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Huntington’s Disease

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Abstract

Huntington’s disease (HD) is a neurodegenerative disorder with autosomal dominant inheritance and complete expression. The genetic defect is caused by CAG trinucleotide expansion on the short arm of chromosome 4, resulting in the production of an expanded polyglutamine region in the mutant huntingtin protein. The illness usually emerges in middle age and is characterized by psychiatric, cognitive, and motor deterioration, with chorea being the most recognizable symptom. HD has a unique position among other neurodegenerative disorders as it bridges the boundaries separating disciplines of neurology, psychiatry, and genetics. Currently, there is no disease-modifying therapies or cure for HD. Therefore, treatment is based largely on lifestyle interventions, supportive management, and symptomatic treatment. With respect to research and drug development, HD can serve as a model for other trinucleotide repeat disorders, protein aggregation disorders, as well as dementia, psychiatric, and movement disorders. Emerging experimental treatment strategies are focusing on gene therapy through the use of antisense oligonucleotides, micro RNA, modulators of gene expression and gene editing. Particular research interest is devoted to the identification of biomarkers that would enable evaluation of the therapies before the clinical onset of the disease.

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References

  1. Huntington G. On chorea. J Neuropsychiatry Clin Neurosci. 2003 Winter;15(1):109–12.

    Article  PubMed  Google Scholar 

  2. Osler W. Historical note on hereditary chorea. In: Browning W, editor. Neurographs. Brooklyn, NY: Albert C. Huntington Publishing; 1908. p. 113–6.

    Google Scholar 

  3. The Huntington’s disease collaborative research group [no authors listed]. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington’s disease chromosomes. Cell. 1993;72(6):971–83.

    Article  Google Scholar 

  4. Conneally PM. Huntington disease: genetics and epidemiology. Am J Hum Genet. 1984;36(3):506–26.

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Pringsheim T, Wiltshire K, Day L, Dykeman J, Steeves T, Jette N. The incidence and prevalence of Huntington’s disease: a systematic review and meta-analysis. Mov Disord. 2012;27(9):1083–91.

    Article  PubMed  Google Scholar 

  6. Harper PS. The epidemiology of Huntington’s disease. Hum Genet. 1992;89(4):365–76.

    Google Scholar 

  7. Kanazawa I, Kondo I, Ikeda JE, Ikeda T, Shizu Y, Yoshida M, et al. Huntington’s disease genetics. NeuroRx. 2004;1(2):255–62.

    Article  Google Scholar 

  8. Sipilä JO, Hietala M, Siitonen A, Päivärinta M, Majamaa K. Epidemiology of Huntington’s disease in Finland. Parkinsonism Relat Disord [Internert]. 2015;21(1):46–9. http://sciencedirect.com/science/journal/13538020, https://doi.org/10.1016/j.parkreldis.2014.10.025.

    Article  Google Scholar 

  9. Tanner CM, Goldman SM. Epidemiology of movement disorders. Curr Opin Neurol. 1994;7(4):340–5.

    Article  CAS  PubMed  Google Scholar 

  10. Adams P, Falek A, Arnold J. Huntington disease in Georgia: age at onset. Am J Hum Genet. 1988;43(5):695–704.

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Reyes Molón L, Yáñez Sáez RM, López-Ibor Alcocer MI. Juvenile Huntington’s disease: a case report and literature review. Actas Esp Psiquiatr. 2010;38(5):285–94.

    Google Scholar 

  12. Duff K, Paulsen JS, Beglinger LJ, Langbehn DR, Stout JC, Predict-HD Investigators of the Huntington Study Group. Psychiatric symptoms in Huntington’s disease before diagnosis: the predict-HD study. Biol Psychiatry. 2007;62(12):1341–6.

    Google Scholar 

  13. Kirkwood SC, Siemers E, Bond C, Conneally PM, Christian JC, Foroud T. Confirmation of subtle motor changes among presymptomatic carriers of the Huntington disease gene. Arch Neurol. 2000;57(7):1040–4.

    Article  CAS  PubMed  Google Scholar 

  14. Aylward EH, Codori AM, Rosenblatt A, Sherr M, Brandt J, Stine OC, et al. Rate of caudate atrophy in presymptomatic and symptomatic stages of Huntington’s disease. Mov Disord. 2000;15(3):552–60.

    Article  CAS  PubMed  Google Scholar 

  15. Aylward EH, Harrington DL, Mills JA, Nopoulos PC, Ross CA, Long JD, et al. Regional atrophy associated with cognitive and motor function in prodromal Huntington disease. J Huntingtons Dis [Internet]. 2013;2(4):477–89. http://content.iospress.com/journals/journal-of-huntingtons-disease https://doi.org/10.3233/jhd-130076.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Nance M, Paulsen J, Rosenblatt A, Wheelock V. A physician’s guide to the management of Huntington’s disease. New York: Huntigton’s Disease Society of America; 2012. p. 6.

    Google Scholar 

  17. Moskowitz CB, Marder K. Palliative care for people with late-stage Huntington’s disease. Neurol Clin. 2001;19(4):849–65.

    Article  CAS  PubMed  Google Scholar 

  18. Sørensen SA, Fenger K. Causes of death in patients with Huntington’s disease and in unaffected first degree relatives. J Med Genet. 1992;29(12):911–4.

    Article  PubMed  PubMed Central  Google Scholar 

  19. 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(3):223–9.

    PubMed  Google Scholar 

  20. Bird ED, Caro AJ, Pilling JB. A sex related factor in the inheritance of Huntington’s chorea. Ann Hum Genet. 1974;37(3):255–60.

    Article  CAS  PubMed  Google Scholar 

  21. Myers RH, Sax DS, Koroshetz WJ, Mastromauro C, Cupples LA, Kiely DK, et al. Factors associated with slow progression in Huntington’s disease. Arch Neurol. 1991;48(8):800–4.

    Article  CAS  PubMed  Google Scholar 

  22. Lee JM, Ramos EM, Lee JH, Gillis T, Mysore JS, Hayden MR, et al. CAG repeat expansion in Huntington disease determines age at onset in a fully dominant fashion. Neurology [Internet]. 2012;78(10):690–5. http://ovidsp.ovid.com/ovidweb.cgi?T=JS&NEWS=n&CSC=Y&PAGE=toc&D=yrovft&AN=00006114-000000000-00000, https://doi.org/10.1212/wnl.0b013e318249f683.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Duyao M, Ambrose C, Myers R, Novelletto A, Persichetti F, Frontali M, et al. Trinucleotide repeat length instability and age of onset in Huntington’s disease. Nat Genet. 1993;4(4):387–92.

    Article  CAS  PubMed  Google Scholar 

  24. Stine OC, Pleasant N, Franz ML, Abbott MH, Folstein SE, Ross CA. Correlation between the onset age of Huntington’s disease and length of the trinucleotide repeat in IT-15. Hum Mol Genet. 1993;2(10):1547–9.

    Article  CAS  PubMed  Google Scholar 

  25. Craufurd D, Dodge A. Mutation size and age at onset in Huntington’s disease. J Med Genet. 1993;30(12):1008–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Simpson SA, Davidson MJ, Barron LH. Huntington’s disease in Grampian region: correlation of the CAG repeat number and the age of onset of the disease. J Med Genet. 1993;30(12):1014–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Andrew SE, Goldberg YP, Kremer B, Telenius H, Theilmann J, Adam S, et al. The relationship between trinucleotide (CAG) repeat length and clinical features of Huntington’s disease. Nat Genet. 1993;4(4):398–403.

    Article  CAS  PubMed  Google Scholar 

  28. Rosenblatt A, Brinkman RR, Liang KY, Almqvist EW, Margolis RL, Huang CY, et al. Familial influence on age of onset among siblings with Huntington disease. Am J Med Genet. 2001;105(5):399–403.

    Article  CAS  PubMed  Google Scholar 

  29. Carter CJ. Reduced GABA transaminase activity in the Huntington’s disease putamen. Neurosci Lett. 1984;48(3):339–42.

    Article  CAS  PubMed  Google Scholar 

  30. Reynolds GP, Pearson SJ. Decreased glutamic acid and increased 5-hydroxytryptamine in Huntington’s disease brain. Neurosci Lett. 1987;78(2):233–8.

    Article  CAS  PubMed  Google Scholar 

  31. Reiner A, Albin RL, Anderson KD, D’Amato CJ, Penney JB, Young AB. Differential loss of striatal projection neurons in Huntington disease. Proc Natl Acad Sci USA. 1988;85(15):5733–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Storey E, Beal MF. Neurochemical substrates of rigidity and chorea in Huntington’s disease. Brain. 1993;116(5):1201–22.

    Article  PubMed  Google Scholar 

  33. Albin RL, Young AB, Penney JB, Handelin B, Balfour R, Anderson KD, et al. Abnormalities of striatal projection neurons and N-methyl-D-aspartate receptors in presymptomatic Huntington’s disease. N Engl J Med. 1990;322(18):1293–8.

    Article  CAS  PubMed  Google Scholar 

  34. Cepeda C, Murphy KP, Parent M, Levine MS. The role of dopamine in Huntington’s disease. Prog Brain Res [Internet]. 2014;211:235–54. http://www.sciencedirect.com/science/bookseries/00796123, https://doi.org/10.1016/b978-0-444-63425-2.00010-6.

    Google Scholar 

  35. Graveland GA, Williams RS, DiFiglia M. Evidence for degenerative and regenerative changes in neostriatal spiny neurons in Huntington’s disease. Science. 1985;227(4688):770–3.

    Article  CAS  PubMed  Google Scholar 

  36. Ferrante RJ, Kowall NW, Richardson EP Jr. Proliferative and degenerative changes in striatal spiny neurons in Huntington’s disease: a combined study using the section-Golgi method and calbindin D28k immunocytochemistry. J Neurosci. 1991;11(12):3877–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Portera-Cailliau C, Hedreen JC, Price DL, Koliatsos VE. Evidence for apoptotic cell death in Huntington disease and excitotoxic animal models. J Neurosci. 1995;15(5):3775–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Vonsattel JP, Myers RH, Stevens TJ, Ferrante RJ, Bird ED, Richardson EP Jr. Neuropathological classification of Huntington’s disease. J Neuropathol Exp Neurol. 1985;44(6):559–77.

    Article  CAS  PubMed  Google Scholar 

  39. De la Monte SM, Vonsattel JP, Richardson EP Jr. Morphometric demonstration of atrophic changes in the cerebral cortex, white matter, and neostriatum in Huntington’s disease. J Neuropathol Exp Neurol. 1988;47(5):516–25.

    Article  PubMed  Google Scholar 

  40. Lange H, Thörner G, Hopf A, Schröder KF. Morphometric studies of the neuropathological changes in choreatic diseases. J Neurol Sci. 1976;28(4):401–25.

    Article  CAS  PubMed  Google Scholar 

  41. 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.

    Article  CAS  PubMed  Google Scholar 

  42. Singhrao SK, Neal JW, Morgan BP, Gasque P. Increased complement biosynthesis by microglia and complement activation on neurons in Huntington’s disease. Exp Neurol. 1999;159(2):362–76.

    Article  CAS  PubMed  Google Scholar 

  43. Gómez-Tortosa E, MacDonald ME, Friend JC, Taylor SA, Weiler LJ, Cupples LA, et al. Quantitative neuropathological changes in presymptomatic Huntington’s disease. Ann Neurol. 2001;49(1):29–34.

    Article  PubMed  Google Scholar 

  44. Oyanagi K, Takeda S, Takahashi H, Ohama E, Ikuta F. A quantitative investigation of the substantia nigra in Huntington’s disease. Ann Neurol. 1989;26(1):13–9.

    Article  CAS  PubMed  Google Scholar 

  45. Heinsen H, Rüb U, Bauer M, Ulmar G, Bethke B, Schüler M, et al. Nerve cell loss in the thalamic mediodorsal nucleus in Huntington’s disease. Acta Neuropathol. 1999;97(6):613–22.

    Article  CAS  PubMed  Google Scholar 

  46. Kremer HP, Roos RA, Dingjan G, Marani E, Bots GT. Atrophy of the hypothalamic lateral tuberal nucleus in Huntington’s disease. J Neuropathol Exp Neurol. 1990;49(4):371–82.

    Article  CAS  PubMed  Google Scholar 

  47. Kremer HP, Roos RA, Dingjan GM, Bots GT, Bruyn GW, Hofman MA. The hypothalamic lateral tuberal nucleus and the characteristics of neuronal loss in Huntington’s disease. Neurosci Lett. 1991;132(1):101–4.

    Article  CAS  PubMed  Google Scholar 

  48. Sotrel A, Paskevich PA, Kiely DK, Bird ED, Williams RS, Myers RH. Morphometric analysis of the prefrontal cortex in Huntington’s disease. Neurology. 1991;41(7):1117–23.

    Article  CAS  PubMed  Google Scholar 

  49. Hedreen JC, Peyser CE, Folstein SE, Ross CA. Neuronal loss in layers V and VI of cerebral cortex in Huntington’s disease. Neurosci Lett. 1991;133(2):257–61.

    Article  CAS  PubMed  Google Scholar 

  50. Heinsen H, Strik M, Bauer M, Luther K, Ulmar G, Gangnus D, et al. Cortical and striatal neurone number in Huntington’s disease. Acta Neuropathol. 1994;88(4):320–33.

    Article  CAS  PubMed  Google Scholar 

  51. Trottier Y, Devys D, Imbert G, Saudou F, An I, Lutz Y, et al. Cellular localization of the Huntington’s disease protein and discrimination of the normal and mutated form. Nat Genet. 1995;10(1):104–10.

    Article  CAS  PubMed  Google Scholar 

  52. Sharp AH, Loev SJ, Schilling G, Li SH, Li XJ, Bao J, et al. Widespread expression of Huntington’s disease gene (IT15) protein product. Neuron. 1995;14(5):1065–74.

    Article  CAS  PubMed  Google Scholar 

  53. Gutekunst CA, Levey AI, Heilman CJ, Whaley WL, Yi H, Nash NR, et al. Identification and localization of huntingtin in brain and human lymphoblastoid cell lines with anti-fusion protein antibodies. Proc Natl Acad Sci USA. 1995;92(19):8710–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. DiFiglia M, Sapp E, Chase K, Schwarz C, Meloni A, Young C, et al. Huntingtin is a cytoplasmic protein associated with vesicles in human and rat brain neurons. Neuron. 1995;14(5):1075–81.

    Article  CAS  PubMed  Google Scholar 

  55. Gutekunst CA, Li SH, Yi H, Mulroy JS, Kuemmerle S, Jones R, et al. Nuclear and neuropil aggregates in Huntington’s disease: relationship to neuropathology. J Neurosci. 1999;19(7):2522–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Gutekunst CA, Li SH, Yi H, Ferrante RJ, Li XJ, Hersch SM. The cellular and subcellular localization of huntingtin-associated protein 1 (HAP1): comparison with huntingtin in rat and human. J Neurosci. 1998;18(19):7674–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Kegel KB, Kim M, Sapp E, McIntyre C, Castaño JG, Aronin N, et al. Huntingtin expression stimulates endosomal-lysosomal activity, endosome tubulation, and autophagy. J Neurosci. 2000;20(19):7268–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Li SH, Li XJ. Aggregation of N-terminal huntingtin is dependent on the length of its glutamine repeats. Hum Mol Genet. 1998;7(5):777–82.

    Article  CAS  PubMed  Google Scholar 

  59. Perutz MF, Johnson T, Suzuki M, Finch JT. Glutamine repeats as polar zippers: their possible role in inherited neurodegenerative diseases. Proc Natl Acad Sci USA. 1994;91(12):5355–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Gourfinkel-An I, Cancel G, Trottier Y, Devys D, Tora L, Lutz Y, et al. Differential distribution of the normal and mutated forms of huntingtin in the human brain. Ann Neurol. 1997;42(5):712–9.

    Google Scholar 

  61. Scherzinger E, Lurz R, Turmaine M, Mangiarini L, Hollenbach B, Hasenbank R, et al. Huntingtin-encoded polyglutamine expansions form amyloid-like protein aggregates in vitro and in vivo. Cell. 1997;90(3):549–58.

    Article  CAS  PubMed  Google Scholar 

  62. Martindale D, Hackam A, Wieczorek A, Ellerby L, Wellington C, McCutcheon K, et al. Length of huntingtin and its polyglutamine tract influences localization and frequency of intracellular aggregates. Nat Genet. 1998;18(2):150–4.

    Article  CAS  PubMed  Google Scholar 

  63. Kuemmerle S, Gutekunst CA, Klein AM, Li XJ, Li SH, Beal MF, et al. Ferrante RJ. Huntington aggregates may not predict neuronal death in Huntington’s disease. Ann Neurol. 1999;46(6):842–9.

    Google Scholar 

  64. Li SH, Gutekunst CA, Hersch SM, Li XJ. Interaction of huntingtin-associated protein with dynactin P150Glued. J Neurosci. 1998;18(4):1261–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Li SH, Cheng AL, Zhou H, Lam S, Rao M, Li H, et al. Interaction of Huntington disease protein with transcriptional activator Sp1. Mol Cell Biol. 2002;22(5):1277–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Li XJ, Li SH, Sharp AH, Nucifora FC Jr, Schilling G, Lanahan A, et al. A huntingtin-associated protein enriched in brain with implications for pathology. Nature. 1995;378(6555):398–402.

    Article  CAS  PubMed  Google Scholar 

  67. Li Y, Chin LS, Levey AI, Li L. Huntingtin-associated protein 1 interacts with hepatocyte growth factor-regulated tyrosine kinase substrate and functions in endosomal trafficking. J Biol Chem. 2002;277(31):28212–21.

    Article  CAS  PubMed  Google Scholar 

  68. Sittler A, Wälter S, Wedemeyer N, Hasenbank R, Scherzinger E, Eickhoff H, et al. SH3GL3 associates with the Huntingtin exon 1 protein and promotes the formation of polygln-containing protein aggregates. Mol Cell. 1998;2(4):427–36.

    Article  CAS  PubMed  Google Scholar 

  69. Kalchman MA, Graham RK, Xia G, Koide HB, Hodgson JG, Graham KC, et al. Huntingtin is ubiquitinated and interacts with a specific ubiquitin-conjugating enzyme. J Biol Chem. 1996;271(32):19385–94.

    Article  CAS  PubMed  Google Scholar 

  70. Kalchman MA, Koide HB, McCutcheon K, Graham RK, Nichol K, Nishiyama K, et al. HIP1, a human homologue of S. cerevisiae Sla2p, interacts with membrane-associated huntingtin in the brain. Nat Genet. 1997;16(1):44–53.

    Article  CAS  PubMed  Google Scholar 

  71. Wanker EE, Rovira C, Scherzinger E, Hasenbank R, Wälter S, Tait D, et al. HIP-I: a huntingtin interacting protein isolated by the yeast two-hybrid system. Hum Mol Genet. 1997;6(3):487–95.

    Article  CAS  PubMed  Google Scholar 

  72. Metzler M, Legendre-Guillemin V, Gan L, Chopra V, Kwok A, McPherson PS, et al. HIP1 functions in clathrin-mediated endocytosis through binding to clathrin and adaptor protein 2. J Biol Chem. 2001;276(42):39271–6.

    Article  CAS  PubMed  Google Scholar 

  73. Lunkes A, Lindenberg KS, Ben-Haïem L, Weber C, Devys D, Landwehrmeyer GB, et al. Proteases acting on mutant huntingtin generate cleaved products that differentially build up cytoplasmic and nuclear inclusions. Mol Cell. 2002;10(2):259–69.

    Article  CAS  PubMed  Google Scholar 

  74. Zucker B, Kama JA, Kuhn A, Thu D, Orlando LR, Dunah AW, et al. Decreased Lin7b expression in layer 5 pyramidal neurons may contribute to impaired corticostriatal connectivity in huntington disease. J Neuropathol Exp Neurol [Internet]. 2010;69(9):880–95. https://academic.oup.com/jnen, https://doi.org/10.1097/nen.0b013e3181ed7a41.

    Article  CAS  Google Scholar 

  75. Chakraborty J, Rajamma U, Mohanakumar KP. A mitochondrial basis for Huntington’s disease: therapeutic prospects. Mol Cell Biochem [Internet]. 2014;389(1–2):277–91. http://link.springer.com/journal/11010 https://doi.org/10.1007/s11010-013-1951-9.

    Article  PubMed  CAS  Google Scholar 

  76. Gladding CM. Raymond LA Mechanisms underlying NMDA receptor synaptic/extrasynaptic distribution and function. Mol Cell Neurosci. 2011;48(4):308–20.

    Article  CAS  PubMed  Google Scholar 

  77. Deyts C, Galan-Rodriguez B, Martin E, Bouveyron N, Roze E, Charvin D, et al. Dopamine D2 receptor stimulation potentiates PolyQ-Huntingtin-induced mouse striatal neuron dysfunctions via Rho/ROCK-II activation. PLoS One [Internet]. 2009;4(12):e8287. http://www.ncbi.nlm.nih.gov/pmc/journals/440/.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  78. Strand AD, Baquet ZC, Aragaki AK, Holmans P, Yang L, Cleren C, et al. Expression profiling of Huntington’s disease models suggests that brain-derived neurotrophic factor depletion plays a major role in striatal degeneration. J Neurosci [Internet]. 2007;27(43):11758–68. http://www.jneurosci.org/, https://doi.org/10.1523/jneurosci.2461-07.2007.

    Article  CAS  PubMed  Google Scholar 

  79. Li JY, Conforti L. Axonopathy in Huntington’s disease. Exp Neurol [Internet]. 2013;246:62–71. http://www.sciencedirect.com/science/journal/00144886, https://doi.org/10.1016/j.expneurol.2012.08.010.

    Article  PubMed  Google Scholar 

  80. Crotti A, Glass CK. The choreography of neuroinflammation in Huntington’s disease. Trends Immunol. 2015;36(6):364–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Cortes CJ, La Spada AR. The many faces of autophagy dysfunction in Huntington’s disease: from mechanism to therapy. Drug Discov Today [Internet]. 2014;19(7):963–71. http://sciencedirect.com/science/journal/13596446, https://doi.org/10.1016/j.drudis.2014.02.014.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Ellrichmann G, Reick C, Saft C, Linker RA. The role of the immune system in Huntington’s disease. Clin Dev Immunol [Internet]. 2013;2013:541259. http://www.ncbi.nlm.nih.gov/pmc/journals/499/#cdi, https://doi.org/10.1155/2013/541259.

    Article  CAS  Google Scholar 

  83. Rosas HD, Liu AK, Hersch S, Glessner M, Ferrante RJ, Salat DH, et al. Regional and progressive thinning of the cortical ribbon in Huntington’s disease. Neurology. 2002;58(5):695–701.

    Article  CAS  PubMed  Google Scholar 

  84. 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(10):1615–20.

    Article  CAS  PubMed  Google Scholar 

  85. Thieben MJ, Duggins AJ, Good CD, Gomes L, Mahant N, Richards F, et al. The distribution of structural neuropathology in pre-clinical Huntington’s disease. Brain. 2002;125(8):1815–28.

    Article  CAS  PubMed  Google Scholar 

  86. Klöppel S, Henley SM, Hobbs NZ, Wolf RC, Kassubek J, Tabrizi SJ, et al. Magnetic resonance imaging of Huntington’s disease: preparing for clinical trials. Neuroscience [Internet]. 2009;164(1):205–19. http://sciencedirect.com/science/journal/03064522, https://doi.org/10.1016/j.neuroscience.2009.01.045.

    Article  PubMed  CAS  Google Scholar 

  87. Pagano G, Niccolini F, Politis M. Current status of PET imaging in Huntington’s disease. Eur J Nucl Med Mol Imaging [Internet]. 2016;43(6):1171–82. http://link.springer.com/journal/259, https://doi.org/10.1007/s00259-016-3324-6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Nopoulos PC. Huntington disease: a single-gene degenerative disorder of the striatum. Dialogues Clin Neurosci. 2016;18(1):91–8.

    PubMed  PubMed Central  Google Scholar 

  89. Mahant N, McCusker EA, Byth K, Graham S, Huntington Study Group. Huntington’s disease: clinical correlates of disability and progression. Neurology. 2003;61(8):1085–92.

    Article  CAS  PubMed  Google Scholar 

  90. Novak MJ, Tabrizi SJ. Huntington’s disease. BMJ [Internet]. 2010;340:c3109. http://www.ncbi.nlm.nih.gov/pmc/journals/3/ https://doi.org/10.1136/bmj.c3109.

    Article  PubMed  Google Scholar 

  91. Quarrell OW, Nance MA, Nopoulos P, Paulsen JS, Smith JA, Squitieri F. Managing juvenile Huntington’s disease. Neurodegener Dis Manag [Internet]. 2013;3(3). http://www.futuremedicine.com/loi/nmt, https://doi.org/10.2217/nmt.13.18.

    Article  Google Scholar 

  92. Cui SS, Ren RJ, Wang Y, Wang G, Chen SD. Tics as an initial manifestation of juvenile Huntington’s disease: case report and literature review. BMC Neurol [Internet]. 2017;17(1):152. http://www.ncbi.nlm.nih.gov/pmc/journals/48/, https://doi.org/10.1186/s12883-017-0923-1.

  93. Kirkwood SC, Siemers E, Stout JC, Hodes ME, Conneally PM, Christian JC, et al. Longitudinal cognitive and motor changes among presymptomatic Huntington disease gene carriers. Arch Neurol. 1999;56(5):563–8.

    Article  CAS  PubMed  Google Scholar 

  94. Khedraki A, Reed EJ, Romer SH, Wang Q, Romine W, Rich MM, Talmadge RJ, Voss AA. Depressed synaptic transmission and reduced vesicle release sites in Huntington’s disease neuromuscular junctions. J Neurosci. 2017;37(34):8077–91. https://doi.org/10.1523/JNEUROSCI.0313-17.2017.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Danoudis M, Iansek R. Gait in Huntington’s disease and the stride length-cadence relationship. BMC Neurol [Internet]. 2014;14:161. http://www.ncbi.nlm.nih.gov/pmc/journals/48/, https://doi.org/10.1186/s12883-014-0161-8.

  96. Simpson JA, Lovecky D, Kogan J, Vetter LA, Yohrling GJ. Survey of the Huntington’s disease patient and caregiver community reveals most impactful symptoms and treatment needs. J Huntingtons Dis [Internet]. 2016;5(4):395–403. http://content.iospress.com/journals/journal-of-huntingtons-disease.

    Article  PubMed  Google Scholar 

  97. Lange KW, Sahakian BJ, Quinn NP, Marsden CD, Robbins TW. Comparison of executive and visuospatial memory function in Huntington’s disease and dementia of Alzheimer type matched for degree of dementia. J Neurol Neurosurg Psychiatry. 1995;58(5):598–606.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Paulsen JS, Butters N, Sadek JR, Johnson SA, Salmon DP, Swerdlow NR, et al. Distinct cognitive profiles of cortical and subcortical dementia in advanced illness. Neurology. 1995;45(5):951–6.

    Article  CAS  PubMed  Google Scholar 

  99. Bamford KA, Caine ED, Kido DK, Cox C, Shoulson I. A prospective evaluation of cognitive decline in early Huntington’s disease: functional and radiographic correlates. Neurology. 1995;45(10):1867–73.

    Article  CAS  PubMed  Google Scholar 

  100. Paulsen JS. Cognitive impairment in Huntington disease: diagnosis and treatment. Curr Neurol Neurosci Rep [Internet]. 2011;11(5):474–83. http://link.springer.com/journal/11910, https://doi.org/10.1007/s11910-011-0215-x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Schneider SA, Wilkinson L, Bhatia KP, Henley SM, Rothwell JC, Tabrizi SJ. et al. Abnormal explicit but normal implicit sequence learning in premanifest and early Huntington’s disease. Mov Disord [Internet]. 2010;25(10):1343–9. http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1531-8257, https://doi.org/10.1002/mds.22692.

    Article  PubMed  PubMed Central  Google Scholar 

  102. Huntington Study Group [No authors listed]. Unified Huntington’s disease rating scale: reliability and consistency. Mov Disord. 1996;11(2):136–42.

    Google Scholar 

  103. Paulsen JS, Langbehn DR, Stout JC, Aylward E, Ross CA, Nance M, et al. Detection of Huntington’s disease decades before diagnosis: the Predict-HD study. J Neurol Neurosurg Psychiatry. 2008;79(8):874–80.

    Article  CAS  PubMed  Google Scholar 

  104. Foroud T, Siemers E, Kleindorfer D, Bill DJ, Hodes ME, Norton JA, et al. Cognitive scores in carriers of Huntington’s disease gene compared to noncarriers. Ann Neurol. 1995;37(5):657–64.

    Article  CAS  PubMed  Google Scholar 

  105. Unmack Larsen I, Vinther-Jensen T, Gade A, Nielsen JE, Vogel A. Assessing impairment of executive function and psychomotor speed in premanifest and manifest Huntington’s disease gene-expansion carriers. J Int Neuropsychol Soc [Internet]. 2015;21(3):193–202. https://www.cambridge.org/core/journals/journal-of-the-international-neuropsychological-society, https://doi.org/10.1017/s1355617715000090.

    Article  PubMed  Google Scholar 

  106. Duff K, Paulsen JS, Beglinger LJ, Langbehn DR, Wang C, Stout JC, et al. “Frontal” behaviors before the diagnosis of Huntington’s disease and their relationship to markers of disease progression: evidence of early lack of awareness. J Neuropsychiatry Clin Neurosci [Internet]. 2010;22(2):196–207. http://neuro.psychiatryonline.org/journal.aspx?journalid=62, https://doi.org/10.1176/appi.neuropsych.22.2.196.

  107. Mörkl S, Müller NJ, Blesl C, Wilkinson L, Tmava A, Wurm W, et al. Problem solving, impulse control and planning in patients with early- and late-stage Huntington’s disease. Eur Arch Psychiatry Clin Neurosci [Internet]. 2016;266(7):663–71. http://link.springer.com/journal/406, https://doi.org/10.1007/s00406-016-0707-4.

    Article  PubMed  PubMed Central  Google Scholar 

  108. Dumas EM, van den Bogaard SJ, Middelkoop HA, Roos RA. A review of cognition in Huntington’s disease. Front Biosci. 2013;1(5):1–18.

    Article  Google Scholar 

  109. Nance M, Paulsen J, Rosenblatt A, Wheelock V. A physician’s guide to the management of Huntington’s disease. New York: Huntigton’s Disease Society of America; 2012. p. 55.

    Google Scholar 

  110. Feigin A, Ghilardi MF, Huang C, Ma Y, Carbon M, Guttman M, Paulsen JS, Ghez CP, Eidelberg D. Preclinical Huntington’s disease: compensatory brain responses during learning. Ann Neurol. 2006;59(1):53–9.

    Article  PubMed  PubMed Central  Google Scholar 

  111. Johnson SA, Stout JC, Solomon AC, Langbehn DR, Aylward EH, Cruce CB, et al. Beyond disgust: impaired recognition of negative emotions prior to diagnosis in Huntington’s disease. Brain. 2007;130(Pt 7):1732–44.

    Article  PubMed  Google Scholar 

  112. Brandt J, Shpritz B, Munro CA, Marsh L, Rosenblatt A. Differential impairment of spatial location memory in Huntington’s disease. J Neurol Neurosurg Psychiatry. 2005;76(11):1516–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Hamilton JM, Murphy C, Paulsen JS. Odor detection, learning, and memory in Huntington’s disease. J Int Neuropsychol Soc. 1999;5(7):609–15.

    Article  CAS  PubMed  Google Scholar 

  114. Rowe KC, Paulsen JS, Langbehn DR, Duff K, Beglinger LJ, Wang C, et al. Self-paced timing detects and tracks change in prodromal Huntington disease. Neuropsychology [Internet]. 2010;24(4):435–42. http://search.ebscohost.com/direct.asp?db=pdh&jid=NEU&scope=site, https://doi.org/10.1037/a0018905.

    Article  PubMed  PubMed Central  Google Scholar 

  115. Sitek EJ, Sołtan W, Wieczorek D, Schinwelski M, Robowski P, Reilmann R, et al. Self-awareness of motor dysfunction in patients with Huntington’s disease in comparison to Parkinson’s disease and cervical dystonia. J Int Neuropsychol Soc [Internet]. 2011;17(5):788–95. https://www.cambridge.org/core/journals/journal-of-the-international-neuropsychological-society, https://doi.org/10.1017/s1355617711000725.

    Article  PubMed  Google Scholar 

  116. Frank E, Morrow-Odom KL, Abramson RK, Cuturic M. Central auditory and visual processing in Huntington’s disease. J Med Speech Lang Pathol [Internet]. 2009;17(1):3. https://www.pluralpublishing.com/journals_JMSLP.htm.

  117. Saldert C, Fors A, Ströberg S, Hartelius L. Comprehension of complex discourse in different stages of Huntington’s disease. Int J Lang Commun Disord [Internet]. 2010;45(6):656–69. http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1460-6984, https://doi.org/10.3109/13682820903494742.

    Article  Google Scholar 

  118. Shiwach R. Psychopathology in Huntington’s disease patients. Acta Psychiatr Scand. 1994;90(4):241–6.

    Article  CAS  PubMed  Google Scholar 

  119. Van Duijn E, Craufurd D, Hubers AA, Giltay EJ, Bonelli R, Rickards H, et al. Neuropsychiatric symptoms in a European Huntington’s disease cohort (REGISTRY). J Neurol Neurosurg Psychiatry [Internet]. 2014;85(12):1411–8. http://www.ncbi.nlm.nih.gov/pmc/journals/192/, https://doi.org/10.1136/jnnp-2013-307343.

    Article  Google Scholar 

  120. Ghosh R, Tabrizi SJ. Clinical aspects of Huntington’s disease. Curr Top Behav Neurosci. 2015;22:3–31.

    Article  CAS  PubMed  Google Scholar 

  121. Vaccarino AL, Sills T, Anderson KE, Bachoud-Lévi AC, Borowsky B, Craufurd D, et al. Assessment of depression, anxiety and apathy in prodromal and early huntington disease. PLoS Curr [Internet]. 2011;3:RRN1242. http://www.ncbi.nlm.nih.gov/pmc/?term=%22PLoS+Curr%22%5Bjournal%5D.

    PubMed  PubMed Central  Google Scholar 

  122. Epping EA, Kim JI, Craufurd D, Brashers-Krug TM, Anderson KE, McCusker E. Longitudinal psychiatric symptoms in prodromal Huntington’s disease: a decade of data. Am J Psychiatry [Internet]. 2016;173(2):184–92. http://ajp.psychiatryonline.org/journal.aspx?journalid=13, https://doi.org/10.1176/appi.ajp.2015.14121551.

    Article  PubMed  Google Scholar 

  123. Paulsen JS, Nehl C, Hoth KF, Kanz JE, Benjamin M, Conybeare R, et al. Depression and stages of Huntington’s disease. J Neuropsychiatry Clin Neurosci. 2005;17(4):496–502.

    Article  PubMed  Google Scholar 

  124. Mendez MF. Huntington’s disease: update and review of neuropsychiatric aspects. Int J Psychiatry Med. 1994;24(3):189–208.

    Article  CAS  PubMed  Google Scholar 

  125. Fisher CA, Sewell K, Brown A, Churchyard A. Aggression in Huntington’s disease: a systematic review of rates of aggression and treatment methods. J Huntingtons Dis [Internet]. 2014;3(4):319–32. http://content.iospress.com/journals/journal-of-huntingtons-disease, https://doi.org/10.3233/jhd-140127.

    Article  PubMed  Google Scholar 

  126. Lipe H, Schultz A, Bird TD. Risk factors for suicide in Huntingtons disease: a retrospective case controlled study. Am J Med Genet. 1993;48(4):231–3.

    Article  CAS  PubMed  Google Scholar 

  127. Almqvist EW, Bloch M, Brinkman R, Craufurd D, Hayden MR. A worldwide assessment of the frequency of suicide, suicide attempts, or psychiatric hospitalization after predictive testing for Huntington disease. Am J Hum Genet. 1999;64(5):1293–304.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Wetzel HH, Gehl CR, Dellefave-Castillo L, Schiffman JF, Shannon KM, Paulsen JS, et al. Suicidal ideation in Huntington disease: the role of comorbidity. Psychiatry Res [Internet]. 2011;188(3):372–6. http://www.sciencedirect.com/science/journal/09254927, https://doi.org/10.1016/j.psychres.2011.05.006.

    Article  PubMed  PubMed Central  Google Scholar 

  129. Paulsen JS, Hoth KF, Nehl C, Stierman L. Critical periods of suicide risk in Huntington’s disease. Am J Psychiatry. 2005;162(4):725–31.

    Article  PubMed  Google Scholar 

  130. Farrer LA. Suicide and attempted suicide in Huntington disease: implications for preclinical testing of persons at risk. Am J Med Genet. 1986;24(2):305–11.

    Article  CAS  PubMed  Google Scholar 

  131. Cummings J. Behavioral and psychiatric symptoms associated with Huntington disease. In: Weiner WJ, Lang AE, editors. Behavioral neurology of movement disorders. New York: Raven Press; 1995. p. 179–86.

    Google Scholar 

  132. Schoenfeld M, Myers RH, Cupples LA, Berkman B, Sax DS, Clark E. Increased rate of suicide among patients with Huntington’s disease. J Neurol Neurosurg Psychiatry. 1984;47(12):1283–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Lovestone S, Hodgson S, Sham P, Differ AM, Levy R. Familial psychiatric presentation of Huntington’s disease. J Med Genet. 1996;33(2):128–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Nagel M, Rumpf HJ, Kasten M. Acute psychosis in a verified Huntington disease gene carrier with subtle motor signs: psychiatric criteria should be considered for the diagnosis. Gen Hosp Psychiatry [Internet]. 2014;36(3):361.e3–4. http://www.sciencedirect.com/science/journal/01638343, https://doi.org/10.1016/j.genhosppsych.2014.01.008.

    Article  Google Scholar 

  135. Cummings JL, Cunningham K. Obsessive-compulsive disorder in Huntington’s disease. Biol Psychiatry. 1992;31(3):263–70.

    Article  CAS  PubMed  Google Scholar 

  136. Cuturic M, Abramson RK, Vallini D, Frank EM, Shamsnia M. Sleep patterns in patients with Huntington’s disease and their unaffected first-degree relatives: a brief report. Behav Sleep Med [Internet]. 2009;7(4):245–54. http://www.tandfonline.com/loi/hbsm, https://doi.org/10.1080/15402000903190215.

    Article  PubMed  Google Scholar 

  137. Wiegand M, Möller AA, Lauer CJ, Stolz S, Schreiber W, Dose M, et al. Nocturnal sleep in Huntington’s disease. J Neurol. 1991;238(4):203–8.

    Article  CAS  PubMed  Google Scholar 

  138. Pflanz S, Besson JA, Ebmeier KP, Simpson S. The clinical manifestation of mental disorder in Huntington’s disease: a retrospective case record study of disease progression. Acta Psychiatr Scand. 1991;83(1):53–60.

    Article  CAS  PubMed  Google Scholar 

  139. Kirkwood SC, Siemers E, Viken R, Hodes ME, Conneally PM, Christian JC, et al. Longitudinal personality changes among presymptomatic Huntington disease gene carriers. Neuropsychiatry Neuropsychol Behav Neurol. 2002;15(3):192–7.

    PubMed  Google Scholar 

  140. Cardoso F, Seppi K, Mair KJ, Wenning GK, Poewe W. Seminar on choreas. Lancet Neurol. 2006;5(7):589–602.

    Article  PubMed  Google Scholar 

  141. Rosencrantz R, Schilsky M. Wilson disease: pathogenesis and clinical considerations in diagnosis and treatment. Semin Liver Dis [Internet]. 2011;31(3):245–59. https://www.thieme-connect.de/products/ejournals/journal/10.1055/s-00000069, https://doi.org/10.1055/s-0031-1286056.

    Article  CAS  PubMed  Google Scholar 

  142. Walker RH, Jung HH, Danek A. Neuroacanthocytosis. Handb Clin Neurol. 2011;100:141–51.

    Article  PubMed  Google Scholar 

  143. Stevanin G, Brice A. Spinocerebellar ataxia 17 (SCA17) and Huntington’s disease-like 4 (HDL4). Cerebellum [Intertnet]. 2008;7(2):170–8. http://link.springer.com/journal/12311, https://doi.org/10.1007/s12311-008-0016-1.

    Article  CAS  PubMed  Google Scholar 

  144. Iizuka R, Hirayama K, Maehara KA. Dentato-rubro-pallido-luysian atrophy: a clinico-pathological study. Huntingtin is ubiquitinated and interacts with a specific ubiquitin-conjugating enzyme. J Neurol Neurosurg Psychiatry. 1984;47(12):1288–98.

    Article  CAS  Google Scholar 

  145. Hardie RJ, Pullon HW, Harding AE, Owen JS, Pires M, Daniels GL, et al. Neuroacanthocytosis. A clinical, haematological and pathological study of 19 cases. Brain. 1991;114(Pt 1A):13–49.

    Google Scholar 

  146. Laplanche JL, Hachimi KH, Durieux I, Thuillet P, Defebvre L, Delasnerie-Laupretre N, et al. Prominent psychiatric features and early onset in an inherited prion disease with a new insertional mutation in the prion protein gene. Brain. 1999;122:2375–86.

    Article  PubMed  Google Scholar 

  147. Moore RC, Xiang F, Monaghan J, Han D, Zhang Z, Edstrom L, et al. Huntington disease phenocopy is a familial prion disease. Am J Hum Genet. 2001;69:1385–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Margolis RL, Rudnicki DD, Holmes SE. Huntington’s disease like-2: review and update. Acta Neurol Taiwan. 2005;14:1–8.

    PubMed  Google Scholar 

  149. Kremer B, Goldberg P, Andrew SE, Theilmann J, Telenius H, Zeisler J, et al. A worldwide study of the Huntington’s disease mutation. The sensitivity and specificity of measuring CAG repeats. N Engl J Med. 1994;330(20):1401–6.

    Article  CAS  PubMed  Google Scholar 

  150. Terrenoire G. Huntington’s disease and the ethics of genetic prediction. J Med Ethics. 1992;18(2):79–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Hayden MR, Bloch M, Wiggins S. Psychological effects of predictive testing for Huntington’s disease. Adv Neurol. 1995;65:201–10.

    CAS  PubMed  Google Scholar 

  152. Harper PS. Clinical consequences of isolating the gene for Huntington’s disease. BMJ. 1993;307(6901):397–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. International Huntington Association (IHA) and the World Federation of Neurology (WFN) Research Group on Huntington’s Chorea. [No authors listed]. Guidelines for the molecular genetics predictive test in Huntington’s disease. Neurology. 1994;44(8):1533–6.

    Google Scholar 

  154. Nance M, Paulsen J, Rosenblatt A, Wheelock V. A physician’s guide to the management of Huntington’s disease. New York: Huntigton’s Disease Society of America; 2012. p. 16–23.

    Google Scholar 

  155. Richards FH. Maturity of judgement in decision making for predictive testing for nontreatable adult-onset neurogenetic conditions: a case against predictive testing of minors. Clin Genet. 2006;70(5):396–401.

    Article  CAS  PubMed  Google Scholar 

  156. Oster E, Dorsey ER, Bausch J, Shinaman A, Kayson E, Oakes D, et al. Fear of health insurance loss among individuals at risk for Huntington disease. Am J Med Genet A [Internet]. 2008;146A(16):2070–7. http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1552-4833, https://doi.org/10.1002/ajmg.a.32422.

    Article  PubMed  PubMed Central  Google Scholar 

  157. Quaid KA, Eberly SW, Kayson-Rubin E, Oakes D, Shoulson I; Huntington Study Group PHAROS Investigators and Coordinators. Factors related to genetic testing in adults at risk for Huntington disease: the prospective Huntington at-risk observational study (PHAROS). Clin Genet [Internet]. 2017;91(6):824–31. http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1399-0004, https://doi.org/10.1111/cge.12893.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  158. De Die-Smulders CE, de Wert GM, Liebaers I, Tibben A, Evers-Kiebooms G. Reproductive options for prospective parents in families with Huntington’s disease: clinical, psychological and ethical reflections. Hum Reprod Update [Internet]. 2013;19(3):304–15. https://academic.oup.com/humupd, https://doi.org/10.1093/humupd/dms058.

    Article  CAS  PubMed  Google Scholar 

  159. Bustamante-Aragonés A, Rodríguez de Alba M, Perlado S, Trujillo-Tiebas MJ, Arranz JP, Díaz-Recasens et al. Non-invasive prenatal diagnosis of single-gene disorders from maternal blood. Gene [Internet]. 2012;504(1):144–9. http://sciencedirect.com/science/journal/03781119, https://doi.org/10.1016/j.gene.2012.04.045.

    Article  PubMed  CAS  Google Scholar 

  160. Van den Oever JM, Bijlsma EK, Feenstra I, Muntjewerff N, Mathijssen IB, Bakker E, et al. Noninvasive prenatal diagnosis of Huntington disease: detection of the paternally inherited expanded CAG repeat in maternal plasma. Prenat Diagn [Internet]. 2015;35(10):945–9. http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1097-0223, https://doi.org/10.1002/pd.4593.

    Article  CAS  PubMed  Google Scholar 

  161. Schultz JL, Kamholz JA, Moser DJ, Feely SM, Paulsen JS, Nopoulos PC. Substance abuse may hasten motor onset of Huntington disease: evaluating the enroll-HD database. Neurology [Internet]. 2017;88(9):909–15. http://ovidsp.ovid.com/ovidweb.cgi?T=JS&NEWS=n&CSC=Y&PAGE=toc&D=yrovft&AN=00006114-000000000-00000, https://doi.org/10.1212/wnl.0000000000003661.

    Article  PubMed  PubMed Central  Google Scholar 

  162. Frese S, Petersen JA, Ligon-Auer M, Mueller SM, Mihaylova V, Gehrig SM, et al. Exercise effects in Huntington disease. J Neurol [Internet]. 2017;264(1):32–39. http://link.springer.com/journal/415, https://doi.org/10.1007/s00415-016-8310-1.

    Article  PubMed  CAS  Google Scholar 

  163. Rivadeneyra J, Cubo E, Gil C, Calvo S, Mariscal N, Martínez A. Factors associated with Mediterranean diet adherence in Huntington’s disease. Clin Nutr ESPEN [Internet]. 2016;12:e7–13. http://www.sciencedirect.com/science/journal/24054577, https://doi.org/10.1016/j.clnesp.2016.01.001.

    Article  PubMed  Google Scholar 

  164. Shannon KM, Fraint A. Therapeutic advances in Huntington’s disease. Mov Disord [Internet]. 2015;30(11):1539–46. http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1531-8257, https://doi.org/10.1002/mds.26331.

    Article  PubMed  Google Scholar 

  165. Marosz A, Chlubek D. The risk of abuse of vitamin supplements. Ann Acad Med Stetin. 2014;60(1):60–4.

    Google Scholar 

  166. Klimek ML, Rohs G, Young L, Suchowersky O, Trew M. Multidisciplinary approach to management of a hereditary neurodegenerative disorder: Huntington disease. Axone. 1997;19(2):34–8.

    CAS  PubMed  Google Scholar 

  167. Quinn L, Busse M, Carrier J, Fritz N, Harden J, Hartel L, et al. Physical therapy and exercise interventions in Huntington’s disease: a mixed methods systematic review protocol. JBI Database System Rev Implement Rep [Internet]. 2017;15(7):1783–99. http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=toc&SEARCH=01938924-201606000-00000.kc&LINKTYPE=asBody&LINKPOS=1&D=yrovft, https://doi.org/10.11124/jbisrir-2016-003274.

    Article  PubMed  Google Scholar 

  168. Piira A, van Walsem MR, Mikalsen G, Øie L, Frich JC, Knutsen S. Effects of a two-year intensive multidisciplinary rehabilitation program for patients with Huntington’s disease: a prospective intervention study. Version 2. PLoS Curr [Internet]. 2014 [revised 2014 Jan 1];6. pii: ecurrents.hd.2c56ceef7f9f8e239a59ecf2d94cddac. http://www.ncbi.nlm.nih.gov/pmc/?term=%22PLoS+Curr%22%5Bjournal%5D, https://doi.org/10.1371/currents.hd.2c56ceef7f9f8e239a59ecf2d94cddac.

  169. Zinzi P, Salmaso D, De Grandis R, Graziani G, Maceroni S, Bentivoglio A, et al. Effects of an intensive rehabilitation programme on patients with Huntington’s disease: a pilot study. Clin Rehabil. 2007;21(7):603–13.

    Article  PubMed  Google Scholar 

  170. Cruickshank TM, Thompson JA, Domínguez D JF, Reyes AP, Bynevelt M, Georgiou-Karistianis N, et al. The effect of multidisciplinary rehabilitation on brain structure and cognition in Huntington’s disease: an exploratory study. Brain Behav [Internet]. 2015;5(2):e00312. http://www.ncbi.nlm.nih.gov/pmc/journals/1650/, https://doi.org/10.1002/brb3.312.

    Article  Google Scholar 

  171. Downing NR, Goodnight S, Chae S, Perlmutter JS, McCormack M, Hahn E, et al. Factors associated with end-of-life planning in Huntington disease. Am J Hosp Palliat Care [Internet]. 2017:1049909117708195. http://journals.sagepub.com/home/ajh, https://doi.org/10.1177/1049909117708195.

    Article  Google Scholar 

  172. Dellefield ME, Ferrini R. Promoting Excellence in end-of-life care: lessons learned from a cohort of nursing home residents with advanced Huntington disease. J Neurosci Nurs [Internet]. 2011;43(4):186–92. http://ovidsp.ovid.com/ovidweb.cgi?T=JS&NEWS=n&CSC=Y&PAGE=toc&D=yrovft&AN=01376517-000000000-00000, https://doi.org/10.1097/jnn.0b013e3182212a52.

    Article  Google Scholar 

  173. Veenhuizen RB, Kootstra B, Vink W, Posthumus J, van Bekkum P, Zijlstra M, et al. Coordinated multidisciplinary care for ambulatory Huntington’s disease patients. Evaluation of 18 months of implementation. Orphanet J Rare Dis [Internet]. 2011;6:77. http://www.ncbi.nlm.nih.gov/pmc/journals/401/, https://doi.org/10.1186/1750-1172-6-77.

    Article  PubMed  PubMed Central  Google Scholar 

  174. Bonelli RM, Wenning GK. Pharmacological management of Huntington’s disease: an evidence-based review. Curr Pharm Des. 2006;12(21):2701–20.

    Article  CAS  PubMed  Google Scholar 

  175. Mestre T, Ferreira J, Coelho MM, Rosa M, Sampaio C. Therapeutic interventions for symptomatic treatment in Huntington’s disease. Cochrane Database Syst Rev [Internet]. 2009;(3):CD006456. http://www.thecochranelibrary.com/view/0/index.html, https://doi.org/10.1002/14651858.cd006456.pub2.

  176. Scheifer J, Werner CJ, Reetz K. Clinical diagnosis and management in early Huntington’s disease: a review. Degener Neurol Neuromuscul Dis. 2015;5: 37–50.

    Google Scholar 

  177. Cuturic M, Abramson RK, Moran RR, Hardin JW, Frank EM, Sellers AA. Serum carnitine levels and levocarnitine supplementation in institutionalized Huntington’s disease patients. Neurol Sci. 2013;34(1):93–8.

    Article  PubMed  Google Scholar 

  178. Nance M, Paulsen J, Rosenblatt A, Wheelock V. A physician’s guide to the management of Huntington’s disease. New York: Huntigton’s Disease Society of America; 2012. p. 64–58.

    Google Scholar 

  179. Squitieri F, Cannella M, Porcellini A, Brusa L, Simonelli M, Ruggieri S. Short-term effects of olanzapine in Huntington disease. Neuropsychiatry Neuropsychol Behav Neurol. 2001;14(1):69–72.

    CAS  PubMed  Google Scholar 

  180. Duff K, Beglinger LJ, O’Rourke ME, Nopoulos P, Paulson HL, Paulsen JS. Risperidone and the treatment of psychiatric, motor, and cognitive symptoms in Huntington’s disease. Ann Clin Psychiatry [Internet]. 2008;20(1):1–3. http://portico.org/stable?cs=ISSN_10401237, https://doi.org/10.1080/10401230701844802.

    Article  PubMed  PubMed Central  Google Scholar 

  181. Huntington Study Group. Tetrabenazine as antichorea therapy in Huntington disease: a randomized controlled trial. Neurology. 2006;66(3):366–72.

    Article  CAS  Google Scholar 

  182. Huntington Study Group, Frank S, Testa CM, Stamler D, Kayson E, Davis C, et al. Effect of deutetrabenazine on chorea among patients with Huntington disease: a randomized clinical trial. JAMA. 2016;316(1):40–50. http://www.ncbi.nlm.nih.gov/pmc/journals/48/, https://doi.org/10.1001/jama.2016.8655.

  183. Claassen DO, Carroll B, De Boer LM, Wu E, Ayyagari R, Gandhi S, et al. Indirect tolerability comparison of Deutetrabenazine and Tetrabenazine for Huntington disease. J Clin Mov Disord [Inernet]. 2017;4:3. http://www.clinicalmovementdisorders.com/, https://doi.org/10.1186/s40734-017-0051-5.

  184. Nance M, Paulsen J, Rosenblatt A, Wheelock V. A physician’s guide to the management of Huntington’s disease. New York: Huntigton’s Disease Society of America; 2012. p. 42–4.

    Google Scholar 

  185. Travessa AM, Rodrigues FB, Mestre TA, Ferreira JJ. Fifteen years of clinical trials in Huntington’s disease: a very low clinical drug development success rate. J Huntingtons Dis [Internet]. 2017;6(2):157–63. http://content.iospress.com/journals/journal-of-huntingtons-disease, https://doi.org/10.3233/jhd-170245.

    Article  CAS  PubMed  Google Scholar 

  186. Paulsen JS, Long JD, Johnson HJ, Aylward EH, Ross CA, Williams JK, et al. Clinical and biomarker changes in premanifest Huntington disease show trial feasibility: a decade of the PREDICT-HD Study. Front Aging Neurosci [Internet]. 2014;6:78. http://www.ncbi.nlm.nih.gov/pmc/journals/1239/, https://doi.org/10.3389/fnagi.2014.00078.

  187. Byrne LM, Rodrigues FB, Blennow K, Durr A, Leavitt BR, Roos RAC, et al. Neurofilament light protein in blood as a potential biomarker of neurodegeneration in Huntington’s disease: a retrospective cohort analysis. Lancet Neurol [Internet]. 2017;16(8):601–9. http://www.sciencedirect.com/science/journal/14744422, https://doi.org/10.1016/s1474-4422(17)30124-2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  188. Rodrigues FB, Byrne L, McColgan P, Robertson N, Tabrizi SJ, Leavitt BR, et al. Cerebrospinal fluid total tau concentration predicts clinical phenotype in Huntington’s disease. J Neurochem [Internet]. 2016;139(1):22–5. http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1471-4159, https://doi.org/10.1111/jnc.13719.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  189. Wild EJ, Boggio R, Langbehn D, Robertson N, Haider S, Miller JR, et al. Quantification of mutant huntingtin protein in cerebrospinal fluid from Huntington’s disease patients. J Clin Invest [Internet]. 2015;125(5):1979–86. http://www.ncbi.nlm.nih.gov/pmc/journals/120/, https://doi.org/10.1172/jci80743.

    Article  PubMed  PubMed Central  Google Scholar 

  190. Holmans P, Stone T. Using genomic data to find disease-modifying loci in Huntington’s disease (HD). Methods Mol Biol [Internet]. 2018;1780:443–61. https://link.springer.com/bookseries/7651, https://doi.org/10.1007/978-1-4939-7825-0_20.

    Google Scholar 

  191. Correia K, Harold D, Kim KH, Holmans P, Jones L, Orth M, et al. The genetic modifiers of motor onset age (GeM MOA) website: genome-wide association analysis for genetic modifiers of Huntington’s disease. J Huntingtons Dis [Internet]. 2015;4(3):279–84. http://content.iospress.com/journals/journal-of-huntingtons-disease, https://doi.org/10.3233/jhd-150169.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  192. Keiser MS, Kordasiewicz HB, McBride JL. Gene suppression strategies for dominantly inherited neurodegenerative diseases: lessons from Huntington’s disease and spinocerebellar ataxia. Hum Mol Genet [Internet]. 2016 Apr 15;25(R1):R53–64. https://academic.oup.com/hmg, https://doi.org/10.1093/hmg/ddv442. Epub 2015 Oct 26.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  193. Tabrizi SJ, Leavitt BR, Landwehrmeyer GB, Wild EJ, Saft C, Barker RA, Blair NF et al. Targeting Huntington expression in patients with Huntington’s disease. N Engl J Med [Internet]. 2019;380(24):2307–16. http://www.nejm.org/, https://doi.org/10.1056/nejmoa1900907. Epub 2019 May 6.

    Article  CAS  PubMed  Google Scholar 

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  1. Department of Neurology, University of South Carolina School of Medicine, 8 Medical Park, Suite 420, Columbia, SC, 29203, USA

    Miroslav Cuturic

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  1. Miroslav Cuturic
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  1. International Institute for Brain Health, Zagreb, Croatia

    Vida Demarin

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Cuturic, M. (2020). Huntington’s Disease. In: Demarin, V. (eds) Mind and Brain. Springer, Cham. https://doi.org/10.1007/978-3-030-38606-1_8

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