Assessing the Relationship Between Cerebral Cavernous Malformation-related Seizures and Hypothyroidism: A Propensity-adjusted Multivariate Analysis

Introduction: Previous studies have implicated mitochondrial dysfunction and oxidative stress in seizure pathophysiology, secondary to thyroid hormone (TH) imbalance. However, the influence of TH levels on cerebral cavernous malformation (CCM)-related seizures remains unclear. In this analysis, we investigate the relationship between thyroid disorder history and prevalence of seizures in patients with CCMs.

Methods: A retrospective cohort of patients with CCMs was identified from January 2010 through June 2016 at a large-volume, quaternary cerebrovascular center. Firth’s logistic regression was used to perform a multivariate propensity score adjustment, constructed from demographics, comorbidities, and size of the treated malformation. Modified Rankin scale (mRS), new neurological deficits at discharge and follow-up, and post-operative complications were used as primary outcomes. Standardized mean differences (SMD) was used to quantify effect size for significant associations (p < 0.05).

Results: A total of 203 patients with CCMs were treated during the study period, of which 103 (50.7%) had a pre-operative CCM-related seizure and 16 (7.9%) had a thyroid disorder, exclusively hypothyroidism. Patients with hypothyroidism were older, with a mean age of 53.18 (SMD = 1.149, p < 0.001), and had greater comorbidities (SMD = 0.776, p < 0.001) when compared to patients without hypothyroidism. Notably, patients with hypothyroidism had a lower rate of pre-operative CCM-related seizures (18.8% vs. 53.5%, SMD = 0.775, p = 0.016). On propensity-adjusted multivariate analysis, neurological or functional outcomes between both cohorts were not significantly different. However, hospital length of stay was shorter for patients with hypothyroidism (β = -0.491 (SE = 0.17), p = 0.004).

Conclusion : Hypothyroidism was shown to be protective of preoperative seizures, however, our analysis of seizure outcomes was limited by the patient population. A larger cohort of CCM patients with thyroid disorders, both hypo- and hyperthyroidism, is necessary to determine whether abnormal TH levels influence CCM seizure outcomes.