Secondary Central Nervous System Vasculitis Research Articles

The Contribution of Vessel Wall Magnetic Resonance Imaging to the Diagnosis of Primary and Secondary Central Nervous System Vasculitis.

To describe high-resolution brain vessel wall MRI (VW-MRI) patterns and morphological brain findings in central nervous system (CNS) vasculitis patients. Fourteen patients with confirmed CNS Vasculitis from two tertiary centers underwent VW-MRI using a 3T scanner. The images were reviewed by two neuroradiologists to assess vessel wall enhancement characteristics and locations. Fourteen patients were included (six females; average age 48 ± 19 years). Diagnoses included primary CNS vasculitis (PCNSV) in six patients and secondary CNS vasculitis (SCNSV) in eight, half of which were infection-related. Thirteen patients showed vessel wall enhancement, which was intense in eleven patients (84.6%) and concentric in twelve (92.3%), affecting the anterior circulation in nine patients (69.2%), posterior in two patients (15.4%), and both circulations in two patients (15.4%). The enhancement patterns were similar across different CNS vasculitis types. DWI changes corresponded with areas of vessel wall enhancement in 77% of patients. Conclusions: CNS vasculitis is often associated with intense, concentric vessel wall enhancement in VW-MRI, especially in the anterior circulation. The consistent presence of DWI alterations in affected territories suggests a possible link to microembolization or hypoperfusion. These imaging findings complement parenchymal brain MRI and MRA/DSA data, potentially increasing the possibility of a clinical diagnosis of CNS vasculitis.

Vasculitis in the Central Nervous System: Etiology, Characteristics, and Outcomes in a Large Single-Center Cohort.

For the management of central nervous system (CNS) vasculitis, it is crucial to differentiate between primary and secondary CNS vasculitis and to understand the respective etiologies. We assessed the etiology, characteristics, and outcomes of patients with CNS vasculitis. A single-center retrospective chart review was conducted at the University of Utah, Department of Neurology, between February 2011 and October 2022. The median age of the 44 included patients at diagnosis was 54years; 25.0% were men. Compared to primary CNS vasculitis, secondary CNS vasculitis exhibits higher fever incidence (observed in infectious and connective tissue disorder [CTD]-associated vasculitis), low glucose levels (mostly in infectious vasculitis) and unique cerebrospinal fluid oligoclonal bands (observed in infectious and CTD-associated vasculitis). Patients with inflammatory cerebral amyloid angiopathy (CAA) were older and more commonly had microhemorrhage than primary angiitis of the CNS (PACNS). All patients with CTD-associated vasculitis had a known history of CTD at presentation. Brain biopsies were performed on 10 of 17 PACNS patients and 4 of 8 inflammatory CAA patients, confirming vasculitis in 7 and 4 patients, respectively. Intravenous methylprednisolone was the predominant induction therapy (63.6%), and cyclophosphamide was the most used adjunctive therapy. Cyclophosphamide, rituximab, azathioprine, and mycophenolate mofetil were utilized as maintenance therapy, often with concurrent prednisone. Patients with inflammatory CAA had a higher tendency for relapse rates than PACNS. This study highlights the variations in patients' characteristics, symptoms, and treatment for CNS vasculitis. Understanding these differences can lead to more efficient diagnostic and management strategies.

Systemic lupus erythematosus with autoimmune neurological manifestations in a carrier of chronic granulomatous disease - a rare presentation

Chronic granulomatous disease (CGD) is an uncommon genetic immunodeficiency disorder affecting neutrophil function, characterized by recurrent bacterial and fungal infections. X-linked carriers of CGD have an increased risk of autoimmune disorders, in particular lupus like disorders. We describe the case of a 37 years old female carrier of X-linked CGD, who presented with clinical features and serology consistent with a definite diagnosis of Systemic lupus erythematosus (SLE), with rare immune mediated neurological manifestations including secondary central nervous system (CNS) vasculitis and Longitudinally extensive transverse myelitis (LETM), responsive to immunomodulation. These neurological manifestations have not been described previously in carriers of CGD. We recommend early diagnosis of these immune mechanisms, especially in X-linked carriers of CGD, and appropriate immunomodulation in order to improve life expectancy and improve neurological outcome.

Elevated cerebrospinal fluid levels of total protein in patients with secondary central nervous system vasculitis and giant cell arteritis

Objectives: Secondary central nervous system vasculitis (SCNSV) is an extremely rare, refractory, and fatal disease in patients with giant cell arteritis (GCA). We compared the characteristics of GCA patients with and without SCNSV.Methods: This retrospective, single-center, observational cohort study included 35 patients with GCA admitted to Juntendo University Hospital from April 2009 to March 2019. The primary outcome was all-cause mortality.Results: We diagnosed four patients with GCA and SCNSV (SCNSV group) and 31 patients with GCA but no SCNSV (non-SCNSV group). The mortality rate of the SCNSV and non-SCNSV groups was 100% and 10%, respectively (p = .001). The SCNSV group had lower serum levels of C-reactive protein at the time of GCA diagnosis and higher cerebrospinal fluid (CSF) levels of total protein (102 mg/dL vs. 38 mg/dL, p = .008) and albumin (66 mg/dL vs. 21 mg/dL, p = .008) at the time of SCNSV diagnosis.Conclusion: At the time of SCNSV diagnosis, GCA patients had elevated CSF total protein and albumin levels. CSF examination in GCA patients suspected of having SCNSV may be useful for early diagnosis of SCNSV.

Cyclophosphamide for Suspected Primary Angiitis of the Central Nervous System in a Patient with Human Immunodeficiency Virus: A Case Report

Introduction: Central nervous system (CNS) vasculitis is rare, including in human immunodeficiency virus (HIV), occurring in less than 1% of patients. Systemic vasculitis affecting the CNS is termed secondary CNS vasculitis, whereas primary CNS vasculitis, referred to as primary angiitis of the CNS (PACNS) refers to an extremely rare disease specifically confined to the CNS. Only some cases of PACNS in HIV patients have been reported in literature. Case Report: We report a case of a 46-year-old female with HIV who developed probable primary CNS vasculitis, which was treated with intravenous cyclophosphamide and glucocorticoids for both induction and maintenance. A systematic literature review regarding PACNS and its therapeutic management is presented in this report. There were no clinical trials for PACNS. Based on the American Academy of Neurology (AAN) classes of evidence for therapeutic effectiveness, most data is of intermediate or weak strength. Conclusion: This case highlights diagnostic and clinical features of PACNS and provides

Management of primary and secondary central nervous system vasculitis.

This article summarizes the current evidence on the management of primary and secondary central nervous system (CNS) vasculitis. Two recent retrospective cohort studies have described the treatment and outcomes of patients with adult primary central nervous system vasculitis (PCNSV). Although the majority of the patients (>60%) responded to therapy with glucocorticoids alone or in conjunction with cyclophosphamide (CYC) and tended to improve during the follow-up period, an overall increased mortality was observed. The treatment response and the outcomes appeared primarily related to the size of the vessels involved in the inflammatory process. The involvement of small cortical/leptomeningeal vessels was associated with a more benign course, whereas the involvement of larger/proximal cerebral vessels was related to a less favorable prognosis and identified cases that should be treated more aggressively. Glucocorticoids combined with CYC are the mainstay of therapy for secondary CNS vasculitis. Observational studies have documented the efficacy of rituximab as induction therapy in patients with antineutrophil cytoplasm antibody-associated vasculitis (AAV) and CNS disease, while the role of antitumor necrosis factor (TNF) agents is more controversial. Case series have demonstrated the efficacy of anti-TNF agents in patients with neuro-Behçet's disease. Tocilizumab may also be effective in this condition. Recognition of findings at diagnosis that predict the course or outcomes of PCNSV may serve as guide for therapy. Biological agents may provide benefit to difficult-to-treat patients with CNS involvement secondary to AAV and Behçet's disease.

Angiitis of the autonomic central nervous system

Autonomic central nervous system (CNS) angiitis was classified with primary angiitis of the CNS (PACNS) or CNS angiitis secondary to systemic vasculitis. Mean onset age of PACNS was about 50 years. Typical symptoms were a chronic progressive headache and encephalopathy. Cerebrospinal fluid analysis was compatible with aseptic meningitis. Findings from imaging were varied and included arterial stenosis. Exclusion diagnosis of PACNS mimics and a brain biopsy were required for a definite diagnosis. Some collagen diseases could cause secondary CNS vasculitis. Patients with secondary CNS vasculitis were required more extensive immunosuppression therapy.

Primary and secondary central nervous system vasculitis: clinical manifestations, laboratory findings, neuroimaging, and treatment analysis.

The objectives of this study are to compare the initial clinical, laboratory, and imaging features in primary central nervous system vasculitis (PCNSV) vs secondary central nervous system vasculitis (SCNSV) and follow up after treatment with intravenous cyclophosphamide (IV-CYC) plus glucocorticosteroids (GCS): methylprednisolone (MP). Neurological, laboratory, and neuroimaging findings were analyzed in PCNSV and SCNSV patients. Cerebral biopsy (CB) was performed in nine patients. Both groups received at onset MP plus IV-CYC for 6 months, followed by bimonthly IV-CYC plus prednisone (PND) for 12 months. All patients were followed during 36 months. Thirty patients were included (12 PCNSV and 18 SCNSV). Focal and non-focal neurological manifestations were similar in both groups, headache being the most frequent manifestation in both groups. Fatigue, myalgias, arthralgias, neuropathy, low leukocytes and platelets, elevated erythrocyte sedimentation rate, positive antinuclear antibodies (ANA), anti-double-stranded DNA (dsDNA), antineutrophil cytoplasmic antibodies (ANCA), low complement, and rheumatoid factor were more frequent in SCNSV (p < 0.05). In cerebrospinal fluid, pleocytosis and proteins were higher in PCNSV (p < 0.05). Periventricular and subcortical hyperintense lesions were observed in cranial magnetic resonance imaging in both vasculitides. Cerebral angiography and angioresonance showed narrowing of vasculature in all patients in both groups. CB showed gliosis and lymphocytic infiltration within and around the walls in four patients and granulomatous infiltration in the other patients. After treatment, the Kaplan-Meier survival curve showed a higher relapse-free survival in PCNSV (p < 0.05). Neurological manifestations and neuroimaging findings were similar in both groups of vasculitides, but general symptoms, joint, musculoskeletal, and peripheral neuropathy were preponderant in SCNSV. After treatment with IV-CYC and GCS, patients with PCNSV had a higher relapse-free survival than those with SCNSV.

Distinct Phenotype Clusters in Childhood Inflammatory Brain Diseases: Implications for Diagnostic Evaluation

To identify distinct clusters of children with inflammatory brain diseases based on clinical, laboratory, and imaging features at presentation, to assess which features contribute strongly to the development of clusters, and to compare additional features between the identified clusters. A single-center cohort study was performed with children who had been diagnosed as having an inflammatory brain disease between June 1, 1989 and December 31, 2010. Demographic, clinical, laboratory, neuroimaging, and histologic data at diagnosis were collected. K-means cluster analysis was performed to identify clusters of patients based on their presenting features. Associations between the clusters and patient variables, such as diagnoses, were determined. A total of 147 children (50% female; median age 8.8 years) were identified: 105 with primary central nervous system (CNS) vasculitis, 11 with secondary CNS vasculitis, 8 with neuronal antibody syndromes, 6 with postinfectious syndromes, and 17 with other inflammatory brain diseases. Three distinct clusters were identified. Paresis and speech deficits were the most common presenting features in cluster 1. Children in cluster 2 were likely to present with behavior changes, cognitive dysfunction, and seizures, while those in cluster 3 experienced ataxia, vision abnormalities, and seizures. Lesions seen on T2/fluid-attenuated inversion recovery sequences of magnetic resonance imaging were common in all clusters, but unilateral ischemic lesions were more prominent in cluster 1. The clusters were associated with specific diagnoses and diagnostic test results. Children with inflammatory brain diseases presented with distinct phenotypical patterns that are associated with specific diagnoses. This information may inform the development of a diagnostic classification of childhood inflammatory brain diseases and suggest that specific pathways of diagnostic evaluation are warranted.

Limited utility of current MRI criteria for distinguishing multiple sclerosis from common mimickers: primary and secondary CNS vasculitis, lupus and Sjogren’s syndrome

Background: Magnetic resonance imaging (MRI) criteria play an important role in making an earlier diagnosis of multiple sclerosis (MS) in patients presenting with clinically isolated syndrome. Objective: The objective of this paper is to determine whether MRI criteria may be used to distinguish MS from primary and secondary central nervous system (CNS) vasculitis, lupus, and Sjogren’s syndrome. Methods: MRI criteria were applied retrospectively to images for patients with clinically definite MS (CDMS), primary CNS vasculitis, secondary CNS vasculitis, and autoimmune disorders including systemic lupus erythematosus (SLE) and Sjogren’s syndrome. Classical statistics and Bayesian analyses were performed. Results: Overall modified Barkhof’s MRI criteria were statistically significant in distinguishing CDMS (60%) from SLE/Sjogren’s syndrome (17%, p = 0.0173) but not in distinguishing CDMS from primary CNS vasculitis (50%, p = 0.7376) or secondary CNS vasculitis (58%, p = 1.0000). Four of the five other MRI criteria tested were demonstrated to be superior to modified Barkhof’s criteria in predicting MS: nine or more T2 lesions (a component of Barkhof’s criteria), one or more ovoid periventricular T2 lesions, one or more perpendicular periventricular T2 lesions, and one or more T2 lesions larger than 6 mm. Conclusions: MRI criteria, including the modified Barkhof’s criteria, were unsuccessful in distinguishing MS from primary CNS vasculitis or secondary CNS vasculitis and mildly successful in distinguishing MS from SLE/Sjogren’s syndrome.

AB0769 Clinical, laboratory, neuroimaging and treatment of primary versus secondary central nervous system vasculitis

BackgroundPrimary central nervous system vasculitis (PCNSV) is an uncommon condition in which vascular inflammatory lesions are limited to the brain and spinal cord. Diagnostic criteria include a newly acquired neurological...

AB0472 Primary and secondary central nervous system vasculitis: clinical manifestations, laboratory findings, neuroimaging, and treatment analysis

BackgroundPrimary central nervous system vasculitis (PCNSV) is a challenging clinical problem due to itsnon- specific signs and symptoms, inaccessibility of the central nervous system (CNS) tissue for pathologic examination, lack...

Pediatric Inflammatory Diseases

Central nervous system (CNS) vasculitis can affect both adults and children, but some of these occur almost exclusively in childhood. In children may develop as a primary condition or secondary to an underlying systemic disease. Cerebral vasculitis can be classified on the basis of the diameter of the involved vessels, although there is no univocal consensus. The diagnosis of CNS vasculitis is particularly difficult because the available investigative modalities have limited sensitivities and specificities. The most helpful diagnostic tests include cerebrospinal fluid analysis, MRI (MR angiography/venography (MRA/MRV) of the brain, and angiography. However, brain biopsy may be required to diagnose small vessel vasculitis in order to make differential diagnosis with a wide range of conditions, such as degenerative vasculopathies, embolic diseases, or coagulation disorders. This paper discusses on current understanding of most frequent primary and secondary central nervous system vasculitis in children in which are involved small vessel.

Primary and Secondary Central Nervous System Vasculitis

Central nervous system vasculitis is an increasingly recognized inflammatory brain disease causing devastating neurological deficits and psychiatric manifestations in previously healthy children. Primary central nervous system vasculitis represents an isolated inflammatory attack targeting the cerebral vessels. In contrast, in children with secondary central nervous system vasculitis, an underlying condition can be identified. The spectrum of childhood primary and secondary central nervous system vasculitis is rapidly expanding, as is the differential diagnosis including nonvasculitic inflammatory brain diseases and noninflammatory vasculopathies. Early recognition, rapid diagnostic evaluation, and initiation of treatment have led to improved morbidity and mortality. This review focuses on clinical, laboratory, and neuroimaging characteristics of the distinct subtypes of primary childhood central nervous system vasculitis, reports the etiology of secondary central nervous system vasculitis, provides an overview of the differential diagnosis, and reviews the current approaches in treatment.

Masquerades of Acquired Demyelination in Children

The diagnosis of acquired demyelinating syndromes of the central nervous system in children requires exclusion of other acute central nervous system disorders. In a 23-site national demyelinating disease study, standardized clinical, laboratory, and magnetic resonance imaging (MRI) data were obtained prospectively from onset, and serially at 3, 6, and 12 months and annually. Twenty of 332 (6%) participants (mean [SD] age, 10.21 [4.32] years; 12 (60%) female) were ultimately diagnosed with vascular disorders (primary or secondary central nervous system vasculitis, vasculopathy, stroke, or migraine, n = 11 children), central nervous system malignancy (n = 3), mitochondrial disease (n = 2), or central nervous system symptoms in the accompaniment of confirmed infection (n = 4). Red flags that may serve to distinguish disorders in the differential of acquired demyelination are described.

Central nervous system vasculitis in children

To review the current literature of childhood primary and secondary central nervous system (CNS) vasculitis and to evaluate the growing differential diagnosis of inflammatory and noninflammatory brain diseases. Primary angiitis of the central nervous system in children (cPACNS) is a reversible cause of severe neurological deficits and/or psychiatric symptoms. This disease is classified into subtypes based on distinct clinical and radiological features, treatment strategies, and disease trajectories. Also, the increased diagnostic yield from elective brain biopsies in children has improved our ability to diagnose angiography-negative cPACNS. Over the past few years, the differential diagnosis for cPACNS has rapidly expanded due to the characterization of novel inflammatory and noninflammatory brain diseases. Specifically, vasoconstrictive disorders and neuronal antibody-associated conditions have now been described in children and have overlapping clinical features with cPACNS. This review summarizes the recent data on diagnosis, treatment, and prognosis of cPACNS. It also addresses the evolving differential diagnosis for CNS vasculitis. Our improved understanding of these disorders allows a tailored diagnostic approach leading to rapid diagnosis and initiation of therapy in these potentially reversible conditions.

Central nervous system vasculitis

In the past decade, primary and secondary central nervous system (CNS) vasculitides have been more commonly diagnosed and recognized than previously. With the increasing awareness of these disorders, it is crucial for the treating physician to differentiate between causes of CNS vasculitis and to recognize their marked clinical and pathophysiological heterogeneity. This review focuses on the major forms of primary CNS vasculitis, as well as secondary CNS vasculitis with emphasis on their clinical findings, diagnoses, and treatment. The proposal of reversible cerebral vasoconstriction syndromes (RCVS) as a unifying concept for a group of disorders which are characterized by acute-onset severe recurrent headaches, with or without additional neurologic signs and symptoms, and prolonged but reversible vasoconstriction of the cerebral arteries, has been a major breakthrough in this field over the past decade. Recognition of this common mimic (i.e. RCVS) has allowed optimal management of a sizable group of patients previously confused with pathologically documented CNS vasculitis. Sound treatment decisions are based on accurate diagnosis. It is essential for the clinicians involved in the evaluation of patients with CNS vasculitis to be aware of its mimics especially RCVS. This article provides a comprehensive review of CNS vasculitis and its differential diagnosis. Furthermore, it touches upon workup and treatment of CNS vasculitis.

Central nervous system vasculitis in children

To review the current literature of primary and secondary central nervous system vasculitis in children, to evaluate the evolving classification and to suggest an approach to diagnosis. Central nervous system vasculitis in children is a newly recognized inflammatory brain disease, which may develop as a primary condition, or secondary to an underlying systemic disease. Primary angiitis of the central nervous system of childhood (cPACNS) is a reversible cause of severe neurological impairment, including acute ischemic stroke, intractable seizures and cognitive decline. Once clinically suspected, angiography is a key imaging modality. Primary angiitis of the central nervous system of childhood can be divided into large-medium vessel and small-vessel vasculitis, each presenting with distinct clinical and radiological features. Angiogram-negative, small-vessel primary angiitis of the central nervous system of childhood has a broad differential diagnosis that includes both vascular and nonvascular conditions. Recognition of this disease and a thorough diagnostic evaluation is necessary to identify and possibly reverse severe neurological impairment in children. This review summarizes the recent data on diagnosis and differential diagnosis of primary and secondary central nervous system vasculitis in children. Increasing recognition of this condition in children allows for greater understanding of the spectrum of disease presentation and differential diagnosis of this reversible cause of severe neurological impairment in children.

Central nervous system vasculitis in children

Central nervous system (CNS) vasculitis is an increasingly recognized, often devastating inflammatory brain disease of children and adults. In primary or isolated CNS vasculitis/angiitis of childhood (cPACNS), the vascular inflammation is limited to the brain and spinal cord. Secondary CNS vasculitis occurs in a variety of conditions including infections, collagen vascular diseases, systemic vasculidities, and malignancies. Mimics of CNS vasculitis in children include dissections and noninflammatory vasculopathies. Diagnosis of primary CNS vasculitis in both adults and children is based on the Calabrese criteria. This review summarizes recent data on CNS vasculitis in children; reviews the clinical spectrum at presentation and the role of laboratory tests, neuroimaging, and brain biopsy; and discusses treatment strategies, outcome data, and overlapping conditions of cPACNS.

CLASSIFICATION AND HISTOPATHOLOGIC SPECTRUM OF CENTRAL NERVOUS SYSTEM VASCULITIS

There are many different and diverse causes of central nervous system (CNS) vasculitis, and many nonvasculitic disorders that often mimic CNS vasculitis. CNS vasculitis is usually suspected clinically with compatible or suggestive angiographic findings, but a definitive diagnosis is not possible without biopsy confirmation, especially with CNS vasculitis mimickers. Primary CNS vasculitis, although relatively uncommon, is most important because of its overall unfavorable prognosis. Secondary CNS vasculitis occurs in association with a long list of systemic vasculitic and nonvasculitic disorders with variable brain biopsy findings. Because of the focal and segmental distribution of CNS vasculitis, a positive biopsy is diagnostic for the disease demonstrated, but a single isolated negative biopsy does not necessarily exclude primary or secondary CNS vasculitis.