Cerebellar theta burst stimulation does not improve freezing of gait in patients with Parkinson’s disease

Abstract

Freezing of gait (FOG) in Parkinson’s disease (PD) likely results from dysfunction within a complex neural gait circuitry involving multiple brain regions. Herein, cerebellar activity is increased in patients compared to healthy subjects. This cerebellar involvement has been proposed to be compensatory. We hypothesized that patients with FOG would have a reduced ability to recruit the cerebellum to compensate for dysfunction in other brain areas. In this study cerebellar activity was modified unilaterally by either excitatory or inhibitory theta burst stimulation (TBS), applied during two separate sessions. The ipsilateral cerebellar hemisphere, corresponding to the body side most affected by PD, was stimulated. Seventeen patients with PD showing ‘off’ state FOG participated. The presence of FOG was verified objectively upon inclusion. We monitored gait and bimanual rhythmic upper limb movements before and directly after TBS. Gait was evaluated with a FOG-provoking protocol, including rapid 360° turns and a 10-m walking test with small fast steps. Upper limb movement performance was evaluated with a repetitive finger flexion–extension task. TBS did not affect the amount of freezing during walking or finger tapping. However, TBS did increase gait speed when walking with small steps, and decreased gait speed when walking as fast as possible with a normal step size. The changes in gait speed were not accompanied by changes in corticospinal excitability of M1. Unilateral cerebellar TBS did not improve FOG. However, changes in gait speed were found which suggests a role of the cerebellum in PD.Electronic supplementary materialThe online version of this article (doi:10.1007/s00415-017-8479-y) contains supplementary material, which is available to authorized users.

Nonpharmacological, Nonsurgical Treatments for Freezing of Gait in Parkinson's Disease: A Systematic Review

“…In order to avoid studies with lower statistical power, 15 studies reporting samples with <10 patients were excluded. The therapies evaluated in those studies included visual cueing (laser light, staircase climbing) auditory cueing, tactile cueing, cueing exercise program, cognitive training, physical training, rTMS, and tDCS . All these approaches have been covered as well in the articles included in our review.…”

Invasive and Noninvasive Brain Stimulation in Parkinson's Disease: Clinical Effects and Future Perspectives

“…Some studies tested the effects of TBS on other PD symptoms, such as FOG. However, neither single session of iTBS applied to the left PM nor to the cerebellar hemisphere ipsilateral to the more affected limb improved FOG . Therefore, the clinical effects of TBS on PD remained inconclusive due to the small number of high‐quality studies.…”

Brain imaging of locomotion in neurological conditions

“…One study also reported an improvement of the TUG test after rTMS of the dorsolateral prefrontal cortex [105] and another showed that gait variability and FOG occurrence were decreased after high frequency rTMS over the medial prefrontal cortex [37]. In contrast, neither cerebellum [80], nor premotor cortex stimulation [207] have a positive influence on FOG in PD. Contrasting results have been obtained for the supplementary motor area: whereas a benefit of rTMS for anticipatory postural adjustments duration [77] and FOG [98] were shown; one study did not report significant effects compared with sham stimulation [105].…”