- weeks-old SER. The present results suggest that prophylactic treatment with LEV in preseizure-manifesting SERs inhibits hippocampal sclerosis-like neuronal degeneration and/or regeneration.

Topics: Animals; Anticonvulsants; Brain-Derived Neurotrophic Factor; Hippocampus; Levetiracetam; Neurons; Neuroprotective Agents; Piracetam; Placebos; Rats; Rats, Mutant Strains; Rats, Sprague-Dawley; Sclerosis; Seizures

We previously showed that gene expression of synaptic vesicle protein 2A (SV2A), the binding site for the antiepileptic drug levetiracetam, is reduced during epileptogenesis in the rat. Since absence of SV2A has been associated with increased epileptogenicity, changes in expression of SV2A could have consequences for the progression of epilepsy. Therefore we investigated hippocampal SV2A protein expression of temporal lobe epilepsy (TLE) patients and in rats during epileptogenesis and in the chronic epileptic phase.. SV2A immunocytochemistry and Western blot analysis were performed on the hippocampus of autopsy controls, patients that died from status epilepticus (SE), and pharmacoresistant TLE patients. In addition, in epileptic rats, SV2A expression was determined after SE during the acute, latent, and chronic epileptic phase.. In control tissue, presynaptic SV2A was expressed in all hippocampal subfields, with strongest expression in mossy fiber terminals. SV2A positive puncta were distributed in a patchy pattern over the somata and dendrites of neurons. SV2A decreased throughout the hippocampus of TLE patients with hippocampal sclerosis (HS), compared to autopsy control, SE, and non-HS tissue. In most rats, SV2A was already decreased in the latent period especially in the inner molecular layer and stratum lucidum. Similarly as in humans, SV2A was also decreased throughout the hippocampus of chronic epileptic rats, specifically in rats with a progressive form of epilepsy.. These data support previous findings that reduced expression of SV2A could contribute to the increased epileptogenicity. Whether this affects the effectiveness of levetiracetam needs to be further investigated.

Topics: Adolescent; Adult; Animals; Anticonvulsants; Blotting, Western; Child; Disease Models, Animal; Epilepsy, Temporal Lobe; Female; Hippocampus; Humans; Infant; Levetiracetam; Male; Membrane Glycoproteins; Microscopy, Confocal; Middle Aged; Nerve Tissue Proteins; Piracetam; Rats; Sclerosis; Status Epilepticus; Young Adult

Hippocampal sclerosis (HS) has been described as a relevant factor for the development of topiramate-related depression and cognitive deficits. The aim of our study was to clarify whether patients with temporal lobe epilepsy (TLE) and HS were also at risk during therapy with levetiracetam (LEV).. Data of 156 patients was analysed: 78 with TLE and HS and 78 with TLE and normal MRI matched for age, starting dose and titration schedule of LEV. Patients were selected from a population of consecutive patients started on LEV between 2000 and 2002.. No differences were observed in prevalence of cognitive adverse events and depression between the two groups.. LEV treatment is not associated with cognitive adverse events and depression in patients with hippocampal sclerosis.

Topics: Adult; Anticonvulsants; Cognition Disorders; Depression; Epilepsy, Temporal Lobe; Female; Hippocampus; Humans; Levetiracetam; Male; Piracetam; Sclerosis