Post-Radiation Motor Neuron Disease
Abstract & Commentary
By Michael Rubin, MD
Professor of Clinical Neurology, Weill Cornell Medical College
Dr. Rubin reports no financial relationships relevant to this field of study.
Synopsis:Post-radiation lower motor neuron disease mimics spinal muscular atrophy rather than classical amyotrophic lateral sclerosis.
Source: Abraham A, Drory VE. Postradiation lower motor neuron syndrome:
Case series and literature review. J Neurol 2013;260:1802-1806.
If included in the treatment field, radiation therapy can cause injury to the central or peripheral nervous system that may occur during the course of therapy (acute), within weeks to 3 months (early delayed), or beyond 3 months (delayed). Spinal cord syndromes include a self-limited transient myelopathy occurring 2-6 months following spinal cord irradiation, characterized by the development of Lhermitte's sign, resolving spontaneously within a year, and attributed to reversible demyelination of the posterior columns of the spinal cord. It does not presage chronic progressive myelitis. More disabling consequences of spinal cord irradiation include acute paralysis due to cord ischemia, intramedullary spinal cord hemorrhage, and a lower motor neuron syndrome; the latter is due to involvement of either the anterior horn cell or cauda equina and is the subject of this case series.
Medical records of patients seen between 2005-2012 with a lower-limb, post-radiation, lower motor neuron syndrome were reviewed. Inclusion criteria encompassed the presence of slowly progressive leg weakness in a patient with prior distal spinal cord and cauda equina radiation; signs of lower motor neuron involvement including fasciculations, muscle atrophy, and depressed or absent deep tendon reflexes; and electrophysiological studies demonstrating denervation in leg muscles. Spinal imaging and cerebrospinal fluid (CSF) studies had to be normal, except for the inclusion of patients with elevated CSF protein, and no alternative diagnosis could be present. Similar patients found by PubMed review of the literature were included for analysis.
Five patients were identified and supplemented by 45 similar cases found in the literature. Among the five cases, three underwent distal spinal cord and cauda equina irradiation for seminoma and two for lymphoma. Total radiation dosage for the two patients on whom it was available was 2500 cGy and 2800 cGy, and the mean latency to onset of symptoms was 15 years (range 10-19 years). Distal weakness, bilateral (n = 3) or unilateral (n = 2), with depressed or absent reflexes were the characteristic findings, with two patients having thigh fasciculations and two noting a subjective, stocking distribution, sensory disturbance, objectively documented in only one patient, expressed as decreased light touch. None had sphincteric symptoms, and all continued to slowly deteriorate but remained ambulatory. Nerve conduction studies revealed low motor amplitudes in four patients and sensory abnormalities in only one, with positive sharp waves, large polyphasic motor units, and a decreased interference pattern on needle electromyography, predominantly in L4-5-S1 myotomes. Among 45 patients collected from the literature, mean age was 33 years, average radiation dose was 5225 cGy, and mean latency to symptom onset was 9 years (range 3 months to 27 years). Males predominated (89%), with testicular cancer (67%) and lymphoma (23%) accounting for the majority of cases, and 10% due to cancer of the kidney, cervix, or breast; pheochromocytoma; or medulloblastoma. Among 16 patients who underwent spinal MRI, seven showed gadolinium enhancement of the cauda equina. Sensory nerve conduction studies were normal in 96% of patients.
Post-radiation lower motor neuron disease mimics sporadic progressive spinal muscular atrophy (PSMA), which itself is incorrectly diagnosed in up to 20% of cases. As several of these mimics are treatable, correct diagnosis is imperative.1 Multifocal motor neuropathy with conduction block is the disorder most often mistaken for PSMA, but, in addition to post-radiation lower motor neuron disease, other mimics include chronic inflammatory demyelinating polyneuropathy, inflammatory myopathy, myasthenia gravis, myopathy, syringomyelia, and idiopathic chronic axonal neuronal neuropathy. When the upper limbs and/or cranial muscles are involved, Hirayama’s disease, brachial neuritis, Kennedy’s syndrome, and distal myopathy or inclusion body myositis are other considerations.
- Visser J, et al. Mimic syndromes in sporadic cases of progressive spinal muscular atrophy. Neurology 2002;58:1593-1596.