The Clinical Impact of Methotrexate-Induced Stroke-Like Neurotoxicity in Paediatric Departments: An Italian Multi-Centre Case-Series

IntroductionStroke-like syndrome (SLS) is a rare subacute neurological complication of intrathecal or high-dose (>= 500 mg) Methotrexate (MTX) administration. Its clinical features, evoking acute cerebral ischaemia with fluctuating course symptoms and a possible spontaneous resolution, have elicited interest among the scientific community. However, many issues are still open on the underlying pathogenesis, clinical, and therapeutic management and long-term outcome. Materials and MethodsWe retrospectively analyzed clinical, radiological and laboratory records of all patients diagnosed with SLS between 2011 and 2021 at 4 National referral centers for Pediatric Onco-Hematology. Patients with a latency period that was longer than 3 weeks between the last MTX administration of MTX and SLS onset were excluded from the analysis, as were those with unclear etiologies. We assessed symptom severity using a dedicated arbitrary scoring system. Eleven patients were included in the study. ResultsThe underlying disease was acute lymphoblastic leukemia type B in 10/11 patients, while fibroblastic osteosarcoma was present in a single subject. The median age at diagnosis was 11 years (range 4-34), and 64% of the patients were women. Symptoms occurred after a mean of 9.45 days (+/- 0.75) since the last MTX administration and lasted between 1 and 96 h. Clinical features included hemiplegia and/or cranial nerves palsy, paraesthesia, movement or speech disorders, and seizure. All patients underwent neuroimaging studies (CT and/or MRI) and EEG. The scoring system revealed an average of 4.9 points (+/- 2.3), with a median of 5 points (maximum 20 points). We detected a linear correlation between the severity of the disease and age in male patients. ConclusionsSLS is a rare, well-characterized complication of MTX administration. Despite the small sample, we have been able to confirm some of the previous findings in literature. We also identified a linear correlation between age and severity of the disease, which could improve the future clinical management.

Automated summary

This study retrospectively analyzed clinical, radiological, and laboratory records of 11 patients with SLS. The results showed that SLS is a rare complication of MTX treatment, characterized by symptoms such as hemiplegia, sensory abnormalities, and speech disorders. There is a linear correlation between the severity of the disease and age.