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

Official title

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

Overview

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.

Interventions

• 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.

Primary outcome measures

• Toronto Western Spasmodic Rating Scale (TWSTRS) score [Time frame: Baseline, after training (week 6) and 6 weeks after the end of training (week 12)]

Secondary outcome measures (8)

• Cervical range of motion [Time frame: Baseline, after training (week 6) and 6 weeks after the end of training (week 12)]
• Cervical Dystonia Impact Scale (CDIP-58) score [Time frame: Baseline, after training (week 6) and 6 weeks after the end of training (week 12)]
• Beck Depression inventory (BDI) score [Time frame: Baseline, after training (week 6) and 6 weeks after the end of training (week 12)]
• Hamilton Anxiety Rating Scale (HAM-A) score [Time frame: 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) [Time frame: Baseline, after training (week 6)]
• Brain functional changes during functional magnetic resonance imaging (MRI) task [Time frame: Baseline, after training (week 6)]
• Brain functional changes during functional magnetic resonance imaging (MRI) "conventional" resting state [Time frame: Baseline, after training (week 6)]
• Brain functional changes during functional magnetic resonance imaging (MRI) "sensory trick" resting state [Time frame: Baseline, after training (week 6)]

Eligibility criteria

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).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Supportive care

Study locations

Italy · 1 center

• IRCCS Ospedale San Raffaele — Milan

Identifiers

NCT: NCT06881147 · DYT_sensory_trick

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗