title: Knowledge gaps and research recommendations for essential tremor.
abstract: Essential tremor (ET) is a common cause of significant disability, but its etiologies and pathogenesis are poorly understood. Research has been hampered by the variable definition of ET and by non-standardized research approaches. The National Institute of Neurological Disorders and Stroke (USA) invited experts in ET and related fields to discuss current knowledge, controversies, and gaps in our understanding of ET and to develop recommendations for future research. Discussion focused on phenomenology and phenotypes, therapies and clinical trials, pathophysiology, pathology, and genetics. Across all areas, the need for collaborative and coordinated research on a multinational level was expressed. Standardized data collection using common data elements for genetic, clinical, neurophysiological, and pathological studies was recommended. Large cohorts of patients should be studied prospectively to collect bio-samples, characterize the natural history of the clinical syndrome including patient-oriented outcomes, investigate potential etiologies of various phenotypes, and identify pathophysiological mechanisms. In particular, cellular and system-level mechanisms of tremor oscillations should be elucidated because they may yield effective therapeutic targets and biomarkers. A neuropathology consortium was recommended to standardize postmortem analysis and further characterize neuropathological observations in the cerebellum and elsewhere. Furthermore, genome-wide association studies on large patient cohorts (>10,000 patients) may allow the identification of common genes contributing to risk, and whole exome or genome sequencing may enable the identification of genetic risk and causal mutations in cohorts and well-characterized families.
authors: Department of Neurology, University Hospital Schleswig Holstein, Kiel, Germany.
authors: Franziska
authors: F
authors: Hopfner
authors: National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA. Electronic address: dietrich.haubenberger@nih.gov.
authors: Dietrich
authors: D
authors: Haubenberger
authors: National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
authors: Wendy R
authors: WR
authors: Galpern
authors: National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
authors: Katrina
authors: K
authors: Gwinn
authors: National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
authors: Ashlee
authors: A
authors: Van't Veer
authors: National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
authors: Samantha
authors: S
authors: White
authors: Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, University College of London, United Kingdom.
authors: Kailash
authors: K
authors: Bhatia
authors: Mayo Clinic College of Medicine, Mayo Clinic Arizona, Scottsdale, AZ, USA.
authors: Charles H
authors: CH
authors: Adler
authors: The Feinstein Institute for Medical Research, Manhasset, NY, USA.
authors: David
authors: D
authors: Eidelberg
authors: Methodist Neurological Institute, Houston, TX, USA.
authors: William
authors: W
authors: Ondo
authors: Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.
authors: Glenn T
authors: GT
authors: Stebbins
authors: Parkinson's Disease Research Education & Clinical Center, San Francisco Veterans Affairs Medical Center & Department of Neurology, University of California San Francisco, CA, USA.
authors: Caroline M
authors: CM
authors: Tanner
authors: Radboud University Medical Centre, Donders Institute for Brain, Cognition and Behaviour, Department of Neurology, Nijmegen, The Netherlands.
authors: Rick C
authors: RC
authors: Helmich
authors: Department of Neurosurgery, Hopkins Hospital, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors: Fred A
authors: FA
authors: Lenz
authors: Department of Pathology & Immunology, Department of Neuroscience, Program in Developmental Biology, Baylor College of Medicine, Houston, TX, USA.
authors: Roy V
authors: RV
authors: Sillitoe
authors: Department of Applied Physiology and Kinesiology, Center for Movement Disorders and Neurorestoration, Department of Biomedical Engineering, University of Florida, Gainesville, FL, USA.
authors: David
authors: D
authors: Vaillancourt
authors: Department of Neurology, University of Minnesota Medical School, Minneapolis, MN, USA.
authors: Jerrold L
authors: JL
authors: Vitek
authors: Department of Neurology, Department of Chronic Disease Epidemiology, Center for Neuroepidemiology and Clinical Neurological Research, Yale School of Medicine, Yale University, New Haven, CT, USA.
authors: Elan D
authors: ED
authors: Louis
authors: Department of Neurology, Barrow Neurological Institute, Phoenix, AZ, USA.
authors: Holly A
authors: HA
authors: Shill
authors: C.S. Kubik Laboratory for Neuropathology, Massachusetts General Hospital, Boston, MA, USA.
authors: Matthew P
authors: MP
authors: Frosch
authors: Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.
authors: Tatiana
authors: T
authors: Foroud
authors: Department of Neurology, University Hospital Schleswig Holstein, Kiel, Germany.
authors: Gregor
authors: G
authors: Kuhlenbäumer
authors: Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
authors: Andrew
authors: A
authors: Singleton
authors: Parkinson's and Movement Disorders Center and Department of Neurology, Virginia Commonwealth University, Richmond, VA, USA.
authors: Claudia M
authors: CM
authors: Testa
authors: National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
authors: Mark
authors: M
authors: Hallett
authors: Department of Neurology, Southern Illinois University School of Medicine, Springfield, IL, USA.
authors: Rodger
authors: R
authors: Elble
authors: Department of Neurology, University Hospital Schleswig Holstein, Kiel, Germany.
authors: Günther
authors: G
authors: Deuschl
mesh_terms: D000818:Animals; D035843:Biomedical Research / Q000379:methods / Q000592:standards; D020329:Essential Tremor / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D019359:Knowledge
keywords: Common data elements; Essential tremor; Genetic association studies; Neuropathology