Anatomical categorization of isolated non-focal dystonia: novel and existing patterns using a data-driven approach.

According to expert consensus, dystonia can be classified as focal, segmental, multifocal, and generalized, based on the affected body distribution. To provide an empirical and data-driven approach to categorizing these distributions, we used a data-driven clustering approach to compare frequency and co-occurrence rates of non-focal dystonia in pre-defined body regions using the Dystonia Coalition (DC) dataset. We analyzed 1,618 participants with isolated non-focal dystonia from the DC database. The analytic approach included construction of frequency tables, variable-wise analysis using hierarchical clustering and independent component analysis (ICA), and case-wise consensus hierarchical clustering to describe associations and clusters for dystonia affecting any combination of eighteen pre-defined body regions. Variable-wise hierarchical clustering demonstrated closest relationships between bilateral upper legs (distance = 0.40), upper and lower face (distance = 0.45), bilateral hands (distance = 0.53), and bilateral feet (distance = 0.53). ICA demonstrated clear grouping for the a) bilateral hands, b) neck, and c) upper and lower face. Case-wise consensus hierarchical clustering at k = 9 identified 3 major clusters. Major clusters consisted primarily of a) cervical dystonia with nearby regions, b) bilateral hand dystonia, and c) cranial dystonia. Our data-driven approach in a large dataset of isolated non-focal dystonia reinforces common segmental patterns in cranial and cervical regions. We observed unexpectedly strong associations between bilateral upper or lower limbs, which suggests that symmetric multifocal patterns may represent a previously underrecognized dystonia subtype.

Déclaration de conflit d'intérêts

JRY’s institution receives grant funding on his behalf from the National Institutes of Health (NIH). BB has received research grant support from the Dystonia Coalition (DC), the Parkinson’s Foundation (PF), the VCU School of Medicine, the Administration for Community Living, and the Dystonia Medical Research Foundation (DMRF). He has received honoraria from the International Parkinson and Movement Disorder Society (MDS) and serves on the medical advisory board of the Benign Essential Blepharospasm Research Foundation (BEBRF) and the National Spasmodic Torticollis Association. HJ has grant support (recent, active, or pending) from the US government (National Institutes of Health), private philanthropic organizations (Cure Dystonia Now), and industry (Addex, Aeon, Revance, Jazz) and has also served on advisory boards or as a consultant for Addex, Allergan, Apello, CoA Therapeutics, Cavion, Daiichi Sankyo, Ipsen, PureTech, Retrophin, Revance and Takaha/Ene. HJ has received honoraria or stipends for lectures or administrative work from the MDS and has also served on the Scientific Advisory Boards for several private foundations including the BEBRF, Cure Dystonia Now, the DMRF, the Tourette Association of America, and Tyler’s Hope for a Cure. JF is funded through an internal grant at the University of Colorado and through a philanthropic grant from the Mowry family. AW reports grant support from the NIH R01NS122943 as PI and RO1 NS121120-01 as a Co-I and reports past funding from BEBRF, DC, DMRF, and National Organization for Rare Disorders. AW has received consultant fees from Merz, Jazz and Acadia and is the current Vice President for the Tremor Research Group and recent advisor for Supernus and Biogen-Sage. AM has been funded by the DMRF, Sunflower Parkinson’s Disease Foundation and the PF. KD has received honoraria from the PF for web support. SP’s institution receives grant funding on her behalf from the NIH (P20 GM109899; U54 NS116025), Department of Defense (W81XWH-19-CTRR-CTA); Aeon, Scion, and she is a member of the Medical Scientific Advisory Committee for the DMRF and the BEBRF (uncompensated); she has received honoraria from American Academy of Neurology and the MDS for educational lectures. AD is funded by Teva (NCT04173260) and serves as site PI for trials from Cerevel, Teva, Lundbeck, and Annovis Bio. NS is an investigator in studies funded by F. Hoffmann-LaRoche Ltd., Neuraly, Inc., UCB Biopharma SPRL, Cerevel Therapeutics, Abbvie, Inc., Praxis Precision Medicines, Inc., DMRF, and NIH grant P50NS108675, and has been a consultant and received honoraria from The Huntington Study Group LTD., and PSG EARSTIM DSMB. SAN’s institution receives grant funding on his behalf from the NIH, DMRF, and Dysphonia International, and he is a member of the Medical Scientific Advisory Committee for the DMRF (uncompensated). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.