Acta Neuropathologica

, Volume 112, Issue 1, pp 43–51 | Cite as

Frequency and clinicopathological characteristics of alcoholic cerebellar degeneration in Japan: a cross-sectional study of 1,509 postmortems

  • Osamu Yokota
  • Kuniaki Tsuchiya
  • Seishi Terada
  • Kenichi Oshima
  • Hideki Ishizu
  • Masaaki Matsushita
  • Shigetoshi Kuroda
  • Haruhiko Akiyama
Original Paper


Alcoholic cerebellar degeneration (ACD) is a pivotal neurological complication in alcoholics. However, although there are a few autopsy reports and some data on its frequency, it is considered very rare in Japan. The aims of this study were (1) to estimate the frequency of the disease in Japanese autopsy cases, and (2) to examine the clinicopathological features of symptomatic and asymptomatic cases of ACD. We reviewed the records of 1,509 Japanese autopsies obtained from three autopsy series in Japan, and selected all 55 cases (3.6%) with alcoholism. On neuropathological reexamination, ACD was confirmed in six male alcoholics [0.4% of all subjects; 10.9% of all alcoholics; mean age at death 59.3±13.4 years (± SD)], including three asymptomatic cases. These frequencies were much lower than some previous Western findings, but more common than that has been expected in Japan. The frequencies of memory impairment and ataxia in ACD cases were significantly higher than those in alcoholics without any alcohol-related pathologies. In ACD cases, loss of Purkinje cells, narrowing of the width of the molecular layer, and tissue rarefaction in the granular layer were observed in the anterior and superior portions of the vermis of the cerebellum. In adjacent regions, the Purkinje cell and molecular layers were more mildly affected. The distribution of severely affected regions was more restricted in the asymptomatic cases than in the symptomatic cases. This study confirmed the frequency of asymptomatic cerebellar degeneration in alcoholics, suggesting that early intervention in alcoholism in the subclinical phase is important to prevent the development of cerebellar symptoms.


Alcohol Alcohol dependence Asymptomatic Cerebellar degeneration Frequency 



We would like to thank Ms. M. Onbe (Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences) and Ms. A. Kajitani (Department of Laboratory Medicine, Zikei Institute of Psychiatry) for collecting clinical information, and Mr. A. Sasaki for help with the creation of the manuscript. This work was supported by a grant in aid for scientific research from the Ministry of Education, Culture, Sports, Science and Technology (14570957) and a research grant from the Zikei Institute of Psychiatry.


  1. 1.
    Akai J, Akai K, Arai K (1987) Alcoholic cerebellar degeneration: a case study. Rinsho Shinkeigaku 27:1480–1485PubMedGoogle Scholar
  2. 2.
    American Psychiatric Association (1994) Diagnostic and statistical manual of mental disorders, 4th edn (DSM-IV). American Psychiatric Association, Washington DCGoogle Scholar
  3. 3.
    Ando S, Murakami K (1985) Cerebellar degeneration in chronic alcoholism: with special reference to an autopsied case showing the restricted form of cerebellar cortical degeneration. No To Shinkei 37:329–336PubMedGoogle Scholar
  4. 4.
    Baker KG, Harding AJ, Halliday GM, Kril JJ, Harper CG (1999) Neuronal loss in functional zones of the cerebellum of chronic alcoholics with and without Wernicke’s encephalopathy. Neuroscience 91:429–438PubMedCrossRefGoogle Scholar
  5. 5.
    Caine D, Halliday GM, Kril JJ, Harper CG (1997) Operational criteria for the classification of chronic alcoholics: identification of Wernicke’s encephalopathy. J Neurol Neurosurg Psychiatry 62:51–60PubMedGoogle Scholar
  6. 6.
    Estrin WJ (1987) Alcoholic cerebellar degeneration is not a dose-dependent phenomenon. Alcohol Clin Exp Res 11:372–375PubMedCrossRefGoogle Scholar
  7. 7.
    Glanz J, Grant B, Monteiro M, Tabakoff B; WHO/ISBRA study on state and trait markers of alcohol use and dependence investigators (2002) WHO/ISBRA study on state and trait markers of alcohol use and dependence: analysis of demographic, behavioral, physiologic, and drinking variables that contribute to dependence and seeking treatment. International Society on Biomedical Research on Alcoholism. Alcohol Clin Exp Res 26: 1047–1061Google Scholar
  8. 8.
    Harper C (1979) Wernicke’s encephalopathy: a more common disease than realized. A neuropathological study of 51 cases. J Neurol Neurosurg Psychiatry 42:226–231PubMedCrossRefGoogle Scholar
  9. 9.
    Harper C, Dixon G, Sheedy D, Garrick T (2003) Neuropathological alterations in alcoholic brains. Studies arising from the New South Wales Tissue Resource Centre. Prog Neuropsychopharmacol Biol Psychiatry 27:951–961PubMedCrossRefGoogle Scholar
  10. 10.
    Helzer JE, Canino GJ, Yeh EK, Bland RC, Lee CK, Hwu HG, Newman S (1990) Alcoholism–North America and Asia. A comparison of population surveys with the diagnostic interview schedule. Arch Gen Psychiatry 47:313–319PubMedGoogle Scholar
  11. 11.
    Hillbom M, Muuronen A, Holm L, Hindmarsh T (1986) The clinical versus radiological diagnosis of alcoholic cerebellar degeneration. J Neurol Sci 73:45–53PubMedCrossRefGoogle Scholar
  12. 12.
    Ishii N, Nishihara Y, Horie A (1980) Clinico-pathological studies on 62 autopsy cases of chronic alcoholics. Seishin Igaku (Clinical Psychiatry) 22:639–646Google Scholar
  13. 13.
    Iwabuchi K, Yagishita S, Itoh Y, Amano N, Saitoh A (1990) An autopsied case of alcoholic cerebellar degeneration with spastic paraplegia and neuropathy. No To Shinkei 42:489–496PubMedGoogle Scholar
  14. 14.
    Kawakami N, Shimizu H, Haratani T, Iwata N, Kitamura T (2004) Lifetime and 6-month prevalence of DSM-III-R psychiatric disorders in an urban community in Japan. Psychiatry Res 121:293–301PubMedCrossRefGoogle Scholar
  15. 15.
    Kessler RC, McGonagle KA, Zhao S, Nelson CB, Hughes M, Eshleman S, Wittchen HU, Kendler KS (1994) Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States. Results from the National Comorbidity Survey. Arch Gen Psychiatry 51:8–19PubMedGoogle Scholar
  16. 16.
    Kril JJ, Butterworth RF (1997) Diencephalic and cerebellar pathology in alcoholic and nonalcoholic patients with end-stage liver disease. Hepatology 26:837–841PubMedCrossRefGoogle Scholar
  17. 17.
    Kromhout D, Bloemberg BP, Feskens EJ, Hertog MG, Menotti A, Blackburn H (1996) Alcohol, fish, fibre and antioxidant vitamins intake do not explain population differences in coronary heart disease mortality. Int J Epidemiol 25:753–759PubMedCrossRefGoogle Scholar
  18. 18.
    Lindboe CF, Loberg EM (1988) The frequency of brain lesions in alcoholics. Comparison between the 5-year periods 1975–1979 and 1983–1987. J Neurol Sci 88:107–113PubMedCrossRefGoogle Scholar
  19. 19.
    Luft AR, Skalej M, Schulz JB, Welte D, Kolb R, Burk K, Klockgether T, Voight K (1999) Patterns of age-related shrinkage in cerebellum and brainstem observed in vivo using three-dimensional MRI volumetry. Cortex 9:712–721CrossRefGoogle Scholar
  20. 20.
    Maschke M, Weber J, Bonnet U, Dimitrova A, Bohrenkamper J, Sturm S, Muller BW, Gastpar M, Diener HC, Forsting M, Timmann D (2005) Vermal atrophy of alcoholics correlate with serum thiamine levels but not with dentate iron concentrations as estimated by MRI. J Neurol 252:704–711PubMedCrossRefGoogle Scholar
  21. 21.
    Matsushita M, Hanawa S (1983) An autopsied case with alcoholic cerebellar degeneration. Seishin Shinkeigaku Zasshi 85:542–560PubMedGoogle Scholar
  22. 22.
    Melgaard B, Ahlgren P (1986) Ataxia and cerebellar atrophy in chronic alcoholics. J Neurol 233:13–15PubMedCrossRefGoogle Scholar
  23. 23.
    Mizutani T, Maeda S, Hayakawa K, Tanaka U, Hirahata S, Kamoshita H, Taketani T, Morimatsu Y (1988) Paraneoplastic cortical cerebellar degeneration. A neuropathological study of an autopsy case in comparison with cortical cerebellar degeneration in alcoholics. Acta Neuropathol (Berl) 77:206–212Google Scholar
  24. 24.
    Nicolas JM, Fernandez-Sola J, Robert J, Antunez E, Cofan M, Cardenal C, Sacanella E, Estruch R, Urbano-Marquez A (2000) High ethanol intake and malnutrition in alcoholic cerebellar shrinkage. QJM 93:449–456PubMedCrossRefGoogle Scholar
  25. 25.
    Nukada A (1973) Urbanization and consumption of alcoholic beverages. J Hum Ergol (Tokyo) 1:29–44Google Scholar
  26. 26.
    Phillips SC, Harper CG, Kril J (1987) A quantitative histological study of the cerebellar vermis in alcoholic patients. Brain 110:301–314PubMedCrossRefGoogle Scholar
  27. 27.
    Raz N, Dupuis JH, Briggs SD, McGavran C, Acker JD (1998) Differential effects of age and sex on the cerebellar hemispheres and the vermis: a prospective MR study. AJNR Am J Neuroradiol 19:65–71PubMedGoogle Scholar
  28. 28.
    Smith EM (1982) An analysis of cohort mortality from tongue cancer in Japan, England and Wales and the United States. Int J Epidemiol 11:329–335PubMedCrossRefGoogle Scholar
  29. 29.
    Stamler J, Elliott P, Chan Q for the INTERMAP Research Group (2003) INTERMAP Appendix Tables, Tables of Contents (Tables B). J Hum Hypertens 17:759–775Google Scholar
  30. 30.
    Sullivan EV, Deshmukh A, Desmond JE, Lim KO, Pfefferbaum A (2000) Cerebellar volume decline in normal aging, alcoholism, and Korsakoff’s syndrome: relation to ataxia. Neuropsychology 14:341–352PubMedCrossRefGoogle Scholar
  31. 31.
    Torvik A, Torp S (1986) The prevalence of alcoholic cerebellar atrophy. A morphometric and histological study of an autopsy material. J Neurol Sci 75:43–51PubMedCrossRefGoogle Scholar
  32. 32.
    Torvik A, Lindboe CF, Rogde S (1982) Brain lesions in alcoholics. A neuropathological study with clinical correlations. J Neurol Sci 56:233–248PubMedCrossRefGoogle Scholar
  33. 33.
    Tsuchiya K, Watabiki S, Shiojiri T, Matsumoto A, Tsukagoshi H (1993) Alcoholic cerebellar degeneration with pyramidal sign–in relation to alcoholic myelopathy. No To Shinkei 45:169–175PubMedGoogle Scholar
  34. 34.
    Tsuchiya K, Ozawa E, Saito F, Irie H, Mizutani T (1994) Neuropathology of late cortical cerebellar atrophy in Japan: distribution of cerebellar change on an autopsy case and review of Japanese cases. Eur Neurol 34:253–262PubMedCrossRefGoogle Scholar
  35. 35.
    Victor M, Laureno R (1978) Neurologic complications of alcohol abuse: epidemiologic aspects. Adv Neurol 19:603–617PubMedGoogle Scholar
  36. 36.
    Victor M, Adams RD, Mancall EL (1959) A restricted form of cerebellar degeneration occurring in alcoholic patients. Arch Neurol 1:579–688Google Scholar
  37. 37.
    Yokota O, Sasaki K, Fujisawa Y, Takahashi J, Terada S, Ishihara T, Nakashima H, Kugo A, Ata T, Ishizu H, Kuroda S (2005) Frequency of early and late-onset dementias in a Japanese memory disorders clinic. Eur J Neurol 12:782–790PubMedCrossRefGoogle Scholar
  38. 38.
    Zhou BF, Stamler J, Dennis B, Moag-Stahlberg A, Okuda N, Robertson C, Zhao L, Chan Q, Elliott P; INTERMAP Research Group (2003) Nutrient intakes of middle-aged men and women in China, Japan, United Kingdom, and United States in the late 1990s: the INTERMAP study. J Hum Hypertens 17:623–630Google Scholar

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Osamu Yokota
    • 1
    • 2
  • Kuniaki Tsuchiya
    • 1
    • 3
  • Seishi Terada
    • 2
  • Kenichi Oshima
    • 4
  • Hideki Ishizu
    • 5
  • Masaaki Matsushita
    • 4
  • Shigetoshi Kuroda
    • 2
  • Haruhiko Akiyama
    • 1
  1. 1.Department of NeuropathologyTokyo Institute of Psychiatry TokyoJapan
  2. 2.Department of NeuropsychiatryOkayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOkayamaJapan
  3. 3.Department of Laboratory Medicine and PathologyTokyo Metropolitan Matsuzawa HospitalTokyoJapan
  4. 4.Department of PsychiatryTokyo Metropolitan Matsuzawa HospitalTokyoJapan
  5. 5.Department of Laboratory and MedicineZikei Institute of PsychiatryOkayamaJapan

Personalised recommendations