Meet the Challenge of Primary CNS Vasculitis

Cerebral and meningeal biopsy remains the gold standard for the diagnosis of PCNSV.^6,14 In expert hands, the procedure is relatively safe, with a risk of persistent complications in only about 1% of cases. Diagnostic histopathological features of PCNSV include transmural vascular inflammation affecting small and medium-sized leptomeningeal and parenchymal arterial vessels.¹⁴ Granulomatous vasculitis is the most common pattern of vasculitis. Beta-4 amyloid deposition is present in almost 50% of biopsies with this pattern (see Figure 1) but not seen in other histopathological patterns. Lymphocytic vasculitis is the second most predominant pattern. Necrotizing vasculitis is the least frequently seen pattern. In such cases, the appearance is similar to that seen in polyarteritis nodosa, with transmural fibrinoid necrosis.

Vasculitis affects vessels in a skipped and segmental pattern; therefore, because of sampling error, a negative biopsy does not exclude the diagnosis of vasculitis. Biopsy of a radiographically abnormal area is preferable to random sampling of the nondominant frontal lobe or temporal tip. Miller et al showed that 78% of the targeted biopsies were diagnostic, whereas none of the blind biopsies demonstrated vasculitis.¹⁴ Stereotactic guidance may be used for deeper lesions but is usually unnecessary for the commonly biopsied, more superficial lesions.

Clinical Manifestations and Laboratory Tests

Imaging of patients with primary central nervous system vasculitis.

Figure 2A: Cerebral angiogram shows multiple stenosis of the right and left posterior cerebellar arteries and the right posterior cerebral artery (arrows)

Figure 2B: Magnetic resonance angiography of the brain shows stenosis of the left posterior cerebral artery and the right middle cerebral artery (arrows).

Clinical manifestations of PVCNS at the time of diagnosis are listed in Table 3¹ These findings are nonspecific, and multiple manifestations are usually present. Although the onset of the disease may be acute, it is more frequently insidious and slowly progressive.

Headache, which is the most common symptom of PCNSV, may be generalized or localized, often slowly worsening, and may spontaneously remit for periods. Cognitive impairment is the second most frequent manifestation. Focal neurological manifestations are present in a large proportion of patients. Other manifestations such as ataxia, seizures, and intracranial hemorrhage are less frequent. Systemic symptoms such as fever and weight loss are uncommon. Symptoms related to spinal cord involvement may occasionally be the presenting manifestation.

Laboratory blood tests including acute phase reactants are usually normal in PCNSV.

CSF analysis is abnormal in 80% to 90% of cases.¹ Changes include a mildly increased leukocyte count and total protein concentration. CSF analysis should include appropriate stains, culture, serologic and molecular tests, and flow cytometry studies to exclude infections or malignancy.

Special Subsets

Several clinical subsets of PCNSV, which may differ in terms of prognosis and optimal management, have been identified (see Table 4).