Effects of non-invasive brain stimulation in dystonia: a systematic review and meta-analysis

Abstract

Background: Deep brain stimulation is a highly effective treatment of dystonia but is invasive and associated with risks, such as intraoperative bleeding and infections. Previous research has used non-invasive brain stimulation (NIBS) in an attempt to alleviate symptoms of dystonia. The results of these studies, however, have been variable, leaving efficacy unclear. Objectives: This study aimed to evaluate the effects of NIBS on symptoms of dystonia and determine whether methodological characteristics are associated with variability in effect size. Methods: Web of Science, Embase, and MEDLINE Complete databases were searched for articles using any type of NIBS as an intervention in dystonia patients, with changes in dystonia symptoms the primary outcome of interest. Results: Meta-analysis of 27 studies demonstrated a small effect size for NIBS in reducing symptoms of dystonia (random-effects Hedges’ g = 0.21, p = .002). Differences in the type of NIBS, type of dystonia, and brain region stimulated had a significant effect on dystonia symptoms. Meta-regression revealed that 10 sessions of active stimulation and the application of concurrent motor training programs resulted in significantly larger mean effect sizes. Conclusion: NIBS has yielded small improvements to dystonic symptoms, but effect sizes depended on methodological characteristics, with more sessions of stimulation producing a larger response. Future research should further investigate the application of NIBS parallel to motor training, in addition to providing a greater quantity of sessions, to help define optimal parameters for NIBS protocols in dystonia. Registration: PROSPERO 2020, CRD42020175944.

Brain metabolic response to repetitive transcranial magnetic stimulation to lesion network in cervical dystonia

“…However, the CD network included a hub in the cerebral cortex [16], and authors suggested a that this site could form a therapeutic target for NIBS. Given the relatively poor success rate of previous noninvasive brain stimulation targets in dystonia [11,34], we sought to test the neurobiological effects of modulation of this site.…”

“…Multiple different rTMS targets have previously been probed to treat dystonia, including M1, S1, ACC, dorsal premotor cortex, and cerebellum [11], yet there is no consensus as to the optimal target(s), and the overall efficacy of rTMS in dystonia has remained weak [11,34]. Only two studies have previously targeted S1, both applying conventional low-frequency rTMS, in specific types of dystonia.…”

“…The most widely used NIBS method is repetitive transcranial magnetic stimulation (rTMS), which is already an effective treatment option for multiple neurological and psychiatric disorders, including 10Hz rTMS or intermittent theta burst stimulation (iTBS) to the left dorsolateral prefrontal cortex (DLPFC) in depression, and 10Hz rTMS to the primary motor cortex in neuropathic pain [8][9][10]. In CD, a recent meta-analysis demonstrated that numerous rTMS targets have been probed, yet the results have so far been variable, with considerable heterogeneity in study methods [11]. One of the major barriers to the discovery of an effective NIBS protocol in CD is that we do not yet know what the optimal treatment target is: although CD has traditionally been viewed as a disorder of the basal ganglia, neuroimaging studies have implicated numerous other brain regions, suggesting that CD may actually be a brain network disorder [12][13][14][15].…”

“…has not yet been investigated in detail [11]. In addition, more broadly, although there is great hope for lesion network mapping as a method to localize treatment targets for brain stimulation [17][18][19][20], to date, there are no published studies investigating the effect of neuromodulation to a target selected based on lesion network mapping findings, in any clinical condition [11,21].…”