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

Abstract

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.

The Therapeutic Potential of Non-Invasive and Invasive Cerebellar Stimulation Techniques in Hereditary Ataxias

“…At the group level, there was no noticeable change in serum brain-derived neurotrophic factor (BDNF) concentration. However, upon segregation of samples by genotype, BDNF levels were found to have increased in all three individuals with the Val66Val genotype and decreased in the three patients with the Val66Met genotype [ 132 ].…”

Effects of Repetitive Transcranial Magnetic Stimulation on Cerebellar Metabolism in Patients With Spinocerebellar Ataxia Type 3

“…Though rTMS can improve the symptoms of SCAs, the mechanism for the improvement is unclear. The previous studies have shown that the therapeutic effect of rTMS on cerebellar ataxia may be due to either the cerebellar modulation of motor cortex excitability by rTMS involving the cerebellar-thalamus-cortical (CTC) pathway ( Sanna et al, 2021 ) or the reduction of oxidative stress, the increase of cerebellar hemispheric blood flow ( Ihara et al, 2005 ), and the effects on cerebellar-cortical plasticity ( Song et al, 2020 ). The magnetic resonance spectroscopy (MRS) provides a non-ionizing and non-invasive method to measure the alteration of cerebellar metabolism ( Hall et al, 2012 ), which has been widely used in the cross-sectional studies of SCAs and admitted as a reliable means in the assessment of the efficacy of SCAs ( Lei et al, 2011 ; Lirng et al, 2012 ; Adanyeguh et al, 2015 ; Krahe et al, 2020 ).…”