Clinical Features of Machado-Joseph Disease

  • Nuno Mendonça
  • Marcondes C. FrançaJr.
  • António Freire Gonçalves
  • Cristina Januário
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1049)

Abstract

Machado-Joseph disease (MJD) also known as Spinocerebellar ataxia type 3, is a hereditary neurodegenerative disease associated with severe clinical manifestations and premature death. Although rare, it is the most common autosomal dominant spinocerebellar ataxia worldwide and has a distinct geographic distribution, reaching peak prevalence in certain regions of Brazil, Portugal and China. Due to its clinical heterogeneity, it was initially described as several different entities and as had many designations over the last decades. An accurate diagnosis become possible in 1994, after the identification of the MJD1 gene. Among its wide clinical spectrum, progressive cerebellar ataxia is normally present. Other symptoms include pyramidal syndrome, peripheral neuropathy, oculomotor abnormalities, extrapyramidal signs and sleep disorders. On the basis of the presence/absence of important extra-pyramidal signs, and the presence/absence of peripheral signs, five clinical types have been defined. Neuroimaging studies like MRI, DTI and MRS, can be useful as they can characterize structural and functional differences in specific subgroups of patients with MJD. There is no effective treatment for MJD. Symptomatic therapies are used to relieve some of the clinical symptoms and physiotherapy is also helpful in improving quality of live. Several clinical trials have been carried out using different molecules like sulfamethoxazole-trimethoprim, varenicline and lithium carbonate, but the results of these trials were negative or showed little benefit. Future studies sufficiently powered and adequately designed are warranted.

Keywords

Machado-Joseph disease Spinocerebellar ataxia type 3 Polyglutamine diseases Natural history Pharmacological treatment 

Notes

Conflict of Interest:

Nuno Mendonça is a full time AbbVie Deutschland GmbH & Co. KG employee and may hold AbbVie stock and/or stock options.

The content of this work is not associated with the author responsibilities as an AbbVie employee.

References

  1. 1.
    Romanul FC et al (1977) Azorean disease of the nervous system. N Engl J Med 296(26):1505–1508Google Scholar
  2. 2.
    Schols L et al (2004) Autosomal dominant cerebellar ataxias: clinical features, genetics, and pathogenesis. Lancet Neurol 3(5):291–304Google Scholar
  3. 3.
    Jardim LB et al (2001) A survey of spinocerebellar ataxia in South Brazil—66 new cases with Machado-Joseph disease, SCA7, SCA8, or unidentified disease-causing mutations. J Neurol 248:870–876Google Scholar
  4. 4.
    Silveira I et al (1998) Analysis of SCA1, DRPLA, MJD, SCA2, and SCA6 CAG repeats in 48 Portuguese ataxia families. Am J Med Genet 81:134–138Google Scholar
  5. 5.
    Vale J et al (2010) Autosomal dominant cerebellar ataxia: frequency analysis and clinical characterization of 45 families from Portugal. Eur J Neurol 17(1):124–128Google Scholar
  6. 6.
    Zhao Y et al (2002) Prevalence and ethnic differences of autosomal-dominant cerebellar ataxia in Singapore. Clin Genet 62:478–481Google Scholar
  7. 7.
    Tang B et al (2000) Frequence of SCA1, SCA2, SCA3/MJD, SCA6, SCA7, and DRPLA CAG trinucleotide repeat expansion in patients with hereditary spinocerebellar ataxia from Chinese kindreds. Arch Neurol 57:540–544Google Scholar
  8. 8.
    van de Warrenburg BP et al (2002) Spinocerebellar ataxias in the Netherlands: prevalence and age at onset variance analysis. Neurology 58:702–708Google Scholar
  9. 9.
    Schols L et al (1997) Autosomal dominant cerebellar ataxia: phenotypic differences in genetically defined subtypes? Ann Neurol 42:924–932Google Scholar
  10. 10.
    Maruyama H et al (2002) Difference in disease-free survival curve and regional distribution according to subtype of spinocerebellar ataxia: a study of 1,286 Japanese patients. Am J Med Genet 114:578–583Google Scholar
  11. 11.
    Shibata-Hamaguchi A et al (2009) Prevalence of spinocerebellar degenerations in the Hokuriku district in Japan. Neuroepidemiology 32:176–183Google Scholar
  12. 12.
    Kraft S et al (2005) Adult onset spinocerebellar ataxia in a Canadian movement disorders clinic. Can J Neurol Sci 32:450–458Google Scholar
  13. 13.
    Moseley ML et al (1998) Incidence of dominant spinocerebellar and Friedreich triplet repeats among 361 ataxia families. Neurology 51:1666–1671Google Scholar
  14. 14.
    Alonso E et al (2007) Distinct distribution of autosomal dominant spinocerebellar ataxia in the Mexican population. Mov Disord 22:1050–1053Google Scholar
  15. 15.
    Storey E et al (2000) Frequency of spinocerebellar ataxia types 1, 2, 3, 6, and 7 in Australian patients with spinocerebellar ataxia. Am J Med Genet 95:351–357Google Scholar
  16. 16.
    Saleem Q et al (2000) Molecular analysis of autosomal dominant hereditary ataxias in the Indian population: high frequency of SCA2 and evidence for a common founder mutation. Hum Genet 106:179–187Google Scholar
  17. 17.
    Bryer A et al (2003) The hereditary adult-onset ataxias in South adult-onset ataxias in South Africa. J Neurol Sci 216:47–54Google Scholar
  18. 18.
    Brusco A et al (2004) Molecular genetics of hereditary spinocerebellar ataxia: mutation analysis of spinocerebellar ataxia genes and CAG/CTG repeat expansion detection in 225 Italian families. Arch Neurol 61:727–733Google Scholar
  19. 19.
    Coutinho P (1992) Doença de Machado-Joseph: Tentativa de definição. Ph.D. Dissertation, Instituto de Ciências Biomédicas Abel Salazar, PortoGoogle Scholar
  20. 20.
    Maciel P et al (2001) Improvement in the molecular diagnosis of Machado-Joseph disease. Arch Neurol 58:1821–1827Google Scholar
  21. 21.
    Bettencourt C et al (2008) Analysis of segregation patterns in Machado-Joseph disease pedigrees. J Hum Genet 53:920–923Google Scholar
  22. 22.
    Nakano KK et al (1972) Machado disease. A hereditary ataxia in Portuguese emigrants to Massachusetts. Neurology 22:49–55Google Scholar
  23. 23.
    Rosenberg R, Nyhan W, Bay C, Shore P (1976) Autosomal dominant striatonigral degeneration. A clinical, pathologic, and biochemical study of a new genetic disorder. Neurology 26:14–703CrossRefGoogle Scholar
  24. 24.
    Woods BT et al (1972) Nigro-spino-dentatal degeneration with nuclearophthalmoplegia. A unique and partially treatable clinico-pathological entity. J Neurol Sci 17:149–166Google Scholar
  25. 25.
    Coutinho P et al (1978) Autosomal dominant system degeneration in Portuguese families of the Azores Islands. A new genetic disorder involving cerebellar, pyramidal, extrapyramidal and spinal cord motor functions. Neurology 28:703–709Google Scholar
  26. 26.
    Kawaguchi Y et al (1994) CAG expansions in a novel gene for Machado-Joseph disease at chromosome 14q32.1. Nat Genet 8:221–228Google Scholar
  27. 27.
    Cancel G et al (1995) Marked phenotypic heterogeneity associated with expansion of a CAG repeat sequence at the spinocerebellar ataxia 3/Machado-Joseph disease locus. Am J Hum Genet 57:809–816Google Scholar
  28. 28.
    Gaspar C et al (1996) Linkage disequilibrium analysis in Machado-Joseph disease patients of different ethnic origins. Hum Genet 98:620–624Google Scholar
  29. 29.
    Sequeiros J et al (1993) Epidemiology and clinical aspects of Machado-Joseph disease. Adv Neurol 61:139–153Google Scholar
  30. 30.
    Stevanin G et al (1995) Linkage disequilibrium at the Machado-Joseph disease/spinal cerebellar ataxia 3 locus: evidence for a common founder effect in French and Portuguese-Brazilian families as well as a second ancestral Portuguese-Azorean mutation. Am J Hum Genet 57:1247–1250Google Scholar
  31. 31.
    Takiyama Y et al (1995) Evidence for inter-generational instability in the CAG repeat in the MJD1 gene and for conserved haplotypes at flanking markers amongst Japanese and Caucasian subjects with Machado-Joseph disease. Hum Mol Genet 4:1137–1146Google Scholar
  32. 32.
    Gaspar C et al (2001) Ancestral origins of the Machado-Joseph disease mutation: a worldwide haplotype study. Am J Hum Genet 68:523–528Google Scholar
  33. 33.
    Lima M et al (1998) Origins of a mutation: population genetics of Machado-Joseph disease in the Azores (Portugal). Hum Biol 70:1011–1023Google Scholar
  34. 34.
    Rosenberg R (1995) Autosomal dominant cerebellar phenotypes: the genotype has settled issue. Neurology 45:1–5CrossRefPubMedGoogle Scholar
  35. 35.
    Mittal U et al (2005) Founder haplotype for Machado-Joseph disease in the Indian population: novel insights from history and polymorphism studies. Arch Neurol 62:637–640Google Scholar
  36. 36.
    Martins S et al (2007) Asian origin for the worldwide-spread mutational event in Machado–Joseph disease. Arch Neurol 64:1502–1508Google Scholar
  37. 37.
    Martins S et al (2012) Mutational origin of Machado–Joseph disease in the Australian Aboriginal communities of Groote Eylandt and Yirrkala. Arch Neurol 69:746–751Google Scholar
  38. 38.
    Rosenberg R (1992) Machado-Joseph disease: an autosomal dominant motor system degeneration. Mov Disord 7:193–203CrossRefPubMedGoogle Scholar
  39. 39.
    Sudarsky LCP (1995) Machado-Joseph disease. Clin Neuro sci 3:17–22Google Scholar
  40. 40.
    Lima L et al (1980) Clinical criteria for diagnosis of Machado-Joseph disease: report of a non-Azorena Portuguese family. Neurology 30:319–322Google Scholar
  41. 41.
    Carvalho DR et al (2008) Homozygosity enhances severity in spinocerebellar ataxia type 3. Pedriatr Neurol 38(4):296–299Google Scholar
  42. 42.
    Kieling C et al (2007) Survival estimates for patients with Machado-Joseph disease (SCA3). Clin Genet 72(6):543–545Google Scholar
  43. 43.
    Suite ND et al (1986) Machado-Joseph disease in a Sicilian-American family. J Neurogenet 2(2):177–182Google Scholar
  44. 44.
    Sakai T et al (1996) Machado-Joseph disease: A proposal of spastic paraplegic subtype. Neurology 46(3):846–847Google Scholar
  45. 45.
    Pedroso JL et al (2013) Nonmotor and extracerebellar features in Machado-Joseph disease: a review. Mov Disord 28:1200–1208Google Scholar
  46. 46.
    Raggi A et al (2010) Sleep disorders in neurodegenerative diseases. Eur J Neurol 17:1326–1338Google Scholar
  47. 47.
    D’Abreu A et al (2009) Sleep symptoms and their clinical correlates in Machado-Joseph disease. Acta Neurol Scand 119:277–280Google Scholar
  48. 48.
    Pedroso JL et al (2011) Sleep disorders in cerebellar ataxias. Arq Neuropsiquiatr 69:253–257Google Scholar
  49. 49.
    Pedroso JL et al (2011) Sleep disorders in Machado-Joseph disease: frequency, discriminative thresholds, predictive values, and correlation with ataxia-related motor and non-motor features. Cerebellum 10:291–295Google Scholar
  50. 50.
    Rub U et al (2008) New insights into the pathoanatomy of spinocerebellar ataxia type 3 (Machado-Joseph disease). Curr Opin Neurol 21:111–116Google Scholar
  51. 51.
    Schmahmann JD et al (2006) Cognition, emotion and the cerebellum. Brain 129:288–292Google Scholar
  52. 52.
    Stoodley CJ et al (2010) Evidence for topographic organization in the cerebellum of motor control versus cognitive and affective processing. Cortex 46:831–844Google Scholar
  53. 53.
    Radvany J et al (1999) Machado Joseph disease of Azorean ancestry in Brazil: the Catarina kindred. Neurological, neuroimaging, psychiatric and neuropsychological findings in the largest known family, the Catarina kindred. Arq Neuropsiquiatr 51:21–30Google Scholar
  54. 54.
    Zawacki TM et al (2002) Executive and emotional dysfunction in Machado-Joseph disease. Mov Disord 17:1004–1010Google Scholar
  55. 55.
    Maruff P et al (1996) Cognitive deficits in Machado-Joseph disease. Ann Neurol 40:421–427Google Scholar
  56. 56.
    Kawai Y et al (2004) Cognitive impairments in Machado-Joseph disease. Arch Neurol 61:1757–1760Google Scholar
  57. 57.
    Braga-Neto P et al (2011) Cerebellar cognitive affective syndrome in Machado Joseph disease: core clinical features. Cerebellum 11:549–556Google Scholar
  58. 58.
    Schmitz-Hubsch T et al (2010) Self-rated health status in spinocerebellar ataxia—results from a European multicenter study. Mov Disord 25:587–595Google Scholar
  59. 59.
    Schmitz-Hubsch T et al (2011) Depression comorbidity in spinocerebellar ataxia. Mov Disord 26:870–876Google Scholar
  60. 60.
    Braga-Neto P et al (2012) Cognitive deficits in Machado-Joseph disease correlate with hypoperfusion of visual system areas. Cerebellum 11:1037–1044Google Scholar
  61. 61.
    Braga-Neto P et al (2012) Cognitive and olfactory deficits in Machado-Joseph disease: a dopamine transporter study. Parkinsonism Relat Disord 18:854–858Google Scholar
  62. 62.
    Cecchin CR et al (2007) Depressive symptoms in Machado-Joseph disease (SCA3) patients and their relatives. Commun Genet 10:19–26Google Scholar
  63. 63.
    Rodrigues CS et al (2002) Presymptomatic testing for neurogenetic diseases in Brazil: assessing who seeks and who follows through with testing. J Genet Couns 21:101–112Google Scholar
  64. 64.
    Saute JA et al (2010) Depressive mood is associated with ataxic and non-ataxic neurological dysfunction in SCA3 patients. Cerebellum 9:603–605Google Scholar
  65. 65.
    Fernandez-Ruiz J et al (2003) Olfactory dysfunction in hereditary ataxia and basal ganglia disorders. Neuroreport 14:1339–1341Google Scholar
  66. 66.
    Connelly T et al (2003) Olfactory dysfunction in degenerative ataxias. J Neurol Neurosurg Psychiatr 74:1435–1437Google Scholar
  67. 67.
    Abele M et al (2003). Olfactory dysfunction in cerebellar ataxia and multiple system atrophy. J Neurol 250:1453–1455Google Scholar
  68. 68.
    Velazquez-Perez L et al (2006) Spinocerebellar ataxia type 2 olfactory impairment shows a pattern similar to other major neurodegenerative diseases. J Neurol 253:1165–1169Google Scholar
  69. 69.
    Moscovich M et al (2012) Olfactory impairment in familial ataxias. J Neurol Neurosurg Psychiatry 83:970–974Google Scholar
  70. 70.
    Braga-Neto P et al (2011) Clinical correlates of olfactory dysfunction in spinocerebellar ataxia type 3. Parkinsonism Relat Disord 17:353–356Google Scholar
  71. 71.
    Coutinho P et al (1986) The peripheral neuropathy in Machado-Joseph disease. Acta Neuropathol (Berl) 71:119–124Google Scholar
  72. 72.
    Kinoshita A et al (1995) Clinicopathological study of the peripheral nervous system in Machado-Joseph disease. J Neurol Sci 130:48–58Google Scholar
  73. 73.
    Pedroso JL et al (2011) Is neuropathy involved with restless legs syndrome in Machado-Joseph disease? Eur Neurol 66:200–203Google Scholar
  74. 74.
    van de Warrenburg BPC et al (2004) Peripheral nerve involvement in spinocerebellar ataxias. Arch Neurol 61:257–261Google Scholar
  75. 75.
    Franca MC Jr et al (2009) Prospective study of peripheral neuropathy in Machado-Joseph disease. Muscle Nerve 40:1012–1018Google Scholar
  76. 76.
    Klockgether T et al (1999) Age related axonal neuropathy in spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD). J Neurol Neurosurg Psychiatry 66:222–224Google Scholar
  77. 77.
    Friedman JH et al (2008) Fatigue and daytime somnolence in Machado-Joseph disease (spinocerebellar ataxia type 3). Mov Disord 23:1323–1324Google Scholar
  78. 78.
    Franca MC Jr et al (2008) Muscle excitability abnormalities in Machado-Joseph disease. Arch Neurol 65:525–529Google Scholar
  79. 79.
    Kanai K et al (2003) Muscle cramp in Machado-Joseph disease: altered motor axonal excitability properties and mexiletine treatment. Brain 126:965–973Google Scholar
  80. 80.
    Franca MC Jr et al (2007) Chronic pain in Machado-Joseph disease: a frequent and disabling symptom. Arch Neurol 64:1767–1770Google Scholar
  81. 81.
    Yeh TH et al (2005) Autonomic dysfunction in Machado-Joseph disease. Arch Neurol 62:630–636Google Scholar
  82. 82.
    Franca MC Jr et al (2010) Clinical correlates of autonomic dysfunction in patients with Machado-Joseph disease. . Acta Neurol Scand 121:422–425Google Scholar
  83. 83.
    Pradhan C et al (2008) Spinocerebellar ataxias type 1, 2 and 3: a study of heart rate variability. Acta Neurol Scand 117:337–342Google Scholar
  84. 84.
    Yamanaka Y et al (2012) Cutaneous sympathetic dysfunction in patients with Machado-Joseph disease. Cerebellum 11:1057–1060Google Scholar
  85. 85.
    van Gaalen J et al (2011) Movement disorders in spinocerebellar ataxias. Mov Disord 26:792–800Google Scholar
  86. 86.
    Schols L et al (2000) Extrapyramidal motor signs in degenerative ataxias. Arch Neurol 57:1495–1500Google Scholar
  87. 87.
    Schmitz-Hubsch T et al (2008) Spinocerebellar ataxia types 1, 2, and 6. Disease severity and nonataxia symptoms. Neurology 71:982–989Google Scholar
  88. 88.
    Tuite PJ et al (1995) Dopa- responsive parkinsonism phenotype of Machado-Joseph disease: confirmation of 14q CAG expansion. Ann Neurol 38:684–687Google Scholar
  89. 89.
    Bettencourt C et al (2011) Parkinsonism pheno- type in Machado-Joseph disease (MJD/SCA3): a two-case report [serial online]. BMC Neurol 11:131Google Scholar
  90. 90.
    Socal MP et al (2009) Intrafamilial variability of Parkinson phenotype in SCAs: novel cases due to SCA2 and SCA3 expansions. Parkinsonism Relat Disord 15:374–378Google Scholar
  91. 91.
    Gwinn-Hardy K et al (2001) Spinocerebellar ataxia type 3 phenotypically resembling Parkinson disease in a black family. Arch Neurol 58:296–299Google Scholar
  92. 92.
    Subramony SH et al (2002) Ethnic differences in the expression of neurodegenerative disease: Machado–Joseph disease in Africans and Caucasians. Mov Disord 17:1068–1071Google Scholar
  93. 93.
    Lu CS et al (2004) The parkinsonian phenotype of spinocerebellar ataxia type 3 in a Taiwanese family. Parkinsonism Relat Disord 10:369–373Google Scholar
  94. 94.
    Pedroso JL et al (2012) Transcranial sonography: Brazilian experience. Arq Neuropsiquiatr 70:313–314Google Scholar
  95. 95.
    Teive HAG et al (2012) Spinocerebellar ataxias—Genotype-phenotype correlation in 104 Brazilian families. Clinics (Sao Paulo) 67:443–449Google Scholar
  96. 96.
    Siebert M et al (2012) Glucocerebrosidase gene variants in parkinsonism patients with Machado-Joseph/spinocerebellara ataxia 3. Parkinsonism Relat Disord 18:185–190Google Scholar
  97. 97.
    Pedroso JL et al (2011) Akathisia: an unusual movement disorder in Machado-Joseph disease. Parkinsonism Relat Disord 17:12–13Google Scholar
  98. 98.
    Horimoto Y et al (2011) Longitudinal study on MRI intensity changes of Machado-Joseph disease: correlation between MRI findings and neuropathological changes. J Neurol:1657–1664Google Scholar
  99. 99.
    Imon Y et al (1998) A necropsied case of Machado-Joseph disease with a hyperintense signal of transverse pontine fibres on long TR sequences of magnetic resonance images. J Neurol Neurosurg Psychiatry 64:140–141Google Scholar
  100. 100.
    Murata Y et al (1998) Characteristic magnetic resonance imaging findings in Machado-Joseph disease. Arch Neurol 55:33–37Google Scholar
  101. 101.
    Yamada S et al (2005) Linear high intensity area along the medial margin of the internal segment of the globus pallidus in Machado-Joseph disease patients. J Neurol Neurosurg Psychiatry 76:573–575Google Scholar
  102. 102.
    Lee YC et al (2009) The ‘hot cross bun’ sign in the patients with spinocerebellar ataxia. Eur J Neurol 16:513–516Google Scholar
  103. 103.
    De Oliveira MS et al (2010) MRI-texture analysis of corpus callosum, thalamus, putamen, and caudate in Machado-Joseph disease. J Neuroimaging 22:46–52Google Scholar
  104. 104.
    D’Abreu A et al (2012) Neocortical atrophy in Machado-Joseph disease: a longitudinal neuroimaging study. J Neuroimaging 22:285–291Google Scholar
  105. 105.
    de Rezende TJ et al (2015) Cerebral cortex involvement in Machado-Joseph disease. Eur J Neurol 11:277– 83 (e23–24)Google Scholar
  106. 106.
    Schulz JB et al (2010) Visualization, quantification and correlation of brain atrophy with clinical symptoms in spinocerebellar ataxia types 1, 3 and 6. Neuroimage 49:158–68Google Scholar
  107. 107.
    Reetz K et al (2013) Ataxia Study Group Investigators. Genotype-specific patterns of atrophy progression are more sensitive than clinical decline in SCA1, SCA3 and SCA6. Brain 136:905–17Google Scholar
  108. 108.
    Guimarães RP (2013) A multimodal evaluation of microstructural white matter damage in spinocerebellar ataxia type 3. Mov Disord 28:1125–1132Google Scholar
  109. 109.
    D’Abreu A et al (2009) Axonal dysfunction in the deep white matter in Machado-Joseph disease. J Neuroimaging 19:9–12Google Scholar
  110. 110.
    Wang PS et al (2012) Association between proton magnetic resonance spectroscopy measurements and CAG repeat number in patients with spinocerebellar ataxias 2, 3, or 6. PLoS One 7:e47479Google Scholar
  111. 111.
    Lirng JF et al (2012) Differences between spinocerebellar ataxias and multiple system atrophy-cerebellar type on proton magnetic resonance spectroscopy. PLoS One 7:e47925Google Scholar
  112. 112.
    Jacobi H et al (2013) Biological and clinical characteristics of individuals at risk for spinocerebellar ataxia types 1, 2, 3, and 6 in the longitudinal RISCA study: analysis of baseline data. Lancet Neurol 12:630Google Scholar
  113. 113.
    Nunes MB, Martinez AR, Rezende TJ et al (2015) Dystonia in Machado–Joseph disease: Clinical profile, therapy and anatomical basis. Parkinsonism Relat Disord 21:1441–1447Google Scholar
  114. 114.
    Etchebehere EC et al (2001) Brain single- photon emission computed tomography and magnetic resonance imaging in Machado-Joseph disease. Arch Neurol 58:1257–1263Google Scholar
  115. 115.
    Taniwaki T et al (1997) Positron emission tomography (PET) in Machado-Joseph disease. J Neurol Sci 145:63–67Google Scholar
  116. 116.
    Soong BW et al (1998) Positron emission tomography in asymptomatic gene carriers of Machado-Joseph disease. J Neurol Neurosurg Psychiatry 64:499–504Google Scholar
  117. 117.
    Ogawa M (2004) Pharmacological treatments of cerebellar ataxia. Cerebellum 3:107–111CrossRefPubMedGoogle Scholar
  118. 118.
    Correia M et al (1995) Evaluation of the effect of sulphametoxazole and trimethoprim in patients with Machado-Joseph disease. Rev Neurol 23:632–634Google Scholar
  119. 119.
    Buhmann C et al (2003) Dopaminergic response in Parkinsonian phenotype of Machado–Joseph disease. Mov Disord 18:219–221Google Scholar
  120. 120.
    Wilder-Smith E et al (2003) Spinocerebellar ataxia type 3 presenting as an L-DOPA responsive dystonia phenotype in a Chinese family. J Neurol Sci 213:25–28Google Scholar
  121. 121.
    Nandagopal R et al (2004) Dramatic levodopa responsiveness of dystonia in a sporadic case of spinocerebellar ataxia type 3. Postgrad Med J 80:363–365Google Scholar
  122. 122.
    D’Abreu A et al (2010) Caring for Machado- Joseph disease: current understanding and how to help patients. Relat Disord 16:2–7Google Scholar
  123. 123.
    Zesiewicz TA et al (2012) A randomized trial of varenicline (Chantix) for the treatment of spinocerebellarataxia type 3. Neurology 78:545–550Google Scholar
  124. 124.
    Azulay JP et al (1994) Contrast sensitivity improvement with sulfamethoxazole and trimethoprim in a patient with Machado-Joseph disease without spasticity. J Neurol Sci 123:95–99Google Scholar
  125. 125.
    Mello KA et al (1988) Effect of sulfamethoxazole and trimethoprim on neurologic dysfunction in a patient with Joseph’s disease. Arch Neurol 45:210–213Google Scholar
  126. 126.
    Sakai T et al (1995) Sulfamethoxazoletrimethoprim double-blind, placebo-controlled, crossover trial in Machado-Joseph disease: sulfamethoxazole-trimethoprim increases cerebrospinal fluid level of biopterin. J Neural Transm Gen Sect 102:159–172Google Scholar
  127. 127.
    Thorsten Schulte RM (2001) Double-blind crossover trial of trimethoprim-sulfamethoxazole in spinocerebellar ataxia type 3/Machado-Joseph disease. Arch Neurol 58:1451–1457CrossRefGoogle Scholar
  128. 128.
    Saute JA et al (2014) A Randomized, phase 2 clinical trial of lithium carbonate in Machado-Joseph disease. Mov Disord 29:568–573Google Scholar
  129. 129.
    Kieling C et al (2008) A neurological examination score for the assessment of spinocerebellar ataxia 3 (SCA3). Eur J Neurol 15:371–376Google Scholar
  130. 130.
    Schmitz-Hübsch T et al (2006) Scale for the assessment and rating of ataxia. Neurology 66:1717–1720Google Scholar
  131. 131.
    Du Montcel ST et al (2008) Composite cerebellar functional severity score: Validation of a quantitative score of cerebellar impairment. Brain 131:1352–1361Google Scholar
  132. 132.
    Saute JA et al (2015) Planning future clinical trials in Machado Joseph disease: Lessons from a phase 2 trial. J Neurol Sci 358:72–76Google Scholar
  133. 133.
    Monte TL et al (2003) Use of fluoxetine for treatment of Machado-Joseph disease: an open-label study. Acta Neurol Scand 107:207–210Google Scholar
  134. 134.
    Takei A et al (2004) Effects of tandospirone on “5-HT1A receptor-associated symptoms” in patients with Machado-Josephe disease: an open-label study. Clin Neuropharmacol 27:9–13Google Scholar
  135. 135.
    Liu C-S et al (2005) Clinical and molecular events in patients with Machado–Joseph disease underlamotrigine therapy. Acta Neurol Scand 111:385–390Google Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  • Nuno Mendonça
    • 1
    • 2
  • Marcondes C. FrançaJr.
    • 3
  • António Freire Gonçalves
    • 2
    • 4
  • Cristina Januário
    • 2
    • 4
  1. 1.CNC—Center for Neuroscience and Cell BiologyCoimbraPortugal
  2. 2.Faculty of MedicineUniversity of CoimbraCoimbraPortugal
  3. 3.Department of NeurologyUniversity of Campinas (UNICAMP)CampinasBrazil
  4. 4.Neurology DepartmentCoimbra University Hospital CenterCoimbraPortugal

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