The role of melatonin in Multiple Sclerosis

Melatonin is a neurohormone mainly produced by the pineal gland following a circadian rhythm. It is characterized as a pleiotropic factor because it not only regulates the wake–sleep rhythm but also exerts antinociceptive, antidepressant, anxiolytic, and immunomodulating properties. Recent studies suggest that dysregulation of melatonin secretion is associated with the pathogenesis of various autoimmune diseases, such as, rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and multiple sclerosis (MS). MS is an autoimmune disorder characterized by an abnormal immune response directed against the myelin sheath in the central nervous system, demyelination, oligodendrocyte death, and axonal degeneration. Recent evidence reveals that melatonin secretion is dysregulated in MS patients, suggesting that melatonin could be a potential target for therapeutic intervention. Here, we summarize the available literature regarding the role of melatonin in immune processes relevant for experimental autoimmune encephalomyelitis (EAE), MS, and the current clinical trials of melatonin supplementation in MS patients. © 2019, Fondazione Società Italiana di Neurologia

Genes, brain dynamics and art: the genetic underpinnings of creativity in dancing, musicality and visual arts

Creativity, art and artistic creation in music, dance and visual arts are brain activities specific to humans. Their genetic background remained unexplored for years, but many recent studies have uncovered significant associations with cognition-related genes and loci. These studies are summarized in the present article. Creativity is a trait with heavy genetic influences, which are also associated with mental disorders and altruism. Associated genes include dopaminergic, serotoninergic and other genes (a1-antitrypsin, neuregulin, Brain-derived neurotrophic factor). Music is another complex phenotype with important genetic background. Studies in musicians and their families have highlighted the contribution of loci (e.g., 4q22) and specific genes (vasopressin receptor 1α and serotonin transporter). The latter two are also associated with dancing. Although few studies have investigated visual arts, they appear to be influenced by genetic differences, which could explain the increased prevalence of synesthesia in artists and individuals with autism. Lastly, although genes play an important role in creativity and art, epigenetics and the environment should not be overlooked. The genetic exploration of artistic creativity may provide useful knowledge on cognition, behavior and brain function. It may also enable targeted and personalized art therapy in health and disease. © 2021 The Author(s)

Psycho-neuro-endocrino-immunologic issues in multiple sclerosis: a critical review of clinical and therapeutic implications

Multiple sclerosis (MS) is a multifactorial, chronic, immune-mediated, and neurodegenerative disease, having a well-known hypothalamic-pituitary-adrenal (HPA) axis dysfunction. Several hormones have a great impact in the immune dysregulation, psychology, and cognitive status of patients with MS, as also in the fertility and response to treatment. In this comprehensive review, as an introduction, we mention basic data concerning MS: epidemiology, genetics, immunogenetics, epigenetics, pathophysiology, and neuroimmunology. Hormonal components of the disease cascade, mainly glucocorticoids (stress-related hormone), estrogens, prolactin and dehydroepiandrosterone (sex-related hormones), melatonin, and vitamin D, are discussed, aiming at focusing on core data regarding the impact of these hormones in MS pathophysiology, severity of the disease, correlation with comorbid mental disorders, and fertility. A great focus is given in the pre- and post-pregnancy period of MS patients, in the context of the disease-modifying treatments (DMTs) and HPA status, having in mind that there are only very limited knowledge and few papers on this specific life period of these women, having MS. All this data are presented in the main text and also in the workable tables, for the first time, suggesting targeted topics that need to be addressed in the near future. © 2020, Hellenic Endocrine Society

Spastic paretic hemifacial contracture (SPHC) in a patient with multiple sclerosis. A clinical, EMG and neuroimaging study

We present the case of a 42-year-old woman with a 4-year history of definite multiple sclerosis (MS) and sustained contracture of the left hemiface with marked left deviation of the nose, deepened left nasolabial groove, narrowed palpebral fissure and weakness of the contracting muscles. Needle electromyography showed continuous resting activity of irregularly firing motor unit potentials (MUP) in the left orbicularis oculi (OO) and orbicularis oris, but not in the left frontalis. Simultaneous recording of maximal voluntary contraction of the OO on both sides showed marked preponderance on the right. Blink reflex findings were consistent with an injury in the pons, mainly in the vicinity of the left facial nucleus. A magnetic resonance imaging study showed multiple supra- and infra-tentorial white matter lesions, as well as multiple lesions at the level of the pons. Complete recovery was observed after 3months. This condition has been described in cases of brainstem tumor as spastic paretic hemifacial contracture (SPHC). Up to now SPHC has not been explicitly associated with MS and, in this case, it could be arguably attributed to hyperexcitability of the facial neurons due to demyelination of the corticofacial fibers. © 2004 Elsevier SAS. All rights reserved

Massage therapy as a complementary treatment for Parkinson's disease: A Systematic Literature Review

Objective: There is no definite cure for Parkinson's disease (PD); therefore, the goals for symptomatic treatment are to improve quality of life and manage the motor and non-motor symptoms of the disease. Although massage is the one of the commonest used forms of complementary and alternative medicine (CAM), there is no systematically-oriented review focusing specifically on the efficacy of the different massage techniques on PD.Aim of this review was to evaluate the quality of evidence referring to massage therapy for PD. Design: A systematic search was conductedin the MEDLINE database to identify the efficacy of massage on PD between 01/01/1970 and 06/12/2019. Results: A total of 12 studies were analyzed in this systematic review. Massage therapy seems to induce relaxation in most cases, which is accompanied by biological measures involving urine stress hormones. Quality of life has been shown to be improved upon various therapeutic massage styles, involving classical whole-body therapeutic massage and reflexology. Non-motor symptoms, such as sleep disturbances, pain, fatigue, anxiety and depressive symptoms have been demonstrated to be improved upon different massage techniques, including classical deep therapeutic massage, Traditional Japanese (Anma) massage, Thai massage, neuromuscular therapy and Yin Tui Na massage. Regarding motor symptoms, classical therapeutic massage, Traditional Japanese (Anma) massage, Thai massage, and neuromuscular therapy seemed to improve motor symptoms, whereas Yin Tui Na technique combined with acupuncture was associated with worse motor scores. Conclusions: Despite the methodological concerns regarding the existing evidence, there is a wide range of safe massage techniques with beneficial effects on both motor and non-motor symptoms of PD. Longitudinal studies are needed to justify the introduction of massage therapy into clinical practice. © 202

A novel cognitive-behavioral stress management method for multiple sclerosis. A brief report of an observational study

Objectives: Psychological stress is an important risk factor for multiple sclerosis (MS) onset, relapse, neurological symptoms and psychosocial adjustment to the disease. Mounting evidence suggests that stress management could halt the disease progression and improve patients’ wellbeing. The aim of this study was to investigate the effectiveness of a novel cognitive-behavioral stress management technique (called Pythagorean Self-Awareness Intervention–PSAI) routinely used in our clinics in patients with MS. Methods: In this observational study, 148 MS patients receiving PSAI for 8-weeks were compared patients who followed only usual care. Measurements included cognitive function, psychological distress and physical fatigue. Propensity score (PS) methods (given the observational design) and linear mixed models were employed to address study’s endpoints. Results: A total of 128 (86.5%) of MS patients fulfilled the PS criteria for analyses (72 in the PSAI group and 56 in the control group). Patients of tertiary education, longer disease duration, higher cognitive score and psychological distress were more likely to choose to participate in the PSAI group. PSAI patients were found with statistical significant beneficial changes in cognitive speed processing, verbal memory, stress, anxiety, depression and fatigue. Based on the numbers-needed-to-treat of the weighted data, PSAI was particularly effective in improving cognitive speed processing (NNT = 10) and stress (NNT = 12). Discussion: PSAI can benefit cognitive function and psychological distress in MS patients. Future studies should expand these results in randomized trials and by using longer follow-up and MS activity-related endpoints. Abbreviations: BICAMS: Brief International Cognitive Assessment for Multiple Sclerosis BVMT-R: Brief Visuospatial Memory Test Revised CVLT: California Verbal Learning Test DASS: Depression Anxiety Stress Scale EDSS: Expanded Disability Status Scale MS: Multiple Sclerosis NNT: Numbers Needed to Treat PS: Propensity Score PSAI: Pythagorean Self-Awareness Intervention RR: Relapsing Remitting SDMT: Symbol Digits Modalities Test VAS-PF: Visual Analogue Scale Physical Fatigue. © 2018, © 2018 Informa UK Limited, trading as Taylor & Francis Group

Psychosocial and Trauma-Related Stress and Risk of Dementia: A Meta-Analytic Systematic Review of Longitudinal Studies

Stress has deleterious effects on brain health and yet, the prognostic value of psychosocial stress regarding the most common types of dementias, including Alzheimer disease, is still unclear. The primary aim of this systematic review was to explore the association between psychosocial stress and late onset dementia. We classified 24articles from Medline, PsycINFO, CINAHL, and Web of Science, as pertaining toxic categories of psychosocial and trauma-related stress (low socio-economic status [SES] related inequalities, marital status, posttraumatic stress disorder, work stress, “vital exhaustion” [VE], and, combined stressors). Using the Quality of Prognosis Studies in Systematic Reviews tool, we judged the quality of evidence to be low. This systematic review provided some non-robust, yet suggestive evidence that the above psychosocial types of stress are associated with increased risk of dementia in later life. Future robust, longitudinal studies with repeated validated measures of psychosocial stress and dementiaare required to strengthen or refute these findings. © The Author(s) 2020

HLA-DRB1*15:01 and Epstein-Barr virus in a multiple sclerosis patient with psoriasis, nasopharyngeal and breast cancers. Lessons for possible hidden links for autoimmunity and cancer

Background Multiple sclerosis (MS) patients have a low general cancer risk and cases of neoplastic comorbidity are attributed by many researchers in chance, or therapeutical side-effects. Human leucocyte antigen (HLA) class II allele DRB1*15:01 is considered the main genetic factor independently associated with increased susceptibility for MS in Caucasians. Epstein-Barr virus (EBV) has also been proven to be a core triggering factor in MS initiation and progress, mainly in HLA-DRB1*15:01 positive MS patients. Case report We present an exceptional case of a Greek-origin woman, carrying a distinct immunogenetic profile (HLA-A*26:01-Cw*06:02-DRB1*15:01), which gradually developed psoriasis, nasopharyngeal carcinoma (NPC), MS, breast cancer, uterine leiomyoma and other neoplasms. Discussion EBV plays a fundamental role in the pathogenesis of both autoimmunity (i.e. MS) and cancer (i.e. NPC). Our patient's immunogenetic profile included HLA alleles which are associated with psoriasis (Cw*06:02), NPC (A*26:01), MS (DRB1*15:01) and increased risk of MS, in patients carrying EBV (DRB1*15:01). We made a targeted review of the literature finding data supporting an EBV-HLA interaction mechanism behind our patient's unique combination of disorders, suggesting that beyond the standard role of each factor, their combination could act as the hidden link, in initiation or/and comorbidity of autoimmunity and cancer. © 2014 Elsevier B.V

Structural MRI correlates of cognitive function in multiple sclerosis

Background: Cognitive impairment (CI) has been associated with numerous magnetic resonance imaging (MRI) indices in multiple sclerosis (MS) patients. In this study we investigated the association of a large set of 2D and 3D MRI markers with cognitive function in MS. Methods: A sample of 61 RRMS patients (mean age 41.8 ± 10.6 years old, 44 women, mean disease duration 137.9 ± 83.9 months) along with 51 age and gender matched healthy controls was used in this cross-sectional study. Neuropsychological and other tests, along with a large set of 2D/3D MRI evaluations were made. Results: 44.3% of patients had CI. CI patients had more disability, physical fatigue than non-CI patients and more psychological distress than non-CI patients and HCs. Also, CI patients had significantly larger third ventricle width and volume, smaller coprus callosum index and larger lesion volume than non-CI patients. These MRI markers also significantly predicted cognitive scores after adjusting for age and education, explaining about 30.6% of the variance of the total cognitive score. Conclusions: Selected linear and volumetric MRI indices predict cognitive function in MS. Future studies should expand these results by exploring longitudinal changes and producing normative data. © 2018 Elsevier B.V