CNS Vasculitis

What Causes CNS Vasculitis?

CNS vasculitis occurs when blood vessels in the brain or spinal column become swollen and damaged. Scientists are not sure what causes the condition, but it is likely triggered by a reaction of the body’s immune system. Sometimes an underlying disease or infection causes the immune system to mistakenly attack healthy cells, resulting in damage to otherwise normal tissue. This is referred to as an autoimmune reaction.

Because CNS vasculitis is often associated with autoimmune disorders or infections, scientists suspect that the same autoimmune response causes vasculitis in the brain.

Some conditions that may be associated with CNS vasculitis include:

• Systemic lupus erythematosus
• Dermatomyositis
• Sarcoidosis
• Rheumatoid arthritis
• Bacterial or viral infections
• Granulomatosis with polyangiitis GPA)
• Eosinophilic granulomatosis with polyangiitis (EGPA)
• Microscopic polyangiitis
• Cyoglobulinemic vasculitis
• Behçet’s syndrome

Is CNS Vasculitis Hereditary?

Scientists do not yet know if genes significantly increase the risk of CNS vasculitis. Some studies have shown that people with a family history of the condition may be at a low level of increased risk, but no definite associations between CNS vasculitis and a particular gene have yet been found. Instead, vasculitis likely occurs because of a complex interaction of multiple genes and environmental factors.

Some of the disorders that commonly underlie CNS vasculitis have an inherited component, so people with a family history of those disorders may be at increased risk of developing the condition.

How Is CNS Vasculitis Detected?

CNS vasculitis is treatable, but if it is left untreated, severe and potentially life-threatening complications are possible. Therefore, it is crucial to identify and treat the disorder as soon as possible.

Early warning signs of vasculitis can include:

• Headaches
• Irritability
• Fatigue
• Aches and pains
• Skin rashes
• Vision problems
• Sensitivity to bright lights or loud sounds
• Learning difficulties
• Weight loss

How Is CNS Vasculitis Diagnosed?

A doctor may suspect CNS vasculitis if a patient shows symptoms characteristic of the disorder and/or evidence of any condition commonly associated with vasculitis. The diagnostic process will usually include evaluating the patient’s medical history and conducting physical and neurological exams. Further diagnostic steps may consist of:

• Blood tests to measure cell counts and look for indicators of inflammation
• Imaging exams such as magnetic resonance imaging (MRI) or computerized tomography (CT) to look for evidence of blood-vessel inflammation in the brain or elsewhere
• Lumbar puncture (spinal tap) to look for evidence of inflammation in the cerebrospinal fluid (CSF)
• Biopsy of brain tissue

PLEASE CONSULT A PHYSICIAN FOR MORE INFORMATION.

How Is CNS Vasculitis Treated?

CNS vasculitis typically improves with treatment. The disorder is commonly treated in two phases, with the first phase aiming to get the inflammation under control and the second phase focused on preventing future inflammation. The phases include:

• Induction Therapy. Treatment in this phase includes high doses of steroids and/or medications to suppress the immune system. These medications are administered intravenously. This initial phase may last several months.
• Maintenance Therapy. In the second phase, treatment usually includes different immunosuppressive drugs and, sometimes, lower doses of steroids. This phase is typically long-term and, in some cases, may be life-long.

Treatment programs will also include any necessary treatment for the underlying disorder that caused the vasculitis. In some cases where neurological symptoms persist, physical, occupational, or speech therapy may be required.

How Does CNS Vasculitis Progress?

Untreated CNS vasculitis can lead to long-term and potentially life-threatening complications. Possible long-term effects of the disorder include:

• Severe headaches
• Strokes
• Seizures
• Brain swelling that causes mood or personality changes
• Vision loss
• Persistent sensation problems (numbness or tingling)
• Damage to kidneys, liver, or other organs

How Is CNS Vasculitis Prevented?

Because CNS vasculitis is often associated with a triggering disorder or infection, prompt treatment of underlying diseases and avoiding infections is the best preventive strategy.

To protect yourself from the common infections that may cause vasculitis, take these steps:

• Vaccinate yourself and your children against common viruses such as measles, mumps, rubella, and chickenpox. If you’re traveling to foreign destinations, ask your doctor if you need vaccinations against locally prevalent viruses, bacteria, or protozoa.
• Wash your hands and practice good hygiene to prevent the spread of viruses and bacteria. Teach your children these practices, too.
• Don’t share utensils, food, or beverages.

CNS Vasculitis Caregiver Tips

Some people with CNS vasculitis also suffer from other brain-related issues, a condition called co-morbidity. Here are a few of the disorders commonly associated with cerebral vasculitis:

• People with CNS vasculitis are at increased risk for depression.
• CNS vasculitis significantly increases the risk of stroke.
• People with systemic lupus, one of the common causes of CNS vasculitis, are at increased risk for anxiety disorders, mood disorders, and suicide.

CNS Vasculitis Brain Science

CNS vasculitis can affect the brain in more than one way.

• Inflamed blood vessels may deteriorate over time, resulting in a weak spot in the vessel wall. This weak spot may bulge outward, a condition called an aneurysm. Aneurysms may rupture, causing bleeding in the brain. This event deprives brain tissue of vital oxygen and is referred to as a hemorrhagic stroke.
• Blood inside the inflamed blood vessels may be more prone to clotting. When clots form inside the vessels and block the free flow of blood, the brain cells nourished by the vessels may not get the oxygen they need. This type of event is called an ischemic stroke.

CNS Vasculitis Research

Title: Autologous Peripheral Blood Stem Cell Transplant for Neurologic Autoimmune Diseases

Stage: Recruiting

Principal investigator: Richard A. Nash

Colorado Blood Cancer Institute

Denver, CO

This phase II trial studies the side effects and how well carmustine, etoposide, cytarabine, and melphalan together with antithymocyte globulin before a peripheral blood stem cell transplant works in treating patients with autoimmune neurologic disease that did not respond to previous therapy. In autoimmune neurological diseases, the patient’s own immune system ‘attacks’ the nervous system, which might include the brain/spinal cord and/or the peripheral nerves. Giving high-dose chemotherapy, including carmustine, etoposide, cytarabine, melphalan, and antithymocyte globulin, before a peripheral blood stem cell transplant weakens the immune system and may help stop the immune system from ‘attacking’ a patient’s nervous system. When the patient’s own (autologous) stem cells are infused, they help the bone marrow make red blood cells, white blood cells, and platelets so the blood counts can improve.

Title: Pediatric Vasculitis Initiative (PedVas)

Stage: Recruiting

Principal investigator: Bhavana Patel, DO

University of Florida

Gainesville, FL

Childhood chronic vasculitis describes a group of rare, life-threatening diseases with the commonality of inflammation of blood vessels in vital organs such as kidneys, lungs, and brain. Most knowledge about them comes from adult patients. Severe disease requires aggressive life-saving treatments with steroids and some cancer drugs, which can themselves cause damage, and increase risks of cancer and severe infections. Conversely, milder disease can be treated with less toxic drugs. Different classification and “scoring tools” are used to define the types and severity of vasculitis and measure the damage caused by disease or drugs. In turn, these help direct how aggressively to treat a patient and measure outcomes. However, none of these tools have been assessed in children, and the best balance of disease and treatment risks against outcome for children is not known. Although the causes of these diseases in children and adults are probably the same, the effects of the disease and the response (good and bad) to drugs will differ in growing children. Because specialists may see only one new child with vasculitis each year, obtaining enough information to learn about childhood vasculitis requires cooperation. We will use an international web-based registry to which doctors from 50 or more centers can contribute patient data. We will determine the features that help better classify and diagnose children than adults. Information on patients will be collected and analyzed through the internet, similarly classified, and “scored” so that the most successful treatments can be identified. Children with vasculitis are less likely to have diseases associated with aging, alcohol, smoking, etc., and therefore may be a better group to study the underlying biology of vasculitis. We will use this opportunity and collect spit, blood, and tissue from registry patients for laboratory study to find biomarkers to better classify, define and direct optimal treatment and outcomes.

For children with vasculitis who are enrolled in the study, clinical information will be obtained from the medical chart from the time of diagnosis, post-induction (3-6 months post-diagnosis) visit, 12-month clinic visit, and their most recent clinic visit or last clinic visit before discharge to adult care (i.e., final outcome visit). Information that will be collected includes laboratory test results, biopsy and imaging results, disease activity, clinical history, and medications. Blood, urine, and saliva samples will also be collected at each clinic visit. If the subject experiences a disease flare, clinical data and biological samples will be collected at the time of the flare and at a later date after the disease remits.

The PedVas study is linked to an adult vasculitis initiative called DCVAS: Diagnosis and Classification Criteria in Vasculitis. Our DCVAS co-investigators and collaborators will recruit up to 250 adults at or near the time of diagnosis of the following forms of vasculitis: GPA, MPA, EGPA, TA, and UCV. Clinical data will be collected as part of the DCVAS study, including laboratory test results, disease activity, and clinical history. Blood will also be collected and analyzed in parallel with samples collected from children with vasculitis. Finally, a DNA biobank will be created and will house samples from approximately 700 adults and representing all forms of vasculitis. Recruitment will proceed according to DCVAS approved protocols, and it will be conducted at participating DCVAS centers after the patient has formally consented to participation in the DCVAS study.

Title: Studies of the Natural History, Pathogenesis, and Outcome of Idiopathic Systemic Vasculitis

Stage: Recruiting

Principal investigator: Peter C Grayson, MD

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Bethesda, MD

This protocol aims to study the natural history of idiopathic systemic vasculitis in children and adults. The idiopathic vasculitides are a group of rare, systemic diseases involving inflammation of arteries and other tissue with resulting organ- and life-threatening disease courses. The different forms of idiopathic vasculitis are typically classified based upon the predominant size of the arteries affected in each condition, including small vessel vasculitis [granulomatosis with polyangiitis (GPA, Wegener s), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA, Churg-Strauss)]; medium vessel vasculitis [polyarteritis nodosa (PAN)]; and large vessel vasculitis [giant cell arteritis (GCA), Takayasu s arteritis (TAK), idiopathic aortitis (IA)]. Although patients with each type of vasculitis manifest disease-specific aspects of illness, substantial disease and treatment burdens are common to patients with vasculitis. For each type of idiopathic vasculitis, the disease course is often chronic, relapse is common and unpredictable, organ and tissue damage can accrue over time, new symptoms can occur late into the disease course, and treatment is often associated with toxicity and serious side effects.

This natural history protocol aims to establish a cohort of pediatric and adult patients with vasculitis to prospectively evaluate the signs and symptoms, imaging findings, and blood and tissue biomarkers associated with pathogenesis and disease outcomes. In the small vessel vasculitides, where considerable progress has been made towards identifying pathologic mechanisms of disease, we will focus on elucidating the pathogenic role of neutrophils, selected biomarkers such as SERPINA1, and novel candidate biomarkers in circulating blood and at local tissue sites, including the nasal mucosa. In the medium and large vessel vasculitides, we will identify novel candidate biomarkers for disease pathogenesis and outcomes and develop disease activity indices that incorporate existing and novel clinical, laboratory, genomic, and imaging biomarkers. For all types of vasculitis, a goal of the protocol is to identify patients for possible entry into future treatment studies.