Objective:

To determine whether longitudinal changes in notable markers of bone metabolism serum 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, calcium, and parathyroid hormone (PTH) are associated with new-onset seizures in adults.

Background:

Vitamin D deficiency has been implicated in altered neuronal excitability through calcium dysregulation, but large-scale human data linking this deficiency to seizure onset are limited. Understanding these relationships may improve prevention strategies for seizure disorders as well as better understanding of pathophysiology in patients with concurrent epilepsy and metabolic bone disease. 

Design/Methods:

We performed a retrospective cohort analysis using de-identified EHR data from the All of Us Research Program, an ongoing NIH initiative that collects diverse health, genetic, and lifestyle data from participants across the United States to advance precision medicine research. Adults aged ≥ 20 years with available markers of bone metabolism and idiopathic adult-onset epilepsy were included. Analyses assessed baseline distributions, longitudinal changes in vitamin D and calcium homeostasis, and the incidence of adult-onset seizures and bone disease. Ongoing analyses incorporate multivariable logistic regression models adjusting for demographic and clinical covariates, including medications, renal and liver function, and osteoporosis.

Results:

Preliminary analysis indicates participants with persistently low or declining 25-hydroxyvitamin D and calcium levels exhibit higher odds of idiopathic seizures in adulthood. These associations are further evaluated in multivariable models to account for potential confounding factors.

Conclusions:

 Deficient vitamin D status and altered calcium–PTH homeostasis may contribute to seizure susceptibility in adults. The cohort studied from the All of Us Research program includes diverse, medically underserved populations across America, which has a higher prevalence of vitamin D deficiency. These findings demonstrate the need for further exploration of metabolic pathways in adult-onset epilepsy and may inform preventive screening and management strategies, especially beneficial to at-risk populations.