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Abstract: An 18-year-old man presented with encephalopathy, headache, tremor, and left hemiparesis. 18 F-FDG brain PET/MRI revealed pronounced hypometabolism in the right cerebral hemisphere corresponding to extensive T2/FLAIR signal abnormality, with accompanying miliary enhancement and microhemorrhages in this region. The differential diagnosis favored an autoimmune or inflammatory origin, rather than an infectious or neoplastic etiology. Brain biopsy demonstrated nonnecrotizing granulomatous inflammation affecting the vessel walls, without evidence of glial neoplasm, lymphoma, or infection. Treatment with corticosteroids was subsequently initiated, with favorable clinical response., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Cerebral amyloid angiopathy (CAA) is a progressive neurodegenerative small vessel disease that is associated with intracranial hemorrhage and cognitive impairment in the elderly. The clinical and radiographic presentations have many overlapping features with vascular cognitive impairment, hemorrhagic stroke, and Alzheimer disease (AD). Amyloid-β-related angiitis (ABRA) is a form of primary CNS vasculitis linked to CAA, with the development of spontaneous autoimmune inflammation against amyloid in the vessel wall with resultant vasculitis. The diagnosis of ABRA and CAA is important. ABRA is often fatal if untreated and requires prompt immunosuppression. Important medical therapies such as anticoagulation and antiamyloid agents for AD are contraindicated in CAA. Here, we present a biopsy-proved case of ABRA with underlying occult CAA. Initial 1.5T and 3T MR imaging did not suggest CAA per the Boston Criteria 2.0. ABRA was not included in the differential diagnosis due to the lack of any CAA-related findings on conventional MR imaging. However, a follow-up 7T MR imaging revealed extensive cortical/subcortical cerebral microbleeds, cortical superficial siderosis, and intragyral hemorrhage in extensive detail throughout the supratentorial brain regions, which radiologically supported the diagnosis of ABRA in the setting of CAA. This case suggests an increased utility of high-field MR imaging to detect occult hemorrhagic neuroimaging findings with the potential to both diagnose more patients with CAA and diagnose them earlier., (© 2024 by American Journal of Neuroradiology.)

Background and Objectives: Cerebral amyloid angiopathy-related inflammation (CAA-RI) and biopsy-positive primary angiitis of the CNS (BP-PACNS) have overlapping clinicoradiologic presentations. It is unknown whether clinical and radiologic features can differentiate CAA-RI from BP-PACNS and whether both diseases have different relapse rates. The objectives of this study were to compare clinicoradiologic presentations and relapse rates in patients with CAA-RI vs BP-PACNS., Methods: Patients with CAA-RI and BP-PACNS were enrolled from 2 retrospective multicenter cohorts. Patients with CAA-RI were biopsy-positive or met probable clinicoradiologic criteria. Patients with BP-PACNS had histopathologic confirmation of CNS angiitis, with no secondary etiology. A neuroradiologist read brain MRIs, blinded to the diagnosis of CAA-RI or BP-PACNS. Clinicoradiologic features were compared using univariable logistic regression models. Relapse rates were compared using a univariable Fine-Gray subdistribution hazard model, with death as a competing risk., Results: This study enrolled 104 patients with CAA-RI (mean age 73 years, 48% female sex) and 52 patients with BP-PACNS (mean age 45 years, 48% female sex). Patients with CAA-RI more often had white matter hyperintense lesions meeting the probable CAA-RI criteria (93% vs 51%, p < 0.001), acute subarachnoid hemorrhage (15% vs 2%, p = 0.02), cortical superficial siderosis (27% vs 4%, p < 0.001), ≥1 lobar microbleed (94% vs 26%, p < 0.001), past intracerebral hemorrhage (17% vs 4%, p = 0.04), ≥21 visible centrum semiovale perivascular spaces (34% vs 4%, p < 0.01), and leptomeningeal enhancement (70% vs 27%, p < 0.001). Patients with BP-PACNS more often had headaches (56% vs 31%, p < 0.01), motor deficits (56% vs 36%, p = 0.02), and nonischemic parenchymal gadolinium enhancement (82% vs 16%, p < 0.001). The prevalence of acute ischemic lesions was 18% in CAA-RI and 22% in BP-PACNS ( p = 0.57). The features with the highest specificity for CAA-RI were acute subarachnoid hemorrhage (98%), cortical superficial siderosis (96%), past intracerebral hemorrhage (96%), and ≥21 visible centrum semiovale perivascular spaces (96%). The probable CAA-RI criteria had a 71% sensitivity (95% CI 44%-90%) and 91% specificity (95% CI 79%-98%) in differentiating biopsy-positive CAA-RI from BP-PACNS. The rate of relapse in the first 2 years after remission was lower in CAA-RI than in BP-PACNS (hazard ratio 0.46, 95% CI 0.22-0.96, p = 0.04)., Conclusion: Clinicoradiologic features differed between patients with CAA-RI and those with BP-PACNS. Specific markers for CAA-RI were hemorrhagic signs of subarachnoid involvement, past intracerebral hemorrhage, ≥21 visible centrum semiovale perivascular spaces, and the probable CAA-RI criteria. A biopsy remains necessary for diagnosis in some cases of CAA-RI. The rate of relapse in the first 2 years after disease remission was lower in CAA-RI than in BP-PACNS.

Objective: 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., Methods: From the multicentre 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., Results: Two hundred 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 (odds ratio [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-ischaemic 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-ischaemic parenchymal or leptomeningeal gadolinium enhancement (adjusted OR 8.27; 95% CI: 1.78, 38.46; P < 0.01) and absence of ≥1 acute brain infarct (adjusted OR 0.13; 95% CI: 0.03, 0.65; P = 0.01) were significantly associated with a positive biopsy., Conclusion: 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., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Competing Interests: The authors have no conflict of interest to declare.

Objective: 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)., Methods: 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., Results: 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., Interpretation: 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;96:194-203., (© 2024 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

A 79-year-old woman presented with difficulty walking and disturbance of consciousness. Magnetic resonance imaging revealed diffuse white matter lesions and abnormal signals along the surface of the brain and sulci. A brain biopsy revealed granulomatous vasculitis with eosinophil infiltration. There was no peripheral blood eosinophilia or evidence of angiitis in other organs, and primary angiitis of the central nervous system (PACNS) with pathological findings of eosinophilic granulomatosis with polyangiitis (EGPA) was diagnosed. Steroids and other immunosuppressant therapies showed only limited effects. PACNS with pathological findings of EGPA is extremely rare, and a prompt brain biopsy is necessary for a diagnosis.

Primary CNS vasculitis (PCNSV) is uncommonly considered in the differential diagnosis of tumor-like lesions. This case report of tumefactive PCNSV highlights imaging features that should increase clinical suspicion for CNS vasculitis, potentially lending to earlier diagnosis and treatment. A 62-year-old man presented with a 1-month history of focal motor seizures and cortical sensory loss localizing to the right frontoparietal lobe. Noncontrast head CT was suggestive of glioma, resulting in intravenous dexamethasone administration and admission to neurosurgery. MRI appearance was atypical for glioma, with relative preservation of regional anatomy, intralesional microhemorrhage, and patchy peripheral enhancement. Despite normal CT angiogram, CSF, and serum inflammatory markers, brain biopsy was suggestive of lymphocytic vasculitis. Extensive workup for secondary causes was negative, and he was diagnosed with tumefactive PCNSV. Treatment with corticosteroids and cyclophosphamide resulted in sustained clinical and radiologic improvement. Tumefactive PCNSV is an angiogram-negative small-vessel vasculitis that has a lymphocytic histologic pattern. Tumefactive PCNSV constitutes over 10% of PCNSV cases and can be recognized by the presence of intralesional microhemorrhages, absence of diffusion restriction, and a patchy or nodular enhancement pattern. The most important mimicker is CNS lymphoma, which has a similar imaging and histologic pattern. If individuals with tumefactive PCNSV do not have a sustained immunotherapy response, repeat biopsy should be promptly performed.

Background: Unruptured intracranial aneurysms (UIAs) are rarely reported in primary central nervous system vasculitis (PCNSV). In this study we described the clinical findings, response to therapy, and outcomes of UIA in a large cohort of PCNSV patients., Methods: We retrospectively studied 216 consecutive patients with PCNSV, selected by predetermined diagnostic criteria, who were seen during a 40-year period. UIAs were identified on cerebral angiography. The clinical, laboratory, radiologic and pathologic findings, management, and outcomes of patients with UIA were described and compared with those without UIA., Results: 12/216 (5.5 %) PCNSV patients had at least one UIA. Two patients underwent biopsies; one yielded negative results, while the other showed necrotizing vasculitis. Eleven patients had evidence of UIA on angiogram at diagnosis. One patient developed an aneurysm during the follow-up associated with a worsening of vasculitic radiological findings. The most common presenting symptom for PCNSV in the setting of UIA was headache (67 %), followed by persistent neurologic deficit or stroke (50 %). Most patients with UIA presented with multiple cerebral infarcts on MRI (67 %), one patient had subarachnoid hemorrhage, and one left parieto-occipital intracerebral hematoma, both unrelated to the aneurysm. Black blood imaging was performed in 4 patients and 2 showed segmental circumferential mural enhancement involving multiple vessels. Two patients had 2 UIAs, while the other 10 had 1. The most frequent UIA location was internal carotid artery (50 %), followed by anterior cerebral artery (21 %). Ten of the UIAs were < 5 mm in diameter, and 3 were 5-7 mm in diameter; the size was not available for one. All UIAs were unchanged in size and configuration during follow-up (median: 18.5 months; range 1-151 months) and no new aneurysms were detected. Compared to the 204 patients with PCNSV without a UIA, no significant clinical differences were observed, except for a reduced disability at last follow-up (p = 0.038)., Conclusions: UIAs uncommonly occur in PCNSV., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background and Objective: Primary angiitis of the central nervous system (PACNS) is a rare form of vasculitis solely affecting the vessels of the brain, spinal cord, and leptomeninges. A range of magnetic resonance imaging (MRI) features have been associated with PACNS, including cerebral infarction, hemorrhage, and parenchymal or leptomeningeal contrast enhancement., Methods and Results: We describe a 51-year-old man with a case of PACNS manifesting as akinetic mutism with progressive leukoencephalopathy., Discussion: Progressive leukoencephalopathy has not been well defined as a manifestation of PACNS. We review a small number of cases with comparable features, providing additional context on this PACNS manifestation with consideration of clinical subtypes., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Primary central nervous system vasculitis (PACNS) is a vasculitic disorder affecting small to medium-sized blood vessels primarily in the central nervous system,involving the brain,spinal cord,and meninges.Tumor-like PNCAS,a rare subtype of PACNS,is often misdiagnosed as intracranial malignancy,and that with spinal cord involvement is even more uncommon.The lack of specific clinical symptoms and imaging manifestations poses a challenge to the diagnosis of PACNS.This report presents a case of tumor-like PACNS with spinal cord involvement based on the pathological evidence,aiming to enrich the knowledge about this condition.

A 53-year-old woman was admitted to our hospital because of increasingly frequent transient speech disturbance and left upper limb weakness. Brain magnetic resonance imaging and angiography revealed multiple intracranial stenoses, including the proximal right middle cerebral artery (MCA), without evidence of infarction. The diagnosis of primary angiitis of the central nervous system was established based on circumferential vascular wall thickening with contrast enhancement observed in the right MCA. Following the administration of dual antiplatelet therapy and intravenous methylprednisolone pulse therapy, the patient experienced complete cessation of symptoms, and the stenosis gradually improved without infarction. The risk of infarct development in crescendo transient ischemic attacks may differ between inflammatory vascular stenosis and atherosclerosis.

Affections of the central nervous system (CNS) rarely occur in Lyme neuroborreliosis (LNB). CNS manifestations can have residual neurological symptoms despite antibiotic treatment. We explored the spectrum of CNS affections in patients with LNB in a tertiary care center in a region endemic for Lyme borreliosis. We retrospectively included patients treated at a tertiary care center from January 2020-December 2021 fulfilling the case criteria for LNB as stated in the current German guideline on LNB. Clinical data, cerebrospinal fluid (CSF) findings and MRI imaging were collected. We included 35 patients with LNB, 24 with early manifestations and 11 with CNS-LNB. CNS-LNB patients had encephalomyelitis (n = 6) or cerebral vasculitis (n = 5). Patients with early LNB and CNS-LNB differed regarding albumin CSF/serum quotient and total protein in CSF. Duration from onset of symptoms until diagnosis was statistically significantly longer in patients with encephalomyelitis. MRI findings were heterogeneous and showed longitudinal extensive myelitis, perimedullar leptomeningeal enhancement, pontomesencephalic lesions or cerebral vasculitis. CNS-LNB can present with a variety of clinical syndromes and MRI changes. No clear pattern of MRI findings in CNS-LNB could be identified. The role of MRI consists in ruling out other causes of neurological symptoms., (© 2024. The Author(s).)

Introduction: Severe and less common neurological manifestations of SARS-CoV-2 infection include acute ischemic stroke, intracerebral hemorrhage, central venous sinus thrombosis, and vasculitis. In this report, we present a case of a 42-year-old man with acute ischemic stroke due to SARS-CoV-2 infection-associated central nervous system vasculitis that improved with steroid therapy., Case Report: A 42-year-old man with SARS-CoV-2 infection presented with non-fluent aphasia and right-sided hemiparesis. Computed tomography angiography revealed an occlusion of the proximal left middle cerebral artery (MCA), with acute infarcts in the left posterior parietal, lentiform nucleus, and cortical frontal cortex on magnetic resonance imaging (MRI). Patient developed pulmonary emboli and was discharged on apixaban and atorvastatin. Four weeks later, the patient presented with recurring symptoms and was found to have worsening left MCA stenosis. MRI and MR angiography revealed a penumbra within the left MCA territory and pruning of the distal branches with severe stenosis. Laboratory workup for autoimmune causes of vasculitis was unrevealing. High-dose intravenous steroid treatment was initiated. Subsequent MRI and MR angiography revealed improved flow in the left cerebral vasculature and no novel ischemic infarcts., Conclusion: Central nervous system vasculitis is a rare manifestation of SARS-CoV-2 infection. This case suggests that high-dose intravenous steroids may have a therapeutic role in this patient population. Steroid use, in combination with vasopressor support to augment cerebral blood flow, may prevent further stroke burden., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Primary CNS Vasculitis (PCNSV) is a rare, diverse, and polymorphic CNS blood vessel inflammatory condition. Due to its rarity, clinical variability, heterogeneous imaging results, and lack of definitive laboratory markers, PCNSV diagnosis is challenging. This retrospective cohort analysis identified patients with histological diagnosis of PCNSV. Demographic data, clinical presentation, neuroimaging studies, and histopathologic findings were recorded. We enrolled 56 patients with a positive biopsy of CNS vasculitis. Most patients had cerebral hemisphere or brainstem symptoms. Most brain MRI lesions were bilateral, diffuse discrete to confluent white matter lesions. Frontal lobe lesions predominated, followed by inferior cerebellar lesions. Susceptibility-weighted imaging (SWI) hemorrhages in 96.4% (54/56) of patients, either solitary microhemorrhages or a combination of micro and macrohemorrhages. Contrast-enhanced T1-WIs revealed parenchymal enhancement in 96.3% (52/54 patients). The most prevalent pattern of enhancement observed was dot-linear (87%), followed by nodular (61.1%), perivascular (25.9%), and patchy (16.7%). Venulitis was found in 19 of 20 individuals in cerebral DSA. Hemorrhages in SWI and dot-linear enhancement pattern should be incorporated as MINOR diagnostic criteria to diagnose PCNSV accurately within an appropriate clinical context. Microhemorrhages in SWI and venulitis in DSA, should be regarded as a potential marker for PCNSV., (© 2024. The Author(s).)

Autoimmune vasculitides affect the cerebral vasculature significantly in a considerable number of cases. When immunosuppressive treatments fail to prevent stenosis in cerebral vessels, treatment options for affected patients become limited. In this case series, we present four cases of pharmacoresistant vasculitis with recurrent transient ischemic attacks (TIAs) or stroke successfully treated with either extracranial-intracranial (EC-IC) bypass surgery or endovascular stenting. Both rescue treatments were effective and safe in the selected cases. Our experience suggests that cases of pharmacoresistant cerebral vasculitis with recurrent stroke may benefit from rescue revascularization in combination with maximum medical management., (© 2024. The Author(s).)

Primary central nervous system vasculitis (PCNSV) is a vasculitis limited to the brain and spinal cord. Induction therapy often consists of steroids and cyclophosphamide. Maintenance therapy includes a prednisone taper and may be combined with medications such as azathioprine or mycophenolate mofetil. Relapse is common in PCNSV and an increased dose of steroids is often given, sometimes with a change in therapy. Medications such as rituximab and mycophenolate mofetil may be good alternatives in those who do not respond to initial treatment or who have relapse of disease. Mortality rates of 8% to 9% are reported in the literature., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Primary angiitis of the central nervous system (PACNS) is a rare and potentially severe form of vasculitis that is limited to the brain, spinal cord, and meninges. Despite extensive research, the etiology and underlying immunologic mechanisms of PACNS remain largely unknown. PACNS presents with a variety of clinical, radiological, and pathologic features, but it is generally characterized by inflammation and destruction of the walls of blood vessels in the CNS, which can lead to tissue ischemia and/or hemorrhage. Three main histopathologic patterns have been identified, namely granulomatous, lymphocytic, and necrotizing vasculitis., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Vasculitis is a complication of several infectious diseases affecting the central nervous system, which may result in ischemic and/or hemorrhagic stroke, transient ischemic attack, and aneurysm formation. Infectious agents may directly infect the endothelium causing vasculitis or indirectly affect the vessel wall through an immunological cascade. Clinical manifestations usually overlap with those of noninfectious vascular diseases, making diagnosis challenging. Neuroimaging enables the identification of inflammatory changes in intracranial vasculitis. In this article, we review the imaging features of infectious vasculitis of bacterial, viral, fungal and parasitic causes., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Childhood cerebral vasculitis is a condition that affects the blood vessels in the brain of children and is rare but life-threatening. Imaging plays a crucial role in the diagnosis and monitoring of the disease. This article describes the classification, diagnostic algorithm, and various imaging modalities used in the evaluation of childhood cerebral vasculitis and the imaging findings associated with primary and secondary vasculitis. Understanding the imaging features of this condition can assist in early diagnosis, effective treatment, and improve outcomes., (Published by Elsevier Inc.)

A 48-year-old woman was referred with an 18-year history of focal-onset seizures. She also reported years-long slowly progressive right-sided weakness that was corroborated on examination. Repeated brain MRIs over 15 years showed multifocal left hemispheric T2 fluid-attenuated inversion recovery-hyperintense lesions with patchy enhancement and microhemorrhages, no diffusion restriction, and a left cerebellar infarct (Figure 1, A-F). Only 2 nonspecific white matter lesions were seen contralaterally, indicating largely unihemispheric disease. Differential diagnosis included unilateral primary angiitis of the CNS (PACNS), Rasmussen encephalitis, and myelin oligodendrocyte glycoprotein antibody-associated disease. 1 Serum and CSF testing for autoimmune, infectious, and malignant etiologies and whole-body fluorodeoxyglucose-PET, whole-exome genetic sequencing, and MR vessel-wall imaging were nondiagnostic. Brain biopsy revealed vasculitis (Figure 2, A-F), and the patient was diagnosed with unilateral PACNS. Treatment with mycophenolate mofetil has been initiated. Unilateral PACNS is a rare unihemispheric disease characterized by an indolent course and seizures, recognition of which is critical to accurate diagnosis. 1,2 .

Introduction: Systemic lupus erythematosus (SLE) is a heterogenous, devastating autoimmune inflammatory disease with multiorgan involvement. A variety of neurological and psychiatric symptoms may be caused by nervous system involvement, termed neuropsychiatric systemic lupus erythematosus., Case Report: We describe a young man newly diagnosed with SLE who had a stroke as an initial symptom and was found to have cerebral large-vessel vasculitis and Fahr syndrome., Conclusions: The novelties of this report are the extensive cerebral calcification demonstrated on head computerized tomography in a patient with SLE, and the depiction of an underlying vasculitis on high-resolution magnetic resonance vessel wall imaging. It is our aim to describe this atypical form of neuropsychiatric systemic lupus erythematosus onset and to make known the usefulness of the new magnetic resonance imaging techniques for the diagnosis of cerebral large-vessel vasculitis., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

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 39 years (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 24.5 months (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 12 months (95% CI: 6.8-17.2). Angiography was repeated in 16 patients after a median duration of 13 months (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., (© 2023. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Childhood primary angiitis of the central nervous system (cPACNS) is a vasculitis of unknown etiology that is confined to the central nervous system (CNS) and can lead to repeated cerebral infarctions if left untreated. Several cases of cPACNS after COVID-19 have been reported. Herein, we present a case of post-vaccination cPACNS. A 9-year-old healthy boy presented with persistent headache and fever after receiving the second COVID-19 vaccine (BNT162b2/Pfizer-BioNtech) dose. Brain magnetic resonance angiography (MRA) performed on the sixth day of symptom onset after vaccination revealed stenosis of the left middle cerebral artery; the patient was referred to our department on the 12th day of symptom onset. Blood tests indicated only minimal evidence of inflammation, whereas cerebrospinal fluid examination indicated pleocytosis. Brain magnetic resonance imaging (MRI) revealed vascular wall thickening and contrast enhancement of the artery with worsened stenosis. We diagnosed the patient as having cPACNS and treated him with three courses of methylprednisolone pulse therapy. The headaches and fever disappeared with improvement of vascular stenosis. The patient has been in remission for more than 1 year since cPACNS onset. This is the first report of a case of cPACNS after mRNA vaccination for COVID-19. Most previous cases of COVID-19-associated cPACNS presented with ischemic stroke. However, the present case could be treated for vasculitis prior to stroke and thus had a favorable prognosis. The mRNA vaccine for COVID-19 differs from other existing vaccines, and further accumulation of data of cases is required to determine adverse CNS reactions.

Objectives: Less than 1 % of patients with Lyme Neuroborreliosis (LNB) present with a cerebrovascular event. Ischaemic strokes occur more commonly than parenchymal or subarachnoid haemorrhages. If cerebral vasculitis due to LNB is suspected, antibiotic treatment should be started immediately, which will normally lead to remission. Very rarely progression and recurrent strokes are observed despite sufficient antibiotic therapy, even if steroids are added. Currently there are no guidelines on the adequate treatment of cerebral vasculitis due to LNB which is not responsive to antibiotics and steroids, but in very few reported cases cyclophosphamide led to disease stabilisation. We reviewed the literature regarding cyclophosphamide treatment in these patients and want to share our experience of cyclophosphamide therapy in progressive cerebral vasculitis due to LNB., Results: We report a 71-year-old female patient with cerebral vasculitis and multiple strokes as a complication of LNB. Progression could only be halted by additional immunosuppressive treatment using cyclophosphamide. However, at that point the patient had already suffered severe ischaemic brain damage. Similarly, in existing case reports cyclophosphamide had been administered only at a time when patients already showed serious neurological deficits., Conclusion: Cerebral vasculitis in patients with LNB is very rare and normally responds to antibiotic treatment. A minority of patients show disease progression despite antibiotics and steroids. Our case report strengthens the recommendation that in those patients - even if signs of progressive vasculitis are only detectable on imaging and not clinically - cyclophosphamide should be considered without delay to prevent further cerebrovascular events., Competing Interests: Declaration of Competing Interest 1. Conflicting interests The Authors declare that there is no conflict of interest. 2. Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. 3. Informed consent Written informed consent from the patient´s legal guardian has been obtained., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Vasculitis is a complication of several infectious diseases affecting the central nervous system, which may result in ischemic and/or hemorrhagic stroke, transient ischemic attack, and aneurysm formation. The infectious agent may directly infect the endothelium, causing vasculitis, or indirectly affect the vessel wall through an immunological mechanism. The clinical manifestations of these complications usually overlap with those of non-infectious vascular diseases, making diagnosis challenging. Intracranial vessel wall magnetic resonance imaging (VWI) enables the evaluation of the vessel wall and the diseases that affect it, providing diagnostic data beyond luminal changes and enabling the identification of inflammatory changes in cerebral vasculitis. This technique demonstrates concentric vessel wall thickening and gadolinium enhancement, associated or not with adjacent brain parenchymal enhancement, in patients with vasculitis of any origin. It permits the detection of early alterations, even before a stenosis occurs. In this article, we review the intracranial vessel wall imaging features of infectious vasculitis of bacterial, viral, and fungal etiologies., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Hydrocephalus is a known complication of central nervous system (CNS) vasculitis secondary to infectious diseases. We present an unusual case of primary CNS vasculitis (PCNSV) complicated by communicating hydrocephalus. A patient in their 50s with a few months' history of headache, psychomotor slowing and frequent falls presented with an acute left temporo-parieto-occipital infarction. Angiography revealed multiple arterial irregularities in the anterior circulation bilaterally, CSF was inflammatory and the remaining study was negative, fulfilling criteria for possible PCNSV. One month after successful treatment with corticosteroid, there was worsening of gait, urinary incontinence and neuropsychiatric symptoms. The investigation was remarkable only for active hydrocephalus. An external ventricular shunt was placed, followed by a ventriculoperitoneal shunt, and cyclophosphamide was started with subsequent recovery. Our discussion is that communicating hydrocephalus in PCNSV, due to impaired CSF flow, should be considered on subacute/chronic worsening of patients with PCNSV., Competing Interests: Competing interests: Yes., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To determine the diagnostic accuracy for high-resolution vessel wall image (HR-VWI) and brain biopsy according to angiographical classification in patients with primary central nervous system vasculitis (PCNSV)., Methods: We extracted the patients with PCNSV who underwent the complete brain MRI protocol and cerebral vascular image from Cleveland Clinic prospective CNS vasculopathy Bioregistry. The large-medium vessel variant (LMVV) was defined as patients with cerebral vasculature indicating vasculitis in proximal or middle arterial segments, whereas vessel involvements in smaller distal branches or normal angiography were considered as the small vessel variant (SVV). We compared clinical demographics, magnetic resonance imaging (MRI) findings, and diagnostic approaches between two variants., Results: In this case-control study that included 34 PCNSV patients, the LMVV group comprised a total of 11 patients (32.4%), and 23 patients (67.6%) were classified as the SVV group. The LMVV had more strong/concentric vessel wall enhancement on HR-VWI (LMVV: 90% (9/10) vs. SVV: 7.1% (1/14), p<0.001). By contrast, meningeal/parenchymal contrast enhancement lesion was more frequently observed in the SVV group (p=0.006). The majority of SVV was diagnosed by brain biopsy (SVV: 78.3% vs. LMVV: 30.8%, p=0.022). The diagnostic accuracy of the brain biopsy was 100% (18/18) in SVV and 57.1% (4/7) in LMVV, respectively (p=0.015)., Conclusions: Diagnostic approach for PCNSV differs concerning the affected vessel size. HR-VWI is a useful imaging modality for the diagnosis of LMVV. Brain biopsy remains the gold standard for proving PCNSV with SVV but is still positive in almost one-third of LMVV.

Cerebral vasculitis is increasingly recognized as a common cause of pediatric arterial stroke. It can present with focal neurological deficits, psychiatric manifestations, seizures, and encephalopathy. The etiopathogenesis of childhood cerebral vasculitis (CCV) is multifactorial, making an inclusive classification challenging. In this review, we describe the common and uncommon CCV with a comprehensive discussion of etiopathogenesis, the role of various imaging modalities, and advanced techniques in diagnosing CCV. We also highlight the implications of relevant clinical, laboratory, and genetic findings to reach the final diagnosis. Based on the clinicoradiological findings, a stepwise diagnostic approach is proposed to facilitate CCV diagnosis and rule out potential mimics. Identification of key clinical manifestations, pertinent blood and cerebrospinal fluid results, and evaluation of central nervous system vessels for common and disease-specific findings will be emphasized. We discuss the role of magnetic resonance imaging, MR angiography, and vessel wall imaging as the imaging investigation of choice, and reservation of catheter angiography as a problem-solving tool. We emphasize the utility of brain and leptomeningeal biopsy for diagnosis and exclusion of imitators and masqueraders., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

A 23-year-old female patient with primary vasculitis of the central nervous system simulating a brain tumor is described. The clinical picture was represented by migraine-like headaches, ataxia, transient numbness of the right leg, the lips, double vision, a slight decrease of cognitive functions. MRI of the brain revealed a tumor-like focus in the cerebellum, intensively accumulating contrast, containing micro-hemorrhages (SWI mode). Small single ischemic foci in the brain hemispheres and brain stem were also found. MR angiography (3T) did not found any pathology. Examination of the cerebrospinal fluid revealed a small cytosis (mainly T-lymphocytes) and a slight increase in protein. The results of the analysis of cerebrospinal fluid for syphilis, tuberculosis and the herpetic group of viruses were negative, type 1 oligoclonal synthesis was found. Blood tests for toxoplasmosis, antibodies to aquaporin, anti-neutrophil antibodies, markers of systemic inflammation were within normal limits. Different diagnoses were assumed: demyelinating disease, encephalitis, multiple encephalomyelitis, lymphoma. The diagnosis was established only by a brain biopsy - lymphocytic vasculitis was revealed. According to the immunohistochemical study, T-helpers predominated in the infiltrates. After pulse therapy with Metylprednisolon (1000 mg intravenously drip №. 5), the patient's condition almost returned to normal. It was recommended to take prednisolone per os (starting dose 60 mg) for 7 months.

Purpose: To investigate the predictors of the improvement for patients with isolated intracranial vasculitis stenoses using high-resolution vessel wall magnetic resonance imaging (HR VW-MRI)., Methods: We retrospectively reviewed data from consecutive patients with confirmed intracranial vasculitis under the same conventional conservative treatment based on a prospectively established HR VW-MRI database between December 2016 and December 2020. According to the changes between the degree of stenosis at baseline compared to follow-up MR angiography, the patients were divided into an improvement group and a non-improvement group. A multivariate analysis was performed to identify the predictive factors associated with the improvement of stenoses secondary to intracranial vasculitis., Results: Overall, 41 patients (mean age 32.0 ± 10.1 years, 16 females) with isolated intracranial vasculitis stenoses were included (41.5 % [17/41] in the improvement group, and 58.5 % [24/41] were in the non-improvement group). The degree of wall enhancement on follow-up imaging was significantly reduced compared with that on the baseline imaging in the improvement group (P = 0.004). The multivariate analysis showed that the degree of enhancement (OR, 0.219, 95 % CI, 0.054 to 0.881; P = 0.033) at baseline was an independent predictive factor associated with the improvement in the intracranial vasculitis stenoses., Conclusions: In patients with isolated intracranial vasculitis stenoses, the less enhancement the vessel wall was, the more likely the degree of stenosis would be reduced by conventional conservative therapy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: Small vessel primary angiitis of the central nervous system is a rare and often severe disease characterized by central nervous system-restricted inflammatory vasculitis on histopathology. Diagnosis requires brain biopsy for confirmation and is suggested prior to starting immunotherapy when feasible. However, emerging evidence suggests that other neuroinflammatory conditions may have a clinical and radiographic phenotype that mimics small vessel primary angiitis, at times with overlapping pathologic features as well. Such diagnoses, including myelin oligodendrocyte glycoprotein antibody-associated disease and central nervous system-restricted hemophagocytic lymphohistiocytosis, can be non-invasively diagnosed with serum antibody or genetic testing that would prompt different monitoring and treatment paradigms. To determine the ultimate diagnosis of patients who were suspected prior to biopsy to have small vessel primary angiitis, we reviewed the clinical, radiographic, and pathological features of a cohort of patients at a single center undergoing brain biopsy for non-oncologic indications., Methods: Clinical data were retrospectively extracted from the medical record. Pathology and neuroimaging review was conducted., Results: We identified 21 patients over a 19-year time-period, of whom 14 (66.7%) were ultimately diagnosed with entities other than small vessel primary angiitis that would have obviated the need for brain biopsy. Diagnoses included anti-myelin oligodendrocyte glycoprotein antibody associated disease (n = 9), central nervous system-restricted hemophagocytic lymphohistiocytosis (n = 3), anti-GABA A receptor encephalitis (n = 1), and Aicardi-Goutières syndrome (n = 1)., Interpretation: This study highlights the importance of pursuing now readily available non-invasive testing for mimicking diagnoses before performing a brain biopsy for suspected small vessel primary angiitis of the central nervous system. ANN NEUROL 2023;93:109-119., (© 2022 American Neurological Association.)

Background: Primary angiitis of the central nervous system is a rare inflammatory vasculopathy and it is a difficult diagnosis to make because of its kaleidoscopic presentation and its multiple mimics, including multiple sclerosis., Case Presentation: A 21-year-old men presented a four-year history of progressive gait deterioration. Magnetic resonance imaging of the brain and spine showed hyperintense round-shaped lesions on T2 images, many with contrast enhancement, in supra/infratentorial and spinal segments. He received treatment for multiple sclerosis but presented clinical worsening, and follow-up neuroimaging showed persistent contrast enhancement lesions and a cerebellar hematoma. Brain biopsy was performed and demonstrated inflammatory infiltrations in blood vessels. The patient received 6 monthly schedules of 5 g methylprednisolone and 1 g cyclophosphamide with clinical stabilization., Discussion: Our patient presented a primary angiitis central nervous system according to the Birnbaum and Hellmann proposed criteria. This case reinforces the importance of advancing the differential diagnosis of patients that present red flags in brain neuroimaging., Conclusion: The presence of the micro/macrobleeds and persistent contrast enhancing lesions should raise the suspicion of vasculitis in the differential diagnosis of multiple sclerosis., Competing Interests: Declaration of Competing Interest The authors Samira Luisa Apóstolos Pereira and Dagoberto Callegaro have participated in the production of presentations and material for Biogen and Novartis., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objectives: Invasive aspergillosis is a threat for immunocompromised patients. We present a case series of aggressive cerebral vasculitis caused by Aspergillus spp. infection in immunocompromised patients., Methods: We present a retrospective case series of three autopsy-proven invasive cerebral aspergillosis with diffuse vasculitis affecting large caliber cerebral vessels., Results: Three patients were immunosuppressed: one on rituximab, one on corticosteroids, and one with a renal transplant. Two of these patients were diagnosed with cerebral aspergillosis on postmortem., Conclusion: Aspergillus cerebral vasculitis is a rare form of invasive aspergillosis that should be considered in an immunocompromised individual with suggestive lesions on imaging. It should be suspected as a possible cause of aseptic neutrophil meningitis., Competing Interests: Declaration of Competing Interest The authors declare they have no conflict of interests., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Primary CNS Vasculitis (PCNSV) is a rare inflammatory disorder affecting the blood vessels of the central nervous system. Patients present with a combination of headaches, seizures, and focal neurological deficits. There is usually a diagnostic delay. Treatment is based on observational studies and expert opinion. Our objective was to identify clinical, laboratory, neuroimaging, pathologic or management-related associations with 2 year outcome in patients with primary CNS vasculitis. We conducted a cohort study at a single tertiary care referral centre of prospectively (2018-2019) and retrospectively (2010-2018) identified individuals with primary CNS vasculitis (diagnosis was proven by either brain biopsy or cerebral digital subtraction angiography). Clinical, imaging and histopathologic findings, treatment, and functional outcomes were recorded. Univariate and stepwise multiple logistic regression were applied. P-value<0.05 was considered statistically significant. The main outcome measures were documentation of clinical improvement or worsening (defined by mRS scores) and identification of independent predictors of good functional outcome (mRS 0-2) at 2 years. We enrolled eighty-two biopsy and/or angiographically proven PCNSV cases. The median age at presentation was 34 years with a male predilection and a median diagnostic delay of 23 months. Most patients presented with seizures (70.7%). All patients had haemorrhages on MRI. Histologically lymphocytic subtype was the commonest. Corticosteroids with cyclophosphamide was the commonest medication used. The median mRS at follow-up of 2 years was 2 (0-3), and 65.2% of patients achieved a good functional outcome. Myelitis and longer duration of illness before diagnosis were associated with poorer outcomes. The presence of hemorrhages on SWI sequence of MRI might be a sensitive imaging marker. Treatment with steroids and another immunosuppressant probably reduced relapse rates in our cohort. We have described the third largest PCNSV cohort and multi-centre randomised controlled trials are required to study the relative efficacy of various immunosuppressants.Study registration: CTRI/2018/03/012721., (© 2022. The Author(s).)

Introduction: Isolated spinal cord angiitis (ISCA) is very rare disease. But, it is frequently encountered in the differential diagnosis of atypical spinal cord syndromes., Case Presentation and Review of the Literature: We present a 31-year-old male who presented with progressive paraparesis, and diagnosed with pathologically confirmed ISCA. Longitudinal cystic transverse myelitis was documented in spinal MRI. He responded well to cyclophosphamide and steroid combination, and no relapse was noted during the 4-year follow-up. A standard systematic analysis of the germane literature disclosed 15 more ISCA cases. In total 16 cases (mean age: 46.5, 10 males), ISCA was diagnosed with pathological evaluation in all (Biopsy in 11, Autopsy in 5). MRI lesion is characterized by usually multisegmental longitudinal and sometimes cystic expansile lesions. In seven cases, it was described as "(pseudo)tumoral" by the authors. Albeit absence of elevation of CSF protein/WBC or "compatible" spinal MRI lesion may aid to exclude ISCA to some extent, pathological confirmation is currently necessary for the diagnosis. In 11 cases, ISCA was treated similar to primary supratentorial vasculitis. Mortality rate is 31%., Discussion: ISCA diagnosis, a typical example of which we have presented here, can only be established by tissue examination. However, noninvasive diagnostic criteria are critically needed. Our data suggest that this can only be possible with multinational multicenter prospective registry., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Primary angiitis of the central nervous system is a rare disease characterized by vasculitis of the central nervous system without any systemic involvement. This review aims to provide an insight into the existing stagnancies in the diagnostic approach and management of this disease. The clinical presentation is typically nonspecific, ranging from headaches, altered sensorium, and seizures to recurrent ischemic strokes. The definitive diagnosis can only be ascertained by histopathological studies of tissue obtained from a brain biopsy. While angiography can provide clues to diagnosis, it has often been normal, even in biopsy-proven cases. Primary angiitis of the central nervous system continues to be a diagnostic challenge as little progress has been made over the years in the diagnosis and management strategies. Considering the vast list of mimickers of primary angiitis of the central nervous system and the existence of a significant proportion of imaging-negative and biopsy-negative cases, it becomes imperative to devise universally accepted diagnostic criteria for this disease. Steroids in combination with cyclophosphamide are the agents used to achieve remission. Rituximab can be an alternative. The treatment-related toxicity of cyclophosphamide warrants larger trials for alternative drugs to be studied., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objectives: High-resolution vessel wall imaging (HR-VWI) often demonstrates strong and concentric vessel wall enhancement (VWE) in patients with central nervous system vasculitis (CNS-V). However, little is known about follow-up VWE characteristics and monitoring the response to treatments. The aim of this study was to investigate serial VWE patterns and its clinical practice through the management of CNS-V., Methods: We extracted 9 patients with diagnosed of CNS-V who underwent serial HR-VWI (baseline, 1st follow-up, and 2nd follow-up) from Cleveland Clinic CNS vasculopathy registry. VWE were analysed in 17 intracranial artery segments. VWE was graded on a 3-point scale (0; none, 1; mild/eccentric, and 2; strong/concentric). VWE grade for each arterial segment was summed to create a total VWE score. We investigated the relationship between serial VWE patterns and clinical course., Results: In unique 153 intracranial arterial segments, 39 arteries (25.5%) had strong/concentric VWE on baseline HR-VWI. The positive rates of concentric VWE have decreased to 12.4% (19/153) at 1st follow-up and (10/153) 6.5% at 2nd follow-up, respectively (p<0.001). Mean total VWE scores have significantly decreased over time courses (p=0.034). Two patients had relapse at 1st follow-up image. In relapse cases, mean total VWE scores have worsened at 1st follow-up (baseline:2.0 to 1st follow-up: 6.0). After intensive immunosuppressive treatment, mean VWE scores have improved at 2nd follow-up (1st follow-up: 6.0 to 2nd follow-up: 2.0)., Conclusions: Decreasing contrast VWE at follow-up images may indicate good response to treatment in CNS-V. By contrast, relapse patients might have temporal VWE worsening during the clinical course.

Background: Primary Central Nervous System Vasculitis (PCNSV) is responsible for 3%-5% of strokes before age 50. It presents with clinical, radiological, and pathological variability. Optimal management is unknown given the absence of randomized clinical trials., Aims of the Study: Explore whether tocilizumab, an anti-interleukin-6 monoclonal antibody, is an effective treatment for refractory PCNSV., Methods: Patients with PCNSV treated with tocilizumab in a single tertiary center were reviewed., Results: Three patients were identified. In two of them, MRI-revealed ischemic lesions. The other presented with a subcortical hemispheric pseudotumoral lesion. Brain biopsy was inconclusive in two patients. Due to a significant number of relapses and clinical deterioration despite other immunosuppressive drugs, tocilizumab was initiated and induced a long remission period up to 44 months. Observed side effects were a fungic infection, neutropenia and thrombocytopenia (both transitory), and a pulmonary embolism in one of the cases., Conclusions: Tocilizumab might be a therapeutic option for PCNSV (Class IV evidence), given its efficacy and safety. We propose a novel pathway for diagnosis and therapeutics of PCNSV with the purpose of improving the diagnosis, monitoring, and prognosis of this heterogeneous disorder, setting the framework for future use of tocilizumab in this condition., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)