From a guideline:
Due to the inhibitory effect of methotrexate on DHPR and the interaction with dihydrofolate reductase (DHFR), this treatment may lead to HPA and early neurotoxicity, possibly combined with folate deficiency .
What is the meaning of "early neurotoxicity"? An early-stage neurotoxicity that has not yet progressed to a more severe form? Or a neurotoxicity at an early age, meaning that methotrexate should be avoided in children? Or a neurotoxicity that developed too early for the person's age, "a neurotoxicity that is untypical because it developed too early"?
Reference 153 leads to an article in French, so it's hard for me to understand the meaning. I'm a Russian.
Netter, J. C., Dhondt, J. L., Rance, F., & Petrus, M. (1991). Neurotoxicité précoce du méthotrexate à haute dose et déficit en tétrahydrobioptérine [Early neurotoxicity of high-dose of methotrexate and tetrahydrobiopterin deficiency]. Archives francaises de pediatrie, 48(10), 719–722. https://pubmed.ncbi.nlm.nih.gov/1793349/
Opladen, T., López-Laso, E., Cortès-Saladelafont, E., Pearson, T. S., Sivri, H. S., Yildiz, Y., ... & Hübschmann, O. K. (2020). Consensus guideline for the diagnosis and treatment of tetrahydrobiopterin (BH4) deficiencies. Orphanet Journal of Rare Diseases, 15(126). https://doi.org/10.1186/s13023-020-01379-8