Physiotherapy and Botox for Cervical Dystonia: Impact of Sensory Tricks and Brain Imaging Insights

Effects of Physiotherapy Combined With Botulinum Neurotoxin in Patients With Cervical Dystonia With and Without an Effective Sensory Trick: Clinical and Functional MRI Findings

The primary aim of this study is to investigate improvements of dystonia severity in patients with cervical dystonia (CD) with (DYT-trick) and without sensory trick (DYT-no-trick) following 6 weeks of physiotherapy combined with botulinum toxin injection (BoNT).

The recruited patients will be divided into two groups according to the presence of an effective sensory trick (DYT trick and DYT no-trick groups).

The researchers analyzing clinical, neurophysiological and MRI data as well as the statistician will be blind about the allocation of subjects to the two groups. Considering the different clinical phenotypes of patients (DYT-trick and DYT-no-trick) clinical evaluators and physiotherapists cannot be blind.

All patients will perform the routinely BoNT injection and after 1 week they will start a multimodal physiotherapy program lasting 6 weeks, 3 times a week for 45 minutes each session. The physiotherapy treatment will include soft tissue mobilization of inoculated muscles, stretching exercises of the inoculated muscles, strengthening of antagonist muscles, and motor learning exercises (attentive strategies, feedback-based cervical active exercises). Exercises will be progressively difficult (increase of active range of motion -ROM) according to clinical improvements during the 6 weeks of treatment.

Clinical assessments will be performed at baseline (T0), after 6 weeks of treatment (W6) and before the next BoNT injection (about 12 weeks of follow-up, W12) to evaluate disease severity (TWSTRS), pain, active cervical range of motion, disability, quality of life and mood. Cervical movements during TWSTRS will be monitored using the Virtual Reality Rehabilitation System (VRRS), which includes the usage of magneto-inertial sensors to objectively assess joint positions and quality of movement. MRI evaluations will be performed at T0 and at W6 to investigate resting state functional Magnetic Resonance Imaging (fMRI) changes and fMRI changes of brain activation during the simulation and imagination of sensory trick.

SAI paradigm is obtained combing transcranial magnetic stimulation (TMS) with peripheral electrical stimulation techniques. It will be performed at baseline (before BoNT injection and physiotherapist training) and after week 6 of physiotherapist training.

A group of healthy subjects similar for age and sex to patients will be recruited to perform cognitive assessment and MRI at baseline.

Study Overview

• Status: Enrolling by invitation
• Conditions: Cervical Dystonia
• Intervention / Treatment: Behavioral: Multimodal physiotherapy program

• Study Type: Interventional
• Enrollment (Estimated): 49
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Italia
    • Milano, Italia, Italy, 20132
      • IRCCS Ospedale San Raffaele

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria fo patients with Cervical Dystonia:

• Adult onset idiopathic CD according to established diagnostic criteria (Albanese et al., Eur J Neur, 2011) with and without an effective sensory trick will be eligible for the study

Exclusion Criteria for all participants

• presence of fixed postures because of skeletal neck deformity;
• history of (other) systemic, neurologic, psychiatric diseases, head injury, cardiovascular events, and cerebrovascular alterations visible at an MRI scan;
• alcohol and/or psychotropic drugs abuse;
• contraindication to perform MRI scan (cardiac pace-maker or other types of cardiac catheters, splinters or metallic shards, metallic prosthesis not compatible with magnetic field generated by MRI, claustrophobia).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patients with Cervical Dystonia and an effective sensory trick (DYT-trick); Patients with an effective sensory trick will undergo a multimodal physiotherapy program for 6 weeks	Behavioral: Multimodal physiotherapy program; Multimodal physiotherapy program of 6 weeks (3 times a week for 45 minutes), each session will include: Soft tissue mobilization of inoculated muscles;; Stretching exercises of the inoculated muscles;; Strengthening of antagonist muscles;; Motor learning exercises (attentive strategies, feedback-based cervical active exercises). Exercises will be progressively difficult (increase of active ROM) according to clinical improvements.
Experimental: Patients with Cervical Dystonia and without an effective sensory trick (DYT-no-trick); Patients without an effective sensory trick will undergo a multimodal physiotherapy program for 6 weeks	Behavioral: Multimodal physiotherapy program; Multimodal physiotherapy program of 6 weeks (3 times a week for 45 minutes), each session will include: Soft tissue mobilization of inoculated muscles;; Stretching exercises of the inoculated muscles;; Strengthening of antagonist muscles;; Motor learning exercises (attentive strategies, feedback-based cervical active exercises). Exercises will be progressively difficult (increase of active ROM) according to clinical improvements.
No Intervention: Healthy subjects; Age- and sex-matched healthy subjects recruited to compare clinical and MRI characteristics at baseline.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Toronto Western Spasmodic Rating Scale (TWSTRS) score	Rating scale measuring severity, disability and pain associated with cervical dystonia (score 0-85, higher score = worse condition)	Baseline, after training (week 6) and 6 weeks after the end of training (week 12)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cervical Dystonia Impact Scale (CDIP-58) score	Questionnaire assessing the impact of cervical dystonia on activities of daily living, mood and health (score 0-100, higher score = higher impact)	Baseline, after training (week 6) and 6 weeks after the end of training (week 12)
Beck Depression inventory (BDI) score	Evaluates depression (score 0-63, higher score = worse depressive symptoms)	Baseline, after training (week 6) and 6 weeks after the end of training (week 12)
Hamilton Anxiety Rating Scale (HAM-A) score	Evaluates anxiety (score 0-56, higher score = worse anxiety symptoms)	Baseline, after training (week 6) and 6 weeks after the end of training (week 12)
Short-latency afferent inhibition (SAI) paradigm using transcranial magnetic stimulation (TMS)	TMS will be performed with a high power Magstim 200. A figure-of-eight Coil (70 mm external diameter) will be positioned over the hand area of the motor cortex. Motor evoked potentials (MEPs) will be recorded from first dorsal interosseous muscle (FDI) of the hand not performing the sensory trick. Resting motor threshold (RMT) will be determined starting below the expected threshold, with 5% stimulator output increments. RMT will be reported as percentage of maximum stimulator output (% MSO). To assess the SAI a conditioning electrical pulses will be applied through a bipolar electrode to the median nerve (not involved in sensory trick) at the wrist (cathode proximal). SAI will be randomly applied in two conditions: (A) at rest, with the patient's head positioned according to its dystonic pattern and (B) while patients will be performing the sensory trick	Baseline, after training (week 6)
Brain functional changes during functional magnetic resonance imaging (MRI) task	A block design (ABAB) will be used, in which activation periods (A) alternated with resting-state periods (B). During activation periods (at the acoustic signal "go") DYT-trick patients will be asked to imagine their own effective sensory trick while DYT no-trick will imagine a simulation of sensory trick. Before scanning, participants will familiarize with the experimental condition.	Baseline, after training (week 6)
Brain functional changes during functional magnetic resonance imaging (MRI) "conventional" resting state	Subjects will be instructed to remain motionless and to keep their eyes closed	Baseline, after training (week 6)
Brain functional changes during functional magnetic resonance imaging (MRI) "sensory trick" resting state	Before scanning DYT subjects will be asked to execute (DYT-trick) or to simulate (DYT-no-trick) the sensory trick (i.e. slight touch on the cheek/chin) and to maintain it for the entire scanning. During scanning, DYT subjects will be instructed to remain motionless and to keep their eyes closed.	Baseline, after training (week 6)
Cervical range of motion	Measure cervical active ROM (flexion, extension and lateral flexion) using electromagnetic sensors and the Virtual Reality Rehabilitation System (VRRS)	Baseline, after training (week 6) and 6 weeks after the end of training (week 12)

Collaborators and Investigators

• Sponsor: IRCCS San Raffaele
• Collaborators: Ospedale San Luca, Istituto Auxologico Italiano, Milano
• Investigators: Principal Investigator: Massimo MF Filippi, MD, IRCCS Ospedale San Raffaele

Study record dates

Study Major Dates

• Study Start (Actual): April 13, 2019
• Primary Completion (Estimated): January 1, 2026
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: February 11, 2025
• First Submitted That Met QC Criteria: March 11, 2025
• First Posted (Actual): March 18, 2025

Study Record Updates

• Last Update Posted (Actual): May 1, 2025
• Last Update Submitted That Met QC Criteria: April 29, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neurologic Manifestations; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Dyskinesias; Dystonia; Dystonic Disorders; Torticollis
• Other Study ID Numbers: DYT_sensory_trick

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No