Anti-myelin antibodies predict the clinical outcome after a first episode suggestive of MS

2007 ◽  
Vol 13 (9) ◽  
pp. 1086-1094 ◽  
Author(s):  
V. Tomassini ◽  
L. De Giglio ◽  
M. Reindl ◽  
P. Russo ◽  
I. Pestalozza ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Brain Mri ◽  
First Episode ◽  
Time Interval ◽  
Serum Samples ◽  
Double Positive ◽  
Baseline Serum ◽  
Patients At Risk ◽  
In Cis

The aim of this study was to test the contribution of anti-myelin antibodies in predicting conversion from clinically isolated syndrome (CIS) to multiple sclerosis (MS) when considering either Poser's or McDonald's diagnostic criteria. Fifty-one patients with CIS and abnormal brain MRI were imaged monthly for six months and then at 12, 18, 24, 36 months. At baseline serum samples testing antibodies against myelin oligodendrocyte glycoprotein (anti-MOG) and myelin basic protein (anti-MBP) were collected. During the 36-month follow-up, 26 (51%) patients developed a relapse thus becoming clinically definite MS (CDMS) according to Poser's criteria; 46 (90.2%) patients converted to MS according to McDonald's criteria. Out of 51 patients, 28 (54.9%) had either double or single positivity for anti-myelin antibodies. Antibody status significantly predicted MS according to Poser's criteria ( P = 0.004), but did not according to the McDonald's criteria. When compared to antibody negative patients, the risk of developing a relapse was 8.9 (95% CI: 2.7—29.8; P < 0.001) for anti-MBP positive (anti-MBP+) patients and 1.5 (95% CI: 0.4—5.4; P = 0.564) for those anti-MOG positive (anti-MOG+); double positive patients (ie, anti-MBP+/anti-MOG+) had a risk of relapse's occurrence equal to 3.4 (95% CI: 1.1—10.2; P = 0.031). Also, the antibody status predicted the median time span from CIS to CDMS, that was of 36 months in the anti-MOG-/anti-MBP- group, 33 months in the anti-MOG+/anti-MBP- group, 24 months in the anti-MOG+/anti-MBP+ group and 12 months in the anti-MOG-/anti-MBP+ patients ( P = 0.003 by ANOVA). Our data support the prognostic value of anti-myelin antibodies in CIS patients at risk of CDMS, with positive patients showing shorter time interval to relapse occurrence than negative patients. Multiple Sclerosis 2007; 13: 1086—1094. http://msj.sagepub.com

scholarly journals Partial acute transverse myelitis is a predictor of multiple sclerosis in children

2014 ◽  
Vol 20 (11) ◽  
pp. 1485-1493 ◽  
Author(s):  
P Meyer ◽  
N Leboucq ◽  
N Molinari ◽  
A Roubertie ◽  
M Carneiro ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Prognostic Factors ◽  
Severe Disease ◽  
Brain Mri ◽  
Age At Onset ◽  
Transverse Myelitis ◽  
First Episode ◽  
Acute Transverse Myelitis ◽  
Subsequent Risk

Background: Acute transverse myelitis (ATM) in children is a rare and often severe disease for which there are few known prognostic factors, particularly the subsequent risk of multiple sclerosis (MS) diagnosis. Objectives: To determine the clinical course and prognostic factors after a first episode of ATM in children. Methods: Thirty children below 16 years of age diagnosed with a first neurological episode of ATM were included retrospectively. Clinical evaluation, treatment, laboratory, and MRI data were collected. Results: Median age at onset was 11 years (range 3–15 years). Follow-up data were available for a median of 4 years (range 0.5–16.7 years). Five patients subsequently had a diagnosis of MS (17%), which was associated with acute partial transverse myelitis (odds ratio 5; 95% confidence interval 2.3–11), with a 60% probability of having a relapse at five years ( p < 0.01). The 2011 Verhey criteria correctly identified MS in children with the highest specificity (96%) and sensitivity (80%). Conclusion: Acute partial transverse myelitis and brain MRI abnormalities at initial presentation are significantly predictive of a subsequent diagnosis of MS in children with ATM. These findings suggest that closer brain MRI monitoring after acute partial transverse myelitis might make the earlier introduction of disease-modifying therapies possible.

scholarly journals Decreased Cerebrospinal Fluid Antioxidative Capacity Is Related to Disease Severity and Progression in Early Multiple Sclerosis

Biomolecules ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 1264
Author(s):  
Margarete M. Voortman ◽  
Anna Damulina ◽  
Lukas Pirpamer ◽  
Daniela Pinter ◽  
Alexander Pichler ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Disease Activity ◽  
Neuronal Damage ◽  
Brain Mri ◽  
Time Interval ◽  
Antioxidative Capacity ◽  
Subclinical Disease ◽  
Relapsing Remitting

Background: Oxidative stress-induced neuronal damage in multiple sclerosis (MS) results from an imbalance between toxic free radicals and counteracting antioxidants, i.e., antioxidative capacity (AOC). The relation of AOC to outcome measures in MS still remains inconclusive. We aimed to compare AOC in cerebrospinal fluid (CSF) and serum between early MS and controls and assess its correlation with clinical/radiological measures. Methods: We determined AOC (ability of CSF and serum of patients to inhibit 2,2′-azobis(2-amidinopropane) dihydrochloride-induced oxidation of dihydrorhodamine) in clinically isolated syndrome (CIS)/early relapsing-remitting MS (RRMS) (n = 55/11) and non-inflammatory neurological controls (n = 67). MS patients underwent clinical follow-up (median, 4.5; IQR, 5.2 years) and brain MRI at 3 T (baseline/follow-up n = 47/34; median time interval, 3.5; IQR, 2.1 years) to determine subclinical disease activity. Results: CSF AOC was differently regulated among CIS, RRMS and controls (p = 0.031) and lower in RRMS vs. CIS (p = 0.020). Lower CSF AOC correlated with physical disability (r = −0.365, p = 0.004) and risk for future relapses (exp(β) = 0.929, p = 0.033). No correlations with MRI metrics were found. Conclusion: Decreased CSF AOC was associated with increased disability and clinical disease activity in MS. While our finding cannot prove causation, they should prompt further investigations into the role of AOC in the evolution of MS.

Prognostic value of free light chains lambda and kappa in early multiple sclerosis

2016 ◽  
Vol 23 (11) ◽  
pp. 1496-1505 ◽  
Author(s):  
Margarete M Voortman ◽  
Tatjana Stojakovic ◽  
Lukas Pirpamer ◽  
Margit Jehna ◽  
Christian Langkammer ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Prognostic Value ◽  
Oligoclonal Bands ◽  
Light Chains ◽  
Time Interval ◽  
Free Light Chains ◽  
Magnetic Resonance Imaging Mri ◽  
Relapsing Remitting Multiple Sclerosis ◽  
In Cis

Background: Cerebrospinal fluid (CSF) immunoglobulin free light chains (FLC) have been suggested as quantitative alternative to oligoclonal bands (OCB) in the diagnosis of multiple sclerosis (MS). However, little is known on their role in predicting clinical and paraclinical disease progression, particularly in early stages. Objective: To assess the prognostic value of FLC in OCB-positive patients with clinically isolated syndrome (CIS) suggestive of MS and early MS. Methods: We determined FLC kappa (KFLC) and lambda (LFLC) in CSF and serum by nephelometry in 61 patients (CIS ( n = 48), relapsing-remitting multiple sclerosis ( n = 13)) and 60 non-inflammatory neurological controls. Median clinical follow-up time in CIS was 4.8 years (interquartile range (IQR), 1.5–6.5 years). Patients underwent 3T magnetic resonance imaging (MRI) at baseline and follow-up (median time interval, 2.2 years; IQR, 1.0–3.7 years) to determine T2 lesion load (T2LL) and percent brain volume change (PBVC). Results: CSF FLC were significantly increased in CIS/MS compared to controls (all p < 0.001). A lower KFLC/LFLC CSF ratio was associated with CIS-clinically definite multiple sclerosis (CDMS) conversion (hazard ratio (HR) = 2.89; 95% confidence interval (CI) = 1.17–7.14; p < 0.05). No correlations were found for FLC variables with T2LL or PBVC. Conclusion: Our study confirms increased intrathecal synthesis of FLC in CIS/MS which supports their diagnostic contribution. The KFLC/LFLC CSF ratio appears to have a prognostic value in CIS beyond OCB.

Atypical myelitis in patients with multiple sclerosis: Characterization and comparison with typical multiple sclerosis and neuromyelitis optica spectrum disorders

2020 ◽  
pp. 135245852090699
Author(s):  
K Bigaut ◽  
C Lambert ◽  
L Kremer ◽  
C Lebrun ◽  
M Cohen ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Neuromyelitis Optica ◽  
Transverse Myelitis ◽  
First Episode ◽  
Neuromyelitis Optica Spectrum Disorders ◽  
Disability Status ◽  
Plane Transverse ◽  
Spectrum Disorders ◽  
Extensive Transverse Myelitis

Background: Atypical myelitis in multiple sclerosis (MS) is characterized by extensive myelitis in the longitudinal (longitudinally extensive transverse myelitis) or axial plane (transverse myelitis). Objective: To characterize a cohort of MS patients with atypical myelitis. Methods: Atypical myelitis was extracted from the French and Luxembourg MS databases and compared to two cohorts of MS patients with typical myelitis and neuromyelitis optica spectrum disorders (NMOSDs) patients with myelitis. Results: We enrolled 28 MS patients with atypical myelitis, 68 MS patients with typical myelitis and 119 NMOSD patients with a first episode of myelitis. MS patients with atypical myelitis were characterized by a mean age of 34.0 (±10.7) years and 64.3% were women. In 82.1% of the patients, atypical myelitis was the first episode of MS. Mean Expanded Disability Status Scale (EDSS) scores at nadir and 3–6 months after onset were 4.1 ± 2.1 and 3.3 ± 2, respectively. Differences between groups revealed a predominance of cervicothoracic myelitis and a higher level of disability in NMOSD patients. Disability in MS patients with atypical myelitis was more severe than in the MS patients with typical myelitis; 28% had already converted to progressive MS within our mean follow-up of 39.6 (±30.4) months. Conclusion: Atypical myelitis may be the first presentation of MS and is associated with poorer prognosis.

scholarly journals 1716. Baseline Serum C-Reactive Protein Level Predicts Mortality in Cryptococcal Meningitis

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S629-S629
Author(s):  
Supavit Chesdachai ◽  
Nicole Engen ◽  
Joshua Rhein ◽  
Lillian Tugume ◽  
Tadeo kiiza. Kandole ◽  
...  
Keyword(s):  
Cryptococcal Meningitis ◽  
Surrogate Marker ◽  
First Episode ◽  
Event Analysis ◽  
C Reactive Protein ◽  
Serum Samples ◽  
Hiv Viral Load ◽  
Baseline Serum ◽  
Reactive Protein ◽  
Serum Crp

Abstract Background C-reactive protein (CRP) is an acute-phase protein produced by the liver in response to systemic inflammation. CRP is a helpful surrogate biomarker widely used in various infections, particularly for following the progression and resolution of infection. We aimed to determine the association between baseline CRP level and cryptococcal meningitis outcome. Methods We reviewed 168 prospectively enrolled HIV-infected Ugandans with confirmed first-episode cryptococcal meningitis. Baseline serum samples collected within 5 days from diagnosis had CRP levels measured and categorized into quartiles. We compared baseline serum CRP with 18-week survival using unadjusted time-to-event analysis. Results Of 168 participants, the first quartile of baseline serum CRP was 83.6 mg/L. Baseline CD4 count, HIV viral load, and cerebrospinal fluid results did not differ by quartile. Participants with CRP > 49.5 mg/L more likely presented with Glasgow Coma Scale <15 (P = 0.03). The 18-week mortality rate was 54.8% (46/84) in the highest two quartile CRP groups (49.5 mg/L), 40.5% (17/42) in the mid-range CRP group (29–49.5 mg/L), and 14.3% (6/42) in the low CRP group (<29 mg/L) (P < 0.001) (Figure 1). Conclusion Higher baseline serum CRP is associated with increased mortality in HIV-infected individuals with first-episode cryptococcal meningitis. The serum CRP could be a surrogate marker for undiagnosed co-infections or may reflect immune dysregulation leading to worse outcomes in persons with advanced AIDS and concomitant cryptococcal meningitis. Additional studies investigating more specific inflammatory biomarkers and the longitudinal trend in CRP with effective therapy would be informative. Disclosures All authors: No reported disclosures.

Increased plasma 8,12-iso-iPF2alpha- VI levels in relapsing multiple sclerosis patients are not predictive of disease progression

2012 ◽  
Vol 18 (8) ◽  
pp. 1092-1098 ◽  
Author(s):  
CE Teunissen ◽  
M Sombekke ◽  
L van Winsen ◽  
J Killestein ◽  
F Barkhof ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Multiple Sclerosis ◽  
Disease Progression ◽  
Plasma Levels ◽  
Lesion Load ◽  
Disability Status ◽  
Relapsing Remitting ◽  
Multiple Sclerosis Patients ◽  
In Cis

Background: Oxidative stress plays an important role in multiple sclerosis (MS). Isoprostanes are biomarkers for oxidative stress and have been related to neurological disease progression. Objective: To study whether plasma isoprostane levels were related to disease progression in MS. Methods: Plasma levels of 8,12-iso-iPF2alpha-VI were determined in 17 patients with clinically isolated syndrome (CIS), 41 relapsing–remitting MS (RRMS) patients and 5 primary progressive MS (PPMS) patients and related to MRI and clinical disease parameters. Results: Isoprostane levels were similar in CIS (60.9, interquartile range (IQR): 47.7–77.7 pg/ml) and RRMS patients (65.3, IQR: 51.9–82.8 pg/ml). The plasma levels were lower in PPMS patients (42.5, IQR: 37.1–49.9) pg/ml, p<0.05) compared to CIS and RRMS patients in this cohort, which was not confirmed in a second cohort. Baseline isoprostane levels were not related to clinical progression defined by conversion form CIS to RRMS or change in Expanded Disability Status Scale (EDSS) or MS Functional Composite (MSFC) scores during six years of follow-up (CIS + RRMS), nor to change in volume of gadolinium enhancing lesions, T2 lesion load or T1 hypointense lesion load during 2.8 years of follow-up (CIS + RRMS). Conclusion: These results do not support a strong role of 8,12-iso-iPF2alpha-VI in the prediction of disease progression in MS.

scholarly journals Disease-modifying therapies modulate retinal atrophy in multiple sclerosis

Neurology ◽  
2017 ◽  
Vol 88 (6) ◽  
pp. 525-532 ◽  
Author(s):  
Julia Button ◽  
Omar Al-Louzi ◽  
Andrew Lang ◽  
Pavan Bhargava ◽  
Scott D. Newsome ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
First Year ◽  
Time Interval ◽  
Inclusion Criteria ◽  
Disease Modifying Therapies ◽  
Relapsing Remitting ◽  
Retinal Atrophy ◽  
Disease Modifying ◽  
Relapsing Remitting Multiple Sclerosis

Objective:To retrospectively investigate whether disease-modifying therapies (DMTs) exert differential effects on rates of retinal atrophy in relapsing-remitting multiple sclerosis (RRMS), as assessed using optical coherence tomography (OCT).Methods:A total of 402 patients with RRMS followed at the Johns Hopkins MS Center who underwent Cirrus-HD OCT were assessed for eligibility. Inclusion criteria included at least 1 year of OCT follow-up and adherence to a single DMT during the period of follow-up. Combined thickness of the ganglion cell + inner plexiform (GCIP) and other retinal layers was computed utilizing automated macular segmentation. Retinal thickness changes were analyzed using mixed-effects linear regression.Results:The effects of glatiramer acetate (GA; n = 48), natalizumab (NAT; n = 46), and interferon-β-1a subcutaneously (IFNSC; n = 35) and intramuscularly (IFNIM; n = 28) were assessed. Baseline analyses revealed no significant differences between groups in terms of age, sex, optic neuritis history, or follow-up duration. During follow-up, relative to NAT-treated patients, IFNSC- and GA-treated patients exhibited 0.37 μm/y (p < 0.001) and 0.14 μm/y (p = 0.035) faster rates of GCIP thinning, respectively, adjusting for the interval between initiation of DMT and OCT monitoring (gap time), age, sex, relapses, and disease duration. In the IFNSC group, GCIP thinning was 1.53 μm/y faster during the first year of therapy vs during the time interval afterwards (p < 0.001).Conclusions:Rates of GCIP atrophy in patients with RRMS vary according to DMT utilization. Our findings support OCT for monitoring neurodegenerative treatment effects in the retina, an easily accessible tissue, and as a practical outcome measure in RRMS clinical trials.

scholarly journals Fatigue after a first attack of suspected multiple sclerosis

2017 ◽  
Vol 24 (7) ◽  
pp. 974-981 ◽  
Author(s):  
Roos M van der Vuurst de Vries ◽  
Jan JA van den Dorpel ◽  
Julia Y Mescheriakova ◽  
Tessel F Runia ◽  
Naghmeh Jafari ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Depression Scale ◽  
Common Symptom ◽  
Disability Status ◽  
Definite Multiple Sclerosis ◽  
Fatigue Severity ◽  
Clinically Definite Multiple Sclerosis ◽  
In Cis

Background: Fatigue is reported by more than 75% of multiple sclerosis (MS) patients. In an earlier study, we showed that fatigue is not only a common symptom in patients at time of clinically isolated syndrome (CIS; fatigued 46%) but also predicts subsequent diagnosis of clinically definite multiple sclerosis (CDMS). The course of fatigue after CIS is unknown. Objective: We aimed to explore the long-term course of fatigue after CIS. Methods: In this study, 235 CIS patients, aged 18–50 years, were prospectively followed. Patients filled in the Krupp’s Fatigue Severity Scale (FSS) and the Hospital Anxiety and Depression Scale (HADS) at baseline and annually. After reaching CDMS diagnosis, Expanded Disability Status Scale (EDSS) was obtained annually. Mixed-effects models were used to analyse longitudinal FSS measurements. Results: Fatigue at baseline was an independent predictor for CDMS diagnosis (hazard ratio (HR): 2.6, 95% confidence interval (CI): 1.6–4.4). The evolution of FSS was the same in CIS patients who remained monophasic and patients who were diagnosed with CDMS during follow-up. However, FSS increased by 0.86 units after reaching CDMS diagnosis ( p = 0.01). After this increase, the FSS course remained unaltered ( p = 0.44). Conclusion: Fatigue, which is often present at time of CIS, probably persists over time and increases after a second attack.

Conversion from clinically isolated syndrome to multiple sclerosis: A large multicentre study

2015 ◽  
Vol 21 (8) ◽  
pp. 1013-1024 ◽  
Author(s):  
J Kuhle ◽  
G Disanto ◽  
R Dobson ◽  
R Adiutori ◽  
L Bianchi ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Clinically Isolated Syndrome ◽  
Nuclear Antigen ◽  
Oligoclonal Bands ◽  
Serum Samples ◽  
T2 Lesions ◽  
Definite Multiple Sclerosis ◽  
Epstein Barr ◽  
Csf Oligoclonal Bands

Background and objective: We explored which clinical and biochemical variables predict conversion from clinically isolated syndrome (CIS) to clinically definite multiple sclerosis (CDMS) in a large international cohort. Methods: Thirty-three centres provided serum samples from 1047 CIS cases with at least two years’ follow-up. Age, sex, clinical presentation, T2-hyperintense lesions, cerebrospinal fluid (CSF) oligoclonal bands (OCBs), CSF IgG index, CSF cell count, serum 25-hydroxyvitamin D3 (25-OH-D), cotinine and IgG titres against Epstein-Barr nuclear antigen 1 (EBNA-1) and cytomegalovirus were tested for association with risk of CDMS. Results: At median follow-up of 4.31 years, 623 CIS cases converted to CDMS. Predictors of conversion in multivariable analyses were OCB (HR = 2.18, 95% CI = 1.71–2.77, p < 0.001), number of T2 lesions (two to nine lesions vs 0/1 lesions: HR = 1.97, 95% CI = 1.52–2.55, p < 0.001; >9 lesions vs 0/1 lesions: HR = 2.74, 95% CI = 2.04–3.68, p < 0.001) and age at CIS (HR per year inversely increase = 0.98, 95% CI = 0.98–0.99, p < 0.001). Lower 25-OH-D levels were associated with CDMS in univariable analysis, but this was attenuated in the multivariable model. OCB positivity was associated with higher EBNA-1 IgG titres. Conclusions: We validated MRI lesion load, OCB and age at CIS as the strongest independent predictors of conversion to CDMS in this multicentre setting. A role for vitamin D is suggested but requires further investigation.

scholarly journals Temporal Lobe Epilepsy as a Unique Manifestation of Multiple Sclerosis

2003 ◽  
Vol 30 (3) ◽  
pp. 228-232 ◽  
Author(s):  
Antonio Gambardella ◽  
Paola Valentino ◽  
Angelo Labate ◽  
Grazia Sibilia ◽  
Francesca Ruscica ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
Brain Mri ◽  
Epileptic Seizures ◽  
Cortical Lesion ◽  
Temporal Region ◽  
Antiepileptic Medication ◽  
Long Term Follow Up

Objective:To report on five patients with temporal lobe epilepsy (TLE) as the unique manifestation of multiple sclerosis (MS).Methods:Among 350 consecutive MS patients, we identified 16/350 (4.6%) who also had epileptic seizures. Here, we review their electrophysiological and clinical features.Results:Five of these 16 patients (four female, one male; mean age 34.2 years; range 31 to 38) with MS and epileptic seizures had an extremely homogeneous clinical picture characterized by TLE as the unique manifestation of MS, even at long follow-up (mean: five years; range 4 to 10). In all patients, seizures started in the second or third decade. Brain MRI revealed at least one juxta-cortical lesion within the temporal region. Antiepileptic medication was always effective.Conclusions:The present study provides the first evidence of a peculiar form of MS characterized by TLE as the unique manifestation of the disease with no disability or MS relapses at long-term follow-up.

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