Objective:

We present a unique case of CNS vasculitis and subacute combined degeneration in the setting of intrathecal methotrexate, with educational teaching points.  Present a rare and unique neurological pathological process through an extensive review of the patient's history of present illness, neurological examination, review of radiographic imaging, treatment, and follow-up post hospitalization.

Background:

Methotrexate is an anti-metabolite drug used to prevent or treat central nervous system involvement in the management of hematological malignancies. Its high-dose systemic administration with IT-MTX is used for CNS-directed therapy. These therapeutic measures may cause neuronal damage, more specifically MTX-induced leukoencephalopathy and myelopathy. We present a unique case of a patient with Chronic Myeloid Leukemia with CNS involvement, who developed both MTX induced myelopathy and CNS vasculitis confirmed on neuronal imaging.

Design/Methods:

Present a rare and unique case report of a neurological pathological process.

Results:

A 54-year-old man with chronic myeloid leukemia (CML) and CNS involvement in remission, on Asciminib, developed progressive bilateral lower extremity weakness, paresthesia, and bowel and bladder dysfunction following eight intrathecal chemotherapy treatments with methotrexate (MTX) and cytarabine. MRI of the neuroaxis revealed longitudinally extensive, non-enhancing T2 hyperintensity in the dorsal columns of the thoracic spinal cord, consistent with MTX-induced myelopathy. An extensive diagnostic workup, including imaging, serum, and CSF analysis for nutritional, inflammatory, autoimmune, and neoplastic etiologies, was unremarkable. A diagnostic cerebral angiogram revealed distal arterial beading in multiple vascular territories, findings consistent with CNS vasculitis. 

Conclusions:

This case presents a complex diagnostic challenge. The differential diagnosis included paraneoplastic CNS vasculitis, tyrosine kinase inhibitor-associated CNS vasculitis, and Methotrexate-induced CNS vasculitis. Although paraneoplastic CNS vasculitis has been previously reported in the context of lymphoma, and several case reports have noted cerebrovascular arterial