Reversible cerebral vasoconstriction syndrome (RCVS, sometimes called Call-Fleming syndrome) is a disease characterized by a weeks-long course of

thunderclap headache A thunderclap headache is a headache that is severe and has a sudden onset. It is defined as a severe headache that takes seconds to minutes to reach maximum intensity. Although approximately 75% are attributed to "primary" headaches—headache d ...

s, sometimes

focal neurologic signs Focal neurologic signs, also known as focal neurological deficits or focal CNS signs, are impairments of nerve, spinal cord, or brain function that affects a specific region of the body, e.g. weakness in the left arm, the right leg, paresis, or ...

, and occasionally

seizure A seizure is a sudden, brief disruption of brain activity caused by abnormal, excessive, or synchronous neuronal firing. Depending on the regions of the brain involved, seizures can lead to changes in movement, sensation, behavior, awareness, o ...

s. Symptoms are thought to arise from transient abnormalities in the

blood vessel Blood vessels are the tubular structures of a circulatory system that transport blood throughout many Animal, animals’ bodies. Blood vessels transport blood cells, nutrients, and oxygen to most of the Tissue (biology), tissues of a Body (bi ...

s of the

brain The brain is an organ (biology), organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It consists of nervous tissue and is typically located in the head (cephalization), usually near organs for ...

. In some cases, it may be associated with

childbirth Childbirth, also known as labour, parturition and delivery, is the completion of pregnancy, where one or more Fetus, fetuses exits the Womb, internal environment of the mother via vaginal delivery or caesarean section and becomes a newborn to ...

vasoactive A vasoactive substance is an endogenous agent or pharmaceutical drug that has the effect of either increasing or decreasing blood pressure and/or heart rate through its vasoactivity, that is, vascular activity (effect on blood vessels). By adjust ...

or illicit drug use, or

complications of pregnancy Complications of pregnancy are health problems that are related to or arise during pregnancy. Complications that occur primarily during childbirth are termed obstetric labor complications, and problems that occur primarily after childbirth are ter ...

. 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. Deficits persist in a small minority of patients, with severe complications or death being very rare. Because symptoms resemble a variety of life-threatening conditions,

differential diagnosis In healthcare, a differential diagnosis (DDx) is a method of analysis that distinguishes a particular disease or condition from others that present with similar clinical features. Differential diagnostic procedures are used by clinicians to di ...

is necessary.

Signs and symptoms

The key symptom of RCVS is recurrent

s, which over 95% of patients experience. In two-thirds of cases, it is the only symptom. These headaches are typically bilateral, very severe and peak in intensity within a minute. They may last from minutes to days, and may be accompanied by

nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. It can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the throat. Over 30 d ...

photophobia Photophobia is a medical symptom of abnormal intolerance to visual perception of light. As a medical symptom, photophobia is not a morbid fear or phobia, but an experience of discomfort or pain to the eyes due to light exposure or by presence o ...

phonophobia Phonophobia, also called ligyrophobia or sonophobia, is a fear of or aversion to loud sounds (for example firecrackers)—a type of specific phobia. It is a very rare phobia which is often the symptom of hyperacusis. Sonophobia can refer to the ...

vomiting Vomiting (also known as emesis, puking and throwing up) is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose. Vomiting can be the result of ailments like food poisoning, gastroenteritis, pre ...

. Some patients experience only one headache, but on average there are four attacks over a period of one to four weeks. A milder, residual headache persists between severe attacks for half of patients. 1–17% of patients experience

s. 8–43% of patients show neurologic problems, especially visual disturbances, but also

hemiplegia Hemiparesis, also called unilateral paresis, is the weakness of one entire side of the body ('' hemi-'' means "half"). Hemiplegia, in its most severe form, is the complete paralysis of one entire side of the body. Either hemiparesis or hemiplegia ...

ataxia Ataxia (from Greek α- negative prefix+ -τάξις rder= "lack of order") is a neurological sign consisting of lack of voluntary coordination of muscle movements that can include gait abnormality, speech changes, and abnormalities in e ...

dysarthria Dysarthria is a speech sound disorder resulting from neurological injury of the motor component of the motor–speech system and is characterized by poor articulation of phonemes. It is a condition in which problems effectively occur with the ...

aphasia Aphasia, also known as dysphasia, is an impairment in a person's ability to comprehend or formulate language because of dysfunction in specific brain regions. The major causes are stroke and head trauma; prevalence is hard to determine, but aph ...

, and

numbness Hypoesthesia or numbness is a common side effect of various medical conditions that manifests as a reduced sense of touch or sensation, or a partial loss of sensitivity to Sensory receptor, sensory stimuli. In everyday speech this is generally r ...

. These neurologic issues typically disappear within minutes or a few hours; more persistent symptoms may indicate a

stroke Stroke is a medical condition in which poor cerebral circulation, blood flow to a part of the brain causes cell death. There are two main types of stroke: brain ischemia, ischemic, due to lack of blood flow, and intracranial hemorrhage, hemor ...

Posterior reversible encephalopathy syndrome Posterior reversible encephalopathy syndrome (PRES), also known as reversible posterior leukoencephalopathy syndrome (RPLS), is a rare condition in which parts of the brain are affected by swelling, usually as a result of an underlying cause. Some ...

is present in a small minority of patients. This condition features the unique property that the patient's cerebral

arteries An artery () is a blood vessel in humans and most other animals that takes oxygenated blood away from the heart in the systemic circulation to one or more parts of the body. Exceptions that carry deoxygenated blood are the pulmonary arteries in ...

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 Subarachnoid hemorrhage (SAH) is bleeding into the subarachnoid space—the area between the arachnoid (brain), arachnoid membrane and the pia mater surrounding the human brain, brain. Symptoms may include a thunderclap headache, severe heada ...

and cerebral

aneurysm An aneurysm is an outward :wikt:bulge, bulging, likened to a bubble or balloon, caused by a localized, abnormal, weak spot on a blood vessel wall. Aneurysms may be a result of a hereditary condition or an acquired disease. Aneurysms can also b ...

, but in RCVS only 25% of patients have symptoms post subarachnoid hemorrhage.

Causes

The direct cause of the symptoms is believed to be either

constriction Constriction is a method used by several snake species to kill or subdue their prey. Although some species of venomous and mildly venomous snakes do use constriction to subdue their prey, most snakes which use constriction lack venom. The snake ...

dilation wiktionary:dilation, Dilation (or dilatation) may refer to: Physiology or medicine * Cervical dilation, the widening of the cervix in childbirth, miscarriage etc. * Coronary dilation, or coronary reflex * Dilation and curettage, the opening of ...

of blood vessels in the brain. The

pathogenesis In pathology, pathogenesis is the process by which a disease or disorder develops. It can include factors which contribute not only to the onset of the disease or disorder, but also to its progression and maintenance. The word comes . Descript ...

is not known definitively, and the condition is likely to result from multiple different disease processes. Up to two-thirds of RCVS cases are associated with an underlying condition or exposure, particularly

or recreational drug use,

(

eclampsia Eclampsia is the onset of seizures (convulsions) in a pregnant woman with pre-eclampsia. Pre-eclampsia is a hypertensive disorder of pregnancy that presents with three main features: new onset of high blood pressure, large amounts of proteinuria ...

and

pre-eclampsia Pre-eclampsia is a multi-system disorder specific to pregnancy, characterized by the new onset of hypertension, high blood pressure and often a significant amount of proteinuria, protein in the urine or by the new onset of high blood pressure a ...

), and the adjustment period following childbirth called ''puerperium''. Vasoactive drug use is found in about 50% of cases. Implicated drugs include

selective serotonin reuptake inhibitors Selective serotonin reuptake inhibitors (SSRIs) are a class of drugs that are typically used as antidepressants in the treatment of major depressive disorder, anxiety disorders, and other psychological conditions. SSRIs primarily work by blo ...

, weight-loss pills such as Hydroxycut, alpha- sympathomimetic

decongestant A decongestant, or nasal decongestant, is a type of pharmaceutical drug that is used to relieve nasal congestion in the upper respiratory tract. The active ingredient in most decongestants is either pseudoephedrine or phenylephrine (the latter o ...

s, acute

migraine Migraine (, ) is a complex neurological disorder characterized by episodes of moderate-to-severe headache, most often unilateral and generally associated with nausea, and light and sound sensitivity. Other characterizing symptoms may includ ...

medications,

pseudoephedrine Pseudoephedrine, sold under the brand name Sudafed among others, is a sympathomimetic medication which is used as a decongestant to treat nasal congestion. It has also been used off-label for certain other indications, like treatment of lo ...

epinephrine Adrenaline, also known as epinephrine, is a hormone and medication which is involved in regulating visceral functions (e.g., respiration). It appears as a white microcrystalline granule. Adrenaline is normally produced by the adrenal glands a ...

cocaine Cocaine is a tropane alkaloid and central nervous system stimulant, derived primarily from the leaves of two South American coca plants, ''Erythroxylum coca'' and ''Erythroxylum novogranatense, E. novogranatense'', which are cultivated a ...

, and

cannabis ''Cannabis'' () is a genus of flowering plants in the family Cannabaceae that is widely accepted as being indigenous to and originating from the continent of Asia. However, the number of species is disputed, with as many as three species be ...

, among many others. It sometimes follows

blood transfusion Blood transfusion is the process of transferring blood products into a person's Circulatory system, circulation intravenously. Transfusions are used for various medical conditions to replace lost components of the blood. Early transfusions used ...

s, certain surgical procedures, swimming, bathing,

high altitude Altitude is a distance measurement, usually in the vertical or "up" direction, between a reference datum and a point or object. The exact definition and reference datum varies according to the context (e.g., aviation, geometry, geographical s ...

experiences, sexual activity, exercise, or coughing. Symptoms can take days or a few months to manifest after a trigger. Following a study and publication in 2007, it is also thought

SSRI Selective serotonin reuptake inhibitors (SSRIs) are a class of drugs that are typically used as antidepressants in the treatment of major depressive disorder, anxiety disorders, and other psychological conditions. SSRIs primarily work by ...

s, uncontrolled

hypertension Hypertension, also known as high blood pressure, is a Chronic condition, long-term Disease, medical condition in which the blood pressure in the artery, arteries is persistently elevated. High blood pressure usually does not cause symptoms i ...

, endocrine abnormality, and neurosurgical trauma are indicated to potentially cause

vasospasm Vasospasm refers to a condition in which an arterial spasm leads to vasoconstriction. This can lead to tissue ischemia (insufficient blood flow) and tissue death (necrosis). Along with physical resistance, vasospasm is a main cause of ischemi ...

Diagnosis

The clinician should first rule out conditions with similar symptoms, such as

ischemic stroke Stroke is a medical condition in which poor blood flow to a part of the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop ...

pituitary apoplexy Pituitary apoplexy is bleeding into or impaired blood supply of the pituitary gland. This usually occurs in the presence of a tumor of the pituitary, although in 80% of cases this has not been diagnosed previously. The most common initial sympt ...

, cerebral artery dissection,

meningitis Meningitis is acute or chronic inflammation of the protective membranes covering the brain and spinal cord, collectively called the meninges. The most common symptoms are fever, intense headache, vomiting and neck stiffness and occasion ...

, and

spontaneous cerebrospinal fluid leak A cerebrospinal fluid leak (CSF leak or CSFL) is a medical condition where the cerebrospinal fluid (CSF) that surrounds the brain and spinal cord leaks out of one or more holes or tears in the dura mater. A CSF leak is classed as either spontaneo ...

. This may involve a

CT scan A computed tomography scan (CT scan), formerly called computed axial tomography scan (CAT scan), is a medical imaging technique used to obtain detailed internal images of the body. The personnel that perform CT scans are called radiographers or ...

, lumbar puncture,

MRI Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to generate pictures of the anatomy and the physiological processes inside the body. MRI scanners use strong magnetic fields, magnetic field gradients, and rad ...

, and other tests.

has a similar presentation, and is found in 10–38% of RCVS patients. RCVS is diagnosed by detecting diffuse reversible cerebral vasoconstriction. Catheter

angiography Angiography or arteriography is a medical imaging technique used to visualize the inside, or lumen, of blood vessels and organs of the body, with particular interest in the arteries, veins, and the heart chambers. Modern angiography is perfo ...

is ideal, but

computed tomography angiography Computed tomography angiography (also called CT angiography or CTA) is a computed tomography technique used for angiography—the visualization of arteries and veins—throughout the human body. Using contrast injected into the blood vessels, im ...

and

magnetic resonance angiography Magnetic resonance angiography (MRA) is a group of techniques based on magnetic resonance imaging (MRI) to image blood vessels. Magnetic resonance angiography is used to generate images of arteries (and less commonly veins) in order to evaluate ...

can identify about 70% of cases. Multiple angiographies may be necessary. Because other diseases (such as

atherosclerosis Atherosclerosis is a pattern of the disease arteriosclerosis, characterized by development of abnormalities called lesions in walls of arteries. This is a chronic inflammatory disease involving many different cell types and is driven by eleva ...

) have similar angiographic presentations, it can only be conclusively diagnosed if vasoconstriction resolves within 12 weeks.

Treatment

As of 2014, no treatment strategy has yet been investigated in a

randomized clinical trial A randomized controlled trial (or randomized control trial; RCT) is a form of scientific experiment used to control factors not under direct experimental control. Examples of RCTs are clinical trials that compare the effects of drugs, surgical t ...

Verapamil Verapamil, sold under various trade names, is a calcium channel blocker medication used for the treatment of high blood pressure, angina (chest pain from not enough blood flow to the heart), and supraventricular tachycardia. It may also be use ...

nimodipine Nimodipine, sold under the brand name Nimotop among others, is a calcium channel blocker used in preventing vasospasm secondary to subarachnoid hemorrhage (a form of cerebral hemorrhage). It was originally developed within the calcium channel b ...

, and other

calcium channel blockers Calcium channel blockers (CCB), calcium channel antagonists or calcium antagonists are a group of medications that disrupt the movement of calcium () through calcium channels. Calcium channel blockers are used as antihypertensive drugs, i.e., a ...

may help reduce the intensity and frequency of the headaches. A clinician may recommend rest and the avoidance of activities or vasoactive drugs which trigger symptoms (see § Causes).

Analgesic An analgesic drug, also called simply an analgesic, antalgic, pain reliever, or painkiller, is any member of the group of drugs used for pain management. Analgesics are conceptually distinct from anesthetics, which temporarily reduce, and in s ...

s and

anticonvulsant Anticonvulsants (also known as antiepileptic drugs, antiseizure drugs, or anti-seizure medications (ASM)) are a diverse group of pharmacological agents used in the treatment of epileptic seizures. Anticonvulsants are also used in the treatme ...

s can help manage pain and seizures, respectively.

Prognosis

All symptoms normally resolve within three weeks, and may only last days. Permanent deficits are seen in a minority of patients, ranging from under 10% to 20% in various studies. Less than 5% of patients experience progressive vasoconstriction, which can lead to stroke, progressive

cerebral edema Cerebral edema is excess accumulation of fluid ( edema) in the intracellular or extracellular spaces of the brain. This typically causes impaired nerve function, increased pressure within the skull, and can eventually lead to direct compres ...

, or even death. Severe complications appear to be more common in

postpartum The postpartum (or postnatal) period begins after childbirth and is typically considered to last for six to eight weeks. There are three distinct phases of the postnatal period; the acute phase, lasting for six to twelve hours after birth; the ...

mothers.

Epidemiology

The incidence of RCVS is unknown, but it is believed to be "not uncommon", and likely under-diagnosed. One small, possibly biased study found that the condition was eventually diagnosed in 45% of

outpatients A patient is any recipient of health care services that are performed by healthcare professionals. The patient is most often ill or injured and in need of treatment by a physician, nurse, optometrist, dentist, veterinarian, or other heal ...

with sudden headache, and 46% of outpatients with thunderclap headache. The average age of onset is 42, but RCVS has been observed in patients aged from 19 months to 70 years. Children are rarely affected. It is more common in females, with a female-to-male ratio of 2.4:1.

History

Case studies A case study is an in-depth, detailed examination of a particular case (or cases) within a real-world context. For example, case studies in medicine may focus on an individual patient or ailment; case studies in business might cover a particular fi ...

of the condition first appeared in the 1960s, but it was not then recognized as a distinct entity. In 1983, French researchers published a case series of 11 patients, terming the condition ''acute benign cerebral angiopathy''. Gregory Call and Marie Fleming were the first two authors of a report in which doctors from

Massachusetts General Hospital Massachusetts General Hospital (Mass General or MGH) is a teaching hospital located in the West End neighborhood of Boston, Massachusetts. It is the original and largest clinical education and research facility of Harvard Medical School/Harvar ...

, led by C. Miller Fisher, described 4 patients, alongside 12 previous case studies, with the characteristic symptoms and abnormal cerebral angiogram findings. The name ''Call-Fleming syndrome'' refers to these researchers. A 2007 review by Leonard Calabrese and colleagues proposed the name ''reversible cerebral vasoconstriction syndrome'', which has since gained widespread acceptance. This name merges various conditions that were previously treated as distinct entities, including Call-Fleming syndrome, postpartum angiopathy, and drug-induced angiopathy. Other names may still be used for particular forms of the condition.

References

External links

{{Medicine Headaches Syndromes