Skip to main content
SpringerLink
Log in

The Role of the Cerebellum in Huntington’s Disease: a Systematic Review

  • Review
  • Published:
The Cerebellum Aims and scope Submit manuscript

Abstract

Huntington’s disease (HD) is a rare neurological disorder characterized by progressive motor, cognitive, and psychiatric disturbances. Although striatum degeneration might justify most of the motor symptoms, there is an emerging evidence of involvement of extra-striatal structures, such as the cerebellum. To elucidate the cerebellar involvement and its afferences with motor, psychiatric, and cognitive symptoms in HD. A systematic search in the literature was performed in MEDLINE, LILACS, and Google Scholar databases. The research was broadened to include the screening of reference lists of review articles for additional studies. Studies available in the English language, dating from 1993 through May 2020, were included. Clinical presentation of patients with HD may not be considered as the result of an isolated primary striatal dysfunction. There is evidence that cerebellar involvement is an early event in HD and may occur independently of striatal degeneration. Also, the loss of the compensation role of the cerebellum in HD may be an explanation for the clinical onset of HD. Although more studies are needed to elucidate this association, the current literature supports that the cerebellum may integrate the natural history of neurodegeneration in HD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Data Availability

All data generated or analyzed during this study are included in this published article.

Abbreviations

3-HK:

3-Hydroxykynurenine

CAG:

Cytosine-adenine-guanine

CD:

Cerebellar degeneration

CHD:

Childhood-onset Huntington’s disease

DTI:

Diffusion tensor imaging

FA:

Fractional anisotropy

fMRI:

Functional magnetic resonance image

GM:

Gray matter

HD:

Huntington’s disease

IT15:

Interesting transcript 15

IL:

Interleukin

KYNA:

Kynurenate

MeSH:

Medical Subject Heading

MMP9:

Matrix metallopeptidase 9

JHD:

Juvenile Huntington’s disease

MMSE:

Mini-Mental State Examination

MoCA:

Montreal Cognitive Assessment

MRI:

Magnetic resonance image

mtDNA:

Mitochondrial DNA

OH8dG:

8-Hydroxy-2-deoxyguanosine

PET:

Positron emission tomography

preHD:

Premanifest HD

PRISMA:

Preferred Reporting Items for Systematic Reviews and Meta-Analyses

QUIN:

Quinolinate

RAN:

Repeat-associated non-ATG

SCA:

Spinocerebellar ataxia

SDMT:

Symbol Digit Modalities Test

Tb4:

Thymosin b-4

TFC:

Total functional capacity

UHDRS:

Unified Huntington’s Disease Rating Scale

VBM:

Voxel-based morphometry

WM:

White matter

VOSP:

Visual Object and Space Perception Battery

References

  1. Huntington's Disease Collaborative Research Group. A novel gene containing a trinucleotide repeat that is expanded an unstable on Huntington's disease chromosomes. Cell. 1993;72:971–83. https://doi.org/10.1016/0092-8674(93)90585-e.

    Article  Google Scholar 

  2. Ross CA, Aylward EH, Wild EJ, et al. Huntington disease: natural history, biomarkers and prospects for therapeutics. Nat Rev Neurol. 2014;10:204–16. https://doi.org/10.1038/nrneurol.2014.24.

    Article  CAS  PubMed  Google Scholar 

  3. Telford R, Vattoth S. Anatomy of deep brain nuclei with special reference to specific diseases and deep brain stimulation localization. Neuroradiol J. 2014;27(1):29–43. https://doi.org/10.15274/NRJ-2014-10004.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Douaud G, Gaura V, Ribeiro MJ, Lethimonnier F, Maroy R, Verny C, et al. Distribution of grey matter atrophy in Huntington's disease patients: a combined ROI-based and voxel-based morphometric study. NeuroImage. 2006;4:1562–75. https://doi.org/10.1016/j.neuroimage.2006.05.057.

    Article  Google Scholar 

  5. Thieben MJ, Duggins AJ, Good CD, et al. The distribution of structural neuropathology in preclinical Huntington’s disease. Brain. 2002;125:1815–28. https://doi.org/10.1093/brain/awf179.

    Article  CAS  PubMed  Google Scholar 

  6. Bhide PG, Day M, Sapp E, Schwarz C, Sheth A, Kim J, et al. Expression of normal and mutant huntingtin in the developing brain. J Neurosci. 1996;16:5523–35. https://doi.org/10.1523/JNEUROSCI.16-17-05523.1996.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Singh-Bain MK, Mehrabi NF, Sehji T, et al. Cerebellar degeneration correlates with motor symptoms in Huntington’s disease. Ann Neurol. 2019;85(3):396–405. https://doi.org/10.1002/ana.25413.

    Article  CAS  Google Scholar 

  8. Fennema-Notestine C, Archibald SL, Jacobson MW, Corey-Bloom J, Paulsen JS, Peavy GM, et al. In vivo evidence of cerebellar atrophy and cerebral white matter loss in Huntington disease. Neurology. 2004;63:989–95. https://doi.org/10.1212/01.wnl.0000138434.68093.67.

    Article  CAS  PubMed  Google Scholar 

  9. 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. 2012;23(2):165–77. https://doi.org/10.1111/j.1750-3639.2012.00629.x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Azevedo PC, Guimarães RP, Piccinin CC, et al. Cerebellar gray matter alterations in Huntington disease: a voxel-based morphometry study. Cerebellum. 2017;16(5–6):923–8. https://doi.org/10.1007/s12311-017-0865-6.

    Article  CAS  PubMed  Google Scholar 

  11. Guell X, Gabrieli JDE, Schmahmann JD. Embodied cognition and the cerebellum: perspectives from the dysmetria of thought and the universal cerebellar transform theories. Cortex. 2018;100:140–8. https://doi.org/10.1016/j.cortex.2017.07.005.

    Article  PubMed  Google Scholar 

  12. Schmahmann JD, Guell X, Stoodley CJ, Halko MA. The theory and neuroscience of cerebellar cognition. Annu Rev Neurosci. 2019;42:337–64. https://doi.org/10.1146/annurev-neuro-070918-050258.

    Article  CAS  PubMed  Google Scholar 

  13. Romer AL, Knodt AR, Houts R, Brigidi BD, Moffitt TE, Caspi A, et al. Structural alterations within cerebellar circuitry are associated with general liability for common mental disorders. Mol Psychiatry. 2018;23(4):1084–90. https://doi.org/10.1038/mp.2017.57.

    Article  CAS  PubMed  Google Scholar 

  14. Jiang Y, Duan M, Chen X, Zhang X, Gong J, Dong D, et al. Aberrant prefrontal thalamic-cerebellar circuit in schizophrenia and depression: evidence from a possible causal connectivity. Int J Neural Syst. 2019;29(5):1850032. https://doi.org/10.1142/S0129065718500326.

    Article  PubMed  Google Scholar 

  15. Sathyanesan A, Zhou J, Scafidi J, Heck DH, Sillitoe RV, Gallo V. Emerging connections between cerebellar development, behaviour and complex brain disorders. Nat Rev Neurosci. 2019;20(5):298–313. https://doi.org/10.1038/s41583-019-0152-2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Rees EM, Farmer R, Cole JH, et al. Cerebellar abnormalities in Huntington’s disease: a role in motor and psychiatric impairment? Mov Disord. 2014;29(13):1648–54. 6. https://doi.org/10.1002/mds.25984.

    Article  PubMed  Google Scholar 

  17. Haines DE, Gregory AM. Fundamental neuroscience for basic and clinical applications. 5th ed. Philadelphia; 2018. p. 394–412.

  18. Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6(7):e1000097. https://doi.org/10.1371/journal.pmed.1000097.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Ishikawa A, Oyanagi K, Tanaka K, Igarashi S, Sato T, Tsuji S. A non-familial Huntington’s disease patient with grumose degeneration in the dentate nucleus. Acta Neurol Scand. 1999;99(5):322–6. https://doi.org/10.1111/j.1600-0404.1999.tb00684.x.

    Article  CAS  PubMed  Google Scholar 

  20. Vonsattel JPG. Huntington disease models and human neuropathology: similarities and differences. Acta Neuropathol. 2007;115:55–69. https://doi.org/10.1007/s00401-007-0306-6.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Sakai K, Ishida C, Morinaga A, Takahashi K, Yamada M. Case study: somatic sprouts and halo-like amorphous materials of the Purkinje cells in Huntington’s disease. Cerebellum. 2015;14:707–10. https://doi.org/10.1007/s12311-015-0678-4.

    Article  CAS  PubMed  Google Scholar 

  22. Rüb U, Seidel K, Heinsen H, Vonsattel JP, den Dunnen WF, Korf HW. Huntington’s disease (HD): the neuropathology of a multisystem neurodegenerative disorder of the human brain. Brain Pathol. 2016;26(6):726–40. https://doi.org/10.1111/bpa.12426.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Aronin N, Chase K, Young C, Sapp E, Schwarz C, Matta N, et al. CAG expansion affects the expression of mutant huntingtin in the Huntington’s disease brain. Neuron. 1995;15(5):1193–201. https://doi.org/10.1016/0896-6273(95)90106-x.

    Article  CAS  PubMed  Google Scholar 

  24. Kahlem P, Djian P. The expanded CAG repeat associated with juvenile Huntington disease shows a common origin of most or all neurons and glia in human cerebrum. Neurosci Lett. 2000;286(3):203–7. https://doi.org/10.1016/s0304-3940(00)01029-6.

    Article  CAS  PubMed  Google Scholar 

  25. Bañez-Coronel M, Ayhan F, Tarabochia AD, Zu T, Perez BA, Tusi SK, et al. RAN translation in Huntington disease. Neuron. 2015;88(4):667–77. https://doi.org/10.1016/j.neuron.2015.10.038.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Guidetti P, Luthicarter R, Augood S, Schwarcz R. Neostriatal and cortical quinolinate levels are increased in early grade Huntington’s disease. Neurobiol Dis. 2004;17(3):455–61. https://doi.org/10.1016/j.nbd.2004.07.006.

    Article  CAS  PubMed  Google Scholar 

  27. Browne SE, Bowling AC, Macgarvey U, Baik MJ, Berger SC, Muquit MMK, et al. Oxidative damage and metabolic dysfunction in Huntington’s disease: selective vulnerability of the basal ganglia. Ann Neurol. 1997;41(5):646–53. https://doi.org/10.1002/ana.410410514.

    Article  CAS  PubMed  Google Scholar 

  28. Polidori MC, Mecocci P, Browne SE, Senin U, Beal MF. Oxidative damage to mitochondrial DNA in Huntington’s disease parietal cortex. Neurosci Lett. 1999;272(1):53–6. https://doi.org/10.1016/s0304-3940(99)00578-9.

    Article  CAS  PubMed  Google Scholar 

  29. Sapp E, Kegel KB, Aronin N, Hashikawa T, Uchiyama Y, Tohyama K, et al. Early and progressive accumulation of reactive microglia in the Huntington disease brain. J Neuropathol Exp Neurol. 2001;60(2):161–72. https://doi.org/10.1093/jnen/60.2.161.

    Article  CAS  PubMed  Google Scholar 

  30. Silvestroni A, Faull RLM, Strand AD, Möller T. Distinct neuroinflammatory profile in post-mortem human Huntingtonʼs disease. NeuroReport. 2009;20(12):1098–103. https://doi.org/10.1097/wnr.0b013e32832e34ee.

    Article  PubMed  Google Scholar 

  31. Kanzato N, Saito M, Horikiri T, Komine Y, Nakagawa M, Matsuzaki T. Atypical rigid form of Huntington’s disease: a case with peripheral amyotrophy and congenital defects of a lower limb. Intern Med. 1998;37(11):978–81. https://doi.org/10.2169/internalmedicine.37.978.

    Article  CAS  PubMed  Google Scholar 

  32. Squitieri F, Berardelli A, Nargi E, Castellotti B, Mariotti C, Cannella M, et al. Atypical movement disorders in the early stages of Huntington's disease: clinical and genetic analysis. Clin Genet. 2000;58(1):50–6. https://doi.org/10.1034/j.1399-0004.2000.580108.x.

    Article  CAS  PubMed  Google Scholar 

  33. Squitieri F, Pustorino G, Cannella M, Toscano A, Maglione V, Morgante L, et al. Highly disabling cerebellar presentation in Huntington disease. Eur J Neurol. 2003;10(4):443–4. https://doi.org/10.1046/j.1468-1331.2003.00601.x.

    Article  CAS  PubMed  Google Scholar 

  34. Seneca S, Fagnart D, Keymolen K, Lissens W, Hasaerts D, Debulpaep S, et al. Early onset Huntington disease: a neuronal degeneration syndrome. Eur J Pediatr. 2004;163(12):717–21. https://doi.org/10.1007/s00431-004-1537-3.

    Article  PubMed  Google Scholar 

  35. Gonzalez-Alegre P, Afifi AK. Clinical characteristics of childhood-onset (juvenile) Huntington disease: report of 12 patients and review of the literature. J Child Neurol. 2006;21:223–9. https://doi.org/10.2310/7010.2006.00055.

    Article  PubMed  Google Scholar 

  36. Wojaczyńska-Stanek K, Adamek D, Marszał E, Hoffman-Zacharska D. Huntington disease in a 9-year-old boy: clinical course and neuropathologic examination. J Child Neurol. 2006;21(12):1068–73. https://doi.org/10.1177/7010.2006.00244.

    Article  PubMed  Google Scholar 

  37. Sakazume S, Yoshinari S, Oguma E, Utsuno E, Ishii T, Narumi Y, et al. A patient with early onset Huntington disease and severe cerebellar atrophy. Am J Med Genet A. 2009;149A(4):598–601. https://doi.org/10.1002/ajmg.a.32707.

    Article  CAS  PubMed  Google Scholar 

  38. 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 Huntington’s Dis. 2017;6(4):337–48. https://doi.org/10.3233/jhd-170261.

    Article  CAS  Google Scholar 

  39. Nicolas G, Devys D, Goldenberg A, Maltête D, Hervé C, Hannequin D, et al. Juvenile Huntington disease in an 18-month-old boy revealed by global developmental delay and reduced cerebellar volume. Am J Med Genet. 2011;155:815–8. https://doi.org/10.1002/ajmg.a.33911.

    Article  CAS  Google Scholar 

  40. Liu ZJ, Sun YM, Ni W, Dong Y, Shi SS, Wu ZY. Clinical features of Chinese patients with Huntington's disease carrying CAG repeats beyond 60 within HTT gene. Clin Genet. 2014;85(2):189–93. https://doi.org/10.1111/cge.12120.

    Article  CAS  PubMed  Google Scholar 

  41. Rosas HD, Koroshetz WJ, Chen YI, Skeuse C, Vangel M, Cudkowicz ME, et al. Evidence for more widespread cerebral pathology in early HD: an MRI-based morphometric analysis. Neurology. 2003;60:1615–20. https://doi.org/10.1212/01.wnl.0000065888.88988.6e.

    Article  CAS  PubMed  Google Scholar 

  42. Huntington Study Group. Unified Huntington’s disease rating scale: reliability and consistency. Mov Disord. 1996;11:136–42. https://doi.org/10.1002/mds.870110204.

    Article  Google Scholar 

  43. Scharmuller W, Ille R, Schienle A. Cerebellar contribution to anger recognition deficits in Huntington’s disease. Cerebellum. 2013;6:819–25. https://doi.org/10.1007/s12311-013-0492-9.

    Article  Google Scholar 

  44. Galvez V, Ramírez-García G, Hernandez-Castillo CR, Bayliss L, Díaz R, Lopez-Titla MM, et al. Extrastriatal degeneration correlates with deficits in the motor domain subscales of the UHDRS. J Neurol Sci. 2018;385:22–9. https://doi.org/10.1016/j.jns.2017.11.040.

    Article  PubMed  Google Scholar 

  45. Wolf RC, Thomann PA, Sambataro F, Wolf ND, Vasic N, Landwehrmeyer GB, et al. Abnormal cerebellar volume and corticocerebellar dysfunction in early manifest Huntington’s disease. J Neurol. 2015;262:859–69. https://doi.org/10.1007/s00415-015-7642-6.

    Article  CAS  PubMed  Google Scholar 

  46. Wolf R, Thomann P, Thomann A, Vasic N, Wolf N, Landwehrmeyer G, et al. Brain structure in preclinical Huntington’s disease: a multi-method approach. J Neurol Neurosurg Psychiatry. 2012;83(1):A26.3–A27. https://doi.org/10.1136/jnnp-2012-303524.82.

    Article  Google Scholar 

  47. Hobbs NZ, Henley SM, Ridgway GR, 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;81:756–63. https://doi.org/10.1136/jnnp.2009.190702.

    Article  PubMed  Google Scholar 

  48. Gomez-Anson B, Alegret M, Munoz E, et al. Prefrontal cortex volume reduction on MRI in preclinical Huntington’s disease relates to visuomotor performance and CAG number. Parkinsonism Rel Disord. 2009;15:213–9. https://doi.org/10.1016/j.parkreldis.2008.05.010.

    Article  CAS  Google Scholar 

  49. Zimbelman JL, Paulsen JS, Mikos A, Reynolds NC, Hoffmann RG, Rao SM. fMRI detection of early neural dysfunction in preclinical Huntington’s disease. J Int Neuropsychol Soc. 2007;13(5):758–69. https://doi.org/10.1017/s1355617707071214.

    Article  PubMed  Google Scholar 

  50. Tereshchenko AV, Schultz JL, Bruss JE, Magnotta VA, Epping EA, Nopoulos PC. Abnormal development of cerebellar-striatal circuitry in Huntington disease. Neurology. 2020;94(18):e1908–15. https://doi.org/10.1212/wnl.0000000000009364.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Feigin A, Tang C, Ma Y, Mattis P, Zgaljardic D, Guttman M, et al. Thalamic metabolism and symptom onset in preclinical Huntington's disease. Brain. 2007;130(Pt11):2858–67. https://doi.org/10.1093/brain/awm217.

    Article  CAS  PubMed  Google Scholar 

  52. Gaura V, Lavisse S, Payoux P, Goldman S, Verny C, Krystkowiak P, et al. Association between motor symptoms and brain metabolism in early Huntington disease. JAMA Neurol. 2017;74(9):1088–96. https://doi.org/10.1001/jamaneurol.2017.1200.

    Article  PubMed  PubMed Central  Google Scholar 

  53. 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;79:130–5. https://doi.org/10.1136/jnnp.2007.116244.

    Article  CAS  PubMed  Google Scholar 

  54. Ho VB, Chuang S, Rovira M, Koo B. Juvenile Huntington disease: CT and MR features. Am J Neuroradiol. 1995;16:1405–12.

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Laccone F, Christian W. A recurrent expansion of a maternal allele with 36 CAG repeats causes Huntington disease in two sisters. Am J Hum Genet. 2000;66:1145–8. https://doi.org/10.1086/302810.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Gambardella A, Muglia M, Labate A, Magariello A, Gabriele AL, Mazzei R, et al. Juvenile Huntington’s disease presenting as progressive myoclonic epilepsy. Neurology. 2001;57(4):708–11. https://doi.org/10.1212/wnl.57.4.708.

    Article  CAS  PubMed  Google Scholar 

  57. Nahhas FA, Garbern J, Krajewski KM, Roa BB, Feldman GL. Juvenile onset Huntington disease resulting from a very large maternal expansion. Am J Med Genet A. 2005;137A(3):328–31. https://doi.org/10.1002/ajmg.a.30891.

    Article  CAS  PubMed  Google Scholar 

  58. Daniel CWL, Chloe MMAK, Kam MAU, et al. Clinical and genetic characterization of Huntington disease among Hong Kong Chinese – a 5-year review. Biomed J Sci Tech Res. 2018;4(4):4100–6. https://doi.org/10.26717/bjstr.2018.04.001099.

    Article  Google Scholar 

  59. Dong Y, Sun YM, Liu ZJ, Ni W, Shi SS, Wu ZY. Chinese patients with Huntington's disease initially presenting with spinocerebellar ataxia. Clin Genet. 2013;2013:380–3. https://doi.org/10.1111/j.1399-0004.2012.01927.x.

    Article  CAS  Google Scholar 

  60. Rodríguez-Quiroga SA, Gonzalez-Morón D, Garretto N, Kauffman MA. Huntington's disease masquerading as spinocerebellar ataxia. BMJ Case Rep. 2013:bcr2012008380. https://doi.org/10.1136/bcr-2012-008380.

  61. 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;39:1129–36. https://doi.org/10.1590/S0100-879X2006000800016.

    Article  CAS  PubMed  Google Scholar 

  62. Sprengelmeyer R, Orth M, Müller HP, Wolf RC, Grön G, Depping MS, et al. The neuroanatomy of subthreshold depressive symptoms in Huntington’s disease: a combined diffusion tensor imaging (DTI) and voxel-based morphometry (VBM) study. Psychol Med. 2013;44(09):1867–78. https://doi.org/10.1017/s003329171300247x.

    Article  PubMed  Google Scholar 

  63. Henley SM, Novak MJ, Frost C, King J, Tabrizi SJ, Warren JD. Emotion recognition in Huntington’s disease: a systematic review. Neurosci Biobehav Rev. 2012;361:237–53. https://doi.org/10.1016/j.neubiorev.2011.06.002.

    Article  Google Scholar 

  64. Paradiso S, Turner BM, Paulsen JS, Jorge R, Ponto LLB, Robinson RG. Neural bases of dysphoria in early Huntington’s disease. Psychiatry Res Neuroimaging. 2008;162(1):73–87. https://doi.org/10.1016/j.pscychresns.2007.04.001.

    Article  Google Scholar 

  65. Wolf RC, Vasic N, Schönfeldt-Lecuona C, Ecker D, Landwehrmeyer GB. Cortical dysfunction in patients with Huntington’s disease during working memory performance. Hum Brain Mapp. 2009;30(1):327–39. https://doi.org/10.1002/hbm.20502.

    Article  PubMed  Google Scholar 

  66. Georgiou-Karistianis N, Stout JC, Domínguez DJF, et al. Functional magnetic resonance imaging of working memory in Huntington’s disease: cross-sectional data from the IMAGE-HD study. Hum Brain Mapp. 2013;35(5):1847–64. https://doi.org/10.1002/hbm.22296.

    Article  PubMed  PubMed Central  Google Scholar 

  67. Deckel AW, Weiner R, Szigeti D, Clark V, Vento J. Altered patterns of regional cerebral blood flow in patients with Huntington's disease: a SPECT study during rest and cognitive or motor activation. J NucIMed. 2000;41:773.

    CAS  Google Scholar 

  68. Brandt J, Leroi I, O’Hearn E, Rosenblatt A, Margolis RL. Cognitive impairments in cerebellar degeneration: a comparison with Huntington’s disease. J Neuropsychiatry Clin Neurosci. 2004;16:176–84. https://doi.org/10.1176/jnp.16.2.176.

    Article  PubMed  Google Scholar 

  69. Fusilli C, Migliore S, Mazza T, Consoli F, de Luca A, Barbagallo G, et al. Biological and clinical manifestations of juvenile Huntington’s disease: a retrospective analysis. Lancet Neurol. 2018;17(11):986–93. https://doi.org/10.1016/S1474-4422(18)30294-1.

    Article  PubMed  Google Scholar 

  70. Rüb U, Heinsen H, Brunt ER, Landwehrmeyer B, den Dunnen WF, Gierga K, et al. The human premotor oculomotor brainstem system - can it help to understand oculomotor symptoms in Huntington's disease? Neuropathol Appl Neurobiol. 2009;35:4–15. https://doi.org/10.1111/j.1365-2990.2008.00994.x.

    Article  PubMed  Google Scholar 

  71. Piu P, Pretegiani E, Rosini F, Serchi V, Zaino D, Chiantini T, et al. The cerebellum improves the precision of antisaccades by a latency-duration trade-off. Prog Brain Res. 2019;249:125–39. https://doi.org/10.1016/bs.pbr.2019.04.018.

    Article  PubMed  Google Scholar 

  72. Middleton F. Basal ganglia and cerebellar loops: motor and cognitive circuits. Brain Res Rev. 2000;31(2–3):236–50. https://doi.org/10.1016/s0165-0173(99)00040-5.

    Article  CAS  PubMed  Google Scholar 

  73. Novak MJU, Warren JD, Henley SMD, Draganski B, Frackowiak RS, Tabrizi SJ. Altered brain mechanisms of emotion processing in pre-manifest Huntington’s disease. Brain. 2012;135(4):1165–79. https://doi.org/10.1093/brain/aws024.

    Article  PubMed  PubMed Central  Google Scholar 

  74. Holtbernd F, Tang CC, Feigin A, Dhawan V, Ghilardi MF, Paulsen JS, et al. Longitudinal changes in the motor learning-related brain activation response in presymptomatic Huntington’s disease. PLoS One. 2016;11(5):e0154742. https://doi.org/10.1371/journal.pone.0154742.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Wolf RC, Sambataro F, Vasic N, Baldas EM, Ratheiser I, Bernhard Landwehrmeyer G, et al. Visual system integrity and cognition in early Huntington’s disease. Eur J Neurosci. 2014;40(2):2417–26. https://doi.org/10.1111/ejn.12575.

    Article  PubMed  Google Scholar 

  76. Ille R, Schäfer A, Scharmüller W, Enzinger C, Schöggl H, Kapfhammer HP, et al. Emotion recognition and experience in Huntington disease: a voxel-based morphometry study. J Psychiatry Neurosci. 2011;36(6):383–90. https://doi.org/10.1503/jpn.100143.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Funding

No authors have received any funding from any institution, including personal relationships, interests, grants, employment, affiliations, patents, inventions, honoraria, consultancies, royalties, stock options/ownership, or expert testimony for the last 12 months.

Author information

Authors and Affiliations

  1. Movement Disorders Unit, Neurology Service, Internal Medicine Department, Hospital de Clínicas, Federal University of Paraná, Rua General Carneiro 1103/102, Centro, Curitiba, Paraná, Brazil

    Gustavo L. Franklin, Alex T. Meira & Hélio A. G. Teive

  2. Neurological Diseases Group, Graduate Program in Internal Medicine, Internal Medicine Department, Hospital de Clínicas, Federal University of Paraná, Curitiba, Paraná, Brazil

    Carlos Henrique F. Camargo & Hélio A. G. Teive

  3. Vila Velha University, Vila Velha, Espírito Santo, Brazil

    Nayra S. C. Lima

Authors
  1. Gustavo L. Franklin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Carlos Henrique F. Camargo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alex T. Meira
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nayra S. C. Lima
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hélio A. G. Teive
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

G.L.F, CHC, ATM, NSCL, H.A.G.T: research project: (a) conception, (b) organization, (c) execution. G.L.F, CHC, ATM, NSCL, H.A.G.T: statistical analysis: (a) design, (b) execution, (c) review and critique. G.L.F, CHC, ATM, NSCL, H.A.G.T: manuscript: (a) writing of the first draft, (b) review and critique, statistical analysis: (c) review.

Corresponding author

Correspondence to Gustavo L. Franklin.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Highlights

• Huntington’s disease (HD) is a heterogeneous disease characterized by multiple movement disorders, cognitive symptoms, and psychiatric symptoms.

• The role of the cerebellum in HD was classically seen as not relevant.

• There is emerging evidence of the involvement of the cerebellum in HD’s natural history and pathophysiology.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Franklin, G.L., Camargo, C.H.F., Meira, A.T. et al. The Role of the Cerebellum in Huntington’s Disease: a Systematic Review. Cerebellum 20, 254–265 (2021). https://doi.org/10.1007/s12311-020-01198-4

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12311-020-01198-4

Keywords

Search

Navigation