Multiple Sclerosis (MS) patients present a decrease of antioxidants and neuroprotective and immunoregulatory vitamins and an increase of total homocysteine (tHcy), cholesterol (CHL), HDL-cholesterol, ...and of cellular stress markers, variably associated with the different phases of the disease. We compared the blood levels of uric acid, folic acid, vitamins B12, A, and E, tHcy, CHL, HDL-cholesterol, and triglycerides in forty MS patients during a phase of clinical inactivity with those of eighty healthy controls, matched for age and sex. We found higher levels of tHcy (p = 0.032) and of HDL-cholesterol (p = 0.001) and lower levels of vitamin E (p = 0.001) and the ratio vitamin E/CHL (p = 0.001) in MS patients. In conclusion, modifications of some biochemical markers of cell damage were detected in MS patients during a phase of clinical inactivity.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Epidemiological studies conducted in Sicily and Sardinia, the two major Mediterranean islands, showed elevated incidence and prevalence of multiple sclerosis (MS)and a recent increase in disease ...frequency.
To confirm the central highlands of Sicily as areas of increasing MS prevalence and elevated incidence, we performed a follow-up study based on the town of Caltanissetta (Sicily), southern Italy.
We made a formal diagnostic reappraisal of all living patients found in the previous study performed in 1981. All possible information sources were used to search for patients affected by MS diagnosed according to the Poser criteria. We calculated prevalence ratios, for patients affected by MS who were living and resident in the study area on December 31, 2002. Crude and age- and sex-specific incidence ratios were computed for the period from January 1, 1993, to December 31, 2002.
The prevalence of definite MS rose in 20 years from 69.2 (retrospective prevalence rate) to 165.8/100,000 population. We calculated the incidence of definite MS for the period 1970-2000. These rates calculated for 5-year periods increased from 2.3 to 9.2/100,000/year.
This survey shows the highest prevalence and incidence figures of MS in the Mediterranean area and confirms central Sicily as a very-high-risk area for MS.
Archaeological settings are intrinsically dynamic, undergoing transformations over time that significantly impact the archaeological record. These changes result from both deliberate human ...interventions and natural degradation processes. Post-depositional phenomena often distort our understanding of ancient contexts, complicating the identification of the original arrangement and hindering the interpretation of archaeological findings. This issue is particularly pronounced in funerary contexts, such as burials, which are susceptible to various natural and human-induced alterations. This study shows the potential of analysing funerary contexts within a processual framework and reconstructing them in a dynamic 3D environment. By employing metrically and morphologically accurate 3D reconstructions, it becomes possible to simulate, isolate, and analyze post-depositional phenomena. The precision of 3D simulation increases significantly when considering factors such as gravity. The goal of this study is to assess changes resulting from transformative phenomena, with a specific focus on creating a sequential representation that elucidates the burial's transformation processes, spanning from deposition to excavation phases.
Myelin oligodendrocyte glycoprotein-immunoglobulin G associated disease (MOGAD) is an autoimmune demyelinating disorder of the central nervous system (CNS) which usually occurs with recurrent optic ...neuritis, transverse myelitis, acute disseminating encephalomyelitis, or brainstem encephalitis. To date, the anti-CD 20 drug rituximab (RTX) is employed in MOGAD although some authors reported the efficacy of Tocilizumab (TCZ) in refractory patients. We present the case of a woman affected by refractory MOGAD who was treated with TCZ after therapy with RTX had failed to prevent relapses. We also conducted a current literature review on TCZ use in MOGAD. A 57-year-old Caucasian woman affected by MOGAD with severe motor impairment and cognitive dysfunction was treated from 2020 to February 2022 with RTX. However, she experienced progressive clinical and cognitive worsening associated with white matter lesions mimicking leukodystrophy. In February 2022, the patient started therapy with TCZ administered with improvement of cognitive performance, walking ability, and brainstem functions. During TCZ, our patient reached the condition of NEDA-3 (no relapse, no increase in disability, no MRI activity on neuroimaging follow-up performed in September 2023). Moreover, the patient experienced paucisymptomatic SARS-CoV-2 infection that did not modify TCZ schedule. To date, there are few evidence on the efficacy and safety of TCZ in MOGAD. However, all the reviewed cases showed that TCZ represents an effective therapy in drug-resistant MOGAD. Our case highlights the efficacy of TCZ in drug resistant MOGAD and strengthens previous reports of TCZ safety and efficacy in MOGAD.
Background
MS is a neurodegenerative autoimmune disease resulting from a complex interaction of genetic and environmental factors. Among these, vitamin D and genetic variants associated with vitamin ...D‐metabolism gain great attention. The aim of our study was to assess five SNPs in NADSYN1 and CYP2R1 genes in relation to serum 25‐OH‐vitamin D3 levels in MS patients and controls.
Methods
25‐OH‐vitamin D3 levels and genotyping of CYP2R1‐ and NADSYN1‐SNPs were investigated both in MS patients and in healthy controls.
Results
The analysis revealed lower 25‐OH‐vitamin D3 concentrations in MS patients than in controls and an association of rs10766197 CYP2R1 SNP with MS risk. After stratifying MS patients according to gender, we found that the minor allele A of rs10766197 had a higher frequency in men in comparison to women affected by MS. Additionally, the presence of allele A in men was associated with disease progression, assessed by EDSS and MSSS scores.
Conclusion
The findings of our study open new perspectives for a role of CYP2R1 in both risk and progression of MS, with sex‐related differences.
We investigated the association among vitamin D, SNPs in genes related to vitamin D metabolism, namely CYP2R1 and DHCR7/NADSYN1 and multiple sclerosis (MS). Our findings identify a role for rs10766197 CYP2R1 in MS risk. Moreover, we found an association of rs10766197 with disease progression only in men affected by MS.
Abstract Marburg's disease (MD) is an extremely rare and aggressive form of multiple sclerosis (MS). In some cases, MD presents with tumefactive demyelinating lesions with a “tumor-like” appearance ...in MRI images, for which it may be difficult to achieve a form of differential diagnosis between definitive tumors or abscesses. Here we report a case of MD histopathologically confirmed after neuronavigationguided biopsy. Postoperative course was uneventful and following discharge, the patient attended outpatient follow-up appointments and received i.v. cyclophopsphamide, achieving progressive clinical remission. A nine-month follow-up brain MRI scan with gadolinium showed no signs of progressing demyelinating disease with an evident reduction of the biopsied lesion, and almost complete retrogression of the other two lesions. In our opinion, and through the analysis of currently available literature, early neuronavigation-guided biopsy is a highly recommend, valuable, and safe diagnostic tool; it is also preferable to stereotactic biopsy, since its benefits include a very low bleeding rate and brain damage risk, with minimum mortality and morbidity rates. It also allows the identification of the specific histological pattern, helping to select the best medical treatment approach and contributing to increase patient outcome and life expectancy.
Disability accrual in multiple sclerosis may occur as relapse-associated worsening or progression independent of relapse activity. The role of progression independent of relapse activity in early MS ...is yet to be established. The objective of this multicentre, observational, retrospective cohort study was to investigate the contribution of relapse-associated worsening and progression independent of relapse activity to confirmed disability accumulation in patients with clinically isolated syndrome and early relapsing-remitting multiple sclerosis, assessed within one year from onset and with follow-up >/= 5 years (n = 5169). Data were extracted from the Italian Multiple Sclerosis Register. Confirmed disability accumulation was defined by an increase in Expanded Disability Status Scale score confirmed at 6 months, and classified per temporal association with relapses. Factors associated with progression independent of relapse activity and relapse-associated worsening were assessed using multivariable Cox regression models. Over a follow-up period of 11.5 ± 5.5 years, progression independent of relapse activity occurred in 1427 (27.6%) and relapse-associated worsening in 922 (17.8%) patients. Progression independent of relapse activity was associated with older age at baseline (HR = 1.19; 95CI 1.13-1.25, p < 0.001), having a relapsing-remitting course at baseline (HR = 1.44; 95CI 1.28-1.61, p < 0.001), longer disease duration at baseline (HR = 1.56; 95%CI 1.28-1.90, p < 0.001), lower Expanded Disability Status Scale at baseline (HR = 0.92; 95CI 0.88-0.96, p < 0.001), lower number of relapses before the event (HR = 0.76; 95CI 0.73-0.80, p < 0.001). Relapse-associated worsening was associated with younger age at baseline (HR = 0.87; 95CI 0.81-0.93, p < 0.001), having a relapsing-remitting course at baseline (HR = 1.55; 95CI 1.35-1.79, p < 0.001), lower Expanded Disability Status Scale at baseline (HR = 0.94; 95CI 0.89-0.99, p = 0.017), higher number of relapses before the event (HR = 1.04; 95CI 1.01-1.07, p < 0.001). Longer exposure to disease modifying drugs was associated with a lower risk of both progression independent of relapse activity and relapse-associated worsening (p < 0.001). This study provides evidence that in early relapsing-onset multiple sclerosis cohort, progression independent of relapse activity was an important contributor to confirmed disability accumulation. Our findings indicate that insidious progression appears even in the earliest phases of the disease, suggesting that inflammation and neurodegeneration can represent a single disease continuum, in which age is one of the main determinants of disease phenomenology.
Un piccolo vaso scolpito in clorite dalla civiltà dell’Halil Rud (nell’area di Jiroft, Kerman, Iran, c. 2500 a.C.), caratterizzato da una raffinata iconografia zoomorfa, è stato documentato tramite ...un modello digitale in 3D ottenuto con un sistema a luce strutturata. Il modello digitale non solo ha documentato in modo realistico tramite un nuovo formato 3D la complessa raffigurazione in rilievo, ma ha anche permesso osservazioni analitiche che sarebbero state impossibili tramite le fotografie tradizionali ed il disegno a mano. Lo studio dunque fornisce le linee guida di una metodologia innovativa per la registrazione e l’interpretazione dell’eccezionale produzione artistica degli scultori di clorite dell’Halil Rud. L’iconografia del vaso di clorite viene poi discussa in termini di identificazione zoologica, comportamento di gruppo e abitudini riproduttive della specie ritratta; l’ipotesi finale è che gli animali e il loro ambiente vegetale possano essere stati intesi come una metafora antropologica, incentrata sul ruolo dominante dei maschi nelle famiglie nucleari.
An ever-expanding number of disease-modifying drugs for multiple sclerosis have become available in recent years, after demonstrating efficacy in clinical trials. In the real-world setting, however, ...disease-modifying drugs are prescribed in patient populations that differ from those included in pivotal studies, where extreme age patients are usually excluded or under-represented. In this multicentre, observational, retrospective Italian cohort study, we evaluated treatment exposure in three cohorts of patients with relapsing-remitting multiple sclerosis defined by age at onset: paediatric-onset (≤18 years), adult-onset (18-49 years) and late-onset multiple sclerosis (≥50 years). We included patients with a relapsing-remitting phenotype, ≥5 years follow-up, ≥3 Expanded Disability Status Scale (EDSS) evaluations and a first neurological evaluation within 3 years from the first demyelinating event. Multivariate Cox regression models (adjusted hazard ratio with 95% confidence intervals) were used to assess the risk of reaching a first 12-month confirmed disability worsening and the risk of reaching a sustained EDSS of 4.0. The effect of disease-modifying drugs was assessed as quartiles of time exposure. We found that disease-modifying drugs reduced the risk of 12-month confirmed disability worsening, with a progressive risk reduction in different quartiles of exposure in paediatric-onset and adult-onset patients adjusted hazard ratios in non-exposed versus exposed >62% of the follow-up time: 8.0 (3.5-17.9) for paediatric-onset and 6.3 (4.9-8.0) for adult-onset, P < 0.0001 showing a trend in late-onset patients adjusted hazard ratio = 1.9 (0.9-4.1), P = 0.07. These results were confirmed for a sustained EDSS score of 4.0. We also found that relapses were a risk factor for 12-month confirmed disability worsening in all three cohorts, and female sex exerted a protective role in the late-onset cohort. This study provides evidence that sustained exposure to disease-modifying drugs decreases the risk of disability accumulation, seemingly in a dose-dependent manner. It confirms that the effectiveness of disease-modifying drugs is lower in late-onset patients, although still detectable.
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