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.

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.

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.

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.

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.

Clinical overview and outcome in a cohort of children with polyarteritis nodosa.

OBJECTIVES: Polyarteritis nodosa (PAN) is a rare vasculitis in childhood and poor information is known about its long-term outcome. Our aim was to describe the clinical features, at onset and during the disease course, of childhood-onset PAN and identify a potential correlation with persistent organ damage and worse outcome in a cohort of paediatric patients with a confirmed diagnosis of PAN. METHODS: A retrospective collection of demographic and clinical data of 52 Caucasian children diagnosed with PAN, fulfilling the EULAR/PRES diagnostic criteria, recruited from eight paediatric rheumatologic centres and one transition unit, was performed. A statistical correlation was made between clinical involvement at onset or during the overall disease course and patients' final outcome. RESULTS: Data from 52 patients (31 males, 21 females) were collected: their mean age at onset was 7.9 years (median 6.3) and mean follow-up period was 6.2 years (median 5.4). At the last follow-up visit, 27 patients (51.9%) were off therapy in clinical remission, 17 (32.7%) were in clinical remission while on medication, and 6 (11.6%) had a persistent or relapsing disease course. Two patients (3.8%) deceased because of severe cerebral involvement. Cranial nerve palsy during the disease course was significantly correlated with a worse prognosis (p=0.011). The presence of nephrogenic hypertension at onset and seizures during the disease course were significantly associated with the development of irreversible organ damage (p= 0.040 and 0.011, respectively). CONCLUSIONS: Childhood PAN is a severe disease with substantial risk of long-term morbidities. In our cohort of patients the worst outcome was significantly correlated with renal and neurological involvement.

Primary angiitis of the central nervous system and reversible cerebral vasoconstriction syndrome.

Primary angiitis of the central nervous system (PACNS) is one of the most devastating pathologic processes that affect the central nervous system (CNS). It results in exclusive inflammation and destruction of CNS blood vessels. Progressive debilitating unexplained neurological deficit associated with abnormal cerebrospinal fluid (CSF) analysis findings is the typical picture of the disease. CNS biopsy is the gold standard diagnostic test. Immunosuppressive therapy is the core treatment. Reversible cerebral vasoconstriction syndrome (RCVS) is a main mimic of PACNS. RCVS is characterized clinically by recurrent thunderclap headache with or without neurological deficit and normal CSF analysis findings and angiographically by reversible diffuse segmental vasospasm of intracranial vessels. A stepwise diagnostic approach should be followed to differentiate PACNS from RCVS and exclude the other clinical, radiographic, and angiographic mimics.

Childhood primary angiitis of the central nervous system: identifying disease trajectories and early risk factors for persistently higher disease activity.

OBJECTIVE: To compare clinical, laboratory, and imaging characteristics of childhood primary angiitis of the central nervous system (PACNS) subtypes at diagnosis and during followup; to characterize disease activity trajectories in childhood PACNS subtypes; and to identify early risk factors for higher disease activity. METHODS: We performed a single-center cohort study of consecutive children diagnosed as having childhood PACNS. Demographic, clinical, laboratory, and imaging data were collected at diagnosis and during standardized clinic visits. Outcome measures included disease activity measured by physician's global assessment. Descriptive statistics were used to assess characteristics of the study cohort, and longitudinal data were analyzed using linear mixed-effects regression. RESULTS: The study cohort consisted of 45 patients with childhood PACNS; 26 had angiography-negative childhood PACNS and 19 had angiography-positive childhood PACNS. There were 24 females, the median age at diagnosis was 9.8 years, and the median followup period was 1.8 years. Patients with angiography-negative childhood PACNS were more likely to be female and to present with seizures, cognitive dysfunction, vision abnormalities, high levels of inflammatory markers, and bilateral findings on magnetic resonance imaging (MRI). Motor deficits and ischemic MRI lesions were more common in angiography-positive disease. Disease activity decreased significantly after treatment in all patients. Distinct trajectories of disease activity over time were identified for both childhood PACNS subtypes. Patients with angiography-negative childhood PACNS had persistently higher disease activity. Seizures at presentation also predicted higher disease activity over time. CONCLUSION: Distinct subtypes of childhood PACNS have unique disease activity trajectories. Patients with angiography-negative disease and seizures at presentation experience higher disease activity. Early recognition of this high-risk cohort may enable the treating physician to initiate targeted therapies and prevent long-term brain injury.

Headache and vasculitis.

Although headaches are common in the general population and have many causes, headaches secondary to inflammatory processes in the blood vessels in the Central Nervous System (CNS) are not so common. The most common types of vasculitis that are associated with headaches include primary CNS vasculitis, systemic necrotizing arteritis, granulomatous vasculitis, and systemic collagen diseases. It is important to differentiate between "true" vasculitides and a condition known and reversible cerebral vasoconstriction syndrome (RCVS). While treatment for many of the vasculitides consists of anti-inflammatory medications, this approach may produce significant complications in RCVS. It is up to the clinician to judiciously use imaging and laboratory data to reach the proper diagnosis and therefore offer the correct treatment to these patients.

Rapidly progressive primary central nervous system vasculitis.

OBJECTIVE: To describe a subset of cases in a large cohort of patients with primary CNS vasculitis (PCNSV) who appear to have a rapidly progressive clinical course. METHOD: In the present study, we use our updated cohort of 131 consecutive patients with PCNSV seen over the 25-year period of 1983-2007 at Mayo Clinic, Rochester, MN, USA. The diagnosis of PCNSV was based on brain/spinal cord biopsy or cerebral angiography. The modified Rankin scale was used to identify rapidly progressive disease and included patients with Rankin scores indicating severe disability or death at diagnosis or within 6 months after the diagnosis. We compared patients with rapidly progressive disease to those without. RESULTS: Compared with the 120 patients without rapidly progressive vasculitis, the 11 patients with rapidly progressive vasculitis more frequently had paraparesis/quadriparesis at presentation, angiographic presence of bilateral, large-vessel vasculitis and MRI evidence of cerebral infarctions; those infarctions were more frequently multiple and bilateral, and more frequently involved both the cortex and subcortical regions on initial MRI. Granulomatous and/or necrotizing histopathological patterns of vasculitis were observed in patients with positive biopsies. CONCLUSION: Rapidly progressive PCNSV appears to form a subset of PCNSV at the worst end of the clinical spectrum of this vasculitis, characterized by bilateral, multiple, large cerebral vessel lesions and multiple CNS infarctions.

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.

Human immunodeficiency virus-associated cytomegalovirus infection with multiple small vessel cerebral infarcts in the setting of early immune reconstitution.

Cytomegalovirus (CMV) infection is an important cause of neurologic disease in the context of advanced human immunodeficiency virus (HIV) infection and is recognized as a cause of immune reconstitution inflammatory syndrome (IRIS) after initiation of highly active antiretroviral therapy (HAART). Central nervous system vasculitis secondary to CMV has only rarely been described in the context of HIV, despite the established ability of CMV to infect microvascular endothelial cells in the brain. However, we report a case that demonstrates the association between CMV and multiple small vessel cerebral infarct lesions after initiation of HAART.

Cerebellar infarction caused by primary central nervous system angiitis of childhood: case report.

BACKGROUND: Cerebellar infarction of childhood is rare, and is difficult in pathological diagnosis. We describe a case of radiographically diagnosed primary central nervous system angiitis of childhood. SUMMARY: A 7-year-old boy experienced dizziness and headache persisting for 7 days. Diffusion-weighted images of magnetic resonance (MR) showed high signals in the left cerebellar hemisphere and vermis. The MR angiogram (MRA) findings were normal. A conventional angiogram demonstrated severe stenoses and occlusions at distal portion of left posterior inferior cerebellar artery, and irregularity in the wall of the cervical portion of the left vertebral artery (VA). Although he recovered without any neurologic deficits, an angiogram 3 months after admission showed occlusion at the cervical portion of left VA and filling of the distal VA with collateral arteries from the deep cervical artery. He was doing well, with no additional changes demonstrated on MRA, 12 months after the onset. CONCLUSION: Although MRA can detect abnormality within the proximal intracranial vessels, angiography is essential, especially in cases with distal stenoses. Repeated angiography in primary central nervous system angiitis of childhood is necessary at least 3 months after the onset, even if the patient has no symptom.

The possible contribution of angiitis to the onset of benign paroxysmal positional vertigo (BPPV).

OBJECTIVE: The aim was to evaluate the oxidative stress and the angiitis in patients with BPPV. METHOD: Patients with benign paroxysmal positional vertigo (BPPV) within 14 days of onset were analyzed. The level of diacron reactive oxygen metabolites (d-ROM) and circulating soluble vascular cell adhesion molecule 1 (VCAM-1), were evaluated. As a treatment the patients were taught to perform the Brandt-Daroff exercise at home by themselves. The prognosis of BPPV, which is measured as the time until the disappearance of positional nystagmus by a physician during the outpatient visit each week, the relation among the level of oxygen metabolites, vascular molecule and the duration until remission were analyzed. RESULTS: The patients who required longer time for the disappearance of positional nystagmus showed high d-ROM and VCAM levels, whereas those who required shorter time for remission showed lower d-ROM and VCAM levels. CONCLUSION: There is an increased expression of VCAM-1 and d-ROM confirming the existence of an angiitis and supporting the vascular involvement in BPPV. The identification of the high levels of d-ROM and VCAM-1 can open the way to selective pharmacological treatments able to correct the oxidative stress and activation of endothelial cells.

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).

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.