Nerve lesions after therapy for childhood acute lymphoblastic leukemia.
BACKGROUND
The objective of the current study was to use somatosensory evoked potentials (SEP) to detect signs of nerve lesions in the peripheral nerve and in the central nervous system (CNS) after 3 years of treatment for childhood acute lymphoblastic leukemia (ALL).


METHODS
The somatosensory potentials evoked by stimulation of the median nerve and posterior tibial nerve were recorded in 31 children with ALL after 3 years of therapy. All patients were examined clinically. The 14 standard risk patients had been treated with chemotherapy according to the Nordic regimen, and the 17 intermediate risk or high risk patients had been treated with chemotherapy and cranial irradiation according to the ALL BFM-83 protocol.


RESULTS
A decrease in amplitudes was observed at the brachial plexus and spinal cord (C7) in the median SEP, and at the knee, spinal cord (Th12), and cortex in the tibial SEP, indicating axonal injury within the entire CNS in the patients with ALL compared with healthy age-, gender-, and height-matched controls. Prolongation of the SEP latencies was found within the spinal cord, indicating demyelination. These SEP changes had persisted for 2 years since the last injection/infusion of vincristine or methotrexate, which are the principal neurotoxic drugs used in chemotherapy for ALL. Clinical signs of nerve injury such as depressed deep tendon reflexes and gross or fine motor difficulties were found in approximately 33% of the patients and dysdiadochokinesia in 50%.


CONCLUSIONS
Treatment of ALL in children principally with vincristine and methotrexate causes long-standing axonal injury throughout the nervous system and demyelination within the spinal cord. These changes are associated with clinical neurologic findings.
Harila-Saari
A H
AH
Department of Pediatrics, University of Oulu, Finland.
Vainionpää
L K
LK
Kovala
T T
TT
Tolonen
E U
EU
Lanning
B M
BM
D000293:Adolescent; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001369:Axons / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D001917:Brachial Plexus / Q000187:drug effects / Q000503:physiopathology / Q000528:radiation effects; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D016371:Cranial Irradiation; D003711:Demyelinating Diseases / Q000175:diagnosis / Q000209:etiology; D005073:Evoked Potentials, Somatosensory / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D008475:Median Nerve / Q000187:drug effects / Q000503:physiopathology / Q000528:radiation effects; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D009048:Motor Skills / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D010523:Peripheral Nervous System Diseases / Q000175:diagnosis / Q000209:etiology*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000532:radiotherapy; D011596:Psychomotor Disorders / Q000209:etiology / Q000503:physiopathology; D012026:Reflex, Stretch / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D012307:Risk Factors; D013116:Spinal Cord / Q000187:drug effects / Q000503:physiopathology / Q000528:radiation effects; D013118:Spinal Cord Diseases / Q000175:diagnosis / Q000209:etiology*; D013979:Tibial Nerve / Q000187:drug effects / Q000503:physiopathology / Q000528:radiation effects; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects
D000964:Antimetabolites, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D014750:Vincristine; D008727:Methotrexate