A review of findings from research on risk for suicide among older adult veterans by Sulllivan and colleagues1 identified several factors, including diagnosis with posttraumatic stress disorder and social isolation associated with increased risk for self-harm among older adult veterans. While this review will surely raise awareness of characteristics associated with suicide among older Veterans, the assumptions underlying much of the reviewed literature limit utility of these findings. In the following sections, we provide a critical review of existing research, identify gaps in previous efforts and suggest ways for research and clinical services to improve on existing services.

PURPOSE:To assess the potential of a joint dual-energy computerized tomography (CT) reconstruction process (statistical image reconstruction method built on a basis vector model (JSIR-BVM)) implemented on a 16-slice commercial CT scanner to measure high spatial resolution stopping-power ratio (SPR) maps with uncertainties of less than 1%. METHODS:JSIR-BVM was used to reconstruct images of effective electron density and mean excitation energy from dual-energy CT (DECT) sinograms for 10 high-purity samples of known density and atomic composition inserted into head and body phantoms. The measured DECT data consisted of 90 and 140 kVp axial sinograms serially acquired on a Philips Brilliance Big Bore CT scanner without beam-hardening corrections. The corresponding SPRs were subsequently measured directly via ion chamber measurements on a MEVION S250 superconducting synchrocyclotron and evaluated theoretically from the known sample compositions and densities. Deviations of JSIR-BVM SPR values from their theoretically calculated and directly measured ground-truth values were evaluated for our JSIR-BVM method and our implementation of the Hünemohr-Saito (H-S) DECT image-domain decomposition technique for SPR imaging. A thorough uncertainty analysis was then performed for five different scenarios (comparison of JSIR-BVM stopping-power ratio/stopping power (SPR/SP) to International Commission on Radiation Measurements and Units benchmarks; comparison of JSIR-BVM SPR to measured benchmarks; and uncertainties in JSIR-BVM SPR/SP maps for patients of unknown composition) per the Joint Committee for Guides in Metrology and the Guide to Expression of Uncertainty in Measurement, including the impact of uncertainties in measured photon spectra, sample composition and density, photon cross section and I-value models, and random measurement uncertainty. Estimated SPR uncertainty for three main tissue groups in patients of unknown composition and the weighted proportion of each tissue type for three proton treatment sites were then used to derive a composite range uncertainty for our method. RESULTS:Mean JSIR-BVM SPR estimates deviated by less than 1% from their theoretical and directly measured ground-truth values for most inserts and phantom geometries except for high-density Delrin and Teflon samples with SPR error relative to proton measurements of 1.1% and -1.0% (head phantom) and 1.1% and -1.1% (body phantom). The overall root-mean-square (RMS) deviations over all samples were 0.39% and 0.52% (head phantom) and 0.43% and 0.57% (body phantom) relative to theoretical and directly measured ground-truth SPRs, respectively. The corresponding RMS (maximum) errors for the image-domain decomposition method were 2.68% and 2.73% (4.68% and 4.99%) for the head phantom and 0.71% and 0.87% (1.37% and 1.66%) for the body phantom. Compared to H-S SPR maps, JSIR-BVM yielded 30% sharper and twofold sharper images for soft tissues and bone-like surrogates, respectively, while reducing noise by factors of 6 and 3, respectively. The uncertainty (coverage factor k = 1) of the DECT-to-benchmark values comparison ranged from 0.5% to 1.5% and is dominated by scanning-beam photon-spectra uncertainties. An analysis of the SPR uncertainty for patients of unknown composition showed a JSIR-BVM uncertainty of 0.65%, 1.21%, and 0.77% for soft-, lung-, and bony-tissue groups which led to a composite range uncertainty of 0.6-0.9%. CONCLUSIONS:Observed JSIR-BVM SPR estimation errors were all less than 50% of the estimated k = 1 total uncertainty of our benchmarking experiment, demonstrating that JSIR-BVM high spatial resolution, low-noise SPR mapping is feasible and is robust to variations in the geometry of the scanned object. In contrast, the much larger H-S SPR estimation errors are dominated by imaging noise and residual beam-hardening artifacts. While the uncertainties characteristic of our current JSIR-BVM implementation can be as large as 1.5%, achieving < 1% total uncertainty is feasible by improving the accuracy of scanner-specific scatter-profile and photon-spectrum estimates. With its robustness to beam-hardening artifact, image noise, and variations in phantom size and geometry, JSIR-BVM has the potential to achieve high spatial-resolution SPR mapping with subpercentage accuracy and estimated uncertainty in the clinical setting.

Background: Major Depressive Disorder (MDD) is a leading cause of disease morbidity. Combined treatment with antidepressant medication (ADM) plus psychotherapy yields a much higher MDD remission rate than ADM-only. But 77% of US MDD patients are nonetheless treated with ADM-only despite strong patient preferences for psychotherapy. This mismatch is due at least in part to a combination of cost considerations and limited availability of psychotherapists, although stigma and reluctance of PCPs to refer patients for psychotherapy are also involved. Internet-based Cognitive Behavior Therapy (i-CBT) addresses all of these problems. Methods: Enrolled patients (n=3,360) will be those who are beginning ADM-only treatment of MDD in primary care facilities throughout West Virginia, one of the poorest and most rural states in the country. Participating treatment providers and study staff at West Virginia University School of Medicine (WVU) will recruit patients and, after obtaining informed consent, administer a baseline self-report questionnaire (SRQ) and then randomize patients to 1 of 3 treatment arms with equal allocation: ADM-only, ADM + self-guided i-CBT, and ADM + guided i-CBT. Follow-up SRQs will be administered 2, 4, 8, 13, 16, 26, 39, and 52 weeks after randomization. The trial has two primary objectives: to evaluate aggregate comparative treatment effects across the 3 arms; and to estimate heterogeneity of treatment effects (HTE). The primary outcome will be episode remission based on a modified version of the patient-centered Remission from Depression Questionnaire (RDQ). The sample was powered to detect predictors of HTE that would increase the proportional remission rate by 20% by optimally assigning individuals as opposed to randomly assigning them into three treatment groups of equal size. Aggregate comparative treatment effects will be estimated using intent-to-treat analysis methods. Cumulative inverse probability weights will be used to deal with loss to follow-up. A wide range of self-report predictors of MDD heterogeneity of treatment effects based on previous studies will be included in the baseline SRQ. A state-of-the-art ensemble machine learning method will be used to estimate HTE.Discussion: The study is innovative in using a rich baseline assessment and in having a sample large enough to carry out a well-powered analysis of heterogeneity of treatment effects. We anticipate finding that self-guided and guided i-CBT will both improve outcomes compared to ADM-only. We also anticipate finding that the comparative advantages of adding i-CBT to ADM will vary significantly across patients. We hope to develop a stable individualized treatment rule that will allow patients and treatment providers to improve aggregate treatment outcomes by deciding collaboratively when ADM treatment should be augmented with i-CBT. Trial registration: The Appalachian Mind Health Initiative (AMHI; registry name) was prospectively registered on 10/9/19 (ClinicalTrials.gov Identifier: NCT04120285).

PurposeTo investigate via Monte Carlo simulations, the impact of scan subject size, antiscatter grid (ASG), collimator size, and bowtie filter on the distribution of scatter radiation in a typical realistically modeled third generation 16 slice diagnostic computed tomography (CT) scanner.MethodsFull radiation transport was simulated with Geant4 in a realistic CT scanner geometric model, including the imaging phantom, bowtie filter (BTF), collimators and detector assembly, except for the ASGs. An analytical method was employed to quantify the probable transmission through the ASG of each photon intersecting the detector array. Normalized scatter profiles (NSP) and scatter‐to‐primary‐ratio (SPR) profiles were simulated for 90 and 140 kVp beams for different size phantoms and slice thicknesses. The impact of CT scatter on the reconstructed attenuation coefficient factor was also studied as were the modulating effects of phantom‐ and patient‐tissue heterogeneities on scatter profiles. A method to characterize the relative spatial frequency content of sinogram signals was developed to assess the latter.ResultsFor the 21.4‐cm diameter phantom, NSP and SPR increase linearly with collimator opening for both tube potentials, with the 90 kVp scan exhibiting slightly larger NSP and SPR. The BTF modestly modulates scatter under the phantom center, reducing the prominent off‐axis lobes by factors of 1.1–1.3. The ASG reduces scatter on the central axis NSP threefold, and reduces scatter at the detectors outside the phantom shadow by factors of 25 to 500. For the phantoms with diameters of 27 and 32 cm, the scatter increases roughly three‐ and fourfold, respectively, demonstrating that scatter monotonically increases with phantom size, despite deployment of the ASG and BTF. In the absence of a scan subject, the ASG reduces the signal profile arising photons scattered by the BTF. Without ASG, the in‐air scatter profile is relatively flat compared to the scatter profile when the ASG is present. For both 90 and 140 kVp photon spectra, the calculated attenuation coefficient decreases linearly with increasing collimation size. For both homogeneous and heterogeneous objects, NSPs are dominated by low spatial frequency content compared to the primary signal. However, the SPR, which quantifies the local magnitude of nonlinear detector response and is dominated by the high frequency content of the primary profile, can contribute strongly to high‐spatial frequency streaking artifacts near high‐density structures in reconstructed image artifacts.ConclusionPublic‐domain Monte Carlo codes, Geant‐4 in particular, is a feasible method for characterizing CT detector response to scattered‐ and off‐focal radiation. Our study demonstrates that the ASG substantially reduces the scatter radiation and reshapes scatter‐radiation profiles and affects the accuracy with which the detector array can measure narrow‐beam attenuation due its inability to distinguish between true uncollided primary and narrow‐angle coherently scattered photons. Hence, incorporating the impact of detector array collimation into the forward‐projection signal formation models used by iterative reconstruction algorithms is necessary to use CT for accurately characterizing material properties. While tissue heterogeneities exercise a modest influence on local NPS shape and magnitude, they do not add significant high spatial frequency content.

Proton radiotherapy has the potential to provide clinically effective treatment and highly conformal dose delivery when the rapid dose falloff at the end of its proton-beam range is correctly aligned to the distal margin of the clinical target volume. However, in current clinical practice an additional 2-3.5% safety margin must be added to the proton range to account for uncertainties in the estimation of proton-beam range when using stopping-power ratios (SPRs) derived from single-energy CT scans. Several approaches have been proposed to estimate stopping power by using dual-energy CT (DECT) and have been shown through theoretical analysis to outperform single-energy CT (SECT) under the presence of tissue composition and density variations. Our lab previously proposed a joint statistical image reconstruction (JSIR) method built on a basis-vector model (BVM) tissue parameterization for SPR estimation, which was shown to perform comparatively better than other DECT image- and sinogram-domain decomposition approaches on simulated as well as experimental data. This comparison, however, assumed theoretical SPR values calculated from the samples’ known compositions and densities as ground truth and used the mean excitation energy and effective electron density from ICRU reports along with a simplified version of the Bethe-Bloch equation to determine SPR reference values. Furthermore, CT scans were acquired with an assumed ideal point source at a narrow beam collimation; thus, the signal formation assumed by our JSIR process neglected scatter and off-focal radiation. In this paper, we verify the accuracy of our method by comparing the SPR values derived from JSIR-BVM to direct measurements of relative SPR, as well as present a preliminary study on the impact of fan-beam scatter radiation on JSIR-BVM SPR prediction accuracy.

Objective: Pilot-study of plasma exchange(PLEX) in painful neuropathy(PN), evaluating effects on neuropathic pain, local inflammatory cytokines measured in cutaneous interstitial fluid(CIF) collected from experimentally-induced skin blisters(EISB), serological inflammatory markers, quality of life measures, and stimulated skin-wrinkling via topical eutectic mixture of local anesthetics(SSW-EMLA) to the distal digit pulp. Background: CIF cytokines from EISB are elevated in diabetic patients compared to healthy controls(Illigens et al, AAN2012) and may play a role in diabetic PN. SSW-EMLA may correlate with neuropathy severity and autonomic dysfunction(Wilder-Smith et al). PLEX reduces inflammation and is used in few inflammatory neuropathies, but not in diabetic or idiopathic PN. Design/Methods: University-IRB-approved open-label pilot-study of 3-alternate-days of PLEX in 6 patients with diabetic or idiopathic PN, refractory to standard pain medications, which remained unchanged. We compared pre-and post-PLEX pain scales(Likert of highest and lowest pain in a 10-scale and Visual-Analog-Scales), depression, quality of life, as well as labwork(CIF cytokine analysis from foot EISB using ELISA bead-based multiplex assay, erythrocyte sedimentation rate and c-reactive protein), and SSW-EMLA(for sympathetic function, using digital photographs of the distal digit pulps(Teoh et al). Results: All subjects(4 diabetic, 2 idiopathic) tolerated well and had no complications from outpatient peripheral IV PLEX, EISB or CIF collection. EISB were painless, inducing 8mm-blisters on dorsum of foot after 90–120minutes of low-20mmHg vacuum pressure. Pain reduction lasted longer than 7 days. Depression scores were unchanged. ESR and CRP were elevated and reduced after PLEX. Results for 34 cytokines from CIF were complex and will be presented in table format. SSW-EMLA improved in only 1 subject. Conclusions: This pilot-study raises the possibility of treatable and modifiable inflammatory factors in chronic PN. The CIF cytokine analysis is complex, but the EISB method may be a promising tool to study local milieu of inflammatory and neurogenic changes in PN. Further research is needed. Study Supported by: TerumoBCT. Dr. De Sousa was the winner of 2012 Plasma Exchange Innovation Award funded by TerumoBCT. This award was used to conduct this study. Disclosure: Dr. De Sousa has nothing to disclose. Dr. Webb has nothing to disclose. Dr. Moon has nothing to disclose.

PurposeRange errors constrain treatment planning by limiting choice of ion beam angles and requiring large margins. Ionoacoustic range verification requires recovering the location of an acoustic source from low frequency signals. A priori information is applied to stably overcome resolution limits of inverse acoustic source imaging in this simulation study. In particular, the accuracy and robustness of ionoacoustic range verification for lateral and oblique delivery of high‐energy protons to the prostate is examined.MethodsDose maps were computed using GEANT4 Monte Carlo simulations via the TOPAS user interface. Thermoacoustic pulses were propagated using k‐Wave software, with initial pressures corresponding to instantaneous dose deposition and piecewise constant maps of tissue properties derived from the planning CT. A database of dose maps with corresponding thermoacoustic emissions and Bragg peak locations, referred to as “control points,” were precomputed. Corresponding thermoacoustic emissions were also precomputed. Pulses were recorded at four coplanar locations corresponding to the outer surface of a virtual transrectal array. To model experimental beam delivery, k‐Wave results were convolved in time with a Gaussian envelope to account for noninstantaneous proton delivery by a synchrocyclotron. Thermoacoustic pulses were bandlimited below 150 kHz, and amplitudes were directly proportional to charge delivered. To test robustness of our method, white noise was added. Range was estimated in a two‐step process. The first step obtained a preliminary range estimate by one‐way beamforming. The second step was taken using data corresponding to the “control point” nearest to the preliminary range estimate. For each receiver, the time of flight difference, ∆t, between the measured and control thermoacoustic signals were accurately estimated by applying the Fourier shift theorem. Receiver‐Bragg peak distance was then estimated by adding vs∆t to the known distance of the control point, where vs is soundspeed. A linear system of equations based upon all receiver locations and distances was solved to recover the Bragg peak location. All simulations were performed relative to the planning CT. Because ultrasound (US) images were not available, results were overlaid onto the planning CT.ResultsBeamformed estimates from noise‐free data tracked all beam locations within 1 cm. Final estimates for oblique and lateral beams were accurate to within 1.0 and 1.6 mm respectively. Average errors of final range estimates for oblique beams from data with SNR = 0 dB were no greater than 2.0 mm.ConclusionsIonoacoustic range verification may improve current practice. Ionoacoustic range estimates can be inherently co‐registered to ultrasound images of underlying anatomy. To ensure estimates are robust in clinical practice, dose maps based upon the planning CT should be overlaid onto ultrasound volumes acquired at time of treatment and acoustic simulations re‐computed to provide a database of control points and corresponding thermoacoustic emissions. Computation times for beamformed estimates are already fast enough for online range verification, but are not accurate enough for a measurement aperture limited to the surface of a transrectal ultrasound probe. Accelerated acoustic simulations will be required to enable online two‐stage correction, but offline calculation is already suitable for adaptive planning.

BACKGROUND Human ANK2 (ankyrin-B) loss-of-function variants are directly linked with arrhythmia phenotypes. However, in atypical non ion channel arrhythmia genes such as ANK2 that lack the same degree of robust structure/function and clinical data, it may be more difficult to assign variant disease risk based simply on variant location, minor allele frequency, and/or predictive structural algorithms. The human ankyrin-B p.L1622I variant found in arrhythmia probands displays significant diversity in minor allele frequency across populations.OBJECTIVE The objective of this study was to directly test the in vivo impact of ankyrin-B p.L1622I on cardiac electrical phenotypes and arrhythmia risk using a new animal model.METHODS We tested arrhythmia phenotypes in a new "knock-in" animal model harboring the human ankyrin-B p.L1622I variant.RESULTS Ankyrin-B p.L1622I displays reduced posttranslational expression in vivo, resulting in reduced cardiac ankyrin-B expression and reduced association with binding-partner Na/Ca exchanger. Ankyrin-B-L1622I/L1622I mice display changes in heart rate, atrioventricular and intraventricular conduction, and alterations in repolarization. Furthermore, ankyrin-B-L1622I/L1622I mice display catecholamine-dependent arrhythmias. At the cellular level, ankyrin-B-L1622L/L1622I myocytes display increased action potential duration and severe arrhythmogenic afterdepolarizations that provide a mechanistic rationale for the arrhythmias.CONCLUSION Our findings support in vivo arrhythmogenic phenotypes of an ANK2 variant with unusual frequency in select populations. On the basis of our findings and current clinical data, we support classification of p.L1622I as a "mild" loss-of-function variant that may confer arrhythmia susceptibility in the context of secondary risk factors including environment, medication, and/or additional genetic variation.

β2-Spectrin is critical for integrating membrane and cytoskeletal domains in excitable and nonexcitable cells. The role of β2-spectrin for vertebrate function is illustrated by dysfunction of β2-spectrin-based pathways in disease. Recently, defects in β2-spectrin association with protein partner ankyrin-B were identified in congenital forms of human arrhythmia. However, the role of β2-spectrin in common forms of acquired heart failure and arrhythmia is unknown. We report that β2-spectrin protein levels are significantly altered in human cardiovascular disease as well as in large and small animal cardiovascular disease models. Specifically, β2-spectrin levels were decreased in atrial samples of patients with atrial fibrillation compared with tissue from patients in sinus rhythm. Furthermore, compared with left ventricular samples from nonfailing hearts, β2-spectrin levels were significantly decreased in left ventricle of ischemic- and nonischemic heart failure patients. Left ventricle samples of canine and murine heart failure models confirm reduced β2-spectrin protein levels. Mechanistically, we identify that β2-spectrin levels are tightly regulated by posttranslational mechanisms, namely Ca(2+)- and calpain-dependent proteases. Furthermore, consistent with this data, we observed Ca(2+)- and calpain-dependent loss of β2-spectrin downstream effector proteins, including ankyrin-B in heart. In summary, our findings illustrate that β2-spectrin and downstream molecules are regulated in multiple forms of cardiovascular disease via Ca(2+)- and calpain-dependent proteolysis.

Anti-citrullinated protein antibodies (ACPA) are important serological markers in the diagnosis of rheumatoid arthritis (RA) and are part of the recent disease classification criteria. However, there is a strong need for reliable markers for measuring and predicting joint damage and disease activity. Recently, antibodies directed against carbamylated antigens (anti-CarP antibodies) were identified. A total of 120 RA patients were tested for anti-CCP antibodies using different methods and for anti-CarP antibodies using carbamylated fetal calf serum according to the method described by Shi et al. Additionally, ACPA fine specificities (to three citrullinated peptides) were measured. Disease activity was assessed at baseline using the disease activity score 28 (DAS28) in 80 patients. For 40 RA patients, joint erosion score (JES) was established. The median JES was 14.1 with a standard deviation of 11.5. Anti-CarP antibodies were correlated with joint erosion score (ρ = 0.34, 95 % CI 0.03–0.59; p = 0.0332). No correlation between ACPA and joint erosion score was observed. No individual marker correlated with DAS28. When one ACPA peptide was combined with anti-CarP antibodies in a score (ACPA peptide 1 divided by anti-CarP), a statistically relevant correlation was found (p = 0.0264). In this small cohort, the presence of anti-CarP antibodies, but not ACPA correlate with joint erosion score. Anti-CarP antibodies combined with ACPA fine specificities correlated with DAS28. Therefore, anti-CarP antibodies might represent a promising marker to predict joint damage and disease activity in RA patients.

Muscle & NerveVolume 53, Issue 2 p. 165-168 Editorial Editorial by concerned physicians: Unintended effect of the orphan drug act on the potential cost of 3,4-diaminopyridine Ted M. Burns MD, Corresponding Author Ted M. Burns MD Department of Neurology, University of Virginia, Charlottesville, Virginia, 22908 USA T.M.B. and G.A.S. are co–first authors.Correspondence to: T.M. Burns; e-mail: [email protected]Search for more papers by this authorGordon A. Smith MD, Gordon A. Smith MD Department of Neurology University of Utah, Salt Lake City, Utah, USA T.M.B. and G.A.S. are co–first authors.Search for more papers by this authorJeffrey A. Allen MD, Jeffrey A. Allen MD Department of Neurology, University of Minnesota, Minneapolis, Minnesota, USASearch for more papers by this authorAnthony A. Amato MD, Anthony A. Amato MD Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USASearch for more papers by this authorW. David Arnold MD, W. David Arnold MD Department of Neurology and Physical Medicine and Rehabilitation, Ohio State University, Columbus, Ohio, USASearch for more papers by this authorRichard Barohn MD, Richard Barohn MD Department of Neurology, University of Kansas, Kansas City, Kansas, USASearch for more papers by this authorMichael Benatar MD, PhD, Michael Benatar MD, PhD Department of Neurology, University of Miami, Miami, Florida, USASearch for more papers by this authorShawn J. Bird MD, Shawn J. Bird MD Department of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, USASearch for more papers by this authorMark Bromberg MD, Mark Bromberg MD Department of Neurology University of Utah, Salt Lake City, Utah, USASearch for more papers by this authorNizar Chahin MD, Nizar Chahin MD Department of Neurology, University of Connecticut, Farmington, Connecticut, USASearch for more papers by this authorEmma Ciafaloni MD, Emma Ciafaloni MD Department of Neurology, University of Rochester, Rochester, New York, USASearch for more papers by this authorJeffrey A. Cohen MD, Jeffrey A. Cohen MD Department of Neurology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USASearch for more papers by this authorAndrea Corse MD, Andrea Corse MD Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USASearch for more papers by this authorBrian A. Crum MD, Brian A. Crum MD Department of Neurology, Mayo Clinic, Rochester, Minnesota, USASearch for more papers by this authorWilliam S. David MD, William S. David MD Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USASearch for more papers by this authorElliot Dimberg MD, Elliot Dimberg MD Department of Neurology, Mayo Clinic, Jacksonville, Florida, USASearch for more papers by this authorEduardo A. De Sousa MD, Eduardo A. De Sousa MD Department of Neurology, University of Oklahoma, Oklahoma City, Oklahoma, USASearch for more papers by this authorPeter D. Donofrio MD, Peter D. Donofrio MD Department of Neurology, Vanderbilt University, Nashville, Tennessee, USASearch for more papers by this authorP. James B. Dyck MD, P. James B. Dyck MD Department of Neurology, Mayo Clinic, Rochester, Minnesota, USASearch for more papers by this authorAndrew G. Engel MD, Andrew G. Engel MD Department of Neurology, Mayo Clinic, Rochester, Minnesota, USASearch for more papers by this authorErik R. Ensrud MD, Erik R. Ensrud MD Department of Neurology, Boston Veterans Affairs, Boston, Massachusetts, USASearch for more papers by this authorMark Ferrante MD, Mark Ferrante MD Department of Neurology, University of Tennessee Health Science Center, Memphis, Tennessee, USASearch for more papers by this authorMiriam Freimer MD, Miriam Freimer MD Department of Neurology, Ohio State University, Columbus, Ohio, USASearch for more papers by this authorKarissa L. Gable MD, Karissa L. Gable MD Department of Neurology, Duke University, Durham, North Carolina, USASearch for more papers by this authorSummer Gibson MD, Summer Gibson MD Department of Neurology University of Utah, Salt Lake City, Utah, USASearch for more papers by this authorJames M. Gilchrist MD, James M. Gilchrist MD Department of Neurology, Southern Illinois University School of Medicine, Springfield, Illinois, USASearch for more papers by this authorJonathan M. Goldstein MD, Jonathan M. Goldstein MD Department of Neurology, Hospital for Special Surgery, New York, New York, USASearch for more papers by this authorClifton L. Gooch MD, Clifton L. Gooch MD Department of Neurology, University of South Florida, Tampa, Florida, USASearch for more papers by this authorBrent P. Goodman MD, Brent P. Goodman MD Department of Neurology, Mayo Clinic, Scottsdale, Arizona, USASearch for more papers by this authorDmitri Gorelov DO, Dmitri Gorelov DO Crystal Run Healthcare, Middletown, New York, USASearch for more papers by this authorSidney M. Gospe Jr. MD, PhD, Sidney M. Gospe Jr. MD, PhD Department of Neurology, University of Washington, Seattle, Washington, USASearch for more papers by this authorNamita A. Goyal MD, Namita A. Goyal MD Department of Neurology, University of California Irvine, Irvine, California, USASearch for more papers by this authorAmanda C. Guidon MD, Amanda C. Guidon MD Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USASearch for more papers by this authorJeffrey T. Guptill MD, Jeffrey T. Guptill MD Department of Neurology, Duke University, Durham, North Carolina, USASearch for more papers by this authorLaurie Gutmann MD, Laurie Gutmann MD Division of Neurology, University of Iowa, Iowa City, Iowa, USASearch for more papers by this authorLudwig Gutmann MD, Ludwig Gutmann MD Division of Neurology, University of Iowa, Iowa City, Iowa, USASearch for more papers by this authorKelly Gwathmey MD, Kelly Gwathmey MD Department of Neurology, University of Virginia, Charlottesville, Virginia, 22908 USASearch for more papers by this authorYadollah Harati MD, Yadollah Harati MD Department of Neurology, Baylor College of Medicine, Houston, Texas, USASearch for more papers by this authorC. Michel Harper Jr. MD, C. Michel Harper Jr. MD Department of Neurology, Mayo Clinic, Rochester, Minnesota, USASearch for more papers by this authorMichael K. Hehir MD, Michael K. Hehir MD Department of Neurology, University of Vermont, Burlington, Vermont, USASearch for more papers by this authorLisa D. Hobson-Webb MD, Lisa D. Hobson-Webb MD Department of Neurology, Duke University, Durham, North Carolina, USASearch for more papers by this authorJames F. Howard Jr. MD, James F. Howard Jr. MD Department of Neurology, University of North Carolina, Chapel Hill, North Carolina, USASearch for more papers by this authorCarlayne E. Jackson MD, Carlayne E. Jackson MD Department of Neurology and Otolaryngology, University of Texas Health Science Center, San Antonio, Texas, USASearch for more papers by this authorNicholas Johnson MD, Nicholas Johnson MD Department of Neurology University of Utah, Salt Lake City, Utah, USASearch for more papers by this authorSarah M. Jones MD, Sarah M. Jones MD Department of Neurology, University of Virginia, Charlottesville, Virginia, 22908 USASearch for more papers by this authorVern C. Juel MD, Vern C. Juel MD Department of Neurology, Duke University, Durham, North Carolina, USASearch for more papers by this authorHenry J. Kaminski MD, Henry J. Kaminski MD Department of Neurology, George Washington University, Washington, DC, USASearch for more papers by this authorChafic Karam MD, Chafic Karam MD Department of Neurology, University of North Carolina, Chapel Hill, North Carolina, USASearch for more papers by this authorKathleen D. Kennelly MD, PhD, Kathleen D. Kennelly MD, PhD Department of Neurology, Mayo Clinic, Jacksonville, Florida, USASearch for more papers by this authorSami Khella MD, Sami Khella MD Department of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, USASearch for more papers by this authorJulie Khoury MD, Julie Khoury MD Department of Neurology, Oregon Health Science University, Portland, Oregon, USASearch for more papers by this authorJohn C. Kincaid MD, John C. Kincaid MD Department of Neurology, Indiana University, Indianapolis, Indiana, USASearch for more papers by this authorJohn T. Kissel MD, John T. Kissel MD Department of Neurology, Ohio State University, Columbus, Ohio, USASearch for more papers by this authorNoah Kolb MD, Noah Kolb MD Department of Neurology University of Utah, Salt Lake City, Utah, USASearch for more papers by this authorDavid Lacomis MD, David Lacomis MD Department of Neurology and Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania, USASearch for more papers by this authorShafeeq Ladha MD, Shafeeq Ladha MD Department of Neurology, Barrow Neurological Institute, Phoenix, Arizona, USASearch for more papers by this authorDaniel Larriviere MD, JD, Daniel Larriviere MD, JD Department of Neurology, Ochsner Neuroscience Institute, New Orleans, Louisiana, USASearch for more papers by this authorRichard A. Lewis MD, Richard A. Lewis MD Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, California, USASearch for more papers by this authorYuebing Li MD, Yuebing Li MD Department of Neurology, Cleveland Clinic, Cleveland, Ohio, USASearch for more papers by this authorWilliam J. Litchy MD, William J. Litchy MD Department of Neurology, Mayo Clinic, Rochester, Minnesota, USASearch for more papers by this authorEric Logigian MD, Eric Logigian MD Department of Neurology, University of Rochester, Rochester, New York, USASearch for more papers by this authorJau-Shin Lou MD, PhD, Jau-Shin Lou MD, PhD Department of Neurology, University of North Dakota, Sanford Health, Fargo, North Dakota, USASearch for more papers by this authorDaniel J.L. MacGowen MD, Daniel J.L. MacGowen MD Department of Neurology, Department of Neurology, Mount Sinai Beth Israel Hospital, New York, New York, USASearch for more papers by this authorRicardo Maselli MD, Ricardo Maselli MD Department of Neurology, University of California, Davis, Sacramento, California, USASearch for more papers by this authorJanice M. Massey MD, Janice M. Massey MD Department of Neurology, Duke University, Durham, North Carolina, USASearch for more papers by this authorMichelle L. Mauermann MD, Michelle L. Mauermann MD Department of Neurology, Mayo Clinic, Rochester, Minnesota, USASearch for more papers by this authorKatherine D. Mathews MD, Katherine D. Mathews MD Division of Neurology, University of Iowa, Iowa City, Iowa, USASearch for more papers by this authorMatthew N. Meriggioli MD, Matthew N. Meriggioli MD Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois, USASearch for more papers by this authorRobert G. Miller MD, Robert G. Miller MD Department of Neurosciences, California Pacific Medical Center, San Francisco, California, USASearch for more papers by this authorJoon-Shik Moon MD, PhD, Joon-Shik Moon MD, PhD Department of Neurology, University of Oklahoma, Oklahoma City, Oklahoma, USASearch for more papers by this authorTahseen Mozaffar MD, Tahseen Mozaffar MD Department of Neurology, University of California Irvine, Irvine, California, USASearch for more papers by this authorSharon P. Nations MD, Sharon P. Nations MD Department of Neurology and Neurotherapeutics, University Texas Southwestern, Dallas, Texas, USASearch for more papers by this authorRichard J. Nowak MD, Richard J. Nowak MD Department of Neurology, Yale School of Medicine, New Haven, Connecticut, USASearch for more papers by this authorLyle W. Ostrow MD, PhD, Lyle W. Ostrow MD, PhD Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USASearch for more papers by this authorRobert M. Pascuzzi MD, Robert M. Pascuzzi MD Department of Neurology, Indiana University, Indianapolis, Indiana, USASearch for more papers by this authorAmanda Peltier MD, Amanda Peltier MD Department of Neurology, Vanderbilt University, Nashville, Tennessee, USASearch for more papers by this authorKatherine Ruzhansky MD, Katherine Ruzhansky MD Department of Neurology, Medical University of South Carolina, Charleston, South Carolina, USASearch for more papers by this authorDavid P. Richman MD, David P. Richman MD Department of Neurology, University of California, Davis, Sacramento, California, USASearch for more papers by this authorMark A. Ross MD, Mark A. Ross MD Department of Neurology, Mayo Clinic, Scottsdale, Arizona, USASearch for more papers by this authorDEVON I. Rubin MD, DEVON I. Rubin MD Department of Neurology, Mayo Clinic, Jacksonville, Florida, USASearch for more papers by this authorJames A. Russell DO, James A. Russell DO Department of Neurology, Lahey Hospital and Medical Center, Burlington, Massachusetts, USASearch for more papers by this authorGeorge M. Sachs MD, PhD, George M. Sachs MD, PhD Department of Neurology, Alpert Medical School of Brown University, Providence, Rhode Island, USASearch for more papers by this authorMohammad Kian Salajegheh MD, Mohammad Kian Salajegheh MD Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USASearch for more papers by this authorDavid S. Saperstein MD, David S. Saperstein MD Phoenix Neurological Associates, Phoenix, Arizona, USASearch for more papers by this authorStephen Scelsa MD, Stephen Scelsa MD Department of Neurology, Department of Neurology, Mount Sinai Beth Israel Hospital, New York, New York, USASearch for more papers by this authorDuygu Selcen MD, Duygu Selcen MD Department of Neurology, Mayo Clinic, Rochester, Minnesota, USASearch for more papers by this authorAziz Shaibani MD, Aziz Shaibani MD Nerve and Muscle Center of Texas, Houston, Texas, USASearch for more papers by this authorPerry B. Shieh MD, Perry B. Shieh MD Department of Neurology, University of California at Los Angeles, Los Angeles, California, USASearch for more papers by this authorNicholas J. Silvestri MD, Nicholas J. Silvestri MD Department of Neurology, University of Buffalo, Buffalo, New York, USASearch for more papers by this authorJ. Rob Singleton MD, J. Rob Singleton MD Department of Neurology University of Utah, Salt Lake City, Utah, USASearch for more papers by this authorBenn E. Smith MD, Benn E. Smith MD Department of Neurology, Mayo Clinic, Scottsdale, Arizona, USASearch for more papers by this authorYuen T. So MD, PhD, Yuen T. So MD, PhD Department of Neurology, Stanford University, Palo Alto, California, USASearch for more papers by this authorGuillermo Solorzano MD, Guillermo Solorzano MD Department of Neurology, University of Virginia, Charlottesville, Virginia, 22908 USASearch for more papers by this authorEric J. Sorenson MD, Eric J. Sorenson MD Department of Neurology, Mayo Clinic, Rochester, Minnesota, USASearch for more papers by this authorJayashri Srinivasen MD, Jayashri Srinivasen MD Department of Neurology, Lahey Hospital and Medical Center, Burlington, Massachusetts, USASearch for more papers by this authorJinny Tavee MD, Jinny Tavee MD Department of Neurology, Cleveland Clinic, Cleveland, Ohio, USASearch for more papers by this authorRabi Tawil MD, Rabi Tawil MD Department of Neurology, University of Rochester, Rochester, New York, USASearch for more papers by this authorPariwat Thaisetthawatkul MD, Pariwat Thaisetthawatkul MD Department of Neurology, University of Nebraska, Omaha, Nebraska, USASearch for more papers by this authorCharles Thornton MD, Charles Thornton MD Department of Neurology, University of Rochester, Rochester, New York, USASearch for more papers by this authorJaya Trivedi MD, Jaya Trivedi MD Department of Neurology, Yale School of Medicine, New Haven, Connecticut, USASearch for more papers by this authorSteven Vernino MD, PhD, Steven Vernino MD, PhD Department of Neurology and Neurotherapeutics, University Texas Southwestern, Dallas, Texas, USASearch for more papers by this authorAnnabel K. Wang MD, Annabel K. Wang MD Department of Neurology, Veterans Affairs Long Beach Healthcare System, Long Beach, California, USASearch for more papers by this authorTyler A. Webb MD, Tyler A. Webb MD Department of Neurology, University of Oklahoma, Oklahoma City, Oklahoma, USASearch for more papers by this authorMichael D. Weiss MD, Michael D. Weiss MD Department of Neurology, University of Washington, Seattle, Washington, USASearch for more papers by this authorAnthony J. Windebank MD, Anthony J. Windebank MD Department of Neurology, Mayo Clinic, Rochester, Minnesota, USASearch for more papers by this authorGil I. Wolfe MD, Gil I. Wolfe MD Department of Neurology, University of Buffalo, Buffalo, New York, USASearch for more papers by this author Ted M. Burns MD, Corresponding Author Ted M. Burns MD Department of Neurology, University of Virginia, Charlottesville, Virginia, 22908 USA T.M.B. and G.A.S. are co–first authors.Correspondence to: T.M. Burns; e-mail: [email protected]Search for more papers by this authorGordon A. Smith MD, Gordon A. Smith MD Department of Neurology University of Utah, Salt Lake City, Utah, USA T.M.B. and G.A.S. are co–first authors.Search for more papers by this authorJeffrey A. Allen MD, Jeffrey A. Allen MD Department of Neurology, University of Minnesota, Minneapolis, Minnesota, USASearch for more papers by this authorAnthony A. Amato MD, Anthony A. Amato MD Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USASearch for more papers by this authorW. David Arnold MD, W. David Arnold MD Department of Neurology and Physical Medicine and Rehabilitation, Ohio State University, Columbus, Ohio, USASearch for more papers by this authorRichard Barohn MD, Richard Barohn MD Department of Neurology, University of Kansas, Kansas City, Kansas, USASearch for more papers by this authorMichael Benatar MD, PhD, Michael Benatar MD, PhD Department of Neurology, University of Miami, Miami, Florida, USASearch for more papers by this authorShawn J. Bird MD, Shawn J. Bird MD Department of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, USASearch for more papers by this authorMark Bromberg MD, Mark Bromberg MD Department of Neurology University of Utah, Salt Lake City, Utah, USASearch for more papers by this authorNizar Chahin MD, Nizar Chahin MD Department of Neurology, University of Connecticut, Farmington, Connecticut, USASearch for more papers by this authorEmma Ciafaloni MD, Emma Ciafaloni MD Department of Neurology, University of Rochester, Rochester, New York, USASearch for more papers by this authorJeffrey A. Cohen MD, Jeffrey A. Cohen MD Department of Neurology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USASearch for more papers by this authorAndrea Corse MD, Andrea Corse MD Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USASearch for more papers by this authorBrian A. Crum MD, Brian A. Crum MD Department of Neurology, Mayo Clinic, Rochester, Minnesota, USASearch for more papers by this authorWilliam S. David MD, William S. David MD Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USASearch for more papers by this authorElliot Dimberg MD, Elliot Dimberg MD Department of Neurology, Mayo Clinic, Jacksonville, Florida, USASearch for more papers by this authorEduardo A. De Sousa MD, Eduardo A. De Sousa MD Department of Neurology, University of Oklahoma, Oklahoma City, Oklahoma, USASearch for more papers by this authorPeter D. Donofrio MD, Peter D. Donofrio MD Department of Neurology, Vanderbilt University, Nashville, Tennessee, USASearch for more papers by this authorP. James B. Dyck MD, P. James B. Dyck MD Department of Neurology, Mayo Clinic, Rochester, Minnesota, USASearch for more papers by this authorAndrew G. Engel MD, Andrew G. Engel MD Department of Neurology, Mayo Clinic, Rochester, Minnesota, USASearch for more papers by this authorErik R. Ensrud MD, Erik R. Ensrud MD Department of Neurology, Boston Veterans Affairs, Boston, Massachusetts, USASearch for more papers by this authorMark Ferrante MD, Mark Ferrante MD Department of Neurology, University of Tennessee Health Science Center, Memphis, Tennessee, USASearch for more papers by this authorMiriam Freimer MD, Miriam Freimer MD Department of Neurology, Ohio State University, Columbus, Ohio, USASearch for more papers by this authorKarissa L. Gable MD, Karissa L. Gable MD Department of Neurology, Duke University, Durham, North Carolina, USASearch for more papers by this authorSummer Gibson MD, Summer Gibson MD Department of Neurology University of Utah, Salt Lake City, Utah, USASearch for more papers by this authorJames M. Gilchrist MD, James M. Gilchrist MD Department of Neurology, Southern Illinois University School of Medicine, Springfield, Illinois, USASearch for more papers by this authorJonathan M. Goldstein MD, Jonathan M. Goldstein MD Department of Neurology, Hospital for Special Surgery, New York, New York, USASearch for more papers by this authorClifton L. Gooch MD, Clifton L. Gooch MD Department of Neurology, University of South Florida, Tampa, Florida, USASearch for more papers by this authorBrent P. Goodman MD, Brent P. Goodman MD Department of Neurology, Mayo Clinic, Scottsdale, Arizona, USASearch for more papers by this authorDmitri Gorelov DO, Dmitri Gorelov DO Crystal Run Healthcare, Middletown, New York, USASearch for more papers by this authorSidney M. Gospe Jr. MD, PhD, Sidney M. Gospe Jr. MD, PhD Department of Neurology, University of Washington, Seattle, Washington, USASearch for more papers by this authorNamita A. Goyal MD, Namita A. Goyal MD Department of Neurology, University of California Irvine, Irvine, California, USASearch for more papers by this authorAmanda C. Guidon MD, Amanda C. Guidon MD Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USASearch for more papers by this authorJeffrey T. Guptill MD, Jeffrey T. Guptill MD Department of Neurology, Duke University, Durham, North Carolina, USASearch for more papers by this authorLaurie Gutmann MD, Laurie Gutmann MD Division of Neurology, University of Iowa, Iowa City, Iowa, USASearch for more papers by this authorLudwig Gutmann MD, Ludwig Gutmann MD Division of Neurology, University of Iowa, Iowa City, Iowa, USASearch for more papers by this authorKelly Gwathmey MD, Kelly Gwathmey MD Department of Neurology, University of Virginia, Charlottesville, Virginia, 22908 USASearch for more papers by this authorYadollah Harati MD, Yadollah Harati MD Department of Neurology, Baylor College of Medicine, Houston, Texas, USASearch for more papers by this authorC. Michel Harper Jr. MD, C. Michel Harper Jr. MD Department of Neurology, Mayo Clinic, Rochester, Minnesota, USASearch for more papers by this authorMichael K. Hehir MD, Michael K. Hehir MD Department of Neurology, University of Vermont, Burlington, Vermont, USASearch for more papers by this authorLisa D. Hobson-Webb MD, Lisa D. Hobson-Webb MD Department of Neurology, Duke University, Durham, North Carolina, USASearch for more papers by this authorJames F. Howard Jr. MD, James F. Howard Jr. MD Department of Neurology, University of North Carolina, Chapel Hill, North Carolina, USASearch for more papers by this authorCarlayne E. Jackson MD, Carlayne E. Jackson MD Department of Neurology and Otolaryngology, University of Texas Health Science Center, San Antonio, Texas, USASearch for more papers by this authorNicholas Johnson MD, Nicholas Johnson MD Department of Neurology University of Utah, Salt Lake City, Utah, USASearch for more papers by this authorSarah M. Jones MD, Sarah M. Jones MD Department of Neurology, University of Virginia, Charlottesville, Virginia, 22908 USASearch for more papers by this authorVern C. Juel MD, Vern C. Juel MD Department of Neurology, Duke University, Durham, North Carolina, USASearch for more papers by this authorHenry J. Kaminski MD, Henry J. Kaminski MD Department of Neurology, George Washington University, Washington, DC, USASearch for more papers by this authorChafic Karam MD, Chafic Karam MD Department of Neurology, University of North Carolina, Chapel Hill, North Carolina, USASearch for more papers by this authorKathleen D. Kennelly MD, PhD, Kathleen D. Kennelly MD, PhD Department of Neurology, Mayo Clinic, Jacksonville, Florida, USASearch for more papers by this authorSami Khella MD, Sami Khella MD Department of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, USASearch for more papers by this authorJulie Khoury MD, Julie Khoury MD Department of Neurology, Oregon Health Science University, Portland, Oregon, USASearch for more papers by this authorJohn C. Kincaid MD, John C. Kincaid MD Department of Neurology, Indiana University, Indianapolis, Indiana, USASearch for more papers by this authorJohn T. Kissel MD, John T. Kissel MD Department of Neurology, Ohio State University, Columbus, Ohio, USASearch for more papers by this authorNoah Kolb MD, Noah Kolb MD Department of Neurology University of Utah, Salt Lake City, Utah, USASearch for more papers by this authorDavid Lacomis MD, David Lacomis MD Department of Neurology and Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania, USASearch for more papers by this authorShafeeq Ladha MD, Shafeeq Ladha MD Department of Neurology, Barrow Neurological Institute, Phoenix, Arizona, USASearch for more papers by this authorDaniel Larriviere MD, JD, Daniel Larriviere MD, JD Department of Neurology, Ochsner Neuroscience Institute, New Orleans, Louisiana, USASearch for more papers by this authorRichard A. Lewis MD, Richard A. Lewis MD Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, California, USASearch for more papers by this authorYuebing Li MD, Yuebing Li MD Department of Neurology, Cleveland Clinic, Cleveland, Ohio, USASearch for more papers by this authorWilliam J. Litchy MD, William J. Litchy MD Department of Neurology, Mayo Clinic, Rochester, Minnesota, USASearch for more papers by this authorEric Logigian MD, Eric Logigian MD Department of Neurology, University of Rochester, Rochester, New York, USASearch for more papers by this authorJau-Shin Lou MD, PhD, Jau-Shin Lou MD, PhD Department of Neurology, University of North Dakota, Sanford Health, Fargo, North Dakota, USASearch for more papers by this authorDaniel J.L. MacGowen MD, Daniel J.L. MacGowen MD Department of Neurology, Department of Neurology, Mount Sinai Beth Israel Hospital, New York, New York, USASearch for more papers by this authorRicardo Maselli MD, Ricardo Maselli MD Department of Neurology, University of California, Davis, Sacramento, California, USASearch for more papers by this authorJanice M. Massey MD, Janice M. Massey MD Department of Neurology, Duke University, Durham, North Carolina, USASearch for more papers by this authorMichelle L. Mauermann MD, Michelle L. Mauermann MD Department of Neurology, Mayo Clinic, Rochester, Minnesota, USASearch for more papers by this authorKatherine D. Mathews MD, Katherine D. Mathews MD Division of Neurology, University of Iowa, Iowa City, Iowa, USASearch for more papers by this authorMatthew N. Meriggioli MD, Matthew N. Meriggioli MD Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois, USASearch for more papers by this authorRobert G. Miller MD, Robert G. Miller MD Department of Neurosciences, California Pacific Medical Center, San Francisco, California, USASearch for more papers by this authorJoon-Shik Moon MD, PhD, Joon-Shik Moon MD, PhD Department of Neurology, University of Oklahoma, Oklahoma City, Oklahoma, USASearch for more papers by this authorTahseen Mozaffar MD, Tahseen Mozaffar MD Department of Neurology, University of California Irvine, Irvine, California, USASearch for more papers by this authorSharon P. Nations MD, Sharon P. Nations MD Department of Neurology and Neurotherapeutics, University Texas Southwestern, Dallas, Texas, USASearch for more papers by this authorRichard J. Nowak MD, Richard J. Nowak MD Department of Neurology, Yale School of Medicine, New Haven, Connecticut, USASearch for more papers by this authorLyle W. Ostrow MD, PhD, Lyle W. Ostrow MD, PhD Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USASearch for more papers by this authorRobert M. Pascuzzi MD, Robert M. Pascuzzi MD Department of Neurology, Indiana University, Indianapolis, Indiana, USASearch for more papers by this authorAmanda Peltier MD, Amanda Peltier MD Department of Neurology, Vanderbilt University, Nashville, Tennessee, USASearch for more papers by this authorKatherine Ruzhansky MD, Katherine Ruzhansky MD Department of Neurology, Medical University of South Carolina, Charleston, South Carolina, USASearch for more papers by this authorDavid P. Richman MD, David P. Richman MD Department of Neurology, University of California, Davis, Sacramento, California, USASearch for more papers by this authorMark A. Ross MD, Mark A. Ross MD Department of Neurology, Mayo Clinic, Scottsdale, Arizona, USASearch for more papers by this authorDEVON I. Rubin MD, DEVON I. Rubin MD Department of Neurology, Mayo Clinic, Jacksonville, Florida, USASearch for more papers by this authorJames A. Russell DO, James A. Russell DO Department of Neurology, Lahey Hospital and Medical Center, Burlington, Massachusetts, USASearch for more papers by this authorGeorge M. Sachs MD, PhD, George M. Sachs MD, PhD Department of Neurology, Alpert Medical School of Brown University, Providence, Rhode Island, USASearch for more papers by this authorMohammad Kian Salajegheh MD, Mohammad Kian Salajegheh MD Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USASearch for more papers by this authorDavid S. Saperstein MD, David S. Saperstein MD Phoenix Neurological Associates, Phoenix, Arizona, USASearch for more papers by this authorStephen Scelsa MD, Stephen Scelsa MD Department of Neurology, Department of Neurology, Mount Sinai Beth Israel Hospital, New York, New York, USASearch for more papers by this authorDuygu Selcen MD, Duygu Selcen MD Department of Neurology, Mayo Clinic, Rochester, Minnesota, USASearch for more papers by this authorAziz Shaibani MD, Aziz Shaibani MD Nerve and Muscle Center of Texas, Houston, Texas, USASearch for more papers by this authorPerry B. Shieh MD, Perry B. Shieh MD Department of Neurology, University of California at Los Angeles, Los Angeles, California, USASearch for more papers by this authorNicholas J. Silvestri MD, Nicholas J. Silvestri MD Department of Neurology, University of Buffalo, Buffalo, New York, USASearch for more papers by this authorJ. Rob Singleton MD, J. Rob Singleton MD Department of Neurology University of Utah, Salt Lake City, Utah, USASearch for more papers by this authorBenn E. Smith MD, Benn E. Smith MD Department of Neurology, Mayo Clinic, Scottsdale, Arizona, USASearch for more papers by this authorYuen T. So MD, PhD, Yuen T. So MD, PhD Department of Neurology, Stanford University, Palo Alto, California, USASearch for more papers by this authorGuillermo Solorzano MD, Guillermo Solorzano MD Department of Neurology, University of Virginia, Charlottesville, Virginia, 22908 USASearch for more papers by this authorEric J. Sorenson MD, Eric J. Sorenson MD Department of Neurology, Mayo Clinic, Rochester, Minnesota, USASearch for more papers by this authorJayashri Srinivasen MD, Jayashri Srinivasen MD Department of Neurology, Lahey Hospital and Medical Center, Burlington, Massachusetts, USASearch for more papers by this authorJinny Tavee MD, Jinny Tavee MD Department of Neurology, Cleveland Clinic, Cleveland, Ohio, USASearch for more papers by this authorRabi Tawil MD, Rabi Tawil MD Department of Neurology, University of Rochester, Rochester, New York, USASearch for more papers by this authorPariwat Thaisetthawatkul MD, Pariwat Thaisetthawatkul MD Department of Neurology, University of Nebraska, Omaha, Nebraska, USASearch for more papers by this authorCharles Thornton MD, Charles Thornton MD Department of Neurology, University of Rochester, Rochester, New York, USASearch for more papers by this authorJaya Trivedi MD, Jaya Trivedi MD Department of Neurology, Yale School of Medicine, New Haven, Connecticut, USASearch for more papers by this authorSteven Vernino MD, PhD, Steven Vernino MD, PhD Department of Neurology and Neurotherapeutics, University Texas Southwestern, Dallas, Texas, USASearch for more papers by this authorAnnabel K. Wang MD, Annabel K. Wang MD Department of Neurology, Veterans Affairs Long Beach Healthcare System, Long Beach, California, USASearch for more papers by this authorTyler A. Webb MD, Tyler A. Webb MD Department of Neurology, University of Oklahoma, Oklahoma City, Oklahoma, USASearch for more papers by this authorMichael D. Weiss MD, Michael D. Weiss MD Department of Neurology, University of Washington, Seattle, Washington, USASearch for more papers by this authorAnthony J. Windebank MD, Anthony J. Windebank MD Department of Neurology, Mayo Clinic, Rochester, Minnesota, USASearch for more papers by this authorGil I. Wolfe MD, Gil I. Wolfe MD Department of Neurology, University of Buffalo, Buffalo, New York, USASearch for more papers by this author First published: 10 December 2015 https://doi.org/10.1002/mus.25009Citations: 19 A full listing of author disclosures is available online as supplementary material. 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Background— The cardiac cytoskeleton plays key roles in maintaining myocyte structural integrity in health and disease. In fact, human mutations in cardiac cytoskeletal elements are tightly linked to cardiac pathologies, including myopathies, aortopathies, and dystrophies. Conversely, the link between cytoskeletal protein dysfunction and cardiac electric activity is not well understood and often overlooked in the cardiac arrhythmia field. Methods and Results— Here, we uncover a new mechanism for the regulation of cardiac membrane excitability. We report that βII spectrin, an actin-associated molecule, is essential for the posttranslational targeting and localization of critical membrane proteins in heart. βII spectrin recruits ankyrin-B to the cardiac dyad, and a novel human mutation in the ankyrin-B gene disrupts the ankyrin-B/βII spectrin interaction, leading to severe human arrhythmia phenotypes. Mice lacking cardiac βII spectrin display lethal arrhythmias, aberrant electric and calcium handling phenotypes, and abnormal expression/localization of cardiac membrane proteins. Mechanistically, βII spectrin regulates the localization of cytoskeletal and plasma membrane/sarcoplasmic reticulum protein complexes, including the Na/Ca exchanger, ryanodine receptor 2, ankyrin-B, actin, and αII spectrin. Finally, we observe accelerated heart failure phenotypes in βII spectrin–deficient mice. Conclusions— Our findings identify βII spectrin as critical for normal myocyte electric activity, link this molecule to human disease, and provide new insight into the mechanisms underlying cardiac myocyte biology.

Background: We evaluated the analytical and clinical performances of a novel, automated chemiluminescent immunoassay in comparison with several anti-citrullinated protein antibody (ACPA) assays (2nd and 3rd generations) based on various platforms and technologies.Methods: Samples from rheumatoid arthritis (RA) patients (n = 141) and controls (n = 153) were collected based on an ordered ACPA test. All samples were tested with QUANTA Flash (R) CCP3, QUANTA Lite (R) CCP3, QUANTA Lite (R) CCP3.1, CCPlus and EliA (R) CCP assays. Rheumatoid factor (RF) was determined using Quantex RF(II). An additional cohort consisting of RA patients from three different sources (116,79 and 50 samples), 61 juvenile idiopathic arthritis (JIA) patients and 233 controls were used in an extended evaluation on QUANTA Flash (R) CCP3 only. Precision and linearity of the QUANTA Flash (R) CCP3 were assessed according to CLSI guidelines.Results: All ACPA assays showed good qualitative and quantitative agreements. The Quanta Flash CCP3 assay showed good analytical and clinical performance. Based on the extended cohort, the sensitivity, specificity and likelihood ratios of the novel Quanta Flash (R) CCP3 were defined as 70.2%, 97.4% and 27.3/0.31, respectively.Conclusion: Good agreements between different ACPA assays based on diverse platforms were found. Quanta Flash CCP3 is a reliable test for the fully automated and rapid detection of ACPA. (C) 2014 Elsevier B.V. All rights reserved.

Objective: To describe a patient with relapsing-remitting multiple sclerosis and a new medullary lesion manifested by cardiomyopathy. Background: Stress also known by the term Takotsubo cardiomyopathy, is a condition of transient cardiac apical ballooning and left ventricular dysfunction, secondary to focal myocardial stunning. Several mechanisms of neurologic injury have been implicated in the development of this condition, including subarachnoid hemorrhage, brainstem stroke and abscess. We describe a case of bilateral medullary multiple sclerosis lesions manifesting as stress cardiomyopathy. Design/Methods: Case Report: A 51-year old woman with a history of relapsing-remitting multiple sclerosis presented with acute retrosternal chest pain, shortness of breath, left hemi-hypoesthesia and a T7 sensory level. Magnetic resonance imaging showed contrast-enhancing lesions in the right medulla and thoracic spine. Of note, a surveillance brain MRI obtained two months prior to presentation, showed a left contrast-enhancing medullary lesion. Cardiac angiography showed normal coronary arteries with congestive heart failure and typical features of cardiomyopathy. Results: She was treated with a four-day course of high-dose intravenous steroids. Ejection fraction normalized (55-65%) on a repeat echocardiogram 10 weeks later. Conclusions: Stress cardiomyopathy is increasingly suspected to be neurogenic in etiology. This case not only supports this theory, but also reports multiple sclerosis to be a potential cause of neurologic dysfunction leading to this cardiac phenomenon. In addition, it fortifies the theory that bilateral medullary lesions are required for many instances of autonomic dysfunction. Disclosure: Dr. Webb has nothing to disclose. Dr. Reyna has nothing to disclose. Dr. Blair has nothing to disclose. Dr. Foreman has nothing to disclose.

With the Navy's development of the integrated electric warship, large amounts of electrical energy will be made available, thus allowing the addition of pulsed weaponry and sensors. Electromagnetic railguns will increase the thermal load on such a ship by an order of magnitude or more over a conventional gun. To represent the expected loads, a numerical model has been created to simulate the system-level energy balance for a capacitive-based railgun system and is currently in development for a rotating machine-based system. In order to better study the system-level effects of the increased thermal burden, multiple shot profiles and scenarios were used. The simulation outputs are used as inputs to a ship-based, thermal management architecture built in the dynamic thermal software package ProTRAX. Our analysis quantifies additional thermal management capacity that will be necessary for the future all-electric ship and provides the first step in simulating potential ship wide thermal management systems of pulsed loads in a dynamic sense.