A PET study on the characterization of partially reversible radiogenic lower motor neurone disease

Abstract

Objective: To investigate the pathomechanism of the rare radiogenic lower motor neurone disease (LMND) on the basis of a case history involving a partial functional recovery. Patient: A 31-year-old seminoma patient received postoperative para-aortic and para-iliac telecobalt irradiation with a biologically eective dose of 88 Gy 2 (44 Gy in 2 Gy fractions/day, with an estimated a/b of 2 Gy) delivered to the spinal cord following a single cycle of chemotherapy. LMND developed 4 months after the completion of radiotherapy. The patient exhibited¯accid paraparesis of the lower extremities (without sensory or vegetative signs), followed by a worsening after further chemotherapy, due to pulmonary metastatization. A gradual spontaneous functional improvement commenced and led several years later to a stabilized state involving moderately severe symptoms. Methods: In the 15th year of the clinical course, magnetic resonance imaging (MRI) and positron emission tomography (PET) with [18 F]¯uorodeoxyglucose (FDG) and [ 11 C]methionine were conducted. Four lines of experiments (clonogenic assay using ®broblasts isolated from a skin biopsy sample of the patient, comet assay, micronucleus assay, and the testing of chromosome aberrations after in vitro irradiation of peripheral blood samples) were performed in a search for an increased individual radiosensitivity. Results: MRI investigations failed to reveal any pathological change. PET demonstrated an increased FDG accumulation, but a negligible [ 11 C]methionine uptake in the irradiated spinal cord segments. The radiobiological investigations did not indicate any sign of an increased individual radiosensitivity. Conclusions: We suggest that the observed partial functional recovery and stabilization of the symptoms of radiogenic LMND may be explained by the higher than normal density of sodium channels expressed along the demyelinated axons of the restored conduction. The increased energy demands of this type of conduction are proved by a higher metabolic rate (increased FDG uptake) of the irradiated spinal cord segments without a substantial regenerative process (lack of detectable protein synthesis).

Changes in18F-Fluorodeoxyglucose Uptake in the Spinal Cord in a Healthy Population on Serial Positron Emission Tomography/Computed Tomography

“…However, those studies were done in patients with a cancer history and were conducted without follow-up PET/CT. Therapy such as radiation therapy, chemotherapy, or surgery might affect FDG uptake in the spinal cord 8-12. Also, many diseases, including spinal metastasis,13,14 spinal sarcoidosis,15,16 and myelopathy,17-19 can increase FDG uptake in the spinal cord.…”

Characteristics of radiogenic lower motor neurone disease, a possible link with a preceding viral infection

“…paresis, a complete neurological case history was a prerequisite for inclusion: only 47 such well-documented radiogenic LMND cases (Table 1) were found. [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] Successive publications often included previous case reports; accordingly, only the latest publications are listed.…”

“…In these cases, the gray matter injuries are manifested primarily in the arms. [1][2][3][4]8,9 In most cases of radiogenic LMND, however, the only clinical sign of the radiation injury [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] is the flaccid paresis. The disease involves basically the legs, exhibiting a chronic, progressive and irreversible clinical course.…”