QUANTITATIVE-ANALYSIS OF CEREBRAL VASCULOPATHY IN PATIENTS WITH FABRY-DISEASE

Objective: This study's purpose was to obtain a quantitative natural h istory of the cerebrovascular involvement in Fabry disease. Background : Fabry disease is an X-linked recessive disorder due to ol-galactosid ase A deficiency. Progressive accumulation of ceramidetrihexoside with in the intima and media of cerebral blood vessels causes ischemic lesi ons in the majority of affected patients. Determination of the natural history of the cerebral vasculopathy in Fabry disease is important to assess the effects of therapeutic intervention in this disorder. Meth ods: A longitudinal MRI study of 50 patients who had a total of 129 MR I scans was performed. The burden of cerebrovascular disease was deter mined using direct linear measurement. Results: On T2-weighted MRI sca ns, 32% of the patients had no lesions (mean age, 33 years), 16% had g ray matter lesions only (mean age, 36 years), 26% had lesions in white matter only (mean age, 43 years), and 26% had lesions in white and gr ay matter (mean age, 47 years). Disease burden increased with age, but no patient younger than 26 had lesions on MRI. All patients older tha n 54 had cerebrovascular involvement. The distribution of MRI-detectab le lesions was typical of a small-vessel disease. Only 37.5% of patien ts with cerebral lesions had neurologic symptoms. Conclusion: These fi ndings provide a predictable outcome measure to assess the effect of m olecular interventions on the cerebrovascular circulation in Fabry dis ease.