Bands In Cerebrospinal Fluid Research Articles

B-083 Sensitivity of the Sebia Hydragel 6 electrophoresis/immunofixation assay for detection of beta-2 transferrin in dilute cerebrospinal fluid (CSF): assessment by image analysis

Abstract Background Beta-2 transferrin (asialo transferrin) greater than 2-sialo transferrin is characteristic of cerebrospinal fluid (CSF). Our neurosurgery department recently requested availability of an in-house assay to evaluate post-surgical drainage fluids for presence of CSF. The Sebia Hydragel 6 beta-2 transferrin electrophoresis/immunofixation profile can be used as a qualitative (positive/negative) assay for this purpose. As a starting point for evaluation of the assay, we examined the sensitivity of the assay for detection of the beta-2 transferrin band in dilute CSF. This was performed by quantitative image analysis. Methods Assays were conducted according to manufacturer's instructions. Our proband sample was pooled CSF. Successive dilutions were by factors of 2 (1, 1/2, 1/4, 1/8, 1/16, 1/32). Electrophoresis/ immunofixation was performed simultaneously for these samples across lanes in 6-lane gels. We performed quantitative assessment of the electrophoretic bands for beta-2 transferrin by image analysis. The gel image was scanned to an electronic file (600 dpi png) using a desktop scanner. Grayscale pixel data were obtained using Python and the Python Image Library (PIL). Total grayscale integrals for staining of beta-2 transferrin bands were computed and compared across dilutions of the proband sample. Results For CSF dilutions, the assay was invariably visually positive down to dilutions of 1/16. By image analysis, this cutoff had signal/noise ratio (S/N) of 3.5. Across dilutions, band integrals were dependent on dilutions according to a simple hyperbola (representative example: see Figure). Conclusions The Sebia Hydragel 6 electrophoresis/immunofixation assay for qualitative assessment of presence of beta-2 transferrin was found to be suitable for unambiguous detection of beta-2 transferrin in CSF down to 1/16 dilution of CSF. By image analysis, the dose vs. response curve (density of staining for beta-2 transferrin across dilutions of CSF) was non-linear.

Area Postrema Syndrome as the Onset of Neuromyelitis Optica in a Pediatric Patient: Case Report

AbstractArea postrema syndrome, characterized by nausea, emesis, and persistent hiccups can be the initial manifestation of demyelinating diseases of the central nervous system.We report a 4-year-old girl who presented with intractable vomiting that was noted to have signs of demyelination in the area postrema. MRI of the spine revealed longitudinally extensive myelitis in the cervical and thoracic spine. Neuromyelitis optica spectrum disorder (NMOSD) was suspected. Serum anti-aquaporin 4 antibodies were positive. Oligoclonal bands in cerebrospinal fluid were negative.NMOSDs are extremely rare in the pediatric population, this being the second case reported in Colombia. It is crucial to consider the possibility of such neurological disorders in the setting of intractable vomiting.

The combined application of oligoclonal bands in cerebrospinal fluid and IgG intrathecal synthesis indicators and biochemical markers in the diagnosis of multiple sclerosis

Objective: To establish and verify a diagnostic model for distinguishing multiple sclerosis (MS) from other neurological diseases with similar symptoms by usingcerebrospinal fluid oligoclonal band (CSF-OCB)combined with IgG intrathecal synthesis indicators and biochemical markers. Methods: Multiple sclerosis (MS) patients admitted to the Neurology Department of Beijing Tiantan Hospital affiliated with Capital Medical University from January 2014 to December 2022 were selected as the case group, while patients with similar neurological symptoms were selected as the control group. Using the case-control study design, a retrospective analysis was conducted on the detection of age, gender, oligoclonal bands in cerebrospinal fluid, IgG intrathecal synthesis indicators and biochemical indicators for all study subjects. The differential diagnosis model was determined by the multiple logistic regression analysis, and the receiver operating characteristic (ROC) curve was used to analyze the diagnostic efficiency of the differential diagnosis model for neurological diseases with similar symptoms to MS and other conditions. Results: This study included 167 patients in the case group and 335 patients in the control group, of which 128 patients in the case group and 265 patients in the control group were used to construct the model, and 39 patients in the case group and 70 patients in the control group were used for model validation. The differential diagnostic model constructed by a multivariate logistic regression model was Y=0.871×CSF-OCB-0.051×CSFprotein-0.231×CSFchloride+1.183×gender-0.036×LDH+35.770. The model showed that the area under the curve, sensitivity and specificity were respectively 0.916, 87.3% and 87.6%. The Delong test results showed that the diagnostic efficacy of the model was significantly different from OCB, IgG intrathecal synthesis indicators, and OCB combined with IgG intrathecal synthesis indicators (P<0.05). The new model validation showed that the actual diagnostic consistency rate for the MS group was 84.6%, while the actual diagnostic consistency rate for the control group was 90.0%. Conclusion: This study combines OCB, IgG intrathecal synthesis indicators, and biochemical indicators to establish a diagnostic prediction model for neurological diseases with similar clinical symptoms in MS. This model may have good differential diagnostic value and can better assist clinical diagnosis in the early stages of disease progression in MS patients.

Pure spinal multiple sclerosis: A case series of a possible new entity

BackgroundRecent literature describes a condition similar to multiple sclerosis (MS) but with demyelinating lesions limited to the spinal cord. This condition, referred to as “pure spinal” MS, might benefit from disease-modifying treatment (DMT). MethodsWe screened the medical records of approximately 8000 patients with demyelinating diseases at the Isfahan MS clinic in Iran. Criteria for inclusion in the case series were adults with a demyelinating disease limited to the spinal cord, positive oligoclonal IgG bands in cerebrospinal fluid (CSF), and negative results for other potential diagnoses. ResultsSeven people with pure spinal MS were identified (all women, mean age [SD]: 40.14 [6.17] years at the first visit, mean follow-up duration [SD]: 98 [39.41] months). Two had a family history of conventional MS in their siblings. All patients exhibited lower limb weakness and tested negative for anti-MOG and anti-AQP4 antibodies. They experienced relapsing-remitting partial myelitis, with new spinal cord lesions on MRI but no extraspinal CNS lesions. DMT significantly reduced relapse rates in all patients, and two showed no increase in EDSS scores. ConclusionPure spinal MS might be an atypical form of MS. Those affected may benefit from DMT; therefore, further investigation and consideration in the upcoming revisions of the McDonald criteria are recommended.

Predicting the conversion from clinically isolated syndrome to multiple sclerosis: An explainable machine learning approach

IntroductionPredicting the conversion of clinically isolated syndrome (CIS) to clinically definite multiple sclerosis (CDMS) is critical to personalizing treatment planning and benefits for patients. The aim of this study is to develop an explainable machine learning (ML) model for predicting this conversion based on demographic, clinical, and imaging data. MethodThe ML model, Extreme Gradient Boosting (XGBoost), was employed on the public dataset of 273 Mexican mestizo CIS patients with 10-year follow-up. The data was divided into a training set for cross-validation and feature selection, and a holdout test set for final testing. Feature importance was determined using the SHapley Additive Explanations library (SHAP). Then, two experiments were conducted to optimize the model's performance by selectively adding variables and selecting the most contributive variables for the final model. ResultsNine variables including age, gender, schooling, motor symptoms, infratentorial and periventricular lesion at imaging, oligoclonal band in cerebrospinal fluid, lesion and symptoms types were significant. The model achieved an accuracy of 83.6 %, AUC of 91.8 %, sensitivity of 83.9 %, and specificity of 83.4 % in cross-validation. In the final testing, the model achieved an accuracy of 78.3 %, AUC of 85.8 %, sensitivity of 75 %, and specificity of 81.1 %. Finally, a web-based demo of the model was created for testing purposes. ConclusionThe model, focusing on feature selection and interpretability, effectively stratifies risk for treatment decisions and disability prevention in MS patients. It provides a numerical risk estimate for CDMS conversion, enhancing transparency in clinical decision-making and aiding in patient care.

African-Americans With Multiple Sclerosis Have a Higher Proportion of B-Cell Lineage Cells in Their Cerebrospinal Fluid (CSF) Than White Patients (P9-3.010)

<h3>Objective:</h3> To compare proportions of B-cell lineage CD19+ and CD20+ cells in CSF of African-Americans (AA) and White (W) patients with MS. <h3>Background:</h3> Compared to W patients, AA patients with MS are more likely to have oligoclonal bands in CSF; have higher IgG index in CSF; and have higher circulating plasmablasts in blood. It is unknown whether the proportion of B-cells in CSF differs between AA and white patients in MS. <h3>Design/Methods:</h3> Demographics, disease-related information, and treatment history were retrospectively collected on patients with neurologist-diagnosed MS who self-identified as AA or W, received care at NYU MS Care Center, and underwent flow cytometry of CSF during diagnostic work-up. Lymphocyte subsets (B-lymphocytes, T-lymphocytes, NK cells), monocytes and plasma cells were analyzed with flow cytometry (BD FACSCanto™ and FACSCanto™ II Cell Analyzers). <h3>Results:</h3> 20 AA and 57 W MS patients fulfilled inclusion criteria. The groups had similar age at lumbar puncture, sex ratio, CSF cell counts, protein and glucose CSF concentrations, and oligoclonal band number. IgG index was higher in AA compared to W (<i>1.08 v 0.87, p=0.044</i>). With respect to mononuclear cell counts in CSF, AA had higher proportions of CD19+ (<i>5.45% AA v. 2.27% W, p=0.0061</i>) and CD20+ (<i>5.00% AA v. 1.95% W, p=0.0046</i>) cells, but did not significantly differ in proportion of CD4+, CD8+, CD38+ bright B-cells, NK cells and monocytes. Sensitivity analyses that excluded all patients on disease-modifying therapy at the time of lumbar puncture (n=8) yielded similar conclusions. <h3>Conclusions:</h3> B-cells are overrepresented in the CSF of African American patients with MS relative to Whites. Whether this finding bears on the increased severity of MS disease course in AA patients warrants investigation. <b>Disclosure:</b> Mr. Xue has nothing to disclose. Dr. Arbini has nothing to disclose. Mr. Melton has received personal compensation for serving as an employee of Janssen Pharmaceuticals. Dr. Kister has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentech-Roche. The institution of Dr. Kister has received research support from Genentech. Dr. Kister has received publishing royalties from a publication relating to health care.

Experience with anti NMDA receptor antibody encephalitis in a tertiary care hospital in Pakistan

Background and objective: &#x0D; Anti NMDA receptor (Anti-NMDAR) antibody encephalitis is an increasingly recognized form of auto immune encephalitis. The objective of this study was to determine the demographic, clinical and laboratory factors associated with this syndrome. &#x0D; Methods:&#x0D; All cases presenting to neurology, Pakistan institute of medical sciences, Islamabad, from June 2017 till January 2020 were reviewed retrospectively. Patients fulfilling the diagnostic criteria for Anti NMDA receptor (Anti-NMDAR) antibody encephalitis were included. All patients were evaluated with cerebrospinal fluid (CSF)routine examination, MRI brain, autoimmune encephalitis profile and for presence of oligoclonal bands (OCB) in CSF. Statistical analysis was done using SPSS version 23.0.&#x0D; Results:&#x0D; A total of 7 patients were diagnosed as having Anti-NMDARantibody encephalitis. Five patients were female and two were male. Four patients had some type of psychiatric disturbances upon presentation of these behavioral abnormalities and irritability were found in all four. Orofacial abnormal movements were found in four patients while one patient had myoclonic seizures.&#x0D; Conclusion:&#x0D; Anti-NMDARreceptor encephalitis is a common cause of encephalitis associated with neurological and psychiatric symptoms. Delay in diagnosis can occur due to non-specific symptoms and signs present in early stages of illness,this can lead to long term neurological disability.

Tubulointerstitial nephritis and uveitis syndrome post-COVID-19.

Tubulointerstitial nephritis and uveitis syndrome post-COVID-19.

Assessment of oligoclonal bands in cerebrospinal fluid and serum of dogs with meningoencephalitis of unknown origin.

Meningoencephalitis of unknown origin (MUO) is an inflammatory disease of the canine central nervous system (CNS) that shares several features with multiple sclerosis (MS) in humans. In approximately 95% of MS patients, ≥ two immunoglobulin G (IgG) oligoclonal bands (OCBs) are detectable exclusively in the cerebrospinal fluid (CSF). To investigate OCBs in CSF and serum in dogs affected by MUO, intervertebral disc disease (IVDD), idiopathic epilepsy (IE), intracranial neoplasia (IN), steroid-responsive meningitis-arteritis (SRMA), and diseases outside the CNS. We hypothesize that the highest prevalence of CSF-specific OCBs (≥ two OCBs uniquely in the CSF) would be found in dogs affected by MUO. Client-owned dogs (n = 121) presented to the neurology service due to neurological deficits. Prospective study. Measurement of IgG concentration in CSF and serum via a canine IgG ELISA kit. OCB detection via isoelectric focusing (IEF) and immunoblot. Presence of CSF-specific OCBs was significantly higher in dogs with MUO (57%) compared to 22% in IN, 6% in IE, 15% in SRMA, 13% in IVDD, and 0% in the non-CNS group (p < .001). Dogs with MUO were 9.9 times more likely to show CSF-specific OCBs than all other diseases together (95% confidence interval, 3.7-26.4; p < .001). MUO showed the highest prevalence of CSF-specific OCBs, indicating an inflammatory B cell response. Future studies are needed to evaluate the prevalence in the specific MUO subtypes and a possible similarity with human MS.

Cholesterol levels in plasma and cerebrospinal fluid in patients with clinically isolated syndrome and relapsing-remitting multiple sclerosis

Cholesterol is essential for myelin formation, but may also modulate mechanisms involved in adaptive immune responses. It is unclear whether lack of remyelination in multiple sclerosis (MS) results from an insufficient capacity of oligodendrocyte precursor cells to differentiate or from cholesterol insufficiency. Several studies have assessed the potential association of lipid profile and its metabolism with demyelination, disability, and disease progression. The aim of the present study was to measure cholesterol levels in plasma and cerebrospinal fluid (CSF) of patients with relapsing remitting MS (RRMS) or with clinically isolated syndrome (CIS), and to investigate whether there is an association between cholesterol levels and disease characteristics.Sixty-two patients with CIS and 46 patients with RRMS were included in the study. All patients had low EDSS and were medication-free at assessment. Forty-eight subjects within the same age range served as controls. Cholesterol concentrations were measured in plasma and in CSF by the same enzymatic – colorimetric method, and were related to clinical status, disease activity in magnetic resonance imaging (MRI) and presence of oligoclonal bands in CSF (OBs).Significantly lower levels of plasma and CSF cholesterol were found in patients compared to controls. Patients with OBs showed significantly lower levels of CSF cholesterol but not plasma cholesterol compared to OBs-negative patients. A positive correlation of plasma cholesterol with age and of CSF cholesterol with EDSS was found.Our results suggest that low CSF cholesterol in MS patients with positive OBs might reflect extensive demyelination and a more aggressive disease course associated with an increased humoral immune response against membrane components.

Analysis of factors correlated with spinal clinically isolated syndrome conversion to multiple sclerosis.

The present study aims to explore the factors influencing spinal clinically isolated syndrome (CIS) conversion to multiple sclerosis (MS). Sixty-one patients diagnosed with spinal CIS from January 2010 to November 2020 were divided into a non-progressing (CIS) group with 27 patients, and a conversion to MS (MS) group with 34 patients, based on whether they had converted to MS. The clinical presentation at onset, the Expanded Disability Status Scale (EDSS) before and after steroid therapy, the results of magnetic resonance imaging (MRI), the oligoclonal bands in cerebrospinal fluid (CSF-OCB), and the evoked potentials (EPs) were retrospectively analysed. Differences in gender and age were not statistically significant between the MS and CIS groups. The median time to relapse was 12 months for the MS group, with an upper quartile of 23.7 months, and 91.2% of patients relapsed within three years. In univariate analysis, patients with CIS beginning with sensory symptoms had a lower level of progression to MS (OR = 0.311). Patients with Kurtzke Functional Systems Scores (FSSs) of pyramidal functions ≥ 2 (OR = 3.582) and positive CSF-OCB (OR = 5.208) quickly progressed to MS. There was no significant difference between the two groups in terms of spinal cord lesions < 3 vertebral segments, gadolinium enhancing lesions, or abnormal EPs. The difference in the EDSS scores before and after steroid therapy was higher in the MS group than in the CIS group (p = 0.001). Differences of ≥ 1.5 in the EDSS scores before and after steroid therapy were risk factors for CIS conversion to MS (OR = 9.333). Patients with spinal CIS with pure sensory abnormalities at onset were less likely to convert to MS (OR = 0.311), and the risk factors were, in order of risk, the difference in EDSS score before and after steroid therapy (≥ 1.5; OR = 9.333), positive CSF-OCB (OR = 5.208), and those with an FSS of the pyramidal functions score ≥ 2; OR = 3.582). The present study serves as a simple 'first step'. Any potential predictors identified should be validated via future prospective studies.

Factors Related to the Progression of Clinically Isolated Syndrome to Multiple Sclerosis: A Retrospective Study in Lithuania.

Background and Objectives: Multiple sclerosis (MS) is a demyelinating disease which usually manifests as clinically isolated syndrome (CIS). Approximately 70% of patients with CIS progress to MS. Therefore, there is a pressing need to identify the most accurate predictive factors of CIS developing into MS, some of which could be a clear clinical phenotype of early MS as well as lesions in magnetic resonance imaging (MRI), pathological findings in cerebrospinal fluid (CSF) and evoked potentials (EP) tests. The problem is of outstanding importance since early MS diagnosis and treatment prevents long-term disability. The aim of our study is to analyze the factors that could influence the progression of CIS to MS. Materials and Methods: This study is a retrospective data analysis which included patients with their primary CIS diagnosis between 1st January 2015 and 1st January 2020. The prevalence and predictive value of clinical symptoms, MRI lesions, pathological CSF and EP findings were evaluated in accordance with the final diagnosis and compared between the sexes and age groups. Results: Out of 138 CIS patients, 49 (35.5%) patients progressed to MS. MS patients were more likely to have a diminished sense of vibration and proprioception (χ2 = 9.033, p = 0.003) as well as spinal cord MRI lesions (χ2 = 7.209, p = 0.007) in comparison with the non-MS group. Positive oligoclonal bands (OCBs) in CSF (χ2 = 34.859, p ≤ 0.001) and pathological brainstem auditory evoked potential (BAEP) test findings (χ2 = 10.924, p ≤ 0.001) were more prevalent in the MS group. Diminished sense of vibration and proprioception increased the risk for developing MS by 13 times (p = 0.028), whereas positive OCBs in CSF increased the risk by 100 times (p < 0.001). MS patients that were older than 50 years were more likely to exhibit positive Babinski’s reflex (χ2 = 6.993, p = 0.03), decreased muscle strength (χ2 = 13.481, p = 0.001), ataxia (χ2 = 8.135, p = 0.017), and diminished sense of vibration and proprioception (χ2 = 7.918, p = 0.019) in comparison with both younger age groups. Conclusions: Diminished sense of vibration and proprioception, spinal cord MRI lesions, positive OCBs and pathological BAEP test findings were more common among patients that developed MS. Diminished sense of vibration and proprioception along with positive CSF OCBs are predictors of CIS progressing to MS. Older patients that develop MS have more symptoms in general, such as positive Babinski’s reflex, decreased muscle strength, ataxia, and diminished sense of vibration and proprioception.

Comparison of Two Different Canine Anti-IgG Antibodies for Assessment of Oligoclonal Bands in Cerebrospinal Fluid and Serum of Dogs via Isoelectric Focusing Followed by an Immunoblot.

Isoelectric focusing followed by immunoblotting is a method routinely used in human medicine to assess the presence of oligoclonal bands (OCBs) in cerebrospinal fluid (CSF) and serum. The detection of OCBs is a valuable diagnostic test, especially important in patients with the suspicion of multiple sclerosis (MS), in which at least two OCBs are found in the CSF not present in paired serum samples in up to 95% of patients. So far, presence of OCBs in CSF and serum of dogs has only been investigated in a small cohort of dogs diagnosed with degenerative myelopathy and healthy dogs. The main objective of the current study was to describe the method used for OCB detection and compare two different canine anti-IgG antibodies: a canine rabbit-anti-IgG antibody (Jackson ImmunoResearch) vs. a canine goat-anti-IgG antibody (Bio-Rad). The method was performed according to the instructions of the commercial kit used. The canine goat-anti-IgG antibody showed a better performance than the canine rabbit-anti-IgG antibody. The availability of the technique of OCB detection in the dog paves the way for further studies, especially in the field of inflammatory diseases of the canine central nervous system, and comparison between specific human and canine diseases.

Biomarkers related to the intrathecal humoral immune response as laboratory tools for multiple sclerosis diagnosis

In cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients, the intrathecal synthesis (IS) of affinity-maturated IgG class antibodies secreted by transmigrated B cells, is considered as a hallmark of the disease. It is classically revealed by CSF isofocusing test (detection of IgG Oligoclonal bands (OCB) in CSF, considered as “the gold standard”), Total IgG Index and/or Reiber diagram. Our aim is to analyse the comparative performance of different CSF testing techniques for MS diagnosis.

Stiff person syndrome and prior temporal lobectomy: Is it a case of misplaced autoimmunity?

AbstractBackgroundStiff person syndrome (SPS) is a rare autoimmune disorder, characterized by progressive rigidity and muscle spasms affecting the axial and limb muscles. Anti‐glutamic acid decarboxylase (anti‐GAD65) antibodies are linked to pathogenesis of both epilepsy and SPS. We aim to highlight epilepsy surgery as a potential trigger for development of SPS.Case presentationA 35‐year‐old female with medically refractory temporal lobe epilepsy underwent right amygdala‐hippocampectomy in 2009. The patient was seizure‐free until 2019 when she developed spells of severe muscle spasms, palpitations, dyspnea, and restlessness. Examination revealed increased spasticity in bilateral lower extremities, a wide based gait, and hyperreflexia with crossed adductor sign and bilateral Babinski sign. Serum and cerebrospinal fluid (CSF) labs were obtained, and two typical spells occurred during continuous video electroencephalogram (cvEEG) monitoring. Typical spells did not correlate with seizure activity on cvEEG. CSF analysis showed normal opening pressure, Gram stain, culture, cell count, protein, and glucose. Serum and CSF GAD65 antibody levels were 5153 nMol/L and 53 nMol/L, respectively, along with 14 oligoclonal bands in CSF. Diagnosis of SPS was made. Treatment with diazepam caused improvement in spells and myalgia.ConclusionThe diagnosis of SPS can be delayed in a patient with history of epilepsy. Although SPS and epilepsy are often linked by anti‐GAD antibodies as common etiology, it is possible that epilepsy surgery might be a trigger for development of SPS in a small subset. Development of autoimmunity to neuronal GAD65 protein, exposed during surgery, is suspected in pathogenesis.

Establishment and consistency verification of the standard operation procedure for laboratory detection of immunoglobulin G oligoclonal bands in cerebrospinal fluid

Objective: To establish the standard operation procedure (SOP) for detection of oligoclonal band (OCB) in cerebrospinal fluid (CSF) and verify consistency by using this SOP in different laboratories. Methods: The SOP for detection of CSF-OCB fluid was successfully established by an expert feedback approach. Neuroimmunology laboratories in 3 representative Chinese three-tier research hospitals were selected for this study, and commercially available protein electrophoresis automation systems and detection SOP were set up. The quality control product was provided by the College of American Pathologists (CAP) and Sebiacompany were used for interior quality and compared to each other, respectively. Seventeen serum and CSF paired samples were tested and compared using the same SOP. Kappa test or Kendall W test were adopted to evaluate the inter-laboratory consistency among different hospitals. Results: The results of repeated testings in a single hospital suggested that the 2-and 4-fold dilution for CSF-OCB were reported as positive, while 64-and 128-fold dilution were reported as negative. Positive or negative inconsistencies were reported in 8-, 16-, and 32-fold dilution. After increasing the number of repetitions, the results showed that both 16-and 32-fold dilution were reported as negative, and 8-fold dilution exhibited negative results (2 positive results for 40 repetitions, coincidence rate=95%).The results of multi-center inter-laboratory quality assessment showed that the detection consistency rate among 3 hospitals was 100% (Kappa value =1). Conclusions: The SOP to detect CSF-OCB established in this study demonstrates a good repeatability and stability. Therefore,such SOP would be a good reference for diagnostic laboratories to detect CSF-OCB in China.

Neurofilament light chain as a biomarker for diagnosis of multiple sclerosis.

The treatments for multiple sclerosis (MS) have improved over the past 25 years, but now the main question for physicians is deciding who should receive treatment, for how long, and when to switch to other options. These decisions are typically based on treatment tolerance and a reasonable expectation of long-term efficacy. A significant unmet need is the lack of accurate laboratory measurements for diagnosis, and monitoring of treatment response, including deterioration and disease progression. There are few validated biomarkers for MS, and in practice, physicians employ two biomarkers discovered fifty years ago for MS diagnosis, often in combination with MRI scans. These biomarkers are intrathecal IgG and oligoclonal bands in the CSF (cerebrospinal fluid). Neurofilament light chain (NfL) is a relatively new biomarker for MS diagnosis and follow up. Neurofilaments are neuron-specific cytoskeleton proteins that can be measured in various body compartments. NfL is a new biomarker for MS that can be measured in serum samples, but this still needs further study to specify the laboratory cut-off values in clinical practice. In the present review we discuss the evidence for NfL as a reliable biomarker for the early detection and management of MS. Moreover, we highlight the correlation between MRI and NfL, and ask whether they can be combined.

Autoimmune Encephalitis in Late-Onset Seizures: When to Suspect and How to Treat.

Objective: This study was conducted to elucidate prevalence, clinical features, outcomes, and best treatment in patients with late-onset seizures due to autoimmune encephalitis (AE).Methods: This is a single-institution prospective cohort study (2012–2019) conducted at the Epilepsy Center at the University of Greifswald, Germany. A total of 225 patients aged ≥50 years with epileptic seizures were enrolled and underwent an MRI/CT scan, profiling of neural antibodies (AB) in serum and cerebrospinal fluid (CSF), and neuropsychological testing. On the basis of their work-up, patients were categorized into the following three cohorts: definite, suspected, or no AE. Patients with definite and suspected AE were subsequently treated with immunosuppressive therapy (IT) and/or anti-seizure drug (ASD) therapy and were followed up (FU) regarding clinical and seizure outcome.Results: Of the 225 patients, 17 (8%) fulfilled the criteria for definite or suspected AE according to their AB profile and MRI results. Compared with patients with no evidence of AE, those with AE were younger (p = 0.028), had mesial temporal neuropsychological deficits (p = 0.001), frequently had an active or known malignancy (p = 0.006) and/or a pleocytosis (p = 0.0002), and/or had oligoclonal bands in CSF (p = 0.001). All patients with follow-up became seizure-free with at least one ASD. The Modified Rankin scale (mRS) at hospital admission was low for patients with AE (71% with mRS ≤2) and further decreased to 60% with mRS ≤2 at last FU.Significance: AE is an important etiology in late-onset seizures, and seizures may be the first symptom of AE. Outcome in non-paraneoplastic AE was favorable with ASD and IT. AB testing in CSF and sera, cerebral MRI, CSF analysis, and neuropsychological testing for mesial temporal deficits should be part of the diagnostic protocol for AE following late-onset seizures.

Apport du dosage des chaînes légères libres kappa et lambda dans le diagnostic de la sclérose en plaques

AbstractThe demonstration of intrathecal immunoglobulin synthesis by detection of oligoclonal bands in cerebrospinal fluid contributes to the diagnosis of multiple sclerosis as defined in the Mc Donald’s criteria, revised in 2017. Although being considered as a gold standard technique (sensitive and specific) for identifying oligoclonal bands in cerebrospinal fluid, isoelectric focusing remains time-consuming, requires skilled technician and its interpretation is operator-dependent. An alternative lies in measuring κ and λ free light chains, secreted by plasma cells in cerebrospinal fluid and serum. The assay, performed by immunonephelometry or immunoturbidimetry on automated systems, allows a quantitative measurement and is faster than detection of oligoclonal bands. Preliminary studies have shown similar performances of intrathecal κ free light chains measurement as compared to oligoclonal bands results in multiple sclerosis diagnosis. Further large studies in routine practice are now mandatory to confirm the potential of this approach.

Prognostic factors for relapse and outcome in pediatric acute transverse myelitis

ObjectiveIt may be difficult for clinicians to estimate the prognosis of pediatric acute transverse myelitis (ATM). The aim of this study was to define prognostic factors for relapsing disease and poor outcome in pediatric ATM. MethodsThis prospective cohort study included 49 children, 18 boys and 31 girls (median age 13.1 years, IQR 6.5–16.2) with a first episode of ATM. Factors associated with relapsing disease and poor outcome (Expanded Disability Status Scale (EDSS) ≥ 4) were assessed during a median follow-up of 37 months (IQR 18–75). ResultsIn total, 14 patients (29%) experienced ≥ 1 relapse(s) and nine patients (18%) had a poor outcome. Factors at onset associated with relapsing disease included higher age (16.1 vs. 11.6 years, p = 0.002), longer time to maximum severity of symptoms (5.5 vs. 3 days, p = 0.01), lower maximum EDSS score (4.0 vs. 6.5, p = 0.003), short lesion on spinal MRI (64 vs. 21%, p = 0.006), abnormalities on brain MRI (93 vs. 44%, p = 0.002) and presence of oligoclonal bands in cerebrospinal fluid (67 vs. 14%, p = 0.004). The only factor associated with poor outcome was presence of a spinal cord lesion on MRI without cervical involvement (56 vs. 14%, p = 0.02). ConclusionPediatric ATM patients presenting with clinical, radiological and laboratory features associated with multiple sclerosis (MS) are at risk for relapsing disease. In absence of these known MS risk factors at onset of disease these patients are at low risk for relapses. Only a minority of pediatric ATM patients in this cohort have a poor outcome.