TABLE 1.

Pediatric Cases of Persistent Methotrexate Neurotoxicity in the Absence of Radiation

Patient No.	Diagnosis	Age (y)	Sex	Therapy Protocol	Days since IT MTX	Stage of Therapy	Initial Physical Findings	Treatment	Persistent Deficits
1	ALL	17	F	Per COG AALL1131	37	Maintenance cycle 4	Auditory hallucinations, cranial nerve deficits, respiratory distress requiring ventilation	Antimicrobials aminophylline steroids IVIG plasmapheresis rituximab	Quadriplegia, ventilator dependence
2	ALL	20	F	Per COG AALL1131	11	Interim maintenance	Confusion, disinhibition, tingling, slurred speech, ataxia, respiratory distress requiring ventilation	Antimicrobials, dextromethorphan, aminophylline	Encephalopathy
3	ALL	17	M	UKALL2003	6	Consolidation	Disorientation, agitation, dysphasia	Antimicrobials	Deficit in executive functioning (particularly word processing)
4	ALL	14	F	UKALL2003	6	Consolidation	Quadriparesis, aphasia, respiratory distress requiring ventilation	Aminophylline folinic acid	Quadriplegia and dysarthria
5	ALL	17	M	UKALL2003	8	Consolidation	Arm monoparesis, confusion, aphasia	Anticonvulsants Antimicrobials	Persistent impairment in short-term memory and ataxia
6	ALL	7	F	CoALL 08–09	4	Induction	Somnolence, respiratory distress requiring ventilation, impaired speech, and motor function	Antimicrobials antifungals antivirals folinic acid aminophylline	Persistent limitations in cognitive function

Patients 1 and 2 reflect the patients in this series reflecting cases 1 and 2, respectively, and patients 3 to 5 reflect the survey findings from Bond et al⁴ in the UKALL 2003 trial, and patient 6 obtained from Löbel et al.⁵ Of note, patient 6 received nitrous oxide during her intrathecal methotrexate administration and this was felt by the author to be a possible contributing factor.

ALL indicates acute lymphoblastic leukemia; IVIG, intravenous immunoglobulin.