Primary central nervous system vasculitis. A rare disease with high mortality.

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...

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.

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

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

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.

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

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

IntroductionPrimary central nervous system vasculitis (primary CNS vasculitis) is a rare inflammatory disorder that affects small-to-medium-sized cerebral vessels, often leading to recurrent strokes. Diagnosis is vague due to non-specific neurological symptoms. Imaging findings, cerebrospinal fluid (CSF) analysis and exclusion of systemic vasculitis are essential for diagnosis. Early immunosuppressive therapy is crucial, but the prognosis remains unpredictable.Case descriptionA 45-year-old female with diabetes, hypertension and multiple ischaemic strokes presented with altered consciousness due to hypoglycaemia. Initial workup at a different hospital suggested cerebral vasculitis based on the findings of cerebral angiography. She had negative systemic vasculitis markers and was treated with corticosteroids and rituximab and discharged. On admission to our facility, an MRI of the brain revealed multiple infarcts of varying ages, and a CTA showed arterial beading, suggestive of primary CNS vasculitis. CSF analysis demonstrated elevated protein and IgG without pleocytosis. Despite high-dose corticosteroids and rituximab, she developed progressive neurological deterioration with new infarcts in the vertebrobasilar territory, leading to brainstem dysfunction and brain death.ConclusionPrimary CNS vasculitis remains a diagnostic and therapeutic challenge because of its diverse presentation and similarities with other vascular conditions. This case emphasises the importance of early recognition, comprehensive diagnostic evaluation and aggressive treatment to prevent irreversible neurological decline. Disease progression can be rapid even with treatment, highlighting the need for further research to enhance early detection and optimise management strategies.LEARNING POINTSPhysicians should be alert in diagnosing primary CNS vasculitis in a young patient with recurrent strokes affecting multiple vascular territories, particularly when systemic vasculitis markers are negative.Imaging studies, such as MRI and computed tomography angiography (CTA), play an essential role in diagnosing primary CNS vasculitis, with findings such as arterial beading and a multi-infarct pattern helping differentiate it from atherosclerotic diseases.Early recognition and aggressive high-dose corticosteroid and immunosuppressive (rituximab) therapy are essential in primary CNS vasculitis, as delayed treatment can result in rapid neurological deterioration, as seen in this case.

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.

Primary Central Nervous System Vasculitis Presenting as Spinal Subdural Hematoma

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

Spinal cord involvement has been observed rarely in primary central nervous system vasculitis (PCNSV), and histopathologically proven isolated cord angiitis usually involves the thoracic level or terminal conus1,2. We report a very rare case of isolated cervical cord involvement in PCNSV. The diagnosis was first made by spinal magnetic resonance imaging (MRI) to survey the possible etiologies of cervical myelopathy, and finally confirmed …

The aim of this review was to cover the recent major advances made in the fields of clinical assessment, diagnosis and treatment of adult primary central nervous system vasculitis (PCNSV). To prevent misdiagnosis, particularly with the reversible cerebral vasoconstriction syndromes, new criteria on the basis of the levels of certainty of the diagnosis of PCNSV have been proposed. Advances in the neuroimaging techniques visualizing the wall of intracranial blood vessels have improved the capacity to distinguish inflammatory from noninflammatory vascular lesions. These techniques could play in the future an important role in the diagnosis of PCNSV. Studies of larger numbers of cases have revealed a more varied histopathological inflammatory picture and disclosed an association with amyloid angiopathy. It has also been recognized that PCNSV is a heterogeneous disorder encompassing clinical subsets that differ in terms of prognosis and therapy. Finally, differently from earliest reports that suggested a poor prognosis with a fatal outcome in the majority of the cases, a large recent study from Mayo Clinic has described a more favorable course with good response to therapy and a favorable outcome in 81% of cases. Our better understanding of the PCNSV spectrum and its subsets will facilitate early recognition. This may facilitate earlier treatment and may prevent irreversible or even lethal outcomes.

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.