Central nervous system (CNS) vasculitis is not a single disease but a collection of conditions that cause inflammatory damage of blood vessels in the brain and spinal cord. About half of the cases have no known cause and are therefore classified as primary vasculitis of the CNS. The other half of the cases arise in the setting of some other disorder, often a rheumatic disease such as systemic lupus erythematosus, and are classified as secondary forms of CNS vasculitis. Primary vasculitis of the CNS has been referred to by many names. Bowing to tradition, this chapter will use the term “primary angiitis of the CNS” (PACNS).

CNS vasculitis presents a two-handed clinical challenge. On the one hand, clinicians need to recognize and treat those rare patients whose strokes and other neurologic deficits result from CNS vasculitis. On the other hand, clinicians need to avoid overdiagnosis of CNS vasculitis and must realize that the angiographic and magnetic resonance imaging (MRI) abnormalities observed in CNS vasculitis can be mimicked by infection, tumor, and other conditions.

• Common presentation includes headache, encephalopathy, and multiple strokes.
  
• Brain MRI sensitive but not specific.
  
• Most patients in whom PACNS is suspected have some other disorder.
  
• Angiographic abnormalities are suggestive but not specific.
  
• Definitive diagnosis requires brain biopsy.

PACNS is a disease of unknown cause characterized by vasculitis limited to the brain and spinal cord. PACNS is rare; at large medical centers, PACNS constitutes only about 1% of all cases of systemic vasculitis. The annual incidence is 2.4 cases per 1,000,000 person-years. Evidence suggests that PACNS is not one disease. Indeed, the clinical picture of PACNS that emerges from reviewing the literature depends a great deal on whether the analysis focuses on biopsy-proven cases (BP-PACNS) or cases defined by angiography (AD-PACNS) without biopsy proof. Some clinicians have speculated that AD-PACNS may be caused by spasm rather than by inflammation. The term “benign angiography of the CNS” or reversible cerebral vasoconstriction syndrome is sometimes applied to cases of AD-PACNS. Table 40–1 outlines the clinical pictures of both BP-PACNS and AD-PACNS.

Symptoms and Signs

The average age of onset in one study of 101 patients with BP-PACNS or AD-PACNS was 47 years (range 17–84). BP-PACNS chiefly affects middle-aged men. The initial presentation is typically headache and encephalopathy, and multifocal strokes develop later. BP-PACNS usually develops insidiously, unfolding with additive neurologic deficits over weeks or months before the diagnosis is suspected. Strokes in the absence of diffuse cortical dysfunction would be most unusual for BP-PACNS. However, the presentation of BP-PACNS is highly variable. Some patients may appear to have had one stroke, but PACNS is suspected after an MRI reveals multiple strokes of varying age. In other patients, headache may be the dominating feature. In some patients who have headache and what appear to be mass lesions on MRI, a brain tumor is suspected. Diffuse cortical dysfunction can manifest as either a decline in cognitive ability or an alteration in consciousness. The English teacher who can no longer spell accurately or the bank teller who cannot count change exemplifies how cognitive changes from diffuse cortical dysfunction may present. Seizure and brainstem or cranial nerve dysfunction develops in approximately one third of patients. Spinal cord involvement occurs less commonly. Isolated dementia is a very rare presentation of BP-PACNS. It is a common misconception that BPPACNS is associated with systemic symptoms such as fever, weight loss, or sweats. In reality, such symptoms develop in less than 10% of cases.

The clinical picture of AD-PACNS, also designated in some series as reversible cerebral vasoconstriction syndrome, differs in several important ways. AD-PACNS preferentially affects women four times more commonly than men. The average age of onset is 40, the onset is sudden, and the most prominent presenting symptom is a severe headache. Focal findings of seizure or stroke develop in approximately 60% of patients (see Table 40–1). Diffuse cortical abnormalities develop less commonly. In AD-PACNS, as in BP-PACNS, systemic symptoms and signs are usually absent. As will be discussed in greater detail below, AD-PACNS patients also differ from BP-PACNS patients by having fewer cerebrospinal fluid abnormalities and responding to relatively short courses of glucocorticoids.

Laboratory Findings

In BP-PACNS, about one fifth of the patients have anemia (usually mild), one half have an elevated white blood cell count, and two thirds have an elevated erythrocyte sedimentation rate. The hematocrit and erythrocyte sedimentation rate are less frequently abnormal in AD-PACNS cases. The cerebrospinal fluid (CSF) is abnormal in nearly 90% of BP-PACNS cases and in about 50% of AD-PACNS cases. The most common abnormalities are an elevated CSF protein (with a mean of 177 mg/dL and a median of 100 mg/dL) and a CSF lymphocytosis (with a mean of 77 cells/mcL). A CSF cell count exceeding 250/mcL rarely occurs in PACNS. In AD-PACNS, the CSF abnormalities are typically very mild. CSF protein levels are usually below 60 mg/dL and the CSF white blood cell count is usually less than 10 cells/mcL. In one study of 48 patients with AD-PACNS, the median leukocyte count in the CSF was only 4 cells/mcL, and the medial total CSF protein was 54 mg/dL. Less than 10% of AD-PACNS patients have CSF with a protein >70 mg/dL or a white blood count >10/mcL.