Faculty Bibliography
Searched for:
school:SOM
Department/Unit:Neurology
Total Results:
22957
Castleman Disease Presenting with Pseudotumour Cerebri and Myasthenia Gravis: A Case Report and Literature Review [Case Report]
Castleman disease (CD) is a rare lymphoproliferative disorder that may present with various autoimmune, inflammatory, or neurologic syndromes. This is a case of a 21-year-old woman who presented with signs and symptoms of pseudotumour cerebri (PTC) who subsequently developed myasthenia gravis (MG), and was incidentally found to have a large mass in the posterior mediastinum. Upon resection, the mass was classified as unicentric CD involved with follicular dendritic cell sarcoma. Following treatment with IVIG in the setting of progressive weakness and dyspnea, she has had complete symptom resolution while maintained on a low dose of pyridostigmine for the last two years. There are 13 cases of MG and five cases of optic disc edema described as PTC associated with CD in the literature, but to our knowledge, this is the sole case reported of the intersection of all three conditions in one patient. Increased serum levels of interleukin-6 and vascular endothelial growth factor may provide clues as to the association of CD with these neurologic syndromes.
PMCID:6619924
PMID: 31312243
ISSN: 0165-8107
CID: 5524332
Human Fibrinogen for Maintenance and Differentiation of Induced Pluripotent Stem Cells in Two Dimensions and Three Dimensions
Human fibrin hydrogels are a popular choice for use as a biomaterial within tissue engineered constructs because they are biocompatible, nonxenogenic, autologous use compatible, and biodegradable. We have recently demonstrated the ability to culture induced pluripotent stem cell (iPSC)-derived retinal pigment epithelium on fibrin hydrogels. However, iPSCs themselves have relatively few substrate options (e.g., laminin) for expansion in adherent cell culture for use in cell therapy. To address this, we investigated the potential of culturing iPSCs on fibrin hydrogels for three-dimensional applications and further examined the use of fibrinogen, the soluble precursor protein, as a coating substrate for traditional adherent cell culture. iPSCs successfully adhered to and proliferated on fibrin hydrogels. The two-dimensional culture with fibrinogen allows for immediate adaption of culture models to a nonxenogeneic model. Similarly, multiple commercially available iPSC lines adhered to and proliferated on fibrinogen coated surfaces. iPSCs cultured on fibrinogen expressed similar levels of the pluripotent stem cell markers SSea4 (98.7% ± 1.8%), Oct3/4 (97.3% ± 3.8%), TRA1-60 (92.2% ± 5.3%), and NANOG (96.0% ± 3.9%) compared with iPSCs on Geltrex. Using a trilineage differentiation assay, we found no difference in the ability of iPSCs grown on fibrinogen or Geltrex to differentiate to endoderm, mesoderm, or ectoderm. Finally, we demonstrated the ability to differentiate iPSCs to endothelial cells using only fibrinogen coated plates. On the basis of these data, we conclude that human fibrinogen provides a readily available and inexpensive alternative to laminin-based products for the growth, expansion, and differentiation of iPSCs for use in research and clinical cell therapy applications. Stem Cells Translational Medicine 2019;8:512-521.
PMCID:6525556
PMID: 30768863
ISSN: 2157-6580
CID: 5592992
Practice Current: How do you diagnose and treat post-concussive headache?
A common complaint after concussion is the development of new or worsening headaches which can make it difficult or even impossible for patients to work or function in their day-to-day lives. Uncertainties associated with the complaints and a wide variety of approaches exist regarding the appropriate work-up and management of these patients. Areas of ongoing debate include the need for neuroimaging; optimal, acute, and preventative treatment; and proper counseling and expectation management. Given the wide variety of potential approaches and the lack of consensus, we sought expert opinion from around the globe on how to evaluate and manage patients with headache following concussion. Similar questions were posed to the rest of our readership in an online survey (links.lww.com/CPJ/A96), the results of which are also presented.
PMCID:6615645
PMID: 31341715
ISSN: 2163-0402
CID: 4956432
A catalog of genetic loci associated with kidney function from analyses of a million individuals
Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through trans-ancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these, 147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
PMID: 31152163
ISSN: 1546-1718
CID: 3936112
Mental health symptoms and disorders in elite athletes: a systematic review on cultural influencers and barriers to athletes seeking treatment
OBJECTIVE:To summarise the literature on the barriers to athletes seeking mental health treatment and cultural influencers of mental health in elite athletes. DESIGN/METHODS:Systematic review DATA SOURCES: PubMed, Cochrane, Scopus, SportDiscus (Ebsco), and PsycINFO (ProQuest) up to November 2018. ELIGIBILITY CRITERIA FOR SELECTING STUDIES/UNASSIGNED:Qualitative and quantitative original studies of elite athletes (those who competed at the professional, Olympic, or collegiate/university levels), published in any language. RESULTS:Stigma, low mental health literacy, negative past experiences with mental health treatment-seeking, busy schedules, and hypermasculinity are barriers to elite athletes seeking mental health treatment. Cultural influencers of mental health in elite athletes include: (1) the lack of acceptance of women as athletes; (2) lower acceptability of mental health symptoms and disorders among non-white athletes; (3) non-disclosure of religious beliefs; and (4) higher dependence on economic benefits. Coaches have an important role in supporting elite athletes in obtaining treatment for mental illness. Brief anti-stigma interventions in elite athletes decrease stigma and improve literary about mental health. CONCLUSION/CONCLUSIONS:There is a need for various actors to provide more effective strategies to overcome the stigma that surrounds mental illness, increase mental health literacy in the athlete/coach community, and address athlete-specific barriers to seeking treatment for mental illness. In this systematic review, we identified strategies that, if implemented, can overcome the cultural factors that may otherwise limit athletes seeking treatment. Coaches are critical for promoting a culture within elite athletes' environments that encourages athletes to seek treatment.
PMID: 31092400
ISSN: 1473-0480
CID: 4174012
Mental health in elite athletes: International Olympic Committee consensus statement (2019)
Mental health symptoms and disorders are common among elite athletes, may have sport related manifestations within this population and impair performance. Mental health cannot be separated from physical health, as evidenced by mental health symptoms and disorders increasing the risk of physical injury and delaying subsequent recovery. There are no evidence or consensus based guidelines for diagnosis and management of mental health symptoms and disorders in elite athletes. Diagnosis must differentiate character traits particular to elite athletes from psychosocial maladaptations.Management strategies should address all contributors to mental health symptoms and consider biopsychosocial factors relevant to athletes to maximise benefit and minimise harm. Management must involve both treatment of affected individual athletes and optimising environments in which all elite athletes train and compete. To advance a more standardised, evidence based approach to mental health symptoms and disorders in elite athletes, an International Olympic Committee Consensus Work Group critically evaluated the current state of science and provided recommendations.
PMID: 31097450
ISSN: 1473-0480
CID: 4174062
Legal Objections to Use of Neurologic Criteria to Declare Death in the United States: 1968-2017
BACKGROUND:There have been a number of recent prominent lawsuits challenging the use of neurologic criteria to declare death in the United States. METHODS:To put these lawsuits into perspective, we conducted a search of Nexis Uni® to identify cases from the past 50 years that involved objections to the use of neurologic criteria to declare death in the United States. RESULTS:We identified lawsuits about 67 decedents (59 state and 8 federal) from 34 different regions which were filed for crime related issues (n=42), hospital related issues (n=20), insurance related issues (n=2) and other issues related to time of death (n=3). The judicial opinions about the lawsuits addressed: 1) acceptance of the use of neurologic criteria to declare death (n=55), 2) criteria to declare death (n=3), 3) management of decedents after death by neurologic criteria (n=13), 4) identification of the time of death (n=4) and 5) rights of the dead (n=3). The outcomes of these cases were heterogeneous. CONCLUSION/CONCLUSIONS:Since the incorporation of neurologic criteria into the medical practice of declaration of death, there have been a number of legal objections to its use. To avoid the rendering of variable opinions by the courts, there is a need for consistent legislative modification throughout the country to address 1) the specific criteria to employ when declaring death by neurologic criteria, 2) management of religious objections to use of neurologic criteria to declare death and 3) management after declaration of death by neurologic criteria.
PMID: 30935891
ISSN: 1931-3543
CID: 3783922
Genome-wide analyses as part of the international FTLD-TDP whole-genome sequencing consortium reveals novel disease risk factors and increases support for immune dysfunction in FTLD
Frontotemporal lobar degeneration with neuronal inclusions of the TAR DNA-binding protein 43 (FTLD-TDP) represents the most common pathological subtype of FTLD. We established the international FTLD-TDP whole-genome sequencing consortium to thoroughly characterize the known genetic causes of FTLD-TDP and identify novel genetic risk factors. Through the study of 1131 unrelated Caucasian patients, we estimated that C9orf72 repeat expansions and GRN loss-of-function mutations account for 25.5% and 13.9% of FTLD-TDP patients, respectively. Mutations in TBK1 (1.5%) and other known FTLD genes (1.4%) were rare, and the disease in 57.7% of FTLD-TDP patients was unexplained by the known FTLD genes. To unravel the contribution of common genetic factors to the FTLD-TDP etiology in these patients, we conducted a two-stage association study comprising the analysis of whole-genome sequencing data from 517 FTLD-TDP patients and 838 controls, followed by targeted genotyping of the most associated genomic loci in 119 additional FTLD-TDP patients and 1653 controls. We identified three genome-wide significant FTLD-TDP risk loci: one new locus at chromosome 7q36 within the DPP6 gene led by rs118113626 (p value = 4.82e - 08, OR = 2.12), and two known loci: UNC13A, led by rs1297319 (p value = 1.27e - 08, OR = 1.50) and HLA-DQA2 led by rs17219281 (p value = 3.22e - 08, OR = 1.98). While HLA represents a locus previously implicated in clinical FTLD and related neurodegenerative disorders, the association signal in our study is independent from previously reported associations. Through inspection of our whole-genome sequence data for genes with an excess of rare loss-of-function variants in FTLD-TDP patients (n ≥ 3) as compared to controls (n = 0), we further discovered a possible role for genes functioning within the TBK1-related immune pathway (e.g., DHX58, TRIM21, IRF7) in the genetic etiology of FTLD-TDP. Together, our study based on the largest cohort of unrelated FTLD-TDP patients assembled to date provides a comprehensive view of the genetic landscape of FTLD-TDP, nominates novel FTLD-TDP risk loci, and strongly implicates the immune pathway in FTLD-TDP pathogenesis.
PMID: 30739198
ISSN: 1432-0533
CID: 3691682
Breaking a taboo: why the International Olympic Committee convened experts to develop a consensus statement on mental health in elite athletes [Editorial]
PMID: 31097449
ISSN: 1473-0480
CID: 4174052
Short Takes [Editorial]
PMID: 30898415
ISSN: 1873-5150
CID: 3776232
