Search

Immunohistochemical studies have identified complement component C1q in MS lesions. We aimed to compare serum (sC1q) and CSF (csfC1q) levels in a large cohort of MS patients (pwMS) (n = 222) with those of healthy controls (HC, n = 52), individuals with other immune (IND, n = 14), and non-immune neurological disorders (nIND, n = 15), and to analyze their correlation with other biomarkers. pwMS were divided into three series based on their origin. CSF samples were unavailable for HC. All three pwMS cohorts had lower sC1q levels compared to HC and IND. csfC1q was higher in one pwMS cohort, with a trend in another, and correlated with IgG, Free Kappa Light Chains, GFAP, and Chitinase-3 Like Protein-1 in CSF. Our findings suggest a significant role for C1q in MS pathophysiology, potentially serving as a biomarker for disease identification. • sC1q levels were lower in pwMS compared to both HC and patients with nIND. • There were no differences in sC1q levels between pwMS and those with other IND. • csfC1q correlated with IgG, FLKC, GFAP, and CHI3L1 in CSF, but not with NfL. • C1q levels in pwMS remained consistent irrespective of acute inflammatory activity. [ABSTRACT FROM AUTHOR]

Contactin-associated protein 1 (Caspr1) is widespread in both the peripheral and central nervous systems (CNS). However, anti-Caspr1 antibody-positive nodopathy associated with CNS symptoms has not previously been reported. In this case, a 69-year-old man presented with polyneuropathy and memory loss. The patient had negative myoclonus, positive myoclonus, and pseudoathetosis in the upper limbs, and we detected anti-Caspr1 antibodies in the serum and cerebrospinal fluid. Therefore, anti-Caspr1 nodopathy was diagnosed. After rituximab treatment, all symptoms of polyneuropathy, involuntary movements, and memory impairment improved. In conclusion, anti-Caspr1 antibodies might also affect the CNS; therefore, CNS symptoms of anti-Caspr1 nodopathy require attention. • We report a novel case of anti-Caspr1 antibody-positive nodopathy associated with CNS symptoms. • The patient's symptoms included involuntary movements and memory impairment. • CNS symptoms improved after rituximab treatment. • We speculate that anti-Caspr1 antibody-positive nodopathy may be involved in CNS disturbances. • Clinicians should pay attention to CNS symptoms and anti-Caspr1 antibodies in CSF. [ABSTRACT FROM AUTHOR]

The classification of autoimmune encephalitis (AE) is based on the presence of different types of antibodies. Currently, the clinical manifestations and treatment regimens of patients with all types of AE exhibit similarities. However, the presence of immunological distinctions among different types of AE remains uncertain. In this study, we prospectively collected clinical data, as well as blood and cerebrospinal fluid (CSF) samples from patients diagnosed with MOG antibody-associated disease (MOGAD) or GFAP astrocytopathy (GFAP-A), in order to assess changes in inflammatory biomarkers such as immunoglobulin oligoclonal bands, cytokines in serum and CSF, as well as peripheral blood lymphocyte subtypes within different subsets. To further distinguish the immune response in patients with MOGAD and GFAP-A from that of healthy individuals, we prospectively recruited 20 hospitalized patients diagnosed with AE. Among them, 15 (75%) tested positive for MOG antibodies, 4 (20%) tested positive for GFAP antibodies, and 1 (5%) tested positive for both MOG and GFAP antibodies. These patients were then followed up for a period of 18 months. Compared to healthy controls (HC), AE patients exhibited elevated levels of MIP-1beta, SDF-1alpha, IL-12p70, IL-5, IL-1RA, IL-8 and decreased levels of IL-23, IL-31, IFN-alpha, IL-7, TNF-beta and TNF-alpha in serum. The CSF of AE patients showed increased levels of IL-1RA, IL-6 and IL-2 while decreased levels of RANTES, IL-18,IL-7,TNF-beta,TNF-alpha,RANTES,Eotaxin,and IL-9. The level of MCP-1 in the CSF of GFAP-A patients was found to be lower compared to that of MOGAD patients, while RANTES levels were higher. And the levels of IL-17A, Eotaxin, GRO-alpha, IL-8, IL-1beta, MIP-1beta were higher in the CSF of patients with epilepsy. The presence of intrathecal immune responses is also observed in patients with spinal muscular atrophy (SMA). However, no biomarker was found to be associated with disease severity in patients with AE. Among the 17 patients, recovery was observed, while 2 patients experienced persistent symptoms after an 18-month follow-up period. Additionally, within one year of onset, 8 patients had a single recurrence. Therefore, the immunological profiles of MOGAD and GFAP-A patients differ from those of normal individuals, and the alterations in cytokine levels may also exhibit a causal association with the clinical presentations, such as seizure. • The immunological profile of MOGAD and GMAP-A patients is different from that of normal people. • Changes in cytokine levels may also be causally related to clinical manifestations, such as seizures. • It offers clinical data validation for changes in cytokine levels observed in animal models of autoimmune encephalitis. • Autoimmune encephalitis in acute phase of the immune treatment is very necessary. [ABSTRACT FROM AUTHOR]

Neurosarcoidosis, a rare granulomatous disease, causes inflammation and damage to the central nervous system (CNS). A major diagnostic challenge in neurosarcoidosis is the absence of well-defined biomarkers. The need for biopsy to make the diagnosis can lead to delays and misdiagnosis if histopathology is inaccessible or indeterminate, highlighting the need for more accessible diagnostic indicators. The current gold standard for a "definite" neurosarcoidosis diagnosis requires biopsy of CNS tissue revealing non-caseating granulomas. However, such biopsies are inherently invasive and carry associated procedural risks. Notably, angiotensin-converting enzyme (ACE), commonly associated with systemic sarcoidosis, is recognized as a poor biomarker for neurosarcoidosis due to its lack of accuracy in the context of CNS involvement. Furthermore, imaging in neurosarcoidosis, while widely utilized and important for narrowing the diagnosis, lacks specificity. Decades of research have yielded molecular and immunologic biomarkers—soluble interleukin-2 receptor (IL-2R), serum amyloid A1, the CD4/CD8 ratio, neopterin, interferon-gamma (IFN-γ), and chemokine ligand 2 (CCL2)—that hold potential for improving diagnostic accuracy. However, these biomarkers are not yet established in clinical care as they may be difficult to obtain and are derived from small studies. They also suffer from a lack of specificity against other inflammatory and infectious central nervous system diseases. New biomarkers are needed for use alongside those previously discovered to improve diagnosis of this rare disease. This review synthesizes existing literature on neurosarcoidosis biomarkers, aiming to establish a foundation for further research in this evolving field. It also consolidates information on biomarkers of systemic sarcoidosis such as IL-8 and soluble CD40L that have not yet been studied in neurosarcoidosis but hold potential as markers of CNS disease. • Diagnosis of neurosarcoidosis often requires biopsy. Improved biomarkers could enable earlier diagnosis and treatment. • Research has found promising biomarkers like soluble IL-2 receptor, serum amyloid A, and CD4/CD8 ratio, but they require further validation. • Biomarkers like TNF-alpha and IL-6 may be therapeutic targets. CD40L and TL1A need further investigation. [ABSTRACT FROM AUTHOR]

Rheumatoid meningitis (RM) is an extra-articular complication of rheumatoid arthritis (RA). Although reports of RM sine arthritis exist, most patients with this presentation were diagnosed with RA within one year of RM onset. There are no established biomarkers reflecting the disease activity of RM. This case report highlights the elevation of matrix metalloprotease (MMP)-9 levels during the acute phase of RM and decline during remission. Additionally, this is the first case report of RA diagnosed three years after the onset of RM. It is important to further validate the utility of MMP-9 and conduct long-term follow-up of RM sine arthritis. [Display omitted] [ABSTRACT FROM AUTHOR]

We report the first description of spinal cord mycobacterial spindle cell pseudotumor. A patient with newly diagnosed advanced HIV presented with recent-onset bilateral leg weakness and was found to have a hypermetabolic spinal cord mass on structural and molecular imaging. Biopsy and cultures from blood and cerebrospinal fluid confirmed spindle cell pseudotumor due to Mycobacterium avium-intracellulare. Despite control of HIV and initial reduction in pseudotumor volume on antiretrovirals and antimycobacterials (azithromycin, ethambutol, rifampin/rifabutin), he ultimately experienced progressive leg weakness due to pseudotumor re-expansion. Here, we review literature and discuss multidisciplinary diagnosis, monitoring and management challenges, including immune reconstitution inflammatory syndrome. [Display omitted] • We report the first case of mycobacterial spindle cell pseudotumor of the spinal cord. • The patient was newly diagnosed with HIV when he developed progressive bilateral leg weakness. • Diagnosis was made by structural/metabolic imaging, cultures and biopsy. • Treatment with azithromycin, ethambutol, rifampin/rifabutin led to pseudotumor size reduction. • Pseudotumor rebound co-occurred with rising CD8 T cell count, suggesting role of immune reconstitution. [ABSTRACT FROM AUTHOR]

New-Onset Refractory Status Epilepticus (NORSE) is a rare and severe form of refractory status epilepticus without an apparent underlying cause at presentation or prior history of epilepsy. We aimed to describe the clinical features, etiology, treatment, and outcomes of NORSE in adults in a quaternary-level hospital in Saudi Arabia. In this retrospective cohort study, inclusion criteria involved patients over 14 years old who met the 2018 consensus definition for NORSE. Patients were identified using a combination of medical record admission labels 'status epilepticus' and 'encephalitis', and continuous EEG reports documenting status epilepticus. Demographic, clinical, and radiological data were collected and then analyzed for factors correlated with specific etiologies, better functional outcomes, and future diagnosis of epilepsy. We found 24 patients presenting with NORSE between 2010 and 2021. Fever/infectious symptoms were the most common prodrome. Elevated inflammatory serum and cerebrospinal fluid markers in most patients. Brain MRI revealed T2/FLAIR hyperintensity patterns, predominantly affecting limbic and perisylvian structures. The etiology of NORSE varied, with immune-related causes being the most common. Long-term outcomes were poor, with a high mortality rate and most survivors developing drug-resistant epilepsy. This study provides valuable insights into NORSE's clinical characteristics, highlighting the heterogeneity of this condition. The poor outcome is likely related to the progressive nature of the underlying disease, where refractory seizures are a clinical symptom. Thus, we propose to focus future research on the etiology rather than the NORSE acronym. • The most common etiology was NMDA encephalitis, ADEM, and antiphospholipid syndrome. • The hippocampus, Amygdala, and insula are the most affected structures. • The most common abnormal finding on PET scans is a pattern of hypometabolism. • Fever, confusion, and headache are the most common symptoms. • Hippocampal and cortical atrophy on MRI resulted in poor functional outcomes. [ABSTRACT FROM AUTHOR]

The influx of pathogenic aquaporin-4 antibodies (AQP4-Abs) across the blood–spinal cord barrier (BSCB) is crucial for the development and exacerbation of neuromyelitis optica (NMO). We examined whether prophylactic intravenous administration of anti-repulsive guidance molecule-a antibodies (RGMa-Abs) has disease-modifying effects on BSCB dysfunction using an NMO model elicited by peripheral administration of AQP4-Abs to rats. RGMa-Ab treatment attenuated the acute exacerbation of perivascular astrocytopathy in the spinal cord and clinical symptoms, which were highly correlated with neurofilament light chain levels in both the cerebrospinal fluid (CSF) and serum. Additionally, RGMa-Ab treatment suppressed the expression of proinflammatory cytokines/chemokines and the infiltration of inflammatory cells into the spinal cord. CSF analysis of NMO rats revealed that RGMa-Ab treatment improved the CSF/serum albumin ratio and suppressed AQP4-Abs influx. RGMa inhibition using RGMa-Abs is suggested as a potential therapeutic option for BSCB dysfunction associated with NMO. [Display omitted] • Intravenous administration of RGMa-Abs suppressed IL-17 in CSF of an NMO rat model. • RGMa-Abs improved the CSF/serum albumin ratio and suppressed further AQP4-Abs influx. • RGMa inhibition using RGMa-Abs is a potential therapeutic option for NMO. [ABSTRACT FROM AUTHOR]

Cerebrospinal fluid (CSF) eosinophilia is associated with a narrow differential, primarily including parasitic and fungal infections, neoplasm, and chemical meningitis. It has rarely been reported in neuroinflammatory conditions including as a finding of CSF cytology in two autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy cases. Here we describe a case of autoimmune GFAP astrocytopathy with classic clinical and radiographic features as well as presence of eosinophils in the CSF. This case highlights a potential association of eosinophils in the CSF with autoimmune GFAP astrocytopathy, which may suggest its inclusion in the differential diagnosis of eosinophilic meningitis, encephalitis, or myelitis. [ABSTRACT FROM AUTHOR]

To evaluate B-cell involvement in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), 11 patients with CIDP, 8 patients with Guillain–Barré syndrome and 13 patients with idiopathic normal pressure hydrocephalus (iNPH) were studied. CSF cytokine and chemokine (IL-10, IL-15, TNF-α, TGF-β1, GM-CSF, BAFF, CXCL10, and CXCL13) levels were measured by ELISA. The CSF CXCL13 level was significantly higher in patients with CIDP than in those with iNPH. The CSF CXCL13 level was significantly higher in CIDP patients with higher annualized relapse rates and higher modified Rankin scale scores. The CSF CXCL13 level is elevated in CIDP, especially in those with higher disease activity. • We evaluated several cytokines/chemokines associated with B cells in CSF samples. • CSF CXCL13 was significantly elevated in patients with CIDP. • CSF CXCL13 was associated with higher relapse rates. • CSF CXCL13 was also associated with higher disability. • The chemokine CXCL13, a major B-cell chemoattractant, seemed to be involved in CIDP. [ABSTRACT FROM AUTHOR]

Uric acid (UA) is an important natural antioxidant and strong peroxynitrite scavenger, but little is known about central nervous system (CNS) levels of UA in patients with anti- N -methyl- d -aspartate receptor encephalitis (NMDARE). Cerebrospinal fluid (CSF) and serum levels of UA were determined in 72 patients with anti-NMDARE and 111 controls with non-inflammatory neurological diseases (NINDs). Serum UA levels were also evaluated in 132 healthy controls (HCs). CSF neuron-specific enolase (NSE) and blood-brain barrier (BBB) index were evaluated in patients with anti-NMDARE. The association of CSF UA levels with anti-NMDARE and its clinical parameters were evaluated in the patients. CSF UA levels were lower in patients with anti-NMDARE than in patients with NINDs, especially in patients with severe impairments (modified Rankin Scale [mRS] scores >3 vs. ≤ 3, p = 0.006). Furthermore, serum UA levels in patients with anti-NMDARE were significantly lower than in patients with NINDs and HCs. CSF UA levels were significantly associated with mRS scores, and serum UA levels in patients with anti-NMDARE. Furthermore, CSF/serum UA ratio was significantly associated with BBB index. CSF UA levels associated with disease severity and serum UA levels in patients with anti-NMDARE. And CSF/serum UA ratio correlated with BBB index, indicating that CSF and serum UA levels change similarly with BBB permeability in anti-NMDARE patients. [ABSTRACT FROM AUTHOR]

Blood-brain barrier (BBB) breakdown is an essential mechanism in inflammatory diseases of the central nervous system. However, the association between BBB integrity and autoimmune encephalitis (AE) has not been investigated. Our study aimed to analyze this relationship in patients with AE between BBB integrity with clinical manifestations and therapeutic responses. Our study enrolled 147 patients with AE who were newly diagnosed at the First Affiliated Hospital of Zhengzhou University between August 2015 and December 2021. Patients were classified into normal or damaged BBB groups based on cerebrospinal fluid (CSF) albumin/serum albumin (QAlb). To evaluate the severity of the illness, we used the modified Rankin Scale (mRS) and the Clinical Assessment Scale for Autoimmune Encephalitis (CASE). We found a higher proportion of males, higher CSF protein, immunoglobulin IgG, and 24-h intrathecal IgG synthesis rate in the damaged BBB group. The improvement rate was lower in the damaged BBB group, but we found that double- or triple-combination immunotherapy had better clinical outcomes than single immunotherapy. In addition, there was a positive correlation between the CASE score and mRS score, and a positive correlation between the CASE score or mRS score and QAlb on admission. BBB integrity is closely related to the clinical features and treatment responses of newly diagnosed AE. Patients with AE and a damaged BBB may benefit from combination immunotherapy. • We analyzed the relationship between BBB integrity and AE patients. • AE patients with damaged BBB have a poor response to first-line immunotherapy. • AE patients with damaged BBB were more likely to have low level of consciousness. [ABSTRACT FROM AUTHOR]

The clinical features of autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy remain to be elucidated. We describe here the clinical features of 14 patients with GFAP astrocytopathy confirmed by detection of GFAP-IgG in cerebrospinal fluid (CSF). The novel findings of this study are as follows. First, over half of the patients presented with movement disorders (tremor, myoclonus, and ataxia), autonomic dysfunction (mainly urinary dysfunction), and hyponatremia. Second, most patients showed transient elevation of adenosine deaminase activity levels in CSF. Finally, some patients showed bilateral hyperintensities in the posterior part of the thalamus on brain magnetic resonance imaging. Unlabelled Image • We described patients with autoimmune GFAP astrocytopathy in Japan. • They presented with movement disorders, urinary dysfunction, and hyponatremia. • Brain MRI showed the bilateral hyperintensities of posterior part of the thalamus. • The CSF ADA levels were transiently elevated during early stage of this disease. • They were treated with corticosteroid and had a good outcome without relapse. [ABSTRACT FROM AUTHOR]

Laboratory tests to assist in the diagnosis and monitoring of neuroinflammatory diseases are scarce. The soluble form of the CD27 molecule (sCD27) is shed in high concentrations by activated T cells and can be detected in the cerebrospinal fluid. The aim of this study was to investigate whether CSF quantitation of sCD27 could discriminate between inflammatory and non-inflammatory neurological diseases. The concentration of sCD27 was measured using a commercially available ELISA in 803 well-defined subjects from a study cohort comprised of 338 patients with neuroinflammatory disease, 338 with non-inflammatory neurological disease and 127 controls without neurological disease. The median value of cerebrospinal fluid sCD27 was 64 pg/mL (IQR 0–200) in controls, 58 pg/mL (IQR 0–130) in patients with non-inflammatory disease and 740 pg/mL (IQR 230–1800) in patients with inflammatory disease. The likelihood ratio of having an inflammatory disease was 10 (sensitivity 74% and specificity 93%) if the sCD27 concentration was >250 pg/mL. In patients with a known inflammatory condition, the likelihood ratio of having an infection was 10 (sensitivity 40% and specificity 96%) if the sCD27 concentration was >2500 pg/mL. The likelihood of having an inflammatory neurological condition is increased with elevated concentrations of sCD27 in cerebrospinal fluid. Rapid tests of sCD27 should be developed to assist clinicians in diagnosis of neuroinflammatory disease. • Inflammatory conditions are associated with elevated concentrations of sCD27 in CSF. • The likelihood ratio of having an inflammatory disease was 10 if sCD27 > 250 pg/mL. • The likelihood ratio of having an infection was 10 if sCD27>2500 pg/mL. [ABSTRACT FROM AUTHOR]

Abstract Hypertrophic pachymeningitis (HP) is a rare neurologic disease causing inflammatory fibrous thickening of the brain and spinal dura mater. We investigated the cerebrospinal fluid cytokine profile of HP by measuring 28 cytokines/chemokines/growth factors with a multiplexed fluorescent immunoassay in 8 patients with HP (6 idiopathic, 1 IgG4-related, 1 anti-neutrophil cytoplasmic antibody-related), and 11 with other non-inflammatory neurologic diseases (OND). Interleukin (IL)-4, IL-5, IL-9, IL-10, TNF-α, and CXCL8/IL-8 levels were significantly higher in idiopathic HP (IHP) than OND. Cluster analyses disclosed two major clusters: one mainly consisted of IHP and the other of OND, suggesting a unique cytokine profile in IHP. Graphical abstract Unlabelled Image Highlights • Cerebrospinal fluid Th2 cytokines are increased in hypertrophic pachymeningitis (HP). • Th2 cytokines consist of a large cluster unique to idiopathic HP by cluster analyses. • Elevated Th2 cytokines can promote proliferation of plasma cells and fibroblasts. [ABSTRACT FROM AUTHOR]

Abstract Tacrolimus-induced encephalopathy presents with acute neurological symptoms such as headache, seizures, visual disturbances, hemiplegia, and altered mental status. A 60-year-old woman, presented to our clinic with a 4-month history of severe headache. She recently underwent kidney transplantation and was taking tacrolimus. MRI scan showed diffuse and symmetric alterations involving both supratentorial and infratentorial white matter. Cerebral spinal fluid assessment for infectious diseases were negative but elevated total protein level and oligoclonal bands positivity were reported. Treatment with steroid bolus, along with tacrolimus tapering, provided clinico-radiological improvement. This is the first case of tacrolimus-induced neurotoxicity strongly suggestive of an immune-mediated pathogenesis. Graphical abstract Unlabelled Image Highlights • A case of tacrolimus-induced leukoencephalopathy showing symmetric and diffuse white matter involvement • Associated with a marked albuminocytologic dissociation and oligoclonal bands positivity in the CSF • Showing a marked clinical and radiological improvement after intravenous steroid treatment • Findings in line with a drug-induced autoimmune reaction [ABSTRACT FROM AUTHOR]

Abstract Patients with acute and chronic inflammatory demyelinating neuropathies exhibit elevated serum and cerebrospinal fluid (CSF) levels of terminal complement activation products and therapeutic inhibition of complement activation is currently tested for its safety and efficacy in patients with Guillain-Barré syndrome (GBS). Here, we determined serum levels of the complement activation products C3a, C5a and the soluble terminal complement complex (sTCC) in 39 individuals with chronic inflammatory demyelinating polyneuropathy (CIDP) who participated in one of the largest ever conducted clinical trial in patients with CIDP (ICE trial) and received Intravenous Immunoglobulin (IVIG) or placebo (albumin) in 3 week intervals for up to 24 weeks. In placebo-treated patients with spontaneous disease remission, serum sTCC levels moderately decreased over time. Levels of complement activation products were, however, not modulated by IVIG and remained unchanged in patients with a beneficial response to IVIG therapy as compared to those with steady or worsened disease. These results suggest that the therapeutic efficacy of IVIG in CIDP is based on immunomodulatory mechanisms different from complement inhibition. Terminal complement activation merits further investigation as a surrogate marker for disease progression and therapeutic target in patients with CIDP. Graphical abstract Unlabelled Image [ABSTRACT FROM AUTHOR]

Abstract During peripheral infection, excessive production of pro-inflammatory cytokines in the aged brain from primed microglia induces exaggerated behavioral pathologies. While the pro-inflammatory cytokine IL-6 increases in the brain with age, its role in microglia priming is not known. This study examined the functional role of IL-6 signaling on microglia priming. Our hypothesis is that IL-6 signaling mediates primed states of microglia in the aged. An initial study assessed age-related alteration in IL-6 signaling molecules; sIL-6R and sgp130 were measured in cerebrospinal fluid of young and aged wild-type animals. Subsequent studies of isolated microglia from C57BL6/J (IL-6+/+) and IL-6 knock-out (IL-6−/−) mice showed significantly less MHC-II expression in aged IL-6−/− compared to IL-6+/+ counterparts. Additionally, adult and aged IL-6+/+ and IL-6−/− animals were administered lipopolysaccharide (LPS) to simulate a peripheral infection; sickness behaviors and hippocampal cytokine gene expression were measured over a 24 h period. Aged IL-6−/− animals were resilient to LPS-induced sickness behaviors and recovered more quickly than IL-6+/+ animals. The age-associated baseline increase of IL-1β gene expression was ablated in aged IL-6−/− mice, suggesting IL-6 is a key driver of cytokine activity from primed microglia in the aged brain. We employed in vitro studies to understand molecular mechanisms in priming factors. MHC-II and pro-inflammatory gene expression (IL-1β, IL-10, IL-6) were measured after treating BV.2 microglia with sIL-6R and IL-6 or IL-6 alone. sIL-6R enhanced expression of both pro-inflammatory genes and MHC-II. Taken together, these data suggest IL-6 expression throughout life is involved in microglia priming and increased amounts of IL-6 following peripheral LPS challenge are involved in exaggerated sickness behaviors in the aged. Graphical abstract Unlabelled Image Highlights • IL-6 trans-signaling is involved in microglia priming. • Microglia in aged mice are more susceptible to IL-6-induced priming. • Ablation of IL-6 signaling significantly reduces exaggerated LPS-induced sickness behaviors in aged animals. [ABSTRACT FROM AUTHOR]

Abstract The contribution of B cells to the pathogenesis of relapsing-remitting multiple sclerosis (RRMS) is currently of great interest due to the positive outcomes of treatment with B cell-depleting monoclonal antibodies. In this exploratory study we examined the phenotype and cytokine response of B cells from untreated patients with RRMS and healthy controls. The CNS migration potential of the individual blood B cell subpopulations was evaluated according to the expression of CD49d, ALCAM, CXCR3, and CCR7, and cerebrospinal fluid (CSF) samples were analyzed to establish the phenotype of migrated B cells. The frequency of the individual blood B cell subsets expressing CD5, CD43, CD69, CD80, CD83, DC-SIGN and CD138 was similar in patients with RRMS and healthy controls. However, a higher percentage of CD27−IgD−IgM+ memory B cells were found in the blood of patients with RRMS, a population also identified in the CSF samples. We also observed an increased percentage of B cells producing LTα and a higher level of TGFβ1 in patients with RRMS. Altogether, we found that patients with RRMS have an increased frequency of blood CD27−IgD−IgM+ memory B cells that are recruited to the CSF together with other memory B cell populations. Furthermore, we report an increased B cell production of LTα and TGFβ1 in patients with RRMS. Graphical abstract Unlabelled Image Highlights • CD27−IgD−IgM+ B cells are increased in RRMS blood and present in CSF • B cells from patients with RRMS produce more LTα and TGFβ1 than healthy controls • Transitional B cells produce most TGFβ1while IL-10+ cells are mainly memory cells [ABSTRACT FROM AUTHOR]

Abstract We compared cerebrospinal fluid levels of lactate, β2-microglobulin and angiotensin-converting enzyme (ACE) between 438 untreated patients with multiple sclerosis and 276 patients with non-inflammatory neurological disorders. Age-adjusted β2-microglobulin and lactate were significantly higher and ACE was significantly lower in MS patients than in controls. β2-microglobulin and ACE positively correlated with high significance both in MS patients and controls. While disease duration negatively correlated and progression index, defined as EDSS score divided by disease duration in years, positively correlated with age-adjusted lactate levels, both did neither correlate with β2-microglobulin nor with ACE. Both CSF β2-microglobulin and ACE deserve further investigation as biomarkers of multiple sclerosis pathophysiology. Graphical abstract Unlabelled Image Highlights • CSF levels of β2-microglobulin, lactate and ACE significantly increase with age • Age-adjusted CSF β2-microglobulin and lactate are higher, while ACE is lower in multiple sclerosis patients than controls • Only lactate but not β2-microglobulin nor ACE correlates with MS disease duration and severity • CSF β2-microglobulin and ACE deserve further investigation as biomarkers of multiple sclerosis pathophysiology [ABSTRACT FROM AUTHOR]

To investigate the clinical characteristics of autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy in children. We reviewed the medical records of Children's Hospital of Chongqing Medical University from January 2020 to September 2021 and retrospectively analysed the clinical features, magnetic resonance imaging (MRI) findings, laboratory findings, treatment and outcome of children with autoimmune GFAP astrocytopathy. Sixteen patients were included: 6 and 10 tested positive for GFAP-IgG in cerebrospinal fluid (CSF) and both CSF and serum, respectively. The median patient age was 115 months (range: 36–180 months), and 7 patients (43.8%) were male. All patients had the clinical syndrome of encephalitis/meningoencephalitis with or without myelitis: encephalitis (8), meningoencephalitis (3), encephalomyelitis (1) and meningoencephalomyelitis (4). The most common clinical symptoms were fever (11), altered consciousness (11), headache (10) and seizure (9). Four patients developed central respiratory failure for which mechanical ventilation was needed. All patients showed hyperintense T2-weighted lesions on brain MRI in the cerebral white matter (13), brainstem (11), basal ganglia (11), thalamus (9), and cerebellum (3). Nine patients (56%) had abnormal hyperintense lesions in the bilateral basal ganglia and thalamus. Six of 12 patients who underwent gadolinium-enhanced brain MRI showed abnormal enhancement images, and five of them showed linear perivascular radial enhancement. The modified Rankin scale (mRS) score decreased significantly in most patients after immunotherapy. Two patients with coexisting neural autoantibodies relapsed; however, 15 patients who were followed up successfully had favorable outcomes at the last follow-up. Children with autoimmune GFAP astrocytopathy usually have a clinical syndrome of encephalitis/meningoencephalitis with or without myelitis. Except for the linear perivascular radial gadolinium enhancement pattern, hyperintense lesions in the bilateral basal ganglia and thalamus might be another characteristic brain MRI finding of autoimmune GFAP astrocytopathy in children. Although a few patients with coexisting neural autoantibodies might relapse, children with autoimmune GFAP astrocytopathy usually have favorable outcomes after immunotherapy. • Children with autoimmune GFAP astrocytopathy usually manifest as encephalitis/meningoencephalitis with or without myelitis. • Hyperintense lesions in the bilateral basal ganglia and thalamus might be another characteristic brain MRI finding of autoimmune GFAP astrocytopathy in children. • Children with autoimmune GFAP astrocytopathy usually have favorable outcomes after immunotherapy [ABSTRACT FROM AUTHOR]

Cerebrospinal fluid (CSF) soluble CD27 (sCD27) is a sensitive biomarker of intrathecal inflammation. Although generally considered a biomarker of T cell activation, CSF sCD27 has been shown to correlate with biomarkers of B cell activity in multiple sclerosis. We analyzed CSF from 40 patients with relapsing-remitting multiple sclerosis (RRMS) and nine symptomatic controls using flow cytometry and multiplex electrochemiluminescence immunoassays. CSF sCD27 levels were increased in RRMS and correlated with IgG index, soluble B cell maturation antigen, cell count, B cell frequency and CD8+ T cell frequency. We provide new data indicating that CSF sCD27 is associated with CD8+ T cells and B cells in RRMS. [Display omitted] • Levels of CSF sCD27 and sBCMA are increased in RRMS in comparison to controls. • CSF sCD27 correlates with CSF CD8+ T cell and CSF B cell frequency in RRMS. • CSF sCD27 is associated with B cell activation markers sBCMA and IgG index. [ABSTRACT FROM AUTHOR]

Anti-gamma-aminobutyric-acid-B receptor (GABAbR) encephalitis is a rare form of autoimmune encephalitis. Until now, there are few biomarkers that can indicate the severity and prognosis of patients with anti-GABAbR encephalitis. The objective of this study was to exam the changes of chitinase-3-like protein 1 (YKL-40) in patients with anti-GABAbR encephalitis. In addition, whether YKL-40 could indicate the disease severity was also evaluated. The clinical features of 14 patients with anti-GABAbR encephalitis and 21 patients with anti- N -methyl- d -aspartate receptor (NMDAR) encephalitis were retrospectively studied. YKL-40 levels in serum and cerebral fluid (CSF) of patients were detected by enzyme-linked immunosorbent assay. The correlation of modified Rankin Scale (mRS) score of encephalitis patients and YKL40 levels were analyzed. YKL-40 levels in CSF were significantly higher in patients with anti-GABAbR encephalitis or anti-NMDAR encephalitis than those in controls. YKL-40 levels between these two encephalitis groups were not different. Moreover, YKL-40 levels in CSF from patients with anti-GABAbR encephalitis were positively correlated with the mRS score at admission and at 6-month follow-up. YKL-40 level is elevated in CSF from patients with anti-GABAbR encephalitis at early disease stage. YKL-40 may be a potential biomarker indicating the prognosis of patients with anti-GABAbR encephalitis. [ABSTRACT FROM AUTHOR]

Background Immunoglobulin against myelin oligodendrocyte glycoprotein (MOG-IgG) is a potential demyelinating disease-associated autoantibody. Whether clinical features of MOG antibody-associated demyelinating diseases change with age remains unclear. Object To investigate the different clinical features between pediatric-onset and adult-onset MOG-IgG-seropositive patients in a relatively large cohort. Methods A total of 816 consecutive patients with suspected demyelinating disease were prospectively enrolled from three tertiary academic centers in South China from February 2016 to December 2016. Sixteen pediatric-onset cases (≤14 years old) and 34 adult-onset cases (>14 years old) seropositive for MOG-IgG were identified. Differences in clinical features between the two groups were investigated. Results There was a significant difference in the cumulative incidence of first relapse among the two groups ( P  = .008). Cerebral symptoms were significantly higher in pediatric-onset patients than in adult-onset patients, either at disease onset (pediatric-onset group, 10/16(62.5%); adult-onset group, 8/34(23.53%); P  = .007) or throughout the course of disease (pediatric-onset group, 11/16(68.8%); adult-onset group, 10/34(29.4%); P  = .009). Optic nerve symptoms were more common in adult-onset groups, but no significant difference was found between the two groups. A significantly higher rate of pediatric-onset patients (9/16, 56.3%) met the acute disseminated encephalomyelitis criteria compared with adult-onset patients (2/34, 5.9%) ( P  = .0003), and isolated optic neuritis was mainly diagnosed in adult-onset patients (pediatric-onset group, 2/16(12.5%); adult-onset group, 14/34(41.2%); P  = .043). The MOG-IgG titer showed a significant positive correlation with total protein levels in cerebrospinal fluid, but only in adult-onset patients ( r  = 0.95; P  = .0004). On magnetic resonance imaging, extensive white matter lesions were observed in both groups, and the number was much higher in pediatric-onset (7/15, 46.7%) than in adult-onset patients (4/29, 13.8%) ( P  = .043). At the last follow-up, more pediatric-onset patients (10/16, 62.5%) experienced complete recovery (EDSS 0.0 at last follow up) compared with adult-onset patients (9/34, 26.5%) ( P  = .014). Conclusions Distinctive features are present between pediatric-onset and adult-onset patients with MOG-IgG. Further studies are required to determine the different underlying pathogenesis of MOG antibody at different ages. [ABSTRACT FROM AUTHOR]

Primary angiitis of the central nervous system (PACNS) is a rare and heterogeneous inflammatory disease of the CNS vasculature with poorly understood pathophysiology. Comprehensive immune-cell phenotyping revealed increased frequencies of leukocytes in the cerebrospinal fluid (CSF) of PACNS patients compared to patients with multiple sclerosis, ischemic stroke, and somatoform disorders (n = 18 per group). Changes in the intrathecal immune-cell profile were heterogeneous in PACNS. While proportions of T-cell subsets remained unaltered, some PACNS patients showed a shift toward NK- or B cells. Intrathecal immunoglobulin synthesis was observed in a subgroup of PACNS patients with an increased frequency of antibody producing plasma cells. [ABSTRACT FROM AUTHOR]

We tested the performance of MRZ-reaction, an intrathecal humoral immune response against-Measles (M), Rubella (R) and Varicella Zoster (Z) viruses, in multiple sclerosis (MS) diagnosis. The MRZ-reaction was significantly more positive in MS than in non-MS group with a specificity of 91.9%. In MS group, the RZ-profile was the most prevalent and the R-specific antibody-index was correlated to the number of oligoclonal bands (OCB) in CSF. Interestingly, the MRZ-reaction was detected in 53% of OCB-negative-MS patients. The MRZ-reaction seems to be a relevant CSF diagnostic marker of MS disease. The likely relation between its positivity and the vaccination status deserves to be investigated. [ABSTRACT FROM AUTHOR]

In this prospective evaluation of serum and CSF samples, all but two CSF GFAPα-IgG positive patients had autoimmune meningoencephalomyelitis while serum GFAPα-IgG positivity alone was less specific. Phenotypes were diverse among patients that were serum positive only. Adult and pediatric clinical presentations were similar. Most patients were immunotherapy responsive. Co-existing NMDA-R-IgG and cancer were associated with lack of response to first-line immunotherapy. Among patients with follow-up information, 18% had relapses. This study demonstrates CSF GFAPα-IgG is a specific autoimmune meningoencephalomyelitis biomarker, with favorable corticosteroid response. Lack of response should prompt evaluation for co-existing NMDA-R-IgG or malignancy. [ABSTRACT FROM AUTHOR]

Immunoglobulin G (IgG) harbors a conserved N-glycosylation site which is important for its effector functions. Changes in glycosylation of IgG occur in many autoimmune diseases but also in physiological conditions. Therefore, the glycosylation pattern of serum IgG is well characterized. However, limited data is available on the glycosylation pattern of IgG in cerebrospinal fluid (CSF) compared to serum. Here, we report significantly reduced levels of bisected glycans in CSF IgG. Galactosylation and sialylation of IgG4 also differed significantly. Therefore, we propose a common mechanism mediating glycosylation changes of IgG at the transition from serum to CSF in steady state conditions. [ABSTRACT FROM AUTHOR]

We report the case of a patient who presented with progressive unsteadiness and narcoleptic attacks followed by behavioral change and psychosis, without visual disturbances or seizures. MRI revealed multiple areas of fluid attenuation inversion recovery (FLAIR) high-intensity lesions involving the cerebellum, brainstem, thalamus and third ventricular peri-ependymal region consistent with demyelination. Both the serum myelin oligodendrocyte glycoprotein-antibodies (MOG-Abs) and cerebral spinal fluid (CSF) anti- N -methyl- d -as-partate receptor (NMDAR) antibodies were positive using transfected cell based assays. The patient presented simultaneously with symptoms of MOG antibody disease and anti-NMDAR encephalitis, an unusual clinical scenario, indicating the co-existence of the two disorders. [ABSTRACT FROM AUTHOR]

There is mounting evidence that prospective memory (PM) is impaired during HIV infection despite treatment. In this prospective study, 66 adults (43 HIV+ and 23 HIV negative) underwent PM assessment and cerebrospinal fluid (CSF) examination. HIV+ participants had significantly lower PM but significantly higher CSF concentrations of CXCL10 and quinolinic acid (QUIN). Higher CSF phosphorylated Tau (pTau) was associated with worse PM. In a secondary analysis excluding outliers, higher QUIN correlated with higher pTau. CSF QUIN is thus elevated during HIV infection despite antiretroviral therapy and could indirectly contribute to impaired PM by influencing the formation of pTau. [ABSTRACT FROM AUTHOR]

Despite growing evidence that cytokines and chemokines are expressed in humans and rats after heat stress, the cellular mechanisms underlying the effects on the brain after heatstroke (HS) are not fully understood. In this study, we observed time course changes of chemokines in rat brain tissues and elucidated what kinds of cortical cells were affected after HS. Male SD rats were anesthetized and randomly separated into two groups as follows: (a) normothermic sham and (b) HS rats. Rats were sacrificed at different time points (0, 1, 3, 6, and 12 h after heat exposure, n = 5 in each group) to the end of the experiment in order to extract the mRNA/proteins of cortical tissues. Cerebrospinal fluid (CSF) of sham and HS rats was also collected before sacrifice. In the HS group, an elevated body temperature (Tco > 40 °C) and abnormality of cortical cells (e.g., pyknotic nuclei) were observed. When compared to the sham group, expression levels of either mRNAs or proteins of chemokines and their receptors (including CXCL1, MIP2, MCP1, CXCR1, CXCR2, and CCR2) peaked at different time points after heat exposure. We also found that CXCR2 was expressed in the cortex of rat brain and was colocalized with neurons and microglia after HS. Hence, MCP1, MIP2, and CXCR2 might play important roles in the brain after HS, possibly indicating a new direction for treating HS. [ABSTRACT FROM AUTHOR]

Anti- N -methyl- d -aspartate receptor (NMDAR) encephalitis is an autoimmune disorder of the central nervous system whose pathogenesis involves interleukin (IL)-6 and IL-17A. We examined the correlations between CSF concentrations of the acute-phase protein pentraxin 3 (PTX3), the chronic inflammatory mediator CD40L, IL-6, and IL-17A in anti-NMDAR encephalitis, and the impact on clinical outcome. PTX3, CD40L, IL-6, and IL-17A were significantly higher in the CSF of patients with anti-NMDAR encephalitis than in controls. Within the former, PTX3 levels correlated positively with IL-6 and the mRS, and CD40L levels with IL-17A and the mRS. Higher PTX3 and CD40L levels may reflect the underlying neuroinflammation. [ABSTRACT FROM AUTHOR]

We collected serum-cerebrospinal fluid (CSF)-paired samples during the acute phase of clinical episodes in MS and NMO patients, together with paired samples from non-MS/NMO patients, to compare the quotients of proteins and electrolytes among them. In NMO, the quotient of chloride was significantly higher in the acute phase of optic neuritis and brain lesions, but it was significantly lower in the acute phase of myelitis. Such findings were not observed in MS or in non-MS/NMO cases. With the coexistence of serum anti-AQP4-Ab, chloride imbalance between serum and CSF could be associated with the clinical episodes in NMO. [ABSTRACT FROM AUTHOR]

Mycoplasma pneumoniae ( Mp ) triggers Guillain-Barré syndrome (GBS) and elicits anti-galactocerebroside (GalC) antibodies. Specifically anti-GalC IgG is associated with Mp -GBS, possibly because of its better ability to cross the blood-nerve barrier (BNB). We here investigated CSF for the presence of anti-GalC in GBS. Intrathecal anti-GalC was found in 46% of Mp -GBS patients ( n = 6/13), in contrast to 16% of GBS controls ( n = 4/25) and 0% of non-GBS controls ( n = 0/7). The antibodies most likely originated from increased BNB permeability and/or intrathecal synthesis. Intrathecal anti-GalC IgG was specifically associated with Mp -GBS, further supporting that anti-GalC IgG contributes to the pathogenesis of GBS. [ABSTRACT FROM AUTHOR]

Central neuropathic pain (CNP) is common and disabling among patients with multiple sclerosis (MS). The pathological mechanisms underlying CNP in MS are not well understood. We explored whether NGF is implicated in the pathogenesis of CNP in MS. We measured NGF concentration in the CSF of 73 patients affected by MS, 15 with and 58 without CNP and 14 controls. We found increased levels of NGF in the CSF of patients with CNP compared to patients without and to controls. This finding supports the hypothesis that NGF plays a role in MS related CNP. [ABSTRACT FROM AUTHOR]

Neuroinflammation- and neurodegeneration-induced nerve injury may represent important components of neuropsychiatric lupus (NPSLE). Myelin-associated neurite outgrowth inhibitor (Nogo)-a and its receptor, NgR1, limit recovery of the adult central nervous system after injury. We detected a soluble Nogo-a product in the cerebral spinal fluid of patients with NPSLE. In a mouse model of lupus, aging was associated with an increase in Nogo-a positive neurons, diminished myelin sheaths, enhanced pro-inflammatory cytokines, and impaired cognition and memory. Treatment with the Nogo-66 antagonist promoted myelin repair, improved cognition and memory, and downregulated pro-inflammatory factors. Our data imply the Nogo-a/NgR1 pathway is involved in NPSLE. [ABSTRACT FROM AUTHOR]

The soluble membrane attack complex (sMAC) represents the terminal product of the complement cascade. We enrolled 47 HIV + adults (12 of whom underwent a second visit at least 24 weeks after starting therapy) as well as 11 HIV negative controls. At baseline, cerebrospinal fluid (CSF) sMAC was detectable in 27.7% of HIV + individuals. CSF sMAC correlated with CSF HIV RNA levels and was more likely to be detectable in HIV + individuals on cART compared to HIV negative controls. In HIV + participants, there were negative association trends between sMAC and neurocognitive performance but these did not reach statistical significance. [ABSTRACT FROM AUTHOR]

To address the diagnostic performances of cerebrospinal fluid (CSF) free light chains (FLC) measurements compared to oligoclonal bands (OCB) to support multiple sclerosis (MS) diagnosis. kFLC index showed the highest diagnostic accuracy to detect MS patients with the highest AUC compared to OCB, IgG index, IF kFLC R, kFLC H, λFLC index and IF λFLC. FLC indices are biomarkers of intrathecal Immunoglobulin synthesis and central nervous system (CNS) inflammation. kFLC index can discriminate between MS and other CNS inflammatory disorders, while λFLC index is less informative for MS but can play a role to support the diagnosis of other inflammatory CNS disorders. [Display omitted] • CSF Oligoclonal bands analysis is qualitative and has several limitations. • CSF FLC indices are diagnostic biomarkers of immunoglobulin intrathecal synthesis. • kFLC index has higher sensitivity and NPV but lower specificity than OCB in MS. • λFLC can support the diagnosis of inflammatory diseases other than MS. • IF do not add significant diagnostic value in respect with the kFLC index. [ABSTRACT FROM AUTHOR]

Immune responses in the central nervous system (CNS) are highly compartmentalized and cerebrospinal fluid (CSF) in particular often reflects CNS pathology better than peripheral blood. While CSF leukocytes are known to be distinct from blood, the immediate effects of peripheral leukocyte depletion on CSF leukocytes have not been studied in humans. We here analyzed CSF and blood from two relapsing-remitting multiple sclerosis (RRMS) patients early after peripheral leukocyte depletion with the anti-CD52 antibody alemtuzumab compared to untreated RRMS and control patients using single cell RNA-sequencing. As expected for alemtuzumab, most leukocyte lineages including T cells were synchronously depleted from CSF and blood, while - surprisingly - pDCs were maintained in CSF but depleted from blood by alemtuzumab. Transcriptionally, genes associated with migration were elevated only in the CSF after alemtuzumab. Predicted cellular interactions indicated a central role of pDCs and enhanced migration signaling in the CSF after alemtuzumab. The CSF and blood compartments are thus partially uncoupled, emphasizing that the CNS is only partially accessible even for treatments profoundly affecting the blood. • Immune responses in the central nervous system (CNS) are highly compartmentalized. • pDCs were maintained in CSF but depleted from blood by alemtuzumab. • Genes associated with migration were elevated only in the CSF after alemtuzumab. • The CSF and blood compartments are thus partially uncoupled. [ABSTRACT FROM AUTHOR]

To systematically evaluate the risk factors of post-encephalitis epilepsy (PEE). Systematic computerized searches of databases such as Cochrane Library, PubMed and EMBASE were performed. The meta-analysis of pooled odds ratios and 95% confidence intervals for PEE risk were calculated. Sixteen studies with 2504 patients were included for meta-analysis. The results showed that PEE was associated with coma, seizure, status epilepticus, cranial MRI abnormality, focal EEG abnormality, and positive herpes simplex virus (HSV) in cerebrospinal fluid (CSF). Coma, seizures or status epilepticus, abnormal MRI and focal EEG, and HSV in CSF were the risk factors of PEE. [Display omitted] • Coma, seizures or status epilepticus, abnormal MRI and focal EEG, and positive HSV in CSF were the risk factors of PEE. • Continuing to take ASM after acute phase could reduce the risk of PEE. • Southerners with coma and seizures in China are more likely to develop PEE than northerners. [ABSTRACT FROM AUTHOR]

The transactivator of transcription (Tat) is a HIV regulatory protein which promotes viral replication and chemotaxis. HIV-1 shows extensive genetic diversity, HIV - 1 subtype C being the most dominant subtype in the world. Our hypothesis is the frequency of CSF CD3+CD56+ and CD3−CD56dim is reduced in HIV-1C compared to HIV-1B due to the Tat C30S31 substitution in HIV-1C. 34 CSF and paired blood samples (PWH, n = 20; PWoH, n = 14) were studied. In PWH, the percentage of CD3+CD56+ was higher in CSF than in blood (p < 0.001), comparable in both compartments in PWoH (p = 0.20). The proportion of CD3−CD56dim in CSF in PWH was higher than PWoH (p = 0.008). There was no subtype differences. These results showed CNS compartmentalization of NKT cell response in PWH. [Display omitted] • The impact of HIV-1 Tat on the innate immune response, analyzed by flow cytometry, is not subtype-dependent. • There was elevated CD3+CD56+ cells in the CSF, but not peripheral blood of PWH compared to PWoH. • In PWH there was redistribution of CD3+CD56+ cells from PB to the CNS, and compartmentalization in CNS. • There was an increase in CD3−CD56dim in the CSF of PWH when compared to the PWoH group. [ABSTRACT FROM AUTHOR]

We examined anti-complement C1q (C1q) autoantibody levels in serum and cerebrospinal fluid (CSF) samples of patients with neuromyelitis optica spectrum disorders (NMOSD). We analyzed the correlations between anti-C1q autoantibody levels and the clinical and other CSF characteristics of NMOSD. Serum and CSF anti-C1q autoantibody levels increased during the acute phase of NMOSD, reverting to the same levels as controls during remission. CSF anti-C1q autoantibody levels during the acute phase correlated with several markers reflecting disease severity, Expanded Disability Status Scale worsening, spinal cord lesion length in cases with myelitis, CSF protein and interleukin-6 levels, and CSF/serum albumin ratios. [ABSTRACT FROM AUTHOR]

Autoimmune neurologic syndromes can be paraneoplastic (associated with malignancies and/or onconeural antibodies), or non-paraneoplastic. Their clinical presentation is often similar. As prognosis is related to malignancy treatment, better biomarkers are needed to identify patients with malignancy. We investigated cerebrospinal fluid (CSF) markers of neuronal (neurofilament light chain, NFL and total tau protein, T-tau) and glial (glial fibrillary acidic protein) damage. CSF-NFL and T-tau were increased in both paraneoplastic and non-paraneoplastic autoimmune syndromes. Patients with manifest malignancies were older, had less epilepsy, more focal central and peripheral neurological signs and symptoms, and worse long-term outcome, than those without malignancy. CSF-NFL-levels predicted long-term outcome but were not diagnostic for malignancy, after age adjustment. [ABSTRACT FROM AUTHOR]

Background Multiple sclerosis (MS) is an inflammatory and neurodegenerative disorder of the central nervous system (CNS). Reliable biomarkers are urgently needed for its diagnosis and management, and as clues to its pathogenesis, in which EBV is implicated. Objective To measure IgG antibodies against EBV nuclear antigen-1 (EBNA-1) and innate inflammation status in paired serum and cerebrospinal fluid (CSF) samples from untreated relapsing-remitting MS (RRMS) patients. Materials and methods Anti-EBNA-1 IgG titers and IL-8, IL-1β, IL-6, IL-10, TNF-α and IL-12p70 cytokine levels were measured in 20 untreated RRMS-patients and 17 healthy controls. Results We found higher serum anti-EBNA-1 IgG and IL-8 levels in RRMS-patients than in healthy controls. Interestingly, levels of IL-8 – relative to total protein – were much higher in the CSF, whereas the anti-EBNA-1 antibodies were significantly higher in the sera. More detailed analysis showed that anti-EBNA-1 antibodies relative to total IgG were also higher in the serum in the majority of RRMS patients compared to CSF. Levels of anti-EBNA-1 IgG and IL-8 showed a strong correlation between serum and CSF. Conclusion These findings in newly diagnosed RRMS-patients imply anti-EBNA-1 antibody production mainly in the periphery and innate immune responses preferentially in the CNS. Both their potential as disease biomarkers and their implications for the pathogenesis of MS warrant further investigation. [ABSTRACT FROM AUTHOR]

In this study, we aimed to assess the levels of B cell activating factor from the tumor necrosis factor family (BAFF) and a proliferation-inducing ligand (APRIL) in cerebrospinal fluid (CSF) of patients with anti– N -methyl- d -aspartate receptor (NMDAR) encephalitis and determine their correlation with clinical outcome. BAFF and APRIL concentrations in CSF and serum from 40 patients with anti-NMDAR encephalitis and 20 controls were measured by enzyme-linked immunosorbent assay (ELISA). Compared with controls, the levels of both BAFF and APRIL in CSF were significantly increased in patients with anti-NMDAR encephalitis ( p < 0.001 and p < 0.001). Patients with unfavorable outcome had higher levels of BAFF and APRIL in CSF than those who had favorable outcome ( p < 0.05 and p < 0.05). BAFF and APRIL levels in CSF were elevated and associated with clinical outcome in patients with anti-NMDAR encephalitis, indicating that they may be valuable biomarkers to this disease. [ABSTRACT FROM AUTHOR]

We examined progranulin (PGRN) levels in cerebrospinal fluid (CSF) samples during the acute phase in 15 patients with neuromyelitis optica spectrum disorders (NMOSD) and compared the results with those from 17 patients with multiple sclerosis (MS), 30 patients with other inflammatory neurological diseases (OIND), and 20 non-inflammatory controls (NIC). CSF PGRN levels of NMOSD patients were significantly higher than those of MS patients and NICs. These levels correlated with CSF interleukin-6 levels, CSF cell counts, CSF protein levels, improvements in the Expanded Disability Status Scale score, and affected total spinal cord lesion length in the NMOSD patients. [ABSTRACT FROM AUTHOR]

Soluble CD40 ligand (sCD40L) is reported to disrupt the blood–brain barrier (BBB). Cerebrospinal fluid (CSF) and serum sCD40L levels were measured in 29 multiple sclerosis (MS), 29 neuromyelitis optica spectrum disorder (NMOSD), and 27 disease control (DC) patients. In MS, serum sCD40L levels were higher than in DCs and positively correlated with the CSF/serum albumin ratio (Qalb). In NMOSD, CSF sCD40L levels were significantly increased compared to DCs, and were correlated to Qalb, CSF cell counts, protein concentrations, and interleukin-6 levels. sCD40L could be involved in BBB disruption in MS, whereas it may contribute to CNS inflammation in NMOSD. [ABSTRACT FROM AUTHOR]

Treating MS has been difficult. One successful drug is Ocrelizumab (anti-CD20), used for the chronic relapsing MS (RMS) and the progressive MS (PMS) forms. TH40 cells are pathogenic effector T cells that increase in percentage and numbers during chronic inflammation. Here we show that in the earliest MS course, clinically isolated syndrome (CIS), TH40 cells expand in number. In PMS TH40 cell numbers remain expanded demonstrating sustained chronic inflammation. In RMS TH40 cells were found in CSF and express CD20. Ocrelizumab reduced TH40 cells to healthy control levels in patients. During treatment inflammatory cytokine producing TH40 cells were decreased. [Display omitted] • Increased TH40 cell percentages in peripheral blood are biomarkers for Multiple Sclerosis chronic inflammation. TH40 cell increases, significantly above healthy controls (HC), are detected in Relapsing MS (RMS), but also in a cohort of clinically isolated syndrome (CIS) an early form of MS. These increases demonstrate that a cohort of CIS are experiencing chronic inflammation as a precursor to RMS. • Chronic inflammation is demonstrated in the progressive forms of MS as evidenced by the peripheral blood increases in TH40 cells. In both secondary and primary progressive MS peripheral blood TH40 cell numbers are significantly increased above HC. • TH40 cells are detected in cerebrospinal fluid of RMS patients, but not in HC. The percentage of TH40 cells in CSF is the same as that in peripheral blood of MS patients. TH40 cells breach the central nervous system. • Ocrevus an anti-CD20 monoclonal antibody that reduces B cells in the periphery, also impacts TH40 cell numbers in MS patients. Prior to treatment TH40 cell numbers were significantly increased above HC, during treatment TH40 cell numbers reduced to HC levels and at 12 months post treatment, TH40 cells returned to near pre-treatment numbers. Ocrevus treatment caused significant reduction in TH40 cells while other disease modulating therapies (DMT) did not. • During Ocrevus treatment, the remnant TH40 cells from MS patients produced overall less inflammatory cytokines and increased levels of regulatory cytokines. [ABSTRACT FROM AUTHOR]

Although immune checkpoint inhibitors (ICIs) are widely used to treat unresectable malignant tumors, they can cause undesirable side effects called immune-related adverse events, including neurological toxicities. Here, we describe a case of ICI-related peripheral neuropathy (irPN) with characteristic cerebrospinal fluid (CSF) findings. In addition to pleocytosis and increased protein levels, the present case showed increased levels of CSF soluble interleukin-2 receptor (sIL-2R), IL-6, and IL-10, suggesting activated T cell-related autoimmunity. We believe that CSF cytokines and sIL-2R could be novel biomarkers of irPN. [ABSTRACT FROM AUTHOR]