eMedicine Specialties > Neurology > Movement and Neurodegenerative Diseases

Olivopontocerebellar Atrophy: Treatment & Medication

Author: Christina J Azevedo MD, Staff Physician, Department of Neurology, Dartmouth-Hitchcock Medical Center
Coauthor(s): Stephen A Berman, MD, PhD, Professor, Department of Internal Medicine, Section of Neurology, Dartmouth Medical School; Chief, Neurology Service, White River Junction Veterans Medical Center
Contributor Information and Disclosures

Updated: Feb 12, 2009

Treatment

Medical Care

Care of olivopontocerebellar atrophy (OPCA) is directed to the treatment of symptoms.

  • Dopaminergic agents, such as levodopa, bromocriptine, or amantadine, have shown minimal benefit.
  • Propranolol has been used for tremor, but the clinical response is generally minimal.
  • A small study of 18 patients investigated the use of combined estrogen and buspirone therapy for OPCA. This was based on the neuroprotective effects of estrogen and the idea that buspirone modulates the serotonergic motor output from the cerebellum. The buspirone group showed significant improvements in finger-to-nose and rapid alternating movements at 1 month; however, at 12 months (which was the end of the study) there was no statistically significant improvement in any test of cerebellar function. There were trends toward improvement in dysarthria, heel-to-shin testing, and gait speed. No benefit was seen by adding estrogen.110
  • Supportive care with gait-assisting devices is especially important to minimize falls.

Surgical Care

  • At times, patients may require enteral feeding to decrease the risk of aspiration.
  • Percutaneous endoscopic gastrostomy and jejunostomy tube (J-tube) placement may be necessary.

Consultations

  • Consultations with physical and occupational therapists are helpful to increase mobility; the use of assistive devices can significantly increase functional ability.
  • A swallowing evaluation can be a very important part of the early consultation.
  • Now that genetic testing is available, it can be performed to confirm the diagnosis of autosomal dominant OPCAs. These patients may not develop symptoms until after the onset of their reproductive years; therefore, family members must be evaluated early if a diagnosis of autosomal dominant OPCA is made. Referral for genetic counseling is advisable in these individuals. Not all patients wish to learn of their risks in the absence of an available treatment, while some individuals may use the information for family planning and other types of planning for the future.

Diet

As dysphagia progresses with the disease, a pureed diet or enteral feeding may be required.

Activity

Activity should be allowed ad libitum; however, appropriate measures should be used to minimize falls.

Medication

As previously stated, to date, medical therapy has provided only minimal benefits.

Dopaminergic agents

Used to improve parkinsonian and tremor-related symptoms.


Levodopa/carbidopa (Sinemet)

Direct dopaminergic agent. Carbidopa prevents peripheral decarboxylation of levodopa, thus facilitating entry into CNS. Comes in different strengths of 25/100 mg, 25/250 mg, and 10/100 mg.

Adult

Initial dose: 25/100 mg PO tid; can titrate upwards depending on adverse effect profile

Pediatric

Not established

Hydantoins, pyridoxine, phenothiazine, and hypotensive agents may decrease effects; antacids and MAOIs increase toxicity

Documented hypersensitivity; narrow-angle glaucoma; malignant melanoma or undiagnosed skin lesions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Certain adverse CNS effects (eg, dyskinesias) may occur at lower dosages and earlier in therapy with SR form; caution in patients with history of myocardial infarction, arrhythmias, asthma, or peptic ulcer disease; sudden discontinuation may cause worsening of Parkinson disease; high-protein diets should be distributed throughout day to avoid fluctuations in levodopa absorption


Amantadine (Symmetrel)

Unknown mechanism of action; may release dopamine from remaining dopaminergic terminals in Parkinson patients or from other central sites. Less effective than levodopa in treating Parkinson disease; slightly more effective than anticholinergic agents.

Adult

100 mg PO bid

Pediatric

Not established

Drugs with anticholinergic or CNS stimulant activity increase toxicity; hydrochlorothiazide plus triamterene may increase plasma concentrations

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in liver disease, uncontrolled psychosis, eczematoid dermatitis, seizures, and those receiving CNS stimulant drugs; reduce dose in renal disease when treating Parkinson disease; do not abruptly discontinue this medication

Antihypertensive agents

Pharmacologic therapy should be individualized based on a patient's age, race, known pathophysiologic variables, and concurrent conditions. Treatment should be designed to lower blood pressure safely and effectively and to avoid or reverse hyperlipidemia, glucose intolerance, and left ventricular hypertrophy.


Propranolol (Inderal, Betachron E-R)

Nonselective beta-adrenergic agonist; mechanism of action for tremor suppression not fully known.

Adult

Initial dose: 40 mg PO bid; can be increased to 120-240 mg/d

Pediatric

Not established

Aluminum salts, barbiturates, NSAIDs, penicillins, calcium salts, cholestyramine, and rifampin may decrease effects; calcium channel blockers, cimetidine, loop diuretics, and MAOIs may increase toxicity; may increase toxicity of hydralazine, haloperidol, benzodiazepines, and phenothiazines

Documented hypersensitivity; uncompensated CHF; bradycardia; cardiogenic shock; AV conduction abnormalities

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Beta-adrenergic blockade may decrease signs of acute hypoglycemia and hyperthyroidism; abrupt withdrawal may exacerbate symptoms of hyperthyroidism, including thyroid storm; withdraw drug slowly and monitor closely

More on Olivopontocerebellar Atrophy

Overview: Olivopontocerebellar Atrophy
Differential Diagnoses & Workup: Olivopontocerebellar Atrophy
Treatment & Medication: Olivopontocerebellar Atrophy
Follow-up: Olivopontocerebellar Atrophy
References
[ CLOSE WINDOW ]

References

  1. Friedreich N. Ueber degenerative atrophie der spinalen Hinterstrange. Virchow Arch Path Anat. 1863;26:391-419.

  2. Friedreich N. Ueber degenerative atrophie der spinalen Hinterstrange. Virchow Arch Path Anat. 1863;27:1-26.

  3. Marie P. Sur l'heredo-ataxie cerebelleuse.Clinique des maladies nerveuses. Semaine Med, Paris. 1893;13:444-7.

  4. Marie P, Foix C, Alajouanine T. De l'atrophie cerebelleuse tardive a predominance corticale. Revue Neurologique, Paris. 1922;38:849-85; 1082-111.

  5. Dejerine J, Thomas A. L'atrophie olivo-ponto-cerebelleuse. Nouv Icon de la Salpet. 1900;13:330-70.

  6. Greenfield JG. The Spino-cerebellar Degenerations. Springfield, Ill: Charles C. Thomas; 1954.

  7. Harding AE. The clinical features and classification of the late onset autosomal dominant cerebellar ataxias. A study of 11 families, including descendants of the 'the Drew family of Walworth'. Brain. Mar 1982;105(Pt 1):1-28. [Medline].

  8. Konigsmark BW, Weiner LP. The olivopontocerebellar atrophies: a review. Medicine (Baltimore). May 1970;49(3):227-41. [Medline].

  9. Skre H, Berg K. Cerebellar ataxia and total albinism: a kindred suggesting pleitotropism or linkage. Clin Genet. 1974;5(3):196-204. [Medline].

  10. Paulson H, Ammache Z. Ataxia and hereditary disorders. Neurol Clin. 2001;Aug;19(3):759-82, viii. [Medline].

  11. Gilman S, Little R, Johanns J, et al. Evolution of sporadic olivopontocerebellar atrophy into multiple system atrophy. Neurology. Aug 22 2000;55(4):527-32. [Medline].

  12. Jellinger KA. Neuropathological spectrum of synucleinopathies. Mov Disord. Sep 2003;18 Suppl 6:S2-12. [Medline].

  13. Banfi S, Servadio A, Chung MY, et al. Identification and characterization of the gene causing type 1 spinocerebellar ataxia. Nat Genet. Aug 1994;7(4):513-20. [Medline].

  14. Burk K, Abele M, Fetter M, Dichgans J, Skalej M, Laccone F, et al. Autosomal dominant cerebellar ataxia type I clinical features and MRI in families with SCA1, SCA2 and SCA3. Brain. Oct 1996;119 ( Pt 5):1497-505. [Medline].

  15. Fickler A. Klinische und pathologisch-anatomische Beitraege zu den Erkrankungen des Kleinhirns. Dtsch Z Nervenheilk. 1911;41:306-75.

  16. Winkler C. A case of olivo-pontine cerebellar atrophy and our conceptions of neo- and palaio-cerebellum. Schweiz Arch Neurol Psychiat. 1923;13:684-702.

  17. Schut JW, Haymaker W. Hereditary ataxia: pathologic study of 5 cases of common ancestry. J Neuropath Clin Neurol. 1951;1:183-213.

  18. Carter HR, Sukavajana C. Familial cerebello-olivary degeneration with late development of rigidity and dementia. Neurology. Dec 1956;6(12):876-84. [Medline].

  19. Illarioshkin SN, Tanaka H, Markova ED, et al. X-linked nonprogressive congenital cerebellar hypoplasia: clinical description and mapping to chromosome Xq. Ann Neurol. Jul 1996;40(1):75-83. [Medline].

  20. Bertini E, des Portes V, Zanni G, et al. X-linked congenital ataxia: a clinical and genetic study. Am J Med Genet. May 1 2000;92(1):53-6. [Medline].

  21. Chou SM, Gilbert EF, Chun RW, et al. Infantile olivopontocerebellar atrophy with spinal muscular atrophy (infantile OPCA + SMA). Clin Neuropathol. Jan-Feb 1990;9(1):21-32. [Medline].

  22. Barth PG. Pontocerebellar hypoplasias. An overview of a group of inherited neurodegenerative disorders with fetal onset. Brain Dev. Nov-Dec 1993;15(6):411-22. [Medline].

  23. Rajab A, Mochida GH, Hill A, et al. A novel form of pontocerebellar hypoplasia maps to chromosome 7q11-21. Neurology. May 27 2003;60(10):1664-7. [Medline].

  24. Albrecht S, Schneider MC, Belmont J, Armstrong DL. Fatal infantile encephalopathy with olivopontocerebellar hypoplasia and micrencephaly. Report of three siblings. Acta Neuropathol (Berl). 1993;85(4):394-9. [Medline].

  25. Patel MS, Becker LE, Toi A, et al. Severe, fetal-onset form of olivopontocerebellar hypoplasia in three sibs: PCH type 5?. Am J Med Genet A. Mar 15 2006;140(6):594-603. [Medline].

  26. Colella S, Nardo T, Botta E, et al. Identical mutations in the CSB gene associated with either Cockayne syndrome or the DeSanctis-cacchione variant of xeroderma pigmentosum. Hum Mol Genet. May 1 2000;9(8):1171-5. [Medline].

  27. Kanda T, Oda M, Yonezawa M, et al. Peripheral neuropathy in xeroderma pigmentosum. Brain. Aug 1990;113 (Pt 4):1025-44. [Medline].

  28. De Sanctis C, Cacchione A. L'idiozia xerodermica [xerodermic idiocy]. Rivista Sperimentale di Freniatria e Medicina Legale delle Alienazioni Mentali. 1932;56:269-92.

  29. Agamanolis DP, Potter JL, Naito HK, et al. Lipoprotein disorder, cirrhosis, and olivopontocerebellar degeneration in two siblings. Neurology. May 1986;36(5):674-81. [Medline].

  30. Harding BN, Dunger DB, Grant DB, Erdohazi M. Familial olivopontocerebellar atrophy with neonatal onset: a recessively inherited syndrome with systemic and biochemical abnormalities. J Neurol Neurosurg Psychiatry. Mar 1988;51(3):385-90. [Medline].

  31. Menzel P. Beitrage zur Kenntnis der hereditaren Ataxie und Kleinhirnatrophie. Archiv fur Psychiatrie und Nervenkrankheiten, Berlin. 1891;22:160-90.

  32. Waggoner RW, Lowenberg K, Speicher KG. Hereditary cerebellar ataxia: report of a case and genetic study. Arch Neurol Psychiat. 1938;39:570-86.

  33. Schut JW. Hereditary ataxia: clinical study through six generations. Arch Neurol Psychiat. 1950;63:535-68.

  34. Orr HT, Chung MY, Banfi S, et al. Expansion of an unstable trinucleotide CAG repeat in spinocerebellar ataxia type 1. Nat Genet. Jul 1993;4(3):221-6. [Medline].

  35. Boller F, Segarra JM. Spino-pontine degeneration. Eur Neurol. 1969;2(6):356-73. [Medline].

  36. Wadia NH, Swami RK. A new form of heredo-familial spinocerebellar degeneration with slow eye movements (nine families). Brain. 1971;94(2):359-74. [Medline].

  37. Ueyama H, Kumamoto T, Nagao S, et al. Clinical and genetic studies of spinocerebellar ataxia type 2 in Japanese kindreds. Acta Neurol Scand. Dec 1998;98(6):427-32. [Medline].

  38. Nakano KK, Dawson DM, Spence A. Machado disease. A hereditary ataxia in Portuguese emigrants to Massachusetts. Neurology. Jan 1972;22(1):49-55. [Medline].

  39. Kawaguchi Y, Okamoto T, Taniwaki M, et al. CAG expansions in a novel gene for Machado-Joseph disease at chromosome 14q32.1. Nat Genet. Nov 1994;8(3):221-8. [Medline].

  40. Gardner K, Alderson K, Galster B. Autosomal dominant spinocerebellar ataxia: clinical description of a distinct hereditary ataxia and genetic localization to chromosome 16 (SCA4) in a Utah kindred. Neurology. 1994;44:A361 only.

  41. Hellenbroich Y, Bubel S, Pawlack H, et al. Refinement of the spinocerebellar ataxia type 4 locus in a large German family and exclusion of CAG repeat expansions in this region. J Neurol. Jun 2003;250(6):668-71. [Medline].

  42. Ishikawa K, Toru S, Tsunemi T, et al. An autosomal dominant cerebellar ataxia linked to chromosome 16q22.1 is associated with a single-nucleotide substitution in the 5' untranslated region of the gene encoding a protein. Am J Hum Genet. Aug 2005;77(2):280-96. [Medline].

  43. Ikeda Y, Dick KA, Weatherspoon MR, et al. Spectrin mutations cause spinocerebellar ataxia type 5. Nat Genet. Feb 2006;38(2):184-90. [Medline].

  44. Subramony SH, Fratkin JD, Manyam BV, Currier RD. Dominantly inherited cerebello-olivary atrophy is not due to a mutation at the spinocerebellar ataxia-I, Machado-Joseph disease, or Dentato-Rubro-Pallido-Luysian atrophy locus. Mov Disord. Mar 1996;11(2):174-80. [Medline].

  45. Zhuchenko O, Bailey J, Bonnen P, et al. Autosomal dominant cerebellar ataxia (SCA6) associated with small polyglutamine expansions in the alpha 1A-voltage-dependent calcium channel. Nat Genet. Jan 1997;15(1):62-9. [Medline].

  46. David G, Abbas N, Stevanin G, et al. Cloning of the SCA7 gene reveals a highly unstable CAG repeat expansion. Nat Genet. Sep 1997;17(1):65-70. [Medline].

  47. Koob MD, Moseley ML, Schut LJ, et al. An untranslated CTG expansion causes a novel form of spinocerebellar ataxia (SCA8). Nat Genet. Apr 1999;21(4):379-84. [Medline].

  48. Ikeda Y, Shizuka M, Watanabe M, et al. Molecular and clinical analyses of spinocerebellar ataxia type 8 in Japan. Neurology. Feb 22 2000;54(4):950-5. [Medline].

  49. Factor SA, Qian J, Lava NS, et al. False-positive SCA8 gene test in a patient with pathologically proven multiple system atrophy. Ann Neurol. Mar 2005;57(3):462-3. [Medline].

  50. Grewal RP, Tayag E, Figueroa KP, et al. Clinical and genetic analysis of a distinct autosomal dominant spinocerebellar ataxia. Neurology. Nov 1998;51(5):1423-6. [Medline].

  51. Zu L, Figueroa KP, Grewal R, Pulst SM. Mapping of a new autosomal dominant spinocerebellar ataxia to chromosome 22. Am J Hum Genet. Feb 1999;64(2):594-9. [Medline].

  52. Grewal RP, Achari M, Matsuura T, et al. Clinical features and ATTCT repeat expansion in spinocerebellar ataxia type 10. Arch Neurol. Aug 2002;59(8):1285-90. [Medline].

  53. Worth PF, Giunti P, Gardner-Thorpe C, et al. Autosomal dominant cerebellar ataxia type III: linkage in a large British family to a 7.6-cM region on chromosome 15q14-21.3. Am J Hum Genet. Aug 1999;65(2):420-6. [Medline].

  54. Holmes SE, O'Hearn EE, McInnis MG, Gorelick-Feldman DA, et al. Expansion of a novel CAG trinucleotide repeat in the 5' region of PPP2R2B is associated with SCA12. Nat Genet. Dec 1999;23(4):391-2. [Medline].

  55. Fujigasaki H, Verma IC, Camuzat A, et al. SCA12 is a rare locus for autosomal dominant cerebellar ataxia: a study of an Indian family. Ann Neurol. Jan 2001;49(1):117-21. [Medline].

  56. Waters MF, Minassian NA, Stevanin G, et al. Mutations in voltage-gated potassium channel KCNC3 cause degenerative and developmental central nervous system phenotypes. Nat Genet. Apr 2006;38(4):447-51. [Medline].

  57. Yamashita I, Sasaki H, Yabe I, et al. A novel locus for dominant cerebellar ataxia (SCA14) maps to a 10.2-cM interval flanked by D19S206 and D19S605 on chromosome 19q13.4-qter. Ann Neurol. Aug 2000;48(2):156-63. [Medline].

  58. Brkanac Z, Bylenok L, Fernandez M, et al. A new dominant spinocerebellar ataxia linked to chromosome 19q13.4-qter. Arch Neurol. Aug 2002;59(8):1291-5. [Medline].

  59. Chen DH, Brkanac Z, Verlinde CL, et al. Missense mutations in the regulatory domain of PKC gamma: a new mechanism for dominant nonepisodic cerebellar ataxia. Am J Hum Genet. Apr 2003;72(4):839-49. [Medline].

  60. Yabe I, Sasaki H, Chen DH, et al. Spinocerebellar ataxia type 14 caused by a mutation in protein kinase C gamma. Arch Neurol. Dec 2003;60(12):1749-51. [Medline].

  61. Storey E, Gardner RJ, Knight MA, et al. A new autosomal dominant pure cerebellar ataxia. Neurology. Nov 27 2001;57(10):1913-5. [Medline].

  62. Knight MA, Kennerson ML, Anney RJ, et al. Spinocerebellar ataxia type 15 (sca15) maps to 3p24.2-3pter: exclusion of the ITPR1 gene, the human orthologue of an ataxic mouse mutant. Neurobiol Dis. Jul 2003;13(2):147-57. [Medline].

  63. Hara K, Fukushima T, Suzuki T, et al. Japanese SCA families with an unusual phenotype linked to a locus overlapping with SCA15 locus. Neurology. Feb 24 2004;62(4):648-51. [Medline].

  64. Miyoshi Y, Yamada T, Tanimura M, et al. A novel autosomal dominant spinocerebellar ataxia (SCA16) linked to chromosome 8q22.1-24.1. Neurology. Jul 10 2001;57(1):96-100. [Medline].

  65. Nakamura K, Jeong SY, Uchihara T, et al. SCA17, a novel autosomal dominant cerebellar ataxia caused by an expanded polyglutamine in TATA-binding protein. Hum Mol Genet. Jul 1 2001;10(14):1441-8. [Medline].

  66. Rolfs A, Koeppen AH, Bauer I, et al. Clinical features and neuropathology of autosomal dominant spinocerebellar ataxia (SCA17). Ann Neurol. Sep 2003;54(3):367-75. [Medline].

  67. Maltecca F, Filla A, Castaldo I, et al. Intergenerational instability and marked anticipation in SCA-17. Neurology. Nov 25 2003;61(10):1441-3. [Medline].

  68. Brkanac Z, Fernandez M, Matsushita M, et al. Autosomal dominant sensory/motor neuropathy with Ataxia (SMNA): Linkage to chromosome 7q22-q32. Am J Med Genet. May 8 2002;114(4):450-7. [Medline].

  69. Schelhaas HJ, Ippel PF, Hageman G, et al. Clinical and genetic analysis of a four-generation family with a distinct autosomal dominant cerebellar ataxia. J Neurol. Feb 2001;248(2):113-20. [Medline].

  70. Verbeek DS, Schelhaas JH, Ippel EF, et al. Identification of a novel SCA locus (SCA19) in a Dutch autosomal dominant cerebellar ataxia family on chromosome region 1p21-q21. Hum Genet. Oct 2002;111(4-5):388-93. [Medline].

  71. Chung MY, Lu YC, Cheng NC, Soong BW. A novel autosomal dominant spinocerebellar ataxia (SCA22) linked to chromosome 1p21-q23. Brain. 2003;June; 126(Pt 6):1293-9. [Medline].

  72. Schelhaas HJ, Verbeek DS, Van de Warrenburg BP, Sinke RJ. SCA19 and SCA22: evidence for one locus with a worldwide distribution. Brain. Jan 2004;127(Pt 1):E6; author reply E7. [Medline].

  73. Knight MA, Gardner RJ, Bahlo M, et al. Dominantly inherited ataxia and dysphonia with dentate calcification: spinocerebellar ataxia type 20. Brain. May 2004;127(Pt 5):1172-81. [Medline].

  74. Devos D, Schraen-Maschke S, Vuillaume I, et al. Clinical features and genetic analysis of a new form of spinocerebellar ataxia. Neurology. Jan 23 2001;56(2):234-8. [Medline].

  75. Vuillaume I, Devos D, Schraen-Maschke S, et al. A new locus for spinocerebellar ataxia (SCA21) maps to chromosome 7p21.3-p15.1. Ann Neurol. Nov 2002;52(5):666-70. [Medline].

  76. Verbeek DS, van de Warrenburg BP, Wesseling P, et al. Mapping of the SCA23 locus involved in autosomal dominant cerebellar ataxia to chromosome region 20p13-12.3. Brain. Nov 2004;127(Pt 11):2551-7. [Medline].

  77. Stevanin G, Bouslam N, Thobois S, et al. Spinocerebellar ataxia with sensory neuropathy (SCA25) maps to chromosome 2p. Ann Neurol. Jan 2004;55(1):97-104. [Medline].

  78. Yu GY, Howell MJ, Roller MJ, et al. Spinocerebellar ataxia type 26 maps to chromosome 19p13.3 adjacent to SCA6. Ann Neurol. Mar 2005;57(3):349-54. [Medline].

  79. van Swieten JC, Brusse E, de Graaf BM, et al. A mutation in the fibroblast growth factor 14 gene is associated with autosomal dominant cerebellar ataxia [corrected]. Am J Hum Genet. Jan 2003;72(1):191-9. [Medline].

  80. Cagnoli C, Mariotti C, Taroni F, et al. SCA28, a novel form of autosomal dominant cerebellar ataxia on chromosome 18p11.22-q11.2. Brain. Jan 2006;129(Pt 1):235-42. [Medline].

  81. Naito H, Oyanagi S. Familial myoclonus epilepsy and choreoathetosis: hereditary dentatorubral-pallidoluysian atrophy. Neurology. Aug 1982;32(8):798-807. [Medline].

  82. Koide R, Ikeuchi T, Onodera O, et al. Unstable expansion of CAG repeat in hereditary dentatorubral-pallidoluysian atrophy (DRPLA). Nat Genet. Jan 1994;6(1):9-13. [Medline].

  83. VanDyke DH, Griggs RC, Murphy MJ, Goldstein MN. Hereditary myokymia and periodic ataxia. J Neurol Sci. May 1975;25(1):109-18. [Medline].

  84. Hanson PA, Martinez LB, Cassidy R. Contractures, continuous muscle discharges, and titubation. Ann Neurol. Feb 1977;1(2):120-4. [Medline].

  85. Gancher ST, Nutt JG. Autosomal dominant episodic ataxia: a heterogeneous syndrome. Mov Disord. 1986;1(4):239-53. [Medline].

  86. Browne DL, Gancher ST, Nutt JG, et al. Episodic ataxia/myokymia syndrome is associated with point mutations in the human potassium channel gene, KCNA1. Nat Genet. Oct 1994;8(2):136-40. [Medline].

  87. Brandt T, Strupp M. Episodic ataxia type 1 and 2 (familial periodic ataxia/vertigo). Audiol Neurootol. Nov-Dec 1997;2(6):373-83. [Medline].

  88. Eunson LH, Rea R, Zuberi SM, et al. Clinical, genetic, and expression studies of mutations in the potassium channel gene KCNA1 reveal new phenotypic variability. Ann Neurol. Oct 2000;48(4):647-56. [Medline].

  89. Parker HL. Periodic ataxia. Collected Papers of the Mayo Clinic. 1946;642-5.

  90. White JC. Familial periodic nystagmus, vertigo, and ataxia. Arch Neurol. Mar 1969;20(3):276-80. [Medline].

  91. Subramony SH, Schott K, Raike RS, et al. Novel CACNA1A mutation causes febrile episodic ataxia with interictal cerebellar deficits. Ann Neurol. Dec 2003;54(6):725-31. [Medline].

  92. Spacey SD, Materek LA, Szczygielski BI, Bird TD. Two novel CACNA1A gene mutations associated with episodic ataxia type 2 and interictal dystonia. Arch Neurol. Feb 2005;62(2):314-6. [Medline].

  93. Imbrici P, Eunson LH, Graves TD, et al. Late-onset episodic ataxia type 2 due to an in-frame insertion in CACNA1A. Neurology. Sep 27 2005;65(6):944-6. [Medline].

  94. Steckley JL, Ebers GC, Cader MZ, McLachlan RS. An autosomal dominant disorder with episodic ataxia, vertigo, and tinnitus. Neurology. Oct 23 2001;57(8):1499-502. [Medline].

  95. Cader MZ, Steckley JL, Dyment DA, et al. A genome-wide screen and linkage mapping for a large pedigree with episodic ataxia. Neurology. Jul 12 2005;65(1):156-8. [Medline].

  96. Farmer TW, Mustain VM. Vestibulocerebellar ataxia. A newly defined hereditary syndrome with periodic manifestations. Arch Neurol. May 1963;8:471-80. [Medline].

  97. Vance JM, Pericak-Vance MA, Payne CS. Linkage and genetic analysis in adult onset periodic vestibulo-cerebellar ataxia: report of a new family. Am J Hum Genet. 1984;36:78S.

  98. Damji KF, Allingham RR, Pollock SC, et al. Periodic vestibulocerebellar ataxia, an autosomal dominant ataxia with defective smooth pursuit, is genetically distinct from other autosomal dominant ataxias. Arch Neurol. Apr 1996;53(4):338-44. [Medline].

  99. Escayg A, Jones JM, Kearney JA, et al. Calcium channel beta 4 (CACNB4): human ortholog of the mouse epilepsy gene lethargic. Genomics. May 15 1998;50(1):14-22. [Medline].

  100. Escayg A, De Waard M, Lee DD, et al. Coding and noncoding variation of the human calcium-channel beta4-subunit gene CACNB4 in patients with idiopathic generalized epilepsy and episodic ataxia. Am J Hum Genet. May 2000;66(5):1531-9. [Medline].

  101. Herrmann A, Braathen GJ, Russell MB. [Episodic ataxias]. Tidsskr Nor Laegeforen. Aug 11 2005;125(15):2005-7. [Medline].

  102. Auburger G, Ratzlaff T, Lunkes A, et al. A gene for autosomal dominant paroxysmal choreoathetosis/spasticity (CSE) maps to the vicinity of a potassium channel gene cluster on chromosome 1p, probably within 2 cM between D1S443 and D1S197. Genomics. Jan 1 1996;31(1):90-4. [Medline].

  103. Müller U, Steinberger D, Németh AH. Clinical and molecular genetics of primary dystonias. Neurogenetics. Mar 1998;1(3):165-77. [Medline].

  104. Ferguson FR, Critchley M. A clinical study of an heredo-familial disease resembling disseminated sclerosis. Brain. 1929;52:203-25.

  105. Gayle Jr RF, Williams JP. A familial disease of the central nervous system resembling multiple sclerosis. Sth Med J. 1933;26:242-6.

  106. Mahloudji M. Hereditary spastic ataxia simulating disseminated sclerosis. J Neurol Neurosurg Psychiatry. Dec 1963;26:511-3. [Medline].

  107. Meijer IA, Hand CK, Grewal KK, et al. A locus for autosomal dominant hereditary spastic ataxia, SAX1, maps to chromosome 12p13. Am J Hum Genet. Mar 2002;70(3):763-9. [Medline].

  108. Grewal KK, Stefanelli MG, Meijer IA, et al. A founder effect in three large Newfoundland families with a novel clinically variable spastic ataxia and supranuclear gaze palsy. Am J Med Genet A. 2004;Dec 15;131(3):249-54. [Medline].

  109. Ochrynik T, Bulski T, Modzelewski M, Szatkowski M. Olivopontocerebellar atrophy in MRI spectroscopy– case report. Pol J Radiol. 2007;72(pt 1):100-2.

  110. Heo JH, Lee ST, Chu K, Kim M. The efficacy of combined estrogen and buspirone treatment in olivopontocerebellar atrophy. J Neurol Sci. Aug 15 2008;271(1-2):87-90. [Medline].

  111. Armstrong RA, Lantos PL, Cairns NJ. Spatial patterns of alpha-synuclein positive glial cytoplasmic inclusions in multiple system atrophy. Mov Disord. Jan 2004;19(1):109-12. [Medline].

  112. Barth PG, Blennow G, Lenard HG, et al. The syndrome of autosomal recessive pontocerebellar hypoplasia, microcephaly, and extrapyramidal dyskinesia (pontocerebellar hypoplasia type 2): compiled data from 10 pedigrees. Neurology. Feb 1995;45(2):311-7. [Medline].

  113. Barth PG, Vrensen GF, Uylings HB, et al. Inherited syndrome of microcephaly, dyskinesia and pontocerebellar hypoplasia: a systemic atrophy with early onset. J Neurol Sci. Jun 1990;97(1):25-42. [Medline].

  114. Berciano J. Olivopontocerebellar atrophy. A review of 117 cases. J Neurol Sci. Feb 1982;53(2):253-72. [Medline].

  115. Berciano J, Boesch S, Pérez-Ramos JM, Wenning GK. Olivopontocerebellar atrophy: toward a better nosological definition. Mov Disord. Oct 2006;21(10):1607-13. [Medline].

  116. Berciano J, Tolosa E. Olivopontocerebellar atrophy. In: Jankovic J, Tolosa E, eds. Parkinson's Disease and Movement Disorders. Baltimore, Md: Williams & Wilkins; 1993:163-89.

  117. Berent S, Giordani B, Gilman S, et al. Patterns of neuropsychological performance in multiple system atrophy compared to sporadic and hereditary olivopontocerebellar atrophy. Brain Cogn. Nov 2002;50(2):194-206. [Medline].

  118. Bird TD. Hereditary Ataxia Overview. GeneReviews. 2006;[Full Text].

  119. Boder E, Sedgwick RP. Ataxia-telangiectasia; a familial syndrome of progressive cerebellar ataxia, oculocutaneous telangiectasia and frequent pulmonary infection. Pediatrics. 1958;Apr; 21(4):526-54. [Medline].

  120. Brown S. On hereditary ataxia, with a series of twenty-one cases. Brain. 1892;15:250-82.

  121. Cervinkova M, Mandakova P, Síma P. Changes in proliferation activity and relative distributions of lymphoid cell subpopulations in congenitally athymic nu/nu mice and Lurcher mice with spontaneous olivopontocerebellar degeneration. Folia Microbiol (Praha). 2006;51(5):497-505. [Medline].

  122. Chokroverty S, Khedekar R, Derby B, et al. Pathology of olivopontocerebellar atrophy with glutamate dehydrogenase deficiency. Neurology. Nov 1984;34(11):1451-5. [Medline].

  123. Dekoskey ST, Kaufer DI, Lopez OL. Bradley WG, Daroff, RB, Fenichel GM, Jankovic J, eds. Neurology in Clinical Practice. Boston, Mass: Butterworth-Heinemann; 2005:1928.

  124. Duvoisin RC, Chokroverty S, Lepore F, Nicklas W. Glutamate dehydrogenase deficiency in patients with olivopontocerebellar atrophy. Neurology. Oct 1983;33(10):1322-6. [Medline].

  125. Fahn S, Przedborski S. Parkinsonism: multiple system atrophy. In: Rowland L, ed. Merritt's Neurology. 11th ed. New York, NY: Lippincott Williams & Wilkins; 2005:836-7.

  126. Hammond EJ, Wilder BJ. Evoked potentials in olivopontocerebellar atrophy. Arch Neurol. Jun 1983;40(6):366-9. [Medline].

  127. Holmes GM. A form of familial degeneration of the cerebellum. Brain. 1907;30:466-89.

  128. Ishizawa K, Komori T, Arai N, Mizutani T, Hirose T. Glial cytoplasmic inclusions and tissue injury in multiple system atrophy: A quantitative study in white matter (olivopontocerebellar system) and gray matter (nigrostriatal system). Neuropathology. Jun 2008;28(3):249-57. [Medline].

  129. Koeppen AH. The hereditary ataxias. J Neuropathol Exp Neurol. Jun 1998;57(6):531-43. [Medline].

  130. Kofler M, Muller J, Seppi K, Wenning GK. Exaggerated auditory startle responses in multiple system atrophy: a comparative study of parkinson and cerebellar subtypes. Clin Neurophysiol. Mar 2003;114(3):541-7. [Medline].

  131. Kuriyama N, Mizuno T, Iida A, et al. Autonomic nervous evaluation in the early stages of olivopontocerebellar atrophy. Auton Neurosci. Dec 30 2005;123(1-2):87-93. [Medline].

  132. Landis DM, Rosenberg RN, Landis SC, et al. Olivopontocerebellar degeneration. Clinical and ultrastructural abnormalities. Arch Neurol. Nov 1974;31(5):295-307. [Medline].

  133. Louis-Bar D. Sur un syndrome progressif cormprenant des telangiectasies capillaires cutanees et conjonctivales symetriques, e disposition naevoïde et des troubles cerebelleux. Confinia Neurologica. 1941;4:32-42.

  134. Luo W, Ouyang Z, Guo Y, Chen Y, Ding M. Spinal muscular atrophy combined with sporadic olivopontocerebellar atrophy. Clin Neurol Neurosurg. Sep 2008;110(8):855-8. [Medline].

  135. Mascalchi M, Cosottini M, Lolli F, Salvi F, Tessa C, Macucci M, et al. Proton MR spectroscopy of the cerebellum and pons in patients with degenerative ataxia. Radiology. May 2002;223(2):371-8. [Medline].

  136. McKusick VA et al. Online Mendelian Inheritance in Man (OMIM). [Full Text].

  137. Nonne M. Uber eine eigentumliche familiare Erkrankungsform des Zentralnervensystems. Archiv Psychiatrie Nervenkrankheiten, Berlin. 1891;22:283-316.

  138. Oshima K. Olivopontocerebellar atrophy (OPCA) in corticobasal degeneration (CBD): a quantitative study of three cases of atypical CBD: OI-A22. Neuropathology. 2007;27(pt 2):166.

  139. Papp MI, Kahn JE, Lantos PL. Glial cytoplasmic inclusions in the CNS of patients with multiple system atrophy (striatonigral degeneration, olivopontocerebellar atrophy and Shy-Drager syndrome). J Neurol Sci. Dec 1989;94(1-3):79-100. [Medline].

  140. Papp MI, Lantos PL. Accumulation of tubular structures in oligodendroglial and neuronal cells as the basic alteration in multiple system atrophy. J Neurol Sci. Feb 1992;107(2):172-82. [Medline].

  141. Penney JB. Multiple systems atrophy and nonfamilial olivopontocerebellar atrophy are the same disease. Ann Neurol. May 1995;37(5):553-4. [Medline].

  142. Rinne JO, Burn DJ, Mathias CJ, et al. Positron emission tomography studies on the dopaminergic system and striatal opioid binding in the olivopontocerebellar atrophy variant of multiple system atrophy. Ann Neurol. May 1995;37(5):568-73. [Medline].

  143. Roper AH, Brown RH. Adam's and Victor's The Principles of Neurology. 8th ed. New York, NY: McGraw-Hill; 2005:925-6; 935-6.

  144. Sorbi S, Tonini S, Giannini E, et al. Abnormal platelet glutamate dehydrogenase activity and activation in dominant and nondominant olivopontocerebellar atrophy. Ann Neurol. Mar 1986;19(3):239-45. [Medline].

  145. Syllaba L, Henner K. Contribution a l'etude de l'indendance de l'athetose double idiopathique et congenitale. Atteinte familiale, syndrome dystrophique, signe du resau vasculaire conjonctival, integrite psychique. Revue neurologique. 1926;1:541-60.

  146. Testa D, Tiranti V, Girotti F. Unusual association of sporadic olivopontocerebellar atrophy and motor neuron disease. Neurol Sci. Dec 2002;23(5):243-5. [Medline].

[ CLOSE WINDOW ]

Further Reading

[ CLOSE WINDOW ]

Keywords

spinocerebellar ataxia, dysarthria, dysphagia, ataxia, olivopontocerebellar atrophy, multiple system atrophy, MSA, autosomal dominant cerebellar atrophy, spinocerebellar atrophy, ADCA, Menzel OPCA, Menzel ataxia, Schut-Haymaker OPCA, Schut-Haymaker ataxia, Dejerine-Thomas ataxia, Holguin ataxia, Wadia-Swami syndrome, Sanger-Brown ataxia, Holmes ataxia, Marie ataxia, Nonne syndrome, ataxia of Holmes, SCA, OPCA

[ CLOSE WINDOW ]

Contributor Information and Disclosures

Author

Christina J Azevedo MD, Staff Physician, Department of Neurology, Dartmouth-Hitchcock Medical Center
Christina J Azevedo MD is a member of the following medical societies: American Academy of Neurology, American College of Physicians, and Oregon Medical Association
Disclosure: Nothing to disclose.

Coauthor(s)

Stephen A Berman, MD, PhD, Professor, Department of Internal Medicine, Section of Neurology, Dartmouth Medical School; Chief, Neurology Service, White River Junction Veterans Medical Center
Stephen A Berman, MD, PhD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Neurology, and Phi Beta Kappa
Disclosure: Nothing to disclose.

Medical Editor

Howard A Crystal, MD, Professor, Departments of Neurology and Pathology, State University of New York Downstate; Consulting Staff, Department of Neurology, University Hospital and Kings County Hospital Center
Howard A Crystal, MD is a member of the following medical societies: American Academy of Neurology and American Neurological Association
Disclosure: Medivations Honoraria Consulting

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Nestor Galvez-Jimenez, MD, MSc, MHA, Chairman, Department of Neurology, Program Director, Movement Disorders, Department of Neurology, Division of Medicine, Cleveland Clinic Florida
Nestor Galvez-Jimenez, MD, MSc, MHA is a member of the following medical societies: American Academy of Neurology, American College of Physicians, and Movement Disorders Society
Disclosure: Nothing to disclose.

Chief Editor

Selim R Benbadis, MD, Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, University of South Florida School of Medicine, Tampa General Hospital
Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, and American Medical Association
Disclosure: Nothing to disclose.

 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.