Reversible cerebral vasoconstriction syndrome

Reversible cerebral vasoconstriction syndrome
Specialty	Neurology

Reversible cerebral vasoconstriction syndrome (RCVS, sometimes called Call-Fleming syndrome) is a disease characterized by a weeks-long course of thunderclap headaches, sometimes focal neurologic signs, and occasionally seizures.^[1] Symptoms are thought to arise from transient abnormalities in the blood vessels of the brain.^[1] In some cases, it may be associated with childbirth, vasoactive or illicit drug use, or complications of pregnancy.^[1] If it occurs after delivery it may be referred to as postpartum cerebral angiopathy.

For the vast majority of patients, all symptoms disappear on their own within three weeks.^[1] Deficits persist in a small minority of patients, with severe complications or death being very rare.^[1] Because symptoms resemble a variety of life-threatening conditions, differential diagnosis is necessary.^[1]

The key symptom of RCVS is recurrent thunderclap headaches, which over 95% of patients experience.^[1] In two-thirds of cases, it is the only symptom.^[1] These headaches are typically bilateral, very severe and peak in intensity within a minute.^[1] They may last from minutes to days, and may be accompanied by nausea, photophobia, phonophobia or vomiting.^[1] Some patients experience only one headache, but on average there are four attacks over a period of one to four weeks.^[1] A milder, residual headache persists between severe attacks for half of patients.^[1]

1–17% of patients experience seizures. 8–43% of patients show neurologic problems, especially visual disturbances, but also hemiplegia, ataxia, dysarthria, aphasia, and numbness.^[1] These neurologic issues typically disappear within minutes or a few hours; more persistent symptoms may indicate a stroke.^[1] Posterior reversible encephalopathy syndrome is present in a small minority of patients.^[2][3][4]

This condition features the unique property that the patient's cerebral arteries can spontaneously constrict and relax back and forth over a period of time without intervention and without clinical findings. Vasospasm is common post subarachnoid hemorrhage and cerebral aneurysm, but in RCVS only 25% of patients have symptoms post subarachnoid hemorrhage.^[5]

The direct cause of the symptoms is believed to be either constriction or dilation of blood vessels in the brain.^[1] The pathogenesis is not known definitively, and the condition is likely to result from multiple different disease processes.^[6]

Up to two-thirds of RCVS cases are associated with an underlying condition or exposure, particularly vasoactive or recreational drug use, complications of pregnancy (eclampsia and pre-eclampsia), and the adjustment period following childbirth called puerperium.^[1] Vasoactive drug use is found in about 50% of cases.^[6] Implicated drugs include selective serotonin reuptake inhibitors, weight-loss pills such as Hydroxycut, alpha-sympathomimetic decongestants, acute migraine medications, pseudoephedrine, epinephrine, cocaine, and cannabis, among many others.^[1] It sometimes follows blood transfusions, certain surgical procedures, swimming, bathing, high altitude experiences, sexual activity, exercise, or coughing.^[1] Symptoms can take days or a few months to manifest after a trigger.^[6]

Following a study and publication in 2007, it is also thought SSRIs, uncontrolled hypertension, endocrine abnormality, and neurosurgical trauma are indicated to potentially cause vasospasm.^[7]

The clinician should first rule out conditions with similar symptoms, such as subarachnoid hemorrhage, ischemic stroke, pituitary apoplexy, cerebral artery dissection, meningitis, and spontaneous cerebrospinal fluid leak.^[1] This may involve a CT scan, lumbar puncture, MRI, and other tests.^[1] Posterior reversible encephalopathy syndrome has a similar presentation, and is found in 10–38% of RCVS patients.^[1]

RCVS is diagnosed by detecting diffuse reversible cerebral vasoconstriction.^[1] Catheter angiography is ideal, but computed tomography angiography and magnetic resonance angiography can identify about 70% of cases.^[1] Multiple angiographies may be necessary.^[1] Because other diseases (such as atherosclerosis) have similar angiographic presentations, it can only be conclusively diagnosed if vasoconstriction resolves within 12 weeks.^[1]

As of 2014, no treatment strategy has yet been investigated in a randomized clinical trial.^[1] Verapamil, nimodipine, and other calcium channel blockers may help reduce the intensity and frequency of the headaches.^[1] A clinician may recommend rest and the avoidance of activities or vasoactive drugs which trigger symptoms (see § Causes).^[1] Analgesics and anticonvulsants can help manage pain and seizures, respectively.^[1]

All symptoms normally resolve within three weeks, and may only last days.^[1] Permanent deficits are seen in a minority of patients, ranging from under 10% to 20% in various studies.^[1] Less than 5% of patients experience progressive vasoconstriction, which can lead to stroke, progressive cerebral edema, or even death.^[1] Severe complications appear to be more common in postpartum mothers.^[6]

The incidence of RCVS is unknown, but it is believed to be "not uncommon", and likely under-diagnosed.^[1][6] One small, possibly biased study found that the condition was eventually diagnosed in 45% of outpatients with sudden headache, and 46% of outpatients with thunderclap headache.^[1]

The average age of onset is 42, but RCVS has been observed in patients aged from 19 months to 70 years.^[1] Children are rarely affected.^[1] It is more common in females, with a female-to-male ratio of 2.4:1.^[6]

Case studies of the condition first appeared in the 1960s, but it was not then recognized as a distinct entity.^[6] In 1983, French researchers published a case series of 11 patients, terming the condition acute benign cerebral angiopathy.^[1] Gregory Call and Marie Fleming were the first two authors of a report in which doctors from Massachusetts General Hospital, led by C. Miller Fisher, described 4 patients, alongside 12 previous case studies, with the characteristic symptoms and abnormal cerebral angiogram findings.^[6][8] The name Call-Fleming syndrome refers to these researchers.^[1]

A 2007 review by Leonard Calabrese and colleagues proposed the name reversible cerebral vasoconstriction syndrome, which has since gained widespread acceptance.^[1][9] This name merges various conditions that were previously treated as distinct entities, including Call-Fleming syndrome, postpartum angiopathy, and drug-induced angiopathy.^[6] Other names may still be used for particular forms of the condition.^[1]