Migraine and Episodic Ataxia Type 2: A Clinical, Genetic, Neurotologic, and Magnetic Resonance Spectroscopy Study
Hanna Harno
*"Oculomotor and other neurotologic dysfunction in migraine is evident, but results are not consistent. About 40% of familial hemiplegic migraine type 1 (FHM1) patients show permanent cerebellar signs, whereas familial hemiplegic migraine type 2 (FHM2) patients show normal neurologic status interictally. Episodic ataxia type 2 (EA2) patients can develop permanent cerebellar signs in the course of the disease and show pronounced nystagmus interictally before any other cerebellar signs are detectable. In this study, we examined quantitatively oculomotor function and other neurotologic findings in episodic ataxia type 2 (EA2) with a novel CACNA1A splice site mutation, in the common types of migraine, and in familial hemiplegic migraine type 2 (FHM2).
The neurotologic results for common types of migraine (36 patients and 43 controls) indicate that oculomotor dysfunction originates from the vestibulocerebellum for both migraine with aura (MA) and migraine without aura (MO). In video-oculography (VOG), abnormal nystagmus occurred in migraine subjects, but not in controls. Additionally, in migraine, increased body sway in posturography and decreased accuracy in saccadic tests suggested subclinical vestibulocerebellar dysfunction.
To our knowledge, quantitative oculomotor tests have not previously been performed on FHM2 patients. They usually show normal neurologic status interictally, as was the case with our FHM2 patients. However, the oculomotor tests on nine FHM2 patients suggested subclinical changes in postural control and in oculomotor function.
EA2 patients have well-characterized eye-movement abnormalities. They localize to the vestibulocerebellum with gaze-evoked, rebound, or downbeat nystagmus. We studied the effect of acetazolamide on baseline oculomotor and postural dysfunction in three EA2 family members on acetazolamide. Recordings were made with and without medication. After a wash-out period, we showed that with acetazolamide, interictal oculomotor and postural function in these patients improved.
Proton (1H) magnetic resonance spectroscopy (MRS) of the brain in EA2 has shown high lactate peaks, but no changes in N-acetylaspartate (NAA) or in other 1H MRS metabolite ratios. We studied nine mostly nonataxic EA2 family members with a specifi c CACNA1A mutation by 1H MRS to evaluate metabolite changes in the cerebellar hemispheres, the vermis, and the thalamus. These EA2 patients, showing no atrophy in the cerebellum in MRI, showed decreased total creatine (tCr) in the cerebellar hemispheres and in the vermis. These results suggest cerebellar Purkinje cell dysfunction in EA2, possibly reflecting early signs of CACNA1A dysfunction.
In summary, this study suggests that MA and MO share similar abnormalities in interictal neurotologic dysfunction that may reflect central vestibular and cerebellar etiology. The results for FHM2 with subclinical abnormalities in neurotologic testing shared similar features with MA and MO as to defective oculomotor function. EA2 patients showed improved oculomotor function from baseline dysfunction with acetazolamide. Significantly decreased cerebellar tCr may reflect, in EA2, the first signs of intrinsic dysfunction of a CACNA1A mutation."*