Dissociable effects of medication on visual–vestibular brain excitability by visual motion stimuli in episodic ataxia type 2

The clinical hallmark of episodic ataxia type 2 (EA2) consists of episodes of recurrent severe vestibulo-cerebellar dysfunction, characterized by marked postural unsteadiness and oscillopsia. Triggering factors of EA2 attacks, such as physical exertion and sensory stimulation, the high comorbidity with migraine, and the increased risk of epilepsy in EA2 suggest abnormal brain excitability. To investigate this, we assessed brain excitability in response to visual (checkerboard) and visual motion (optic flow) stimuli using interictal functional magnetic resonance imaging. Visual stimulation elicited strong bilateral neural activity in the primary visual cortex (V1-V3) and in motion-sensitive visual areas (V5) in 21 EA2 patients and 21 age-matched healthy participants (HP). Compared to HP, EA2 patients revealed decreased activity in the primary visual cortex (V1), cerebellar Crus I and II and caudal vermis but increased activation of multisensory vestibular processing areas (posterior insula, superior temporal and supramarginal gyrus, inferior parietal lobe). Interestingly, the abnormal excitability in the vestibular processing cortex areas was primarily found in patients without medication (4-aminopyridine, acetazolamide) but hardly seen in patients on medication. Our findings in treatment-naïve patients reflect disease-inherent changes in visual cortical excitability in EA2, which may be reversible through anti-episodic medication. As excitability by visual motion stimuli in multi-sensory vestibular processing cortical areas was largely found in patients on medication it may also indicate an inhibitory effect on the physiological reciprocal inhibitory visual-vestibular interaction as a multisensory mechanism for self-motion perception: the annoying oscillopsia of EA2 patients is counterbalanced by decreased visual cortex activity and hence smaller inhibition of the vestibular cortex.