Unraveling the Possible Routes of SARS-COV-2 Invasion into the Central Nervous System

Purpose of Review: To describe the possible neuroinvasion pathways of Severe Acute Respiratory Syndrome-related Coronavirus-2 (SARS-CoV-2), the virus responsible for the Coronavirus disease-19 (Covid-19) pandemic. Recent Findings: We present data regarding the family of Coronaviruses (CoVs) and the central nervous system (CNS), and describe parallels between SARS-CoV-2 and other members of the family, which have been investigated in more depth and combine these findings with the recent advancements regarding SARS-CoV-2. Summary: SARS-CoV-2 like other CoVs is neuroinvasive, neurotropic and neurovirulent. Two main pathways of CNS penetration seem to be the strongest candidates, the hematogenous and the neuronal. Τhe olfactory route in particular appears to play a significant role in neuroinvasion of coronaviruses and SARS-CoV-2, as well. However, existing data suggest that other routes, involving the nasal epithelium in general, lymphatic tissue and the CSF may also play roles in SARS-CoV-2 invasion into the CNS

Study of genetic biomarkers in patients with multiple sclerosis

Introduction: Multiple sclerosis (MS) is a chronic disease of the central nervous system (CNS). Myeloid lineage cells (microglia and macrophages) may participate in the pathogenic mechanisms leading to MS. CD33 rs3865444 is a promoter variant previously associated with Alzheimer’s disease, whose role in MS remains obscure. Adenosine receptor subtype A2a (ADORA2A) and cytochrome P450 1A2 (CYP1A2) are involved into pathophysiological pathways such as caffeine metabolism and oxidative stress, which are associated with neurodegeneration and neuroinflammation. The aim of the current study was to examine the possible association between the CD33 rs3865444, the ADORA2A rs5760423 and the CYP1A2 rs762551 genetic variants and MS.Methods: We genotyped 1396 patients with MS and 400 healthy controls for the presence of the CD33 rs3865444, the ADORA2A rs5760423 and the CYP1A2 rs762551 variants. The SNPStats software was used to calculate odds ratios (ORs) with the respective 95% confidence intervals (CIs), assuming five genetic models (co-dominant, dominant, recessive, over-dominant, and log-additive), with the G allele as the reference allele, for CD33 rs3865444 and ADORA2A rs5760423, whereas for CYP1A2 rs762551 the reference allele was A. The value of 0.05 was set as the threshold for statistical significance.Results: CD33 rs3865444 was associated with MS risk in the dominant (GG vs. GT + TT; OR (95% C.I.) = 0.79 (0.63–0.99), p = 0.041) and the over-dominant (GG + TT vs. GT; OR (95% C.I.) = 0.77 (0.61–0.97), p = 0.03) modes of inheritance. Given that the GG genotype was more frequent, and the GT genotype was less frequent in MS patients compared to controls the observed difference in MS risk may be stemming from either the GG (as a risk factor) or the GT (as a protective factor) genotype of CD33 rs3865444. Furthermore, the ADORA2A rs5760423 and the CYP1A2 rs762551 variants were not associated with MS risk.Conclusions: Our preliminary results suggest a possible contribution of CD33 rs3865444 to MS. Therefore, larger multiethnic studies should be conducted, investigating the role of CD33 rs3865444 in MS.Εισαγωγή: Η πολλαπλή σκλήρυνση (ΠΣ) είναι μια χρόνια νόσος του κεντρικού νευρικού συστήματος (ΚΝΣ). Τα κύτταρα της μυελικής σειράς (μικρογλοιακά κύτταρα και μακροφάγα) μπορεί να συμμετέχουν στους παθογενετικούς μηχανισμούς της ΠΣ. Το CD33 rs3865444 είναι μια μετάλλαξη του υποκινητή που έχει συσχετιστεί με τη νόσο Alzheimer, του οποίου ο ρόλος στη ΠΣ παραμένει ασαφής. Ο υποδοχέας της αδενοσίνης A2a (ADORA2A) και το κυτόχρωμα P450 1A2 (CYP1A2) εμπλέκονται σε μονοπάτια όπως το οξειδωτικό στρες και ο μεταβολισμός της καφεΐνης, που σχετίζονται με τη νευροεκφύλιση και τη νευροφλεγμονή. Ο στόχος αυτής της μελέτης ήταν να διερευνήσει την πιθανή συσχέτιση μεταξύ των γενετικών παραλλαγών του CD33 rs3865444, του ADORA2A rs5760423 και του CYP1A2 rs762551 και της ΠΣ.Μέθοδοι: Συνολικά γονοτυπήθηκαν 1396 ασθενείς με ΠΣ και 400 υγιείς μάρτυρες για την παρουσία των μεταλλάξεων CD33 rs3865444, ADORA2A rs5760423 και CYP1A2 rs762551. Οι λόγοι πιθανοτήτων (ORs) με τα αντίστοιχα διαστήματα εμπιστοσύνης 95% (CIs), υπολογίστηκαν με το λογισμικό SNPStats, υποθέτοντας πέντε γενετικά μοντέλα (συν-επικρατητικό, επικρατητικό, υπολειπόμενο, υπερεπικρατητικό και log-additive), με το αλληλόμορφο G για το CD33 rs3865444 και ADORA2A rs5760423 ως αλληλόμορφο αναφοράς, και το Α για το CYP1A2 rs762551 ως αλληλόμορφο αναφοράς. Ως όριο στατιστικής σημαντικότητας ορίστηκε η τιμή 0,05.Αποτελέσματα: Το CD33 rs3865444 συσχετίστηκε με τον κίνδυνο ΠΣ στον επικρατητικό (GG έναντι GT + TT; OR (95% C.I.) = 0,79 (0,63–0,99), p = 0,041) και τον υπερεπικρατητικό (GG + TT έναντι GT ; Ή (95% C.I.) = 0,77 (0,61–0,97), p = 0,03) τρόπο κληρονομικότητας. Δεδομένου ότι ο γονότυπος GG ήταν πιο συχνός και ο γονότυπος GT ήταν λιγότερο συχνός σε ασθενείς με ΠΣ σε σύγκριση με τους μάρτυρες, η παρατηρούμενη διαφορά στον κίνδυνο ΠΣ μπορεί να προέρχεται είτε από τον γονότυπο GG (ως παράγοντας κινδύνου) είτε από τον GT (ως προστατευτικός παράγοντας) του CD33 rs3865444. Επιπλέον, οι μεταλλάξεις ADORA2A rs5760423 και CYP1A2 rs762551 δεν συσχετίστηκαν με κίνδυνο ΠΣ.Συμπεράσματα: Τα προκαταρκτικά μας αποτελέσματα υποδηλώνουν πιθανή εμπλοκή του CD33 rs3865444 στον κίνδυνο της ΠΣ. Ως εκ τούτου, είναι ανάγκη να διεξαχθούν μεγαλύτερες πολυκεντρικές μελέτες, για την περαιτέρω διερεύνηση του ρόλου του CD33 rs3865444 στην ΠΣ

Risk Factor Genes in Patients with Dystonia: A Comprehensive Review.

Background: Dystonia is a movement disorder with high heterogeneity regarding phenotypic appearance and etiology that occurs in both sporadic and familial forms. The etiology of the disease remains unknown. However, there is increasing evidence suggesting that a small number of gene alterations may lead to dystonia. Although pathogenic variants to the familial type of dystonia have been extensively reviewed and discussed, relatively little is known about the contribution of single-nucleotide polymorphisms (SNPs) to dystonia. This review focuses on the potential role of SNPs and other variants in dystonia susceptibility. Methods: We searched the PubMed database for peer-reviewed articles published in English, from its inception through January 2018, that concerned human studies of dystonia and genetic variants. The following search terms were included: “dystonia” in combination with the following terms: 1) “polymorphisms” and 2) “SNPs” as free words. Results: A total of 43 published studies regarding TOR1A, BDNF, DRD5, APOE, ARSG, NALC, OR4X2, COL4A1, TH, DDC, DBH, MAO, COMT, DAT, GCH1, PRKRA, MR-1, SGCE, ATP1A3, TAF1, THAP1, GNAL, DRD2, HLA-DRB, CBS, MTHFR, and MS genes, were included in the current review. Discussion: To date, a few variants, which are possibly involved in several molecular pathways, have been related to dystonia. Large cohort studies are needed to determine robust associations between variants and dystonia with adjustment for other potential cofounders, in order to elucidate the pathogenic mechanisms of dystonia and the net effect of the genes

Cognitive Deficits in Myopathies

Myopathies represent a wide spectrum of heterogeneous diseases mainly characterized by the abnormal structure or functioning of skeletal muscle. The current paper provides a comprehensive overview of cognitive deficits observed in various myopathies by consulting the main libraries (Pubmed, Scopus and Google Scholar). This review focuses on the causal classification of myopathies and concomitant cognitive deficits. In most studies, cognitive deficits have been found after clinical observations while lesions were also present in brain imaging. Most studies refer to hereditary myopathies, mainly Duchenne muscular dystrophy (DMD), and myotonic dystrophies (MDs); therefore, most of the overview will focus on these subtypes of myopathies. Most recent bibliographical sources have been preferred

Anti-MOG Positive Bilateral Optic Neuritis and Brainstem Encephalitis Secondary to COVID-19 Infection: A Case Report

(1) Introduction: There have been numerous reports on the neuroinvasive competence of SARS-CoV-2. Here, we present a case with anti-MOG positive bilateral optic neuritis and brainstem encephalitis secondary to COVID-19 infection. Additionally, we present a review of the current literature regarding the manifestation of anti-MOG positive optic neuritis as well as anti-MOG positive encephalitis after COVID-19 infection. (2) Case Report: A 59-year-old female patient, with a recent history of COVID-19 infection, presented a progressive reduction of visual acuity and bilateral retrobulbar pain for the last 20 days. An ophthalmological examination revealed a decreased visual acuity (counting fingers) and a bilateral papilledema. An MRI scan of the brain revealed a mild thickening of the bilateral optic nerves and high-intensity lesions in the medial and right lateral pons. A high titer of IgG and IgM antibodies against SARS-CoV-2 in serum and antibodies against myelin oligodendrocyte glycoprotein (anti-MOG) in serum and CSF were revealed. The diagnosis of anti-MOG brainstem encephalitis and optic neuritis was set. (3) Conclusions: The history of COVID-19 infection should raise awareness about these autoimmune and infection-triggered diseases, such as anti-MOG antibody disease

ADORA2A rs5760423 and CYP1A2 rs762551 Polymorphisms as Risk Factors for Parkinson’s Disease

Background: Parkinson’s disease (PD) is the second commonest neurodegenerative disease. The genetic basis of PD is indisputable. Both ADORA2A rs5760423 and CYP1A2 rs762551 have been linked to PD, to some extent, but the exact role of those polymorphisms in PD remains controversial. Objective: We assessed the role of ADORA2A rs5760423 and CYP1A2 rs762551 on PD risk. Methods: We genotyped 358 patients with PD and 358 healthy controls for ADORA2A rs5760423 and CYP1A2 rs762551. We also merged and meta-analyzed our data with data from previous studies, regarding these two polymorphisms and PD. Results: No significant association with PD was revealed (p > 0.05), for either ADORA2A rs5760423 or CYP1A2 rs762551, in any of the examined genetic model of inheritance. In addition, results from meta-analyses yield negative results. Conclusions: Based on our analyses, it appears rather unlikely that ADORA2A rs5760423 or CYP1A2 rs762551 is among the major risk factors for PD, at least in Greek patients with PD

Multiple Sclerosis: Shall We Target CD33?

Background: Multiple sclerosis (MS) is a chronic disease of the central nervous system (CNS). Myeloid lineage cells (microglia and macrophages) may participate in the pathogenic mechanisms leading to MS. CD33 is a transmembrane receptor, mainly expressed by myeloid lineage cells. CD33 rs3865444 is a promoter variant previously associated with Alzheimer’s disease, whose role in MS remains obscure. Objective: To assess the role of CD33 rs3865444 in MS risk. Methods: We genotyped 1396 patients with MS and 400 healthy controls for the presence of the CD33 rs3865444 variant. Odds ratios (ORs) with the respective 95% confidence intervals (CIs), were calculated with the SNPStats software, assuming five genetic models (co-dominant, dominant, recessive, over-dominant, and log-additive), with the G allele as the reference allele. The value of 0.05 was set as the threshold for statistical significance. Results: CD33 rs3865444 was associated with MS risk in the dominant (GG vs. GT + TT; OR (95% C.I.) = 0.79 (0.63–0.99), p = 0.041) and the over-dominant (GG + TT vs. GT; OR (95% C.I.) = 0.77 (0.61–0.97), p = 0.03) modes of inheritance. Given that the GG genotype was more frequent and the GT genotype was less frequent in MS patients compared to controls—while the observed frequency of the TT genotype did not differ between the two groups—the observed difference in MS risk may be stemming from either the GG (as a risk factor) or the GT (as a protective factor) genotype of CD33 rs3865444. Conclusions: Our preliminary results suggest a possible contribution of CD33 rs3865444 to MS. Therefore, larger multiethnic studies should be conducted, investigating the role of CD33 rs3865444 in MS

<i>ADORA2A rs5760423</i> and <i>CYP1A2 rs762551</i> Polymorphisms as Risk Factors for Parkinson’s Disease

Background: Parkinson’s disease (PD) is the second commonest neurodegenerative disease. The genetic basis of PD is indisputable. Both ADORA2A rs5760423 and CYP1A2 rs762551 have been linked to PD, to some extent, but the exact role of those polymorphisms in PD remains controversial. Objective: We assessed the role of ADORA2A rs5760423 and CYP1A2 rs762551 on PD risk. Methods: We genotyped 358 patients with PD and 358 healthy controls for ADORA2A rs5760423 and CYP1A2 rs762551. We also merged and meta-analyzed our data with data from previous studies, regarding these two polymorphisms and PD. Results: No significant association with PD was revealed (p > 0.05), for either ADORA2A rs5760423 or CYP1A2 rs762551, in any of the examined genetic model of inheritance. In addition, results from meta-analyses yield negative results. Conclusions: Based on our analyses, it appears rather unlikely that ADORA2A rs5760423 or CYP1A2 rs762551 is among the major risk factors for PD, at least in Greek patients with PD

Thinking Outside the Ischemia Box: Advancements in the Use of Multiple Sclerosis Drugs in Ischemic Stroke

Ischemic stroke (IS) is a major cause of death and disability, despite early intervention. Thrombo-inflammation, the inflammatory process triggered by ischemia, is a concept that ties IS with multiple sclerosis (MS), under the wider ‘umbrella’ of neuroinflammation, i.e., the inflammation of the nervous tissue. Drawing from this, numerous studies have explored the potential of MS disease-modifying drugs in the setting of IS. In this review, we present the available studies and discuss their potential in ameliorating IS outcomes. Based on our search, the vast majority of the studies have been conducted on animals, yielding mostly positive results. Two clinical trials involving natalizumab showed that it does not confer any benefits, but four human studies regarding fingolimod have showcased its potential in improving recovery prospects. However, concerns on safety and other issues are raised, and basic questions still need to be answered