Reversible Cerebral Vasoconstriction Syndrome Secondary to Escitalopram

Discussion

RCVS is a rare condition with an estimated incidence of 2.7 cases per million adults in the USA.² It commonly affects patients between ages of 20-50 with a 2.4-fold female predominance.³ The exact pathogenesis of RCVS remains unclear. A multitude of factors such as genetic predisposition, endothelial dysfunction, inflammation, blood brain barrier disruption, autonomic dysfunction, oxidative stress, sympathetic overdrive, and dysregulation of cerebral vascular tone are all suspected to play a role in RCVS.^4-7 Due to the similarity in presentation of RCVS with post subarachnoid hemorrhage vasospasm, the same mediators involved in vasospasm such as serotonin, endothelin-1, nitric oxide, epinephrine, and prostaglandins have been theorized to play a role in the cerebral vascular tone disruption associated with RCVS.⁸

The most common presenting symptom in RCVS is a headache, and sometimes it can be the only presenting symptom.⁹ Less frequently, patients can present with focal neurological deficits.¹⁰ Our patient presented with bilateral neurological deficits followed by recurrent headaches 3 days later. The headache associated with RCVS is a severe “thunderclap headache”, like the headache associated with subarachnoid hemorrhage (SAH). However, the headache is typically intermittent and recurrent, unlike the constant SAH headaches.¹¹ The headache associated with RCVS can often be severe and difficult to treat. Our patient’s headache was refractory to treatment with several pharmacologic agents including nonsteroidal anti-inflammatory drugs, acetaminophen, intravenous magnesium sulfate, and opioids. Ultimately, she was treated with intra-arterial administration of verapamil, which resulted in a rapid and sustained neurological improvement, as well as resolution of her headache.

To further complicate differentiating RCVS from SAH, more than 30% of RCVS patients develop SAH.¹² CT findings, however, can provide crucial clues. SAH following RCVS typically accumulates in the hemispheric convexities instead of the sylvian fissure or the cisterns, unlike aneurysmal SAH.^12,13 In addition, CTA can assist in ruling out aneurysm as the cause of the SAH. However, the sensitivity and specificity of CTA begin to decrease for aneurysms smaller than 3mm.^14,15 Digital subtraction angiography (DSA) is considered the gold standard for RCVS. Not only does DSA assist in ruling out cerebral aneurysms, but also multifocal segmental cerebral artery vasoconstriction seen on DSA is considered virtually pathognomonic for RCVS.¹⁶ Our patient’s CT, as shown in Figure 1, demonstrated convex SAH and DSA revealed bilateral anterior cerebral artery focal stenosis, as shown in Figure 2.

Intra-arterial verapamil has been shown to have both therapeutic and diagnostic value in RCVS. A 32% change in vessel caliber during angiography has been associated with a sensitivity of 100% and a specificity of 88.2% for RCVS.¹⁷ Intra-arterial administration of calcium channel blockers reverses vasoconstriction and improves vascular caliber of not just the target artery, but also other adjoining vessels, including the contralateral arteries. Our patient’s vessel caliber improved significantly after the intra-arterial calcium channel blocker administration. Her neurological symptoms improved dramatically post intraarterial treatment.

Another tool that can aid in diagnosing RCVS is the RCVS₂ score. The RCVS₂ score comprises five questions, with different weights assigned to each answer. The total score can range from −2 to +10, with +10 having the highest likelihood of RCVS. The scoring system is shown in Table 1. A RCVS₂ score ≥5 has 99% specificity and 90% sensitivity for diagnosing RCVS, and a score ≤2 had 100% specificity and 85% sensitivity, respectively, for excluding RCVS.¹⁸ The RCVS₂ score, however, has some major limitations. The RCVS₂ score gives you a score of +5 for the presence of thunderclap headaches. As a result, RCVS₂ score, while it has great utility in differentiating RCVS from intracranial vascular pathologies, the scoring system has poor functionality in distinguishing RCVS score from other differentials that cause thunderclap headaches. A combination of clinical and angiographic findings are often preferred and required for the diagnosis of RCVS.¹⁹ Our patient had a RCVS₂ score of 10, indicating a very high likelihood of RCVS. The combination of high RCVS₂ score, clinical history and presentation, and radiographic findings, along with improvement after intraarterial verapamil confirmed the diagnosis of RCVS in our patient.

An important component of the RCVS₂ score is the identifying trigger. A trigger is identified in 25%–60% of RCVS cases.²⁰ A wide variety of triggers, including strenuous activity, valsalva maneuvers, medications, recreational drugs, pregnancy, and interventional procedures, have been reported as triggers for RCVS.^21,22 Our patient’s trigger was likely her selective serotonin reuptake inhibitor (SSRI) medication use. The vasoactive and sympathomimetic nature of SSRIs are thought to be the primary mechanism of SSRI associated RCVS.²³ The risk of SSRI associated RCVS seems to be independent of the timing of SSRI initiation.²⁴ The risk also seems to be independent of the type of SSRI used as well as the dosage.²⁵ Our patient was taking maximum dose of escitalopram (20mg daily) for 10 years prior to developing RCVS.