Present-Day Essential Tremor Medical Research Outlined:

Experts Reach Consensus on Research Priorities

In the quest to advance Essential Tremor (ET) research that could lead to better understanding and development of successful treatments, medical professionals in the movement disorder field collaborated on a white paper published in December, 2016 entitled “Knowledge Gaps and Research Recommendations for Essential Tremor.”

ET_poster (1)The paper developed out of a workshop these professionals attended in May 2015 and their subsequent brainstorming discussions. The non-profit ET patient advocacy organization HopeNET, which has for several years sought to connect the ET patient community to the medical research community, proudly played a role in the occurrence of the workshop, which was hosted by the National Institutes of Neurological Disease and Stroke (NINDS) in Bethesda, Maryland, USA, and included over 60 participants.

The resulting paper is a valuable guideline for the future. It is certain to be of interest to the ET community who will be glad to learn that medical professionals are indeed working to further knowledge of this movement disorder! The summary below serves as a layperson’s general overview of the detailed paper to convey information in terms that are more understandable to a general audience. Science-curious readers can pursue the paper in full through ScienceDirect here [1].

The causes of ET are poorly understood. Despite widespread occurrence, no medications have been created specifically to treat it. The goals of making ET less elusive and coordinating research efforts were driving forces behind the workshop discussions. One big challenge is limited knowledge about both the genetics and the neural pathway mechanisms involved in ET. Another has to do with inconsistencies in making an ET diagnosis. The fact that ET has multiple causes makes any simple definition of it inadequate.

Clinical research methods and approaches have been inconsistent. And without standardized procedures in place, analyses and findings disagree. The authors do an excellent job of taking an in-depth look at what they do and do not know about ET. Perhaps most importantly they take it a step further: they come to a consensus on recommendations for research in these areas: phenomenology and phenotypes, therapies/ clinical trials, physiology, pathology and genetics.

The authors recall the classic ET definition given roughly 20 years ago, as set forth by the International Parkinson and Movement Disorder Society (MDS). They mention that since that time there has been speculation about other characteristics that may need to be added to the definition such as, modest changes or abnormalities in these areas: cerebellar [2], cognitive [3] and hearing function [4, 5], plus dystonia [6].

The authors discuss how it is common for ET patients to present with new symptoms that do not fit in to the existing ET definition, changes that call into question the validity of the diagnosis. ET also appears to share overlapping features with other conditions [7]. New symptoms and overlapping features have encumbered clinicians, but they still believe a revised, workable definition is necessary clinically for the purpose of making inroads and facilitating important collaborative research.

They agree on new criteria and propose that ET going forward be considered as an isolated tremor “syndrome” rather than a single disease or condition since it has been established that ET has multiple causes.

The following are the authors’ recommended diagnostic criteria for defining ET as an “isolated tremor syndrome” in an individual:

  • Bi-brachial action tremor (postural or kinetic)
  • Duration of 3 years or more
  • With or without head tremor or tremor in other locations
  • No other diagnostic neurologic signs (e.g. overt dystonia or parkinsonism)
  • No identifiable endogenous (e.g., autoimmune disease) or exogenous (e.g., toxins) disturbances that could cause tremor
  • Difficulty with tandem walking is permissible, but no abnormality of gait [8]

Bi-brachial pertains to the 2 arms. Postural refers to holding a limb against gravity as in for example, holding arms out in front of the body, and kinetic refers to tremor that occurs when in action. The authors acknowledge that there are isolated tremors that do not meet the proposed ET criteria. They make clear this clinical ET definition is not meant as a detriment to continued research on other isolated tremors.

Given the absence of an identified ET gene or an identified biomarker to help with a diagnosis, emphasis is placed by the authors on gathering and classifying symptoms as fully as possible, with quality data collection and standardization efforts in place, including use of common data elements (CDEs). How is tremor measured in a clinical setting? Various tremor rating scales are used and the authors are calling for their evaluation. The rating scales include clinical assessment scales, patient-reported ratings/scales, and motion transducers, which are those devices that measure tremor amplitude or severity. Recommendations are made for development of a tremor monitor, among other technological devices. It is however pointed out that gaining insight from measuring the tremor is not as conclusive as it would seem since tremor amplitude or the severity of the oscillation can fluctuate at various times and the significance of those fluctuations is not known.

Regarding therapies or treatments for ET, the common drugs presently used were created to treat other conditions like epilepsy, high blood pressure and anxiety and were repurposed for ET when found to reduce tremor in some people. The paper explains briefly how these agents are thought to work at the cellular level. Besides the commonly used beta-blockers, anti-epilepsy drugs and benzodiazepines, clinical research has established ethanol, aka alcohol, as effective in its ability to reduce tremor amplitude for many people. Its effectiveness has led to studies in past years that isolate ethanol-related molecules such as sodium oxybate, 1-Octanol and octanoic acid, and these may turn into possible future treatments. They also seek to better understand how certain surgical interventions have met some success in reducing tremor: deep brain stimulation (DBS) and magnetic resonance focused ultrasound, both of which target and lesion the ventral intermediate nucleus (VIM) portion of the thalamus in the brain.

At the physiological level, researchers have identified a particular central nervous system circuit they think may be responsible for tremor oscillation in ET called the corticobulbocerebellothalamocortical circuit, and they are calling for investigation of it.

Genetics research findings make clear to the authors that the path to increased ET knowledge may be found in focusing on large patient cohort studies worldwide in order to make certain associations. Background is given on some important studies that have been done such as the Icelandic genome-wide association study (GWAS) that suggests the gene LINGO1 has possible associations to ET [9]. Common data elements, collection and storage of DNA bio-samples and coordinated multinational efforts are strongly encouraged.

The paper builds an awareness of scientific research being done in the ET field. The workshop provided an opportunity for experts to discuss present-day ET challenges. The authors discovered shared goals that ultimately revolve around deepening knowledge and making new treatments available, improving data, standardizing approaches, and evaluating therapies. It is a guideline for future research projects that, if adopted by researchers, could see momentum build in the direction of better outcomes for ET.

Lisa Gannon





[1] F. Hopfner, D. Haubenberger, W.R. Galpern, K. Gwinn, A. Van’t Veer, S. White, …, G. Deuschl. Knowledge gaps and research recommendations for essential tremor. Parkinsonism and Related Disorders 33 (2016) 27-35. Retrieved from

[2] J. Benito-Leon, A. Labiano-Fontcuberta, Linking essential tremor to the cerebellum: clinical evidence, Cerebellum 15(3)(2016) 253-262.

[3] E.D. Louis, J. Benito-Leon, S. Vega-Quiroga, F. Bermejo-Pareja, Neurological Disorders in Central Spain Study, Faster rate of cognitive decline in essential tremor cases than controls: a prospective study, Eur. J. Neurol. 17(10)(2010) 1291-1297]

[4, 5] W. G. Ondo, L. Sutton, K. Dat Vuong, D. Lai, J. Jankovic, Hearing impairment in essential tremor, Neurology 61 (8)(2003) 1093-1097.

Benito-Leon, E.D. Louis, F. Bermejo-Parmejo-Pareja, Neurological Disorders in Central Spain Study, Reported hearing impairment in essential tremor: a population based case-control study, Neuroepidemiology 29(3—4)(2007) 213-217.

[6] J. Jankovic. Essential tremor: a heterogenous disorder, Mov. Disord. 17(4)(2002) 638-644.

[7] R.J. Elble, What is essential tremor? Curr. Neurol. Neurosci. Rep. 13(6)(2013) 353.

[8] F. Hopfner, et al. Knowledge gaps and research recommendations for essential tremor. Parkinsonism and Related Disorders 33 (2016) 27-35,

[9] H. Stefansson, S. Steinberg, H. Petursson, O. Gustafsson, I.H. Gudjonsdottir, G.A. Jonsdottir, …, K. Stefansson. Variant in the sequence of the LINGO1 gene confers risk of essential tremor. Nat. Genet. 41 (3)(2009) 277–279.

Dr. Dietrich Haubenberger of NINDS/NIH Gives Presentation On ET Outlook

title-page-et2016-presentationWhen we founded HopeNET 5 years ago, we felt that the thing that the ET community needed most at that time was HOPE – hence the name. In the meantime, we have strived hard to bring some hope to all with ET. Accordingly, HopeNET played a key role in having the ET conference at NIH in May 2015. Since that conference, there has been a big increase on the part of industry in developing new treatments for ET. Dr. Dietrich Haubenberger of NIH is probably in the best position to know what is going on with ET. He came to the Falls Church, Virginia ET support group on October 14th and made the attached presentation, Essential Tremor 2016: A look into the pipeline. There has never been a better time than right now for hope – for all of us in the ET community.

— Peter

Personal Stories – Deb, age 73

Deb’s ET began about 5 years ago. Before retiring from the Navy she had an encounter where the updraft from a landing helicopter picked her up, flipped her over and dropped her on the ground, 3 times.  The ET started about a year after this as a slight tremor in her left hand, her writing hand. It spread more recently to the other hand, and the left hand has gotten worse to where people notice it now. The more she concentrates on not spilling, she spills, ie, when eating a bowl of soup. The soup does not make it to her mouth unless she uses two hands. Deb sings and also notices the tremor impedes her holding sheet music in her hands.

She has hit her head about 5 times in life and has had 3 concussions. Long before the helicopter accident she was in a terrible car accident, in a stopped car that was hit by a car moving at 85mph and threw her vehicle 50 feet. Deb had two compressed discs in her spine, the cranial and lumbar.  However, she definitely attributes the helicopter accident to the onset of her tremor. She went to her neurologist for the tremor about a year ago when it became more noticeable and went on Primidone. She continues to take it but finds it doesn’t seem to work.

She doesn’t recall anyone in her family having had a tremor. She has had her frustrations from ET, such as her writing became so bad that when her bank once asked her to write to get money out, the amount she wrote out was not even legible. Also she tires more easily because of trying to hard to control the tremor.

Before Deb retired she worked in a laboratory and did precise work that required her to be steady. She was thinking of going back to work in the medical field she was trained in to make some money but says it wouldn’t be possible now with her tremor because it makes her too unsteady.

In term of coping, she finds wine calms her tremor down so she will have some at dinner, 3 champagne glasses full. But while wine works, whiskey does not. She has started to do stretching exercises and wants to try Tai Chi. The idea is to stabilize the impulses from the thalamus. She hopes NIH will have their octanoic acid study resume again so that medicine will be made available that mimics the effects of alcohol on tremor without the drunken aspect.

Interviewed by Lisa Gannon
Silver Spring, MD Support Group Member

Other personal stories:


Congressional Briefing May 7, 2014

On Wednesday, May 7, we conducted a briefing to staff members of both houses of Congress. A representative from NIH also attended. The speakers were (1) Claudia Testa, MD, PhD, Associate Professor of Neurology, Virginia Commonwealth University, Associate Director of Clinical Research, VCU’s Parkinson’s & Movement Disorder Center, Joan Massey Chair in Clinical Parkinson’s Disease, (2) Sara Donaldson and Prudy Bradley, sisters with Essential Tremor (ET) that are part of a family in which all 12 siblings have or had ET, (3) Soren Lowell, PhD Assistant Professor, Department of Communication Sciences & Disorders, Syracuse University, and (4) myself.

Dr. Testa provided an overview of Essential Tremor (1) what its are effects – the problems its causes for those who have it, (2) what is known about ET, and (3) what we can do to help those with ET. Prudy and Sara then got up. Sara’s voice tremor is so bad, she can’t speak (she has a pen & pad of paper with her all the time). As a result, Prudy spoke for both of them and related how ET had impacted the quality of their lives. Dr. Lowell is currently conducting a study, funded by NIH, on the impact of Octanoic Acid on Voice Tremor caused by ET. I concluded the presentation by relating how I was fired from a senior management position as a direct result of my voice tremor.

There was real interest on the part of those who attended. A number stayed afterwards to learn more about Essential Tremor.

Peter Muller
Executive Director

Shaking On Capitol Hill

April 2, 2014 — A handful of members from the Essential Tremor Support Group that meets monthly at Leisure World in Silver Spring made a trip to Capitol Hill to meet with Congressman Chris Van Hollen’s Legislative Assistant for Healthcare, Erika Appel, to discuss concerns over quality of life for people with Essential Tremor, a neurological condition.

E.T. can present with hand tremors, voice tremors, loss of voice, head tremors, and leg tremors. Prudy of Ashburn attended with her sister, Sara, of Derwood, in order to speak for Sara who cannot talk because of the condition. Sara began having a wavering voice years ago and as the condition progressed she lost her voice completely and faces not only social isolation but real danger from not being able to communicate. Another attendee was Thom who came with his wife Mary so she could speak to how it is for a family member supporting the person with E.T. Thom had Deep Brain Stimulation, brain surgery that involves a pacemaker placed below the neck that helps control the electrical signals and calm the tremor. Unfortunately for Thom, the electrical wire placed in the brain is close enough to the speech center to have impaired his speech which is slurred as a result. Charley, another member, lost his job last December when he was asked to take early retirement and suspects that his tremor may be in part to blame since he was an ESOL teacher who taught writing, which is of course quite difficult when your writing is illegible from the tremor. And lastly I attended, a 50 year old woman, and experience like many others the anxiety-like physical and psychological effects of the tremor and its negative impact on work and social life. As the condition progressively gets worse, I fear for my future in terms of unemployment [my excessive shaking at job interviews does not likely help me get the job] and disability [since the tremor is not bad at all times, I certainly would not qualify for disability, but in situations such as job interviews it is truly a disability].

Prudy spoke and gave some perspective on E.T. in the U.S. She recollected statistics from several years ago that approximately 1 million people have Parkinson’s Disease whereas E.T. affects about 10 million. Most in our group think people with the condition do not know they have it and attribute their symptoms to anxiety or nerves. It has been well-established that having an alcoholic drink helps many with this condition, that the octanol in alcohol helps diminish the tremor for a short time, and NIH has conducted research studies to isolate the octanoic acid from alcohol for use in pill form. These studies are years old, and there is frustration among this group that development of pharmaceutical octanoic acid is stalled. While there is the newer focused ultrasound treatment, and Sara mentioned she thought there were 9000 on the waiting list, we lamented over the lack of knowledge among neurologists about our condition, and about the complete lack of development of any drug specifically made to treat E.T. The few medicines that are prescribed were developed decades ago for other conditions like high blood pressure and epilepsy and happened to alleviate the tremor for only some people. It was encouraging that Erika Appel wanted to look into the condition further and wondered why a drug had not been developed if there is a market of so many people who have the condition.

The next thing for HopeNET is the May 7th congressional briefing on E.T. sponsored by Congressman Moran’s office.

Lisa Gannon, Silver Spring Support Group Member

Octanoic Acid in alcohol responsive essential tremor – A randomized controlled study

There is no medication available that has been designed specifically for Essential Tremor. The National Institutes of Health studied One Octanol/ Octanoic Acid for about ten years before putting the study on hold in May 2012. As I participated in several stages of the study, I know it works and is safe. It is very important that this study be completed, and people with Essential Tremor finally have a drug designed for their condition.

Peter Muller

Octanoic Acid in alcohol responsive essential tremor – A randomized controlled study (pdf)