A Multimodal Approach to Cervical Dystonia Treatment With Association of Botulinum Toxin and Motor Learning Techniques

Study Overview
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Brief Summary
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the aim of this study protocol is to describe, using a longitudinal study, a multimodal approach of treatment of cervical dystonia with botulinum toxin (BoNTA) and a new rehabilitation protocol named SPRInt (Sensory-motor perceptive rehabilitation integrated) approach based on motor learning techniques and spatial rehabilitation.

Detailed Description
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Longitudinal study utilizing a multimodal treatment protocol developing in six months time: Phase 1 : BoNTA injections localized in dystonic cervical muscles with EMG/US guides performed after polygraphy and kinematic analysis of cervical region Times: T0: pre treatment; T1: 6 weeks after T0 considered BoNTA pharmacological peak effect; T2: 12 weeks after T0 considered from guidelines and pharmaceutical data sheet the lowest BoNTA effect. Phase 2: BoNTA performed in the same way of Phase 1 associated to SPRInt protocol Times: T2: before combination of BoNTA and rehabilitation treatment (18 sessions of 45 minutes three times a week); T3: 6 weeks after T2 considered BoNTA pharmacological peak effect and the end of SPRInt protocol; T4: 12 weeks after T2 considered from guidelines and pharmaceutical data sheet the lowest BoNTA effect and follow up of SPRInt-consolidation. The SPRInt approach aims are to improve body perception, posture and movement quality and to restore body axis by using specific sensory feedbacks, both intrinsic (IFB) and extrinsic (EFB), and motor exercises (ME) with specific rhythmic temporal structure.The ME can be focused on different body parts (eyes, head, neck, trunk, arm) and involve different spatial planes (frontal, sagittal, horizontal, multiplanar). The exercises can be performed with eyes closed and with an external passive motor leading in order to improve proprioception and facilitate sensory integration by excluding visual or verbal information that can be misleading for the patient. The ability to perceive and integrate intrinsic feedback is the fundamental element to create mental image that define body scheme and motor behaviour. The extrinsic feedback can be continuous or discontinuous (on-off timing) and gives the patient information about the performance or result by positive or negative reinforcement; this process can be important to motivate and empower the patient in reaching new skills. The final goal for the patient is to reinforce and retain the informations collected with working memory and then stored with the consolidation process which ends in learning new skills (ie rescue postural axis) and improving motor tasks (ie move the head in the opposite position). At each time point these test are performed: CLINICAL SCALES i. Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Severity Disability Pain ii. Quality of life iii. Depression Beck Scale iv. Zung Self Rating Anxiety Scale v. Rey Test to test visuo spatial abilities MOVEMENT ANALYSIS and KINEMATIC AND EMG MAPPING of cervical region ( head and neck) FUNCTIONAL MAGNETIC RESONANCE BRAIN STUDY to perform brain measurements of functional connectivity (resting state-Default Mode Network), morphometry (volume, area, cortical thickness, cortical curvature, node degree) and tractography.

Official Title
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Multimodal Treatment of Cervical Dystonia With Botulinum Toxin Injections Associated With a Sensory-motor Perceptive Rehabilitation Integrated Approach (SPRInt) Based on Motor Learning Techniques

Conditions
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Cervical Dystonia,Primary

Intervention / Treatment
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* Combination Product: Botulinum Toxin+SPRInt


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: more than 18 yo diagnosis of idiopathic cervical dystonia disease duration more than 6 months Exclusion Criteria: diagnosis of secondary dystonia on previously performed neuroimaging data (ie structural lesion of cervical spine, vascular or traumatic brain injuries) history of neuroleptic drug treatment (antidopaminergic drugs) associated neurological illness botulinum toxin treatment in the 3 previous months before recruitment head tremor without dystonic posturing

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Botulinum toxin+SPRInt protocol<br>patients affected by cervical dystonia receive botulinum toxin treatment (EMG-US guided injections in dystonic muscles) for two times at T0 and T2; after T2 patients are treated also with SPRInt rehabilitation protocol based on motor learning techniques. | Combination Product: Botulinum Toxin+SPRInt<br>* Botulinum toxin injections in association with rehabilitative approach to cervical dystonia (SPRInt)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dystonia phenomenology improvement | a clinical assessment of dystonia will be conducted at each study visit using TWSTRS | every six weeks during six months time | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| quality of life | a clinical assessment of dystonia severity will be conducted at each study visit using quality of life scale (EQ5D5L) | every six weeks during six months time | 
| brain plasticity | study of functional connectivity using functional magnetic resonance | every six weeks during six months time | 
| depression | depression scale (BECK) | every six weeks during six months time | 
| anxiety | anxiety scale (ZUNG) | every six weeks during six months time | 
| structural grey matter plasticity | brain study of morphometry using functional magnetic resonance | every six weeks during six months time | 
| structural white matter plasticity | tractography of brain areas using functional magnetic resonance | every six weeks during six months time | 
| kinematic assessment of dystonia severity | visit with optoelectronic system | every six weeks during six months time |