To facilitate and improve the diagnostic and therapeutic process by systematically reviewing studies on patients with primary angiitis of the CNS (PACNS).
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.
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.
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.
Purpose
Primary angiitis of the central nervous system (PACNS) is a heterogeneous, rare, and poorly understood inflammatory disease. We aimed at non-invasive imaging of activated ...microglia/macrophages in patients with PACNS by PET-MRI targeting the translocator protein (TSPO) with
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FDPA-714 to potentially assist differential diagnosis, therapy monitoring, and biopsy planning.
Methods
In total, nine patients with ischemic stroke and diagnosed or suspected PACNS underwent
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FDPA-714-PET-MRI. Dynamic PET scanning was performed for 60 min after injection of 233 ± 19 MBq
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FDPA-714, and MRI was simultaneously acquired.
Results
In two PACNS patients,
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FDPA-714 uptake patterns exceeded MRI correlates of infarction, whereas uptake was confined to the infarct in four patients where initial suspicion of PACNS could not be confirmed. About three patients with PACNS or cerebral predominant lymphocytic vasculitis showed no or only faintly increased uptake. Short-term
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FDPA-714-PET follow-up in a patient with PACNS showed reduced lesional
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FDPA-714 uptake after anti-inflammatory treatment. Biopsy in the same patient pinpointed the source of tracer uptake to TSPO-expressing immune cells.
Conclusions
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FDPA-714-PET imaging may facilitate the diagnosis and treatment monitoring of PACNS. Further studies are needed to fully understand the potential of TSPO-PET in deciphering the heterogeneity of the disease.
The European Stroke Organisation (ESO) guideline on Primary Angiitis of the Central Nervous System (PACNS), developed according to ESO standard operating procedures (SOP) and Grading of ...Recommendations, Assessment, Development and Evaluation (GRADE) methodology, was elaborated to assist clinicians in the diagnostic and treatment pathway of patients with PACNS in their decision making. A working group involving vascular neurologists, neuroradiologists, rheumatologists, a neuropathologist and a methodologist identified 17 relevant clinical questions; these were addressed according to the patient/population, intervention, comparison and outcomes (PICO) framework and systematic literature reviews were performed. Notably, each PICO was addressed with respect to large vessel (LV)-PACNS and small vessel (SV)-PACNS. Data to answer many questions were scarce or lacking and the quality of evidence was very low overall, so, for some PICOs, the recommendations reflect the ongoing uncertainty. When the absence of sufficient evidence precluded recommendations, Expert Consensus Statements were formulated. In some cases, this applied to interventions in the diagnosis and treatment of PACNS which are embedded widely in clinical practice, for example patterns of cerebrospinal fluid (CSF) and Magnetic Resonance Imaging (MRI) abnormalities. CSF analysis for hyperproteinorrachia and pleocytosis does not have evidence supporting their use as diagnostic tools. The working group recommended that caution is employed in the interpretation of non-invasive vascular imaging due to lack of validation and the different sensitivities in comparison with digital subtraction angiography (DSA) and histopathological analyses. Moreover, there is not a neuroimaging pattern specific for PACNS and neurovascular issues are largely underreported in PACNS patients. The group’s recommendations on induction and maintenance of treatment and for primary or secondary prevention of vascular events also reflect uncertainty due to lack of evidence. Being uncertain the role and practical usefulness of current diagnostic criteria and being not comparable the main treatment strategies, it is suggested to have a multidisciplinary team approach in an expert center during both work up and management of patients with suspected PACNS. Highlighting the limitations of the currently accepted diagnostic criteria, we hope to facilitate the design of multicenter, prospective clinical studies and trials. A standardization of neuroimaging techniques and reporting to improve the level of evidence underpinning interventions employed in the diagnosis and management of PACNS. We anticipate that this guideline, the first comprehensive European guideline on PACNS management using GRADE methodology, will assist clinicians to choose the most effective management strategy for PACNS.
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