Factors Determining the Efficacy of Botulinum Toxin for Arm Tremor in Dystonia

Tremor occurs in up to 55% of dystonia patients, which is known as dystonic tremor syndrome (DTS). Tremor can be present in the body part affected by dystonia (dystonic tremor, DT), or an unaffected body part (tremor associated with dystonia, TAWD). DTS can be treated with botulinum neurotoxin (BoNT) injections, but BoNT is effective in only about 60-70% of patients. It is unknown which patients benefit most from BoNT treatment. The investigators aim to explore the associations between clinical and pathophysiological tremor characteristics and BoNT efficacy. To do so, the investigatorswill measure clinical, electrophysiological, ultrasonographic and (functional) magnetic resonance imaging ((f)MRI) characteristics before the start of BoNT treatment and measure BoNT efficacy after three three-monthly BoNT sessions.

Rationale: Tremor occurs in up to 55% of dystonia patients, which is known as dystonic tremor syndrome (DTS). Tremor can be present in the body part affected by dystonia (dystonic tremor, DT), or an unaffected body part (tremor associated with dystonia, TAWD). DTS can be treated with botulinum neurotoxin (BoNT) injections, but BoNT is effective in only about 60-70% of patients. It is unknown which patients benefit from BoNT treatment. This highlights the need for personalized treatment.

Objective: The primary objective is to explore the associations between clinical, electrophysiological, ultrasonographic and (functional) magnetic resonance imaging ((f)MRI) tremor characteristics and BoNT efficacy in DTS of the upper extremity. The secondary objectives are to:

* Explore the clinical, electrophysiological, ultrasonographic and (f)MRI differences between DT and TAWD of the upper extremity.
* Explore the agreement between a clinical assessment, polymyography (PMG) and muscle ultrasound (MUS) on muscle selection in DTS of the upper extremity.

Study design: An uncontrolled multi-centre low-intervention clinical trial where subjects participate for ± 8 months Study population: 60 adults with DTS (± 30 DT/ 30 TAWD) of the upper extremity who start 12-weekly BoNT treatment in normal clinical practice.

Main study parameters/endpoints: the associations between clinical, electrophysiological, ultrasonographic, and (f)MRI tremor characteristics at baseline and BoNT efficacy (change in TRG Essential Tremor Rating Assessment Scale (TETRAS) from baseline to 28 weeks).

Secondary trial endpoints:

* The clinical, electrophysiological, ultrasonographic and (f)MRI differences between DT and TAWD at baseline.
* The agreement between a clinical assessment, PMG and MUS on muscle selection. Intervention: Participants are treated with three consecutive BoNT sessions in normal clinical practice. Participants will undergo additional diagnostic procedures: 2 clinical assessments, 2 PMGs, 1 MUS recordings and 1 fMRI assessment and will fill in 2 questionnaires before and after the BoNT sessions.

Eligibility Criteria:
Inclusion Criteria:

* Clinical diagnosis of dystonic tremor or tremor associated with dystonia according to the 2018 consensus statement on the classification of tremors
* Tremor of one or both upper extremities
* Starting botulinum toxin injections as part of normal clinical practice
* Age ≥ 18 years

Exclusion Criteria:

* Acquired aetiology of dystonic tremor syndrome
* Previous botulinum toxin treatment of the to be treated upper extremity for ≥ 4 consecutive sessions
* In case of previous botulinum toxin treatment of the to be treated upper extremity for ≤3 consecutive sessions: the last botulinum toxin injections ≤ 6 months before study enrolment
* Unstable dose medications for dystonia and tremor ≤ 1 month before study enrolment
* Deep brain stimulation implantation ≤ 6 months before study enrolment
* Unstable deep brain stimulation variables ≤ 1 month before study enrolment
* Comorbidity interfering with study participation
* Known hypersensitivity for components of Dysport
* Infection at the upper extremity
* Pregnancy, trying to conceive and breastfeeding
* Insufficient knowledge of the Dutch or English language

Exclusion criteria for MRI scanning:

* Contraindications for MRI (e.g. previous brain surgery, claustrophobia, active implant, epilepsy, metal objects in the upper body that are incompatible with MRI)
* Moderate to severe head tremor while lying supine (to avoid artefacts caused by extensive head motion during scanning).
* Inability to provoke postural tremor while lying supine.