Filamentous degeneration of neurons. A possible feature of cytosine arabinoside neurotoxicity.
BACKGROUND
The use of high-dose cytosine arabinoside (Ara-C) may be complicated by a characteristic form of cerebellar neurotoxicity. Other reported manifestations of neurologic dysfunction include signs of possible cranial neuropathies, for which a neuropathologic substrate has not been previously reported.


METHODS
A 43-year-old man was treated for refractory acute promyelocytic leukemia with a regimen of high-dose Ara-C. He died after dysarthria, ophthalmoplegia, and severe cerebellar neurotoxicity developed.


RESULTS
The postmortem examination revealed a peculiar subacute neuronopathy that involved preponderantly brain stem tegmental and spinal motor neurons. The neuronopathy was characterized by hypereosinophilic perikarya and karyolytic nuclei. The perikaryal changes resulted from accumulations of argyrophilic masses of filaments that stained positively with neurofilament antibodies and ultrastructurally were shown to be composed of bundles of intermediate filaments.


CONCLUSIONS
This report indicates that Ara-C neurotoxicity, possibly aggravated in our patient by oliguric renal failure, is not confined to the cerebellum but involves cranial nerve and spinal motor neurons, which in turn may explain the cranial neuropathies that sometimes complicate the use of high-dose Ara-C therapy.
Vogel
H
H
Department of Pathology (Neuropathology), Stanford University Medical Center, CA 94305.
Horoupian
D S
DS
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001933:Brain Stem / Q000187:drug effects / Q000648:ultrastructure; D002467:Cell Nucleus / Q000187:drug effects / Q000648:ultrastructure; D003561:Cytarabine / Q000009:adverse effects*; D006801:Humans; D007382:Intermediate Filaments / Q000187:drug effects*; D007683:Kidney Tubular Necrosis, Acute / Q000139:chemically induced; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy; D008297:Male; D009046:Motor Neurons / Q000187:drug effects* / Q000648:ultrastructure; D009410:Nerve Degeneration; D009474:Neurons / Q000187:drug effects / Q000648:ultrastructure; D013116:Spinal Cord / Q000187:drug effects / Q000648:ultrastructure
D003561:Cytarabine