Nerve lesions after therapy for childhood acute lymphoblastic leukemia

Cancer. 1998 Jan 1;82(1):200-7. doi: 10.1002/(sici)1097-0142(19980101)82:1<200::aid-cncr25>3.0.co;2-5.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antimetabolites, Antineoplastic / administration & dosage
  • Antimetabolites, Antineoplastic / adverse effects
  • Antineoplastic Agents, Phytogenic / administration & dosage
  • Antineoplastic Agents, Phytogenic / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Axons / drug effects
  • Axons / physiology
  • Axons / radiation effects
  • Brachial Plexus / drug effects
  • Brachial Plexus / physiopathology
  • Brachial Plexus / radiation effects
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Combined Modality Therapy
  • Cranial Irradiation
  • Demyelinating Diseases / diagnosis
  • Demyelinating Diseases / etiology
  • Evoked Potentials, Somatosensory / physiology
  • Female
  • Humans
  • Male
  • Median Nerve / drug effects
  • Median Nerve / physiopathology
  • Median Nerve / radiation effects
  • Methotrexate / administration & dosage
  • Methotrexate / adverse effects
  • Motor Skills / drug effects
  • Motor Skills / physiology
  • Motor Skills / radiation effects
  • Peripheral Nervous System Diseases / diagnosis
  • Peripheral Nervous System Diseases / etiology*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / radiotherapy
  • Psychomotor Disorders / etiology
  • Psychomotor Disorders / physiopathology
  • Reflex, Stretch / drug effects
  • Reflex, Stretch / physiology
  • Reflex, Stretch / radiation effects
  • Risk Factors
  • Spinal Cord / drug effects
  • Spinal Cord / physiopathology
  • Spinal Cord / radiation effects
  • Spinal Cord Diseases / diagnosis
  • Spinal Cord Diseases / etiology*
  • Tibial Nerve / drug effects
  • Tibial Nerve / physiopathology
  • Tibial Nerve / radiation effects
  • Vincristine / administration & dosage
  • Vincristine / adverse effects

Substances

  • Antimetabolites, Antineoplastic
  • Antineoplastic Agents, Phytogenic
  • Vincristine
  • Methotrexate