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Illustrative case: reversible cerebral vasoconstriction syndrome presenting with left temporal lobe hematoma. (A) Computed tomography of the head showing large left temporal hematoma (white arrows), early signs of midline shift and left uncal herniation (black arrow). (B) Anterior posterior view on a conventional angiography showing moderate vessel narrowing of the supraclinoid segment of the left internal carotid artery (ICA), A1 segment of the anterior cerebral artery, and the M1 segment of the middle cerebral artery. (C) Lateral view on a conventional angiography again showing moderate vessel narrowing of the supraclinoid segment of the left ICA. (D) Anterior–posterior view on a conventional angiography again after intra-arterial vasodilator therapy showing mild improvement in the caliber of the left A1 segment. (E) Anterior–posterior view on a conventional angiography at a 3 months follow-up showing normalization of the vessel narrowing. (F) Lateral view on a conventional angiography at a 3 months follow-up showing normalization of the vessels narrowing.
Source publication
Reversible cerebral vasoconstriction syndrome (RCVS) is classically diagnosed based on the presence of severe thunderclap headache, focal neurologic symptoms, and the radiographic findings of reversible diffuse segmental cerebral vasoconstriction. We present a diagnostic test that may assist in the clinical diagnosis and facilitate treatment.
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Contexts in source publication
Context 1
... neurologic exam progressed rapidly to decreased level of consciousness that necessitated intubation to protect airways. Computed tomography and CTA was done and showed left temporoparietal hematoma with surrounding edema and associated mass effect, midline shift, and mild left uncal herniation along with signs of bilateral ICA caliber abnormalities (Fig 2, A). Patient un- derwent an emergent craniotomy to prevent further her- niation. ...
Context 2
... un- derwent an emergent craniotomy to prevent further her- niation. A DSA was obtained to better delineate the etiology of the intracranial bleed and showed smooth moderate narrowing of the supraclinoid left ICA, middle cerebral artery, and anterior cerebral artery branches pre- dominately the A1 and M1 segments (Fig 2, B-C). Nicardi- pine infusion in both ICAs resulted in improvement in the vessel narrowing (Fig 2, D). ...
Context 3
... DSA was obtained to better delineate the etiology of the intracranial bleed and showed smooth moderate narrowing of the supraclinoid left ICA, middle cerebral artery, and anterior cerebral artery branches pre- dominately the A1 and M1 segments (Fig 2, B-C). Nicardi- pine infusion in both ICAs resulted in improvement in the vessel narrowing (Fig 2, D). At the 3 month follow-up, the patient had a minimal neurologic dysfunction and a sig- nificant improvement in the vessel narrowing on DSA (Fig 2, E-F). ...
Citations
... Intra-arterial vasodilator infusion is frequently offered even in clinically stable patients to treat the angiographic findings; some centers advocate using this interventional procedure for early diagnosis based on the angiographic response to vasodilator infusion. 16,22 We have recently shown that the diagnosis can be made with alacrity based on bedside clinical and brain imaging features alone 7,23 and that our criteria have nearly 100% specificity in distinguishing RCVS from PACNS. 7 Hence, the use of potentially risky invasive procedures cannot be justified for diagnostic purposes, 24 particularly since the outcome is usually excellent. ...
Objective:
Factors predicting poor outcome in patients with the reversible cerebral vasoconstriction syndrome (RCVS) have not been identified.
Methods:
In this single-center retrospective study, we analyzed the clinical, brain imaging, and angiography data in 162 patients with RCVS. Univariable and multivariable regression analysis were performed to identify predictors of persistent (nontransient) clinical worsening, radiologic worsening, early angiographic progression, and poor discharge outcome (modified Rankin Scale score 4-6).
Results:
The mean age was 44 ± 13 years; 78% of patients were women. Persistent clinical worsening occurred in 14% at 6.6 ± 4.1 days after symptom onset, radiologic worsening in 27% (mainly new infarcts), and angiographic progression in 15%. Clinical worsening correlated with angiographic progression and new nonhemorrhagic lesions. Age and sex did not independently predict any type of worsening. Infarction on baseline imaging predicted poor outcome. Prior serotonergic antidepressant use predicted clinical and angiographic worsening but not poor outcome. Intra-arterial vasodilator therapy independently predicted clinical worsening and poor discharge outcome but was offered to more severe cases. Glucocorticoid treatment proved to be an independent predictor of clinical, imaging, and angiographic worsening and poor outcome. Of the 23 patients with clinical worsening, 17 received glucocorticoids (15 within the preceding 2 days). There were no significant differences in baseline brain lesions and angiographic abnormalities between glucocorticoid-treated and untreated patients.
Conclusion:
Patients with RCVS at risk for worsening can be identified on basis of baseline features. Iatrogenic factors such as glucocorticoid exposure may contribute to worsening.
Background: Although nimodipine is commonly used to treat reversible cerebral vasoconstriction syndrome (RCVS), its disease-modifying effects are not yet understood. We aimed to investigate the effect of nimodipine and treatment initiation timing on the prevention of worsened vasoconstriction.
Methods: We prospectively recruited patients with recent-onset (within 3 weeks of the first thunderclap headache), angiogram-proven RCVS. All participants underwent transcranial Doppler (TCD) examination to evaluate the mean flow velocities (MFVs) of the bilateral middle cerebral arteries at baseline and were serially followed-up after 10, 20, 30, and 90 days. Oral nimodipine treatment was initiated after the baseline TCD study, and patients were split into early and late treatment groups based on the time from onset to initial nimodipine administration. To estimate the worsening of vasoconstriction, we calculated the area of total time spent with MFVs above the baseline value (MFV area). We tested the correlation between the number of days from onset to treatment initiation and MFV area and performed linear regression analysis to examine the independent association between earlier treatment and MFV area.
Results: A total of 32 patients with RCVS (mean age: 51.5 ± 10.3 years; 91% female) completed this study. Baseline TCD assessment was performed at a mean of 7.1 ± 4.2 days after thunderclap headache onset. We observed that earlier treatment with nimodipine correlated with reduced MFV area (r = 0.37, p = 0.038). Furthermore, this association remained significant after adjusting for other clinical variables (regression coefficient 0.673, adjusted p = 0.023) in the multivariable linear regression.
Conclusions: Early oral nimodipine treatment prevents worsening of vasoconstriction, suggesting that nimodipine may have a disease-modifying effect in RCVS treatment.
Reversible cerebral vasoconstriction syndrome (RCVS) is a poorly understood but increasingly recognized entity, likely multifactorial in nature and characterized by diffuse cerebral vasospasm that presents as sudden, intense, and fluctuating headaches. Due to insufficient evidence, there is currently no consensus on RCVS treatment guidelines. However, nicardipine, an L-type calcium channel blocker, may prove effective in RCVS treatment because of its ability to penetrate the blood-brain barrier. We report the concomitant use of intrathecal (IT) nicardipine and continuous intraarterial (IA) nicardipine infusion via microcatheter placed in the intracranial circulation for the treatment of a 58-year-old female with severe refractory RCVS. On presentation, this patient was noted to have a non-traumatic non-aneurysmal subarachnoid hemorrhage secondary to RCVS. Initially managed with oral verapamil, she later developed refractory symptomatic vasoconstriction requiring multiple angiograms for spasmolysis via balloon angioplasty and IA nicardipine. Due to the refractory nature of her spasm despite the IA therapy, we decided to attempt intrathecal nicardipine, starting at 4 mg q12 h via an external ventricular drain. This dose was escalated to 4 mg q6 h. The patient stabilized for 24 h but again decompensated, requiring continuous IA spasmolysis via a microcatheter placed in the left middle cerebral artery and left for continuous IA nicardipine infusion (5 mg/h). The patient showed slow incremental improvement clinically and a decrease in vasospasms on imaging, ultimately suffering minimal stroke burden. This patient's hospital course demonstrates that nicardipine, administered intrathecally or intraarterially, could be beneficial in select patients with refractory RCVS as a means of minimizing repeat angiography/angioplasty. Further studies are needed to better define a treatment paradigm for these patients.
Reversible segmental narrowing of the intracranial arteries has been described since several decades in numerous clinical settings, using variable nosology. Twenty-one years ago, we tentatively proposed the unifying concept that these entities, based on similar clinical-imaging features, represented a single cerebrovascular syndrome. This 'reversible cerebral vasoconstriction syndrome' or RCVS has now come of age. A new ICD-10 code has been established, enabling larger-scale studies. The RCVS2 scoring system provides high accuracy in confirming RCVS diagnosis and excluding mimics such as primary angiitis of the central nervous system. Several groups have characterized its clinical-imaging features. RCVS predominantly affects women. Recurrent worst-ever (thunderclap) headaches are typical at onset. While initial brain imaging is often normal, approximately one-third to half develop complications such as convexity subarachnoid hemorrhages, lobar hemorrhages, ischemic strokes located in arterial 'watershed' territories and reversible edema, alone or in combination. Vasoconstriction evolves over hours to days, first affecting distal and then the more proximal arteries. An overlap between RCVS and primary thunderclap headache, posterior reversible encephalopathy syndrome, Takotsubo cardiomyopathy, transient global amnesia, and other conditions has been recognized. The pathophysiology remains largely unknown. Management is mostly symptomatic: headache relief with analgesics and oral calcium-channel blockers, removal of vasoconstrictive factors, and avoidance of glucocorticoids which can significantly worsen outcome. Intra-arterial vasodilator infusions provide variable success. Overall, 90-95% of admitted patients achieve complete or major resolution of symptoms and clinical deficits within days to weeks. Recurrence is exceptional, although 5% can later develop isolated thunderclap headaches with or without mild cerebral vasoconstriction.
Background/Objective
Reversible cerebral vasoconstriction syndrome may be underdiagnosed. It can be accompanied by various complications, mainly intracerebral hemorrhage and ischemic stroke. The clinical presentation of this condition varies according to its localization. The aims of this review are to raise awareness of the disease, especially in the presence of corresponding risk factors; to connect its precipitating factors, pathophysiology, and complications; and to compare various differential diagnoses of vasoconstriction.
Methods
A review of the literature in PubMed/MEDLINE and Google Scholar was conducted from May 1997 until May 2022.
Results
Reversible cerebral vasoconstriction syndrome, which is a clinical–radiological syndrome, is mainly characterized by the occurrence of thunderclap headache and widespread vasoconstriction. The most common precipitating factors are the use of vasoactive substances and postpartum status. The pathophysiology is currently assumed to include two mechanisms: sympathetic overactivity and endothelial dysfunction. From these mechanisms, it is possible to derive potential complications as well as the most important differential diagnoses: posterior reversible encephalopathy syndrome, convexity subarachnoid hemorrhage, ischemic and hemorrhagic stroke, and primary angiitis of the central nervous system.
Conclusion
In general, the outcome of reversible cerebral vasoconstriction syndrome is very good. Vasospasm as well as thunderclap headache attacks can be fully reversible, and > 90% of patients are functionally independent at discharge.
Objective
This narrative review of the literature concerns persistent headache attributed to past non-traumatic subarachnoid hemorrhage (SAH), based off demographic and clinical features, what are pathophysiologic mechanisms by which these headaches occur, which medical and interventional treatments have the most evidence for pain alleviation, and what pre-clinical evidence is there for emerging treatments for these patients.
Background
Following initial stabilization and treatment of spontaneous SAH, most commonly due to aneurysmal rupture, headache in the immediate inpatient setting and persisting after discharge are an important cause of morbidity. These headaches often receive heterogenous treatment of uncertain efficacy, and the risk factors and pathophysiology of their development has received little study.
Methods
A narrative review of current literature discussing post-SAH headache was conducted using a literature search in PubMed with search term combinations including “post subarachnoid hemorrhage pain”, “subarachnoid hemorrhage headache”, and “post subarachnoid hemorrhage headache”. Clinical studies mentioning headache after SAH and/or treatment in the abstract/title were included through March, 2022.
Results and Conclusion
Post-SAH headaches are shown to decrease quality of life, have a multi-modal pathophysiology in their occurrence, and only a select few medications (reviewed herein) have been demonstrated to have efficacy in alleviation of these headaches, while also harboring possible risks including vasospasm and re-bleeding. An effective treatment paradigm of these headaches will include trials of evidence-based therapeutics, rapid reduction of opioid medications if not effective, and consideration of multi-modal pain control strategies including nerve blocks.
Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by recurrent thunderclap headache and reversible multifocal vasoconstrictions of the cerebral arteries. There are no treatment guidelines despite its potential for precarious outcomes. A 52-year-old woman with recurrent episodes of severe headache was diagnosed with RCVS and treated with oral nimodipine, which has been widely used for RCVS. However, her vessel status worsened despite treatment for several days and only improved after administration of intra-arterial (IA) and per os (PO) verapamil, which has been used to reverse vasoconstrictions in variant angina. Based on this case and literatures, we propose an alternative strategy using verapamil. The presence of a vascular reaction after an IA verapamil challenge during initial digital subtraction angiography can diagnose RCVS while also serving as an emergent treatment. Based on the response to IA verapamil, PO verapamil can be prescribed if there are no contraindications or side effects.
Background and purpose:
There is mounting evidence supporting the benefit of intra-arterial administration of vasodilators in diagnosing reversible cerebral vasoconstriction syndrome. We prospectively quantified the degree of luminal diameter dilation after intra-arterial administration of verapamil and its accuracy in diagnosing reversible cerebral vasoconstriction syndrome.
Materials and methods:
Patients suspected of having intracranial arteriopathy on noninvasive imaging and referred for digital subtraction angiography were enrolled in a prospective registry. Intra-arterial verapamil was administered in vascular territories with segmental irregularities. The caliber difference (Caliberpost - Caliberpre) and the proportion of caliber change ([(Caliberpost - Caliberpre)/Caliberpre] × 100%) were used to determine the response to verapamil. The diagnosis of reversible cerebral vasoconstriction syndrome was made on the basis of clinical and imaging features at a follow-up appointment, independent of the reversibility of verapamil. Receiver operating characteristic curve analysis was performed to determine the best threshold.
Results:
Twenty-six patients were included, and 9 (34.6%) were diagnosed with reversible cerebral vasoconstriction syndrome. A total of 213 vascular segments were assessed on diagnostic angiography. Every patient with a final diagnosis of reversible cerebral vasoconstriction syndrome responded to intra-arterial verapamil. The maximal proportion of change (P < .001), mean proportion of change (P = .002), maximal caliber difference (P = .004), and mean caliber difference (P = .001) were statistically different between patients with reversible cerebral vasoconstriction syndrome and other vasculopathies. A maximal proportion of change ≥32% showed a sensitivity of 100% and a specificity of 88.2% to detect reversible cerebral vasoconstriction syndrome (area under the curve = 0.951). The Reversible Cerebral Vasoconstriction Syndrome-2 score of ≥5 points achieved a lower area under the curve (0.908), with a sensitivity of 77.8% and a specificity of 94.1%.
Conclusions:
Objective measurement of the change in the arterial calibers after intra-arterial verapamil is accurate in distinguishing reversible cerebral vasoconstriction syndrome from other vasculopathies. A proportion of change ≥32% has the best diagnostic performance.
Purpose of review
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.
Recent findings
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.
Conclusion
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.
