Cerebellar theta burst stimulation does not improve freezing of gait in patients with Parkinson\u2019s disease

Arno M Janssen,Ivan Toni,Dick F Stegeman,Moniek A M Munneke,Alice Nieuwboer,Thomas Van Der Kraan,Anke H Snijders,Bastiaan R Bloem,Jorik Nonnekes

doi:10.1007/s00415-017-8479-y

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.

Highlights

Freezing of gait (FOG) is a disabling feature of Parkinson’s disease (PD), resulting in mobility problems and frequent falls [1, 2]
No significant effect of stimulation, time, task or interaction between factors was found for FOG duration when all turn and gait conditions were included as separate tasks, nor when all turns were combined and all gait trajectory conditions were combined (Table 2)
The main result is that both theta burst stimulation (TBS) protocols did not significantly alter freezing duration in the upper limbs, nor during gait

Summary

Introduction

Freezing of gait (FOG) is a disabling feature of Parkinson’s disease (PD), resulting in mobility problems and frequent falls [1, 2]. Lesions in a single brain area can occasionally induce FOG [5], FOG generally results from a widespread dysfunction within a neural gait circuitry involving the supplementary motor area (SMA) [6], the mesencephalic locomotor region [6, 7] and the cerebellar locomotor region [8, 9]. Recent work has emphasized the tight interplay between the cerebellum and the basal ganglia [10, 11]. Cerebellar activity is increased in PD patients compared to healthy subjects [12, 13]. This hyper-activation in the cerebellum may be an adaptive mechanism that compensates for the defective basal ganglia [11, 12, 14,15,16]

Methods

Results

Conclusion