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DOI: 10.1055/s-0045-1811728
Cerebellar and extra-cerebellar symptoms in movement disorders
Authors

Abstract
The cerebellum and basal ganglia are integrated structures of the motor system, classically viewed as separate entities with different roles. Interactions between these structures were believed to occur mainly at the cortical level. However, neuroanatomical studies have resulted in a shift in this perspective. Symptoms attributed to basal ganglia disorders may arise from aberrant cerebellar circuit activity, and, conversely, cerebellar dysfunction may manifest due to pathological changes in basal ganglia pathways. In this narrative review, we present multiple disorders of the basal ganglia and cerebellum, highlighting their intricate interactions.
Authors' Contributions
Conceptualization: JLP; Data curation: DLB, VRP; Formal analysis: DLB, VRP; Funding acquisition: JLP; Investigation: DLB, VRP; Methodology: DLB, VRP; Project administration: JLP; Resources: JLP; Software: JLP; Supervision: JLP; Validation: JLP; Visualization: HBF, OGPB; Writing – original draft: DLB, VRP Writing – review & editing: HBF, OGPB.
Data Availability Statement
No new data were generated or analyzed in this study.
Editor-in-Chief: Hélio A. G. Teive https://orcid.org/0000-0003-2305-1073.
Associate Editor: Vitor Tumas https://orcid.org/0000-0003-2402-2709.
Publikationsverlauf
Eingereicht: 30. März 2025
Angenommen: 15. Juli 2025
Artikel online veröffentlicht:
19. September 2025
© 2025. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/)
Thieme Revinter Publicações Ltda.
Rua Rego Freitas, 175, loja 1, República, São Paulo, SP, CEP 01220-010, Brazil
Dayany Leonel Boone, Victor Rebelo Procaci, Henrique Ballalai Ferraz, Orlando Graziani Povoas Barsottini, José Luiz Pedroso. Cerebellar and extra-cerebellar symptoms in movement disorders. Arq Neuropsiquiatr 2025; 83: s00451811728.
DOI: 10.1055/s-0045-1811728
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References
- 1 Bostan AC, Strick PL. The basal ganglia and the cerebellum: nodes in an integrated network. Nat Rev Neurosci 2018; 19 (06) 338-350
- 2 Bostan AC, Dum RP, Strick PL. Cerebellar networks with the cerebral cortex and basal ganglia. Trends Cogn Sci 2013; 17 (05) 241-254
- 3 Bostan AC, Dum RP, Strick PL. The basal ganglia communicate with the cerebellum. Proc Natl Acad Sci U S A 2010; 107 (18) 8452-8456
- 4 Hoshi E, Tremblay L, Féger J, Carras PL, Strick PL. The cerebellum communicates with the basal ganglia. Nat Neurosci 2005; 8 (11) 1491-1493
- 5 Jackson NN, Stagray JA, Snell HD. Cerebellar contributions to dystonia: unraveling the role of Purkinje cells and cerebellar nuclei. Dystonia 2025; 4: 14006
- 6 Washburn S, Oñate M, Yoshida J, Vera J, Bhuvanasundaram R, Khatami L. et al. The cerebellum directly modulates the substantia nigra dopaminergic activity. Nat Neurosci 2024; 27 (03) 497-513
- 7 Yoshida J, Oñate M, Khatami L, Vera J, Nadim F, Khodakhah K. Cerebellar Contributions to the Basal Ganglia Influence Motor Coordination, Reward Processing, and Movement Vigor. J Neurosci 2022; 42 (45) 8406-8415
- 8 Van der Heijden ME, Brown AM, Kizek DJ, Sillitoe RV. Neural spiking signatures predict behavioral phenotypes of cerebellar movement disorders. Neuroscience 2024; x: x
- 9 Tax CMW, Genc S, MacIver CL, Nilsson M, Wardle M, Szczepankiewicz F. et al. Ultra-strong diffusion-weighted MRI reveals cerebellar grey matter abnormalities in movement disorders. Neuroimage Clin 2023; 38: 103419
- 10 Pedroso JL, Carvalho AA, Bezerra MLE, Braga-Neto P, Abrahão A, Albuquerque MVC. et al. Unusual movement disorders in spinocerebellar ataxias. Parkinsonism Relat Disord 2013; 19 (09) 834-835
- 11 Van Gaalen J, Giunti P, Van de Warrenburg BP. Movement disorders in spinocerebellar ataxias. Mov Disord 2011; 26 (05) 792-800
- 12 Lu CS, Wu Chou YH, Yen TC, Tsai CH, Chen RS, Chang HC. Dopa-responsive parkinsonism phenotype of spinocerebellar ataxia type 2. Mov Disord 2002; 17 (05) 1046-1051
- 13 Buhmann C, Bussopulos A, Oechsner M. Dopaminergic response in Parkinsonian phenotype of Machado-Joseph disease. Mov Disord 2003; 18 (02) 219-221
- 14 Braga-Neto P, Felicio AC, Hoexter MQ, Pedroso JL, Dutra LA, Alessi H. et al. Cognitive and olfactory deficits in Machado-Joseph disease: a dopamine transporter study. Parkinsonism Relat Disord 2012; 18 (07) 854-858
- 15 Procaci VR, Hora RPCD, Barsottini OGP, Pedroso JL. Tremulous SCA3: The Complex Connection between the Cerebellum and Basal Ganglia. Cerebellum 2025; 24 (03) 62
- 16 Riess O, Rüb U, Pastore A, Bauer P, Schöls L. SCA3: neurological features, pathogenesis and animal models. Cerebellum 2008; 7 (02) 125-137
- 17 Azevedo MPC, Lobo CC, Schmitt GS, Matos PCAAP, Barsottini OGP, José Pedroso JL. et al. Nigrostriatal dysfunction in RFC1-related disorder/CANVAS. Parkinsonism Relat Disord 2023; 115: 105854
- 18 Matos PCAAP, Rezende TJR, Schmitt GS, Bonadia LC, Reis F, Martinez ARM. et al. Brain Structural Signature of RFC1-Related Disorder. Mov Disord 2021; 36 (11) 2634-2641
- 19 Huin V, Coarelli G, Guemy C, Boluda S, Debs R, Mochel F. et al. Motor neuron pathology in CANVAS due to RFC1 expansions. Brain 2022; 145 (06) 2121-2132
- 20 Huang Y, Zhen Z, Deng L, Ou P, Shi L, Shi F. et al. Beyond the cerebellum: perivascular space burden in spinocerebellar ataxia type 3 extends to multiple brain regions. Brain Commun 2025; 7 (02) fcaf118
- 21 Wu J, Cheng X, Ji D, Niu H, Yao S, Lv X. et al. The Phenotypic and Genotypic Spectrum of CSF1R-Related Disorder in China. Mov Disord 2024; 39 (05) 798-813
- 22 Tai H, Wang A, Zhang Y, Liu S, Pan Y, Li K. et al; China NIID Collaboration Alliance. Clinical Features and Classification of Neuronal Intranuclear Inclusion Disease. Neurol Genet 2023; 9 (02) e200057
- 23 Pedroso JL, Vale TC, Freitas JL, Araújo FMM, Meira AT, Braga Neto P. et al. Movement disorders in hereditary spastic paraplegias. Arq Neuropsiquiatr 2023; 81 (11) 1000-1007
- 24 Fay-Karmon T, Hassin-Baer S. The spectrum of tremor among carriers of the FMR1 premutation with or without the fragile X-associated tremor/ataxia syndrome (FXTAS). Parkinsonism Relat Disord 2019; 65: 32-38
- 25 Gövert F, Abrante L, Becktepe J, Balint B, Ganos C, Hofstadt-van Oy U. et al. Distinct movement disorders in contactin-associated-protein-like-2 antibody-associated autoimmune encephalitis. Brain 2023; 146 (02) 657-667
- 26 Rezende Filho FM, Vale TC, Pedroso JL, Braga-Neto P, Barsottini OG. Facial grimacing and clinical correlates in spinocerebellar ataxia type 3. J Neurol Sci 2019; 397: 138-140
- 27 Kuo PH, Gan SR, Wang J, Lo RY, Figueroa KP, Tomishon D. et al. Dystonia and ataxia progression in spinocerebellar ataxias. Parkinsonism Relat Disord 2017; 45: 75-80
- 28 Rossi M, Balint B, Millar Vernetti P, Bhatia KP, Merello M. Genetic Dystonia-ataxia Syndromes: Clinical Spectrum, Diagnostic Approach, and Treatment Options. Mov Disord Clin Pract 2018; 5 (04) 373-382
- 29 Ruiz PJG, Mayo D, Hernandez J, Cantarero S, Ayuso C. Movement disorders in hereditary ataxias. J Neurol Sci 2002; 202 (1-2): 59-64
- 30 Pearson TS. More Than Ataxia: Hyperkinetic Movement Disorders in Childhood Autosomal Recessive Ataxia Syndromes. Tremor Other Hyperkinet Mov (N Y) 2016; 6: 368
- 31 De Riggi M, De Giorgi A, Pollini L, Angelini L, Paparella G, Cannavacciuolo A. et al. CACNA1G Causes Dominantly Inherited Myoclonus-Ataxia with Intellectual Disability: A Case Report. Cerebellum 2024; 23 (06) 2679-2683
- 32 Rossi M, Van der Veen S, Merello M, Tijssen MAJ, Van de Warrenburg B. Myoclonus-Ataxia Syndromes: A Diagnostic Approach. Mov Disord Clin Pract 2020; 8 (01) 9-24
- 33 Synofzik M, Schüle R, Schulze M, Gburek-Augustat J, Schweizer R, Schirmacher A. et al. Phenotype and frequency of STUB1 mutations: next-generation screenings in Caucasian ataxia and spastic paraplegia cohorts. Orphanet J Rare Dis 2014; 9: 57
- 34 Pedroso JL, de Freitas MET, Albuquerque MVC, Saraiva-Pereira ML, Jardim LB, Barsottini OGP. Should spinocerebellar ataxias be included in the differential diagnosis for Huntington's diseases-like syndromes?. J Neurol Sci 2014; 347 (1-2): 356-358
- 35 Verhagen MMM, Last JI, Hogervorst FBL, Smeets DFCM, Roeleveld N, Verheijen F. et al. Presence of ATM protein and residual kinase activity correlates with the phenotype in ataxia-telangiectasia: a genotype-phenotype study. Hum Mutat 2012; 33 (03) 561-571
- 36 Teive HAG, Camargo CHF, Munhoz RP. More than ataxia - Movement disorders in ataxia-telangiectasia. Parkinsonism Relat Disord 2018; 46: 3-8
- 37 Eilam R, Peter Y, Elson A, Rotman G, Shiloh Y, Groner Y, Segal M. Selective loss of dopaminergic nigro-striatal neurons in brains of Atm-deficient mice. Proc Natl Acad Sci U S A 1998; 95 (21) 12653-12656
- 38 Mount HTJ, Martel JC, Fluit P, Wu Y, Gallo-Hendrikx E, Cosi C, Marien MR. Progressive sensorimotor impairment is not associated with reduced dopamine and high energy phosphate donors in a model of ataxia-telangiectasia. J Neurochem 2004; 88 (06) 1449-1454
- 39 Vernino S, Tuite P, Adler CH, Meschia JF, Boeve BF, Boasberg P. et al. Paraneoplastic chorea associated with CRMP-5 neuronal antibody and lung carcinoma. Ann Neurol 2002; 51 (05) 625-630
- 40 Baladron J, Vitay J, Fietzek T, Hamker FH. The contribution of the basal ganglia and cerebellum to motor learning: A neuro-computational approach. PLOS Comput Biol 2023; 19 (04) e1011024
- 41 Gibson AR, Horn KM, Pong M. Nucleus reticularis tegmenti pontis: a bridge between the basal ganglia and cerebellum for movement control. Exp Brain Res 2023; 241 (05) 1271-1287
- 42 Cooper IS, Crighel E, Amin I. . Clinical and Physiological Effects of Stimulation of the Paleocerebellum in Humans. J Am Geriatr Soc 1973; 21 (01) 40-43
- 43 Cajigas I, Morrison MA, Luciano MS, Starr PA. Cerebellar deep brain stimulation for the treatment of movement disorders in cerebral palsy. J Neurosurg 2023; 139 (03) 605-614
- 44 Benussi A, Batsikadze G, França C, Cury RG, Maas RPPWM. The Therapeutic Potential of Non-Invasive and Invasive Cerebellar Stimulation Techniques in Hereditary Ataxias. Cells 2023; 12 (08) 1193
- 45 Tai CH, Tseng SH. Cerebellar deep brain stimulation for movement disorders. Neurobiol Dis 2022; 175: 105899
- 46 Benussi A, Dell'Era V, Cotelli MS, Turla M, Casali C, Padovani A, Borroni B. Long term clinical and neurophysiological effects of cerebellar transcranial direct current stimulation in patients with neurodegenerative ataxia. Brain Stimul 2017; 10 (02) 242-250
- 47 Maas RPPWM, Teerenstra S, Toni I, Klockgether T, Schutter DJLG, Van de Warrenburg BPC. Cerebellar Transcranial Direct Current Stimulation in Spinocerebellar Ataxia Type 3: a Randomized, Double-Blind, Sham-Controlled Trial. Neurotherapeutics 2022; 19 (04) 1259-1272
- 48 Benussi A, Koch G, Cotelli M, Padovani A, Borroni B. Cerebellar transcranial direct current stimulation in patients with ataxia: A double-blind, randomized, sham-controlled study. Mov Disord 2015; 30 (12) 1701-1705
- 49 Zhang X, Hancock R, Santaniello S. Transcranial direct current stimulation of cerebellum alters spiking precision in cerebellar cortex: A modeling study of cellular responses. PLOS Comput Biol 2021; 17 (12) e1009609
- 50 Chen XY, Lian YH, Liu XH, Sikandar A, Li MC, Xu HL. et al. Effects of Repetitive Transcranial Magnetic Stimulation on Cerebellar Metabolism in Patients With Spinocerebellar Ataxia Type 3. Front Aging Neurosci 2022; 14: 827993
- 51 França C, Andrade DCd, Silva V, Galhardoni R, Barbosa ER, Teixeira MJ, Cury RG. Effects of cerebellar transcranial magnetic stimulation on ataxias: A randomized trial. Parkinsonism Relat Disord 2020; 80: 1-6
- 52 Postuma RB, Berg D, Stern M, Poewe W, Olanow CW, Oertel W. et al. MDS clinical diagnostic criteria for Parkinson's disease. Mov Disord 2015; 30 (12) 1591-1601
- 53 Maiti B, Koller JM, Snyder AZ, Tanenbaum AB, Norris SA, Campbell MC, Perlmutter JS. Cognitive correlates of cerebellar resting-state functional connectivity in Parkinson disease. Neurology 2020; 94 (04) e384-e396
- 54 Kawabata K, Watanabe H, Bagarinao E, Ohdake R, Hara K, Ogura A. et al. Cerebello-basal ganglia connectivity fingerprints related to motor/cognitive performance in Parkinson's disease. Parkinsonism Relat Disord 2020; 80: 21-27
- 55 Kerestes R, Laansma MA, Owens-Walton C, Perry A, van Heese EM, Al-Bachari S. et al; ENIGMA-Parkinson's Study. Cerebellar Volume and Disease Staging in Parkinson's Disease: An ENIGMA-PD Study. Mov Disord 2023; 38 (12) 2269-2281
- 56 Dahlberg LS, Lungu O, Doyon J. Cerebellar Contribution to Motor and Non-motor Functions in Parkinson's Disease: A Meta-Analysis of fMRI Findings. Front Neurol 2020; 11: 127
- 57 Gardoni A, Agosta F, Sarasso E, Basaia S, Canu E, Leocadi M. et al. Cerebellar alterations in Parkinson's disease with postural instability and gait disorders. J Neurol 2023; 270 (03) 1735-1744
- 58 Li D, Jiang C, Liu J, Fan Y, Hao X, Fu M. et al. Repeated transcranial magnetic stimulation on the bilateral cerebellum to improve symptoms of ataxia with multiple system atrophy: a prospective, randomized, sham-controlled pilot study. Neurol Sci 2025; 46 (04) 1875-1882
- 59 Hamid M, Slimani S, Alloussi H, Bourazza A. Cerebellar form of multiple system atrophy: A case report. Radiol Case Rep 2024; 19 (09) 3724-3728
- 60 Wills AJ, Jenkins IH, Thompson PD, Findley LJ, Brooks DJ. Red nuclear and cerebellar but no olivary activation associated with essential tremor: a positron emission tomographic study. Ann Neurol 1994; 36 (04) 636-642
- 61 Louis ED, Shungu DC, Chan S, Mao X, Jurewicz EC, Watner D. Metabolic abnormality in the cerebellum in patients with essential tremor: a proton magnetic resonance spectroscopic imaging study. Neurosci Lett 2002; 333 (01) 17-20
- 62 Neychev VK, Gross RE, Lehéricy S, Hess EJ, Jinnah HA. The functional neuroanatomy of dystonia. Neurobiol Dis 2011; 42 (02) 185-201
- 63 Thomsen M, Lange LM, Zech M, Lohmann K. Genetics and Pathogenesis of Dystonia. Annu Rev Pathol 2024; 19: 99-131
- 64 Louis ED, Faust PL, Vonsattel JPG, Honig LS, Rajput A, Robinson CA. et al. Neuropathological changes in essential tremor: 33 cases compared with 21 controls. Brain 2007; 130 (Pt 12): 3297-3307
- 65 Tarrano C, Zito G, Galléa C, Delorme C, McGovern EM, Atkinson-Clement C. et al. Microstructure of the cerebellum and its afferent pathways underpins dystonia in myoclonus dystonia. Eur J Neurol 2024; 31 (12) e16460
- 66 Carbon M, Raymond D, Ozelius L, Saunders-Pullman R, Frucht S, Dhawan V. et al. Metabolic changes in DYT11 myoclonus-dystonia. Neurology 2013; 80 (04) 385-391
- 67 Ritz K, van Schaik BD, Jakobs ME, van Kampen AH, Aronica E, Tijssen MA, Baas F. SGCE isoform characterization and expression in human brain: implications for myoclonus-dystonia pathogenesis?. Eur J Hum Genet 2011; 19 (04) 438-444
- 68 Eidelberg D, Moeller JR, Antonini A, Kazumata K, Nakamura T, Dhawan V. et al. Functional brain networks in DYT1 dystonia. Ann Neurol 1998; 44 (03) 303-312
- 69 Fremont R, Tewari A, Khodakhah K. Aberrant Purkinje cell activity is the cause of dystonia in a shRNA-based mouse model of Rapid Onset Dystonia-Parkinsonism. Neurobiol Dis 2015; 82: 200-212
- 70 Ganos C, Kassavetis P, Erro R, Edwards MJ, Rothwell J, Bhatia KP. The role of the cerebellum in the pathogenesis of cortical myoclonus. Mov Disord 2014; 29 (04) 437-443
- 71 Pena AB, Caviness JN. Physiology-Based Treatment of Myoclonus. Neurotherapeutics 2020; 17 (04) 1665-1680
- 72 Santos AB, Hong A, Hong I, Villegas JD. Exploring the Symptoms of and Insights Into Idiopathic Opsoclonus-Myoclonus-Ataxia Syndrome in Adults. Cureus 2024; 16 (10) e71568
- 73 Vonsattel JPG, Keller C, Del Pilar Amaya M. Neuropathology of Huntington's disease. Handb Clin Neurol 2008; 89: 599-618
- 74 Rüb U, Hoche F, Brunt ER, Heinsen H, Seidel K, Del Turco D. et al. Degeneration of the cerebellum in Huntington's disease (HD): possible relevance for the clinical picture and potential gateway to pathological mechanisms of the disease process. Brain Pathol 2013; 23 (02) 165-177
- 75 Singh-Bains MK, Mehrabi NF, Sehji T, Austria MDR, Tan AYS, Tippett LJ. et al. Cerebellar degeneration correlates with motor symptoms in Huntington disease. Ann Neurol 2019; 85 (03) 396-405
- 76 Padron-Rivera G, Diaz R, Vaca-Palomares I, Ochoa A, Hernandez-Castillo CR, Fernandez-Ruiz J. Cerebellar Degeneration Signature in Huntington's Disease. Cerebellum 2021; 20 (06) 942-945
- 77 Hobbs NZ, Henley SMD, Ridgway GR, Wild EJ, Barker RA, Scahill RI. et al. The progression of regional atrophy in premanifest and early Huntington's disease: a longitudinal voxel-based morphometry study. J Neurol Neurosurg Psychiatry 2010; 81 (07) 756-763
- 78 Ruocco HH, Lopes-Cendes I, Li LM, Santos-Silva M, Cendes F. Striatal and extrastriatal atrophy in Huntington's disease and its relationship with length of the CAG repeat. Braz J Med Biol Res 2006; 39 (08) 1129-1136
- 79 Ruocco HH, Bonilha L, Li LM, Lopes-Cendes I, Cendes F. Longitudinal analysis of regional grey matter loss in Huntington disease: effects of the length of the expanded CAG repeat. J Neurol Neurosurg Psychiatry 2008; 79 (02) 130-135
- 80 Santos-Lobato BL, Rocha JSS, Rocha LC. Case report: Cerebellar sparing in juvenile Huntington's disease. Front Neurol 2023; 13: 1089193
- 81 Latimer CS, Flanagan ME, Cimino PJ, Jayadev S, Davis M, Hoffer ZS. et al. Neuropathological Comparison of Adult Onset and Juvenile Huntington's Disease with Cerebellar Atrophy: A Report of a Father and Son. J Huntingtons Dis 2017; 6 (04) 337-348
- 82 Franklin GL, Camargo CHF, Meira AT, Lima NSC, Teive HAG. The Role of the Cerebellum in Huntington's Disease: a Systematic Review. Cerebellum 2021; 20 (02) 254-265