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. 1972 Jun;47(253):344–354. doi: 10.1136/adc.47.253.344

Encephalopathy in Acute Leukaemia Associated with Methotrexate Therapy

H E M Kay, P J Knapton, J P O'Sullivan, D G Wells, Ruth F Harris, Elizabeth M Innes, J Stuart, F C M Schwartz, Eileen N Thompson
PMCID: PMC1648136  PMID: 4504035

Abstract

Seven patients are described in whom dementia developed during treatment with methotrexate for meningeal leukaemia. The patients presented with confusion, tremor, ataxia, irritability, and somnolence. There were major epileptic fits in two cases and in one case there was progression to coma and death. Necropsy findings in the latter showed infarcted areas in the temporal and parietal lobes, with no evidence of active leukaemic disease or of viral encephalitis. The condition has not responded to radiotherapy and no positive evidence of viral encephalitis has been obtained. On the other hand, when treated with folinic and folic acid the deterioration has been arrested and there has been some improvement; thus the condition appears to be due to methotrexate. The occurrence of so many cases within the past year of a condition not previously described is probably attributable to the introduction of intensive cytotoxic therapy directed against meningeal leukaemia.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Back E. H. Death after intrathecal methotrexate. Lancet. 1969 Nov 8;2(7628):1005–1005. doi: 10.1016/s0140-6736(69)90554-6. [DOI] [PubMed] [Google Scholar]
  2. Bagshawe K. D., Magrath I. T., Golding P. R. Intrathecal methotrexate. Lancet. 1969 Dec 6;2(7632):1258–1258. doi: 10.1016/s0140-6736(69)90796-x. [DOI] [PubMed] [Google Scholar]
  3. Butcher D. M., Hardisty R. M., Lange L., Pampiglione G. EEG studies in children with leukaemia. Electroencephalogr Clin Neurophysiol. 1970 Feb;28(2):209–210. [PubMed] [Google Scholar]
  4. COBB W., HILL D. Electroencephalogram in subacute progressive encephalitis. Brain. 1950;73(3):392–404. doi: 10.1093/brain/73.3.392. [DOI] [PubMed] [Google Scholar]
  5. Clarysse A. M., Cathey W. J., Cartwright G. E., Wintrobe M. M. Pulmonary disease complicating intermittent therapy with methotrexate. JAMA. 1969 Sep 22;209(12):1861–1868. [PubMed] [Google Scholar]
  6. Dow W. I. Electroencephalogram in anticonvulsant-induced folate deficiency. Br Med J. 1971 Apr 24;2(5755):207–207. doi: 10.1136/bmj.2.5755.207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Guyer R. J., Crowther D. Active immunotherapy in treatment of acute leukaemia. Br Med J. 1969 Nov 15;4(5680):406–407. doi: 10.1136/bmj.4.5680.406. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hersh E. M., Wong V. G., Henderson E. S., Freireich E. J. Hepatotoxic effects of methotrexate. Cancer. 1966 Apr;19(4):600–606. doi: 10.1002/1097-0142(196604)19:4<600::aid-cncr2820190420>3.0.co;2-3. [DOI] [PubMed] [Google Scholar]
  9. Kay H. E., Knapton P. J., O'Sullivan J. P., Wells D. G., Harris R. F., Innes E. M., Stuart J., Schwartz F. C., Thompson E. N. Severe neurological damage associated with methotrexate therapy. Lancet. 1971 Sep 4;2(7723):542–542. doi: 10.1016/s0140-6736(71)90456-9. [DOI] [PubMed] [Google Scholar]
  10. Naiman J. L., Rupprecht L. M., Tanyeri G., Philippidis P. Intrathecal methotrexate. Lancet. 1970 Mar 14;1(7646):571–571. doi: 10.1016/s0140-6736(70)90812-3. [DOI] [PubMed] [Google Scholar]
  11. Pasquinucci G., Pardini R., Fedi F. Intrathecal methotrexate. Lancet. 1970 Feb 7;1(7641):309–310. doi: 10.1016/s0140-6736(70)90687-2. [DOI] [PubMed] [Google Scholar]
  12. Pinkel D., Hernandez K., Borella L., Holton C., Aur R., Samoy G., Pratt C. Drug dosage and remission duration in childhood lymphocytic leukemia. Cancer. 1971 Feb;27(2):247–256. doi: 10.1002/1097-0142(197102)27:2<247::aid-cncr2820270202>3.0.co;2-c. [DOI] [PubMed] [Google Scholar]
  13. RICHTER D. FACTORS INFLUENCING THE PROTEIN METABOLISM OF THE BRAIN. Br Med Bull. 1965 Jan;21:76–80. doi: 10.1093/oxfordjournals.bmb.a070361. [DOI] [PubMed] [Google Scholar]
  14. Ragab A. H., Frech R. S., Vietti T. J. Osteoporotic fractures secondary to methotrexate therapy of acute leukemia in remission. Cancer. 1970 Mar;25(3):580–585. doi: 10.1002/1097-0142(197003)25:3<580::aid-cncr2820250313>3.0.co;2-m. [DOI] [PubMed] [Google Scholar]
  15. Reynolds E. H. Effects of folic acid on the mental state and fit-frequency of drug-treated epileptic patients. Lancet. 1967 May 20;1(7499):1086–1088. doi: 10.1016/s0140-6736(67)92654-2. [DOI] [PubMed] [Google Scholar]
  16. Rosner F., Lee S. L., Kagen M., Morrison A. N. Intrathecal methotrexate. Lancet. 1970 Jan 31;1(7640):249–250. doi: 10.1016/s0140-6736(70)90620-3. [DOI] [PubMed] [Google Scholar]
  17. Strachan R. W., Henderson J. G. Dementia and folate deficiency. Q J Med. 1967 Apr;36(142):189–204. [PubMed] [Google Scholar]

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