Dystonic Tremor Syndrome
Conditions
Keywords
Botulinum neurotoxin, Botulinum toxin, Dystonia, Dystonic tremor syndrome, Dystonic tremor, Tremor associated with dystonia, Upper extremity, Functional magnetic resonance imaging, fMRI, Muscle ultrasound
Brief summary
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.
Detailed description
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.
Interventions
DIAGNOSTIC_TESTPolymyography
We will measure muscle activity using surface electromyography and tremor using inertial measurement units while subjects perform rest, posturing and kinetic tasks.
DIAGNOSTIC_TESTMuscle ultrasound
We will obtain B-mode images and videos of upper extremity muscles of the most affected upper extremity.
DIAGNOSTIC_TEST(Functional) magnetic resonance imaging
Subjects will undergo (f)MRI scanning involving concurrent electromyography, accelerometry and functional magnetic resonance imaging.
DIAGNOSTIC_TESTClinical assessment
We will assess tremor and dystonia severity using clinical scales.
DIAGNOSTIC_TESTQuestionnaires
We will collect patient-reported outcomes.
Three consequetive botulinum toxin injections of the upper extremities
Sponsors
Radboud University Medical Center
Canisius-Wilhelmina Hospital
Donders Centre for Cognitive Neuroimaging
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Uncontrolled multi-centre low-intervention clinical trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tremor severity assessed by the TRG Essential Tremor Rating Assessment Scale (TETRAS) | Baseline, 28 weeks | The primary outcome is the clinical tremor severity measured by the TRG Essential Tremor Rating Assessment Scale (TETRAS) at 28 weeks. The scale ranges between 0 and 112 points, with higher scores indicating a more severe tremor. The TETRAS consists of two subcategories: a 12-item activities of daily living subscale and a 9-item performance scale. The daily living subscale is scored by interviewing the participant. The performance scale is rated by observing the participants while they are performing multiple tasks. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Tremor severity assessed by the Fahn-Tolosa-Marin Tremor Rating Scale (FTM-TRS) | Baseline, 28 weeks | FTM-TRS \[0-152\]: higher scores indicate a more severe tremor. |
| Dystonia severity assessed by the Burke-Fahn-Marsden Dystonia Rating Scale (BFM-DRS) | Baseline, 28 weeks | BFM-DRS \[0-150\]: higher scores indicate more severe dystonia. |
| Additional neurological signs assessed by the Standardised Tremor Elements Assessment (STEA) | Baseline | STEA \[0-27\]: higher scores make a diagnosis of dystonic tremor syndrome instead of essential tremor more likely. |
| Quality of life assessed by the Quality of Life Essential Tremor Questionnaire (QUEST) | Baseline, 28 weeks | QUEST \[0-120\]: higher scores indicate greater dissatisfaction. |
| Psychological stress assessed by the Perceived stress scale (PSS) | Baseline, 28 weeks | PSS \[0-4\]: higher scores indicate higher levels of perceived stress |
| Pain assessed by the Numeric Pain Rating Scale (NPRS) | Baseline, 28 weeks | NPRS \[0-10\]: 0 indicates no pain and 10 the worst imaginable pain |
| Patient-reported change in tremor severity assessed by the Patient Global Impression of Change (PGIC) | 28 weeks | PGIC \[-3: much worse, -2: moderately worse, -1: slightly worse, 0: no change, 1: slightly better, 2: moderately better, 3: much better\] |
| Electrophysiological characteristics | Baseline, 28 weeks | e.g. tremor power, dominant frequency, frequency-width at half-width power, intermuscular coherence, tremulous muscles |
| Ultrasonographic tremulous activity | Baseline | — |
| Tremor related cerebral activity | Baseline | Quantified using functional MRI scanning |
| Botulinum toxin parameters | Baseline, 12 and 24 weeks | e.g. injection schemes, rationale for muscle selection, adherence |
Countries
Netherlands
Contacts
PRINCIPAL_INVESTIGATORAnke Snijders, PhD
Radboud University Medical Center
Outcome results
None listed