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Kozák M, Kovács E, Nagy-Vince M, Tóth A, Boczán J. Prevalence of Elevated CK Levels, Myositis-Specific and Myositis-Associated Antibodies, Myositis, and Other Neuromuscular Diseases in Myasthenia Gravis Patients-Experience from an Eastern European Tertiary Center. J Clin Med 2025; 14:2449. [PMID: 40217903 PMCID: PMC11989389 DOI: 10.3390/jcm14072449] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2025] [Revised: 03/25/2025] [Accepted: 04/01/2025] [Indexed: 04/14/2025] Open
Abstract
Background: Myasthenia gravis (MG) and idiopathic inflammatory myopathy (IIM) are autoimmune diseases that affect the musculoskeletal system. The association of the two diseases is rare. Their management is different, so it is important to recognize the concomitant presentation. Methods: In this cross-sectional study, we study the presence of CK elevation, myositis-specific and myositis-associated antibodies (MSA/MAA), and vitamin D levels in a cohort of 101 MG patients. Electromyography, limb magnetic resonance imaging (MRI), and, in some cases, muscle biopsy were performed when IIM was suspected. We reviewed the patients' medical records to access the results of these tests if they had been performed previously. Results: CK elevation was detected in 10 patients (9.9%). We identified one case of anti-Jo-1 antibody-positive polymyositis and two cases of possible myositis. MSA/MAA antibodies were not found in the patients with high CK levels, except for the one with anti-Jo-1-positive IIM. One patient with elevated CK levels had an overlapping muscular dystrophy. MSA/MAA antibodies were detected in 19 patients (18.8%). A total of 37% had high-titer antibodies and concomitant systemic autoimmune diseases, while 63% had low-titer antibodies, most of whom had no systemic autoimmune disease. Low serum vitamin D levels were found in 67.3% of patients. Comparison of myasthenia gravis composite (MGC) scores between patients with low and normal vitamin D levels did not show a statistically significant difference. Conclusions: Our results may raise awareness among neuromuscular specialists caring for MG patients of the possibility of associated myositis or other neuromuscular diseases and the need to assess vitamin D levels. Although deficiency was frequent, its impact on MG severity remains unclear, necessitating further investigation into its immunological relevance.
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Affiliation(s)
- Márk Kozák
- Department of Neurology, Faculty of Medicine, University of Debrecen, 22 Móricz Zsigmond krt., 4032 Debrecen, Hungary;
| | - Edina Kovács
- Department of Developmental Neurology, Szent Margit Budapest Hospital, 132 Bécsi út, 1032 Budapest, Hungary;
| | - Melinda Nagy-Vince
- Division of Clinical Immunology, Faculty of Medicine, University of Debrecen, 22 Móricz Zsigmond krt., 4032 Debrecen, Hungary;
| | - Attila Tóth
- Division of Clinical Physiology, Department of Cardiology, Faculty of Medicine, University of Debrecen, 22 Móricz Zsigmond krt., 4032 Debrecen, Hungary;
| | - Judit Boczán
- Department of Neurology, Faculty of Medicine, University of Debrecen, 22 Móricz Zsigmond krt., 4032 Debrecen, Hungary;
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Zhang T, Zhong J, Ji X, Sun J, Cui Y, Wang S. Vitamin D add on the standard treatment for myasthenia gravis symptoms following total gastrectomy: a case report. BMC Neurol 2024; 24:188. [PMID: 38840065 PMCID: PMC11151543 DOI: 10.1186/s12883-024-03687-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2024] [Accepted: 05/22/2024] [Indexed: 06/07/2024] Open
Abstract
BACKGROUND Myasthenia gravis (MG) is a long-term autoimmune disorder that affects the neuromuscular junction, causing muscle weakness and fatigue as its primary clinical features. Vitamin D is crucial for both the autoimmune response and skeletal muscle function. CASE PRESENTATION Here, we presented a case report documenting the substantial improvement in symptoms experienced by a patient who underwent subtotal gastrectomy for gastric cancer following high-dose Vitamin D supplementation. The patient developed generalized MG two months after the surgery and did not respond adequately to pyridostigmine therapy, experiencing a progressive deterioration of the condition. A significant reduction in vitamin D concentration was observed following subtotal gastrectomy. In response, high-dose vitamin D supplementation was administered to the patient. Within one week of treatment, swallowing symptoms improved, enabling the consumption of a small amount of liquid food. By the second week, substantial swallowing and neck function improvements were evident. After one month, the patient regained the ability to straighten the neck while walking and consumed a regular diet despite persistent difficulties chewing hard food. CONCLUSIONS This case underscores the therapeutic potential of vitamin D in alleviating MG symptoms, particularly in individuals with compromised vitamin D levels following gastrectomy. The observed improvements present a new perspective on the possible involvement of vitamin D supplementation in the management of postoperative MG cases.
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Affiliation(s)
- Tao Zhang
- Department of Acupuncture, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, No.23 Museum Back Street, Dongcheng District, Beijing, 100010, China
- Department of Neurology, Inner Mongolia Hospital affiliated to Beijing Hospital of Traditional Chinese Medicine, Bayannur city, Inner Mongolia Autonomous Region, 015000, China
| | - Junhong Zhong
- Department of Acupuncture, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, No.23 Museum Back Street, Dongcheng District, Beijing, 100010, China
| | - Xu Ji
- Department of Acupuncture, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, No.23 Museum Back Street, Dongcheng District, Beijing, 100010, China
| | - Jingqing Sun
- Department of Acupuncture, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, No.23 Museum Back Street, Dongcheng District, Beijing, 100010, China
| | - Yingxue Cui
- Department of Acupuncture, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, No.23 Museum Back Street, Dongcheng District, Beijing, 100010, China.
| | - Shaosong Wang
- Department of Acupuncture, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, No.23 Museum Back Street, Dongcheng District, Beijing, 100010, China.
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Finocchietti M, Crescioli G, Paoletti O, Brunori P, Sciancalepore F, Tuccori M, Addis A, Vannacci A, Lombardi N, Kirchmayer U, The CAESAR Study Group. Drug Use Patterns in Myasthenia Gravis: A Real-World Population-Based Cohort Study in Italy. J Clin Med 2024; 13:3312. [PMID: 38893023 PMCID: PMC11172965 DOI: 10.3390/jcm13113312] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2024] [Revised: 05/27/2024] [Accepted: 05/30/2024] [Indexed: 06/21/2024] Open
Abstract
Background: In the context of a comparative study of efficacy and safety of drugs used in rare neuromuscular and neurodegenerative diseases (CAESAR-call AIFA_FV_2012-13-14), we assessed the use patterns of drugs indicated for myasthenia gravis (MG). Methods: A retrospective cohort study was conducted based on administrative healthcare data. For a cohort of MG patients, prevalent and incident use of pyridostigmine (Py) and other indicated drugs in the first year after case identification was evaluated. Prevalent combined use of major therapies (azathioprine (Az), prednisone (Pr), vitamin D (Vd)) stratified by Py use was assessed, and a comparison between therapies at the time of MG identification and during the first year of follow-up was performed. Results: We included 2369 MG patients between 2013 and 2019. Among them, prevalent and incident Py users were 38.4% and 22.0%, respectively. In the first year of follow-up, the use of Pr was observed in 74.5% of Py prevalent users and in 82.0% of Py incident users, respectively; the use of Az was observed in 24.9% and 23.0%, respectively; and the use of Vd was observed in 53.3% and 48.2%, respectively. Among 910 Py prevalent users, 13.1% also used Az, Pr, and Vd, while 15.3% used none of these. Among 938 non-Py users, 2.7% used Az, Pr, and Vd, while 53.8% used none of these. During the first year, an increase in combined therapies was evident in incident Py users. Conclusions: Our results suggest that, for some MG patients, there may be a need for treatments that combine a rapid onset of benefit with long-term and consistent disease control. These issues may be addressed by the new treatments currently being developed. To date, more studies are needed to address the heterogeneity, quality, and generalizability of the existing data and to evaluate patterns of use, efficacy, and safety of new or emerging therapies for MG.
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Affiliation(s)
- Marco Finocchietti
- Department of Epidemiology, Lazio Regional Health Service, 00147 Rome, Italy; (M.F.); (A.A.); (U.K.)
| | - Giada Crescioli
- Section of Pharmacology and Toxicology, Department of Neurosciences, Psychology, Drug Research and Child Health, University of Florence, 50122 Florence, Italy; (G.C.); (A.V.)
- Tuscan Regional Centre of Pharmacovigilance, 50139 Florence, Italy;
| | - Olga Paoletti
- Pharmacoepidemiology Unit, Regional Health Agency of Tuscany, 50141 Florence, Italy;
| | - Paola Brunori
- Neurophysiopathology, Perugia Hospital, 06129 Perugia, Italy;
| | - Francesco Sciancalepore
- National Center for Disease Prevention and Health Promotion, Italian National Institute of Health, 00161 Rome, Italy;
| | - Marco Tuccori
- Tuscan Regional Centre of Pharmacovigilance, 50139 Florence, Italy;
- Unit of Pharmacology and Pharmacovigilance, Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy
| | - Antonio Addis
- Department of Epidemiology, Lazio Regional Health Service, 00147 Rome, Italy; (M.F.); (A.A.); (U.K.)
| | - Alfredo Vannacci
- Section of Pharmacology and Toxicology, Department of Neurosciences, Psychology, Drug Research and Child Health, University of Florence, 50122 Florence, Italy; (G.C.); (A.V.)
- Tuscan Regional Centre of Pharmacovigilance, 50139 Florence, Italy;
| | - Niccolò Lombardi
- Section of Pharmacology and Toxicology, Department of Neurosciences, Psychology, Drug Research and Child Health, University of Florence, 50122 Florence, Italy; (G.C.); (A.V.)
- Tuscan Regional Centre of Pharmacovigilance, 50139 Florence, Italy;
| | - Ursula Kirchmayer
- Department of Epidemiology, Lazio Regional Health Service, 00147 Rome, Italy; (M.F.); (A.A.); (U.K.)
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Wang J, Zhou H, Chen H, Feng H, Chang T, Sun C, Guo R, Ruan Z, Bi F, Li J, Wang J, Wang K, Ma G, Lei S, Wang C, Wang Z, Huang F, Zhang S, Wen Q, Wang Y, Sun Y, Li Y, Xie N, Liu H, Jiang Y, Lei L, Fan Z, Su S, Lu Y, Di L, Xu M, Wang M, Chen H, Wang S, Wen X, Zhu W, Duo J, Huang Y, Zheng D, Da Y. Environmental factors affecting the risk of generalization for ocular-onset myasthenia gravis: a nationwide cohort study. QJM 2024; 117:109-118. [PMID: 37802883 DOI: 10.1093/qjmed/hcad225] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2023] [Revised: 09/20/2023] [Indexed: 10/08/2023] Open
Abstract
BACKGROUND The environmental effects on the prognosis of ocular myasthenia gravis (OMG) remain largely unexplored. AIM To investigate the association between specific environmental factors and the generalization of OMG. DESIGN The cohort study was conducted in China based on a nationwide multicenter database. METHODS Adult patients with OMG at onset, who were followed up for at least 2 years until May 2022, were included. We collected data on demographic and clinical factors, as well as environmental factors, including latitude, socioeconomic status (per capita disposable income [PDI] at provincial level and education) and smoking. The study outcome was the time to the development of generalized myasthenia gravis (GMG). Cox models were employed to examine the association between environmental exposures and generalization. Restricted cubic spline was used to model the association of latitude with generalization risk. RESULTS A total of 1396 participants were included. During a median follow-up of 5.15 (interquartile range [IQR] 3.37-9.03) years, 735 patients developed GMG within a median of 5.69 (IQR 1.10-15.66) years. Latitude of 20-50°N showed a U-shaped relation with generalization risk, with the lowest risk at around 30°N; both higher and lower latitudes were associated with the increased risk (P for non-linearity <0.001). Living in areas with lower PDI had 1.28-2.11 times higher risk of generalization. No significant association was observed with education or smoking. CONCLUSIONS Latitude and provincial-level PDI were associated with the generalization of OMG in China. Further studies are warranted to validate our findings and investigate their potential applications in clinical practice and health policy.
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Affiliation(s)
- Jingsi Wang
- Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Hongyu Zhou
- Department of Neurology, West China Hospital, Sichuan University, Chengdu, China
| | - Hongxi Chen
- Department of Neurology, West China Hospital, Sichuan University, Chengdu, China
| | - Huiyu Feng
- Department of Neurology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Ting Chang
- Department of Neurology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China
| | - Chao Sun
- Department of Neurology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China
| | - Rongjing Guo
- Department of Neurology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China
| | - Zhe Ruan
- Department of Neurology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China
| | - Fangfang Bi
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, China
| | - Jing Li
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, China
| | - Jianwen Wang
- Department of Neurology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Kang Wang
- Department of Neurology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Gaoting Ma
- Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Shaoyuan Lei
- Department of Evidence-Based Medicine, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Chunxiu Wang
- Department of Evidence-Based Medicine, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Zhihong Wang
- National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Feifei Huang
- National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Shu Zhang
- Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Qi Wen
- Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Yaye Wang
- Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Yanan Sun
- Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Yun Li
- Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Nairong Xie
- Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Haoran Liu
- Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Yuting Jiang
- Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Lin Lei
- Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Zhirong Fan
- Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Shengyao Su
- Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Yan Lu
- Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Li Di
- Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Min Xu
- Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Min Wang
- Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Hai Chen
- Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Suobin Wang
- Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Xinmei Wen
- Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Wenjia Zhu
- Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Jianying Duo
- Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Yue Huang
- Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Deqiang Zheng
- Department of Epidemiology and Health Statistics, School of Public Health, Capital Medical University, Beijing, China
| | - Yuwei Da
- Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China
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Di Molfetta IV, Bordoni L, Gabbianelli R, Sagratini G, Alessandroni L. Vitamin D and Its Role on the Fatigue Mitigation: A Narrative Review. Nutrients 2024; 16:221. [PMID: 38257114 PMCID: PMC10818509 DOI: 10.3390/nu16020221] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2023] [Revised: 01/02/2024] [Accepted: 01/04/2024] [Indexed: 01/24/2024] Open
Abstract
Vitamin D has historically been associated with bone metabolism. However, over the years, a growing body of evidence has emerged indicating its involvement in various physiological processes that may influence the onset of numerous pathologies (cardiovascular and neurodegenerative diseases, rheumatological diseases, fertility, cancer, diabetes, or a condition of fatigue). This narrative review investigates the current knowledge of the pathophysiological mechanisms underlying fatigue and the ways in which vitamin D is implicated in these processes. Scientific studies in the databases of PubMed, Scopus, and Web of Science were reviewed with a focus on factors that play a role in the genesis of fatigue, where the influence of vitamin D has been clearly demonstrated. The pathogenic factors of fatigue influenced by vitamin D are related to biochemical factors connected to oxidative stress and inflammatory cytokines. A role in the control of the neurotransmitters dopamine and serotonin has also been demonstrated: an imbalance in the relationship between these two neurotransmitters is linked to the genesis of fatigue. Furthermore, vitamin D is implicated in the control of voltage-gated calcium and chloride channels. Although it has been demonstrated that hypovitaminosis D is associated with numerous pathological conditions, current data on the outcomes of correcting hypovitaminosis D are conflicting. This suggests that, despite the significant involvement of vitamin D in regulating mechanisms governing fatigue, other factors could also play a role.
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Affiliation(s)
- Ippolita Valentina Di Molfetta
- Chemistry Interdisciplinary Project, School of Pharmacy, University of Camerino, Via Madonna delle Carceri, 62032 Camerino, Italy; (I.V.D.M.); (L.A.)
| | - Laura Bordoni
- Unit of Molecular Biology and Nutrigenomics, School of Pharmacy, University of Camerino, Via Gentile III da Varano, 62032 Camerino, Italy; (L.B.); (R.G.)
| | - Rosita Gabbianelli
- Unit of Molecular Biology and Nutrigenomics, School of Pharmacy, University of Camerino, Via Gentile III da Varano, 62032 Camerino, Italy; (L.B.); (R.G.)
| | - Gianni Sagratini
- Chemistry Interdisciplinary Project, School of Pharmacy, University of Camerino, Via Madonna delle Carceri, 62032 Camerino, Italy; (I.V.D.M.); (L.A.)
| | - Laura Alessandroni
- Chemistry Interdisciplinary Project, School of Pharmacy, University of Camerino, Via Madonna delle Carceri, 62032 Camerino, Italy; (I.V.D.M.); (L.A.)
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Wright TJ, Pyles RB, Sheffield-Moore M, Deer RR, Randolph KM, McGovern KA, Danesi CP, Gilkison CR, Ward WW, Vargas JA, Armstrong PA, Lindsay SE, Zaidan MF, Seashore J, Wexler TL, Masel BE, Urban RJ. Low growth hormone secretion associated with post-acute sequelae SARS-CoV-2 infection (PASC) neurologic symptoms: A case-control pilot study. Mol Cell Endocrinol 2024; 579:112071. [PMID: 37816478 DOI: 10.1016/j.mce.2023.112071] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2023] [Revised: 09/04/2023] [Accepted: 09/16/2023] [Indexed: 10/12/2023]
Abstract
OBJECTIVE To determine if patients that develop lingering neurologic symptoms of fatigue and "brain fog" after initial recovery from coronavirus disease 2019 (COVID-19) have persistent low growth hormone (GH) secretion as seen in other conditions with similar symptom etiology. DESIGN In this case-control observational pilot study, patients reporting lingering neurologic post-acute sequelae of SARS-CoV-2 (PASC, n = 10) symptoms at least 6 months after initial infection were compared to patients that recovered from COVID-19 without lingering symptoms (non-PASC, n = 13). We compared basic blood chemistry and select metabolites, lipids, hormones, inflammatory markers, and vitamins between groups. PASC and non-PASC subjects were tested for neurocognition and GH secretion, and given questionnaires to assess symptom severity. PASC subjects were also tested for glucose tolerance and adrenal function. RESULTS PASC subjects reported significantly worse fatigue, sleep quality, depression, quality of life, and gastrointestinal discomfort compared to non-PASC. Although PASC subjects self-reported poor mental resilience, cognitive testing did not reveal significant differences between groups. Neurologic PASC symptoms were not linked to inflammatory markers or adrenal insufficiency, but were associated with reduced growth hormone secretion. CONCLUSIONS Neurologic PASC symptoms are associated with gastrointestinal discomfort and persistent disruption of GH secretion following recovery from acute COVID-19. (www. CLINICALTRIALS gov; NCT04860869).
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Affiliation(s)
- Traver J Wright
- Department of Internal Medicine, The University of Texas Medical Branch, Galveston, Texas, 77555, USA
| | - Richard B Pyles
- Department of Pediatrics, The University of Texas Medical Branch, Galveston, Texas, 77555, USA
| | - Melinda Sheffield-Moore
- Department of Internal Medicine, The University of Texas Medical Branch, Galveston, Texas, 77555, USA
| | - Rachel R Deer
- Department of Nutrition, Metabolism, and Rehabilitation Sciences, The University of Texas Medical Branch, Galveston, Texas, 77555, USA
| | - Kathleen M Randolph
- Department of Internal Medicine, The University of Texas Medical Branch, Galveston, Texas, 77555, USA
| | - Kristen A McGovern
- Department of Internal Medicine, The University of Texas Medical Branch, Galveston, Texas, 77555, USA
| | - Christopher P Danesi
- Department of Internal Medicine, The University of Texas Medical Branch, Galveston, Texas, 77555, USA
| | - Charles R Gilkison
- Department of Internal Medicine, The University of Texas Medical Branch, Galveston, Texas, 77555, USA
| | - Weston W Ward
- School of Medicine, The University of Texas Medical Branch, Galveston, Texas, 77555, USA
| | - Jayson A Vargas
- School of Medicine, The University of Texas Medical Branch, Galveston, Texas, 77555, USA
| | - Peyton A Armstrong
- School of Medicine, The University of Texas Medical Branch, Galveston, Texas, 77555, USA
| | - Sarah E Lindsay
- Department of Internal Medicine, The University of Texas Medical Branch, Galveston, Texas, 77555, USA
| | - Mohammed F Zaidan
- Department of Internal Medicine, The University of Texas Medical Branch, Galveston, Texas, 77555, USA
| | - Justin Seashore
- Department of Internal Medicine, The University of Texas Medical Branch, Galveston, Texas, 77555, USA
| | - Tamara L Wexler
- Department of Rehabilitation Medicine, NYU Grossman School of Medicine, New York, 10016, USA; Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, 19104, USA
| | - Brent E Masel
- Department of Neurology, The University of Texas Medical Branch, Galveston, Texas, 77555, USA; Centre for Neuro Skills, Bakersfield, California, 93313, USA
| | - Randall J Urban
- Department of Internal Medicine, The University of Texas Medical Branch, Galveston, Texas, 77555, USA.
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Huang EJC, Wu MH, Wang TJ, Huang TJ, Li YR, Lee CY. Myasthenia Gravis: Novel Findings and Perspectives on Traditional to Regenerative Therapeutic Interventions. Aging Dis 2023; 14:1070-1092. [PMID: 37163445 PMCID: PMC10389825 DOI: 10.14336/ad.2022.1215] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2022] [Accepted: 12/15/2022] [Indexed: 05/12/2023] Open
Abstract
The prevalence of myasthenia gravis (MG), an autoimmune disorder, is increasing among all subsets of the population leading to an elevated economic and social burden. The pathogenesis of MG is characterized by the synthesis of autoantibodies against the acetylcholine receptor (AChR), low-density lipoprotein receptor-related protein 4 (LRP4), or muscle-specific kinase at the neuromuscular junction, thereby leading to muscular weakness and fatigue. Based on clinical and laboratory examinations, the research is focused on distinguishing MG from other autoimmune, genetic diseases of neuromuscular transmission. Technological advancements in machine learning, a subset of artificial intelligence (AI) have been assistive in accurate diagnosis and management. Besides, addressing the clinical needs of MG patients is critical to improving quality of life (QoL) and satisfaction. Lifestyle changes including physical exercise and traditional Chinese medicine/herbs have also been shown to exert an ameliorative impact on MG progression. To achieve enhanced therapeutic efficacy, cholinesterase inhibitors, immunosuppressive drugs, and steroids in addition to plasma exchange therapy are widely recommended. Under surgical intervention, thymectomy is the only feasible alternative to removing thymoma to overcome thymoma-associated MG. Although these conventional and current therapeutic approaches are effective, the associated adverse events and surgical complexity limit their wide application. Moreover, Restivo et al. also, to increase survival and QoL, further recent developments revealed that antibody, gene, and regenerative therapies (such as stem cells and exosomes) are currently being investigated as a safer and more efficacious alternative. Considering these above-mentioned points, we have comprehensively reviewed the recent advances in pathological etiologies of MG including COVID-19, and its therapeutic management.
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Affiliation(s)
- Evelyn Jou-Chen Huang
- Department of Ophthalmology, Taipei Medical University Hospital, Taipei, Taiwan.
- Department of Ophthalmology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
| | - Meng-Huang Wu
- Department of Orthopedics, Taipei Medical University Hospital, Taipei, Taiwan.
- Department of Orthopaedics, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
| | - Tsung-Jen Wang
- Department of Ophthalmology, Taipei Medical University Hospital, Taipei, Taiwan.
- Department of Ophthalmology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
| | - Tsung-Jen Huang
- Department of Orthopedics, Taipei Medical University Hospital, Taipei, Taiwan.
- Department of Orthopaedics, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
| | - Yan-Rong Li
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Linkou Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Taoyuan, Taiwan.
| | - Ching-Yu Lee
- Department of Orthopedics, Taipei Medical University Hospital, Taipei, Taiwan.
- Department of Orthopaedics, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
- International PhD Program for Cell Therapy and Regeneration Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.
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8
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Fan Y, Huang H, Chen X, Chen Y, Zeng X, Lin F, Chen X. Causal effect of vitamin D on myasthenia gravis: a two-sample Mendelian randomization study. Front Nutr 2023; 10:1171830. [PMID: 37538922 PMCID: PMC10394469 DOI: 10.3389/fnut.2023.1171830] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2023] [Accepted: 07/05/2023] [Indexed: 08/05/2023] Open
Abstract
Introduction Observational studies suggest that vitamin D supplementation may be effective in preventing myasthenia gravis (MG). However, the causal relationship between circulating vitamin D levels and MG remains unclear. This study aimed to examine the genetic causality of circulating vitamin D and MG using data from large population-based genome-wide association studies (GWAS). Methods SNPs (single nucleotide polymorphisms) strongly associated with exposure were selected. Two-sample Mendelian Randomization (MR) was performed with inverse variance weighting (IVW), MR-Egger (Mendelian randomization-Egger), weight median and MR-PRESSO (Mendelian randomization pleiotropy residual sum and outlier) methods. Heterogeneity was tested via IVW and MR-Egger. Pleiotropy was tested using MR-Egger intercept test and MR-PRESSO method. MR-PRESSO was also used to detect outliers. Leave-one-out analysis was used to identify SNPs with potential effect. Reverse MR analysis was also performed. Result In IVW, circulating vitamin D levels had no causal effect on MG [OR = 0.91 (0.67-1.22), p = 0.532] and MG had no causal effect on circulating vitamin D [OR = 1.01 (099-1.02), p = 0.663]. No heterogeneity or pleiotropy was observed (p > 0.05). Other MR methods also agreed with IVW results. Conclusion This study provides the causal relationship between genetically predicted circulating vitamin D levels and MG and provides new insights into the genetics of MG.
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Affiliation(s)
- Yidan Fan
- The First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Huaiying Huang
- The First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Xiangda Chen
- The First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Yuexuan Chen
- The First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Xiashi Zeng
- The First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Fenwei Lin
- Guangdong East Hospital of Guangmei Development Zone Hospital of the Third Affiliated Hospital of Sun Yat-sen University, Meizhou, China
| | - Xu Chen
- The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
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9
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Larrosa-Domínguez M. Vitamin D and myasthenia gravis. Neurologia 2023; 38:61-62. [PMID: 36462625 DOI: 10.1016/j.nrleng.2021.11.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2021] [Accepted: 11/19/2021] [Indexed: 12/02/2022] Open
Affiliation(s)
- M Larrosa-Domínguez
- Universitat Rovira i Virgili, Departamento de Enfermería, Facultad de Enfermería, Tarragona, Spain.
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10
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Wang J, Wu S, Zhang Y, Yang J, Hu Z. Gut microbiota and calcium balance. Front Microbiol 2022; 13:1033933. [PMID: 36713159 PMCID: PMC9881461 DOI: 10.3389/fmicb.2022.1033933] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2022] [Accepted: 11/30/2022] [Indexed: 12/31/2022] Open
Abstract
Microorganisms living on the surface and inside the human body play an important role in the physiological activities of the human body. The largest microecosystem in the human body is the gut microbiome. Calcium disorders are found in many diseases. For example, patients with chronic renal insufficiency present with secondary hyperparathyroidism, which is caused by a calcium imbalance in the body. In addition, calcium dysregulation may affect lipid metabolism in the liver through the calmodulator pathway, leading to cirrhosis, etc. Currently, a considerable number of probiotics have been proven to enhance the body's absorption of calcium. This paper reviews the effects of intestinal flora and related factors such as short-chain fatty acids, estrogen, immune factors and vitamin D on calcium balance.
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Affiliation(s)
- Jiali Wang
- Department of Pulmonary and Critical Care Medicine, Peking University Third Hospital, BeiJing, China
| | - Shuang Wu
- Xiangya School of Medicine, Central South University, Changsha, Hunan, China
| | - Yinshan Zhang
- Xiangya School of Medicine, Central South University, Changsha, Hunan, China
| | - Jiao Yang
- Department of Pathology, Changsha Medical School, Changsha, Hunan, China,*Correspondence: Jiao Yang,
| | - Zhongliang Hu
- Department of Pathology, Xiangya Hospital, Central South University, Changsha, China,Zhongliang Hu,
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11
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Mekky RY, Elemam NM, Eltahtawy O, Zeinelabdeen Y, Youness RA. Evaluating Risk: Benefit Ratio of Fat-Soluble Vitamin Supplementation to SARS-CoV-2-Infected Autoimmune and Cancer Patients: Do Vitamin-Drug Interactions Exist? Life (Basel) 2022; 12:1654. [PMID: 36295089 PMCID: PMC9604733 DOI: 10.3390/life12101654] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2022] [Revised: 10/15/2022] [Accepted: 10/18/2022] [Indexed: 11/17/2022] Open
Abstract
COVID-19 is a recent pandemic that mandated the scientific society to provide effective evidence-based therapeutic approaches for the prevention and treatment for such a global threat, especially to those patients who hold a higher risk of infection and complications, such as patients with autoimmune diseases and cancer. Recent research has examined the role of various fat-soluble vitamins (vitamins A, D, E, and K) in reducing the severity of COVID-19 infection. Studies showed that deficiency in fat-soluble vitamins abrogates the immune system, thus rendering individuals more susceptible to COVID-19 infection. Moreover, another line of evidence showed that supplementation of fat-soluble vitamins during the course of infection enhances the viral clearance episode by promoting an adequate immune response. However, more thorough research is needed to define the adequate use of vitamin supplements in cancer and autoimmune patients infected with COVID-19. Moreover, it is crucial to highlight the vitamin-drug interactions of the COVID-19 therapeutic modalities and fat-soluble vitamins. With an emphasis on cancer and autoimmune patients, the current review aims to clarify the role of fat-soluble vitamins in SARS-CoV-2 infection and to estimate the risk-to-benefit ratio of a fat-soluble supplement administered to patients taking FDA-approved COVID-19 medications such as antivirals, anti-inflammatory, receptor blockers, and monoclonal antibodies.
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Affiliation(s)
- Radwa Y. Mekky
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, October University for Modern Sciences and Arts (MSA University), Cairo 12622, Egypt
| | - Noha M. Elemam
- Sharjah Institute for Medical Research (SIMR), College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates
| | - Omar Eltahtawy
- Molecular Genetics Research Team (MGRT), Pharmaceutical Biology Department, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo 12622, Egypt
| | - Yousra Zeinelabdeen
- Molecular Genetics Research Team (MGRT), Pharmaceutical Biology Department, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo 12622, Egypt
- Faculty of Medical Sciences, University Medical Center Groningen (UMCG), University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands
| | - Rana A. Youness
- Molecular Genetics Research Team (MGRT), Pharmaceutical Biology Department, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo 12622, Egypt
- Biology and Biochemistry Department, School of Life and Medical Sciences, University of Hertfordshire Hosted by Global Academic Foundation, Cairo 12622, Egypt
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12
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Fletcher J, Bishop EL, Harrison SR, Swift A, Cooper SC, Dimeloe SK, Raza K, Hewison M. Autoimmune disease and interconnections with vitamin D. Endocr Connect 2022; 11:EC-21-0554. [PMID: 35196255 PMCID: PMC9010814 DOI: 10.1530/ec-21-0554] [Citation(s) in RCA: 40] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2022] [Accepted: 02/23/2022] [Indexed: 11/18/2022]
Abstract
Vitamin D has well-documented effects on calcium homeostasis and bone metabolism but recent studies suggest a much broader role for this secosteroid in human health. Key components of the vitamin D system, notably the vitamin D receptor (VDR) and the vitamin D-activating enzyme (1α-hydroxylase), are present in a wide array of tissues, notably macrophages, dendritic cells and T lymphocytes (T cells) from the immune system. Thus, serum 25-hydroxyvitamin D (25D) can be converted to hormonal 1,25-dihydroxyvitamin D (1,25D) within immune cells, and then interact with VDR and promote transcriptional and epigenomic responses in the same or neighbouring cells. These intracrine and paracrine effects of 1,25D have been shown to drive antibacterial or antiviral innate responses, as well as to attenuate inflammatory T cell adaptive immunity. Beyond these mechanistic observations, association studies have reported the correlation between low serum 25D levels and the risk and severity of human immune disorders including autoimmune diseases such as inflammatory bowel disease, multiple sclerosis, type 1 diabetes and rheumatoid arthritis. The proposed explanation for this is that decreased availability of 25D compromises immune cell synthesis of 1,25D leading to impaired innate immunity and over-exuberant inflammatory adaptive immunity. The aim of the current review is to explore the mechanistic basis for immunomodulatory effects of 25D and 1,25D in greater detail with specific emphasis on how vitamin D-deficiency (low serum levels of 25D) may lead to dysregulation of macrophage, dendritic cell and T cell function and increase the risk of inflammatory autoimmune disease.
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Affiliation(s)
- Jane Fletcher
- Nutrition Nurses, University Hospitals Birmingham NHS Trust, Queen Elizabeth Hospital Birmingham, Mindelsohn Way, Edgbaston, Birmingham, UK
- School of Nursing, Institute of Clinical Sciences, University of Birmingham, Edgbaston, Birmingham, UK
| | - Emma L Bishop
- Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK
| | - Stephanie R Harrison
- Leeds Institute of Rheumatic and Musculoskeletal Medicine, Chapel Allerton Hospital, Leeds, UK
| | - Amelia Swift
- School of Nursing, Institute of Clinical Sciences, University of Birmingham, Edgbaston, Birmingham, UK
| | - Sheldon C Cooper
- Gastroenterology Department, University Hospitals Birmingham NHS Trust, Queen Elizabeth Hospital Birmingham, Mindelsohn Way, Edgbaston, Birmingham, UK
| | - Sarah K Dimeloe
- Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK
| | - Karim Raza
- Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK
| | - Martin Hewison
- Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK
- Correspondence should be addressed to M Hewison:
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Akkan Suzan A, Kahraman Koytak P, Uluc K, Tanridag T. Physical and mental fatigue in myasthenia gravis and its correlation with other symptoms. Acta Neurol Belg 2022; 122:915-923. [PMID: 35334084 DOI: 10.1007/s13760-022-01919-y] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2021] [Accepted: 03/07/2022] [Indexed: 11/01/2022]
Abstract
INTRODUCTION Muscle weakness and easy fatigability are the clinical hallmarks of myasthenia gravis (MG). However, fatigue perception, which can be seen quite often in myasthenic patients, and its effect on the quality of life, irrespective of motor deficit, has not been elucidated yet. The aim is to evaluate the frequency of fatigue in myasthenic patients with nearly full muscle strength and the effect of fatigue on quality of life by assessing its correlation with other symptoms. METHODS Fifty-three patients with ocular or mild generalized MG in remission or minimal manifestations completed the questionnaires measuring the severity of MG and quality of life (MG Composite Scale and MG-Activities of Daily Living Profile). Both patient group and control group (53 healthy volunteers)completed the scales assessing fatigue [Fatigue Assessment Scale (FAS) and Fatigue Impact Scale (FIS)], depression [Beck Depression Inventory (BDI)] and sleep (Epworth Sleepiness Scale). Disease severity was assessed using MG Foundation of America (MGFA) and MGFA Post-Intervention Status classifications. RESULTS FAS, FIS physical and BDI scores were significantly higher in patients compared to the control group (p = 0.003, p = 0.001, and p = 0.003, respectively) and fatigue was associated with depression and daytime sleepiness. Inpatient group, depressive symptoms and daytime sleepiness were higher in females (p = 0.019 and p = 0.013). The mean values of FIS total and cognitive scores were higher in patients with generalized MG (p = 0.033 and p = 0.045). Fatigue scores correlated with motor signs. DISCUSSION Fatigue can be seen in MG independently from muscle weakness and is an important symptom worsening the quality of life.
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14
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Epidemiology of myasthenia gravis in the province of Ourense (Galicia, Spain). NEUROLOGÍA (ENGLISH EDITION) 2022; 38:75-81. [PMID: 35249845 DOI: 10.1016/j.nrleng.2020.06.013] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2019] [Accepted: 06/12/2020] [Indexed: 11/20/2022] Open
Abstract
INTRODUCTION Myasthenia gravis (MG) is an autoimmune disease affecting nerve transmission at the level of the neuromuscular junction, and typically causes fluctuating muscle weakness. Epidemiological studies show an increase in MG prevalence, particularly among the older population. OBJECTIVE We performed a retrospective epidemiological study to determine the incidence and prevalence of MG in the province of Ourense (Galicia, Spain), characterised by population ageing. MATERIAL AND METHODS Patients were selected from our clinical neuromuscular diseases database by searching for patients with an active prescription for pyridostigmine bromide. Incidence was estimated for the period 2009-2018. We calculated prevalence at 31/12/2018. According to census data for the province of Ourense, the population on 1/1/2019 was 307 651, of whom 96 544 (31.4%) were aged ≥ 65 years. RESULTS We identified 80 cases of MG, with a prevalence rate of 260 cases/1 000 000 population (95% CI, 202.7-316.4), rising to 517.9/1 000 000 population in those aged ≥ 65 (95% CI, 363.2-672.9). Cumulative incidence in the study period was 15.4 cases per 1 000 000 person-years. Early onset (≤ 50 years) was recorded in 29.1% of cases. CONCLUSION The prevalence of MG in our health district is one of the highest published figures, and the disease is highly prevalent in the older population.
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15
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Vitamina D y miastenia gravis. Neurologia 2022. [DOI: 10.1016/j.nrl.2021.11.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
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16
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The Atrophic Effect of 1,25(OH) 2 Vitamin D 3 (Calcitriol) on C2C12 Myotubes Depends on Oxidative Stress. Antioxidants (Basel) 2021; 10:antiox10121980. [PMID: 34943083 PMCID: PMC8750283 DOI: 10.3390/antiox10121980] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Revised: 11/30/2021] [Accepted: 12/07/2021] [Indexed: 11/17/2022] Open
Abstract
Dysfunctional mitochondrial metabolism has been linked to skeletal muscle loss in several physio-pathological states. Although it has been reported that vitamin D (VD) supports cellular redox homeostasis by maintaining normal mitochondrial functions, and VD deficiency often occurs in conditions associated with skeletal muscle loss, the efficacy of VD supplementation to overcome muscle wasting is debated. Investigations on the direct effects of VD metabolites on skeletal muscle using C2C12 myotubes have revealed an unexpected pro-atrophic activity of calcitriol (1,25VD), while its upstream metabolites cholecalciferol (VD3) and calcidiol (25VD) have anti-atrophic effects. Here, we investigated if the atrophic effects of 1,25VD on myotubes depend on its activity on mitochondrial metabolism. The impact of 1,25VD and its upstream metabolites VD3 and 25VD on mitochondria dynamics and the activity of C2C12 myotubes was evaluated by measuring mitochondrial content, architecture, metabolism, and reactive oxygen species (ROS) production. We found that 1,25VD induces atrophy through protein kinase C (PKC)-mediated ROS production, mainly of extramitochondrial origin. Consistent with this, cotreatment with the antioxidant N-acetylcysteine (NAC), but not with the mitochondria-specific antioxidant mitoTEMPO, was sufficient to blunt the atrophic activity of 1,25VD. In contrast, VD3 and 25VD have antioxidant properties, suggesting that the efficacy of VD supplementation might result from the balance between atrophic pro-oxidant (1,25VD) and protective antioxidant (VD3 and 25VD) metabolites.
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17
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Wang L, Zhao XM, Wang FY, Wu JC, Wang Y. Effect of Vitamin D Supplementation on the Prognosis of Post-stroke Fatigue: A Retrospective Cohort Study. Front Neurol 2021; 12:690969. [PMID: 34803866 PMCID: PMC8602338 DOI: 10.3389/fneur.2021.690969] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2021] [Accepted: 09/30/2021] [Indexed: 11/13/2022] Open
Abstract
Objective: We aimed to evaluate the effect of vitamin D supplementation in post-stroke fatigue (PSF) patients with vitamin D deficiency on fatigue symptoms and outcomes. Methods: Patients with primary acute ischemic stroke (AIS) were recruited consecutively from July 2016 to June 2018. Post-stroke fatigue patients were screened out with the Fatigue Severity Scale (FSS) questionnaire, serum concentrations of 25-hydroxyvitamin D [25-(OH)-D] were assessed with enzyme-linked immunosorbent assay (ELISA), and neurological function was evaluated with FSS and modified Rankin Scale (mRS) scoring criteria. Post-stroke fatigue patients with vitamin D deficiency were divided into two groups: a study group in which patients received vitamin D supplementation (cholecalciferol, 600 IU/day) along with usual care, and a control group in which patients received usual care alone. At the end of 1 and 3 months after treatment, all PSE patients accepted re-measurement of serum vitamin D and re-evaluation of fatigue and neurological function. Results: A total of 532 AIS patients were consecutively recruited to participate in this study. Patients without PSF, non-vitamin D deficiency, pre-stroke fatigue, or vitamin D supplementation were excluded from the study. In addition, patients who were lost to follow-up were also excluded. Finally, 139 out of 532 (26.1%) patients with PSF and vitamin D deficiency received vitamin D supplementation treatment. Fatigue Severity Scale score was significantly lower in the study group than in the control group at 1 month (t = -4.731, p < 0.01) and 3 months (t = -7.937, p < 0.01) after treatment. One month after treatment, mRS score in the study group was lower than that in the control group without statistical difference (t = -0.660, p > 0.05), whereas mRS was significantly higher in the study group than in the control group at 3 months after treatment (t = -4.715, p < 0.01). Conclusions: Our results indicated that vitamin D supplementation could improve fatigue symptoms and neurological outcomes in PSF patients with vitamin D deficiency. Subject to replication in other settings, a randomized controlled trial (RCT) might be undertaken to validate the potential beneficial impact of vitamin D supplementation in post-stroke patients found to be vitamin D deficient.
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Affiliation(s)
- Long Wang
- Department of Neurology, The Second People's Hospital of Hefei, Hefei, China.,Department of Neurology, General Hospital of Wan Bei Coal and Electrical Group, Suzhou, China
| | - Xue-Min Zhao
- Department of Neurology, General Hospital of Wan Bei Coal and Electrical Group, Suzhou, China
| | - Fu-Yu Wang
- Department of Pharmacy, The Second People's Hospital of Hefei, Hefei, China
| | - Jun-Cang Wu
- Department of Neurology, The Second People's Hospital of Hefei, Hefei, China
| | - Yu Wang
- Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
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18
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Justo ME, Aldecoa M, Cela E, Leoni J, González Maglio DH, Villa AM, Aguirre F, Paz ML. Low Vitamin D Serum Levels in a Cohort of Myasthenia Gravis Patients in Argentina. Photochem Photobiol 2021; 97:1145-1149. [PMID: 33866582 DOI: 10.1111/php.13432] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2021] [Accepted: 04/12/2021] [Indexed: 11/29/2022]
Abstract
There are limited and controversial studies that address the role of vitamin D (vitD), a vitamin with immunomodulatory effects, in myasthenia gravis (MG), a neuromuscular autoimmune disease. We aimed to assess 25-hydroxy vitamin D (25(OH)D) levels and to evaluate possible associations with the clinical severity and other biomarkers of the disease. Serum levels of 25(OH)D, anti-acetylcholine receptor antibodies and complement factor C5a were measured in MG patients (n = 66) and healthy volunteers (HV) (n = 25). Participants were evaluated through questionnaires to determine vitD intake and sunlight exposure. Severity scores were registered for MG patients. We found an 89.4% of MG individuals with nonsufficient levels of vitD, in comparison with 68.0% in the group of HV (OR = 3.96; P = 0.024). In addition, there was an inverse correlation between 25(OH)D levels and one of the scores (P = 0.037 r = -0.26, CI95 = -0.49 to -0.0087). However, when we compared 25(OH)D median serum levels between MG patients and HV, no statistically significant differences have been found. This is the first report of vitD status in a cohort of Argentinean MG patients, where we found that patients are more likely to have nonsufficient levels of vitD compared to healthy people and that patients with more severe disease have lower levels of vitD.
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Affiliation(s)
- Mariano E Justo
- Facultad de Farmacia y Bioquímica, Departamento de Microbiología, Inmunología, Biotecnología y Genética, Cátedra de Inmunología, Universidad de Buenos Aires, Buenos Aires, Argentina.,Instituto de Estudios de la Inmunidad Humoral "Prof. Dr. Ricardo A. Margni" (IDEHU), CONICET - Universidad de Buenos Aires, Buenos Aires, Argentina
| | - Mayra Aldecoa
- Sección de Neuroinmunología y Electrofisiología, División Neurología, Hospital José María Ramos Mejía, Centro Argentino de Neuroinmunología (CADENI), Facultad de Medicina - Universidad de Buenos Aires, Buenos Aires, Argentina
| | - Eliana Cela
- Facultad de Farmacia y Bioquímica, Departamento de Microbiología, Inmunología, Biotecnología y Genética, Cátedra de Inmunología, Universidad de Buenos Aires, Buenos Aires, Argentina.,Instituto de Estudios de la Inmunidad Humoral "Prof. Dr. Ricardo A. Margni" (IDEHU), CONICET - Universidad de Buenos Aires, Buenos Aires, Argentina
| | - Juliana Leoni
- Instituto de Estudios de la Inmunidad Humoral "Prof. Dr. Ricardo A. Margni" (IDEHU), CONICET - Universidad de Buenos Aires, Buenos Aires, Argentina
| | - Daniel H González Maglio
- Facultad de Farmacia y Bioquímica, Departamento de Microbiología, Inmunología, Biotecnología y Genética, Cátedra de Inmunología, Universidad de Buenos Aires, Buenos Aires, Argentina.,Instituto de Estudios de la Inmunidad Humoral "Prof. Dr. Ricardo A. Margni" (IDEHU), CONICET - Universidad de Buenos Aires, Buenos Aires, Argentina
| | - Andrés M Villa
- Sección de Neuroinmunología y Electrofisiología, División Neurología, Hospital José María Ramos Mejía, Centro Argentino de Neuroinmunología (CADENI), Facultad de Medicina - Universidad de Buenos Aires, Buenos Aires, Argentina
| | - Florencia Aguirre
- Sección de Neuroinmunología y Electrofisiología, División Neurología, Hospital José María Ramos Mejía, Centro Argentino de Neuroinmunología (CADENI), Facultad de Medicina - Universidad de Buenos Aires, Buenos Aires, Argentina
| | - Mariela L Paz
- Facultad de Farmacia y Bioquímica, Departamento de Microbiología, Inmunología, Biotecnología y Genética, Cátedra de Inmunología, Universidad de Buenos Aires, Buenos Aires, Argentina.,Instituto de Estudios de la Inmunidad Humoral "Prof. Dr. Ricardo A. Margni" (IDEHU), CONICET - Universidad de Buenos Aires, Buenos Aires, Argentina
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García Estévez DA, López Díaz LM, Pardo Parrado M, Pérez Lorenzo G, Sabbagh Casado NA, Ozaita Arteche G, Rodríguez Gómez D. Epidemiology of myasthenia gravis in the province of Ourense (Galicia, Spain). Neurologia 2020; 38:S0213-4853(20)30215-2. [PMID: 32900528 DOI: 10.1016/j.nrl.2020.06.011] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2019] [Revised: 05/24/2020] [Accepted: 06/12/2020] [Indexed: 10/23/2022] Open
Abstract
INTRODUCTION Myasthenia gravis (MG) is an autoimmune disease affecting nerve transmission at the level of the neuromuscular junction, and typically causes fluctuating muscle weakness. Epidemiological studies show an increase in MG prevalence, particularly among the older population. OBJECTIVE We performed a retrospective epidemiological study to determine the incidence and prevalence of MG in the province of Ourense (Galicia, Spain), characterised by population ageing. MATERIAL AND METHODS Patients were selected from our clinical neuromuscular diseases database by searching for patients with an active prescription for pyridostigmine bromide. Incidence was estimated for the period 2009-2018. We calculated prevalence at 31/12/2018. According to census data for the province of Ourense, the population on 1/1/2019 was 307,651, of whom 96,544 (31.4%) were aged ≥ 65 years. RESULTS We identified 80 cases of MG, with a prevalence rate of 260 cases/1 000 000 population (95% CI, 202.7-316.4), rising to 517.9/1 000 000 population in those aged ≥ 65 (95% CI, 363.2-672.9). Cumulative incidence in the study period was 15.4 cases per 1 000 000 person-years. Early onset (≤ 50 years) was recorded in 29.1% of cases. CONCLUSION The prevalence of MG in our health district is one of the highest published figures, and the disease is highly prevalent in the older population.
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Affiliation(s)
- D A García Estévez
- Servicio de Neurología, Complejo Hospitalario Universitario de Ourense, Ourense, España.
| | - L M López Díaz
- Servicio de Neurología, Complejo Hospitalario Universitario de Ourense, Ourense, España
| | - M Pardo Parrado
- Servicio de Neurología, Complejo Hospitalario Universitario de Ourense, Ourense, España
| | - G Pérez Lorenzo
- Servicio de Neurología, Complejo Hospitalario Universitario de Ourense, Ourense, España
| | - N A Sabbagh Casado
- Servicio de Neurología, Complejo Hospitalario Universitario de Ourense, Ourense, España
| | - G Ozaita Arteche
- Servicio de Neurología, Complejo Hospitalario Universitario de Ourense, Ourense, España
| | - D Rodríguez Gómez
- Servicio de Neurología, Complejo Hospitalario Universitario de Ourense, Ourense, España
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Fatigue, self-efficacy and psychiatric symptoms influence the quality of life in patients with myasthenia gravis in Tianjin, China. J Clin Neurosci 2020; 79:84-89. [DOI: 10.1016/j.jocn.2020.06.023] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2020] [Revised: 06/09/2020] [Accepted: 06/29/2020] [Indexed: 11/19/2022]
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Rai SK, Gupta TP, Kashid M, Shaki O, Chakrabarty BK, Upreti V. Can self-perceived easy fatigability be a predictor of vitamin D deficiency in young Indian women? J Family Med Prim Care 2020; 9:997-1002. [PMID: 32318457 PMCID: PMC7113952 DOI: 10.4103/jfmpc.jfmpc_862_19] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2019] [Revised: 01/10/2020] [Accepted: 01/13/2020] [Indexed: 12/25/2022] Open
Abstract
Background Easy fatigability is a common presenting complaint in Indian women who visited primary care hospitals. Many medical conditions like cancer, chronic bronchial asthma, prolonged use of glucocorticosteroid, renal disorder, and hypothyroidism have been associated with low levels of vitamin D. Correction of vitamin D level improves the symptom of fatigue. Whether low vitamin D causes fatigue in otherwise healthy women is the subject of research. Aim This prospective nonrandomized and therapeutic study observed the prevalence of hypovitaminosis D in women with fatigue and the effect of correction of vitamin D level in fatigue-like symptoms. Material and Methods One thousand two hundred adult women, who presented in our primary care hospital with complaints of easy fatigue, otherwise no associated medical illness were included. They completed the fatigue assessment questionnaire (FAQ). Patients with hypovitaminosis D received cholecalciferol (60000 IU) therapy for 5 weeks. Scores of pre- and post-treatment FAQs were noted and compared. Results The prevalence of low vitamin D was noted in 84.8% women who presented with main complaints of fatigue. After the correction of vitamin D level, fatigue symptom scores improved significantly (P < 0.001) in 82.6% of the women in all five-subscale categories of the FAQ. Conclusion We observed a high prevalence of low serum vitamin D level in women who presents with fatigue with no medical illness. A significant improvement was noted in the severity of their fatigue symptoms after the correction of vitamin D levels with cholecalciferol therapy.
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Affiliation(s)
- Sanjay Kumar Rai
- Department of Orthopaedics, 151 Base Hospital, Guwahati, Assam, India
| | - Tej Pratap Gupta
- Department of Orthopaedics, 151 Base Hospital, Guwahati, Assam, India
| | - Manoj Kashid
- Department of Orthopaedics, SMBT Medical Colleges, Igatpuri, Nasik, Maharashtra, India
| | - Omna Shaki
- Department of Trauma and Emergency, 151 Base Hospital, Guwahati, Assam, India
| | | | - Vimal Upreti
- Department of Medicine, 151 Base Hospital, Guwahati, Assam, India
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22
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Vitamin D and Demyelinating Diseases: Neuromyelitis Optica (NMO) and Multiple Sclerosis (MS). Autoimmune Dis 2020; 2020:8718736. [PMID: 32373353 PMCID: PMC7187724 DOI: 10.1155/2020/8718736] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2019] [Accepted: 11/30/2019] [Indexed: 12/18/2022] Open
Abstract
Vitamin D deficiency is prevalent in all ages regardless of climate or geographical location and evidence is emerging that the incidence of autoimmune diseases is increasing worldwide. Women make up a large proportion of autoimmune disease diagnoses, underscoring the importance of fully elucidating the complex synergistic relationships between estrogens and vitamin D. Vitamin D receptor-activating drugs appear to enhance remyelination in patients diagnosed with multiple sclerosis (MS) and other demyelinating diseases such as neuromyelitis optica (NMO). This review is intended to update health practitioners about the potential role of vitamin D deficiency demyelination and to motivate future research on dietary recommendations for vitamin D in preventing and treating demyel1nating diseases.
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23
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Murdaca G, Tonacci A, Negrini S, Greco M, Borro M, Puppo F, Gangemi S. Emerging role of vitamin D in autoimmune diseases: An update on evidence and therapeutic implications. Autoimmun Rev 2019; 18:102350. [PMID: 31323357 DOI: 10.1016/j.autrev.2019.102350] [Citation(s) in RCA: 192] [Impact Index Per Article: 32.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2019] [Accepted: 03/08/2019] [Indexed: 12/24/2022]
Abstract
Vitamin D plays a key role in in calcium homeostasis and, thus, provides an important support in bone growth by aiding in the mineralization of the collagen matrix. However, vitamin D performs various immunomodulatory, anti-inflammatory, antioxidant and anti-fibrotic actions. Autoimmune diseases result from an aberrant activation of the immune system, whereby the immune response is directed against harmless self-antigens. Does vitamin D play a role in the pathophysiology of autoimmune diseases? And, if so, what is its role? In the last decade, researchers' interest in vitamin D and its correlations with autoimmune diseases has considerably increased. We conducted a literature review, covering the period January 1, 2009 through March 30, 2019, in PubMed. We analyzed more than 130 studies in order to find a correlation between vitamin D levels and its effect upon several autoimmune diseases. The analysis demonstrated an inverse association between vitamin D and the development of several autoimmune diseases, such as SLE, thyrotoxicosis, type 1 DM, MS, iridocyclitis, Crohn's disease, ulcerative colitis, psoriasis vulgaris, seropositive RA, polymyalgia rheumatica. International multicenter study could allow us to confirm the data already present in the literature in the single clinical studies and to evaluate when to effectively supplement vitamin D in patients who do not take corticosteroids.
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Affiliation(s)
- Giuseppe Murdaca
- Clinical Immunology Unit, Department of Internal Medicine, University of Genoa and Ospedale Policlinico San Martino,Genoa, Italy.
| | - Alessandro Tonacci
- Clinical Physiology Institute, National Research Council of Italy (IFC-CNR), Pisa, Italy
| | - Simone Negrini
- Clinical Immunology Unit, Department of Internal Medicine, University of Genoa and Ospedale Policlinico San Martino,Genoa, Italy
| | - Monica Greco
- Clinical Immunology Unit, Department of Internal Medicine, University of Genoa and Ospedale Policlinico San Martino,Genoa, Italy
| | - Matteo Borro
- Clinical Immunology Unit, Department of Internal Medicine, University of Genoa and Ospedale Policlinico San Martino,Genoa, Italy
| | - Francesco Puppo
- Clinical Immunology Unit, Department of Internal Medicine, University of Genoa and Ospedale Policlinico San Martino,Genoa, Italy
| | - Sebastiano Gangemi
- School and Operative Unit of Allergy and Clinical Immunology, Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy
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24
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Havdahl A, Mitchell R, Paternoster L, Davey Smith G. Investigating causality in the association between vitamin D status and self-reported tiredness. Sci Rep 2019; 9:2880. [PMID: 30814568 PMCID: PMC6393455 DOI: 10.1038/s41598-019-39359-z] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2018] [Accepted: 01/21/2019] [Indexed: 12/22/2022] Open
Abstract
Self-reported tiredness or low energy, often referred to as fatigue, has been linked to low levels of circulating 25-hydroxyvitamin D (25OHD), a biomarker of vitamin D status. Although it is uncertain if the association is causal, fatigue is a common indication for testing, and correcting, low 25OHD-levels. We used two-sample Mendelian randomization to test for genetic evidence of a causal association between low 25OHD-levels and fatigue. Genetic-25OHD associations were estimated from the largest genome-wide association study of vitamin D to date, and genetic-fatigue associations were estimated in 327,478 individuals of European descent in UK Biobank, of whom 19,526 (5.96%) reported fatigue (tiredness or low energy nearly every day over the past two weeks). Using seven genome-wide significant 25OHD-reducing genetic variants, there was little evidence for a causal effect of 25OHD on fatigue (odds ratio for fatigue was 1.05 with 95% confidence interval of 0.87–1.27 per 1-SD decrease in log-transformed 25OHD). There was also little evidence of association between any individual 25OHD-reducing variant and fatigue. Our results suggest that a clinically relevant protective effect of 25OHD-levels on fatigue is unlikely. Therefore, vitamin D supplementation of the general population to raise 25OHD-levels is not likely to be useful in preventing fatigue.
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Affiliation(s)
- Alexandra Havdahl
- Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, BS8 2BN, United Kingdom. .,Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, BS8 2BN, United Kingdom. .,Nic Waals Institute, Lovisenberg Diaconal Hospital, Oslo, 0853, Norway. .,Department of Mental Disorders, Norwegian Institute of Public Health, Oslo, N-0213, Norway.
| | - Ruth Mitchell
- Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, BS8 2BN, United Kingdom.,Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, BS8 2BN, United Kingdom
| | - Lavinia Paternoster
- Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, BS8 2BN, United Kingdom.,Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, BS8 2BN, United Kingdom
| | - George Davey Smith
- Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, BS8 2BN, United Kingdom.,Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, BS8 2BN, United Kingdom.,National Institute for Health Research Bristol Biomedical Research Centre, University Hospitals Bristol NHS Foundation Trust and University of Bristol, Bristol, United Kingdom
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25
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Petersen I, Noelle J, Buchholz A, Kroencke S, Daseking M, Grabhorn E. Fatigue in pediatric liver transplant recipients and its impact on their quality of life. Pediatr Transplant 2019; 23:e13331. [PMID: 30588722 DOI: 10.1111/petr.13331] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2018] [Revised: 10/29/2018] [Accepted: 11/02/2018] [Indexed: 01/14/2023]
Abstract
The aim of the study was to investigate the occurrence of fatigue in 100 pediatric liver transplant recipients aged 2-18 years and its impact on their health-related quality of life (HRQL). HRQL and fatigue were measured using the PedsQL 4.0 Inventory and the PedsQL Multidimensional Fatigue Scale, which encompasses three subscales: general fatigue, sleep/rest fatigue, and cognitive fatigue. The impact of the different domains of fatigue and of clinical and sociodemographic factors on the HRQL was identified with stepwise multiple regression analyses. Parent proxy-reports were available for all 100 participants (2-18 years), and child self-reports were available for 71 patients (8-18 years). Across all domains, participants and their parents reported significantly more fatigue than healthy peers in a large PedsQL validation study. Thirty-seven percent of patients and 57% of parents scored clinically relevant levels of fatigue. In the multiple regression analyses, none of the clinical and sociodemographic factors contributed to the HRQL for child self-report. Only general and cognitive fatigue were significant predictors of patients' HRQL, explaining 66% of the variance in the PedsQL total score. For parent proxy-report, general and cognitive fatigue also significantly predicted child's HRQL. Further predictors were child's age and family income. The regression model explained 65% of the variance. These findings demonstrate the importance of assessing fatigue during regular follow-up examinations. Further research is urgently needed to better understand the underlying mechanisms of fatigue. Improvement of fatigue symptoms is essential for better HRQL, for cognitive functioning, and for school achievement.
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Affiliation(s)
- Irene Petersen
- Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.,University Transplant Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Janka Noelle
- University Transplant Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.,Department of Medical Psychology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Angela Buchholz
- University Transplant Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.,Department of Medical Psychology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Sylvia Kroencke
- University Transplant Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.,Department of Medical Psychology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Monika Daseking
- Department of Educational Psychology, Helmut Schmidt University, Hamburg, Germany
| | - Enke Grabhorn
- Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.,University Transplant Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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26
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Westerberg E, Landtblom AM, Punga AR. Lifestyle factors and disease-specific differences in subgroups of Swedish Myasthenia Gravis. Acta Neurol Scand 2018; 138:557-565. [PMID: 30155967 DOI: 10.1111/ane.13017] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2018] [Revised: 06/19/2018] [Accepted: 08/20/2018] [Indexed: 11/30/2022]
Abstract
PURPOSE To evaluate disease-specific differences between Myasthenia Gravis (MG) subgroups and compare patterns of lifestyle between MG patients and population controls. METHODS All MG patients (n = 70) in Jönköping County, Sweden, were invited to answer a disease-specific questionnaire, containing questions about disease-specific data, lifestyle, comorbidity, and mental fatigue. The patients were clinically evaluated. Four hundred age- and gender-matched population controls were invited to answer the nondisease-specific part of the questionnaire. Disease-specific issues were compared between MG subgroups. Lifestyle-related factors and concomitant conditions were compared to the population controls. RESULTS Forty MG patients and 188 population controls participated in the study. In the late-onset MG (LOMG; N = 18) subgroup, the male predominance was higher than previously reported. In the early-onset MG (EOMG; N = 17) subgroup, time to diagnosis was longer, fatigue was higher, and bulbar weakness was the dominant symptom (65%). Compared to their matched population controls, LOMG patients were more obese (OR = 13.7, P = 0.015), ate less fish (OR = 4.1, P = 0.012), tended to smoke more (OR = 4.1, P = 0.086), and tended to be employed as manual laborers more often (OR = 2.82, P = 0.083). Mental health problems and sickness benefits were more common among MG patients than in controls, and MG patients were less regularly doing focused physical activity. CONCLUSIONS It is important to consider disease-specific differences when tailoring the management of individual MG patients. There is a need for improved knowledge on how to apply primary and secondary prevention measures to lifestyle disorders in MG patients without risk of deterioration.
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Affiliation(s)
- Elisabet Westerberg
- Department of Neuroscience and Clinical Neurophysiology; Uppsala University; Uppsala Sweden
| | | | - Anna Rostedt Punga
- Department of Neuroscience and Clinical Neurophysiology; Uppsala University; Uppsala Sweden
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27
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Fatigue in patients with myasthenia gravis. J Neurol 2018; 265:2312-2321. [DOI: 10.1007/s00415-018-8995-4] [Citation(s) in RCA: 37] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2018] [Revised: 07/31/2018] [Accepted: 07/31/2018] [Indexed: 02/02/2023]
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28
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Frigstad SO, Høivik ML, Jahnsen J, Cvancarova M, Grimstad T, Berset IP, Huppertz-Hauss G, Hovde Ø, Bernklev T, Moum B, Jelsness-Jørgensen LP. Fatigue is not associated with vitamin D deficiency in inflammatory bowel disease patients. World J Gastroenterol 2018; 24:3293-3301. [PMID: 30090009 PMCID: PMC6079290 DOI: 10.3748/wjg.v24.i29.3293] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2018] [Revised: 06/17/2018] [Accepted: 06/27/2018] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate if vitamin D deficiency is associated with fatigue in patients with inflammatory bowel disease (IBD).
METHODS IBD patients were recruited from nine hospitals in the southeastern and western regions of Norway to participate in a multicenter cross-sectional study lasting from March 2013 to April 2014. Data were collected by interviews, from medical records and laboratory tests. The Fatigue Questionnaire (FQ) was used to measure fatigue. Linear and logistic regression models were applied to explore the possible association between vitamin D deficiency and total fatigue scores and chronic fatigue, respectively. The analyses were adjusted for age, gender, disease activity, depressive symptoms and sleep disturbance.
RESULTS In total, 405 patients were included in the analyses, of which 227 (56%) had Crohn’s disease (CD) and 178 (44%) had ulcerative colitis (UC). Vitamin D deficiency (< 50 nmol/L) was present in half (203/405) of the patients. Chronic fatigue was reported by 116 (29%) of all included patients with substantial fatigue reported by 194 (48%). Vitamin D levels were neither associated with total fatigue nor with chronic fatigue. Higher total fatigue scores and chronic fatigue were both associated with increased disease activity scores in patients with UC and CD, but not with increased CRP or fecal calprotectin. In UC patients, female gender was associated with fatigue in the univariate analysis, but no such difference was found when adjusted for elevated disease activity scores. Sleep disturbance and more depressive symptoms were associated with total fatigue scores in both UC and CD patients, but with chronic fatigue only in CD patients.
CONCLUSION In this study, no significant association between fatigue and vitamin D deficiency in IBD patients was revealed.
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Affiliation(s)
- Svein Oskar Frigstad
- Department of Medicine, Vestre Viken Bærum Hospital, Gjettum 1346, Norway
- Department of Research, Østfold Hospital Kalnes, Grålum 1714, Norway
| | - Marte Lie Høivik
- Department of Gastroenterology, Oslo University Hospital, Oslo 0424, Norway
| | - Jørgen Jahnsen
- Department of Gastroenterology, Akershus University Hospital, Lørenskog 1478, Norway
| | - Milada Cvancarova
- Faculty of Health Sciences, Oslo Metropolitan University, Oslo 0130, Norway
| | - Tore Grimstad
- Department of Gastroenterology, Stavanger University Hospital, Stavanger 4068, Norway
| | | | | | - Øistein Hovde
- Department of Medicine, Innlandet Hospital Trust, Gjøvik 2819, Norway
| | - Tomm Bernklev
- Department of Research and Development, Vestfold Hospital Trust, Tønsberg 3103, Norway
| | - Bjørn Moum
- Department of Gastroenterology, Oslo University Hospital, Oslo 0424, Norway
| | - Lars-Petter Jelsness-Jørgensen
- Department of Gastroenterology, Østfold Hospital Kalnes, Grålum 1714, Norway
- Department of Health Sciences, Østfold University College, Halden 1757, Norway
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29
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Vitamin D3 inhibits the proliferation of T helper cells, downregulate CD4+ T cell cytokines and upregulate inhibitory markers. Hum Immunol 2018. [DOI: 10.1016/j.humimm.2018.03.001] [Citation(s) in RCA: 43] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
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30
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Kang SY, Kang JH, Choi JC, Song SK, Oh JH. Low serum vitamin D levels in patients with myasthenia gravis. J Clin Neurosci 2018; 50:294-297. [DOI: 10.1016/j.jocn.2018.01.047] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2017] [Accepted: 01/08/2018] [Indexed: 12/14/2022]
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31
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Duval G, Rolland Y, Schott AM, Blain H, Dargent-Molina P, Walrand S, Duque G, Annweiler C. Association of hypovitaminosis D with triceps brachii muscle fatigability among older women: Findings from the EPIDOS cohort. Maturitas 2018; 111:47-52. [PMID: 29673831 DOI: 10.1016/j.maturitas.2018.02.007] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2017] [Revised: 01/21/2018] [Accepted: 02/08/2018] [Indexed: 12/22/2022]
Abstract
BACKGROUND Vitamin D affects physical performance in older adults. Its effects on muscles, notably on muscle strength, remain unclear. The objective of this cross-sectional study was to determine whether hypovitaminosis D is associated with triceps brachii muscle fatigability in community-dwelling older women. METHODS A randomized subset of 744 women aged ≥75years from the EPIDOS cohort was categorized into two groups according to triceps brachii muscle fatigability, defined as loss of strength >5% between two consecutive maximal isometric voluntary contractions. Hypovitaminosis D was defined using consensual threshold values (i.e., serum 25-hydroxyvitamin D concentration [25OHD] ≤10 ng/mL, ≤20 ng/mL, and ≤30 ng/mL). Age, body mass index, comorbidities, use psychoactive drugs, physical activity, first triceps strength measure, hyperparathyroidism, serum concentrations of calcium, albumin and creatinine, season and study centers were used as potential confounders. RESULTS The prevalence of hypovitaminosis D ≤ 30 ng/mL was greater among women with muscle fatigability compared with the others (P = .009). There was no between-group difference using the other definitions of hypovitaminosis D. The serum 25OHD concentration was inversely associated with the between-test change in triceps strength (adjusted β = -0.09 N, P = .04). Hypovitaminosis D ≤ 30 ng/mL was positively associated with triceps fatigability (adjusted OR = 3.15, P = .02). CONCLUSIONS Vitamin D concentration was inversely associated with the ability to maintain strength over time in this cohort of community-dwelling older women. This is a relevant new orientation of research toward understanding the involvement of vitamin D in muscle function.
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Affiliation(s)
- G Duval
- Department of Geriatric Medicine, Research Center on Autonomy and Longevity (CeRAL), Angers University Hospital; University Memory Clinic of Angers; UPRES EA 4638, University of Angers, Angers, France
| | - Y Rolland
- Department of Geriatrics, Toulouse University Hospital, INSERM U1027, University of Toulouse III, Toulouse, France
| | - A M Schott
- Department IMER, Lyon University Hospital, EA 4129, RECIF, University of Lyon, INSERM U831, Lyon, France
| | - H Blain
- Department of Internal Medicine and Geriatrics, Montpellier University Hospital, University of Montpellier 1, Montpellier, France
| | - P Dargent-Molina
- INSERM UMR 1153, Centre of Research in Epidemiology and Statistics Sorbonne Paris Cité (CRESS), Developmental Origins of Health and Disease (ORCHAD) Team, F-94807, Villejuif, France; Paris Descartes University, F-75006, Paris, France
| | - S Walrand
- Unité de Nutrition Humaine, Laboratoire de Nutrition Humaine, University of Clermont, Ferrand, France
| | - G Duque
- Australian Institute for Musculoskeletal Science (AIMSS), The University of Melbourne and Western Health, St. Albans, Victoria, Australia; Department of Medicine, Melbourne Medical School - Western Precinct, The University of Melbourne, St. Albans, Victoria, Australia
| | - C Annweiler
- Department of Geriatric Medicine, Research Center on Autonomy and Longevity (CeRAL), Angers University Hospital; University Memory Clinic of Angers; UPRES EA 4638, University of Angers, Angers, France; Robarts Research Institute, Department of Medical Biophysics, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, Ontario, Canada.
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32
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Wang Z, Yan Y. Immunopathogenesis in Myasthenia Gravis and Neuromyelitis Optica. Front Immunol 2017; 8:1785. [PMID: 29312313 PMCID: PMC5732908 DOI: 10.3389/fimmu.2017.01785] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2017] [Accepted: 11/29/2017] [Indexed: 12/13/2022] Open
Abstract
Myasthenia gravis (MG) and neuromyelitis optica (NMO) are autoimmune channelopathies of the peripheral neuromuscular junction (NMJ) and central nervous system (CNS) that are mainly mediated by humoral immunity against the acetylcholine receptor (AChR) and aquaporin-4 (AQP4), respectively. The diseases share some common features, including genetic predispositions, environmental factors, the breakdown of tolerance, the collaboration of T cells and B cells, imbalances in T helper 1 (Th1)/Th2/Th17/regulatory T cells, aberrant cytokine and antibody secretion, and complement system activation. However, some aspects of the immune mechanisms are unique. Both targets (AChR and AQP4) are expressed in the periphery and CNS, but MG mainly affects the NMJ in the periphery outside of CNS, whereas NMO preferentially involves the CNS. Inflammatory cells, including B cells and macrophages, often infiltrate the thymus but not the target—muscle in MG, whereas the infiltration of inflammatory cells, mainly polymorphonuclear leukocytes and macrophages, in NMO, is always observed in the target organ—the spinal cord. A review of the common and discrepant characteristics of these two autoimmune channelopathies may expand our understanding of the pathogenic mechanism of both disorders and assist in the development of proper treatments in the future.
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Affiliation(s)
- Zhen Wang
- Key Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest China, College of Life Sciences, Shaanxi Normal University, Xi'an, China.,Tianjin Medical University General Hospital, Tianjin Neurological Institute, Tianjin, China
| | - Yaping Yan
- Key Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest China, College of Life Sciences, Shaanxi Normal University, Xi'an, China
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34
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Guan Y, Lv F, Meng Y, Ma D, Xu X, Song Y, Wang O, Jiang Y, Xia W, Xing X, Zhang J, Li M. Association between bone mineral density, muscle strength, and vitamin D status in patients with myasthenia gravis: a cross-sectional study. Osteoporos Int 2017; 28:2383-2390. [PMID: 28439619 DOI: 10.1007/s00198-017-4041-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2016] [Accepted: 04/04/2017] [Indexed: 12/18/2022]
Abstract
UNLABELLED Myasthenia gravis (MG) patients had low proximal hip BMD, which could be explained by reduced muscle strength, elevated bone resorption markers, vitamin D deficiency, and increased PTH levels in those with MG compared to controls. INTRODUCTION Muscle strength is closely correlated with bone mineral density (BMD) and vitamin D status. Here, we evaluated muscle strength, BMD, and vitamin D status in a large sample of Chinese patients with MG. METHODS In this cross-sectional survey, 86 patients with MG without glucocorticoid treatment and 86 healthy controls were included. Serum levels of 25-hydroxyvitamin D [25OHD], parathyroid hormone (PTH), bone turnover markers (BTMs), and BMD were measured and compared between the two groups. Grip strength and one-leg standing time (OLST) were also assessed in MG patients. RESULTS Low grip strength and short OLST were found in 11 (12.8%) and 12 (14.0%) MG patients, respectively. There were 3 (3.5%) MG patients with low bone mass for chronological age. Serum beta C-terminal telopeptide and PTH levels were higher (p < 0.001 and p = 0.001, respectively), and BMD at the femoral neck and trochanter were lower in MG patients (p < 0.001 and p < 0.001, respectively) compared to healthy controls. In patients with MG, grip strength was positively correlated with BMD. Serum 25OHD levels were lower in MG patients than in healthy controls (17.36 ± 6.64 vs. 22.11 ± 7.28 ng/ml, p < 0.001). CONCLUSION Grip strength was positively correlated with BMD in Chinese patients with MG. MG patients tended to have low proximal hip BMD, which may partially be explained by reduced muscle strength, vitamin D deficiency, increased PTH levels, and elevated bone resorption markers compared to controls.
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Affiliation(s)
- Y Guan
- Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - F Lv
- Department of Endocrinology, Key Laboratory of Endocrinology of Ministry of Health; Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Shuaifuyuan No. 1, Dongcheng District, Beijing, 100730, China
| | - Y Meng
- Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - D Ma
- Department of Endocrinology, Key Laboratory of Endocrinology of Ministry of Health; Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Shuaifuyuan No. 1, Dongcheng District, Beijing, 100730, China
| | - X Xu
- Department of Endocrinology, Key Laboratory of Endocrinology of Ministry of Health; Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Shuaifuyuan No. 1, Dongcheng District, Beijing, 100730, China
| | - Y Song
- Department of Endocrinology, Key Laboratory of Endocrinology of Ministry of Health; Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Shuaifuyuan No. 1, Dongcheng District, Beijing, 100730, China
| | - O Wang
- Department of Endocrinology, Key Laboratory of Endocrinology of Ministry of Health; Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Shuaifuyuan No. 1, Dongcheng District, Beijing, 100730, China
| | - Y Jiang
- Department of Endocrinology, Key Laboratory of Endocrinology of Ministry of Health; Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Shuaifuyuan No. 1, Dongcheng District, Beijing, 100730, China
| | - W Xia
- Department of Endocrinology, Key Laboratory of Endocrinology of Ministry of Health; Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Shuaifuyuan No. 1, Dongcheng District, Beijing, 100730, China
| | - X Xing
- Department of Endocrinology, Key Laboratory of Endocrinology of Ministry of Health; Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Shuaifuyuan No. 1, Dongcheng District, Beijing, 100730, China
| | - J Zhang
- Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - M Li
- Department of Endocrinology, Key Laboratory of Endocrinology of Ministry of Health; Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Shuaifuyuan No. 1, Dongcheng District, Beijing, 100730, China.
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Abstract
Low serum levels of vitamin D have been associated with fatigue in both healthy and clinical populations. Our aim was to evaluate the effect of vitamin D supplementation on fatigue in kidney transplant recipients (KTRs). In total, 137 patients after kidney transplant and 119 age- and sex-matched healthy volunteers were recruited. Serum levels of 25-hydroxyvitamin D (25(OH)D) were measured by competitive protein-binding assay. Fatigue was assessed using the subscale fatigue of the Checklist Individual Strength (CIS). Of all KTRs, 60 patients without initial vitamin D3 supplementation were started on vitamin D3 supplementation (cholecalciferol) 800 IU/d, with a follow-up examination after 3.0 to 9.0 months (mean, 6 months). Fatigue was found in 40.1% of KTRs. Serum 25(OH)D levels were inversely and independently associated with CIS scores in KTRs (P = .002). In the 60 patients who received vitamin D3 supplementation, 25(OH)D was overall increased at follow-up with 18.5% (P = .004) and CIS scores improved with 10.0% (P = .007). As vitamin D has beneficial effects on fatigue scores in KTRs, we suggest monitoring this parameter in KTRs and supplementation with vitamin D3 when vitamin D levels are low.
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Affiliation(s)
- Bin Han
- Department of Nephrology, First Affiliated Hospital of Jiaxing University, Jiaxing
| | - Xiao Wu
- Department of Gastrointestinal Surgery, People's Hospital of Yueqing
| | - Yong Guo
- Department of Nephrology and Transplantation, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
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Nowak A, Boesch L, Andres E, Battegay E, Hornemann T, Schmid C, Bischoff-Ferrari HA, Suter PM, Krayenbuehl PA. Effect of vitamin D3 on self-perceived fatigue: A double-blind randomized placebo-controlled trial. Medicine (Baltimore) 2016; 95:e5353. [PMID: 28033244 PMCID: PMC5207540 DOI: 10.1097/md.0000000000005353] [Citation(s) in RCA: 49] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
BACKGROUND Vitamin D deficiency is frequent and has been associated with fatigue in uncontrolled trials. METHODS This is the first double-blind placebo-controlled clinical trial to investigate the efficacy of per os vitamin D3 (cholecalciferol) in treating fatigue among otherwise healthy persons with low serum 25-hydroxyvitamin D (25(OH)D) levels. We enrolled 120 individuals (mean age 29 ± 6 years, 53% women) presenting with fatigue and vitamin D deficiency (serum 25(OH)D < 20 μg/L). Participants were randomized to a single oral dose of 100,000 units of vitamin D or placebo. The primary endpoint was intra-individual change in the fatigue assessment scale (FAS) at 4 weeks after treatment. RESULT The mean age of the participants was 29 ± 6 years, 53% were women. Mean FAS decreased significantly more in the vitamin D group (-3.3 ± 5.3; 95% confidence interval [CI] for change -14.1 to 4.1) compared with placebo (-0.8 ± 5.3; 95% CI for change -9.0 to 8.7); (P = 0.01). Amelioration of fatigue was reported more frequently in vitamin D than in placebo group (42 [72%] vs. 31 [50%]; P = 0.01; odds ratio [OR] 2.63, 95% CI for OR 1.23-5.62). Among all participants, improvement in fatigue score correlated with the rise in 25(OH)D level (R = -0.22, P = 0.02). CONCLUSION Vitamin D treatment significantly improved fatigue in otherwise healthy persons with vitamin D deficiency.This study was registered at the www.ClinicalTrials.gov Protocol ID NCT02022475.
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Affiliation(s)
| | | | | | | | - Thorsten Hornemann
- Institute for Clinical Chemistry, University Hospital Zurich and University of Zurich
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Hoffmann S, Ramm J, Grittner U, Kohler S, Siedler J, Meisel A. Fatigue in myasthenia gravis: risk factors and impact on quality of life. Brain Behav 2016; 6:e00538. [PMID: 27781147 PMCID: PMC5064345 DOI: 10.1002/brb3.538] [Citation(s) in RCA: 63] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2016] [Revised: 06/08/2016] [Accepted: 06/27/2016] [Indexed: 11/12/2022] Open
Abstract
OBJECTIVES Emerging evidence suggests that fatigue in myasthenia gravis (MG) is a relevant problem that negatively impacts activities of daily living (ADL). The relationship between fatigue and quality of life (QoL) has never been systematically explored in MG patients. The study aimed to assess the prevalence of fatigue and its relation to ADL and QoL as well as to identify factors associated with fatigue in MG. MATERIAL AND METHODS This was a cross-sectional observational study in patients with confirmed diagnosis of MG independent of disease severity. Prevalence of fatigue was assessed using the Chalder Fatigue Scale (CFQ). Impact of fatigue on ADL and QoL was assessed by the MG activities of daily living profile (MG-ADL) and the MG-specific quality-of-life instrument (MG-QoL), respectively. Association of fatigue with sociodemographics, clinical characteristics of MG, and comorbidities including mood and anxiety disorders as well as sleep disorders was investigated using multivariable logistic regression analyses. RESULTS Overall, 200 MG patients were included. The observed rate of fatigue was 56.1%, of those 70.4% fulfilled the criteria of chronic fatigue (CF) with a duration of ≥6 months. Relevant fatigue was strongly associated to ADL and QoL. Factors associated with relevant fatigue were disease severity and depressive state. Furthermore, positive muscle-specific tyrosine kinase (MuSK) antibody status showed a strong association with relevant fatigue. CONCLUSIONS MG patients have a high prevalence of fatigue which negatively impacts ADL and QoL. MG-specific clinical characteristics are related to fatigue and might help to identify MG patients at risk for fatigue.
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Affiliation(s)
- Sarah Hoffmann
- NeuroCure Clinical Research Center Charité - Universitätsmedizin Berlin Berlin Germany; Department of Neurology Charité - Universitätsmedizin Berlin Berlin Germany
| | - Johanna Ramm
- NeuroCure Clinical Research Center Charité - Universitätsmedizin Berlin Berlin Germany
| | - Ulrike Grittner
- Center for Stroke Research (CSB)Charité - Universitätsmedizin Berlin Berlin Germany; Department for Biostatistics and Clinical Epidemiology Charité - Universitätsmedizin Berlin Berlin Germany
| | - Siegfried Kohler
- NeuroCure Clinical Research Center Charité - Universitätsmedizin Berlin Berlin Germany; Department of Neurology Charité - Universitätsmedizin Berlin Berlin Germany
| | - Jana Siedler
- NeuroCure Clinical Research Center Charité - Universitätsmedizin Berlin Berlin Germany
| | - Andreas Meisel
- NeuroCure Clinical Research Center Charité - Universitätsmedizin Berlin Berlin Germany; Department of Neurology Charité - Universitätsmedizin Berlin Berlin Germany
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Manning E, Goldstein JM. Myasthenia Gravis in the Elderly: Differential Diagnosis and Management. CURRENT GERIATRICS REPORTS 2016. [DOI: 10.1007/s13670-016-0170-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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Prevalence of Vitamin D Deficiency in Spring and Summer Months in Central Pennsylvania Neuromuscular Clinic: A Study Complementary to the Pilot Study Published in Journal of Clinical Neuromuscular Disease in June 2015 for Fall and Winter Months. J Clin Neuromuscul Dis 2016; 17:223-5. [PMID: 27224439 DOI: 10.1097/cnd.0000000000000104] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Chroni E, Dimisianos N, Punga AR. Low vitamin D levels in healthy controls and patients with autoimmune neuromuscular disorders in Greece. Acta Neurol Belg 2016; 116:57-63. [PMID: 26183131 DOI: 10.1007/s13760-015-0512-2] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2015] [Accepted: 07/07/2015] [Indexed: 12/23/2022]
Abstract
Normal autoimmune function is dependent on adequate levels of activated vitamin D, 25 hydroxy vitamin D [25(OH)D]. A recent study presented deficiency of 25(OH)D levels in Swedish MG patients. We aimed to study 25(OH)D levels in patients with MG and autoimmune polyneuropathies (PNP) at a southern latitude in Greece. Plasma levels of 25(OH)D were analyzed in Greek patients with MG (n = 19), immune-mediated PNP (N = 11) and in 30 Greek healthy age- and sex-matched controls. Ten MG patients received supplementation with vitamin D3. The MG Composite Score (MGC) and MG quality of life assessed disease severity in MG patients, whereas the INCAT Disability Scale assessed clinical features in the PNP patients. MG patients with and without vitamin D3 supplementation had higher 25(OH)D levels (mean 58.8 ± 16.3 and 62.0 ± 22.4 nmol/L, respectively) than PNP patients (mean 42.1 ± 11.5 nmol/L, p = 0.01) and healthy controls (mean 45.7 ± 13.8 nmol/L, p = 0.01). Plasma 25(OH)D levels was lower with age in all groups. There were no correlations between 25(OH)D and disease duration, MGC score, or INCAT score. Vitamin D deficiency was found in all Greek patient groups and healthy controls. Levels of 25(OH)D were higher in MG patients with as well as without vitamin D supplementation compared to healthy controls, whereas CIDP/GBS patients had levels similar to controls.
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Affiliation(s)
- Elisabeth Chroni
- Department of Neurology, School of Medicine, University of Patras, Patras, Greece
| | - Nikolaos Dimisianos
- Department of Neurology, School of Medicine, University of Patras, Patras, Greece
| | - Anna Rostedt Punga
- Department of Clinical Neurophysiology, Institute of Neuroscience, Uppsala University Hospital, Uppsala University, 75185, Uppsala, Sweden.
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Surprising prevalence of unrecognized vitamin D3 deficiency in fall and winter months in neuromuscular clinics in Central Pennsylvania: a pilot study. J Clin Neuromuscul Dis 2016; 16:199-201. [PMID: 25996965 DOI: 10.1097/cnd.0000000000000075] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVES The Harvard biomarker study published in October 2013 in Neurology journal showed a deficiency of vitamin D in 17.6% patients with Parkinson disease compared with 9.3% controls (adults without neurological symptoms). Similar determination among neuromuscular disease patients is lacking. METHODS A retrospective analysis of vitamin D levels was performed on 73 patients seen between September and March in the Neuromuscular Central Pennsylvania tertiary referral clinic. Patient selection was random. Patients with amyotrophic lateral sclerosis were excluded from this study. RESULTS The prevalence of vitamin D deficiency was significantly above the Harvard Biomarker control values considering similar climatic and ethnic factors. CONCLUSIONS Although 25-hydroxy-D3, produced in liver and skin, can be low in fall and winter, significant lower levels were seen (P > 000.1) among the patients seen randomly in our neuromuscular clinic compared with recently published controls. Similar studies from different geographical zones of the Unite States considering seasonal influences are worth studying. Whether checking vitamin D3 blood level should become a standard practice is the bigger issue.
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Vitamin D deficiency and its role in neurological conditions: A review. Rev Neurol (Paris) 2016; 172:109-22. [DOI: 10.1016/j.neurol.2015.11.005] [Citation(s) in RCA: 59] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2015] [Revised: 10/25/2015] [Accepted: 11/02/2015] [Indexed: 12/14/2022]
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Cadegiani FA. Remission of Severe Myasthenia Gravis After Massive-Dose Vitamin D Treatment. AMERICAN JOURNAL OF CASE REPORTS 2016; 17:51-4. [PMID: 26822380 PMCID: PMC4734680 DOI: 10.12659/ajcr.894849] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND Vitamin D has been shown to be related to autoimmune diseases, such as multiple sclerosis and psoriasis. Correlations have been reported between vitamin D levels and prevalence and severity of other autoimmune disorders, and also between vitamin D therapy and disease improvement and remission. CASE REPORT This is a case report of a patient with severe and refractory myasthenia gravis (MG) who followed a "high-dose vitamin D treatment", a massive-dose treatment (80,000 to 120,000 IU/day) promoted by a medical center in Brazil (but still not proven), and she had her first complete remission after this type of treatment with increased vitamin D serum levels (400 to 700 ng/mL). CONCLUSIONS This case report may reinforce the reported correlation between vitamin D level and disease severity and introduces a possible new use for vitamin D as a potential target for treating autoimmune diseases. We recommend large, double-blind, placebo-controlled, randomized studies using high-dose vitamin D treatment for refractory autoimmune diseases to reliably assess this pharmacotherapy target for these diseases.
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Masoudi Alavi N, Madani M, Sadat Z, Haddad Kashani H, Reza Sharif M. Fatigue and Vitamin D Status in Iranian Female Nurses. Glob J Health Sci 2015; 8:196-202. [PMID: 26755458 PMCID: PMC4954906 DOI: 10.5539/gjhs.v8n6p196] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2014] [Accepted: 12/18/2014] [Indexed: 12/20/2022] Open
Abstract
Introduction: Given that nurses are among professions with frequent problems of fatigue, and given the nature of their profession that provides little exposure to sunlight and the subsequent deficiency of vitamin D, the present study examined the relation between fatigue and circulating vitamin D levels in female nurses working in Shahid Beheshti Hospital, Kashan, Iran in 2013. Material and Methods: This cross-sectional study was conducted in 200 female nurses working in Shahid Beheshti Hospital. To measure fatigue, fatigue questionnaire containing 9 questions eliciting the subject’s feeling in scales of 1 to 7, getting a possible score of 9 to 63, and Visual Analogue Scale in which nurses specified their fatigue in a band of zero to 10 were used. The 25-hydroxyvitamin D, which is the most important vitamin D metabolite, also was determined. The data was analyzed by SPSS-16. The Pearson’s correlation of coefficients, t-test, and multiple regression analysis were used in this study. Results: The mean fatigue score of nurses was 38.76±12.66 in questionnaire and 5.73±2.12 in Visual Analog Scale. The 89 per cent of nurses suffered from vitamin D deficiency, 9.5 percent of them had normal level and 1.5 per cent had toxicity level of vitamin D. There was a significant relationship between vitamin D level and fatigue scores (P<0.0001), and visual fatigue scores (P<0.0001). According to multivariate regression analysis, vitamin D level accounted for 13 per cent of the fatigue based on data on questionnaire and 18.6 per cent of fatigue according to Visual Analog Scale. Conclusion: High prevalence of fatigue among nurses could be attributed to vitamin D deficiency.
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Affiliation(s)
- Negin Masoudi Alavi
- Trauma Nursing Research Center, Kashan University of Medical Sciences, Kashan, I. R. Iran.
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45
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Alahgholi-Hajibehzad M, Kasapoglu P, Jafari R, Rezaei N. The role of T regulatory cells in immunopathogenesis of myasthenia gravis: implications for therapeutics. Expert Rev Clin Immunol 2015; 11:859-70. [DOI: 10.1586/1744666x.2015.1047345] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
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46
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Alahgholi-Hajibehzad M, Oflazer P, Aysal F, Durmuş H, Gülşen-Parman Y, Marx A, Deymeer F, Saruhan-Direskeneli G. Regulatory function of CD4+CD25++ T cells in patients with myasthenia gravis is associated with phenotypic changes and STAT5 signaling: 1,25-Dihydroxyvitamin D3 modulates the suppressor activity. J Neuroimmunol 2015; 281:51-60. [DOI: 10.1016/j.jneuroim.2015.03.008] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2015] [Revised: 03/06/2015] [Accepted: 03/07/2015] [Indexed: 10/23/2022]
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47
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Vitamin D deficiency in patients with primary immune-mediated peripheral neuropathies. J Neurol Sci 2014; 345:184-8. [DOI: 10.1016/j.jns.2014.07.040] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2014] [Revised: 07/15/2014] [Accepted: 07/17/2014] [Indexed: 12/14/2022]
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Roy S, Sherman A, Monari-Sparks MJ, Schweiker O, Hunter K. Correction of Low Vitamin D Improves Fatigue: Effect of Correction of Low Vitamin D in Fatigue Study (EViDiF Study). NORTH AMERICAN JOURNAL OF MEDICAL SCIENCES 2014; 6:396-402. [PMID: 25210673 PMCID: PMC4158648 DOI: 10.4103/1947-2714.139291] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Background: Fatigue is a common presenting complaint of patients in the primary care offices. Low levels of vitamin D have been associated with fatigue in cancer patients. Normalization of vitamin D level improves their fatigue. Whether low vitamin D plays a role in fatigue in medically stable patients is not known. Aims: This prospective non-randomized therapeutic study observed the prevalence of low vitamin D in fatigue and the effect of normalization of vitamin D on fatigue. Material and Methods: One hundred and seventy four adult patients, who presented in our primary care office with fatigue and stable chronic medical conditions,completed fatigue assessment questionnaires. Patients with low vitamin D levels received ergocalciferol therapy for 5 weeks. Scores of pre- and post-treatment fatigue assessment questionnaires were compared. Results: Prevalence of low vitamin D was 77.2% in patients who presented with fatigue. After normalization of vitamin D levels fatigue symptom scores improved significantly (P < 0.001) in all five subscale categories of fatigue assessment questionnaires. Conclusion: The prevalence of low vitamin D is high in patients who present with fatigue and stable chronic medical conditions, if any. Normalization of vitamin D levels with ergocalciferol therapy significantly improves the severity of their fatigue symptoms.
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Affiliation(s)
- Satyajeet Roy
- Department of Medicine, Cooper University Hospital, Cooper Medical School of Rowan University, Camden, New Jersey, USA
| | - Anthony Sherman
- Department of Medicine, Cooper University Hospital, Cooper Medical School of Rowan University, Camden, New Jersey, USA
| | - Mary Joan Monari-Sparks
- Department of Medicine, Cooper University Hospital, Cooper Medical School of Rowan University, Camden, New Jersey, USA
| | - Olga Schweiker
- Department of Medicine, Cooper University Hospital, Cooper Medical School of Rowan University, Camden, New Jersey, USA
| | - Krystal Hunter
- Cooper Research Institute, Cooper University Hospital, Cooper Medical School of Rowan University, Camden, New Jersey, USA
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Berrih-Aknin S. Myasthenia Gravis: paradox versus paradigm in autoimmunity. J Autoimmun 2014; 52:1-28. [PMID: 24934596 DOI: 10.1016/j.jaut.2014.05.001] [Citation(s) in RCA: 89] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2014] [Accepted: 05/07/2014] [Indexed: 12/12/2022]
Abstract
Myasthenia Gravis (MG) is a paradigm of organ-specific autoimmune disease (AID). It is mediated by antibodies that target the neuromuscular junction. The purpose of this review is to place MG in the general context of autoimmunity, to summarize the common mechanisms between MG and other AIDs, and to describe the specific mechanisms of MG. We have chosen the most common organ-specific AIDs to compare with MG: type 1 diabetes mellitus (T1DM), autoimmune thyroid diseases (AITD), multiple sclerosis (MS), some systemic AIDs (systemic lupus erythematous (SLE), rheumatoid arthritis (RA), Sjogren's syndrome (SS)), as well as inflammatory diseases of the gut and liver (celiac disease (CeD), Crohn's disease (CD), and primary biliary cirrhosis (PBC)). Several features are similar between all AIDs, suggesting that common pathogenic mechanisms lead to their development. In this review, we address the predisposing factors (genetic, epigenetic, hormones, vitamin D, microbiota), the triggering components (infections, drugs) and their interactions with the immune system [1,2]. The dysregulation of the immune system is detailed and includes the role of B cells, Treg cells, Th17 and cytokines. We particularly focused on the role of TNF-α and interferon type I whose role in MG is very analogous to that in several other AIDS. The implication of AIRE, a key factor in central tolerance is also discussed. Finally, if MG is a prototype of AIDS, it has a clear specificity compared to the other AIDS, by the fact that the target organ, the muscle, is not the site of immune infiltration and B cell expansion, but exclusively that of antibody-mediated pathogenic mechanisms. By contrast, the thymus in the early onset subtype frequently undergoes tissue remodeling, resulting in the development of ectopic germinal centers surrounded by high endothelial venules (HEV), as observed in the target organs of many other AIDs.
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Affiliation(s)
- Sonia Berrih-Aknin
- Sorbonne Universités, UPMC Univ Paris 06, Myology Research Center UM76, F-75013 Paris, France; INSERM U974, F-75013 Paris, France; CNRS FRE 3617, F-75013 Paris, France; Institute of Myology, F-75013 Paris, France.
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50
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Madani M, Masoudi Alavi N, Taghizadeh M. Non-Specific Musculoskeletal Pain and Vitamin D Deficiency in Female Nurses in Kashan, Iran. ACTA ACUST UNITED AC 2014. [DOI: 10.3109/10582452.2014.907858] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
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