Reversible Cerebral Vasoconstriction Syndrome: A Review of Diagnostic Imaging and Mimics

Microvascular brain injury is well recognized in neuropsychiatric systemic lupus erythematosus (SLE), but cerebral large artery involvement is being debated. Three females with SLE, aged 9 to 14years, had immunosuppressive treatment intensification because of lupus nephritis. Within the following days or weeks, they presented with intense cephalalgia - isolated or associated with neurological symptoms - and no or mild hypertension. Magnetic resonance angiography showed multiple stenoses within the circle of Willis. One patient had subsequent small subcortical cerebral infarction. Two patients were treated for neuropsychiatric SLE; one patient was treated for reversible cerebral vasoconstriction syndrome (RCVS). Angiography normalized within a few weeks in all three patients. Retrospectively, clinical and radiological features suggest that RCVS was the most likely diagnosis in all patients. Multidisciplinary analysis of clinical and angiographic features is recommended, as RCVS is rare in children and its recognition may help to adjust treatment. WHAT THIS PAPER ADDS: Reversible vasoconstriction syndrome was observed in paediatric systemic lupus erythematosus. Thorough imaging analysis was necessary to address this diagnosis in paediatric patients.

Objective: To develop a method to distinguish reversible cerebral vasoconstriction syndrome (RCVS) from other large/medium-vessel intracranial arteriopathies. Methods: We identified consecutive patients from our institutional databases admitted 2013-2017 with newly diagnosed RCVS (n=30) or non-RCVS arteriopathy (n=80). Admission clinical and imaging features were compared. Multivariate logistic regression modelling was used to develop a discriminatory score. Score validity was tested in a separate cohort of patients with RCVS and its closest mimic, primary angiitis of the central nervous system (PACNS). Additionally, key variables were used to develop a bedside approach to distinguish RCVS from non-RCVS arteriopathies. Results: The RCVS group had significantly more women, vasoconstrictive triggers, thunderclap headaches, normal brain imaging results, and better outcomes. Beta coefficients from the multivariate regression model yielding the best c-statistic (0.989) were used to develop the RCVS 2 score (range, -2 to +10; R ecurrent/single thunderclap headache; C arotid artery involvement; V asoconstrictive trigger; S ex; S ubarachnoid hemorrhage). Score ≥5 had 99% specificity and 90% sensitivity for diagnosing RCVS, and score ≤2 had 100% specificity and 85% sensitivity for excluding RCVS. Scores 3-4 had 86% specificity and 10% sensitivity for diagnosing RCVS. The score showed similar performance to distinguish RCVS from PACNS in the validation cohort. A clinical approach based on recurrent thunderclap headaches, trigger and normal brain scans, or convexity subarachnoid hemorrhage, correctly diagnosed 25 of 37 patients with RCVS 2 scores 3-4 across the derivation and validation cohorts. Conclusion: RCVS can be accurately distinguished from other intracranial arteriopathies upon admission, using widely available clinical and imaging features.

This article describes the causes, clinical and imaging features, management, and prognosis of posterior reversible encephalopathy syndrome (PRES) and reversible cerebral vasoconstriction syndrome (RCVS), in which the underlying pathophysiology is related to reversible dysregulation of the cerebral vasculature. PRES and RCVS are descriptive terms, each bringing together conditions with similar clinical-imaging manifestations. Headache, visual symptoms, seizures, and confusion occur in both syndromes. RCVS is usually heralded by recurrent thunderclap headaches, whereas encephalopathy and seizures are typical in PRES. In PRES, brain imaging shows reversible vasogenic edema that is typically symmetric and located in subcortical regions (mostly posterior predominant). In RCVS, brain imaging is often normal; cerebral angiography shows segmental vasoconstriction-vasodilatation affecting the circle of Willis arteries and their branches. Aside from shared clinical features, significant imaging overlap exists. Both PRES and RCVS can be complicated by ischemic and hemorrhagic brain lesions; angiographic abnormalities frequently occur in PRES and vasogenic edematous lesions in RCVS. Common triggers (eg, eclampsia, vasoconstrictive and chemotherapeutic agents) have been identified. Abnormal cerebrovascular tone and endothelial dysfunction may explain both syndromes. Management of these syndromes includes the removal of identified triggers, symptomatic treatment of headache or seizures, and moderate blood pressure control. Both syndromes are self-limited, with clinical recovery occurring within days to weeks. Long-term deficits and mortality are uncommon. PRES and RCVS have been well characterized and acknowledged to have significant overlap. Advances in our understanding of pathophysiology and risk factors for poor outcome are expected to optimize the management of these not uncommon syndromes.

Syndrome de vasoconstriction cérébrale réversible : une cause de céphalée en coup de tonnerre peu connue chez l’enfant

PRES and RCVS: Two Distinct Entities or a Spectrum of the Same Disease?

Introduction Reversible cerebral vasoconstriction syndrome (RCVS) is a less considered etiology of acute severe headache in the pediatric population. It is classically characterized by thunderclap headache that is recurrent and reversible multifocal cerebral artery narrowing. While it has been linked to vasoactive medication, immunosuppression, and systemic illness, case reports in the field of pediatric hematology‐oncology are rare. No previous cases have linked RCVS with tovorafenib, an oral pan‐RAF inhibitor in clinical investigation for pediatric BRAF V600E‐mutated malignancies. Because RCVS can be imitated by other neurologic disorders and noninvasive vascular testing can be normal, the diagnosis usually necessitates catheter‐based angiography. Intra‐arterial calcium channel blockers have been utilized in endovascular therapy to obtain both diagnostic accuracy and immediate therapeutic benefit. We describe the first documented case of childhood RCVS associated with tovorafenib with successful endovascular diagnosis and intra‐arterial verapamil treatment. Materials and Methods A 12‐year‐old female with multifocal osseous relapsed Langerhans cell histiocytosis (LCH) harboring BRAF V600E mutation started tovorafenib in February 2025. After six cycles, she developed recurrent thunderclap headache that woke her up from sleep, sometimes followed by brief confusion characteristic of postictal states. Tovorafenib was withheld, and she was evaluated via multidisciplinary evaluation. Comparison brain MRI revealed minimal Chiari I malformation and small sphenoid hyperintensity on the left side. Head and neck CT angiogram was normal. EEG, with 2‐hour study during symptomatic attack, revealed no epileptiform discharge. Ophthalmological examination revealed no papilledema. Because of the persistence of thunderclap headache and nonrevealing noninvasive studies, diagnostic cerebral angiography was done. Results Digital subtraction angiography disclosed focal segmental narrowing of the right A3 segment of the anterior cerebral artery characteristic of RCVS. Verapamil (5 mg) was administered intra‐arterially, with resultant immediate angiographic resolution of the vasospasm. Lumbar puncture ruled out infection and inflammation. The patient was switched to oral verapamil with rapid resolution of her thunderclap headaches. Interestingly, tovorafenib was resumed on hospitalization day with continuation of verapamil, and no additional RCVS events were experienced. Discharge on oral verapamil with follow‐up as scheduled in neurology, neurosurgery, and oncology clinics was successful. Conclusion This case highlights the critical importance of endovascular evaluation and treatment of potential pediatric RCVS, especially when vasoconstriction is not detected by noninvasive imaging. In this patient, both therapeutic and diagnostic angiography was in keeping with RCVS and reversible following intra‐arterial verapamil infusion. Temporal correlation of tovorafenib exposure and onset of symptoms, together with angiographic response to calcium channel blockade, is compatible with drug‐related mechanism. One possible explanation would be inhibition of RAF pathway altering vascular smooth muscle or endothelial tone, which predisposes to vasoconstriction. To our knowledge, this is the first description of tovorafenib‐associated RCVS. This presentation underscores the need to heighten awareness of RCVS as an emergent side effect of new targeted therapies in children. Early diagnosis, multidisciplinary assessment, and prompt endovascular therapy will prevent morbidity and enable resumption of potentially life‐extending oncologic therapy. Additional pharmacovigilance and further study are necessary to better clarify the incidence, pathogenesis, and treatment of this new complication.

(1) Background: Reversible cerebral vasoconstriction syndrome (RCVS) encompasses a clinical and radiological diagnosis characterized by recurrent thunderclap headache, with or without focal deficits due to multifocal arterial vasoconstriction and dilation. RCVS can be correlated to pregnancy and exposure to certain drugs. Currently, the data on prevalence of RCVS in the postpartum period is lacking. We aim to investigate the prevalence of RCVS in the postpartum period and the rate of hemorrhagic complications of RCVS among the same group of patients; (2) Methods: We conducted the metanalysis by using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), and Meta-Analyses and Systematic Reviews of Observational Studies in Epidemiology (MOOSE) protocol. To analyze the Bias, we used the Ottawa Newcastle scale tool. We included only full-text observational studies conducted on humans and written in English. We excluded Literature Reviews, Systematic Reviews, and Metanalysis. Additionally, we excluded articles that did not document the prevalence of RCVS in the postpartum period (3). Results: According to our analysis, the Prevalence of RCVS in the postpartum period was 129/1083 (11.9%). Of these, 51/100 (52.7%) patients had hemorrhagic RCVS vs. 49/101 (49.5%) with non-hemorrhagic RCVS. The rates of Intracerebral Hemorrhage (ICH) and Subarachnoid Hemorrhage (SAH) were (51.6% and 10.7%, respectively. ICH seems to be more common than.; (4) Conclusions: Among patients with RCVS, the prevalence in PP patients is relativity high. Pregnant women with RCVS have a higher recurrence of hemorrhagic vs. non-hemorrhagic RCVS. Regarding the type of Hemorrhagic RCVS, ICH is more common than SAH among patients in the postpartum period. Female Sex, history of migraine, and older age group (above 45) seem to be risk factors for H-RCVS. Furthermore, recurrence of RCVS is associated with a higher age group (above 45). Recurrence of RCVS is more commonly idiopathic than being triggered by vasoactive drugs in the postpartum period.

To describe advances in the diagnosis and management of reversible cerebral vasoconstriction syndrome (RCVS), a group of conditions with reversible multifocal narrowing of intracranial arteries. Over the last decade, multiple cohort studies have characterized RCVS and distinguished it from primary angiitis of the central nervous system and aneurysmal subarachnoid hemorrhage. Onset with recurrent thunderclap headaches (TCH) occurs in 85–90% of patients; most authors believe that RCVS and primary TCH are similar conditions. Rare cases with concurrent takotsubo cardiomyopathy or extracranial artery narrowing have been published. Stroke and brain edema can develop in up to 40% of inpatients; however, the discharge and 10-year outcome is invariably benign. Pregnancy-associated RCVS may have worse outcome. The pathophysiology remains relatively unknown. There is no specific treatment. Management involves pain relief and removal of identified vasoconstrictive factors. Calcium-channel blockers may help to relieve headaches. Glucocorticoids are associated with significantly worse outcome. The role of intra-arterial vasodilator infusion remains uncertain. The recently developed “RCVS2 score” enables accurate bedside diagnosis with up to 99% specificity and 90% sensitivity, obviating the need for invasive tests such as lumbar puncture, brain biopsy and catheter angiography to exclude mimics or confirm the diagnosis. RCVS can now be accurately diagnosed using clinical and imaging features available upon presentation. Advances in knowledge about the risk factors, prognosis, and potential harmful effects of certain therapeutic strategies, are expected to optimize the management of this increasingly well recognized syndrome.

Introduction Reversible cerebral vasoconstriction syndrome (RCVS) is a rare but increasingly recognized cause of thunderclap headaches and non‐aneurysmal subarachnoid hemorrhage (SAH). Characterized by reversible multifocal narrowing of cerebral arteries, often in response to various triggers including vasoactive agents, stress, less commonly, thermal stimuli such as those during showering have been implicated. We report a unique case of RCVS triggered by a routine shower, resulting in convexal SAH and angiographically confirmed vasospasm. Case Presentation A 65‐year‐old woman with no significant medical history presented with a sudden‐onset headache while showering. She had been discharged from the emergency department three days earlier for a similar headache that had resolved with medical treatment. she reported that her initial headache began after getting out of the pool following a swimming session. On re‐presentation, she was neurologically intact and hemodynamically stable, but again noted that her headache started shortly after she began showering but again resolved with medical treatment. She denied any use of illicit drugs, medications, or supplements. Non‐contrast CT head revealed subarachnoid hemorrhage within the interhemispheric fissure and medial cortical sulci of the bilateral frontal and parietal lobes. CT angiography identified a 4 mm focal dilatation of the left anterior cerebral artery's inferior internal parietal branch, with no evidence of aneurysm or vascular malformation which prompted a catheter angiogram.A diagnostic cerebral angiogram demonstrated distal vasospasm predominantly involving the right anterior cerebral artery and bilateral middle cerebral arteries. Intra‐arterial verapamil was administered, resulting in marked improvement in vessel caliber. The patient was started on oral verapamil and discharged in stable condition after she was able to tolerate a shower prior to discharge from the hospital. Discussion RCVS should be considered in the differential diagnosis of thunderclap headaches and atypical non‐aneurysmal SAH, especially in patients lacking structural lesions or vascular malformations. Though less common, thermal stimuli and showering can provoke autonomic dysregulation, leading to cerebral vasoconstriction. Early cerebral angiography and prompt intra‐arterial therapy can result in rapid improvement. Recognition of atypical triggers is critical for timely diagnosis and prevention of recurrence or unnecessary interventions. Conclusion This case highlights a rare instance of shower induced RCVS presenting with convexal SAH and emphasizes the importance of early neurovascular imaging in similar presentations. Clinicians should maintain a high index of suspicion for RCVS in patients with recurrent thunderclap headaches, even in the absence of traditional risk factors or obvious triggers. image

37 - Reversible Cerebral Vasoconstriction Syndromes

Introduction: Reversible cerebral vasoconstriction syndrome (RCVS) and central nervous system (CNS) vasculitis often have similar initial clinical presentation, laboratory findings and imaging features creating a diagnostic dilemma. High-resolution-3-Tesla Magnetic Resonance Imaging with Gadolinium contrast (HR-MRI) is a non-invasive method to look at intracranial vessel wall characteristics. Methods: A retrospective analysis of all patients with a diagnosis of RCVS or CNS vasculitis that underwent HR-MRI at our institution was performed. Inclusion criteria for RCVS were clinical presentation, no aneurysmal subarachnoid hemorrhage, normal cerebrospinal fluid and reversible multifocal intracranial vessel stenosis whereas criteria for CNS vasculitis were cases with positive brain biopsy or typical clinical presentation, course and laboratory markers with rheumatology and stroke neurology agreement in diagnosis. Demographics, clinical presentation, laboratory testing, imaging studies and outcomes were collected. Results: Eleven patients with RCVS [10 (90.9%) females, mean age 45.2] and 8 with CNS vasculitis [6 primary CNS vasculitis, 6 (75%) males, mean age 43.5] were included in the study. No abnormal vessel wall enhancement or thickening was seen in any of the RCVS patients in areas of vessel stenosis. Six (75%) of CNS vasculitis patients had vessel wall thickening or enhancement (p=0.001 for comparison to RCVS) and the remaining 2 patients had HR-MRI performed 6 and 10 years after diagnosis and chronic treatment. All RCVS patients who had follow up HR-MRI demonstrated resolution of the multifocal stenosis. Two out of 4 CNS vasculitis patients with subsequent HR-MRI imaging had decrease in vessel wall thickening and enhancement after immunosuppressive therapy. Conclusion: In acute stages of presentation, HR-MRI may be useful in differentiating RCVS from CNS vasculitis. It may also be useful in following the disease course to look for resolution of intracranial vessel stenosis in RCVS or treatment response in vasculitis. Further studies are needed to confirm the utility of HR-MRI in diagnosis and disease progression in RCVS and vasculitis.

To develop a method to distinguish reversible cerebral vasoconstriction syndrome (RCVS) from other large/medium-vessel intracranial arteriopathies. We identified consecutive patients from our institutional databases admitted in 2013-2017 with newly diagnosed RCVS (n = 30) or non-RCVS arteriopathy (n = 80). Admission clinical and imaging features were compared. Multivariate logistic regression modeling was used to develop a discriminatory score. Score validity was tested in a separate cohort of patients with RCVS and its closest mimic, primary angiitis of the CNS (PACNS). In addition, key variables were used to develop a bedside approach to distinguish RCVS from non-RCVS arteriopathies. The RCVS group had significantly more women, vasoconstrictive triggers, thunderclap headaches, normal brain imaging results, and better outcomes. Beta coefficients from the multivariate regression model yielding the best c-statistic (0.989) were used to develop the RCVS2 score (range -2 to +10; recurrent/single thunderclap headache; carotid artery involvement; vasoconstrictive trigger; sex; subarachnoid hemorrhage). Score ≥5 had 99% specificity and 90% sensitivity for diagnosing RCVS, and score ≤2 had 100% specificity and 85% sensitivity for excluding RCVS. Scores 3-4 had 86% specificity and 10% sensitivity for diagnosing RCVS. The score showed similar performance to distinguish RCVS from PACNS in the validation cohort. A clinical approach based on recurrent thunderclap headaches, trigger and normal brain scans, or convexity subarachnoid hemorrhage correctly diagnosed 25 of 37 patients with RCVS2 scores 3-4 across the derivation and validation cohorts. RCVS can be accurately distinguished from other intracranial arteriopathies upon admission, using widely available clinical and imaging features. This study provides Class II evidence that the RCVS2 score accurately distinguishes patients with RCVS from those with other intracranial arteriopathies.

112. Reversible cerebral vasoconstriction syndrome associated with pregnancy in peripartum period

Reversible cerebral vasoconstriction syndrome (RCVS) is one of the most important differential diagnosis in patients with thunderclap headache (TCH). We aimed to develop a new scoring system for RCVS in patients with TCH. We retrospectively analyzed 72 patients enrolled in the prospective study of TCH conducted in 2015–2016 (derivation set). We identified possible predictors for the diagnosis of RCVS and constructed a prediction model (RCVS–TCH score) using the multivariable logistic regression model. Diagnostic performance was validated to an independent validation set from our headache registry. The derivation set comprised 41 patients with RCVS and 31 with non-RCVS, and the validation set included 253 patients with TCH (165 with RCVS and 88 with non-RCVS). The RCVS–TCH score (range: 0–12) contained four predictors: recurrent TCHs, female sex, triggering factor for TCH (single or multi) and blood pressure surge. The C-index of RCVS–TCH score was 0.929 (95% CI = 0.874–0.984). The RCVS–TCH score ≥ 7 had a sensitivity of 80% and a specificity of 97% in discriminating RCVS from non-RCVS. In the validation set, RCVS–TCH score showed a C-index of 0.861 (95% CI = 0.815–0.908). In our study, the RCVS–TCH showed good performance, which may aid the diagnosis of RCVS among patients with TCH.

Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by recurrent thunderclap headaches with reversible cerebral vasoconstriction, and often precipitated by the postpartum state and vasoactive medications. We describe a case of a patient with RCVS induced by amezinium metilsulfate, a sympathomimetic drug, in whom magnetic resonance angiography (MRA) initially revealed diffusely dilated cerebral arteries. A 34-year-old woman was prescribed amezinium metilsulfate for hypotension. Twelve days later, she suffered from abrupt severe headaches and was referred to our department. She had no neurological deficits; however, MRA revealed diffusely dilated anterior, middle, and posterior cerebral arteries with vasoconstriction. She was tentatively diagnosed with RCVS and successfully treated with verapamil for headache. Nevertheless, follow-up MRAs disclosed widespread segmental vasoconstriction that resolved in two months. Diffuse cerebrovascular dilation has not been addressed but may be associated with RCVS pathophysiology. In addition, physicians should bear in mind that amezinium metilsulfate can potentially induce RCVS.