Dr. United Medical and Dental College (UMDC), Sindh, Pakistan
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Introduction: Primary central nervous lymphoma (CNS) is a sub-type of non-Hodgkin lymphoma which was previously treated with whole brain radiation. Treatment has now evolved to initiating with high-dose methotrexate (HD-MTX) based combination regimen with rituximab. Patients with normal kidney function and overall good functional status qualify for combination-based HD-MTX treatment. Major side effects of HD-MTX include bone marrow suppression, renal impairment, pneumonitis, hepatic toxicity, and opportunistic infections. Seizures are a rare side effect, mostly reported in case reports or noted in children treated for acute lymphoblastic anemia. We report a case of an adult patient who had been tolerating his chemotherapy well up until his acute neurological changes during his seventh cycle of treatment.
Description: A 66-year-old male with primary CNS lymphoma was admitted for HD-MTX therapy cycle seven. Following completion of chemotherapy, his peak serum methotrexate level was 17 µmol/L which was decreasing gradually with appropriate leucovorin rescue and supportive hydration. On day four post-chemotherapy, with methotrexate levels down to 4 µmol/L, he developed acute left-hand weakness and diplopia. Emergent brain MRI showed no evidence of acute infarction or disease progression. Electroencephalography (EEG) revealed epileptic discharges suggestive of subclinical seizures. He was initiated on four antiepileptic regimens due to difficulty with controlling his seizures, which eventually subsided on a stable regimen.
Discussion: There have been several case reports and research studies which report neurotoxicity secondary to MTX in children treated for lymphoma. Neurotoxicity is a very rare side effect in adult populations. Though HD-MTX is not directly epileptogenic, it is thought that the accumulation can result in neurotoxic manifestations. According to literature review, there could be alteration of the folate metabolism in the CNS or in the lesion, possibly resulting in elevated homocysteine levels causing neuronal excitability. Additionally, there may be a genetic component which is associated with neurotoxicity. This case highlights the importance of understanding rare side effects of HD-MTX and understanding prompt management.
