AUTHOR=Mostile Giovanni , Geroin Christian , Erro Roberto , Luca Antonina , Marcuzzo Enrico , Barone Paolo , Ceravolo Roberto , Mazzucchi Sonia , Pilotto Andrea , Padovani Alessandro , Romito Luigi Michele , Eleopra Roberto , Dallocchio Carlo , Arbasino Carla , Bono Francesco , Bruno Pietro Antonio , Demartini Benedetta , Gambini Orsola , Modugno Nicola , Olivola Enrica , Bonanni Laura , Albanese Alberto , Ferrazzano Gina , De Micco Rosa , Zibetti Maurizio , Calandra-Buonaura Giovanna , Petracca Martina , Morgante Francesca , Esposito Marcello , Pisani Antonio , Manganotti Paolo , Stocchi Fabrizio , Coletti Moja Mario , Di Vico Ilaria Antonella , Tesolin Lucia , De Bertoldi Francesco , Ercoli Tommaso , Defazio Giovanni , Zappia Mario , Nicoletti Alessandra , Tinazzi Michele TITLE=Data-driven clustering of combined Functional Motor Disorders based on the Italian registry JOURNAL=Frontiers in Neurology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2022.987593 DOI=10.3389/fneur.2022.987593 ISSN=1664-2295 ABSTRACT=Introduction

Functional Motor Disorders (FMDs) represent nosological entities with no clear phenotypic characterization, especially in patients with multiple (combined FMDs) motor manifestations. A data-driven approach using cluster analysis of clinical data has been proposed as an analytic method to obtain non-hierarchical unbiased classifications. The study aimed to identify clinical subtypes of combined FMDs using a data-driven approach to overcome possible limits related to “a priori” classifications and clinical overlapping.

Methods

Data were obtained by the Italian Registry of Functional Motor Disorders. Patients identified with multiple or “combined” FMDs by standardized clinical assessments were selected to be analyzed. Non-hierarchical cluster analysis was performed based on FMDs phenomenology. Multivariate analysis was then performed after adjustment for principal confounding variables.

Results

From a study population of n = 410 subjects with FMDs, we selected n = 188 subjects [women: 133 (70.7%); age: 47.9 ± 14.4 years; disease duration: 6.4 ± 7.7 years] presenting combined FMDs to be analyzed. Based on motor phenotype, two independent clusters were identified: Cluster C1 (n = 82; 43.6%) and Cluster C2 (n = 106; 56.4%). Cluster C1 was characterized by functional tremor plus parkinsonism as the main clinical phenotype. Cluster C2 mainly included subjects with functional weakness. Cluster C1 included older subjects suffering from anxiety who were more treated with botulinum toxin and antiepileptics. Cluster C2 included younger subjects referring to different associated symptoms, such as pain, headache, and visual disturbances, who were more treated with antidepressants.

Conclusion

Using a data-driven approach of clinical data from the Italian registry, we differentiated clinical subtypes among combined FMDs to be validated by prospective studies.