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Huntington’s Disease

  • Miroslav CuturicEmail author
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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.

Keywords

Huntington chorea Huntingtin CAG trinucleotide repeat Polyglutamine Gene therapy 

References

  1. 1.
    Huntington G. On chorea. J Neuropsychiatry Clin Neurosci. 2003 Winter;15(1):109–12.PubMedCrossRefGoogle Scholar
  2. 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. 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.CrossRefGoogle Scholar
  4. 4.
    Conneally PM. Huntington disease: genetics and epidemiology. Am J Hum Genet. 1984;36(3):506–26.PubMedPubMedCentralGoogle Scholar
  5. 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.PubMedCrossRefGoogle Scholar
  6. 6.
    Harper PS. The epidemiology of Huntington’s disease. Hum Genet. 1992;89(4):365–76.Google Scholar
  7. 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.CrossRefGoogle Scholar
  8. 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.CrossRefGoogle Scholar
  9. 9.
    Tanner CM, Goldman SM. Epidemiology of movement disorders. Curr Opin Neurol. 1994;7(4):340–5.PubMedCrossRefGoogle Scholar
  10. 10.
    Adams P, Falek A, Arnold J. Huntington disease in Georgia: age at onset. Am J Hum Genet. 1988;43(5):695–704.PubMedPubMedCentralGoogle Scholar
  11. 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. 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. 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.PubMedCrossRefGoogle Scholar
  14. 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.PubMedCrossRefGoogle Scholar
  15. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  16. 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. 17.
    Moskowitz CB, Marder K. Palliative care for people with late-stage Huntington’s disease. Neurol Clin. 2001;19(4):849–65.PubMedCrossRefGoogle Scholar
  18. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  19. 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.PubMedGoogle Scholar
  20. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  21. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  22. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  23. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  24. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  25. 25.
    Craufurd D, Dodge A. Mutation size and age at onset in Huntington’s disease. J Med Genet. 1993;30(12):1008–11.PubMedPubMedCentralCrossRefGoogle Scholar
  26. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  27. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  28. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  29. 29.
    Carter CJ. Reduced GABA transaminase activity in the Huntington’s disease putamen. Neurosci Lett. 1984;48(3):339–42.PubMedCrossRefPubMedCentralGoogle Scholar
  30. 30.
    Reynolds GP, Pearson SJ. Decreased glutamic acid and increased 5-hydroxytryptamine in Huntington’s disease brain. Neurosci Lett. 1987;78(2):233–8.PubMedCrossRefPubMedCentralGoogle Scholar
  31. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  32. 32.
    Storey E, Beal MF. Neurochemical substrates of rigidity and chorea in Huntington’s disease. Brain. 1993;116(5):1201–22.PubMedCrossRefPubMedCentralGoogle Scholar
  33. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  34. 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. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  36. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  37. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  38. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  39. 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.PubMedCrossRefGoogle Scholar
  40. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  41. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  42. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  43. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  44. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  45. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  46. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  47. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  48. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  49. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  50. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  51. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  52. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  53. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  54. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  55. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  56. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  57. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  58. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  59. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  60. 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. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  62. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  63. 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. 64.
    Li SH, Gutekunst CA, Hersch SM, Li XJ. Interaction of huntingtin-associated protein with dynactin P150Glued. J Neurosci. 1998;18(4):1261–9.PubMedPubMedCentralCrossRefGoogle Scholar
  65. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  66. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  67. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  68. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  69. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  70. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  71. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  72. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  73. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  74. 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.CrossRefGoogle Scholar
  75. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  76. 76.
    Gladding CM. Raymond LA Mechanisms underlying NMDA receptor synaptic/extrasynaptic distribution and function. Mol Cell Neurosci. 2011;48(4):308–20.PubMedCrossRefPubMedCentralGoogle Scholar
  77. 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/.PubMedPubMedCentralCrossRefGoogle Scholar
  78. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  79. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  80. 80.
    Crotti A, Glass CK. The choreography of neuroinflammation in Huntington’s disease. Trends Immunol. 2015;36(6):364–73.PubMedPubMedCentralCrossRefGoogle Scholar
  81. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  82. 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.CrossRefGoogle Scholar
  83. 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.PubMedCrossRefGoogle Scholar
  84. 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.PubMedCrossRefGoogle Scholar
  85. 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.PubMedCrossRefGoogle Scholar
  86. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  87. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  88. 88.
    Nopoulos PC. Huntington disease: a single-gene degenerative disorder of the striatum. Dialogues Clin Neurosci. 2016;18(1):91–8.PubMedPubMedCentralGoogle Scholar
  89. 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.PubMedCrossRefGoogle Scholar
  90. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  91. 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.CrossRefGoogle Scholar
  92. 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. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  94. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  95. 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. 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.PubMedCrossRefGoogle Scholar
  97. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  98. 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.PubMedCrossRefGoogle Scholar
  99. 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.PubMedCrossRefGoogle Scholar
  100. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  101. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  102. 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. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  104. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  105. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  106. 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. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  108. 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.CrossRefGoogle Scholar
  109. 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. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  111. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  112. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  113. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  114. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  115. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  116. 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. 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.CrossRefGoogle Scholar
  118. 118.
    Shiwach R. Psychopathology in Huntington’s disease patients. Acta Psychiatr Scand. 1994;90(4):241–6.PubMedCrossRefPubMedCentralGoogle Scholar
  119. 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.CrossRefGoogle Scholar
  120. 120.
    Ghosh R, Tabrizi SJ. Clinical aspects of Huntington’s disease. Curr Top Behav Neurosci. 2015;22:3–31.PubMedCrossRefGoogle Scholar
  121. 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.PubMedPubMedCentralGoogle Scholar
  122. 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.PubMedCrossRefGoogle Scholar
  123. 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.PubMedCrossRefGoogle Scholar
  124. 124.
    Mendez MF. Huntington’s disease: update and review of neuropsychiatric aspects. Int J Psychiatry Med. 1994;24(3):189–208.PubMedCrossRefGoogle Scholar
  125. 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.PubMedCrossRefGoogle Scholar
  126. 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.PubMedCrossRefGoogle Scholar
  127. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  128. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  129. 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.PubMedCrossRefGoogle Scholar
  130. 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.PubMedCrossRefGoogle Scholar
  131. 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. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  133. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  134. 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.CrossRefGoogle Scholar
  135. 135.
    Cummings JL, Cunningham K. Obsessive-compulsive disorder in Huntington’s disease. Biol Psychiatry. 1992;31(3):263–70.PubMedCrossRefPubMedCentralGoogle Scholar
  136. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  137. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  138. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  139. 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.PubMedPubMedCentralGoogle Scholar
  140. 140.
    Cardoso F, Seppi K, Mair KJ, Wenning GK, Poewe W. Seminar on choreas. Lancet Neurol. 2006;5(7):589–602.PubMedCrossRefPubMedCentralGoogle Scholar
  141. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  142. 142.
    Walker RH, Jung HH, Danek A. Neuroacanthocytosis. Handb Clin Neurol. 2011;100:141–51.PubMedCrossRefPubMedCentralGoogle Scholar
  143. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  144. 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.CrossRefGoogle Scholar
  145. 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. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  147. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  148. 148.
    Margolis RL, Rudnicki DD, Holmes SE. Huntington’s disease like-2: review and update. Acta Neurol Taiwan. 2005;14:1–8.PubMedPubMedCentralGoogle Scholar
  149. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  150. 150.
    Terrenoire G. Huntington’s disease and the ethics of genetic prediction. J Med Ethics. 1992;18(2):79–85.PubMedPubMedCentralCrossRefGoogle Scholar
  151. 151.
    Hayden MR, Bloch M, Wiggins S. Psychological effects of predictive testing for Huntington’s disease. Adv Neurol. 1995;65:201–10.PubMedPubMedCentralGoogle Scholar
  152. 152.
    Harper PS. Clinical consequences of isolating the gene for Huntington’s disease. BMJ. 1993;307(6901):397–8.PubMedPubMedCentralCrossRefGoogle Scholar
  153. 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. 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. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  156. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  157. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  158. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  159. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  160. 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.PubMedCrossRefGoogle Scholar
  161. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  162. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  163. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  164. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  165. 165.
    Marosz A, Chlubek D. The risk of abuse of vitamin supplements. Ann Acad Med Stetin. 2014;60(1):60–4.Google Scholar
  166. 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.PubMedPubMedCentralGoogle Scholar
  167. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  168. 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. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  170. 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.CrossRefGoogle Scholar
  171. 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.CrossRefGoogle Scholar
  172. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  173. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  174. 174.
    Bonelli RM, Wenning GK. Pharmacological management of Huntington’s disease: an evidence-based review. Curr Pharm Des. 2006;12(21):2701–20.PubMedCrossRefPubMedCentralGoogle Scholar
  175. 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. 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. 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.PubMedCrossRefGoogle Scholar
  178. 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. 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.PubMedGoogle Scholar
  180. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  181. 181.
    Huntington Study Group. Tetrabenazine as antichorea therapy in Huntington disease: a randomized controlled trial. Neurology. 2006;66(3):366–72.CrossRefGoogle Scholar
  182. 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. 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. 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. 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.PubMedCrossRefGoogle Scholar
  186. 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. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  188. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  189. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  190. 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. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  192. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  193. 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.PubMedCrossRefPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Department of NeurologyUniversity of South Carolina School of MedicineColumbiaUSA

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