levetiracetam and Cerebellar-Ataxia

This study examined the effects of carbamazepine (CBZ) or levetiracetam (LEV) and sub-therapeutic doses of the combination of the two conventional antiepileptics on some of the markers of motor coordination. Twenty-four male Wistar rats (140 ± 5 g) were randomized into 4 groups (n = 6). Group I rats received physiological saline (0.2 ml), group II were administered CBZ (25.0 mg/kg), group III received LEV (50 mg/kg), while group IV rats were given sub-therapeutic doses of CBZ (12.5 mg/kg) and LEV (25 mg/kg) intraperitoneally for 28 days. Thereafter the animals were subjected to behavioral and biochemical investigations, while the frontal lobe and cerebellar tissue were preserved for histological investigation. Data were subjected to descriptive and inferential statistics, and the results presented as mean ± SEM, analyzed using one-way Analysis of variance (ANOVA) and Student- Newman Keuls post hoc analysis where appropriate. p < 0.05 was considered statistically significant. There was significant alteration in fine and skilled movement after the CBZ, and CBZ + LEV chronic treatment compared with the control. The CBZ, and CBZ + LEV combination treatment increased the frontal lobe and cerebellar activities of acetylcholinesterase, malondialdehyde concentration, tissue necrotic factor alpha and decreased the activities of super oxide dismutase relative to the control. Disorganization of the histoarchitecture of the frontal lobe and cerebellum was characterized by cellular atrophy, chromatolysis and hyalinization. Chronic CBZ, and CBZ + LEV combination treatment produced psychomotor dysfunction and neurotoxicity in this order CBZ + LEV > CBZ > LEV in the rats.

Topics: Animals; Anticonvulsants; Ataxia; Carbamazepine; Cerebellar Ataxia; Cerebellum; Drug Therapy, Combination; Levetiracetam; Male; Motor Activity; Piracetam; Rats; Rats, Wistar

ATP1A3 related disease is a clinically heterogeneous condition currently classified as alternating hemiplegia of childhood, rapid-onset dystonia-parkinsonism and cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss. Recently, it has become apparent that a remarkably large subgroup is suffering from often difficult-to-treat epilepsy. The aim of the present study was to assess the prevalence and efficacy of commonly used anti-epileptic-drugs (AEDs) in patients with ATP1A3 related seizures. Therefore, we performed a retrospective study of patients in combination with a systematic literature-based review. Inclusion criteria were: verified ATP1A3 mutation, seizures and information about AED treatment. The literature review yielded records for 188 epileptic ATP1A3 patients. For 14/188 cases, information about anti-epileptic treatment was available. Combined with seven unpublished records of ATP1A3 patients, a sample size of 21 patients was reached. Most used AED were levetiracetam (n = 9), phenobarbital (n = 8), valproic acid (n = 7), and topiramate (n = 5). Seizure reduction was reported for 57% of patients (n = 12). No individual AEDs used (either alone or combined) had a success rate over 50%. There was no significant difference in the response rate between various AEDs. Ketogenic diet was effective in 2/4 patients. 43% of patients (n = 9) did not show any seizure relief. Even though Epilepsy is a significant clinical issue in ATP1A3 patients, only a minority of publications provide any information about patients' anti-epileptic treatment. The findings of treatment effectiveness in only 57% (or lower) of patients, and the non-existence of a clear first-line AED in ATP1A3 related epilepsy stresses the need for further research.

Topics: Adult; Anticonvulsants; Cerebellar Ataxia; Child; Dystonic Disorders; Epilepsy; Female; Hearing Loss, Sensorineural; Hemiplegia; Humans; Levetiracetam; Male; Mutation; Optic Atrophy; Reflex, Abnormal; Retrospective Studies; Seizures; Sodium-Potassium-Exchanging ATPase; Topiramate; Valproic Acid