Data-driven clustering of combined Functional Motor Disorders based on the Italian registry

Giovanni Mostile^{1

2}, Christian Geroin³, Roberto Erro⁴, Antonina Luca¹, Enrico Marcuzzo³, Paolo Barone⁴, Roberto Ceravolo⁵, Sonia Mazzucchi⁵, Andrea Pilotto^{6

7}, Alessandro Padovani⁶, Luigi Michele Romito⁸, Roberto Eleopra⁸, Carlo Dallocchio⁹, Carla Arbasino⁹, Francesco Bono¹⁰, Pietro Antonio Bruno¹⁰, Benedetta Demartini¹¹, Orsola Gambini¹¹, Nicola Modugno¹², Enrica Olivola¹², Laura Bonanni^{13

14}, Alberto Albanese¹⁵, Gina Ferrazzano¹⁶, Rosa De Micco¹⁷, Maurizio Zibetti¹⁸, Giovanna Calandra-Buonaura^{19

20}, Martina Petracca²¹, Francesca Morgante^{22

23}, Marcello Esposito^{24

25}, Antonio Pisani^{26

27}, Paolo Manganotti²⁸, Fabrizio Stocchi²⁹, Mario Coletti Moja³⁰, Ilaria Antonella Di Vico³, Lucia Tesolin³¹, Francesco De Bertoldi³¹, Tommaso Ercoli³², Giovanni Defazio³², Mario Zappia¹, Alessandra Nicoletti¹, Michele Tinazzi³

Affiliations

¹ Section of Neurosciences, Department "G.F. Ingrassia", University of Catania, Catania, Italy.
² Oasi Research Institute-IRCCS, Troina, Italy.
³ Neurology Unit, Movement Disorders Division, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy.
⁴ Center for Neurodegenerative Diseases (CEMAND), Department of Medicine, Surgery and Dentistry-Scuola Medica Salernitana, University of Salerno, Baronissi, Italy.
⁵ Neurology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
⁶ Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
⁷ FERB Onlus, Ospedale S. Isidoro, Bergamo, Italy.
⁸ Parkinson and Movement Disorders Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
⁹ Department of Medical Area, Neurology Unit, ASST Pavia, Pavia, Italy.
¹⁰ Botulinum Toxin Center, Neurology Unit A.O.U. Mater Domini, Catanzaro, Italy.
¹¹ Aldo Ravelli Research Center for Neurotechnology and Experimental Brain Therapeutics, Department of Health Sciences, University of Milan, Milan, Italy.
¹² IRCCS Neuromed, Pozzilli, Italy.
¹³ Department of Medicine and Aging Sciences, University G. d'Annunzio, Chieti, Italy.
¹⁴ Department of Medicine and Aging Sciences, University G. d'Annunzio, Pescara, Italy.
¹⁵ IRCCS Humanitas Research Hospital, Milan, Italy.
¹⁶ Department of Human Neurosciences, Università La Sapienza, Rome, Italy.
¹⁷ Department of Advanced Medical and Surgery Sciences, University of Campania-Luigi Vanvitelli, Naples, Italy.
¹⁸ Department of Neuroscience-Rita Levi Montalcini, University of Turin, Turin, Italy.
¹⁹ Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
²⁰ IRCCS, Institute of Neurological Sciences of Bologna, Bologna, Italy.
²¹ Movement Disorder Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
²² Neurosciences Research Centre, Molecular and Clinical Sciences Neurosciences Research Centre, Molecular and Clinical Sciences Research Institute, St George's University of London, London, United Kingdom.
²³ Department of Experimental and Clinical Medicine, University of Messina, Messina, Italy.
²⁴ Clinical Neurophysiology Unit, Cardarelli Hospital, Naples, Italy.
²⁵ Department of Neurosciences, Reproductive and Odontostomatological Sciences, University of Naples-Federico II, Naples, Italy.
²⁶ IRCCS Mondino Foundation, Pavia, Italy.
²⁷ Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy.
²⁸ Clinical Neurology Unit, Department of Medical, Surgical and Health Services, University of Trieste, Trieste, Italy.
²⁹ University and Institute of Research and Medical Care San Raffaele, Rome, Italy.
³⁰ Ospedale degli Infermi, Biella, Italy.
³¹ Psichiatria, Ospedale San Maurizio, Bolzano, Italy.
³² Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy.

PMID: 36518193
PMCID: PMC9742245
DOI: 10.3389/fneur.2022.987593

Data-driven clustering of combined Functional Motor Disorders based on the Italian registry

Giovanni Mostile et al. Front Neurol. 2022.

. 2022 Nov 28:13:987593.

doi: 10.3389/fneur.2022.987593. eCollection 2022.

Authors

Affiliations

¹ Section of Neurosciences, Department "G.F. Ingrassia", University of Catania, Catania, Italy.
² Oasi Research Institute-IRCCS, Troina, Italy.
³ Neurology Unit, Movement Disorders Division, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy.
⁴ Center for Neurodegenerative Diseases (CEMAND), Department of Medicine, Surgery and Dentistry-Scuola Medica Salernitana, University of Salerno, Baronissi, Italy.
⁵ Neurology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
⁶ Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
⁷ FERB Onlus, Ospedale S. Isidoro, Bergamo, Italy.
⁸ Parkinson and Movement Disorders Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
⁹ Department of Medical Area, Neurology Unit, ASST Pavia, Pavia, Italy.
¹⁰ Botulinum Toxin Center, Neurology Unit A.O.U. Mater Domini, Catanzaro, Italy.
¹¹ Aldo Ravelli Research Center for Neurotechnology and Experimental Brain Therapeutics, Department of Health Sciences, University of Milan, Milan, Italy.
¹² IRCCS Neuromed, Pozzilli, Italy.
¹³ Department of Medicine and Aging Sciences, University G. d'Annunzio, Chieti, Italy.
¹⁴ Department of Medicine and Aging Sciences, University G. d'Annunzio, Pescara, Italy.
¹⁵ IRCCS Humanitas Research Hospital, Milan, Italy.
¹⁶ Department of Human Neurosciences, Università La Sapienza, Rome, Italy.
¹⁷ Department of Advanced Medical and Surgery Sciences, University of Campania-Luigi Vanvitelli, Naples, Italy.
¹⁸ Department of Neuroscience-Rita Levi Montalcini, University of Turin, Turin, Italy.
¹⁹ Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
²⁰ IRCCS, Institute of Neurological Sciences of Bologna, Bologna, Italy.
²¹ Movement Disorder Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
²² Neurosciences Research Centre, Molecular and Clinical Sciences Neurosciences Research Centre, Molecular and Clinical Sciences Research Institute, St George's University of London, London, United Kingdom.
²³ Department of Experimental and Clinical Medicine, University of Messina, Messina, Italy.
²⁴ Clinical Neurophysiology Unit, Cardarelli Hospital, Naples, Italy.
²⁵ Department of Neurosciences, Reproductive and Odontostomatological Sciences, University of Naples-Federico II, Naples, Italy.
²⁶ IRCCS Mondino Foundation, Pavia, Italy.
²⁷ Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy.
²⁸ Clinical Neurology Unit, Department of Medical, Surgical and Health Services, University of Trieste, Trieste, Italy.
²⁹ University and Institute of Research and Medical Care San Raffaele, Rome, Italy.
³⁰ Ospedale degli Infermi, Biella, Italy.
³¹ Psichiatria, Ospedale San Maurizio, Bolzano, Italy.
³² Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy.

PMID: 36518193
PMCID: PMC9742245
DOI: 10.3389/fneur.2022.987593

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.

Keywords: Functional Motor Disorders; clinical phenotypes; cluster analysis; data-driven phenotyping; functional neurological disorder.

Copyright © 2022 Mostile, Geroin, Erro, Luca, Marcuzzo, Barone, Ceravolo, Mazzucchi, Pilotto, Padovani, Romito, Eleopra, Dallocchio, Arbasino, Bono, Bruno, Demartini, Gambini, Modugno, Olivola, Bonanni, Albanese, Ferrazzano, De Micco, Zibetti, Calandra-Buonaura, Petracca, Morgante, Esposito, Pisani, Manganotti, Stocchi, Coletti Moja, Di Vico, Tesolin, De Bertoldi, Ercoli, Defazio, Zappia, Nicoletti and Tinazzi.

PubMed Disclaimer

Conflict of interest statement

The 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.

References

1. Tinazzi M, Morgante F, Marcuzzo E, Erro R, Barone P, Ceravolo R, et al. . Clinical correlates of functional motor disorders: an Italian multicenter study. Mov Disord Clin Pract. (2020) 7:920–9. 10.1002/mdc3.13077 - DOI - PMC - PubMed
1. Tinazzi M, Geroin C, Marcuzzo E, Cuoco S, Ceravolo R, Mazzucchi S, et al. . Functional motor phenotypes: to lump or to split? J Neurol. (2021) 268:4737–43. 10.1007/s00415-021-10583-w - DOI - PMC - PubMed
1. Erro R, Vitale C, Amboni M, Picillo M, Moccia M, Longo K, et al. . The heterogeneity of early Parkinson's disease: a cluster analysis on newly diagnosed untreated patients. PLoS ONE. (2013) 8:e70244. 10.1371/journal.pone.0070244 - DOI - PMC - PubMed
1. Mostile G, Terranova R, Rascunà C, Terravecchia C, Cicero CE, Giuliano L, et al. . Clinical-Instrumental patterns of neurodegeneration in Essential Tremor: a data-driven approach. Parkinsonism Relat Disord. (2021) 87:124–9. 10.1016/j.parkreldis.2021.05.011 - DOI - PubMed
1. Tinazzi M, Geroin C, Erro R, Marcuzzo E, Cuoco S, Ceravolo R, et al. . Functional motor disorders associated with other neurological diseases: beyond the boundaries of “organic” neurology. Eur J Neurol. (2021) 28:1752–8. 10.1111/ene.14674 - DOI - PubMed

LinkOut - more resources

Full Text Sources
Miscellaneous
- NCI CPTAC Assay Portal

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Data-driven clustering of combined Functional Motor Disorders based on the Italian registry

Affiliations

Data-driven clustering of combined Functional Motor Disorders based on the Italian registry

Authors

Affiliations

Abstract

Conflict of interest statement

References

LinkOut - more resources

Full Text Sources

Miscellaneous