Frequency and characteristics of severe relapse in giant cell arteritis.

OBJECTIVES: To assess the frequency and characteristics of severe relapse in patients with giant cell arteritis (GCA) in a real-life setting. METHODS: In a monocentric database of 530 patients, we retrospectively analysed patients who experienced at least one relapse and distinguished severe from nonsevere relapses. Severe relapse was defined by the occurrence of an ischaemic event (ophthalmologic, neurologic, digestive, limb ischaemia), the occurrence of an aortic complication (i.e. new or worsening of aortic dilation, aortic dissection), or new or worsening of vascular stenosis. RESULTS: From the cohort of 530 patients, 242 (45.7%) patients experienced relapse at least once, including 13 (2.5% of the cohort) who experienced severe relapse. Among the 464 recorded relapses, 14 (3% of all relapses) were severe. Severe relapse corresponded to the following vascular events: a peripheral limb ischaemia in 6 patients, a visual event in 3 patients (including 2 acute anterior ischaemic anterior neuropathies), an aortic complication in 3 patients, a mesenteric ischaemia in one patient and an ischaemic stroke in one patient.When compared with the 229 patients who experienced nonsevere relapses, severe relapse patients were younger at diagnosis (p= 0.02), more frequently showed limb claudication at baseline (p< 0.0001) and fewer GCA-related cranial signs (p< 0.0001). At diagnosis, more large-vessel vasculitis on imaging (82% vs 36%, p= 0.002) were observed in patients with severe relapse. The death rate did not differ between patients with severe and nonsevere relapses. CONCLUSION: In a real-life setting, relapse affects nearly half of GCA patients, but severe relapse is rare.

Comparison of patients with biopsy positive and negative primary angiitis of the central nervous system.

OBJECTIVE: There is limited evidence on when to obtain a central nervous system (CNS) biopsy in suspected primary angiitis of the central nervous system (PACNS). Our objective was to identify which clinical and radiological characteristics were associated with a positive biopsy in PACNS. METHODS: From the multicenter retrospective Cohort of Patients with Primary Vasculitis of the CNS (COVAC), we included adults with PACNS based on a positive CNS biopsy or otherwise unexplained intracranial stenoses with additional findings supportive of vasculitis. Baseline findings were compared between patients with a positive and negative biopsy using logistic regression models. RESULTS: 200 patients with PACNS were included, among which a biopsy was obtained in 100 (50%) and was positive in 61 (31%). Patients with a positive biopsy were more frequently female (OR 2.90, 95% CI 1.25-7.10, p = 0.01) and more often presented with seizures (OR 8.31, 95% CI 2.77-33.04, p < 0.001) or cognitive impairment (OR 2.58, 95% CI 1.11-6.10, p = 0.03). On imaging, biopsy positive patients more often had non-ischemic parenchymal or leptomeningeal gadolinium enhancement (OR 52.80, 95% CI 15.72-233.06, p < 0.001) or ≥ 1 cerebral microbleed (OR 8.08, 95% CI 3.03-25.13, p < 0.001), and less often had ≥ 1 acute brain infarct (OR 0.02, 95% CI 0.004-0.08, p < 0.001). In the multivariable model, non-ischemic parenchymal or leptomeningeal gadolinium enhancement (aOR 8.27, 95% CI 1.78-38.46), p < 0.01) and absence of ≥ 1 acute brain infarct (aOR 0.13, 95% CI 0.03-0.65, p = 0.01) were significantly associated with a positive biopsy. CONCLUSIONS: Baseline clinical and radiological characteristics differed between biopsy positive and negative PACNS. These results may help physicians individualize the decision to obtain a CNS biopsy in suspected PACNS.

The diagnostic challenge of patients with anti-U1-RNP antibodies.

Anti-U1-RNP antibodies are necessary for the diagnosis of mixed connective tissue disease (MCTD), but they are also prevalent in other connective tissue diseases, especially systemic lupus erythematosus (SLE), from which distinction remains challenging. We aimed to describe the presentation and outcome of patients with anti-U1-RNP antibodies and to identify factors to distinguish MCTD from SLE. We retrospectively applied the criteria sets for MCTD, SLE, systemic sclerosis (SSc) and rheumatoid arthritis (RA) to all patients displaying anti-U1-RNP antibodies in the hospital of Caen from 2000 to 2020. Thirty-six patients were included in the analysis. Eighteen patients (50%) satisfied at least one of the MCTD classifications, 11 of whom (61%) also met 2019 ACR/EULAR criteria for SLE. Twelve other patients only met SLE without MCTD criteria, and a total of 23 patients (64%) met SLE criteria. The most frequent manifestations included Raynaud's phenomenon (RP, 91%) and arthralgia (67%). We compared the characteristics of patients meeting only the MCTD (n = 7), SLE (n = 12), or both (n = 11) criteria. Patients meeting the MCTD criteria were more likely to display SSc features, including sclerodactyly (p < 0.01), swollen hands (p < 0.01), RP (p = 0.04) and esophageal reflux (p < 0.01). The presence of scleroderma features (swollen hands, sclerodactyly, gastro-oesophageal reflux), was significantly associated with the diagnosis of MCTD. Conversely, the absence of those manifestations suggested the diagnosis of another definite connective tissue disease, especially SLE.

Tolerance of glucocorticoids in giant cell arteritis: a study of patient-reported adverse events.

OBJECTIVE: To assess patients' self-reported glucocorticoid (GC)-related adverse events (AEs) in a GCA population. METHODS: A questionnaire was sent to the 100 patients most recently diagnosed with GCA in a tertiary centre. This questionnaire included open- and close-ended questions on the disease and GC effects. Eight primary AE areas were analysed: cardiovascular, metabolic, muscle, cognitive and psychologic, bone, cutaneous and hairiness, infective and visual complications. Including derivative subitems from preceding areas, a total of 18 GC-related AEs were analysed separately and according to GC duration. RESULTS: Ninety patients were analysed and 89 (99%) reported at least one GC-related AE [median 6 (range 1-11)]. Cognitive and psychological changes, primarily insomnia (72%), affected 90% of patients. Cutaneous changes and muscle loss affected 70% of patients, with frequent impairment of physical autonomy (P = 0.007) associated with this event. Metabolic issues, especially weight gain (40%) and diabetes mellitus (20%), affected 49% of patients. Conversely, vision troubles and bone fractures were mentioned by 42% and 9% of patients, respectively, and more frequently in patients who received GCs for >18 months (P = 0.01 and P = 0.007, respectively). Cardiovascular changes and infections affected 30% and 26% of patients, respectively. CONCLUSION: This real-life study of GC tolerance assessed using a self-evaluation provides pragmatic and updated data reminding us that GC tolerance remains more noteworthy than ever. This study suggests carefully monitoring GC-related AEs during follow-up and encourages GC-sparing strategies in some patients.

Real-life analysis of the causes of death in patients consecutively followed for giant cell arteritis in a French centre of expertise.

OBJECTIVES: To describe, in a real-life setting, the direct causes of death in a cohort of consecutive patients with GCA. METHODS: We retrospectively analysed the deaths that occurred in a cohort of 470 consecutive GCA patients from a centre of expertise between January 2000 and December 2019. Among the 120 patients who died, we retrieved data from the medical files of 101 patients. RESULTS: Cardiovascular events were the dominant cause of death (n = 41, 41%) followed by infections (n = 22, 22%), geriatric situations (i.e. falls or senile deterioration; n = 17, 17%) and cancers (n = 15, 15%). Patients in each of these four groups were compared with the other deceased patients pooled together. Patients who died from cardiovascular events were more frequently male (46 vs 27%; P = 0.04) with a past history of coronary artery disease (29 vs 8%; P = 0.006). Patients who died from infections mostly had ongoing glucocorticoid treatment (82 vs 53%; P = 0.02) with higher cumulative doses (13 994 vs 9150 mg; P = 0.03). Patients who died from geriatric causes more frequently had osteoporosis (56 vs 17%; P = 0.0009) and had mostly discontinued glucocorticoid treatment (76 vs 33%; P = 0.001). The predictive factors of death in multivariate analysis were a history of coronary disease [hazard ratio (HR) 2.39; 95% CI 1.27, 4.21; P = 0.008], strokes at GCA diagnosis (HR 2.54; 95% CI 1.05, 5.24; P = 0.04), any infection during follow-up (HR 1.93; 95% CI 1.24, 2.98; P = 0.004) and fever at GCA diagnosis (HR 1.99; 95% CI 1.16, 3.28; P = 0.01). CONCLUSION: Our study provides real-life insight on the cause-specific mortality in GCA patients.

Steroid-sparing effect of anakinra in giant-cell arteritis: a case series with clinical, biological and iconographic long-term assessments.

OBJECTIVES: The treatment of GCA relies on corticosteroids but is burdened by a high rate of relapses and adverse effects. Anti-IL-6 treatments show a clear benefit with a significant steroid-sparing effect, but late relapses occur after treatment discontinuation. In addition to IL-6, IL-1 also appears to play a significant role in GCA pathophysiology. We report herein the efficacy of anakinra, an IL-1 receptor antagonist, in six GCA patients exhibiting corticosteroid dependence or resistance, specifically analysing the outcome of aortitis in four of them. METHODS: This retrospective study analysed the cases of all GCA patients treated with anakinra from the French Study Group for Large Vessel Vasculitis. RESULTS: After a median duration of anakinra therapy of 19 (18-32) months, all six patients exhibited complete clinical and biological remission. Among the four patients with large-vessel involvement, one had a disappearance of aortitis under anakinra and three showed a decrease in vascular uptake. After a median follow-up of 56 (48-63) months, corticosteroids were discontinued in four patients, and corticosteroid dosage could be decreased to 5 mg/day in two patients. One patient relapsed 13 months after anakinra introduction in the context of increasing the daily anakinra injection interval to every 48 h. Three patients experienced transient injection-site reactions, and one patient had pneumonia. CONCLUSION: In this short series, anakinra appears to be an efficient and safe steroid-sparing agent in refractory GCA, with a possible beneficial effect on large-vessel involvement.

Chronic hepatic involvement in the clinical spectrum of A20 haploinsufficiency.

BACKGROUND & AIMS: Secondary to tumour necrosis factor-alpha induced protein 3 (TNFAIP3) mutations, A20 haploinsufficiency (HA20) is a recently described autoinflammatory disease with clinical features similar to those of Behçet's and Crohn's diseases but with a constantly expanding clinical spectrum. Here, we describe HA20 liver involvement in three new patients from the same family. METHODS: We retrospectively assessed clinical, biological and/or histological findings for eight patients over three generations of the same family with heterozygous mutations in the TNFAIP3 gene (c.259C > T, p.Arg87*). RESULTS: The eight patients exhibited the following: aphthous ulcers (8/8, bipolar in 7), autoimmune features (6/8, including 5 with definitive autoimmune disease diagnoses, ie, type I diabetes, Hashimoto thyroiditis, pernicious anaemia, and/or 5 with antinuclear antibodies ≥320), pustulosis/folliculitis (5/8), abdominal pain (4/8), arthralgia (3/8), enlarged cervical lymph nodes (3/8) and pericarditis (1/8). In addition, three patients (twin sisters and their grandmother aged 23 and 70 years, respectively) exhibited persistent mild hepatic cytolysis associated with splenomegaly (n = 3), hepatomegaly (n = 1) and/or liver atrophy (n = 1) on echography. We could not detect any other causes of chronic liver diseases. Liver biopsies from three patients displayed hepatic fibrosis, hepatocyte injury and/or CD4+ /CD8+ T lymphocyte infiltration, and patterns of inflammatory cells and NLRP3 or NF-κB immunostaining differed from the predominant neutrophil infiltration observed in skin or some digestive tract biopsies. CONCLUSIONS: This study reinforces the dual involvement of innate and adaptive immunity in HA20 according to both acute and chronic injury and the organ involved and widens its clinical spectrum to include chronic hepatic involvement.

2018 Update of the EULAR recommendations for the management of large vessel vasculitis.

BACKGROUND: Since the publication of the European League Against Rheumatism (EULAR) recommendations for the management of large vessel vasculitis (LVV) in 2009, several relevant randomised clinical trials and cohort analyses have been published, which have the potential to change clinical care and therefore supporting the need to update the original recommendations. METHODS: Using EULAR standardised operating procedures for EULAR-endorsed recommendations, the EULAR task force undertook a systematic literature review and sought opinion from 20 experts from 13 countries. We modified existing recommendations and created new recommendations. RESULTS: Three overarching principles and 10 recommendations were formulated. We recommend that a suspected diagnosis of LVV should be confirmed by imaging or histology. High dose glucocorticoid therapy (40-60 mg/day prednisone-equivalent) should be initiated immediately for induction of remission in active giant cell arteritis (GCA) or Takayasu arteritis (TAK). We recommend adjunctive therapy in selected patients with GCA (refractory or relapsing disease, presence of an increased risk for glucocorticoid-related adverse events or complications) using tocilizumab. Methotrexate may be used as an alternative. Non-biological glucocorticoid-sparing agents should be given in combination with glucocorticoids in all patients with TAK and biological agents may be used in refractory or relapsing patients. We no longer recommend the routine use of antiplatelet or anticoagulant therapy for treatment of LVV unless it is indicated for other reasons. CONCLUSIONS: We have updated the recommendations for the management of LVV to facilitate the translation of current scientific evidence and expert opinion into better management and improved outcome of patients in clinical practice.

Prognosis of large vessel involvement in large vessel vasculitis.

OBJECTIVES: To assess prognosis factors and outcome of large vessel involvement (LVI) in large vessels vasculitis (LVV) patients. METHODS: Retrospective multicenter study of characteristics and outcomes of 417 patients with LVI including 299 Takayasu arteritis (TAK) and 118 Giant cell arteritis (GCA-LVI) were analyzed. Logistic regression analysis assessed prognosis factors in LVV patients. Outcome of LVI among TAK and GCA-LVI patients (ischemic complications, aneurysms complications, relapses and revascularization) were assessed. RESULTS: In multivariable analysis, stroke/transient ischemic attack [HR: 3.63 (1.46-9.04), p = 0.006] was independently associated with vascular complications in LVV. The 10-years aneurysm free survival was significantly lower [67% (48-93) vs 89% (84-95), p = 0.02] in GCA-LVI compare to TAK patients. The 5-years relapse free survival was significantly lower [47% (37-60) vs 69% (63-75), p < 0.001,] in GCA-LVI compare to TAK patients. The 10-years revascularization free survival was significantly lower [55% (48-64) vs 76% (59-99), p < 0.001] in TAK compare to GCA-LVI patients. After a median follow-up of 5 years, 16 (5.4%) TAK and 7 (5.9%) GCA-LVI patients died, mainly of aneurysm (26%) and ischemic complications (26%). CONCLUSION: This large nationwide cohort of LVI provided prognosis factors of vascular complications in LVV patients. TAK and GCA-LVI have different long-term outcome in term of aneurysm development, relapse and revascularization.

Vascular Presentation and Outcomes of Patients With Giant Cell Arteritis and Isolated Symptomatic Limb Involvement.

OBJECTIVE: The aims of this study were to describe and assess the vascular outcomes of patients with giant cell arteritis (GCA) presenting with only symptomatic isolated limb involvement (LI-GCA). METHODS: We recruited patients from 5 tertiary centers who were diagnosed with GCA based on histology or vasculitis demonstration on imaging and who presented with isolated symptomatic limb involvement at diagnosis. For each included patient, we randomly selected 3 control patients who satisfied the 5 criteria from the American College of Rheumatology at diagnosis. RESULTS: We included 27 LI-GCA patients and 81 control patients. Compared with the controls, the patients with LI-GCA were younger (p = 0.005), exhibited a more delayed diagnosis (p = 0.006), and had lower C-reactive protein levels (p = 0.001), but they did not show more cardiovascular risk factors. Glucocorticoid use (starting and tapering doses) and relapse rates did not differ in the 2 groups, but the patients with LI-GCA received longer treatment (p = 0.02). Cardiovascular complications occurred in 67% of the patients with LI-GCA versus 21% of the control patients (p < 0.0001), especially ischemic events (p < 0.0001) including stroke (p = 0.03) and myocardial infarction (p = 0.01). Vascular surgery was required in 44% of the patients with LI-GCA versus 2% of the controls (p < 0.0001). Excluding vascular surgery, the cumulative incidence of cardiovascular complications was higher in the patients with LI-GCA (log-rank test: p < 0.0001) than in the controls (hazard ratio, 5.73; 95% confidence interval, 2.94-11.28; p < 0.0001). CONCLUSIONS: Compared with the typical cranial form of GCA, LI-GCA has a worse cardiovascular-related prognosis. Further studies are required to determine the best management of these patients.

Different patterns and specific outcomes of large-vessel involvements in giant cell arteritis.

Large-vessel involvement (LVI) in giant cell arteritis (GCA) includes different clinical and imaging patterns that are rarely described separately at diagnosis and whose specific cardiovascular outcomes are unknown. We conducted a nationwide retrospective study and included GCA patients with LVI demonstrated on imaging at diagnosis between 2007 and 2017. We analyzed the prognosis of three different imaging patterns of LVI present at diagnosis, with some of them overlapping but with the first one present in all patients: 1) inflammation of the aorta and/or its branches; 2) dilation of the aorta; and 3) stenosis of the aortic branches. A control group of GCA patients without LVI was constituted. We included 183 patients with LVI and 105 controls without LVI. Altogether, among the 183 patients who all showed inflammation of the aorta and/or its main branches, concomitant aortic dilation and large-vessel stenosis were observed in 27 (15%) and 55 (30%) patients, respectively. During the follow-up period, new cardiovascular events occurred in 49% and 11% of LVI patients and controls, respectively (p < 0.0001). Inflammation of the aorta and/or its branches (HR: 3.42 [2.09-5.83], p < 0.0001) and large-artery stenosis (HR: 2.75 [1.80-4.15], p < 0.0001) were independent predictive factors of new cardiovascular events. Conversely, the use of an immunosuppressant besides corticosteroids was a protective factor against new cardiovascular events (HR: 0.44 [0.29-0.66], p < 0.0001) and the development of aortic dilation (HR: 0.43 [0.23-0.77], p = 0.005). This study suggests different forms of cardiovascular events according to the initial imaging pattern of LVI.

The different clinical patterns of giant cell arteritis.

OBJECTIVES: To estimate the frequency of different clinical patterns in giant-cell arteritis (GCA) at onset. METHODS: All GCA patients consecutively followed-up in two referral centers for GCA with a biopsy-proven diagnosis and/or large-vessel vasculitis (LVV) demonstrated on imaging were analysed. RESULTS: We analysed the initial clinical presentation of 693 patients with a median age of 75 [48-94] years and including 486 (70%) women. We identified four different clinical patterns: isolated cranial GCA (in 80%), symptomatic LVV with or without associated cranial signs (9%), isolated fever or inflammatory response (9%), and isolated polymyalgia rheumatica with vasculitis (2%). A silent LVV was found in 110 (45%) out of the 247 patients without large-vessel symptoms who underwent imaging at GCA diagnosis. Symptomatic LVV patients were more frequently GC-dependent compared to other patterns (p=0.03) and showed the longest treatment duration (median: 37 [15-212] months versus <30 months for other clinical phenotypes; p=0.001). CONCLUSIONS: This study suggests that 80% of GCA patients display a typical presentation, whereas the other 20% showed rarer presentations. Patients with symptomatic LVV required longer treatment duration.

Chronic intestinal pseudo-obstruction with dilated biliary tract as a spectrum of stiff person syndrome in a nondiabetic patient.

Stiff person syndrome (SPS) is a rare and challenging neuromuscular junction disorder with typical musculoskeletal manifestations associated with anti-GAD65 antibodies, extra rheumatological manifestations, including neuropsychiatric symptoms and severe dysautonomic troubles. Chronic intestinal pseudo-obstruction (CIPO) is also a rare condition corresponding to a sub-occlusive syndrome, resulting from the functional or structural impairment of smooth neuromuscular tissues of the intestinal tract. In the clinical spectrum of SPS, CIPO has rarely been described and dilated biliary tract has never been described. This present report is therefore the first in the context of anti-GAD65 antibodies with the additional involvement of the biliary tract. Here, we report the case of a 44-year-old woman hospitalized for a rapidly progressive CIPO associated with dilated biliary tract, revealing a typical SPS with slowly progressive rheumatologic complaints relegated to the background. The concomitant improvement of the neuromuscular function on skeletal, intestinal and biliary tree systems with the good outcomes of anti-GAD65 titer under immunosuppressant drugs, allowed us to link all three organic involvements to the antibody pathogenicity on the respective neuromuscular junctions. Therefore, we discussed their common pathogeny based on our patient's treatment outcome.

Treatment and Long-Term Outcomes of Primary Central Nervous System Vasculitis.

Background and Purpose- We aimed to analyze the long-term outcomes of patients with primary central nervous system vasculitis according to the different therapeutic strategies used to induce remission. Methods- We assessed the rate of prolonged remission (defined by the absence of relapse at ≥12 months after diagnosis) and the functional status at last follow-up in patients with primary central nervous system vasculitis included in the French cohort, who achieved a first remission according to the 3 main groups of treatments administered: glucocorticoids only (group 1); induction treatment with glucocorticoids and an immunosuppressant, but no maintenance (group 2); and combined treatment with glucocorticoids and an immunosuppressant for induction followed by maintenance therapy (group 3). Good functional status was defined as a modified Rankin Scale score ≤2 at the last follow-up. Results- Remission was achieved with the initial induction treatment in 106 (95%) of the 112. Prolonged remission without relapse was observed in 70 (66%) patients after 57 (12-198) months of follow-up. A good functional status at last follow-up (ie, modified Rankin Scale score ≤2) was observed in 63 (56%) patients. Overall mortality was 8%. The initial severity and the radiological presentations were comparable in the 3 treatment groups. More prolonged remissions ( P=0.003) and a better functional status at the last follow-up ( P=0.0004) were observed in group 3. In multivariate analysis, the use of maintenance therapy was associated with prolonged remission (odds ratio, 4.32 [1.67-12.19]; P=0.002) and better functional status (odds ratio, 8.09 [3.24-22.38]; P<0.0001). Conclusions- This study suggests that maintenance therapy with an immunosuppressant combined with glucocorticoids lead to the best long-term clinical and functional outcomes in patients with primary central nervous system vasculitis after having achieved remission with either glucocorticoids alone or in combination with another immunosuppressant.

Mortality causes and trends associated with giant cell arteritis: analysis of the French national death certificate database (1980-2011).

OBJECTIVES: Comprehensive analyses of cause-specific death patterns in GCA are sparse. We studied the patterns and time trends in GCA-related mortality using a large death certificate database. METHODS: We obtained multiple-cause-of-death data from the French national death certificate database for 1980-2011. GCA-associated deaths were defined as decedents ⩾55 years old with GCA listed as an underlying or non-underlying cause of death. Time trends of death rates were analysed and the mean age at death with GCA and in the general population ⩾55 years old were calculated. Standardized mortality odds ratios (SMORs) were calculated for 17 selected causes of death (based on 2000-11 data). RESULTS: The analyses pertained to approximately 15 000 death certificates listing GCA (including approximately 6300 for 2000-11). Annual standardized death rates for GCA increased to a peak in 1997 and then decreased (Spearman's correlation test, both P < 0.0001). Mean age at death was higher for GCA than for general population decedents (Student's t-test, P < 0.0001). GCA deaths were frequently or strongly associated with aortic aneurysm and dissection (1.85% of death certificates, SMOR: 3.09, 95% CI: 2.48, 3.82), hypertensive disease (20.78%, SMOR: 2.22, 95% CI: 1.97, 2.50), diabetes mellitus (11.27%, SMOR: 1.96, 95% CI: 1.72, 2.23), certain infectious and parasitic diseases (12.12%, SMOR: 1.76, 95% CI: 1.55, 2.00) and ischaemic heart disease (16.54%, SMOR: 1.45, 95% CI: 1.35, 1.64). CONCLUSION: GCA is associated with increased risk of dying from large-vessel disease, other cardiovascular diseases and potentially treatment-related co-morbidities. These findings help provide better insights into the outcomes of GCA.

Primary Angiitis of the Central Nervous System: Magnetic Resonance Imaging Spectrum of Parenchymal, Meningeal, and Vascular Lesions at Baseline.

BACKGROUND AND PURPOSE: Primary angiitis of the central nervous system remains challenging. To report an overview and pictorial review of brain magnetic resonance imaging findings in adult primary angiitis of the central nervous system and to determine the distribution of parenchymal, meningeal, and vascular lesions in a large multicentric cohort. METHODS: Adult patients from the French COVAC cohort (Cohort of Patients With Primary Vasculitis of the Central Nervous System), with biopsy or angiographically proven primary angiitis of the central nervous system and brain magnetic resonance imaging available at the time of diagnosis were included. A systematic imaging review was performed blinded to clinical data. RESULTS: Sixty patients met inclusion criteria. Mean age was 45 years (±12.9). Patients initially presented focal deficit(s) (83%), headaches (53%), cognitive disorder (40%), and seizures (38.3%). The most common magnetic resonance imaging finding observed in 42% of patients was multiterritorial, bilateral, distal acute stroke lesions after small to medium artery distribution, with a predominant carotid circulation distribution. Hemorrhagic infarctions and parenchymal hemorrhages were also frequently found in the cohort (55%). Acute convexity subarachnoid hemorrhage was found in 26% of patients and 42% demonstrated pre-eminent leptomeningeal enhancement, which is found to be significantly more prevalent in biopsy-proven patients (60% versus 28%; P=0.04). Seven patients had tumor-like presentations. Seventy-seven percent of magnetic resonance angiographic studies were abnormal, revealing proximal/distal stenoses in 57% and 61% of patients, respectively. CONCLUSIONS: Adult primary angiitis of the central nervous system is a heterogenous disease, with multiterritorial, distal, and bilateral acute stroke being the most common pattern of parenchymal lesions found on magnetic resonance imaging. Our findings suggest a higher than previously thought prevalence of hemorrhagic transformation and other hemorrhagic manifestations.

Adult primary angiitis of the central nervous system: isolated small-vessel vasculitis represents distinct disease pattern.

Objectives: We aimed to identify whether presentations and outcomes in adult patients with isolated small-vessel primary angiitis of the CNS (PACNS) would differ from other patients with large/medium-vessel involvement. Methods: In the French PACNS cohort, we compared the characteristics, treatments and outcomes of patients with isolated small-vessel disease (normal CT, MR and/or conventional angiograms, brain biopsy positive for vasculitis) with other patients who had large/medium-vessel involvement (vessel abnormalities on CT, MR or conventional angiograms). A good functional outcome was defined as a modified Rankin scale ⩽2 at last follow-up, regardless of the occurrence of relapse. Results: Among the 102 patients in the cohort, 26 (25%) had isolated small-vessel PACNS, whereas the 76 others demonstrated large/medium-vessel involvement. Patients with isolated small-vessel PACNS had more seizures (P < 0.0001), cognitive (P = 0.02) or consciousness impairment (P = 0.03) and more dyskinesias (P = 0.002) but less focal deficits (P = 0.0002) than other PACNS patients. They also had more abnormal cerebrospinal fluid analysis (P = 0.008) and gadolinium enhancements on MRI (P = 0.001) but less frequent acute ischaemic lesions (P < 0.0001) than patients with large/medium-vessel involvement. Treatments and modified Rankin scale at last follow-up did not differ between groups. Thirty-two (31%) patients relapsed; 14 (54%) with isolated small-vessel PACNS vs 18 (24%) with large/medium-vessel involvement (P = 0.004). Eight patients died, with no difference between the groups (P = 0.97). Conclusion: In our cohort, adult patients with isolated small-vessel PACNS presented some distinct disease features and relapsed more often than other PACNS patients who had large/medium-vessel involvement. Functional outcomes and mortality did not differ.

Maintenance therapy is associated with better long-term outcomes in adult patients with primary angiitis of the central nervous system.

Objective: We aimed to analyse the effect of maintenance therapy after induction on the outcomes of adult patients with primary angiitis of the CNS (PACNS). Methods: We analysed long-term outcomes (relapse, survival and functional status) of patients enrolled in the French multicentre PACNS cohort who achieved remission after induction treatment and with ⩾12 months' follow-up, according to whether or not they received maintenance therapy. Good outcome was defined as relapse-free survival and good functional status (modified Rankin scale ⩽ 2) at last follow-up. Results: Ninety-seven patients [46 (47%) female, median age: 46 (18-78) years at diagnosis] were followed up for a median of 55 (5-198) months. Induction treatment consisted of glucocorticoids in 95 (98%) patients, combined with an immunosuppressant in 80 (83%) patients, mostly CYC. Maintenance therapy was prescribed in 48 (49%) patients, following CYC in 42 of them. Maintenance therapy was started 4 (3-18) months after glucocorticoid initiation. At last follow-up, good outcomes were observed in 32 (67%) patients who had received maintenance therapy vs 10 (20%) who had not (P < 0.0001). Thirty-two (33%) patients experienced relapse [10 (22%) had received maintenance therapy while 22 (45%) had not, P = 0.01]; four subsequently died from relapse. In the multivariate analysis, maintenance therapy was the only independent predictor of good outcome [odds ratio (OR) = 7.8 (95% CI: 3.21, 20.36), P < 0.0001]. Conclusion: The results of this long-term follow-up study suggest that maintenance therapy in adults with PACNS is associated with better functional outcomes and lower relapse rates. Further studies are needed to confirm these findings.