Background: Episodic ataxia type 2 is an autosomal dominant channelopathy, caused by genetic variants in the voltage-dependent calcium channel a-1 subunit (CACNA1A), which is characterized by intermittent episodes of vertigo and ataxia. A slow progression of cerebellar signs is commonly observed in the course of the disease. Treatment with the carbonic anhydrase inhibitor acetazolamide is recommended.
Methods: We report the cases of two patients with EA-2 and migraine, linked to a novel CACNA1A mutation associated with disabling ictal and interictal disease, which did not respond to acetazolamide.
Results: A 30-year-old woman and a 50-year-old man, who was a ski instructor, reported disabling episodes of rotatory vertigo and progressive interictal ataxia. In both cases, the disease progressed despite treatment with acetazolamide. The concomitant use of topiramate and 4-aminopyridine significantly reduced the frequency and severity of relapses and migraine and improved the interictal cerebellar progression in both cases.
Conclusions: We propose combined applications of topiramate and 4-aminopyridine in refractory cases and those with poor tolerance to acetazolamide and also in those with frequent associated migraine. The effectiveness of this combination of drugs for treating intermittent ataxic episodes and interictal signs in EA-2 has not been previously reported.
Keywords: 4-Aminopyridine; CACNA1A mutations; Episodic ataxia type 2; Ictal symptoms; Interictal progression; Topiramate.
© 2022. Fondazione Società Italiana di Neurologia.