Living with Essential Tremor (ET)

Forum Held on Partnering with NIH: Essential Tremor Patient Advocates Look to Build Relationships with Scientific Community

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For two days in late September, the National Institute of Neurological Disorders and Stroke, NINDS, on the NIH campus held its eighth Nonprofit Forum called “Progress Through Partnership,” which provided a wonderful way for nonprofits who support and educate about their specific medical condition to learn how clinical and translational research at NINDS works. Forty-three health organizations or patient foundations were there in attendance.

Two things were notable about this forum, one being that Dr. Story Landis, Director of NINDS gave remarks along with others from NINDS in which she as well as the others made it clear that they want a closer relationship with the patient foundations and nonprofit organizations. With a closer relationship, they can conduct more effective research as a result of understanding patients’ needs, and it makes it easier to recruit patients. Also of note was that the forum panel consisted of patient advocates who had created nonprofits/ foundations that in the not-so-distant past partnered with NIH in finding treatments. They were there to report on their accomplishments to us. What encouragement! A few were foundations for rare diseases that affect between 2200 to 1 million people, which makes it more remarkable that they were able to make progress and see pharmaceutical products come to market.

Panel speakers were generally people who either had a condition themselves or with family members who had it. The panel was impressive not because they had perfectly figured out how to work with NIH to make things happen but for their personal perseverance and accomplishments. In the process they got to know NIH clinical researchers and worked together with NIH to reach the mutual goal of stimulating research and seeking cures or clinical interventions. Outside of NINDS they made inroads through the use of lobbyists, created patient registries, raised research funds, sought grants, conducted their own surveys, and created or identified Centers of Excellence such as university medical centers that have been established to conduct research and provide the best care for patients with a particular condition.

One speaker described how their nonprofit that supports the rare disease Ataxia went from having zero pharmaceuticals to having many in part because they created a patient registry that could easily and very quickly help the pharma companies get patients for a study. This information should bring hope to those with Essential Tremor since it is not a rare condition but one that affects 7 million potential customers of a medication.

Lisa Gannon
Silver Spring Support Group

Click here to see the 2 day videocast of the “Progress Through Partnership: NINDS 8th Annual Nonprofit Forum”

How Many People in the USA Have Essential Tremor? Deriving a Population Estimate Based on Epidemiological Data

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During the past year, it became apparent as we spoke to Congressional Legislative Assistants for Healthcare that we needed more facts about Essential Tremor – if we were to adequately present our case. A doctor, who has ET and is active in the Columbia Support Group, suggested to me that we needed more epidemiology on ET. Accordingly, I contacted Dr. Elan Louis at Columbia University. He is both a neurologist and an epidemiologist. The result of our conversation was that Dr. Louis agreed, and he did this study. I am very thankful to him.

Peter Muller

How Many People in the USA Have Essential Tremor? Deriving a Population Estimate Based on Epidemiological Data
Elan D. Louis 1,2,3,4* & Ruth Ottman 1,3,4,5

1GH Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY, USA, 2 Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY, USA, 3 Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA, 4 Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA, 5 Division
of Epidemiology, New York State Psychiatric Institute, New York, NY, USA

Abstract

Background: Essential tremor (ET) is often reported to be among the most prevalent movement disorders, yet the precise number of cases in the USA is not known. The goal of the current analyses was to use published data from epidemiological studies to derive an estimate of the number of people currently residing in the USA who have ET.
Methods: A PubMed search was conducted to identify population-based prevalence studies of ET. The methodology of 34 identified studies was assessed. Then the three most methodologically rigorous studies were selected, and age-specific prevalence data were abstracted. US census data from 2012 were used to determine the population in the USA by 10-year age categories.
Results: Using data from three studies, estimates of the number of ET cases (2012) ranged from 6.38 to 7.63 million (mean57.01 million). This corresponds to approximately 2.2% of the US population.
Discussion: Knowing the number of ET cases in the USA is important in terms of estimating the medical burden on communities and society, and providing an objective metric on which to base health resource planning.
Keywords: Essential tremor, population, epidemiology, prevalence, public health
Citation: Louis ED, Ottman R. How many people in the USA have essential tremor? Deriving a population estimate based on epidemiological data. Tremor Other Hyperkinet Mov. 2014; 4. doi: 10.7916/D8TT4P4B
*To whom correspondence should be addressed. E-mail: EDL2@columbia.edu
Editor: Julian Benito-Leon, Hospital ‘‘12 de Octubre’’, Spain
Received: June 19, 2014 Accepted: July 21, 2014 Published: August 13, 2014
Copyright: ©2014 Louis et al. This is an open-access article distributed under the terms of the Creative Commons Attribution–Noncommercial–No Derivatives License, which permits the user to copy, distribute, and transmit the work provided that the original author(s) and source are credited; that no commercial use is made of the work; and that the work is not altered or transformed.
Funding: None.
Financial Disclosures: Dr. Louis has received research support from the National Institutes of Health: NINDS #R01 NS042859 (principal investigator), NINDS #R01 NS39422 (principal investigator), NINDS #R01 NS086736 (principal investigator), NINDS #R01 NS073872 (principal investigator), NINDS #R01 NS085136 (principal investigator), NINDS #T32 NS07153-24 (principal investigator), NINDS #R21 NS077094 (co-Investigator), NINDS #R01 NS36630 (co-Investigator), NIEHS P30 ES09089 (co-investigator), and CTSA grant number UL1 RR024156. He has also received support from the Parkinson’s Disease Foundation, the Arlene Bronstein Essential Tremor Research Fund (Columbia University), and the Claire O9Neil Essential Tremor Research Fund (Columbia University). Dr. Ottman serves on the scientific advisory board for and holds stock options in Trigeminal Solutions, Inc; received funding for travel from the E ´ cole des Hautes Etudes en Sante´ Publique; and received research support from the NIH through #U01 NS077276 (MPI), #U01 NS077367 (MPI), #R01 NS078419 (PI), P50 HG007257 (Co-I), #NIH R01 NS073872 (Co-I), and #R01 AG041797 (Co-I).
Conflict of Interest: The authors report no conflict of interest.

Introduction

Essential tremor (ET) is often reported to be among the most prevalent movement disorders, and it is the most common cause of abnormal tremor in humans.1 The incidence of ET rises with age.2,3 Furthermore, the reported increased risk of mortality associated with ET is modest,4 and, therefore, incident cases accumulate with time,
contributing to the often-observed age-associated rise in disease prevalence.1,5,6

Despite its reportedly high prevalence, the precise number of ET cases in the USA is not known. One often-cited paper, published in 1995, estimated that 13.5 million Americans had ET,7 and given the growth in the US population over the past 19 years, one would expect that an even larger number of Americans now have ET. However, the methods used to derive the estimate of 13.5 million are not completely transparent.7 Websites for disease-specific organizations, such as the International Essential Tremor Foundation, report that there are an estimated 10 million Americans with ET. Again, the basis for this
estimate is not clear.

Knowing the number of ET cases is important for estimating the medical burden on communities and society, and providing an objective metric on which to base health resource planning. The goal of the current analyses was to use published data from epidemiological studies to derive an estimate of the number of people currently residing
in the USA who have ET.

Table 1.  Prevalence data for ET (per 100) by Age Category in Four Selected Studies

Age Category (Years)1
Dogu et al.5 (Turkey)
Glick et al.18(Israel)
Sur et al. 20(Turkey)
Seijo-Martinez et al.14 (Spain)
18-30
0.79
31-40
0.83
40-49
2.8
1.562
50-59
3.5
2.892
60-69
5.9
3.882
65-69
0.57
65-74
7.35
70-79
6.5
0.72
75-84
9.92
71 and older
9.34
80 and older
8.7
1.47
85 and older
11.24

Abbreviaton: ET, Essential Tremor
1 Several studies used different age cut points.
2 Actual age categories were 41-50, 51-60, and 61-70 years.

Methods

A PubMed search was conducted in May 2014 in order to identify published population-based prevalence studies of ET. The search terms were ‘‘prevalence’’, ‘‘incidence’’, ‘‘epidemiology’’, ‘‘population’’, and ‘‘essential tremor’’, and all full-length English language papers were identified. One full-length paper in Chinese was excluded.8 The search yielded 34 population-based prevalence studies.1,9–14 The methodology of each identified study was assessed, and methodologically more rigorous studies were selected for further review. The methodological issues of greatest importance were as follows: 1) all subjects in the sample received an in-person neurological examination
or the study provided information to indicate that the sensitivity of the screening questionnaire used during the first phase of case ascertainment was high, 2) neurologists assigned the ET diagnoses, 3) the study used diagnostic criteria that sufficiently separate ET from other entities such as enhanced physiological tremor, which are common in the population, and 4) the study provided separate age-specific estimates of prevalence. Age-specific prevalence data from the selected studies were then abstracted. US census data from 2012 were used to derive counts of the population in the USA by 10-year age categories.15

Results

The search identified 34 population-based prevalence studies, including 28 reviewed by Louis et al. in 2010 and six published after that point.1,9–14 Of these 34 studies, 16 were identified in which: 1) the method of case ascertainment involved either neurological examination of all subjects in a population sample or administration of a screening questionnaire followed by neurological examination, and the sensitivity of the screen was provided, and 2) estimates of prevalence were provided within age strata.5,6,11,12,14,16–26 Of these 16,5,6,11,12,14,16–26 12 used diagnostic criteria for ET that are not ideally suited to epidemiological investigations (e.g., the Consensus Statement of the Movement Disorder Society27) because they do not sufficiently separate ET from other entities such as enhanced physiological tremor, and/or used non-neurologists to assign ET diagnoses, which is not optimal. Four studies remained; these were conducted in Israel,18 Turkey,5,20 and Spain.14 The age-specific prevalence of ET is displayed for each of these four studies (Table 1).5,14,18,20 One of these studies18 focused exclusively on a specific ethnic group (Arab villagers in Northern Israel) and the prevalence estimates were one order of magnitude lower than those reported in the other three studies;5,14,20 hence it was excluded, leaving three remaining studies.5,14,20

Prevalence data from each of the three remaining studies were used, in conjunction with 2012 US Census data, to estimate the number of individuals in the USA with ET in 2012. First, using data from the study in Istanbul, Turkey,20 one would estimate that 6.38–6.78 million individuals in the USA have ET. This estimate used age-specific ET prevalence data from Istanbul for ages 18 and older. For individuals who were younger than age 18, we used incidence data for ET from Rochester, Minnesota,3 which indicated that 14 of 266 (5.3%) ET cases arise prior to age 20 years. Using these data, we made two alternative assumptions. The first assumption was that none of the ET cases whose tremor began prior to age 20 was still younger than 20; the second assumption was that all of these ET cases were still younger than 20. The alternative assumptions resulted in two different estimates, 6.38 and 6.78 million for assumptions 1 and 2, respectively. Second, using data from the study in Mersin, Turkey,5 we estimated that 7.23–7.63 million individuals in the USA have ET. To derive this estimate, we used the published age-specific estimates from Mersin for ages 40 or older. To include younger individuals, we used data from the study in Istanbul20 for individuals aged 18–40, and data from Rochester, Minnesota3 for individuals aged 18 and younger. We made the same two alternative assumptions described above about the current ages of childhood onset cases. Third, using data from the study in Spain,14 we estimated that 6.75–7.15 million individuals in the USA have ET. This estimate was based on published age-specific estimates from Spain for individuals aged 65 or older. For younger individuals, we used data from the study in Istanbul20 for those aged 18–65 and data from Rochester, Minnesota3 for those aged 18 or younger. Again, we used the same two alternative assumptions as in the other studies about the current ages of childhood onset cases. For all three studies, the estimates of the number of individuals with ET in the USA (2012) range from 6.38–7.63 million (mean57.01 million).

Discussion

In the current study, we estimated that approximately 7 million people in the USA have ET.  This represents 2.2% of the US population. By comparison, the number of people with Parkinson’s disease, another tremor disorder, is estimated at 0.5–1 million, or about 0.15–0.3% of the population.

ET is one of the most common neurological diseases, and with 7 million people in the country affected, it is expected to result in considerable health care expenditures. Its effects on loss of work productivity have not been determined on a broad societal level. One study reported that 25% of ET cases were forced to change jobs or take early retirement because of tremor;28 however, the ET cases were recruited to a specialty care center rather than from the population, so it is difficult to extrapolate these data to cases in the general population, who often have tremor that is milder than that seen in clinic patients.29,30 No studies have attempted to estimate the magnitude of health care expenditures associated with ET, yet this is an issue of great import.

There are a number of important caveats to consider. All of the three selected epidemiological studies had design features that were most likely to have optimally captured ET cases and assigned valid diagnoses; however, they were carried outside of the USA.5,14,20 Despite this, age-specific prevalence estimates across the same age categories in these three studies were largely in agreement with one another, making it likely that they are a reasonable approximation of the true prevalence of ET and a reasonable starting point for approximating the prevalence of ET in the USA. In addition, there is currently no alternative but to use these data. The second issue is that data on the prevalence of ET in children were derived from a single study of the incidence rather than the prevalence of ET. Hence, the estimates we used made two opposing assumptions to provide the reader with both the most and the least conservative estimates. Regardless, the incidence and prevalence of ET are very low in children, and the two diametrically opposed assumptions resulted in estimates that were in the same general range.

In summary, the current study estimates that 7.01 million individuals in the USA have ET. This corresponds to approximately 2.2% of the US population. Knowing the number of ET cases is important for estimating the medical burden on communities and society, and providing an objective metric on which to base health resource planning.

Acknowledgment

The authors wish to acknowledge Nicole Schupf, PhD, DrPH, for her critical reading of the manuscript and constructive suggestions.

References

1. Louis ED, Ferreira JJ. How common is the most common adult movement disorder? Update on the worldwide prevalence of essential tremor. Mov Disord 2010;25:534–541, doi: http://dx.doi.org/10.1002/mds.22838.
2. Benito-Leon J, Bermejo-Pareja F, Louis ED. Incidence of essential tremor in three elderly populations of central Spain. Neurology 2005;64:1721–1725, doi: http://dx.doi.org/10.1212/01.WNL.0000161852.70374.01.
3. Rajput AH, Offord KP, Beard CM, Kurland LT. Essential tremor in Rochester, Minnesota: A 45-year study. J Neurol Neurosurg Psychiatry 1984;47:466–470, doi: http://dx.doi.org/10.1136/jnnp.47.5.466.
4. Louis ED, Benito-Leon J, Ottman R, Bermejo-Pareja F. A population based study of mortality in essential tremor. Neurology 2007;69:1982–1989, doi: http://dx.doi.org/10.1212/01.wnl.0000279339.87987.d7.
5. Dogu O, Sevim S, Camdeviren H, et al. Prevalence of essential tremor: Door-to-door neurologic exams in Mersin Province, Turkey. Neurology 2003;61:1804–1806, doi: http://dx.doi.org/10.1212/01.WNL.0000099075.19951.8C.
6. Benito-Leon J, Bermejo-Pareja F, Morales JM, Vega S, Molina JA. Prevalence of essential tremor in three elderly populations of central Spain. Mov Disord 2003;18:389–394, doi: http://dx.doi.org/10.1002/mds.10376.
7. Lundervold DA, Poppen R. Biobehavioral rehabilitation for older adults with essential tremor. Gerontologist 1995;35:556–559, doi: http://dx.doi.org/10. 1093/geront/35.4.556.
8. Liu Y, Zhang XY, Tang YZ, et al. [Investigation on prevalence rate of essential tremor in population aged 55 years old and above in Kashkar, between 2008 and 2009]. Zhonghua yi xue za zhi 2011;91:1067–1069.
9. Barbosa MT, Caramelli P, Cunningham MC, Maia DP, Lima-Costa MF, Cardoso F. Prevalence and clinical classification of tremor in elderly—A community-based survey in Brazil. Mov Disord 2013;28:640–646, doi: http://dx.doi.org/10.1002/mds.25355.
10. Ozel L, Demir R, Ozdemir G, et al. Investigation of the prevalence of essential tremor in individuals aged 18–60 in Erzurum. Acta Neurologica Belgica 2013;113:127–131, doi: http://dx.doi.org/10.1007/s13760-012-0147-5.
11. Aharon-Peretz J, Badarny S, Ibrahim R, Gershoni-Baruch R, Hassoun G. Essential tremor prevalence is low in the Druze population in northern Israel. Tremor Other Hyperkinet Mov 2012;2:http://tremorjournal.org/article/view/81.
12. Okubadejo NU, Bankole IA, Ojo OO, Ojini FI, Danesi MA. Prevalence of essential tremor in urban Lagos, Nigeria: A door-to-door community-based study. BMC Neurol 2012;12:110, doi: http://dx.doi.org/10.1186/1471-2377-12-110.
13. Louis ED, Hafeman D, Parvez F, et al. Prevalence of essential tremor in Araihazar, Bangladesh: A population-based study. Neuroepidemiology 2011;36:71–76, doi: http://dx.doi.org/10.1159/000323389.
14. Seijo-Martinez M, Del Rio MC, Alvarez JR, et al. Prevalence of essential tremor on Arosa Island, Spain: A community-based, door-to-door survey. Tremor Other Hyperkinet Mov 2013;3:http://tremorjournal.org/article/view/192.
15. United States Census Bureau. Current population survey. Annual social and economic supplement, 2012. Internet release data: December 2013. http://www.census.gov/population/age/data/2012comp.html
16. Hornabrook RW, Nagurney JT. Essential tremor in Papua, New Guinea. Brain 1976;99:659–672, doi: http://dx.doi.org/10.1093/brain/99.4.659.
17. Salemi G, Savettieri G, Rocca WA, et al. Prevalence of essential tremor:A door-to-door survey in Terrasini, Sicily. Sicilian Neuro-Epidemiologic Study Group. Neurology 1994;44:61–64, doi: http://dx.doi.org/10.1212/WNL.44.1.61.
18. Glik A, Masarwa M, Abuful A, et al. Essential tremor might be less frequent than Parkinson’s disease in North Israel Arab villages. Mov Disord 2009; 24:119–122, doi: http://dx.doi.org/10.1002/mds.22324.
19. Mancini ML, Stracci F, Tambasco N, Sarchielli P, Rossi A, Calabresi P. Prevalence of essential tremor in the territory of Lake Trasimeno, Italy: Results of a population-based study. Mov Disord 2007;22:540–545, doi: http://dx.doi.org/10.1002/mds.21349.
20. Sur H, Ilhan S, Erdogan H, Ozturk E, Tasdemir M, Boru UT. Prevalence of essential tremor: A door-to-door survey in Sile, Istanbul, Turkey. Parkinsonism Relat Disord 2009;15:101–104, doi: http://dx.doi.org/10.1016/j.parkreldis.2008.03.009.
21. Louis ED, Marder K, Cote L, et al. Differences in the prevalence of essential tremor among elderly African Americans, whites, and Hispanics in northern Manhattan, NY. Arch Neurol 1995;52:1201–1205, doi: http://dx.doi.org/10.1001/archneur.1995.00540360079019.
22. Louis ED, Thawani SP, Andrews HF. Prevalence of essential tremor in a multiethnic, community-based study in northern Manhattan, New York, N.Y. Neuroepidemiology 2009;32:208–214, doi: http://dx.doi.org/10.1159/000195691.
23. Bergareche A, De La Puente E, Lopez De Munain A, et al. Prevalence of essential tremor: A door-to-door survey in Bidasoa, Spain. Neuroepidemiology 2001;20:125–128, doi: http://dx.doi.org/10.1159/000054771.
24. Rautakorpi I, Takala J, Marttila RJ, Sievers K, Rinne UK. Essential tremor in a Finnish population. Acta Neurol Scand 1982;66:58–67, doi: http://dx.doi.org/10.1111/j.1600-0404.1982.tb03129.x.
25. Moghal S, Rajput AH, D9Arcy C, Rajput R. Prevalence of movement disorders in elderly community residents. Neuroepidemiology 1994;13:175–178, doi: http://dx.doi.org/10.1159/000110376.
26. Khatter AS, Kurth MC, Brewer MA, et al. Prevalence of tremor and Parkinson’s disease. Parkinsonism Relat Disord 1996;2:205–208, doi: http://dx.doi.org/10.1016/S1353-8020(96)00027-2.
27. Deuschl G, Bain P, Brin M. Consensus statement of the Movement Disorder Society on Tremor. Ad Hoc Scientific Committee. Mov Disord 1998; 13(Suppl 3):2–23.
28. Bain PG, Findley LJ, Thompson PD, et al. A study of hereditary essential tremor. Brain 1994;117(Pt 4):805–824, doi: http://dx.doi.org/10.1093/brain/117.4.805.
29. Dogu O, Louis ED, Sevim S, Kaleagasi H, Aral M. Clinical characteristics of essential tremor in Mersin, Turkey—A population-based door-to-door study. J Neurol 2005;252:570–574, doi: http://dx.doi.org/10.1007/s00415-005-0700-8.
30. Louis ED, Ford B, Wendt KJ, Cameron G. Clinical characteristics of essential tremor: Data from a community-based study. Mov Disord 1998;13:803–808, doi: http://dx.doi.org/10.1002/mds.870130508.

(PDF Version)

How Many People in the USA Have Essential Tremor? Deriving a Population Estimate Based on Epidemiological Data

by

During the past year, it became apparent as we spoke to Congressional Legislative Assistants for Healthcare that we needed more facts about Essential Tremor – if we were to adequately present our case. A doctor, who has ET and is active in the Columbia Support Group, suggested to me that we needed more epidemiology on ET. Accordingly, I contacted Dr. Elan Louis at Columbia University. He is both a neurologist and an epidemiologist. The result of our conversation was that Dr. Louis agreed, and he did this study. I am very thankful to him.

Peter Muller

How Many People in the USA Have Essential Tremor? Deriving a Population Estimate Based on Epidemiological Data
Elan D. Louis 1,2,3,4* & Ruth Ottman 1,3,4,5

1GH Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY, USA, 2 Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY, USA, 3 Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA, 4 Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA, 5 Division
of Epidemiology, New York State Psychiatric Institute, New York, NY, USA

Abstract

Background: Essential tremor (ET) is often reported to be among the most prevalent movement disorders, yet the precise number of cases in the USA is not known. The goal of the current analyses was to use published data from epidemiological studies to derive an estimate of the number of people currently residing in the USA who have ET.
Methods: A PubMed search was conducted to identify population-based prevalence studies of ET. The methodology of 34 identified studies was assessed. Then the three most methodologically rigorous studies were selected, and age-specific prevalence data were abstracted. US census data from 2012 were used to determine the population in the USA by 10-year age categories.
Results: Using data from three studies, estimates of the number of ET cases (2012) ranged from 6.38 to 7.63 million (mean57.01 million). This corresponds to approximately 2.2% of the US population.
Discussion: Knowing the number of ET cases in the USA is important in terms of estimating the medical burden on communities and society, and providing an objective metric on which to base health resource planning.
Keywords: Essential tremor, population, epidemiology, prevalence, public health
Citation: Louis ED, Ottman R. How many people in the USA have essential tremor? Deriving a population estimate based on epidemiological data. Tremor Other Hyperkinet Mov. 2014; 4. doi: 10.7916/D8TT4P4B
*To whom correspondence should be addressed. E-mail: EDL2@columbia.edu
Editor: Julian Benito-Leon, Hospital ‘‘12 de Octubre’’, Spain
Received: June 19, 2014 Accepted: July 21, 2014 Published: August 13, 2014
Copyright: ©2014 Louis et al. This is an open-access article distributed under the terms of the Creative Commons Attribution–Noncommercial–No Derivatives License, which permits the user to copy, distribute, and transmit the work provided that the original author(s) and source are credited; that no commercial use is made of the work; and that the work is not altered or transformed.
Funding: None.
Financial Disclosures: Dr. Louis has received research support from the National Institutes of Health: NINDS #R01 NS042859 (principal investigator), NINDS #R01 NS39422 (principal investigator), NINDS #R01 NS086736 (principal investigator), NINDS #R01 NS073872 (principal investigator), NINDS #R01 NS085136 (principal investigator), NINDS #T32 NS07153-24 (principal investigator), NINDS #R21 NS077094 (co-Investigator), NINDS #R01 NS36630 (co-Investigator), NIEHS P30 ES09089 (co-investigator), and CTSA grant number UL1 RR024156. He has also received support from the Parkinson’s Disease Foundation, the Arlene Bronstein Essential Tremor Research Fund (Columbia University), and the Claire O9Neil Essential Tremor Research Fund (Columbia University). Dr. Ottman serves on the scientific advisory board for and holds stock options in Trigeminal Solutions, Inc; received funding for travel from the E ´ cole des Hautes Etudes en Sante´ Publique; and received research support from the NIH through #U01 NS077276 (MPI), #U01 NS077367 (MPI), #R01 NS078419 (PI), P50 HG007257 (Co-I), #NIH R01 NS073872 (Co-I), and #R01 AG041797 (Co-I).
Conflict of Interest: The authors report no conflict of interest.

Introduction

Essential tremor (ET) is often reported to be among the most prevalent movement disorders, and it is the most common cause of abnormal tremor in humans.1 The incidence of ET rises with age.2,3 Furthermore, the reported increased risk of mortality associated with ET is modest,4 and, therefore, incident cases accumulate with time,
contributing to the often-observed age-associated rise in disease prevalence.1,5,6

Despite its reportedly high prevalence, the precise number of ET cases in the USA is not known. One often-cited paper, published in 1995, estimated that 13.5 million Americans had ET,7 and given the growth in the US population over the past 19 years, one would expect that an even larger number of Americans now have ET. However, the methods used to derive the estimate of 13.5 million are not completely transparent.7 Websites for disease-specific organizations, such as the International Essential Tremor Foundation, report that there are an estimated 10 million Americans with ET. Again, the basis for this
estimate is not clear.

Knowing the number of ET cases is important for estimating the medical burden on communities and society, and providing an objective metric on which to base health resource planning. The goal of the current analyses was to use published data from epidemiological studies to derive an estimate of the number of people currently residing
in the USA who have ET.

Table 1.  Prevalence data for ET (per 100) by Age Category in Four Selected Studies

Age Category (Years)1
Dogu et al.5 (Turkey)
Glick et al.18(Israel)
Sur et al. 20(Turkey)
Seijo-Martinez et al.14 (Spain)
18-30
0.79
31-40
0.83
40-49
2.8
1.562
50-59
3.5
2.892
60-69
5.9
3.882
65-69
0.57
65-74
7.35
70-79
6.5
0.72
75-84
9.92
71 and older
9.34
80 and older
8.7
1.47
85 and older
11.24

Abbreviaton: ET, Essential Tremor
1 Several studies used different age cut points.
2 Actual age categories were 41-50, 51-60, and 61-70 years.

Methods

A PubMed search was conducted in May 2014 in order to identify published population-based prevalence studies of ET. The search terms were ‘‘prevalence’’, ‘‘incidence’’, ‘‘epidemiology’’, ‘‘population’’, and ‘‘essential tremor’’, and all full-length English language papers were identified. One full-length paper in Chinese was excluded.8 The search yielded 34 population-based prevalence studies.1,9–14 The methodology of each identified study was assessed, and methodologically more rigorous studies were selected for further review. The methodological issues of greatest importance were as follows: 1) all subjects in the sample received an in-person neurological examination
or the study provided information to indicate that the sensitivity of the screening questionnaire used during the first phase of case ascertainment was high, 2) neurologists assigned the ET diagnoses, 3) the study used diagnostic criteria that sufficiently separate ET from other entities such as enhanced physiological tremor, which are common in the population, and 4) the study provided separate age-specific estimates of prevalence. Age-specific prevalence data from the selected studies were then abstracted. US census data from 2012 were used to derive counts of the population in the USA by 10-year age categories.15

Results

The search identified 34 population-based prevalence studies, including 28 reviewed by Louis et al. in 2010 and six published after that point.1,9–14 Of these 34 studies, 16 were identified in which: 1) the method of case ascertainment involved either neurological examination of all subjects in a population sample or administration of a screening questionnaire followed by neurological examination, and the sensitivity of the screen was provided, and 2) estimates of prevalence were provided within age strata.5,6,11,12,14,16–26 Of these 16,5,6,11,12,14,16–26 12 used diagnostic criteria for ET that are not ideally suited to epidemiological investigations (e.g., the Consensus Statement of the Movement Disorder Society27) because they do not sufficiently separate ET from other entities such as enhanced physiological tremor, and/or used non-neurologists to assign ET diagnoses, which is not optimal. Four studies remained; these were conducted in Israel,18 Turkey,5,20 and Spain.14 The age-specific prevalence of ET is displayed for each of these four studies (Table 1).5,14,18,20 One of these studies18 focused exclusively on a specific ethnic group (Arab villagers in Northern Israel) and the prevalence estimates were one order of magnitude lower than those reported in the other three studies;5,14,20 hence it was excluded, leaving three remaining studies.5,14,20

Prevalence data from each of the three remaining studies were used, in conjunction with 2012 US Census data, to estimate the number of individuals in the USA with ET in 2012. First, using data from the study in Istanbul, Turkey,20 one would estimate that 6.38–6.78 million individuals in the USA have ET. This estimate used age-specific ET prevalence data from Istanbul for ages 18 and older. For individuals who were younger than age 18, we used incidence data for ET from Rochester, Minnesota,3 which indicated that 14 of 266 (5.3%) ET cases arise prior to age 20 years. Using these data, we made two alternative assumptions. The first assumption was that none of the ET cases whose tremor began prior to age 20 was still younger than 20; the second assumption was that all of these ET cases were still younger than 20. The alternative assumptions resulted in two different estimates, 6.38 and 6.78 million for assumptions 1 and 2, respectively. Second, using data from the study in Mersin, Turkey,5 we estimated that 7.23–7.63 million individuals in the USA have ET. To derive this estimate, we used the published age-specific estimates from Mersin for ages 40 or older. To include younger individuals, we used data from the study in Istanbul20 for individuals aged 18–40, and data from Rochester, Minnesota3 for individuals aged 18 and younger. We made the same two alternative assumptions described above about the current ages of childhood onset cases. Third, using data from the study in Spain,14 we estimated that 6.75–7.15 million individuals in the USA have ET. This estimate was based on published age-specific estimates from Spain for individuals aged 65 or older. For younger individuals, we used data from the study in Istanbul20 for those aged 18–65 and data from Rochester, Minnesota3 for those aged 18 or younger. Again, we used the same two alternative assumptions as in the other studies about the current ages of childhood onset cases. For all three studies, the estimates of the number of individuals with ET in the USA (2012) range from 6.38–7.63 million (mean57.01 million).

Discussion

In the current study, we estimated that approximately 7 million people in the USA have ET.  This represents 2.2% of the US population. By comparison, the number of people with Parkinson’s disease, another tremor disorder, is estimated at 0.5–1 million, or about 0.15–0.3% of the population.

ET is one of the most common neurological diseases, and with 7 million people in the country affected, it is expected to result in considerable health care expenditures. Its effects on loss of work productivity have not been determined on a broad societal level. One study reported that 25% of ET cases were forced to change jobs or take early retirement because of tremor;28 however, the ET cases were recruited to a specialty care center rather than from the population, so it is difficult to extrapolate these data to cases in the general population, who often have tremor that is milder than that seen in clinic patients.29,30 No studies have attempted to estimate the magnitude of health care expenditures associated with ET, yet this is an issue of great import.

There are a number of important caveats to consider. All of the three selected epidemiological studies had design features that were most likely to have optimally captured ET cases and assigned valid diagnoses; however, they were carried outside of the USA.5,14,20 Despite this, age-specific prevalence estimates across the same age categories in these three studies were largely in agreement with one another, making it likely that they are a reasonable approximation of the true prevalence of ET and a reasonable starting point for approximating the prevalence of ET in the USA. In addition, there is currently no alternative but to use these data. The second issue is that data on the prevalence of ET in children were derived from a single study of the incidence rather than the prevalence of ET. Hence, the estimates we used made two opposing assumptions to provide the reader with both the most and the least conservative estimates. Regardless, the incidence and prevalence of ET are very low in children, and the two diametrically opposed assumptions resulted in estimates that were in the same general range.

In summary, the current study estimates that 7.01 million individuals in the USA have ET. This corresponds to approximately 2.2% of the US population. Knowing the number of ET cases is important for estimating the medical burden on communities and society, and providing an objective metric on which to base health resource planning.

Acknowledgment

The authors wish to acknowledge Nicole Schupf, PhD, DrPH, for her critical reading of the manuscript and constructive suggestions.

References

1. Louis ED, Ferreira JJ. How common is the most common adult movement disorder? Update on the worldwide prevalence of essential tremor. Mov Disord 2010;25:534–541, doi: http://dx.doi.org/10.1002/mds.22838.
2. Benito-Leon J, Bermejo-Pareja F, Louis ED. Incidence of essential tremor in three elderly populations of central Spain. Neurology 2005;64:1721–1725, doi: http://dx.doi.org/10.1212/01.WNL.0000161852.70374.01.
3. Rajput AH, Offord KP, Beard CM, Kurland LT. Essential tremor in Rochester, Minnesota: A 45-year study. J Neurol Neurosurg Psychiatry 1984;47:466–470, doi: http://dx.doi.org/10.1136/jnnp.47.5.466.
4. Louis ED, Benito-Leon J, Ottman R, Bermejo-Pareja F. A population based study of mortality in essential tremor. Neurology 2007;69:1982–1989, doi: http://dx.doi.org/10.1212/01.wnl.0000279339.87987.d7.
5. Dogu O, Sevim S, Camdeviren H, et al. Prevalence of essential tremor: Door-to-door neurologic exams in Mersin Province, Turkey. Neurology 2003;61:1804–1806, doi: http://dx.doi.org/10.1212/01.WNL.0000099075.19951.8C.
6. Benito-Leon J, Bermejo-Pareja F, Morales JM, Vega S, Molina JA. Prevalence of essential tremor in three elderly populations of central Spain. Mov Disord 2003;18:389–394, doi: http://dx.doi.org/10.1002/mds.10376.
7. Lundervold DA, Poppen R. Biobehavioral rehabilitation for older adults with essential tremor. Gerontologist 1995;35:556–559, doi: http://dx.doi.org/10. 1093/geront/35.4.556.
8. Liu Y, Zhang XY, Tang YZ, et al. [Investigation on prevalence rate of essential tremor in population aged 55 years old and above in Kashkar, between 2008 and 2009]. Zhonghua yi xue za zhi 2011;91:1067–1069.
9. Barbosa MT, Caramelli P, Cunningham MC, Maia DP, Lima-Costa MF, Cardoso F. Prevalence and clinical classification of tremor in elderly—A community-based survey in Brazil. Mov Disord 2013;28:640–646, doi: http://dx.doi.org/10.1002/mds.25355.
10. Ozel L, Demir R, Ozdemir G, et al. Investigation of the prevalence of essential tremor in individuals aged 18–60 in Erzurum. Acta Neurologica Belgica 2013;113:127–131, doi: http://dx.doi.org/10.1007/s13760-012-0147-5.
11. Aharon-Peretz J, Badarny S, Ibrahim R, Gershoni-Baruch R, Hassoun G. Essential tremor prevalence is low in the Druze population in northern Israel. Tremor Other Hyperkinet Mov 2012;2:http://tremorjournal.org/article/view/81.
12. Okubadejo NU, Bankole IA, Ojo OO, Ojini FI, Danesi MA. Prevalence of essential tremor in urban Lagos, Nigeria: A door-to-door community-based study. BMC Neurol 2012;12:110, doi: http://dx.doi.org/10.1186/1471-2377-12-110.
13. Louis ED, Hafeman D, Parvez F, et al. Prevalence of essential tremor in Araihazar, Bangladesh: A population-based study. Neuroepidemiology 2011;36:71–76, doi: http://dx.doi.org/10.1159/000323389.
14. Seijo-Martinez M, Del Rio MC, Alvarez JR, et al. Prevalence of essential tremor on Arosa Island, Spain: A community-based, door-to-door survey. Tremor Other Hyperkinet Mov 2013;3:http://tremorjournal.org/article/view/192.
15. United States Census Bureau. Current population survey. Annual social and economic supplement, 2012. Internet release data: December 2013. http://www.census.gov/population/age/data/2012comp.html
16. Hornabrook RW, Nagurney JT. Essential tremor in Papua, New Guinea. Brain 1976;99:659–672, doi: http://dx.doi.org/10.1093/brain/99.4.659.
17. Salemi G, Savettieri G, Rocca WA, et al. Prevalence of essential tremor:A door-to-door survey in Terrasini, Sicily. Sicilian Neuro-Epidemiologic Study Group. Neurology 1994;44:61–64, doi: http://dx.doi.org/10.1212/WNL.44.1.61.
18. Glik A, Masarwa M, Abuful A, et al. Essential tremor might be less frequent than Parkinson’s disease in North Israel Arab villages. Mov Disord 2009; 24:119–122, doi: http://dx.doi.org/10.1002/mds.22324.
19. Mancini ML, Stracci F, Tambasco N, Sarchielli P, Rossi A, Calabresi P. Prevalence of essential tremor in the territory of Lake Trasimeno, Italy: Results of a population-based study. Mov Disord 2007;22:540–545, doi: http://dx.doi.org/10.1002/mds.21349.
20. Sur H, Ilhan S, Erdogan H, Ozturk E, Tasdemir M, Boru UT. Prevalence of essential tremor: A door-to-door survey in Sile, Istanbul, Turkey. Parkinsonism Relat Disord 2009;15:101–104, doi: http://dx.doi.org/10.1016/j.parkreldis.2008.03.009.
21. Louis ED, Marder K, Cote L, et al. Differences in the prevalence of essential tremor among elderly African Americans, whites, and Hispanics in northern Manhattan, NY. Arch Neurol 1995;52:1201–1205, doi: http://dx.doi.org/10.1001/archneur.1995.00540360079019.
22. Louis ED, Thawani SP, Andrews HF. Prevalence of essential tremor in a multiethnic, community-based study in northern Manhattan, New York, N.Y. Neuroepidemiology 2009;32:208–214, doi: http://dx.doi.org/10.1159/000195691.
23. Bergareche A, De La Puente E, Lopez De Munain A, et al. Prevalence of essential tremor: A door-to-door survey in Bidasoa, Spain. Neuroepidemiology 2001;20:125–128, doi: http://dx.doi.org/10.1159/000054771.
24. Rautakorpi I, Takala J, Marttila RJ, Sievers K, Rinne UK. Essential tremor in a Finnish population. Acta Neurol Scand 1982;66:58–67, doi: http://dx.doi.org/10.1111/j.1600-0404.1982.tb03129.x.
25. Moghal S, Rajput AH, D9Arcy C, Rajput R. Prevalence of movement disorders in elderly community residents. Neuroepidemiology 1994;13:175–178, doi: http://dx.doi.org/10.1159/000110376.
26. Khatter AS, Kurth MC, Brewer MA, et al. Prevalence of tremor and Parkinson’s disease. Parkinsonism Relat Disord 1996;2:205–208, doi: http://dx.doi.org/10.1016/S1353-8020(96)00027-2.
27. Deuschl G, Bain P, Brin M. Consensus statement of the Movement Disorder Society on Tremor. Ad Hoc Scientific Committee. Mov Disord 1998; 13(Suppl 3):2–23.
28. Bain PG, Findley LJ, Thompson PD, et al. A study of hereditary essential tremor. Brain 1994;117(Pt 4):805–824, doi: http://dx.doi.org/10.1093/brain/117.4.805.
29. Dogu O, Louis ED, Sevim S, Kaleagasi H, Aral M. Clinical characteristics of essential tremor in Mersin, Turkey—A population-based door-to-door study. J Neurol 2005;252:570–574, doi: http://dx.doi.org/10.1007/s00415-005-0700-8.
30. Louis ED, Ford B, Wendt KJ, Cameron G. Clinical characteristics of essential tremor: Data from a community-based study. Mov Disord 1998;13:803–808, doi: http://dx.doi.org/10.1002/mds.870130508.

(PDF Version)

A Faded Cottage by Diann Shaddox

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‘A Faded Cottage’ fuses fact with fiction to depict a compelling love story, based around an artist suffering from Essential Tremor. The love story imparts a powerful message, while acting as a real-life vehicle for vital Essential Tremor awareness. While the protagonist in ‘A Faded Cottage’ may appear to have a unique story, his battle with Essential Tremor (causing rhythmic trembling of the hands, head, voice, legs, or trunk) is shared with over 10 million Americans and millions more worldwide. The book is a stark reminder of the prevalence of this often ignored disorder.

‘A Faded Cottage’ is a South Carolina love story about a man with Essential Tremor.
When a love letter written by a teenage boy becomes lost after a summer filled with passion, it brings about an incredible love story of two people being reunited, after thirty years.

When Essential Tremors take over a famous artist’s body, a simple feat of holding a paintbrush turns Quaid Witherspoon’s life upside down, becoming a bitter man. This is his journal of how he battles fate, not of his entire life, but of two weeks. Quaid had everything money could buy, except the two things he loved the most, his love of painting great masterpieces, and the only woman he had ever loved. The calming waters off the coast of South Carolina calls Quaid back to Hathaway Cove, to a small, faded cottage, one with a leaning front porch, worn paint so similar to him, flawed. The same beach where he began painting as a young boy, the place he met his one true love, and the place he let her go.

Sandy, Quaid’s love from his past, learns he is wondering about her, just as she is wondering about him. Their love is alive, meeting for the first time in thirty years, letting the years fade away, but fate has another twist. Sandy keeps a secret, letting them have their two weeks.

What if you were able to relive your life and rediscover you teenage love… Would you?
www.diannshaddox.com  & www.diannshaddoxfoundation.org

Cerebral Cortex Advance Access published June 24, 2014

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It is well-established that during goal-directed motor tasks, patients with essential tremor have increased oscillations in the 0–3 and 3–8 Hz bands. It remains unclear if these increased oscillations relate to activity in specific brain regions. This study used task-based functional magnetic resonance imaging to compare the brain activity associated with oscillations in grip force output between patients with essential tremor, patients with Parkinson’s disease who had clinically evident tremor, and healthy controls. The findings demonstrate that patients with essential tremor have increased brain activity in the motor cortex and supplementary motor area compared with controls, and this activity correlated positively with 3–8 Hz force oscillations. Brain activity in cerebellar lobules I–V was reduced in essential tremor compared with controls and correlated negatively with 0–3 Hz force oscillations.

Widespread differences in brain activity were observed between essential tremor and Parkinson’s disease. Using functional connectivity analyses during the task evidenced reduced cerebellar-cortical functional connectivity in patients with essential tremor compared with controls and Parkinson’s disease. This study provides new evidencethat in essential tremor 3–8 Hz force oscillations relate to hyperactivity in motor cortex, 0–3 Hz force oscillations relate to the hypoactivity in the cerebellum, and cerebellar-cortical functional connectivity is impaired.

Read more: http://www.thehopenet.org/court_cercortex_2014.pdf

Cerebral Cortex Advance Access published June 24, 2014

by

It is well-established that during goal-directed motor tasks, patients with essential tremor have increased oscillations in the 0–3 and 3–8 Hz bands. It remains unclear if these increased oscillations relate to activity in specific brain regions. This study used task-based functional magnetic resonance imaging to compare the brain activity associated with oscillations in grip force output between patients with essential tremor, patients with Parkinson’s disease who had clinically evident tremor, and healthy controls. The findings demonstrate that patients with essential tremor have increased brain activity in the motor cortex and supplementary motor area compared with controls, and this activity correlated positively with 3–8 Hz force oscillations. Brain activity in cerebellar lobules I–V was reduced in essential tremor compared with controls and correlated negatively with 0–3 Hz force oscillations.

Widespread differences in brain activity were observed between essential tremor and Parkinson’s disease. Using functional connectivity analyses during the task evidenced reduced cerebellar-cortical functional connectivity in patients with essential tremor compared with controls and Parkinson’s disease. This study provides new evidencethat in essential tremor 3–8 Hz force oscillations relate to hyperactivity in motor cortex, 0–3 Hz force oscillations relate to the hypoactivity in the cerebellum, and cerebellar-cortical functional connectivity is impaired.

Read more: http://www.thehopenet.org/court_cercortex_2014.pdf

Analysis of Visual-Motor Task Electrophysiological Activity During Deep Brain Stimulation for Treatment-Resistant Movement Disorders Study

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INTRODUCTION
We invite you to take part in a research study at the National Institutes of Health (NIH) and Suburban Hospital.

First, we want you to know that:

Taking part in NIH research is entirely voluntary.

You may choose not to take part, or you may withdraw from the study at any time. In either case, you will not lose any benefits to which you are otherwise entitled. However, to receive care at the NIH, you must be taking part in a study or be under evaluation for study participation.

You may receive no benefit from taking part. The research may give us knowledge that may help people in the future.

Second, some people have personal, religious or ethical beliefs that may limit the kinds of medical or research treatments they would want to receive (such as blood transfusions). If you have such beliefs, please discuss them with your NIH doctors or research team before you agree to the study.

Now we will describe this research study. Before you decide to take part, please take as much time as you need to ask any questions and discuss this study with anyone at NIH, or with family, friends or your personal physician or other health professional.

Purpose of This Study
The aim of this study is to better understand activity in particular areas of the brain that might be involved in Parkinson’s disease and Essential tremor, and how the activity may change after deep brain stimulation (DBS) surgery in these disorders.

Facts That Led us to This Study
Previous research has shown what areas of the brain might be involved in symptoms of Parkinson’s disease and Essential tremor. This research has led to the use of DBS to treat these conditions. Some of the brain areas that might not function properly in people with these disorders are also involved in making decisions. To learn more about these brain areas, we will use a test that involves decision making to study brain cell activity before, during and after DBS surgery for these conditions. We will look at brain activity before and after surgery using a technique called magnetoencephalography (MEG). We will look at brain activity during surgery by recording directly from the surface of the brain.

Study Population
6 people with Parkinson’s disease, and 6 people with Essential tremor will participate in this study.

Inclusion Criteria
To be eligible to participate in this study, you must:

  1. Be at least 18 years old and have been diagnosed with Parkinson’s disease or Essential tremor.
  2. Be scheduled to have DBS for your condition.

Exclusion Criteria
You may not be eligible for this study if you:

  1. Have untreated depression or another psychiatric disorder
  2. Use illegal drugs
  3. Are pregnant
  4. Are uncomfortable in small, closed spaces (are claustrophobic)
  5. Have any metal in your body that would make having an MRI scan unsafe or would interfere with the MRI scan such as: cardiac pacemaker; implanted cardiac defibrillator; aneurysm clip; neuro or bone stimulator; insulin or infusion pump; implanted drug infusion device; cochlear, otologic, or ear implant; prostate radiation seeds; IUD (intrauterine device); transdermal nitroglycerin patch; any type of prosthesis (eye, penile); heart valve prosthesis; shunt (spinal/intraventricular); wire sutures or surgical staples; bone/joint pin, screw, nail, plate; body tattoos or makeup (eyeliner/lip); body piercing that cannot be removed; breast tissue expander; or other metal

Procedures
Study overview:
This study requires 5 study sessions over several months. The first 2 sessions will be in the NIH outpatient clinic before your surgery. The 3rd session will be during your surgery at Suburban Hospital. The 4th and 5th sessions will be at NIH, 3 and 6 months after your surgery.

Study session #1:
During the first study visit, we will ask you about your medical history and perform a neurological examination. Women who are able to get pregnant will have a pregnancy test. You will not be able to participate if you are pregnant. You will also have an MRI scan of your brain. This visit will last about 3 hours.

MRI uses a strong magnetic field and radio waves to take pictures of your brain. The MRI scanner is a metal cylinder surrounded by a strong magnetic field. During the MRI scan, you will lie on a table that can slide in and out of the cylinder. You will be in the scanner about 20 minutes. While in the scanner you will hear loud knocking noises and you will be fitted with earplugs or earmuffs to muffle the sound. You can communicate with the MRI staff at all times during your scan, and you may ask to be moved out of the machine at anytime.

Study sessions #2, #4 and #5:
Study session #2 will be no more than 6 weeks before your surgery. Study session #4 will be 3 months after your surgery, and session #5 will be 6 months after surgery. During each of these visits we will conduct neuropsychological testing that will include standard assessment scales. We will record the activity of your brain using magnetoencephalography (MEG) while you are performing a decision-making task. Each of these sessions will last about 3 hours.

Neuropsychological testing may include tests of your memory, attention, concentration and thinking. We may ask you to be interviewed, complete questionnaires, take pen-and-paper or computerized tests and perform simple actions.

For the decision-making task, you will sit in a chair at a computer. Two symbols will be shown on the computer screen. You will have to choose one of the symbols as quickly as possible by clicking on a mouse button. Choosing one of the symbols will earn you money; the other will cause you to lose money. You will be told if you won or lost money only after you have made your choice. The total amount of money you won will be displayed at the top of the screen. You should try to win as much money as possible. This is a computer game and you will not actually win any payment. The decision making task will take about 30 minutes.

During the task, we will record the electrical activity of two muscles of your right arm using EMG. Small metal disks or sticky pad electrodes will be taped to the skin over the muscles that we choose. The electrodes will be removed after you have completed the task.

MEG is a procedure to record very small magnetic field changes produced by the activity of your brain. During MEG recording, you will be seated comfortably in the MEG recording room and a cone containing magnetic field detectors will be lowered onto your head. The recording will be made while you are seated in front of a computer screen, performing the visual motor reward task.

Study session # 3 (during surgery):
As part of your DBS surgery, the surgeon will need to make holes in your skull to implant the DBS electrodes deep in the brain. For research purposes, during the surgery after the holes have been placed, the surgeon will put a small strip of electrodes on the surface of your brain. The strip of electrodes may be placed on the brain surface on both sides of your brain. The electrodes will be used to record the activity of your brain cells while you are performing the decision making task and while you are resting. The strip of electrodes will be removed after you complete the task. The research part of the surgery will then be over. Placing the strip of electrodes and recording brain activity during the task will add about 30 minutes to your operation. Then the surgeon will complete your DBS surgery.

If you are a patient with Parkinson’s disease or Essential tremor, some of your medications, including Sinemet (carbidopa/levodopa), Stalevo (carbidopa/levodopa/entacapone), Requip (ropinirole) and Mirapex (pramipexole) may interfere with the results of the imaging tests or studies during surgery. You will be asked to stop your medications the night before visits 2, 3, 4 and 5. During deep brain stimulation surgery, the medications may interfere with our evaluation of your symptoms. Stopping your medications before visits 2,4, and 5 will allow us to replicate your clinical condition during surgery in visit 3. The brief discontinuation of medication is usually done overnight to minimize discomfort. You will be off of your medications for about 12 hours. You will be able to take the medications again after the MEG or surgery procedure is completed.

Risks, Inconveniences and Discomforts
Research recording during surgery: Having the strip of electrodes placed on your brain and the extra 30 minutes of surgical time for the research tests may slightly increase the risk of infection beyond the infection risk of 3-4% for DBS surgery itself. Moreover, the risk of bruise to the brain surface or subdural hematoma (bleeding between the brain and the skull) is noted with placement of a subdural electrode strip. If a subdural hematoma is observed following surgery, this will be monitored closely with repeat head scans. If a subdural hematoma is associated with significant pressure on the brain or shift of the brain from its normal position, a surgery (which includes removal and replacement of a portion of your skull) will be performed to remove the blood.

Withholding medications in patients with movement disorders:
Withholding your medications for Parkinson’s disease or Essential tremor can make your symptoms such as tremor or freezing worse. If being off your medications for 12 hours is known to significantly worsen your symptoms, you can be admitted to Suburban Hospital or NIH Clinical Center the night before the visits for monitoring. Of note, you should not stop taking your medications without first speaking with your prescribing physician. If you are hospitalized at Suburban hospital the night before surgery, your insurance provider will be billed; however, you may be responsible for co-payment or deductible charges.

History, neurological examination, MEG, and decision-making task: There are no medical risks associated with these procedures.

Neuropsychological tests are not harmful, but may be frustrating or stressful. We only ask that you try your best. No one performs perfectly on these tasks. You may refuse to answer any question or to stop a test at any time and for any reason.

MRI: People are at risk for injury from the MRI magnet if they have pacemakers or other implanted electrical devices, brain stimulators, some types of dental implants, aneurysm clips (metal clips on the wall of a large artery), metallic prostheses (including metal pins and rods, heart valves, and cochlear implants), permanent eyeliner, implanted delivery pump, or shrapnel fragments. Welders and metal workers are also at risk for injury because of possible small metal fragments in the eye of which they may be unaware. You will be screened for these conditions before having any scan, and if you have any, you will not receive an MRI scan. If you have a question about any metal objects being present in your body, you should inform the staff. In addition, all magnetic objects (for example, watches, coins, jewelry, and credit cards) must be removed before entering the MRI scan room.

It is not known if MRI is completely safe for a developing fetus. Therefore, all women of childbearing potential will have a pregnancy test performed no more than 24 hours before each MRI scan. The scan will not be done if the pregnancy test is positive.

People with fear of confined spaces may become anxious during an MRI. Those with back problems may have back pain or discomfort from lying in the scanner. The noise from the scanner is loud enough to damage hearing, especially in people who already have hearing loss. Everyone having a research MRI scan will be fitted with hearing protection. Please notify the investigators if you have hearing or ear problems. You will be asked to complete an MRI screening form for each MRI scan you have. There are no known long-term risks of MRI scans.

Potential Benefits
There is no benefit to you from participating in this research study. However, we hope to learn more about brain activity in Parkinson’s disease and Essential tremor, which might help others in the future.

Right of Withdrawal and Conditions for Early Withdrawal
You may withdraw from the study at any time and for any reason without loss of benefits or privileges to which you are otherwise entitled. We can remove you from the study at any time if we think that continuation is not in your best medical interest or if you are unable to comply with the requirements of the study.

Results From this Study
The information we obtain from this study will not provide information on your health. You will not receive any individual results from the testing sessions or brain recording. Your results will be compared to decision-making task performance and MEG recordings from healthy volunteers participating in a similar NIH protocol.

Alternatives to Participation
The alternative to participating in this study is to have the DBS surgery without any of the research procedures.

Compensation and Travel costs
You will not be compensated for your participation and transportation will not be provided. Moreover, the costs of the above research procedures, including the strip electrodes, will not be passed on to you or your insurance provider.

Posting of Research Results on www.ClinicalTrials.gov
A description of this clinical trial will be available on http://www.Clinicaltrials.gov, as required by U.S. Law. This web site will not include information that can identify you. At most the Web site will include a summary of the results. You can search this website at any time.

OTHER PERTINENT INFORMATION

  1. Confidentiality. When results of an NIH research study are reported in medical journals or at scientific meetings, the people who take part are not named and identified. In most cases, the NIH will not release any information about your research involvement without your written permission. However, if you sign a release of information form, for example, for an insurance company, the NIH will give the insurance company information from your medical record. This information might affect (either favorably or unfavorably) the willingness of the insurance company to sell you insurance.
    The Federal Privacy Act protects the confidentiality of your NIH medical records. However, you should know that the Act allows release of some information from your medical record without your permission, for example, if it is required by the Food and Drug Administration (FDA), members of Congress, law enforcement officials, or authorized hospital accreditation organizations.
  2. Policy Regarding Research-Related Injuries.. In general, no long-term medical care or financial compensation for research-related injuries will be provided by the National Institutes of Health, the Clinical Center or the Federal Government regardless of where the research is conducted. However, you have the right to pursue legal remedy if you believe that your injury justifies such action.
    Medical Faculty Associates, Inc., Suburban Hospital, and The George Washington University do not have programs to provide payment for long-term injuries or medical care or financial compensation for research-related injuries regardless of where the research is conducted.
    Payments. The amount of payment to research volunteers is guided by the National Institutes of Health policies. In general, patients are not paid for taking part in research studies at the National Institutes of Health. Reimbursement of travel and subsistence will be offered consistent with NIH guidelines.
  3. Problems or Questions. If you have any problems or questions about this study, or about your rights as a research participant, or about any research-related injury, contact the Principal Investigator, Dr. Mark Hallett; building 10, room 7D37, telephone: 301-496-5528. Other researchers you may call are: Dr. Donald Shields, of Medical Faculty Associates, Inc. at 202-741-2750.
  4. You may also call the Clinical Center Patient Representative at 301-496-2626 or the Suburban Hospital Ombudsman, Dr. Theodore Abraham at 401-502-7974. The George Washington University Office of Human Research is available at (202) 994-2715.
  5. Consent Document. Please keep a copy of this document in case you want to read it again.

Please see CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY (pdf) for full documentation and consent document.

Analysis of Visual-Motor Task Electrophysiological Activity During Deep Brain Stimulation for Treatment-Resistant Movement Disorders Study

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INTRODUCTION
We invite you to take part in a research study at the National Institutes of Health (NIH) and Suburban Hospital.

First, we want you to know that:

Taking part in NIH research is entirely voluntary.

You may choose not to take part, or you may withdraw from the study at any time. In either case, you will not lose any benefits to which you are otherwise entitled. However, to receive care at the NIH, you must be taking part in a study or be under evaluation for study participation.

You may receive no benefit from taking part. The research may give us knowledge that may help people in the future.

Second, some people have personal, religious or ethical beliefs that may limit the kinds of medical or research treatments they would want to receive (such as blood transfusions). If you have such beliefs, please discuss them with your NIH doctors or research team before you agree to the study.

Now we will describe this research study. Before you decide to take part, please take as much time as you need to ask any questions and discuss this study with anyone at NIH, or with family, friends or your personal physician or other health professional.

Purpose of This Study
The aim of this study is to better understand activity in particular areas of the brain that might be involved in Parkinson’s disease and Essential tremor, and how the activity may change after deep brain stimulation (DBS) surgery in these disorders.

Facts That Led us to This Study
Previous research has shown what areas of the brain might be involved in symptoms of Parkinson’s disease and Essential tremor. This research has led to the use of DBS to treat these conditions. Some of the brain areas that might not function properly in people with these disorders are also involved in making decisions. To learn more about these brain areas, we will use a test that involves decision making to study brain cell activity before, during and after DBS surgery for these conditions. We will look at brain activity before and after surgery using a technique called magnetoencephalography (MEG). We will look at brain activity during surgery by recording directly from the surface of the brain.

Study Population
6 people with Parkinson’s disease, and 6 people with Essential tremor will participate in this study.

Inclusion Criteria
To be eligible to participate in this study, you must:

  1. Be at least 18 years old and have been diagnosed with Parkinson’s disease or Essential tremor.
  2. Be scheduled to have DBS for your condition.

Exclusion Criteria
You may not be eligible for this study if you:

  1. Have untreated depression or another psychiatric disorder
  2. Use illegal drugs
  3. Are pregnant
  4. Are uncomfortable in small, closed spaces (are claustrophobic)
  5. Have any metal in your body that would make having an MRI scan unsafe or would interfere with the MRI scan such as: cardiac pacemaker; implanted cardiac defibrillator; aneurysm clip; neuro or bone stimulator; insulin or infusion pump; implanted drug infusion device; cochlear, otologic, or ear implant; prostate radiation seeds; IUD (intrauterine device); transdermal nitroglycerin patch; any type of prosthesis (eye, penile); heart valve prosthesis; shunt (spinal/intraventricular); wire sutures or surgical staples; bone/joint pin, screw, nail, plate; body tattoos or makeup (eyeliner/lip); body piercing that cannot be removed; breast tissue expander; or other metal

Procedures
Study overview:
This study requires 5 study sessions over several months. The first 2 sessions will be in the NIH outpatient clinic before your surgery. The 3rd session will be during your surgery at Suburban Hospital. The 4th and 5th sessions will be at NIH, 3 and 6 months after your surgery.

Study session #1:
During the first study visit, we will ask you about your medical history and perform a neurological examination. Women who are able to get pregnant will have a pregnancy test. You will not be able to participate if you are pregnant. You will also have an MRI scan of your brain. This visit will last about 3 hours.

MRI uses a strong magnetic field and radio waves to take pictures of your brain. The MRI scanner is a metal cylinder surrounded by a strong magnetic field. During the MRI scan, you will lie on a table that can slide in and out of the cylinder. You will be in the scanner about 20 minutes. While in the scanner you will hear loud knocking noises and you will be fitted with earplugs or earmuffs to muffle the sound. You can communicate with the MRI staff at all times during your scan, and you may ask to be moved out of the machine at anytime.

Study sessions #2, #4 and #5:
Study session #2 will be no more than 6 weeks before your surgery. Study session #4 will be 3 months after your surgery, and session #5 will be 6 months after surgery. During each of these visits we will conduct neuropsychological testing that will include standard assessment scales. We will record the activity of your brain using magnetoencephalography (MEG) while you are performing a decision-making task. Each of these sessions will last about 3 hours.

Neuropsychological testing may include tests of your memory, attention, concentration and thinking. We may ask you to be interviewed, complete questionnaires, take pen-and-paper or computerized tests and perform simple actions.

For the decision-making task, you will sit in a chair at a computer. Two symbols will be shown on the computer screen. You will have to choose one of the symbols as quickly as possible by clicking on a mouse button. Choosing one of the symbols will earn you money; the other will cause you to lose money. You will be told if you won or lost money only after you have made your choice. The total amount of money you won will be displayed at the top of the screen. You should try to win as much money as possible. This is a computer game and you will not actually win any payment. The decision making task will take about 30 minutes.

During the task, we will record the electrical activity of two muscles of your right arm using EMG. Small metal disks or sticky pad electrodes will be taped to the skin over the muscles that we choose. The electrodes will be removed after you have completed the task.

MEG is a procedure to record very small magnetic field changes produced by the activity of your brain. During MEG recording, you will be seated comfortably in the MEG recording room and a cone containing magnetic field detectors will be lowered onto your head. The recording will be made while you are seated in front of a computer screen, performing the visual motor reward task.

Study session # 3 (during surgery):
As part of your DBS surgery, the surgeon will need to make holes in your skull to implant the DBS electrodes deep in the brain. For research purposes, during the surgery after the holes have been placed, the surgeon will put a small strip of electrodes on the surface of your brain. The strip of electrodes may be placed on the brain surface on both sides of your brain. The electrodes will be used to record the activity of your brain cells while you are performing the decision making task and while you are resting. The strip of electrodes will be removed after you complete the task. The research part of the surgery will then be over. Placing the strip of electrodes and recording brain activity during the task will add about 30 minutes to your operation. Then the surgeon will complete your DBS surgery.

If you are a patient with Parkinson’s disease or Essential tremor, some of your medications, including Sinemet (carbidopa/levodopa), Stalevo (carbidopa/levodopa/entacapone), Requip (ropinirole) and Mirapex (pramipexole) may interfere with the results of the imaging tests or studies during surgery. You will be asked to stop your medications the night before visits 2, 3, 4 and 5. During deep brain stimulation surgery, the medications may interfere with our evaluation of your symptoms. Stopping your medications before visits 2,4, and 5 will allow us to replicate your clinical condition during surgery in visit 3. The brief discontinuation of medication is usually done overnight to minimize discomfort. You will be off of your medications for about 12 hours. You will be able to take the medications again after the MEG or surgery procedure is completed.

Risks, Inconveniences and Discomforts
Research recording during surgery: Having the strip of electrodes placed on your brain and the extra 30 minutes of surgical time for the research tests may slightly increase the risk of infection beyond the infection risk of 3-4% for DBS surgery itself. Moreover, the risk of bruise to the brain surface or subdural hematoma (bleeding between the brain and the skull) is noted with placement of a subdural electrode strip. If a subdural hematoma is observed following surgery, this will be monitored closely with repeat head scans. If a subdural hematoma is associated with significant pressure on the brain or shift of the brain from its normal position, a surgery (which includes removal and replacement of a portion of your skull) will be performed to remove the blood.

Withholding medications in patients with movement disorders:
Withholding your medications for Parkinson’s disease or Essential tremor can make your symptoms such as tremor or freezing worse. If being off your medications for 12 hours is known to significantly worsen your symptoms, you can be admitted to Suburban Hospital or NIH Clinical Center the night before the visits for monitoring. Of note, you should not stop taking your medications without first speaking with your prescribing physician. If you are hospitalized at Suburban hospital the night before surgery, your insurance provider will be billed; however, you may be responsible for co-payment or deductible charges.

History, neurological examination, MEG, and decision-making task: There are no medical risks associated with these procedures.

Neuropsychological tests are not harmful, but may be frustrating or stressful. We only ask that you try your best. No one performs perfectly on these tasks. You may refuse to answer any question or to stop a test at any time and for any reason.

MRI: People are at risk for injury from the MRI magnet if they have pacemakers or other implanted electrical devices, brain stimulators, some types of dental implants, aneurysm clips (metal clips on the wall of a large artery), metallic prostheses (including metal pins and rods, heart valves, and cochlear implants), permanent eyeliner, implanted delivery pump, or shrapnel fragments. Welders and metal workers are also at risk for injury because of possible small metal fragments in the eye of which they may be unaware. You will be screened for these conditions before having any scan, and if you have any, you will not receive an MRI scan. If you have a question about any metal objects being present in your body, you should inform the staff. In addition, all magnetic objects (for example, watches, coins, jewelry, and credit cards) must be removed before entering the MRI scan room.

It is not known if MRI is completely safe for a developing fetus. Therefore, all women of childbearing potential will have a pregnancy test performed no more than 24 hours before each MRI scan. The scan will not be done if the pregnancy test is positive.

People with fear of confined spaces may become anxious during an MRI. Those with back problems may have back pain or discomfort from lying in the scanner. The noise from the scanner is loud enough to damage hearing, especially in people who already have hearing loss. Everyone having a research MRI scan will be fitted with hearing protection. Please notify the investigators if you have hearing or ear problems. You will be asked to complete an MRI screening form for each MRI scan you have. There are no known long-term risks of MRI scans.

Potential Benefits
There is no benefit to you from participating in this research study. However, we hope to learn more about brain activity in Parkinson’s disease and Essential tremor, which might help others in the future.

Right of Withdrawal and Conditions for Early Withdrawal
You may withdraw from the study at any time and for any reason without loss of benefits or privileges to which you are otherwise entitled. We can remove you from the study at any time if we think that continuation is not in your best medical interest or if you are unable to comply with the requirements of the study.

Results From this Study
The information we obtain from this study will not provide information on your health. You will not receive any individual results from the testing sessions or brain recording. Your results will be compared to decision-making task performance and MEG recordings from healthy volunteers participating in a similar NIH protocol.

Alternatives to Participation
The alternative to participating in this study is to have the DBS surgery without any of the research procedures.

Compensation and Travel costs
You will not be compensated for your participation and transportation will not be provided. Moreover, the costs of the above research procedures, including the strip electrodes, will not be passed on to you or your insurance provider.

Posting of Research Results on www.ClinicalTrials.gov
A description of this clinical trial will be available on http://www.Clinicaltrials.gov, as required by U.S. Law. This web site will not include information that can identify you. At most the Web site will include a summary of the results. You can search this website at any time.

OTHER PERTINENT INFORMATION

  1. Confidentiality. When results of an NIH research study are reported in medical journals or at scientific meetings, the people who take part are not named and identified. In most cases, the NIH will not release any information about your research involvement without your written permission. However, if you sign a release of information form, for example, for an insurance company, the NIH will give the insurance company information from your medical record. This information might affect (either favorably or unfavorably) the willingness of the insurance company to sell you insurance.
    The Federal Privacy Act protects the confidentiality of your NIH medical records. However, you should know that the Act allows release of some information from your medical record without your permission, for example, if it is required by the Food and Drug Administration (FDA), members of Congress, law enforcement officials, or authorized hospital accreditation organizations.
  2. Policy Regarding Research-Related Injuries.. In general, no long-term medical care or financial compensation for research-related injuries will be provided by the National Institutes of Health, the Clinical Center or the Federal Government regardless of where the research is conducted. However, you have the right to pursue legal remedy if you believe that your injury justifies such action.
    Medical Faculty Associates, Inc., Suburban Hospital, and The George Washington University do not have programs to provide payment for long-term injuries or medical care or financial compensation for research-related injuries regardless of where the research is conducted.
    Payments. The amount of payment to research volunteers is guided by the National Institutes of Health policies. In general, patients are not paid for taking part in research studies at the National Institutes of Health. Reimbursement of travel and subsistence will be offered consistent with NIH guidelines.
  3. Problems or Questions. If you have any problems or questions about this study, or about your rights as a research participant, or about any research-related injury, contact the Principal Investigator, Dr. Mark Hallett; building 10, room 7D37, telephone: 301-496-5528. Other researchers you may call are: Dr. Donald Shields, of Medical Faculty Associates, Inc. at 202-741-2750.
  4. You may also call the Clinical Center Patient Representative at 301-496-2626 or the Suburban Hospital Ombudsman, Dr. Theodore Abraham at 401-502-7974. The George Washington University Office of Human Research is available at (202) 994-2715.
  5. Consent Document. Please keep a copy of this document in case you want to read it again.

Please see CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY (pdf) for full documentation and consent document.

Personal Stories – Deb, age 73

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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:
Charley
Sheila
Dale
Doris
Deb

We need your help!

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We need your help! We want you to help us by contacting the nearest district office of your Congressman or Senator and then meet with them to personally discuss how ET affects you or someone you know.

We have found that the personal touch really helps in these conversations versus the rote “facts” about ET.

Please get in touch with us so we can discuss this further and provide guidance to you on how best to contact the offices.

Please share with your support groups, etc. Thank you for your participation.