Real-world safety and effectiveness of cenobamate in patients with focal onset seizures: Outcomes from an Expanded Access Program.

OBJECTIVE: This study investigated early, real-world outcomes with cenobamate (CNB) in a large series of patients with highly drug-resistant epilepsy within a Spanish Expanded Access Program (EAP). METHOD: This was a multicenter, retrospective, observational study in 14 hospitals. Inclusion criteria were age ≥18 years, focal seizures, and EAP authorization. Data were sourced from patient clinical records. Primary effectiveness endpoints included reductions (100%, ≥90%, ≥75%, and ≥50%) or worsening in seizure frequency at 3-, 6-, and 12-month visits and at the last visit. Safety endpoints included rates of adverse events (AEs) and AEs leading to discontinuation. RESULTS: The study included 170 patients. At baseline, median epilepsy duration was 26 years and median number of seizures/month was 11.3. The median number of prior antiseizure medications (ASMs) and concomitant ASMs were 12 and 3, respectively. Mean CNB dosages/day were 176 mg, 200 mg, and 250 mg at 3, 6, and 12 months. Retention rates were 98.2%, 94.5%, and 87% at 3, 6, and 12 months. At last available visit, the rate of seizure freedom was 13.3%; ≥90%, ≥75%, and ≥50% responder rates were 27.9%, 45.5%, and 63%, respectively. There was a significant reduction in the number of seizures per month (mean: 44.6%; median: 66.7%) between baseline and the last visit (P < 0.001). Responses were maintained regardless of the number of prior or concomitant ASMs. The number of concomitant ASMs was reduced in 44.7% of patients. The cumulative percentage of patients with AEs and AEs leading to discontinuation were 68.2% and 3.5% at 3 months, 74.1% and 4.1% at 6 months, and 74.1% and 4.1% at 12 months. The most frequent AEs were somnolence and dizziness. SIGNIFICANCE: In this highly refractory population, CNB showed a high response regardless of prior and concomitant ASMs. AEs were frequent but mostly mild-to-moderate, and few led to discontinuation.

Ophthalmic features of spinocerebellar ataxia type 7.

BACKGROUND: Patients with spinocerebellar ataxia 7 (SCA7) are known to develop ocular abnormalities. The purpose of this study was to characterize these abnormalities in greater detail and with the aid of newer quantitative technologies. METHODS: Seven patients with SCA7 diagnosed by genetic analysis at La Paz Hospital (Madrid, Spain), a country-wide referral center for ataxias, were included in the study. Demographic data and ocular features were recorded from a complete ophthalmologic examination, specular microscopy, corneal topography (Pentacam), and optical coherence tomography (OCT). RESULTS: All 7 patients had decreased visual acuity associated with varying degrees of macular pigmentary changes on ophthalmoscopy. All 7 had lower corneal endothelial cell densities than expected for their age, and 5 had increased corneal volume, although none had corneal edema. Patients with mild disease showed retinal thinning at the fovea. In patients with more advanced disease, retinal thinning was present also in the outer zone of the macula. Mean peripapillary retinal nerve fiber layer thickness was decreased in all patients; however, the temporal quadrant was spared except in advanced disease. CONCLUSIONS: This study of 7 patients with SCA7 amplifies previous reports of ophthalmic abnormalities in this condition by providing data from specular microscopy, corneal topography, and OCT. Abnormalities were present in the anterior and posterior ocular segments, as well as in eye movements and pupillary reactions. Visual dysfunction, present in all patients, was associated with retinal thinning. Decreased endothelial cell density and increased corneal thickness were common.