Makindo Medical Notes

Related Subjects: |Neurological History taking |Causes of Stroke

Sneddon Syndrome 🌀🧠 is a rare progressive disorder defined by the combination of livedo reticularis/livedo racemosa (skin changes) and cerebrovascular disease (stroke/TIA). It often affects young women, is linked with autoimmune disease, and carries a high risk of cognitive decline and dementia.

📖 About

• Rare: ~4 per million, mostly women aged 20–40.
• First described by Sneddon in 1966 as a syndrome of stroke + livedo reticularis.
• Progressive course — ~50% develop dementia over time.

⚙️ Aetiology & Pathophysiology

• Non-inflammatory thrombotic vasculopathy: small- and medium-vessel occlusion.
• Arterial lesions may mimic arteriovenous malformations or moyamoya-like changes.
• Genetic: CECR1 (ADA2 deficiency) mutations reported in some cases.
• Leads to chronic ischaemia → infarcts, microbleeds, and atrophy.

🤝 Associations

• Systemic lupus erythematosus (SLE) 🦋
• Antiphospholipid syndrome (aPL) 🧪
• Behçet disease
• Mixed connective tissue disease

🩺 Clinical Features

• 🔁 Recurrent neurological events: TIAs/strokes → hemiplegia, aphasia, hemianopia, sensory loss.
• 💥 Can present with subarachnoid haemorrhage or spinal strokes.
• 🌐 Skin:
  • Livedo racemosa: fixed, violaceous, net-like mottling on legs, arms, buttocks, trunk; worsens with cold or pregnancy.
  • Livedo reticularis: transient mottling of extremities, cold-induced.
• 🧠 Other neuro: chronic headaches, dizziness, seizures, chorea, cognitive decline.
• ⚡ Hypertension often present.
• 👁 Other organ involvement: kidney, heart, eyes, peripheral nerves.

🔍 Differentials

• Reversible cerebral vasoconstriction syndrome (RCVS)
• MELAS (mitochondrial encephalopathy)
• Vascular dementia
• Migraine with aura
• Cerebral angiitis (vasculitis)

🧪 Investigations

• Bloods: Immunology usually negative (ANA, ENA, RF). But aPL antibodies (anticardiolipin, lupus anticoagulant, anti-β2GPI) are + in ~60%.
• MRI brain: white matter hyperintensities, lacunar infarcts, microbleeds, atrophy.
• Cerebral angiography: may be normal or show small-vessel irregularities.
• Skin biopsy: non-inflammatory arteriopathy → subendothelial proliferation, fibrosis, luminal narrowing.

💊 Management

• 🩸 Anticoagulation: often used in high-risk/aPL-positive patients.
• 💊 Antiplatelets: reasonable in lower risk or aPL-negative cases.
• 💉 ACE inhibitors: may reduce endothelial proliferation.
• 🧬 Immunosuppression: e.g., rituximab may help in aPL-positive cases with inflammatory features.
• 🎯 Risk factor control: strict BP management, lifestyle modification.

📌 Exam & OSCE Pearls

• Young woman + strokes + livedo racemosa = think Sneddon syndrome.
• Differentiate livedo racemosa (persistent, widespread, systemic) from livedo reticularis (cold-induced, peripheral).
• Always check for antiphospholipid antibodies and autoimmune disease.
• Long-term outlook: high risk of progressive vascular dementia despite therapy.

📚 References

• Kalashnikova LA, et al. Sneddon’s syndrome: clinical and neuroimaging study. Cerebrovasc Dis. 2003.
• Nicolas G, et al. Sneddon syndrome revisited: genetic insights and update. Stroke. 2014.
• Behjati R, et al. Sneddon’s syndrome: a review. Orphanet J Rare Dis. 2013.