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Cadasil - genetic and ultrastructural diagnosis. Case report
Julio Cesar Vasconcelos da Silva1, Leila Chimelli2, Felipe Kenji Sudo3
1Neuropsychologist; MSc in Internal Medicine/Neurology- x; PhD Student at the Institute of Psychiatry, UFRJ, Rio de Janeiro - Brazil.
Insights
Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) diagnosis requires careful evaluation. Even initially negative skin biopsies may reveal characteristic GOM deposits upon further analysis, confirming the genetic disorder.
Area of Science:
- Neurology
- Genetics
- Pathology
Background:
- Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a hereditary cerebrovascular disease caused by NOTCH3 gene mutations.
- Diagnosis typically involves genetic testing and/or skin biopsy to identify characteristic vascular changes.
Observation:
- A female patient presented with transient ischemic attacks and progressive subcortical dementia.
- Neuroimaging revealed extensive leukoaraiosis and lacunar infarcts, consistent with CADASIL.
- Initial skin biopsy ultrastructural examination for GOM was negative.
Findings:
- Genetic analysis confirmed NOTCH3 mutations, establishing the diagnosis of CADASIL.
- Subsequent analysis of new sections from the same skin biopsy identified granular osmiophilic material (GOM) inclusions.
- This highlights the potential for delayed or missed diagnosis if initial negative findings are solely relied upon.
Implications:
- Negative ultrastructural findings in skin biopsies should not rule out CADASIL.
- Re-examination or further analysis of skin biopsy specimens may be crucial for detecting GOM.
- This underscores the importance of comprehensive diagnostic approaches for hereditary cerebrovascular disorders.
Abstract:
Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a hereditary disorder which affects the cerebral vasculature due to mutations in the NOTCH 3 gene. The diagnosis may be established through genetic testing for detection of these mutations and/or by skin biopsy. We report a case of the disorder in a female patient, who presented recurrent transient ischemic attacks that evolved to progressive subcortical dementia. Neuroimaging disclosed extensive leukoaraiosis and lacunar infarcts. The genetic analysis for NOTCH 3 was confirmatory. The ultrastructural examination of the skin biopsy sample, initially negative, confirmed the presence of characteristic changes (presence of granular osmiophilic material inclusions [GOM]), after the analysis of new sections of the same specimen. The present findings indicate that negative findings on ultrastructural examinations of biopsy should not exclude the diagnosis of the disease and that further analyses of the sample may be necessary to detect the presence of GOM.
