Abstract
Reversible cerebral vasoconstriction syndrome (RCVS) is a rare but significant cause of intracranial arteriopathy and stroke in young adults. The syndrome encompasses a spectrum of disorders radiologically characterized by reversible narrowing and dilation of intracranial arteries, often triggered by vasoactive drugs or the postpartum period. The hallmark clinical feature of RCVS is thunderclap headache with or without other neurological signs. Though endothelial dysfunction and sympathetic hyperactivation are hypothesized to be key mechanisms, the exact pathogenesis of RCVS is still unclear. RCVS’s diagnosis could be challenging, since vasospasm proceeds centripetally, initially involving distal small pial and cortical arteries, and angiographic studies, especially brain magnetic resonance angiography (MRA) and computed tomography angiography (CTA), may miss it in the early phase of the disease, while early signs such as vascular hyperintensities may be visible on T2/FLAIR sequences before vasospasm onset. Catheter angiography is the gold standard and it could be used to assess vasospasm reversibility post-intra-arterial vasodilator administration. Treatment is mainly symptomatic, and nimodipine is the most commonly administered therapy, given orally or intra-arterially in severe cases. Since many aspects of RCVS remain partially known, further research is needed to better understand the complex pathophysiology of this unique clinical condition and to optimize specific management strategies.
Key Points
- Epidemiology and Prevalence: RCVS is estimated to occur in approximately three per million adults, but the true incidence is likely higher due to underdiagnosis. It is a leading cause of intracranial arteriopathy and stroke in young adults, with a higher prevalence in females aged 40–55 years.
- Clinical Presentation: The primary symptom of RCVS is thunderclap headache, described as the most severe headache in life, reaching peak intensity in under a minute. It can be triggered by activities such as coughing, bathing, exertion, sexual activity, and emotional stress, often recurring over a four-week period.
- Pathophysiology and Mechanisms: RCVS is thought to result from dysregulation of cerebral vascular tone and endothelial dysfunction. Increased sympathetic activity and oxidative stress lead to vasoconstriction, potentially exacerbated by genetic predisposition and circulating microRNAs affecting vascular tone.
- Triggering Factors: Vasoactive drugs, including selective serotonin reuptake inhibitors (SSRIs), immunosuppressants, chemotherapy agents, and sympathomimetic drugs, are major contributors to RCVS. Other triggers include pregnancy, preeclampsia, tumors, vascular conditions, and high-risk activities such as exertion and the Valsalva maneuver.
- Imaging and Diagnosis: Initial imaging, including MRI and MRA, may be normal, with vasospasm only becoming visible over time. Early vascular hyperintensities on T2/FLAIR sequences may provide clues before angiographic evidence emerges. Digital subtraction angiography is the gold standard for diagnosis, often revealing a “sausage on a string” appearance of cerebral vessels.
- Complications and Prognosis: RCVS can lead to cerebral ischemia, hemorrhage, and posterior reversible encephalopathy syndrome (PRES). The peak vasoconstriction phase occurs 9–13 days after symptom onset. Though reversible, severe cases can result in long-term complications, including chronic headaches and depression.
- Differential Diagnosis: RCVS must be distinguished from conditions like subarachnoid hemorrhage, primary angiitis of the central nervous system (PACNS), and cerebral venous thrombosis. The RCVS2 score is used for diagnostic confirmation, with a score ≥5 offering 99% specificity.
- Management and Treatment: First-line treatment includes calcium channel blockers like nimodipine, administered orally or intra-arterially in severe cases. Vasodilators such as magnesium and intra-arterial milrinone may be used in refractory cases, while corticosteroids should be avoided due to potential worsening of outcomes.
- Long-Term Outcomes and Recurrence: Most patients recover with good functional outcomes, but up to 10% experience recurrence. Chronic headaches persist in nearly half of patients post-recovery, with depression being a common comorbidity. Long-term avoidance of known triggers is recommended.
- Research Gaps and Future Directions: Despite growing evidence, the precise mechanisms underlying RCVS remain unclear. Further studies are needed to explore the role of genetics, oxidative stress, and vascular tone regulation, as well as to evaluate novel therapeutic approaches for better patient management.
