Clinical findings and magnetic resonance imaging in severe cyclosporine-related neurotoxicity after allogeneic bone marrow transplantation.
OBJECTIVE
Severe neurotoxicity is a recognized complication of cyclosporin A (cyclosporine, CSA). Neuroimaging studies typically show reversible brain lesions, predominantly confined to the white matter. Our aim was to delineate clinical characteristics and to specify results of magnetic resonance imaging (MRI) and computerised tomography (CT) scan findings.


METHODS
Cases of severe cyclosporine-related neurotoxicity (SNCT) were identified among a series of 129 consecutive allogeneic transplant recipients. Clinical features were analysed, including CSA levels, electrolytes, cholesterolemia and magnesemia. MRI and/or CT scans were obtained within 24 h to 4 d after the onset of neurotoxicity.


RESULTS
Six patients (4.6%) developed a prodromal phase (headache and/or hypertension), followed by SCNT, including generalized seizures (n = 5), occipital blindness (n = 1) and hemiparesis (n = 1). There was no correlation between the laboratory findings and the onset of SNCT. All patients were on corticosteroid treatment. MRI studies showed hyperintensity lesions, predominantly in the posterior cerebrum, with both subcortical and cortical involvement in 4 out of 5 patients. Cerebellar involvement (n = 4) was also a frequent finding. The signal abnormalities, corresponding to the anastomotic border zones between major cerebral and cerebellar arteries, were limited to the respective cortical areas.


CONCLUSIONS
Association of corticosteroids is a trigger in the development of SCNT. MRI is recommended for the early identification of the transient brain lesions in patients with a prodromal phase. The more specific distribution of the lesions in the anastomotic border zones suggests vascular injury as a contributing factor in the pathology of SNCT.
Trullemans
F
F
BMT-Unit, Brussels, Belgium. Fabienne.Trullemans@az.vub.ac.be
Grignard
F
F
Van Camp
B
B
Schots
R
R
D000293:Adolescent; D000328:Adult; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D016026:Bone Marrow Transplantation; D001921:Brain / Q000473:pathology*; D001929:Brain Edema / Q000139:chemically induced / Q000473:pathology; D002531:Cerebellum / Q000473:pathology; D002540:Cerebral Cortex / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D002784:Cholesterol / Q000097:blood; D016572:Cyclosporine / Q000009:adverse effects* / Q000097:blood; D004357:Drug Synergism; D005260:Female; D005500:Follow-Up Studies; D006261:Headache / Q000139:chemically induced; D019337:Hematologic Neoplasms / Q000628:therapy; D006801:Humans; D006973:Hypertension / Q000139:chemically induced; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000097:blood; D007223:Infant; D008274:Magnesium / Q000097:blood; D008279:Magnetic Resonance Imaging; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use; D008875:Middle Aged; D009422:Nervous System Diseases / Q000097:blood / Q000139:chemically induced* / Q000473:pathology; D010291:Paresis / Q000139:chemically induced; D012640:Seizures / Q000139:chemically induced; D013601:T-Lymphocytes; D014184:Transplantation, Homologous; D014786:Vision Disorders / Q000821:virology
D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D002784:Cholesterol; D008274:Magnesium; D008775:Methylprednisolone