Methotrexate
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Dysarthria and hemiparesis: case report A 21-year-old man developed hemiparesis and dysarthria as a manifestation of neurotoxicity during treatment with methotrexate for ABC-type diffuse large B-cell lymphoma (DLBCL). The man, who had ABC-type DLBCL, received four courses of R-Hyper-CVAD chemotherapy (hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone and rituximab) with three alternating courses of rituximab plus methotrexate/cytarabine [Ara-Ca]. At the end of treatment, he exhibited a complete metabolic response. He again presented after 3 months due to left cranial nerve palsy, isolated leptomeningeal relapse and CSF involvement. Subsequently, he received a course of high dose of methotrexate 3 g/m2 course on day 1, and 1 course of intrathecal chemotherapy with methotrexate 12 mg, along with hydrocortisone and cytarabine. On day 5, Ommaya reservoir was placed for further chemotherapy treatment. On day 6 and on day 9, he received two more intraventricular chemotherapy courses, and was discharged on day 9 of hospitalisation. Twenty days after the relapse, he received a course of R-ICE (carboplatin, etoposide, rituximab and ifosfamide) for stem cell chemomobilisation. He continued receiving intraventricular chemotherapy weekly on day 16 and day 23. However, after 2 days (25 days after the initial diagnosis), he developed drowsiness and malaise. After 48 hours, he exhibited left hand clumsiness, which progressed into complete left-side hemiparesis of the lower and upper extremities and left side of the face accompanied by dysarthric speech [time to reaction onset not stated]. The man underwent various examinations, which showed normal results except for pancytopenia. Consequently, unspecified broad-spectrum antibiotics were started. Later, infectious aetiology was ruled out and hence, the antibiotics were discontinued. No pathological finding were seen in angio-CT and cranial CT. Conventional MRI revealed new lesions with mild hyperintensity on fluid-attenuated inversion recovery (FLAIR) sequences in the white matter. However, no lesions were seen T1 sequence. The catheter was placed correctly without any liquid reflux surrounding it. With respect to suspicion of disease progression high dose dexamethasone was started. Within 24 hours, his symptoms resolved without any neurological sequelae. Thereafter, he continued to receive the systemic and intraventricular chemotherapy, which included methotrexate without any recurrence of symptoms. Fifteen days later, a control MRI revealed normal results. Author comment: "[Methotrexate]-induced subacute neurotoxicity is a rare complication that typically progresses with involvement of the basal ganglia." Oarbeascoa G, et al. Methotrexate-induced subacute neurotoxicity surrounding an ommaya reservoir in a patient with lymphoma. American Journal of Case Reports 20: 1002-1005, 2019. Available from: URL: http://doi.org/10.12659/AJCR.915632 803431790 - Spain
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