False-Negative Tests in CADASIL
Background: The diagnosis of CADASIL is normally confirmed by screening DNA for mutations of Notch 3 gene or by skin biopsy. The pathological hallmark of this disease is the presence of characteristic granular osmiophilic material within the basal membrane of vascular smooth-muscle cells. Objective: We report the first CADASIL case with negative results for both genetic analysis and skin biopsy. Methods: A 69-year-old woman presented with recurrent TIA and strokes, seizures, and dementia. MRI revealed diffuse periventricular white matter abnormalities. Extensive investigation failed to reveal the cause of the disease. Analysis for CADASIL were performed. Results: The patient had no mutations in the Notch 3 gene, had a normal skin biopsy, but showed characteristic CADASIL abnormalities on brain pathological examination. Ultrastructural analysis of the brain showed marked destruction of smooth muscle cells with an accumulation of granular osmiophilic material in the muscular layer. Conclusion: Our findings suggest that negative results in the skin biopsy and genetic test do not exclude the disease, and a leptomeningeal biopsy should be considered in such cases. CADASIL may be more common than previously reported.