Clinical and therapeutic challenges of smouldering multiple sclerosis.

INTRODUCTION: Assessment of the clinical course, neuroimaging and histopathological changes suggests that multiple sclerosis (MS) should not be defined merely as a focal inflammatory disease of the central nervous system (CNS) because the essence of the disease is due to a diffuse, 'smouldering', pathophysiological process. STATE OF THE ART: Progression independent of relapse activity (PIRA) is the clinical indicator of smouldering MS. Multiple pathomechanical factors determining smouldering MS have been identified, i.e. continuous activation of microglia, which is the source of smouldering inflammation and the failure of remyelination in MS. CLINICAL IMPLICATIONS: Our paper presents new neuroimaging markers, including paramagnetic rim lesions (PRLs) and slowly expanding lesions (SELs), potential methods for clinical evaluation and promising therapeutic options, i.e. Bruton's tyrosine kinase inhibitors that prevent PIRA in smouldering MS. With the duration of MS, the efficacy of the current immunomodulatory treatment is reduced, and its effect is insufficient to control smouldering MS. FUTURE DIRECTIONS: Innovative insights into the pathophysiology and clinical course warrant the need for a holistic approach to MS. The efforts of clinicians should be aimed at indicating subtle neurological deficits in physical performance and cognitive functioning to characterise the disease progression in its early stages. Undoubtedly, a new era for MS is coming in which new resonance markers will be used together with clinical methods to assess smouldering MS, and the treatment will include combination therapy with consideration of drugs that reduce relapse rates and therapy aimed at inhibiting disease progression.

Optical coherence tomography angiography as a potential tool in differential diagnosis of multiple sclerosis and rheumatic disorders with central nervous system involvement.

PURPOSE: The aim of this study is to analyse whether optical coherence tomography angiography (angio-OCT, OCTA) measurements can be a useful tool to differentiate central nervous system (CNS) involvement in rheumatic disorders (RD) from multiple sclerosis (MS). METHODS: A total of 85 patients- 41 with MS, 21 with RD with CNS involvement and 23 healthy controls were included in the study. All individuals underwent OCTA and the following parameters were measured in each eye separately: average foveal and parafoveal vessel density (VD), average foveal and parafoveal vessel length (VL) of the superficial capillary plexus (SCP) and deep capillary plexus (DCP), as well as area, perimeter, and circularity of the foveal avascular zone. RESULTS: OCTA showed a VD reduction in the foveal region of the SCP in eyes of RD patients when compared to MS patients (21.96 ± 3.39 vs.23.88 ± 3.05 (p = 0.003)). There have been no significant differences in any of the assessed parameters that is average VD and total average VL in the foveal area of the SCP as well as of the DCP in the general population comprising healthy controls, MS and RD groups (p > 0.05 for all). CONCLUSIONS: Our results suggest that an OCTA finding of decreased VD in the foveal region of the SCP may be considered as a potentially useful biomarker of RD in comparison with MS patients.

Optical Coherence Tomography in the Differential Diagnosis of Patients with Multiple Sclerosis and Patients with MRI Nonspecific White Matter Lesions.

In the differential diagnosis of nonspecific white matter lesions (NSWMLs) detected on magnetic resonance imaging (MRI), multiple sclerosis (MS) should be taken into consideration. Optical coherence tomography (OCT) is a promising tool applied in the differential diagnostic process of MS. We tested whether OCT may be useful in distinguishing between MS and NSWMLs patients. In patients with MS (n = 41) and NSWMLs (n = 19), the following OCT parameters were measured: thickness of the peripapillary Retinal Nerve Fibre Layer (pRNFL) in superior, inferior, nasal, and temporal segments; thickness of the ganglion cell-inner plexiform layer (GCIPL); thickness of macular RNFL (mRNFL); and macular volume (MV). In MS patients, GCIPL was significantly lower than in NSWMLs patients (p = 0.024). Additionally, in MS patients, mRNFL was significantly lower than in NSWMLs patients (p = 0.030). The average segmental pRNFL and MV did not differ between MS and NSWMLs patients (p > 0.05). GCIPL and macular RNFL thinning significantly influenced the risk of MS (18.6% [95% CI 2.7%, 25.3%]; 27.4% [95% CI 4.5%, 62.3%]), and reduced GCIPL thickness appeared to be the best predictor of MS. We conclude that OCT may be helpful in the differential diagnosis of MS and NSWMLs patients in real-world settings.

Late onset multiple sclerosis - multiparametric MRI characteristics.

INTRODUCTION: Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) with heterogenic character. Typical age of onset is between 20 and 35 years. Clinically definite multiple sclerosis (CDMS) can occur also in patients older than 50 years. This type of MS is called Late Onset Multiple Sclerosis (LOMS). Until now, the differences in clinical course, type of first symptoms, and prognosis of LOMS have not been well established. Also the MRI characteristics of patients with LOMS have not been determined. Neither conventional nor nonconventional MRI features are known to be typical for LOMS. CLINICAL RATIONALE FOR THE STUDY: To investigate the MRI characteristics of LOMS patients based on conventional and non-conventional techniques. MATERIALS AND METHODS: Twenty patients with LOMS were included in the study and 17 patients with typical onset of MS (TOMS) served as a comparative group. The two groups were matched in terms of disease duration and EDSS score. Conventional (T1- and T2-weighted images) and non-conventional (magnetization transfer images, proton magnetic resonance spectroscopy) MRI techniques were performed in all participants. Parameters from both techniques were compared between LOMS and TOMS groups. RESULTS: Patients with late onset of MS had lower Brain Parenchyma Fraction (BPF) (p < 0.001) and Grey Matter Fraction (GMF) values (p = 0.008) than the TOMS group. There was no statistical differences in White Matter Fraction (WMF) values between the groups (p = 0.572). Patients with LOMS and TOMS statistically differed in the peak height (p = 0.018), peak location (p < 0.001), and MTR mean value (p < 0.001). Patients with LOMS manifested lower concentrations of NAA+NAAG and NAA+NAAG/Cr than patients with TOMS (p = 0.009 and p < 0.001 respectively). No statistical difference was found between the groups in terms of mean mIn (p = 0.346) and mean GPC+PCh (p = 0.563). We did not find a statistical difference in T1- and T2- lesion load (p = 0.1, p = 0.3 respectively) although T1/T2 lesion ratio was higher in the LOMS group. CONCLUSION AND CLINICAL IMPLICATIONS: MRI parameters in patients with LOMS differed significantly from those obtained from the TOMS group. Our results, which indicate that in LOMS patients brain tissue damage is more advanced than in TOMS patients, may contribute to a better understanding of the heterogeneity of MS.

Recommendations of the Polish Medical Society of Radiology and the Polish Society of Neurology for a protocol concerning routinely used magnetic resonance imaging in patients with multiple sclerosis.

Magnetic resonance imaging (MRI) is a widely used method for the diagnosis of multiple sclerosis that is essential for the detection and follow-up of the disease. OBJECTIVE: The Polish Medical Society of Radiology (PLTR) and the Polish Society of Neurology (PTN) present the second version of their recommendations for investigations routinely conducted in magnetic resonance imaging departments in patients with multiple sclerosis. This version includes new data and practical comments for electroradiology technologists and radiologists. The recommended protocol aims to improve the MRI procedure and, most importantly, to standardise the method of conducting scans in all MRI departments. This is crucial for the initial diagnostics necessary for establishing a diagnosis, as well as for MS patient monitoring, which directly translates into significant clinical decisions. INTRODUCTION: Multiple sclerosis (MS) is a chronic immune mediated inflammatory demyelinating disease of the central nervous system (CNS), the aetiology of which is still unknown. The nature of the disease lies in a CNS destruction process disseminated in time (DIT) and space (DIS). MRI detects focal lesions in the white and grey matter with high sensitivity (although with significantly lower specificity in the latter). It is also the best tool to assess brain atrophy in patients with MS in terms of grey matter volume (GMV) and white matter volume (WMV) as well as local atrophy (by measuring the volume of thalamus, corpus callosum, subcortical nuclei, and hippocampus) as parameters that correlate with disability progression and cognitive dysfunctions. Progress in MR techniques, as well as advances in postprocessing the obtained data, has driven the dynamic development of computer programs that allow for a more repeatable assessment of brain atrophy in both cross-sectional and longitudinal studies. MR imaging is unquestionably the best diagnostic tool available to follow up the course of the disease and support clinicians in choosing the most appropriate treatment strategy for their MS patient. However, to diagnose and follow up MS patients on the basis of MRI in accordance with the latest standards, the MRI study must adhere to certain quality criteria. Such criteria are the subject of this paper.

Recommendations of the Polish Medical Society of Radiology and the Polish Society of Neurology for the routinely used magnetic resonance imaging protocol in patients with multiple sclerosis.

Magnetic resonance imaging (MRI) is a widely used method for the diagnosis of multiple sclerosis (MS) that is essential for the detection and follow-up of the disease. The Polish Medical Society of Radiology (PLTR) and the Polish Society of Neurology (PTN) present the second version of the recommendations for examinations routinely conducted in magnetic resonance imaging departments in patients with MS, which include new data and practical comments for electroradiology technicians and radiologists. The recommended protocol aims to improve the MRI procedure and, most importantly, to standardise the method of conducting scans in all MRI departments. This is crucial for the initial diagnostics that are necessary to establish a diagnosis as well as monitor patients with MS, which directly translates into significant clinical decisions. MS is a chronic idiopathic inflammatory demyelinating disease of the central nervous system (CNS), the aetiology of which is still unknown. The nature of the disease lies in the CNS destruction process disseminated in time and space. MRI detects focal lesions in the white and grey matter with high sensitivity (with significantly less specificity in the latter). It is also the best tool to assess brain atrophy in patients with MS in terms of grey matter volume and white matter volume as well as local atrophy (by measuring the volume of thalamus, corpus callosum, subcortical nuclei, hippocampus) as parameters that correlate with disability progression and cognitive dysfunctions. Progress in magnetic resonance techniques, as well as the abilities of postprocessing the obtained data, has become the basis for the dynamic development of computer programs that allow for a more repeatable assessment of brain atrophy in both cross-sectional and longitudinal studies. MRI is unquestionably the best diagnostic tool used to follow up the course of the disease and to treat patients with MS. However, to diagnose and follow up the patients with MS on the basis of MRI in accordance with the latest standards, an MRI study must meet certain quality criteria, which are the subject of this paper.

Guidelines of the Polish Medical Society of radiology for the routinely used MRI protocol in patients with multiple sclerosis.

Magnetic resonance imaging is widely used in diagnosing multiple sclerosis as a basic method for detecting and monitoring the disease. INTRODUCTION: Polish Medical Society of Radiology presents the second version of the recommendations for the routinely conducted MRI in multiple sclerosis, which include new data and practical remarks for radiographers and radiologists. The recommended protocol aims to improve the imaging procedure and, most importantly, to standardize conducting MRI scans in all MRI departments. This is crucial for monitoring the patients with MS, which directly contributes to essential clinical decisions. AIM OF THE GUIDELINES: Multiple sclerosis (MS) is a chronic inflammatory demyelinating and degenerative disease of the central nervous system (CNS) with its etiology still unknown. The fundamental requirement of the disease is the CNS destruction process disseminated in time (DIT) and space (DIS). MR imaging detects focal lesions in white and gray matter with high sensitivity and is the best way to assess brain atrophy in MS patients. It is unquestionably the best diagnostic tool to follow-up the clinical course of the disease and treatment of MS patients. However, to achieve a diagnosis based on MRI scans, and follow-up MS patients according to the latest standards, an MRI scan has to meet certain quality criteria that are the subject of this work.

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.

Predictive value of brain atrophy, serum biomarkers and information processing speed for early disease progression in multiple sclerosis.

Introduction: Multiple sclerosis (MS) is a chronic autoimmune-mediated demyelinating disease of the central nervous system (CNS). A clinical presentation of the disease is highly differentiated even from the earliest stages of the disease. The application of stratifying tests in clinical practice would allow for improving clinical decision-making including a proper assessment of treatment benefit/risk balance. Methods: This prospective study included patients with MS diagnosed up to 1 year before recruitment. We analyzed serum biomarkers such as CXCL13, CHI3L1, OPN, IL-6, and GFAP and neurofilament light chains (NfLs); brain MRI parameters of linear atrophy such as bicaudate ratio (BCR), third ventricle width (TVW); and information processing speed were measured using the Symbol Digit Modalities Test (SDMT) during the 2 years follow-up. Results: The study included a total of 50 patients recruited shortly after the diagnosis of MS diagnosis (median 0 months; range 0-11 months), and the mean time of observation was 28 months (SD = 4.75). We observed a statistically significant increase in the EDSS score (Wilcoxon test: Z = 3.06, p = 0.002), BCR (Wilcoxon test: Z = 4.66, p < 0.001), and TVW (Wilcoxon test: Z = 2.84, p = 0.005) after 2 years of disease. Patients who had a significantly higher baseline level of NfL suffered from a more severe disease course as per the EDSS score (Mann-Whitney U-test: U = 107, Z = -2,74, p = 0.006) and presence of relapse (Mann-Whitney U-test: U = 188, Z = -2.01, p = 0.044). In the logistic regression model, none of the parameters was a significant predictor for the achieving of no evidence of disease activity status (NEDA). In the model considering all assessed parameters, only the level of NfL had a significant impact on disease progression, measured as the increase in EDSS (logistic regression: ß = 0.002, p = 0.017). Conclusion: We confirmed that NfL levels in serum are associated with more active disease. Moreover, we found that TVW at the time of diagnosis was associated with an impairment in cognitive function measured by information processing speed at the end of the 2-year observation. The inclusion of serum NfL and TVW assessment early in the disease may be a good predictor of disease progression independent of NEDA.

Magnetic Resonance Imaging in Primary Progressive Multiple Sclerosis Patients : Review.

The recently developed effective treatment of primary progressive multiple sclerosis (PPMS) requires the accurate diagnosis of patients with this type of disease. Currently, the diagnosis of PPMS is based on the 2017 McDonald criteria, although the contribution of magnetic resonance imaging (MRI) to this process is fundamental. PPMS, one of the clinical types of MS, represents 10%-15% of all MS patients. Compared to relapsing-remitting MS (RRMS), PPMS differs in terms of pathology, clinical presentation and MRI features. Regarding conventional MRI, focal lesions on T2-weighted images and acute inflammatory lesions with contrast enhancement are less common in PPMS than in RRMS. On the other hand, MRI features of chronic inflammation, such as slowly evolving/expanding lesions (SELs) and leptomeningeal enhancement (LME), and brain and spinal cord atrophy are more common MRI characteristics in PPMS than RRMS. Nonconventional MRI also shows differences in subtle white and grey matter damage between PPMS and other clinical types of disease. In this review, we present separate diagnostic criteria, conventional and nonconventional MRI specificity for PPMS, which may support and simplify the diagnosis of this type of MS in daily clinical practice.

A Loop That Matters-An Unusual Case of Bow Hunter's Syndrome.

Bow Hunter's syndrome (BHS), also known as rotational vertebral artery occlusion (VAO), is a rare entity in which vertebral artery is reversibly compressed due to rotation or extension of the head, causing vertebrobasilar insufficiency. Because of VAO, BHS should be considered as a possible life-threatening condition. Diverse aetiologies of BHS may trigger a broad spectrum of non-specific symptoms and may result in frequent misdiagnosis of this disorder in daily clinical practice. Herein, we present a case of BHS caused by previously non-described vascular aetiology.

The influence of COVID-19 pandemic lockdown on the physical activity of people with multiple sclerosis. The role of online training.

BACKGROUND: COVID-19 pandemic has affected people with multiple sclerosis (PwMS) on various levels. Pandemic lockdown influenced the access to typical measures of physical activity such as out-door training or gym exercises. METHODS: We performed a survey assessing physical activity during pandemic lockdown among PwMS treated in our MS center. The questionnaire encompassed questions regarding physical activity before and during lockdown, including the employment of online technologies. RESULTS: The survey was completed by 262 PwMS. Physical activity before lockdown was declared by 74.4% of PwMS, regular exercises were declared by 30.9% of participants. Among physically active PwMS 50.5% limited their physical activity during the COVID-19 lockdown. The decrease in physical activity was reported more frequently by PwMS with higher levels of disability, particularly declaring regular exercises before lockdown. In the opinion of 39,7% of PwMS online training could replace standard exercises, however only 19,9% of PwMS were actively looking for online training during the lockdown. The interest in online exercise was greatest in the group ≤30 years of age and EDSS ≤2. Synchronous exercises were the preferred online training, particularly among PwMS with EDSS≥4. CONCLUSION: Our findings indicate a need for systematic educational and organizational measures, promoting physical activity among PwMS and acknowledging pandemic conditions.

Safety of Vaccines against SARS-CoV-2 among Polish Patients with Multiple Sclerosis Treated with Disease-Modifying Therapies.

(1) Background: The present study aims to report the side effects of vaccination against coronavirus disease 2019 (COVID-19) among patients with multiple sclerosis (MS) who were being treated with disease-modifying therapies (DMTs) in Poland. (2) Methods: The study included 2261 patients with MS who were being treated with DMTs, and who were vaccinated against COVID-19 in 16 Polish MS centers. The data collected were demographic information, specific MS characteristics, current DMTs, type of vaccine, side effects after vaccination, time of side-effect symptom onset and resolution, applied treatment, relapse occurrence, and incidence of COVID-19 after vaccination. The results were presented using maximum likelihood estimates of the odds ratio, t-test, Pearson's chi-squared test, Fisher's exact p, and logistic regression. The statistical analyses were performed using STATA 15 software. (3) Of the 2261 sampled patients, 1862 (82.4%) were vaccinated with nucleoside-modified messenger RNA (mRNA) vaccines. Mild symptoms after immunization, often after the first dose, were reported in 70.6% of individuals. Symptoms included arm pain (47.5% after the first dose and 38.7% after the second dose), fever/chills/flu-like symptoms (17.1% after the first dose and 20.5% after the second dose), and fatigue (10.3% after the first dose and 11.3% after the second dose). Only one individual presented with severe side effects (pro-thrombotic complications) after vaccination. None of the DMTs in the presented cohort were predisposed to the development of side effects. Nine patients (0.4%) had a SARS-CoV-2 infection confirmed despite vaccination. (4) Conclusions: Vaccination against SARS-CoV-2 is safe for people with MS who are being treated with DMTs. Most adverse events following vaccination are mild and the acute relapse incidence is low.

Analysis of Side Effects Following Vaccination Against COVID-19 Among Individuals With Multiple Sclerosis Treated With DMTs in Poland.

Background and Objectives: Since vaccination against COVID-19 is available for over a year and the population of immunized individuals with autoimmune disorders is higher than several months before, an evaluation of safety and registered adverse events can be made. We conducted a large study of side effects following the COVID-19 vaccine among patients with multiple (MS) sclerosis treated with disease-modifying therapies (DMTs) and analyzed factors predisposing for particular adverse events. Methods: We gathered data of individuals with MS treated with DMTs from 19 Polish MS Centers, who reported at least one adverse event following COVID-19 vaccination. The information was obtained by neurologists using a questionnaire. The same questionnaire was used at all MS Centers. To assess the relevance of reported adverse events, we used Fisher's exact test, t-test, and U-Menn-Whutney test. Results: A total of 1,668 patients with MS and reports of adverse events after COVID-19 vaccination were finally included in the study. Besides one case marked as "red flag", all adverse events were classified as mild. Pain at the injection site was the most common adverse event, with a greater frequency after the first dose. Pain at the injection site was significantly more frequent after the first dose among individuals with a lower disability (EDSS ≤2). The reported adverse events following immunization did not differ over sex. According to age, pain at the injection site was more common among individuals between 30 and 40 years old, only after the first vaccination dose. None of the DMTs predisposed for particular side effects. Conclusions: According to our findings, vaccination against COVID-19 among patients with MS treated with DMTs is safe. Our study can contribute to reducing hesitancy toward vaccination among patients with MS.

Thalamus Atrophy in the Peri-Pregnancy Period in Clinically Stable Multiple Sclerosis Patients: Preliminary Results.

Radiological activity in the post-partum period in MS patients is a well-known phenomenon, but there is no data concerning the influence of pregnancy on regional brain atrophy. The aim of this article was to investigate local brain atrophy in the peri-pregnancy period (PPP) in patients with MS. Thalamic volume (TV); corpus callosum volume (CCV) and classical MRI activity (new gadolinium enhancing lesions (Gd+), new T2 lesions, T1 lesions volume (T1LV) and T2 lesions volume (T2LV)) were analyzed in 12 clinically stable women with relapsing-remitting MS and with MRI performed in the PPP. We showed that there was a significant decrease in TV (p = 0.021) in the PPP. We also observed a significant increase in the T1 lesion volume (p = 0.028), new gadolinium-enhanced and new T2 lesions (in 46% and 77% of the scans, respectively) in the post-partum period. Our results suggest that the PPP in MS may be associated not only with classical MRI activity but, also, with regional brain atrophy.

The Role of Optical Coherence Tomography in Differential Diagnosis of Multiple Sclerosis and Autoimmune Connective Tissue Diseases with CNS Involvement.

The purpose of this study was to examine whether application of optical coherence tomography (OCT) measurements can provide a useful biomarker for distinguishing central nervous system (CNS) involvement in autoimmune connective tissue diseases (CTD) from multiple sclerosis (MS). An observational study included non-optic neuritis eyes of 121 individuals: 59 patients with MS, 30 patients with CNS involvement in CTD, and 32 healthy controls. OCT examination was performed in all subjects to measure retinal nerve fiber layer (RNFL) thickness, ganglion cell complex (GCC) thickness, ganglion cell layer-inner plexiform layer (GCIPL) thickness, and volume of the macula. There was a significant group effect with regard to superior optic disc RNFL, macular RNFL, GCC, and GCIPL thickness, and macular volume. Post-hoc analysis revealed that MS patients have significantly smaller macular volume and thinner superior optic disc RNFL, macular RNFL, GCC, and GCIPL compared to healthy controls. CTD patients have significantly smaller superior optic disc RNFL, GCIPL, and GCC thickness compared to healthy controls. However, no significant group differences were observed between the patient groups (MS vs. CTD) on any outcome. Although a prominent retinal thinning may be a useful biomarker in MS patients, in a general population of individuals with a confirmed CNS involvement the use of OCT is not specific enough to discriminate between MS and autoimmune CTD.

Regional myo-inositol concentration in mild cognitive impairment Using 1H magnetic resonance spectroscopic imaging.

The goal was to assess regional patterns of metabolite abnormalities in mild cognitive impairment (MCI) and Alzheimer disease (AD) patients using proton magnetic resonance spectroscopy imaging at 1.5 Tesla. Fourteen MCI, 17 AD, and 16 healthy control (HC) subjects were studied. MCI was associated with higher myo-inositol (mIn) concentration in right parietal white matter compared with HC and lower mIn levels in frontal white matter compared with AD. AD was associated with higher mIn concentration in frontal and parietal white matter compared with HC. N-acetylaspartate (NAA) concentration of white matter was similar in all groups, whereas NAA concentration of gray matter showed a trend toward lower values in the right parietal lobe in AD compared with MCI and HC. A mIn increase in white matter in absence of significant NAA reduction suggests that mIn is a more robust and sensitive marker of white matter pathology in AD and MCI than NAA. Furthermore, the dissociation between mIn and NAA alterations in white matter could provide important information regarding the role of glial and neuronal damage in MCI and AD.

Real-world effectiveness of fingolimod in Polish group of patients with relapsing-remitting multiple sclerosis.

OBJECTIVES: Fingolimod is indicated for the treatment of relapsing-remitting multiple sclerosis (RRMS) patients with highly aggressive disease characterized by frequent relapses and active magnetic resonance imaging. Its efficacy has been demonstrated in three large phase III trials, used in the regulatory submissions throughout the world. Fingolimod in licensed in Europe since 2011 but with a growing number of disease-modifying drugs (DMD) becoming available for RRMS, it is important to gather real-world evidence data regarding long-term effectiveness in treated patients with MS. The aim of this study was to assess fingolimod effectiveness in a real life Polish group of RRMS patients receiving fingolimod as second line treatment. PATIENTS AND METHODS: The observational study with retrospective data collection was performed at 13 sites that were asked to document eligible patients in consecutive chronological order to avoid selection bias. Demographic and clinical data from 253 adult patients with RRMS treated with fingolimod were analyzed. RESULTS: Mean treatment time with fingolimod was 42 months. Relapses reduction during 3 years treatment period was observed (2.0 v 0.2) and majority of patients were free of relapses. Mean EDSS score was stable during the time of observation. The proportion of patients who were free from any clinical disease activity, i.e. without relapses and disability progression, was over 70%. During the first and second year of observation significant reduction of new MRI lesions was observed. CONCLUSION: In the Polish group of patients with RRMS treated with fingolimod, the majority of them showed freedom from relapses, disability progression and reduction of new MRI lesions. Switching from injectable immunomodulatory drugs to fingolimod is associated with fewer relapses and lower disability progression.

Optical coherence tomography in multiple sclerosis: thickness of the retinal nerve fiber layer as a potential measure of axonal loss and brain atrophy.

BACKGROUND: Axonal distribution within the retinal nerve fiber layer (RNFL) measured by optical coherence tomography (OCT) correlates with axonal viability and integrity. OBJECTIVE: To investigate correlations between RNFL and MRI measures of axonal loss in MS patients. METHODS: Fifty one remitting-relapsing MS patients, 20 with a history of optic neuritis (MS-ON), 31 without optic neuritis (MS N-ON), and 12 healthy control subjects (HC) were included in the study. RNFL was measured by OCT and brain atrophy was assessed by MRI. RESULTS: The average RNFL in the affected eye (AE) in the MS-ON group was significantly lower than the RNFL in the MS N-ON (p = 0.01) and in HC (p = 0.01). The average RNFL in the unaffected eye (UE) and RNFL in MS N-ON were also lower than HC, but this value did not achieve significance. In MS N-ON a lower average RNFL was associated with an increased T1 lesion volume (p = 0.03) and T2-lesion volume (p = 0.001). The RNFL in MS N-ON was also associated with a reduction of BPF and %gm fraction (p = 0.01, p = 0.02 respectively). In MS-ON there was a much weaker, non-significant correlation between RNFL thickness and T1, T2 volume, BPF, %gm and %wm fractions that might have resulted from a pronounced post-inflammatory local optic nerve atrophy in AE. CONCLUSION: The RNFL measured by OCT may be useful as a surrogate marker for assessment of brain atrophy in MS.

Cognitive impairment in patients with relapsing-remitting multiple sclerosis. The correlation with MRI lesion volume.

BACKGROUND AND PURPOSE: The aim of this study was to assess cognitive impairment in patients with relapsing-remitting multiple sclerosis (RR-MS) and to evaluate the correlation of cognitive impairment with physical disability and MRI lesion volume. MATERIAL AND METHODS: Sixty patients with RR-MS and 50 healthy controls were assessed using neuropsychological tests. All the patients were subjected to MRI examination using PD/T2 and T1 sequences, and clinical evaluation with the EDSS scale was applied. RESULTS: Selective cognitive impairment was found in 40% of the RR-MS group, and broad, overall cognitive dysfunction was found in 15% of patients. A correlation was found between neurological signs and memory deficits and psychomotor speed. The mean total lesion volume (TLV) was significantly higher in patients with selective and overall cognitive impairment than in those without (8060 vs. 3183 mm3, p=0.001; 7234 vs. 3138 mm3, p=0.004, respectively). There was no difference in TLV between RR-MS patients with selective or overall cognitive impairment (8060 vs. 7234 mm3, p=0.134). Moderate correlations were found between nonverbal memory, verbal fluency and abstract reasoning tests and TLV. CONCLUSIONS: Cognitive impairment is present in more than 50% of patients with RR-MS, and they are mainly selective deficits. The correlation between physical disability and cognitive impairment was not significant, except for memory deficits and psychomotor speed. There is a correlation between TLV and presence of cognitive impairment, but no correlation between TLV and pattern of cognitive impairment.