Follow-up Of Multiple Sclerosis Patients Research Articles

SENSITIVITY OF PLATELET-LYMPHOCYTE RATIO, MONOCYTE-LYMPHOCYTE RATIO, NEUTROPHIL-LYMPHOCYTE RATIO, RED BLOOD CELL DISTRIBUTION WIDTH AND SYSTEMIC IMMUNE INFLAMMATORY INDEX IN MULTIPLE SCLEROSIS PATIENTS: RELATIONSHIP WITH DISEASE SUBTYPES AND DISABILITY

OBJECTIVE: Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system (CNS). Although it is not clear how autoimmune responses occur, it is known that peripheral blood cells may promote the initiation and exacerbation of the inflammatory response in MS. The aim of this study was to evaluate the sensitivity and specificity of neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR), platelet-lymphocyte ratio (PLR), erythrocyte distribution width (RDW) and systemic immune inflammation index (SIII) in MS and to determine their relationship with disability. MATERIAL AND METHODS: In this single-center, retrospective case-control study, 104 patients with MS and 65 healthy individuals were included. Disability was assessed with the Expanded Disability Status Scale (EDSS) score, and patients were classified as mild (EDSS<3), moderate (3.5 ≤ EDSS ≥4.5), and severe (EDSS≥5) disabilities. NLR, MLR, PLR, RDW and SIII values were calculated according to the complete blood counts of the patients and the control group. Inflammation markers between the control group and MS patients, MS subtypes, and relapsing-remitting MS (RRMS) attack and remission periods were compared. the relationship between these markers and duration of illness, number of attacks and disability was examined. RESULTS: MLR and RDW were higher in MS than the controls. There was no significant difference in these values between MS subtypes. It was observed that RDW increased as the disease duration, number of attacks and EDSS increased. CONCLUSIONS: In our study, in evaluating inflammation it was seen that MLR and RDW were more determinative than PLR, NLR and SIII. The fact that RDW is higher in MS patients and is affected by disease disability indicates that RDW may have an important role in the follow-up of MS patients and in evaluating the degree of disability.

Using Objective Speech Analysis Techniques for the Clinical Diagnosis and Assessment of Speech Disorders in Patients with Multiple Sclerosis.

Multiple sclerosis (MS) is one of the chronic and neurodegenerative diseases of the central nervous system (CNS). It generally affects motor, sensory, cerebellar, cognitive, and language functions. It is thought that identifying MS speech disorders using quantitative methods will make a significant contribution to physicians in the diagnosis and follow-up of MS patients. In this study, it was aimed to investigate the speech disorders of MS via objective speech analysis techniques. The study was conducted on 20 patients diagnosed with MS according to McDonald's 2017 criteria and 20 healthy volunteers without any speech or voice pathology. Speech data obtained from patients and healthy individuals were analyzed with the PRAAT speech analysis program, and classification algorithms were tested to determine the most effective classifier in separating specific speech features of MS disease. As a result of the study, the K-nearest neighbor algorithm (K-NN) was found to be the most successful classifier (95%) in distinguishing pathological sounds which were seen in MS patients from those in healthy individuals. The findings obtained in our study can be considered as preliminary data to determine the voice characteristics of MS patients.

A prospective observational longitudinal study with a two-year follow-up of multiple sclerosis patients on Cladribine

BackgroundCladribine was approved for the treatment of multiple sclerosis (MS). Real-world data is very limited. ObjectivesTo study the effectiveness and the safety of Cladribine treatment in only one group of MS patients after treatment with Cladribine for two years. MethodsThis observational, longitudinal prospective study. Eligible subjects were relapsing remitting MS patients who had at least two-year follow-up after Cladribine treatment. The primary endpoint was the proportion of relapse free patients. Secondary endpoints were ARR, change in EDSS scores, the proportion of patients with CDP, MRI activity, and NEDA-3 status, also the rate of occurrence of AEs. Patients were assessed for primary and secondary endpoints at the end of two years of follow-up. ResultsOf a total of seventy-two patients, 59 (81.9 %) were females, mean age of 36.32 + 10.06 years old, mean disease duration 7.21 + 6.19. Most patients (n = 32; 44.4 %) were naïve to any treatment. Forty patients (55.6 %) completed two courses of treatment. The primary endpoint showed that most of our cohort was relapse free (85 % versus 25 %; P < 0.001), Secondary endpoints showed that ARR was significantly reduced 0.15 + 0.36 versus 0.85 + 0.53; P < 0.01). Most of the cohort 90 % have no progression of disability. Few subjects had new T2 lesions (7.5 % versus 70.8 %; P < 0.001 and gadolinium enhancement 5 % versus 66.7 %; P < 0.001) in MRI compared to baseline. No evidence of disease activity 3 (NEDA-3) was achieved in 30 (75 %) patients. It was achieved in 87.5 % of naive patients versus 66.7 % in patients who received prior disease modification drugs before Cladribine initiation. Infections 6 (n = 6; 8.4 %) lymphocytopenia (n = 3; 4.2 %), and elevated liver enzymes (n = 1; 1.4 %) were reported. ConclusionCladribine treatment reduced significantly relapse rate and MRI activity. It was safe and tolerable. Early initiation of cladribine is associated with favorable outcomes.

The brainstem in multiple sclerosis: MR identification of tracts and nuclei damage

ObjectiveTo evaluate the 3D Fast Gray Acquisition T1 Inversion Recovery (FGATIR) sequence for MRI identification of brainstem tracts and nuclei damage in multiple sclerosis (MS) patients.MethodsFrom april to december 2020, 10 healthy volunteers and 50 patients with remitted-relapsing MS (58% female, mean age 36) underwent MR imaging in the Neuro-imaging department of the C.H.N.O. des Quinze-Vingts, Paris, France. MRI was achieved on a 3 T system (MAGNETOM Skyra) using a 64-channel coil. 3D FGATIR sequence was first performed on healthy volunteers to classify macroscopically identifiable brainstem structures. Then, FGATIR was assessed in MS patients to locate brainstem lesions detected with Proton Density/T2w (PD/T2w) sequence.ResultsIn healthy volunteers, FGATIR allowed a precise visualization of tracts and nuclei according to their myelin density. Including FGATIR in MR follow-up of MS patients helped to identify structures frequently involved in the inflammatory process. Most damaged tracts were the superior cerebellar peduncle and the transverse fibers of the pons. Most frequently affected nuclei were the vestibular nuclei, the trigeminal tract, the facial nerve and the solitary tract.ConclusionCombination of FGATIR and PD/T2w sequences opened prospects to define MS elective injury in brainstem tracts and nuclei, with particular lesion features suggesting variations of the inflammatory process within brainstem structures. In a further study, hypersignal quantification and microstructure information should be evaluated using relaxometry and diffusion tractography. Technical improvements would bring novel parameters to train an artificial neural network for accurate automated labeling of MS lesions within the brainstem.

MRI of the Entire Spinal Cord-Worth the While or Waste of Time? A Retrospective Study of 74 Patients with Multiple Sclerosis.

Spinal cord lesions are included in the diagnosis of multiple sclerosis (MS), yet spinal cord MRI is not mandatory for diagnosis according to the latest revisions of the McDonald Criteria. We investigated the distribution of spinal cord lesions in MS patients and examined how it influences the fulfillment of the 2017 McDonald Criteria. Seventy-four patients with relapsing-remitting MS were examined with brain and entire spinal cord MRI. Sixty-five patients received contrast. The number and anatomical location of MS lesions were assessed along with the Expanded Disability Status Scale (EDSS). A Chi-square test, Fischer’s exact test, and one-sided McNemar’s test were used to test distributions. MS lesions were distributed throughout the spinal cord. Diagnosis of dissemination in space (DIS) was increased from 58/74 (78.4%) to 67/74 (90.5%) when adding cervical spinal cord MRI to brain MRI alone (p = 0.004). Diagnosis of dissemination in time (DIT) was not significantly increased when adding entire spinal cord MRI to brain MRI alone (p = 0.04). There was no association between the number of spinal cord lesions and the EDSS score (p = 0.71). MS lesions are present throughout the spinal cord, and spinal cord MRI may play an important role in the diagnosis and follow-up of MS patients.

Telephone-based assessment of multiple sclerosis patients at Ain Shams University Hospital in the coronavirus disease 2019 pandemic

BackgroundAssessment of multiple sclerosis (MS) patients during the era of the coronavirus disease 2019 (COVID-19) pandemic was confronted with the overwhelmed healthcare facilities in Egypt and fear of the patients to get infected while attending the follow-up visits. This study aimed to assess the value of telephone-based assessments in the follow-up of MS patients. It includes one hundred and five patients who participated in the study and completed 3 telephone-based assessments which are the Hauser Ambulation index, Multiple Sclerosis Neuropsychology Questionnaire (MSNQ), and Symptoms of Multiple Sclerosis Scale (SMSS).ResultsThe Hauser Ambulation index was significantly correlated with the latest Expanded Disability Status Scale (EDSS) score done within 1 month from the telephone call (r=0.738, P<0.001). The analysis of MSNQ scores showed that one-third of the study population had evidence of cognitive and/or neuropsychological impairment. Post hoc analysis regarding the cognitive and psychological impairment component of SMSS revealed that the patients who answered “Never” had significantly lower MSNQ scores compared to those who answered “Sometimes” (P=0.016), “Often” (P=0.022), and “Always” (P=0.001). The comparison of the EDSS scores of the patients regarding the sensory-motor impairment component of SMSS showed a non-significant difference.ConclusionThe Hauser Ambulation index may be a reliable telephone-based tool for the assessment of physical disability. The MSNQ and the cognitive and psychological impairment component of SMSS can be used for the assessment of cognitive and psychological impairment among patients with MS.

Update on brain MRI for the diagnosis and follow-up of MS patients

Over the past decades, MRI has become a major tool in the diagnosis and the follow-up of patients with multiple sclerosis (MS), especially for monitoring the effectiveness of therapy. The recent international recommendations issued for the standardization of neurological and radiological clinical practices converge on many points. In this setting, recommendations made by the “Observatoire français de la sclérose en plaques”, the French MS registry, can be distinguished by its interdisciplinary complementarity, its longevity, its size, and its positions in direct connection with the clinic. Hence, after suspicions of gadolinium deposition in the brain, with multiple warning from the American and European health authorities, a national consultation took place and resulted in limitation to useful injections. The precautionary principle prevailing, the patient receives a limited quantity of contrast product even if no clinically harmful manifestation has been detected to date. The result of this round table bringing together neurologists and neuroradiologists from specialized centers was published in the form of a recommendation in early 2020. The interest of this project also lies in the constant improvement of the management of patients with MS and the possibility of developing advanced techniques to assist the clinician. The aim of this review is to explain to the neurologist, the interest of following this imaging protocol both in his/her clinical practice and in the possibilities that this opens up.

Early detection with speckle tracking echocardiography of biventricular systolic dysfunction, and its relationship with fatigue, in patients with multiple sclerosis

Funding AcknowledgementsType of funding sources: None.BackgroundFatigue is a frequent and debilitating symptom of multiple sclerosis (MS), affecting 90% of patients. Symptoms seems multifactorial, but little is known about the contribution of cardiovascular morpho-functional alterations linked to comorbidities, to lifestyle, to MS itself or to drugs (i.e. mitoxantrone).Aimto investigate the presence of cardiac alterations in MS patients, and to evaluate their impact on fatigue.Methods 24 patients with relapsing-remitting MS (RR-MS) underwent an electrocardiogram (ECG), a transthoracic echocardiographic (TTE), a six minutes walking test (6MWT) with Borg scale (BS), and two fatigue self-assessment scales, the Fatigue Severity Scale (FSS) and the Modified Fatigue Impact Scale (MFIS). The patients were divided into 2 groups: group 1, without traditional cardiovascular risk factors (CVRF: smoke, hypertension, diabetes, hypercholesterolemia; n = 12, 11 females), and group 2, with at least one CVRF (n = 12, 5 females). None of the patients had ever been on mitoxantrone therapy. No new control group was studied due to the SARS-CoV-2 pandemic restrictions , so the comparison was performed with general healthy population in internationally validated previous studies.ResultsNo arrhythmias were found. In both MS groups all the TTE left ventricular (LV) systolic function parameters were depressed compared to the healthy population, but only the mean global longitudinal strain (GLS), the mean longitudinal strain rate (LSR) of LV and estimated pulmonary artery systolic pressure (PAPs) were statistically significant depressed compared to the healthy general population (p < 0.005): see table. This reduction was observed in both MS groups, while there were non significant differences among the two groups. TTE LV function depression significantly correlated to variation of parameters of fatigue , especially considering LV GLS in relation to BS values.ConclusionsSubclinical biventricular systolic dysfunction is present in MS patients, and it seems to be linked to the disease itself without being influenced by CVRF. This dysfunction, detected by speckle tracking echocardiographic techniques, seems to contribute to the symptom of fatigue in patients with MS. It is important to include TTE in the workup and follow-up of MS patients, in order to promptly treat cardiac dysfunction and relieve fatigue.Echocardiography and LV strainMS totalMS no CVRFMS + CVRFHealthy populationLV GLS17.7 ± 2.2*18.0 ± 2.1*17.4 ± 2.4*22.6 ± 1.7LV LSR1.0 ± 0.1*1.0 ± 0.1*1.0 ± 0.2*1.2 ± 0.1PAPs25.0 ± 2.6*24.8 ± 2.9*25.2 ± 2.5*14.0 ± 6.0* p < 0.05 vs healthy population

Cognitive impairment in multiple sclerosis: diagnosis and monitoring

IntroductionCognitive impairment (CI) has a prevalence of 45–70% in people with multiple sclerosis (MS), producing a negative impact on their quality of life, personal life, and work. Early detection of CI has become an important aspect to be considered for an adequate follow-up, to optimize social adaptation and to implement specific cognitive rehabilitation strategies. The aim of this work is to propose a suitable cognitive evaluation of patients with MS based on available and efficient tools for diagnosis and monitoring purposes well supported by literature review and clinical experience.MethodsA multidisciplinary panel of professionals from the field of neurology, neuropsychology, and neuroimaging performed a literature review of the topic of cognitive impairment assessment. This was combined and completed with their clinical experience to produce a set of recommendations.ResultsSome limitations to cognitive evaluation are described: shortage of time and resources during the neurology consultation, scarceness or absence of specialized professionals’ availability, importance of tests adaptation, and doubts about its use to define therapeutic efficiency. We recommend a baseline and annual screening evaluation, and we suggest a baseline and periodic neuropsychological assessment. The latter ought to change to a recommendation with the presence of either positive screening test, or subjective to cognitive complaints, screening-test results and patient or family report mismatch, or in specific social/work situations.ConclusionsCognitive evaluation should be performed on all patients diagnosed with MS and throughout follow-up. It is necessary to support the creation of multidisciplinary MS teams to optimize the evaluation and follow-up of MS patients.

Multiple Sclerosis in Pregnancy and its Role in Female Fertility: A Systematic Review.

Multiple sclerosis (MS) is a neurological disease that typically affects young women of reproductive age. There are still many questions and heterogeneous clinical approaches partly due to the lack of consensus and guidelines. For many years, women with MS have been discouraged from getting pregnant for fears that the disease might negatively affect the fetus or increase their obstetric risk or for claims that the disease might decrease fertility. However, fertility does not seem to be impaired to a larger extent in women with MS. Therefore, all healthcare providers involved in the follow-up of multiple sclerosis patients must be prepared to discuss future fertility, pregnancy, and others matters, in addition to providing them with the best possible counseling. This study presents data based on updated evidence and discusses fertility and pregnancy in patients with MS with respect to the impacts of pregnancy on the risk and prognostic factors tied to MS, and the impact of MS on pregnancy outcomes and fertility treatments administered to females with MS. In conclusion, a clear relationship between infertility and MS has not been established. There seems to exist a link between disease aggressiveness and progression with several processes that might impair fertility. However, MS does not stand as a contraindication to assisted reproductive technology. From the several studies analyzed, it is possible to conclude that pregnancy is possible in women with MS. It is important to discuss and plan the ideal moment to start treatment and managing pregnancy and contraception aiming at better results.

Recommendations about Multiple Sclerosis Management during Pregnancy, Partum and Post-Partum: Consensus Position of the Portuguese Multiple Sclerosis Study Group

Multiple sclerosis typically affects young women of reproductive age. Therefore, all healthcare professionals involved in the follow-up of multiple sclerosis patients must be prepared to discuss pregnancy and breastfeeding issues and provide the best possible counselling. However, there are still many doubts and heterogeneous clinical approaches partly due to the lack of consensus and guidelines. Concerning the handling of disease modifying therapies during pregnancy and postpartum, existing uncertainties have been complicated by the increase in the number of treatments available in recent years. This article aims to present the state-of-the-art and provide guidance based on the best level of available evidence and expert opinion regarding the management of multiple sclerosis patients at different stages: pregnancy planning, pregnancy, partum, and the postpartum period.

What is the Relevance of the Systematic Use of Gadolinium During the MRI Follow-Up of Multiple Sclerosis Patients Under Natalizumab?

Multiple sclerosis (MS) patients represent apopulation potentially affected by the intracerebral accumulation of gadolinium-based contrast agents (GBCA) due to repeated magnetic resonance imaging (MRI) performed during their lifetime; however, MRI is still the best tool to monitor MS inflammatory activity. This study aimed to evaluate the relevance of GBCA injections during the MRI follow-up of MS patients under natalizumab (Tysabri) treatment. The MRI data results were retrospectively reviewed in amonocentric study (University Hospital of Toulouse, France) from all consecutive patients treated with natalizumab from January 2014 to January 2017. For each examination during the whole MRI follow-up, new lesions (enhancing and non-enhancing) were analyzed. Atotal of 129 patients were included in this study (65% female, mean age = 41years, mean treatment duration 6.5years, 50% positive for John Cunningham virus) and benefited from 735 MRIs with GBCA. Only 3MRIs showed anew enhancing lesion, systematically encountered after treatment discontinuation. According to this study based on the clinical and radiological practice, the systematic use of GBCA seems of limited relevance in the MRI follow-up of asymptomatic patients treated continuously with natalizumab.

Neurofilament Light Chain as a Biomarker in Multiple Sclerosis.

Due to the unpredictable course and heterogenous treatment response in multiple sclerosis (MS), there is a clear need for biomarkers that reflect disease activity in the clinical follow-up of these patients. Neurofilaments are neuron-specific components of the cytoskeleton that can be assayed in different body compartments. They have been explored as potential biomarkers for many years. Neurofilament light chain (NF-L) appears the most promising biomarker in MS patients, and there is now little doubt that NF-L should have a role in the follow-up of MS patients. Newer assays and techniques for NF-L detection available in serum samples confirms the usefulness of NF-L as a biomarker. Nevertheless, there is still a need for prospective studies, and studies to determine clinical useful cut-off values. This review evaluates the strengths and weaknesses of NF-L as a biomarker in patients with MS.

Recommendations About Multiple Sclerosis Management During Pregnancy, Partum and Post-Partum: Consensus Position of The Portuguese Multiple Sclerosis Study Group and The Portuguese Society of Obstetrics and Maternal-Fetal Medicine

Multiple sclerosis typically affects young women of reproductive age. Therefore, all healthcare providers involved in the follow-up of multiple sclerosis patients must be prepared to discuss pregnancy and breastfeeding issues, and provide the best possible counselling. However, there are still many doubts and heterogeneous clinical approaches partly due to the lack of consensus and guidelines. Concerning the handling of disease modifying therapies during pregnancy and the postpartum period, uncertainties have been complicated by the increase in recent years of the number of available treatments. This article aims to present the state-of-the-art and provide guidance based on the best level of available evidence and expert opinion regarding the management of multiple sclerosis patients at different stages: pregnancy planning, pregnancy, partum, and the postpartum period.

Validity of apparent diffusion coefficient (ADC) value in diagnosis and follow-up of multiple sclerosis patients in different clinical subtypes

BackgroundMultiple sclerosis (MS) is a chronic disease with a wide range of pathologic changes that modify the apparent diffusion coefficient (ADC) value. Patients & methodsA prospective study included Forty two MS patients, underwent conventional and diffusion weighted MR imaging with ADC measurement in plaques and normally appearing white matter (NAWM), compared with normal white matter (NWM) of a control group (n = 21). They were followed-up six months later. ResultsSignificantly higher ADC values were found in acute and secondary progressive cases than relapsing remitting (RR) cases and all values were higher than in normal white matter. A higher ADC values was found in NAWM than control cases and in the newly developed plaques relative to old plaques in all types. A cut off ADC value 1.02 ± 0.20 × 10−3 mm2/sec was detected for MS diagnosis, a value 1.41 ± 0.10 × 10−3 mm2/sec to separate between acute and chronic RR cases and 1.2 ± 0.10 × 10−3 mm2/sec to differentiate chronic sub-types. ConclusionADC value has the validity in diagnosis and follow-up of MS patients with different clinical sub-types.

Health-related quality of life in multiple sclerosis patients with accompanying diseases

Introduction : Multiple sclerosis (MS) is a progressive demyelinating neurologic disease characterized by a different extent of comorbidity. Everydaily life is challenging for these patients because of physical and psychological impairments. The purpose of this study was to comparatively analyze the relationships between several health-related quality of life aspects of MS patients` in case of accompanying diseases. Material and methods : Health-related uality of life of 80 MS patients, 56 females and 24 males, at a mean age of 49 years, was examined by means of Short Form-36 questionnaire. Forty patients presented with at least one accompanying chronic disease. Results : These patients presented with similar Expanded Disability Status Scale scores of 2.0 or 2.5. Most questionnaire scores differed between MS patients without and with comorbidity. Usually, comorbidity additionally worsened patients` quality of life. There were statistically significant differences between the patients with MS alone and those with MS and comorbidity concerning the depression ( t =5.877; p<0.0001); the troubles with concentration/thinking ( t =4.822; p<0.0001); the troubles with memory ( t =4.020; p<0.0001); the feeling of fatigue ( t =4.148; p<0.0001), and the feeling of happiness ( t =-3.399; p<0.001). Conclusion : The hot topic of the health-related quality of life of the patients with MS and comorbidities necessitates further interdisciplinary research. Correct treatment and follow-up of MS patients and particularly of those with common accompanying cardiovascular and other neurological diseases could contribute to long-lasting preservation of acceptable individual quality of life.

Impact of multiple sclerosis on quality of life: Comparison with systemic lupus erythematosus

ObjectiveTo report the impact of multiple sclerosis (MS) on patients’ quality of life (QoL) compared to systemic lupus erythematosus (SLE) using the 36-Item Short Form (SF-36) health questionnaire in Argentina. Patients and methodsCross-sectional study. All consecutive MS patients, SLE and healthy controls (HC) were included. Demographics, clinical and radiological aspects, EDSS and SF-36 were assessed. ResultsA total of 191 subjects were included (MS=74, SLE=30 and HC=87). When we compared, using 2 standard deviations below the normal mean, the SF-36 subscales scores between MS and SLE, we found that MS patients experienced significant deterioration in general health (p<0.0001), vitality (p=0.009), current health (p<0.0001) and previous year health perception (p=0.003). Additional evaluated areas did not show significant differences. MS patients scored significantly lower in all categories compared to HC, except for bodily pain. An inverse correlation between EDSS and SF-36 total (R2=0.59, β −11.08, p<0.0001) and subscale scores was observed after applying regression analysis. ConclusionMS behaves as a systemic disease from the functional point of view. Patient-reported QoL scales scores provide comprehensive additional prognostic information beyond the EDSS score. Therefore, adding the SF-36 questionnaire in clinical practice might be useful for the assessment and follow-up of MS patients.

Follow-up of multiple sclerosis patients treated with Endotherapia (GEMSP).

Endotherapia (GEMSP) is a novel therapeutic approach for multiple sclerosis (MS). The aim of the present study was to demonstrate the efficiency of Endotherapia in the follow-up of 193 patients with MS. The efficiency coefficient that was evaluated was the Expanded Disability Status Scale (EDSS) score, which is a functional scale of MS progression. The evaluated score of each patient during follow-up visits was compared with the theoretical score of the disease progression without GEMSP. The evolution of the EDSS score was evaluated according to the inclusion score. The quantitative global study of the EDSS score highlighted a statistically significant difference between the final average scores of the treatment with GEMSP (M) and worldwide reference (R) groups. The improvement of the M group compared with the R group was 24.5%. According to the final EDSS scores, the study highlighted a difference in favor of the M group with 62.0% for scores ≤3, 7.8% for scores between 3 and 6 and 19.6% for scores ≥6. According to the qualitative evolution of the EDSS scores, the improvements in favor of group M were 49.3% for scores ≤3, 79.1% for scores between 3 and 6 and 19.5% for scores ≥6. The qualitative study of the EDSS score showed a statistically significant success percentage; the success percentages were between 59.1 and 90.0%. In a larger population of MS patients, the data confirm the beneficial effects of GEMSP that were previously reported in pre-clinical and clinical studies. In addition, 78% of patients showed an improvement or deceleration of the disease.

JC polyomavirus expression and bell-shaped regulation of its SF2/ASF suppressor during the follow-up of multiple sclerosis patients treated with natalizumab.

Natalizumab is effective against multiple sclerosis (MS), but is associated with progressive multifocal leukoencephalopathy (PML), fatal disease caused by the JCV polyomavirus. The SF2/ASF (splicing factor2/alternative splicing factor) inhibits JCV in glial cells. We wondered about SF2/ASF modulation in the blood of natalizumab-treated patients and if this could influence JCV reactivation. Therefore, we performed a longitudinal study of MS patients under natalizumab, in comparison to patients under fingolimod and to healthy blood donors. Blood samples were collected at time intervals. The expression of SF2/ASF and the presence and expression of JCV in PBMC were analyzed. A bell-shaped regulation of SF2/ASF was observed in patients treated with natalizumab, increased in the first year of therapy, and reduced in the second one, while slightly changed, if any, in patients under fingolimod. Notably, SF2/ASF was up-regulated, during the first year, only in JCV DNA-positive patients, or with high anti-JCV antibody response; the expression of the JCV T-Ag protein in circulating B cells was inversely related to SF2/ASF protein expression. The SF2/ASF reduction, parallel to JCV activation, during the second year of therapy with natalizumab, but not with fingolimod, may help explain the increased risk of PML after the second year of treatment with natalizumab, but not with fingolimod. We propose that SF2/ASF has a protective role against JCV reactivation in MS patients. This study suggests new markers of disease behavior and, possibly, help in re-evaluations of therapy protocols.

The clinical perspective: How to personalise treatment in MS and how may biomarkers including imaging contribute to this?

Background: Multiple sclerosis (MS) is a highly heterogeneous disease, both in its course and in its response to treatments. Effective biomarkers may help predict disability progression and monitor patients’ treatment responses. Objective: The aim of this review was to focus on how biomarkers may contribute to treatment individualisation in MS patients. Methods: This review reflects the content of presentations, polling results and discussions on the clinical perspective of MS during the first and second Pan-European MS Multi-stakeholder Colloquia in Brussels in May 2014 and 2015. Results: In clinical practice, magnetic resonance imaging (MRI) measures play a significant role in the diagnosis and follow-up of MS patients. Together with clinical markers, the rate of MRI-visible lesion accrual once a patient has started treatment may also help to predict subsequent treatment responsiveness. In addition, several molecular (immunological, genetic) biomarkers have been established that may play a role in predictive models of MS relapses and progression. To reach personalised treatment decisions, estimates of disability progression and likely treatment response should be carefully considered alongside the risk of serious adverse events, together with the patient’s treatment expectations. Conclusion: Although biomarkers may be very useful for individualised decision making in MS, many are still research tools and need to be validated before implementation in clinical practice.