A data mining approach for classification of orthostatic and essential tremor based on MRI‐derived brain volume and cortical thickness

[Abstract] Objective - Orthostatic tremor (OT) is an extremely rare, misdiagnosed, and underdiagnosed disorder affecting adults in midlife. There is debate as to whether it is a different condition or a variant of essential tremor (ET), or even, if both conditions coexist. Our objective was to use data mining classification methods, using magnetic resonance imaging (MRI)‐derived brain volume and cortical thickness data, to identify morphometric measures that help to discriminate OT patients from those with ET. Methods - MRI‐derived brain volume and cortical thickness were obtained from 14 OT patients and 15 age‐, sex‐, and education‐matched ET patients. Feature selection and machine learning methods were subsequently applied. Results - Four MRI features alone distinguished the two, OT from ET, with 100% diagnostic accuracy. More specifically, left thalamus proper volume (normalized by the total intracranial volume), right superior parietal volume, right superior parietal thickness, and right inferior parietal roughness (i.e., the standard deviation of cortical thickness) were shown to play a key role in OT and ET characterization. Finally, the left caudal anterior cingulate thickness and the left caudal middle frontal roughness allowed us to separate with 100% diagnostic accuracy subgroups of OT patients (primary and those with mild parkinsonian signs). Conclusions - A data mining approach applied to MRI‐derived brain volume and cortical thickness data may differentiate between these two types of tremor with an accuracy of 100%. Our results suggest that OT and ET are distinct conditions.National Institutes of Health (United States); #R01, NS39422National Institutes of Health (United States), #R01, NS094607National Institutes of Health (United States); #R01, NS085136National Institutes of Health (United States); #R01, NS073872National Institutes of Health (United States); #R01, NS085136National Institutes of Health (United States); #R01, NS088257European Commission; ICT‐2011‐287739Ministerio de Economía y Competitividad; RTC‐2015‐3967‐1Agencia Española de Investigación de la Salud; FIS PI12/01602Agencia Española de Investigación de la Salud; FIS PI16/00451Madrid Robotics Digital Innovation Hub; S2018/NMT‐433

Diffusion tensor imaging in orthostatic tremor: a tract‐based spatial statistics study

[Abstract] Objective The pathogenesis of orthostatic tremor (OT) is unknown. We investigated OT‐related white matter changes and their correlations with scores from a neuropsychological testing battery. Methods Diffusion tensor imaging measures were compared between 14 OT patients and 14 age‐ and education‐matched healthy controls, using whole‐brain tract‐based spatial statistics analysis. Correlations between altered diffusion metrics and cognitive performance in OT group were assessed. Results In all cognitive domains (attention, executive function, visuospatial ability, verbal memory, visual memory, and language), OT patients’ cognitive performance was significantly worse than that of healthy controls. OT patients demonstrated altered diffusivity metrics not only in the posterior lobe of the cerebellum (left cerebellar lobule VI) and in its efferent cerebellar fibers (left superior cerebellar peduncle), but also in medial lemniscus bilaterally (pontine tegmentum), anterior limb of the internal capsule bilaterally, right posterior limb of the internal capsule, left anterior corona radiata, right insula, and the splenium of corpus callosum. No relationship was found between diffusion measures and disease duration in OT patients. Diffusion white matter changes, mainly those located in right anterior limb of the internal capsule, were correlated with poor performance on tests of executive function, visuospatial ability, verbal memory, and visual memory in OT patients. Interpretation White matter changes were preferentially located in the cerebellum, its efferent pathways, as well as in the pontine tegmentum and key components of the frontal–thalamic–cerebellar circuit. Further work needs to be done to understand the evolution of these white matter changes and their functional consequences.National Institutes of Health; R01 NS39422National Institutes of Health; R01 NS094607National Institutes of Health; R01 NS085136National Institutes of Health; R01 NS073872National Institutes of Health; R01 NS088257European Commission. Grant Number: ICT‐2011‐287739Ministerio de Ecnomía y Competitividad; RTC‐2015‐3967‐1Spanish Health Research Agency; FIS PI12/01602Spanish Health Research Agency; FIS PI16/00451Ministerio de Ecnomía y Competitividad; DPI‐2015‐68664‐C4‐1‐

New methods for the assessment of Parkinson’s Disease (2005 to 2015): a systematic review

"BACKGROUND: The past decade has witnessed a highly dynamic and growing expansion of novel methods aimed at improving the assessment of Parkinson's disease with technology (NAM-PD) in laboratory, clinical, and home environments. However, the current state of NAM-PD regarding their maturity, feasibility, and usefulness in assessing the main PD features has not been systematically evaluated. METHODS: A systematic review of articles published in the field from 2005 to 2015 was performed. Of 9,503 publications identified in PubMed and the Web of Science, 848 full papers were evaluated, and 588 original articles were assessed to evaluate the technological, demographic, clinimetric, and technology transfer readiness parameters of NAM-PD. RESULTS: Of the studies, 65% included fewer than 30 patients, < 50% employed a standard methodology to validate diagnostic tests, 8% confirmed their results in a different dataset, and 87% occurred in a clinic or lab. The axial features domain was the most frequently studied, followed by bradykinesia. Rigidity and nonmotor domains were rarely investigated. Only 6% of the systems reached a technology level that justified the hope of being included in clinical assessments in a useful time period. CONCLUSIONS: This systematic evaluation provides an overview of the current options for quantitative assessment of PD and what can be expected in the near future. There is a particular need for standardized and collaborative studies to confirm the results of preliminary initiatives, assess domains that are currently underinvestigated, and better validate the existing and upcoming NAM-PD. © 2016 International Parkinson and Movement Disorder Society."Funding agency: The research leading to these results has received funding from “Consejería de Educación, Juventud y Deporte of Comunidad de Madrid” and the People Programme (Marie Curie Actions) of the European Union's Seventh Framework Programme (FP7/2007-2013) under REA Grant 291820.info:eu-repo/semantics/acceptedVersio

Outcomes of cerebral venous thrombosis due to vaccine-induced immune thrombotic thrombocytopenia after the acute phase

© 2022 American Heart Association, Inc.Background: Cerebral venous thrombosis (CVT) due to vaccine-induced immune thrombotic thrombocytopenia (VITT) is a severe condition, with high in-hospital mortality rates. Here, we report clinical outcomes of patients with CVT-VITT after SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) vaccination who survived initial hospitalization. Methods: We used data from an international registry of patients who developed CVT within 28 days of SARS-CoV-2 vaccination, collected until February 10, 2022. VITT diagnosis was classified based on the Pavord criteria. Outcomes were mortality, functional independence (modified Rankin Scale score 0–2), VITT relapse, new thrombosis, and bleeding events (all after discharge from initial hospitalization). Results: Of 107 CVT-VITT cases, 43 (40%) died during initial hospitalization. Of the remaining 64 patients, follow-up data were available for 60 (94%) patients (37 definite VITT, 9 probable VITT, and 14 possible VITT). Median age was 40 years and 45/60 (75%) patients were women. Median follow-up time was 150 days (interquartile range, 94–194). Two patients died during follow-up (3% [95% CI, 1%–11%). Functional independence was achieved by 53/60 (88% [95% CI, 78%–94%]) patients. No new venous or arterial thrombotic events were reported. One patient developed a major bleeding during follow-up (fatal intracerebral bleed). Conclusions: In contrast to the high mortality of CVT-VITT in the acute phase, mortality among patients who survived the initial hospitalization was low, new thrombotic events did not occur, and bleeding events were rare. Approximately 9 out of 10 CVT-VITT patients who survived the acute phase were functionally independent at follow-up.This study was funded by the Netherlands Organisation for Health Research and Development (ZonMw, grant number 10430072110005), the Dr. C.J. Vaillant Foundation, and Hospital District of Helsinki and Uusimaa (grant TYH2022223).info:eu-repo/semantics/publishedVersio

Cerebral venous sinus thrombosis due to vaccine-induced immune thrombotic thrombocytopenia in middle-income countries

Background: Adenovirus-based COVID-19 vaccines are extensively used in low- and middle-income countries (LMICs). Remarkably, cases of cerebral venous sinus thrombosis due to vaccine-induced immune thrombotic thrombocytopenia (CVST-VITT) have rarely been reported from LMICs. Aims: We studied the frequency, manifestations, treatment, and outcomes of CVST-VITT in LMICs. Methods: We report data from an international registry on CVST after COVID-19 vaccination. VITT was classified according to the Pavord criteria. We compared CVST-VITT cases from LMICs to cases from high-income countries (HICs). Results: Until August 2022, 228 CVST cases were reported, of which 63 were from LMICs (all middle-income countries [MICs]: Brazil, China, India, Iran, Mexico, Pakistan, Turkey). Of these 63, 32 (51%) met the VITT criteria, compared to 103 of 165 (62%) from HICs. Only 5 of the 32 (16%) CVST-VITT cases from MICs had definite VITT, mostly because anti-platelet factor 4 antibodies were often not tested. The median age was 26 (interquartile range [IQR] 20–37) versus 47 (IQR 32–58) years, and the proportion of women was 25 of 32 (78%) versus 77 of 103 (75%) in MICs versus HICs, respectively. Patients from MICs were diagnosed later than patients from HICs (1/32 [3%] vs. 65/103 [63%] diagnosed before May 2021). Clinical manifestations, including intracranial hemorrhage, were largely similar as was intravenous immunoglobulin use. In-hospital mortality was lower in MICs (7/31 [23%, 95% confidence interval (CI) 11–40]) than in HICs (44/102 [43%, 95% CI 34–53], p = 0.039). Conclusions: The number of CVST-VITT cases reported from LMICs was small despite the widespread use of adenoviral vaccines. Clinical manifestations and treatment of CVST-VITT cases were largely similar in MICs and HICs, while mortality was lower in patients from MICs.</p

Sex differences in cerebral venous sinus thrombosis after adenoviral vaccination against COVID-19

Introduction: Cerebral venous sinus thrombosis associated with vaccine-induced immune thrombotic thrombocytopenia (CVST-VITT) is a severe disease with high mortality. There are few data on sex differences in CVST-VITT. The aim of our study was to investigate the differences in presentation, treatment, clinical course, complications, and outcome of CVST-VITT between women and men. Patients and methods: We used data from an ongoing international registry on CVST-VITT. VITT was diagnosed according to the Pavord criteria. We compared the characteristics of CVST-VITT in women and men. Results: Of 133 patients with possible, probable, or definite CVST-VITT, 102 (77%) were women. Women were slightly younger [median age 42 (IQR 28–54) vs 45 (28–56)], presented more often with coma (26% vs 10%) and had a lower platelet count at presentation [median (IQR) 50x109/L (28–79) vs 68 (30–125)] than men. The nadir platelet count was lower in women [median (IQR) 34 (19–62) vs 53 (20–92)]. More women received endovascular treatment than men (15% vs 6%). Rates of treatment with intravenous immunoglobulins were similar (63% vs 66%), as were new venous thromboembolic events (14% vs 14%) and major bleeding complications (30% vs 20%). Rates of good functional outcome (modified Rankin Scale 0-2, 42% vs 45%) and in-hospital death (39% vs 41%) did not differ. Discussion and conclusions: Three quarters of CVST-VITT patients in this study were women. Women were more severely affected at presentation, but clinical course and outcome did not differ between women and men. VITT-specific treatments were overall similar, but more women received endovascular treatment.</p

Sex differences in cerebral venous sinus thrombosis after adenoviral vaccination against COVID-19

Introduction: Cerebral venous sinus thrombosis associated with vaccine-induced immune thrombotic thrombocytopenia (CVST-VITT) is a severe disease with high mortality. There are few data on sex differences in CVST-VITT. The aim of our study was to investigate the differences in presentation, treatment, clinical course, complications, and outcome of CVST-VITT between women and men. Patients and methods: We used data from an ongoing international registry on CVST-VITT. VITT was diagnosed according to the Pavord criteria. We compared the characteristics of CVST-VITT in women and men. Results: Of 133 patients with possible, probable, or definite CVST-VITT, 102 (77%) were women. Women were slightly younger [median age 42 (IQR 28–54) vs 45 (28–56)], presented more often with coma (26% vs 10%) and had a lower platelet count at presentation [median (IQR) 50x109/L (28–79) vs 68 (30–125)] than men. The nadir platelet count was lower in women [median (IQR) 34 (19–62) vs 53 (20–92)]. More women received endovascular treatment than men (15% vs 6%). Rates of treatment with intravenous immunoglobulins were similar (63% vs 66%), as were new venous thromboembolic events (14% vs 14%) and major bleeding complications (30% vs 20%). Rates of good functional outcome (modified Rankin Scale 0-2, 42% vs 45%) and in-hospital death (39% vs 41%) did not differ. Discussion and conclusions: Three quarters of CVST-VITT patients in this study were women. Women were more severely affected at presentation, but clinical course and outcome did not differ between women and men. VITT-specific treatments were overall similar, but more women received endovascular treatment.</p

Measurement of the (eta c)(1S) production cross-section in proton-proton collisions via the decay (eta c)(1S) -&gt; p(p)over-bar

The production of the $\eta_c (1S)$ state in proton-proton collisions is probed via its decay to the $p \bar{p}$ final state with the LHCb detector, in the rapidity range $2.0 6.5$ GeV/c. The cross-section for prompt production of $\eta_c (1S)$ mesons relative to the prompt $J/\psi$ cross-section is measured, for the first time, to be $\sigma_{\eta_c (1S)}/\sigma_{J/\psi} = 1.74 \pm 0.29 \pm 0.28 \pm 0.18 _{B}$ at a centre-of-mass energy $\sqrt{s} = 7$ TeV using data corresponding to an integrated luminosity of 0.7 fb$^{-1}$, and $\sigma_{\eta_c (1S)}/\sigma_{J/\psi} = 1.60 \pm 0.29 \pm 0.25 \pm 0.17 _{B}$ at $\sqrt{s} = 8$ TeV using 2.0 fb$^{-1}$. The uncertainties quoted are, in order, statistical, systematic, and that on the ratio of branching fractions of the $\eta_c (1S)$ and $J/\psi$ decays to the $p \bar{p}$ final state. In addition, the inclusive branching fraction of $b$-hadron decays into $\eta_c (1S)$ mesons is measured, for the first time, to be $B ( b \rightarrow \eta_c X ) = (4.88 \pm 0.64 \pm 0.25 \pm 0.67 _{B}) \times 10^{-3}$, where the third uncertainty includes also the uncertainty on the $J/\psi$ inclusive branching fraction from $b$-hadron decays. The difference between the $J/\psi$ and $\eta_c (1S)$ meson masses is determined to be $114.7 \pm 1.5 \pm 0.1$ MeV/c$^2$.The production of the $\eta _c (1S)$ state in proton-proton collisions is probed via its decay to the $p\overline{p}$ final state with the LHCb detector, in the rapidity range $2.0 6.5 \mathrm{{\,GeV/}{ c}}$ . The cross-section for prompt production of $\eta _c (1S)$ mesons relative to the prompt ${{ J}}/{\psi }$ cross-section is measured, for the first time, to be $\sigma _{\eta _c (1S)}/\sigma _{{{{ J}}/{\psi }}} = 1.74\, \pm \,0.29\, \pm \, 0.28\, \pm \,0.18 _{{\mathcal{B}}}$ at a centre-of-mass energy ${\sqrt{s}} = 7 {~\mathrm{TeV}}$ using data corresponding to an integrated luminosity of 0.7 fb$^{-1}$ , and $\sigma _{\eta _c (1S)}/\sigma _{{{{ J}}/{\psi }}} = 1.60 \pm 0.29 \pm 0.25 \pm 0.17 _{{\mathcal{B}}}$ at ${\sqrt{s}} = 8 {~\mathrm{TeV}}$ using 2.0 fb$^{-1}$ . The uncertainties quoted are, in order, statistical, systematic, and that on the ratio of branching fractions of the $\eta _c (1S)$ and ${{ J}}/{\psi }$ decays to the $p\overline{p}$ final state. In addition, the inclusive branching fraction of ${b}$ -hadron decays into $\eta _c (1S)$ mesons is measured, for the first time, to be ${\mathcal{B}}( b {\rightarrow } \eta _c X ) = (4.88\, \pm \,0.64\, \pm \,0.29\, \pm \, 0.67 _{{\mathcal{B}}}) \times 10^{-3}$ , where the third uncertainty includes also the uncertainty on the ${{ J}}/{\psi }$ inclusive branching fraction from ${b}$ -hadron decays. The difference between the ${{ J}}/{\psi }$ and $\eta _c (1S)$ meson masses is determined to be $114.7 \pm 1.5 \pm 0.1 {\mathrm {\,MeV\!/}c^2}$ .The production of the $\eta_c (1S)$ state in proton-proton collisions is probed via its decay to the $p \bar{p}$ final state with the LHCb detector, in the rapidity range $2.0 6.5$ GeV/c. The cross-section for prompt production of $\eta_c (1S)$ mesons relative to the prompt $J/\psi$ cross-section is measured, for the first time, to be $\sigma_{\eta_c (1S)}/\sigma_{J/\psi} = 1.74 \pm 0.29 \pm 0.28 \pm 0.18 _{B}$ at a centre-of-mass energy $\sqrt{s} = 7$ TeV using data corresponding to an integrated luminosity of 0.7 fb$^{-1}$, and $\sigma_{\eta_c (1S)}/\sigma_{J/\psi} = 1.60 \pm 0.29 \pm 0.25 \pm 0.17 _{B}$ at $\sqrt{s} = 8$ TeV using 2.0 fb$^{-1}$. The uncertainties quoted are, in order, statistical, systematic, and that on the ratio of branching fractions of the $\eta_c (1S)$ and $J/\psi$ decays to the $p \bar{p}$ final state. In addition, the inclusive branching fraction of $b$-hadron decays into $\eta_c (1S)$ mesons is measured, for the first time, to be $B ( b \rightarrow \eta_c X ) = (4.88 \pm 0.64 \pm 0.29 \pm 0.67 _{B}) \times 10^{-3}$, where the third uncertainty includes also the uncertainty on the $J/\psi$ inclusive branching fraction from $b$-hadron decays. The difference between the $J/\psi$ and $\eta_c (1S)$ meson masses is determined to be $114.7 \pm 1.5 \pm 0.1$ MeV/c$^2$

A study of CP violation in B-+/- -&gt; DK +/- and B-+/- -&gt; D pi(+/-) decays with D -&gt; (KSK +/-)-K-0 pi(-/+) final states

A first study of CP violation in the decay modes $B^\pm\to [K^0_{\rm S} K^\pm \pi^\mp]_D h^\pm$ and $B^\pm\to [K^0_{\rm S} K^\mp \pi^\pm]_D h^\pm$, where $h$ labels a $K$ or $\pi$ meson and $D$ labels a $D^0$ or $\overline{D}^0$ meson, is performed. The analysis uses the LHCb data set collected in $pp$ collisions, corresponding to an integrated luminosity of 3 fb$^{-1}$. The analysis is sensitive to the CP-violating CKM phase $\gamma$ through seven observables: one charge asymmetry in each of the four modes and three ratios of the charge-integrated yields. The results are consistent with measurements of $\gamma$ using other decay modes