Diagnosis Of Multiple Sclerosis Patients Research Articles

The Importance of Proteomics in Saliva and Tears as Potential Non-invasive Methods for Identifying Biomarkers in the Prognosis and Diagnosis of Multiple Sclerosis Patients

: Over the past two decades, the advancement of analytical examinations like proteomics for investigating neuronal-related biomarkers has emerged as one of the most important and effective tools for clinical evaluation and prognosis. However, there remains an unmet need in this area. With advances in quantifying methods and detection in omics research, including proteomics and metabolomics, the close association of the salivary glands and tears with the nervous system has become increasingly evident. As noninvasive specimens, saliva and tears serve as attractive substitutes for neuronal biomarkers, containing numerous proteins and metabolites that represent various ailments in neurodegenerative illnesses like multiple sclerosis (MS). These noninvasive biomarkers might potentially correlate with susceptibility, severity, and pathogenesis of neurological disorders and could be utilized in early diagnosis and prognosis. Therefore, tear and salivary proteomics present novel insights into understanding disease progression and offer personalized treatment options with greater sensitivity. This approach helps highlight the most relevant experimental outcomes related to tear and salivary biomarkers for multiple sclerosis.

Cerebrospinal fluid neurofilament light chain in acute optic neuritis and its predictive ability of multiple sclerosis

BackgroundStudies on the capability of cerebrospinal fluid neurofilament light chain (cNfL) to predict multiple sclerosis (MS) conversion in clinically isolated syndromes have yielded varying results.ObjectivesTo expand our understanding of cNfL in optic neuritis (ON) and investigate whether incorporating cNfL into the 2017 McDonald criteria could accelerate the diagnosis of MS in patients with ON.MethodscNfL was measured in diagnostic samples from 74 patients with verified ON. MS was diagnosed using the 2017 McDonald criteria with a minimum observation time of two years from ON onset.Results20.5% of 44 MS-converters did not fulfil the 2017 McDonald criteria at ON onset. A doubling of cNfL was associated with 207% (74%–514%) higher odds of MS (p = 0.00042, adjusted for age). Fulfilment of ≥ 1 MRI criterion for dissemination in space (DIS) and presence of brain contrast-enhancing lesions were associated with higher cNfL. Furthermore, cNfL correlated with inter-eye differences in retinal nerve fiber layer (RNFL) thickness (Spearman’s ρ = 0.46, p = 8 × 10–5). Incorporating cNfL ≥ 906 pg/mL as a substitute for either dissemination in time or one MRI criterion for DIS increased the sensitivity (90.9% vs. 79.6%) and accuracy (91.9% vs. 87.8%), but also reduced the specificity (93.3% vs. 100%) of the 2017 McDonald criteria.ConclusioncNfL was related to MS diagnostic parameters and the degree of RNFL swelling. Clinical use of cNfL may aid in identification of ON patients with increased risk of MS until larger studies have elaborated on the potential loss of specificity if used diagnostically.

Diffusion-Weighted Images and Contrast-Enhanced MRI in the Diagnosis of Different Stages of Multiple Sclerosis of the Central Nervous System.

Introduction Multiple sclerosis (MS) is one of the most prevalent disorders of the central nervous system (CNS), and it can be observed in the field of radiological cross-sectional magnetic resonance imaging (MRI). The prevalence of MS in Saudi Arabia has increased as compared to the past few years. MRI is the gold standard non-invasive modality of choice in MS diagnosis according to the National Multiple Sclerosis Society (NMSS), New York City. This study aimed to highlight the significance of using diffusion-weighted images (DWIs) and the use of contrast media in the MS protocol, as well as the importance of identifying the suitable time of imaging after contrast enhancement to detect active lesions. Methods A retrospective cross-sectional study was conducted of 100 MS patients with an age range of 17 to 56 years. The data set included 41 active cases and 59 inactive cases. All patients had an MRI standard protocol of both the brain and spine in addition to DWI sequence and contrast agent (CA) injection, with images taken in early and delayed time. Results Of the patients, 71% were female and 29% were male. Active MS disease was more significant at younger ages than at older ages. Active lesions were significantly enhanced in delayed contrast images and showed high signal intensity in both the DWI and apparent diffusion coefficient (ADC) map, while inactive lesions showed no enhancement after contrast injection and showed an iso-signal intensity in both the DWI and ADC map. Conclusion The use of CA has developed over the years in the diagnosis of MS patients. In this study, the relationship between active lesions, DWI, and delayed contrast enhancement is very strong. In future research, we recommend adding a DWI sequence for the suspected active MS spine lesions in addition to delayed enhancement time in active MS after contrast injection to increase MRI sensitivity toward active MS lesions of the brain and spinal cord as well.

Single Test to ARrive at Multiple Sclerosis (STAR-MS) diagnosis: A prospective pilot study assessing the accuracy of the central vein sign in predicting multiple sclerosis in cases of diagnostic uncertainty

Background: Misdiagnosis is common in multiple sclerosis (MS) as a proportion of patients present with atypical clinical/magnetic resonance imaging (MRI) findings. The central vein sign has the potential to be a non-invasive, MS-specific biomarker. Objective: To test the accuracy of the central vein sign in predicting a diagnosis of MS in patients with diagnostic uncertainty at disease presentation using T2*-weighted, 3 T MRI. Methods: In this prospective pilot study, we recruited individuals with symptoms unusual for MS but with brain MRI consistent with the disease, and those with a typical clinical presentation of MS whose MRI did not suggest MS. We calculated the proportion of lesions with central veins for each patient and compared the results to the eventual clinical diagnoses. The optimal central vein threshold for diagnosis was established. Results: Thirty-eight patients were scanned, 35 of whom have received a clinical diagnosis. Median percentage of lesions with central veins was 51% in MS and 28% in non-MS. A threshold of 40.7% lesions with central veins resulted in 100% sensitivity and 73.9% specificity. Conclusion: The central vein sign assessed with a clinically available T2* scan can successfully diagnose MS in cases of diagnostic uncertainty. The central vein sign should be considered as a diagnostic biomarker in MS.

Association of Retinal Ganglion Cell Layer Thickness With Future Disease Activity in Patients With Clinically Isolated Syndrome

Clinically isolated syndrome (CIS) describes a first clinical incident suggestive of multiple sclerosis (MS). Identifying patients with CIS who have a high risk of future disease activity and subsequent MS diagnosis is crucial for patient monitoring and the initiation of disease-modifying therapy. To investigate the association of retinal optical coherence tomography (OCT) results with future disease activity in patients with CIS. This prospective, longitudinal cohort study took place between January 2011 and May 2017 at 2 German tertiary referral centers. A total of 179 patients with CIS were screened (80 in Berlin and 99 in Munich). Patients underwent neurological examination, magnetic resonance imaging (MRI), and OCT. Only eyes with no previous optic neuritis were considered for OCT analysis. The primary outcome was not meeting the no evidence of disease activity (NEDA-3) criteria; secondary outcomes were MS diagnosis (by the 2010 McDonald criteria) and worsening of disability. The primary measure was OCT-derived ganglion cell and inner plexiform layer thickness; the secondary measures included peripapillary retinal nerve fiber layer thickness, inner nuclear layer thickness, and MRI-derived T2-weighted lesions. A total of 97 of the 179 screened patients (54.2%) were enrolled in the study at a median of 93 (interquartile range [IQR], 62-161) days after a first demyelinating event. The median follow-up duration (Kaplan-Meier survival time) was 729 (IQR, 664-903) days. Of 97 patients with CIS (mean age 33.6 [7.9] years; 61 [62.9%] female), 58 (59%) did not meet NEDA-3 criteria during the follow-up period. A Kaplan-Meier analysis showed a significant probability difference in not meeting NEDA-3 criteria by ganglion cell and inner plexiform later thickness (thinnest vs thickest tertile: hazard ratio [HR], 3.33 [95% CI, 1.70-6.55; P < .001; log-rank P = .001). A follow-up diagnosis of MS was more likely for patients with low ganglion cell and inner plexiform layer thickness (thinnest vs thickest tertile: HR, 4.05 [95% CI, 1.93-8.50]; P < .001). Low peripapillary retinal nerve fiber layer thickness likewise indicated risk of not meeting NEDA-3 criteria (thinnest vs thickest tertile: HR, 2.46 [95% CI, 1.29-4.66]; P = .01; log-rank P = .02). Inner nuclear layer thickness and T2-weighted lesion count were not associated with not meeting NEDA-3 criteria. Retinal ganglion cell and inner plexiform layer thickness might prove a valuable imaging marker for anticipating future disease activity and diagnosis of MS in patients with CIS, which can potentially support patient monitoring and initiation of disease-modifying therapy.

Magnetic poly(2-hydroxyethyl methacrylate) microspheres for affinity purification of monospecific anti-p46 kDa/Myo1C antibodies for early diagnosis of multiple sclerosis patients.

The aim of the present study is to develop new magnetic polymer microspheres with functional groups available for easy protein and antibody binding. Monodisperse macroporous poly(2-hydroxyethyl methacrylate) (PHEMA-COOH) microspheres ~4 µm in diameter and containing ∼1 mmol COOH/g were synthesized by multistep swelling polymerization of 2-hydroxyethyl methacrylate (HEMA), ethylene dimethacrylate (EDMA), and 2-[(methoxycarbonyl)methoxy]ethyl methacrylate (MCMEMA), which was followed by MCMEMA hydrolysis. The microspheres were rendered magnetic by precipitation of iron oxide inside the pores, which made them easily separable in a magnetic field. Properties of the resulting magnetic poly(2-hydroxyethyl methacrylate) (mgt.PHEMA) particles with COOH functionality were examined by scanning and transmission electron microscopy (SEM and TEM), static volumetric adsorption of helium and nitrogen, mercury porosimetry, Fourier transform infrared (FTIR) and atomic absorption spectroscopy (AAS), and elemental analysis. Mgt.PHEMA microspheres were coupled with p46/Myo1C protein purified from blood serum of multiple sclerosis (MS) patients, which enabled easy isolation of monospecific anti-p46/Myo1C immunoglobulin G (IgG) antibodies from crude antibody preparations of mouse blood serum. High efficiency of this approach was confirmed by SDS/PAGE, Western blot, and dot blot analyses. The newly developed mgt.PHEMA microspheres conjugated with a potential disease biomarker, p46/Myo1C protein, are thus a promising tool for affinity purification of antibodies, which can improve diagnosis and treatment of MS patients.

Serum Glutamate Is a Predictor for the Diagnosis of Multiple Sclerosis.

One neurotransmitter, glutamate, has been implicated in the autoimmune demyelination seen in multiple sclerosis (MS). Glutamate is present in many tissues in the body, so consideration should be given to whether the serum level of glutamate is likely well correlated with the activity of the disease. This research aimed to compare the serum glutamate levels from patients diagnosed with MS with those from an age-matched control population. A review of this data could shed light upon whether the serum testing of glutamate using Enzyme-Linked Immunosorbent Assay (ELISA) is a reliable indicator of MS activity. Serum samples were obtained from 55 patients with different patterns of MS and from 25 healthy adults as a control group. The ELISA technique was used to determine the glutamate levels in the serum samples. The mean serum glutamate level for patients with MS was 1.318 ± 0.543 nmol/ml and that of the controls was 0.873 ± 0.341 nmol/ml. The serum glutamate levels showed an area under the curve via the receiver operating characteristics (ROC) of 0.738, which was significant (p value = 0.001). The present study is the first to establish a strong connection between the serum glutamate levels and MS patients, where there was statistically significant elevation of serum glutamate in MS patients; hence this elevation might be used as a monitor to help in the diagnosis of MS patients.

Radiologically Definite Multiple Sclerosis (RDMS) as a New Terminology in Demyelinating Disease

Dear editor &#x0D; Multiple sclerosis (MS) is the most common inflammatory demyelinating disease of the central nervous system. MS is characterized by dissemination in time and place. Dissemination can be clinically (clinically definite multiple sclerosis) or radiologically by magnetic resonance imaging (MRI). Correct diagnosis of MS needs dissemination both in time and in place and also exclusion of all other neurological diseases that can mimic MS. Clinically, dissemination in time is defined as two episodes of neurological symptoms occurrence, separated at least one month apart, and dissemination in place is characterized as the presence of symptoms or signs in at least two different parts of central nervous system (CNS) (e.g. visual, sensory, motor, etc.). Radiologically dissemination in space (DIS) was defined as the presence of clinically silent lesions in T2-weighted MRI in two of four locations including juxtacortical, preventricular, infratentorial, and spinal cord and dissemination in time (DIT) as the presence of simultaneous gadolinium enhancing and non enhancing lesions in MRI [1,2].&#x0D;  There are some terminologies which are frequently used in patients with demyelinating disorders including clinically definite MS (CDMS), clinically isolated syndrome (CIS) and radiologically isolated syndrome (RIS) [1-3]. CDMS is defined as two attacks of neurological symptoms in two different neurological systems (e.g. optic neuritis and myelitis) separated and apart for at least one month [1]. Radiologically isolated syndrome (RIS) was used in persons with MRI findings suggestive of MS without typical symptoms and signs [3].&#x0D; CIS is defined as the first episode of neurological symptoms and signs suggestive of MS. The onset of MS in 85% of patients presents as CIS. This terminology is widely used in clinical practice. By definition, CIS is always clinically isolated in time. Around 50-70% of patients with CIS have white matter lesions in brain or spinal MRI. On the other hand, CIS usually represents a wide clinical spectrum of diseases of CNS and can be present in a multitude of clinical manifestation [1, 2].&#x0D; At present time, MRI is the most important tool for diagnosis of MS in patients with CIS and the application of MRI for diagnosis of MS has been increased during the past few years [4]. Today, the diagnosis of MS is possible very earlier than before due to the wide integration of MRI in McDonalds’ criteria (2010). MacDonald’s criteria mostly rely on MRI findings to facilitate the early diagnosis of MS [1, 4]. By using the new MacDonald’s criteria some patients who presented with CIS can be diagnosed as MS if MRI fulfills dissemination in time and space. For patients who fulfill the criteria of both DIT and DIS, the term of CDMS is used; but for patients who have had one attack of neurological symptoms and fulfill DIT and DIS radiologically (by MRI) there is no appropriate terminology and all of them are classified as CIS [2, 4]. We know that this terminology is somewhat ambiguous, because CIS may be the first presentation of many neurological diseases including demyelinating diseases, inflammatory diseases such as vasculitis or non-inflammatory non-demyelinating diseases like vascular lesions [2].&#x0D; We recommend the term of radiologically definite MS (RDMS) for patients who have had one attack of neurological symptoms and fulfill DIT and DIS radiologically by MRI. Because many neurologists are not completely familiar with the term CIS and some are confused about it, we need an appropriate terminology to use in every day’s clinical practice. Also, early diagnosis of MS in patients with CIS is very important. Because early treatment of patients with CIS by disease modifying drugs including Beta-Interferon can delay turning into CDMS and also decreases brain atrophy and new brain lesions. All current disease modifying drugs have been shown to be effective in treating CIS [5]. But it is clear that all patients with CIS do not require these treatments and only those patients who show dissemination in time and space by MRI should be treated by these agents [2, 6].&#x0D; In conclusion, radiologicaly definite MS (RDMS) is the recommended terminology for patients who have one attack of neurological symptoms and radiologically fulfill DIT and DIS criteria and these patients should be treated by disease modifying agents as well.

Application of the 2010 McDonald criteria for the diagnosis of multiple sclerosis in a Spanish cohort of patients with clinically isolated syndromes

Background: Recently the International Panel on Diagnosis of Multiple Sclerosis (MS) has proposed new magnetic resonance imaging (MRI) criteria for the diagnosis of MS in patients with clinically isolated syndromes (CIS). We aimed to evaluate the accuracy of these new criteria for lesions dissemination in space (DIS) and time (DIT), from a single MRI scan, to predict conversion from CIS to clinically definite MS. Methods: We studied 67 CIS patients with baseline MRI performed within the first 3 months after onset. The follow-up was of at least 24 months. The sensitivity, specificity and accuracy of Barkhof–Tintoré criteria and the new proposed MRI criteria for DIS and DIT were calculated with SPSS v.15.0. Results: The mean age for clinical onset was 30 years and 64% of patients were female. The overall conversion rate was 74%. In our cohort, Barkhof–Tintoré criteria showed a sensitivity of 71.43%, a specificity of 66.67%, with an accuracy of 73.1%. New DIS criteria showed a sensitivity of 85.71%, a specificity of 64.71% and an accuracy of 80.30%. We also evaluated the new DIT criteria with a single MRI scan in 54 patients with baseline scans that included gadolinium-enhanced images. The sensitivity of the test was 52.63% with a specificity of 75.00% and an accuracy of 59.26%. Conclusion: New DIS criteria are simpler and more sensitive than previous criteria. The sensitivity of DIT criterion using a single MRI scan was rather low, as other previous studies showed, reflecting its stringency, but it could improve the accuracy of early MS diagnosis in that group of patients with typical CIS and gadolinium-enhancing and non-enhancing lesions on their baseline scans. These results reinforce their use in MS diagnosis.

Computerised volumetric analysis of lesions in multiple sclerosis using new semi-automatic segmentation software.

The paper describes the application of new semi-automatic segmentation software to the task of detection of anatomical structures and lesion and their three-dimensional (3D) visualisation in 23 patients with secondary progressive multiple sclerosis (MS). The purpose is to study the correlation between magnetic resonance imaging (MRI) parameters (volumes of plaques and cerebrospinal fluid spaces) and clinical deficits (neurological deficits in the form of EDSS and RFSS scores, and neuropsychological deficits). The software operates in PC/Windows and PC/NeXTstep environments and utilises graphical user interfaces. Quantitative accuracy is measured by performing segmentation of fluid-filled syringes (relative error of 1.5%), and reproducibility is measured by intra- and inter-observer studies (3% and 7% variability, respectively). The mean volumes of MS plaques show significant correlations with the total RFSS scores (p = 0.04). Relative intracranial cerebrospinal fluid (CSF) space volumes show statistically significant correlation with EDSS scores (p = 0.01). The mean volume of MS plaques shows a significant correlation with the overall neuropsychological deficits (p = 0.03). 3D visualisation helps to understand the relationship of lesions to the surrounding brain structures. The use of semiautomatic segmentation techniques is recommended in the clinical diagnosis of MS patients.

Role of urologist in diagnosis ofmultiple sclerosis

This report presents 7 patients with confirmed cases of multiple sclerosis (MS) in whom the diagnosis of MS was first suspected by the urologist. Review of these 7 cases identifies three factors that increased the suspicion of MS at the time of urologic evaluation: a history of neurologic symptoms, abnormalities on a brief neurologic examination, and abnormal basic urodynamic evaluation. Urologists attuned to the possible diagnosis of MS in patients who present with symptoms of voiding dysfunction can facilitate the proper diagnosis with a basic office evaluation.