Primary angiitis of the central nervous system: Clinical profiles and outcomes of 45 patients.

OBJECTIVE: To describe the clinical profile, treatment response and predictors of outcome in patients with primary angiitis of the central nervous system (PACNS) from a single tertiary care center. METHODOLOGY: Retrospective analysis of consecutive patients diagnosed with PACNS from January 2000 to December 2015. Outcome was defined as poor when the 6-month modified Rankin scale (mRS) was ≥3. RESULTS: The median age of the 45 patients included in this study was 36 (range 19-70) years at disease onset and 31 (68.9%) were males. The initial presentation was ischemic stroke in 15 (33.3%), hemorrhagic stroke in 4 (8.9%), headache in 11 (24.4%), seizures in 8 (17.8%) and cognitive dysfunction in 5 (11.1%) patients. Diagnosis was confirmed by a four vessel cerebral digital subtraction angiogram (DSA), biopsy and by both biopsy and DSA in 26 (57.8%), 15 (33.3%) and 4 (8.9%) patients, respectively. All patients received glucocorticoids and 14 patients received in addition either cyclophosphamide or azathioprine as their first treatment. The median duration of follow-up was 33.1 (0.7-356) months. A poor 6-month outcome was observed in 12 (26.7%) patients. Relapse occurred in 25 (55.6%) patients and 7 (15.6%) died. Predictors of a poor outcome consisted of cognitive dysfunction at diagnosis (80% vs 20%; P = 0.014) and NIHSS ≥5 (62.5% vs 37.5%; P <.0005). None of the patients with a normal EEG had a poor outcome (P = 0.046). Predictors of relapse were a higher NIHSS at admission (P =.032) and a normal DSA (P = 0.002). CONCLUSION: In this cohort, severe deficits and cognitive symptoms at onset and an abnormal EEG were associated with a poor 6-month outcome.

Mass-forming primary angiitis of central nervous system with Rosai-Dorfmann disease-like massive histiocytosis with emperipolesis.

Primary angiitis of the central nervous system (PACNS) is a vasculitis restricted to the CNS without systemic involvement. We report a case of PACNS that was radiologically tumor-mimicking, and pathologically similar to the Rosai-Dorfmann disease. A 20-year-old woman presented with a focal facial motor seizure. Magnetic resonance image revealed heterogeneously enhanced well-demarcated solitary cerebral mass in the posterior frontal lobe. Histopathologically, the lesion showed lymphoplasmacytic vasculitis with massive parenchymal infiltration of large histiocytes with emperipolesis. Diffuse ischemic change, necrosis, hemorrhage of the brain parenchyma with neuronophagia, and extensive reactive gliosis by gemistocytic astrocytes were accompanying microscopic features. The patient was doing well for 3 years after complete resection of the lesion, except for occasional occurrence of alcohol- or sleep deprivation-associated seizure. We describe this unique case to provide evidence that mass formation can be developed in PACNS by accompanying parenchymal lymphohistiocytic infiltration, necrosis, and marked reactive gliosis.

Ruptured Saccular Aneurysm Caused by Necrotizing Arteritis of the Polyarteritis Nodosa Type in Primary Angiitis of Central Nervous System.

Primary angiitis of central nervous system (PACNS) is a rare idiopathic vasculitis that typically involves small arteries. An 18-year-old woman was operated on for resection of a ruptured aneurysm in a cerebral artery. Multiple aneurysms of cerebral arteries had been detected by neuroimaging examinations since the age of 12, and she had been administered drugs following a diagnosis of PACNS since the age of 15. The resected aneurysm was a ruptured saccular aneurysm occurring in a medium-sized artery. Histologically, necrotizing arteritis of the polyarteritis nodosa (PAN) type was noted in the aneurysmal wall. It consisted of an admixture of acute and healing stages. In the acute stage, fibrinoid necrosis in the intima and media and intense inflammatory cell infiltrate in the entire wall were present. The inflammatory cells mainly consisted of lymphocytes, including plasma cells, neutrophils, and macrophages. In the healing stage, disappearance of fibrinoid necrosis, fibrosis in the intima and media, and scarce inflammatory cells were noted. The acute stage was mainly present near the ruptured site. From these findings, the aneurysm was considered to have been caused by necrotizing arteritis of the PAN type. Although saccular aneurysmal formation in a medium-sized artery is rare in PACNS, an understanding of aneurysms produced by necrotizing arteritis of the PAN type offers useful information for the diagnosis and treatment of PACNS.

Perfusion and spectroscopy magnetic resonance imaging in a case of lymphocytic vasculitis mimicking brain tumor.

BACKGROUND: Lymphocytic vasculitis of the central nervous system is an uncommon subtype of primary angiitis of the central nervous system (PACNS) - a rare inflammatory disorder affecting parenchymal and leptomeningeal arteries and veins. CASE REPORT: Establishing diagnosis on the basis of neuroimaging only is difficult, as it can mimic a brain tumor. Thus, histological diagnosis is essential for appropriate management. We present a case of biopsy-proven lymphocytic vasculitis mimicking a brain tumor on neuroimaging that was subsequently successfully treated with steroid therapy. We also discuss the findings in perfusion MR (PWI) and MR spectroscopy (MRS). CONCLUSIONS: Regional hypoperfusion on PWI and elevation of glutamate and glutamine levels on MRS (without associated typical tumor spectra) are common findings in inflammatory disorders, including PACNS, and can be useful in differential diagnosis with tumors.

Mycophenolate mofetil as induction and maintenance immunosuppressive therapy in adult primary central nervous system vasculitis: A prospective observational study.

To observe the clinical and angiographic effectiveness of mycophenolate mofetil (MMF) as induction and maintenance immunosuppressive therapy in primary central nervous system vasculitis (PCNSV). In this open-label prospective study done at a tertiary care neurology centre, adult patients with PCNSV, diagnosed by Calabrese's criteria, were recruited from 2017 to 2021 and treated with glucocorticoids, MMF and standard of care. Patients were followed-up and clinical and angiographic changes were recorded. Total 26 patients were recruited with median age 39 years (34-49) with a slight female predilection (61.5%). Angiographic diagnoses were: small vessels disease 11.5%; large vessels disease 42.3% and both in 46.2%. Median duration of follow-up was 24.5 months (14.25-38). Proportion of patients with severe disability (modified Rankin Score (mRS) 4-6) at baseline was 73.08% (19/26) which reduced to 7.69% (2/26) (p < 0.001). At the last follow-up mRS = 0 was achieved in 38.5% (10/26) and mRS of ≤ 1 was achieved in 69.2% (18/26). Median time to achieve a mRS ≤ 1 was 12 months (95% CI: 6.8-17.2). Angiography was repeated in 16 patients after a median duration of 13 months (10.5-19.7), out of which 10 (62.5%) showed improvement and 5 (31.2%) showed non-progression of lesions. MMF may be an effective immunosuppressive therapy in adult PCNSV as both induction and maintenance. Serial DSA of brain may be useful to monitor the effect of treatment. Key Points • Mycophenolate mofetil is effective as induction and maintenance immunosuppressive therapy in PCNSV. • Repeat angiogram may be useful to monitor treatment response in PCNSV.

Primary Angiitis of the Central Nervous System - Diagnosis and Management.

Primary angiitis of central nervous system (PACNS) is a rare idiopathic disorder affecting blood vessels of brain, spinal cord, and meninges, consequently leading to infarct and less frequently hemorrhage. CNS vasculitis can also occur as part of systemic vasculitis or secondary to autoimmune diseases or infections. The clinical manifestations of PACNS are non-specific and no single laboratory investigation or neuroimaging finding can reliably diagnose this condition. Histopathological evidence of transmural inflammation of blood vessels of CNS is the gold standard, but is generally pursued subsequent to conventional angiogram (CA) because of its invasive nature. The differentials of PACNS are exhaustive and include systemic vasculitis, secondary vasculitis, non-inflammatory intracranial vasculopathies, demyelination, and neoplasm. These alternative conditions can often be distinguished by history, examination, immunological testing, cerebrospinal fluid analysis, and neuroimaging. CA can detect vasculitic changes in the large to medium cerebral arteries but the specificity is low. Recent advancements in vessel wall imaging techniques have further enabled the distinction of various intracranial vasculopathies from CNS vasculitis. The disease has considerable morbidity and fatality unless timely treatment with immunosuppressive agents is initiated. Induction therapy with glucocorticoids and cyclophosphamide followed by azathioprine, mycophenolate mofetil, or methotrexate as maintenance therapy is the cornerstone of management. Biological agents such as rituximab and anti-tumour necrosis factor alpha inhibitors (infliximab and etanercept) may be used in refractory cases. This review discusses the approach to the diagnosis, determinants of outcome, and management.

Case Report: Interest of Positron Emission Tomography in Pediatric Small Vessel Primary Angiitis of the Central Nervous System.

Primary angiitis of the central nervous system (PACNS) is a rare inflammatory disease affecting central nervous system vessels. The diagnosis, which requires confirmation by brain biopsy, remains challenging due to unspecific clinical presentation and low specificity of imaging and laboratory exams. In these two pediatric biopsy-proven cases of svPACNS we demonstrate that brain positron emission tomography (PET) show a high metabolic activity that extends beyond brain MRI abnormalities. Therefore, combining MRI and PET abnormalities to adequately guide brain biopsy might increase the diagnostic yield of this rare condition.

Primary Angiitis of Central Nervous System-Tumor-Like Mass Lesions: Report of Six Biopsy Confirmed Cases.

Tumor-like mass lesion is a rare subtype of primary angiitis of the central nervous system (ML-PACNS). This report describes six patients of histologically verified ML-PACNS. The mean age was 44.5 years (range 25-68) and four were males. Presenting symptoms headache (5), focal neurologic deficits (5), and seizures (4). On magnetic resonance imaging (MRI) the lesion was unifocal in two and multifocal in four patients. Consistent radiological findings were mass lesions with heterointense internal morphology with areas of diffusion restriction (DWI), and variable post-contrast enhancement. Pathologically vasculitis was classified as: Granulomatous in one, necrotizing in two and lymphocytic in three. There were two deaths. In conclusion patients with ML-PACNS are likely to be younger and more likely to present with seizures. MRI lesions with hetrointense internal morphology with areas of DWI was a consistent finding and may be a clue for the diagnosis of ML-PACNS.

Clinical and imaging features distinguishing Susac syndrome from primary angiitis of the central nervous system.

INTRODUCTION: To assess clinical and/or imaging features useful to distinguish between Susac syndrome (SuS) and primary angiitis of central nervous system (PACNS). METHODS: Multicenter retrospective analysis of two cohorts of Argentine patients diagnosed with SuS and PACNS. RESULTS: 13 patients diagnosed with SuS (6 women and 7 men, mean age 35 ±â€¯10 years) and 15 with PACNS (10 women and 5 men, mean age 44 ±â€¯18 years) were analyzed. Cognitive impairment (11 out of 13 patients vs. 5 out of 15, p = .006), ataxia (7 out of 13 vs. 2 out of 15, p = .042) and auditory disturbances (7 out of 13 vs. 0 out of 15, p = .003) were more frequent in SuS patients; whereas seizures were more frequent in PACNS patients (8 out of 15 vs. 1 out of 13, p = .035). On MRI, corpus callosum (CC) involvement was observed more often in SuS, with abnormalities in CC genu, in 13 out of 13 SuS patients vs. only 2 out of 15 PACNS patients (p < .001); in CC body these were present in 13 out of 13 SuS patients vs. 1 out of 15 PACNS patients, (p < .001); and in CC splenium in 12 out of 13 Sus patients vs. 1 of 15 PACNS, p < .001). Cortical lesions were more frequent in PACNS patients (10 out of 15 vs. 3 out of 13 SuS patients, p = .02), as were hemorrhages (5 out of 15 vs. 0 out of 13 SuS, p = .04) and multiple basal ganglia infarcts (7 out of 15 vs. 1 out of 13 Sus, p = .037). CONCLUSION: Specific clinical and/or MRI findings may help distinguish SuS from PACNS with potential therapeutic implications.