Hemorrhagic versus non-hemorrhagic presentation of presumed reversible cerebral vasoconstriction syndrome (RCVS): Presentations and outcomes.

INTRODUCTION: Reversible cerebral vasoconstriction syndrome (RCVS) can present with hemorrhage, ischemia, or both. We aim to compare the differences in presentation and outcomes between patients with RCVS. METHODS: The hemorrhagic presentation group had 58 patients, and the non-hemorrhagic presentations had 30 patients. Subgroup analysis compared patients with evidence of one or more types of hemorrhage (n = 53), no evidence of hemorrhage or infarction (n = 23), evidence of infarction only (n = 7), and combination of hemorrhage and infarction (n = 5). Clinical and radiographic data were analyzed. RESULTS: Migraine (p = 0.030) and intracranial tumors (p = 0.004) were more frequent in non-hemorrhagic presentation. Seizures on admission (p = 0.047) and higher than average C-reactive protein (CRP) (p = 0.037) were seen at a higher rate in patients with hemorrhagic presentation. RCVS2 scores were not unexpectedly higher in patients with hemorrhage than non-hemorrhagic presentations (p = 0.010). Outcomes between the hemorrhagic and non-hemorrhagic groups were comparable. Subgroup analysis found a higher subset of patients with opiate use (p = 0.046) in the hemorrhage-only group. Patients with hemorrhage presented with a thunderclap headache (p < 0.001) more often when compared to the other three groups. RCVS2 score was not unexpectedly higher in the hemorrhage-only group compared with the other groups (p = 0.004). CONCLUSION: A history of migraines was associated with ischemia, while intracranial tumor was significantly associated with evidence of either an infarct, or no changes on imaging. Exposure to opiates, and seizures or thunderclap headache on presentation were associated with hemorrhage. If our data are reproducible, the RCVS2 score may benefit from inclusion of other, small hemorrhages as criterion for diagnosis for RCVS.

Hyperdense Vessel Sign in Brain Computed Tomography as an Early Indication of Reversible Cerebral Vasoconstriction Syndrome: A Case Report.

We herein report a case of reversible cerebral vasoconstriction syndrome (RCVS) with an unusual presentation of hyperdense blood vessels. A 53-year-old woman developed thunderclap headache. Brain computed tomography (CT) showed hyperdensity of the anterior cerebral artery. Brain magnetic resonance imaging revealed cerebral infarctions in the left anterior cerebral artery (ACA) territory and cerebellum. The left ACA presented with a hyperintense vessel sign, although magnetic resonance angiography (MRA) appeared normal. One week later, stenotic changes were confirmed using MRA. The vasoconstriction disappeared on day 20, and the patient was diagnosed with RCVS. CT-defined hyperdense vessel signs can be observed at an early stage of RCVS, leading to ischemic events.

Spontaneous Non-Aneurysmal Convexity Subarachnoid Hemorrhage: A Scoping Review of Different Etiologies beyond Cerebral Amyloid Angiopathy.

Spontaneous convexity subarachnoid hemorrhage (cSAH) is a vascular disease different from aneurysmal SAH in neuroimaging pattern, causes, and prognosis. Several causes might be considered in individual patients, with a limited value of the patient's age for discriminating among these causes. Cerebral amyloid angiopathy (CAA) is the most prevalent cause in people > 60 years, but reversible cerebral vasoconstriction syndrome (RCVS) has to be considered in young people. CAA gained attention in the last years, but the most known manifestation of cSAH in this context is constituted by transient focal neurological episodes (TFNEs). CAA might have an inflammatory side (CAA-related inflammation), whose diagnosis is relevant due to the efficacy of immunosuppression in resolving essudation. Other causes are hemodynamic stenosis or occlusion in extracranial and intracranial arteries, infective endocarditis (with or without intracranial infectious aneurysms), primary central nervous system angiitis, cerebral venous thrombosis, and rarer diseases. The diagnostic work-up is fundamental for an etiological diagnosis and includes neuroimaging techniques, nuclear medicine techniques, and lumbar puncture. The correct diagnosis is the first step for choosing the most effective and appropriate treatment.

Cerebrospinal Fluid Proteome Map Reveals Molecular Signatures of Reversible Cerebral Vasoconstriction Syndrome.

Reversible cerebral vasoconstriction syndrome (RCVS) is a complex neurovascular disorder characterized by repetitive thunderclap headaches and reversible cerebral vasoconstriction. The pathophysiological mechanism of this mysterious syndrome remains underexplored and there is no clinically available molecular biomarker. To provide insight into the pathogenesis of RCVS, this study reported the first landscape of dysregulated proteome of cerebrospinal fluid (CSF) in patients with RCVS (n = 21) compared to the age- and sex-matched controls (n  = 20) using data-independent acquisition mass spectrometry. Protein-protein interaction and functional enrichment analysis were employed to construct functional protein networks using the RCVS proteome. An RCVS-CSF proteome library resource of 1054 proteins was established, which illuminated large groups of upregulated proteins enriched in the brain and blood-brain barrier (BBB). Personalized RCVS-CSF proteomic profiles from 17 RCVS patients and 20 controls reveal proteomic changes involving the complement system, adhesion molecules, and extracellular matrix, which may contribute to the disruption of BBB and dysregulation of neurovascular units. Moreover, an additional validation cohort validated a panel of biomarker candidates and a two-protein signature predicted by machine learning model to discriminate RCVS patients from controls with an area under the curve of 0.997. This study reveals the first RCVS proteome and a potential pathogenetic mechanism of BBB and neurovascular unit dysfunction. It also nominates potential biomarker candidates that are mechanistically plausible for RCVS, which may offer potential diagnostic and therapeutic opportunities beyond the clinical manifestations.

Glue embolization of ruptured pseudoaneurysm secondary to reversible cerebral vasoconstriction syndrome: An illustrative case.

BACKGROUND: Reversible cerebral vasoconstriction syndrome (RCVS) is an increasingly recognized condition characterized by thunderclap headache with or without other neurological deficits and diffuse vasoconstriction of cerebral arteries. Altered cerebrovascular tone may produce hemorrhage or stroke. METHODS: A retrospective review of patients with RCVS at our institution (2000-2023) yielded one case of pseudoaneurysm secondary to RCVS. RESULTS: Diagnostic cerebral angiogram demonstrated diffuse multifocal segmental narrowing consistent with RCVS and a left M4 pseudoaneurysm in proximity to the cortical hemorrhage. The pseudoaneurysm was treated with branch vessel sacrifice using nBCA glue in a 1 : 3 ratio with ethiodized oil. After securing the source of hemorrhage, the patient received an intra-arterial infusion of Verapamil. CONCLUSION: This unique presentation of pseudoaneurysm secondary to RCVS in this patient highlights the impact of hemodynamic alteration as a possible source of bleeding and demonstrates a potential management strategy. Endovascular management with nBCA glue embolization successfully treated this lesion.

An Autopsy Case of Reversible Cerebral Vasoconstriction Syndrome After a Severe Acute Respiratory Syndrome Coronavirus 2 Vaccination.

A 73-year-old man with chronic obstructive pulmonary disease received the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine. The following day, the patient developed a headache, followed by a tonic-clonic seizure and decreased consciousness. Magnetic resonance imaging of the head revealed no signs of stroke but multiple vasoconstrictions. Despite antiepileptic therapy, the seizure persisted, and the patient died 40 hours after vaccination. An autopsy revealed multiple brain ischemia without any vascular lesions, suggesting reversible cerebral vasoconstriction syndrome (RCVS). In this case, RCVS was diagnosed radiographically and pathologically. Our case suggests that RCVS could be a cause of headache and epilepsy following the SARS-CoV-2 mRNA vaccination.

Reversible Cerebral Vasoconstriction Syndrome Mimicking Eclampsia.

This report describes the case of an 18-year-old Micronesian pregnant woman at 32 weeks gestation, initially presumed to have eclampsia but later diagnosed with reversible cerebral vasoconstriction syndrome (RCVS). She presented with seizures, altered mental status, nystagmus, lower extremity weakness, and absent reflexes. An extensive workup ruled out infectious and autoimmune causes, but a computed tomography angiogram (CTA) revealed severe cerebral vasoconstriction. Treatment included levetiracetam, intravenous magnesium, and nimodipine. The case highlights the challenge of differentiating RCVS from eclampsia in the postpartum period, emphasizing the importance of considering alternative diagnoses and brain CTA when RCVS is suspected, with calcium channel blockers potentially contributing to favorable neurological outcomes.

Frequency of ischaemic stroke and intracranial haemorrhage in patients with reversible cerebral vasoconstriction syndrome (RCVS) and posterior reversible encephalopathy syndrome (PRES) - A systematic review.

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) and reversible cerebral vasoconstriction syndrome (RCVS) may cause ischaemic stroke and intracranial haemorrhage. The aim of our study was to assess the frequency of the afore-mentioned outcomes. METHODS: We performed a PROSPERO-registered (CRD42022355704) systematic review and meta-analysis accessing PubMed until 7 November 2022. The inclusion criteria were: (1) original publication, (2) adult patients (≥18 years), (3) enrolling patients with PRES and/or RCVS, (4) English language and (5) outcome information. Outcomes were frequency of (1) ischaemic stroke and (2) intracranial haemorrhage, divided into subarachnoid haemorrhage (SAH) and intraparenchymal haemorrhage (IPH). The Cochrane Risk of Bias tool was used. RESULTS: We identified 848 studies and included 48 relevant studies after reviewing titles, abstracts and full text. We found 11 studies on RCVS (unselected patients), reporting on 2746 patients. Among the patients analysed, 15.9% (95% CI 9.6%-23.4%) had ischaemic stroke and 22.1% (95% CI 10%-39.6%) had intracranial haemorrhage. A further 20.3% (95% CI 11.2%-31.2%) had SAH and 6.7% (95% CI 3.6%-10.7%) had IPH. Furthermore, we found 28 studies on PRES (unselected patients), reporting on 1385 patients. Among the patients analysed, 11.2% (95% CI 7.9%-15%) had ischaemic stroke and 16.1% (95% CI 12.3%-20.3%) had intracranial haemorrhage. Further, 7% (95% CI 4.7%-9.9%) had SAH and 9.7% (95% CI 5.4%-15%) had IPH. CONCLUSIONS: Intracranial haemorrhage and ischaemic stroke are common outcomes in PRES and RCVS. The frequency reported in the individual studies varied considerably.

Reversible cerebral vasoconstriction syndrome and posterior reversible encephalopathy syndrome following vaccination: analysis of the VAERS database and systematic review.

Objectives: This study aimed to analyze the Vaccine Adverse Event Reporting System (VAERS) database and systematically review the literature to provide a comprehensive analysis of reversible cerebral vasoconstriction syndrome (RCVS) and posterior reversible encephalopathy syndrome (PRES) secondary to vaccination. Methods: The authors analyzed the VAERS database and conducted a systematic review following PRISMA guidelines. The inclusion criteria for VAERS data were a score of ≥3 on the RCVS2 score and/or radiographic findings consistent with the diagnosis of RCVS or PRES. The systematic review was registered with PROSPERO. Results: Our combined data set included 29 cases (9 RCVS and 20 PRES). Most cases were women (72.4%) with a mean age of 50.7 years (SD 19.4 years). Most cases were associated with COVID-19 mRNA vaccines (58.6% Moderna, 20.7% Pfizer). Hypertension (37.9%), hyperlipidemia (13.7%), chronic kidney disease (CKD) (10.3%), and end-stage renal disease (6.8%) were common comorbidities. Furthermore, 20.6% (6/29) of cases were on immunosuppression therapy for various reasons. The mean time to symptom onset was 10.49 days after vaccination (SD 18.60), and the mean duration of hospitalization was 7.42 days (SD 5.94). The symptoms reported the most frequently were headache (41.3%), elevated blood pressure (31.0%), and emesis (17.2%). Typical radiographic findings included T2/FLAIR hyperintensities affecting the parieto-occipital lobes, indicative of vasogenic and/or cytotoxic edema. Conclusions: This study provides a comprehensive analysis of postvaccine RCVS and PRES. Both disease states were seen most often in those with pre-existing risk factors such as female sex, age over 50, hypertension, renal disease, and immunosuppression. Vaccines and their associated immune response may cause endothelial dysfunction leading to cerebral vasospasm and loss of cerebral autoregulation. However, further research is required to understand the underlying pathophysiological mechanisms. Despite the associations found, the absolute risk of these syndromes remains extremely low compared to the immense benefits of vaccination.

Reversible cerebral vasoconstriction syndrome shows different clinical pictures at different times during the perinatal period: Two case reports.

OBJECTIVE: With the development of diagnostic imaging, a new clinical entity called reversible cerebral vasoconstriction syndrome (RCVS), which is considered to be a cause of secondary headache, has emerged. We herein present two cases of RCVS with different patterns of clinical progression. CASE REPORT: Case 1 occurred during labor, whereas case 2 occurred after delivery. Neither case presnted thunderclap headache at the onset of symptoms. Hypertensive disorders of pregnancy did not occur during the pregnancy or the puerperium in either case. Neurological symptoms following mild headache (Case 1: coma; Case 2: paralysis of the right extremities) were observed. CONCLUSION: Even when a patient has no risk factors for RCVS and had no severe headache, it is important not to miss any of the neurological symptoms. Magnetic resonance imaging (MRI) strongly supports the diagnosis, even during pregnancy. In addition, the diagnosis should always be reviewed while excluding eclampsia.

Dynamic changes in glymphatic function in reversible cerebral vasoconstriction syndrome.

BACKGROUND: The pathophysiology of the reversible cerebral vasoconstriction syndrome (RCVS) remains enigmatic and the role of glymphatics in RCVS pathophysiology has not been evaluated. We aimed to investigate RCVS glymphatic dynamics and its clinical correlates. METHODS: We prospectively evaluated the glymphatic function in RCVS patients, with RCVS subjects and healthy controls (HCs) recruited between August 2020 and November 2023, by calculating diffusion-tensor imaging along the perivascular space (DTI-ALPS) index under a 3-T MRI. Clinical and vascular (transcranial color-coded duplex sonography) investigations were conducted in RCVS subjects. RCVS participants were separated into acute (≤ 30 days) and remission (≥ 90 days) groups by disease onset to MRI interval. The time-trend, acute stage and longitudinal analyses of the DTI-ALPS index were conducted. Correlations between DTI-ALPS index and vascular and clinical parameters were performed. Bonferroni correction was applied to vascular investigations (q = 0.05/11). RESULTS: A total of 138 RCVS patients (mean age, 46.8 years ± 11.8; 128 women) and 42 HCs (mean age, 46.0 years ± 4.5; 35 women) were evaluated. Acute RCVS demonstrated lower DTI-ALPS index than HCs (p < 0.001) and remission RCVS (p < 0.001). A continuously increasing DTI-ALPS trend after disease onset was demonstrated. The DTI-ALPS was lower when the internal carotid arteries resistance index and six-item Headache Impact test scores were higher. In contrast, during 50-100 days after disease onset, the DTI-ALPS index was higher when the middle cerebral artery flow velocity was higher. CONCLUSIONS: Glymphatic function in patients with RCVS exhibited a unique dynamic evolution that was temporally coupled to different vascular indices and headache-related disabilities along the disease course. These findings may provide novel insights into the complex interactions between glymphatic transport, vasomotor control and pain modulation.

Reversible Cerebral Vasoconstriction Syndrome Associated With Oxybutynin Use; a Brief Review of Pathophysiology.

Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by reversible vasospasm of the central nervous system vasculature. It usually presents as a classic thunderclap headache, but complications like a stroke, seizure, or intracranial hemorrhage may occur at the onset. Most cases are linked temporally to secondary agents. The most common suggested mechanism underlying the RCVS is vascular tone dysregulation. Our report describes the RCVS incidence associated with oxybutynin use in a young female. We aim to describe the potential pathophysiology linking oxybutynin use and RCVS.

Reversible cerebral vasoconstriction syndrome following intracranial hypotension in a postpartum patient: a case report and literature review.

Introduction: Reversible cerebral vasoconstriction syndrome (RCVS) is a potentially life-threatening neurological disorder, rarely linked to intracranial hypotension. The presentation showed a patient with intracranial hypotension after peridural anesthesia who experienced RCVS during the early postpartum period, suggesting a potential involvement of intracranial hypotension in RCVS occurrence. Case report: A young female of 29 years of age initially developed an orthostatic headache after undergoing a painless delivery with lumbar epidural anesthesia. Intracranial hypotension was considered the underlying cause. Her headache was partially resolved after intravenous fluid therapy and strict bed rest. After 2 days, the patient had a new onset thunderclap headache with generalized seizures, cortical blindness, and elevated blood pressure. An MRI scan revealed high signal intensity within the temporal, parietal, and occipital lobes, left caudate nucleus, and right cerebellum on T2-FLAIR imaging with vasogenic edema. MR angiography indicated multifocal, segmental, diffuse narrowing affecting the cerebral arteries that are large and medium. An RCVS2 score was six, and the patient was diagnosed with RCVS. She was managed conservatively, quickly improving her symptoms. After 10 days, a follow-up MRI indicated a significant reduction in the abnormal signal, and a substantial resolution of the constriction of the cerebral artery constriction was confirmed by MR angiography. Conclusion: Intracranial hypotension could potentially lead to RCVS in postpartum patients, and it may be triggered by cerebral vasospasm secondary to intracranial hypotension.

Headache Attributed to Reversible Cerebral Vasoconstriction Syndrome (RCVS).

Reversible cerebral vasoconstriction syndrome (RCVS) is a condition with variable outcomes presenting a new onset thunderclap headache accompanied by focal neurological symptoms or seizures. It can be idiopathic or arise secondarily to a variety of trigger factors. The condition is increasingly recognized in clinical practice, but many facets remain poorly understood. This article aims to clarify the headache characteristics in RCVS, the temporal association of angiographic findings, the potential association of the condition with SARS-CoV-2 infection, and the clinical presentation of RCVS in children and is based on a systematic PRISMA search for published analytical or large descriptive observational studies. Data from 60 studies that fulfilled specific criteria were reviewed. Most people with RCVS exhibit a typical thunderclap, explosive, or pulsatile/throbbing headache, or a similar acute and severe headache that takes longer than 1 min to peak. Atypical presentations or absence of headaches are also reported and may be an underrecognized phenotype. In many cases, headaches may persist after resolution of RCVS. Focal deficits or seizures are attributed to associated complications including transient ischemic attacks, posterior reversible encephalopathy syndrome, ischemic stroke, cerebral edema, and intracranial hemorrhage. The peak of vasoconstriction occurs usually within two weeks after clinical onset, possibly following a pattern of centripetal propagation, and tends to resolve completely within 3 months, well after symptoms have subsided. There are a few reports of RCVS occurring in relation to SARS-CoV-2 infection, but potential underlying pathophysiologic mechanisms and etiological associations have not been confirmed. RCVS occurs in children most often in the context of an underlying disease. Overall, the available data in the literature are scattered, and large-scale prospective studies and international collaborations are needed to further characterize the clinical presentation of RCVS.

Recurrent Reversible Cerebral Vasoconstriction Syndrome: A Report of Two Cases.

Reversible cerebral vasoconstriction syndrome (RCVS) is a rare neurological condition that classically presents with recurrent, thunderclap headaches and radiographic findings of multifocal narrowing of cerebral vasculature. Complications of RCVS may include ischemic or hemorrhagic strokes. Sympathomimetic agents including cannabinoids have been associated as precipitants in many cases. RCVS is classically considered to be reversible, although cases of recurrent RCVS have been described in the literature. In this report, we describe two cases of recurrent RCVS, which were precipitated by recurrent exposures to inciting agents. The first patient was found to have a history of repeated exposure to tetrahydrocannabinol (THC) and suffered from recurrent multifocal ischemic strokes with evidence of persistent multifocal narrowing of cerebral vasculature by cerebral arteriography. The second case describes a patient with a history of use of ashwagandha, medical marijuana, and serotonin-norepinephrine reuptake inhibitors (SNRIs) who experienced multiple intracranial hemorrhages with radiographic evidence of multifocal narrowing of cerebral vessels as well.

Case report: Meningitis: a cause of reversible cerebral vasoconstriction syndrome?

Introduction: Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by thunderclap headache and reversible cerebral arteries vasoconstriction. The pathophysiology remains unclear, but many triggers were reported. Case reports: We reported two cases of patients with meningitis who developed RCVS confirmed by brain imaging. They presented clinical and CSF features of meningitis that are suspected to be infectious, but no agent was identified. Headache and artery irregularities were resolved with the improvement of CSF. Conclusion: These cases suggest that in the context of meningitis, modification or atypical headaches should lead to brain imaging to rule out RCVS. We hypothesized that CSF inflammation may trigger cerebral arteries vasoconstriction.

Posterior Reversible Leucoencephalopathy Syndrome: Case Series, Comments, and Diagnostic Dilemma.

PURPOSE OF REVIEW: To report a series of patients with clinical and radiological features suggestive of posterior reversible encephalopathy syndrome (PRES) related to diverse etiologies emphasizing its pathophysiological basis. RECENT FINDINGS: Posterior reversible encephalopathy syndrome (PRES) may present with a broad range of clinical symptoms from headache and visual disturbances to seizure and altered mentation. Typical imaging findings include posterior-circulation predominant vasogenic edema. Although there are many well-documented diseases associated with PRES, the exact pathophysiologic mechanism has yet to be fully elucidated. Generally accepted theories revolve around disruption of the blood-brain barrier secondary to elevated intracranial pressures or endothelial injury induced by ischemia from a vasoconstrictive response to rising blood pressure or toxins/cytokines. While clinical and radiographic reversibility is common, long-standing morbidity and mortality can occur in severe forms. In patients with malignant forms of PRES, aggressive care has markedly reduced mortality and improved functional outcomes. Various factors that have been associated with poor outcome include altered sensorium, hypertensive etiology, hyperglycemia, longer time to control the causative factor, elevated C reactive protein, coagulopathy, extensive cerebral edema, and hemorrhage on imaging. Reversible cerebral vasoconstriction syndromes (RCVS) and primary angiitis of the central nervous system (PACNS) are invariably considered in the differential diagnosis of new cerebral arteriopathies. Recurrent thunderclap headache (TCH), and single TCH combined with either normal neuroimaging, border zone infarcts, or vasogenic edema, have 100% positive predictive value for diagnosing RCVS or RCVS-spectrum disorders. Diagnosis of PRES in some circumstances can be challenging and structural imaging may not be sufficient to distinguish it from other differential diagnostic considerations like ADEM. Advanced imaging techniques, such as MR spectroscopy or positron emission tomography (PET) can provide additional information to determine the diagnosis. Such techniques are more useful to understand the underlying vasculopathic changes in PRES and may answer some of the unresolved controversies in pathophysiology of this complex disease. Eight patients with PRES resulting from different etiologies varying from pre-eclampsia/eclampsia, post-partum headache with seizures, neuropsychiatric systemic lupus erythematosus, snake bite, Dengue fever with encephalopathy, alcoholic liver cirrhosis with hepatic encephalopathy, and lastly reversible cerebral vasoconstriction syndrome (RCVS). Additionally, a diagnostic dilemma between PRES and acute disseminated encephalomyelitis (ADEM) was notable in one patient. Some of these patients did not have or only very transiently had arterial hypertension. PRES may underlie the clinical conundrum of headache, confusion, altered sensorium, seizures, and visual impairment. PRES need not necessarily be always associated with high blood pressure. Imaging findings may also be variable. Both clinicians and radiologists need to familiarize themselves with such variabilities.