Primary Angiitis Of The Central Nervous System Research Articles

P.126 An unlikely impersonator of primary brain tumours: Illustrative case report and literature review of primary angiitis of the central nervous system

Background: Primary angiitis of the central nervous system (PACNS) is a rare inflammatory condition affecting the parenchymal and leptomeningeal vessels of the CNS. PACNS presenting as a solitary mass lesion (ML-PACNS) constitutes a rare subtype of this pathology. Herein we present the first case reported in Canada of ML-PACNS, presenting with clinical and radiographic findings consistent with a high grade glial neoplasm, as well as a review of the literature on ML-PACNS. Methods: Review of the literature from 1987-2023 was conducted using PubMed to identify features of ML-PACNS and possible treatment paradigms. Results: A number of case reports of ML-PACNS were identified, as well as 6 retrospective analyses of a total of 67 patients. Features such as faster rate of symptom onset, and investigations such as MRI vessel-wall imaging and MR spectroscopy were suggested for identification of ML-PACNS. Treatment was highly variable, but followed guidelines for other neuroinflammatory disorders. Conclusions: Preoperative differentiation between ML-PACNS and CNS neoplasms is difficult due to their similar clinical and radiographic features. However, making this distinction is crucial as PACNS mass lesions can regress entirely with immunosuppressive therapy, potentially obviating the requirement for surgical intervention. Beyond diagnostics, further research is required to establish and validate a treatment paradigm.

Cortical Microhemorrhage Presentation of Small Vessel Primary Angiitis of the Central Nervous System.

Primary angiitis of the central nervous system (PACNS) is a rare vasculitis restricted to the brain, spinal cord, and leptomeninges. This study aimed to describe the imaging characteristics of patients with small vessel PACNS (SV-PACNS) using 7 T magnetic resonance imaging (MRI). This ongoing prospective observational cohort study included patients who met the Calabrese and Mallek criteria and underwent 7 T MRI scan. The MRI protocol includes T1-weighted magnetization-prepared rapid gradient echo imaging, T2 star weighted imaging, and susceptibility-weighted imaging. Two experienced readers independently reviewed the neuroimages. Clinical data were extracted from the electronic patient records. The findings were then applied to a cohort of patients with large vessel central nervous system (CNS) vasculitis. We included 21 patients with SV-PACNS from December 2021 to November 2023. Of these, 12 (57.14%) had cerebral cortical microhemorrhages with atrophy. The pattern with microhemorrhages was described in detail based on the gradient echo sequence, leading to the identification of what we have termed the "coral-like sign." The onset age of patients with coral-like sign (33.83 ± 9.93 years) appeared younger than that of patients without coral-like sign (42.11 ± 14.18 years) (P = 0.131). Furthermore, the cerebral lesions in patients with cortical microhemorrhagic SV-PACNS showed greater propensity toward bilateral lesions (P = 0.03). The coral-like sign was not observed in patients with large vessel CNS vasculitis. The key characteristics of the coral-like sign represent cerebral cortical diffuse microhemorrhages with atrophy, which may be an important MRI pattern of SV-PACNS. ANN NEUROL 2024.

Primary angiitis of the central nervous system.

Primary angiitis of the central nervous system (CNS) is an uncommon inflammatory disorder, with highly variable clinical presentation. It needs to be differentiated from several mimickers, such as CNS involvement in systemic vasculitides, connective tissue disorders, infectious disease, and leukodystrophy as well as neoplastic diseases. The diagnosis requires a combination of clinical and laboratory investigations, multimodal imaging, and histopathological examination, which should be available for confirmation. In the present paper, the histopathological features of primary angiitis of the CNS are described and highlighted to help pathologists avoid misdiagnosis of a treatable acquired disease.

Tumor-like Lesions in Primary Angiitis of the Central Nervous System: The Role of Magnetic Resonance Imaging in Differential Diagnosis.

Primary Angiitis of the Central Nervous System (PACNS) is a rare disease and its diagnosis is a challenge for several reasons, including the lack of specificity of the main findings highlighted in the current diagnostic criteria. Among the neuroimaging pattern of PACNS, a tumefactive form (t-PACNS) is a rare subtype and its differential diagnosis mainly relies on neuroimaging. Tumor-like mass lesions in the brain are a heterogeneous category including tumors (in particular, primary brain tumors such as glial tumors and lymphoma), inflammatory (e.g., t-PACNS, tumefactive demyelinating lesions, and neurosarcoidosis), and infectious diseases (e.g., neurotoxoplasmosis). In this review, the main features of t-PACNS are addressed and the main differential diagnoses from a neuroimaging perspective (mainly Magnetic Resonance Imaging-MRI-techniques) are described, including conventional and advanced MRI.

The Hemorrhagic Side of Primary Angiitis of the Central Nervous System (PACNS).

Primary Angiitis of the Central Nervous System (PACNS) is a rare cerebrovascular disease involving the arteries of the leptomeninges, brain and spinal cord. Its diagnosis can be challenging, and the current diagnostic criteria show several limitations. Among the clinical and neuroimaging manifestations of PACNS, intracranial bleeding, particularly intracerebral hemorrhage (ICH), is poorly described in the available literature, and it is considered infrequent. This review aims to summarize the available data addressing this issue with a dedicated focus on the clinical, neuroradiological and neuropathological perspectives. Moreover, the limitations of the actual data and the unanswered questions about hemorrhagic PACNS are addressed from a double point of view (PACNS subtyping and ICH etiology). Fewer than 20% of patients diagnosed as PACNS had an ICH during the course of the disease, and in cases where ICH was reported, it usually did not occur at presentation. As trigger factors, both sympathomimetic drugs and illicit drugs have been proposed, under the hypothesis of an inflammatory response due to vasoconstriction in the distal cerebral arteries. Most neuroradiological descriptions documented a lobar location, and both the large-vessel PACNS (LV-PACNS) and small-vessel PACNS (SV-PACNS) subtypes might be the underlying associated phenotypes. Surprisingly, amyloid beta deposition was not associated with ICH when histopathology was available. Moreover, PACNS is not explicitly included in the etiological classification of spontaneous ICH. This issue has received little attention in the past, and it could be addressed in future prospective studies.

Abstract TP177: Functional Outcome Prediction in Primary Angiitis of the Central Nervous System

Introduction: Predicting the probability of functional independence in patients with primary angiitis of the central nervous system (PACNS) may help guide treatment decisions and prognostication. We sought to develop a prediction model for functional independence in adults with PACNS. Methods: Adults with PACNS were included from an international, multicenter, retrospective, observational cohort (COVAC). Clinical and imaging variables were collected prior to immunosuppressant treatment. Univariable and multivariable logistic regression models were used to identify baseline variables associated with functional independence (modified Rankin Score 0-2), measured 12 months after diagnosis. Results: Among the 194 patients included, 60 (31%) were diagnosed with PACNS based on a positive biopsy. At 12 months, 124 (65%) patients were functionally independent and 12 (6%) were dead. In multivariable logistic regression models, variables predictive of functional independence at 12 months were presence of ≥ 1 intracranial stenosis on CT- or MR-angiogram (aOR 3.33, 95% CI: 1.34-8.77, p=0.01), headache (aOR 2.66, 95% CI: 1.29-5.62, p<0.01), and absence of an altered level of consciousness (aOR 0.09, 95% CI: 0.02-0.28, p<0.001), an acute brain infarct (aOR 0.13, 95% CI: 0.04-0.34, p<0.001), or cognitive impairment (aOR 0.32, 95% CI: 0.15-0.68, p<0.01). A predictive model including these five variables showed good discrimination (c-statistic: 0.79, 95% CI: 0.72-0.86). Purely lymphocytic PACNS (n=34) was not associated with higher odds of functional independence than granulomatous or necrotizing PACNS (n=26) (OR 0.97, 95% CI: 0.33-2.83, p=0.96). Conclusions: This study identified baseline clinical and imaging variables that may predict functional independence in adults with PACNS. Validation of these results is required in an independent cohort.

Primary Angiitis of Central Nervous System related intracranial aneurysm with spontaneous occlusion after immunomodulatory treatment.

Primary Angiitis of the Central Nervous System (PACNS) is an uncommon disease with kaleidoscopic clinical manifestations. Ischemic strokes are commoner than their hemorrhagic counterpart. Intracranial pseudoaneurysms are rarely reported in PACNS cohorts. We hereby describe the case of a 39-year-old female, who presented for evaluation of acute onset of left middle cerebral artery (MCA) ischemic stroke, with cerebral angiogram showing multifocal stenosis and irregularities in intracranial blood vessels with an aneurysm arising from the lenticulostriate branch of the left MCA M1 segment. A diagnosis of probable PACNS was made and patient initiated on immunomodulatory treatment with corticosteroids. 12 weeks follow up neuroimaging studies revealed resolution of the previously described intracranial aneurysm, thereby postulating the possibility of a pseudoaneurysm related to the underlying angiitis.

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.

Comparison of patients with biopsy positive and negative primary angiitis of the central nervous system.

There is limited evidence on when to obtain a central nervous system (CNS) biopsy in suspected primary angiitis of the central nervous system (PACNS). Our objective was to identify which clinical and radiological characteristics were associated with a positive biopsy in PACNS. From the multicenter retrospective Cohort of Patients with Primary Vasculitis of the CNS (COVAC), we included adults with PACNS based on a positive CNS biopsy or otherwise unexplained intracranial stenoses with additional findings supportive of vasculitis. Baseline findings were compared between patients with a positive and negative biopsy using logistic regression models. 200 patients with PACNS were included, among which a biopsy was obtained in 100 (50%) and was positive in 61 (31%). Patients with a positive biopsy were more frequently female (OR 2.90, 95% CI 1.25-7.10, p = 0.01) and more often presented with seizures (OR 8.31, 95% CI 2.77-33.04, p < 0.001) or cognitive impairment (OR 2.58, 95% CI 1.11-6.10, p = 0.03). On imaging, biopsy positive patients more often had non-ischemic parenchymal or leptomeningeal gadolinium enhancement (OR 52.80, 95% CI 15.72-233.06, p < 0.001) or ≥ 1 cerebral microbleed (OR 8.08, 95% CI 3.03-25.13, p < 0.001), and less often had ≥ 1 acute brain infarct (OR 0.02, 95% CI 0.004-0.08, p < 0.001). In the multivariable model, non-ischemic parenchymal or leptomeningeal gadolinium enhancement (aOR 8.27, 95% CI 1.78-38.46), p < 0.01) and absence of ≥ 1 acute brain infarct (aOR 0.13, 95% CI 0.03-0.65, p = 0.01) were significantly associated with a positive biopsy. Baseline clinical and radiological characteristics differed between biopsy positive and negative PACNS. These results may help physicians individualize the decision to obtain a CNS biopsy in suspected PACNS.

Posterior Reversible Leucoencephalopathy Syndrome: Case Series, Comments, and Diagnostic Dilemma.

To report a series of patients with clinical and radiological features suggestive of posterior reversible encephalopathy syndrome (PRES) related to diverse etiologies emphasizing its pathophysiological basis. Posterior reversible encephalopathy syndrome (PRES) may present with a broad range of clinical symptoms from headache and visual disturbances to seizure and altered mentation. Typical imaging findings include posterior-circulation predominant vasogenic edema. Although there are many well-documented diseases associated with PRES, the exact pathophysiologic mechanism has yet to be fully elucidated. Generally accepted theories revolve around disruption of the blood-brain barrier secondary to elevated intracranial pressures or endothelial injury induced by ischemia from a vasoconstrictive response to rising blood pressure or toxins/cytokines. While clinical and radiographic reversibility is common, long-standing morbidity and mortality can occur in severe forms. In patients with malignant forms of PRES, aggressive care has markedly reduced mortality and improved functional outcomes. Various factors that have been associated with poor outcome include altered sensorium, hypertensive etiology, hyperglycemia, longer time to control the causative factor, elevated C reactive protein, coagulopathy, extensive cerebral edema, and hemorrhage on imaging. Reversible cerebral vasoconstriction syndromes (RCVS) and primary angiitis of the central nervous system (PACNS) are invariably considered in the differential diagnosis of new cerebral arteriopathies. Recurrent thunderclap headache (TCH), and single TCH combined with either normal neuroimaging, border zone infarcts, or vasogenic edema, have 100% positive predictive value for diagnosing RCVS or RCVS-spectrum disorders. Diagnosis of PRES in some circumstances can be challenging and structural imaging may not be sufficient to distinguish it from other differential diagnostic considerations like ADEM. Advanced imaging techniques, such as MR spectroscopy or positron emission tomography (PET) can provide additional information to determine the diagnosis. Such techniques are more useful to understand the underlying vasculopathic changes in PRES and may answer some of the unresolved controversies in pathophysiology of this complex disease. Eight patients with PRES resulting from different etiologies varying from pre-eclampsia/eclampsia, post-partum headache with seizures, neuropsychiatric systemic lupus erythematosus, snake bite, Dengue fever with encephalopathy, alcoholic liver cirrhosis with hepatic encephalopathy, and lastly reversible cerebral vasoconstriction syndrome (RCVS). Additionally, a diagnostic dilemma between PRES and acute disseminated encephalomyelitis (ADEM) was notable in one patient. Some of these patients did not have or only very transiently had arterial hypertension. PRES may underlie the clinical conundrum of headache, confusion, altered sensorium, seizures, and visual impairment. PRES need not necessarily be always associated with high blood pressure. Imaging findings may also be variable. Both clinicians and radiologists need to familiarize themselves with such variabilities.

A case of unexpected death due to primary angiitis of the central nervous system.

Primary angiitis of the central nervous system (PACNS) is a rare and fatal cerebral vasculitis mainly involving the arteriole of the pia mater, cerebral cortex, and spinal cord. It has an insidious onset atypical symptoms. In this paper, we reported an unexpected death due to cerebral hemorrhage caused by PACNS. According to the typical clinical manifestations (headache, dizziness, weakness of the limbs, temporary blurred vision, etc.) and pathological examination (wide degeneration and fibrinoid necrosis of blood vessel walls with inflammatory cell infiltration), as well as hematoxylin-eosin staining, immunohistochemistry for CD15 + and gram staining, we finally determined that the patient died due to cerebral vascular rupture and hemorrhage caused by PACNS. This case illustrates the value and key points of autopsy in evaluating sudden deaths.

Vasculitis in the Central Nervous System: Treatment and Outcomes in a Large Single-Center Cohort (P9-5.014)

<h3>Objective:</h3> To describe the demographics, treatment, and outcomes of patients presenting with vasculitis involving the central nervous system (CNS) at a major referral center covering a five-state catchment area in the Intermountain West. <h3>Background:</h3> CNS vasculitis is inflammation of blood vessel walls in the brain or spine that can be life-threatening and/or result in ischemic strokes. Markers suggestive of CNS inflammation include cerebrospinal fluid (CSF) pleocytosis and/or elevated protein level, and on neuroaxis imaging, the presence of parenchymal, leptomeningeal, or vessel wall enhancement. At the time of symptom onset, the diagnostic evaluation focuses on classifying the size of the involved vessels and determining if the vasculitis is a primary angiitis of the CNS or if it is occurring secondary to another process elsewhere in the body, such as a systemic vasculitis, connective tissue disorder, infection, malignancy, or toxic/drug exposure. <h3>Design/Methods:</h3> A retrospective chart review for patients within the University of Utah Health system queried all International Classification of Diseases (ICD) 9 codes for 437.4 (Cerebral arteritis) and ICD10 codes for I67.7 (Cerebral arteritis, not elsewhere classified) with one encounter with a neurologist. Of the 144 total patients identified between January 2012 to October 2022, we further confirmed the diagnosis based on neurologists’ review of each record and categorized patients further to determine if the CNS presentation of vasculitis was primary, secondary, or indeterminate/uncertain. <h3>Results:</h3> We described the demographic characteristics of vasculitis patients with CNS involvement seen at the University of Utah, as well as presenting symptoms, relevant comorbidities, distinct imaging findings (including a focus on imaging modality), CSF abnormalities, treatments, and outcomes. <h3>Conclusions:</h3> This is a comprehensive characterization of patients with vasculitis involving the CNS in a large area of the Intermountain West. Understanding the differences in these patient characteristics, symptoms, and variability in diagnostic and treatment plans will inform better, more efficient approaches. <b>Disclosure:</b> Dr. Hoshina has nothing to disclose. Alen Delic has nothing to disclose. Mr. Wong has nothing to disclose. Dr. Lyden has nothing to disclose. Dr. Kadish has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. The institution of Dr. Kadish has received research support from Alexion Pharmaceuticals. Dr. Clardy has received personal compensation for serving as an employee of Veterans Health Administration (VHA). Dr. Clardy has received personal compensation for serving as an employee of University of Utah Health. Dr. Clardy has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Neurology/AAN Publications. The institution of Dr. Clardy has received research support from Sumaira Foundation for NMO. The institution of Dr. Clardy has received research support from Western Institute for Veteran Research. The institution of Dr. Clardy has received research support from NIH/NINDS. Dr. Clardy has received personal compensation in the range of $500-$4,999 for serving as a AAN Summer Meeting CoDirector Travel and Lodging with AAN. Dr. Clardy has received personal compensation in the range of $500-$4,999 for serving as a Grand Rounds Travel and Lodging with U of Iowa. Dr. Clardy has received personal compensation in the range of $500-$4,999 for serving as a Speaker Honoraria for Grand Rounds with Barrow Neurological Institute. Dr. Clardy has received personal compensation in the range of $500-$4,999 for serving as a Speaker Honoraria for Grand Rounds with Beaumont Health.

Amyloid beta-related angiitis in a patient with light chain systemic Amyloidosis: A rare co-morbidity. (P9-5.013)

<h3>Objective:</h3> To report a rare comorbidity of amyloid beta-related angiitis (ABRA) and systemic light chain amyloidosis (AL) <h3>Background:</h3> ABRA is a rare central nervous system (CNS) disorder with overlapping features of primary angiitis of the CNS and cerebral amyloid angiopathy. ABRA pathophysiology differs from extremely rare CNS involvement in AL. This is the first report of ABRA and AL comorbidity. <h3>Design/Methods:</h3> Case Report <h3>Results:</h3> A 73 year old Caucasian female with AL, prior autologous stem cell transplantation followed by relapse and daratumumab therapy resulting in complete response, presented with subacute development of headaches, global dysphasia and right sided homonymous hemianopia. Brain magnetic resonance imaging (MRI) demonstrated an increased T2/Fluid attenuated inversion recovery signal along the left parietal occipital cortex with mild restricted diffusion and microhemorrhages. Cerebrospinal fluid (CSF) studies showed: pleocytosis (30 nucleated cells/mm3) consisting of mature granulocytes, small mature lymphocytes and rare plasma cells, no monotypic B-cell, overtly aberrant T-cell, or expanded large granular lymphocyte population, no malignant cells; hyperproteinorachia (214 mg/dL); and no markers of intrathecal immunoglobulin G synthesis. Infectious CSF studies, CSF autoimmune encephalopathy panel and rheumatological work up were unremarkable. Steroid treatment (methylprednisolone, 1000 mg/day for 5 days intravenously, followed by a slow oral taper) led to a resolution in visual field deficit and a significant improvement in speech patterns. New microhemorrhages with new foci of restricted diffusion in the left posterior parietal/occipital region and posterior right centrum semiovale were shown on brain MRI three months later. Brain biopsy was performed with no neurological complications and pathology was consistent with ABRA. Liquid chromatography-tandem mass spectrometry of the brain tissue detected a peptide profile consistent with amyloid-beta precursor type amyloid deposition. The patient continued on oral steroid taper and is starting cyclophosphamide. <h3>Conclusions:</h3> Although ABRA is pathophysiologically distinct from and unrelated to AL, those two conditions may rarely co-exist. <b>Disclosure:</b> Dr. Javed has nothing to disclose. The institution of Dr. Jensen has received research support from ASCO / Conquer Cancer Foundation. The institution of Dr. Jensen has received research support from AHRQ. Dr. A Tuchman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Shattuck Labs. Dr. A Tuchman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen. An immediate family member of Dr. Allenzara has received personal compensation for serving as an employee of Atai . An immediate family member of Dr. Allenzara has stock in Atai company stock . An immediate family member of Dr. Ishizawar has received personal compensation for serving as an employee of EMD MilliporeSigma. Dr. Cho has nothing to disclose. Dr. Yap has nothing to disclose. The institution of Dr. Dujmovic Basuroski has received research support from Alexion Pharmaceuticals, Inc. The institution of Dr. Dujmovic Basuroski has received research support from Biogen MA Inc. The institution of Dr. Dujmovic Basuroski has received research support from EMD Serono Research and Development Institute, Inc . The institution of Dr. Dujmovic Basuroski has received research support from Celgene Corporation/Bristol-Myers Squibb. The institution of Dr. Dujmovic Basuroski has received research support from The Bodford Family Transverse Myelitis Center Fund.

PRIMARY ANGIITIS OF THE CENTRAL NERVOUS SYSTEM - A DIAGNOSTIC CHALLENGE.

Primary angiitis of the central nervous system (PACNS) is a rare and severe disease confined to the central nervous system, i.e., the brain and spinal cord. The etiology, pathogenesis and immune mechanism of PACNS have not yet been completely elucidated. The diagnosis is challenging; it is based upon constellation of clinical picture, cerebrospinal fluid analysis, imaging methods or tissue biopsy as the gold standard. In differential diagnosis of PACNS, it is necessary to rule out infectious, malignant or systemic inflammatory diseases, as well as reversible cerebral vasoconstriction syndrome. Immunosuppressants are cornerstone therapy for PACNS, although evidence-based strategies for the management are lacking so far. PACNS is an entity with considerable morbidity and mortality. Awareness of this rare and heterogeneous disease is crucial for establishing early diagnosis and treatment initiation.

Soluble TREM2 is a potential biomarker for the severity of primary angiitis of the CNS.

Primary angiitis of the central nervous system (PACNS) is a severe inflammatory disease, and soluble triggering receptor expressed on myeloid cells 2 (sTREM2) has been reported to be associated with inflammation of the CNS. However, the role of sTREM2 in PACNS remains unknown. We obtained serum and cerebrospinal fluid (CSF) samples from 18 patients diagnosed with PACNS, as well as 14 patients diagnosed with other neurological disorders with no evidence of inflammation. sTREM2 concentrations in the samples were detected by enzyme-linked immunosorbent assay. And routine CSF measurements of PACNS patients were analysed, including number of White Blood Cells (WBC), protein, Immunoglobulin G (IgG) index and CSF/serum quotients. Levels of inflammatory cytokines, including tumor necrosis factor-α, interleukin (IL)-6, IL-8, IL-1β, and complement C4, also were tested. The modified Rankin scale (mRS), National Institutes of Health Stroke Scale (NIHSS), and activities of daily living (ADL) scores were obtained as indicators of disease severity. In PACNS patients, cerebral lesion volume was evaluated by magnetic resonance imaging. sTREM2 levels in serum and CSF were significantly elevated in PACNS patients and significantly associated with the mRS, NIHSS and ADL scores as well as inflammatory cytokine levels. Additionally, positive correlations were observed between the cerebral lesion volume and the sTREM2 levels in both blood and CSF. Higher sTREM2 levels in either the blood or CSF seemed to predict a good prognosis in PACNS patients. Our results indicate an association between serum and CSF sTREM2 levels and the severity of neurological damage. Thus, sTREM2 represents a potential biomarker for monitoring disease and potentially predicting the prognosis of PACNS patients.

Diagnosis and management of adult primary angiitis of the central nervous system: an international survey on current practices.

Primary angiitis of the central nervous system (PACNS) is a rare disease, for which no validated guidelines exist. We report the findings of a survey on the clinical practice of physicians who manage adults with PACNS. An online survey was distributed through neurology, internal medicine, and rheumatology societies in Canada and Europe. Participants who were directly involved as treating physicians for at least two adult patients with PACNS were eligible for the survey. Ninety-six physicians completed the survey. Most participants were neurologists (n = 38, 40%), internists (n = 34, 35%) or rheumatologists (n = 22, 23%). Participants obtained a CNS biopsy in a median of 25% (IQR: 5-50%) of suspected PACNS cases. When determining the degree to which eight scenarios justified a CNS biopsy, participants achieved fair inter-rater agreement (Gwet's AC2 0.30, 95% CI 0.23-0.41). For induction therapy, 81 (84%) participants reported using glucocorticoids and cyclophosphamide in > 50% of patients. After obtaining remission, 85 (89%) participants systematically introduced or maintained immunosuppressive therapy. Glucocorticoids were prescribed for a median of 12months. Maintenance therapy with another immunosuppressant was continued for a median of 24months. In patients who achieved remission, we explored how eight scenarios with different imaging and CSF results supported an increase in treatment. Inter-rater agreement was substantial if the patient was symptomatic (0.66, 95% CI 0.58-0.80) and moderate (0.50, 95% CI 0.45-0.60) if asymptomatic. This survey illustrates current real-world management of PACNS and emphasizes several areas for which physicians still lack study-based evidence and/or clinical practice guidelines.

Childhood Small-Vessel Primary Angiitis of the Central Nervous System: Overlap With MOG-Associated Disease.

Childhood (c) primary angiitis of the central nervous system (PACNS) is a rare condition that most often affects small vessels (SV), is nearly exclusively lymphocytic, and devoid of vessel necrosis. Diagnosis of cSV-PACNS is challenging. We noted possible histological overlap of cSV-PACNS with myelin oligodendrocyte glycoprotein disease (MOGAD) on biopsy, prompting a 10-year retrospective review of our experience. Database-search for brain biopsy cases, age <18 years, performed for an acquired neurological deficit with suspicion of vasculitis, with histological evidence of lymphocytic small-vessel inflammation. We identified 7 patients; 2/7 were serum-positive for anti-MOG antibodies and 1/7 for anti-NMDA antibodies. The remaining 4/7 proved to be idiopathic lymphocytic vasculitis/cSV-PACNS. All 7 showed overlapping features of lymphocytes permeating parenchymal SV walls, vessel wall distortion without fibrinoid necrosis, and absence of microglial clusters or intravascular thrombi. Tissue infarction was confined to a single case of idiopathic lymphocytic vasculitis. Although demyelination was diligently sought, only subtle demyelination was identified in the 2 MOGAD cases and absent in the remainder. There is considerable histological overlap between cSV-PACNS and at least some cases of MOGAD or anti-NMDA-encephalitis; at diagnosis, the differential should include cSV-PACNS but correct classification requires post-biopsy serological testing.

Inflammatory Disorders of the Central Nervous System Vessels: Narrative Review.

Inflammatory disorders of the central nervous system (CNS) vessels, also called CNS vasculitides, can cause substantial disability or even be fatal. Inflammation of the CNS vessels can be caused by primary angiitis of the CNS (PACNS), inflammatory cerebral amyloid angiopathy, or systemic inflammatory disorders. Clinical symptoms of these disorders are often non-specific, such as encephalopathy, cognitive and affective abnormalities, headache and focal neurological symptoms. Diagnostic workup includes a thorough neuropsychiatric examination, blood and cerebrospinal fluid analysis and magnetic resonance imaging (MRI) of the brain and its vessels. Biopsy of the brain remains the gold standard diagnostic test. Timely diagnosis and treatment initiation is of high importance, as it might prevent severe complications, such as ischemic and hemorrhagic stroke. In this review, we describe the specific characteristics of primary and secondary non-infectious CNS vasculitides which help to establish the diagnosis, discuss the peculiarities of the diagnostic workup and present current treatment recommendations.

Outcomes among patients with primary angiitis of the CNS: A Nationwide United States analysis

BackgroundPrimary angiitis of the central nervous system (PACNS) is a relapsing-remitting disease with a heterogeneous course. Case series have delineated the long-term disease course but not acute outcomes or their determinants. The national United States hospital burden of PACNS has not been quantified. MethodsAnalysis of the United States Nationwide Readmissions Database (2016–2018) to characterize the frequency of PACNS hospitalizations, demographic features, inpatient mortality, and discharge outcomes. ResultsDuring the 3-year study period, unweighted 1843 (weighted 3409) patients with PACNS were admitted to the 1078 Healthcare Cost and Utilization Project HCUP participating hospitals; with weighting, this value indicates that 1136 patients were admitted each year to US hospitals, representing yearly 0.01 cases per 100 000 national hospitalizations. The majority of patients were hospitalized in metropolitan teaching hospitals (81.6%). The median age at admission was 54.9 (IQR: 44.0–66.5) years and 59.4% were women. Neurologic manifestations included ischemic stroke in 38.2%, transient ischemic attack in 20.2%, seizure disorder in 22.8%, and intracranial hemorrhage in 13.0%. Overall, 60.0% of patients were discharged home, 35.0% discharged to a rehabilitation facility or nursing home and 5.0% died before discharge. Patient features independently associated with the discharge to another facility or death included older age (odds ratio [OR], 1.03 [95% CI, [1.03–1.04]]), male sex (OR, 1.22 [1.04–1.43]), intraparenchymal hemorrhage (OR, 1.41 [1.08–1.84]), ischemic stroke (OR, 2.79 [2.38–3.28]), and seizure disorder (OR, 1.57 [1.31–1.89]). ConclusionOur study showed PACNS is still a rare inflammatory disorder of the blood vessels of the central nervous system suggesting an annual hospitalization of 5.1 cases per 1,000,000 person-years in the more diverse and contemporary US population. Overall, 4 in 10 had unfavorable discharge outcome, being unable to be discharged home, and 1 in 20 died before discharge.

Primary angiitis of the central nervous system and reversible cerebral vasoconstriction syndrome: analysis of the National Inpatient Sample.

Primary angiitis of the central nervous system (PACNS) and reversible cerebral vasoconstriction syndrome (RCVS) are two rare syndromes that affect the cerebral vasculature. Both conditions have been shown to cause severe neurologic complications. Distinguishing these two conditions in clinical practice is often challenging. Here, we compare the clinical features and outcomes of RCVS and PACNS hospitalizations against the general adult inpatient population. We conducted a retrospective review of hospitalizations with a diagnosis of PACNS or RCVS from 2016 to 2018 in the National Inpatient Sample (NIS) database. Multivariate analysis was performed to calculate adjusted odds ratios (ORadj) for hospital outcomes. In the NIS, 3305 hospitalizations had a diagnosis of RCVS and 6035 hospitalizations had a diagnosis of PACNS. RCVS hospitalizations had a significantly greater association with cerebral aneurysms (ORadj 23.80), hemiplegia/hemiparesis following subarachnoid hemorrhage (SAH) (ORadj 324.09), ischemic stroke (ORadj 7.59), and nontraumatic SAH (ORadj 253.61). PACNS hospitalizations had a significantly greater association with hemiplegia/hemiparesis following cerebrovascular accident (CVA) (ORadj 6.16), ischemic stroke (ORadj 11.55), nontraumatic SAH (ORadj 7.29), seizure (ORadj 2.49), and in-hospital mortality (ORadj 2.85). We performed an analysis of the NIS to better understand RCVS and PACNS hospitalizations. Severe neurologic events including CVA and SAH were elevated in both, but SAH and related hemiplegia/hemiparesis were extremely common among RCVS hospitalizations. In-hospital mortality was elevated in PACNS but not RCVS. This information can be used to help clinicians better understand, distinguish, and diagnose these conditions. Key Points • Despite clear description of RCVS and PACNS in the medical literature, there remains a scarcity of national population-based studies comparing these two entities against the general adult inpatient population. • This study aims to fill knowledge gaps in this area. • Here, we compare the clinical features and outcomes of RCVS and PACNS hospitalizations against the general adult inpatient population.