Myelopathy mimicking subacute combined degeneration in a Down syndrome patient with methotrexate treatment for B lymphoblastic leukemia: Report of an autopsy case

Kaishi Satomi, Mari Yoshida, Kentaro Matsuoka, Hajime Okita, Yosuke Hosoya, Yoko Shioda, Masa aki Kumagai, Tetsuya Mori, Yukio Morishita, Masayuki Noguchi, Atsuko Nakazawa

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

We report clinicopathological features of a 23-year-old woman with Down syndrome (DS) presenting with subacute myelopathy treated with chemotherapy, including intravenous and intrathecal administration of methotrexate (MTX), and with allogenic bone-marrow transplantation for B lymphoblastic leukemia. Autopsy revealed severe demyelinating vacuolar myelopathy in the posterior and lateral columns of the spinal cord, associated with macrophage infiltration, marked axonal loss and some swollen axons. Pathological changes of posterior and lateral columns were observed from the medulla oblongata to lumbar cord. Proximal anterior and posterior roots were preserved. Cerebral white matter was relatively well preserved. There were no vascular lesions or meningeal dissemination of leukemia. Longitudinal extension of cord lesions was extensive, unlike typical cases of subacute combined degeneration (SACD), but distribution of lesions and histological findings were similar to that of SACD. DS patients show heightened sensitivity to MTX because of their genetic background. Risk factors for toxic myelopathy of DS are discussed, including delayed clearance of MTX despite normal renal function, alterations in MTX polyglutamation and enhanced folic acid depletion due to gene dosage effects of chromosome 21. Alteration of folate metabolism and/or vitamin B12 levels through intravenous or intrathecal administration of MTX might exist, although vitamin B12 and other essential nutrients were managed using intravenous hyperalimentation. To the best of our knowledge, this is the first report of an autopsy case that shows myelopathy mimicking SACD in a DS patient accompanied by B lymphoblastic leukemia. The case suggests a pathophysiological mechanism of MTX-related myelopathy in DS patients with B lymphoblastic leukemia mimicking SACD.

Original languageEnglish
Pages (from-to)414-419
Number of pages6
JournalNeuropathology
Volume34
Issue number4
DOIs
Publication statusPublished - 2014
Externally publishedYes

Fingerprint

Subacute Combined Degeneration
Spinal Cord Diseases
Down Syndrome
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Methotrexate
Autopsy
Vitamin B 12
Folic Acid
Spinal Cord
Therapeutics
Chromosomes, Human, Pair 21
Medulla Oblongata
Gene Dosage
Total Parenteral Nutrition
Poisons
Homologous Transplantation
Bone Marrow Transplantation
Intravenous Administration
Blood Vessels
Axons

Keywords

  • Down syndrome
  • Methotrexate
  • Myelopathy
  • Precursor B-cell lymphoblastic leukemia-lymphoma
  • Subacute combined degeneration

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Medicine(all)

Cite this

Myelopathy mimicking subacute combined degeneration in a Down syndrome patient with methotrexate treatment for B lymphoblastic leukemia : Report of an autopsy case. / Satomi, Kaishi; Yoshida, Mari; Matsuoka, Kentaro; Okita, Hajime; Hosoya, Yosuke; Shioda, Yoko; Kumagai, Masa aki; Mori, Tetsuya; Morishita, Yukio; Noguchi, Masayuki; Nakazawa, Atsuko.

In: Neuropathology, Vol. 34, No. 4, 2014, p. 414-419.

Research output: Contribution to journalArticle

Satomi, K, Yoshida, M, Matsuoka, K, Okita, H, Hosoya, Y, Shioda, Y, Kumagai, MA, Mori, T, Morishita, Y, Noguchi, M & Nakazawa, A 2014, 'Myelopathy mimicking subacute combined degeneration in a Down syndrome patient with methotrexate treatment for B lymphoblastic leukemia: Report of an autopsy case', Neuropathology, vol. 34, no. 4, pp. 414-419. https://doi.org/10.1111/neup.12114
Satomi, Kaishi ; Yoshida, Mari ; Matsuoka, Kentaro ; Okita, Hajime ; Hosoya, Yosuke ; Shioda, Yoko ; Kumagai, Masa aki ; Mori, Tetsuya ; Morishita, Yukio ; Noguchi, Masayuki ; Nakazawa, Atsuko. / Myelopathy mimicking subacute combined degeneration in a Down syndrome patient with methotrexate treatment for B lymphoblastic leukemia : Report of an autopsy case. In: Neuropathology. 2014 ; Vol. 34, No. 4. pp. 414-419.
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AU - Kumagai, Masa aki

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