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Meta-Analysis
. 2021 Oct 18;8(6):e1093.
doi: 10.1212/NXI.0000000000001093. Print 2021 Nov.

Primary Angiitis of the CNS: A Systematic Review and Meta-analysis

Carolin Beuker  1 , Daniel Strunk  1 , Rajesh Rawal  1 , Antje Schmidt-Pogoda  1 , Nils Werring  1 , Lennart Milles  1 , Tobias Ruck  1 , Heinz Wiendl  1 , Sven Meuth  1 , Heike Minnerup  2 , Jens Minnerup  2
Affiliations
Meta-Analysis

Primary Angiitis of the CNS: A Systematic Review and Meta-analysis

Carolin Beuker et al. Neurol Neuroimmunol Neuroinflamm. .

Abstract

Background and objectives: To facilitate and improve the diagnostic and therapeutic process by systematically reviewing studies on patients with primary angiitis of the CNS (PACNS).

Methods: We searched PubMed, looking at the period between 1988 and February 2020. Studies with adult patients with PACNS were included. We extracted and pooled proportions using fixed-effects models. Main outcomes were proportions of patients with certain clinical, imaging, and laboratory characteristics and neurologic outcomes.

Results: We identified 46 cohort studies including a total of 911 patients (41% biopsy confirmed, 43% angiogram confirmed, and 16% without clear assignment to the diagnostic procedure). The most frequent onset symptoms were focal neurologic signs (63%), headache (51%), and cognitive impairment (41%). Biopsy- compared with angiogram-confirmed cases had higher occurrences of cognitive impairment (55% vs 39%) and seizures (36% vs 16%), whereas focal neurologic signs occurred less often (56% vs 95%). CSF abnormalities were present in 75% vs 65% and MRI abnormalities in 97% vs 98% of patients. Digital subtraction angiography was positive in 33% of biopsy confirmed, and biopsy was positive in 8% of angiogram-confirmed cases. In 2 large cohorts, mortality was 23% and 8%, and the relapse rate was 30% and 34%, during a median follow-up of 19 and 57 months, respectively. There are no randomized trials on the treatment of PACNS. The initial treatment usually includes glucocorticoids and cyclophosphamide.

Discussion: PACNS is associated with disabling symptoms, frequent relapses, and significant mortality. Differences in symptoms and neuroimaging results and low overlap between biopsy and angiogram suggest that biopsy- and angiogram-confirmed cases represent different histopathologic types of PACNS. The optimal treatment is unknown.

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Conflict of interest statement

D. Strunk, C. Beuker, R. Rawal, A. Schmidt-Pogoda, T. Ruck, L. Milles, and H. Minnerup declare no conflict of interest. S. Meuth has received honoraria for lecturing, travel expenses for attending meetings, and financial research support from Almirall, Bayer HealthCare, Biogen, Diamed, Genzyme, MedDay Pharmaceuticals, Merck Serono, Novartis, Novo Nordisk, ONO Pharma, Roche, Sanofi-Aventis, Chugai Pharma, QuintilesIMS, and Teva. H. Wiendl is a member of the following scientific advisory boards/steering committees: Biogen, Sanofi Genzyme, MedDay Pharmaceuticals, Merck Serono, Novartis, and Roche. H. Wiendl has received speaker honoraria and travel support from Alexion, Biogen, Cognomed, Evgen, Sanofi Genzyme, Impulze, KWHC, Merck Serono, Novartis, PeerVoice, Pennside, and PSL Group. H. Wiendl has received compensation as a consultant from AbbVie, Actelion, Biogen, Sanofi Genzyme, Novartis, and Roche. H. Wiendl has received research support from Biogen, Sanofi Genzyme, GlaxoSmithKline, Roche, and Solace Pharmaceuticals UK. J. Minnerup has received grants from Deutsche Forschungsgemeinschaft, Bundesministerium für Bildung und Forschung (BMBF), Else Kröner-Fresenius-Stiftung, EVER Pharma Jena GmbH, and Ferrer International, travel grants from Boehringer Ingelheim, and speaking fees from Bayer Vital. Go to Neurology.org/NN for full disclosures.

Figures

Figure 1
Figure 1. Imaging Characteristics of Biopsy- and Angiogram-Confirmed Cases
All estimators represent the proportions of abnormal results in relation to the number of performed examinations. The size of the estimator is proportional to the size of the cohort in the respective study. The indicator I-squared indicates the heterogeneity of the data. Error bars indicate 95% CIs. Abnormalities may, e.g., consist of infarction, hemorrhage, or gadolinium enhancement or other characteristics as defined by the respective author. CI = confidence intervals; gd = gadolinium.
Figure 2
Figure 2. Imaging and Histologic Characteristics: Overlap Between Biopsy- and Angiogram-Confirmed Cases
All estimators represent the proportions of abnormal results in relation to the number of performed examinations. The size of the estimator is proportional to the size of the cohort in the respective study. The indicator I-squared indicates the heterogeneity of the data. Error bars indicate 95% CIs. The term abnormal refers to findings typical of primary angiitis of the CNS (PACNS). CI = confidence interval; DSA, digital subtraction angiography; MRA, magnetic resonance angiography.
Figure 3
Figure 3. CSF Abnormalities in Biopsy- and Angiogram-Confirmed Cases
All estimators represent the proportions of abnormal results in relation to the number of performed examinations. The size of the estimator is proportional to the size of the cohort in the respective study. The indicator I-squared indicates the heterogeneity of the data. Error bars indicate 95% CIs. CSF is considered abnormal when the cell count exceeds 4/µL (pleocytosis) or the protein concentration exceeds 450 mg/L. CI = confidence interval.
Figure 4
Figure 4. PACNS—A Disease Spectrum
There are overlapping (para-)clinical attributes between biopsy- (blue bars) and angiogram-confirmed (red bars) cases of PACNS, and also distinct characteristics. DSA = digital subtraction angiography; GD = gadolinium; MRA = magnetic resonance angiography; PACNS = primary angiitis of the CNS.
See this image and copyright information in PMC

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MeSH terms

Supplementary concepts