Imaging Findings of Cerebral Amyloid Angiopathy, A\u3b2-Related Angiitis (ABRA), and Cerebral Amyloid Angiopathy-Related Inflammation

Vascular inflammation is present in a subset of patients with cerebral amyloid angiopathy (CAA) and has a major influence in determining the disease manifestations. Radiological characterization of this subset is particularly important to achieve early recognition and treatment. We conducted this study to investigate the role of imaging in differentiating CAA with and without inflammation. We reviewed neuroimaging findings for 54 patients seen at Mayo Clinic over 25 years with pathological evidence of CAA and with available neuroimaging at the time of diagnosis. Clinical data were also recorded. Patients were grouped into CAA alone (no vascular inflammation), A\u3b2-related angiitis or ABRA (angiodestructive inflammation), and CAA-related inflammation or CAA-RI (perivascular inflammation). Imaging findings at presentation were compared among patient subgroups. Radiological features supporting a diagnosis of ABRA or CAA-RI were identified. Radiologic findings at diagnosis were available in 27 patients with CAA without inflammation, 22 with ABRA, and 5 with CAA-RI. On MRI, leptomeningeal disease alone or with infiltrative white matter was significantly more frequent at presentation in patients with ABRA or CAA-RI compared with those with CAA (29.6% vs. 3.7%, P=0.02; and 40.7% vs. 3.7%, P=0.002, respectively), whereas lobar hemorrhage was more frequent in patients with CAA (62.3% vs. 7.4%, P=0.0001). Overall, leptomeningeal involvement at presentation was present in 70.4% of patients with ABRA or CAA-RI and in only 7.4% of patients with CAA (P=0.0001). The sensitivity and specificity of leptomeningeal enhancement to identify patients with ABRA or CAA-RI were 70.4% and 92.6%, respectively, whereas the positive likelihood ratio (LR) was 9.5. The sensitivity and specificity of intracerebral hemorrhage to identify patients with CAA were 62.9% and 92.6%, respectively, whereas the positive LR was 8.5. Microbleeds were found in 70.4% of patients with inflammatory CAA at presentation. In conclusion, leptomeningeal enhancement and lobar hemorrhage at presentation may enable differentiation between CAA with and without inflammation. The identification at initial MRI of diffuse cortical-subcortical microbleeds in elderly patients presenting with infiltrative white matter process or prominent leptomeningeal enhancement is highly suggestive of vascular inflammatory CAA

An Update of the Mayo Clinic Cohort of Patients with Adult Primary Central Nervous System Vasculitis

Primary central nervous system vasculitis (PCNSV) is an uncommon condition in which lesions are limited to vessels of the brain and spinal cord. Because the clinical manifestations are not specific, the diagnosis is often difficult, and permanent disability and death are frequent outcomes. This study is based on a cohort of 163 consecutive patients with PCNSV who were examined at the Mayo Clinic over a 29-year period from 1983 to 2011. The aim of the study was to define the characteristics of these patients, which represents the largest series in adults reported to date. A total of 105 patients were diagnosed by angiographic findings and 58 by biopsy results. The patients diagnosed by biopsy more frequently had at presentation cognitive dysfunction, greater cerebrospinal fluid total protein concentrations, less frequent cerebral infarcts, and more frequent leptomeningeal gadolinium-enhanced lesions on magnetic resonance imaging (MRI), along with less mortality and disability at last follow-up. The patients diagnosed by angiograms more frequently had at presentation hemiparesis or a persistent neurologic deficit or stroke, more frequent infarcts on MRI and an increased mortality. These differences were mainly related to the different size of the vessels involved in the 2 groups. Although most patients responded to therapy with glucocorticoids alone or in conjunction with cyclophosphamide and tended to improve during the follow-up period, an overall increased mortality rate was observed. Relapses occurred in one-quarter of the patients and were less frequent in patients treated with prednisone and cyclophosphamide compared with those treated with prednisone alone. The mortality rate and degree of disability at last follow-up were greater in those with increasing age, cerebral infarctions on MRI, angiographic large vessel involvement, and diagnosis made by angiography alone, but were lower in those with gadolinium-enhanced lesions on MRI and in those with cerebral amyloid angiopathy. The annual incidence rate of PCNSV was estimated at 2.4 cases per 1,000,000 person-years. PCNSV appears to consist of several subsets defined by the size of the vessels involved, the clinical characteristics at presentation, MRI findings, and histopathological patterns on biopsy. Early recognition and treatment may reduce poor outcomes

Adult primary central nervous system vasculitis treatment and course: Analysis of one hundred sixty-three patients

Objective To describe the treatment and outcomes of patients with primary central nervous system (CNS) vasculitis. Methods We retrospectively studied a cohort of 163 consecutive patients with primary CNS vasculitis who were seen at the Mayo Clinic over a 29-year period. We analyzed treatments, treatment responses, and factors predictive of outcomes. Results A favorable response was observed in 85% of patients treated with prednisone alone and in 80% of patients treated with prednisone and cyclophosphamide. Relapses were observed in 27% of patients, and 25% of patients had discontinued therapy by the time of the last followup visit. Treatment with prednisone alone was associated with more frequent relapses (odds ratio [OR] 2.90), while large vessel involvement (OR 6.14) and cerebral infarcts at the time of diagnosis (OR 3.32) were associated with a poor response to treatment. Prominent gadolinium-enhanced cerebral lesions or meninges were linked with continued treatment at the last followup encounter (OR 2.28). Higher disability scores at the last followup visit were associated with increasing age at the time of diagnosis (OR 1.44) and cerebral infarctions (OR 3.74), while lower disability scores were associated with gadolinium-enhanced cerebral lesions or meninges (OR 0.35) and cerebral amyloid angiopathy (OR 0.24). Increased mortality was associated with increasing age at diagnosis (hazard ratio [HR] 1.39), diagnosis by angiography (HR 3.28), cerebral infarction (HR 4.44), and large vessel involvement (HR 4.98), while reduced mortality was associated with gadolinium-enhanced cerebral lesions or meninges (HR 0.20). Conclusion The majority of patients with primary CNS vasculitis responded to treatment. Recognition of findings at diagnosis that predict the course or outcome may aid in decision-making regarding therapy

The importance of skip lesions in temporal arteritis

Aim—To determine the frequency of skip lesions in an unselected series of temporal artery biopsies and compare the results with other series. Methods—The study was a retrospective review of 102 consecutive temporal artery biopsies taken in a five year period (1992–1997) in one large hospital. Results—35 cases (34.3%) showed evidence of active cranial vasculitis with pathological evidence of inflammation of the intima or media, with or without giant cells. Three of these cases (8.5%) showed apparent skip lesions: normal intima, media, and adventitia in one segment while in other segments there was clear evidence of active vasculitis. Immunocytochemical stains for leucocyte common antigen (LCA) and CD15 were helpful in identifying the absence of intimal or medial inflammatory cell infiltrates within skip lesions. Skip lesions have been described in up to 28.3% of cases in some series, while others have not found evidence of skip lesions or have identified them in a much smaller percentage of cases. Conclusions—In this series skip lesions were relatively rare, accounting for 8.5% of cases of active vasculitis. The degree of inflammation in temporal arteritis is discontinuous. Immunostaining for inflammatory cells, for example LCA and CD15, may be helpful in identifying the presence of an inflammatory cell infiltrate in skip lesion segments of the temporal artery. Key Words: temporal arteritis • inflammation • skip lesion • immunohistochemistr

Mycophenolate mofetil in primary central nervous system vasculitis

Objective: To evaluate the efficacy and safety of mycophenolate mofetil (MMF) in adult primary central nervous system vasculitis (PCNSV). Methods: We studied a cohort of 163 patients with PCNSV who were seen at the Mayo Clinic from 1983 to 2011. We compared patients treated with MMF and those receiving other therapies. Results: We identified 16 patients treated with MMF. MMF in combination with GCs achieved a favorable response in most patients. A significant proportion of patients treated with MMF had a less severe disability at last follow-up compared to those receiving other therapies (p = 0.023) and cyclophosphamide and prednisone (p = 0.017). No statistically significant differences were observed regarding relapses and ability to discontinue therapy at last follow-up. A trend to a more favorable treatment response was observed in patients treated with MMF compared to those treated with other therapies (p = 0.075). Only 1 patient suspended MMF for severe leukopenia. Conclusion: MMF seems to be an effective and safe therapy for adult PCNSV

Rituximab therapy for primary central nervous system vasculitis: A 6 patient experience and review of the literature

Objectives: To assess the efficacy and safety of Rituximab (RTX) in adult primary central nervous system vasculitis (PCNSV). Methods: We retrospectively assessed the effect of RTX in 6 patients with PCNSV. Five of the 6 were refractory to high dose glucocorticoids (GCs) and/or conventional immunosuppressants (IS). The sixth was newly diagnosed and received RTX in combination with GCs. Clinical evaluation, laboratory tests, and imaging modalities were performed at initial RTX administration and during the follow-up. Treatment response was assessed using the treating physician's global opinion regarding response and the degree of disability using the modified Rankin scale (mRS). We also performed a literature review for previous use of RTX in PCNSV using PubMed, Ovid Medline, and the Cochrane library. Results: The six patients (3 females) had a median age at diagnosis of 50.5 years (range 17\u201368 years). All had active disease when RTX was started. In 4 patients, RTX administration was associated with a marked reduction in the number of flares (from 18 before starting RTX to 3 after). One patient, after an initial improvement, had 2 flares when B cells were depleted and he was not able to reduce prednisone below 20 mg/day. A 6th patient had a flare when B cells recovered and retreatment with RTX re-induced and maintained remission. The median mRS score at last visit (median: 2; range 0\u20134) was lower than that prior to treatment (median 3; range 1\u20135). The median prednisone daily dose before RTX administration was significantly higher than that at last follow-up (p =.006). In the literature review, we identified 5 papers describing 7 patients treated with RTX. Six patients responded to RTX with clinical and MRI improvement with no reported flares after RTX treatment. Conclusions: Our data support a potential role for RTX treatment in selected patients with PCNSV