By Ava L. Liberman, MD
Synopsis: Reversible cerebral vasoconstriction syndrome (RCVS) is a rare disorder characterized by thunderclap headaches and cerebral vasoconstriction resolving within 90 days. A retrospective study of 80 patients found favorable outcomes, with most treated using calcium channel blockers. However, challenges in RCVS diagnosis and classification may affect reported outcomes
Source: Girfanova M, Martinez-Majander N, Mannismaki L, et al. Retrospective analysis of 80 patients diagnosed with reversible cerebral vasoconstriction syndrome in the Helsinki Metropolitan Area. Eur J Neurol. 2025;21(2):e16564.
Reversible cerebral vasoconstriction syndrome (RCVS) is an increasingly recognized disorder characterized by severe headaches, with or without other acute neurological symptoms, and diffuse segmental constriction of cerebral arteries that resolves spontaneously within three months. RCVS is a rare disease with an estimated age- and sex-standardized incidence of RCVS hospitalizations in U.S. adults of only three per million per year.1
In the current study, the authors described a cohort of RCVS patients older than 16 years of age seen at the Helsinki University Central Hospital from Jan. 1, 2016, to Dec. 31, 2022, and evaluated the incidence of post-RCVS complications. Retrospective methods were used to identify and confirm the diagnosis of definite or probable RCVS based on documentation of the following key clinical features: secondary thunderclap headache or severe recurrent headache, cerebral vasoconstriction of at least one vessel, and resolution of vasoconstriction within 90 days in the absence of primary angiitis of the central nervous system (CNS) or aneurysmal subarachnoid hemorrhage (SAH). They also included individuals presenting with focal neurological deficits, even in the absence of the characteristic headache, if they had vasoconstriction that subsequently resolved within 90 days.
A total of 80 RCVS patients were identified; the mean age was 41 years and 41% were female. The median time to RCVS diagnosis from symptom onset was six days, with a wide interquartile range of 0-31 days. Most patients in the study had an identifiable trigger, with the most common one being sexual intercourse, consistent with previous reports. Although vasoconstriction was visible in all 80 included patients, only four patients had parenchymal lesions or SAH. For treatment, all but one included patient received a calcium channel blocker.
The authors found that all patients were alive at the time of the writing of this manuscript. However, 90-day functional status measured using the modified Rankin Scale (mRS) was available for only 69 patients (86%). Sixty-seven patients had an mRS score of 0-2 and two had an mRS score of 2. Among the 80 included patients, new diagnoses made during 90-day follow-up were arterial hypertension for 11 patients (including one found to have a pheochromocytoma), anxiety and depression for two patients, primary hyperaldosteronism for one patient, cluster headaches for one patient, and Factor V Leiden mutation for one patient. The authors concluded that their finding of frequent good outcomes after RCVS is different than some prior research and may reflect advances in RCVS care or may be the result of unique features of this particular study.
Commentary
While it is always challenging to generalize from the results of cross-sectional cohort studies using exclusively retrospective data from a single center, interpreting the current study is further complicated by the fact that identifying patients with RCVS rarely is straightforward.
To begin with, although leveraging administrative claims data to study a rare disease often is fruitful, the ICD-10 code for RCVS has been shown to have imperfect specificity (90%; 95% confidence interval, 79% to 96%).1 Furthermore, as the authors themselves acknowledge, patients with parenchymal changes because of RCVS during the study period are more likely than those without parenchymal damage to lack the RCVS ICD-10 code. Failure to include more severe RCVS cases will bias the results of cohort studies toward more favorable outcomes. Additionally, in clinical practice, it can be challenging to diagnose RCVS, particularly when associated with SAH, which itself can result in vasospasm.
We previously found that delayed diagnosis of RCVS/PRES occurs in nearly 5% of cases in the United States using multistate data.2 Single-center studies, like the one presented here, cannot identify patients who are labeled erroneously with a benign condition (e.g., migraine headache) at their index encounter and who are subsequently seen for the same complaint at another center, where the correct diagnosis of a dangerous disease (e.g., RCVS, stroke) is made. And, even when multiple centers are included, instances where RCVS is never accurately diagnosed (e.g., devastating intracerebral hemorrhage where vessel imaging is not obtained, or the patient is unable to tolerate vessel imaging) will be missed, confounding accurate case identification in RCVS.
Another important issue in RCVS identification is the fact that both RCVS and posterior reversible encephalopathy syndrome (PRES) are descriptive terms that bring together conditions with similar clinical-imaging manifestations. For instance, whereas seizures and encephalopathy are seen more often in PRES, and RCVS usually is heralded by thunderclap headache, both entities can involve visual symptoms, other headaches, seizures, and confusion. Similarly, while brain imaging often is normal in RCVS and vasogenic edema is seen in PRES, both can be complicated by ischemic and hemorrhagic brain lesions. These two entities also have a similar purported pathophysiology, transiently impaired cerebral autoregulation, making the term syndromes of cerebrovascular dysregulation a conceptually useful one for RCVS and PRES.3
Prior work detailing outcomes after RCVS may have included patients who were labeled in the current study as having PRES, or vice versa, given the aforementioned overlaps. Exclusion of all PRES patients after detailed review of medical records is a strength of the current study, but this exclusion may complicate comparing the outcome results presented here to those of some other published work and may explain why so few RCVS patients had parenchymal lesions in this cohort.
Thus, while this study contributes to our understating of clinical outcomes in a subset of RCVS patients, detailing the spectrum of disability after syndromes of cerebrovascular dysregulation likely is a more useful approach and will require additional investigations.
Ava Liberman, MD, is Assistant Professor of Neurology, New York Presbyterian Hospital/Weill Cornell Medicine.
References
1. Magid-Bernstein J, Omran SS, Parikh NS, et al. Reversible cerebral vasoconstriction syndrome: Symptoms, incidence, and resource utilization in a population-based US cohort. Neurology. 2021;97(3):e248-e253.
2. Liberman AL, Zhang C, Parikh NS, et al. Misdiagnosis of posterior reversible encephalopathy syndrome and reversible cerebral vasoconstriction syndrome in the emergency department. J Am Heart Assoc. 2023;12(19):e030009.
3. Singhal AB. Posterior reversible encephalopathy syndrome and reversible cerebral vasoconstriction syndrome as syndromes of cerebrovascular dysregulation. Continuum (Minneap Minn). 2021;27(5):1301-1320.
Reversible cerebral vasoconstriction syndrome (RCVS) is a rare disorder characterized by thunderclap headaches and cerebral vasoconstriction resolving within 90 days. A retrospective study of 80 patients found favorable outcomes, with most treated using calcium channel blockers. However, challenges in RCVS diagnosis and classification may affect reported outcomes.
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