Rapidly Progressive Primary Central Nervous System Vasculitis: A Rare Case with Multifocal Small and Medium Vessel Involvement

The diagnosis of primary central nervous system (CNS) vasculitis is often difficult. There are neither specific clinical features nor a classical clinical course, and no blood or imaging investigations that...

Amyloid Beta-Related Angiitis—A Case Report and Comprehensive Review of Literature of 94 Cases

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.

A43-YEAR-OLDWOMAN presented with progressive left visual loss, gait impairment, and urinary incontinence. Examination revealed paraparetic gait, pyramidal deep tendon reflexes, and bilateral Babinskisign.Hererythrocytesedimentation rate was raised. Extensive diagnostic workup (including measurement of antinuclear antibody, extractable nuclear antigen, antineutrophil cytoplasmic antibody, antiphospholipid antibodies, angiotensin-convertingenzyme,and antibodiestoaquaporin-4)ruledout systemicorinfectiousvasculitis.The results of cerebrospinal fluid biochemicalandmicrobiologicalanalysiswerenegative.Oligoclonalbands were absent. Spinal magnetic resonanceimaging(MRI)disclosedacervicodorsal T2-hyperintense lesion withcervicaltractswelling(Figure, A); brain MRI showed acute ischemiclesionsinwatershedareasofthe left centrum semiovale (Figure, B). Magneticresonanceangiographyrevealed bilateral middle cerebral artery occlusion. Catheter angiography confirmed these findings (Figure, C) and evidenced narrowing of the left ophthalmic artery (Figure, D), posterior cerebral artery (Figure, E), and right anterior cerebralartery,withactivationofleptomeningeal collateral circulation. Althoughneuromyelitisopticaor multiple sclerosis are common in young women with this clinical onset, laboratory results, characteristicmultifocalintracranialvesselnarrowing or occlusion, and ischemic parenchymalinvolvementintheabsenceofknownvasculiticcausesled to the diagnosis of primary central nervous system (PCNS) vasculitis. After treatment with high-dose intravenous methylprednisolone sodium succinate followed by oral cyclophosphamide, the spinal lesion recovered within 2 weeks, whereas vascular MRI findings also persisted, unchanged, at 8-month follow-up. The patient regained the ability to walk independently, but mild visual and bladder dysfunctions persisted. COMMENT

ABSTRACTA 49-year-old lady, hypertensive with dyslipidaemia, had thalamic bleed with intracranial multiple micro-haemorrhages. An extensive search was done and vasculitis was ruled out in the patient. Henceforth, she remained strict with medications and maintained blood pressure and lipids under control. After a lucid interval of 3 years, she attended emergency with complex partial seizure. We detected extensive microbleeds (significant increment) in magnetic resonance imaging of the brain and periventricular ischemic changes. A cerebrospinal fluid study and digital subtraction angiography of the brain were consistent with primary central nervous system (CNS) vasculitis (small vessel). She improved and currently is well on follow-up with immunosuppressive therapy. Interesting learning part in our case was late presentation of the patient with primary CNS vasculitis after a latency. It implies requirement of strong suspicion and stringent follow-up in these types of patients.

Primary CNS vasculitis (PCNSV) is uncommon, difficult to diagnose, and potentially fatal or at least likely to cause major and persistent neurological deficits, and yet appears highly treatable (although controlled clinical trials remain to be done). Here, we summarize recent advances in the recognition and diagnosis of PCNSV, the crucial role of biopsy and histopathological confirmation of the diagnosis, and currently recommended approaches to treatment. We also sign post areas of potentially fruitful future collaborative study that might advance this difficult disease.

To summarize the current literature on central nervous system vasculitis in childhood because this condition remains a diagnostic and therapeutic challenge. Central nervous system vasculitis in childhood may be primary or secondary to a variety of conditions including infections, collagen vascular diseases, systemic vasculitides, and malignancies. Conditions that result in vasospasm or are associated with noninflammatory vasculopathies may mimic the features of central nervous system vasculitis. Recent studies have described the clinical spectrum of CNS vasculitis in childhood. The most common presenting features are headaches and focal neurologic deficits. The diagnosis of central nervous system vasculitis remains particularly difficult because the available investigative modalities have limited sensitivities and specificities. The most helpful diagnostic tests include cerebrospinal fluid analysis, MRI of the brain, and angiography. However, brain biopsy may be required to diagnose small vessel vasculitis. This review summarizes recent data on primary central nervous system vasculitis and some of the secondary CNS vasculitides in children. Awareness of the presenting clinical features of CNS vasculitis should lead to consideration of the diagnosis. Awareness of the sensitivity and specificity of the various diagnostic tests should lead to the more prudent use of invasive diagnostic tests including angiography and brain biopsy.

FRI0505 Long-Term Efficacy and Safety of Mycophenolate Mofetil in Childhood Primary Central Nervous System Vasculitis

Primary central nervous system vasculitis and its mimicking diseases – clinical features, outcome, comorbidities and diagnostic results – A case control study

Primary CNS Vasculitis - An Overview Abstract. Cerebral vasculitis, especially the primary vasculitis of the central nervous systems (primary CNS vasculitis), are rare inflammatory diseases of the small- and medium-sized vessels of the CNS. The pathogenesis of primary CNS vasculitis is unclear. Infectious triggers are hypothesized to induce an activation of the immune system with resulting inflammation of the blood vessels within the CNS. Clinically, primary CNS vasculitis presents heterogeneously with leading symptoms such as headache, memory impairment and other neurological deficits. A broad diagnostic work-up prior to treatment initiation is crucial. Treatment consists of immunotherapy (pulse and maintenance therapy) and requires long-term neurological treatment and follow-up due to the increased risk of recurrence of the disease.

To assess the efficacy and safety of Rituximab (RTX) in adult primary central nervous system vasculitis (PCNSV). We retrospectively assessed the effect of RTX in 6 patients with PCNSV. Five of the 6 were refractory to high dose glucocorticoids (GCs) and/or conventional immunosuppressants (IS). The sixth was newly diagnosed and received RTX in combination with GCs. Clinical evaluation, laboratory tests, and imaging modalities were performed at initial RTX administration and during the follow-up. Treatment response was assessed using the treating physician's global opinion regarding response and the degree of disability using the modified Rankin scale (mRS). We also performed a literature review for previous use of RTX in PCNSV using PubMed, Ovid Medline, and the Cochrane library. The six patients (3 females) had a median age at diagnosis of 50.5 years (range 17-68 years). All had active disease when RTX was started. In 4 patients, RTX administration was associated with a marked reduction in the number of flares (from 18 before starting RTX to 3 after). One patient, after an initial improvement, had 2 flares when B cells were depleted and he was not able to reduce prednisone below 20 mg/day. A 6th patient had a flare when B cells recovered and retreatment with RTX re-induced and maintained remission. The median mRS score at last visit (median: 2; range 0-4) was lower than that prior to treatment (median 3; range 1-5). The median prednisone daily dose before RTX administration was significantly higher than that at last follow-up (p = .006). In the literature review, we identified 5 papers describing 7 patients treated with RTX. Six patients responded to RTX with clinical and MRI improvement with no reported flares after RTX treatment. Our data support a potential role for RTX treatment in selected patients with PCNSV.

Association of primary central nervous system vasculitis with the presence of specific human leucocyte antigen gene variant

Primary Central Nervous System Vasculitis Presenting as Spinal Subdural Hematoma

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.

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