Cognitive impairment has been reported at all phases and all subtypes of multiple sclerosis. It remains a major cause of neurological disability in young and middle-aged adults suffering from the ...disease. The severity and type of cognitive impairment varies considerably among individuals and can be observed both in early and in later stages. The areas which have commonly shown more deficits are: information processing speed, complex attention, memory, and executive function. Even though an alteration in both the white matter and in the gray matter has been found in patients with multiple sclerosis and cognitive impairment, the underlying process still remains unknown. Standardized neurological examinations fail to detect emerging cognitive deficits and self-reported cognitive complaints by the patients can be confounded by other subjective symptoms. This review is a comprehensive and short update of the literature on cognitive dysfunctions, the possible confounders and the impact of quality of life in patients with multiple sclerosis.
Abstract
To evaluate whether preventive treatment can modify endothelial and oxidative biomarkers of vascular disease risk in patients with high-frequency episodic and chronic migraine. In this ...observational, prospective pilot study, 88 prophylactic treatment-naïve patients with episodic and chronic migraine and 56 healthy sex/age matched controls underwent ultrasonography exams and blood tests at baseline, and again in the migraine patients after 3 months’ treatment with metoprolol or topiramate. Biomarkers for endothelial function and oxidative stress were analyzed. At baseline, patients with migraine in the low-frequency episodic group had differences exclusively in nitrates 17.6 versus 27.33 µM;
p
= 0.046 compared to the controls. However, when comparing the group comprised of patients with high-frequency episodic migraine and chronic migraine versus controls, statistically significant differences appeared in hsCRP 2.68 versus 1.64 mg/dL;
p
= 0.049, vWF antigen (133% vs. 110%;
p
= 0.020, vWF activity (111% vs. 90%;
p
= 0.010) and isoprostane levels (181 vs. 238 µM;
p
= 0.05). Only in the chronic migraine subgroup did we found statistically significant differences in CIMT (0.60 vs. 0.54 mm;
p
= 0.042) which were significantly greater than in the controls. After treatment, patients who respond to preventive treatment exhibited significantly higher levels of nitrates (24.2–13.8 µM;
p
= 0.022) and nitrites (10.4–3.43 µM;
p
= 0.002) compared than non-responders. Moreover, biomarker levels improved in treatment-responsive patients with migraine; hsCRP levels decreased from 2.54 to 1.69 mg/dL (
p
< 0.05), vWF activity levels decreased from 124 to 103 IU/dL (
p
= 0.003) and prothrombin activity decreased from 1.01 to 0.93 (
p
= 0.01). These differences were also observed in the high-frequency and chronic migraine subgroup and reach statistical significance in the case of hsCRP, which decreased from 2.12 to 0.83 mg/dL (
p
= 0.048). Patients with migraines have differences in biomarker levels compared to controls, suggesting endothelial and oxidative dysfunction. The greatest differences in biomarker levels compared to controls are observed in migraine patients in the high-frequency and chronic migraine subgroups. Based on our results, preventive treatment is capable of modifying markers of endothelial dysfunction and oxidative stress in migraine patients, even in cases of chronic and high-frequency migraine.
Shared decision-making is a cornerstone of patient-centred care. The 9-item Shared Decision-Making Questionnaire (SDM-Q-9) is a brief self-assessment tool for measuring patients' perceived level of ...involvement in decision-making related to their own treatment and care. Information related to the psychometric properties of the SDM-Q-9 for multiple sclerosis (MS) patients is limited. The objective of this study was to assess the performance of the items composing the SDM-Q-9 and its dimensional structure in patients with relapsing-remitting MS.
A non-interventional, cross-sectional study in adult patients with relapsing-remitting MS was conducted in 17 MS units throughout Spain. A nonparametric item response theory (IRT) analysis was used to assess the latent construct and dimensional structure underlying the observed responses. A parametric IRT model, General Partial Credit Model, was fitted to obtain estimates of the relationship between the latent construct and item characteristics. The unidimensionality of the SDM-Q-9 instrument was assessed by confirmatory factor analysis.
A total of 221 patients were studied (mean age = 42.1 ± 9.9 years, 68.3% female). Median Expanded Disability Status Scale score was 2.5 ± 1.5. Most patients reported taking part in each step of the decision-making process. Internal reliability of the instrument was high (Cronbach's α = 0.91) and the overall scale scalability score was 0.57, indicative of a strong scale. All items, except for the item 1, showed scalability indices higher than 0.30. Four items (items 6 through to 9) conveyed more than half of the SDM-Q-9 overall information (67.3%). The SDM-Q-9 was a good fit for a unidimensional latent structure (comparative fit index = 0.98, root-mean-square error of approximation = 0.07). All freely estimated parameters were statistically significant (P < 0.001). All items presented standardized parameter estimates with salient loadings (>0.40) with the exception of item 1 which presented the lowest loading (0.26). Items 6 through to 8 were the most relevant items for shared decision-making.
The SDM-Q-9 presents appropriate psychometric properties and is therefore useful for assessing different aspects of shared decision-making in patients with multiple sclerosis.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract Cerebellar ataxia is one of the most frequent syndromes associated with autoantibodies against glutamic acid decarboxylase (GAD-ab). Antibodies recognize the isoform GAD65, which is the ...standard biomarker, but additional immunoreactivity against GAD67 is found in high proportion of patients with GAD-ab-associated neurological disorders. We describe the case of a 59-year-old woman who presented with pancerebellar syndrome of subacute onset (9 weeks to nadir). In the etiological study, high titers of GAD-ab were found, but these only recognized the GAD67 isoform and not the GAD65. Screening of GAD67-ab should be considered in late-onset cerebellar ataxia when GAD65-ab are absent.
Metabolomic and lipidomic analyses have been used for the profiling of neurodegenerative processes, both in targeted and untargeted approaches. In this work we have applied these techniques to the ...study of CSF samples of multiple sclerosis (MS) patients (n = 9), compared with samples of non‐MS individuals (n = 9) using mass‐spectrometry. We have used western‐blot and analyzed cell culture to confirm pathogenic pathways suggested by mass‐spectrometric measurements. The results of the untargeted approach of metabolomics and lipidomics suggest the existence of several metabolites and lipids discriminating both populations. Applying targeted lipidomic analyses focused to a pathogenic pathway in MS, oxidative stress, reveal that the lipid peroxidation marker 8‐iso‐prostaglandin F2α is increased in CSF from MS patients. Furthermore, as lipid peroxidation exerts its pathogenical effects through protein modification, we studied the incidence of protein lipoxidation, revealing specific increases in carboxymethylated, neuroketal and malondialdehyde‐mediated protein modifications in proteins of CSF from MS patients, despite the absence of their precursors glyoxal and methylglyoxal. Finally, we report that the level of neuroketal‐modified proteins correlated with a hitherto unknown increased amount of autoantibodies against lipid peroxidation‐modified proteins in CSF, without compensation by signaling induced by lipid peroxidation via peroxisome proliferator‐activated receptor γ (PPARγ). The results, despite the limitation of being obtained in a small population, strongly suggest that autoimmunity against in situ produced epitopes derived from lipid peroxidation can be a relevant pathogenic factor in MS.
A wrong response against wrong lipids: lipid peroxidation autoantibodies in multiple sclerosis. This study was aimed at obtaining a metabolomic and lipidomic fingerprint of multiple sclerosis. The results reveal both increased and specific lipid peroxidation in this disease, which is associated to the presence of autoantibodies against proteins modified with lipid peroxidation. This data uncovers a potential novel, lipid‐peroxidation based, autoimmune response in multiple sclerosis pathophysiology
Literature suggest that oxidative stress (OS) may be involved in the multiple sclerosis (MS) pathogenesis, in which the immune system is known to play a key role. However, to date, the OS in ...peripheral lymphocytes and its contribution to the disease remain unknown. The aim of the present study was to explore the influence of OS in peripheral lymphocytes of MS patients. To that end, a cross-sectional, observational pilot study was conducted (n = 58: 34 MS and 24 healthy subjects control group). We have measure superoxide production and protein mitochondrial complex levels in peripheral blood mononuclear cells (PBMCs) isolated from MS patients and control. Lactate levels and the antioxidant capacity were determined in plasma. We adjusted the comparisons between study groups by age, sex and cell count according to case. Results demonstrated that PBMCs, specifically T cells, from MS patients exhibited significantly increased superoxide anion production compared to control group (p = 0.027 and p = 0.041 respectively). Increased superoxide production in PBMCs was maintained after the adjustment (p = 0.044). Regarding mitochondrial proteins, we observe a significant decrease in the representative proteins content of the mitochondrial respiratory chain complexes I-V in PBMCs of MS patients (p = 0.002, p = 0.037, p = 0.03, p = 0.044 and p = 0.051, respectively), which was maintained for complexes I, III and V after the adjustment (p = 0.026; p = 0.033; p = 0.033, respectively). In MS patients, a trend towards increased plasma lactate concentration was detected (8.04 mg lactate/dL 5.25, 9.49 in the control group, 11.36 mg lactate/dL 5.41, 14.81 in MS patients) that was statistically significant after the adjustment (p = 0.013). This might be indicative of compromised mitochondrial function. Finally, antioxidant capacity was also decreased in plasma from MS patients, both before (p = 0.027) and after adjusting for sex and age (p = 0.006). Our findings demonstrate that PBMCs of MS patients show impaired mitochondrial redox status and deficient antioxidant capacity. These results demonstrate for first time the existence of mitochondrial alterations in the cells immune cells of MS patients already at the peripheral level.
Amyotrophic lateral sclerosis (ALS) is a multisystemic, progressive, neurodegenerative disorder. Despite it being generally fatal within a period of 2-4 years, it is highly heterogeneous; as a ...result, survival periods may vary greatly among individual patients. Biomarkers can serve as tools for diagnosis, prognosis, indicators of therapeutic response, and future therapeutics. Free-radical-dependent mitochondrial damage is believed to play a crucial role in neurodegeneration in ALS. Mitochondrial aconitase, which is also known as aconitase 2 (Aco2), is a key Krebs cycle enzyme and is involved in the regulation of cellular metabolism and iron homeostasis. Aco2 is very sensitive to oxidative inactivation and can aggregate and accumulate in the mitochondrial matrix, causing mitochondrial dysfunction. Loss of Aco2 activity may therefore reflect increased levels of mitochondrial dysfunction due to oxidative damage and could be relevant to ALS pathogenesis. The aim of our study was to confirm changes in mitochondrial aconitase activity in peripheral blood and to determine whether such changes are dependent on, or independent of, the patient's condition and to propose the feasibility of using them as possible valid biomarkers to quantify the progression of the disease and as a predictor of individual prognosis in ALS.
We measured the Aco2 enzymatic activity in the platelets of blood samples taken from 22 controls and 26 ALS patients at different stages of disease development. We then correlated antioxidant activity with clinical and prognostic variables.
Aco2 activity was significantly lower in the 26 ALS patients than in the 22 controls (
< 0.05). Patients with higher levels of Aco2 activity survived longer than those with lower levels (
< 0.05). Aco2 activity was also higher in patients with earlier onset (
< 0.05) and in those with predominantly upper motor neuron signs.
Aco2 activity seems to be an independent factor that could be used in the long-term survival prognosis of ALS. Our findings suggest that blood Aco2 could be a leading candidate for use as a biomarker to improve prognosis. More studies are needed to confirm these results.
Maintaining some productivity of the Creole yam (Dioscorea alata L.), affected by anthracnose (Colletotrichum gloeosporioides), from agrochemicals, generates changes in soil fertility, water quality ...and in the agricultural ecosystem of peasant agri-food production, but the proportion in which the management of an endemic fungus impacts and therefore persistent over time is unknown. This situation leads to investigate the environmental, economic, and social impact caused by the management of anthracnose in the cultivation of yam in the municipality of Colosó, department of Sucre, Colombia. A descriptive quantitative methodology was followed; A sample of 135 producers participated from techniques such as direct observation, interviews, surveys, focus groups and for the trade-off analysis of environmental, economic and social impacts the Leopold matrix. The results show a peasant production composed mainly of men (96%), of mestizo origin (91.6%), aged 41 to 60 years (55%); level of education in primary (56.5%) and baccalaureate (20.6%); They plant areas of 1.0 to 1.75 hectares (60.1%) and little technical assistance. Soil (47.3%) was impacted by accumulation of agrochemicals and water when contaminated (71.7%). Leopold's matrix considered the transformation of the territory around tutoring, soil loss, contamination of water bodies and burning of crop residues. In conclusion, maintaining the productivity of the Creole yam cultivar involves establishing the trade-off of the relationship between the planned solutions and the impacts on ecosystems in terms of environmental costs.
Minimizing the risk of relapse is essential in multiple sclerosis (MS). As none of the treatments currently available are capable of completely preventing relapses, treatment of these episodes ...remains a cornerstone of MS care. The objective of this manuscript is to reduce uncertainty and improve quality of care of this neurological process. This article addresses definitions of key concepts, recommendations for clinical examination, classification criteria, magnetic resonance imaging, biomarkers, and specific therapeutic counsels including special populations such as pregnant and breastfeeding women, and children. An algorithm for treating MS relapses is also provided.
Peripheral blood biomarkers able to predict disease activity in multiple sclerosis (MS) patients have not been identified yet. Here, we analyzed the immune phenotype of T lymphocyte subpopulations in ...peripheral blood samples from 66 RRMS patients under DMF (n=22) or fingolimod (n=44) treatment, by flow cytometry. A correlation study between the percentage and absolute cell number of each lymphocyte subpopulation with the presence of relapses or new MRI lesions during 12-month follow-up was performed. Patients who had undergone relapses showed at baseline higher percentage of Th1CM cells (relapsed: 11.60±4.17%vs. nonrelapsed: 9.25±3.17%, p<0.05) and Th1Th17CM cells (relapsed: 15.65±6.15%vs. nonrelapsed: 10.14±4.05%, p<0.01) before initiating DMF or fingolimod treatment. Kaplan-Meier analysis revealed that patients with Th1Th17CM (CD4+CCR7+CD45RA-CCR6+CXCR3+) cells>11.48% had a 50% relapse-free survival compared to patients with Th1Th17CMcells<11.48% whose relapse-free survival was 88% (p=0.013, log-rank test). Additionally, a high percentage of Th1Th17CM cells was also found in patients with MRI activity (MRI activity: 14.02±5.87%vs. no MRI activity: 9.82±4.06%, p<0.01). Our results suggest that the percentage of Th1Th17CM lymphocytes at baseline is a predictive biomarker of activity during the first 12 months of treatment, regardless of the treatment.
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