Central Nervous System Vasculitis

Many forms of vasculitis may involve the central nervous system (CNS), including Behcet’s disease, polyarteritis nodosa, vasculitis associated with connective tissue diseases such as lupus (systemic lupus erythematosus; SLE), and others. Most of these diseases can produce vasculitis or other problems outside of the brain. In the description of CNSV that follows, however, we confine our comments to a more specific type of vasculitis in which: 1) the disease process is confined — by definition — to the CNS; and 2) no known infection can be identified within the CNS (the CNS includes both the brain and spinal cord. The latter, however, is involved in only a minority of cases).

CNSV symptoms and signs are frequently subtle, subacute, and often non–specific in nature. These characteristics, combined with the fact that confirmation of the diagnosis requires that an invasive procedure (either an angiogram or a brain biopsy) be performed on a delicate organ system — the brain — qualifies CNSV as one of the most challenging diagnoses to make in medicine.

First Description

The first “modern” description of CNSV appeared in 1959. However, review of the medical literature reveals sporadic reports of probable CNSV as early as 1922. Before the availability of modern diagnostic techniques, CNSV was rarely diagnosed during life; rather, the diagnosis generally was rendered only at autopsy. The availability of advanced imaging techniques for the CNS (e.g., magnetic resonance imaging, angiography) now frequently permit the diagnosis to be made during life, and allow treatment to begin.

Central Nervous System (CNS) Vasculitis has been called by other names including isolated angiitis of the CNS (“IACNS”), emphasizing the confinement of the disease process to the brain and the spinal cord. Another name for this disorder has been granulomatous angiitis of the nervous system (“GANS”), a name that draws attention to a pathological feature of the disease seen in some, but not all, cases. More recently, the preferred name for this form of vasculitis has been  primary angiitis of the central nervous system (“PACNS”). Finally, recognition that a subgroup of patients appear to have milder disease courses has led to the designation of benign angiopathy (as opposed to “angiitis”) of the CNS, or “BACNS”. For the remainder of this discussion, we will discuss CNSV in the context of being subdivided into two more or less distinct categories: Primary Angiitis of the Central Nervous System (PACNS) and Benign Angiopathy of the Central Nervous System (BACNS).

Who gets Central Nervous System Vasculitis?

Note: It is important to acknowledge that the diseases that we now group under the headings of “PACNS” AND “BACNS” probably represent a number of different diseases or disorders, associated with different causes and requiring different treatments.

PACNS: The distribution of PACNS is nearly equally between the sexes, with perhaps a slight male predominance (4:3). The mean age of people affected by the disease is approximately 42 years, but the range is wide: the disease has been detected in children as young as 3, and also frequently occurs in elderly people.

BACNS: In contrast, patients with BACNS tend to be young women, often those with previous histories of headaches (such as migraines). These patients often have histories of heavy nicotine or caffeine use, over–the–counter cold remedy use (e.g., ephedrine), and oral contraceptive or estrogen replacement therapy, but the precise relationship (if any) of these exposures to the development of BACNS remains unclear.

Classic Symptoms of CNS Vasculitis

The clinical manifestations of PACNS and BACNS may be identical, and include many neurologic symptoms and signs: headache, focal weakness (such as occurs with a stroke), seizures, bleeding within the CNS, confusion, disorders of memory, and altered consciousness. All of these symptoms and signs are non-specific, and can be mimicked by a variety of other conditions. Thus, despite the “benign” part of the designation “BACNS”, some patients with so–called “benign“ angiopathy of the CNS sustain significant neurological damage.

There are two main differences in the clinical presentations of PACNS and BACNS. First, whereas PACNS patients are more likely to develop symptoms subacutely and remain undiagnosed for months, those with BACNS are more likely to have relatively acute presentations and be diagnosed within weeks of onset (in either case, however, making the diagnosis is challenging). Second, without treatment, patients with PACNS tend to have progressively downhill courses that often lead to death. In contrast, BACNS patients may require less aggressive treatment than PACNS. A common difficulty comes in sorting out which patients are more likely to have clinical courses characteristic of BACNS, and which require the more aggressive treatment approach called for by PACNS.

Because some of the symptoms and signs of CNSV are easily mimicked by other diseases (e.g., strokes caused by atherosclerosis, viral encephalitis, tumor, tuberculosis, severe migraine headaches, and multiple sclerosis), patients with CNSV are often misdiagnosed initially.

What Causes Central Nervous System Vasculitis?

The cause(s) of CNSV is not known. Certainly, viral infections may cause clinical syndromes that mimic PACNS and BACNS, and it is very possible that viral infections (which remain difficult to diagnose) initiate the inflammatory process that somehow becomes self–sustaining. Although anecdotal experience and case series associate BACNS with heavy nicotine or caffeine use as well as with oral contraceptive and cold remedy use, the true associations between these exposures and the development of BACNS remain uncertain.

It is comforting to many patients and their families that genetics do not appear to play a clinically significant role: it is extraordinarily rare for CNSV to occur in two people in the same family.

How is Central Nervous System Vasculitis Diagnosed?

Because many diseases may mimic CNSV and because the treatments for CNSV are potentially dangerous, it is essential to confirm the diagnosis before starting treatment. Nearly all patients therefore require either an angiogram or biopsy of the brain. Tests such as magnetic resonance imaging (MRI) studies and lumbar punctures (spinal taps) are also helpful in the work–up of a patient with possible CNSV.

Because angiography is less invasive than a brain biopsy, this test is often performed before biopsy. The classic angiographic findings in CNSV include “beading” (alternating dilatations and narrowings of blood vessels), aneurysms, and other irregularities within blood vessels (see image below). It must be recognized, however, that many conditions not caused by vasculitis (e.g., spasm of the blood vessels) can cause an angiographic appearance that is impossible to distinguish from true vasculitis.

Angio

Because the diagnosis cannot be proven with 100% certainty by angiography, consideration is often given to performing a brain biopsy. Before initiating treatment with the combination of cyclophosphamide and steroids (see Treatment, below), serious consideration should be given to performing this procedure. If non–invasive imaging studies such as an MRI indicate a site of probable pathology within the brain, the neurosurgeon may opt to perform the biopsy at that site if it is surgically accessible. Pictured below are examples of two non–invasive imaging studies that show abnormalities.

Skull Veins

If no obvious site for biopsy is identified by non–invasive studies or by angiography, the brain biopsy is usually performed on the non–dominant side of the patient’s brain (that is, if the patient is right–handed — and therefore “left–brained” — the biopsy is performed on the right side of the brain). Biopsy of the brain’s covering, the meninges, is usually performed at the same time (this increases the chance that the procedure will yield a piece of tissue containing pathology). Although brain biopsy remains the “gold standard” in the diagnosis of CNSV, 25% of the time a brain biopsy will be negative even in the setting of true vasculitis; i.e., the likelihood of a “false–negative” biopsy is unfortunately rather high.

Treatment and Course of CNS Vasculitis

PACNS: Until recently, CNS vasculitis was a fatal condition in a high percentage of cases, with death following diagnosis in a mean of 45 days after diagnosis. The availability of powerful immunosuppressive therapy, however, has significantly improved the prognosis for people with this condition. Some patients with PACNS respond well to treatment with high doses of steroids alone. Others require the addition of cyclophosphamide to the steroid regimen. In many cases, a reasonable approach is to attempt to control the disease with high doses of steroids first (e.g., for one month), adding cyclophosphamide only if steroids fail or if patients begin to develop unacceptable side–effects of steroid treatment.

Balancing control of the disease with the possibility of serious side–effects of treatment is often challenging. For PACNS, treatment must often be continued for a year or more.

BACNS: Patients who fit the typical patient profile of BACNS and who have clinical presentations compatible with that diagnosis may be candidates for less intensive treatment regimens than those used in clear–cut cases of PACNS. Patients believed to have BACNS may be treated with calcium–channel blockers (a class of drug used to treat high blood pressure and spasm of blood vessels that occurs in a variety of conditions) for a few weeks, along with a comparatively short course of steroids (prednisone). No firm guidelines exist regarding the length of therapy, however, and decisions about the length of treatment must be made on a case–by–case basis.

What's New in CNS Vasculitis?

Although progress has been slow in the understanding and treatment of CNSV, the prognosis for patients with PACNS is probably significantly better than it was two or three decades ago because of better imaging techniques (which permit earlier diagnosis) and recognition of the effectiveness of cyclophosphamide and prednisone. The search for more specific imaging techniques continues. Advances in molecular biology and in the development of more specific therapies for other diseases mediated by the immune system may lead to less toxic therapies for CNSV in the future.

Another important breakthrough has been the recognition during the 1990s of BACNS, a subgroup of CNSV patients who have a better long–term prognosis than PACNS and who may require shorter courses of therapy.

In medical terms, by David Hellmann, M.D.

A discussion of Central Nervous System Vasculitis written in medical terms by David Hellmann, M.D. (F.A.C.P.) for the Rheumatology Section of the Medical Knowledge Self–Assessment Program published and copyrighted by the American College of Physicians (Edition 11, 1998). The American College of Physicians has given us permission to make this information available to patients contacting our Website:

Primary angiitis of the central nervous system is a rare disease characterized by vasculitis of small and medium arteries in the brain and spinal cord. Presentations are highly variable, but the triad of headache, organic brain syndrome, and multifocal neurologic deficits is most suggestive. Most affected patients do not have systemic symptoms, signs, or abnormal routine blood tests, including ESR.

Noninvasive tests have limited sensitivity and specificity. MRI is most sensitive, being abnormal in more than 80% of patients. The diagnosis is very rare when both the lumbar puncture (with regards to cells and protein level) and the MRI are normal. Angiography showing beading produced by alternating stenosis and dilation suggests the diagnosis but is not specific. Analysis of biopsy specimens of brain cortex and leptomeninges can help establish the diagnosis. In the absence of positive results on biopsy specimen analysis, the diagnosis of primary angiitis of the central nervous system should be doubted.

Cocaine use, malignant hypertension, preeclampsia, and intravascular lymphoma can mimic this disease. The best therapy has not been established: many patients are treated with prednisone and cyclophosphamide.

All information contained within the Johns Hopkins Vasculitis Center website is intended for educational purposes only. Visitors are encouraged to consult other sources and confirm the information contained within this site. Consumers should never disregard medical advice or delay in seeking it because of something they may have read on this website.