Recruiting NCT03042962
Brain Networks in Dystonia
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: MRI, Blood draw.
- Who it may be relevant to
- Registry conditions: Spasmodic Dysphonia, Singer's Dystonia, Writer's Cramp, Musician's Focal Hand Dystonia. Basic parameters: 21 years — 80 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- United States
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
Overview
To date, there is only limited knowledge about the distinct neural abnormalities that lead to the development of different forms of focal dystonia. The goal of this study is to dissect the pathophysiological mechanisms underlying this clinical phenomenon using multi-level brain network analysis in patients with focal dystonia.
Detailed description
Among the many causes of craniofacial disease are focal dystonias such as blepharospasm (BSP) and oromandibular dystonia (OMD), affecting the eyes and jaw, respectively, as well as Meige Syndrome, which combines features of both. Craniofacial dystonias are poorly understood and have limited treatment options. The investigators hypothesize that craniofacial dystonia (CFD) may be caused by both rare and common genetic variants. To identify neural correlates of different genetic causes of CFD, the investigators will perform structural and functional whole-brain imaging and examine the organization of the neural network in these patients compared to healthy individuals and their unaffected blood relatives.
Interventions
- Other MRI
Functional and structural MRI of the brain will be conducted to identify disorder specific neural markers - Procedure Blood draw
Blood samples will be collected, the DNA will be extracted and banked for genetic studies
Primary outcome measures
- Incidence of brain structural and functional changes [Time frame: 5 years]
Eligibility criteria
Inclusion criteria
- Patients will have clinically documented focal dystonia
- Unaffected relatives of patients with focal dystonia
- Healthy controls will be healthy volunteers with a negative history of neurological, laryngeal or psychiatric problems
- Age from 21 to 80 years.
- Native English speakers.
- Right-handedness (based on Edinburgh Handedness Inventory).
Exclusion criteria
- Subjects who are incapable of giving an informed consent.
- Pregnant or breastfeeding women until a time when they are no longer pregnant or breastfeeding. All women of childbearing potential will have a urine pregnancy test performed, which must be negative for participation in the imaging studies.
- Subjects with past or present medical history of (a) neurological problems, such as stroke, movement disorders (other than dystonia in the patient groups), brain tumors, traumatic brain injury with loss of consciousness, ataxias, myopathies, myasthenia gravis, demyelinating diseases, alcoholism, drug depend-ence; (b) psychiatric problems, such as schizophrenia, major and/or bipolar depression, obsessive-compulsive disorder; (c) laryngeal problems, such as vocal fold paralysis, paresis, vocal fold nodules and polyps, carcinoma, chronic laryngitis.
- Patients who are not symptomatic due to treatment with botulinum toxin injections into the laryngeal muscles. The duration of positive effects of botulinum toxin vary from patient to patient but lasts on average for 3-4 months. All patients will be evaluated to ensure that they are fully symptomatic prior to entering the study.
- Patients with other forms of dystonia.
- Patients who have dystonia symptoms at rest in order to avoid the potential confound of dystonic spasms occurring during the scanning.
- To avoid the possibility of confounding effects of drugs acting upon the central nervous system, all study participants will be questioned about any prescribed or over-the-counter medications as part of their initial intake screening. Those patients who receive medication(s) affecting the central nervous system will be excluded from the study.
- The patients will be asked whether they have undergone any head, neck, or hand surgeries, which resulted in changes in regional anatomy or innervation. Because brain, hand and laryngeal surgery may potentially lead to the brain structure and function re-organization, all patients with history of brain, hand and/or laryngeal surgery will be excluded from the study.
- Subjects who have tattoos, ferromagnetic objects in their bodies (e.g., implanted stimulators, surgical clips, prosthesis, artificial heart valve, etc.) that cannot be removed for the purpose of study participation.
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: Yes
Study design
- Observational model
- Cohort
Study locations
United States · 1 center
- Massachusetts Eye and Ear — Boston
Publications
- Battistella G, Termsarasab P, Ramdhani RA, Fuertinger S, Simonyan K. Isolated Focal Dystonia as a Disorder of Large-Scale Functional Networks. Cereb Cortex. 2017 Feb 1;27(2):1203-1215. doi: 10.1093/cercor/bhv313. PMID 26679193
- Fuertinger S, Simonyan K. Stability of Network Communities as a Function of Task Complexity. J Cogn Neurosci. 2016 Dec;28(12):2030-2043. doi: 10.1162/jocn_a_01026. Epub 2016 Aug 30. PMID 27575646
- Rittiner JE, Caffall ZF, Hernandez-Martinez R, Sanderson SM, Pearson JL, Tsukayama KK, Liu AY, Xiao C, Tracy S, Shipman MK, Hickey P, Johnson J, Scott B, Stacy M, Saunders-Pullman R, Bressman S, Simonyan K, Sharma N, Ozelius LJ, Cirulli ET, Calakos N. Functional Genomic Analyses of Mendelian and Sporadic Disease Identify Impaired eIF2alpha Signaling as a Generalizable Mechanism for Dystonia. Neuro PMID 27939583
- Fuertinger S, Simonyan K. Connectome-Wide Phenotypical and Genotypical Associations in Focal Dystonia. J Neurosci. 2017 Aug 2;37(31):7438-7449. doi: 10.1523/JNEUROSCI.0384-17.2017. Epub 2017 Jul 3. PMID 28674168
- Simonyan K, Barkmeier-Kraemer J, Blitzer A, Hallett M, Houde JF, Jacobson Kimberley T, Ozelius LJ, Pitman MJ, Richardson RM, Sharma N, Tanner K; The NIH/NIDCD Workshop on Research Priorities in Spasmodic Dysphonia/Laryngeal Dystonia. Laryngeal Dystonia: Multidisciplinary Update on Terminology, Pathophysiology, and Research Priorities. Neurology. 2021 May 25;96(21):989-1001. doi: 10.1212/WNL.000000 PMID 33858994
- Worthley A, Simonyan K. Suicidal Ideations and Attempts in Patients With Isolated Dystonia. Neurology. 2021 Mar 16;96(11):e1551-e1560. doi: 10.1212/WNL.0000000000011596. Epub 2021 Jan 27. PMID 33504639
- Valeriani D, Simonyan K. A microstructural neural network biomarker for dystonia diagnosis identified by a DystoniaNet deep learning platform. Proc Natl Acad Sci U S A. 2020 Oct 20;117(42):26398-26405. doi: 10.1073/pnas.2009165117. Epub 2020 Oct 1. PMID 33004625
- Hanekamp S, Simonyan K. The large-scale structural connectome of task-specific focal dystonia. Hum Brain Mapp. 2020 Aug 15;41(12):3253-3265. doi: 10.1002/hbm.25012. Epub 2020 Apr 20. PMID 32311207
Identifiers
NCT: NCT03042962 · 2019P001183 · R01DE030464