Localised multiple sclerosis-like disease after irradiation of the cervicothoracic spinal cord.

ABSTRACT

BACKGROUND: Radiation has been discussed as a potential causative factor for Multiple Sclerosis (MS). However, it is unresolved whether radiation increases the aggressiveness of the immune system or whether it alters the nervous tissue to become vulnerable to a pre-existing autoimmune attackdisposition. We report a patient with an MS-like disease confined to the irradiated part of his central nervous system (CNS). CASE REPORT within the course of a year, a 29 year-old man developed three relapses that were distinguishable regarding their neurological signs and symptoms. Clinically and on MRI, all relapses were localised to the cervico-thoracic spinal cord (sensory level Th6, monoparesis right leg, sign of Lhermitte). Four years before, he had been diagnosed with supradiaphragmatic Hodgkin´s lymphoma stage IIa. Four courses of chemotherapy with the ABVD-protocol and irradiation with 29,5 Gray led to complete tumour remission. Consecutive MR-imaging of the brain and spinal cord revealed fluctuating and partially contrast-enhancing lesions exclusively in those sections of the spinal cord that were localised in the field irradiated four years before. Treatment with pulsed i.v. steroids led to improvement. CSF analysis showed mild pleocytosis and isolated oligoclonal bands. Extensive work-up for differential diagnoses was negative. Genetic sequencing for DNA repair enzymes and in-vitro assays of the patients peripheral blood mononuclear cells for increased sensitivity to irradiation was unrevealing. CONCLUSION: The fact that this patients MS-like disease was strictly confined to the irradiated parts of the body suggests that the co-occurrence of Hodgkins and MS-like disease was not simple coincidence but that they are pathogenetically linked. An increased aggressiveness of the immune system caused by the radiation is an unlikely explanation as the autoimmune attack would not be expected to spare the non-radiated parts of the CNS. We propose that in our patient the nervous tissue in the radiation clinical target volume was altered by radiation. This alteration of antigenic make-up, in turn, may have enabled an MS-specific autoimmune attack by a pre-existent immunological mechanism. This hypothesis is supported by experimental studies of induction of experimental autoimmune encephalitis (EAE) in irradiated rats.