Case Report: Reversible Cerebral Vasoconstriction Syndrome Presenting as Vasospastic Angina

Clinical Presentation

CP, age 47, presented to the emergency department (ED) with chest pain, headache, nausea, and vomiting. Past medical history was remarkable for Graves’ disease, hyperlipidemia, and hypothyroidism. CP’s medications included aspirin (81 mg/day as a preventative measure and atorvastatin 80 mg for hyperlipidemia).

The day of admission, 1 to 2 hours after chest pain, CP experienced a severe thunderclap headache, which recurred twice during the hospital stay.

Diagnostic Studies

In the ED, CP had an elevated troponin level (700 ng/L) consistent with nonST elevation myocardial infarction (NSTEMI) and an electrocardiogram (ECG) that showed nonspecific changes except tachycardia. Upon admission to cardiology, a coronary angiogram was performed and was negative for critical stenosis and atherosclerotic changes. CP’s low-density lipoprotein level at admission was 135 mg/dL. Based on age, no history of coronary artery disease, elevated troponin, nonspecific ECG changes, and normal cardiac angiogram, the cardiology team diagnosed CP with vasospastic angina. After the thunderclap headache occurred, however, CP had a full work-up for subarachnoid hemorrhage (SAH) with no focal neurologic findings and a National Institutes of Health Stroke Scale (NIHSS) score of 0. Lumbar puncture and cerebrospinal fluid analysis were unremarkable.

Neuroimaging

CP had brain MRI and MR angiography that showed no significant abnormalities except a tiny, scattered stroke in the left parietal lobe (Figure 1A) and questionable segmental beading in the distal M1 and M2 segments of the middle cerebral arteries (MCAs; Figure 1B). Transcranial Doppler (TCD) study (Figure 2) showed high mean systolic velocity in both MCA M2 segments with bruit and increased Lindegaard ratio (LR), consistent with moderate vasospasm (mean flow velocity [MFV] right side 145 cm/second, LR: 4; left side 152 cm/second, LR: 5). After the 2 recurrences of thunderclap headache, a cerebral angiogram was performed (Figure 3) and confirmed diffuse vasospasm intracranially.

Management and Follow-up

Based on the overall clinical picture, CP was treated with high-dose verapamil (120 mg 3 times/day), intravenous (IV) normal saline (200 mL/hour), magnesium sulfate (2-4 g/day), and acetaminophen for pain. Over a 7-day period, IV normal saline was tapered to 50 mL/hour and treatment with high-dose verapamil and magnesium sulfate continued. On day 6 after admission, CP’s troponin level decreased from 850 ng/L to 50 ng/L, and TCD showed significant improvement in MFV (80- 85 cm/second). On day 10, CP had been pain-free for 72 hours and was discharged with prescriptions for oral verapamil and magnesium.

Follow-up management was conservative with regular evaluations because CP did not have a major intracranial hemorrhage, focal neurologic deficits, or seizures.

Discussion

We searched the English-language literature for all published cases of reversible cerebral vasoconstriction syndeom (RCVS). Medline/PubMed and Google Scholar databases were searched using “Reversible cerebral vasoconstriction syndrome” and “RCVS” as keywords. To find additional pertinent publications, we manually searched the references sections of the retrieved articles. This discussion only includes cases of RCVS with extracerebral symptoms or complications.

We describe the clinical outcome of cardiac involvement in RCVS that resolved completely after administration of calcium channel blockers (CCB), magnesium, analgesics, and hydration. Evidence for extracranial or cardiac involvement in RCVS is sparse^1-8 (Table).

RCVS is characterized as a group of disorders with prolonged but reversible vasoconstriction of the cerebral arteries. Clinical presentations of RCVS are generally homogeneous, with thunderclap headache as the primary symptom, with or without visual alterations, seizures, or other neurologic deficits. Significant complications of RCVS occur mainly in the first week of the clinical course and include nonaneurysmal SAH (22%), leukoencephalopathy (9%), and in the second week, mainly ischemic events including ischemic stroke (20%).⁹ These complications can lead to symptoms of vision loss, aphasia, and hemiparesis that can often lead to permanent residual neurologic deficits.¹⁰

Although extracerebral vascular involvement has been reported in RCVS, including narrowing of renal and carotid arteries,^2,11,12 cardiac manifestations are exceedingly rare, with only 4 previous cases reported.^3,4 The case presented in this article highlights such a cardiac manifestation: prinzmetal or vasospastic angina. Although the exact pathophysiology is uncertain, cardiac vascular involvement may be subject to the same stress and alteration of vascular tone relating to localized vasoconstriction in RCVS.

Neuroimaging

Although CT and CT angiography are faster to obtain and less prone to motion artifact, MRI and MR angiography are often used to avoid radiation exposure and iodinated contrast. On brain MRI, the presence of hyperintense vessels has been hypothesized to be a biomarker for RCVS because these show abnormal flow in small vessels¹³ before detection of vasoconstriction.¹⁴ MRI is often combined with MR angiography, which has an 80% sensitivity rate for RCVS-related cerebral vasoconstriction,¹⁵ similar to CT angiography. In this case, there was a segmental focus on diffusion-weighted imaging (DWI), combined with narrowing and spasm of the posterior and anterior arteries on MR angiography, which are diagnostic for RCVS.

TCD is used as a diagnostic tool to assess cerebral vasomotor reactivity and dynamic vessel imaging, which is often abnormal in RCVS cases.¹⁶ Additionally, TCD provides prognostic and predictive value to monitor the resolution of vasoconstriction and response to pharmacotherapies¹⁷ and assess the risk of developing posterior reversible encephalopathy syndrome (PRES) and stroke.16 CP’s elevated MFV that was greater than 120 m/second and MCA to extracranial internal carotid artery (ICA) ratio (Lindegaard index/LR) greater than 2 were highly sensitive and specific to identifying angiographic vasospasm.

Digital subtraction cerebral angiography is the current criterion standard for diagnosing RCVS,15 allows visualization of real-time vessel flow and measurement of the caliber of more minor peripheral vessels, and provides the ability to monitor therapeutic response.¹⁸ CP had diffuse vasospasm in their distal MCA and anterior cerebral artery (ACA) branches, allowing local administration verapamil in the identified vessels.

Treatment

CCBs are often the mainstay of treatment for RCVS with a combination of magnesium, steroids, anticoagulants, or analgesics.¹⁹ Previous studies support the role of CCBs in the resolution of cardiac and RCVS symptoms.1 A proposed mechanism of CCBs in addressing vasospasm is blockade of calcium flow into cells binding the L-type voltage-gated calcium channels in the myocardium and brain to cause vasodilation. In this case, cardiac and neurologic improvement occurred after treatment with a high-dose CCB (verapamil), IV normal saline, magnesium, and acetaminophen, supporting findings of existing literature on the proposed management of concomitant cardiac conditions and RCVS.

Although extracerebral vascular abnormalities are not commonly associated with RCVS, this case indicates that treatment of cardiac conditions may play a role in achieving a positive outcome. Multiorgan and extracerebral vascular involvement may be a part of the spectrum of RCVS and further prospective studies of RCVS should investigate this hypothesis.

Summary

Vasospastic angina and RCVS have been minimally reported in the literature.⁴ This report represents a unique case of cardiac manifestation in RCVS that resolved entirely with the use of CCBs, magnesium sulfate, hydration, and analgesics. It is important to consider RCVS in the differential diagnosis of sudden onset thunderclap headaches in cardiac disorders and diagnose them through MRI, MR angiography, TCD, and cerebral angiography.

Early diagnosis and treatment may result in the resolution of symptoms related to both conditions and prevent further progression.