AUTHOR=Santangelo Andrea , Bartolini Emanuele , Nuzzi Giulia , Foiadelli Thomas , Michev Alexandre , Mina Tommaso , Trambusti Irene , Fichera Valeria , Bonuccelli Alice , Massimetti Gabriele , Peroni Diego G. , De Marco Emanuela , Coccoli Luca , Luti Laura , Bernasconi Sayla , Nardi Margherita , Menconi Maria Cristina , Casazza Gabriella , Pruna Dario , Mura Rosamaria , Marra Chiara , Zama Daniele , Striano Pasquale , Cordelli Duccio M. , Battini Roberta , Orsini Alessandro TITLE=The Clinical Impact of Methotrexate-Induced Stroke-Like Neurotoxicity in Paediatric Departments: An Italian Multi-Centre Case-Series JOURNAL=Frontiers in Neurology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2022.920214 DOI=10.3389/fneur.2022.920214 ISSN=1664-2295 ABSTRACT=Introduction

Stroke-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 Methods

We 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.

Results

The 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.

Conclusions

SLS 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.