Intellectual Disability in Episodic Ataxia Type 2: Beyond Paroxysmal Vertigo and Ataxia

Background and Purpose Episodic ataxia type 2 (EA2) is characterized by recurrent vertigo and ataxia due to mutations in CACNA1A that encodes the alpha 1A-subunit of the P/Q-type voltage-gated calcium channel. This study aimed to determine intellectual function in EA2. Methods During 2019-2023, 13 patients (6 males, age range=10-52 years, median age=29 years) with a genetically confirmed diagnosis of EA2 had their intellectual function evaluated using the Korean versions of the Wechsler Intelligence Scales (version IV) for adults or children in 3 referral-based university hospitals in South Korea. Results The full-scale intelligence quotients (FSIQs) among the 13 patients were below the average (90-109) in 11, low average (80-89) in 5 (38.5%), borderline (70-79) in 1 (7.7%), and indicated intellectual disability (<= 69) in 5 (38.5%). These patterns of cognitive impairments were observed in all four of the following subtests: verbal comprehension, perceptual reasoning, working memory, and processing speed. The FSIQ was not correlated with the ages at onset for vertigo and ataxia (Pearson correlation: p=0.40). Conclusions Patients with EA2 may have hidden intellectual disabilities even without a history of epilepsy or administration of antiepileptic drugs, and should be considered for genetic counseling and therapeutic interventions. Given the availability of medication to control episodic vertigo and ataxia, early diagnosis and management are important in preventing irreversible brain dysfunction in EA2.