Repetitive transcranial magnetic stimulation for functional tremor: A randomized, double‐blind, controlled study

Background Diagnosis of functional movement disorders and specifically functional tremor (FT) (representing 50% of them) remains demanding. Additionally, due to heterogeneity of the disorders, structured concepts and guidelines for diagnosis and therapy are difficult to establish. Ascertaining the state of knowledge to derive instructions for operating procedures is the aim of this review. Main text Based on a standardized systematic literature research using the term “psychogenic tremor” in the MEDLINE database dating back ten years, 76 studies were evaluated. Conventional features of FT are variability of frequency and amplitude. Further, response to distraction by motor and cognitive tasks is a key diagnostic feature in differentiation between organic and functional origin. A variety of electrophysiological tests have been evaluated including surface electromyography and accelerometry to establish laboratory-supported criteria for diagnosing tremor. Also, finger tapping tests have been used to identify FT, showing positive potential as supplementary evidence. Imaging studies in general are mostly underpowered and imaging cannot be used on an individual basis. Therapeutic studies in FT often have a diagnostic component. Cognitive behavioral therapy should be the preferred psychological treatment independent of additional psychiatric symptoms. Other psychotherapeutic methods show lack of evidence concerning FT. Relaxation techniques and physiotherapy are an important additional feature, especially in children and adolescents. In regard to drug therapy, randomized and blinded trials are not available. A significant decrease in rating scales could be detected after active, not sham repetitive transcranial magnetic stimulation with a long-lasting effect. Also root magnetic stimulation seems to be effective. The clinical feature of tremor entrainment in FT can be used in combination with biofeedback as so-called tremor retrainment, using self-modulation of frequency and severity, to bring the movements under volitional control. Conclusion Diagnosis and treatment of FT is challenging and should include a combination of intensive clinical examination and targeted addition of standardized testing, especially electrophysiological methods. Often therapeutic effects have a diagnostic component. A multimodal strategy, considering psychological factors as a potential origin as well as maintaining effects seems to be most effective.

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“…This effect still existed 12 months after the start of the invention. A relevant effect of hypnosis could not be shown [31] (HR).…”

Section: Functional Brain Imaging (Spect)mentioning

confidence: 89%

Diagnosis and therapy of functional tremor a systematic review illustrated by a case report

Bartl

Kewitsch

Hallett

et al. 2020

Neurol. Res. Pract.

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“… 11–15 However, few of these RCTs reported gains in other important outcomes (eg, comorbid psychological/physical symptoms, quality of life/global functioning, healthcare resource use). Despite post-treatment improvements in core FND symptoms following rTMS to M1, Taib et al , 14 for example, did not observe superior improvements in health-related quality of life (SF-36 vitality/general health) for active rTMS relative to sham-TMS, and no improvements were observed in psychological symptoms. Similarly, McWhirter et al 15 reported improvements in subjective symptoms immediately following spTMS of M1 relative to standard care, but no associated improvements in self-reported mental or physical health (SF-12) or clinician-rated disability (Modified Rankin Scale).…”

Section: Introductionmentioning

confidence: 95%

Trial Of Neurostimulation In Conversion Symptoms (TONICS): a feasibility randomised controlled trial of transcranial magnetic stimulation for functional limb weakness

et al. 2020

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ObjectivesTranscranial magnetic stimulation (TMS) has been used therapeutically for functional (conversion) motor symptoms but there is limited evidence for its efficacy and the optimal protocol. We examined the feasibility of a novel randomised controlled trial (RCT) protocol of TMS to treat functional limb weakness.DesignA double-blind (patient, outcome assessor) two parallel-arm, controlled RCT.SettingSpecialist neurology and neuropsychiatry services at a large National Health Service Foundation Trust in London, UK.ParticipantsPatients with a diagnosis of functional limb weakness (Diagnostic and Statistical Manual of Mental Disorders - Fifth Edition). Exclusion criteria included comorbid neurological or major psychiatric disorder, contraindications to TMS or previous TMS treatment.InterventionsPatients were randomised to receive either active (single-pulse TMS to primary motor cortex (M1) above resting motor threshold) or inactive treatment (single-pulse TMS to M1 below resting motor threshold). Both groups received two TMS sessions, 4 weeks apart.Outcome measuresWe assessed recruitment, randomisation and retention rates. The primary outcome was patient-rated symptom change (Clinical Global Impression–Improvement scale, CGI-I). Secondary outcomes included clinician-rated symptom change, psychosocial functioning and disability. Outcomes were assessed at baseline, both TMS visits and at 3-month follow-up.ResultsTwenty-two patients were recruited and 21 (96%) were successfully randomised (active=10; inactive=11). Nineteen (91%) patients were included at follow-up (active=9; inactive=10). Completion rates for most outcomes were good (80%–100%). Most patients were satisfied/very satisfied with the trial in both groups, although ratings were higher in the inactive arm (active=60%, inactive=92%). Adverse events were not more common for the active treatment. Treatment effect sizes for patient-rated CGI-I scores were small-moderate (Cliff’s delta=−0.1–0.3, CIs−0.79 to 0.28), reflecting a more positive outcome for the active treatment (67% and 44% of active arm-rated symptoms as ‘much improved’ at session 2 and follow-up, respectively, vs 20% inactive group). Effect sizes for secondary outcomes were variable.ConclusionsOur protocol is feasible. The findings suggest that supramotor threshold TMS of M1 is safe, acceptable and potentially beneficial as a treatment for functional limb weakness. A larger RCT is warranted.Trial registration numberNCT51225587.

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“…In the field of FMD, the use of rTMS as a therapeutic tool is still in its infancy. The published literature includes case report series and a small number of sham-controlled trials, characterized by a substantial variability in design and stimulation parameters (16–19). Importantly, these studies evaluated rTMS effects on clinical and behavioral outcomes of FMD, while it is unknown whether rTMS induces neuromodulatory and neuroplastic changes in relevant brain networks, which may underlie the observed clinical effects.…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Targeting fronto-limbic dysfunctions via intermittent theta burst stimulation as a novel treatment for Functional Movement Disorders

Parker

Horovitz

et al. 2021

Preprint

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Background. Neuroimaging studies suggest that corticolimbic dysfunctions, including increased amygdala reactivity to emotional stimuli and heightened fronto-amygdala coupling, play a central role in the pathophysiology of functional movement disorders (FMD), although there is no direct causal evidence of this relationship. Transcranial magnetic stimulation (TMS) has the potential to probe and modulate brain networks implicated in neuropsychiatric disorders, including FMD. Therefore, in this proof-of-concept study, we investigated safety, tolerability and preliminary efficacy of fronto-amygdala neuromodulation via targeted left prefrontal intermittent theta burst stimulation (iTBS) on brain and behavioral manifestations of FMD. Methods. Six subjects with a clinically defined diagnosis of FMD received three open-label iTBS sessions per day, for two consecutive study visits. Safety and tolerability were assessed throughout the trial. Amygdala reactivity to emotionally valenced stimuli presented during an fMRI task and fronto-amygdala connectivity at rest were evaluated at baseline and after each stimulation visit, together with subjective levels of arousal and valence in response to affective stimuli. FMD symptom severity was assessed at baseline, during treatment and 24 hours after receiving the last iTBS session. Results. Multiples doses of iTBS were well-tolerated by all participants. Intermittent TBS significantly decreased fronto-amygdala connectivity and also influenced amygdala reactivity to emotional stimuli. These neurocircuitry changes were associated to a significant decrease in negative valence and an increase in positive valence levels following iTBS. Furthermore, we also observed a marked reduction in FMD symptom severity post stimulation. Conclusions. Corticolimbic modulation via iTBS represents a promising treatment for FMD that warrants additional research.

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Repetitive transcranial magnetic stimulation for functional tremor: A randomized, double‐blind, controlled study

Cited by 36 publications

References 45 publications

Diagnosis and therapy of functional tremor a systematic review illustrated by a case report

Diagnosis and therapy of functional tremor a systematic review illustrated by a case report

Trial Of Neurostimulation In Conversion Symptoms (TONICS): a feasibility randomised controlled trial of transcranial magnetic stimulation for functional limb weakness

Targeting fronto-limbic dysfunctions via intermittent theta burst stimulation as a novel treatment for Functional Movement Disorders

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