1. University of Massachusetts Medical School
eEdE-41 - The Many Presentations of Reversible Cerebral Vasoconstriction Syndrome (RCVS), A Great Masquerader
Katyucia De Macedo Rodrigues, Eduardo Scortegagna Jr., Deepak Takhtani, Ajit Puri, Sathish Dundamadappa, Rania Hito
University of Massachusetts Medical School

2. The authors have no relevant conflict of interest to declare
Disclosure
The authors have no relevant conflict of interest to declare

3. Purpose
Classically presenting as a thunderclap headache, RCVS may mimic a number of different entities, making the initial diagnosis challenging in the absence of high clinical suspicion. Our aim is to present a case based review of RCVS, demonstrating common and uncommon imaging findings on CT, MRI, CT angiography (CTA), MR angiography (MRA) and conventional digital subtraction angiography (DSA).

4. What is RCVS?
The precise pathophysiology of Reversible Cerebral Vasoconstriction Syndrome (RCVS) remains unclear. It is believed that a transient disorder of vascular tone regulation leads to inappropriate arterial constrictions, which occur in a segmental fashion affecting multiple arteries in different vascular territories. An inciting factor may or may not be identified. Sympathomimetic or vasoactive agents, including amphetamines, phenylpropanolamine, pseudoephedrine, serotonergic antidepressants, nicotine, caffeine, cannabis, and triptan or ergot-containing medications are among common triggers.
Click here for a comprehensive list of inciting factor associated with RCVS

5. Conditions and Triggers associated with RCVS
• Pregnancy
• Lysergic acid diethylamide (LSD)
• Systemic Lupus eythematous
• Pseudoephedrine
• Amphetamine derivatives
• Anti-phospholipid Antibody Syndrome
• Epinephrine
• Migraine
• Ergotamine tartrate
• Primary thunderclap headache
• Carotid endarterectomy
• Bromocriptine
• Primary cough headache
• Neurosurgical procedures
• Hydroxycut (weight-loss aid)
• Benign sexual headache
• Tonsilectomy
• Selective serotonin reuptake inhibitors
• Hypercalcemia
• Neck surgery
• Porphyria
• Blood product transfusion/ Red blood cell transfusion
• Serotonin noradrenaline reuptake inhibitors
• Pheochromocytoma
• Intravenous immune globulins (IVIg)
• Bronchial carcinoid tumor
• Sumatriptan and other triptans
• Unruptured saccular cerebral aneurysm
• Tacrolimus
• High Altitude
• Cyclophosphamide
• Swimming
• Head trauma
• Erythropoietin
• Bathing
• Spinal subdural hematoma
• Interfereron alpha
• Carotid glomus tumor
• Nicotine patch
• Post-bone marrow transplant
Back to presentation
• Oral contraceptive pills/hormonal agents
• Thrombotic Thrombocytopenic Purpura
• Cocaine, Ecstasy, Marijuana

6. Historical Background
RCVS is a unifying term for a manifestation that may occur in different clinical settings. It encompasses the previously described “Call-Fleming syndrome”, “postpartum angiopathy”, “migrainous vasospasm”, “migraine angiitis”, “drug-induced angiopathy”, “benign angiopathy of the central nervous system (CNS)”, and “CNS pseudovasculitis”.
In 2007, Calabrese et al proposed the term RCVS to unify the common vascular manifestation of these different entities, coursing with similar clinical, laboratory, and angiographic findings. Specific diagnostic criteria were also suggested.

7. Diagnostic Criteria
Multiple segmental vasoconstrictions on vascular imaging studies;
Aneurysmal hemorrhage is excluded;
Normal or near normal CSF (protein level 􏰀 80 mg%, leukocytes 􏰀10 mm3, normal glucose level);
Severe headache with or without other neurological manifestation;
Resolution of vasoconstrictions within 12 weeks.

8. Clinical presentation
Patients most commonly present with severe headache that escalates in a few seconds (thunderclap headaches). It usually persists for days before a diagnosis is made.
Patients with prior history of migraines usually report a headache that is different in quality, intensity or location as compared to prior migraine episodes.
Symptoms related to complications, such as stroke or TIA, can be present, usually manifesting within 1 to 2 weeks.
There is a common association between PRES and RCVS, likely related to the vasoactive tone deregulation on both entities, with unclear boundaries between the two processes. Approximately 85% of patients with PRES demonstrate some degree of vasoconstriction on vascular imaging.

9. Case based review of radiological findings

10. Case 1
26 year old female sprayed with pepper spray on face and eyes, developed severe headache several hours later A B C
A - NCCT, B - FLAIR and C - Diffusion weighted imaging (DWI): Initial non vascular imaging shows no significant abnormality.

11. A B
A: CTA image showing multiple segmental vasoconstrictions along the right middle cerebral artery (MCA) branches. B: Magnified view of A with arrows pointing at arterial constrictions. C: MRA shows multiple small segmental vasoconstrictions along both posterior cerebral arteries. C

12. Workup for vasculitis negative
Workup for vasculitis negative. Patient showed dramatic improvement of headaches after oral administration of verapamil. Discharged asymptomatic with no recurrence of symptom at 4 and 44 month follow up. A B
A: DSA shows multiples segmental vasoconstriction in branches of right MCA, right posterior cerebral artery (PCA) and anterior cerebral artery (ACA). Black arrows show some of the vasoconstrictions. White box show area magnified in B. B: Black arrows show vasoconstriction in ACA branches. C: DSA showing multiple segmental narrowing along both PCAs. D: Magnified view of C, showing vasoconstrictions of distal left PCA (arrows). C D

13. Radiological findings
Conventional imaging in the absence of complication is typically normal. Initial vascular imaging may be normal in the first week. A high clinical suspicion is imperative for pursuing additional radiological evidence of transient vasoconstriction.
In typical clinical presentations with normal initial imaging, a provisional diagnosis of possible RCVS should be considered until follow up images confirm or exclude the diagnosis.

14. Case 2
50 year old male with prior history of migraine headaches and post coital headaches, presenting with severe headache worsening in the last 2 days A B C D
A: NCCT shows subtle sulcal subarachnoid hemorrhage (SAH) in the left cerebral convexity (arrow), which is demonstrated in the sagittal reformat in B. C: Axial FLAIR showing high signal within the left central sulcus, confirming the presence of SAH, which is also demonstrated on the susceptibility weighted angiography images (SWAN) .

15. A B
A: Initial MRA shows multiple segmental arterial narrowing (arrows) involving branches of bilateral MCAs and PCAs. B: 2 month followup MRA showing resolution of vasoconstrictions with oral treatment with of calcium channel blocker.

16. Radiological findings
RCVS can present with subarachnoid hemorrhage (SAH) that is usual sulcal in the cerebral convexities.
SAH related to ruptured aneurysm is more often centered in basal cisterns and around the circle of Willis.
Non aneurysmal idiopathic hemorrhage is centered in the perimesencephalic cistern.
Cortical Venous thrombosis can present with sulcal SAH in the cerebral convexities, similar to the appearance of RCVS. Additional clinical information and radiological studies may be necessary to establish a diagnosis.

17. Radiological Findings
Role of imaging studies:
Demonstrate multifocal segmental vasoconstriction;
Exclude possible alternative diagnosis, such as primary angiitis of the central nervous system (PACNS), aneurysmal bleed, venous thrombosis and amyloid angiopathy;
Evaluate for possible complications, such as infarct, intracranial bleed and parenchymal edema.

18. 56 year old male with right leg weakness and right arm paresthesia
Case 3
56 year old male with right leg weakness and right arm paresthesia A B C D
Axial DWI showing small cortical infarct in the medial aspect of the posterior right frontal lobe in A and in the deep white matter of the left frontal lobe in B. CTA shows narrowing of the M1 segment of the left MCA in C and multifocal segmental narrowing of the left MCA branches in D.

19. A B
DSA before (A) and after (B) intra-arterial (IA) administration of verapamil showing improvement of arterial narrowing.
Patient maintained on oral verapamil and discharged home with resolution of symptoms.

20. Radiological findings
RCVS may evolve with symptoms related to stroke or TIA.
Should be suspected in patients with typical history and stroke involving multiple vascular territories in the absence of significant atheromatous disease or identifiable embolic source.
Infarcts usually in watershed zones.

21. Case 4
48 year old female with worst headache of her life, vomiting and photophobia several hours after being hit on face mask by a paintball A B C
A: Axial FLAIR demonstrates increased signal within the sulci of the high cerebral convexities. B: Axial DWI fails to show restricted diffusivity correlating with FLAIR abnormal signal. C: Axial post intravenous contrast T1 weighted-images demonstrate increased enhancement correlating with FLAIR signal abnormality.

22. A B
CTA demonstrate segmental vasoconstrictions in ACAs branches (A) and right MCA branches (B). Note distal caliber greater than proximal, instead of expected normal smooth tapering of vessel caliber.

23. A B
DSA of right internal carotid artery (RICA) before (A) and after (B) the IA administration of verapamil. Note the significant interval improvement of arterial vasoconstrictions.
Lumbar puncture was negative for SAH. Patient discharged home on oral verapamil without symptoms or deficits.

24. Radiological findings
Hyperintense vessel sign on FLAIR is one of the possible presentations of RCVS.
It mimics high FLAIR signal seen in cases of SAH, inflammatory meningeal processes or leptomeningeal spread of tumor.
High signal is related to slow flow within affected branches.
CSF analysis typically negative for SAH.

25. Case 5
59-year-old woman admitted for 5 days due to Crohn's disease flare, developing sudden onset of loss of vision in both eyes. A B C
A: Axial FLAIR images demonstrates increased signal within the occipital lobes, corresponding cytotoxic edema on the DWI (B) and ADC map (C). Findings raised suspicion for posterior reversible encephalopathy syndrome (PRES).

26. A B
CTA angiogram shows multifocal vasoconstrictions in the right MCA and bilateral ACA branches. The possibility of vasculitis was also raised.

27. B A
DSA of RICA before (A) and after (B) the IA administration of verapamil shows significant interval improvement of vasoconstrictions.
Patient discharged home with symptoms related to occipital strokes – severe bilateral visual loss - with a diagnosis of RCVS.

28. Follow up MR angiogram 40 days later shows no residual vasospasm.

29. Radiological findings
There is significant overlap between PRES and RCVS with PRES-like reversible cerebral edema encountered in 9% to 38% of patients with RCVS, while most patients with PRES (􏰂85%) demonstrate some element of RCVS-like cerebral vasoconstriction when conventional angiography is performed.
Distinction between the two entities may not be possible due to similar causative disorders.

30. Radiological findings
Primary Angiitis of the Central Nervous System (PACNS) affects older men and demonstrate abnormal CSF analysis, with increased white blood cell count and protein.
Thunderclap headache is rarely associated with PACNS. Instead, patients complain of insidious pain, which is chronic in duration.
On imaging, PACNS will often demonstrate multiple infarcts of different ages and has a low rate of hemorrhagic complications.
Association with PRES is also unusual for PACNS.
Differentiation between PACNS and RCVS is imperative, giving significant differences in management and prognosis.

31. Case 6
59 year old female presenting with severe headaches and vomiting. Drug screen positive for citalopram and pseudoephedrine A B C D
A: NCCT showing left parietal intraparenchymal hemorrhage and SAH within left cerebral sulci. B: Axial FLAIR redemonstrating the intraparenchymal hematoma and SAH, as well as small left convexity subdural hematoma. C: Axial T2 weighted-images confirms findings in B. D: Axial post contrast T1 weighted-images do not show any underlying enhancing lesion.

32. Relative cerebral blood volume maps (rCBV) demonstrate decreased perfusion related to the intraparenchymal hematoma (orange arrow), as well as asymmetric perfusion in other areas, secondary to vasoconstrictions (blue arrows).

33. Radiological findings
RCVS can be complicated by intraparenchymal hematoma with or without sulcal hemorrhage.
Findings may raise suspicion for amyloid angiopathy, underlying neoplasm or vascular pathology, such as arteriovenous malformation (AVM) or venous thrombosis.
Amyloid angiopathy patients are usually older males with brain imaging showing hemorrhages of different ages.
Advanced and angiographic images may be necessary to exclude underlying neoplasm or vascular pathology, respectively.

34. Management No specific guideline as no trial in the literature.
Avoiding inciting factor if able to identify.
Close monitoring for early detection of possible complications.
Pain relief and supportive measures for associated symptoms.
Calcium-channel block to revert vasospasm.
Intra-arterial vasodilators in patients with major complications.
Angioplasty as last resort in refractory cases.

35. Summary
Increased awareness about different imaging presentations of RCVS is desired to direct appropriate and timely clinical management.
Atypical subarachnoid hemorrhage, unexplained cerebral edema and hemorrhage, as well as single or multivessel diffuse narrowing with a relatively normal appearing brain should raise suspicion of RCVS.
Patients with a typical presentation and normal imaging findings should be presumed RCVS to have until follow up vascular imaging is performed.

36. References
Marder CP, Donohue MM, Weinstein JR, Fink KR. Multimodal imaging of reversible cerebral vasoconstriction syndrome: a series of 6 cases. AJNR Am J Neuroradiol Aug;33(7):
Mehdi A, Hajj-Ali RA. Reversible cerebral vasoconstriction syndrome: a comprehensive update. Curr Pain Headache Rep Sep;18(9):443.
Calabrese LH, Dodick DW, Schwedt TJ, Singhal AB. Narrative review: reversible cerebral vasoconstriction syndromes. Ann Intern Med ;146(1):34–44.
Miller TR, Shivashankar R, Mossa-Basha M, Gandhi D. Reversible Cerebral Vasoconstriction Syndrome, Part 1: Epidemiology, Pathogenesis, and Clinical Course. AJNR Am J Neuroradiol Jan 15.
Miller TR, Shivashankar R, Mossa-Basha M, Gandhi D. Reversible Cerebral Vasoconstriction Syndrome, Part 2: Diagnostic Work-Up, Imaging Evaluation, and Differential Diagnosis. AJNR Am J Neuroradiol Jan 22.
Papathanasiou A, Zouvelou V, Breen DP, Phillips TJ, Misbahuddin A, Chawda S, de Silva R. Reversible cerebral vasoconstriction syndrome as a cause of thunderclap headache: a retrospective case series study. Am J Emerg Med Dec 19. pii: S (14)

37. References
Kameda T, Namekawa M, Shimazaki H, Minakata D, Matsuura T, Nakano I. Unique combination of hyperintense vessel sign on initial FLAIR and delayed vasoconstriction on MRA in reversible cerebral vasoconstriction syndrome: a case report. Cephalalgia Nov;34(13):
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Ioannidis I, Nasis N, Agianniotaki A, Katsouda E, Andreou A. Reversible cerebral vasoconstriction syndrome: treatment with multiple sessions of intra-arterial nimodipine and angioplasty. Interv Neuroradiol Sep;18(3):
Calic Z, Cappelen-Smith C, Zagami AS. The Reversible Cerebral Vasoconstriction Syndrome. Intern Med J Dec 16.

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