Central Nervous System Vasculitis Research Articles

Moyamoya disease mimicking primary central nervous system vasculitis: A case report

Rationale: Both Moyamoya disease (MMD) and primary central nervous system vasculitis (PCNSV) cause cerebrovascular stenosis resulting in similar ischemic neurological events, although therapeutic approaches are distinct from each other. High-resonance vascular wall imaging (HRVWI) with contrast-enhanced magnetic resonance imaging (MRI) is believed to be useful to differentiate PCNSV from MMD by detecting enhancement of cerebral vascular walls. However, recent studies have reported that the vascular walls of major arteries and superficial cerebral arteries are also enhanced by HRVWI in some MMD cases. Patient concerns: A 40-year-old Chinese woman admitted to our hospital with transient weakness of the right hand for a week. A cerebral infarction of the left frontal lobe was detected by diffusion-weighted brain MRI. Magnetic resonance angiography demonstrated severe stenosis of the left middle cerebral artery (MCA) and extensive vascular narrowing. Magnetic resonance angiography incidentally taken 3 years before admission showed only a mild stenosis at the proximal portion of right MCA with intact left internal carotid artery (ICA) and MCA. Moreover, on HRVWI with contrast-enhanced MRI after admission, the wall of ICA was strongly enhanced, and the superficial cerebral arteries were also highly enhanced, which initially suggested PCNSV. Despite these findings, reticular blood vessels were confirmed by digital subtraction angiography, and p.R4810K polymorphism in the ring finger protein 213 gene was detected. Diagnosis: Based on these result, the patient was diagnosed with MMD. Interventions: Bypass surgery was performed. Outcomes: Ischemic events have never been experienced since surgery. Lessons: Our MMD case demonstrated marked asymmetrical progression of cerebral artery stenosis, and enhanced vascular walls of ICA and superficial cerebral arteries by HRVWI, which made differential diagnosis from PCNSV difficult. Genetic analysis of SNP in the ring finger protein 213 gene should be performed to rule out MMD to avoid misdiagnosis of PCNSV particularly in Asian population.

Current and future advances in practice: a practical approach to the diagnosis and management of primary central nervous system vasculitis

Abstract Primary CNS vasculitis (CNSV) is a rare, idiopathic autoimmune disease that, if untreated, can cause significant morbidity and mortality. It is a challenging diagnosis due to multiple mimics that can be difficult to differentiate, given that the CNS is an immunologically privileged and structurally isolated space. As such, diagnosis requires comprehensive multimodal investigations. Usually, a brain biopsy is required to confirm the diagnosis. Treatment of CNSV involves aggressive immunosuppression, but relapses and morbidity remain common. This expert review provides the reader with a deeper understanding of presentations of CNSV and the multiple parallel diagnostic pathways that are required to diagnose CNSV (and recognize its mimics), highlights the important knowledge gaps that exist in the disease and also highlights how we might be able to care for these patients better in the future.

Central nervous system vasculitis

La vasculitis primaria del Sistema Nervioso Central (VPSNC) se refiere a un grupo de enfermedades que resultan de la inflamación y destrucción de los vasos sanguíneos de la médula espinal, encéfalo y meninges, tanto en el sector venoso como arterial, esto puede conducir a la oclusión o formación de aneurismas, con las consiguientes alteraciones isquémico-hemorrágicas.1 La presentación es heterogénea y poco sistematizable. El diagnóstico se establece con un cuadro clínico compatible, una angiografía o biopsia del parénquima encefálico y/o meninges que evidencien vasculitis. Presentamos el caso de un paciente portador de retrovirus con probable VPSNC con clínica compatible, hallazgos imagenológicos sugestivos, con escasa alteración de LCR y EEG.2

Intravenous immunoglobulin and rituximab in a treatment‐refractory COVID‐19‐associated central nervous system vasculitis: A case report and literature review

AbstractCentral nervous system (CNS) vasculitis is an uncommon inflammatory disease that affects the brain and spinal cord. It might present with headache, focal neurological deficits, seizures and encephalopathy. CNS vasculitis might be triggered by systemic vasculitides, connective tissue diseases, malignancies and infectious agents, including severe acute respiratory syndrome coronavirus 2. Diagnosis requires a combination of clinical presentation, serological and cerebral spinal fluid analysis, radiological findings (magnetic resonance imaging and conventional angiography), and brain biopsy. In the lack of randomized prospective studies, the treatment approach is based on retrospective cohort studies, anecdotal reports and therapeutic approaches derived from other vasculitides. In this report, we present a case of a 55‐year‐old man who presented with hemiparesthesia 39 days after coronavirus disease 2019 (COVID‐19) infection. During the disease course, the patient developed right‐sided hemiparesis and was referred to our center. Conventional angiogram suggested CNS vasculitis. After an extensive work‐up, systemic vasculitis was excluded. Despite having been treated with pulse steroid and cyclophosphamide, the patient experienced relapses. As we administered intravenous immunoglobulin and rituximab, remission was achieved both in clinical and radiological aspects. In this study, we present the first case of treatment‐refractory CNS vasculitis associated with COVID‐19, which was treated successfully with intravenous immunoglobulin and rituximab. Second, we report a review of COVID‐19‐related CNS vasculitis articles and applied treatment strategies published in English. To elucidate the mechanism of COVID‐19‐related CNS vasculitis, further research is needed.

Primary Central Nervous System Vasculitis Following Alemtuzumab Treatment for Multiple Sclerosis: A Case Report and Literature Review.

Cerebral vasculitides are often devastating conditions that require immediate diagnosis and treatment. We report a pathologically proven clinical case of primary central nervous system vasculitis in a 50-year-old man with a diagnosis of relapsing-remitting multiple sclerosis after alemtuzumab therapy, which required additional immunosuppression to control this life-threatening condition. In patients presenting subacute neurological deterioration after alemtuzumab therapy, primary central nervous system vasculitis should be considered as a differential diagnosis among other autoimmune conditions.

Selective immune suppression using interleukin-6 receptor inhibitors for management of immune-related adverse events

BackgroundManagement of immune-related adverse events (irAEs) is important as they cause treatment interruption or discontinuation, more often seen with combination immune checkpoint inhibitor (ICI) therapy. Here, we retrospectively evaluated the...

Coronavirus Disease 2019-Associated Neurological Manifestations in Children: A Large Single-Center Experience With Rare Cases

BackgroundWe aimed to analyze pediatric patients with coronavirus disease 2019 (COVID-19) with a diverse spectrum of neurological manifestations in a single center since neurological involvement in children is still poorly understood. MethodsWe performed a retrospective study on 912 children aged between zero and 18 years who had a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test result and symptoms of COVID-19 from March 2020 to March 2021 in a single center. ResultsAmong 912 patients, 37.5% (n = 342) had neurological symptoms and 62.5% (n = 570) had no neurological symptoms. The mean age of patients with neurological symptoms was significantly higher (14.2 ± 3.7 vs 9.9 ± 5.7; P < 0.001). Three hundred and twenty-two patients had nonspecific symptoms (ageusia, anosmia, parosmia, headache, vertigo, myalgia), whereas 20 patients had specific involvement (seizures/febrile infection-related epilepsy syndrome, cranial nerve palsy, Guillain-Barré syndrome and variants, acute disseminated encephalomyelitis, central nervous system vasculitis). The mean age of the patients with nonspecific neurological symptoms was significantly higher (14.6 ± 3.1 vs 7.7 ± 5.7; P < 0.001). ConclusionThis study presents a large number of patients with a diverse spectrum of neurological manifestations. The rare neurological manifestations reported in our study will contribute to better understanding the neurological involvement of SARS-CoV-2 in children. The study also points out the differences of SARS-CoV-2-related neurological manifestations between patients at different ages. Physicians should be alert about recognizing the early neurological manifestations of the SARS-CoV-2 in children.

Cyclophosphamide for severe acute forms of central nervous system inflammatory disorders

Cyclophosphamide (CYC) may be an effective treatment in patients who fail first line therapy for severe central nervous system (CNS) inflammatory disorders including CNS vasculitis, neuromyelitis optica, autoimmune encephalitis, tumefactive and aggressive multiple sclerosis (MS). We performed a retrospective analysis of 46 patients treated with CYC after failing first line therapy for severe CNS inflammatory conditions. Primary outcomes included modified Rankin Scale (mRS) for patients classified into a non-MS group, Expanded Disability Status Score (EDSS) for MS patients, and Targeted Neurological Deficit score (TND) for all patients. Secondary outcome included neuroimaging studies following CYC treatment. By the second follow up period (average of 7 months) mRS in the non-MS group improved from 3.7 to 2.2 and EDSS in the MS group improved from 5.6 to 3.8. Average TND score at 7 months was 2.8 (mild-marked improvement). At first follow up (average 5.6 months), 76.2% (32/42) patients had either stable or improving imaging, and 83.3% (30/36) patients had stable or improving imaging at second follow up (average 13.6 months). Adverse events were reported by 31.9% of patients with most common being nausea and vomiting, headache, alopecia, and hyponatremia. Treatment with CYC can result in disease stabilization of severe CNS inflammatory diseases and is generally well tolerated.

Segmental cutaneous leukocytoclastic vasculitis associated with herpes zoster: a case report and literature review.

Varicella zoster virus (VZV) infection may cause large or medium vessel vasculitis, including granulomatous arteritis of the nervous system and central nervous system vasculitis. However, small vessel vasculitis, such as cutaneous leukocytoclastic vasculitis (LCV) associated with localized cutaneous VZV infection, herpes zoster, is uncommon. Herein, we present the case of a 75- year-old man with segmental leukocytoclastic vasculitis associated with herpes zoster on the leg. To the best of our knowledge, there are four cases of segmental leukocytoclastic vasculitis in herpes zoster reported in the English literature; we compared our case with these previous reports. Our review of five patients suggests that most patients were immunosuppressed. We also found that the leg is susceptible to LCV associated with herpes zoster. Anti-viral treatment was effective for LCV as well as herpes zoster. Prior reports have proposed etiologies inducing LCV; for example, immune complexes are mediated by vessel wall damage. In support of this, histopathology in our case showed a C3-positive reaction with the small vessel walls in the dermis in direct immunofluorescence. Although the mechanism of LCV associated with herpes zoster remains unclear, we should consider LCV while diagnosing and treating patients with herpes zoster, especially immunosuppressed patients.

Primary EBV Lymphoproliferative Disease Responsive to Therapy in a Patient with CTLA4-Haploinsufficiency

Epstein-Barr virus lymphoproliferative disease (EBV-LPD) occurs most often in patients with acquired immunosuppression. However, several inborn errors of immunity have been associated with primary EBV-LPD, including pathogenic variants in SH2D1A, ITK, MAGT1, CORO1A, CD27, CTPS1, RASGRP1, and ZAP70 (PMID29942301,34239742). Here, we present a patient with primary EBV-LPD in the setting of CTLA-4 haploinsufficiency. JC is a 25yo male with Evans syndrome, hypogammaglobulinemia, and central nervous system vasculitis who presented to the NIH for evaluation of EBV-LPD. After a complicated course of legionella pneumonia at age 23, he developed recurrent fevers, respiratory distress, hypoxia, and night sweats responsive to dexamethasone. Chest CT revealed innumerable bilateral pulmonary nodules and masses with mediastinal hilar lymphadenopathy and scattered ground glass opacities. Transbronchial biopsy demonstrated EBV-positive B-cell LPD with extensive necrosis and clonal gene rearrangements. He responded well to 1 cycle of rituximab. Two years later, he again had fever, dyspnea on exertion, and hypoxia requiring glucocorticoids. Chest CT revealed ground glass opacities of the lungs, lung nodules/masses, and consolidation. Lung biopsy showed T and B-cell infiltrates, EBV+ B-cells by immunohistochemistry, and a clonal B-cell population (Figure 1). His course was also complicated by concurrent Pneumocystis Jirovecii (PJP) infection. He received 1 cycle of rituximab, trimethoprim-sulfamethoxazole, and sirolimus for treatment of his EBV-LPD, PJP, and underlying CTLA-4 haploinsufficiency respectively with symptomatic and radiologic response (Figure 2). [Display omitted] [Display omitted] NIAID whole exome sequencing (WES) revealed 2 compound heterozygous variants in CTLA-4 in trans: a novel pathogenic variant c.373G > A, p.Gly125Arg, and a non-pathogenic c.326G > A, p.Gly109Glu, shared with his mother(allele frequency of 0.000367 popmaxv.3.1.1 and Cadd score 17). Other variants that may contribute to EBV-LPD are under investigation.EBV-LPD in CTLA-4 haploinsufficiency is rare, previously reported in only 2 pediatric cases (PMID34329649). Additionally, WES revealed compound heterozygous variants in CTLA-4; however, only 1 variant was proven pathogenic. While this patient initially demonstrated excellent response to first line therapy, long-term prognosis is guarded. Abatacept was not included in this patient’s treatment because of an association with progressive LPD in patients with and without CTLA-4 haploinsufficiency. Immune reconstitution with bone marrow transplantation will likely be required for permanent disease control.

Primary central nervous system vasculitis: A diagnostic and therapeutic challenge. A series of 7 patients

IntroductionPrimary central nervous system vasculitis (PCNSV) is a rare disease affecting medium- and small-calibre blood vessels of the central nervous system. ObjectiveThe aim of this study was to analyse clinical findings and diagnostic aspects, with special attention to histopathological findings, as well as the treatments used and treatment response in patients diagnosed with PCNSV at our hospital. Patients and methodsWe conducted a retrospective descriptive analysis of patients with a diagnosis of PCNSV at discharge from our centre and meeting the 1988 Calabrese criteria. To this end, we analysed the hospital discharge records of Hospital General Universitario de Castellón between January 2000 and May 2020. ResultsWe analysed a series of 7 patients who were admitted with transient focal alterations and other less specific symptoms such as headache or dizziness; diagnosis was based on histological findings in 5 cases and on suggestive arteriographic findings in the remaining 2. Neuroimaging results were pathological in all cases, and CSF analysis detected alterations in 3 of the 5 patients who underwent lumbar puncture. All patients received initial treatment with megadoses of corticosteroids followed by immunosuppressive treatment. Progression was unfavourable in 6 cases, with fatal outcomes in 4. ConclusionsDespite the diagnostic challenge of PCNSV, it is essential to attempt to reach a definitive diagnosis using such tools as histopathology and/or arteriography studies, in order to promptly establish appropriate treatment and thus reduce the morbidity and mortality of this condition.

Nivolumab-induced Central Nervous System (CNS) Vasculitis Brought on by a Steroid Taper (P12-13.003)

<h3>Objective:</h3> To illustrate a case of nivolumab-induced CNS vasculitis that developed while tapering steroids and was successfully treated expectantly without immunosuppression <h3>Background:</h3> Immune checkpoint inhibitors (ICIs) with anti-PD-1/PD-L1 and anti-CTLA4 activity are associated with CNS vasculitis. Generally, both intra- and extracranial vasculitides are treated with steroids <h3>Design/Methods:</h3> N/A <h3>Results:</h3> A 75 year-old male received two months of concurrent chemoradiation with weekly carboplatin/paclitaxel for esophageal adenocarcinoma. Esophagectomy was considered, but the patient opted for active surveillance. Three years later, enlarging lung nodules heralded recurrent, metastatic esophageal cancer. Treatment with FOLFOX and nivolumab was initiated. Six months later, due to worsening fatigue, he was transitioned to nivolumab monotherapy. Over the following two weeks, he developed progressive dyspnea. Work-up suggested ICI-associated pneumonitis, and he was started on 50 mg prednisone, with weekly taper. A month later, at 30 mg daily, he developed confusion and was hospitalized. A brain MRI revealed multifocal lesions, some with ring-enhancement, concerning for metastases or abscess. Cerebellar biopsy demonstrated small-vessel CNS vasculitis, but given clinical improvement without treatment the patient was managed expectantly and returned back to baseline over two weeks <h3>Conclusions:</h3> This case of biopsy-proven ICI-associated CNS vasculitis developed while tapering steroids, and was treated conservatively. Steroids are first-line treatment for vasculitis; the development of vasculitis while tapering steroids thus raises the possibility of a rebound effect facilitating the development of vasculitis. Cases of CNS vasculitis that started while tapering steroids have been infrequently reported in the literature, but to our knowledge this is the first description of this phenomenon with ICI-associated CNS vasculitis. Additionally, this patient underwent biopsy with concern for metastasis or abscess, but ultimately did not necessitate treatment for vasculitis. This raises the possibility that active surveillance is a reasonable management strategy in cases of self-resolving ICI-associated CNS vasculitis <b>Disclosure:</b> Dr. Karbhari has nothing to disclose. Dr. Galindo Mendez has nothing to disclose. Dr. Robbins has received personal compensation in the range of $0-$499 for serving as a Consultant for Guidepoint Global Inc. The institution of Dr. Robbins has received research support from Diamond Endowment Fund. The institution of Dr. Robbins has received research support from Reeves Endowment Fund. The institution of Dr. Robbins has received research support from Institute for Ethnomedicine. The institution of Dr. Robbins has received research support from Dartmouth Hitchcock Swigart Ethics Fellowship. Dr. Robbins has received personal compensation in the range of $10,000-$49,999 for serving as a Neurohospitalist with Hayes Locums. Dr. Robbins has received personal compensation in the range of $10,000-$49,999 for serving as a Medical Expert with Vickery &amp; Shepherd. Dr. Robbins has received personal compensation in the range of $10,000-$49,999 for serving as a Medical Expert with Vaccine Injury Compensation Program. Dr. Robbins has received personal compensation in the range of $10,000-$49,999 for serving as a Medical Expert with Kraft Davies PLLC. Dr. Robbins has received personal compensation in the range of $500-$4,999 for serving as a Medical Expert with Northwestern University.

Cerebral Vasculitis in a patient receiving Risankizumab, an Inhibitor of Interleukin-23: First Case Report (P12-3.013)

<h3>Objective:</h3> NA <h3>Background:</h3> Iatrogenic neuroinflammation has been frequently reported in recent years owing to expanding biologic therapies for the treatment of a wide range of disorders including Psoriasis. Here we report a case of Central Nervous System (CNS) vasculitis after initiation of Risankizumab, a monoclonal antibody against Interleukin-23 (IL23) used to treat Psoriasis. <h3>Design/Methods:</h3> Case report. <h3>Results:</h3> A 29-year-old female with moderate psoriasis who was started on Risankizumab about one month prior, presented with encephalopathy and left temporal lobe focal seizures with refractory status epilepticus. Her MRI showed punctate infarcts and areas of enhancement in the left temporal lobe and leptomeninges overlying the left convexity. Extensive work up revealed increased Erythrocyte Sedimentation Rate (72 mm/hr) and positive Cardiolipin (IgM and IgG) and Beta-2 Glycoprotein (IgM and IgG) antibodies suggesting antiphospholipid syndrome (APS) for which she was started on anticoagulation. Lumbar puncture revealed normal opening pressure, glucose, protein and five nucleated cells. Oligoclonal bands, meningitis/encephalitis and autoimmune encephalitis panels were negative. Subsequent brain MRI showed new areas of ischemic lesions. Cerebral angiogram was unremarkable. Biopsy revealed focal perivascular lymphocytes (CD45 and CD3 immunohistochemical stained) infiltration in dural vessels consistent with small-vessel vasculitis. She was treated with high dose steroids with clinical improvement and subsequently planned to treat with Cyclophosphamide. Risankizumab was discontinued due to possible association. <h3>Conclusions:</h3> Iatrogenic neuroinflammation has been increasingly recognized during the new era of biological molecules and monoclonal antibodies for systemic inflammatory disorders and malignancies. Tumor necrosis factor inhibitors and immune checkpoint inhibitors are more commonly associated with neuroinflammation. To the best of our knowledge, this is the first reported case of APS and CNS vasculitis possibly associated with the initiation of IL23 inhibitor Risankizumab. Although causality cannot be established with a single case, it suggests a possible association. <b>Disclosure:</b> Dr. Cabrera Pulla has nothing to disclose. Dr. Amirjanyan has nothing to disclose. Qian Wu has nothing to disclose. Dr. Mui has nothing to disclose. Dr. Imitola has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis . The institution of Dr. Imitola has received research support from biogen. Dr. Imitola has a non-compensated relationship as a Board Member with National MS Society that is relevant to AAN interests or activities. Dr. Imitola has a non-compensated relationship as a Committee Member with International Society for Stem Cell Research that is relevant to AAN interests or activities. Dr. Coban has nothing to disclose.

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.

Mycophenolate mofetil as induction and maintenance immunosuppressive therapy in adult primary central nervous system vasculitis: A prospective observational study.

To observe the clinical and angiographic effectiveness of mycophenolate mofetil (MMF) as induction and maintenance immunosuppressive therapy in primary central nervous system vasculitis (PCNSV). In this open-label prospective study done at a tertiary care neurology centre, adult patients with PCNSV, diagnosed by Calabrese's criteria, were recruited from 2017 to 2021 and treated with glucocorticoids, MMF and standard of care. Patients were followed-up and clinical and angiographic changes were recorded. Total 26 patients were recruited with median age 39years (34-49) with a slight female predilection (61.5%). Angiographic diagnoses were: small vessels disease 11.5%; large vessels disease 42.3% and both in 46.2%. Median duration of follow-up was 24.5months (14.25-38). Proportion of patients with severe disability (modified Rankin Score (mRS) 4-6) at baseline was 73.08% (19/26) which reduced to 7.69% (2/26) (p < 0.001). At the last follow-up mRS = 0 was achieved in 38.5% (10/26) and mRS of ≤ 1 was achieved in 69.2% (18/26). Median time to achieve a mRS ≤ 1 was 12months (95% CI: 6.8-17.2). Angiography was repeated in 16 patients after a median duration of 13months (10.5-19.7), out of which 10 (62.5%) showed improvement and 5 (31.2%) showed non-progression of lesions. MMF may be an effective immunosuppressive therapy in adult PCNSV as both induction and maintenance. Serial DSA of brain may be useful to monitor the effect of treatment. Key Points • Mycophenolate mofetil is effective as induction and maintenance immunosuppressive therapy in PCNSV. • Repeat angiogram may be useful to monitor treatment response in PCNSV.

Close, but no cigar: an unfortunate case of primary angiitis of the central nervous system.

A 64-year-old male with a history of prostate cancer presented to the emergency department with expressive aphasia and severe headache. Previously, he was diagnosed with ischemic strokes at outside hospitals and was subsequently initiated on anticoagulation medication but was later readmitted with a new onset of nontraumatic subarachnoid hemorrhage and later was found to have ischemic changes in the right temporoparietal lobe. He was suspected to have hypercoagulability of malignancy, as he was unresponsive to a wide variety of anticoagulants and his symptoms continued to deteriorate. On presentation, the physical examination was significant for right homonymous hemianopia, with positive antinuclear antibodies and notable erythrocyte sedimentation rate. The results from the full serologic workup was negative. Subsequent imaging of the brain revealed multifocal stenoses in multiple arteries. On further examination, digital subtraction angiography was concerning for vasculopathy, and was initiated on corticosteroids and cyclophosphamide. This is one of the first cases of PACNS in which recurrent strokes were the presenting symptom for PACNS. Vasculitis should be a considered differential in patients with recurrent ischemic strokes and failed anticoagulant therapy. It is important to rule out malignancy and infectious causes due to the wide spectrum of conditions that cause central nervous system vasculitis.

Primary Central Nervous System Vasculitis in Childhood (cPACNS): A Case Series Study

Primary Central Nervous System Vasculitis in Childhood (cPACNS): A Case Series Study

Multiple recurrent aneurysms with angiitis of the central nervous system in a girl: A case report

Primary central nervous system (CNS) vasculitis is a rare immune inflammatory disease confined to the blood vessels of the brain and spinal cord. The total number reported in the world is about 500[1]. Most are negative in cerebral angiography or vascular stenosis and only 1 case of aortic aneurysms reported. A 12-year-old female experienced sudden headache and vomiting. Previous findings of vascular stenosis. Diagnosed as a ruptured aneurysm bleeding. The aneurysm recurred a short time after treatment. Multiple recurrent aneurysms with angiitis of the central nervous system. The patient underwent 2 aneurysm clipping operations, both of which completely clipped the aneurysm. The patient recovered well after surgery. Three months after discharge, DSA reexamination in our hospital showed that the aneurysm was completely clipped without recurrence. Subarachnoid hemorrhage after acute cerebral infarction is rare. In addition, the patient had recurrent aneurysms after the first aneurysm clipping, which emphasized the importance of postoperative drug therapy and blood pressure control.

Central nervous system autoimmune diseases associated with COVID-19: Comprehensive review

The first appearance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) named coronavirus disease 2019 (COVID-19) was reported from Wuhan in December 2019. While this virus displays several respiratory manifestations such as severe pneumonia and acute respiratory distress syndrome, there are several reports of nervous system involvement in the affected patients. Currently, there is a growing number of cases with central nervous system (CNS) autoimmune diseases (ADs) including autoimmune encephalitis (AE), neuromyelitis optica spectrum disorder (NMOSD), CNS vasculitis, acute disseminated encephalomyelitis (ADEM), and multiple sclerosis (MS) secondary to COVID-19 infection. Symptoms of these diseases vary from mainly drowsiness, delirium, and motor deficits in ADEM, MS, and AE and also visual impairment, and sensory problems in NMOSD and transverse myelitis patients. The severity of COVID-19 symptoms was also different from disease to disease. Based on the previous studies moderate corticosteroid therapy or other medication such as intravenous human immunoglobulins (IVIG), and plasma exchange (PLEX) is suggested for the treatment of CNS ADs in COVID patients. Also, patients with a previous history of ADs and other comorbidities such as hypertension, diabetes mellitus, hypercholesterolemia, and ischemic heart disease are at greater risk to develop severe complications of COVID compared to other patients. Current pieces of evidence demonstrated that CNS ADs can occur due to COVID-19 infection and the healthcare system should attention to CNS ADs as a complication of COVID-19. However, further investigations are strongly needed to confirm these findings.

Exploring Gene Expression Profiles in Primary Central Nervous System Vasculitis.

This study was undertaken to explore the gene expression profile of primary central nervous system vasculitis (PCNSV). Brain specimens of 4 patients with granulomatous vasculitis (GV), 5 with lymphocytic vasculitis (LV), 4 with amyloid β-related angiitis (ABRA), and 4 normal controls were studied. RNA-sequencing was performed using the Illumina Hiseq-4,000 platform and the Illumina TruSeq Total-RNA library. Student t test and false discovery rate tests were performed for each of the differentially expressed transcripts. Ingenuity Pathway Analysis was used for the pathway expression analysis. CIBERSORT was used to estimate the abundances of different immune cell subsets in the tissues based on gene expression data. Transcripts differentially expressed between PCNSV and normal brain indicated that endosomal, mitochondrial, and ribosome dysfunction, alterations in protein synthesis, and noncoding RNAs might be involved in PCNSV. Pathway analysis revealed the activation of dendritic cell maturation and antigen processing as well as neuroinflammation in PCNSV versus normal brain, whereas oxidative phosphorylation was inhibited. CIBERSORT estimation of immune cell subsets suggested that activated NK cells, M1 macrophages, memory B cells, and follicular helper T cells were likely to be more prevalent in PCNSV samples. Naïve CD4 T cells and monocytes were mainly estimated to be present in GV and ABRA. Plasma cell and γδ T-cell signatures were mainly found in LV and normal brain. GV showed higher levels of genes associated with macrophage activities and T cells. ABRA showed higher levels of long noncoding RNAs and miR-616. LV showed higher levels of genes encoding immunoglobulins. RNA sequencing confirmed PCNSV heterogeneity. ANN NEUROL 2023;93:120-130.