Leukoencephalopathy following intrathecal methotrexate
Purpose: Methotrexate is an antimetabolite used in the treatment of a variety of oncological and immunological disorders. When administered by the intrathecal route, it can occasionally produce a toxic leukoencephalopathy. We report two patients with methotrexate-induced leukoencephalopathy.
Methods: The clinical and investigation findings for the two patients are described.
Results: Patient 1 was a 19-year-old female with relapsed acute lymphoblastic leukaemia (ALL). Seven days after receiving intrathecal methotrexate for known central nervous system (CNS) involvement, she had two focal motor seizures with secondary generalisation. No focal neurological deficit was detected following the seizures. However, 3 days later, she suddenly developed left-sided weakness and anarthria. Multiple areas of subtle signal hyperintensity were seen in the deep cerebral white matter bilaterally on diffusion-weighted MRI images (DWI). No abnormal cells were detected on repeat CSF examination. She was treated with intravenous aminophylline and she gradually made a full recovery. Patient 2 was a 23-year-old male with relapsed ALL. Sixteen days after receiving intrathecal methotrexate for CNS prophylaxis, he collapsed and was found to have right-sided weakness most severe in the lower limb. After 2 days, his right-sided weakness had resolved but he had developed new left-sided weakness most severe in the upper limb. On MRI scanning the DWI revealed multiple areas of subtle signal hyperintensity in the deep cerebral white matter bilaterally. He was managed conservatively and rapidly made a full recovery.
Conclusions: Treatment with intrathecal methotrexate is occasionally complicated by a transient or relapsing leukoencephalopathy that can present with seizures or stroke-like syndromes. There are typically multiple areas of signal hyperintensity in the deep cerebral white matter on DWI. In mild cases, the neurological deficits may resolve without any specific intervention. In more severe cases, intravenous aminophylline or leucovorin may improve the outcome.