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Quantitative analysis of cerebral vasculopathy in patients with Fabry disease
K E Crutchfield1, N J Patronas, J M Dambrosia
1Developmental and Metabolic Neurology Branch, National Institute of Neurologic Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-1260, USA.
Insights
Cerebrovascular involvement in Fabry disease progresses with age, with all patients over 54 showing lesions. This natural history provides a measure for evaluating new Fabry disease treatments.
Area of Science:
- Neurology
- Genetics
- Medical Imaging
Background:
- Fabry disease is an X-linked disorder caused by alpha-galactosidase A deficiency.
- Ceramidetrihexoside accumulation in cerebral blood vessels leads to ischemic lesions in most patients.
- Understanding the natural history of Fabry disease's cerebral vasculopathy is crucial for assessing therapeutic interventions.
Purpose of the Study:
- To quantitatively determine the natural history of cerebrovascular involvement in Fabry disease.
- To establish a predictable outcome measure for therapeutic interventions.
Main Methods:
- A longitudinal study involving 50 patients and 129 MRI scans.
- Cerebrovascular disease burden was quantified using direct linear measurements on T2-weighted MRI scans.
Main Results:
- Cerebrovascular lesions were observed in 68% of patients, with prevalence increasing with age.
- No lesions were detected in patients under 26; all patients over 54 exhibited cerebrovascular involvement.
- Lesion distribution suggested a small-vessel disease pattern, with only 37.5% of affected patients experiencing neurological symptoms.
Conclusions:
- The study provides a quantitative natural history of cerebrovascular disease in Fabry disease.
- These findings establish a predictable outcome measure for assessing molecular interventions targeting cerebrovascular circulation in Fabry disease.
Objective:
This study's purpose was to obtain a quantitative natural history of the cerebrovascular involvement in Fabry disease.
Background:
Fabry disease is an X-linked recessive disorder due to alpha-galactosidase A deficiency. Progressive accumulation of ceramidetrihexoside within the intima and media of cerebral blood vessels causes ischemic lesions 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.
Methods:
A longitudinal MRI study of 50 patients who had a total of 129 MRI scans was performed. The burden of cerebrovascular disease was determined using direct linear measurement.
Results:
On T2-weighted MRI scans, 32% of the patients had no lesions (mean age, 33 years), 16% had gray 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 gray matter (mean age, 47 years). Disease burden increased with age, but no patient younger than 26 had lesions on MRI. All patients older than 54 had cerebrovascular involvement. The distribution of MRI-detectable lesions was typical of a small-vessel disease. Only 37.5% of patients with cerebral lesions had neurologic symptoms.
Conclusion:
These findings provide a predictable outcome measure to assess the effect of molecular interventions on the cerebrovascular circulation in Fabry disease.