CT densitometry of the brain: a novel method for early detection and assessment of irradiation induced brain edema.

The purpose of the study was to examine if the CT densitometric analysis during radiotherapy (RT) of brain tumors is suitable for the early detection of RT induced brain edema (BE), predicting related neurological progress, and assessing the effects of different edema therapies. Planimetric CT-densitograms were constructed by modifying the "High-Lighting" method. Three theoretical density regions were defined and color-coded on the images of the brain. These were defined as edema (10-20 HU), mild edema, and normal brain (29-38 HU). Corresponding axial CT slices were created at the mid-level of the lesion and that of the periventricular white matter to verify the changes in perifocal and diffuse BE. The monitoring was performed on 50 solitary brain tumor patients treated with RT. During RT courses weekly CT-densitometric examinations were carried out. We experienced that changes in densitograms coincided with clinical symptoms, furthermore, preceded the latter. With the use of preventive edema medication based on diuretics and along with adjunctive edema medication adopted to densitograms, the 5-7 week irradiation was completed without ultimate worsening in performance state in 49 of 50 cases and besides we succeeded in avoiding the routine usage of steroids. Based on our findings the CT-densitometry is suitable for early detection and continuous assessment of BE and preventing patient distress during RT. This simple, reproducible and non-invasive procedure could provide an additional clinical tool for new treatment strategies.

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

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 identified 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.

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

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 effective dose of 88 Gy(2) (44 Gy in 2 Gy fractions/day, with an estimated alpha/beta 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 flaccid 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]fluorodeoxyglucose (FDG) and [(11)C] methionine were conducted. Four lines of experiments (clonogenic assay using fibroblasts 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).