Skip to main content
Journal of Neurology, Neurosurgery, and Psychiatry logoLink to Journal of Neurology, Neurosurgery, and Psychiatry
. 1984 Jan;47(1):65–72. doi: 10.1136/jnnp.47.1.65

Necrotising leukoencephalopathy complicating treatment of childhood leukaemia.

O Robain, O Dulac, J P Dommergues, F Bernaudin, K Diebler, C Kalifa, J Poirier
PMCID: PMC1027643  PMID: 6693915

Abstract

Nine children treated for acute leukemia or lymphosarcoma developed subacute encephalopathy starting with listlessness, depression and impairment of speech. Walking difficulties, ataxia, spasticity and sphincter disorders developed later. Transient intracranial hypertension and abnormal movements respectively developed in two patients. EEG frontal slow waves, raised CSF protein, abnormal white matter radioisotope uptake and CT scan hypodensity with patchy contrast enhancement were evident at the onset. Later, dilated ventricles and calcification appeared in the younger patients. Post-mortem neuropathological studies of three patients disclosed predominantly perivascular myelin loss in areas of white matter necrosis, abnormalities of small vessels and numerous axonal swellings. The spinal cord showed secondary degeneration of the corticospinal tracts. Analysis of the aetiological factors in this series points to the prevailing danger of cranial radiotherapy, probably increased by the young age of patients and by associated drug administration.

Full text

PDF
65

Images in this article

Selected References

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

  1. Clark A. W., Cohen S. R., Nissenblatt M. J., Wilson S. K. Paraplegia following intrathecal chemotherapy: neuropathologic findings and elevation of myelin basic protein. Cancer. 1982 Jul 1;50(1):42–47. doi: 10.1002/1097-0142(19820701)50:1<42::aid-cncr2820500109>3.0.co;2-m. [DOI] [PubMed] [Google Scholar]
  2. Delassalle A., Jacque C., Drouet J., Raoul M., Legrand J. C., Cesselin F. Radioimmunoassay of the myelin basic protein in biological fluids, conditions improving sensitivity and specificity. Biochimie. 1980;62(2-3):159–165. doi: 10.1016/s0300-9084(80)80191-x. [DOI] [PubMed] [Google Scholar]
  3. Devivo D. C., Malas D., Nelson J. S., Land V. J. Leukoencephalopathy in childhood leukemia. Neurology. 1977 Jul;27(7):609–613. doi: 10.1212/wnl.27.7.609. [DOI] [PubMed] [Google Scholar]
  4. Dulac O., Fromange A., Arthuis M. Complications neurologiques des leucémies aiguës. Arch Fr Pediatr. 1981 Mar;38(3):189–193. [PubMed] [Google Scholar]
  5. Gagliano R. G., Costanzi J. J. Paraplegia following intrathecal methotrexate: report of a case and review of the literature. Cancer. 1976 Apr;37(4):1663–1668. doi: 10.1002/1097-0142(197604)37:4<1663::aid-cncr2820370408>3.0.co;2-7. [DOI] [PubMed] [Google Scholar]
  6. Gangji D., Reaman G. H., Cohen S. R., Bleyer W. A., Poplack D. G. Leukoencephalopathy and elevated levels of myelin basic protein in the cerebrospinal fluid of patients with acute lymphoblastic leukemia. N Engl J Med. 1980 Jul 3;303(1):19–21. doi: 10.1056/NEJM198007033030106. [DOI] [PubMed] [Google Scholar]
  7. Gerbaut L., Ponsot G., Dulac O., Olive G., Arthuis M. Profil protéique du liquide céphalo-rachidien chez l'enfant. Détermination des limites de référence. Arch Fr Pediatr. 1981 Jan;38(1):3–9. [PubMed] [Google Scholar]
  8. Hendin B., DeVivo D. C., Torack R., Lell M. E., Ragab A. H., Vietti T. J. Proceedings: Parenchymatous degeneration of the central nervous system in childhood leukemia. Cancer. 1974 Feb;33(2):468–482. doi: 10.1002/1097-0142(197402)33:2<468::aid-cncr2820330223>3.0.co;2-f. [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. Encephalopathy in acute leukaemia associated with methotrexate therapy. Arch Dis Child. 1972 Jun;47(253):344–354. doi: 10.1136/adc.47.253.344. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Laurian Y., Cau D., Jacque C., Breton M. P., Dommergues J. P., Tchernia G. Encéphalopathie après prophylaxie méningée des leucémies aiguës. Nouv Rev Fr Hematol. 1981;23(5):291–297. [PubMed] [Google Scholar]
  11. Loizou L. A., Jefferson J. M., Smith W. T. Subcortical arteriosclerotic encephalopathy (Binswanger's type) and cortical infarcts in a young normotensive patient. J Neurol Neurosurg Psychiatry. 1982 May;45(5):409–417. doi: 10.1136/jnnp.45.5.409. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Meadows A. T., Evans A. E. Effects of chemotherapy on the central nervous system. A study of parenteral methotrexate in long-term survivors of leukemia and lymphoma in childhood. Cancer. 1976 Feb;37(2 Suppl):1079–1085. doi: 10.1002/1097-0142(197602)37:2+<1079::aid-cncr2820370815>3.0.co;2-d. [DOI] [PubMed] [Google Scholar]
  13. Mei Liu H. Reactive neuroaxonal dystrophy in children. Clinical pathological correlation. Acta Neuropathol. 1978 Jun 30;42(3):237–241. doi: 10.1007/BF00690363. [DOI] [PubMed] [Google Scholar]
  14. Price R. A., Jamieson P. A. The central nervous system in childhood leukemia. II. Subacute leukoencephalopathy. Cancer. 1975 Feb;35(2):306–318. doi: 10.1002/1097-0142(197502)35:2<306::aid-cncr2820350203>3.0.co;2-j. [DOI] [PubMed] [Google Scholar]
  15. Rubinstein L. J., Herman M. M., Long T. F., Wilbur J. R. Disseminated necrotizing leukoencephalopathy: a complication of treated central nervous system leukemia and lymphoma. Cancer. 1975 Feb;35(2):291–305. doi: 10.1002/1097-0142(197502)35:2<291::aid-cncr2820350202>3.0.co;2-v. [DOI] [PubMed] [Google Scholar]
  16. Shalen P. R., Ostrow P. T., Glass P. J. Enhancement of the white matter following prophylactic therapy of the central nervous system for leukemia: radiation effects and methotrexate leukoencephalopathy. Radiology. 1981 Aug;140(2):409–412. doi: 10.1148/radiology.140.2.6942436. [DOI] [PubMed] [Google Scholar]
  17. Smith B. Brain damage after intrathecal methotrexate. J Neurol Neurosurg Psychiatry. 1975 Aug;38(8):810–815. doi: 10.1136/jnnp.38.8.810. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Wendling L. R., Cromwell L. D., Latchaw R. E. Computed tomography of intracerebral leukemic masses. AJR Am J Roentgenol. 1979 Feb;132(2):217–220. doi: 10.2214/ajr.132.2.217. [DOI] [PubMed] [Google Scholar]
  19. Wisniewski H., Shelanski M. L., Terry R. D. Effects of mitotic spindle inhibitors on neurotubules and neurofilaments in anterior horn cells. J Cell Biol. 1968 Jul;38(1):224–229. doi: 10.1083/jcb.38.1.224. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Neurology, Neurosurgery, and Psychiatry are provided here courtesy of BMJ Publishing Group

RESOURCES