Background: Elevated homocysteine levels are associated with various neurodegenerative diseases and have even been identified as a risk factor for some of these. Homocysteine levels may be elevated ...in patients with multiple sclerosis (MS) but large studies are lacking and the relation with disease progression remains to be determined. Aim: The aim of the study was to investigate homocysteine levels in patients with MS and in controls, and to study the relationship between homocysteine levels and clinical progression in MS. Methods: Serum homocysteine levels were compared between MS subtypes (n = 219) and controls (n = 152). Homocysteine levels were associated with baseline and follow-up clinical severity scores. Results: The results showed that serum homocysteine values were similar in patients with MS and controls. Baseline scores on the Expanded Disability Status Scale were higher in patients with secondary progressive MS (SPMS) in the top compared with the bottom quartile of homocysteine levels (p = 0.02). The baseline scores on the Multiple Sclerosis Functional Composite (MSFC) and Paced Auditory Serial Addition Test (PASAT), which measures cognitive functioning, were lower in patients with SPMS in the top compared with the bottom quartile of homocysteine levels (MSFC, p = 0.02; PASAT, p = 0.02). High homocysteine levels were associated with a decline in PASAT scores during follow-up in patients with primary progressive MS (p = 0.009). Conclusion: Serum total homocysteine levels are associated with several measures of disease progression in MS but are not elevated in patients with MS compared with controls. The association of homocysteine levels with cognition in patients with progressive MS raises the question of whether homocysteine directly impacts on MS or reflects a more general neurodegenerative process.
Abstract The disproportional increase of the female:male ratio in relapse-onset (relapsing remitting (RR) and secondary progressive (SP)) multiple sclerosis (MS) patients in the last 20 years has ...further raised scientific interest in gender difference in MS. It has been suggested that the immune system, especially cytokines, plays an important role in the gender issue, as can also be seen in other autoimmune diseases. The immune system is influenced by different factors including hormones and seasonal fluctuations (vitamin D). This overview will highlight the gender differences in MS, with emphasis on the cytokines and vitamin D.
To determine if myxovirus resistance protein A (MxA) mRNA is related to clinical disease activity in multiple sclerosis (MS).
Baseline MxA mRNA levels were measured in a prospective cohort of 116 ...untreated patients with early MS and were related to clinical relapses and MRI at baseline and at follow-up.
Low levels of MxA mRNA were associated with the occurrence of relapses (p = 0.002) and contrast-enhancing lesions (CELs) on baseline MRI (p = 0.045). In addition, high baseline MxA mRNA levels were related to a longer time to a first new relapse (hazard ratio HR 0.59; 95% confidence interval CI 0.35-1.00; p = 0.044). Adding the absence of CELs to high MxA mRNA, the predictive value increased (HR 0.35; 95% CI 0.17-0.74; p = 0.006), clearly showing a cumulative value for combining both factors.
MxA mRNA is related to clinical exacerbations, the number of CELs on MRI, and is indicative for the time to a subsequent relapse. If confirmed, MxA mRNA has potential as a biomarker for clinical disease activity in MS.
Multiple sclerosis (MS) lacks reliable biomarkers that reflect disease activity. Recent evidence suggests that an altered sphingolipid metabolism is associated with MS pathogenesis.
To explore acid ...sphingomyelinase (ASM) activity and altered sphingolipid metabolism as potential biomarkers in serum of MS patients, to predict active and progressive disease, and response to disease modifying therapy (DMT).
Levels of serum ASM activity were longitudinally analyzed in 40 clinically isolated syndrome, 64 relapsing remitting (RR) and 10 primary progressive MS patients, and 22 healthy controls (HC). ASM activity and sphingolipid levels were measured in a different sample of 61 RRMS patients using DMT.
A significant difference in ASM activity levels was observed between MS patients and HC (p < 0.001). There was no correlation between ASM activity levels and disease activity, progression or response to DMT. Ceramide (Cer)-C
, Cer-C
and sphingomyelin (SM)-C
, SM-C
, SM-C
and SM-C
showed a significant increase during fingolimod use.
Although higher levels in MS patients were found, ASM activity levels do not show potential as a biomarker for predicting disease activity, progression or response to DMT. Two ceramides and four types of sphingomyelin require further investigation as potential markers for treatment response.
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.
Increased axonal energy demand and mitochondrial failure have been suggested as possible causes for axonal degeneration and disability in multiple sclerosis.
Our objective was to test whether ATP ...depletion precedes clinical, imaging and biomarker evidence for axonal degeneration in multiple sclerosis.
The method consisted of a longitudinal study which included 21 patients with multiple sclerosis. High performance liquid chromatography was used to quantify biomarkers of the ATP metabolism (oxypurines and purines) from the cerebrospinal fluid at baseline. The Expanded Disability Status Scale, MRI brain imaging measures for brain atrophy (ventricular and parenchymal fractions), and cerebrospinal fluid biomarkers for axonal damage (phosphorylated and hyperphosphorylated neurofilaments) were quantified at baseline and 3-year follow-up.
Central ATP depletion (sum of ATP metabolites >19.7 µmol/litre) was followed by more severe progression of disability if compared to normal ATP metabolites (median 1.5 versus 0, p< 0.05). Baseline ATP metabolite levels correlated with change of Expanded Disability Status Scale in the pooled cohort (r= 0.66, p= 0.001) and subgroups (relapsing—remitting patients: r= 0.79, p< 0.05 and secondary progressive/primary progressive patients: r= 0.69, p< 0.01). There was no relationship between central ATP metabolites and either biomarker or MRI evidence for axonal degeneration.
The data suggests that an increased energy demand in multiple sclerosis may cause a quantifiable degree of central ATP depletion. We speculate that the observed clinical disability may be related to depolarisation associated conduction block.
PDF
