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Late Effects of Treatment for Childhood Cancer (PDQ®): Treatment - Health Professional Information [NCI] - Late Effects of the Central Nervous System

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Clinical or radiographic leukoencephalopathy has been reported after cranial irradiation and high-dose systemic methotrexate administration. Younger patients and those given radiation doses greater than 24 Gy are more vulnerable to this complication. White matter changes may be accompanied by such neuroimaging abnormalities as dystrophic calcifications, cerebral lacunae, and cerebral atrophy.

Vinca alkaloid agents (vincristine and vinblastine) and cisplatin may cause peripheral neuropathy. This condition presents during treatment and appears to clinically resolve after completion of therapy. However, higher cumulative doses of vincristine and/or intrathecal methotrexate have been linked to neuromuscular impairments in long-term survivors of childhood ALL, which suggests that persistent effects of these agents may impact functional status in aging survivors.[48]

In a report from the CCSS that compared 4,151 adult survivors of childhood ALL with their siblings, survivors were at an elevated risk for late-onset coordination problems, motor problems, seizures, and headaches. The overall cumulative incidence was 44% at 20 years. Serious headaches were most common, with a cumulative incidence of 25.8% at 20 years followed by focal neurologic dysfunction (21.2%) and seizures (7%). Children who were treated with regimens that included cranial radiation for ALL and those who suffer relapse were at increased risk for late-onset neurologic sequelae.[49]

Table 3. Central Nervous System Late Effects

Predisposing TherapyNeurologic EffectsHealth Screening
IQ = intelligence quotient; IT = intrathecal; IV = intravenous.
Platinum agents (carboplatin, cisplatin)Peripheral sensory neuropathyNeurologic exam
Plant alkaloid agents (vinblastine, vincristine)Peripheral sensory or motor neuropathy (areflexia, weakness, foot drop, paresthesias)Neurologic exam
Methotrexate (high dose IV or IT); cytarabine (high dose IV or IT); radiation impacting the brainClinical leukoencephalopathy (spasticity, ataxia, dysarthria, dysphagia, hemiparesis, seizures); headaches; seizures; sensory deficitsHistory: cognitive, motor, and/or sensory deficits, seizures
Neurologic exam
Radiation impacting cerebrovascular structuresCerebrovascular complications (stroke, moyamoya, occlusive cerebral vasculopathy)History: transient/permanent neurological events
Blood pressure
Neurologic exam
Neurosurgery–brainMotor and/or sensory deficits (paralysis, movement disorders, ataxia, eye problems [ocular nerve palsy, gaze paresis, nystagmus, papilledema, optic atrophy]); seizuresNeurologic exam
Neurology evaluation
Neurosurgery–brainHydrocephalus; shunt malfunctionAbdominal x-ray
Neurosurgery evaluation
Neurosurgery–spineNeurogenic bladder; urinary incontinenceHistory: hematuria, urinary urgency/frequency, urinary incontinence/retention, dysuria, nocturia, abnormal urinary stream
Neurosurgery–spineNeurogenic bowel; fecal incontinenceHistory: chronic constipation, fecal soiling
Rectal exam
Predisposing TherapyNeuropsychological EffectsHealth Screening
Methotrexate (high-dose IV or IT); cytarabine (high-dose IV or IT); radiation impacting the brain; neurosurgery–brainNeurocognitive deficits (executive function, memory, attention, processing speed, etc.); learning deficits; diminished IQ; behavioral changeAssessment of educational and vocational progress
Formal neuropsychological evaluation
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