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Electron microscopy analysis of skin biopsies in CADASIL disease
Carmen Elena Cotrutz1, Anca Indrei, L Bădescu
1Department of Cell and Molecular Biology, Faculty of Medicine, Grigore T Popa University of Medicine and Pharmacy, Iassy, Romania. cotrutz@yahoo.com
Insights
Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is diagnosed via skin biopsy. Electron microscopy reveals characteristic granular osmiophilic material and smooth muscle cell degeneration, aiding in definitive diagnosis.
Area of Science:
- Neurology
- Vascular Biology
- Genetics
Background:
- Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a genetic, non-amyloid, non-atherosclerotic vascular disorder impacting the central nervous system.
- Patients often present with neurological deficits such as motor impairment, facial asymmetry, and speech difficulties, frequently with a family history of early-onset strokes.
Purpose of the Study:
- To investigate the ultrastructural changes in skin biopsies from CADASIL patients.
- To establish the diagnostic utility of electron microscopy in identifying characteristic pathological findings of CADASIL.
Main Methods:
- Skin biopsy samples from six male patients (43-52 years old) were processed for transmission electron microscopy.
- Ultrastructural analysis focused on identifying extracellular deposits and smooth muscle cell (SMC) alterations in dermal arteries.
Main Results:
- All cases exhibited granular osmiophilic material (GOM) in extracellular spaces adjacent to degenerating SMCs.
- Degeneration, loss of SMCs, and evidence of apoptosis were observed, correlating with clinical severity and MRI findings.
- Disturbances in cell adhesion elements were also noted.
Conclusions:
- The presence of GOM deposits and SMC degeneration/loss are characteristic findings sufficient for CADASIL diagnosis.
- Electron microscopy of skin biopsies is a valuable and potentially first-choice method for CADASIL diagnosis and differential diagnosis.
Abstract:
Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is an inherited vascular disorder, non-amyloid and non-atherosclerotic, affecting predominantly the central nervous system. We examined samples of skin biopsies from six patients (men, 43-52-year-old), admitted for treatment in the Neurology Clinic regarding the presence of partial motor impairment on upper and lower right limbs, facial asymmetry and phrasing impairment (three of the patients); These three patients had family history remarkable for early-onset strokes: mother and two brothers deceased by early strokes (40-50-year-old). Skin biopsy samples were fixed in glutaraldehyde and post-fixed in osmium tetroxyde. After dehydration, tissue samples were embedded in Epon. Ultrathin sections were mounted on copper grids and stained with uranyl acetate and lead citrate as usual and examined with a transmission electron microscope Phillips CM100. In all cases ultrastructural study showed granular osmiophilic material (GOM) in extracellular locations, between degenerating smooth muscle cells in dermal arteries or in their indentations. Deposits of GOM varied in size and electron density. Degeneration and loss of smooth muscle cells (SMCs) leads to abnormal enlargement of the space between these cells Ultrastructural analysis in three cases showed chromatin condensation and peripheral aggregation of nuclear material suggesting cells entry to apoptosis. These aspects and the marked destruction of the vascular wall were correlated with MRI findings and the severity of clinical manifestations at these patients. Our study showed that findings of GOM deposits, degeneration and loss of SMCs (probably by apoptosis), cell adhesion elements disturbance are characteristic for CADASIL disease and sufficient for diagnose of certainty. Moreover, electron microscopy analysis of skin biopsies is a useful tool for a differential diagnosis and can be considered as first choice method.
