Showing papers by "Mark Hallett published in 2021"
University of Siena1, University of Göttingen2, UCL Institute of Neurology3, City College of New York4, National Institutes of Health5, Brown University6, University of Toronto7, Università Campus Bio-Medico8, Beth Israel Deaconess Medical Center9, Medical University of South Carolina10, Cincinnati Children's Hospital Medical Center11, Aristotle University of Thessaloniki12, Aalto University13, Paris 12 Val de Marne University14, Vita-Salute San Raffaele University15, University of Trento16, Ludwig Maximilian University of Munich17, Harvard University18, Duke University19, University of Messina20, Copenhagen University Hospital21, Fukushima Medical University22, Ben-Gurion University of the Negev23, University of Tübingen24
TL;DR: New operational guidelines are provided for safety in planning future trials based on traditional and patterned TMS protocols, as well as a summary of the minimal training requirements for operators, and a note on ethics of neuroenhancement.
387 citations
Harvard University1, King's College London2, Shiraz University of Medical Sciences3, University of Geneva4, University of Edinburgh5, University College London6, South London and Maudsley NHS Foundation Trust7, St George's, University of London8, University of Cincinnati9, VU University Amsterdam10, National Institutes of Health11, Ruhr University Bochum12, University of Melbourne13, University Medical Center Groningen14, Children's Hospital at Westmead15, Northwestern University16, Brown University17, University of Toronto18, Stony Brook University19, University of Manitoba20, Mayo Clinic21, University of Alabama at Birmingham22, University of Bern23
TL;DR: The International Functional Neurological Disorder (FND) Neuroimaging Workgroup as discussed by the authors was organized to provide a state-of-the-art assessment of the state of the art in FND research.
55 citations
TL;DR: In this paper, the authors review advances that have occurred over the past decade (2011-2020) across diagnosis, mechanisms, aetiologies, treatments and stigma in patients with motor functional neurological disorder (mFND), that is, functional movement disorder and functional limb weakness.
Abstract: Functional neurological disorder (FND) is a prevalent, disabling and costly condition at the neurology-psychiatry intersection. After being marginalised in the late 20th century, there has been renewed interest in this field. In this article, we review advances that have occurred over the past decade (2011-2020) across diagnosis, mechanisms, aetiologies, treatments and stigma in patients with motor FND (mFND, that is, functional movement disorder and functional limb weakness). In each content area, we also discuss the implications of recent advances and suggest future directions that will help continue the momentum of the past decade. In diagnosis, a major advance has been the emphasis on rule-in physical signs that are specific for hyperkinetic and hypokinetic functional motor symptoms. Mechanistically, greater importance has been given to determining 'how' functional neurological symptoms develop, highlighting roles for misdirected attention, expectation and self-agency, as well as abnormal influences of emotion/threat processing brain areas on motor control circuits. Aetiologically, while roles for adverse life experiences remain of interest in mFND, there is recognition of other aetiologic contributors, and efforts are needed to investigate links between aetiological factors and mechanisms. This decade has seen the first randomised controlled trials for physiotherapy, multidisciplinary rehabilitation and psychotherapy performed in the field, with consensus recommendations for physiotherapy, occupational therapy and outcome measures also published. Across patients, clinicians, healthcare systems and society, stigma remains a major concern. While challenges persist, a patient-centred integrated clinical neuroscience approach is primed to carry forward the momentum of the past decade into the future.
41 citations
Beth Israel Deaconess Medical Center1, University of Göttingen2, University of Barcelona3, UCL Institute of Neurology4, Brown University5, Johns Hopkins University6, Edith Cowan University7, University of British Columbia8, Laval University9, Medical University of South Carolina10, Carnegie Mellon University11, Samsung Medical Center12, Vita-Salute San Raffaele University13, National Institutes of Health14, University of New South Wales15, University of Siena16, Maastricht University17, University of Glasgow18, Fukushima Medical University19, University of Tübingen20, Harvard University21
TL;DR: Recommendations on the structure and content of NIBS training are provided, basic or core competencies and more advanced knowledge and skills are discussed, and recommendations offered regarding didactic and practical curricular components.
36 citations
TL;DR: In this article, the authors reviewed clinical reports and experimental studies on bradykinesia in non-parkinsonian conditions and discussed the major findings, including the need for a new, more accurate, and more widely used definition of BR in the context of movement disorders.
Abstract: Background and purpose Bradykinesia is one of the cardinal motor symptoms of Parkinson's disease. However, clinical and experimental studies indicate that bradykinesia may also be observed in various neurological diseases not primarily characterized by parkinsonism. These conditions include hyperkinetic movement disorders, such as dystonia, chorea, and essential tremor. Bradykinesia may also be observed in patients with neurological conditions that are not seen as "movement disorders," including those characterized by the involvement of the cerebellum and corticospinal system, dementia, multiple sclerosis, and psychiatric disorders. Methods We reviewed clinical reports and experimental studies on bradykinesia in non-parkinsonian conditions and discussed the major findings. Results Bradykinesia is a common motor abnormality in non-parkinsonian conditions. From a pathophysiological standpoint, bradykinesia in neurological conditions not primarily characterized by parkinsonism may be explained by brain network dysfunction. Conclusion In addition to the pathophysiological implications, the present paper highlights important terminological issues and the need for a new, more accurate, and more widely used definition of bradykinesia in the context of movement disorders and other neurological conditions.
22 citations
TL;DR: The laryngeal dystonia was recognized as a multifactorial, phenotypically heterogeneous form of isolated dystonias by the National Institutes of Health (NIH) in 2005 as discussed by the authors.
Abstract: Objective. To delineate research priorities for improving clinical management of laryngeal dystonia, the NIH convened a multi-disciplinary panel of experts for a one-day workshop to examine the current progress in understanding its etiopathophysiology and clinical care. Methods. The participants reviewed the current terminology of disorder and discussed advances in understanding its pathophysiology since a similar workshop was held in 2005. Clinical and research gaps were identified, and recommendations for future directions were delineated. Results. The panel unanimously agreed to adopt the term “laryngeal dystonia” instead of “spasmodic dysphonia” to reflect the current progress in characterizations of this disorder. Laryngeal dystonia was recognized as a multifactorial, phenotypically heterogeneous form of isolated dystonia. Its etiology remains unknown, whereas the pathophysiology likely involves large-scale functional and structural brain network disorganization. Current challenges include the lack of clinically validated diagnostic markers and outcome measures and the paucity of therapies that address the disorder pathophysiology. Conclusion. Research priorities should be guided by challenges in clinical management of laryngeal dystonia. Identification of disorder-specific biomarkers would allow the development of novel diagnostic tools and unified measures of treatment outcome. Elucidation of the critical nodes within neural networks that cause or modulate symptoms would allow the development of targeted therapies that address the underlying pathophysiology. Given the rarity of laryngeal dystonia, future rapid research progress may be facilitated by multi-center, national and international collaborations.
22 citations
TL;DR: In this paper, the authors investigated dynamic functional connectivity (dFC), during resting state functional magnetic resonance imaging, between sensorimotor network and top-down control networks in 36 PD patients (OFF medication, PD-OFF) and 36 healthy volunteers.
Abstract: Background Motor symptoms in Parkinson's disease (PD) patients might be related to high-level task-control deficits. We aimed at investigating the dynamics between sensorimotor network and top-down control networks (frontal-parietal, cingulo-opercular, and cerebellar) in PD and at determining the effects of levodopa on the dynamics of these networks. Methods We investigated dynamic functional connectivity (dFC), during resting state functional magnetic resonance imaging, between sensorimotor network and top-down control networks in 36 PD patients (OFF medication, PD-OFF) and 36 healthy volunteers. We further assessed the effect of medication on dFC in18 PD patients who were also scanned ON medication. Results The dFC analyses identified three discrete states: State I (35.68%) characterized by connections between the cerebellum and sensorimotor network, State II (34.17%) with connections between the sensorimotor and frontal-parietal network, and State III (30.15%) with connection between the sensorimotor and cingulo-opercular network. PD patients have significantly fewer occurrences and overall spent less time (shorter dwell time) in State II compared to healthy controls. After levodopa intake, dwell time improved toward normal. The change in dwell time before and after taking levodopa was negatively related to the respective changes in Unified Parkinson's Disease Rating Scale, Part III. PD-OFF showed significantly decreased connectivity between sensorimotor and control networks and increased connectivity within control networks. These changes were partially improved after levodopa intake. Conclusions Dopamine depletion in PD is associated with abnormalities in temporal and spatial properties between cognitive control and sensorimotor network, possibly contributing to clinical deficits. Levodopa partially restores the network function toward the values observed in healthy volunteers. © 2021 International Parkinson and Movement Disorder Society.
19 citations
Hangzhou Normal University1, Beijing Normal University2, Jiamusi University3, Masaryk University4, University of Florida5, Lille University of Science and Technology6, National Research Council7, China Medical University (PRC)8, University of Salerno9, Seconda Università degli Studi di Napoli10, Zhejiang University11, Colorado State University12, University of British Columbia13, University of Sydney14, University of Ulm15, University of Hong Kong16, Oregon Health & Science University17, Third Military Medical University18, Hebei Medical University19, Northwestern University20, University of Washington21, South London and Maudsley NHS Foundation Trust22, King's College London23, Magna Græcia University24, Sichuan University25, The Mind Research Network26, Chengdu Kinesiology University27, National Institutes of Health28, Capital Medical University29
18 citations
TL;DR: A novel algorithm to characterize tremor using inertial sensors is proposed that can quantify tremor accurately even in the presence of other activities, perhaps providing a step forward for at-home monitoring.
Abstract: Background Assessment of essential tremor is often done by a trained clinician who observes the limbs during different postures and actions and subsequently rates the tremor. While this method has been shown to be reliable, the inter- and intra-rater reliability and need for training can make the use of this method for symptom progression difficult. Many limitations of clinical rating scales can potentially be overcome by using inertial sensors, but to date many algorithms designed to quantify tremor have key limitations. Methods We propose a novel algorithm to characterize tremor using inertial sensors. It uses a two-stage approach that 1) estimates the tremor frequency of a subject and only quantifies tremor near that range; 2) estimates the tremor amplitude as the portion of signal power above baseline activity during recording, allowing tremor estimation even in the presence of other activity; and 3) estimates tremor amplitude in physical units of translation (cm) and rotation (°), consistent with current tremor rating scales. We validated the algorithm technically using a robotic arm and clinically by comparing algorithm output with data reported by a trained clinician administering a tremor rating scale to a cohort of essential tremor patients. Results Technical validation demonstrated rotational amplitude accuracy better than ±0.2 degrees and position amplitude accuracy better than ±0.1 cm. Clinical validation revealed that both rotation and position components were significantly correlated with tremor rating scale scores. Conclusion We demonstrate that our algorithm can quantify tremor accurately even in the presence of other activities, perhaps providing a step forward for at-home monitoring.
16 citations
TL;DR: In this article, a review of clinical neurophysiology studies of human movement is presented, focusing on EMG, EEG, MEG, evoked potentials, coherence, accelerometry, posturography (balance), gait, and sleep studies.
15 citations
TL;DR: Dystonia is a movement disorder characterized by sustained or intermittent muscle contractions causing abnormal postures, repetitive movements, or both as mentioned in this paper, which is not a single disorder but a family of heterogenous disorders with varied clinical manifestations and different causes.
Abstract: Dystonia is a movement disorder characterized by sustained or intermittent muscle contractions causing abnormal postures, repetitive movements, or both. Research in dystonia has been challenged by several factors. First, dystonia is uncommon. Dystonia is not a single disorder but a family of heterogenous disorders with varied clinical manifestations and different causes. The different subtypes may be seen by providers in different clinical specialties including neurology, ophthalmology, otolaryngology, and others. These issues have made it difficult for any single center to recruit large numbers of subjects with specific types of dystonia for research studies in a timely manner. The Dystonia Coalition is a consortium of investigators that was established to address these challenges. Since 2009, the Dystonia Coalition has encouraged collaboration by engaging 56 sites across North America, Europe, Asia, and Australia. Its emphasis on collaboration has facilitated establishment of international consensus for the definition and classification of all dystonias, diagnostic criteria for specific subtypes of dystonia, standardized evaluation strategies, development of clinimetrically sound measurement tools, and large multicenter studies that document the phenotypic heterogeneity and evolution of specific types of dystonia.
Emory University1, University of New Mexico2, Washington University in St. Louis3, University of Florida4, University of Maryland, Baltimore5, Virginia Commonwealth University6, University of Colorado Boulder7, University of Paris8, Baylor College of Medicine9, University of Cincinnati Academic Health Center10, University of Rochester11, University of Memphis12, Johns Hopkins University School of Medicine13, Beth Israel Deaconess Medical Center14, University of Alabama at Birmingham15, Sapienza University of Rome16, Tufts University17, University of Cagliari18
University of Cagliari1, Emory University2, Sapienza University of Rome3, Washington University in St. Louis4, Virginia Commonwealth University5, Baylor College of Medicine6, Rush University Medical Center7, University of Toronto8, Seoul National University Hospital9, Johns Hopkins University10, University of New Mexico11
TL;DR: In this article, a case-finding procedure was proposed to screen blepharospasm in a given population with less effort than would be required by examination of all subjects, and the results support the use of proposed diagnostic criteria in multi-ethnic, multi-center cohorts.
TL;DR: In this article, the use of a ketogenic diet in cohorts with Parkinson's disease was explored, and while not conclusive, the data suggest non-motor symptom benefit, which is useful to understand target engagement and gauge which mechanism could lead to a testable hypothesis.
TL;DR: Recent neuroscience research on FMD is reviewed to discuss how the adoption of a similar integrative framework may facilitate the identification of the mechanisms underlying FMD and could also have potential clinical applicability.
TL;DR: The intriguing clinical phenomenon that people with tic disorders are often able to control specific muscle contractions as part of their tic behaviors to a degree that most humans typically cannot is described.
Abstract: The unifying characteristic of movement disorders is the phenotypic presentation of abnormal motor outputs, either as isolated phenomena or in association with further clinical, often neuropsychiatric, features. However, the possibility of a movement disorder also characterized by supranormal or enhanced volitional motor control has not received attention. Based on clinical observations and cases collected over a number of years, we here describe the intriguing clinical phenomenon that people with tic disorders are often able to control specific muscle contractions as part of their tic behaviors to a degree that most humans typically cannot. Examples are given in accompanying video documentation. We explore medical literature on this topic and draw analogies with early research of fine motor control physiology in healthy humans. By systematically analyzing the probable sources of this unusual capacity, and focusing on neuroscientific accounts of voluntary motor control, sensory feedback, and the role of motor learning in tic disorders, we provide a novel pathophysiological account explaining both the presence of exquisite control over motor output and that of overall tic behaviors. We finally comment on key questions for future research on the topic and provide concluding remarks on the complex movement disorder of tic behaviors. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
TL;DR: In this article, the authors investigated the safety, tolerability and preliminary efficacy of fronto-amygdala neuromodulation via targeted left prefrontal intermittent theta burst stimulation (iTBS) on brain and behavioral manifestations of functional movement disorders (FMD).
Abstract: Neuroimaging studies suggest that corticolimbic dysfunctions, including increased amygdala reactivity to emotional stimuli and heightened fronto-amygdala coupling, play a central role in the pathophysiology of functional movement disorders (FMD). Transcranial magnetic stimulation (TMS) has the potential to probe and modulate brain networks implicated in neuropsychiatric disorders, including FMD. Therefore, the objective of this proof-of-concept study was to investigate the safety, tolerability and preliminary efficacy of fronto-amygdala neuromodulation via targeted left prefrontal intermittent theta burst stimulation (iTBS) on brain and behavioral manifestations of FMD. Six subjects with a clinically defined diagnosis of FMD received three open-label iTBS sessions per day for two consecutive study visits. Safety and tolerability were assessed throughout the trial. Amygdala reactivity to emotionally valenced stimuli presented during an fMRI task and fronto-amygdala connectivity at rest were evaluated at baseline and after each stimulation visit, together with subjective levels of arousal and valence in response to affective stimuli. The FMD symptom severity was assessed at baseline, during treatment and 24 h after the last iTBS session. Multiple doses of iTBS were well-tolerated by all participants. Intermittent TBS significantly decreased fronto-amygdala connectivity and influenced amygdala reactivity to emotional stimuli. These neurocircuitry changes were associated to a marked reduction in FMD symptom severity. Corticolimbic modulation via iTBS represents a promising treatment for FMD that warrants additional research.
University of Sheffield1, Brigham and Women's Hospital2, Henry Ford Hospital3, Wayne State University4, University of Calgary5, Children's Hospitals and Clinics of Minnesota6, King's College London7, National Institutes of Health8, University of Sydney9, Children's Hospital at Westmead10, Rhode Island Hospital11, Brown University12, Aix-Marseille University13, Harvard University14, Arizona State University15, University of Edinburgh16, Yale University17
TL;DR: The most important conditions in the differential diagnosis of epilepsy is the one that manifests as paroxysms of altered behaviour, awareness, sensation or sense of bodily control in ways that often resemble epileptic seizures, but without the abnormal excessive or synchronous electrical activity in the brain that defines these as mentioned in this paper.
Abstract: Amongst the most important conditions in the differential diagnosis of epilepsy is the one that manifests as paroxysms of altered behaviour, awareness, sensation or sense of bodily control in ways that often resemble epileptic seizures, but without the abnormal excessive or synchronous electrical activity in the brain that defines these. Despite this importance, there remains little agreement – and frequent debate – on what to call this condition, known inter alia as psychogenic non-epileptic seizures (PNES), dissociative seizures (DS), functional seizures (FS), non-epileptic attack disorder (NEAD), pseudoseizures, conversion disorder with seizures, and by many other labels besides. This choice of terminology is not merely academic – it affects patients’ response to and understanding of their diagnosis, and their ability to navigate health care systems.This paper summarises two recent discussions hosted by the American Epilepsy Society and Functional Neurological Disorders Society on the naming of this condition. These discussions are conceptualised as the initial step of an exploration of whether it might be possible to build consensus for a new diagnostic label.
TL;DR: In this paper, the role of extragenetic factors in dystonia pathogenesis is discussed and the available clinical evidence for a second hit is analyzed in light of the reduced penetrance of monogenic dystonic syndromes and put into context with evidence from animal and cellular models.
Charité1, Cornell University2, Cincinnati Children's Hospital Medical Center3, Spanish National Research Council4, Hannover Medical School5, University of Lübeck6, Banner Health7, Johns Hopkins University School of Medicine8, UMass Memorial Health Care9, University of Florida Health10, National Institutes of Health11, University Medical Center Groningen12, University of Calgary13
TL;DR: The most common investigations used to rule out secondary causes of tics were imaging (92%), laboratory tests (66%), and neurophysiology (38%), with functional tics being the second most common tic etiology following primary tics as discussed by the authors.
Abstract: Background: Tic disorders belong to the broad spectrum of pediatric and adult movement disorders. The wide variability in clinical presentations, applied assessment tools, and treatments are poorly understood. Objectives: To map practices and knowledge base of movement disorder clinicians concerning clinical features, pathophysiology, and treatment approaches in tic disorders. Methods: A 33-item survey was developed by the Tic Disorders and Tourette syndrome Study Group members of the Movement Disorder Society. The survey was distributed to the complete society membership and included responses from 346 members, 314 of whom reported treating tic disorders. Results: Approximately one third of survey respondents (35%) frequently evaluated patients with tics. The data revealed widespread use of existing guidelines (about 70%) and screening for comorbid disorders (>90%). The most common investigations used to rule out secondary causes of tics were imaging (92%), laboratory tests (66%) and neurophysiology (38%). Functional tics were the second most common tic etiology following primary tics. Only 27% of respondents reported confidence in knowledge about tic pathogenesis. Top rated interventions to treat tics were psychoeducation, cognitive behavioral intervention for tics (CBIT) and treatment for neuropsychiatric comorbidities. Antipsychotics were ranked as the most effective pharmacologic tic intervention. Conclusions: The majority of movement disorders specialists do not frequently encounter tics. There was sparse knowledge about tic pathophysiology. Psychoeducation, CBIT, the treatment of neuropsychiatric comorbidities and use of antipsychotics emerged as the most common interventions to treat tics. These results provide insight into what will be needed to improve the diagnosis and treatment of tic disorders.
TL;DR: In this paper, the cortical coherence of cervical dystonia patients and healthy control subjects was evaluated using surface electrodes placed over motor, premotor, and sensory cortical areas and dystonic muscles.
TL;DR: The anatomy and function of the ocular tissues are outlined with a focus on the tissues most affected in movement disorders, and where possible the underlying cellular basis thought to be driving the pathology is explored.
Abstract: Eye disorders spanning a range of ocular tissue are common in patients with movement disorders. Highlighting these ocular manifestations will benefit patients and may even aid in diagnosis. In this educational review we outline the anatomy and function of the ocular tissues with a focus on the tissues most affected in movement disorders. We review the movement disorders associated with ocular pathology and where possible explore the underlying cellular basis thought to be driving the pathology and provide a brief overview of ophthalmic investigations available to the neurologist. This review does not cover intracranial primary visual pathways, higher visual function, or the ocular motor system.
TL;DR: In this article, the authors investigated brain potentials related to sensory tricks in patients with cervical dystonia and found that the late CNV is increased during sensory tricks, suggesting that sensory tricks may affect mechanisms related to the motor prep phase in the premotor and primary motor areas.
TL;DR: Using activation analyses, it is found that the pre-supplementary motor area (preSMA) and the parietal and cerebellar areas were more activated during the execution phase of freely chosen as compared to instructed movements.
Abstract: Action selection refers to the decision regarding which action to perform in order to reach a desired goal, that is, the "what" component of intention. Whether the action is freely chosen or externally instructed involves different brain networks during the selection phase, but it is assumed that the way an action is selected should not influence the subsequent execution phase of the same movement. Here, we aim to test this hypothesis by investigating whether the modality of movement selection influences the brain networks involved during the execution phase of the movement. Twenty healthy volunteers performed a delayed response task in an event-related functional magnetic resonance imaging design to compare freely chosen and instructed unimanual or bimanual movements during the execution phase. Using activation analyses, we found that the pre-supplementary motor area (preSMA) and the parietal and cerebellar areas were more activated during the execution phase of freely chosen as compared to instructed movements. Connectivity analysis showed an increase of information flow between the right posterior parietal cortex and the cerebellum for freely chosen compared to instructed movements. We suggest that the parieto-cerebellar network is particularly engaged during freely chosen movement to monitor the congruence between the intentional content of our actions and their outcome.
TL;DR: Wang et al. as mentioned in this paper investigated the views of functional movement disorders in Chinese clinicians and found that atypical movement disorder, multiple somatizations, and emotional disturbance were essential or absolutely necessary for clinically definite diagnosis of FMD.
Abstract: Background There is rare reports about opinions and clinical practice of functional movement disorders (FMD) in China. The present survey aimed to investigate the views of FMD in Chinese clinicians. Methods The Chinese version survey of FMD were conducted in nationwide practitioners by means of an online questionnaire. Results Four hundred and thirty-four Chinese clinicians completed a 21-item questionnaire probing diagnostic and management issues in FMD. More than 80% of respondents considered that atypical movement disorder, multiple somatizations, and emotional disturbance were essential or absolutely necessary for clinically definite diagnosis of FMD. About three quarters of respondents requested standard neurological investigations to rule out organic causes. Over half believed that prior diagnosis of an organic disorder (59.9%), lack of associated non-physiologic deficits (51.8%), and evidence of physical injury (50.0%) were 'very influential' or 'extremely influential' for a non-FMD diagnosis. The majority (77.4%) of the respondents may refer patients to a neuropsychiatrist or psychiatrist experienced in FMD, followed by psychologist or psychotherapist experienced in FMD (53.2%). However, lack of guidelines, physician knowledge, and training often limited clinicians' ability in managing patients with FMD. Early diagnosis of FMD, identification and management of concurrent psychiatric disorder, and acceptance of the diagnosis by the patient were considered most important for predicting a favorable prognosis. Conclusions Opinions and clinical practice of Chinese practitioners not only varied among Chinese neurologists, but also differed from international peers. Combined efforts are needed to promote related research and establish practice guidelines in China in the future.
University of Calgary1, St George's, University of London2, University of Messina3, Mayo Clinic4, University of Lübeck5, Sapienza University of Rome6, Virginia Commonwealth University7, Medical College of Wisconsin8, University of California, Davis9, University of Pennsylvania10, University of Cincinnati11, University of Colorado Boulder12, University of Toronto13, Beth Israel Deaconess Medical Center14, Baylor College of Medicine15, University of Memphis16, Tufts University17, Rush University Medical Center18, University of Florida19, Houston Methodist Hospital20, Cornell University21, Johns Hopkins University School of Medicine22, University of New Mexico23, Pierre-and-Marie-Curie University24, Icahn School of Medicine at Mount Sinai25, University of Alberta26, University of California, Riverside27, Washington University in St. Louis28, Emory University29
TL;DR: In this paper, the authors developed and validated a predictive model of anatomic spread of adult-onset isolated dystonia; and evaluated whether presence of tremor associated with dystonias influences model predictions of spread.
Abstract: Background and purpose Several clinical and demographic factors relate to anatomic spread of adult-onset isolated dystonia, but a predictive model is still lacking. The aims of this study were: (i) to develop and validate a predictive model of anatomic spread of adult-onset isolated dystonia; and (ii) to evaluate whether presence of tremor associated with dystonia influences model predictions of spread. Methods Adult-onset isolated dystonia participants with focal onset from the Dystonia Coalition Natural History Project database were included. We developed two prediction models, one with dystonia as sole disease manifestation ("dystonia-only") and one accepting dystonia OR tremor in any body part as disease manifestations ("dystonia OR tremor"). Demographic and clinical predictors were selected based on previous evidence, clinical plausibility of association with spread, or both. We used logistic regressions and evaluated model discrimination and calibration. Internal validation was carried out based on bootstrapping. Results Both predictive models showed an area under the curve of 0.65 (95% confidence intervals 0.62-0.70 and 0.62-0.69, respectively) and good calibration after internal validation. In both models, onset of dystonia in body regions other than the neck, older age, depression and history of neck trauma were predictors of spread. Conclusions This predictive modeling of spread in adult-onset isolated dystonia based on accessible predictors (demographic and clinical) can be easily implemented to inform individuals' risk of spread. Because tremor did not influence prediction of spread, our results support the argument that tremor is a part of the dystonia syndrome, and not an independent or coincidental disorder.
TL;DR: The scientific community responded rapidly to the COVID-19 pandemic by developing novel SARS-CoV-2 vaccines that have been shown to be safe and effective.
Abstract: The scientific community responded rapidly to the COVID-19 pandemic by developing novel SARS-CoV-2 vaccines that have been shown to be safe and effective. Global vaccination programs have been rolled out with variable progress. Some vaccines have been suspended for certain demographic groups in a number of countries as a result of rare associations with cerebral venous sinus thromboses. Vaccine programs are dependent on public trust, which may be affected by safety concerns and vaccine hesitancy, both of which can be fueled by misinformation.