UW Neurological Surgery Recent PubMed Publications

Current Update on Treatment Strategies for Idiopathic Normal Pressure Hydrocephalus.

Curr Treat Options Neurol. 2019 Dec 03;21(12):65

Authors: Isaacs AM, Williams MA, Hamilton MG

Abstract
PURPOSE OF REVIEW: Idiopathic normal pressure hydrocephalus (iNPH) is a surgically treatable neurological disorder of the elderly population that is characterized by abnormal ventricular enlargement due to cerebrospinal fluid (CSF) accumulation and gait disturbance, cognitive impairment, or urinary incontinence. The objective of this review is to present the current diagnostic and treatment approaches for iNPH and to discuss some of the postoperative modalities that complement positive surgical outcomes.
RECENT FINDINGS: Although historically reported patient outcomes following iNPH surgery were dismal and highly variable, recent advances in terms of better understanding of the iNPH disease process, better standardization of iNPH diagnostic and treatment processes arising from the adoption of clinical guidelines for diagnosis, treatment and in research methodologies, and availability of long-term follow-up data, have helped reduce the variations to a much improved 73 to 96% reported good outcomes. With careful evaluation, good patient selection, and advanced surgical techniques, iNPH can be surgically treated to return patients close to their pre-iNPH functional status. Institution of an interdisciplinary effort to rehabilitate patients following surgery may help augment their recovery.

PMID: 31792620 [PubMed]

Anti-PD-L1 antibody direct activation of macrophages contributes to a radiation-induced abscopal response in glioblastoma.

Neuro Oncol. 2019 Dec 03;:

Authors: Ene CI, Kreuser SA, Jung M, Zhang H, Arora S, White Moyes K, Szulzewsky F, Barber J, Cimino PJ, Wirsching HG, Patel A, Kong P, Woodiwiss TR, Durfy SJ, Houghton AM, Pierce RH, Parney IF, Crane CA, Holland EC

Abstract
BACKGROUND: Most glioblastoma recurrences occur near prior radiation treatment sites. Future clinical success will require achieving and optimizing an 'abscopal effect', whereby un-irradiated neoplastic cells outside treatment sites are recognized and attacked by the immune system. Radiation combined with anti-PD-L1 demonstrated modest efficacy in phase II human glioblastoma clinical trials, but the mechanism and relevance of the abscopal effect during this response remains unknown.
METHODS: We modified an immune-competent, genetically-driven mouse glioma model (forced PDGF expression + PTEN loss) where a portion of the tumor burden is irradiated (PDGF) and another un-irradiated luciferase expressing tumor (PDGF+Luciferase) is used as a readout of the abscopal effect following systemic anti-PD-L1 immunotherapy. We assessed relevance of tumor neoepitope during the abscopal response by inducing expression of EGFRvIII (PDGF+EGFRvIII). Statistical tests were two-sided.
RESULTS: Following radiation of one lesion, anti-PD-L1 immunotherapy enhanced the abscopal response to the un-irradiated lesion. In PDGF-driven gliomas without tumor neoepitope (PDGF+Luciferase, n=8), the abscopal response occurred via anti-PD-L1-driven, ERK-mediated, bone marrow-derived macrophage phagocytosis of adjacent un-irradiated tumor cells, with modest survival implications (median survival 41 days vs. radiation alone 37.5 days, P=.03). In PDGF-driven gliomas with tumor neoepitope (PDGF+EGFRvIII, n=8), anti-PD-L1-enhanced abscopal response was associated with macrophage and T-cell infiltration and increased survival benefit (median survival 36 days vs. radiation alone 28 days, P=.001).
CONCLUSION: Our results indicate that anti-PD-L1 immunotherapy enhances a radiation induced abscopal response via canonical T-cell activation and direct macrophage activation in glioblastoma.

PMID: 31793634 [PubMed - as supplied by publisher]

Transcranial Doppler ultrasonography in neurological surgery and neurocritical care.

Neurosurg Focus. 2019 12 01;47(6):E2

Authors: Bonow RH, Young CC, Bass DI, Moore A, Levitt MR

Abstract
Transcranial Doppler (TCD) ultrasonography is an inexpensive, noninvasive means of measuring blood flow within the arteries of the brain. In this review, the authors outline the technology underlying TCD ultrasonography and describe its uses in patients with neurosurgical diseases. One of the most common uses of TCD ultrasonography is monitoring for vasospasm following subarachnoid hemorrhage. In this setting, elevated blood flow velocities serve as a proxy for vasospasm and can herald the onset of ischemia. TCD ultrasonography is also useful in the evaluation and management of occlusive cerebrovascular disease. Monitoring for microembolic signals enables stratification of stroke risk due to carotid stenosis and can also be used to clarify stroke etiology. TCD ultrasonography can identify patients with exhausted cerebrovascular reserve, and after extracranial-intracranial bypass procedures it can be used to assess adequacy of flow through the graft. Finally, assessment of cerebral autoregulation can be performed using TCD ultrasonography, providing data important to the management of patients with severe traumatic brain injury. As the clinical applications of TCD ultrasonography have expanded over time, so has their importance in the management of neurosurgical patients. Familiarity with this diagnostic tool is crucial for the modern neurological surgeon.

PMID: 31786564 [PubMed - indexed for MEDLINE]

Therapies for White Spot Lesions-A Systematic Review.

J Evid Based Dent Pract. 2017 Mar;17(1):23-38

Authors: Paula AB, Fernandes AR, Coelho AS, Marto CM, Ferreira MM, Caramelo F, do Vale F, Carrilho E

Abstract
INTRODUCTION: The first sign of dental caries is denoted by white spot lesions (WSLs) which can be defined as a demineralization of the enamel surface and subsurface, although these lesions can be reversed and do not form cavities. The aim of this systematic review was investigate which remineralization agents are effective for the treatment of WSLs.
MATERIALS AND METHODS: For this systematic review a literature search was conducted on Pubmed, Cochrane Library and ScienceDirect.
RESULTS: The initial search resulted in 273 references. After elimination of duplicate articles, 236 references remained. After reading titles and abstracts, all non-relevant results were excluded, resulting in 45 potentially relevant studies. After reading the full text, 13 references were included.
CONCLUSION: More studies are required for scientific evidence in order to reach a conclusion of the most suitable therapeutic method for the treatment of surface and subsurface demineralization of the enamel.

PMID: 28259311 [PubMed - indexed for MEDLINE]

Alpha Omega Alpha Honor Medical Society: A Commitment to Inclusion, Diversity, Equity, and Service in the Profession of Medicine.

Acad Med. 2020 05;95(5):670-673

Authors: Byyny RL, Martinez D, Cleary L, Ballard B, Barth BE, Christensen S, Eidson-Ton W, Estevez-Ordonez D, Fuhrer J, Kinzie JM, Lee AL, Lynch C, Pfeil S, Schoenbaum E

Abstract
With a motto of "Be Worthy to Serve the Suffering," Alpha Omega Alpha Honor Medical Society (AΩA) supports the importance, inclusion, and development of a culturally and ethnically diverse medical profession with equitable access for all. The underrepresentation of minorities in medical schools and medicine continues to be a challenge for the medical profession, medical education, and AΩA. AΩA has worked, and continues to work, to ensure the development of diverse leaders, fostering within them the objectivity and equity to be inclusive servant leaders who understand and embrace diversity in all its forms.Inclusion of talented individuals from different backgrounds benefits patient care, population health, education, and scientific discovery. AΩA values an inclusive, diverse, fair, and equitable work and learning environment for all and supports the medical profession in its work to achieve a welcoming, inclusive environment in teaching, learning, caring for patients, and collaboration.The diversity of medical schools is changing and will continue to change. AΩA is committed to continuing to work with its members, medical school deans, and AΩA chapters to assure that AΩA elections are unbiased and based on the values of AΩA and the profession of medicine in service to patients and the profession.Progress toward diversity, inclusion, and equity is more than simply checking off a box or responding to criticism-it is about being and developing diverse excellent physicians. AΩA and all those in the medical profession must continue to guide medicine to be unbiased, open, accepting, inclusive, and culturally aware in order to "Be Worthy to Serve the Suffering."

PMID: 31764080 [PubMed - indexed for MEDLINE]

Evidence that genes involved in hedgehog signaling are associated with both bipolar disorder and high BMI.

Transl Psychiatry. 2019 11 21;9(1):315

Authors: Pisanu C, Williams MJ, Ciuculete DM, Olivo G, Del Zompo M, Squassina A, Schiöth HB

Abstract
Patients with bipolar disorder (BD) show higher frequency of obesity and type 2 diabetes (T2D), but the underlying genetic determinants and molecular pathways are not well studied. Using large publicly available datasets, we (1) conducted a gene-based analysis using MAGMA to identify genes associated with BD and body mass index (BMI) or T2D and investigated their functional enrichment; and (2) performed two meta-analyses between BD and BMI, as well as BD and T2D using Metasoft. Target druggability was assessed using the Drug Gene Interaction Database (DGIdb). We identified 518 and 390 genes significantly associated with BD and BMI or BD and T2D, respectively. A total of 52 and 12 genes, respectively, were significant after multiple testing correction. Pathway analyses conducted on nominally significant targets showed that genes associated with BD and BMI were enriched for the Neuronal cell body Gene Ontology (GO) term (p = 1.0E-04; false discovery rate (FDR) = 0.025) and different pathways, including the Signaling by Hedgehog pathway (p = 4.8E-05, FDR = 0.02), while genes associated with BD and T2D showed no specific enrichment. The meta-analysis between BD and BMI identified 64 relevant single nucleotide polymorphisms (SNPs). While the majority of these were located in intergenic regions or in a locus on chromosome 16 near and in the NPIPL1 and SH2B1 genes (best SNP: rs4788101, p = 2.1E-24), five were located in the ETV5 gene (best SNP: rs1516725, p = 1E-24), which was previously associated with both BD and obesity, and one in the RPGRIP1L gene (rs1477199, p = 5.7E-09), which was also included in the Signaling by Hedgehog pathway. The meta-analysis between BD and T2D identified six significant SNPs, three of which were located in ALAS1 (best SNP: rs352165, p = 3.4E-08). Thirteen SNPs associated with BD and BMI, and one with BD and T2D, were located in genes which are part of the druggable genome. Our results support the hypothesis of shared genetic determinants between BD and BMI and point to genes involved in Hedgehog signaling as promising targets.

PMID: 31754094 [PubMed - indexed for MEDLINE]

Serum xanthophyll carotenoids are associated with estimated glomerular filtration rate in an aged cohort.

Sci Rep. 2019 11 19;9(1):17068

Authors: Browne D, Williams MA, Maxwell AP, McGuinness B, Passmore P, Silvestri G, Woodside JV, McKay GJ

Abstract
Progressive renal decline is associated with increasing oxidative stress. However, the majority of studies have investigated endogenous antioxidants in predominantly advanced stages of kidney disease. Many traditional risk factors associated with renal dysfunction have been linked with cognitive decline as the kidneys and brain share comparable anatomic and haemodynamic characteristics that leave them susceptible to common pathogenic mechanisms. The objective of this study was to examine serum dietary antioxidants and their association with renal function characterised by estimated glomerular filtration rate (eGFR) in a cross-sectional analysis of 570 participants. High performance liquid chromatography quantified serum levels of retinol, α-tocopherol, γ-tocopherol and six carotenoids (α-carotene, β-carotene, β-cryptoxanthin, lutein, lycopene and zeaxanthin) in participants. Multiple regression analyses were used to evaluate associations while adjusting for potential confounders. A sensitivity analysis was performed in cognitively-intact participants only. Serum levels of the xanthophyll carotenoid lutein were positively associated with eGFR in analyses adjusted for age (years), gender, smoking, APOE4 status and Alzheimer's disease. Retinol was inversely associated with eGFR, although was no longer significant in the smaller sensitivity analysis. Our findings identify significant associations between the xanthophyll carotenoids and eGFR. Further investigations are required to confirm these findings.

PMID: 31745176 [PubMed - indexed for MEDLINE]

Subdural hemorrhage rebleeding in abused children: frequency, associations and clinical presentation.

Pediatr Radiol. 2019 12;49(13):1762-1772

Authors: Wright JN, Feyma TJ, Ishak GE, Abeshaus S, Metz JB, Brown ECB, Friedman SD, Browd SR, Feldman KW

Abstract
BACKGROUND: Limited documentation exists about how frequently radiologically visible rebleeding occurs with abusive subdural hemorrhages (SDH). Likewise, little is known about rebleeding predispositions and associated symptoms.
OBJECTIVE: To describe the frequency of subdural rebleeding after abusive head trauma (AHT), its predispositions and clinical presentation.
MATERIALS AND METHODS: We evaluated children with SDHs from AHT who were reimaged within a year of their initial hospitalization, retrospectively reviewing clinical details and imaging. We used the available CT and MR images. We then performed simple descriptive and comparative statistics.
RESULTS: Fifty-four of 85 reimaged children (63.5%) with AHT-SDH rebled. No child had new trauma, radiologic evidence of new parenchymal injury or acute neurologic symptoms from rebleeding. From the initial presentation, macrocephaly was associated with subsequent rebleeding. Greater subdural depth, macrocephaly, ventriculomegaly and brain atrophy at follow-up were associated with rebleeding. No other radiologic findings at initial presentation or follow-up predicted rebleeding risk, although pre-existing brain atrophy at initial admission and initial chronic SDHs barely missed significance. Impact injuries, retinal hemorrhages and clinical indices of initial injury severity were not associated with rebleeding. All rebleeding occurred within chronic SDHs; no new bridging vein rupture was identified. The mean time until rebleeding was recognized was 12 weeks; no child had rebleeding after 49 weeks.
CONCLUSION: Subdural rebleeding is common and occurs in children who have brain atrophy, ventriculomegaly, macrocephaly and deep SDHs at rebleed. It usually occurs in the early months post-injury. All children with rebleeds were neurologically asymptomatic and lacked histories or clinical or radiologic findings of new trauma. Bleeds did not occur outside of chronic SDHs. We estimate the maximum predicted frequency of non-traumatic SDH rebleeding accompanied by acute neurological symptoms in children with a prior abusive SDH is 3.5%.

PMID: 31745619 [PubMed - indexed for MEDLINE]

MicroRNA-132-3p suppresses type I IFN response through targeting IRF1 to facilitate H1N1 influenza A virus infection.

Biosci Rep. 2019 12 20;39(12):

Authors: Zhang F, Lin X, Yang X, Lu G, Zhang Q, Zhang C

Abstract
Increasing evidence has indicated that microRNAs (miRNAs) have essential roles in innate immune responses to various viral infections; however, the role of miRNAs in H1N1 influenza A virus (IAV) infection is still unclear. The present study aimed to elucidate the role and mechanism of miRNAs in IAV replication in vitro. Using a microarray assay, we analyzed the expression profiles of miRNAs in peripheral blood from IAV patients. It was found that miR-132-3p was significantly up-regulated in peripheral blood samples from IAV patients. It was also observed that IAV infection up-regulated the expression of miR-132-3p in a dose- and time-dependent manner. Subsequently, we investigated miR-132-3p function and found that up-regulation of miR-132-3p promoted IAV replication, whereas knockdown of miR-132-3p repressed replication. Meanwhile, overexpression of miR-132-3p could inhibit IAV triggered INF-α and INF-β production and IFN-stimulated gene (ISG) expression, including myxovirus protein A (MxA), 2',5'-oligoadenylate synthetases (OAS), and double-stranded RNA-dependent protein kinase (PKR), while inhibition of miR-132-3p enhanced IAV triggered these effects. Of note, interferon regulatory factor 1 (IRF1), a well-known regulator of the type I IFN response, was identified as a direct target of miR-132-3p during HIN1 IAV infection. Furthermore, knockdown of IRF1 by si-IRF1 reversed the promoting effects of miR-132-3p inhibition on type I IFN response. Taken together, up-regulation of miR-132-3p promotes IAV replication by suppressing type I IFN response through its target gene IRF1, suggesting that miR-132-3p could represent a novel potential therapeutic target of IAV treatment.

PMID: 31746331 [PubMed - indexed for MEDLINE]

Full-Endoscopic Lumbar Discectomy.

Neurosurg Clin N Am. 2020 Jan;31(1):1-7

Authors: Sivakanthan S, Hasan S, Hofstetter C

Abstract
Full-endoscopic spine surgery has been developed to decrease approach-related morbidity and provide superior visualization. Using a working channel endoscope, lumbar disc herniations can be approached via two complementary corridors: the transforaminal approach and the interlaminar approach. Indications, contraindications, surgical technique, complications, and outcomes are discussed in this article. Multiple published studies have demonstrated the feasibility, safety, and efficacy of full-endoscopic lumbar discectomies. Emerging evidence suggests that full-endoscopic discectomies result in similar functional outcomes compared with microsurgical technique and are associated with shorter hospital stays, less opioid consumption, and fewer perioperative complications.

PMID: 31739919 [PubMed - indexed for MEDLINE]

Assessing the Interest and Cultural Congruence of Contingency Management as an Intervention for Alcohol Misuse Among Younger American Indian Adults.

Am Indian Alsk Native Ment Health Res. 2019;26(3):38-57

Authors: Hirchak KA, Herron J, Murphy SM, Donovan D, Roll JM, Buchwald D, McDonnell MG, McPherson SM, HONOR Study Team

Abstract
A qualitative study was conducted to assess interest in contingency management (CM) for younger American Indian (AI) adults (18-29 years old), how to culturally and developmentally adapt CM for younger AI adults, and interest in CM relative to culturally grounded treatment approaches. We conducted a total of four focus groups with younger adults and families in two AI communities: a rural reservation and an urban Indian health clinic (n = 32). Four overarching themes emerged suggesting that offering prizes, cultural activities, and activities that capture the attention of younger adults integrated into the CM intervention is ideal for enhancing engagement.

PMID: 31743414 [PubMed - indexed for MEDLINE]

Grp78 Loss in Epithelial Progenitors Reveals an Age-linked Role for Endoplasmic Reticulum Stress in Pulmonary Fibrosis.

Am J Respir Crit Care Med. 2020 01 15;201(2):198-211

Authors: Borok Z, Horie M, Flodby P, Wang H, Liu Y, Ganesh S, Firth AL, Minoo P, Li C, Beers MF, Lee AS, Zhou B

Abstract
Rationale: Alveolar epithelial cell (AEC) injury and dysregulated repair are implicated in the pathogenesis of pulmonary fibrosis. Endoplasmic reticulum (ER) stress in AEC has been observed in idiopathic pulmonary fibrosis (IPF), a disease of aging.Objectives: To investigate a causal role for ER stress in the pathogenesis of pulmonary fibrosis (PF) and therapeutic potential of ER stress inhibition in PF.Methods: The role of ER stress in AEC dysfunction and fibrosis was studied in mice with tamoxifen (Tmx)-inducible deletion of ER chaperone Grp78, a key regulator of ER homeostasis, in alveolar type II (AT2) cells, progenitors of distal lung epithelium, and in IPF lung slice cultures.Measurements and Main Results: Grp78 deletion caused weight loss, mortality, lung inflammation, and spatially heterogeneous fibrosis characterized by fibroblastic foci, hyperplastic AT2 cells, and increased susceptibility of old and male mice, all features of IPF. Fibrosis was more persistent in more severely injured Grp78 knockout (KO) mice. Grp78 KO AT2 cells showed evidence of ER stress, apoptosis, senescence, impaired progenitor capacity, and activation of TGF-β (transforming growth factor-β)/SMAD signaling. Glucose-regulated protein 78 is reduced in AT2 cells from old mice and patients with IPF, and ER stress inhibitor tauroursodeoxycholic acid ameliorates ER stress and fibrosis in Grp78 KO mouse and IPF lung slice cultures.Conclusions: These results support a causal role for ER stress and resulting epithelial dysfunction in PF and suggest ER stress as a potential mechanism linking aging to IPF. Modulation of ER stress and chaperone function may offer a promising therapeutic approach for pulmonary fibrosis.

PMID: 31738079 [PubMed - indexed for MEDLINE]

Myocardial tissue characterisation using echocardiographic deformation imaging.

Cardiovasc Ultrasound. 2019 Nov 15;17(1):27

Authors: Moharram MA, Lamberts RR, Whalley G, Williams MJA, Coffey S

Abstract
Myocardial pathology results in significant morbidity and mortality, whether due to primary cardiomyopathic processes or secondary to other conditions such as ischemic heart disease. Cardiac imaging techniques characterise the underlying tissue directly, by assessing a signal from the tissue itself, or indirectly, by inferring tissue characteristics from global or regional function. Cardiac magnetic resonance imaging is currently the most investigated imaging modality for tissue characterisation, but, due to its accessibility, advanced echocardiography represents an attractive alternative. Speckle tracking echocardiography (STE) is a reproducible technique used to assess myocardial deformation at both segmental and global levels. Since distinct myocardial pathologies affect deformation differently, information about the underlying tissue can be inferred by STE. In this review, the current available studies correlating STE deformation parameters with underlying tissue characteristics in humans are examined, with separate emphasis on global and segmental analysis. The current knowledge is placed in the context of integrated backscatter and the future of echocardiographic based tissue characterisation is discussed. The use of these imaging techniques to more precisely phenotype myocardial pathology more precisely will allow the design of translational cardiac research studies and, potentially, tailored management strategies.

PMID: 31730467 [PubMed - indexed for MEDLINE]

Application of the GRACE, TIMI, and TARRACO Risk Scores in Type 2 Myocardial Infarction.

J Am Coll Cardiol. 2020 01 28;75(3):344-345

Authors: Murphy SP, McCarthy CP, Cohen JA, Rehman S, Jones-O'Connor M, Olshan DS, Singh A, Vaduganathan M, Cui J, Januzzi JL, Wasfy JH

PMID: 31726195 [PubMed - indexed for MEDLINE]

Adoption of the Coronary Artery Disease-reporting and Data System: Reduced Downstream Testing and Cardiology Referral Rates in Patients with Non-obstructive Coronary Artery Disease.

Cureus. 2019 Sep 20;11(9):e5708

Authors: Boster J, Hull R, Williams MU, Berger J, Sharp A, Fentanes E, Maroules C, Cury R, Thomas D

Abstract
Introduction The coronary artery disease-reporting and data system (CAD-RADS) was developed to standardize communication of per-patient maximal stenosis and provide treatment recommendations that may affect downstream testing. Methods Downstream testing, cardiology referral, and cost were abstracted for 1,796 consecutive patients undergoing coronary CT angiography (CCTA) before and after the adoption of the CAD-RADS reporting template at a single-center closed referral hospital system. Cost analysis was based on direct invasive and non-invasive testing utilizing the Center for Medicare & Medicaid Services (CMS) outpatient prospective payment system (OPPS) final rule for 2018. Results Baseline cardiovascular risk factors were balanced between the groups. Overall, referrals for downstream testing were similar between cohorts (10.7% vs 10.8%; p = 0.939). Referral for downstream testing was reduced in the CAD-RADS 1 & 2 cohort compared to non-obstructive coronary artery disease (CAD) by non-standardized reporting (NSR; 5.1% vs 14.4%, p < 0.001). This was offset by more non-diagnostic scans in the CAD-RADS cohort (9.7% vs 4.2%, p < 0.001), resulting in increased downstream testing (28.8% vs 11.4%, p = 0.038). Overall, cardiology referral rates by primary care providers (PCPs) were similar between the groups (12.2% vs 15.8%, p = 0.197). Cardiology referral rates were increased among patients with non-obstructive CAD in the NSR cohort compared with CAD-RADS 1 & 2 patients (20.5% vs 8.6%, p = 0.021). Referrals for invasive coronary angiography were low in both groups overall (3.5% vs 3.2%, p = 0.726). Median downstream testing costs were similar between the groups (p = 0.554). Conclusions Adoption of the CAD-RADS reporting template was associated with a reduction in downstream testing and cardiology referral rates among non-obstructive CAD (CAD-RADS 1 & 2) patients. Thus, CAD-RADS may impact downstream testing in patients in whom further testing can typically be deferred.

PMID: 31720176 [PubMed]

Basilar Artery Ectasia Causing Trigeminal Neuralgia: An Evolved Technique of Transpositional Suture-Pexy.

Oper Neurosurg (Hagerstown). 2018 02 01;14(2):194-199

Authors: Singh H, da Silva HB, Zeinalizadeh M, Elarjani T, Straus D, Sekhar LN

Abstract
BACKGROUND: Microvascular decompression for patients with trigeminal neuralgia (TGN) is widely accepted as one of the modalities of treatment. The standard approach has been retrosigmoid suboccipital craniotomy with placement of a Teflon pledget to cushion the trigeminal nerve from the offending artery, or cauterize and divide the offending vein(s). However, in cases of severe compression caused by a large artery, the standard decompression technique may not be effective.
OBJECTIVE: To describe a unique technique of vasculopexy of the ectatic basilar artery to the tentorium in a patient with TGN attributed to a severely ectatic and tortuous basilar artery. A case series of patients who underwent this technique of vasculopexy for arterial compression is presented.
METHODS: The patient underwent a subtemporal transtentorial approach and the basilar artery was mobilized away from the trigeminal nerve. A suture was then passed through the wall of the basilar artery (tunica media) and secured to the tentorial edge, to keep the artery away from the nerve.
RESULTS: The neuralgia was promptly relieved after the operation, with no complications. A postoperative magnetic resonance imaging scan showed the basilar artery to be away from the trigeminal root. In a series of 7 patients who underwent this technique of vasculopexy, no arterial complications were noted at short- or long-term follow-up.
CONCLUSION: Repositioning and vasculopexy of an ectatic basilar artery for the treatment of TGN is safe and effective. This technique can also be used for other neuropathies that result from direct arterial compression.

PMID: 29351686 [PubMed - indexed for MEDLINE]

Consensus Statement on Sports-Related Concussions in Youth Sports Using a Modified Delphi Approach.

JAMA Pediatr. 2019 Nov 11;:

Authors: Rivara FP, Tennyson R, Mills B, Browd SR, Emery CA, Gioia G, Giza CC, Herring S, Janz KF, LaBella C, Valovich McLeod T, Meehan W, Patricios J, Four Corners Youth Consortium

Abstract
Importance: Given the importance of sports-related concussions among youth athletes, the rapid progress of research on this topic over the last decade, and the need to provide further guidance to youth athletes, their families, medical professionals, and athletic personnel and organizations, a panel of experts undertook a modified Delphi consensus process to summarize the current literature and provide recommendations regarding the prevention, assessment, and management of sports-related concussions for young athletes.
Methods: A consensus panel of 11 experts was created to represent a broad spectrum of expertise in youth sports and concussions. The specific questions to be addressed were developed through an iterative process consisting of 3 rounds, and a review of the literature was conducted to identify research studies related to each question. The consensus panel used a modified Delphi process to reach consensus on the conclusions and recommendations for each question.
Results and Conclusions: In 3 Delphi consensus rounds, 7 questions were addressed by the consensus panel of 11 experts, and 26 recommendations for the prevention, assessment, and management of sports-related concussions among young athletes were developed. For many of the questions addressed in this consensus statement, limitations existed in the quantity and quality of the evidence available to develop specific recommendations for youth sports stakeholders.

PMID: 31710349 [PubMed - as supplied by publisher]

Hospitalizations due to Angioedema without Urticaria in a Portuguese Center: Five Year Retrospective Study.

Acta Med Port. 2019 Nov 04;32(11):714-720

Authors: Cosme J, Spínola A, Ferreira MB, Barbosa MP

Abstract
INTRODUCTION: Hospitalizations due to angioedema are important especially in debilitating or life-threatening situations. The aim of this study was to evaluate the frequency and etiology of angioedema without urticaria in hospital admissions.
MATERIAL AND METHODS: The admissions between 2009 and 2013 in Centro Hospitalar Lisboa Norte with a diagnosis grouped under the ICD9 codes of angioedema were retrospectively analysed. The episodes of angioedema with urticaria were excluded. The admissions were categorized into 2 groups: A - hospitalizations motivated by the angioedema; B - hospitalizations in which the angioedema was an incidental finding.
RESULTS: There were 169 hospitalizations (52% females, 96% adults, mean age 52 ± 20.8 years), distributed by 23 hospital departments, 51% in the Immunoallergology department. The mean annual angioedema admission rate was 72/100 000. In 68% of the cases, angioedema was the cause for the admission; in 32% an incidental finding. In 38% there was upper airway involvement. The etiologies were: hereditary angioedema in 24%, angiotensin converting enzyme inhibitor induced angioedema in 31%, idiopathic angioedema in 21%, thrombolysis induced angioedema in 13%, nonsteroidal anti-inflammatory drug-induced angioedema in 5%.
DISCUSSION: The main etiology was angiotensin converting enzyme inhibitor angioedema, followed by hereditary angioedema and thrombolysis induced angioedema, and these findings concur with the international literature.
CONCLUSION: The mean annual angioedema admission rate was 72/100 000 and there was airway involvement in 38% of hospitalizations.

PMID: 31703184 [PubMed - indexed for MEDLINE]

Multimodal Characterization of the Late Effects of Traumatic Brain Injury: A Methodological Overview of the Late Effects of Traumatic Brain Injury Project.

J Neurotrauma. 2018 07 15;35(14):1604-1619

Authors: Edlow BL, Keene CD, Perl DP, Iacono D, Folkerth RD, Stewart W, Mac Donald CL, Augustinack J, Diaz-Arrastia R, Estrada C, Flannery E, Gordon WA, Grabowski TJ, Hansen K, Hoffman J, Kroenke C, Larson EB, Lee P, Mareyam A, McNab JA, McPhee J, Moreau AL, Renz A, Richmire K, Stevens A, Tang CY, Tirrell LS, Trittschuh EH, van der Kouwe A, Varjabedian A, Wald LL, Wu O, Yendiki A, Young L, Zöllei L, Fischl B, Crane PK, Dams-O'Connor K

Abstract
Epidemiological studies suggest that a single moderate-to-severe traumatic brain injury (TBI) is associated with an increased risk of neurodegenerative disease, including Alzheimer's disease (AD) and Parkinson's disease (PD). Histopathological studies describe complex neurodegenerative pathologies in individuals exposed to single moderate-to-severe TBI or repetitive mild TBI, including chronic traumatic encephalopathy (CTE). However, the clinicopathological links between TBI and post-traumatic neurodegenerative diseases such as AD, PD, and CTE remain poorly understood. Here, we describe the methodology of the Late Effects of TBI (LETBI) study, whose goals are to characterize chronic post-traumatic neuropathology and to identify in vivo biomarkers of post-traumatic neurodegeneration. LETBI participants undergo extensive clinical evaluation using National Institutes of Health TBI Common Data Elements, proteomic and genomic analysis, structural and functional magnetic resonance imaging (MRI), and prospective consent for brain donation. Selected brain specimens undergo ultra-high resolution ex vivo MRI and histopathological evaluation including whole-mount analysis. Co-registration of ex vivo and in vivo MRI data enables identification of ex vivo lesions that were present during life. In vivo signatures of postmortem pathology are then correlated with cognitive and behavioral data to characterize the clinical phenotype(s) associated with pathological brain lesions. We illustrate the study methods and demonstrate proof of concept for this approach by reporting results from the first LETBI participant, who despite the presence of multiple in vivo and ex vivo pathoanatomic lesions had normal cognition and was functionally independent until her mid-80s. The LETBI project represents a multidisciplinary effort to characterize post-traumatic neuropathology and identify in vivo signatures of postmortem pathology in a prospective study.

PMID: 29421973 [PubMed - indexed for MEDLINE]

Use Of Quantitative Modelling To Elucidate The Roles Of The Liver, Gut, Kidney, And Muscle In Ammonia Homeostasis And How Lactulose And Rifaximin Alter This Homeostasis.

Int J Gen Med. 2019;12:367-380

Authors: Levitt MD, Levitt DG

Abstract
Humans must eliminate approximately 1M of ammonia per day while maintaining the blood concentration of this potent neurotoxin at a concentration of only about 30 µM. The mechanisms producing such effective ammonia homeostasis are poorly understood by clinicians due to the multiple organs (liver, gut, kidney and muscle) involved in ammonia homeostasis. Based on literature values we present a novel, simplified description of normal and disordered ammonia and the potential mechanisms whereby the drugs used to treat hepatic encephalopathy, lactulose and rifaximin, lower the blood ammonia concentration. Concepts discussed include the following: 1) only about 44 mmol of ammonia/day (4.4% of total production) reaches the peripheral circulation due to the efficient linkage of amino deamination and the urea cycle in hepatic mitochondria; 2) the gut and kidney contribute roughly equally to delivery of this 44 mmol/day to systemic blood; 3) the bulk of gut ammonia production seemingly originates in the small bowel from bacterial deamination of urea by bacteria and mucosal deamination of circulating and ingested glutamine; 4) the apparent production of ammonia in the small bowel markedly exceeds that quantity that enters the portal blood, indicating that ammonia disposal mechanisms in the small bowel play a major role in ammonia homeostasis. With regard to the hyperammonemia of chronic liver disease: 1) shunting of portal blood around the liver, by itself, can account for commonly observed ammonia elevations; 2) severe portal hypertension causes an increased release of ammonia by the kidney; 3) high blood ammonia is associated with an unexplained massive increase in the muscle uptake of ammonia that could play an important role in limiting hyperammonemia; and 4) a major action of lactulose administration may be the enhancement of ammonia uptake by small bowel bacteria, while the mechanism of action of rifaximin is unclear.

PMID: 31686894 [PubMed]