Background:
The risk factors for conversion from relapsing-remitting to secondary progressive multiple sclerosis remain highly contested.
Objective:
The aim of this study was to determine the ...demographic, clinical and paraclinical features that influence the risk of conversion to secondary progressive multiple sclerosis.
Methods:
Patients with adult-onset relapsing–remitting multiple sclerosis and at least four recorded disability scores were selected from MSBase, a global observational cohort. The risk of conversion to objectively defined secondary progressive multiple sclerosis was evaluated at multiple time points per patient using multivariable marginal Cox regression models. Sensitivity analyses were performed.
Results:
A total of 15,717 patients were included in the primary analysis. Older age (hazard ratio (HR) = 1.02, p < 0.001), longer disease duration (HR = 1.01, p = 0.038), a higher Expanded Disability Status Scale score (HR = 1.30, p < 0.001), more rapid disability trajectory (HR = 2.82, p < 0.001) and greater number of relapses in the previous year (HR = 1.07, p = 0.010) were independently associated with an increased risk of secondary progressive multiple sclerosis. Improving disability (HR = 0.62, p = 0.039) and disease-modifying therapy exposure (HR = 0.71, p = 0.007) were associated with a lower risk. Recent cerebral magnetic resonance imaging activity, evidence of spinal cord lesions and oligoclonal bands in the cerebrospinal fluid were not associated with the risk of conversion.
Conclusion:
Risk of secondary progressive multiple sclerosis increases with age, duration of illness and worsening disability and decreases with improving disability. Therapy may delay the onset of secondary progression.
Background:
Timely initiation of disease modifying therapy is crucial for managing multiple sclerosis (MS).
Objective:
We aimed to validate a previously published predictive model of individual ...treatment response using a non-overlapping cohort from the Middle East.
Methods:
We interrogated the MSBase registry for patients who were not included in the initial model development. These patients had relapsing MS or clinically isolated syndrome, a recorded date of disease onset, disability and dates of disease modifying therapy, with sufficient follow-up pre- and post-baseline. Baseline was the visit at which a new disease modifying therapy was initiated, and which served as the start of the predicted period. The original models were used to translate clinical information into three principal components and to predict probability of relapses, disability worsening or improvement, conversion to secondary progressive MS and treatment discontinuation as well as changes in the area under disability-time curve (ΔAUC). Prediction accuracy was assessed using the criteria published previously.
Results:
The models performed well for predicting the risk of disability worsening and improvement (accuracy: 81%–96%) and performed moderately well for predicting the risk of relapses (accuracy: 73%–91%). The predictions for ΔAUC and risk of treatment discontinuation were suboptimal (accuracy < 44%). Accuracy for predicting the risk of conversion to secondary progressive MS ranged from 50% to 98%.
Conclusion:
The previously published models are generalisable to patients with a broad range of baseline characteristics in different geographic regions.
Background:
The prognostic significance of non-disabling relapses in people with relapsing-remitting multiple sclerosis (RRMS) is unclear.
Objective:
To determine whether early non-disabling relapses ...predict disability accumulation in RRMS.
Methods:
We redefined mild relapses in MSBase as ‘non-disabling’, and moderate or severe relapses as ‘disabling’. We used mixed-effects Cox models to compare 90-day confirmed disability accumulation events in people with exclusively non-disabling relapses within 2 years of RRMS diagnosis to those with no early relapses; and any early disabling relapses. Analyses were stratified by disease-modifying therapy (DMT) efficacy during follow-up.
Results:
People who experienced non-disabling relapses within 2 years of RRMS diagnosis accumulated more disability than those with no early relapses if they were untreated (n = 285 vs 4717; hazard ratio (HR) = 1.29, 95% confidence interval (CI) = 1.00–1.68) or given platform DMTs (n = 1074 vs 7262; HR = 1.33, 95% CI = 1.15–1.54), but not if given high-efficacy DMTs (n = 572 vs 3534; HR = 0.90, 95% CI = 0.71–1.13) during follow-up. Differences in disability accumulation between those with early non-disabling relapses and those with early disabling relapses were not confirmed statistically.
Conclusion:
This study suggests that early non-disabling relapses are associated with a higher risk of disability accumulation than no early relapses in RRMS. This risk may be mitigated by high-efficacy DMTs. Therefore, non-disabling relapses should be considered when making treatment decisions.
Background:
In the absence of evidence from randomised controlled trials, observational data can be used to emulate clinical trials and guide clinical decisions. Observational studies are, however, ...susceptible to confounding and bias. Among the used techniques to reduce indication bias are propensity score matching and marginal structural models.
Objective:
To use the comparative effectiveness of fingolimod vs natalizumab to compare the results obtained with propensity score matching and marginal structural models.
Methods:
Patients with clinically isolated syndrome or relapsing remitting MS who were treated with either fingolimod or natalizumab were identified in the MSBase registry. Patients were propensity score matched, and inverse probability of treatment weighted at six monthly intervals, using the following variables: age, sex, disability, MS duration, MS course, prior relapses, and prior therapies. Studied outcomes were cumulative hazard of relapse, disability accumulation, and disability improvement.
Results:
4608 patients (1659 natalizumab, 2949 fingolimod) fulfilled inclusion criteria, and were propensity score matched or repeatedly reweighed with marginal structural models. Natalizumab treatment was associated with a lower probability of relapse (PS matching: HR 0.67 95% CI 0.62-0.80; marginal structural model: 0.71 0.62-0.80), and higher probability of disability improvement (PS matching: 1.21 1.02 -1.43; marginal structural model 1.43 1.19 -1.72). There was no evidence of a difference in the magnitude of effect between the two methods.
Conclusions:
The relative effectiveness of two therapies can be efficiently compared by either marginal structural models or propensity score matching when applied in clearly defined clinical contexts and in sufficiently powered cohorts.
Objective: Multiple sclerosis (MS) is a chronic, inflammatory and neurodegenerative disease characterized with demyelination and axonal damage in central nervous system (CNS). Inflamasomes, which are ...important part of this inflammatory process, regulate maturation of proinflammatory cytokines. Infamazom complexes are thought to increase in MS attacks. We investigated role of inflammasome complexes (nod-like receptor protein 1 and 3) in serum and cerebrospinal fluid (CSF) levels for MS development.
Methods: Eighteen clinically isolated syndrome (CIS), 19 relapsing remitting multiple sclerosis (RRMS) and 20 healthy control cases were included in the study. Nod-like receptor protein 1 and 3 (NLRP1, NLRP3), inflammasome complex levels and oligoclonal band (OCB) patterns of all the groups were measured in serum and CSF samples using Enzyme-Linked Immuno Sorbent Assay (ELISA) method.
Results: Although NLRP1 and NLRP3 levels in both RRMS and CIS patients measured in serum and CSF were significantly higher than healthy control group, there was no statistically significant difference between RRMS and CIS patients. On the other hand, the levels of NLRP1 and NLRP3 in CSF were significantly higher in OCB pattern positive patients compared to the OCB pattern negative patients.
Conclusion: In this pilot study, it is shown that NLRP1 and NLRP3 inflammasome complexes increased in CSF samples of MS cases and that this tendency occurred during or maybe before the first MS attack. As a result, it was thought that these complexes may have an effect on the formation of the OCB band.
Brucellosis is a zoonotic infection and has endemic characteristics. Neurobrucellosis is an uncommon complication of this infection. The aim of this study was to present unusual clinical ...manifestations and to discuss the management and outcome of a series of 18 neurobrucellosis cases. Initial clinical manifestations consist of pseudotumor cerebri in one case, white matter lesions and demyelinating syndrome in three cases, intracranial granuloma in one case, transverse myelitis in two cases, sagittal sinus thrombosis in one case, spinal arachnoiditis in one case, intracranial vasculitis in one case, in addition to meningitis in all cases. Eleven patients were male and seven were female. The most prevalent symptoms were headache (83%) and fever (44%). All patients were treated with rifampicin, doxycycline plus trimethoprim-sulfamethoxazole or ceftriaxone. Duration of treatment (varied 3-12 months) was determined on basis of the CSF response. In four patients presented with left mild sequelae including aphasia, hearing loss, hemiparesis. In conclusion, although mortality is rare in neurobrucellosis, its sequelae are significant. In neurobrucellosis various clinical and neuroradiologic signs and symptoms can be confused with other neurologic diseases. In inhabitants or visitors of endemic areas, neurobrucellosis should be kept in mind in cases that have unusual neurological manifestations.
•Antibodies to astrocytic cell surface antigens were detected in 5 MS patients.•CLIC1-antibody was identified for the first time in MS and RION patients.•CLIC1-antibody may potentially be utilized as ...a biomarker for the differentiation of MS from NMOSD.
Antibodies to cell surface proteins of astrocytes have been described in chronic inflammatory demyelinating disorders (CIDD) of the central nervous system including multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). Our aim was to identify novel anti-astrocyte autoantibodies in relapsing remitting MS (RRMS) patients presenting predominantly with spinal cord and optic nerve attacks (MS-SCON).
Sera of 29 MS-SCON patients and 36 healthy controls were screened with indirect immunofluorescence to identify IgG reacting with human astrocyte cultures. Putative target autoantigens were investigated with immunoprecipitation (IP) and liquid chromatography-mass/mass spectrometry (LC-MS/MS) studies using cultured human astrocytes. Validation of LC-MS/MS results was carried out by IP and ELISA.
Antibodies to astrocytic cell surface antigens were detected in 5 MS-SCON patients by immunocytochemistry. LC-MS/MS analysis identified chloride intracellular channel protein-1 (CLIC1) as the single common membrane antigen in 2 patients with MS-SCON. IP experiments performed with the commercial CLIC1 antibody confirmed CLIC1-antibody. Home made ELISA using recombinant CLIC1 protein as the target antigen identified CLIC1 antibodies in 9/29 MS-SCON and 3/15 relapsing inflammatory optic neuritis (RION) patients but in none of the 30 NMOSD patients, 36 RRMS patients with only one or no myelitis/optic neuritis attacks and 36 healthy controls. Patients with CLIC1-antibodies showed trends towards exhibiting reduced disability scores.
CLIC1-antibody was identified for the first time in MS and RION patients, confirming once again anti-astrocytic autoimmunity in CIDD. CLIC1-antibody may potentially be utilized as a diagnostic biomarker for differentiation of MS from NMOSD.
Brucellosis is a zoonotic infection and has endemic characteristics. Neurobrucellosis is an uncommon complication of this infection. The aim of this study was to present unusual clinical ...manifestations and to discuss the management and outcome of a series of 18 neurobrucellosis cases. Initial clinical manifestations consist of pseudotumor cerebri in one case, white matter lesions and demyelinating syndrome in three cases, intracranial granuloma in one case, transverse myelitis in two cases, sagittal sinus thrombosis in one case, spinal arachnoiditis in one case, intracranial vasculitis in one case, in addition to meningitis in all cases. Eleven patients were male and seven were female. The most prevalent symptoms were headache (83%) and fever (44%). All patients were treated with rifampicin, doxycycline plus trimethoprim-sulfamethoxazole or ceftriaxone. Duration of treatment (varied 3-12 months) was determined on basis of the CSF response. In four patients presented with left mild sequelae including aphasia, hearing loss, hemiparesis. In conclusion, although mortality is rare in neurobrucellosis, its sequelae are significant. In neurobrucellosis various clinical and neuroradiologic signs and symptoms can be confused with other neurologic diseases. In inhabitants or visitors of endemic areas, neurobrucellosis should be kept in mind in cases that have unusual neurological manifestations.
Fingolimod is the first oral immunomodulatory treatment used as secondary care therapy in the treatment of multiple sclerosis for the last 10 years. The objective of our study is to reveal the ...experiences of the first generic fingolimod active ingredient treatment in different centers across Turkey.
The first generic fingolimod efficacy and safety data of patients followed-up in 29 different clinical multiple sclerosis units in Turkey were analyzed retrospectively. Data regarding efficacy and safety of the patients were transferred to the data system both before the treatment and on the 6th, 12
and 24
month following the treatment. The data were analyzed using the IBM SPSS 20.00. P value of <0.05 was considered to be statistically significant.
A total of 508 multiple sclerosis patients, 331 of whom were women, were included in the study. Upon comparing the Expanded Disability Status values before and after the treatment, a significant decrease was observed, especially at month 6 and thereafter. Since bradycardia occurred in 11 of the patients (2.3%), the first dose had to be longer than 6 hours. During the observation of the first dose, no issues that could prevent the use of the drug occured. Side effects were seen in 49 (10.3%) patients during the course of fingolimod treatment. Respectively, the most frequent side effects were bradycardia, hypotension, headache, dizziness and tachycardia.
The observed results regarding efficacy and safety were similar to clinical trial data in the literature and real life data in terms of the first equivalent with fingolimod active ingredient.
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