Makindo Medical Notes

Related Subjects: |Neurological History taking |Causes of Stroke |Ischaemic Stroke |Hypertension |Small Vessel Disease |CADASIL |CARASIL

🧠 Cerebral Autosomal Recessive Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CARASIL) is a rare hereditary small vessel disease causing recurrent subcortical strokes, progressive dementia, and distinctive systemic features. It is the rarer, autosomal recessive counterpart of CADASIL.

📖 About

• Inheritance: Autosomal recessive (contrast with CADASIL → autosomal dominant).
• Cause: Mutation in HTRA1 gene → impaired regulation of TGF-β signalling and vascular wall degeneration.
• Epidemiology: Mostly reported in Japan & China 🇯🇵🇨🇳 but cases exist worldwide. Extremely rare.

🧬 Pathology

• Marked arteriosclerosis of small penetrating arteries (basal ganglia, thalamus, pons).
• Unlike CADASIL → ❌ No granular osmiophilic material (GOM) or amyloid deposits.
• Diffuse leukoencephalopathy with lacunar infarcts.

🩺 Clinical Features

• Recurrent small-vessel ischaemic strokes → stepwise neurological decline.
• Progressive dementia beginning in 30s–50s.
• Premature alopecia (early baldness, often preceding neuro symptoms ✨ key clue).
• Chronic low back pain → due to spondylosis deformans & lumbar disc herniation.
• Other: Pyramidal signs, gait disturbance, pseudobulbar palsy in later stages.

🔍 Differential Diagnoses

• CADASIL – similar leukoencephalopathy but dominant inheritance + GOM deposits.
• Hypertensive small vessel disease – commoner, lacks alopecia/back pain association.
• Other genetic leukoencephalopathies – e.g. COL4A1-related, mitochondrial leukodystrophies.

🧪 Investigations

• MRI Brain: Widespread white matter hyperintensities (esp. basal ganglia, thalamus, pons), lacunes, subcortical infarcts.
• Genetic Testing: Confirmation via biallelic HTRA1 mutations.
• Spinal Imaging: May show degenerative disc disease correlating with back pain.

💊 Management

• ❌ No disease-modifying therapy.
• Symptomatic: Pain control, physio/rehab for gait & motor deficits, cognitive support.
• Stroke prevention: Vascular risk factor management (BP, diabetes, cholesterol).
• Genetic counselling: Essential due to autosomal recessive inheritance.

📊 Key Exam Pearls

✅ CARASIL = HTRA1 mutation, recessive. ✅ Look for triad: Subcortical strokes + Dementia + Premature alopecia/back pain. ✅ Differentiate from CADASIL (dominant, NOTCH3 mutation, GOM deposits).

📚 References

• Hara K. et al. NEJM 2009 – Discovery of HTRA1 mutation in CARASIL.
• International consensus reviews on hereditary small vessel diseases (Lancet Neurol 2020).