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

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.

Mitochondrial Strokes: Diagnostic Challenges and Chameleons.

Mitochondrial stroke-like episodes (SLEs) are a hallmark of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS). They should be suspected in anyone with an acute/subacute onset of focal neurological symptoms at any age and are usually driven by seizures. Suggestive features of an underlying mitochondrial pathology include evolving MRI lesions, often originating within the posterior brain regions, the presence of multisystemic involvement, including diabetes, deafness, or cardiomyopathy, and a positive family history. The diagnosis of MELAS has important implications for those affected and their relatives, given it enables early initiation of appropriate treatment and genetic counselling. However, the diagnosis is frequently challenging, particularly during the acute phase of an event. We describe four cases of mitochondrial strokes to highlight the considerable overlap that exists with other neurological disorders, including viral and autoimmune encephalitis, ischemic stroke, and central nervous system (CNS) vasculitis, and discuss the clinical, laboratory, and imaging features that can help distinguish MELAS from these differential diagnoses.

Headache in cerebrovascular diseases.

Headache is a common accompanying symptom of cerebrovascular diseases. The most common patterns of headache for different cerebrovascular disorders, aetiology and pathogenesis and diagnostic workup are reviewed with emphasis on distinguishing characteristics. It will be a clinical guide for physicians who treat patients with headache or cerebral vascular disease.

Intracranial Vessel Wall MRI in Cryptogenic Stroke and Intracranial Vasculitis.

INTRODUCTION: Intracranial vasculopathies easily elude classic stroke work-up. We aim in this work to show that vessel wall-MRI could prove an efficient alternative to digital subtraction angiography for the diagnosis of intracranial vasculopathies by identifying intracranial arterial vessel walls anomalies and contrast enhancement, suggestive of angiitis of the central nervous system. MATERIALS AND METHODS: Clinical and imaging characteristics of stroke patients diagnosed with primary angiitis of the central nervous system based on vessel wall-MRI were retrospectively reviewed and the clinical and imaging features of angiitis associated with intracranial vessel walls anomalies and contrast enhancement detailed. RESULTS: Twenty patients were included (mean age was 59 years old). All patients were admitted for focal neurological deficits of sudden onset that were recurrent in 13 subjects. Cognitive impairment, headache and seizures occurred in, respectively, 13, 5, and 2 patients. Cerebrospinal fluid analysis was abnormal in 15 patients. In MRI, FLAIR sequences showed ischemic infarcts in 20 patients and DWI showed acute infarct in 15 patients. Digital subtraction angiography was performed in 11 patients and disclosed proximal and distal multifocal stenosis in 10 patients along distal irregularities in different vascular territories in 7. For all of our patients, VW-MRI revealed a concentric contrast enhancement of arterial walls, localized in multiple vascular territories, suggesting angiitis. Abnormalities on digital subtraction angiography and/or MR-Angiography, and vessel wall-MRI were consistent in all patients. CONCLUSIONS: This report underlies the added value of vessel wall-MRI to the diagnosis of underlying intracranial vasculopathy, particularly primary angiitis of the central nervous system, without the use of invasive endovascular techniques and the yield of vessel wall-MRI in the work-up of cryptogenic stroke.

Recurrent intracranial hemorrhage and cerebral venous sinus thrombosis: an atypical case of Neuro-Behçet's Syndrome.

We report the case of a 22-year-old man with an history of headaches, seizures, cognitive impairment associated with recurrent intracranial hemorrhage (ICH), acute ischemic stroke (AIS), worsened over the last eighteen months for a new onset of uveitis and cerebral venous sinus thrombosis (CVST). After excluding common causes of lobar ICH, and some rare ones according to the diagnostic protocol proposed by Beuker et al, in the suspicion of Primary Angiitis of the Central Nervous System (PACNS), the gradual development of a low-grade fever, a cutaneous rash, and a papulopustular manifestation on lower back after rachicentesis (pathergy phenomenon), allowed us to make a diagnosis of Neuro-Behçet's Syndrome (NBS) without oral/genital aphthous ulcerations, according to the International Study Group for Behçet's Disease classification criteria for BD (ICBD).

Spatial Distribution of Intracranial Vessel Wall Enhancement in Hypertension and Primary Angiitis of the CNS.

We hypothesized a difference in the spatial distribution of intracranial vessel wall enhancement between CNS vasculitis and risk factors for intracranial atherosclerotic disease (ICAD). Fifty-five vessel wall MR imaging (VWI) exams were included in this retrospective observational study. Intracranial arteries were evaluated for vessel wall enhancement by branching pattern (e.g., primary, secondary, and tertiary segments). Demographic and laboratory data as well as ICAD risk factors, including a diagnosis of hypertension, were collected. A diagnosis of primary angiitis of the CNS (PACNS) was confirmed by biopsy or clinical assessment by a stroke neurologist. Univariate and multivariate Poisson regression models were fit for the outcomes. In multivariate analyses, hypertension showed significant associations with primary (ß = 1.31, 95% CI 0.78-1.88, p < 0.0001) and secondary (ß = 1.15, 95% CI 0.29-2.18, p = 0.05) segments, contrasting with PACNS which showed a distal spatial distribution with significant associations with secondary (ß = 0.77, 95% CI 0.14-1.39, p = 0.05) and tertiary (ß = 1.34, 95% CI 0.68-2.01, p < 0.0001) segments. Our results suggest the spatial distribution of vessel wall enhancement is an important consideration when interpreting VWI exams, particularly in patients with a comorbid diagnosis of hypertension. Given the global prevalence of hypertension, these results are impactful and may improve image interpretation of VWI in stroke patients.

[Primary central nervous system vasculitis]. / Pervichnyi vaskulit tsentral'noi nervnoi sistemy.

Primary vasculitis (angiitis) of the central nervous system (PACNS) is a rare disease targeting the vessels of the brain, spinal cord and leptomeninges without systemic involvement. The etiology is not clear enough. The authors review clinical, laboratory and radiological features of PACNS. Clinical manifestations are variable and depend on the caliber of affected vessels. The main clinical manifestations of small sized vessel vasculitis include encephalopathy (cognitive disorders, epileptic seizures), headache and transient cerebral ischemia. The main clinical presentation of vasculitis of medium/large cerebral arteries is ischemic strokes, which usually develop in different vascular territories. CSF findings in the majority of patients show modest lymphocytic pleocytosis, elevated protein level and occasionally the presence of oligoclonal bands. MRI data are not specific and include infarcts, hyperintensity (FLAIR) and sometimes tumor-like lesions. The gold standard for the verification of PACNS affected small-sized arteries is brain and leptomeningeal biopsy. Cerebral angiography allows the verification of vasculitis of medium and large cerebral arteries revealing segmental narrowings (beading). High resolution black blood MRI before and after contrast injection may visualize intracranial vessel wall contrast enhancement - the sign of inflammation in intracranial arteries. Treatment of PACNS includes corticosteroids and cyclophosphamide. In the case of patient intolerance, rituximab and blockers of tumor necrosis factor may be used.

Cognitive deficits in vasculitis of the nervous system: a cross-sectional study.

Objectives: To identify the cognitive and functional deficits in a well-characterized group of patients with vasculitis of the nervous system. Methods: Sixty-seven patients diagnosed with Central Nervous System (CNS) or Peripheral nervous System (PNS) vasculitis over a 14-year period were retrospectively identified. Data on clinical presentation, laboratory, radiographic and tissue biopsy investigations, and treatment were collated. Cognitive, functional and quality of life evaluation assessments were performed in 31 patients who agreed to participate and included Addenbrooke's Cognitive Examination-revised (ACE-R), Nottingham Extended Activities of Daily Living (NEADL) and EQ-5D-3L quality of life questionnaires. Results: CNS vasculitis patients exhibited cognitive impairment, with a mean ACE-R score of 74/100 (standard deviation (SD) 16). NEADL and EQ-5D-3L scores were in the impaired range at 41/66 (SD 21) and 57/81 (SD 22), respectively. Patients with just PNS vasculitis exhibited fewer cognitive deficits with ACE-R and NEADL scores of 87 (SD 8) and 46 (SD 16) respectively. EQ-5D-3L score was in the impaired range of 65 (SD 22). Conclusions: Vasculitis of the nervous system and, in particular, CNS vasculitis causes cognitive impairment and deficits in functional ability. Such patients should be targeted for cognitive rehabilitation.

Relapse rates and long-term outcome in primary angiitis of the central nervous system.

OBJECTIVE: To analyze the treatment response in patients with primary angiitis of the central nervous system (PACNS). METHODS: In a single-center retrospective observational study, we assessed relapses, remission, and long-term outcome by use of the modified Rankin Scale (mRS) under different immunotherapies. Eligible patients had CNS biopsy in favor of PACNS or neuroimaging compatible with PACNS after exclusion of an alternative diagnosis. Regression models, recurrent event, and linear mixed-effects models were used to estimate the annual relapse rate, relapse and outcome predictors. Favorable outcome was defined as mRS < 3. RESULTS: Of 44 patients, 26 (59%) were female, median age at diagnosis was 43.5 (range 14-83) years, and 25 (57%) had biopsy-proven diagnosis. Median follow-up was 5.1 years. Glucocorticoids were administered in 30 patients at diagnosis (68%), 33 patients (75%) received cyclophosphamide, and 86% of patients had maintenance therapy > 24 months. Overall, 201 treatment episodes with 104 relapses and 4 (9%) deaths occurred. 26 patients had relapses (59.1%). The annual relapse rate was 1.4 (CI 1.1-1.8). Male sex was the only significant predictor of relapse (HR = 3.27, 95% CI 1.57-6.82). Remission occurred in 30 patients (68%). Favorable outcome was evident in 80% of patients after 2 years and 66% of patients at last follow-up. CONCLUSIONS: PACNS is a relapsing-remitting disease with a heterogeneous disease course and mostly favorable outcome under immunotherapy. Male patients have a higher relapse risk; no other relapse or outcome predictor could be identified. PACNS subtype stratification is needed to further evaluate predictors of response.

Seltene Präsentation eines schubförmig remittierender Zentralnervensystem Vaskulitis - Fallbericht.

We report an interesting case of a central nervous system vasculitis, presenting with a relapsing remitting nature and a previously unreported profile of cognitive deficits in this variant of the disease.The patient presented with bilateral headache, left eye upper temporal quarter visual field loss, dyschromatopsia and a transient loss of consciousness. He was previously evaluated for similar set of symptoms over the past eight years. There was a clear relapsing-remitting history, with periods of full remission of 4-6 months.MR studies showed bilateral areas of hyperintensities, representative of small "non-characteristic" changes, likely of a vascular origin.The case discusses clinical conundra during the patient's evaluation, examines possible differential diagnoses and comments on the hypothesised role of statin use in similar cases.

Study on the Clinical, Imaging, and Pathological Characteristics of 18 Cases with Primary Central Nervous System Vasculitis.

BACKGROUND: To summarize the characteristics of primary central nervous system vasculitis from clinical, imaging, and pathological aspects by retrospective study. METHODS: From March 2015 to December 2017, the data of the inpatients of primary central nervous system vasculitis in first Hospital of Jilin University were collected, and their clinical manifestation, imaging, and pathological characteristics were analyzed by using a descriptive method. RESULTS: There were 18 patients, 10 males (55.56%) and 8 females (44.44%) separately. The age ranges from 16 years old to 49 years old, with the median age of 32 years old. There were 8 cases (44.44%) of epileptic seizure, 6 cases (33.33%) of abnormal behavior and cognition, 10 cases (55.56%) with sensorimotor abnormalities, 4 cases (22.22%) with dizziness, 4 cases (22.22%) with headache, 2 cases (11.11%) with facial pain, 2 cases (11.11%) with blurred vision, and 2 cases (11.11%) with unstable walking. Eight patients (44.44%) were identified with cerebral spinal fluid abnormalities. There were 12 cases (66.67%) with bilateral lesions and 6 cases (33.33%) with unilateral lesions, including the frontal lobe (18 cases, 100%), the parietal lobe (10 cases, 55.56%), the temporal and occipital lobe (8 cases, 44.44%). There were 12 cases (66.67%) combined with subcortical white matter involvement, 6 cases (33.33%) combined with meningeal involvement, 2 cases (11.11%) complicated with basal ganglia involvement and 2 cases (11.11%) complicated with spinal cord involvement. Most of the lesions were with unclear border (16 cases, 88.89%), 2 cases (11.11%) were with clear border. Cortical atrophy was identified in 6 cases (33.33%). There were 12 cases (66.67%) with the enhancement of the lesions and meningeal. The 3D Vessel Wall magnetic resonance imaging (VW-MRI) showed uniform thickness in all patients (18/18) with contrast enhancement of the vessel wall of the vasculitis artery. CONCLUSIONS: The clinical manifestation and imaging in primary central nervous system vasculitis are diverse. The 3D VW-MRI could achieve quantification assessment of vasculitis and provide more utility for primary angiitis of the central nervous system.

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.

Vascular Imaging Outcomes of Childhood Primary Angiitis of the Central Nervous System.

BACKGROUND: Inflammation affecting cerebral blood vessels is a common cause of stroke in children. Arterial abnormalities on vascular imaging are an important risk factor for stroke recurrence. We aimed to describe the vascular imaging outcomes in children with primary angiitis of the central nervous system after 12 months and identify factors associated with vascular progression and stroke recurrence. METHODS: We retrospectively analyzed clinical and neuroimaging data from the BrainWorks Registry of children with large-vessel primary angiitis of the central nervous system. Neuroimaging was collected at baseline and at least 12-month follow-up, and vascular outcome was categorized as improved, stable, or progressed based on comparison of magnetic resonance angiography. Univariate clinical and neuroimaging predictors were associated with outcome by Fisher exact test. RESULTS: Our study consisted of 27 children; 20 male; median age was 7.92 years (range, two to 15 years). Twelve patients received steroids (44%). Median follow-up time was 16 months (range, 12 to 56 months). Vascular imaging outcome was categorized as improved in 37%, stable in 22%, and progressed in 41% of patients. Discordant progression, defined as progression and improvement occurring simultaneously across multiple vessels, was observed in 26%. Stroke recurred in 15%, occurring exclusively in the group with progression on follow-up imaging (P = 0.02). CONCLUSIONS: After 12 months, 40% of children with primary angiitis of the central nervous system demonstrated progression on vascular imaging, without apparent clinical or angiographic predictors. Stroke recurrence was associated with vascular progression. Discordant progression is a newly described angiographic finding. Further studies are necessary to determine if this represents a unique characteristic of inflammatory arteriopathies.

Cerebral Amyloid Angiopathy (CAA)-Related Inflammation: Comparison of Inflammatory CAA and Amyloid-ß-Related Angiitis.

Cerebral amyloid angiopathy-related inflammation (CAA-ri) is a relatively rare syndrome of reversible encephalopathy and could be divided into two subtypes of inflammatory CAA (ICAA) and amyloid-ß-related angiitis (ABRA) according to histopathology. We present a case of pathologically proved ABRA with partial seizures and headache, and a focal lesion in the right temporal lobes on magnetic resonance imaging. Summarized from previous 139 ABRA and ICAA cases, ABRA is preferred when the lesion is enhanced on MRI and requires combination drug therapy, while ICAA is highly suspected with ApoE genotype of ɛ4/ɛ4. More clinical markers for diagnosis of CAA-ri warrant further researches.

Brain Microvasculature Involvement in ANCA Positive Vasculitis.

OBJECTIVE: Endothelial dysfunction is associated with arterial stiffness, a factor that is increasingly recognised as an important determinant of cardiovascular risk. High-flow organs such as the brain and kidneys are particularly sensitive to excessive pressure and flow pulsatility. High, local blood flow is associated with low microvascular impedance, which facilitates the penetration of excessive pulsatile energy into the microvascular bed leading to tissue damage. Systemic endothelial dysfunction and arterial stiffness have been demonstrated in peripheral vessels in associated vasculitis (AAV). Although, the brain involvement is not infrequent in AAV, it has not been evaluated previously. Our aim is to evaluate the involvement of the brain microvasculature in AAV. METHODS: Twenty-three patients with inactive AAV were studied. Brain blood flow was assessed by transcranial Doppler (TCD) and single-photon positron emission tomography (SPECT), structural brain involvement by brain MRI and cognitive scores by Montreal Cognitive Assessment (MoCA) test. RESULTS: Lower mean flow velocity (MFV) was associated to altered SPECT perfusion, higher white matter changes (WMC), lower MoCA scores and younger age (p < 0.05). Middle cerebral artery pulsatility index (MCA-PI) was related to hypertension, diabetes, lower scores on MoCA, increased vasculitis damage index (VDI) and perfusion impairment in SPECT (p < 0.05). These data were reproduced for all intracranial arteries. Up to 88.9% of patients had WMC on MRI. A higher lesion load was associated with age, decreased MoCA and fewer MFV with higher PI. The multivariable linear regression analysis showed that the greater the lesion loads, greater the bifrontal atrophy, MCA-PI and lower MoCA scores. Up to 60.9% of patients presented a decreased MoCA score (p = 0.012). It appeared to be related to VDI (p = 0.04), WMC (p = 0.004) and altered SPECT (p = 0.05). CONCLUSIONS: The alterations in brain perfusion SPECT, the presence of white matter lesions on MRI, as well as increased PI and RI with lower MFV of the cerebral vessels in TCD suggest the presence of microangiopathy in asymptomatic AAV that could lead to cognitive impairment.