Effect of Cerebellar Stimulation on Gait and Balance Recovery in Patients With Hemiparetic Stroke

Abstract

IMPORTANCE Gait and balance impairment is associated with poorer functional recovery after stroke. The cerebellum is known to be strongly implicated in the functional reorganization of motor networks in patients with stroke, especially for gait and balance functions. OBJECTIVE To determine whether cerebellar intermittent θ-burst stimulation (CRB-iTBS) can improve balance and gait functions in patients with hemiparesis due to stroke. DESIGN, SETTING, PARTICIPANTS This randomized, double-blind, sham-controlled phase IIa trial investigated efficacy and safety of a 3-week treatment of CRB-iTBS coupled with physiotherapy in promoting gait and balance recovery in patients with stroke. Thirty-six patients with consecutive ischemic chronic stroke in the territory of the contralateral middle cerebral artery with hemiparesis were recruited from a neuro-rehabilitation hospital. Participants were screened and enrolled from March 2013 to June 2017. Intention-to-treat analysis was performed.INTERVENTIONS Patients were randomly assigned to treatment with CRB-iTBS or sham iTBS applied over the cerebellar hemisphere ipsilateral to the affected body side immediately before physiotherapy daily during 3 weeks. MAIN OUTCOMES AND MEASURESThe primary outcome was the between-group difference in change from baseline in the Berg Balance Scale. Secondary exploratory measures included the between-group difference in change from baseline in Fugl-Meyer Assessment scale, Barthel Index, and locomotion assessment with gait analysis and cortical activity measured by transcranial magnetic stimulation in combination with electroencephalogram. RESULTSA total of 34 patients (mean [SD] age, 64 [11.3] years; 13 women [38.2%]) completed the study. Patients treated with CRB-iTBS, but not with sham iTBS, showed an improvement of gait and balance functions, as revealed by a pronounced increase in the mean (SE) Berg Balance Scale score (baseline: 34.5 [3.4]; 3 weeks after treatment: 43.4 [2.6]; 3 weeks after the end of treatment: 47.5 [1.8]; P < .001). No overall treatment-associated differences were noted in the Fugl-Meyer Assessment (mean [SE], baseline: 163.8 [6.8]; 3 weeks after treatment: 171.1 [7.2]; 3 weeks after the end of treatment: 173.5 [6.9]; P > .05) and Barthel Index scores (mean [SE], baseline: 71.1 [4.92]; 3 weeks after treatment: 88.8 [2.1]; 3 weeks after the end of treatment: 92.2 [2.4]; P > .05). Patients treated with CRB-iTBS, but not sham iTBS, showed a reduction of step width at the gait analysis (mean [SE], baseline: 16.8 [4.8] cm; 3 weeks after treatment: 14.3 [6.2] cm; P < .05) and an increase of neural activity over the posterior parietal cortex.CONCLUSIONS AND RELEVANCE Cerebellar intermittent θ-burst stimulation promotes gait and balance recovery in patients with stroke by acting on cerebello-cortical plasticity. These results are important to increase the level of independent walking and reduce the risk of falling.

Prospective registration and reporting of trial number in randomised clinical trials: global cross sectional study of the adoption of ICMJE and Declaration of Helsinki recommendations

“…The significantly higher compliance in prospective trial registration in the EU CTR registry compared with the rest of the WHO trial registries, might be attributed to the 2014 legal requirements for registration and publication of the results of clinical trials in the European Union, and to the rigor of the registration process in the EU CTR registry 81. In fact, the authors of a publication of a retrospectively registered trial included in our study reported that they were able to register successfully in ClinicalTrials.gov after their initial trial registration was declined at the EU CTR 70. This process might also explain the tendency for European trials not to register in the EU CTR—only 87 of 2086 European trials identified in our study were registered in the EU CTR.…”

“…To investigate the compliance of the submitting authors and the journal editors with the ICMJE recommendations, the full text content of these trials publications was screened and only 2.8% (8/286) of the authors explained the reason for delayed registration of the trial—that is, registering the trial retrospectively after the enrolment of the first participant. Reasons for delayed registration were lack of awareness or error of omission in five papers, that the registration process took longer than anticipated in two papers, and that in one paper the feasibility of recruitment was to be tested before registration 6869707172737475. Appendix M provides details of this analysis.…”

Non-Invasive Cerebellar Stimulation in Neurodegenerative Ataxia: A Literature Review

“…Several questions remain unanswered and could provide novel targets for future studies. For example, several studies have now shown that the effects of iTBS might be even more relevant than those obtained after rTMS [98], and encouraging results have been achieved in the treatment of gait and balance recovery in patients with stroke after cerebellar iTBS [99,100]. Moreover, transcranial alternating current stimulation (tACS) also has recently emerged as a new technique to modulate cortical oscillations and entrain brain rhythms in specific frequencies [101].…”

Functional near-infrared spectroscopy in conjunction with electroencephalography of cerebellar transcranial direct current stimulation responses in the latent neurovascular coupling space – a chronic stroke study

“…Non-invasive brain stimulation (NIBS) techniques are increasingly being applied to the cerebellum for various movement disorders, including stroke [1], [2]. In these applications for stroke rehabilitation, improvement in gait and standing balance are the primary goals [3], where NIBS is usually delivered to prime the brain for learning processes by mechanisms of long-term potentiation (LTP) and long-term depression (LTD)-like plasticity [4], [5].…”

“…In these applications for stroke rehabilitation, improvement in gait and standing balance are the primary goals [3], where NIBS is usually delivered to prime the brain for learning processes by mechanisms of long-term potentiation (LTP) and long-term depression (LTD)-like plasticity [4], [5]. Cerebellar intermittent θ-burst stimulation has been shown to improve balance and gait functions in patients with hemiparesis due to stroke [6] that is important for independent gait without the risk of falling. Another NIBS technique, transcranial direct current stimulation (tDCS), is a low-cost NIBS technique amenable to home-based therapy [7] that applies a small (1-2mA) direct current (DC) via conductive electrodes placed on the scalp [8].…”