Accepted on 05 Mar 2022
Submitted on 06 Jan 2022
Essential tremor (ET) is defined as an isolated tremor syndrome of bilateral upper limb action, sometimes accompanied by tremor in other locations, that occurs in the absence of other neurological signs such as ataxia and parkinsonism [1]. Some affected patients may experience additional neurologic symptoms, including memory impairment and difficulties with gait or posturing [2, 3]. For many patients, ET leads to significant impairment in the ability to perform activities of daily living and loss of independence [4, 5]. In addition to physical symptoms, patients with ET often suffer from psychiatric symptoms such as worrying, fatigue, and embarrassment [6, 7]. These patients have also demonstrated higher rates of psychiatric comorbidities, such as depression, anxiety, and sleep disturbances, compared with healthy controls [8].
ET is one of the most common movement disorders worldwide and has been reported to occur in approximately 1% of the global population [9, 10, 11]. Among people aged 65 years and older, this prevalence increases to nearly 6% [9]. In the United States, the prevalence of ET among adults was estimated to be 2.6% in 2018 (6.4 million people), which included an estimated rate of 8.2% in people aged 85 years and older [12]. Although ET has often been characterized as a disease that predominantly affects the elderly, some studies have shown a bimodal distribution in the age of onset that peaks during the second and sixth decades of life [13, 14]. ET is familial in approximately half of patients (though estimates vary widely based on the definition used; for example, the presence of at least one first- or second-degree relative with any tremor provides a more liberal estimate, whereas a more conservative estimate is obtained when a specific diagnosis of ET is required among the same relatives) [2, 3, 15], and some studies have suggested that patients with childhood-onset ET are more likely to have familial ET [15, 16, 17].
The size of the pediatric ET population is not well understood. A literature review published in 2009 was unable to identify published epidemiological survey data from any country that focused on ET exclusively in children, and found only 5 studies that reported prevalence data in age-based subgroups that included children [18]. Based on this identified paucity of data prior to 2010, the objective of this review was to identify, evaluate, and synthesize evidence describing the incidence and prevalence of pediatric ET, age of ET onset, and age of ET diagnosis, based on published data in the United States between 2010 and 2020.
A systematic literature search for studies that examined the epidemiology of pediatric ET was conducted with methods consistent with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines [19]. Databases searched included Embase (via Embase.com), MEDLINE (via PubMed), and the Cochrane Database of Systematic Reviews (via the Cochrane Library); search terms included those related to ET, epidemiology, and pediatric populations (including infants, children, and adolescents). Searches were conducted in February 2020 and were restricted to the last 10 years for database searches and the previous 5 years for conference proceedings (see Appendix Tables S1-3 for detailed search strategies).
Studies were included if they reported primary data on pediatric prevalence or incidence of ET or age of onset/diagnosis of ET. In addition, studies were required to include a US-based sample, be observational in design, and be published in English (see Appendix Table S4 for detailed inclusion and exclusion criteria). Search results were screened by 2 reviewers initially by titles and abstracts, followed by a review of the full text by a single reviewer with a second reviewer screening a random sample of 10% of studies. Any disputes were resolved through discussion between reviewers or consultation with a third reviewer.
Data from included studies were extracted by a single reviewer with accuracy confirmed by a second reviewer. The extracted data described the study methodology, patient demographic and clinical characteristics, and ET prevalence, incidence, and age of onset/diagnosis. The quality of included studies was assessed by a single reviewer using a modified version of the Newcastle-Ottawa scale for observational studies that focused exclusively on the selection rating (maximum score of 5) and outcome/exposure rating (maximum score of 3) [20, 21]; comparability ratings were not assessed based on lack of comparative groups in most included studies.
Age of ET onset was summarized using a pooled data analysis, which was stratified for key sample characteristics such as the location of the sample (clinical or community) and the classification of ET (familial or sporadic). Initially, each participant was weighted equally (referred to below as the weighted mean age of onset), and an additional analysis was conducted in which familial and sporadic distributions of age of onset were evaluated and combined in equal weights.
A total of 562 unique articles were identified for screening; of these, 159 were selected for screening by full text. Overall, 8 articles representing 10 independent samples met the inclusion criteria (Figure 1); these included 1 pediatric-only sample and 9 samples from broader populations (Table 1) [15, 22, 23, 24, 25, 26, 27, 28]. Four samples were specific to familial ET [22, 23, 25], and another study reported data for familial ET as a subgroup [15]. Nearly all samples were defined as “clinical” samples because patients were diagnosed, i.e., “definite clinical” samples (or presumed to be diagnosed based on limited information provided, i.e., “probable clinical” samples), in a clinical setting, whereas one study included a sample that recruited patients from a community setting [23].
PRISMA diagram of study selection.
PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses.
Table 1
Study characteristics and age of ET onset for included samples.
| AUTHOR, YEAR | SAMPLE POPULATION | DESIGN | DIAGNOSTIC CRITERIA | PATIENT CHARACTERISTICS | AGE OF ONSET |
|---|---|---|---|---|---|
| SAMPLES INCLUDING ADULTS | |||||
| Hedera 2013 [22] | Vanderbilt/University of Tennessee (probable clinical); familial ET only; N = 104 | Cross-sectional | ET: presence of bilateral postural and kinetic tremors Familial: ≥2 meioses from a proband |
Mean age: 58 ± 7.5 years Mean WHIGET score: 14.8 ± 4.6 Female: 61.5% Familial: 100% |
Mean age: 32.1 ± 11.4 years Range: 8–50 |
| Louis 2015a [15]a | CUMC 2000–2009 (clinical); N = 376 |
Cross-sectional | ET: WHIGET criteria Familial: self-report (≥1 relatives with ET or tremor) |
Mean age: 67.5 ± 15.1 years Mean WHIGET score: 18.8 ± 7.2 Female: 52.1% Familial ET: 62% |
Mean age: 44.7 ± 22.5 years |
| Louis 2015b [23]b | ETCBR 2003–2014 (clinical); N = 177 |
Prospective cohort | ET: WHIGET criteria Familial: self-report of first- or second-degree relatives |
Mean age: 83.7 ± 5.8 years Mean WHIGET score: 24.2 ± 6.7 Female: 61.0% Familial: 27.1% |
Mean age: 42.4 ± 22.9 years |
| WHIGET 1995–2000 (community); familial ET only; N = 106 | Prospective cohort | ET: WHIGET criteria Familial: self-report of first- and second-degree relatives |
Mean age: 69.8 ± 18.4 years Mean WHIGET score: 16.4 ± 6.7 Female: 59.4% Familial: 100% |
Mean age: 56.7 ± 25.6 years | |
| FASET phase 1 2011–2014 (clinical); familial ET only; age of onset ≤50 years; N = 160 | Cross-sectional | ET: physician diagnosis, confirmed by WHIGET criteria Familial: ≥2 living relatives with physician diagnosis of ET |
Mean age: 60.0 ± 18.0 years Mean WHIGET score: 20.1 ± 5.2 Female: 51.3% Familial: 100% |
Mean age: 27.0 ± 17.8 years | |
| Louis 2018 [25] | FASET phase 2 2015–2018 (clinical); other criteria as in phase 1; N = 203 (98 probands; 105 affected relatives) | Cross-sectional | As in phase 1 |
Mean age, years Probands: 68.8 ± 11.2 Affected relatives: 60.9 ± 16.2 Mean WHIGET score Probands: 23.5 ± 6.5 Affected relatives: 17.7 ± 5.9 Female Probands: 59.2% Affected relatives: 60.0% Familial: 100% |
Mean age, years Probands: 28.4 ± 19.4 Affected relatives: 33.4 ± 19.9 |
| Louis 2016 [24] | COGNET 2014–2015 (clinical); age ≥55 years; N = 100 | Prospective cohort | ET: physician diagnosis, confirmed by WHIGET criteria Familial: self-report |
Mean age: 80.5 ± 8.1 years Mean WHIGET score: 21.5 ± 5.8 Female: 55.0% Familial: 50.0% |
Mean age: 39.1 ± 21.2 years Range: 1–83 |
| Ortega-Cubero 2015 [26] | Mayo Clinic (probable clinical); N = 257 cases; 697 controls | Case control | ET: diagnosis by movement disorder specialist Familial: NRc |
Mean age: 73.42 ± 11.73 years Mean WHIGET score: NR Female: 53.3% Familial: NR |
Mean age: 50.66 ± 19.98 years Range: 5–88 |
| Ross 2011 [27] | Emory University (probable clinical); N = 118 cases; 268 controls | Case control | ET: diagnosis by movement disorder specialist Familial: NR |
Mean age: 69.6 ± 12.3 years Mean WHIGET score: NR Female: 57% Familial: NR |
Mean age: 46.0 ± 21.7 years Range: 1-83 |
| PEDIATRIC-ONLY SAMPLES | |||||
| Ghosh 2017 [28] | Cleveland Clinic 1984–2011 (clinical); age <21 and ET onset <18 years; N = 211 | Retrospective cohort | ET: bilateral action tremor of the hands and forearms Familial: based on chart review |
Mean age: 14.09 ± 5.00 yearsd Mean WHIGET score: NRe Female: 38% Familial: 35% |
Mean age: 9.71 ± 5.62 years |
Data are presented as mean ± standard deviation unless otherwise indicated.
a Additional study design data acquired from Louis et al., 2013 [45].
b Additional study design data acquired from Louis et al., 2005 [46] (ETCBR); Louis et al., 1997 [29] (WHIGET); Louis et al., 2013 [47] (FASET).
c Only 1 family member per patient included.
d Mean age at presentation.
e 55% reported functional impairment; 29.4% required medication.
COGNET, Clinical Pathological Study of Cognitive Impairment in Essential Tremor; CUMC, Columbia University Medical Center; ET, essential tremor; ETCBR, Essential Tremor Centralized Brain Repository; FASET, Family Study of Essential Tremor; NR, not reported; WHIGET, Washington Heights-Inwood Genetic Study of Essential Tremor Rating Scale.
No studies reported information on pediatric prevalence or incidence of ET, or age of diagnosis of ET.
Of the 9 broader population (non-pediatric) ET samples, mean ages of patients at the time of assessment ranged from 58 to 84 years, and female patients comprised between 51% and 62% of the sample groups (Table 1). The proportion of patients with familial ET among studies that were not restricted to familial-only (4 samples) ranged from 27% to 62%.
Tremor severity was rated using the Washington Heights-Inwood Genetic Study of ET Tremor Rating Scale (WHIGET) total score in 7 samples. This scale is based on a 23-item examination in which patients are assessed in various postures and when undertaking different movements, with a tremor rating between 0 (no tremor) and 3 (large amplitude tremor) assigned to each item [29]. Mean WHIGET total scores ranged from 14.8 to 24.2 across the identified samples (Table 1).
Mean age of ET onset among samples that included adults ranged from 27.0 years to 56.7 years, although this was impacted by age-based inclusion criteria in some samples (Table 1). In a pooled analysis of all samples that included adults (N = 1601), the weighted mean age of onset was 41.6 years [15, 22, 23, 24, 25, 26, 27]. Age of onset was impacted by whether patients were identified in the clinic or community. When limited to clinical samples (both definite and probable samples; N = 1495), weighted mean age of onset decreased to 40.5 years [15, 22, 24, 25, 26, 27]. When further restricted to definite clinical samples (N = 1016), this decreased further to 38.2 years [15, 24, 25]. In the single community sample identified by the review (N = 106), weighted mean age of onset was 56.7 years [23]. In patients with familial ET (N = 805), the weighted mean age of onset was 36.1 years [15, 22, 23, 25].
Additional information on the age of ET onset was available for one sample (N = 376) from the Columbia University Medical Center [15]. This study provided evidence supporting earlier studies showing that the age of onset distribution appears to be bimodal, with peaks in the second and sixth-to-seventh decades of life, and also demonstrated that the early peak may be predominantly driven by familial cases (Figure 2) [15]. In total, 13% of all ET cases (17.2% familial/6.3% sporadic) reported onset by age 14, and 21.8% of all ET cases (30.6% familial/7.6% sporadic) reported onset by age 18 [15]. When the sample was reweighted to a 50% familial distribution, 11.7% and 19.1% of patients were estimated to have ET onset by ages 14 and 18, respectively.
Age of onset distribution for patients with ET from the Columbia University Medical Center.
Adapted from Louis et al., 2015 [15].
ET, essential tremor.
In the single retrospective chart review study that was restricted to pediatric patients only (N = 211), mean age of onset was 9.7 years and mean age at presentation was 14.1 years [28]. Twenty-eight patients (13%) indicated that they were uncertain about timing of onset, whereas 29% reported onset within the first decade of life and 57% in the second decade [28]. Most patients (71%) did not require medication for ET, and no ET-related functional impairment was observed from the charts of 45% of all patients. None of the 211 pediatric patients had disability so severe that it impaired daily activities [28].
Most studies were assessed to be somewhat representative of the average ET population in each community or clinic based on the Newcastle-Ottawa criteria, as the studies had relatively broad inclusion criteria and used known diagnostic criteria, such as WHIGET. Although some studies did restrict the age of included patients, this is less likely to impact the age of onset findings, particularly among older population samples. No studies reported a high-quality outcome assessment method such as record linkage or independent blind assessment; instead, many relied on self-report, while the lowest scoring studies lacked a clear description of the method of outcome assessment. Complete quality assessment scores can be found in the Appendix (Table S5).
No studies published from 2010 to 2020 were identified that reported incidence or prevalence data for pediatric ET, or information regarding the age of diagnosis, within the United States. A previously published US population-based analysis (using data collected between 1935 and 1979 in Rochester, Minnesota) reported an age- and sex-adjusted incidence rate of ET of 23.7 per 100,000 (1965–79) and a prevalence of 305.6 per 100,000 in 1979 [30]. Among patients aged 0-19 years in this sample, the incidence rate was much lower by comparison at 2.9 per 100,000 over the same period [30]. Studies from other countries have reported prevalence rates of pediatric ET that were very low or effectively zero in community samples [31, 32, 33].
Mean age of onset findings from our review ranged between mid-20s and mid-50s (pooled analysis of weighted mean age: 42 years) and support the presence of a bimodal pattern. However, it should be noted that mean age of onset is a limited measure for describing such bimodal patterns, and additional studies that report the distribution of onset ages would be useful to further elucidate the epidemiology of ET among the pediatric population. Similar bimodal patterns of ET onset age have been demonstrated in other countries [34, 35].
There were notable differences in mean ages of onset, with earlier onset observed in clinical samples compared with the single community sample, and earlier onset observed for patients with familial ET only compared with broader ET populations. These findings could suggest that patients who are identified at an earlier age may be those with the most pronounced/severe disease (making them more likely to be identified from clinical samples versus community samples), whereas community samples may be more likely to capture a broader proportion of older patients who have mild ET. It is possible that milder pediatric cases may be more frequently unidentified or misdiagnosed, while mild ET may be more commonly considered in the differential diagnosis in older patients [36].
Findings also suggest that genetic predisposition to ET could lead to an earlier onset of disease, which has been similarly demonstrated by analyses beyond the scope of this review [16]. Other studies have shown potential differences in the phenotype of ET between patients with early and late onset. In one study, those with onset by age 22 years were more likely to have lower limb tremor and less likely to have head and voice tremor compared with those who had ET onset at age 36 years or later [37]. In another study, patients with ET onset up to age 30 were more likely to have familial ET and lower limb tremor, as well as a significantly longer duration of tremor symptoms, compared with patients with ET onset occurring at ages 55 years and older [35].
Collectively, these findings may suggest that many children who present with symptoms of ET remain undiagnosed until later in life [36]. Some reasons for this could include the fact that children may hide their symptoms; parents, teachers, and other caregivers may not have an adequate understanding of childhood-onset ET to recognize the symptoms; and healthcare providers may misdiagnose ET as a different disorder. There are limited data in the literature that assess potential reasons for late diagnosis, indicating a possible need for increased awareness of pediatric ET that should be supported by additional research. The single pediatric population sample identified by this review showed that there was a 4–5-year gap between mean ages of disease onset and presentation, and also noted that children with ET demonstrated less functional impairment compared with what is typically observed in adults [28]. This is supported by an earlier study in which only 24 of 39 patients with pediatric ET from a clinical sample were receiving active treatment for tremors [36], suggesting that the disease was relatively mild for many of these patients.
Another considerable challenge arises because the difference between physiologic tremor and ET has been well characterized in adults but not children. In a study of 819 children in Spain, mild but consistent tremor was observed in at least one hand for 52% of participants and, although the authors concluded that this was likely due to physiologic tremor rather than ET, the proportion of patients with either underpinning cause remained unclear [38]. In addition, the currently established assessments for ET do not appear to have been validated in pediatric samples. Even among adults, several sets of criteria with different degrees of stringency have been proposed over time to identify patients with ET [1, 39, 40]. For instance, the International Parkinson and Movement Disorder Society’s consensus definition of ET requires at least 3 years of symptom duration, potentially limiting its applicability in children [1]. Furthermore, the accuracy of assessments for other movement disorders such as ataxia and dystonia improve considerably as children mature into early adolescence [41, 42, 43], and a study of hand tremor in 287 children found a distinct difference in tremor frequency pattern between those aged 2 to 9 years compared with those aged 10 to 16 years (higher frequency in the older cohort) [44]. If the same age-related impact on tremor and other symptoms were to hold true for children with ET it could necessitate further study and revisions to the diagnostic criteria to account for both normal child neurologic development and the likelihood that children will experience milder ET compared with adults when it first presents.
Limitations of this review include restrictions to both the period of the literature searched and the geographic location of included studies. In particular, only studies published between 2010 and 2020 were included, although this limit was based on the presence of a comprehensive literature review of global epidemiology studies published in 2009 [18]. In this review, only US-based samples were considered, therefore potentially relevant pediatric ET data from other countries were not identified. In addition, the large proportion of clinical samples in our review (9 out of 10 total samples, including 8 samples in adults) may result in under-representation of age of onset and other epidemiology data in a community-based population. Finally, the studies identified by this review are difficult to compare directly as they do not use consistent criteria for defining ET and in some cases do not account for neurologic comorbidities that could impact the presentation of ET-related symptoms.
Overall, this systematic review revealed a considerable data gap for US-based pediatric ET epidemiology in the literature. Although there are data suggesting that many patients retrospectively recall the onset of ET by age 18, there remains limited information to support the true epidemiology of pediatric ET, including the rate at which patients are diagnosed or treated. Future research to further elucidate the epidemiology of pediatric ET should first aim to clarify whether ET diagnostic criteria require adaptation when applied to children, followed ideally by long-term prospective cohort studies during which regular assessments are made to identify cases of ET throughout childhood development. Though it may be the case that many patients present with less severe disease in childhood, this could represent an opportunity for early identification and monitoring to ensure that adequate treatment and supportive care is available to patients when required.
The additional file for this article can be found as follows:
Supplementary AppendixTables S1 and S5. DOI: https://doi.org/10.5334/tohm.681.s1
The authors thank Marcia Reinhart of Tantalus Medical Communications (Victoria, Canada) for providing medical writing support, which was funded by Sage Therapeutics, Inc. and Biogen in accordance with Good Publication Practice (GPP3) guidelines. The authors thank Stephen Crawford, a former employee of Sage Therapeutics, Inc., for his contribution to development of the study protocol and search criteria.
This work was sponsored by Sage Therapeutics, Inc. and Biogen.
MG and AEL are employees of Sage Therapeutics, Inc., and own stock and stock options. KL reports having received consulting fees from Abbott and Sage and is the President of the International Essential Tremor Foundation.
Bhatia KP, Bain P, Bajaj N, Elble RJ, Hallett M, Louis ED, et al. Consensus Statement on the classification of tremors. from the task force on tremor of the International Parkinson and Movement Disorder Society. Mov Disord. 2018; 33(1): 75–87. DOI: https://doi.org/10.1002/mds.27121
Haubenberger D, Hallett M. Essential tremor. N Engl J Med. 2018; 378(19): 1802–10. DOI: https://doi.org/10.1056/NEJMcp1707928
Shanker V. Essential tremor: diagnosis and management. BMJ. 2019; 366: l4485. DOI: https://doi.org/10.1136/bmj.l4485
Louis ED, Barnes L, Albert SM, Cote L, Schneier FR, Pullman SL, et al. Correlates of functional disability in essential tremor. Mov Disord. 2001; 16(5): 914–20. DOI: https://doi.org/10.1002/mds.1184
Louis ED, Machado DG. Tremor-related quality of life: a comparison of essential tremor vs. Parkinson’s disease patients. Parkinsonism Relat Disord. 2015; 21(7): 729–35. DOI: https://doi.org/10.1016/j.parkreldis.2015.04.019
Louis ED, Rios E. Embarrassment in essential tremor: prevalence, clinical correlates and therapeutic implications. Parkinsonism Relat Disord. 2009; 15(7): 535–8. DOI: https://doi.org/10.1016/j.parkreldis.2008.10.006
Thenganatt MA, Louis ED. Personality profile in essential tremor: a case-control study. Parkinsonism Relat Disord. 2012; 18(9): 1042–4. DOI: https://doi.org/10.1016/j.parkreldis.2012.05.015
Chandran V, Pal PK, Reddy JY, Thennarasu K, Yadav R, Shivashankar N. Non-motor features in essential tremor. Acta Neurol Scand. 2012; 125(5): 332–7. DOI: https://doi.org/10.1111/j.1600-0404.2011.01573.x
Louis ED, McCreary M. How common is essential tremor? Update on the worldwide prevalence of essential tremor. Tremor Other Hyperkinet Mov. 2021; 11(1): 1–14. DOI: https://doi.org/10.5334/tohm.632
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(5): 534–41. DOI: https://doi.org/10.1002/mds.22838
Louis ED, Ottman R, Hauser WA. How common is the most common adult movement disorder? Estimates of the prevalence of essential tremor throughout the world. Mov Disord. 1998; 13(1): 5–10. DOI: https://doi.org/10.1002/mds.870130105
Crawford S, Lally C, Petrillo J, Paskavitz J, Louis E. How many adults in the US have essential tremor? Using data from epidemiological studies to derive age-specific estimates of prevalence [poster 192]. Mov Disord Clin Pract. 2020; 7(S1): S109.
Lou JS, Jankovic J. Essential tremor: clinical correlates in 350 patients. Neurology. 1991; 41(2 (Pt 1)): 234–8. DOI: https://doi.org/10.1212/WNL.41.2_Part_1.234
Bain PG, Findley LJ, Thompson PD, Gresty MA, Rothwell JC, Harding AE, et al. A study of hereditary essential tremor. Brain. 1994; 117(4): 805–24. DOI: https://doi.org/10.1093/brain/117.4.805
Louis ED, Clark LN, Ottman R. Familial versus sporadic essential tremor: what patterns can one decipher in age of onset? Neuroepidemiology. 2015; 44(3): 166–72. DOI: https://doi.org/10.1159/000381807
Louis ED, Ottman R. Study of possible factors associated with age of onset in essential tremor. Mov Disord. 2006; 21(11): 1980–6. DOI: https://doi.org/10.1002/mds.21102
Tallón-Barranco A, Vázquez A, Jiménez-Jiménez FJ, Ortí-Pareja M, Gasalla T, Cabrera-Valdivia F, et al. Clinical features of essential tremor seen in neurology practice: a study of 357 patients. Parkinsonism Relat Disord. 1997; 3(4): 187–90. DOI: https://doi.org/10.1016/S1353-8020(97)00031-X
Ferrara J, Jankovic J. Epidemiology and management of essential tremor in children. Paediatr Drugs. 2009; 11(5): 293–307. DOI: https://doi.org/10.2165/11316050-000000000-00000
Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JP, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ. 2009; 339: b2700. DOI: https://doi.org/10.1136/bmj.b2700
Wells GA, Shea B, O’Connell D, Peterson J, Welch V, Losos M, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses: Ottawa Hospital Research Institute; 2009 [updated 2021>]. Available from: http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp.
Modesti PA, Reboldi G, Cappuccio FP, Agyemang C, Remuzzi G, Rapi S, et al. Panethnic differences in blood pressure in Europe: a systematic review and meta-analysis. PLoS One. 2016; 11(1): e0147601. DOI: https://doi.org/10.1371/journal.pone.0147601
Hedera P, Davis TL, Phibbs FT, Charles PD, LeDoux MS. FUS in familial essential tremor – the search for common causes is still on. Parkinsonism Relat Disord. 2013; 19(9): 818–20. DOI: https://doi.org/10.1016/j.parkreldis.2013.04.009
Louis ED, Hernandez N, Michalec M. Prevalence and correlates of rest tremor in essential tremor: cross-sectional survey of 831 patients across four distinct cohorts. Eur J Neurol. 2015; 22(6): 927–32. DOI: https://doi.org/10.1111/ene.12683
Louis ED, Collins K, Rohl B, Morgan S, Robakis D, Huey ED, et al. Self-reported physical activity in essential tremor: relationship with tremor, balance, and cognitive function. J Neurol Sci. 2016; 366: 240–5. DOI: https://doi.org/10.1016/j.jns.2016.05.034
Louis ED, Hernandez N, Sebastian AA, Clark LN, Ottman R. Validity of probands’ reports and self-reports of essential tremor: data from a large family study in North America. J Neurol Sci. 2018; 393: 45–50. DOI: https://doi.org/10.1016/j.jns.2018.08.006
Ortega-Cubero S, Lorenzo-Betancor O, Lorenzo E, Agúndez JA, Jiménez-Jiménez FJ, Ross OA, et al. TREM2 R47H variant and risk of essential tremor: a cross-sectional international multicenter study. Parkinsonism Relat Disord. 2015; 21(3): 306–9. DOI: https://doi.org/10.1016/j.parkreldis.2014.12.010
Ross OA, Conneely KN, Wang T, Vilarino-Guell C, Soto-Ortolaza AI, Rajput A, et al. Genetic variants of α-synuclein are not associated with essential tremor. Mov Disord. 2011; 26(14): 2552–6. DOI: https://doi.org/10.1002/mds.23909
Ghosh D, Brar H, Lhamu U, Rothner AD, Erenberg G. A series of 211 children with probable essential tremor. Mov Disord Clin Pract. 2017; 4(2): 231–6. DOI: https://doi.org/10.1002/mdc3.12385
Louis ED, Ottman R, Ford B, Pullman S, Martinez M, Fahn S, et al. The Washington Heights-Inwood Genetic Study of Essential Tremor: methodologic issues in essential-tremor research. Neuroepidemiology. 1997; 16(3): 124–33. DOI: https://doi.org/10.1159/000109681
Rajput AH, Offord KP, Beard CM, Kurland LT. Essential tremor in Rochester, Minnesota: a 45-year study. J Neurol Neurosurg Psychiatry. 1984; 47(5): 466–70. DOI: https://doi.org/10.1136/jnnp.47.5.466
Salemi G, Savettieri G, Rocca WA, Meneghini F, Saporito V, Morgante L, et al. Prevalence of essential tremor: a door-to-door survey in Terrasini, Sicily. Neurology. 1994; 44(1): 61–4. DOI: https://doi.org/10.1212/WNL.44.1.61
Hornabrook RW, Nagurney JT. Essential tremor in Papua, New Guinea. Brain. 1976; 99(4): 659–72. DOI: https://doi.org/10.1093/brain/99.4.659
Das SK, Banerjee TK, Roy T, Raut DK, Chaudhuri A, Hazra A. Prevalence of essential tremor in the city of Kolkata, India: a house-to-house survey. Eur J Neurol. 2009; 16(7): 801–7. DOI: https://doi.org/10.1111/j.1468-1331.2009.02589.x
Chuang WL, Lu CS, Huang YZ, Chen RS. Clinical characteristics of essential tremor in Taiwan: an exploratory-comparative study. Eur J Neurol. 2012; 19(1): 135–41. DOI: https://doi.org/10.1111/j.1468-1331.2011.03459.x
Renaud M, Marcel C, Rudolf G, Schaeffer M, Lagha-Boukbiza O, Chanson JB, et al. A step toward essential tremor gene discovery: identification of extreme phenotype and screening of HTRA2 and ANO3. BMC Neurol. 2016; 16(1): 238. DOI: https://doi.org/10.1186/s12883-016-0748-3
Jankovic J, Madisetty J, Vuong KD. Essential tremor among children. Pediatrics. 2004; 114(5): 1203–5. DOI: https://doi.org/10.1542/peds.2004-0031
Prasad S, Bhalsing KS, Jhunjhunwala K, Lenka A, Binu VS, Pal PK. Phenotypic variability of essential tremor based on the age at onset. Can J Neurol Sci. 2019; 46(2): 192–8. DOI: https://doi.org/10.1017/cjn.2018.384
Louis ED, Cubo E, Trejo-Gabriel-Galán JM, Villaverde VA, Benito VD, Velasco SS, et al. Tremor in school-aged children: a cross-sectional study of tremor in 819 boys and girls in Burgos, Spain. Neuroepidemiology. 2011; 37(2): 90–5. DOI: https://doi.org/10.1159/000330352
Louis ED, Ford B, Lee H, Andrews H, Cameron G. Diagnostic criteria for essential tremor: a population perspective. Arch Neurol. 1998; 55(6): 823–8. DOI: https://doi.org/10.1001/archneur.55.6.823
Deuschl G, Bain P, Brin M. Consensus statement of the Movement Disorder Society on Tremor. Mov Disord. 1998; 13(Suppl 3): 2–23. DOI: https://doi.org/10.1002/mds.870131303
Brandsma R, Spits AH, Kuiper MJ, Lunsing RJ, Burger H, Kremer HP, et al. Ataxia rating scales are age-dependent in healthy children. Dev Med Child Neurol. 2014; 56(6): 556–63. DOI: https://doi.org/10.1111/dmcn.12369
Kuiper MJ, Vrijenhoek L, Brandsma R, Lunsing RJ, Burger H, Eggink H, et al. The Burke-Fahn-Marsden Dystonia Rating Scale is age-dependent in healthy children. Mov Disord Clin Pract. 2016; 3(6): 580–6. DOI: https://doi.org/10.1002/mdc3.12339
Lawerman TF, Brandsma R, Burger H, Burgerhof JGM, Sival DA. Age-related reference values for the pediatric Scale for Assessment and Rating of Ataxia: a multicentre study. Dev Med Child Neurol. 2017; 59(10): 1077–82. DOI: https://doi.org/10.1111/dmcn.13507
Marshall J. Physiological tremor in children. J Neurol Neurosurg Psychiatry. 1959; 22(1): 33–5. DOI: https://doi.org/10.1136/jnnp.22.1.33
Louis ED, Gerbin M, Galecki M. Essential tremor 10, 20, 30, 40: clinical snapshots of the disease by decade of duration. Eur J Neurol. 2013; 20(6): 949–54. DOI: https://doi.org/10.1111/ene.12123
Louis ED, Borden S, Moskowitz CB. Essential tremor centralized brain repository: diagnostic validity and clinical characteristics of a highly selected group of essential tremor cases. Mov Disord. 2005; 20(10): 1361–5. DOI: https://doi.org/10.1002/mds.20583
Louis ED, Hernandez N, Ionita-Laza I, Ottman R, Clark LN. Does rate of progression run in essential tremor families? Slower vs. faster progressors. Parkinsonism Related Disord. 2013; 19(3): 363–6. DOI: https://doi.org/10.1016/j.parkreldis.2012.10.005