Primary progressive multiple sclerosis: a distinct syndrome?

Should Spinal MRI Be Routinely Performed in Patients With Clinically Isolated Optic Neuritis?

BackgroundMultiple sclerosis (MS) is a disease with profound heterogeneity in clinical course.ObjectiveTo analyze sources and levels of income among MS patients in relation to disease phenotype with a special focus on identifying differences/similarities between primary progressive MS (PPMS) and secondary progressive MS (SPMS).MethodsA total of 6890 MS patients aged 21−64 years and living in Sweden in 2010 were identified for this cross-sectional study. Descriptive statistics, logistic, truncated linear, and zero-inflated negative binomial regression models were used to estimate differences in income between SPMS, PPMS and relapsing-remitting MS (RRMS) patients.ResultsRRMS patients earned almost twice as much as PPMS and SPMS patients (on average SEK 204,500, SEK 114,500, and SEK 79,800 in 2010, respectively). The difference in earnings between PPMS and SPMS was not statistically significant when analyzed with multivariable regression. The estimated odds ratio for PPMS patients to have income from earnings was not significantly different from SPMS patients (95% CI 0.98 to 1.59). PPMS and RRMS patients were less likely to receive benefits when compared to SPMS patients (by 6% and 27% lower, respectively).ConclusionOur findings argue for similarities between PPMS and SPMS and highlight the socioeconomic importance of preventing RRMS patients convert to SPMS.

Clinical predictors of disease progression in a cohort of Tunisian progressive Multiple Sclerosis

Background: In multiple sclerosis (MS), microRNA (miRNA) dysregulation is mostly reported in different immune cells, but less information is available on circulating miRNAs that exert strong biomarker potential due to their exceptional stability in body fluids. Objective: The aim of this study was to profile expression of circulating miRNAs in primary progressive multiple sclerosis (PPMS) and secondary progressive multiple sclerosis (SPMS) and assess their association with neurological worsening. Methods: The expressions of 84 different miRNAs were profiled in serum of 83 subjects (62 MS and 21 controls) using miScript miRNA techniques. First, they were screened on 18 PPMS and 10 controls; thereafter, 10 most aberrantly expressed miRNAs were validated on a larger cohort. Results: In comparison with controls, upregulation of miR-191-5p was found in both progressive MS subtypes, while miR-376c-3p was overexpressed only in PPMS. Additionally, upregulation of miR-128-3p and miR-24-3p was detected in PPMS when compared to controls and SPMS. Progression index correlated with miR-128-3p in PPMS and miR-375 in SPMS. Conclusion: We detected overexpression of four miRNAs that have not been previously associated with progressive forms of MS. The increased expression of circulating miR-191-5p seems to be associated with progressive forms of MS, while miR-128-3p seems to be associated mostly with PPMS.

In this multicenter study, a new semiautomatic method for segmenting the cervical cord from C2 to C5 was used to investigate the correlation between cord atrophy and clinical disability in a large sample of patients with multiple sclerosis (MS). T2 and 3-dimensional T1-weighted cervical cord scans and dual-echo brain scans were acquired from 143 healthy controls, 22 patients with clinically isolated syndromes (CIS), 101 patients with relapsing-remitting MS (RRMS), 79 patients with secondary progressive MS (SPMS), 58 patients with benign MS (BMS), and 75 patients with primary progressive MS (PPMS) in 3 European centers. Normalized cervical cord cross-sectional area (CSAn) was measured by an active surface cord model. Between-group comparisons were performed using linear mixed-effect models. A nonparametric kernel estimator was used to obtain smoothed plots of CSA along the cervical cord. Cord CSAn was significantly lower in PPMS vs healthy controls, BMS vs RRMS, SPMS vs BMS, and RRMS. From C2 to C5, a net separation and definition of the plots of patients with BMS, PPMS, and SPMS was seen with respect to those of the other study groups. CSAn was correlated with Expanded Disability Status Scale (r = -0.49, p < 0.0001), with a differential effect among disease clinical phenotypes: no association in either CIS or in BMS; association in RRMS (r = -0.30, p = 0.001), SPMS (r = -0.34, p = 0.001), and PPMS (r = -0.27, p = 0.01). Cervical cord atrophy provides a relevant and useful marker for the characterization of clinical heterogeneity of patients with MS. The stability of this measure among different centers supports its use as potential outcome measure to monitor disease progression in multicenter trials.

BackgroundHigh mobility group box protein 1 (HMGB1) is a transcriptional regulator that is receiving increasing attention in autoimmune disorders including multiple sclerosis (MS). Here, we investigated the role of HMGB1 in the peripheral blood compartment from MS patients.MethodsHMGB1 mRNA expression levels were determined by PCR in peripheral blood mononuclear cells (PBMC) of 29 healthy controls and 57 untreated MS patients (26 with relapsing-remitting MS - RRMS, 13 with secondary progressive MS - SPMS, and 18 with primary progressive MS - PPMS). HMGB1 protein levels were measured by ELISA in serum samples from 18 HC and 37 untreated MS patients (13 with RRMS, 14 with SPMS, and 10 with PPMS).ResultsHMGB1 expression levels were increased in PBMC from the whole MS group compared with controls (P = 0.03). Further stratification of the MS group revealed higher expression levels in PBMC from patients with relapse-onset MS, and differences were statistically significant for RRMS patients compared with PPMS patients and controls (P = 4 × 10−5 and P = 0.005, respectively) and also for SPMS patients compared with PPMS patients (P = 0.001). HMGB1 serum levels were increased in the whole MS group compared with controls (P = 2 × 10−4). In MS clinical forms, the highest HMGB1 serum levels were observed in RRMS patients, and differences were statistically significant compared to PPMS patients (P = 5 × 10−5), SPMS patients (P = 0.001), and controls (P = 0.001).ConclusionsThese results point to a role of HMGB1 mRNA and protein levels as disease activity biomarkers to discriminate the more inflammatory relapse-onset MS forms, particularly RRMS, from the less inflammatory PPMS form of the disease.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-015-0269-9) contains supplementary material, which is available to authorized users.

ObjectivesTo evaluate white matter and grey matter T1-weighted (w)/T2w ratio (T1w/T2w ratio) in healthy controls and patients with multiple sclerosis, and its association with clinical disability.MethodsIn this cross-sectional study, 270...

We have carried out a comparative cross-sectional study of patients with relapsing and remitting MS (multiple sclerosis) (RRMS) (n=9), primary progressive MS (PPMS) (n=7), and secondary progressive MS (SPMS) (n=10) using image analysis techniques to determine the number and volume of Gd-DTPA-enhancing lesions. RRMS patients had more lesions than either PPMS or SPMS (ns), and the mean volume of the lesions (p=0.006) and the total volume of enhancing lesions (p<0.03) were significantly larger in patients with RRMS compared with PPMS. The prevalence of blood-brain barrier (BBB) breakdown appears to be similar in PPMS and SPMS, with the higher rate in RRMS suggesting a suppressive effect of disease duration (and/or age). Similarly, the volume of the lesion load overall was negatively correlated with disease duration (p −0.56,p<0.003). Differences between PPMS and RRMS/SPMS patients in the volume of the enhancing lesions may reflect differences in the ability of these patients to suppress the immune-mediated damage to axons which may follow episodic BBB breakdown and which is not visualized on conventional magnetic resonance imaging.

Phenotypic variability in multiple sclerosis (MS) remains poorly understood. At disease onset, the majority of MS patients exhibit a relapsing–remitting MS (RRMS) disease course, and in spite of the availability of effective anti-inflammatory disease-modifying therapies (DMTs), a substantial proportion of patients will eventually evolve into a secondary progressive MS (SPMS) phase.1 Apart from SPMS, about 15% of MS patients show clinical progression from onset without clear remissions, i.e., primary progressive MS (PPMS). The Lublin panel revising the definitions of the clinical course of MS in 2013 acknowledged that some evidence supports PPMS representing a distinct, noninflammatory or at least less inflammatory form of MS.2 The panel emphasized that a spectrum of progressive MS phenotypes exists and that any differences between a secondary and primary progressive course are relative rather than absolute.2 There are data to suggest that in MS the acute inflammatory phase is followed by a chronic state that may include a “smoldering” condition in which inflammation as well as myelin and axonal degeneration may coexist.1 The transition of RRMS into SPMS is characterized by gradual worsening of neurologic disability independently of the occurrence of superimposed relapses.1,2 Currently available therapeutic options in both SP and PPMS are only modestly effective and the approved DMT mainly target the inflammatory component of the disease.1

Dysphagia is one of the most common symptoms in multiple sclerosis (MS) patients. It can reduce the quality of life and increase the risk of mortality by developing complications such as aspiration pneumonia. The present study was conducted to estimate the prevalence of dysphagia in MS patients and investigate the associations between dysphagia and disease characteristics. The Persian version of the DYMUS questionnaire was used to assess dysphagia in 865 patients with MS, including 738 (85.3%) relapsing-remitting MS (RRMS), 106 (12.3%) secondary progressive MS (SPMS), and 21 (2.4%) primary progressive MS (PPMS). Also, demographic and clinical data, including age, sex, smoking status, Expanded Disability Status Scale (EDSS) score, disease duration, disease-modifying therapies exposure, initial symptoms of MS, were recorded. The mean (SD) age was 37.95(9.25) years, and 83.1% of the participants were female. The prevalence of dysphagia was estimated to be 25.4% among all patients. According to the DYMUS questionnaire results, the prevalence of dysphagia in RRMS, SPMS, and PPMS patients was 22.2%, 44.3%, and 42.9%, respectively. After multivariate analysis the current EDSS score (OR = 1.197, CI: 1.062, 1.350, p = 0.003), cerebellar impairment (OR = 1.335, CI: 1.450, 4.716, p = 0.004) and motor dysfunction (OR = 1.651, CI: 1.004, 2.715, p = 0.048) emerged as the risk factors for dysphagia. Since dysphagia, as previously mentioned, is a common symptom in multiple sclerosis, particularly in SPMS and PPMS courses, active screening for this condition is recommended in all patients, particularly those with identified risk factors.

The different clinical subtypes of multiple sclerosis (MS) may reflect underlying differences in affected neuroanatomic regions. Our aim was to analyze the effectiveness of jointly using the inferior subolivary medulla oblongata volume (MOV) and the cross-sectional area of the corpus callosum in distinguishing patients with relapsing-remitting multiple sclerosis (RRMS), secondary-progressive multiple sclerosis (SPMS), and primary-progressive multiple sclerosis (PPMS). We analyzed a cross-sectional dataset of 64 patients (30 RRMS, 14 SPMS, 20 PPMS) and a separate longitudinal dataset of 25 patients (114 MR imaging examinations). Twelve patients in the longitudinal dataset had converted from RRMS to SPMS. For all images, the MOV and corpus callosum were delineated manually and the corpus callosum was parcellated into 5 segments. Patients from the cross-sectional dataset were classified as RRMS, SPMS, or PPMS by using a decision tree algorithm with the following input features: brain parenchymal fraction, age, disease duration, MOV, total corpus callosum area and areas of 5 segments of the corpus callosum. To test the robustness of the classification technique, we applied the results derived from the cross-sectional analysis to the longitudinal dataset. MOV and central corpus callosum segment area were the 2 features retained by the decision tree. Patients with MOV >0.94 cm(3) were classified as having RRMS. Patients with progressive MS were further subclassified as having SPMS if the central corpus callosum segment area was <55.12 mm(2), and as having PPMS otherwise. In the cross-sectional dataset, 51/64 (80%) patients were correctly classified. For the longitudinal dataset, 88/114 (77%) patient time points were correctly classified as RRMS or SPMS. Classification techniques revealed differences in affected neuroanatomic regions in subtypes of multiple sclerosis. The combination of central corpus callosum segment area and MOV provides good discrimination among patients with RRMS, SPMS, and PPMS.

Autoimmune demyelinating disorders, such as multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD), are caused by persistent inflammation and damage to the central nervous system. Cognitive impairment (CI) is a growing challenge in these diseases, underscoring the need for a thorough exploration of its prevalence and risk across various subtypes. This study aimed to assess the prevalence and odds of CI using the Symbol Digit Modalities Test (SDMT) in various MS subtypes and NMOSD. A case-control study involving 616 participants, including healthy controls (HC) and individuals with different MS subtypes (Relapsing Remitting MS (RRMS), Secondary Progressive MS (SPMS), Primary Progressive MS (PPMS)), clinically isolated syndrome (CIS), and NMOSD, was conducted. CI was defined as SDMT z-scores 1.5 standard deviations below the HC average. The chi-square test was used to assess the risk of CI. The prevalence of CI varied across different groups: HC (10.7%), RRMS (33.8%), SPMS (71.3%), PPMS (62.8%), CIS (19.2%), and NMOSD (32.8%). Odds ratios (OR) for CI were significantly increased in RRMS (OR: 4.23, confidence interval (CI): 2.18-8.22, P < 0.001), SPMS (OR: 20.58, CI: 10.36-40.88, P < 0.001), PPMS (OR: 14.02, CI: 5.80-33.86, P < 0.001), and NMOSD (OR: 4.04, CI: 2.07-7.87, P < 0.001) compared to HC. This study emphasizes a significantly increased risk of CI in MS subtypes and NMOSD compared to HC. Although no significant difference in CI risk was found between individuals with RRMS and NMOSD, those with progressive forms of MS exhibited notably higher risks of CI.

Multiple sclerosis (MS)is a long lasting, chronic and auto-immune disease which affects central nervous system. In this auto-immune disease, our own immune system damages the body.It is a disabling disease of spinal cord and brain, specially deteriorates optic nerve of eyes. The disease is caused when immune system of the body attacks on myelin sheath which is a protective layer of neurons; the structural and functional unit of nervous system. This sheath protects the nerve fibers. Damage to myelin sheath exposes the nerve fibers, which slows down or blocks the nerve impulse passing through the nerve. This disease appears between the ageof 20 to 50 years in most cases. Statistics reveal that it is more common in women than men. The causes of this disease are unknown but scientists believe that the risk factor of this disease is the combination of genetics and environment. Its symptoms include effects on body movements involving loss of balance, weakness or numbness in limbs, dizziness, body pains, electric shock sensations specially in neck region,fatigue,difficulty swallowing, slurred speechand vertigo.It also involves problems relating sexual, bowel and bladder functions. It may also cause depression and anxiety.The symptoms are different in children than adults. It starts with acute encephalomyelitis, including fever, stiff neck, seizures, coma and confusion. It these symptoms persist, doctor should be consulted immediately.&#x0D; Research has shown that there are some factors whichcan increase the chances of its development. These factors include;age,climate, Vitamin D and other auto-immune diseases. MS can occur at any age in one’s life but its onset is common between 20 to 50 years. The risk of developing of MS in twin babies is 1 in 4 cases. However, younger and older people can be affected too.Considering the factor of climate, MS is found to be more common in countries found in temperate regions of the world. Statistics have shown that MS was common in people living in New Zealand, Canada, USA and many other European countries. All of us know what is the importance of vitamins. It has been observed that lower levels of Vitamin D and decreased sunlight exposure are related with greater risk of this disease. Many people suffer from auto-immune diseases for example pernicious anemia, Inflammatory bowel disease, Type I Diabetes Mellitus and thyroid problems. Recent studies show that person already facing the trouble of auto-immune disease is at higher risk of getting MS. Multiple sclerosis (MS) has been divided into four basic types: Primary progressive MS (PPMS), Secondary Progressive MS (SPMS), Progressive Relapsing MS (PRMS) and Relapsing Remitting MS (RRMS).&#x0D; Recent findings from a National MS Society estimated that nearly 1 million people in the United States are affected with MS. This is more than double the last reported number, and the first national research on MS prevalence since 1975. The society also estimated that 2.3 million people live with MS globally.&#x0D; There is no specific laboratory or diagnostic test to check for MS. For detection of MS, differential diagnosis is used in which signs, symptoms and patients condition is used to rule out the overall scenario. Some blood tests are recommended by doctors which check specific biomarkers associated with MS. MRIis helpfuland it can reveal some areas of spinal cord and brain to see lesions.Spinal tap in which a small sample of cerebrospinal fluid is removed from the spinal canal for laboratory analysis. This sample can show abnormalities in antibodies that are associated with MS.Electric signals produced by nervous system in response to specific stimuli are recorded in a test called Evoked potential test. It’s unfortunate that there is no complete cure of this disease up-till now. Treatment helps tospeed up the, slowing the progression of the disease and managing MS symptoms to help patient live a better life. Treatment for attacks includes the useof corticosteroids and plasma exchange.&#x0D; Previously, it was thought that this disease is uncommon in Pakistan. But new data shows its prevalence to be 10 in 10,0000 of population. It is affecting the Pakistani population on same patterns as found in West. It is found to be more common in women than men. It has been affecting more people who are passing third decade of life. Among its types, Relapsing-Remitting MS (RRMS) is more common in Pakistan. It’s unfortunate that the reports about this disease are few in numbers and there is a need to conduct a thorough research in hope of finding a complete cure of this disease and making the life of patients affected by it much more comfortable.

Background: Serum uric acid (UA), a natural scavenger of peroxynitrite, has been found to be of lower levels in patients with multiple sclerosis (MS) in some recent preliminary studies.Objective: To evaluate the correlation between serum UA levels and several clinical parameters of MS reliably.Methods: We surveyed studies on the serum UA levels and MS patients with comprehensive search and review of the references. A meta-analysis was performed to demonstrate the potential association between serum UA levels in MS patients and their clinical characteristics by random effects models.Results The serum UA levels were lower in patients with MS than in healthy controls (standardized mean difference (SMD) = −0·68; 95% confidence interval (CI): −0·82 to −0·55), as well as in other inflammatory neurological diseases (OINDs) (SMD = −0·45; 95% CI: −0·60 to −0·30). Similarly, the serum UA levels decreased in MS patients with clinical activity when compared to MS with clinical inactivity (SMD = −0·29; 95% CI: −0·48 to −0·10), as well as in relapsing–remitting MS (RRMS) patients with relapse in comparison to RRMS patients with remission (SMD = 0·64; 95% CI: 0·39 to 0·89). However, the results suggested that serum UA levels did not correlate with higher (or lower) expanded disability status scale (SMD = −0·09; 95% CI: −0·10 to 0·27) and magnetic resonance imaging (MRI) activity (SMD = −0·14; 95% CI: −0·13 to 0·41). In the subtypes of MS group, there were significant differences in serum UA levels between secondary progressive MS (SPMS) and RRMS (SMD = −0·34; 95% CI: 0·16 to 0·52), or primary progressive MS (PPMS) (SMD = −0·58; 95% CI: −0·89 to −0·27), but no significant difference between RRMS and PPMS (SMD = −0·18; 95% CI: −0·44 to 0·08).Conclusions: Our study suggests that UA is relevant to MS. Future research is needed to determine whether the administration of UA levels by inosine might be considered as a novel treatment strategy for MS.

Background: The multiple sclerosis (MS) clinical course and relapses frequency before progression vary widely. Objective: To investigate the influence of age on the MS phenotype. Methods: Among 751 primary progressive (PP = 217) and secondary progressive (SP = 534) MS patients from the London Ontario database, we assessed the relationship of age on the relapse frequency and on the progressive phase evolution, and the impact of relapses on the age at onset of progression. Results: Age at onset did not influence the early attacks frequency, but patients younger at onset had larger number of total attacks before progression (age = 27.4, 31.0 and 32.8 mean years; ⩾4, 2–3 and 1 relapses, respectively) and longer latency to SP. Although frequent early relapses predicted younger age at SP onset, patients with no attacks (primary progressive multiple sclerosis (PPMS)), or 1, 2–3 and ⩾4 relapses during the relapsing-remitting phase started progressing at similar age (38.6, 41.3, 41.4 and 39.2 mean years, respectively). The age at onset of progressive phase did not affect its evolution. Conclusions: Age strongly influences the phenotype before progression. Relapsing-remitting patients younger at onset are more likely to display a predominantly inflammatory course, yet relapses number does not affect the age at onset of progression.