Therapeutic Use of Cerebellar Intermittent Theta Burst Stimulation (iTBS) in a Sardinian Family Affected by Spinocerebellar Ataxia 38 (SCA 38)

Spinocerebellar ataxia 38 (SCA 38) is an autosomal dominant disorder caused by conventional mutations in the ELOVL5 gene which encodes an enzyme involved in the synthesis of very long fatty acids, with a specific expression in cerebellar Purkinje cells. Three Italian families carrying the mutation, one of which is of Sardinian descent, have been identified and characterized. One session of cerebellar intermittent theta burst stimulation (iTBS) was applied to 6 affected members of the Sardinian family to probe motor cortex excitability measured by motor-evoked potentials (MEPs). Afterwards, patients were exposed to ten sessions of cerebellar real and sham iTBS in a cross-over study and clinical symptoms were evaluated before and after treatment by Modified International Cooperative Ataxia Rating Scale (MICARS). Moreover, serum BDNF levels were evaluated before and after real and sham cerebellar iTBS and the role of BDNF Val66Met polymorphism in influencing iTBS effect was explored. Present data show that one session of cerebellar iTBS was able to increase MEPs in all tested patients, suggesting an enhancement of the cerebello-thalamo-cortical pathway in SCA 38. MICARS scores were reduced after ten sessions of real cerebellar iTBS showing an improvement in clinical symptoms. Finally, although serum BDNF levels were not affected by cerebellar iTBS when considering all samples, segregating for genotype a difference was found between Val66Val and Val66Met carriers. These preliminary data suggest a potential therapeutic use of cerebellar iTBS in improving motor symptoms of SCA38.