Cerebrospinal Fluid IgG Research Articles

P-904. Spinal Arachnoiditis and Syringomyelia in Coccidioidomycosis: A Case Series of 53 Adult Patients

Abstract Background Central nervous system (CNS) involvement with coccidioidomycosis (cocci) is a serious infection that is universally fatal if not treated. Prior to the advent of magnetic resonance imaging (MRI), very few reports describe spinal cord involvement and autopsies often omitted spinal cord examination. Accurate and anatomic localization of areas affected by CNS cocci can be challenging due to mental status changes and the presence of brain abnormalities. Here, we describe radiologic and clinical characteristics of 53 cases of CNS cocci who had spinal MRI imaging performed. Methods This retrospective case series reviewed 53 adult patients at the Valley Fever Institute in Bakersfield, California. Patients had confirmed CNS cocci and MRI of at least one segment of the spinal image with and without contrast. A waiver of consent was submitted, and approval was obtained by Kern Medical’s Institutional Review Board. ICD 9 and ICD 10 codes were used to query electronic health record and cross referenced with imaging. Each record reviewed required inclusion criteria of age above 18 years, cerebrospinal fluid (CSF) abnormalities compatible with chronic meningitis and one of the following: positive CSF IgG antibody, CSF complement fixation (CF) or growth of Coccidioides on CSF culture. MRI Imaging with and without contrast of at least one of the following: cervical, thoracic or lumbar spine. Results 77% of the patients were Latinx, 13% African American, 4% Asian and 6% Caucasian. Males make up the majority at 72%. 37% had intrathecal (IT) amphotericin (ABD) injections. Spinal cord abnormalities can be asymptomatic with the most common symptom of back pain followed by radiculopathy. Abnormal findings included leptomeningeal enhancement, arachnoid cysts, masses or adhesions, syringomyelia, myelitis, cord edema, myelomalcia, flattened cord, nerve root "clumping" or solid cauda equina. Conclusion This study suggests the benefit of obtaining neuro axis imaging with and without contrast on all new cases of Coccidioidal meningitis. Spinal cord involvement with CNS cocci is common and contributes to significant morbidity. Contrary to common belief, our study shows that spinal arachnoiditis occurs in patients who were never treated with IT ABD. This may suggest that IT ABD may not cause arachnoiditis. Disclosures All Authors: No reported disclosures

Autoimmune glial fibrillary acidic protein astrocytopathy misdiagnosed as intracranial infectious diseases: case reports and literature review

BackgroundAutoimmune glial fibrillary acidic protein astrocytopathy (A-GFAP-A) is an autoimmune central nervous system(CNS) disease characterized by GFAP IgG as a biomarker. Several cases of individuals with A-GFAP-A initially misdiagnosed as infectious diseases of the central nervous system have been reported in research. We report three cases of A-GFAP-A misdiagnosed as viral meningitis or tuberculous meningitis (TBM). We summarize recent cases of A-GFAP-A misdiagnosed as central nervous system infections through a literature review.Materials and methodsThree cases of A-GFAP-A were initially misdiagnosed as tuberculous or viral meningitis. Their diagnoses of A-GFAP-A were confirmed with positive GFAP-IgG in cerebrospinal fluid (CSF). We searched the PubMed database with the key words of “GFAP astrocytopathy”, “GFAP autoimmunity”, “GFAP autoantibody”, “intracranial infection”, “meningitis”, “misdiagnose”, and within the literature from Jan 1, 2015 to Mar 15, 2024, 40 cases with A-GFAP-A with positive GFAP-IgG in CSF who were previously misdiagnosed with intracranial infection were reported. The causes of misdiagnoses were summarized and analyzed.ResultsCase 1 was a 41-year-old female, presenting with headache, fever, diplopia, and altered consciousness level. Anti-tuberculosis treatment was ineffective. Finally, with positive GFAP IgG in CSF, she was diagnosed with A-GFAP-A. Case 2 was a 74-year-old male, presenting with fever, excessive sweating, fatigue, and memory loss. Anti-tuberculosis treatment was ineffective. With positive GFAP IgG in CSF, he was diagnosed with A-GFAP-A. Case 3 was a 54-year-old male, presenting with fever, personality changes, and memory decline. Antiviral treatment was ineffective. His diagnosis was revised to A-GFAP-A after testing positive for GFAP IgG in CSF. Our study summarized a total of 40 patients with A-GFAP-A who were initially misdiagnosed as intracranial infections. The most common clinical phenotypes among 40 patients were mimicked meningitis, meningoencephalitis, meningoencephalomyelitis, encephalitis and encephalomyelitis.ConclusionA-GFAP-A is a specific autoimmune meningoencephalomyelitis associated with GFAP-IgG, with lesions involved the brain, meninges, and spinal cord. It commonly presents with symptoms such as fever, headache, altered consciousness, tremor, seizures, and autonomic dysfunction. Brain MRI often shows characteristic linear perivascular radial enhancement perpendicular to the ventricles or nonspecific leptomeningeal enhancement. Early detection of GFAP-IgG in serum and CSF is essential for differential diagnosis.

Anti-Tick-Bourne Encephalitis IgM Intrathecal Synthesis as a Prediction Marker in Tick-Borne Encephalitis Patients.

The aim of this study was to evaluate the usefulness of IgM anti-Tick-Borne Encephalitis (anti-TBE) intrathecal synthesis in the diagnosis and prediction of the clinical course of the disease. Thirty-six patients were included in the study (patients reported symptoms such as fever, headache, fatigue, and nausea/vomiting). CRP, White Blood Cells (WBC), pleocytosis, Cerebrospinal Fluid (CSF) protein concentration, CSF albumin concentration, serum IgM, serum IgG, CSF IgM, CSF IgG, IgM Index, IgG Index, and IgG Index/IgM Index ratio were the parameters which were examined in the individuals. An analysis of correlation presented statistical significance between IgM Index and pleocytosis and protein concentration in CSF in the whole group of individuals. IgM Index and IgG Index/IgM Index ratio may be used in the prediction of severity of TBE. The most probable link between the IgM intrathecal production and severity of TBE may be a result of delayed seroconversion to IgG, and therefore not an adequate response to the virus presence.

Elevated Kappa Index in the Absence of Cerebrospinal Fluid IgG Oligoclonal Bands: Contribution of Intrathecal IgM and IgA Synthesis.

The kappa index is a well-established marker of intrathecal synthesis (IS) of immunoglobulin (Ig). Routinely used for diagnostic aims, IgG IS, which can be assessed quantitatively (ad hoc formulas) or qualitatively (oligoclonal bands, OCBs), may fail in detecting a humoral immune response within the central nervous system (CNS). The main aim of this study was to evaluate the kappa index for its ability to detect the presence of CNS humoral immunity and to associate it with a distinct group of disorders, in the absence of IgG IS/OCBs. Within the kappa index-positive, IgG OCB-negative (Kappa+OCB-) patient group, we also examined whether IgM/IgA IS, determined with the IgM/IgA index and CSF IgM OCBs, could contribute to disease group stratification. Diagnoses were classified as multiple sclerosis (MS), or other inflammatory (INFL), infectious (INFECT), or non-inflammatory (Other) central/peripheral nervous system disorders. Sixty-nine Kappa+OCB- patients and 50 controls (24 Kappa-OCB- and 26 Kappa+OCB+ patients) were included in this study. The most frequent diagnosis in the Kappa+OCB- group was MS (27/69), followed by INFECT (16/69). Additional evidence of IS was demonstrated through an elevated IgG/IgM/IgA index or by the presence of IgM OCBs in 59%, and through only IgM/IgA IS in 52% of cases. In INFECT patients, the median IgM/IgA indexes were higher (p < 0.001) than in other groups, with 18 patients (95%) presenting an elevated IgM index, 11 patients (58%) presenting CSF IgM OCBs, and 10 patients (53%) presenting an elevated IgA index. The vast majority of all INFECT (16/19) belonged to the Kappa+OCB- group. Our data confirm that the kappa index performs at the highest level in assessing intrathecal humoral immunity and supporting the diagnosis of both MS and CNS infectious disorders, which are also characterized by the intrathecal production of IgM and IgA.

Kappa Free Light Chains in Multiple Sclerosis as a Marker of Intrathecal Humoral Response: A Sex-Disaggregated Study.

Kappa free light chains (KFLCs) are emerging as promising biomarkers for intrathecal B cell activity for diagnosing multiple sclerosis (MS) through cerebrospinal fluid (CSF) analysis. In this study, we evaluated the ability of KFLC formulas to identify the presence of MS and their agreement with the 'gold standard' of CSF IgG oligoclonal bands (OCBs). A total of 233 patients were included in this study: 149, comprising 43 males and 106 females, had MS, and the remainder, 40 males and 44 females, had other neurological diseases (ONDs). We evaluated the potential of KFLCs in terms of sensitivity, specificity, and accordance. All analyses were conducted using a sex-disaggregated approach. KFLCs showed a high sensitivity for both sexes with respect to the diagnosis of MS, with values between 74.42% and 93.03%. The specificity of the various formulas was much lower for females when compared to males, with values between 45.45% and 59.09%, with a significant difference between the two sexes for the K Index > 5.9 (p = 0.0451). Cohen's kappa showed substantial agreement for men and moderate agreement for women between the KFLC indices and OCB. This study highlights the potential of KFLCs as a biomarker for MS but emphasises the need for sex-specific thresholds to improve diagnostic accuracy.

Intrathecal IgG and IgM synthesis correlates with neurodegeneration markers and corresponds to meningeal B cell presence in MS

Intrathecal synthesis of immunoglobulins (Igs) is a key hallmark of multiple sclerosis (MS). B cells are known to accumulate in the leptomeninges of MS patients and associate with pathology in the underlying cortex and a more severe disease course. However, the role of locally produced antibodies in MS brain pathology is poorly understood. Here, we quantified the protein levels of IgA, IgM, IgG and albumin in serum and cerebrospinal fluid (CSF) samples of 80 MS patients and 28 neurological controls to calculate Ig indices. In addition, we quantified presence of meningeal IgA+, IgM+ and IgG+ B cells in post-mortem brain tissue of 20 MS patients and 6 controls using immunostainings. IgM and IgG, but not IgA, indices were increased in CSF of MS patients compared to controls, with no observed differences between MS disease types. Both IgM and IgG indices correlated significantly with neurofilament light (NfL) levels in CSF, but not with clinical or radiological parameters of disease. Similarly, IgG+ and IgM+ B cells were increased in MS meninges compared to controls, whereas IgA+ B cells were not. Neuronal loss did not differ between sections with low or high IgA+, IgM+ and IgG+ B cells, but was increased in sections with high numbers of all CD19+ meningeal B cells. Similarly, high presence of CD19+ meningeal B cells and IgG+ meningeal B cells associated with increased microglial density in the underlying cortex. Taken together, intrathecal synthesis of IgG and IgM is elevated in MS, which corresponds to an increased number of IgG+ and IgM+ B cells in MS meninges. The significant correlation between intrathecal IgG and IgM production and NfL levels, and increased microglial activation in cortical areas adjacent to meningeal infiltrates with high levels of IgG+ B cells indicate a role for intrathecal IgM- and IgG-producing B cells in neuroinflammatory and degenerative processes in MS.

Fibrinolysis associated proteins and lipopolysaccharide bioactivity in plasma and cerebrospinal fluid in multiple sclerosis

The coagulation cascade and fibrinolysis have links with neuroinflammation and increased activation of the coagulation system has been reported in MS patients. We quantified levels of D-dimer, tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1) and the bioactivity of bacterial lipopolysaccharide (LPS) in cerebrospinal fluid (CSF) and plasma from newly diagnosed untreated MS patients and controls. These molecules showed multiple correlations with each other as well as with age, HLA-DRB1*15:01, body-mass-index and CSF IgG. Our results confirm previous findings of increased plasma PAI-1 and LPS in MS patients compared to controls indicating changes in platelet function and gut permeability in MS.

Elevated cerebrospinal fluid IgG index in herpes simplex encephalitis post-HSV-1 clearance: A preliminary study.

Herpes simplex encephalitis (HSE) is an acute form of encephalitis that can lead to poor neurological outcomes. Although the exact pathogenesis of HSE remains elusive, recent reports suggest a significant role for postinfectious immune-inflammatory processes in the central nervous system (CNS). This study aimed to clarify the association between CNS autoimmune responses and clinical presentation in patients with HSE, focusing on cerebrospinal fluid (CSF) characteristics, particularly the IgG index. We retrospectively analyzed 176 consecutive patients suspected of having aseptic meningitis /encephalitis for chronological changes in CSF findings and clinical presentations. These patients underwent PCR screening for herpesviruses (HV) in their CSF. We identified sevenpatients positive for herpes simplex virus type 1 (HSV-1), 20 patients positive for varicella-zoster virus, and 17 patients who met the criteria for aseptic meningitis but were PCR-negative for HV. Patients in the HSV-1-positive group exhibited a significant increase in the IgG index at the time of PCR-negative conversion compared with on admission (p = 0.0156), while such a change was not observed in the other two groups. Additionally, all patients in the HSV-1-positive group tested negative for anti-neural autoantibodies in CSF and serum samples collected approximately 3 weeks after onset. This study, therefore, highlights that CSF IgG index elevation occurs even after PCR-confirmed HSV-1 clearance, which might indicate immunopathogenesis that is independent of antibody-mediated mechanisms.

A rare complication of measles infection presented with subacute sclerosing panencephalitis: Report of two cases in India

Rationale: Subacute sclerosing panencephalitis (SSPE) is a progressive neurological disorder caused by persistent measles virus infection. SSPE predominantly affects children and adolescents. The symptoms usually develop 6-15 years after measles infection and ultimately leading to death in many cases. Patient concerns: Patient 1 presented with cognitive decline and myoclonus and the Patient 2 presented with diminution of vision with myoclonic jerks. Diagnosis: Based on the clinical features with a characteristic electroencephalogram pattern and the presence of a high titer of anti-measles IgG in serum and cerebrospinal fluid, these patients were diagnosed as SSPE. Interventions: Antiepileptics were started for controlling myoclonus along with supportive treatment. Outcomes: Both patients were discharged on antiepileptics and supportive care. Lessons: Whenever there are unusual clinical manifestations with unknown vaccination status, SSPE can be suspected and the cerebrospinal fluid should be examined for anti-measles antibodies. Our case study also highlights the importance of universal coverage of measles vaccination. To reduce the incidence of measles and associated deaths, it is important to maintain a high level of immunization coverage for the measles vaccine and to strengthen all the integral components of the national immunization program.

NIPAH Virus Encephalitis: Unveiling the Epidemiology, Risk Factors, and Clinical Outcomes – A Systematic Review and Meta-Analysis

ABSTRACT Objective: This study assessed Nipah virus (NiV) encephalitis epidemiology, clinical outcomes, and risk variables to inform treatment and prevention. Methodology: In a PubMed systematic search, 929 citations were found. After screening and eligibility, 22 studies were included. This study obtained age, gender, geographic regions, diagnostic methods, data collection methods, and bias risk. The case fatality rate (CFR) and NiV infection risk variables were evaluated by meta-analysis. Results: Southeast Asia, especially Bangladesh and Malaysia, had the most NiV cases. The major diagnostic method was blood and cerebrospinal fluid IgM and IgG antibody tests, and males predominated. Proxy respondents and matched controls were utilized for risk factor analyses when patients could not answer. The pooled CFR for NiV encephalitis was 61.0%, indicating severity. Risk factors included pigs, nighttime bats near homes, tree climbing, and male gender. Conclusion: Southeast Asian public health is plagued by NiV encephalitis. The high CFR calls for better diagnosis, treatment, and prevention. NiV’s multiple risk factors must be understood for targeted therapy. Future research should fill knowledge gaps and improve NiV infection prevention.

Characteristics of cerebrospinal fluid oligoclonal band in anti-myelin oligodendrocyte glycoprotein (MOG) antibody associated disease

ObjectiveTo analyze the immune parameters of cerebrospinal fluid (CSF) and oligoclonal band (OCB) type in patients with anti-myelin oligodendrocyte glycoprotein (MOG) antibody-associated diseases (MOGAD). MethodsPatients who were seropositive for MOG-IgG and diagnosed with MOGAD according to the diagnosis criteria in the Department of Neurology, Huashan Hospital, Fudan University from December 2020 to June 2022 were retrospectively included in this study. Complete clinical data, blood and cerebrospinal fluid samples were collected from all the participants. Paired serum and CSF MOG-IgG and autoimmune encephalitis antibody were assayed by Cell Based Assay (CBA) based on transfected target antigens. Paired serum and CSF albumin and IgG were detected by turbidimetric scattering method, and OCB was detected by standard operation procedure as described. ResultsA total of 86 patients (44 males and 42 females) with MOGAD were included in this study, with a median age of 30 years (range: 5–82 years). Among all the patients, 73 patients showed OCB type I, 12 patients showed OCB type II, and one patient showed OCB type III. The overall positive rate of CSF-OCB in MOGAD patients was 15.1 %. The 24-h intrathecal synthesis rate of CSF in the OCB-positive group (n = 13) was higher than that in the OCB-negative group [n = 73, 0.62 (0.26) vs 5.11 (13.67), P = 0.003]. Subgroup analysis revealed that the positive rates of CSF-OCB in the single MOG group (n = 61) and the group combined with other antibodies (n = 25) were 14.8 % and 16.0 %, respectively. The incidence of meningoencephalitis (13/61 vs 13/25, P = 0.011) was significantly different between the two groups. The proportion of patients with high (≥1:32) or low (≤1:10) CSF MOG-IgG also showed significant difference in the group combined with other antibodies (P = 0.032). Optic neuritis was more common in the relapse course group (n = 49) than the monophasic course group (n = 37, P < 0.001) No significant diferences of CSF immune parameters were found in the MOG-IgGserum+/CSF− group and the MOG-IgGserum+/CSF + group, and the titer of MOG-IgG in the serum or CSF did not influence CSF immune parameters in different subgroups. ConclusionThe overall positive rate of CSF-OCB in MOGAD patients was 15.1 %. The 24-h intrathecal synthesis rate of cerebrospinal fluid in the OCB-positive group was higher than that in the OCB-negative group. This study illustrated OCB characterization in MOGAD patients, and will shed light on the standardization of OCB test in the study of immune diseases.

The analysis of serum lipids profile in Guillain-Barre syndrome.

Guillain-Barre syndrome (GBS) is an immune-mediated inflammatory peripheral neuropathy. This study aimed to conduct a systematic analysis of the serum lipids profile in GBS. We measured the serum lipids profile in 85 GBS patients and compared it with that of 85 healthy controls matched for age and sex. Additionally, we analyzed the correlation between lipids and the severity, subtypes, precursor infections, clinical outcomes, clinical symptoms, immunotherapy, and other laboratory markers of GBS. Compared to the healthy controls, GBS exhibited significantly elevated levels of Apolipoprotein B (APOB), Apolipoprotein C2 (APOC2), Apolipoprotein C3 (APOC3), Apolipoprotein E (APOE), triglycerides (TG), and residual cholesterol (RC). Conversely, Apolipoprotein A1 (APOA1), Apolipoprotein A2 (APOA2), and high-density lipoprotein (HDL) were substantially lower in GBS. Severe GBS displayed noticeably higher levels of APOC3 and total cholesterol (TC) compared to those with mild disease. Regarding different clinical outcomes, readmitted GBS demonstrated higher RC expression than those who were not readmitted. Moreover, GBS who tested positive for neuro-virus antibody IGG in cerebrospinal fluid (CSF) exhibited heightened expression of APOC3 in comparison to those who tested negative. GBS with cranial nerve damage showed significantly reduced expression of HDL and APOA1 than those without such damage. Additionally, GBS experiencing limb pain demonstrated markedly decreased HDL expression. Patients showed a significant reduction in TC after intravenous immunoglobulin therapy. We observed a significant positive correlation between lipids and inflammatory markers, including TNF-α, IL-1β, erythrocyte sedimentation rate (ESR), white blood cells, monocytes, and neutrophils in GBS. Notably, APOA1 exhibited a negative correlation with ESR. Furthermore, our findings suggest a potential association between lipids and the immune status of GBS. The research demonstrated a strong connection between lipids and the severity, subtypes, clinical outcomes, precursor infections, clinical symptoms, immunotherapy, inflammation, and immune status of GBS. This implies that a low-fat diet or the use of lipid-lowering medications may potentially serve as an approach for managing GBS, offering a fresh viewpoint for clinical treatment of this condition.

A retrospective study of myelin oligodendrocyte glycoprotein antibody-associated disease from a clinical laboratory perspective.

To analyze the differences in laboratory data between patients with myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD), multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). The study included 26 MOGAD patients who visited Beijing Tiantan Hospital from 2018 to 2021. MS and NMOSD patients who visited the clinic during the same period were selected as controls. Relevant indicators were compared between the MOGAD group and the MS/NMOSD groups, and the diagnostic performance of meaningful markers was assessed. The MOGAD group showed a slight female preponderance of 57.7%, with an average onset age of 29.8 years. The absolute and relative counts of neutrophils were higher in the MOGAD group than in the MS group, while the proportion of lymphocytes was lower. The cerebrospinal fluid (CSF) IgG level, IgG index, 24-h IgG synthesis rate, and positive rate of oligoclonal bands (OCB) were lower in MOGAD patients than in the MS group. The area under ROC curve (AUC) was 0.939 when combining the relative lymphocyte count and IgG index. Compared to the NMOSD group, the MOGAD group had higher levels of serum complement C4 and lower levels of serum IgG. The AUC of serum C4 combined with FT4 was 0.783. Statistically significant markers were observed in the laboratory data of MOGAD patients compared to MS/NMOSD patients. The relative lymphocyte count combined with IgG index had excellent diagnostic efficacy for MOGAD and MS, while serum C4 combined with FT4 had better diagnostic efficacy for MOGAD and NMOSD.

The relevance of NMDA receptor antibody-specific index for diagnosis and prognosis in patients with anti-NMDA receptor encephalitis

The clinical implications of the presence of anti-N-methyl-D-aspartate receptor (NMDAR)-specific intrathecal immunoglobulin G synthesis and whether it determines the diagnosis of anti-NMDAR encephalitis have not been thoroughly investigated yet. Thus, the aim of this study was to investigate whether the detection of intrathecal anti-NMDAR-specific IgG synthesis contributes to the diagnostic confirmation of anti-NMDAR encephalitis, to disease severity, and to prognosis in patients with positive serum anti-NMDAR-IgG. In this study, patients with detectable anti-NMDAR IgG in serum and/or cerebrospinal fluid (CSF) were included and separated into two groups that either met the 2016 criteria by Graus et al. of definite anti-NMDAR encephalitis (n = 27) or did not (n = 15). In a total, of 80 paired CSF/serum samples, antibody titers were titrated manually and end-point titer levels were carefully determined in a blinded manner to the subgroup attribution. The disease course was assessed via the modified Rankin Scale (mRS) and prognosis was estimated by the anti-NMDAR Encephalitis One-Year Functional Status (NEOS) score. With respect to whether the diagnostic Graus criteria for definite anti-NMDAR encephalitis were fulfilled, a significantly unequal distribution of intrathecal anti-NMDAR antibody-specific synthesis could be shown with a high negative predictive value in case of a negative anti-NMDAR antibody-specific index (NMDAR AI, p = .008. OR = 23.9, sensitivity = 1.0, specificity = 0.4, negative predictive value = 1). A weak correlation was found between the CSF antibody titer and mRS value at the time of sample collection (rs = .37, p = .008, 95% CI [.09, .59]). During the disease course a higher delta-mRS value formed of the mRS at initial presentation minus that at the last recorded presentation correlated with a higher NMDAR AI at first lumbar puncture (rs = − .56, p = .017, 95% CI [− .83, − .11]). No association with the prognostic NEOS score was found. In conclusion, a negative antibody-specific index for anti-NMDAR IgG antibodies has a highly negative predictive value for the diagnosis of anti-NMDAR encephalitis. Yet, a positive NMDAR AI alone does not allow the diagnosis of anti-NMDAR encephalitis.

IgG index of cerebrospinal fluid can reflect pathophysiology associated with Lewy bodies in Parkinson's disease

BackgroundNeuroinflammation is one of the pathophysiologies of Parkinson's disease (PD). Lewy bodies, the pathological hallmark of PD, emerge as a consequence of α-synuclein aggregation, and neuroinflammation is induced concurrently with this aggregation. Imaging and cerebrospinal fluid (CSF) biomarkers that reflect PD pathophysiology have been developed or are under investigation. The IgG index of CSF is a marker of inflammation, and may also reflect the pathophysiology of PD. AimWe examined if the IgG index reflects the pathophysiology of PD in drug-naïve PD patients. MethodThe subjects were 20 consecutive PD patients who underwent 123I-MIBG scintigraphy for assessment of the heart to mediastinum (H/M) ratio and wash out rate, 123I-Ioflupane SPECT for examination of the specific binding ratio in the striatum, and lumbar puncture before treatment. The CSF IgG index and levels of pathogenic proteins (total α-synuclein, oligomeric α-synuclein, total tau, phosphorylated tau and amyloid Aβ1–42) were determined. The IgG index was compared with the other parameters using Spearman correlation analysis. ResultsThe IgG index showed a significant correlation with the H/M ratio in early (r = −0.563, p = 0.010) and delayed (r = −0.466, p = 0.038) images in 123I-MIBG scintigraphy and with the CSF total tau level (r = −0.513, p = 0.021). ConclusionNeuroinflammation is involved in PD pathophysiology in some patients, and a higher IgG index indicates the presence of neuroinflammation accompanied by emergence of Lewy bodies.

Les sous-classes d’IgG dans le LCR présentent-elles un réel intérêt ?

AbstractSerum total IgG measurement is a common lab act in medical biology. More specialized, serum IgG subclasses measurement plays a key role in IgG4-Re- lated Disease but is also useful for second-line diagnosis in humoral immune deficiencies. In the cerebrospinal fluid (CSF), an index is used as an indicator of the relative amount of CSF IgG compared to serum. Any increase in the index reflects IgG production in the central nervous system. Regarding IgG subclasses in the CSF, medical laboratories are now getting demands, actually to find out if there is any IgG4 subclass. These IgG4 in CSF could be associated with IgG4-related hypertrophic pachymeningitis but without appropriate studies corroborating this, their measurement should be done only when tissue biopsy cannot be performed. Quantitative measurement on serum is validated with nephelometry and turbidimetry assays. Each laboratory has to validate the assays on CSF before giving results. In this mini review, we present the indications of total IgG and IgG subclasses on serum as well as the benefit of IgG subclasses in CSF and the techniques available in a medical laboratory.

A 12-year-old Asian Indian boy with bilateral rapidly progressive necrotizing Macular Retinitis.

To describe clinical and imaging findings in a young boy presenting with bilateral rapidly progressive necrotizing macular retinitis. A 12-year-old Asian Indian boy developed bilateral progressive macular retinitis. He had generalized tonic-clonic seizures for the past 3 months and gave a history of poor scholastic performance with dementia of recent onset. Multimodal imaging comprising and detailed systemic and laboratory work-up was performed. Both eyes showed rapidly progressive full-thickness retinitis lesions observed as disruption of retinal architecture in both eyes. Left eye optical coherence tomography shows full-thickness retinal involvement with sparing of the internal limiting membrane. Electroencephalogram and magnetic resonance imaging (brain) were suggestive of subacute sclerosing panencephalitis and the diagnosis was confirmed by elevated cerebrospinal fluid and serum IgG measles. The patient did not survive despite treatment with systemic interferon therapy. It is important to look for the measles virus as a probable cause of necrotizing retinitis and neurologic symptoms in immunocompetent unvaccinated young patients. Early referral to a neurologist may assist in the early diagnosis of subacute sclerosing panencephalitis and targeted therapy.

Associations of the cerebrospinal fluid lymphocyte population with a clinical presentation of tick-borne encephalitis

In tick-borne encephalitis (TBE), lymphocytes infiltrating central nervous system are indispensable for the infection control, but also potentially immunopathogenic. To clarify their roles, we have evaluated cerebrospinal fluid (CSF) count of the main lymphocyte populations (considered as a proxy of the brain parenchyma lymphocytic infiltrate) in TBE patients and analyzed if they associate with clinical presentation, blood-brain barrier disruption and intrathecal antibody synthesis.We have studied CSF from 96 adults with TBE (50 with meningitis, 40 with meningoencephalitis, 6 with meningoencephalomyelitis), 17 children and adolescents with TBE and 27 adults with non-TBE lymphocytic meningitis. Th CD3+CD4+, Tc CD3+CD8+, double positive T CD3+CD4+CD8+, B CD19+ and NK CD16+/56+ cells were counted cytometrically with a commercial fluorochrome-stained monoclonal antibody set. The associations between the counts and fractions of these cells and clinical parameters were analyzed with non-parametric tests, p<0.05 considered significant.The TBE patients had lower pleocytosis with similar proportions of the lymphocyte populations compared to non-TBE meningitis. The different lymphocyte populations correlated positively with one another, as well as with CSF albumin, IgG and IgM quotients. The higher pleocytosis and expansion of Th, Tc and B cells associated with a more severe disease and neurologic involvement: Th with encephalopathy, myelitis and weakly with cerebellar syndrome, Tc with myelitis and weakly with encephalopathy, B with myelitis and with at least moderately severe encephalopathy. The double-positive T lymphocytes associated with myelitis, but not with other forms of CNS involvement. The fraction of double positive T cells decreased in encephalopathy and the fraction of NK in patients with neurologic deficits. In children with TBE, Tc and B counts were increased at the expense of Th lymphocytes in comparison with adults.The concerted intrathecal immune response, involving the main lymphocyte populations, increases with the clinical severity of TBE, with no evidently protective or pathogenic elements distinguishable. However, the particular populations including B, Th and Tc cells associate with different, though overlapping, spectra of CNS manifestations, suggesting they may be specifically related to TBE manifesting as myelitis, encephalopathy and cerebellitis. The double-positive T and NK cells do not expand evidently with severity and may be most closely associated with the protective anti-TBEV response.

Selective emergence of antibody-secreting cells in the multiple sclerosis brain.

Although distinct brain-homing B cells have been identified in multiple sclerosis (MS), it is unknown how these further evolve to contribute to local pathology. We explored B-cell maturation in the central nervous system (CNS) of MS patients and determined their association with immunoglobulin (Ig) production, T-cell presence, and lesion formation. Exvivo flow cytometry was performed on post-mortem blood, cerebrospinal fluid (CSF), meninges and white matter from 28 MS and 10 control brain donors to characterize B cells and antibody-secreting cells (ASCs). MS brain tissue sections were analysed with immunostainings and microarrays. IgG index and CSF oligoclonal bands were measured with nephelometry, isoelectric focusing, and immunoblotting. Blood-derived B cells were cocultured under T follicular helper-like conditions to evaluate their ASC-differentiating capacity invitro. ASC versus B-cell ratios were increased in post-mortem CNS compartments of MS but not control donors. Local presence of ASCs associated with a mature CD45low phenotype, focal MS lesional activity, lesional Ig gene expression, and CSF IgG levels as well as clonality. Invitro B-cell maturation into ASCs did not differ between MS and control donors. Notably, lesional CD4+ memory T cells positively correlated with ASC presence, reflected by local interplay with T cells. These findings provide evidence that local B cells at least in late-stage MS preferentially mature into ASCs, which are largely responsible for intrathecal and local Ig production. This is especially seen in active MS white matter lesions and likely depends on the interaction with CD4+ memory T cells. Stichting MS Research (19-1057 MS; 20-490f MS), National MS Fonds (OZ2018-003).

Area postrema syndrome with linear enhancement along the surface of the brainstem and fourth ventricle in autoimmune GFAP astrocytopathy

BackgroundGlial fibrillary acidic protein (GFAP) astrocytopathy, a novel autoimmune disease of the nervous system, was first defined in 2016. To our knowledge, area postrema syndrome (APS) with linear enhancement along the surface of the brainstem and fourth ventricle is extremely rare in this disorder.Case presentationA Chinese woman presented with intractable nausea and vomiting after onset of flu-like symptoms. Brain magnetic resonance imaging (MRI) disclosed abnormal signal intensities in the dorsal medulla oblongata including area postrema. Besides, linear enhancement surrounding the surface of the brainstem and fourth ventricle was visualized after gadolinium injection. Cerebrospinal fluid (CSF) analysis showed increased cell count and protein. A cell-based assay was positive for anti-GFAP IgG in CSF. She was diagnosed with autoimmune GFAP astrocytopathy and treated with high-dose glucocorticoid. The patient received a quick recovery with entire resolution of the initial abnormalities.ConclusionsIsolated APS can be the initial manifestation of autoimmune GFAP astrocytopathy. Linear enhancement surrounding the surface of the brainstem and fourth ventricle is another neuroradiological hallmark.