1. ¹Department of Oncotherapy, Semmelweis University, Hungary
2. ²Department of Radiotherapy, National Institute of Oncology, Hungary
3. ³Outpatient Department of Neurology, National Institute of Oncology, Budapest, Hungary
4. ⁴PET Center, University of Debrecen, Debrecen, Hungary
5. ⁵Department of Molecular and Tumor Biology, National Institute of Radiobiology and Radiation Hygiene, Budapest, Hungary
6. ⁶PET Study Group of the Hungarian Academy of Sciences, Debrecen, Hungary

Correspondence: O Ésik, Department of Oncotherapy, Semmelweis University, Ráth György u. 7-9, Budapest, H-1122 Hungary

Abstract

Objective: To investigate the pathogenesis of the rare radiogenic lower motor neurone disease (LMND) on the basis of a meta-analysis of the published case histories.

Materials and methods: The authors reviewed 47 well-documented radiogenic LMND cases from the English literature.

Results: The disease typically occurs following the irradiation of radiosensitive cancers situated near the spinal cord. It arises predominantly (46 cases) in the lower extremities; only one case involved the upper extremities. There is a male predominance (male:female ratio 7.8:1), and the patients are characteristically young (13–40 years, with four exceptions). An overdose does not seem to be a particular risk factor for the development of the disease, as total dose, fraction size and biologically effective dose are typically below 50 Gy, 2 Gy and 128 Gy₂, respectively, which are regarded as safe doses. Other risk factors (chemotherapy, operations, etc) have been identifed only rarely. Radiogenic LMND is manifested in an apparently random manner, 4–312 (mean 48.7) months after the completion of radiotherapy.

Discussion: The complete lack of a dose–effect relationship argues strongly against a pure radiogenic nature of the pathological process. The latency period is typically several years and it varies extremely, which excludes a direct and complete causal relationship between radiotherapy and LMND. As the interaction of ionizing radiation with living tissues is highly unspecific, thus a selective motor injury due to irradiation alone, without comparable effects on the sensory and vegetative fibers, seems improbable.

Conclusions: On analogy with the viral motor neurone diseases, we suppose that radiogenic LMND may be preceded by viral (enterovirus/poliovirus) infection. Based on the meta-analysis, it is suggested that irradiation may be only a single component of the set of factors jointly resulting in the clinical state regarded as radiogenic LMND.