Parkinson's disease (PD) is a neurodegenerative disorder, caused by, so far, unknown pathogenetic mechanisms. There is no doubt that pro-inflammatory immune-mediated mechanisms are pivotal to the ...pathogenicity and progression of the disease. In this review, we highlight the binary role of microglia activation in the pathophysiology of the disorder, both neuroprotective and neuromodulatory. We present how the expression of several cytokines implicated in dopaminergic neurons (DA) degeneration could be used as biomarkers for PD. Viral infections have been studied and correlated to the disease progression, usually operating as trigger factors for the inflammatory process. The gut-brain axis and the possible contribution of the peripheral bowel inflammation to neuronal death, mainly dopaminergic neurons, seems to be a main contributor of brain neuroinflammation. The role of the immune system has also been analyzed implicating a-synuclein in the activation of innate and adaptive immunity. We also discuss therapeutic approaches concerning PD and neuroinflammation, which have been studied in experimental and in vitro models and data stemming from epidemiological studies.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The aim of this ecological study was to investigate what the impact of digital learning due to the COVID-19 pandemic was on the burnout and overall mental health (MH) of medical students.
During the ...unprecedented era of the COVID-19 pandemic, the majority of countries worldwide adopted very strong measures. Universities closed their doors, and education continued through digital learning lectures.
An anonymous questionnaire was administered to all 189 eligible candidates before and during the COVID-19 pandemic. Mental health was assessed via the MH domain of the 36-item Short Form Health Survey (SF-36) and burnout with the Maslach Burnout Inventory-Student Survey (MBI-SS).
The overall response rate was 81.5%. The overall burnout prevalence did not differ significantly between the two periods (pre-COVID-19 18.1% vs. COVID-19 18.2%). However, the burnout prevalence dropped significantly in year 4 (pre-COVID-19 40.7% vs. COVID-19 16.7%,
= 0.011), whereas it increased significantly in year 6 (pre-COVID-19 27.6% vs. COVID-19 50%,
= 0.01). When looking at each MBI-SS dimension separately, we found that emotional exhaustion decreased significantly in year 4 but increased in year 6, and cynicism increased in all years. The overall MH deteriorated significantly between the two periods (pre-COVID-19 58.8 ± 21.6 vs. COVID-19 48.3 ± 23,
< 0.001).
Digital learning in medical studies carries significant risks. Not only does the MH deteriorate, but cynicism levels also increase. Emotional exhaustion was found to increase particularly in final year students, who struggle with the lack of clinical experience just before they start working as qualified junior doctors.
A number of officially approved disease-modifying drugs (DMD) are currently available for the early intervention in patients with relapsing-remitting multiple sclerosis (RRMS). The aim of the present ...study was to systematically evaluate the effect of DMDs on disability progression in RRMS.
We performed a systematic review on MEDLINE and SCOPUS databases to include all available placebo-controlled randomized clinical trials (RCTs) of RRMS patients that reported absolute numbers or percentages of disability progression during each study period. Observational studies, case series, case reports, RCTs without placebo subgroups and studies reporting the use of RRMS therapies that are not still officially approved were excluded. Risk ratios (RRs) were calculated in each study protocol to express the comparison of disability progression in RRMS patients treated with a DMD and those RRMS patients receiving placebo. The mixed-effects model was used to calculate both the pooled point estimate in each subgroup and the overall estimates.
DMDs for RRMS were found to have a significantly lower risk of disability progression compared to placebo (RR = 0.72, 95%CI: 0.66-0.79; p<0.001), with no evidence of heterogeneity or publication bias. In subsequent subgroup analyses, neither dichotomization of DMDs as "first" and "second" line RRMS therapies (RR = 0.72, 95% CI = 0.65-0.80) vs. (RR = 0.72, 95% = 0.57-0.91); p = 0.96 nor the route of administration (injectable or oral) RR = 0.75 (95% CI = 0.64-0.87) vs. RR = 0.74 (95% CI = 0.66-0.83); p = 0.92 had a differential effect on the risk of disability progression. Either considerable (5-20%) or significant (>20%) rates of loss to follow-up were reported in many study protocols, while financial and/or other support from pharmaceutical industries with a clear conflict of interest on the study outcomes was documented in all included studies.
Available DMD are effective in reducing disability progression in patients with RRMS, independently of the route of administration and their classification as "first" or "second" line therapies. Attrition bias needs to be taken into account in the interpretation of these findings.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Introduction
Central post-stroke pain (CPSP) is defined as the neuropathic pain that arises either acutely or in the chronic phase of a cerebrovascular event and is a result of central lesions of the ...somatosensory tract. The aim of this systematic review and meta-analysis was to establish the prevalence of CPSP, to describe its characteristics, and to discuss the associated management challenges.
Methods
After a systematic Medline search, we identified 69 papers eligible to be included.
Results
The pooled prevalence of CPSP in patients with stroke at any location was 11% (95% CI 7–18%), which can increase to more than 50% in the subgroups of patients with medullary or thalamic strokes. CPSP onset coincides with stroke occurrence in 26% of patients (95% CI 18–35%); CPSP manifests within a month since symptom onset in 31% of patients (95% CI 22–42%), and occurs between the first month and the first year in 41% of patients (95% CI 33.9–49.0%). CPSP develops more than 12 months after stroke onset in 5% of patients (95% CI 3–8%).
Conclusions
Clinicians should look for any evidence of central neuropathic pain for at least 12 months after stroke. Both pharmacological and non-pharmacological interventions can be used for the management of CPSP. Lamotrigine has the strongest evidence (Level II of evidence, derived from small randomized controlled trials) for being effective in the management of CPSP. Future research should focus on well-designed trials of pharmacological and non-pharmacological interventions aiming to relief CPSP, which is a very common but often neglected pain syndrome.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
A number of genetic loci were found to be associated with dystonia. Quite a few studies have been contacted to examine possible contribution of TOR1A variants to the risk of dystonia, but their ...results remain conflicting. The aim of the present study was to systematically evaluate the effect of TOR1A gene SNPs on dystonia and its phenotypic subtypes regarding the body distribution.
We performed a systematic review of Pubmed database to identify all available studies that reported genotype frequencies of TOR1A SNPs in dystonia. In total 16 studies were included in the quantitative analysis. Odds ratios (ORs) were calculated in each study to estimate the influence of TOR1A SNPs genotypes on the risk of dystonia. The fixed-effects model and the random effects model, in case of high heterogeneity, for recessive and dominant mode of inheritance as well as the free generalized odds ratio (ORG) model were used to calculate both the pooled point estimate in each study and the overall estimates.
Rs1182 was found to be associated with focal dystonia in recessive mode of inheritance Odds Ratio, OR (95% confidence interval, C.I.): 1.83 (1.14-2.93), Pz = 0.01. In addition, rs1801968 was associated with writer's cramp in both recessive and dominant modes OR (95%C.I.): 5.99 (2.08-17.21), Pz = 0.00009 and 2.48 (1.36-4.51), Pz = 0.003) respectively and in model free-approach ORG (95%C.I.): 2.58 (1.45-4.58).
Our meta-analysis revealed a significant implication of rs1182 and rs1801968 TOR1A variants in the development of focal dystonia and writer's cramp respectively. TOR1A gene variants seem to be implicated in dystonia phenotype.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background and purpose
Primary Sjögren syndrome (pSS) is a chronic, systemic, autoimmune disorder characterized by lymphocytic infiltrates of the exocrine organs, leading to sicca symptoms and ...parotid enlargement. pSS has been linked to various neurological manifestations, including peripheral neuropathy (PN). We aimed to provide a comprehensive analysis of the currently available evidence regarding pSS‐related PN.
Methods
A literature search in the PubMed database was performed, and 49 papers were eligible to be included in this systematic review and meta‐analysis.
Results
The pooled prevalence of PN in pSS is estimated to be 15.0% (95% confidence interval = 10.7%–20.7%). The mean age of pSS patients at PN diagnosis is 59 years. Among the patients with pSS and PN, 83% are females. Neuropathic symptoms usually precede or lead to the pSS diagnosis at a 2:1 ratio in patients with pSS‐related PN. The commonest type of pSS‐related PN is distal axonal polyneuropathy (80% of patients with pSS‐related PN), followed by sensory ganglionopathy. Peripheral and cranial mononeuropathies—particularly trigeminal—are also frequent. Risk factors for developing PN include increasing age and presence of vasculitis. Immune‐mediated pathogenetic mechanisms are discussed. Glucocorticoids are the most commonly used treatment option for managing pSS‐related PN, when associated with vasculitis, followed by the use of intravenous immunoglobulin.
Conclusions
PN is very common in pSS patients. Evidence on long‐term prognosis of PN in pSS is limited, and further research is needed. Research into the use of immunosuppressive medication in nonvasculitic neuropathies in the context of pSS merits further consideration.
The pooled prevalence of peripheral neuropathy in primary Sjögren syndrome (pSS) is estimated to be 15% (95% confidence interval = 11%–21%). pSS‐related neuropathy usually manifests in the 6th decade of life. The commonest type is distal axonal polyneuropathy, followed by sensory ganglionopathy.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Accumulating epidemiological evidence from several populations supports the important role of the Mediterranean-type diet (MeDi) in reducing the risk for age-related diseases such as Alzheimer's ...disease (AD). However, the relevant literature is clearly deficient for most Mediterranean countries that more closely adhere to the originally described MeDi. Greece resides in the Mediterranean basin, and older generations traditionally adhere to a MeDi.
We here present the design and the preliminary baseline characteristics of the Hellenic Longitudinal Investigation of Aging and Diet (HELIAD). The HELIAD is a population-based, multidisciplinary, collaborative study designed to estimate the prevalence and incidence of AD, other dementias, mild cognitive impairment, and other neuropsychiatric conditions of aging in the Greek population and to investigate associations between nutrition and cognitive dysfunction/age-related neuropsychiatric diseases in this Mediterranean population. The study also ascertains several demographic, medical, social, environmental, clinical, nutritional, and neuropsychological determinants and lifestyle activities.
In total, 1,050 participants of a random sample have already completed the initial evaluation. The subjects were, on average, 73.4 (SD = 6.0) years old, 60% of the sample were female, and most of the participants were poorly educated with an average of 5.41 (SD = 3.5) years of education. The performance on the neuropsychological tests was equivalent to the average scores of previous normative Greek samples. More than one third of the population under investigation was considered to be at high risk for malnutrition.
The HELIAD may provide important data for expanding our knowledge regarding the prevalence, incidence, and risk factors of AD and several other neuropsychiatric diseases in the Mediterranean region.
The aim of the present meta-analysis was to evaluate the effect of disease-modifying drugs (DMD) on brain atrophy in patients with relapsing-remitting multiple sclerosis (RRMS) using available ...randomized-controlled trial (RCT) data.
We conducted a systematic review and meta-analysis according to PRISMA guidelines of all available RCTs of patients with RRMS that reported data on brain volume measurements during the study period.
We identified 4 eligible studies, including a total of 1819 RRMS patients (71% women, mean age 36.5 years, mean baseline EDSS-score: 2.4). The mean percentage change in brain volume was found to be significantly lower in DMD versus placebo subgroup (standardized mean difference: -0.19; 95%CI: -0.27--0.11; p<0.001). We detected no evidence of heterogeneity between estimates (I2 = 30%, p = 0.19) nor publication bias in the Funnel plots. Sensitivity analyses stratifying studies according to brain atrophy neuroimaging protocol disclosed no evidence of heterogeneity (p = 0.16). In meta-regression analyses, the percentage change in brain volume was found to be inversely related with duration of observation period in both DMD (meta-regression slope = -0.03; 95% CI: -0.04--0.02; p<0.001) and placebo subgroups (meta-regression slope = -0.05; 95% CI: -0.06--0.04; p<0.001). However, the rate of percentage brain volume loss over time was greater in placebo than in DMD subgroup (p = 0.017, ANCOVA).
DMD appear to be effective in attenuating brain atrophy in comparison to placebo and their benefit in delaying the rate of brain volume loss increases linearly with longer treatment duration.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Accumulating evidence suggests that the extent of brain injury and the clinical outcome after traumatic brain injury (TBI) are modulated, to some degree, by genetic variants. Aquaporin-4 (AQP4) is ...the predominant water channel in the central nervous system and plays a critical role in controlling the water content of brain cells and the development of brain edema after TBI. We sought to investigate the influence of the AQP4 gene region on patient outcome after TBI by genotyping tag single nucleotide polymorphisms (SNPs) along AQP4 gene. A total of 363 patients with TBI (19.6% female) were prospectively evaluated. Data including the Glasgow Coma Scale (GCS) scores at admission, the presence of intracranial hemorrhage, and the 6-month Glasgow Outcome Scale (GOS) scores were collected. Seven tag SNPs across the AQP4 gene were identified based on the HapMap data. Using logistic regression analyses, SNPs and haplotypes were tested for associations with 6-month GOS after adjusting for age, GCS score, and sex. Significant associations with TBI outcome were detected for rs3763043 (OR 95% confidence interval (CI): 5.15 1.60-16.5, p=0.006, for recessive model), rs3875089 (OR 95% CI: 0.18 0.07-0.50 p=0.0009, for allele difference model), and a common haplotype of AQP4 tag SNPs (OR 95% CI: 2.94, 1.34-6.36, p=0.0065). AQP4 tag SNPs were not found to influence the initial severity of TBI or the presence of intracranial hemorrhages. In conclusion, the present study provides evidence for possible involvement of genetic variations in AQP4 gene in the functional outcome of patients with TBI.
PDF
