I was able to participate in the Dystonia Coalition, a multicenter and international dystonia study, for several years while working at the Institute of Neurogenetics in Luebeck (Germany). To emphasize how valuable such international coalitions and databases are, I would like to give a brief overview of the publications in which I was involved. (This only serves as a brief overview and leaves many aspects unanswered. The unanswered content can be found in the corresponding papers.) Many other publications have emerged from this database in which I was not involved. The projects that the MJFF has initiated have the potential to achieve similar successes for PD, so it is up to us to use the data and turn it into publications. I would therefore like to encourage you to do so!
Non-Motor Symptoms:
Non-motor symptoms (NMS) often accompany the motor manifestations in isolated dystonia, occur more frequently than in healthy controls, and have a major impact on the health-related quality of life of patients (HR-QoL) with isolated dystonia.
603 patients with isolated dystonia were examined in the cross-sectional analysis, of which 155 dystonia patients met the inclusion criteria for the longitudinal study design (three assessments within 2 years).
Depressive symptoms were associated with reduced health-related quality of life in all eight subdomains (RAND 36-Item Health Survey) in both the cross-sectional and the longitudinal study design. Symptoms of generalized anxiety disorder and social phobia correlated with a reduced quality of life in all subdomains in the cross-sectional design, while fewer domains were influenced by anxiety in the longitudinal examination. Latent class growth analysis in the longitudinal study design separated two categories of patients with either higher or lower HR-QoL and identified a distinct profile of predictors in each. HR-QoL was more dependent on symptoms of depression and social anxiety in patients with a higher QoL (74.4% ± 16.1), whereas generalized anxiety predicted HR-QoL in the group of patients with a lower HR-QoL (45.5% ± 17.6). Dystonia severity predicted social functioning, but neither dystonic tremor, age, or sex predicted HR-QoL at 2 years.
Further analysis showed that anxiety and social anxiety severity vary by onset site of focal dystonia with anxiety being pronounced in patients with cervical and laryngeal dystonia.
The impact of psychiatric symptoms on HR-QoL emphasizes the importance of incorporating mental health treatment, in particular the therapy of anxiety disorders, into treatment regimens for dystonia.
Junker J, Berman BD, Hall J, Wahba DW, Brandt V, Perlmutter JS, Jankovic J, Malaty IA, Wagle Shukla A, Reich SG, Espay AJ, Duque KR, Patel N, Roze E, Vidailhet M, Jinnah HA, Brüggemann N (2021) Quality of life in isolated dystonia: non-motor manifestations matter. J Neurol Neurosurg Psychiatry https://dx.doi.org/10.1136/jnnp-2020-325193
Junker J, Hall J, Berman BD, Vidailhet M, Roze E, Baumer T, Malaty IA, Shukla AW, Jankovic J, Reich SG, Espay AJ, Duque KR, Patel N, Perlmutter JS, Jinnah HA, Dystonia Coalition Study G, Brandt V, Bruggemann N (2023) Longitudinal predictors of health-related quality of life in isolated dystonia. J Neurol Longitudinal predictors of health-related quality of life in isolated dystonia | Journal of Neurology
Berman BD, Junker J, Shelton E, Sillau SH, Jinnah HA, Perlmutter JS, Espay AJ, Jankovic J, Vidailhet M, Bonnet C, Ondo W, Malaty IA, Rodriguez R, McDonald WM, Marsh L, Zurowski M, Baumer T, Bruggemann N (2017) Psychiatric associations of adult-onset focal dystonia phenotypes. J Neurol Neurosurg Psychiatry https://dx.doi.org/10.1136/jnnp-2016-315461
Alcohol Responsiveness:
Out of 1258 patients of the Dystonia Coalition cohort, almost 30% reported improvement of dystonia after alcohol consumption. The association of alcohol responsiveness with a positive family history of movement disorders, generalized dystonia, and an earlier age at onset suggests that patients with dystonia who have an underlying genetic contribution may be more likely to respond beneficially to alcohol. Furthermore, alcohol responsiveness was associated with an increased risk of spread to muscles beyond the initially affected body region. Alcohol responsiveness was also related to tremor, but not related to sex, age, and severity of dystonia.
Junker J, Brandt V, Berman BD, Vidailhet M, Roze E, Weissbach A, Comella C, Malaty IA, Jankovic J, LeDoux MS, Berardelli A, Barbano R, Reich SG, Perlmutter JS, Jinnah HA, Bruggemann N (2018) Predictors of alcohol responsiveness in dystonia. Neurology https://dx.doi.org/10.1212/WNL.0000000000006551
Berman BD, Groth CL, Sillau SH, Pirio Richardson S, Norris SA, Junker J, Brüggemann N, Agarwal P, Barbano RL, Espay AJ, Vizcarra JA, Klein C, Bäumer T, Loens S, Reich SG, Vidailhet M, Bonnet C, Roze E, Jinnah HA, Perlmutter JS (2020) Risk of spread in adult-onset isolated focal dystonia: a prospective international cohort study. J Neurol Neurosurg Psychiatry 91:314-320. https://dx.doi.org/10.1136/jnnp-2019-321794
Dystonic Tremor:
Of 2362 Dystonia Coalition patients, about half were diagnosed with dystonic tremor. Factors associated with tremor included body region affected by dystonia, severity, and duration of dystonia, and recruitment centers, but not sex or race.
Shaikh AG, Beylergil SB, Scorr L, Kilic-Berkmen G, Freeman A, Klein C, Junker J, Loens S, Brüggemann N, Münchau A, Bäumer T, Vidailhet M, Roze E, Bonnet C, Jankovic J, Jimenez-Shahed J, Patel N, Marsh L, Comella C, Barbano RL, Berman BD, Malaty I, Shukla AW, Reich SG, Ledoux MS, Berardelli A, Ferrazzano G, Stover N, Ondo W, Richardson SP, Saunders-Pullman R, Mari Z, Agarwal P, Adler C, Chouinard S, Fox SH, Brashear A, Truong D, Suchowersky O, Frank S, Factor S, Perlmutter J, Jinnah HA (2020) Dystonia & tremor: A cross-sectional study of the dystonia coalition cohort. Neurology https://dx.doi.org/10.1212/wnl.0000000000011049
Genetic Features of Cervical Dystonia:
This study aimed to characterize the clinical and genetic features of cervical dystonia. Examination of 1000 dystonia patients revealed that coding and noncoding variants in GNAL, THAP1, and TOR1A make small contributions (0.8%) to the pathogenesis of CD.
LeDoux MS, Vemula SR, Xiao J, Thompson MM, Perlmutter JS, Wright LJ, Jinnah HA, Rosen AR, Hedera P, Comella CL, Weissbach A, Junker J, Jankovic J, Barbano RL, Reich SG, Rodriguez RL, Berman BD, Chouinard S, Severt L, Agarwal P, Stover NP (2016) Clinical and genetic features of cervical dystonia in a large multicenter cohort. Neurology Genetics 2:e69. https://dx.doi.org/10.1212/NXG.0000000000000069