Posterior Circulation Ischemia Due to Carotid Artery Dissection with Hyperhomocysteinemia

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Posterior Circulation Ischemia Due to Carotid Artery Dissection with Hyperhomocysteinemia in a 51-Year-Old Man

Clinical Presentation and Initial Assessment

A 51-year-old man presented to the emergency department with sudden-onset slurred speech and quadriplegia. He had no significant medical history, no history of smoking or alcohol use, and no recent trauma. Neurological examination revealed vocal cord paralysis, binocular dyskinesia, glossoplegia (impaired tongue movement), and tetraplegia (muscle strength graded at level 3). Routine blood tests, coagulation profiles, liver/kidney function tests, thyroid function, and tumor markers were within normal ranges. Notably, his low-density lipoprotein (LDL) level was 3.22 mmol/L, and his plasma homocysteine (Hcy) level was markedly elevated at 70.6 µmol/L (reference range: <15 µmol/L). Vitamin B12 levels were normal, ruling out deficiency as a contributor to hyperhomocysteinemia (HHcy). Non-contrast computed tomography (CT) of the head showed no acute hemorrhage or ischemic changes.

Imaging Findings and Diagnostic Workup

Digital Subtraction Angiography (DSA):
Performed on the day of admission, DSA revealed complete occlusion of the left internal carotid artery (ICA). Collateral circulation to the left middle cerebral artery (MCA) was observed via the anterior communicating artery from the right ICA. Additionally, a persistent trigeminal artery (PTA)—a rare embryological remnant connecting the carotid and vertebrobasilar systems—was identified, partially supplying the posterior circulation (Figure 1A–C).

Magnetic Resonance Imaging (MRI):
On hospital day 3, diffusion-weighted MRI (DWI) demonstrated a left cortical infarction (Figure 1D). T1-weighted axial imaging with fat saturation revealed a hyperintense crescent-shaped mural hematoma in the left ICA, consistent with arterial dissection. Contrast-enhanced magnetic resonance angiography (CE-MRA) showed re-canalization of the left ICA with long-segment stenosis and a suspected double lumen (Figure 1E–F). High-resolution MRA (HR-MRA) confirmed the diagnosis of left ICA dissection, revealing a dissection flap and intramural hematoma at the origin of the ICA (Figure 1G).

Genetic Testing:
Genetic analysis identified a homozygous C-to-T substitution at nucleotide 677 (C677T) in the methylenetetrahydrofolate reductase (MTHFR) gene. This mutation reduces the enzyme’s thermostability and activity, impairing homocysteine metabolism and leading to severe HHcy.

Management and Clinical Course

The patient received dual antiplatelet therapy (aspirin 100 mg/day and clopidogrel 75 mg/day) combined with intravenous argatroban (a direct thrombin inhibitor) for the first 7 days. High-intensity statin therapy (atorvastatin 40 mg/day) was initiated to target LDL reduction. To address HHcy, oral vitamin B6 (50 mg/day) and folic acid (5 mg/day) were administered. After one week, anticoagulation was transitioned to warfarin (target INR: 2.0–3.0), which was continued post-discharge.

By hospital day 2, limb muscle strength improved to grade 4+. Speech normalized by day 5, and limb strength recovered to grade 5– (near-normal) by discharge. At 50-day follow-up, CE-MRA demonstrated near-complete resolution of the left ICA dissection (Figure 1H). Warfarin was replaced with aspirin monotherapy at 3 months, with no recurrent ischemic or hemorrhagic events. Post-treatment Hcy levels decreased to 17.9 µmol/L, reflecting partial correction of HHcy.

Pathophysiological Mechanisms

  1. Carotid Artery Dissection (CAD):
    CAD occurs when blood enters the arterial wall, forming an intramural hematoma. In this case, the dissection likely originated from endothelial injury exacerbated by HHcy-induced vascular fragility. The C677T MTHFR mutation impaired folate-dependent remethylation of Hcy, elevating plasma Hcy levels. HHcy promotes oxidative stress, endothelial dysfunction, and matrix metalloproteinase activation, predisposing arteries to dissection.

  2. Role of Persistent Trigeminal Artery (PTA):
    The PTA, present in 0.1–0.6% of the population, provided critical collateral flow to the posterior circulation after left ICA occlusion. However, this anatomical variant also created hemodynamic stress, potentially exacerbating cerebral hypoperfusion during acute ICA occlusion.

  3. Imaging Correlations:

    • DSA: Showed the “flame sign” of ICA occlusion and collateral pathways (Figure 1A–C).
    • T1-weighted MRI: The hyperintense crescent sign (Figure 1F) corresponded to methemoglobin in the subacute hematoma (days 2–5 post-dissection).
    • HR-MRA: Provided detailed visualization of the dissection flap and intramural hematoma (Figure 1G), surpassing conventional angiography in diagnosing vessel wall pathology.

Therapeutic Considerations

The treatment approach balanced thromboembolic risk and hemorrhage potential. Early dual antiplatelet therapy targeted platelet aggregation at the dissection site, while argatroban provided immediate anticoagulation. The transition to warfarin reflected concerns about residual thrombus in the dissected artery. The rapid clinical improvement suggested spontaneous healing of the dissection, a phenomenon observed in 70–90% of CAD cases within 3 months.

Discussion of Key Findings

  1. HHcy as a Risk Factor for CAD:
    Epidemiological studies link HHcy to arterial dissection and ischemic stroke. The MTHFR C677T homozygous genotype, present in 10–15% of populations, increases Hcy levels by 25–50%, as seen in this patient. HHcy-induced endothelial injury and impaired nitric oxide bioavailability likely contributed to ICA dissection.

  2. Imaging Modalities in CAD Diagnosis:

    • DSA: Remains the gold standard for evaluating arterial occlusion and collateral circulation but cannot visualize intramural hematoma.
    • HR-MRA: Offers superior resolution for detecting dissection flaps and hematomas, aiding early diagnosis.
    • CE-MRA: Monitors vascular remodeling during follow-up (Figure 1H).

  3. Prognostic Implications:
    The CADISS trial (2015) found no difference in outcomes between antiplatelet and anticoagulant therapies for extracranial CAD, with stroke recurrence rates of 2–3%. This patient’s favorable outcome aligns with evidence suggesting that most CAD-related strokes occur at dissection onset, with low recurrence risk after healing.

Conclusion

This case highlights posterior circulation ischemia secondary to ICA dissection in a patient with severe HHcy due to MTHFR mutation. The presence of a PTA altered collateral hemodynamics, contributing to both ischemic risk and compensatory perfusion. Advanced imaging techniques, including HR-MRA, were critical for diagnosis and monitoring. The rapid clinical recovery underscores the self-limiting nature of CAD and supports individualized antithrombotic strategies.

doi.org/10.1097/CM9.0000000000001026

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