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Friedreich’s Ataxia and More: Optical Coherence Tomography Findings in Rare Neurological Syndromes

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OCT in Central Nervous System Diseases

Abstract

Optic nerve and retinal involvement are a frequent finding in many neurodegenerative disorders. Optic atrophy can be severe and diffuse or sectorial and can be associated with visual complaints and reduction of visual acuity.

We here report the main optical coherence tomography (OCT) findings in rare neurological syndromes for which OCT data are available.

In Friedreich’s ataxia, which is an autosomal recessive disease, there is evidence of subclinical optic neuropathy. OCT studies describe a diffuse reduction of the retinal nerve fiber layer (RNFL) thickness without a specific and preferential involvement of the papillo-macular bundle.

Jansky-Bielschowsky disease is a late infantile neuronal ceroid lipofuscinosis characterized by both retinal and optic nerve atrophy. Only one OCT study is available describing retinal abnormalities of various degrees.

DNA (cytosine-5)-methyltransferase 1 (DNMT1) disease is an autosomal dominant multisystem disorder characterized by the association of narcolepsy, deafness, sensory neuropathy and optic atrophy. The only OCT study available from our group describes the presence of subclinical optic atrophy more evident in the temporal quadrant.

Hereditary spastic paraplegia due to SPG7 mutation is an autosomal recessive neurodegenerative disorder characterized by spastic paraparesis. RNFL thinning is a frequent and consistent finding in this disease.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an autosomal dominant disorder in which retinal vascular changes and neurodegeneration of the neuroretina are frequent findings.

Wolfram’s disease is a disorder characterized by the occurrence of diabetes mellitus and optic atrophy. The only two OCT studies available report a diffuse optic atrophy which leads to a severe reduction of visual acuity.

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a hereditary spastic ataxia due to progressive degeneration of the cerebellum and spinal cord, characterized by retinal nerve fiber hypertrophy detected by OCT.

Spinocerebellar ataxias (SCAs) are heterogeneous genetically determined disorders for which OCT studies available show variable findings ranging from isolated thinning of the temporal RNFL to retinal photoreceptor abnormalities.

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References

  1. Collins A. Clinical neurogenetics: friedreich ataxia. Neurol Clin. 2013;31:1095–120.

    Article  PubMed  Google Scholar 

  2. Parkinson MH, Boesch S, Nachbauer W, Mariotti C, Giunti P. Clinical features of Friedreich’s ataxia: classical and atypical phenotypes. J Neurochem. 2013;126 Suppl 1:103–17.

    Article  CAS  PubMed  Google Scholar 

  3. Campuzano V, Montermini L, Moltò MD, Pianese L, Cossée M, Cavalcanti F, et al. Friedreich’s ataxia: autosomal recessive disease caused by an intronic GAA triplet repeat expansion. Science. 1996;271:1423–7.

    Article  CAS  PubMed  Google Scholar 

  4. Tan G, Napoli E, Taroni F, Cortopassi G. Decreased expression of genes involved in sulfur amino acid metabolism in frataxin-deficient cells. Hum Mol Genet. 2003;12:1699–711.

    Article  CAS  PubMed  Google Scholar 

  5. Shan Y, Napoli E, Cortopassi G. Mitochondrial frataxin interacts with ISD11 of the NFS1/ISCU complex and multiple mitochondrial chaperones. Hum Mol Genet. 2007;16:929–41.

    Article  CAS  PubMed  Google Scholar 

  6. Martelli A, Puccio H. Dysregulation of cellular iron metabolism in Friedreich ataxia: from primary iron-sulfur cluster deficit to mitochondrial iron accumulation. Front Pharmacol. 2014;5:130.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  7. Rötig A, de Lonlay P, Chretien D, Foury F, Koenig M, Sidi D, et al. Aconitase and mitochondrial iron-sulphur protein deficiency in Friedreich ataxia. Nat Genet. 1997;17:215–7.

    Article  PubMed  Google Scholar 

  8. Lodi R, Cooper JM, Bradley JL, Manners D, Styles P, Taylor DJ, et al. Deficit of in vivo mitochondrial ATP production in patients with Friedreich ataxia. Proc Natl Acad Sci U S A. 1999;96:11492–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Bolinches-Amorós A, Mollá B, Pla-Martín D, Palau F, González-Cabo P. Mitochondrial dysfunction induced by frataxin deficiency is associated with cellular senescence and abnormal calcium metabolism. Front Cell Neurosci. 2014;8:124.

    PubMed  PubMed Central  Google Scholar 

  10. Babcock M, de Silva D, Oaks R, Davis-Kaplan S, Jiralerspong S, Montermini L, et al. Regulation of mitochondrial iron accumulation by Yfh1p, a putative homolog of frataxin. Science. 1997;276:1709–12.

    Article  CAS  PubMed  Google Scholar 

  11. Wong A, Yang J, Cavadini P, Gellera C, Lonnerdal B, Taroni F, et al. The Friedreich’s ataxia mutation confers cellular sensitivity to oxidant stress which is rescued by chelators of iron and calcium and inhibitors of apoptosis. Hum Mol Genet. 1999;8:425–30.

    Article  CAS  PubMed  Google Scholar 

  12. Gomes CM, Santos R. Neurodegeneration in Friedreich’s ataxia: from defective frataxin to oxidative stress. Oxid Med Cell Longev. 2013;2013:487534.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Kersten HM, Roxburgh RH, Danesh-Meyer HV. Ophthalmic manifestations of inherited neurodegenerative disorders. Nat Rev Neurol. 2014;10:349–62.

    Article  PubMed  Google Scholar 

  14. Andermann E, Remillard GM, Goyer C, Blitzer L, Andermann F, Barbeau A. Genetic and family studies in Friedreich’s ataxia. Can J Neurol Sci. 1976;3:287–301.

    CAS  PubMed  Google Scholar 

  15. Carroll WM, Kriss A, Baraitser M, Barrett G, Halliday AM. The incidence and nature of visual pathway involvement in Friedreich’s ataxia. A clinical and visual evoked potential study of 22 patients. Brain. 1980;103:413–34.

    Article  CAS  PubMed  Google Scholar 

  16. Fortuna F, Barboni P, Liguori R, Valentino ML, Savini G, Gellera C, et al. Visual system involvement in patients with Friedreich’s ataxia. Brain. 2009;132:116–23.

    Article  PubMed  Google Scholar 

  17. Noval S, Contreras I, Sanz-Gallego I, Manrique RK, Arpa J. Ophthalmic features of Friedreich ataxia. Eye (Lond). 2012;26:315–20.

    Article  CAS  Google Scholar 

  18. Seyer LA, Galetta K, Wilson J, Sakai R, Perlman S, Mathews K, et al. Analysis of the visual system in Friedreich ataxia. J Neurol. 2013;260:2362–9.

    Article  PubMed  Google Scholar 

  19. Dağ E, Örnek N, Örnek K, Erbahçeci-Timur IE. Optical coherence tomography and visual field findings in patients with Friedreich ataxia. J Neuroophthalmol. 2014;34:118–21.

    Article  PubMed  Google Scholar 

  20. Barboni P, Carbonelli M, Savini G, Ramos Cdo V, Carta A, Berezovsky A, et al. Natural history of Leber’s hereditary optic neuropathy:longitudinal analysis of the retinal nerve fiber layer by optical coherence tomography. Ophthalmology. 2010;117:623–7.

    Article  PubMed  Google Scholar 

  21. Cotman SL, Karaa A, Staropoli JF, Sims KB. Neuronal ceroid lipofuscinosis: impact of recent genetic advances and expansion of the clinicopathologic spectrum. Curr Neurol Neurosci Rep. 2013;13:366.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Wheeler RB, Schlie M, Kominami E, Gerhard L, Goebel HH. Neuronal ceroid lipofuscinosis: late infantile or Jansky Bielschowsky type–re-revisited. Acta Neuropathol. 2001;102:485–8.

    CAS  PubMed  Google Scholar 

  23. Bennett MJ, Rakheja D. The neuronal ceroid-lipofuscinoses. Dev Disabil Res Rev. 2013;17:254–9.

    Article  PubMed  Google Scholar 

  24. Hainsworth DP, Liu GT, Hamm CW, Katz ML. Funduscopic and angiographic appearance in the neuronal ceroid lipofuscinoses. Retina. 2009;29:657–68.

    Article  PubMed  Google Scholar 

  25. Worgall S, Kekatpure MV, Heier L, Ballon D, Dyke JP, Shungu D, et al. Neurological deterioration in late infantile neuronal ceroid lipofuscinosis. Neurology. 2007;69:521–35.

    Article  CAS  PubMed  Google Scholar 

  26. Goebel HH, Zeman W, Damaske E. An ultrastructural study of the retina in the Jansky-Bielschowsky type of neuronal ceroid-lipofuscinosis. Am J Ophthalmol. 1977;83:70–9.

    Article  CAS  PubMed  Google Scholar 

  27. Weleber RG. The dystrophic retina in multisystem disorders: the electroretinogram in neuronal ceroid lipofuscinoses. Eye (Lond). 1998;12:580–90.

    Article  Google Scholar 

  28. Sappington RM, Pearce DA, Calkins DJ. Optic nerve degeneration in a murine model of juvenile ceroid lipofuscinosis. Invest Ophthalmol Vis Sci. 2003;44:3725–31.

    Article  PubMed  Google Scholar 

  29. Weimer JM, Custer AW, Benedict JW, Alexander NA, Kingsley E, Federoff HJ, et al. Visual deficits in a mouse model of Batten disease are the result of optic nerve degeneration and loss of dorsal lateral geniculate thalamic neurons. Neurobiol Dis. 2006;22:284–93.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Mahmood F, Fu S, Cooke J, Wilson SW, Cooper JD, Russell C. A zebrafish model of CLN2 disease is deficient in tripeptidyl peptidase 1 and displays progressive neurodegeneration accompanied by a reduction in proliferation. Brain. 2013;136:1488–507.

    Article  PubMed  Google Scholar 

  31. Groh J, Stadler D, Buttmann M, Martini R. Non-invasive assessment of retinal alterations in mouse models of infantile and juvenile neuronal ceroid lipofuscinosis by spectral domain optical coherence tomography. Acta Neuropathol Commun. 2014;2:54.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Nardocci N, Verga ML, Binelli S, Zorzi G, Angelini L, Bugiani O. Neuronal ceroid-lipofuscinosis: a clinical and morphological study of 19 patients. Am J Med Genet. 1995;57:137–41.

    Article  CAS  PubMed  Google Scholar 

  33. Orlin A, Sondhi D, Witmer MT, Wessel MM, Mezey JG, Kaminsky SM, et al. Spectrum of ocular manifestations in CLN2-associated batten (Jansky-Bielschowsky) disease correlate with advancing age and deteriorating neurological function. PLoS One. 2013;8:e73128.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Klein CJ, Botuyan MV, Wu Y, Ward CJ, Nicholson GA, Hammans S, et al. Mutations in DNMT1 cause hereditary sensory neuropathy with dementia and hearing loss. Nat Genet. 2011;43:595–600.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Winkelmann J, Lin L, Schormair B, Kornum BR, Faraco J, Plazzi G, et al. Mutations in DNMT1 cause autosomal dominant cerebellar ataxia, deafness and narcolepsy. Hum Mol Genet. 2012;21:2205–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Moghadam KK, Pizza F, La Morgia C, Franceschini C, Tonon C, Lodi R, et al. Narcolepsy is a common phenotype in HSAN IE and ADCA-DN. Brain. 2014;137:1643–55.

    Article  PubMed  Google Scholar 

  37. Melberg A, Hetta J, Dahl N, Nennesmo I, Bengtsson M, Wibom R, et al. Autosomal dominant cerebellar ataxia deafness and narcolepsy. J Neurol Sci. 1995;134:119–29.

    Article  CAS  PubMed  Google Scholar 

  38. Lundberg PO, Wranne I, Brun A. Family with optic atrophy and neurological symptoms. Acta Neurol Scand. 1967;43:87–105.

    Article  CAS  PubMed  Google Scholar 

  39. Takasugi M, Yagi S, Hirabayashi K, Shiota K. DNA methylation status of nuclear-encoded mitochondrial genes underlies the tissue-dependent mitochondrial functions. BMC Genomics. 2010;11:481.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  40. Shock LS, Thakkar PV, Peterson EJ, Moran RG, Taylor SM. DNA methyltransferase 1, cytosine methylation, and cytosine hydroxymethylation in mammalian mitochondria. Proc Natl Acad Sci U S A. 2011;108:3630–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Bellizzi D, D’Aquila P, Scafone T, Giordano M, Riso V, Riccio A, et al. The control region of mitochondrial DNA shows an unusual CpG and non-CpG methylation pattern. DNA Res. 2013;20:537–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Lo Giudice T, Lombardi F, Santorelli FM, Kawarai T, Orlacchio A. Hereditary spastic paraplegia: clinical-genetic characteristics and evolving molecular mechanisms. Exp Neurol. 2014;261C:518–39.

    Article  CAS  Google Scholar 

  43. Casari G, De Fusco M, Ciarmatori S, Zeviani M, Mora M, Fernandez P, et al. Spastic paraplegia and OXPHOS impairment caused by mutations in paraplegin, a nuclear-encoded mitochondrial metalloprotease. Cell. 1998;93:973–83.

    Article  CAS  PubMed  Google Scholar 

  44. De Michele G, De Fusco M, Cavalcanti F, Filla A, Marconi R, Volpe G, et al. A new locus for autosomal recessive hereditary spastic paraplegia maps to chromosome 16q24.3. Am J Hum Genet. 1998;63:135–9.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Rugarli EI, Langer T. Translating m-AAA protease function in mitochondria to hereditary spastic paraplegia. Trends Mol Med. 2006;12:262–9.

    Article  CAS  PubMed  Google Scholar 

  46. Nolden M, Ehses S, Koppen M, Bernacchia A, Rugarli EI, Langer T. The m-AAA protease defective in hereditary spastic paraplegia controls ribosome assembly in mitochondria. Cell. 2005;123:277–89.

    Article  CAS  PubMed  Google Scholar 

  47. Atorino L, Silvestri L, Koppen M, Cassina L, Ballabio A, Marconi R, et al. Loss of m-AAA protease in mitochondria causes complex I deficiency and increased sensitivity to oxidative stress in hereditary spastic paraplegia. J Cell Biol. 2003;163:777–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. McDermott CJ, Dayaratne RK, Tomkins J, Lusher ME, Lindsey JC, Johnson MA, et al. Paraplegin gene analysis in hereditary spastic paraparesis (HSP) pedigrees in northeast England. Neurology. 2001;56:467–71.

    Article  CAS  PubMed  Google Scholar 

  49. Ehses S, Raschke I, Mancuso G, Bernacchia A, Geimer S, Tondera D, et al. Regulation of OPA1 processing and mitochondrial fusion by m-AAA protease isoenzymes and OMA1. J Cell Biol. 2009;187:1023–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Klebe S, Depienne C, Gerber S, Challe G, Anheim M, Charles P, et al. Spastic paraplegia gene 7 in patients with spasticity and/or optic neuropathy. Brain. 2012;135:2980–93.

    Article  PubMed  PubMed Central  Google Scholar 

  51. van Gassen KL, van der Heijden CD, de Bot ST, den Dunnen WF, van den Berg LH, Verschuuren-Bemelmans CC, et al. Genotype-phenotype correlations in spastic paraplegia type 7: a study in a large Dutch cohort. Brain. 2012;135:2994–3004.

    Article  PubMed  Google Scholar 

  52. Marcotulli C, Leonardi L, Tessa A, De Negris AM, Cornia R, Pierallini A, et al. Early-onset optic neuropathy as initial clinical presentation in SPG7. J Neurol. 2014;261:1820–1.

    Article  PubMed  Google Scholar 

  53. Wiethoff S, Zhour A, Schöls L, Fischer MD. Retinal nerve fibre layer loss in hereditary spastic paraplegias is restricted to complex phenotypes. BMC Neurol. 2012;12:143.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Chabriat H, Joutel A, Dichgans M, Tournier-Lasserve E, Bousser MG. Cadasil. Lancet Neurol. 2009;8:643–53.

    Article  PubMed  Google Scholar 

  55. O’Sullivan M, Jarosz JM, Martin RJ, Deasy N, Powell JF, Markus HS. MRI hyperintensities of the temporal lobe and external capsule in patients with CADASIL. Neurology. 2001;56:628–34.

    Article  PubMed  Google Scholar 

  56. Joutel A, Corpechot C, Ducros A, Vahedi K, Chabriat H, Mouton P, et al. Notch3 mutations in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a mendelian condition causing stroke and vascular dementia. Ann N Y Acad Sci. 1997;826:213–7.

    Article  CAS  PubMed  Google Scholar 

  57. Belin de Chantemèle EJ, Retailleau K, Pinaud F, Vessières E, Bocquet A, Guihot AL, et al. Notch3 is a major regulator of vascular tone in cerebral and tail resistance arteries. Arterioscler Thromb Vasc Biol. 2008;28:2216–24.

    Article  PubMed  CAS  Google Scholar 

  58. Robinson W, Galetta SL, McCluskey L, Forman MS, Balcer LJ. Retinal findings in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (cadasil). Surv Ophthalmol. 2001;45:445–8.

    Article  CAS  PubMed  Google Scholar 

  59. Roine S, Harju M, Kivelä TT, Pöyhönen M, Nikoskelainen E, Tuisku S, et al. Ophthalmologic findings in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: a cross-sectional study. Ophthalmology. 2006;113:1411–7.

    Article  PubMed  Google Scholar 

  60. Haritoglou C, Rudolph G, Hoops JP, Opherk C, Kampik A, Dichgans M. Retinal vascular abnormalities in CADASIL. Neurology. 2004;62:1202–5.

    Article  CAS  PubMed  Google Scholar 

  61. Pretegiani E, Rosini F, Dotti MT, Bianchi S, Federico A, Rufa A. Visual system involvement in CADASIL. J Stroke Cerebrovasc Dis. 2013;22:1377–84.

    Article  PubMed  Google Scholar 

  62. Parisi V, Pierelli F, Fattapposta F, Bianco F, Parisi L, Restuccia R, et al. Early visual function impairment in CADASIL. Neurology. 2003;60:2008–10.

    Article  CAS  PubMed  Google Scholar 

  63. Rufa A, Malandrini A, Dotti MT, Berti G, Salvadori C, Federico A. Typical pathological changes of CADASIL in the optic nerve. Neurol Sci. 2005;26:271–4.

    Article  CAS  PubMed  Google Scholar 

  64. Parisi V, Pierelli F, Coppola G, Restuccia R, Ferrazzoli D, Scassa C, et al. Reduction of optic nerve fiber layer thickness in CADASIL. Eur J Neurol. 2007;14:627–31.

    Article  CAS  PubMed  Google Scholar 

  65. Rufa A, Pretegiani E, Frezzotti P, De Stefano N, Cevenini G, Dotti MT, et al. Retinal nerve fiber layer thinning in CADASIL: an optical coherence tomography and MRI study. Cerebrovasc Dis. 2011;31:77–82.

    Article  PubMed  Google Scholar 

  66. Wolfram D, Wagener HP. Diabetes mellitus and simple optic atrophy among siblings: report of four cases. Proc Staff Meet Mayo Clin. 1938;13:715–8.

    Google Scholar 

  67. Rigoli L, Di Bella C. Wolfram syndrome 1 and Wolfram syndrome 2. Curr Opin Pediatr. 2012;24:512–7.

    CAS  PubMed  Google Scholar 

  68. Barrett TG, Poulton K, Bundey S. DIDMOAD syndrome; further studies and muscle biochemistry. J Inherit Metab Dis. 1995;18:218–20.

    Article  CAS  PubMed  Google Scholar 

  69. Barrett TG, Bundey SE. Wolfram (DIDMOAD) syndrome. J Med Genet. 1997;34:838–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Barrett TG, Bundey SE, Fielder AR, Good PA. Optic atrophy in Wolfram (DIDMOAD) syndrome. Eye (Lond). 1997;11:882–8.

    Article  Google Scholar 

  71. Inoue H, Tanizawa Y, Wasson J, Behn P, Kalidas K, Bernal-Mizrachi E, et al. A gene encoding a transmembrane protein is mutated in patients with diabetes mellitus and optic atrophy (Wolfram syndrome). Nat Genet. 1998;20:143–8.

    Article  CAS  PubMed  Google Scholar 

  72. Eiberg H, Hansen L, Kjer B, Hansen T, Pedersen O, Bille M, et al. Autosomal dominant optic atrophy associated with hearing impairment and impaired glucose regulation caused by a missense mutation in the WFS1 gene. J Med Genet. 2006;43:435–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Rendtorff ND, Lodahl M, Boulahbel H, Johansen IR, Pandya A, Welch KO, et al. Identification of p.A684V missense mutation in the WFS1 gene as a frequent cause of autosomal dominant optic atrophy and hearing impairment. Am J Med Genet A. 2011;155A:1298–313.

    Article  PubMed  CAS  Google Scholar 

  74. Bai X, Lv H, Zhang F, Liu J, Fan Z, Xu L, et al. Identification of a novel missense mutation in the WFS1 gene as a cause of autosomal dominant nonsyndromic sensorineural hearing loss in all-frequencies. Am J Med Genet A. 2014;164:3052–60.

    Article  CAS  Google Scholar 

  75. Bonnycastle LL, Chines PS, Hara T, Huyghe JR, Swift AJ, Heikinheimo P, et al. Autosomal dominant diabetes arising from a Wolfram syndrome 1 mutation. Diabetes. 2013;62:3943–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Berry V, Gregory-Evans C, Emmett W, Waseem N, Raby J, Prescott D, et al. Wolfram gene (WFS1) mutation causes autosomal dominant congenital nuclear cataract in humans. Eur J Hum Genet. 2013;21:1356–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Carson MJ, Slager UT, Steinberg RM. Simultaneous occurrence of diabetes mellitus, diabetes insipidus, and optic atrophy in a brother and sister. Am J Dis Child. 1977;131:1382–5.

    CAS  PubMed  Google Scholar 

  78. Jackson MJ, Bindoff LA, Weber K, Wilson JN, Ince P, Alberti KG, et al. Biochemical and molecular studies of mitochondrial function in diabetes insipidus, diabetes mellitus, optic atrophy, and deafness. Diabetes Care. 1994;17:728–33.

    Article  CAS  PubMed  Google Scholar 

  79. Shannon P, Becker L, Deck J. Evidence of widespread axonal pathology in Wolfram syndrome. Acta Neuropathol. 1999;98:304–8.

    Article  CAS  PubMed  Google Scholar 

  80. Hilson JB, Merchant SN, Adams JC, Joseph JT. Wolfram syndrome: a clinicopathologic correlation. Acta Neuropathol. 2009;118:415–28.

    Article  PubMed  PubMed Central  Google Scholar 

  81. Ross-Cisneros FN, Pan BX, Silva RA, Miller NR, Albini TA, Tranebjaerg L, et al. Optic nerve histopathology in a case of Wolfram Syndrome: a mitochondrial pattern of axonal loss. Mitochondrion. 2013;13:841–5.

    Article  CAS  PubMed  Google Scholar 

  82. Bababeygy SR, Wang MY, Khaderi KR, Sadun AA. Visual improvement with the use of idebenone in the treatment of Wolfram syndrome. J Neuroophthalmol. 2012;32:386–9.

    Article  PubMed  Google Scholar 

  83. Bucca BC, Klingensmith G, Bennett JL. Wolfram Syndrome: a rare optic neuropathy in youth with type 1 diabetes. Optom Vis Sci. 2011;88:E1383–90.

    Article  PubMed  Google Scholar 

  84. Bouhlal Y, Amouri R, El Euch-Fayeche G, Hentati F. Autosomal recessive spastic ataxia of Charlevoix-Saguenay: an overview. Parkinsonism Relat Disord. 2011;17:418–22.

    Article  PubMed  Google Scholar 

  85. Berciano J, García A, Infante J. Peripheral nerve involvement in hereditary cerebellar and multisystem degenerative disorders. Handb Clin Neurol. 2013;115:907–32.

    Article  PubMed  Google Scholar 

  86. Duquette A, Brais B, Bouchard JP, Mathieu J. Clinical presentation and early evolution of spastic ataxia of Charlevoix-Saguenay. Mov Disord. 2013;28:2011–4.

    Article  PubMed  Google Scholar 

  87. Baets J, Deconinck T, Smets K, Goossens D, Van den Bergh P, Dahan K, et al. Mutations in SACS cause atypical and late-onset forms of ARSACS. Neurology. 2010;75:1181–8.

    Article  CAS  PubMed  Google Scholar 

  88. Bouchard JP, Barbeau A, Bouchard R, Bouchard RW. Autosomal recessive spastic ataxia of Charlevoix-Saguenay. Can J Neurol Sci. 1978;5:61e9.

    Google Scholar 

  89. De Braekeleer M, Giasson F, Mathieu J, Roy M, Bouchard JP, Morgan K. Genetic epidemiology of autosomal recessive spastic ataxia of CharlevoixeSaguenay in northeastern Quebec. Genet Epidemiol. 1993;10:17e25.

    Article  Google Scholar 

  90. Engert JC, Bérubé P, Mercier J, Doré C, Lepage P, Ge B, Bouchard JP, Mathieu J, et al. ARSACS, a spastic ataxia common in northeastern Québec, is caused by mutations in a new gene encoding an 11.5-kb ORF. Nat Genet. 2000;24:120e5.

    Article  CAS  Google Scholar 

  91. Cheetham ME, Caplan AJ. Structure, function and evolution of DnaJ: conservation and adaptation of chaperone function. Cell Stress Chaperones. 1998;3:28e36.

    Article  Google Scholar 

  92. Parfitt DA, Michael GJ, Vermeulen EG, Prodromou NV, Webb TR, Gallo JM, et al. The ataxia protein sacsin is a functional co-chaperone that protects against polyglutamine-expanded ataxin-1. Hum Mol Genet. 2009;18:1556e65.

    Article  CAS  Google Scholar 

  93. Girard M, Larivière R, Parfitt DA, Deane EC, Gaudet R, Nossova N, et al. Mitochondrial dysfunction and Purkinje cell loss in autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS). Proc Natl Acad Sci U S A. 2012;109:1661–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. El Euch-Fayache G, Lalani I, Amouri R, Turki I, Ouahchi K, Hung WY, et al. Phenotypic features and genetic findings in sacsin-related autosomal recessive ataxia in Tunisia. Arch Neurol. 2003;60:982e8.

    Google Scholar 

  95. Grieco GS, Malandrini A, Comanducci G, Leuzzi V, Valoppi M, Tessa A, et al. Novel SACS mutations in autosomal recessive spastic ataxia of Charlevoixe-Saguenay type. Neurology. 2004;62:103e6.

    Article  CAS  Google Scholar 

  96. Criscuolo C, Banfi S, Orio M, Gasparini P, Monticelli A, Scarano V, et al. A novel mutation in SACS gene in a family from southern Italy. Neurology. 2004;62:100e2.

    Article  Google Scholar 

  97. Takiyama Y. Autosomal recessive spastic ataxia of CharlevoixeSaguenay. Neuropathology. 2006;26:368e75.

    Article  Google Scholar 

  98. Bouhlal Y, Zouari M, Kefi M, Ben Hamida C, Hentati F, Amouri R. Autosomal recessive ataxia caused by three distinct gene defects in a single consanguineous family. J Neurogenet. 2008;22:139e48.

    Article  CAS  Google Scholar 

  99. Vermeer S, Meijer RP, Pijl BJ, Timmermans J, Cruysberg JR, Bos MM, et al. ARSACS in the Dutch population: a frequent cause of early-onset cerebellar ataxia. Neurogenetics. 2008;10:87.

    Article  Google Scholar 

  100. Bouhlal Y, El Euch-Fayeche G, Hentati F, Amouri R. A novel SACS gene mutation in a Tunisian family. J Mol Neurosci. 2009;39:333e6.

    Article  CAS  Google Scholar 

  101. Takiyama Y. Sacsinopathies: sacsin-related ataxia. Cerebellum. 2007;6:353–9.

    Article  CAS  PubMed  Google Scholar 

  102. Vingolo EM, Di Fabio R, Salvatore S, Greco G, Bertini E, Lezzi V, et al. Myelinated retinal fibers in autosomal recessive spastic ataxia of Charlevoix-Saguenay. Eur J Neurol. 2011;18:1187–90.

    Article  CAS  PubMed  Google Scholar 

  103. Pablo LE, Garcia-Martin E, Gazulla J, Larrosa JM, Ferreras A, Santorelli FM, et al. Retinal nerve fiber hypertrophy in ataxia of Charlevoix-Saguenay patients. Mol Vis. 2011;17:1871–6.

    PubMed  PubMed Central  Google Scholar 

  104. Desserre J, Devos D, Sautière BG, Debruyne P, Santorelli FM, Vuillaume I, et al. Thickening of peripapillar retinal fibers for the diagnosis of autosomal recessive spastic ataxia of Charlevoix-Saguenay. Cerebellum. 2011;10:758–62.

    Article  PubMed  Google Scholar 

  105. Gazulla J, Benavente I, Vela AC, Marín MA, Pablo LE, Tessa A, Barrena MR, et al. New findings in the ataxia of Charlevoix-Saguenay. J Neurol. 2012;259:869–78.

    Article  PubMed  Google Scholar 

  106. Yu-Wai-Man P, Pyle A, Griffin H, Santibanez-Korev M, Chinnery PF. Abnormal retinal thickening is a common feature among patients with ARSACS-related phenotypes. Br J Ophthalmol. 2014;98:711–3.

    Article  PubMed  PubMed Central  Google Scholar 

  107. Koeppen AH. The pathogenesis of spinocerebellar ataxia. Cerebellum. 2005;4:62–73.

    Article  CAS  PubMed  Google Scholar 

  108. Durr A. Autosomal dominant cerebellar ataxias: polyglutamine expansions and beyond. Lancet Neurol. 2010;9:885–94.

    Article  CAS  PubMed  Google Scholar 

  109. Pula JH, Gomez CM, Kattah JC. Ophthalmologic features of the common spinocerebellar ataxias. Curr Opin Ophthalmol. 2010;21:447–53.

    Article  PubMed  Google Scholar 

  110. Newman NJ, Biousse V. Hereditary optic neuropathies. Eye (Lond). 2004;18(11):1144–60.

    Article  CAS  Google Scholar 

  111. Rufa A, Dotti MT, Galli L, Orrico A, Sicurelli F, Federico A. Spinocerebellar ataxia type 2 (SCA2) associated with retinal pigmentary degeneration. Eur Neurol. 2002;47:128–9.

    Article  PubMed  Google Scholar 

  112. Fukutake T, Kamitsukasa I, Arai K, Hattori T, Nakajima T. A patient homozygous for the SCA6 gene with retinitis pigmentosa. Clin Genet. 2002;61:375–9.

    Article  CAS  PubMed  Google Scholar 

  113. Aleman TS, Cideciyan AV, Volpe NJ, Stevanin G, Brice A, Jacobson SG. Spinocerebellar ataxia type 7 (SCA7) shows a cone-rod dystrophy phenotype. Exp Eye Res. 2002;74:737–45.

    Article  CAS  PubMed  Google Scholar 

  114. Abe T, Tsuda T, Yoshida M, Wada Y, Kano T, Itoyama Y, et al. Macular degeneration associated with aberrant expansion of trinucleotide repeat of the SCA7 gene in 2 Japanese families. Arch Ophthalmol. 2000;118:1415–21.

    Article  CAS  PubMed  Google Scholar 

  115. Pula JH, Towle VL, Staszak VM, Cao D, Bernard JT, Gomez CM. Retinal nerve fibre layer and macular thinning in spinocerebellar ataxia and cerebellar multisystem atrophy. Neuroophthalmology. 2011;35(3):108–14.

    Article  PubMed  PubMed Central  Google Scholar 

  116. Alvarez G, Rey A, Sanchez-Dalmau FB, Muñoz E, Ríos J, Adán A. Optical coherence tomography findings in spinocerebellar ataxia-3. Eye (Lond). 2013;27:1376–81.

    Article  CAS  Google Scholar 

  117. Schöls L, Bauer P, Schmidt T, Schulte T, Riess O. Autosomal dominant cerebellar ataxias: clinical features, genetics, and pathogenesis. Lancet Neurol. 2004;3:291–304.

    Article  PubMed  Google Scholar 

  118. Lebranchu P, Le Meur G, Magot A, David A, Verny C, Weber M, et al. Maculopathy and spinocerebellar ataxia type 1: a new association? J Neuroophthalmol. 2013;33:225–31.

    Article  PubMed  Google Scholar 

  119. Vaclavik V, Borruat FX, Ambresin A, Munier FL. Novel maculopathy in patients with spinocerebellar ataxia type 1 autofluorescence findings and functional characteristics. JAMA Ophthalmol. 2013;131:536–8.

    Article  PubMed  Google Scholar 

  120. Abe T, Abe K, Tsuda T, Itoyama Y, Tamai M. Ophthalmological findings in patients with spinocerebellar ataxia type 1 are not correlated with neurological anticipation. Graefes Arch Clin Exp Ophthalmol. 2001;239:722–8.

    Article  CAS  PubMed  Google Scholar 

  121. Abe T, Abe K, Aoki M, Itoyama Y, Tamai M. Ocular changes in patients with spinocerebellar degeneration and repeated trinucleotide expansion of spinocerebellar ataxia type 1 gene. Arch Ophthalmol. 1997;115:231–6.

    Article  CAS  PubMed  Google Scholar 

  122. Abele M, Bürk K, Andres F, Topka H, Laccone F, Bösch S, et al. Autosomal dominant cerebellar ataxia type I. Nerve conduction and evoked potential studies in families with SCA1, SCA2 and SCA3. Brain. 1997;120:2141–8.

    Article  PubMed  Google Scholar 

  123. Perretti A, Santoro L, Lanzillo B, Filla A, De Michele G, Barbieri F, et al. Autosomal dominant cerebellar ataxia type I: multimodal electrophysiological study and comparison between SCA1 and SCA2 patients. J Neurol Sci. 1996;142:45–53.

    Article  CAS  PubMed  Google Scholar 

  124. Robitaille Y, Schut L, Kish SJ. Structural and immunocytochemical features of olivopontocerebellar atrophy caused by the spinocerebellar ataxia type 1 (SCA-1) mutation define a unique phenotype. Acta Neuropathol. 1995;90:572–81.

    Article  CAS  PubMed  Google Scholar 

  125. Stricker S, Oberwahrenbrock T, Zimmermann H, Schroeter J, Endres M, Brandt AU, et al. Temporal retinal nerve fiber loss in patients with spinocerebellar ataxia type 1. PLoS One. 2011;6:e23024.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Varsányi B, Somfai GM, Lesch B, Vámos R, Farkas A, et al. Optical coherence tomography of the macula in congenital achromatopsia. Invest Ophthalmol Vis Sci. 2007;48:2249–53.

    Article  PubMed  Google Scholar 

  127. Birch DG, Wen Y, Locke K, Hood DC. Rod sensitivity, cone sensitivity, and photoreceptor layer thickness in retinal degenerative diseases. Invest Ophthalmol Vis Sci. 2011;52:7141–7.

    Article  PubMed  PubMed Central  Google Scholar 

  128. Gouw LG, Digre KB, Harris CP, Haines JH, Ptacek LJ. Autosomal dominant cerebellar ataxia with retinal degeneration: clinical, neuropathologic, and genetic analysis of a large kindred. Neurology. 1994;44:1441–7.

    Article  CAS  PubMed  Google Scholar 

  129. Cancel G, Duyckaerts C, Holmberg M, Zander C, Yvert G, Lebre AS, et al. Distribution of ataxin-7 in normal human brain and retina. Brain. 2000;123:2519–30.

    Article  PubMed  Google Scholar 

  130. La Spada AR, Fu Y, Sopher BL, Libby RT, Wang X, Li LY, et al. Polyglutamine-expanded ataxin-7 antagonizes CRX function and induces cone-rod dystrophy in a mouse model of SCA7. Neuron. 2001;31:913–27.

    Article  PubMed  Google Scholar 

  131. Kumar N, Pulido JS. High-definition spectral domain optical coherence tomography in the evaluation of ataxia with visual impairment. Br J Ophthalmol. 2011;95:591–8.

    Article  CAS  PubMed  Google Scholar 

  132. Manrique RK, Noval S, Aguilar-Amat MJ, Arpa J, Rosa I, Contreras I. Ophthalmic features of spinocerebellar ataxia type 7. J Neuroophthalmol. 2009;29:174–9.

    Article  PubMed  Google Scholar 

  133. Ahn JK, Seo JM, Chung H, Yu HG. Anatomical and functional characteristics in atrophic maculopathy associated with spinocerebellar ataxia type 7. Am J Ophthalmol. 2005;139:923–5.

    Article  PubMed  Google Scholar 

  134. McLaughlin ME, Dryja TP. Ocular findings in spinocerebellar ataxia 7. Arch Ophthalmol. 2002;120:655–9.

    PubMed  Google Scholar 

  135. Gowrisankaran S, Anastasakis A, Fishman GA, Alexander KR. Structural and functional measures of inner retinal integrity following visual acuity improvement in a patient with hereditary motor and sensory neuropathy type VI. Ophthalmic Genet. 2011;32:188–92.

    Article  PubMed  PubMed Central  Google Scholar 

  136. Grainger BT, Papchenko TL, Danesh-Meyer HV. Optic nerve atrophy in adrenoleukodystrophy detectable by optic coherence tomography. J Clin Neurosci. 2010;17:122–4.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. IRCCS Institute of Neurological Sciences, Unit of Neurology, Bellaria Hospital, Via Altura, 3, 40139, Bologna, Italy

    Chiara La Morgia MD, PhD

  2. Department of Biomedical and Neuromotor Sciences, University of Bologna, Via Altura, 3, 40139, Bologna, Italy

    Chiara La Morgia MD, PhD

  3. IRCCS Institute of Neurological Sciences, Unit of Neurology, Bellaria Hospital, Bologna, Italy

    Michele Carbonelli MD

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  1. Chiara La Morgia MD, PhD
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Correspondence to Chiara La Morgia MD, PhD .

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  1. Head of Ophthalmology Department, Professor of Ophthalmology,, Poznań, Poland

    Andrzej Grzybowski

  2. Studio Oculistico d’Azeglio, Bologna, Italy

    Piero Barboni

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La Morgia, C., Carbonelli, M. (2016). Friedreich’s Ataxia and More: Optical Coherence Tomography Findings in Rare Neurological Syndromes. In: Grzybowski, A., Barboni, P. (eds) OCT in Central Nervous System Diseases. Springer, Cham. https://doi.org/10.1007/978-3-319-24085-5_8

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