Analysis Of Multiple Sclerosis Research Articles

X Chromosome Analysis in Multiple Sclerosis for Identification of Genes Implicated in Female-biased Disease Presentation (S42.007)

X Chromosome Analysis in Multiple Sclerosis for Identification of Genes Implicated in Female-biased Disease Presentation (S42.007)

Association Between Neurodegenerative Diseases and an Increased Risk of Epilepsy Based on Single Nucleotide Polymorphisms: A Mendelian Randomization Study.

Epilepsy is a common neurological disorder characterized by transient brain dysfunction, attributed to a multitude of factors. The purpose of this study is to explore whether neurodegenerative diseases, specifically Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS), have a causal effect on epilepsy. Mendelian randomization (MR) methods were used to analyze the causal association between neurodegenerative diseases (AD, PD, ALS, and MS) and epilepsy based on single nucleotide polymorphisms from genome-wide association studies, including inverse-variance weighted, weighted median, MR-Egger, and weighted mode methods. The reliability and stability of the MR analysis results were assessed by the MR-Egger intercept, MR-PRESSO, and heterogeneity tests. Forty-three SNPs were selected for the MR analysis of MS and epilepsy. The inverse-variance weighted method showed a significant causal association between MS and increased risk of epilepsy (odds ratio 1.046; 95% confidence interval 1.001-1.093; P = 0.043). However, AD (P = 0.986), PD (P = 0.894), and ALS (P = 0.533) were not causally associated with epilepsy. Sensitivity analysis showed that the results were robust. The MR study confirmed the causal relationship between genetically predicted MS and epilepsy but did not support the causal relationship between genetically predicted AD, PD, and ALS on epilepsy.

Differences in Brain Atrophy Pattern between People with Multiple Sclerosis and Systemic Diseases with Central Nervous System Involvement Based on Two-Dimensional Linear Measures.

Conventional brain magnetic resonance imaging (MRI) in systemic diseases with central nervous system involvement (SDCNS) may imitate MRI findings of multiple sclerosis (MS). In order to better describe the MRI characteristics of these conditions, in our study we assessed brain volume parameters in MS (n = 58) and SDCNS (n = 41) patients using two-dimensional linear measurements (2DLMs): bicaudate ratio (BCR), corpus callosum index (CCI) and width of third ventricle (W3V). In SDCNS patients, all 2DLMs were affected by age (CCI p = 0.005, BCR p < 0.001, W3V p < 0.001, respectively), whereas in MS patients only BCR and W3V were (p = 0.001 and p = 0.015, respectively). Contrary to SDCNS, in the MS cohort BCR and W3V were associated with T1 lesion volume (T1LV) (p = 0.020, p = 0.009, respectively) and T2 lesion volume (T2LV) (p = 0.015, p = 0.009, respectively). CCI was associated with T1LV in the MS cohort only (p = 0.015). Moreover, BCR was significantly higher in the SDCNS group (p = 0.01) and CCI was significantly lower in MS patients (p = 0.01). The best predictive model to distinguish MS and SDCNS encompassed gender, BCR and T2LV as the explanatory variables (sensitivity 0.91; specificity 0.68; AUC 0.86). Implementation of 2DLMs in the brain MRI analysis of MS and SDCNS patients allowed for the identification of diverse patterns of local brain atrophy in these clinical conditions.

Influence of physicians' risk perception on switching treatments between high- efficacy and non-high-efficacy disease‑modifying therapies in multiple sclerosis.

The decision of initiating treatment for multiple sclerosis (MS) with a high-efficacy DMT (HE DMT) or non-high-efficacy DMT (non-HE DMT) is influenced by several factors, including risk perception of patients and physicians. Investigate the influence of physicians' risk perception on decision-making when switching treatments for MS and the reasons for switching. Data were drawn from the Adelphi Real-World MS Disease-Specific Program (a retrospective survey) and analysis included people with RMS identified between 2017- 2021. Of 4129 patients with reasons for switch available, 3538 switched from non-HE DMT and 591 from HE DMT. Overall, 4.7% of patients were switched treatment by their physicians due to the risk of malignancies and infections including PML risk. The proportion of switches that were made due to the risk of PML were 23.9% in the HE DMT and 0.5% in the non-HE DMT groups. The top reasons for switching were relapse frequency (non-HE DMT vs HE-DMT: 26.8% vs 15.2%), lack of efficacy (20.9 vs 11.7) and increased number of MRI lesions (20.3% vs 12.4%). Physicians' risk perception of malignancies and infection excluding PML was not a leading factor when switching treatment. The risk of PML was a key factor, especially for switching patients from HE DMTs. In both groups, lack of efficacy was the key contributing factor for switching. Initiating the treatment with HE DMTs may potentially reduce the number of switches due to sub-optimal efficacy. These findings might help physicians to engage more in discussions with patients about the benefit/risk profile of DMTs.

Semi-supervised clustering of quaternion time series: Application to gait analysis in multiple sclerosis using motion sensor data.

Recent approaches in gait analysis involve the use of wearable motion sensors to extract spatio-temporal parameters that characterize multiple aspects of an individual's gait. In particular, the medical community could largely benefit from this type of devices as they could provide the clinicians with a valuable tool for assessing gait impairment. Motion sensor data are however complex and there is an urgent unmet need to develop sound statistical methods for analyzing such data and extracting clinically relevant information. In this article, we measure gait by following the hip rotation over time and the resulting statistical unit is a time series of unit quaternions. We explore the possibility to form groups of patients with similar walking impairment by taking into account their walking data and their global decease severity with semi-supervised clustering. We generalize a compromise-based method named hclustcompro to unit quaternion time series by combining it with the proper dissimilarity quaternion dynamic time warping. We apply this method on patients diagnosed with multiple sclerosis to form groups of patients with similar walking deficiencies while accounting for the clinical assessment of their overall disability. We also compare the compromise-based clustering approach with the method mergeTrees that falls into a sub-class of ensemble clustering named collaborative clustering. The results provide a first proof of both the interest of using wearable motion sensors for assessing gait impairment and the use of prior knowledge to guide the clustering process. It also demonstrates that compromise-based clustering is a more appropriate approach in this context.

Safety of pathogenetic therapy for multiple sclerosis during the COVID-19 pandemic

The safety of pathogenetic therapy for multiple sclerosis (MS) is a crucial aspect of the therapeutic strategy during the COVID-19 pandemic.&#x0D; Based on our own data, obtained during the study of MS pathogenesis and safety analysis of MS disease-modifying therapies (DMTs), we hereby suggest a classification of DMTs side effects, based on their type, development, and direction of action. There is a need to thoroughly analyse adverse events caused by pathogenetic therapy, with a balanced assessment of the direct vs. adverse effects of immunosuppressive drugs.&#x0D; Based on available literature, in the article, data on the effect of DMTs with various mechanisms of action on severe coronavirus infection are systematized.&#x0D; Interferon- and glatiramer acetate are the safest drugs to use during the COVID-19 pandemic. Teriflunomide, dimethyl fumarate, natalizumab, ocrelizumab, fingolimod, alemtuzumab, and cladribine should be used with caution. Drugs with a minor systemic immunosuppressant effect (e.g. natalizumab) and selective immunosuppressants (e.g. ocrelizumab) are safer than drugs that cause non-selective depletion of T and B cells.&#x0D; It must be stressed that the risk of MS exacerbation and progression due to untimely prescription or cessation of pathogenetic therapy can significantly exceed the potential risk of COVID-19.&#x0D; Long-term safety monitoring is required for DMTs during the COVID-19 pandemic and when the epidemiological situation stabilizes.

EE321 A Re-Examination of a Cost-Minimization Analysis in Multiple Sclerosis: Assessing Biases from the Inaccurate Assumption of Equal Effectiveness Using Probabilistic Sensitivity Analysis (PSA)

Based on “similar” effectiveness, the economics of treating relapsing-remitting multiple sclerosis with fingolimod and natalizumab were studied with a cost-minimization analysis (CMA) in 2012 based on Swedish data. Fingolimod was cost-saving compared with natalizumab. However, studies have shown a difference in efficacy favoring natalizumab, leading to a possibility that, while more costly, it may be cost-effective. This study uses PSA to estimate cost-effectiveness and associated decision uncertainty for the CMA and CEA.

039 Disease modifying treatments and cancer monitoring in MS; the need for a nation-wide disease registry

The immune system is inextricably linked to both cancer and Multiple Sclerosis (MS). National population- based cohort studies in Denmark and Norway have attempted to elucidate the relationship between cancer and MS, but results are conflicting. The advent of highly-efficacious disease modifying treatments (DMTs) in recent years revolutionised MS treatment, but the effect of their immunomodulating mechanism on cancer risk is unclear. Studies thus far have been limited by lack of cancer risk factor data and statistical power. In this pilot study, we identified the relevant data, including patient and cancer characteristics, DMT use, and important risk factors that may confound treatment effects. These data was collected for MS patients with cancer under the care of Salford Royal Foundation Trust. This highlighted the incomplete- ness of records, and the need for a framework for data collection. Moreover, data collection relied on multiple sources. Integration of the resultant question proforma into patient records will be a simple tool to enable reliable, homogeneous data collection. Deepening understanding of the effect of DMTs on cancer risk will improve risk-benefit treatment analysis in MS, thus improving care. Indeed, the institution of a nation-wide patient registry for such data in the UK will facilitate necessary future research.j.das@doctors.org.uk

The effect of lesion filling on brain network analysis in multiple sclerosis using structural magnetic resonance imaging

BackgroundGraph theoretical network analysis with structural magnetic resonance imaging (MRI) of multiple sclerosis (MS) patients can be used to assess subtle changes in brain networks. However, the presence of multiple focal brain lesions might impair the accuracy of automatic tissue segmentation methods, and hamper the performance of graph theoretical network analysis. Applying “lesion filling” by substituting the voxel intensities of a lesion with the voxel intensities of nearby voxels, thus creating an image devoid of lesions, might improve segmentation and graph theoretical network analysis. This study aims to determine if brain networks are different between MS subtypes and healthy controls (HC) and if the assessment of these differences is affected by lesion filling.MethodsThe study included 49 MS patients and 19 HC that underwent a T1w, and T2w-FLAIR MRI scan. Graph theoretical network analysis was performed from grey matter fractions extracted from the original T1w-images and T1w-images after lesion filling.ResultsArtefacts in lesion-filled T1w images correlated positively with total lesion volume (r = 0.84, p < 0.001) and had a major impact on grey matter segmentation accuracy. Differences in sensitivity for network alterations were observed between original T1w data and after application of lesion filling: graph theoretical network analysis obtained from lesion-filled T1w images produced more differences in network organization in MS patients.ConclusionLesion filling might reduce variability across subjects resulting in an increased detection rate of network alterations in MS, but also induces significant artefacts, and therefore should be applied cautiously especially in individuals with higher lesions loads.

Genome-wide polygenic analysis of multiple sclerosis markers

Objective: to perform a genome-wide polygenic analysis of multiple sclerosis (MS) markers in the ethnic groups of Bashkirs, Russians, and Tatars living in the Republic of Bashkortostan (Russian Federation).Patients and methods. Genotyping was performed using allele-specific polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism analysis of genes of the human leukocyte differentiation antigens CD6 (rs17824933), CD40 (rs6074022), CD58 (rs2300747), CD86 (rs9282641), transcription factors SOX8 (rs2744148) and ZBTB46 (rs6062314), beta-mannosidase MANBA (rs228614), C-type lectin domain CLEC16A (rs12708716), ribosomal protein S6 kinase B1 RPS6KB1 (rs180515), and long noncoding RNA gene PVT1 (rs759648) in 644 patients with MS and 1408 controls. Multilocus analysis of the disease associations with combinations of genotypes and alleles of the studied polymorphic loci was performed using the APSampler algorithm.Results and discussion. We determined the distribution of genotype and allele frequencies of the studied polymorphic loci in the ethnic groups of Bashkirs, Russians, and Tatars. We also observed disease associations with CD58 (rs2300747) and RPS6KB1 (rs180515) polymorphic loci in Russian men, CD86 (rs9282641) in Russian, PVT1 (rs759648) in Tatar women, CD40 (rs6074022) in Bashkir men, and identified 19 combinations of genotypes and/or alleles significantly associated with MS.Conclusion. Based on the genome-wide polygenic analysis of MS markers, we identified ethno- and gender-specific combined markers of the disease susceptibility.

Predicting PET-derived myelin content from multisequence MRI for individual longitudinal analysis in multiple sclerosis

Multiple sclerosis (MS) is a demyelinating and inflammatory disease of the central nervous system (CNS). The demyelination process can be repaired by the generation of a new sheath of myelin around the axon, a process termed remyelination. In MS patients, the demyelination–remyelination cycles are highly dynamic. Over the years, magnetic resonance imaging (MRI) has been increasingly used in the diagnosis of MS and it is currently the most useful paraclinical tool to assess this diagnosis. However, conventional MRI pulse sequences are not specific for pathological mechanisms such as demyelination and remyelination. Recently, positron emission tomography (PET) with radiotracer [11C]PIB has become a promising tool to measure in-vivo myelin content changes which is essential to push forward our understanding of mechanisms involved in the pathology of MS, and to monitor individual patients in the context of clinical trials focused on repair therapies. However, PET imaging is invasive due to the injection of a radioactive tracer. Moreover, it is an expensive imaging test and not offered in the majority of medical centers in the world. In this work, by using multisequence MRI, we thus propose a method to predict the parametric map of [11C]PIB PET, from which we derived the myelin content changes in a longitudinal analysis of patients with MS. The method is based on the proposed conditional flexible self-attention GAN (CF-SAGAN) which is specifically adjusted for high-dimensional medical images and able to capture the relationships between the spatially separated lesional regions during the image synthesis process. Jointly applying the sketch-refinement process and the proposed attention regularization that focuses on the MS lesions, our approach is shown to outperform the state-of-the-art methods qualitatively and quantitatively. Specifically, our method demonstrated a superior performance for the prediction of myelin content at voxel-wise level. More important, our method for the prediction of myelin content changes in patients with MS shows similar clinical correlations to the PET-derived gold standard indicating the potential for clinical management of patients with MS.

Multiple cause of death analysis in multiple sclerosis: A population-based study.

To gain a better understanding of the complex patterns of causes that contribute to death due to multiple sclerosis (MS) by assessing the relationship between MS and other causes of death listed on death certificates. Multiple cause of death data for all adult deaths (aged ≥18 years) in British Columbia, Canada, between 1986 and 2013 were accessed. All causes, as listed on the death certificate, whether underlying or contributing, were considered "any mention" causes. The associations between mention of MS on the death certificate and mention of other causes of death were examined by logistic regression, adjusted for age, sex, and calendar year (Bonferroni-corrected α level = 0.002). Findings were also sex-stratified. Among 771,288 deaths, MS was mentioned on 2,153 certificates. If MS was mentioned (versus not mentioned), there was a greater chance that specific conditions contributed to the death: respiratory infection (adjusted odds ratio [aOR], 3.03 [95% confidence interval (CI), 2.73-3.36]), aspiration pneumonia (aOR, 7.15 [95% CI, 6.23-8.22]), urinary tract infection (UTI) (aOR, 10.2 [95% CI, 8.7-12.0]), other infection including sepsis (aOR, 1.34 [95% CI, 1.15-1.56]), and skin disease (aOR, 5.06 [95% CI, 3.96-6.46]). Sex differences existed for urinary tract infection (men: aOR, 14.9 [95% CI, 11.5-19.3]; women: aOR, 8.00 [95% CI, 6.53-9.81]) and chronic respiratory disease (men = aOR, 1.36 [95% CI, 1.14-1.63]; women = aOR, 0.97 [95% CI, 0.84-1.13]). Deaths attributed to MS were commonly caused by infection (especially respiratory and urinary tract-related); conditions associated with advanced disability and immobility, such as aspiration pneumonia; and chronic respiratory disease in men. All are potentially modifiable; interventions that reduce the frequency or severity of these complications could improve survival in MS.

Brain tissue and myelin volumetric analysis in multiple sclerosis at 3T MRI with various in-plane resolutions using synthetic MRI.

Synthetic MRI (SyMRI) enables automatic brain tissue and myelin volumetry based on the quantification of R1 and R2 relaxation rates and proton density. This study aimed to determine the validity of SyMRI brain tissue and myelin volumetry using various in-plane resolutions at 3T in patients with multiple sclerosis (MS). We scanned 19 MS patients and 10 healthy age- and gender-matched controls using a 3T MR scanner with in-plane resolutions of 0.8, 1.8, and 3.6mm. The acquisition times were 5min 8s, 2min 52s, and 2min 1s, respectively. White matter (WM), gray matter (GM), cerebrospinal fluid (CSF), and myelin and non-WM/GM/CSF (NoN) volumes; brain parenchymal volume (BPV); and intracranial volume (ICV) were compared between different in-plane resolutions. These parameters were also compared between both groups, after ICV normalization. No significant differences in measured volumes were noted between the 0.8 and 1.8mm in-plane resolutions, except in NoN and CSF for healthy controls and NoN for MS patients. Meanwhile, significant volumetric differences were noted in most brain tissues when compared between the 3.6 and 0.8 or 1.8mm resolution for both healthy controls and MS patients. The normalized WM volume, myelin volume, and BPV showed significant differences between controls and MS patients at in-plane resolutions of 0.8 and 1.8mm. SyMRI brain tissue and myelin volumetry with in-plane resolution as low as 1.8mm can be useful in the evaluation of MS with a short acquisition time of < 3min.

Commentary: Integrative Analysis of Multiple Sclerosis Using a Systems Biology Approach

Commentary: Integrative Analysis of Multiple Sclerosis Using a Systems Biology Approach

Disability Outcome Measures in Phase III Clinical Trials in Multiple Sclerosis.

Accumulating neurological disability has a substantial impact on the lives of patients with multiple sclerosis (MS). As well as the established Expanded Disability Status Scale (EDSS), several other outcome measures are now available for assessing disability progression in MS. This review extends the findings of a previous analysis of relapsing-remitting MS (RRMS) trials published up to 2012, to determine whether there has been a shift in outcome measures used to assess disability in phase III clinical trials in RRMS and progressive MS. Forty relevant trials were identified (RRMS, n = 16; progressive MS, n = 18; other/mixed phenotypes, n = 6). Sustained EDSS worsening, particularly over 3 months, was included as an endpoint in almost all identified trials. Other disability-related endpoints included the Multiple Sclerosis Functional Composite z-score and scores for the physical component summary of the Multiple Sclerosis Impact Scale and Medical Outcomes Study Short-Form (36-item) Health Survey. Tests assessing manual dexterity, ambulation, vision and cognition were also employed, and in some trials, composite endpoints were used. However, there was no obvious trend in choice of disability outcome measures over time. Sustained EDSS worsening over short time periods continues to be the most widely used measure of disability progression in pivotal MS trials, despite its well-recognised limitations. A new tool set is needed for use in MS clinical trials that detects the benefit of potential treatments that slow (or reverse) progressive disability.Electronic supplementary materialThe online version of this article (10.1007/s40263-018-0530-8) contains supplementary material, which is available to authorized users.

White matter tract-specific quantitative analysis in multiple sclerosis: Comparison of optic radiation reconstruction techniques.

The posterior visual pathway is commonly affected by multiple sclerosis (MS) pathology that results in measurable clinical and electrophysiological impairment. Due to its highly structured retinotopic mapping, the visual pathway represents an ideal substrate for investigating patho-mechanisms in MS. Therefore, a reliable and robust imaging segmentation method for in-vivo delineation of the optic radiations (OR) is needed. However, diffusion-based tractography approaches, which are typically used for OR segmentation are confounded by the presence of focal white matter lesions. Current solutions require complex acquisition paradigms and demand expert image analysis, limiting application in both clinical trials and clinical practice. In the current study, using data acquired in a clinical setting on a 3T scanner, we optimised and compared two approaches for optic radiation (OR) reconstruction: individual probabilistic tractography-based and template-based methods. OR segmentation results were applied to subjects with MS and volumetric and diffusivity parameters were compared between OR segmentation techniques. Despite differences in reconstructed OR volumes, both OR lesion volume and OR diffusivity measurements in MS subjects were highly comparable using optimised probabilistic tractography-based, and template-based, methods. The choice of OR reconstruction technique should be determined primarily by the research question and the nature of the available dataset. Template-based approaches are particularly suited to the semi-automated analysis of large image datasets and have utility even in the absence of dMRI acquisitions. Individual tractography methods, while more complex than template based OR reconstruction, permit measurement of diffusivity changes along fibre bundles that are affected by specific MS lesions or other focal pathologies.

Ocrelizumab: A New B-cell Therapy for Relapsing Remitting and Primary Progressive Multiple Sclerosis.

To review the pharmacology, pharmacokinetics, efficacy, and safety of ocrelizumab, a new B-cell-targeted therapy for multiple sclerosis (MS). A comprehensive search of PubMed and OVID/MEDLINE was conducted using search terms ocrelizumab and multiple sclerosis using the date range of 1946 through October 2017. All English-language, human-subject articles related to ocrelizumab and MS were evaluated. Ocrelizumab was approved in March 2017 for the treatment of relapsing or primary progressive MS (PPMS). A phase II trial established 600 mg intravenously every 6 months as the preferred dosing schedule. Two phase III trials evaluated the efficacy of ocrelizumab in patients with relapsing remitting MS, and individual and pooled analysis demonstrated a significant reduction in annualized relapse rate ( P < 0.001 pooled), disability progression at 12 weeks ( P < 0.001 pooled), and gadolinium-enhancing lesions on magnetic resonance imaging (MRI; P < 0.001). Patients with PPMS were evaluated in a third phase III trial, which showed a significant decrease in disease progression at 12 weeks ( P = 0.03) and volume of T2-weighted lesions on MRI ( P < 0.001). As with other monoclonal antibodies, adverse effects seen with ocrelizumab were primarily infusion-related reactions and infection. Ocrelizumab demonstrated efficacy in the treatment of relapsing and PPMS and is the first therapy approved for patients with PPMS.

Differential brainstem atrophy patterns in multiple sclerosis and neuromyelitis optica spectrum disorders.

Multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD) are central nervous system (CNS) inflammatory demyelinating disorders. It is clinically important to distinguish MS from NMOSD, as treatment and prognosis differ. Brainstem involvement is common in both disorders. To investigate whether the patterns of brainstem atrophy on volumetric analysis in MS and NMOSD were different and correlated with clinical disability. Case-control cross-sectional study. In all, 17 MS, 13 NMOSD, and 18 healthy control (HC) subjects were studied. T1 -weighted and T2 w spin-echo images were acquired with a 3T scanner. Semiautomated segmentation and volumetric measurement of brainstem regions were performed. Anatomical information was obtained from whole brain T1 w images using a 3D magnetization-prepared rapid gradient-echo (MPRAGE) imaging sequence (TR/TE/T: 7.0/3.2/800 msec, voxel size: 1 × 1 × 1 mm3 , scan time: 10 min 41 sec). Independent samples t-test, Mann-Whitney U-test, partial correlation, and multiple regression analysis. Baseline characteristics were similar across the three groups, without significant difference in disease duration (P = 0.354) and EDSS score (P = 0.159) between MS and NMOSD subjects. Compared to HC, MS subjects had significantly smaller normalized whole brainstem (-5.2%, P = 0.027), midbrain (-8.3%, P = 0.0001), and pons volumes (-5.9%, P = 0.048), while only the normalized medulla volume was significantly smaller in NMOSD subjects compared to HC (-8.5% vs. HC, P = 0.024). Normalized midbrain volume was significantly smaller in MS compared to NMOSD subjects (-5.0%, P = 0.014), whereas normalized medulla volume was significantly smaller in NMOSD compared to MS subjects (-8.1%, P = 0.032). Partial correlations and multiple regression analysis revealed that smaller normalized whole brainstem, pons, and medulla oblongata volumes were associated with greater disability on the Expanded Disability Status Scale (EDSS), Functional System Score (FSS)-brainstem and FSS-cerebellar in NMOSD subjects. Differential patterns of brainstem atrophy were observed, with the midbrain being most severely affected followed by pons in MS, whereas only the medulla oblongata was affected in NMOSD. 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;47:1601-1609.

The History of Cerebrospinal Fluid Analysis in Multiple Sclerosis: A Great Development over the Last Centuries

Cerebrospinal Fluid (CSF) analysis acquired a great role in the 1990’s when applied to Multiple Sclerosis (MS) diagnostic work-up. The “watery fluid” by Andreas Vesalius remained unstudied till the introduction of Lumbar Puncture (LP) at the eighteenth century. Technical developments exploded in the 1990’s: when new applications to the CSF analysis opened to the hypothesis of MS as the model of intrathecal synthesis of immunoglobulins.

Retinal ganglion cell analysis in multiple sclerosis and optic neuritis: a systematic review and meta-analysis.

The aim of this study was to summarise existing findings regarding optical coherence tomography (OCT) measurements of ganglion cell layer (GCL) alterations in optic neuritis (ON) and multiple sclerosis (MS). Peer-reviewed studies published prior to April 2016 were searched using PubMed, EMBASE, Web of Science and Scopus. Studies were included if they measured GCL thickness using OCT in patients with either ON, MS or clinically isolated syndrome. For the meta-analysis, we compared GCL thickness in MS patients with and without prior ON, to healthy controls. 42/252 studies were reviewed. In acute ON, studies showed significant thinning of the GCL within the first 5weeks (n=5), earlier than retinal nerve fibre layer (RNFL) thinning. GCL thinning at 1-2months after acute ON predicted visual function at 6months (n=3). The meta-analysis showed that the thickness of the GCL was significantly reduced in MS patients both with and without previous ON compared to healthy controls. GCL thinning was associated with visual function in most studies (n=10) and expanded disability status scale (EDSS) scores (n=6). In acute ON, thinning of the GCL is measurable prior to RNFL thinning, and GCL thickness after 1-2months may predict visual function after 6months. Furthermore, GCL thinning occurs in MS both with and without prior ON, and may be associated with visual function and EDSS score. This suggests that the GCL is a promising biomarker, which may be used to examine in vivo neurodegeneration in ON and MS.