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J Neurol Neurosurg Psychiatry. 2000 March; 68(3): 342–348.
doi: 10.1136/jnnp.68.3.342.
PMCID: PMC1736803
Validity of carbohydrate deficient transferrin and other markers as diagnostic aids in the detection of alcohol related seizures
G. Brathen, K. Bjerve, E. Brodtkorb, and G. Bovim
Department of Clinical Neurosciences, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway. Email: geir.brathen/at/medisin.ntnu.no
Abstract
OBJECTIVE—The role of alcohol misuse in the genesis of seizures is probably often undetected. The aim was to investigate the utility of carbohydrate deficient transferrin (CDT) compared with other biomarkers and clinical examination in the diagnosis of alcohol related seizures.
METHODS—The study included consecutively 158 seizure patients—83 men and 75 women—with mean age 45 (16-79) years. Seizures related to alcohol use were identified by a score [gt-or-equal, slanted]8 in the alcohol use disorders identification test (AUDIT positive). AUDIT was applied as the gold standard to which sensitivity and specificity of the various markers were related. Blood samples were obtained from 150 patients on admission and analysed for ethanol, liver enzymes, and CDT, using AXIS Biochemicals' %CDT-TIA kit.
RESULTS—53 patients (34%) were AUDIT positive. Using the commonly applied decision value for %CDT of 5.0%, a sensitivity of 41% and a specificity of 84% were obtained. Analysis of receiver operator characteristics (ROC) curves disclosed an optimal cut off value for %CDT of 5.4%, which yielded a sensitivity of 39% and a specificity of 88%. At a specificity of 80%, the sensitivity was 43% for %CDT and 26% for GGT. The %CDT sensitivity was markedly higher for men than for women. Compared with GGT, ASAT, ALAT, and ASAT/ALAT ratio, CDT was the best single biomarker for alcohol related seizures. However, even in the subgroup of withdrawal seizures, the sensitivity level barely exceeded 50%. Clinicians scored alcohol as the main cause of the seizure in only 19 cases (12%). In 38 (24%) cases, clinicians suspected that alcohol had a role (sensitivity of 62% at a specificity of 89%). Their ability to identify AUDIT positive patients was better than that of any biomarker, but many cases were missed. Agreement of clinicians' scores to CDT was only fair (κ=0.28). CDT concentrations were significantly increased among alcohol abstaining patients on enzyme-inducing antiepileptic drugs. Six out of 16 patients with false positive CDT results were exposed to such drugs.
CONCLUSIONS—CDT is not recommended as a stand alone marker for alcohol related seizures, but may provide a useful contribution to the overall diagnostic investigation of seizures. Confirmatory studies are needed as to the apparent vulnerability of CDT to antiepileptic drugs.

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Selected References
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  • Earnest, MP; Yarnell, PR. Seizure admissions to a city hospital: the role of alcohol. Epilepsia. 1976 Dec;17(4):387–393. [PubMed]
  • Hillbom, ME. Occurrence of cerebral seizures provoked by alcohol abuse. Epilepsia. 1980 Oct;21(5):459–466. [PubMed]
  • Bråthen, G; Brodtkorb, E; Helde, G; Sand, T; Bovim, G. The diversity of seizures related to alcohol use. A study of consecutive patients. Eur J Neurol. 1999 Nov;6(6):697–703. [PubMed]
  • Pieninkeroinen, IP; Telakivi, TM; Hillbom, ME. Outcome in subjects with alcohol-provoked seizures. Alcohol Clin Exp Res. 1992 Oct;16(5):955–959. [PubMed]
  • Hillbom, ME; Hjelm-Jäger, M. Should alcohol withdrawal seizures be treated with anti-epileptic drugs? Acta Neurol Scand. 1984 Jan;69(1):39–42. [PubMed]
  • Stibler, H. Carbohydrate-deficient transferrin in serum: a new marker of potentially harmful alcohol consumption reviewed. Clin Chem. 1991 Dec;37(12):2029–2037. [PubMed]
  • Allen, JP; Litten, RZ; Anton, RF; Cross, GM. Carbohydrate-deficient transferrin as a measure of immoderate drinking: remaining issues. Alcohol Clin Exp Res. 1994 Aug;18(4):799–812. [PubMed]
  • Nilssen, O; Huseby, NE; Høyer, G; Brenn, T; Schirmer, H; Førde, OH. New alcohol markers--how useful are they in population studies: the Svalbard Study 1988-89. Alcohol Clin Exp Res. 1992 Feb;16(1):82–86. [PubMed]
  • Nyström, M; Peräsalo, J; Salaspuro, M. Carbohydrate-deficient transferrin (CDT) in serum as a possible indicator of heavy drinking in young university students. Alcohol Clin Exp Res. 1992 Feb;16(1):93–97. [PubMed]
  • Stibler, H. Diagnosis of alcohol-related neurological diseases by analysis of carbohydrate-deficient transferrin in serum. Acta Neurol Scand. 1993 Oct;88(4):279–283. [PubMed]
  • Sillanaukee, P; Seppä, K; Löf, K; Koivula, T. CDT by anion-exchange chromatography followed by RIA as a marker of heavy drinking among men. Alcohol Clin Exp Res. 1993 Apr;17(2):230–233. [PubMed]
  • Victor, M; Brausch, C. The role of abstinence in the genesis of alcoholic epilepsy. Epilepsia. 1967 Mar;8(1):1–20. [PubMed]
  • Ng, SK; Hauser, WA; Brust, JC; Susser, M. Alcohol consumption and withdrawal in new-onset seizures. N Engl J Med. 1988 Sep 15;319(11):666–673. [PubMed]
  • Saunders, JB; Aasland, OG; Babor, TF; de la Fuente, JR; Grant, M. Development of the Alcohol Use Disorders Identification Test (AUDIT): WHO Collaborative Project on Early Detection of Persons with Harmful Alcohol Consumption--II. Addiction. 1993 Jun;88(6):791–804. [PubMed]
  • Conigrave, KM; Hall, WD; Saunders, JB. The AUDIT questionnaire: choosing a cut-off score. Alcohol Use Disorder Identification Test. Addiction. 1995 Oct;90(10):1349–1356. [PubMed]
  • MacKenzie, D; Langa, A; Brown, TM. Identifying hazardous or harmful alcohol use in medical admissions: a comparison of audit, cage and brief mast. Alcohol Alcohol. 1996 Nov;31(6):591–599. [PubMed]
  • Turner, C. How much alcohol is in a 'standard drink'? An analysis of 125 studies. Br J Addict. 1990 Sep;85(9):1171–1175. [PubMed]
  • Gram, L. Pharmacokinetics of new antiepileptic drugs. Epilepsia. 1996;37 Suppl 6:S12–S16. [PubMed]
  • Bell, H; Tallaksen, CM; Try, K; Haug, E. Carbohydrate-deficient transferrin and other markers of high alcohol consumption: a study of 502 patients admitted consecutively to a medical department. Alcohol Clin Exp Res. 1994 Oct;18(5):1103–1108. [PubMed]
  • Löf, K; Seppä, K; Itälä, L; Koivula, T; Turpeinen, U; Sillanaukee, P. Carbohydrate-deficient transferrin as an alcohol marker among female heavy drinkers: a population-based study. Alcohol Clin Exp Res. 1994 Aug;18(4):889–894. [PubMed]
  • Godsell, PA; Whitfield, JB; Conigrave, KM; Hanratty, SJ; Saunders, JB. Carbohydrate deficient transferrin levels in hazardous alcohol consumption. Alcohol Alcohol. 1995 Jan;30(1):61–66. [PubMed]
  • Whitfield, JB; Fletcher, LM; Murphy, TL; Powell, LW; Halliday, J; Heath, AC; Martin, NG. Smoking, obesity, and hypertension alter the dose-response curve and test sensitivity of carbohydrate-deficient transferrin as a marker of alcohol intake. Clin Chem. 1998 Dec;44(12):2480–2489. [PubMed]
  • Helander, A; Carlsson, AV; Borg, S. Longitudinal comparison of carbohydrate-deficient transferrin and gamma-glutamyl transferase: complementary markers of excessive alcohol consumption. Alcohol Alcohol. 1996 Jan;31(1):101–107. [PubMed]
  • Huseby, NE; Nilssen, O; Kanitz, RD. Evaluation of two biological markers combined as a parameter of alcohol dependency. Alcohol Alcohol. 1997 32(6):731–737.Nov–Dec; [PubMed]
  • Shultz, EK. Multivariate receiver-operating characteristic curve analysis: prostate cancer screening as an example. Clin Chem. 1995 Aug;41(8 Pt 2):1248–1255. [PubMed]
  • Kaneko, K; Fujimori, S; Yamanaka, H; Akaoka, I. Effect of hypouricemic agents on serum carbohydrate-deficient transferrin in gouty patients. Adv Exp Med Biol. 1994;370:27–30. [PubMed]
  • Meerkerk, GJ; Njoo, KH; Bongers, IM; Trienekens, P; van Oers, JA. The specificity of the CDT assay in general practice: the influence of common chronic diseases and medication on the serum CDT concentration. Alcohol Clin Exp Res. 1998 Jun;22(4):908–913. [PubMed]
  • Anton, RF; Moak, DH. Carbohydrate-deficient transferrin and gamma-glutamyltransferase as markers of heavy alcohol consumption: gender differences. Alcohol Clin Exp Res. 1994 Jun;18(3):747–754. [PubMed]
  • Bell, H; Tallaksen, C; Sjåheim, T; Weberg, R; Raknerud, N; Orjasaeter, H; Try, K; Haug, E. Serum carbohydrate-deficient transferrin as a marker of alcohol consumption in patients with chronic liver diseases. Alcohol Clin Exp Res. 1993 Apr;17(2):246–252. [PubMed]
  • Helander, A; Vabö, E; Levin, K; Borg, S. Intra- and interindividual variability of carbohydrate-deficient transferrin, gamma-glutamyltransferase, and mean corpuscular volume in teetotalers. Clin Chem. 1998 Oct;44(10):2120–2125. [PubMed]
  • Stibler, H; Borg, S; Joustra, M. Micro anion exchange chromatography of carbohydrate-deficient transferrin in serum in relation to alcohol consumption (Swedish Patent 8400587-5). Alcohol Clin Exp Res. 1986 Oct;10(5):535–544. [PubMed]
  • Stauber, RE; Jauk, B; Fickert, P; Häusler, M. Increased carbohydrate-deficient transferrin during pregnancy: relation to sex hormones. Alcohol Alcohol. 1996 Jul;31(4):389–392. [PubMed]
  • La Grange, L; Anton, RF; Garcia, S; Herrbold, C. Carbohydrate-deficient transferrin levels in a female population. Alcohol Clin Exp Res. 1995 Feb;19(1):100–103. [PubMed]
  • Stauber, RE; Vollmann, H; Pesserl, I; Jauk, B; Lipp, R; Halwachs, G; Wilders-Truschnig, M. Carbohydrate-deficient transferrin in healthy women: relation to estrogens and iron status. Alcohol Clin Exp Res. 1996 Sep;20(6):1114–1117. [PubMed]
  • de Jong, G; van Noort, WL; Feelders, RA; de Jeu-Jaspars, CM; van Eijk, HG. Adaptation of transferrin protein and glycan synthesis. Clin Chim Acta. 1992 Nov 16;212(1-2):27–45. [PubMed]
  • Jensen, PD; Peterslund, NA; Poulsen, JH; Jensen, FT; Christensen, T; Ellegaard, J. The effect of iron overload and iron reductive treatment on the serum concentration of carbohydrate-deficient transferrin. Br J Haematol. 1994 Sep;88(1):56–63. [PubMed]
  • Fagerberg, B; Agewall, S; Urbanavicius, V; Attvall, S; Lundberg, PA; Lindstedt, G. Carbohydrate-deficient transferrin is associated with insulin sensitivity in hypertensive men. J Clin Endocrinol Metab. 1994 Sep;79(3):712–715. [PubMed]
  • Lesch, OM; Walter, H; Antal, J; Heggli, DE; Kovacz, A; Leitner, A; Neumeister, A; Stumpf, I; Sundrehagen, E; Kasper, S. Carbohydrate-deficient transferrin as a marker of alcohol intake: a study with healthy subjects. Alcohol Alcohol. 1996 May;31(3):265–271. [PubMed]
  • Chan, AW. Alcoholism and epilepsy. Epilepsia. 1985 26(4):323–333.Jul–Aug; [PubMed]
  • Devetag, F; Mandich, G; Zaiotti, G; Toffolo, GG. Alcoholic epilepsy: review of a series and proposed classification and etiopathogenesis. Ital J Neurol Sci. 1983 Sep;4(3):275–284. [PubMed]
  • Mayfield, D; McLeod, G; Hall, P. The CAGE questionnaire: validation of a new alcoholism screening instrument. Am J Psychiatry. 1974 Oct;131(10):1121–1123. [PubMed]
  • Yersin, B; Trisconi, Y; Paccaud, F; Gutzwiller, F; Magnenat, P. Accuracy of the Michigan Alcoholism Screening Test for screening of alcoholism in patients of a medical department. Arch Intern Med. 1989 Sep;149(9):2071–2074. [PubMed]
  • Kircher, T; Wormstall, H. Alois Alzheimer (1864-1915)--student days and first scientific activities. J Geriatr Psychiatry Neurol. 1997 Jul;10(3):127–129. [PubMed]
  • Graeber, MB. No man alone: the rediscovery of Alois Alzheimer's original cases. Brain Pathol. 1999 Apr;9(2):237–240. [PubMed]
  • Maurer, K; Volk, S; Gerbaldo, H. Auguste D and Alzheimer's disease. Lancet. 1997 May 24;349(9064):1546–1549. [PubMed]
  • Sheng, JG; Zhou, XQ; Mrak, RE; Griffin, WS. Progressive neuronal injury associated with amyloid plaque formation in Alzheimer disease. J Neuropathol Exp Neurol. 1998 Jul;57(7):714–717. [PubMed]
  • Wisniewski, T; Dowjat, WK; Permanne, B; Palha, J; Kumar, A; Gallo, G; Frangione, B. Presenilin-1 is associated with Alzheimer's disease amyloid. Am J Pathol. 1997 Aug;151(2):601–610. [PubMed]
  • Rogaeva, E; Premkumar, S; Song, Y; Sorbi, S; Brindle, N; Paterson, A; Duara, R; Levesque, G; Yu, G; Nishimura, M; Ikeda, M; O'Toole, C; Kawarai, T; Jorge, R; Vilarino, D; Bruni, AC; Farrer, LA; St George-Hyslop, PH. Evidence for an Alzheimer disease susceptibility locus on chromosome 12 and for further locus heterogeneity. JAMA. 1998 Aug 19;280(7):614–618. [PubMed]