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Antineutrophil Cytoplasmic Antibody (ANCA)-Associated CNS Vasculitis

Antibodies reflective of ANCA are directed against certain cytoplasmic proteins within neutrophils and appear to be part of the pathogenesis in certain vasculitides. This is an evolving process both in terms of insight into mechanism and terminology. For example, “Wegener’s granulomatosis” has been suggested to be replaced with “granulomatosis polyangiitis” (GPA). Churg-Strauss syndrome has been proposed to be replaced with eosinophilic granulomatosis with polyangiitis (EGPA). The other commonly cited ANCA-related vasculitic process is microscopic polyangiitis (MPA) [60].

CNS involvement by Wegener’s granulomatosis is quite uncommon [61]. It can be associated with either small to medium-sized cerebral vasculitis, meningitis, or orbital granuloma [62]. There can be extension of the granulomatous process to the cavernous sinus with resultant cavernous sinus syndrome [63]. Cerebral vasculitis is seen in up to 4% of patients and is reported to be the most frequent CNS manifestation [64].

MPA affects small vessels such as arterioles, capillaries, and venules and can be associated with cerebral infarction [65] although reports tend to be few and far between reflective of the rarity of such a disorder. There is the potential for lacunar- type infarct as well as hemorrhagic stroke, and support for the diagnosis can come from elevated ESR and CRP, positive ANCA, and pathological confirmation such as sural nerve biopsy [66].

EGPA affects small- and medium-size vessels. This is a systemic process typically affecting the lungs with asthma and eosinophilia and often with gastrointestinal involvement as well. The necrotizing small vessel vasculitis can also affect the CNS with resultant stroke, ischemic or hemorrhagic [54]. Although rare, it has been proposed that this diagnostic possibility be raised in patients with stroke and hype- reosinophilia [12].

Diagnosis and Treatment

Recognition of the clinical manifestations is key with such a systemic granulomatosis processes as Wegener’s, aka GPA, and Churg-Strauss, aka EGPA. Pathological confirmation of available tissue for biopsy is of utmost importance as aggressive immunosuppressive therapy can be of clear benefit in most patients. In EGPA, for

Table 4.6 Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis types and patterns

Designation

Alternative name

Areas of involvement

CNS manifestations

Wegener’s

granulomatosis

Granulomatosis with polyangiitis

Small and medium blood vessels of multiple organs

Ischemic and hemorrhagic stroke small- and medium- size vessel pattern

Churg-Strauss

syndrome

Eosinophilic granulomatosis with polyangiitis

Pulmonary with eosinophilic asthma, gastrointestinal, and other organs

Ischemic and hemorrhagic stroke with nodular small vessel polyangiitis, seizures, cranial nerve palsies

Microscopic

polyangiitis

Micro-arteriolar necrotizing systemic pattern

Ischemic small vessel infarcts, sino-venous occlusion, hemorrhagic stroke, basilar meningitis

example, the small epineural arteriolar inflammatory process is often identified on peripheral nerve biopsy as neuropathy is a common manifestation of this illness [67] with CNS involvement much less common [68]. Characteristically, one sees necrotizing vasculitis with eosinophilic infiltration along with extravascular granulomas. In this disorder, corticosteroid therapy can be highly effective with one study demonstrating remission in 94% of patients during the first year of therapy [69].

More aggressive ANCA-associated inflammatory disease, especially when associated with cerebral vasculitis, often calls for more potent immunosuppression such as a combination of cyclophosphamide and high-dose glucocorticoids. Gaining acceptance as a replacement for cyclophosphamide is rituximab shown to be noninferior in two ANCA-associated vasculitis studies [70, 71]. Both azathioprine and methotrexate can be alternatives for chronic immunosuppression [72].

It is important to point out that the role of ANCA autoantibodies in the pathogenesis is not clearly defined. For example, Wegener’s granulomatosis can be associated with polyangiitis in ANCA-negative patients [73]. In addition, the presence of ANCA antibodies can overlap with other autoimmune disorders, such as Sjogren’s syndrome, and possibly contribute to the spectrum of manifestations [74]. ANCA- associated vasculitic disorders are outlined in Table 4.6.

 
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