Characterization of Extracranial Giant Cell Arteritis with Intracranial Involvement and its Rapidly Progressive Subtype

Abstract

The objective of this study was to characterize patients with extracranial giant cell arteritis with intracranial involvement. Methods: In a multicenter retrospective study, we included 31 patients with systemic giant cell arteritis (GCA) with intracranial involvement. Clinical characteristics, pattern of arterial involvement, and cytokine profiles were assessed. Patients with GCA without intracranial involvement (n = 17), and with intracranial atherosclerosis (n = 25) served as controls. Results: Erythrocyte sedimentation rate (ESR) was elevated in 18 patients (69.2%) with and in 16 patients (100%) without intracranial involvement (p = 0.02). Headache was complained by 15 patients (50.0%) with and 13 patients (76.5%) without intracranial involvement (p = 0.03). Posterior circulation arteries were affected in 26 patients (83.9%), anterior circulation arteries in 17 patients (54.8%), and both territories in 12 patients (38.7%). Patients with GCA had vertebral artery stenosis proximal and, in contrast, patients with atherosclerosis distal to the origin of posterior inferior cerebellar artery (PICA). Among patients with GCA with intracranial involvement, 11 patients (37.9%) had a rapid progressive disease course characterized by short-term recurrent ischemic events. The median modified Rankin Scale (mRS) at followup in these patients was 4 (interquartile range [IQR] = 2.0-6.0) and 4 patients (36.4%) died. Vessel wall expression of IL-6 and IL-17 was significantly increased in patients with rapid progressive course. Interpretation: Typical characteristics of GCA, headache, and an elevated ESR, are frequently absent in patients with intracranial involvement. However, differentiation of intracranial GCA from atherosclerosis can be facilitated by the typical pattern of vertebral artery stenosis. About one-third of patients with intracranial GCA had a rapid progressive course with poor outcome. IL-17 and IL-6 may represent potential future treatment targets.

Giant-cell arteritis related strokes: scoping review of mechanisms and rethinking treatment strategy?

“…In our review of GCA-related stroke, 22% cases had CRP below 20 mg/L, but only one patient displayed double-negative CRP/ESR [none in Hayreh et al ( 81 ) and Bonnan and Balley 1 , and 0.8% in Parikh et al ( 82 )]. In another series, double-negative CRP/ESR was present in 36% (9/25) of patients with stroke and 18% (3/16) of other GCA patients ( 87 ). Therefore, although SIR is not always dramatic, completely false negative biology for inflammation is not an uncommon finding at onset in GCA-related stroke.…”

“…In this systematic brain assessment study, up to 15% of GCA patients presented with stroke, all of them displaying cervical artery involvement ( 47 ), which is far higher than the usual incidence of clinical stroke. In a series of GCA-related stroke, the frequency of artery lesions is even higher: ICA 48%, MCA 19%, VA 84% (stenosis V3 and V4 segments), BA 16% ( 87 ) ( Figure 3 ). Therefore, the frequency of cervical artery involvement was probably largely underestimated in earlier studies.…”

“…The ophthalmic and ciliary arteries are always involved outside the eyeball and the optic nerve. Classically, the vertebral arteries are severely involved two to three times more often, whereas the internal carotids are mostly spared by GCA ( 9 , 14 , 87 , 115 , 186 ). Autopsy series highlighted the discrepancy of the less severely affected internal carotid lesions, even in the most involved cavernous segment ( 9 , 97 , 115 ).…”

Spectrum of Large and Medium Vessel Vasculitis in Adults: Primary Vasculitides, Arthritides, Connective Tissue, and Fibroinflammatory Diseases

“…In postulated isolated aortitis, GCA needs to be screened for thoroughly [ 2 ]. While GCA was assumed not to cause central nervous system (CNS) vasculitis, vessel-wall MRI changed that paradigm; usually it represents extension of extradural disease and involves the proximal intracranial arteries [ 13 ••].…”

“…+/- Mesenteric, renal, lateral/internal thoracic, infrabrachial, infrapopliteal, coronary, cerebral, ovarian, uterine, breast, skin, liver, testes [ 9 – 13 ••]…”