Επιστημονικές δημοσιεύσεις
1:
Andreas A. Argyriou, Roser Velasco, Foteini Kalofonou, Pantelis Litsardopoulos, Montse Alemany, Dimitrios Rikos, Haralabos P. Kalofonos & Jordi Bruna Gender and age effects on the incidence and severity of chemotherapy-induced neuropathic pain: a propensity score matching analysis
BMC Cancer volume 25, Article number: 1193 (2025)
Abstract
Objective
To determine whether the clinical phenotype of chemotherapy-induced neuropathic pain (CINP) varies based on the gender and age of patients.
Methods
Retrospective, file-based analysis of cancer patients who received any conventional standard of care chemotherapy and were referred to assess the extent of painful chemotherapy-induced peripheral neurotoxicity (CIPN). A Propensity Score Matching Analysis (PSMA) was conducted to create balanced cohorts; accounting for variables that could impact the incidence and severity of CINP in CIPN patients. A total of 205 males and 295 females were initially included, and after PSMA, 191 patients of each gender were equally matched; totaling 382 patients. These patients were divided according to their age to those aged ≤65 years (group I, n=216) and patients aged ≥66 years (group II, n=166). CINP was assessed using the pain intensity numerical rating scale (PI-NRS) and the Douleur Neuropathique-4 questionnaire (DN4). The severity of CIPN was graded with Total Neuropathy Score-clinical (TNSc®).
Results
The incidence of CINP was similar between males and females (27.2% vs. 27.7%; p = 1). The same applied for the DN4 scorings at CINP onset (median 7; p = 0.9). The severity of CINP at the end of chemotherapy, according to PI-NRS, was 7 (range:6–9) for males vs. 7 (range: 5–8) for females (p = 0.09), while at 3 months post-chemotherapy the PI-NRS scorings were comparable (p = 0.56). However, males tended towards higher rates of severe CINP (PI-NRS ≥ 7) [males: 59.5%, females: 40.5%; p = 0.1], compared to female patients, despite having lower CIPN severities, according to TNSc® scoring. No statistically significant differences were observed in the incidence (25% vs. 30.7%; p = 0.214) and severity (mean PI-NRS difference p = 0.584) of CINP between age groups. Older male patients presented a higher likelihood (OR: 1.08; 95CI: 1.01–1.16; p = 0.027) of severe pain (PI-NRS ≥ 7) at the end of chemotherapy, compared to their younger counterparts.
Conclusion
There were no significant differences found between the occurrence and severity of CINP, based on gender or age. However, older men had more severe pain raters (PI-NRS), while scoring lower in TNSc® severities.
2:
Vikelis M, Rikos D, Argyriou AA, Dermitzakis EV, Andreou AP, Russo A. Switching between anti-CGRP monoclonal antibodies in migraine prophylaxis. Expert Rev Neurother. 2025 Feb 5:1-16. doi: 10.1080/14737175.2025.2461766. Epub ahead of print. PMID: 39884968.
Abstract
Introduction: When a first anti-CGRP monoclonal antibody (anti-CGRP mAb) fails, switching to a different anti-CGRP mAb is an option often considered, despite the fact that this approach is not yet systemically studied.
Methods: We present the findings of a systematic review conducted according to the PRISMA recommendations on published studies - of any design - investigating the clinical outcomes after switching for any reason to different anti-CGRP mAbs.
Results: The literature search retrieved 76 records, while 19 papers were eventually reviewed. Most studies were retrospective and/or had a small sample size. A significant proportion of participants experienced an improved treatment response after switching between different anti-CGRP mAbs. Specifically, according to prospective studies' results, the median MMDs were reduced by 12.8 days after 6 months of switching, while up to 48% of episodic and 36% of the chronic migraine patients achieved a >50% response rate.
Conclusions: Switching between different anti-CGRP mAbs may be beneficial, at least for some patients, and should be considered when therapy with a first anti-CGRP mAb fails for any reason. Larger prospective studies, employing standardized protocols for switching or comparative effectiveness trials between mAbs, are anticipated to elucidate this issue further.
3:
Dermitzakis EV, Rikos D, Vikelis M, Xiromerisiou G, Zisopoulou S, Rallis D, Soldatos P, Vlachos GS, Vasiliadis GG, Argyriou AA. Real-World Open-Label Experience with Rimegepant for the Acute Treatment of Migraine Attacks: A Multicenter Pilot Study. Brain Sci. 2024 Nov 22;14(12):1169. doi: 10.3390/brainsci14121169. PMID: 39766367; PMCID: PMC11674050.
https://www.mdpi.com/2076-3425/14/12/1169
Abstract
Objectives: The present open-label multicenter pilot study sought to prospectively evaluate the efficacy and safety of rimegepant in treating migraine attacks. Methods: The primary endpoint was pain freedom at two hours post-dose, while the co-primary efficacy endpoints included a reduction in the headache intensity and freedom from the most bothersome symptoms (MBS) associated with migraine at the same time point. To test the potential efficacy of rimegepant, patients were asked to record in a questionnaire all the relevant changes with each migraine attack treated with rimegepant at two hours post-dose vs. two hours before. The attending neurologists provided information on the basic demographics, medical anamnesis, and migraine history as well as the triptan use history. Results: A total of 54 patients (32 with episodic and 22 with chronic migraine) received rimegepant 75 mg at least once during a single migraine attack (overall, 140 dosage intakes). Pain freedom at 2 h was achieved in 45/140 (32.1%) intakes. Regarding the efficacy of the first rimegepant dose (n = 54), significant reductions in the headache intensity were observed between the pre- and 2 h post-treatment average VAS scores (−4.8 ± 2.8 mean; p < 0.001). Likewise, the same mean reductions in the average VAS scores occurred when the 2 h response to all 140 doses was analyzed (−5 ± 2.8; p < 0.001). Freedom from MBS at 2 h post-dose was achieved for photophobia in 43%, for phonophobia in 53%, and for nausea in 57%. The ability to fully return to everyday activities at 2 h post-dose was achieved in 83/140 instances (59%). We only recorded mild adverse events in 24/140 dosages. Conclusions: Our preliminary results demonstrate that rimegepant is effective, safe, and well tolerated in treating acute migraine attacks.
4:
Argyriou AA, Dermitzakis EV, Xiromerisiou G, Rikos D, Rallis D, Soldatos P, Litsardopoulos P, Andreou AP, Vikelis M. Menopause and its impact on the effectiveness of fremanezumab for migraine prophylaxis: post-hoc analysis of a prospective, real-world Greek registry. Expert Rev Neurother. 2024 Nov;24(11):1119-1126. doi: 10.1080/14737175.2024.2403576. Epub 2024 Sep 16. PMID: 39279446.
ABSTRACT
Objective
This post-hoc analysis of data extracted from a prospective study aimed to explore for the first time if the efficacy of fremanezumab in preventing difficult-to-treat migraine, according to ICHD-III, would differ between pre-menopausal and post-menopausal women.
Methods
A total of 171 (aged 18–70 years) fremanezumab-treated female migraine patients for six consecutive months were classified to those at pre-menopausal (n = 82) or post-menopausal (n = 89). Monthly headache days (MHD), disability, and quality of life (QOL) outcomes were assessed at baseline and at week 24 post-fremanezumab within subgroups and were then compared between them. Safety and tolerability were also assessed.
Results
In both groups, fremanezumab demonstrated significant reductions in MHDs, reduced disability, and higher QOL scores at week 24 post-treatment, compared to baseline. However, the between-subgroup comparison documented that pre-menopausal women and those at post-menopausal comparably benefited with significant reductions in overall MHDs (p = 0.883). Less disability, according to MIDAS (p = 0.696) and HIT-6 scores (p = 0.912), as well as higher QOL scores at week 24 post-fremanezumab, were also comparably evident in both groups. Safety was excellent across both subgroups.
Conclusion
Fremanezumab can be considered a very effective treatment option for preventing migraines in difficult-to-treat women, aged 18–70 years, regardless of their menopausal status.
5:
Vikelis M, Rikos D, Argyriou AA, Papachristou P, Rallis D, Karapanayiotides T, Galanopoulos A, Spingos K, Dimisianos N, Giakoumakis E, Zavridis P, Notas K, Vlachos GS, Soldatos P, Bilias K, Xiromerisiou G, Rudolf J, Dermitzakis EV, Rapoport AM. Preferences and perceptions of 617 migraine patients on acute and preventive migraine treatment attributes and clinical trial endpoints. Expert Rev Neurother. 2024 Aug;24(8):815-826. doi: 10.1080/14737175.2024.2365312. Epub 2024 Jun 13. PMID: 38870024.
ABSTRACT
Background
To identify the preferences and perceptions of migraine patients for acute and preventive treatment options and to investigate which treatment outcomes are the most important.
Design and Methods
The authors performed a choice-format survey in a cohort of migraine patients from Greece and Cyprus. A self-administered questionnaire developed in collaboration with the Greek Society of Migraine Patients was used.
Results
Questionnaires were collected from 617 migraine patients. Efficacy was preferred over safety as the single most important parameter, both in acute and preventive treatment. When analyzing single outcomes, patients prioritized a complete pain remission at 1-hour post-dose for acute therapies. Regarding migraine prevention, a 75% reduction in frequency, intensity of pain, accompanying symptoms and acute medication intake were considered as most important. Conversely, outcomes routinely used in clinical trials, namely complete or partial pain remission at 2-hours post-dose for acute treatment and 50% or 30% reduction in migraine frequency for prevention, were not deemed particularly relevant. Tablet formulation was mostly preferred, both in acute and preventive treatment.
Conclusion
Listening to patients’ needs may add a piece of the puzzle that is generally missing in clinical practice and often explains the lack of adherence in both acute and preventative anti-migraine therapies.
6:
Dermitzakis EV, Argyriou AA, Bilias K, Barmpa E, Liapi S, Rikos D, Xiromerisiou G, Soldatos P, Vikelis M. Results of a Web-Based Survey on 2565 Greek Migraine Patients in 2023: Demographic Data, Imposed Burden and Satisfaction to Acute and Prophylactic Treatments in the Era of New Treatment Options. J Clin Med. 2024 May 8;13(10):2768. doi: 10.3390/jcm13102768. PMID: 38792309; PMCID: PMC11122074.
https://www.mdpi.com/2077-0383/13/10/2768
Abstract
Objective: The Greek Society of Migraine and Headache Patients conducted its third in-line population web-based survey in 2023 to ascertain if the burden of the disease and the patients’ satisfaction with conventional and novel migraine therapies are changing compared to our previous findings from 2018 and 2020.
Methods: The sampling process was based on a random call to participants to reply to a specific migraine-focused self-administered questionnaire, including 83 questions in Greek, which was distributed nationwide through the online research software SurveyMonkey.
Results: We eventually enrolled 2565 patients, the majority of which were females. Our findings clearly demonstrate that migraine is still a burdensome condition. The degree of its impact on all aspects of productivity depends on the monthly frequency of migraine and the response rates to acute and prophylactic treatments. A total of 1029 (42.4%) of the patients had visited the emergency room mainly for unresponsiveness to acute treatments or aura-related symptoms. Triptans seem to be partly effective as acute therapies. OnabotulinumtoxinA seems to be effective for almost half of chronic migraine patients (43.9%) to report adequate satisfaction with this treatment (27.8% were “fairly happy”, 10.6% were “very happy”, and 5.5% were “extremely happy”). Due to their high rates of preventative effectiveness, most respondents treated with anti-CGRP Mabs expressed their optimism concerning their future while living with their migraine (88.25%), as well as towards further improvements in their quality of life (82.8%) status, mostly with fremanezumab.
Conclusions: The patients recognize the usefulness of anti-CGRP Mabs in migraine prevention and consequently seem to be more optimistic than before about living with migraine. Considering the market change that is anticipated with the use of gepants and ditans, larger longitudinal population-based studies are warranted to further explore if the new era of migraine therapeutics might further lessen the burden of the disease.
7:
Rikos D, Vikelis M, Dermitzakis EV, Soldatos P, Rallis D, Rudolf J, Andreou AP, Argyriou AA. Reporting Quality and Risk of Bias Analysis of Published RCTs Assessing Anti-CGRP Monoclonal Antibodies in Migraine Prophylaxis: A Systematic Review. J Clin Med. 2024 Mar 28;13(7):1964. doi: 10.3390/jcm13071964. PMID: 38610729; PMCID: PMC11012539.
https://www.mdpi.com/2077-0383/13/7/1964
Abstract
Objective: Phase II/III randomized clinical trials (RCTs) are vulnerable to many types of bias beyond randomization. Insights into the reporting quality of RCTs involving migraine patients treated with monoclonal antibodies targeting the calcitonin gene-related peptide system (anti-CGRP MAbs) are currently lacking. Our aim was to analyze the reporting quality of phase II/III RCTs involving migraine patients treated with anti-CGRP MAbs.
Methods: A systematic search was performed on the PubMed and EMBASE databases, according to PRISMA guidelines, for relevant RCTs in either episodic or chronic migraine prevention. Additionally, an adapted version of the 2010 CONSORT statement checklist was utilized. The ROBvis online tool was used to document the risk of bias.
Results: From the initially identified 179 articles, we finally found 31 RCTs that were eligible for evaluation. The average CONSORT compliance was 88.7% (69.7–100%), while 93.5% (N = 29) of the articles had a compliance greater than 75%. Twenty-eight CONSORT items were reported in more than 75% of the articles. The average compliance of the analyzed RCTs was 93.9% for Galcanezumab, 91.3% for Fremanezumab, followed by 85.4% for Erenumab and Eptinezumab studies. Implementation of the ROB2 tool showed some concerning “missing information” arising from the inadequate reporting. Specifically, 50% of the studies (N = 16) were categorized as having inadequate information regarding the randomization process.
Conclusions: Adequate reporting quality was disclosed in the evaluated RCTs with anti-CGRP MAbs in migraine prevention. However, some methodological issues need to be highlighted to be addressed in future studies assessing the efficacy of new molecules targeting CGRP or other candidate pathways implicated in migraine pathophysiology.
8:
Argyriou AA, Dermitzakis EV, Rikos D, Xiromerisiou G, Soldatos P, Litsardopoulos P, Vikelis M. Effects of OnabotulinumtoxinA on Allodynia and Interictal Burden of Patients with Chronic Migraine. Toxins (Basel). 2024 Feb 15;16(2):106. doi: 10.3390/toxins16020106. PMID: 38393184; PMCID: PMC10891839.
https://www.mdpi.com/2072-6651/16/2/106
Αbstract
Background: We primarily aimed to ascertain whether treatment with OnabotulinumtoxinA (BoNTA) might influence the extent of the interictal burden and cutaneous allodynia in patients with chronic migraine (CM).
Methods: Seventy CM patients, who received three consecutive cycles of BoNTA, were studied. The interictal burden was assessed with the Migraine Interictal Burden Scale (MIBS-4), while cutaneous allodynia was examined with the Allodynia Symptom Checklist (ASC-12) together with PI-NRS VAS to obtain hair brushing scores, and then these were compared from baseline (T0) to the last efficacy evaluation follow-up (T1). Efficacy outcomes, mostly mean headache days (MHD) and “Headache Impact Test” scores, were also assessed between T0 and T1.
Results: BONTA improved the interictal burden, with a decrease in MIBS-4 scoring by an average of −7 at T1, compared to baseline (p < 0.001). The percentage of patients with a moderate/severe interictal burden was substantially decreased. Likewise, BoNTA reduced the extent of cutaneous allodynia, with a significant reduction in both the ASC-12 (1 vs. 6; p < 0.001) and PI-NRS VAS (1 vs. 5; p < 0.001) to hair brushing median scores at T1, compared to baseline. Reduced MHD rates were significantly associated with a smaller interictal burden at T1. The efficacy of BoNTA, with a significant reduction in MHD and HIT-6 scores at T1 compared to T0, was re-confirmed.
Conclusions: BoNTA resulted in a statistically significant reduction in the interictal burden and also improved cutaneous allodynia. The reduction in ictal burden was associated with the down-scaling of the interictal burden. Hence, BoNTA improved the full spectrum of migraine impairment by diminishing the clinical expression of central sensitization.
9:
Dermitzakis EV, Vikelis M, Xiromerisiou G, Rallis D, Soldatos P, Litsardopoulos P, Rikos D, Argyriou AA. Nine-Month Continuous Fremanezumab Prophylaxis on the Response to Triptans and Also on the Incidence of Triggers, Hypersensitivity and Prodromal Symptoms of Patients with High-Frequency Episodic Migraine. J Clin Med. 2024 Jan 10;13(2):386. doi: 10.3390/jcm13020386. PMID: 38256516; PMCID: PMC10816996.
https://www.mdpi.com/2077-0383/13/2/386
Abstract
Objective: To investigate whether the incidence of triggers, prodromal symptoms, hypersensitivity symptoms accompanying headache and responses to triptans were modified during a continuous 9-month fremanezumab therapy for migraine prophylaxis.
Patients and methods: We studied 63 patients with high-frequency episodic migraine (HFEM). Enrolled patients received fremanezumab for nine consecutive months before defining the response rates and being stratified into treatment responders (≥50–74% reduction in monthly headache days (MHDs)), super responders (≥75%), partial non-responders (<50%) and super non-responders (<30%). Through headache diaries, patients provided data in order to document the impact of fremanezumab on the incidence of triggers, associated symptoms followed by headache and response to triptans (the use of the migraine treatment optimization questionnaire-4 (mTOQ-4)) during the 9-month treatment period.
Results: Fremanezumab had early (after 3 monthly cycles) beneficial effects on the response to triptans in the majority of responders with relevant increases in mTOQ-4 scoring, but also in half of partial non-responders. A significant reduction in median days with migraine-associated symptoms was seen in responders after 6 months of therapy with fremanezumab, mostly for osmophobia, photophobia, phonophobia and nausea/vomiting, but partial non-responders also benefited. Likewise, the incidence of self-reported prodromal symptoms was significantly reduced in responders and was modestly diminished in partial non-responders. Triggers remained unaffected in both responders and non-responders.
Conclusions: Fremanezumab given for at least 6–9 months may exert neuromodulatory effects in the migraine brain. These effects could result both in the inhibition of migraine chronification, but also in the diminishing of the magnitude of migraine-associated symptoms, mostly in responders and in partial non-responders.
10:
Vikelis M, Dermitzakis EV, Xiromerisiou G, Rallis D, Soldatos P, Litsardopoulos P, Rikos D, Argyriou AA. Effects of Fremanezumab on Psychiatric Comorbidities in Difficult-to-Treat Patients with Chronic Migraine: Post Hoc Analysis of a Prospective, Multicenter, Real-World Greek Registry. J Clin Med. 2023 Jul 6;12(13):4526. doi: 10.3390/jcm12134526. PMID: 37445560; PMCID: PMC10342907.
https://www.mdpi.com/2077-0383/12/13/4526
Abstract
Objective: this post hoc analysis aimed to evaluate the efficacy of fremanezumab in difficult-to-treat chronic migraine (CM) patients with and without psychiatric comorbidities (PCs), mainly anxiety and/or depression.
Methods: We assessed data from CM patients with and without PCs who failed at least 3 preventives and eventually received at least 3 consecutive monthly doses of fremanezumab 225 mg. Outcomes included the crude response (≥50% reduction in monthly headache days (MHDs)) rates to fremanezumab from the baseline to the last clinical follow-up. The changes in MHDs; MHDs of moderate/greater severity; monthly days with intake of abortive medication; and the proportion of patients’ changing status from with PCs to decreased/without PCs were also compared. Disability and quality of life (QOL) outcomes were also assessed.
Results: Of 107 patients enrolled, 65 (60.7%) had baseline PCs. The percentage of patients with (n = 38/65; 58.5%) and without (n = 28/42; 66.6%) PCs that achieved a ≥50% reduction in MHDs with fremanezumab was comparable (p = 0.41), whereas MHDs were significantly reduced (difference vs. baseline) in both patients with PCs (mean −8.9 (standard error: 6.8); p < 0.001) and without PCs (−9.8 (7.5); p < 0.001). Both groups experienced significant improvements in all other efficacy, disability, and QOL outcomes at comparable rates, including in MHD reduction. A significant proportion of fremanezumab-treated patients with baseline PCs de-escalated in corresponding severities or even reverted to no PCs (28/65; 43.1%) post-fremanezumab. Conclusions: fremanezumab appears to be effective as a preventive treatment in difficult-to-treat CM patients with and without PCs while also being beneficial in reducing the severity of comorbid anxiety and/or depression.
11:
Dardiotis E, Skouras P, Varvarelis OP, Aloizou AM, Hernández AF, Liampas I, Rikos D, Dastamani M, Golokhvast KS, Bogdanos DP, Tsatsakis A, Siokas V, Mitsias PD, Hadjigeorgiou GM. Pesticides and tremor: An overview of association, mechanisms and confounders. Environ Res. 2023 Jul 15;229:115442. doi: 10.1016/j.envres.2023.115442. Epub 2023 Feb 8. PMID: 36758916.
https://www.sciencedirect.com/science/article/pii/S0013935123002347?via%3Dihub
Abstract
Pesticides are a heterogeneous class of chemicals mainly used for the protection of crops from pests. Because of their very widespread use, acute or/and chronic exposure to these chemicals can lead to a plethora of sequelae inflicting diseases, many of which involve the nervous system. Tremor has been associated with pesticide exposure in human and animal studies. This review is aimed at assessing the studies currently available on the association between the various types of pesticides/insecticides and tremor, while also accounting for potential confounding factors. To our knowledge, this is the first coherent review on the subject. After appraising the available evidence, we call for more intensive research on this topic, as well as intonate the need of implementing future preventive measures to protect the exposed populations and to reduce potential disabilities and social drawbacks.
12:
Rikos D, Siokas V, Mentis AA, Aloizou AM, Liampas I, Tsouris Z, Peristeri E, Stamati P, Hadjigeorgiou GM, Dardiotis E. TREM2 R47H variant and risk for Alzheimer's disease: assessment in a Greek population and updated meta-analysis. Int J Neurosci. 2022 Dec 6:1-9. doi: 10.1080/00207454.2022.2150844. Epub ahead of print. PMID: 36408688.
Abstract
Introduction
Rare coding variants in TREM2 and their association with the susceptibility towards Alzheimer’s disease (AD) were recently studied in various ethnic groups with contradictory results. The T allele of the rs75932628 (p.R47H variant) has shown a positive risk association with AD in several studies; however, neither a study in Greece nor an updated meta-analysis have been conducted.
Objective
To assess the association between TREM2 rs75932628 and late-onset (sporadic) AD in a Greek population, and perform a meta-analysis of current data.
Materials and Methods
The rs75932628 was genotyped in a total of 327 patients with AD and 700 cognitively healthy controls. A systematic search and meta-analyses of studies presenting data regarding rs75932628 in AD cases and controls were also performed.
Results
Three patients vs. none of the controls were found to carry the heterozygous risk allele of the rs75932628, yielding a significant association (p = 0.032), in the Greek sample. In the meta-analysis, the overall odds ratio (OR) under a fixed-effects model was 2.98 (Confidence Interval (CI):2.52–3.53) showing a significant association of the rs75932628-T allele with AD in the overall dataset, based on data from 27 studies (26200 AD cases and 142084controls). Caucasian population-only studies (n = 16) revealed a similar OR of 2.93 (CI:2.45–3.51), whereas Asian population-only studies (n = 5) had a non-significant OR of 0.84 (CI:0.19–3.74).
13:
Rikos D, Siokas V, Burykina TI, Drakoulis N, Dardiotis E, Zintzaras E. Replication of chromosomal loci involved in Parkinson's disease: A quantitative synthesis of GWAS. Toxicol Rep. 2021 Oct 12;8:1762-1768. doi: 10.1016/j.toxrep.2021.10.008. PMID: 34712594; PMCID: PMC8528647.
https://www.sciencedirect.com/science/article/pii/S2214750021001803?via%3Dihub
Abstract
Introduction
Parkinson’s disease is a neurodegenerative disorder with a complex etiology coming from interactions between genetic and environmental factors. Research on Parkinson’s disease genetics has been an effortful struggle, while new technologies and novel study designs served as indispensable boosters. Until now, 90 loci and 20 disease-causing gene mutations have been identified. In this study we describe a novel non-parametric approach to GWAS meta-analysis and its application in PD genetics.
Methods
A literature search was conducted to identify Genome-Wide Association Studies (GWAS) regarding Parkinson’s disease. We applied predefined inclusion criteria and extracted the reported SNPs and their respective position and statistical significance. We divided all chromosomes in approximately equal genetic distance segments called bins and recorded the most significant SNP from each bin and each study and ranked them in terms of their p-value. Ranks from each bin were summed, averaged and added in a heterogeneity-based analysis using the METRADISC-XL software. Weighted and unweighted analysis was performed.
Results
Five-hundred and forty-three SNPs and their respective p-values from 15 studies were matched in their corresponding bins. The METRADISC-XL analysis resulted in 7 bins with a significant p-value. A bin on chromosome 4 where the SNCA gene is located found with genome-wide significant association with Parkinson’s Disease.
Conclusion
This is the first time a non-parametric method is applied in GWAS meta-analysis. The results add some insight on the overall understanding of Parkinson’s disease genetics and serve as a first step of further convergent analysis with Genome-wide linkage studies.
14:
Koute V, Michalopoulou A, Siokas V, Aloizou AM, Rikos D, Bogdanos DP, Kontopoulos E, Grivea IN, Syrogiannopoulos GA, Papadimitriou A, Hadjigeorgiou GM, Dardiotis E. Val66Met polymorphism is associated with decreased likelihood for pediatric headache and migraine. Neurol Res. 2021 Sep;43(9):715-723. doi: 10.1080/01616412.2021.1922181. Epub 2021 May 17. PMID: 34000980.
ABSTRACT
Background: Migraine is a complex multifactorial disorder and its pathogenesis still remains unclear. Evidence suggests the involvement of the activated trigeminovascular pathway, in which BDNF seems to play an important role. Therefore, BDNF polymorphisms are promising candidate susceptibility factors.
Aim: BDNF rs6265 functional polymorphism was analyzed in order to determine its possible association with pediatric headache and migraine risk.
Methods: The research included 120 consecutive pediatric patients who were diagnosed with headache and 120 healthy controls. The diagnosis was in compliance with the International Classification of Headache Disorders. Blood samples were collected from all participants and genotyped for rs6265.
Results: BDNF rs6265 was significantly associated with decreased headache risk, particularly in the dominant model [Odds Ratio, OR (95% confidence interval, C.I.): 0.47 (0.26–0.85), p = 0.011] and the log-additive model [OR (95% C.I.): 0.48 (0.28–0.82), p = 0.0053]. During the sensitivity analysis, the associations were also maintained among patients with migraine.
Conclusions: This is the first study to reveal a significant association of this BDNF variant with headache risk. Additionally, Val66Met was also for the first time related to decreased childhood migraine risk.
15:
Liampas I, Siouras AS, Siokas V, Tsouris Z, Rikos D, Brotis A, Aloizou AM, Dastamani M, Dardiotis E. Migraine in transient global amnesia: a meta-analysis of observational studies. J Neurol. 2022 Jan;269(1):184-196. doi: 10.1007/s00415-020-10363-y. Epub 2021 Jan 2. PMID: 33388926.
https://link.springer.com/article/10.1007/s00415-020-10363-y
Abstract
Purpose
Although many studies have investigated the relationship between transient global amnesia (TGA) and migraine, to date, no meta-analysis has confirmed the existence and size of their association.
Methodology
Literature search involved MEDLINE, EMBASE, CENTRAL and PsycINFO. Observational controlled studies including TGA patients (Caplan, Hodges and Warlow) were retrieved. Quality evaluation was based on the Newcastle-Ottawa scale. The prevalence of migraine was compared in TGA patients vs. healthy controls (HC), as well as in TGA against TIA individuals. Data from case-control, cross-sectional and cohort studies were pooled separately.
Results
Literature search yielded 1178 articles, 12 of which were included in the present meta-analysis. Results from case-control (ten), cohort (one) and cross-sectional (one) studies were compatible with an association between TGA and migraine. The nationwide inpatient cross-sectional study was of lesser value due to its inpatient orientation. The high-quality, population-based, retrospective cohort (158,301 participants per group) determined a higher relative-risk (RR) of TGA for migraine vs. non-migraine individuals [RR = 2.48, 95%confidence-interval (95% CI) = (1.32, 4.87)]. Sensitivity testing based on stricter diagnostic criteria strengthened the estimated association [RR = 3.84, 95% CI = (1.57, 9.38)]. Additionally, pooled data from eight case–control studies (700 TGA, 746 HC) yielded similar results [Odds-Ratio, OR = 2.51, 95% CI = (1.85, 3.41)], with the association mainly driven by the three high-quality studies, rather than the five articles of moderate quality. Finally, pooled findings from four case–control studies of moderate-quality revealed a higher prevalence of migraine among TGA compared to TIA patients [OR = 1.82, 95% CI = (1.22, 2.73)].
Conclusions
A significant association between TGA and migraine was established. The underlying connecting mechanism remains undetermined, yet.
16:
Marogianni C, Georgouli D, Dadouli K, Ntellas P, Rikos D, Hadjigeorgiou GM, Spanaki C, Xiromerisiou G. Identification of a novel de novo KMT2B variant in a Greek dystonia patient via exome sequencing genotype-phenotype correlations of all published cases. Mol Biol Rep. 2021 Jan;48(1):371-379. doi: 10.1007/s11033-020-06057-3. Epub 2020 Dec 9. PMID: 33300088.
https://link.springer.com/article/10.1007/s11033-020-06057-3
Abstract
Mutations in Lysine-Specific Histone Methyltransferase 2B gene (KMT2B) have been reported to be associated with isolated and complex early-onset generalized dystonia. We describe clinico-genetic features on a Greek patient with a novel de novo variant and demonstrate the phenotypic spectrum of KMT2B variants. We performed whole exome sequencing (WES), in a Greek patient with sporadic generalized dystonia. Additionally, we performed a systematic review of all published cases with KMT2B variants. The patient presented with isolated and mild generalized dystonia. We identified a novel splice site variant that was confirmed by Sanger sequencing and was not found in parents. This is the first reported KMT2B variant, in the Greek population. This case report further highlights the growing trend of identifying genetic diseases previously restricted to few cases in many different ethnic groups worldwide via exome sequencing. In the systematic review, we evaluated the mutation pathogenicity in all previously reported cases to investigate possible phenotype-genotype correlations. Greater mutation numbers in different populations will be important and mutation-specific functional studies will be essential to identify the pathogenicity of the various KMT2B variants.
17:
Rikos D, Marogianni C, Provatas A, Bourinaris T, Arnaoutoglou M, Stathis P, Patrinos GP, Dardiotis E, Hadjigeorgiou GM, Xiromerisiou G. Screening for the C9ORF72 expansion in Greek Huntington Disease phenocopies and controls and meta- analysis of current data. Tremor Other Hyperkinet Mov (N Y). 2020 Jun 12;10:5. doi: 10.5334/tohm.61. PMID: 32775019; PMCID: PMC7394208.
https://tremorjournal.org/articles/10.5334/tohm.61
Background: Several European studies examined the role of C9orf72 repeat expansion in patients with Huntington-disease like phenotypes (HD-L). The scope of our study is to investigate the expansion frequency in a Greek HD-L cohort and the meta-analysis of all published cases. This will be of use in genetic counseling of these cases.
Methods: A cohort of 74 patients with HD-L and 67 healthy controls were screened for the C9orf72 expansion status. Case-controls comparison was assessed with the Pearson’s chi-square statistic for a 2 × 2 table. A systematic database search was conducted and seven studies, including the current study, were considered eligible for inclusion in a meta-analysis considering a total of 812 patients with HD phenocopies. Pooled mutation frequency was calculated using a Random Effects model or the Mantel-Haezsel fixed effects model, depending on the observed heterogeneity.
Results: In our cohort, one patient was found to have a pathologic expansion of C9orf72, and none from the control group (chi-square: 0.91, p-value: 0.34). Pooled mutation frequency was found at 2% (CI: 1–3%) with low heterogeneity (I2:15%). Discussion: Based on this meta-analysis the recommendation for genetic testing for C9orf72 expansions is further solidified.
18:
Xiromerisiou G, Kalampokini S, Rikos D, Provatas A, Tsouris Z, Markou K, Ralli S, Dardiotis E. Posterior reversible encephalopathy in a GT1a positive oculopharyngeal variant of Guillain-Barré syndrome: A case-report and review of the literature. Clin Neurol Neurosurg. 2020 Sep;196:106037. doi: 10.1016/j.clineuro.2020.106037. Epub 2020 Jun 22. PMID: 32623212.
https://www.sciencedirect.com/science/article/pii/S0303846720303802?via%3Dihub
Abstract
Guillain-Barre syndrome (GBS) is the most common cause of acute flaccid paralysis and its incidence increases with age, although all age groups can be affected. The cranial subtypes of GBS account for approximately 5% of cases. Posterior reversible encephalopathy syndrome (PRES) is an acute neurological disorder, mostly reversible but with increased morbidity with permanent neurological sequelae in severe cases. The coexistence of these two syndromes is very rare and underdiagnosed.
To the best of our knowledge, there are several dozen cases reported in the literature including ours with the coexistence of these two syndromes in adult patients. We present a rare case of oculopharyngeal type of GBS followed by PRES syndrome. Based on the reviewed cases we discuss various pathogenic mechanisms that support the association between these two entities.
This review illustrates the importance of detecting PRES syndrome in the context of acute inflammatory immune-mediated polyneuropathies especially when the patients present early dysautonomia. We also discuss the importance of early administration of immunoglobulin (IVIG) treatment but the possible risks that poses to the occurrence of PRES syndrome as well.
19:
Dardiotis E, Rikos D, Siokas V, Aloizou AM, Tsouris Z, Sakalakis E, Brotis AG, Bogdanos DP, Hadjigeorgiou GM. Assessment of TREM2 rs75932628 variant's association with Parkinson's disease in a Greek population and Meta-analysis of current data. Int J Neurosci. 2021 Jun;131(6):544-548. doi: 10.1080/00207454.2020.1750388. Epub 2020 Apr 19. PMID: 32250197.
Abstract
Background
Α number of genetic variants are considered to confer susceptibility to Parkinson’s disease (PD). Rs75392628 (R47H), a rare variant of TREM2 gene, has been linked to PD, although its role on PD remains conflicting.
Objective
Detection of a possible contribution of rs75392628 variant of TREM2 gene to PD risk.
Methods
A total of 358 PD patients and 358 healthy controls genotyped for rs75392628. In addition, a meta-analysis was performed by merging our results with those from previous studies.
Results
The rare variant of rs75932628 (47H) of TREM2 gene was not detected on cohort. Meta-analysis of a total of 9271 PD cases and 9777 controls across 14 independent PD data sets from 9 studies, including the present study, did not show any statistically significant effect of rs75392628 on PD risk (ORFE:1.54 95% CI:0.87-2.73. ORRE: 1.54, 95%CI: 0.71-3.32).
20:
Xiromerisiou G, Dadouli K, Marogianni C, Provatas A, Ntellas P, Rikos D, Stathis P, Georgouli D, Loules G, Zamanakou M, Hadjigeorgiou GM. A novel homozygous SACS mutation identified by whole exome sequencing-genotype phenotype correlations of all published cases. J Mol Neurosci. 2020 Jan;70(1):131-141. doi: 10.1007/s12031-019-01410-z. Epub 2019 Nov 7. PMID: 31701440.
https://link.springer.com/article/10.1007/s12031-019-01410-z
Abstract
ARSACS is an autosomal recessive disorder characterized by ataxia, spasticity, and polyneuropathy. A plethora of worldwide distributed mutations have been described so far. Here, we report two brothers, born to non-consanguineous parents, presenting with cerebellar ataxia and peripheral neuropathy. Whole-exome sequencing revealed the presence of a novel homozygous variant in the SACS gene. The variant was confirmed by Sanger sequencing and found at heterozygous state in both parents. This is the first reported mutation in this gene, in Greek population. This case report further highlights the growing trend of identifying genetic diseases previously restricted to single, ethnically isolated regions in many different ethnic groups worldwide. Additionally, we performed a systematic review of all published cases with SACs mutations. ARSACS seems to be an important cause of ataxia and many different types of mutations have been identified, mainly located in exon 10. We evaluated the mutation pathogenicity in all previously reported cases to investigate possible phenotype-genotype correlations. We managed to find a correlation between the pathogenicity of mutations, severity of the phenotype, and age of onset of ARSACS. Greater mutation numbers in different populations will be important and mutation-specific functional studies will be essential to identify the pathogenicity of the various ARSACS variants.
21:
Rikos D, Dardiotis E, Aloizou AM, Siokas V, Zintzaras E, Hadjigeorgiou GM. Reporting Quality of Randomized Controlled Trials in Restless Legs Syndrome Based on the CONSORT Statement. Tremor Other Hyperkinet Mov (N Y). 2019 Jun 18;9. doi: 10.7916/d8-0f2v-aq62. PMID: 31413890; PMCID: PMC6691606.
https://pubmed.ncbi.nlm.nih.gov/31413890/
Abstract
Background: Randomized controlled trials (RCTs) are the cornerstone of modern medical research, and their reporting may not always be optimal. The Consolidated Standards of Reporting Trials (CONSORT) statement is an evidence-based means to improve the quality of RCTs' reporting by providing a checklist of recommended items.The aim of this study was to assess the reporting quality of published RCTs on the restless legs syndrome (RLS), based on a checklist arising from the CONSORT statement.
Methods: Medical electronic databases were searched for RCTs involving patients with RLS. Inclusion criteria were follows: articles must have been published in English and RLS patients must have been randomized into a minimum of two treatment cohorts of different medicinal orientations. CONSORT-recommended items were marked as "reported" or "not reported," and an overall CONSORT compliance metric was calculated. Comparisons among different time periods, CONSORT-endorsing and non-endorsing, and different levels of impact factor journals were made.
Results: Fifty-four eligible trials, published in 21 different scientific journals, were found. The average CONSORT compliance score was 56.6% (23.68-84.21%). CONSORT-endorsing journals had a mean CONSORT compliance of 58.47%, whereas non-endorsing journals had a mean CONSORT compliance of 50.4%. The median CONSORT compliance for articles published in low- (IF<2), medium- (IF 2-7), and high-ranked (IF>7) journals was 52.63, 56.57, and 59.21%, respectively. Only 14 of the 38 CONSORT items (36.8%) were reported in >75% of the articles.
Discussion: This study shows that the reporting of RLS-related RCTs is suboptimal, regardless of the time period, the quality of the publishing journal, and the endorsing or non-endorsing of the CONSORT statement.
22:
Rikos D, Siokas V, Aloizou AM, Tsouris Z, Aslanidou P, Koutsis G, Anagnostouli M, Bogdanos DP, Grigoriadis N, Hadjigeorgiou GM, Dardiotis E. TREM2 R47H (rs75932628) variant is unlikely to contribute to Multiple Sclerosis susceptibility and severity in a large Greek MS cohort. Mult Scler Relat Disord. 2019 Oct;35:116-118. doi: 10.1016/j.msard.2019.07.007. Epub 2019 Jul 20. PMID: 31362167.
https://www.msard-journal.com/article/S2211-0348(19)30301-3/fulltext
Abstract
Background
Multiple Sclerosis is a multifactorial autoimmune disease of the central nervous system, characterized by focal inflammation, demyelination and secondary axonal injury. TREM2 is a signaling protein which participates in the innate immune system by implication to inflammation, proliferation and phagocytosis. The R47H (rs75392628) rare variant of the TREM2 gene has been related to various neurological diseases and leads to impaired signaling, lipoprotein binding, lipoprotein uptake and surface uptake.
Aim
To assess the role of TREM2 rs75932628 on MS risk through a genetic candidate gene association case-control study in a Greek population.
Methods
1246 MS cases and 398 controls were genotyped for this variant.
Results
No MS or healthy subjects carried the variant.
Conclusion
This variant does not seem to play a determining role in the pathogenesis of MS, although further studies examining the presence of TREM2 mutations in other, phylogenetically different populations and the epigenetic regulation of this gene are needed in order to thoroughly investigate its role in MS.
23:
Marogianni C, Rikos D, Provatas A, Dadouli K, Ntellas P, Tsitsi P, Patrinos G, Dardiotis E, Hadjigeorgiou G, Xiromerisiou G. The role of C9orf72 in neurodegenerative disorders: a systematic review, an updated meta-analysis, and the creation of an online database. Neurobiol Aging. 2019 Dec;84:238.e25-238.e34. doi: 10.1016/j.neurobiolaging.2019.04.012. Epub 2019 Apr 24. PMID: 31126629.
https://www.sciencedirect.com/science/article/pii/S0197458019301198?via%3Dihub
Abstract
A pathologic expansion of a noncoding GGGGCC hexanucleotide repeat of the C9orf72 gene has been strongly associated with familial amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD) cases predominantly in Caucasian populations. In the last decade, scientific interest had been drawn to this gene and many studies conducted have shown a possible correlation with other neurodegenerative diseases as well. We performed an extensive literature search for C9orf72 mutation and its frequency in various neurological and psychiatric diseases. In addition, we performed a meta-analysis of the data related to ALS and familial ALS. An online cloud-based database and an interactive map were developed. The overall mutation frequency of C9orf72 is 20% for familial FTD, 16% for familial ALS and around 6%–8% for sporadic ALS and FTD. The updated meta-analysis that we performed showed that the pooled frequency of C9orf72 repeat expansion in patients with familial ALS was 23% (CI: 18%–28%) and in patients with sporadic ALS 3% (CI: 3%–4%). The subgroup analysis regarding the origin of the population revealed significant differences between Caucasian and Asian patients. Our analysis supports the direct causal relation of the C9orf72 expansion in ALS and FTD. On the contrary, the role of C9orf72 in other neurodegenerative disorders remains controversial. The system that we developed—the online database and the interactive map—is hopefully a stepping stone for an ever-growing platform that will aid scientists from all over the world in contributing to the meta-analysis of C9orf72-related publications.
24:
Dardiotis E, Karampinis E, Siokas V, Aloizou AM, Rikos D, Ralli S, Papadimitriou D, Bogdanos DP, Hadjigeorgiou GM. ERCC6L2 rs591486 polymorphism and risk for amyotrophic lateral sclerosis in Greek population. Neurol Sci. 2019 Jun;40(6):1237-1244. doi: 10.1007/s10072-019-03825-3. Epub 2019 Mar 16. PMID: 30879219.
https://link.springer.com/article/10.1007/s10072-019-03825-3
Abstract
Background
Α number of genetic variants have been associated with amyotrophic lateral sclerosis (ALS). A recent study supports that rs591486 across the ERCC6L2 gene and exposure to pesticides seem to have a joint effect on the development of Parkinson’s disease, a disease which shares a few common characteristics with ALS.
Objective
To detect a possible contribution of rs591486 ERCC6L2 to ALS.
Methods
A total of 155 patients with ALS and 155 healthy controls were included in the study and genotyped for rs591486. Using logistic regression analyses (crude and adjusted for age and sex), rs591486 was tested for association with ALS risk. Subgroup analysis based on ALS site of onset was also performed. Cox regression analysis was applied in order for the effect of ERCC6L2 rs591486 on ALS age of onset to be tested.
Results
Adjusted analysis showed that ERCC6L2 rs591486 was associated with an increased risk of ALS development, in dominant [odds ratio, OR (95% confidence interval, CI) 2.15 (1.04–4.46), p = 0.037] and over-dominant [OR (95%CI) = 1.91 (1.01–3.60), p = 0.043], modes. Subgroup analysis based on ALS site of onset revealed an association between ERCC6L2 rs591486 and ALS with limb onset. Results for Cox regression analysis indicated that G/A carriers had a lower age of ALS limb onset when compared to G/G carriers.
25:
Hadjigeorgiou GM, Kountra PM, Koutsis G, Tsimourtou V, Siokas V, Dardioti M, Rikos D, Marogianni C, Aloizou AM, Karadima G, Ralli S, Grigoriadis N, Bogdanos D, Panas M, Dardiotis E. Replication study of GWAS risk loci in Greek multiple sclerosis patients. Neurol Sci. 2019 Feb;40(2):253-260. doi: 10.1007/s10072-018-3617-6. Epub 2018 Oct 26. PMID: 30361804.
https://link.springer.com/article/10.1007/s10072-018-3617-6
Abstract
Objectives
To validate in an ethnically homogeneous Greek multiple sclerosis (MS) cohort, genetic risk factors for the disease, identified through a number of previous multi-ethnic genome-wide association studies (GWAS).
Methods
A total of 1228 MS cases and 1014 controls were recruited in the study, from 3 MS centers in Greece. We genotyped 35 susceptibility SNPs that emerged from previous GWAS or meta-analyses of GWAS. Allele and genotype single locus regression analysis, adjusted for gender and site, was performed. Permutation testing was applied to all analyses.
Results
Six polymorphisms reached statistical significance (permutation p value < 0.05). In particular, rs2760524 of LOC105371664, near RGS1 (permutation p value 0.001), rs3129889 of HLA-DRA, near HLA-DRB1 (permutation p value < 1.00e-04), rs1738074 of TAGAP (permutation p value 0.007), rs703842 of METTL1/CYP27B1 (permutation p value 0.008), rs9596270 of DLEU1 (permutation p value < 1.00e-04), and rs17445836 of LincRNA, near IRF8 (permutation p value 0.001) were identified as susceptibility risk factors in our group.
Conclusion
The current study replicated a number of GWAS susceptibility SNPs, which implies that some similarities between the examined Greek population and the MS genetic architecture of the GWAS populations do exist.
26:
Dardiotis E, Aloizou AM, Siokas V, Tsouris Z, Rikos D, Marogianni C, Aschner M, Kovatsi L, Bogdanos DP, Tsatsakis A. Paraoxonase-1 genetic polymorphisms in organophosphate metabolism. Toxicology. 2019 Jan 1;411:24-31. doi: 10.1016/j.tox.2018.10.012. Epub 2018 Oct 22. PMID: 30359673.
https://www.sciencedirect.com/science/article/pii/S0300483X18304803?via%3Dihub
Abstract
Organophosphates (OPs) are a class of chemicals commonly used in agriculture as pesticides, that can often lead to severe toxicity in humans. Paraoxonase-1 (PON1) belongs to a family of A-esterases and hydrolyses several OPs while also serving other biological roles. Two main genetic polymorphisms have been shown to affect enzymatic ability; an A > G transition in the 192nd position (192 Q/R, rs662), and an A > T at codon 55 (55 M/L, rs854560). In this review, we searched PubMed for relevant articles published from its inception till June 2018 and included publications from 1996 to 2018. We aimed to address the distribution of the polymorphisms in various populations, the way they affect enzymatic activity and the possible use of PON1 as a biomarker. The polymorphisms present great heterogeneity between populations, with the data being clearer over 192 Q/R, and this heterogeneity is related to the phylogenetic origins of each population. Concerning enzymatic activity, the different genotypes react better or worse to different OP substrates, with studies presenting a variety of findings. Detecting the “paraoxonase status” of an individual -referring to PON1 function- seems to be important in predicting OP toxicity, as studies have shown that some specific-genotype individuals present symptoms of toxicity in higher rates than others. We are strongly convinced that in order for the scientific community to reach a consensus over which polymorphisms confer susceptibility to toxicity and whether PON1 can eventually be used as a biomarker, more studies need to be carried out, since the data thus far does not seem to reach a universal conclusion.
27:
Sokratous M, Dardiotis E, Bellou E, Tsouris Z, Michalopoulou A, Dardioti M, Siokas V, Rikos D, Tsatsakis A, Kovatsi L, Bogdanos DP, Hadjigeorgiou GM. CpG Island Methylation Patterns in Relapsing-Remitting Multiple Sclerosis. J Mol Neurosci. 2018 Mar;64(3):478-484. doi: 10.1007/s12031-018-1046-x. Epub 2018 Mar 7. PMID: 29516350.
https://link.springer.com/article/10.1007/s12031-018-1046-x
Abstract
DNA methylation may predispose to multiple sclerosis (MS), as aberrant methylation in the promoter regions across the genome seems to underlie several processes of MS. We have currently determined the methylation status of eight genes in relapsing-remitting MS patients. Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) was used to determine the status of 31 CpG islands, located across eight genes, in 33 healthy individuals and 66 MS patients (33 in relapse and 33 in remission). The methylation levels in the examined sites ranged from 0 to 31%. Methylation positivity for RUNX3 and CDKN2A differed significantly between MS patients and healthy controls. Maximum methylation in RUNX3, CDKN2A, SOCS1, and NEUROG1 genes was significantly different between patients and controls. Roc curves demonstrated that the appropriate cut-offs to distinguish patients from healthy controls were 2% for RUNX3 (OR 3.316, CI 1.207–9.107, p = 0.024) and 3% for CDKN2A (OR 3.077, CI 1.281–7.39, p = 0.018). No difference in methylation was observed between patients in relapse and patients in remission, in any of the genes examined. Methylation patterns of RUNX3 and CDKN2A may be able to distinguish between MS patients and healthy controls, but not between MS patients in relapse and in remission.
28:
Dardiotis E, Siokas V, Pantazi E, Dardioti M, Rikos D, Xiromerisiou G, Markou A, Papadimitriou D, Speletas M, Hadjigeorgiou GM. A novel mutation in TREM2 gene causing Nasu-Hakola disease and review of the literature. Neurobiol Aging. 2017 May;53:194.e13-194.e22. doi: 10.1016/j.neurobiolaging.2017.01.015. Epub 2017 Jan 20. PMID: 28214109.
https://www.sciencedirect.com/science/article/pii/S0197458017300234?via%3Dihub
Abstract
Nasu-hakola disease (NHD) is a rare disease characterized by bone cysts and fractures, frontal lobe syndrome, and progressive presenile dementia. NHD may be the prototype of primary microglial disorders of the CNS or, as they have been coined, “microgliopathies”. Mutations in TREM2 and TYROBP genes are known to cause NHD. Interestingly, recent evidence-associated rare genetic variants of TREM2 gene with increased risk of Alzheimer's disease, frontotemporal dementia, amyotrophic lateral sclerosis, and Parkinson's disease. Here, we report a 33-year-old Greek female with phenotype suggestive of NHD. Full gene sequencing of the TREM2 and TYROBP genes revealed a novel mutation in exon 2 of TREM2 gene, namely c.244G>T (p.W50C) and heterozygosity in the parents and her brother. This report extends the range of TREM2 mutations that cause NHD phenotype. In addition, we provide a comprehensive review of all reported in the literature TREM2 gene mutations and the respective wide spectrum of clinical manifestations that highlights the importance of considering TREM2 gene mutations in a variety of neurodegenerative phenotypes.
29:
Siokas V, Dardiotis E, Tsironi EE, Tsivgoulis G, Rikos D, Sokratous M, Koutsias S, Paterakis K, Deretzi G, Hadjigeorgiou GM. The Role of TOR1A Polymorphisms in Dystonia: A Systematic Review and Meta-Analysis. PLoS One. 2017 Jan 12;12(1):e0169934. doi: 10.1371/journal.pone.0169934. PMID: 28081261; PMCID: PMC5231385.
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0169934
Abstract
Importance
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.
Methods
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.
Results
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)].
Conclusions
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.
30:
Rikos D, Dardiotis E, Tsivgoulis G, Zintzaras E, Hadjigeorgiou GM. Reporting quality of randomized-controlled trials in multiple sclerosis from 2000 to 2015, based on CONSORT statement. Mult Scler Relat Disord. 2016 Sep;9:135-9. doi: 10.1016/j.msard.2016.07.013. Epub 2016 Jul 27. PMID: 27645361.
https://www.msard-journal.com/article/S2211-0348(16)30122-5/fulltext
Abstract
Background
Randomized controlled trials (RCTs) are the best tool to evaluate the effectiveness of clinical interventions. The CONSORT (Consolidated Standards of Reporting Trials) statement is an evidence-based approach to improve the quality of RCTs reporting.
Objective
To evaluate the reporting quality of published RCTs concerning multiple sclerosis from 2000 to 2015 according to a checklist based on the CONSORT statement.
Methods
Electronic databases were searched for English-language RCTs involving patients with multiple sclerosis (MS). Trials were considered eligible when participants were randomly assigned to at least two medicinal treatment arms and included patients with MS. Quality of reporting was assessed using a 39–item questionnaire based on the CONSORT checklist. Articles were grouped in three 5-year periods and comparisons were made using descriptive statistics.
Results and conclusion
The search identified 102 eligible articles for analysis. 20 of the 38 items of the checklist (52.6%) were addressed in 75% or more of the studies. Reporting of more than 75% of CONSORT items (>75% CONSORT compliance) was increased during the three five-year time periods from 2000 to 2015 (p<0.05).
Conclusions
Quality of reporting in RCTs focusing on multiple sclerosis is showing improvement over time, but still remains unsatisfactory. Further improvement of reporting is necessary to assess the validity of clinical research.
Εκπαίδευση
2000-2006
Αριστοτέλειο
Πανεπιστήμιο
Θεσσαλονίκης
Ιατρική Σχολή
Στρατιωτική Σχολή Αξιωματικών Σωμάτων
2014-2015
Πανεπιστήμιο
Θεσσαλίας
Μεταπτυχιακό Δίπλωμα Σπουδών
"Βιοστατιστική, Βιοπληροφρική και μεθοδολογία της Έρευνας"
2016-2022
Πανεπιστήμιο Θεσσαλίας
Διδακτορική Διατριβή
"Γενωμική Σύγκλειση στη νόσο του Parkinson"
