Cerebral vasculitis (sometimes the word angiitis is used instead of "vasculitis") is

vasculitis Vasculitis is a group of disorders that destroy blood vessels by inflammation. Both artery, arteries and veins are affected. Lymphangitis (inflammation of lymphatic vessels) is sometimes considered a type of vasculitis. Vasculitis is primarily c ...

(inflammation of 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 ...

wall) involving 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 ...

and occasionally the

spinal cord The spinal cord is a long, thin, tubular structure made up of nervous tissue that extends from the medulla oblongata in the lower brainstem to the lumbar region of the vertebral column (backbone) of vertebrate animals. The center of the spinal c ...

. It affects all of the vessels: very small blood vessels (

capillaries A capillary is a small blood vessel, from 5 to 10 micrometres in diameter, and is part of the microcirculation system. Capillaries are microvessels and the smallest blood vessels in the body. They are composed of only the tunica intima (the in ...

), medium-size blood vessels (

arteriole An arteriole is a small-diameter blood vessel in the microcirculation that extends and branches out from an artery and leads to capillary, capillaries. Arterioles have vascular smooth muscle, muscular walls (usually only one to two layers of smoo ...

s and

venule A venule is a very small vein in the microcirculation that allows blood to return from the capillary beds to drain into the venous system via increasingly larger veins. Post-capillary venules are the smallest of the veins with a diameter of ...

s), or large blood vessels (

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 ...

and

veins Veins () are blood vessels in the circulatory system of humans and most other animals that carry blood towards the heart. Most veins carry deoxygenated blood from the tissues back to the heart; exceptions are those of the pulmonary and fetal c ...

). If blood flow in a vessel with vasculitis is reduced or stopped, the parts of the body that receive blood from that vessel begins to die, resulting in 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 ...

. It may produce a wide range of

neurological Neurology (from , "string, nerve" and the suffix -logia, "study of") is the branch of medicine dealing with the diagnosis and treatment of all categories of conditions and disease involving the nervous system, which comprises the brain, the s ...

symptoms, such as

headache A headache, also known as cephalalgia, is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of Depression (mood), depression in those with severe ...

, skin rashes, feeling very tired, joint pains, difficulty moving or coordinating part of the body, changes in sensation, and alterations in perception, thought or behavior, as well as the phenomena of a mass lesion in the brain leading to

coma A coma is a deep state of prolonged unconsciousness in which a person cannot be awakened, fails to Nociception, respond normally to Pain, painful stimuli, light, or sound, lacks a normal Circadian rhythm, sleep-wake cycle and does not initiate ...

and

herniation A hernia (: hernias or herniae, from Latin, meaning 'rupture') is the abnormal exit of tissue or an organ, such as the bowel, through the wall of the cavity in which it normally resides. The term is also used for the normal development of the in ...

. Some of its signs and symptoms may resemble

multiple sclerosis Multiple sclerosis (MS) is an autoimmune disease resulting in damage to myelinthe insulating covers of nerve cellsin the brain and spinal cord. As a demyelinating disease, MS disrupts the nervous system's ability to Action potential, transmit ...

. 10% have associated bleeding in the brain.

Signs and symptoms

The most frequent presenting signs and symptoms of primary CNS vasculitis were focal neurological deficits (seen in 63% of cases), headaches (51%) and cognitive impairment (41%). Other presenting symptoms include

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 ...

or other difficulties with speech (35-43%),

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 ...

, visual field deficits, acute or subacute encephalopathy (which may progress to coma), and seizures (16-33%). Spinal cord involvement is rare, especially spinal cord involvement that does not also affect the brain.

Causes

"Primary" angiitis/vasculitis of the central nervous system (PACNS) is said to be present if there is no secondary cause. The exact mechanism of the primary disease is unknown. Possible secondary causes of cerebral vasculitis are

infection An infection is the invasion of tissue (biology), tissues by pathogens, their multiplication, and the reaction of host (biology), host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmis ...

s such as with

varicella zoster virus Varicella zoster virus (VZV), also known as human herpesvirus 3 (HHV-3, HHV3), is one of nine known herpes viruses that can infect humans. It causes chickenpox (varicella) commonly affecting children and young adults, and shingles (herpes zos ...

(chicken pox or shingles), systemic auto-immune diseases such as

systemic lupus erythematosus Lupus, formally called systemic lupus erythematosus (SLE), is an autoimmune disease in which the body's immune system mistakenly attacks healthy tissue in many parts of the body. Symptoms vary among people and may be mild to severe. Common ...

(SLE) and

rheumatoid arthritis Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects synovial joint, joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and h ...

medication Medication (also called medicament, medicine, pharmaceutical drug, medicinal product, medicinal drug or simply drug) is a drug used to medical diagnosis, diagnose, cure, treat, or preventive medicine, prevent disease. Drug therapy (pharmaco ...

s and

drugs A drug is any chemical substance other than a nutrient or an essential dietary ingredient, which, when administered to a living organism, produces a biological effect. Consumption of drugs can be via inhalation, injection, smoking, ingestio ...

(

amphetamine Amphetamine (contracted from Alpha and beta carbon, alpha-methylphenethylamine, methylphenethylamine) is a central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, an ...

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

heroin Heroin, also known as diacetylmorphine and diamorphine among other names, is a morphinan opioid substance synthesized from the Opium, dried latex of the Papaver somniferum, opium poppy; it is mainly used as a recreational drug for its eupho ...

), some forms of

cancer Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...

(

lymphoma Lymphoma is a group of blood and lymph tumors that develop from lymphocytes (a type of white blood cell). The name typically refers to just the cancerous versions rather than all such tumours. Signs and symptoms may include enlarged lymph node ...

leukemia Leukemia ( also spelled leukaemia; pronounced ) is a group of blood cancers that usually begin in the bone marrow and produce high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or '' ...

and

lung cancer Lung cancer, also known as lung carcinoma, is a malignant tumor that begins in the lung. Lung cancer is caused by genetic damage to the DNA of cells in the airways, often caused by cigarette smoking or inhaling damaging chemicals. Damaged ...

) and other forms of systemic vasculitis such as

granulomatosis with polyangiitis Granulomatosis with polyangiitis (GPA), formerly known as Wegener's granulomatosis (WG), after Nazi German physician Friedrich Wegener, is a rare, long-term, systemic disorder that involves the formation of granulomas and vasculitis, inflammatio ...

, polyarteritis nodosa or

Behçet's disease Behçet's disease (BD) is a type of inflammatory disorder which affects multiple parts of the body. The most common symptoms include painful sores on the mucous membranes of the mouth and other parts of the body, inflammation of parts of the ...

which, in addition to causing systemic vasculitis, also affect the brain or spinal cord. It may imitate, and is in turn imitated by, a number of other diseases that affect the blood vessels of the brain diffusely such as fibromuscular dysplasia and

thrombotic thrombocytopenic purpura Thrombotic thrombocytopenic purpura (TTP) is a blood disorder that results in thrombi, blood clots forming in small blood vessels throughout the body. This results in a thrombocytopenia, low platelet count, hemolytic anemia, low red blood cells d ...

. Primary CNS vasculitis has an incidence of 2.4 cases per 1 million people, with an associated mortality of 8-23% and a 25% risk of severe disability. Older age or cognitive impairment at diagnosis, the presence of cerebral infarctions on imaging (stroke), spinal cord involvement, delays in diagnosis and involvement of the medium and large vessels are associated with a poor prognosis and increased mortality in primary CNS vasculitis.

Pathophysiology

Based on biopsy, there are three main types of blood vessel inflammation seen in primary CNS vasculitis. Granulomatous vasculitis (present in 32-61% of cases) presents with well formed granulomas with multi-nucleated giant cells in the blood vessel wall. Lymphocytic vasculitis (24-79% of cases) involves lymphocytic infiltration of blood vessel walls without granulomas. It is associated with less disability and mortality. Necrotizing vasculitis (14-42% of cases) involves transmural (involving the entire blood vessel wall) fibrinoid necrosis. This type is associated with a high risk of intracerebral hemorrhage.

Diagnosis

Diagnosis of primary CNS vasculitis may be made with brain imaging and biopsy of the affected blood vessel. The most definitive diagnostic modality is a biopsy of the affected blood vessel however brain biopsy has a low yield, with up to 30-50% of biopsies being normal in suspected cases. This is due to some cases having an irregular distribution of vessel involvement (making biopsy technically difficult) or larger vessels being unable to be biopsied due to the risk of bleeding.

Digital subtraction angiography Digital subtraction angiography (DSA) is a fluoroscopy technique used in interventional radiology to clearly visualize blood vessels in a bony or dense soft tissue environment. Images are produced using contrast medium by subtracting a "pre-cont ...

is the preferred imaging modality in suspected cases of primary CNS vasculitis and has greater specificity than

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 ...

CT 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 ...

(which have reduced accuracy for assessment of luminal irregularities of medium sized vessels or the posterior circulation of the brain). Typical findings on angiography include smooth wall segmental stenosis of multiple arteriessometimes with post-stenosis dilation or bleeding. In cases involving small vessels, angiography is usually normal and a biopsy is needed to confirm the diagnosis. European guidelines recommend performing a biopsy in suspected cases of small vessel disease with normal angiography. In cases of medium to large vessel disease, with characteristic imaging findings on angiography, a biopsy is usually not required. Biopsy and angiography do not have a high concordance in diagnosis, and in one meta analysis digital subtraction angiography was positive in only 33% of biopsy confirmed disease and biopsy was positive in only 8% of angiographically confirmed cases. High resolution

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 ...

may show hyperenhancement of the blood vessel walls in primary CNS vasculitis and may help to distinguish the lesions form atherosclerotic plaques or reversible cerebral vasoconstriction syndrome which have similar morphology on angiography. MRI usually also shows multiple infarcts, enhancement of the leptomeninges (the lining of the brain) and various parts of the brain and intracranial hemorrhages, sometimes microhemorrhages. A normal MRI makes the diagnosis unlikely. Inflammatory markers such as

C-reactive protein C-reactive protein (CRP) is an annular (ring-shaped) pentameric protein found in blood plasma, whose circulating concentrations rise in response to inflammation. It is an acute-phase protein of hepatic origin that increases following interleukin ...

(CRP) and

erythrocyte sedimentation rate The erythrocyte sedimentation rate (ESR or sed rate) is the rate at which red blood cells in anticoagulated whole blood descend in a standardized tube over a period of one hour. It is a common hematology test, and is a non-specific measure of in ...

(ESR) are usually normal. And analysis of the cerebrospinal fluid shows a non-specific pattern with mildly elevated leukocytes and increased protein, especially in small vessel disease.

Treatment

Glucocorticoids and the immunosuppressant

cyclophosphamide Cyclophosphamide (CP), also known as cytophosphane among other names, is a medication used as chemotherapy and to suppress the immune system. As chemotherapy it is used to treat lymphoma, multiple myeloma, leukemia, ovarian cancer, breast cancer ...

are the mainstays of treatment of primary CNS vasculitis. There is also limited evidence for the use of

mycophenolate mofetil Mycophenolic acid is an immunosuppressant medication used to prevent rejection following organ transplantation and to treat autoimmune conditions such as Crohn's disease and lupus. Specifically it is used following kidney, heart, and live ...

. The treatment is usually done with an induction phase followed by at least 2 years of maintenance therapy. Immunosuppressants

Rituximab Rituximab, sold under the brand name Rituxan among others, is a monoclonal antibody medication used to treat certain autoimmune diseases and types of cancer. It is used for non-Hodgkin lymphoma, chronic lymphocytic leukemia (in children and ad ...

tocilizumab Tocilizumab, sold under the brand name Actemra among others, is an immunosuppressive drug, used for the treatment of rheumatoid arthritis, systemic juvenile idiopathic arthritis, polyarticular juvenile idiopathic arthritis, giant cell arter ...

may be used for refractory disease. 75% of people have a favorable response to therapy. European guidelines recommend aspirin being added on as an adjunct therapy for those with medium or large vessel involvement. Maintenance therapy was associated with lower deaths, lower risk of relapse, less disability and European guidelines recommend at least 2 years of maintenance therapy after induction.

Prognosis

With therapy 21-66% will go into long term remission with 12-59% of patients having subsequent flares or recurrence. 46-73% of patients had good residual neurological function (as measured by Rankin scores) after treatment.

References

External links

{{Cerebrovascular diseases Cerebrovascular diseases Inflammations Rheumatology Steroid-responsive inflammatory conditions