Neurological and Cognitive Effects of Hypothyroidism in Patients With Epilepsy: A Study on Anti‐Seizure Medicines Therapy

The primary objective of this study was to examine neurological disorders and cognitive impairments in patients with secondary hypothyroidism and epilepsy undergoing treatment with antiepileptic medications. The study included 184 patients divided into three groups: Group 1 (subclinical hypothyroidism, n = 60), Group 2 (manifest hypothyroidism, n = 64), and Group 3 (control, n = 60). Patients in Group 2 received levothyroxine therapy (initial dose of 25 μg/day, titrated to 50-100 μg/day), while Groups 1 and 2 were treated with anti-seizure medications (valproic acid, 40 mg/kg/day). Neurological symptoms, including Babinski's reflex abnormalities (χ² = 8.15, p = 0.017) and sensory disturbances (χ² = 12.44, p = 0.005), were significantly more frequent in Group 2 than in Group 1. Cognitive test scores were significantly lower in Group 2 compared to Group 3 across all domains (F(2, 181) = 6.55, p = 0.002 for MMSE; F(2, 181) = 4.70, p = 0.010 for FAB; and F(2, 181) = 5.75, p = 0.006 for CDT), with Group 1 showing intermediate results. Regression analysis identified neurodegenerative disease risk (β = 0.34, CI: 0.20-0.48, p < 0.001), anemia (β = 0.32, CI: 0.15-0.49, p = 0.001), and prolonged stress (β = 0.26, CI: 0.12-0.40, p = 0.002) as significant predictors of cognitive decline, while higher education was protective (β = -0.28, CI: -0.42 to -0.14, p = 0.003). An inverse relationship was observed between TSH levels and cognitive scores (r = -0.55, p < 0.001).