Abstract
Case Description We present a case of methotrexate leukoencephalopathy in a patient with long-term oral methotrexate use in the context of rheumatoid arthritis and T-cell large granular lymphocytic leukaemia (T-LGL). The patient presented with a three week frontal-predominant dysexecutive syndrome. The index MRI demonstrated severe white matter changes frontally and less diffuse cortical and periventricular change. The patient underwent extensive serological and cerebrospinal fluid examination which was negative for infection and malignancy.
The case was discussed at a neuroradiology multidisciplinary meeting and the differential diagnosis of methotrexate leukoencephalopathy was raised. We reviewed the literature for methotrexate leukoencephalopathy case reports with treatment involving combination therapy with high-dose aminophylline and leucovorin. The patient was administered high-dose aminophylline at 12mg/kg and high-dose leucovorin at 2500mg on six consecutive days with cardiac monitoring. This was relatively well-tolerated with only transient sinus tachycardia and emesis.
The patient improved, was discharged to rehabilitation and a repeat MRI at approximately five months post-presentation and demonstrated improvement in the periventricular and parietal regions but ongoing severe bi-frontal white matter changes with new right frontal atrophy and susceptibility-weighted mineralisation. The patient had improved clinically with less frontal disinhibition and dysphasia and a repeat MOCA was 23/30.
Discussion Leukoencephalopathy secondary to methotrexate toxicity is an important differential diagnosis in selected patients, regardless of administration route and new research demonstrates association with methylenetetrahydrofolate reductase (MTHFR) polymorphisms. A trial of high-dose leucovorin and folinic acid therapy is relatively safe and well-tolerated and has shown to have benefit at a case-report level.
