Skip to main content

Advertisement

SpringerLink
Log in

Vermal atrophy of alcoholics correlate with serum thiamine levels but not with dentate iron concentrations as estimated by MRI

  • ORIGINAL CONTRIBUTION
  • Published:
Journal of Neurology Aims and scope Submit manuscript

Abstract

Chronic alcohol consumption is frequently accompanied by cerebellar degeneration. The exact aetiology of alcoholic cerebellar degeneration is still a matter of debate. The aim of the present study was to investigate whether patients with chronic alcohol consumption exhibit a decrease in dentate nuclei intensity as measured by MRI, and if so, whether this decrease correlates with cerebellar atrophy as revealed by MR imaging or with clinical signs of cerebellar ataxia. A decrease in dentate nuclei intensity would indirectly indicate that iron accumulation, and therefore, oxidative stress may play a role in alcoholic cerebellar degeneration.

MRI of 45 alcoholics and 44 ageand sex–matched healthy control subjects was performed using a 3D–T1–weighted fast low angle shot (FLASH) echo sequence. Signal intensities of the dentate nuclei and cerebellar white matter were bilaterally measured. Planimetric measurements of cerebellar size were performed using a 3D–T1–weighted magnetization prepared rapid acquisition gradient echo (MPRAGE) sequence.

Results demonstrated that dentate nuclei intensity was not significantly decreased in patients with chronic alcohol consumption (mean ± SD signal intensity 65.36 ± 13.0) if compared with control subjects (mean ± SD signal intensity 68.95 ± 9.4) (p = 0.15). Dentate nuclei intensity did not correlate with cerebellar size neither in control subjects nor in alcoholics. In contrast, vitamin B1 level correlated with cerebellar size in alcoholics even if the vitamin B1 concentration was within normal values (r = 0.344, p = 0.028). These results support the view that thiamine deficiency rather than direct neurotoxic effects of alcohol is the main causative factor for the development of alcoholic cerebellar degeneration.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Adamolekun B, Eniola A (1993) Thiamine-responsive acute cerebellar ataxia following febrile illness. Cent Afr J Med 39:40–41

    CAS  PubMed  Google Scholar 

  2. Adams PC, Agnew S (1996) Alcoholism in hereditary hemochromatosis revisited: prevalence and clinical consequences among homozygous siblings. Hepatology 23:724–727

    CAS  PubMed  Google Scholar 

  3. Agartz I, Brag S, Franck J, Hammarberg A, Okugawa G, Svinhufvud K, Bergman H (2003) MR volumetry during acute alcohol withdrawal and abstinence: a descriptive study. Alcohol Alcohol 38:71–78

    PubMed  Google Scholar 

  4. Aoki S, Okada Y, Nishimura K, Barkovich AJ, Kjos BO, Brasch RC, Norman D (1989) Normal deposition of brain iron in childhood and adolescence: MR imaging at 1.5 T. Radiology 172:381–385

    CAS  PubMed  Google Scholar 

  5. Baker KG, Harding AJ, Halliday GM, et al. (1999) Neuronal loss in functional zones of the cerebellum of chronic alcoholics with and without Wernicke’s encephalopathy. Neuroscience 91:429–438

    Google Scholar 

  6. Bendszus M, Weijers HG, Wiesbeck G, Warmuth-Metz M, Bartsch AJ, Engels S, Boning J, Solymosi L (2001) Sequential MR imaging and proton MR spectroscopy in patients who underwent recent detoxification for chronic alcoholism: correlation with clinical and neuropsychological data. AJNR Am J Neuroradiol 22:1926–1932

    CAS  PubMed  Google Scholar 

  7. Butterworth RF (1993) Pathophysiology of cerebellar dysfunction in the Wernicke-Korsakoff syndrome. Can J Neurol Sci 20:S123–S126

    PubMed  Google Scholar 

  8. Collins GH, Converse WK (1970) Cerebellar degeneration in thiamine-deficient rats. Am J Pathol 58:219–233

    CAS  PubMed  Google Scholar 

  9. Diener HC, Muller A, Thron A, Poremba M, Dichgans J, Rapp H (1986) Correlation of clinical signs with CT findings in patients with cerebellar disease. J Neurol 233:5–12

    Article  CAS  PubMed  Google Scholar 

  10. Drayer B, Burger P, Darwin R, Riederer S, Herfkens R, Johnson GA (1986) MRI of brain iron. AJR Am J Roentgenol 147:103–110

    CAS  PubMed  Google Scholar 

  11. Fadda F, Rossetti ZL (1998) Chronic ethanol consumption: from neuroadaptation to neurodegeneration. Prog Neurobiol 56:385–431

    CAS  PubMed  Google Scholar 

  12. Fletcher LM, Dixon JL, Purdie DM, Powell LW, Crawford DH (2002) Excess alcohol greatly increases the prevalence of cirrhosis in hereditary hemochromatosis. Gastroenterology 122:281–289

    PubMed  Google Scholar 

  13. Gonthier B, Eysseric H, Soubeyran A, Daveloose D, Saxod R, Barret L (1997) Free radical production after exposure of astrocytes and astrocytic C6 glioma cells to ethanol. Preliminary results. Free Radic Res 27:645–656

    CAS  PubMed  Google Scholar 

  14. Gotz ME, Janetzky B, Pohli S, Gottschalk A, Gsell W, Tatschner T, Ransmayr G, Leblhuber F, Gerlach M, Reichmann H, Riederer P, Boning J (2001) Chronic alcohol consumption and cerebral indices of oxidative stress: is there a link? Alcohol Clin Exp Res 25:717–725

    CAS  PubMed  Google Scholar 

  15. Harper C (1998) The neuropathology of alcohol-specific brain damage, or does alcohol damage the brain? J Neuropathol Exp Neurol 57:101–110

    CAS  PubMed  Google Scholar 

  16. Haubek A, Lee K (1979) Computed tomography in alcoholic cerebellar atrophy. Neuroradiology 18:77–79

    Article  CAS  PubMed  Google Scholar 

  17. Joyce EM (1994) Aetiology of alcoholic brain damage: alcoholic neurotoxicity or thiamine malnutrition? Br Med Bull 50:99–114

    CAS  PubMed  Google Scholar 

  18. Jurczuk M, Brzoska MM, Rogalska J, Moniuszko-Jakoniuk J (2003) Iron body status of rats chronically exposed to cadmium and ethanol. Alcohol Alcohol 38:202–207

    CAS  PubMed  Google Scholar 

  19. Koller WC, Glatt SL, Perlik S, Huckman MS, Fox JH (1981) Cerebellar atrophy demonstrated by computed tomography. Neurology 31:405–412

    CAS  PubMed  Google Scholar 

  20. Lavoie J, Butterworth RF (1995) Reduced activities of thiamine-dependent enzymes in brains of alcoholics in the absence ofWernicke’s encephalopathy. Alcohol Clin Exp Res 19:1073–1077

    CAS  PubMed  Google Scholar 

  21. 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 88:107–113

    CAS  PubMed  Google Scholar 

  22. Marie P, Foix C, Alajouanine T (1922) Atrophie cérébelleuse tardive à prédominance corticale. Rev Neurol (Paris) 38:849–885, 38:1082–1111

    Google Scholar 

  23. Maschke M, Weber J, Dimitrova A, Bonnet U, Bohrenkämper J, Sturm S, Kindsvater K, Müller BW, Gastpar M, Diener HC, Forsting M, Timmann D (2004) Age-related changes of the dentate nuclei in normal adults as revealed by 3D fast low angle shot (FLASH) echo sequence magnetic resonance imaging. J Neurol 251:740–746

    Article  PubMed  Google Scholar 

  24. Miyajima H, Kono S, Takahashi Y, Sugimoto M, Sakamoto M, Sakai N (2001) Cerebellar ataxia associated with heteroallelic ceruloplasmin gene mutation. Neurology 57:2205–2210

    CAS  PubMed  Google Scholar 

  25. Montoliu C, Valles S, Renau-Piqueras J, Guerri C (1994) Ethanol-induced oxygen radical formation and lipid peroxidation in rat brain: effect of chronic alcohol consumption. J Neurochem 63:1855–1862

    CAS  PubMed  Google Scholar 

  26. Morita H, Ikeda S, Yamamoto K, Morita S, Yoshida K, Nomoto S, Kato M, Yanagisawa N (1995) Hereditary ceruloplasmin deficiency with hemosiderosis: a clinicopathological study of a Japanese family. Ann Neurol 37:646–656

    Article  CAS  PubMed  Google Scholar 

  27. 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 93:449–456

    Article  CAS  PubMed  Google Scholar 

  28. Nordmann R, Ribiere C, Rouach H (1987) Involvement of iron and ironcatalyzed free radical production in ethanol metabolism and toxicity. Enzyme 37:57–69

    CAS  PubMed  Google Scholar 

  29. Ogg RJ, Steen RG (1998) Age-related changes in brain T1 are correlated with iron concentration. Magn Reson Med 40:749–753

    CAS  PubMed  Google Scholar 

  30. O’Neill J, Cardenas VA, Meyerhoff DJ (2001) Effects of abstinence on the brain: quantitative magnetic resonance imaging and magnetic resonance spectroscopic imaging in chronic alcohol abuse. Alcohol Clin Exp Res 25:1673–1682

    Article  CAS  PubMed  Google Scholar 

  31. Pannunzio P, Hazell AS, Pannunzio M, Rao KV, Butterworth RF (2000) Thiamine deficiency results in metabolic acidosis and energy failure in cerebellar granule cells: an in vitro model for the study of cell death mechanisms in Wernicke’s encephalopathy. J Neurosci Res 62:286–292

    CAS  PubMed  Google Scholar 

  32. Phillips SC, Harper CG, Kril J (1987) A quantitative histological study of the cerebellar vermis in alcoholic patients. Brain 110:301–314

    PubMed  Google Scholar 

  33. Rajgopal Y, Chetty CS, Vemuri MC (2003) Differential modulation of apoptosis-associated proteins by ethanol in rat cerebral cortex and cerebellum. Eur J Pharmacol 470:117–124

    Article  CAS  PubMed  Google Scholar 

  34. Ron MA, Acker W, Shaw GK, Lishman WA (1982) Computerized tomography of the brain in chronic alcoholism: a Survey and follow-up study. Brain 105:497–514

    PubMed  Google Scholar 

  35. Scheurich A, Muller MJ, Wetzel H, Anghelescu I, Klawe C, Ruppe A, Lorch B, Himmerich H, Heidenreich M, Schmid G, Hautzinger M, Szegedi A (2000) Reliability and validity of the German version of the European Addiction Severity Index (EuropASI). J Stud Alcohol 61:916–919

    CAS  PubMed  Google Scholar 

  36. Scholz E, Diener HC, Dichgans J, Langohr HD, Schied W, Schupmann A (1986) Incidence of peripheral neuropathy and cerebellar ataxia in chronic alcoholics. J Neurol 233:212–217

    Article  CAS  PubMed  Google Scholar 

  37. Shear PK, Sullivan EV, Lane B, Pfefferbaum A (1996) Mammillary body and cerebellar shrinkage in chronic alcoholics with and without amnesia. Alcohol Clin Exp Res 20:1489–1495

    CAS  PubMed  Google Scholar 

  38. 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 14:341–352

    Article  CAS  PubMed  Google Scholar 

  39. Tavares MA, Paula-Barbosa MM, Cadete-Leite A (1987) Chronic alcohol consumption reduces the cortical layer volumes and the number of neurons of the rat cerebellar cortex. Alcohol Clin Exp Res 11:315–319

    CAS  PubMed  Google Scholar 

  40. Thomas LO, Boyko OB, Anthony DC, Burger PC (1993) MR detection of brain iron. AJNR Am J Neuroradiol 14:1043–1048

    CAS  PubMed  Google Scholar 

  41. Timmann-Braun D, Diener HC (2001) Alcoholic cerebellar degeneration (including ataxias that are due to other toxic causes). In: Klockgether T (ed) Handbook of ataxia disorders. Marcel Dekker inc., New York, USA, pp 571–601

  42. Torvik A (1987) Brain lesions in alcoholics: neuropathological observations. Acta Med Scand 717(Suppl):47–54

    CAS  Google Scholar 

  43. Trouillas P, Takayanagi T, Hallett M, Currier RD, Subramony SH, Wessel K, Bryer A, Diener HC, Massaquoi S, Gomez CM, Coutinho P, Ben Hamida M, Campanella G, Filla A, Schut L, Timann D, Honnorat J, Nighoghossian N, Manyam B (1997) International Cooperative Ataxia Rating Scale for pharmacological assessment of the cerebellar syndrome. The Ataxia Neuropharmacology Committee of the World Federation of Neurology. J Neurol Sci 145:205–211

    CAS  PubMed  Google Scholar 

  44. Victor M, Adams RD, Mancall ED (1959) A restricted form of cerebellar cortical degeneration occurring in alcoholic patients. Arch Neurol 1:579–688

    Google Scholar 

  45. Victor M, Adams RD, Collins GH (1989) The Wernicke-Korsakoff syndrome and related neurologic disorders due to alcoholism and malnutrition. F.A Davis, Philadelphia

  46. Vry M, Haerter K, Kastrup O, Gizweski E, Frings M, Maschke M (2004) Vitamine- B12-deficiency causing isolated and partially reversible leukoencephalopathy. J Neurol (in press)

  47. Waldvogel D, van Gelderen P, Hallett M (1999) Increased iron in the dentate nucleus of patients with Friedreich’s ataxia. Ann Neurol 46:123–125

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurology, University Duisburg-Essen, Hufelandstr. 55, 45122, Essen, Germany

    Matthias Maschke MD, A. Dimitrova, J. Bohrenkämper, S. Sturm, H.-Ch. Diener & D. Timmann

  2. Department of Neuroradiology, University of Duisburg-Essen, Hufelandstr. 55, 45122, Essen, Germany

    J. Weber & M. Forsting

  3. Department of Psychiatry and Psychotherapy, University of Duisburg-Essen, Virchowstr. 174, 45147, Essen, Germany

    U. Bonnet, B. W. Müller & M. Gastpar

Authors
  1. Matthias Maschke MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. Weber
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. U. Bonnet
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A. Dimitrova
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J. Bohrenkämper
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. S. Sturm
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. B. W. Müller
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. M. Gastpar
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. H.-Ch. Diener
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. M. Forsting
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. D. Timmann
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Matthias Maschke MD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Maschke, M., Weber, J., Bonnet, U. et al. Vermal atrophy of alcoholics correlate with serum thiamine levels but not with dentate iron concentrations as estimated by MRI. J Neurol 252, 704–711 (2005). https://doi.org/10.1007/s00415-005-0722-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00415-005-0722-2

Key words

Search

Navigation