Infantile spasms (IS) are an age-specific epileptic syndrome with overall poor outcome and are recognized as one of the 'catastrophic epilepsies'. Current conventional therapies including adrenocorticotropic hormone and vigabatrin often fail to control the spasms and improve the long-term outcome, especially in cases with structural/metabolic etiologies. To improve this situation, new treatments with a disease modifying potential must be identified. Recent translational studies have led to the development of several animal models of IS that reflect their multiple etiologies. Among these, the multiple hit model has been used to screen new promising therapies that, in the future, may be explored in clinical trials.
Purpose: To evaluate the efficacy and tolerability of topiramate (TPM) as add-on therapy in Japanese adult patients with refractory epilepsy. Methods: We performed a retrospective open-label study on 39 Japanese adult patients with refractory seizures (aged 18-64 years, average 36.4 years). Twenty-nine patients with symptomatic partial epilepsy, seven with symptomatic generalized epilepsy, two with Lennox-Gastaut syndrome, and one with severe myoclonic epilepsy in infancy were included in the study. TPM was started at a dose of 50 mg/day in 33 patients and 100 mg/day in 6 patients, and adjusted according to individual clinical response at a slow titration of 50 mg/day or less biweekly. We compared the number of seizures in 4-week durations before and 24 weeks after starting TPM therapy. Results: After a follow-up period of 28 weeks, 12 of 39 (31%) responded to TPM at an average dose of 100 mg/day, and four (10%) became seizure free. Thirty-one percent did not respond to TPM and 38% dropped out. Adverse events occurred in 21 patients (54%), 9 of whom discontinued TPM due to serious adverse events such as severe somnolence, depression, leg edema, excitement, and agranulocytosis. Adverse events developed even at the initial TPM dose of 50 mg/day. Conclusion: TPM add-on therapy is effective even at low-dose in Japanese adult patients with refractory epilepsy. However, dose escalation as slow as 25 mg/day every 2 weeks is recommended to avoid adverse effects of TPM.
Although there is no universally accepted definition, traumatic medial temporal lobe epilepsy (traumatic MTLE) can be generally defined as a type of post-traumatic epilepsy with medial temporal epileptogenicity. Previous studies have demonstrated that patients with traumatic MTLE frequently have hippocampal sclerosis (HS) coexisting with traumatic neocortical lesions. We report a 39-year-old MTLE patient with a subcortical lesion in the internal capsule, suspected to be caused by mild diffuse axonal injury. The results of presurgical examinations and intraoperative electrocorticograms were consistent with a diagnosis of MTLE. Therefore, an anterior temporal lobectomy with hippocampectomy was performed. A 3D short tau inversion recovery 3-Tesla MRI scan clearly depicted possibly Wallerian degeneration in the temporal stem, which was continuous with the subcortical lesion. We speculate that Wallerian degeneration in the temporal stem could potentially involve the hippocampus, eventually leading to HS.