[The new diagnostic methods of CADASIL as differential diagnosis of HDLS]

Area of Science:

• Neurology
• Genetics
• Radiology

Background:

• Hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS) and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) are both autosomal dominant white matter diseases.
• HDLS typically presents with cognitive decline or dementia, whereas CADASIL often manifests as migraine or ischemic infarcts.
• Family history of stroke in young patients is a significant indicator for CADASIL.

Purpose of the Study:

• To outline diagnostic criteria and differentiation methods for HDLS and CADASIL.
• To highlight the utility of specific MRI findings and immunohistochemical analysis in diagnosing CADASIL.
• To investigate the pathogenesis of CADASIL through analysis of granular osmiophilic material (GOM).

Main Methods:

• Clinical evaluation including family history assessment.
• Magnetic Resonance Imaging (MRI) analysis, emphasizing coronal views for lesion differentiation.
• Immunohistochemical staining of Notch3 in frozen skin samples and histochemical staining for GOM analysis.

Main Results:

• Temporal pole lesions are characteristic of CADASIL, though not always present.
• Confluent external capsular lesions and multiple white matter medullary infarcts on MRI aid in differentiating CADASIL from non-CADASIL.
• Coronal MRI views are superior to horizontal views for distinguishing ischemic from demyelinated lesions.
• Notch3 immunohistochemistry and detection of GOM in frozen sections are valuable diagnostic tools.

Conclusions:

• Accurate differentiation between HDLS and CADASIL requires a combination of clinical, radiological, and pathological findings.
• Advanced techniques like proteomics (LC/MS/MS) are proposed for further elucidating the pathogenesis of CADASIL by analyzing arterial granular degeneration.
• Notch3 immunohistochemistry and GOM analysis provide crucial diagnostic insights.