Clinical trial NCT03085745: Sensorimotor Mapping in Patients With Writer's Cramp
Official title: Corticomotor Plasticity as a Biomarker for Functional Improvement After Botulinium Treatment in Writer's Cramp
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Writer's Cramp
Keywords: Writer's cramp
Sensorimotor plasticity
TMS
Afferent inhibition
Motor mapping
Sensory mapping
adaptive sensorimotor synergies
fine motor control
Lead sponsor: University Hospital, Grenoble
Sponsor class: OTHER
First posted: 2017-03-21
Enrollment: 15
Sex: ALL
Minimum age (years): 30
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: Writer's cramp (WC) is a form of focal dystonia, a movement disorder characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive movements, postures, or both. It typically manifests while writing, making handwriting impossible in the most severe cases. Treatment can be difficult, but one effective and well-tolerated treatment consists in local muscle injections with botulinum toxin. Although clinical improvement seems to be related to focal muscle chemodenervation, central plasticity changes may occur. The main aim of the study is to characterize and quantify the changes in intrinsic hand muscle cortical representations at rest and during isometric contractions of the finger muscles before and after treatment with botulinum toxin and the changes in sensorimotor integration in patients with writer's cramp.

Detailed description: Fifteen WC patients will be enrolled in the study. A newly developed neuronavigated and robotized Transcranial Magnetic Stimulation (TMS) mapping approach will be used. It will generate a linear mediolateral excitability profile for two intrinsic hand muscle based on the mean Motor Evoked Potentials (MEPs) amplitude at each stimulation site. Changes in excitability profiles will reflect spatial reorganization of cortical motor output maps of the hand muscles. To measure afferent inhibition, the same mapping procedure will be repeated with a brief peripheral electrical stimulation prior the TMS pulse. These Short Afferent Inhibition (SAI) profiles will reflect the influence of the primary sensory cortex over the motor cortex. Finally, the stimulation grid will be translated to the primary somatosensory cortex and a paired pulse TMS paradigm will be applied just after a digital nerve stimulation. It will generate afferent signal processing profiles based on subjective perception for the index finger and the little finger. Participants will be tested before the botulinum toxin injections and at three different time points after the injections (7 days, 1 month and 3 months after). Botulinum toxin injections will be performed using ultrasound guide together with electromyography/nerve stimulation into the clinical affected hand muscles. Muscle selection for injections will be based on clinical criteria of postural deviation of the hand and fingers and responsible muscle forces. The dose will be chosen according to published clinical recommendation concerning starting dose for WC after the clinical examination, usually between 5 and 10 units of Xeomin® both for flexor and extensor hand/forearm muscles.

To precisely assess treatment efficacy, the Writer's Cramp Rating Scale (WCRS) as well as computer-based hand writing analyses and standard sensorimotor tests of hand functions (the Nine Holes Peg Test, a tapping test and a tactile spatial acuity task) will be performed before the injections and at each follow up session.

Eligibility criteria: Inclusion Criteria:

* Suffering from a writer's cramp
* aged 30-80 years old
* Botulinum toxin injection performed in clinical routine for their disease
* Affiliated to a social security system
* Sufficient intellectual capacities to understand the tasks to perform
* Written consent obtained

Exclusion Criteria:

* Impossibility to remain sitting down without pain or discomfort for at least 3 consecutive hours
* History or psychiatric or neurological disease, different from dystonia.
* Subject under judicial oversight
* Subject being within exclusion period
* Subject not reachable in case of emergency,
* Presence of one or several contraindications to TMS
* Subject covered by the following articles from the french Code de la Santé Publique: L1121-5, L1121-6, L1121-7 et L1121-8.

Primary outcomes:
measure: Corticospinal excitability profiles of intrinsic hand muscles
timeFrame: This measure will be performed before the injection of botulinum toxin and 7 days after, 30 days after and 3 months after the injection.
Secondary outcomes:
Other outcomes:
Locations:
city: Grenoble
country: France
facility: Grenoble University Hospital
Study officials:
affiliation: amoro@chu-grenoble.fr
name: Elena MORO, Pr
role: PRINCIPAL_INVESTIGATOR
References: