Glutathione-S-transferase P1 polymorphism and risk for essential tremor

Glutathione- S -transferases (GST) are polymorphic enzymes that participate in the metabolism of carcinogens (including those of tobacco smoke) and pesticides. We investigated the possible association between the GSTP1 genotype and allelic variants and the risk for essential tremor (ET). We studied the frequency of the GSTP1 genotypes and allelic variants in 200 patients with ET and 220 healthy controls using PCR-RFLP method. The association between GSTP1 polymorphism and the exposure to some environmental factors (agricultural work, pesticides, well-water and smoking-cigarettes habit) was also studied in a subgroup of patients. The frequencies of the GSTP1 genotypes and allelic variants did not differ significantly between patients with ET and controls or between patients with ET exposed to agricultural work, well water and cigarette smoking versus those non-exposed. Mutated allelic variants were significantly more frequent in patients with ET exposed to pesticides versus those non-exposed. GSTP1 polymorphism was unrelated with the age of onset of ET. GSTP1 genotypes and allelic variants were not related with the risk for ET with the possible exception of those patients exposed to pesticides.     

Study of possible factors associated with age of onset in essential tremor.

Factors associated with the age of onset of essential tremor (ET) have not been studied in detail. Identification of modifiable factors could lead to strategies to delay disease onset and identification of nonmodifiable factors would be useful while counseling at risk individuals. The objective of this study was to identify factors associated with age of onset of tremor in ET. One hundred ninety-five ET cases were enrolled in an environmental epidemiological study. Clinical questionnaires included questions on age of onset, demographics (age, sex, race, education), early-life exposures (birth order, childhood household size), exposures prior to tremor onset (head trauma, well water, rural living, estrogen replacement therapy), and family history. In unadjusted analyses, age of onset was associated with family history of tremor (40.9 +/- 22.0 years for cases with a family history of tremor vs. 57.3 +/- 18.4 years for cases without a history; P < 0.001), history of head trauma, younger current age, greater tremor severity, and white race. Ninety-one percent of cases with onset before age 20 years had a family history of tremor. Age ofonset was not associated with other variables of interest (e.g., sex, well water, rural living). In an adjusted linear regression model, age of tremor onset was strongly associated with family history of tremor (P < 0.001). The familial form of ET is characterized by an earlier age of onset than the sporadic form. This study did not detect any other exposures that modified the age of onset of ET. Follow-up studies are needed to examine additional factors of potential interest.     

Tremor associated with Klinefelter syndrome – A case series and review of the literature

BackgroundPrevious case series suggested a link between Klinefelter syndrome (KS) and essential tremor (ET) or an ET-like syndrome.MethodsWe investigated three KS-patients with tremor including tremor-analyzes and discuss our data in context to findings from a literature review. The clinical outcome after deep brain stimulation (DBS) is also reviewed.ResultsTremor in KS is predominantly a postural and kinetic tremor that resembles ET. Our patients were further characterized by absent family history for tremor in first degree relatives, lack of subjective alcohol responsiveness inquired by history, and tremor onset in childhood. One of our patients and two cases from literature improved after DBS of the ventral intermediate nucleus (VIM) of the thalamus.ConclusionsTremor in KS shares several features with ET. If other characteristics such as family history, alcohol responsiveness, and age at tremor onset may serve as discriminating factors from ET, needs to be further investigated. First observations suggest that VIM-DBS may be efficacious.     

Long duration asymmetrical postural tremor is likely to predict development of Parkinson's disease and not essential tremor: clinical follow up study of 13 cases

BACKGROUND: Patients presenting with asymmetrical postural tremor with or without mild rest tremor may be diagnosed as having essential tremor (ET), although there is considerable diagnostic uncertainty as to the long term outcome of these patients. OBJECTIVE: In this study, retrospective observations were made on 13 patients presenting originally with asymmetrical postural tremor, initially thought to have ET based on tremor characteristics, alcohol responsiveness, and family history but who subsequently met the criteria of Parkinson's disease (PD). METHODS: The patients were observed and followed up clinically with ancillary imaging using dopamine transporter SPECT scan or levodopa challenge tests in some cases. The diagnosis at original presentation with postural tremor was made with retrospective case note review. RESULTS: After a variable and long latent period all patients developed additional signs suggesting a clinical diagnosis of PD although picking up an initial label of ET. CONCLUSIONS: We suggest exercising caution regarding a diagnosis of ET in patients presenting with late onset asymmetrical postural tremor even if there is no rest tremor. Alcohol sensitivity of tremor, family history of tremor, or responsiveness to beta blockers may not be helpful in diagnosing ET in these cases and some may develop PD in the long term.     

A clinical study of non-parkinsonian and non-cerebellar tremor at a specialty movement disorders clinic

BACKGROUND: No Indian studies have focused on the clinical aspects of tremor. AIMS: To study the distribution of various etiological types of tremor disorders at a Movement Disorders clinic of a large, tertiary care hospital in India and to study the clinical characteristics of essential tremor [ET]. SETTING AND DESIGN: Prospective cross-sectional study at a tertiary care specialty clinic. MATERIAL AND METHODS: Patients presenting with tremor as the chief complaint, with no features suggestive of parkinsonism, cerebellar disorder or acute central nervous system disorder, were included. Patients were classified into different etiological categories from detailed history. All patients diagnosed as ET, were further interrogated for a detailed family history and examined for characteristics of tremor. These patients were then classified into 'definite', 'probable' and 'possible' ET. RESULTS: One hundred and six patients (mean age 44.4 + 15.1 years) were examined during the study period. ET (59.4%) and dystonic tremor (21.7%) were the commonest types. Only 43% patients of ET reported progression; response to alcohol was seen in only a single patient, a positive family history was present in 52.4% and in 36.4% the inheritance was of an autosomal dominant pattern. CONCLUSION: ET and dystonic tremor are the commonest causes of tremor presenting to a specialty Movement Disorders clinic. Most patients with ET have high-frequency tremor, with mild asymmetry in 40% cases. Alcohol responsiveness may not be a useful tool in the diagnosis of ET.     

Association between restless legs syndrome and essential tremor.

After observing that several families with essential tremor (ET) clinically cosegregated with restless legs syndrome (RLS), we prospectively evaluated for the presence of RLS in 100 patients presenting to the Baylor College of Medicine with ET and prospectively examined all patients presenting with RLS for the presence of tremor during the same time frame. Of 100 consecutive ET patients (60 women and 75 with a family history of ET) seen over 19 weeks (current age, 65.2 +/- 16.3 years; age at tremor onset, 37.8 +/- 19.9 years) 33 met all criteria for RLS, of which 25 had never been diagnosed previously. A family history of RLS was reported in 57.6% of these 33 patients and was the only significant predictor of RLS in the ET population. Their International Restless Legs Syndrome Rating Scale score was 16.6 +/- 8.1. Over 19 weeks, we also examined 68 consecutive RLS patients (63.2% women and 54.4% with a family history of RLS) for the presence of tremor. Their current age was 55.8 +/- 14.4 years, and age at RLS onset was 33.7 +/- 19.5 years. Overtly pathological tremor was rare, but trace tremor was very common. Overall, we found a very high rate of undiagnosed RLS in patients presenting for tremor, but unlike other "secondary" forms of RLS, this finding was also associated with a high familial history of RLS, suggesting that they share some genetic similarities.     

Validity of family history in essential tremor

In this study, we found the sensitivity and specificity of family history data given by essential tremor (ET) patients to be 43.3% and 94.4%. Compared to relatives with less severe tremor (tremor score <24), those with more severe tremor (tremor score 24) were more likely to be identified by the ET probands (8/8 vs. 5/22, p=0.001, chi2 14.3). Our study suggests that family history information reported by ET patients was inaccurate, and poorly validated. Clinical and genetic studies in ET should take the limitation of family history data into consideration.     

The relationship of essential tremor to other movement disorders: Report on 678 patients

We examined 678 essential tremor patients in specialty, university, and private practice clinics. The mean age of patients was 65.2 years with a similar number of men and women. Six percent of patients were left-handed. A positive family history of tremor was reported in more than 60% of patients. Alcohol ingestion was reported to decrease tremor in 74% of patients who were cognizant of the effect of alcohol on tremor. Mean age at tremor onset was 45.3 years. An earlier onset of tremor was observed in those patients having a positive family history of tremor. Tremor affected the hands in 90% of patients, head in 50%, voice in 30%, and legs and chin in 15%. Functional disability was common and impairment at work occurred in 18% Propranolol and primidone were the most frequently used drugs and were effective in 40% of patients. Six and one-tenth percent of essential tremor patients had concomitant Parkinson's disease, 6.9% had a coexisting dystonia, and 1.8% had myoclonus. It is concluded that the frequency of Parkinson's disease in essential tremor is more than would be reported in the general population and that other movement disorders are infrequently observed in essential tremor.     

特发性震颤的临床特点

目的　探讨特发性震颤 (ET)的临床特点。方法　对 80例 ET患者的临床资料进行分析。结果80例 ET中男 5 0例 ,女 30例 ,发病年龄 3～ 70岁 ,平均 34.6± 16 .3岁 ,病程 6个月～ 6 0年 ,平均 14.2± 9.9年。45例 (5 6 .3% )患者有阳性家族史 ,多呈常染色体显性遗传。临床主要表现为单症状的姿势性震颤 ,累及部位依次为手 (92 .5 % )、咽喉部 (2 1.3% )、头 (2 0 % )、下颏 (17.5 % )等。 17.5 %患者因震颤致日常生活困难。 34例饮酒患者中 ,91.2 %显示对酒精有反应性。 6 .3%患者并发帕金森病 (PD)。 6 1%患者小剂量心得安治疗有效。结论　本组 ET患者男多于女 ,发病年龄轻 ,呈单峰模式 ,临床表现为单症状姿势性震颤 ,部分病例可伴发PD,小剂量心得安治疗大多有效。     

Familial and environmental risk factors in Parkinson's disease: a case-control study in north-east Italy

BACKGROUND AND OBJECTIVE: The aetiology of Parkinson's disease remains unknown, although both genetic susceptibility and environmental factors are considered putative contributors to its origin. We performed a case-control study to investigate the association of familial and environmental risk factors with Parkinson's disease (PD). METHODS: We studied 136 patients with neurologist confirmed PD and 272 age- and sex-matched controls, affected by neurological diseases not related to PD. The risk of developing idiopathic PD associated with the following familial and environmental factors: positive family history of PD, positive family history of essential tremor (ET), age of mother at subject's birth, rural birth, rural living, well water use, farming as an occupation, exposure to pesticides, head tremor, exposure to general anaesthesia and to ionizing radiations, food restriction, concentration camp imprisonment and smoking has been assessed by using univariate and multivariate statistical techniques. RESULTS: In the conditional multiple logistic regression analysis, positive family history of PD (OR 41.7, 95% CI 12.2-142.5, P < 0.0001), positive family history of ET (OR 10.8, 95% CI 2.6-43.7, P < 0.0001), age of mother at subject's birth (OR 2.6, 95% CI 1.4-3.7, P=0.0013), exposure to general anaesthesia (OR 2.2, 95% CI 1.3-3.8, P=0.0024), farming as an occupation (OR 7.7, 95% CI 1.4-44.1, P=0.0212) and well water use (OR 2.0, 95% CI 1.1-3.6, P=0.0308) exhibited a significant positive association with PD, whereas smoking showed a trend toward an inverse relationship with PD (OR 0.7, 95% CI 0.4-1.1, P < 0.06). CONCLUSIONS: We conclude that both familial and environmental factors may contribute to PD aetiology.     

Clinical characteristics of essential tremor in Taiwan: an exploratory‐comparative study

Background: There are few large‐scale clinical analyses of essential tremor (ET) in Asia. We studied the detailed clinical profile with emphasizing the age of onset, tremor location, specific tremor patterns, and rate of progression (ROP) to delineate the characteristics of Taiwanese ET patients and found the difference between the Taiwanese and the Caucasians ET patients. Methods: All ET patients fulfilled the Movement Disorders Society diagnosis criteria were investigated with a standardized assessment protocol, which including clinical evaluation, uniform severity scoring, self‐reported questionnaires, accelerometry, surface electromyography, and videotaped tremor examination. Results: Of 219 patients recruited from July 2008 to October 2009, 153 completed the study protocol. Their mean age was 58.9 years and 47% were women, and 33.3% had family history (FH). There was bimodal distribution in age of tremor onset in patients without but not in those with FH. Head tremor (HT) was present in 48 of 153 (31%) patients. Patients with HT showed slower tremor frequency and less ROP than those without HT. Sixty‐seven (44%) patients presented with intention tremor (IT). Male gender and voice tremor were predictive factors of IT occurrence. Conclusions: Comparing with the Caucasians, Taiwanese ET patients have different patterns of onset‐age distribution and lack of female predominance in ET with HT. However, patients with IT and without HT also progressed more rapid as found in the Caucasian.     

Organochlorine pesticide exposure in essential tremor: a case-control study using biological and occupational exposure assessments

Essential tremor (ET) is a common neurological disorder. Its etiology and pathogenesis are not well understood and several environmental factors (i.e., toxicants) have been studied. Organochlorine pesticides (OCPs) are potent tremor-producing chemicals. These pervasive environmental contaminants have been linked with other tremor disorders (e.g., Parkinson's disease) but they have not been assessed in ET cases. Our objective was to test the hypothesis that ET is associated with OCP exposure. Serum OCP concentrations and lifetime occupational histories were assessed in ET cases and control subjects. Six serum OCP concentrations (p,p'-DDE, p,p'-DDT, beta-hexachlorocyclo-hexane, oxychlordane, trans-nonachlor, and dieldrin) were assessed. Data from a lifetime occupational history were reviewed by a blinded industrial hygienist. The six serum OCP concentrations were similar in 136 ET cases and 144 control subjects. There was no association in ET cases between the six serum OCP concentrations and total tremor score. Three (2.2%) ET cases versus 9 (6.3%) controls had past occupational exposure to OCPs (OR=0.34, 95% CI=0.09-1.28, p=0.10). Although OCPs have been associated with other tremor disorders, we were not able to find an association between the six most tremorogenic OCPs and ET. Our data suggest that these tremor-producing chemicals are not of major etiological importance in our patients with ET.     

Clinical features of essential tremor seen in neurology practice: a study of 357 patients

To assess the clinical features of essential tremor (ET), we studied 357 patients with diagnostic criteria for this disease who were referred to the Neurology departments of three urban hospitals. This is not a true epidemiological study, and can be biased in favour of patients with functional disability. There was a predominance of affectation of females and a peak of age at onset in the sixth and seventh decades. Family history of tremor was positive in 46.8% of patients. Females showed a a significantly higher frequency of inheritance through maternal than through paternal line, and had a higher frequency of head and voice tremor, than males. When compared with patients without family history, those with family history of tremor had lower age at onset of tremor, and lower frequency of jaw and trunk tremor in non-familial cases.     

Benign essential tremor. A clinical survey of 82 patients from Campania, a region of southern Italy

We report a clinical survey of 82 patients with benign essential tremor (ET). Sixty five patients had a positive family history. Onset age showed two peaks before 20 years and in the sixth decade. Segregation analysis confirmed an autosomal dominant inheritance. Head tremor occurred mainly in aged women, mental symptoms occurred mainly in subjects with a low onset age and a disabling tremor. An early onset age was not related to paternal or maternal transmission. In one family ET was associated with retinitis pigmentosa and ichthyosis.     

High prevalence of reported tremor in Klinefelter syndrome

Several uncontrolled reports in the literature dating from decades ago suggest a link between Klinefelter syndrome (KS) and essential tremor (ET). Aiming to determine whether this association truly exists, we designed a controlled survey to ascertain the prevalence of reported tremor in KS. We identified subjects with KS through our hospital database and recruited controls among men who were accompanying patients to our Neurology Clinic. The presence of tremor and other variables were recorded employing a previously validated questionnaire. Whereas our control population was slightly older and more frequently reported a family history of tremor, the frequency of reported tremor was significantly higher in subjects with KS than controls with onset at a younger age. In addition, a high proportion of subjects with KS indicated gait imbalance. In summary, our study supports the previously reported association of an ET-like syndrome and KS.     

Validity of family history data on essential tremor.

BACKGROUND: In family studies of essential tremor (ET), valid data on the presence of ET in relatives of probands with ET is important. The family history method uses information obtained by interviewing probands with ET to identify ET in their relatives. The validation of this method by direct examination of the relatives has not been performed. OBJECTIVE: To determine the validity of family history data on ET in families in which the proband has ET. METHODS: ET cases (probands) and their respective relatives were enrolled in a genetic study of ET in Washington Heights-Inwood, New York. Each underwent a tremor interview and videotaped examination. Two neurologists rated the severity of tremor and assigned diagnoses (ET versus normal). Probands were asked to identify their relatives who had ET. The validity of the probands' responses was tested against the neurologists' diagnoses. RESULTS: There were 206 subjects: 46 ET cases and 160 relatives. Twelve (7.5%) of 160 relatives were diagnosed with ET (four definite ET and eight probable ET). Probands with ET reported that two of these 12 had tremor (sensitivity of probands' report = 16.7%). Six of the 12 affected relatives (50.0%) reported their own tremor. The probands reported that one of 136 of their unaffected relatives had tremor (specificity of probands' report = 99.3%). CONCLUSIONS: For family studies of ET, information on reportedly unaffected relatives is of limited use given the low sensitivity of family history data. The neurologic examination remains the only valid means of ascertaining cases of ET among relatives.     

Olfactory tests in the diagnosis of essential tremor

Most patients with tremor-dominant Parkinson's disease (PD) have impaired smell function but it is unclear whether this is true for subjects with essential tremor (ET). If ET patients do not exhibit meaningful smell loss, then olfactory testing may help to distinguish PD from ET. We assessed olfactory function in 59 ET and 64 tremor-dominant PD patients using the University of Pennsylvania Smell Identification Test (UPSIT) and olfactory event-related potential (OERP). UPSIT scores were compared to those from 245 healthy controls, and OERPs were compared to those from 74 controls. Unlike the PD test scores, those of ET patients were indistinguishable from controls when the effects of age, age of onset, gender, and smoking were taken into account. ET patients with a family history of tremor scored significantly better than controls on the UPSIT, and their rate of decline with age was slower. The effect was not observed on OERP. Smell testing may help to distinguish between ET and tremor-predominant PD, and patients with family history of tremor may represent a subgroup whose olfactory function is enhanced by some unknown mechanism.     

Clinical features of childhood onset essential tremor

Childhood onset essential tremor (ET) is uncommon. It is not clear as to whether ethnicity-specific differences may influence the phenotypic features. To determine the frequency and clinical characteristics of childhood ET in a tertiary referral center. In a prospective evaluation of 120 consecutive ET patients in a movement disorders clinic, we found a 15.5% (19) frequency of childhood onset ET patients. The mean age of onset and mean age was 10.8 ± 4.1 (6–16) years and 25.7 ± 15.0 (16–73) years consisting of 73.6% (14/19) men and 26.4% (5/19) women. A positive family history of ET was present in 11 of 19 (52.6%). Presence of a head tremor was observed in 2/19 (10.5%). We highlighted a relatively high frequency (15,5%) of childhood ET in our Asian cohort. In addition, we drew attention to the male preponderance and the low frequency of head tremor in childhood ET corroborating study findings in white ET patients. These observations appear to transcend ethnic and cultural differences and lend further support that gender difference may play a role in the pathogenesis and expression of ET.     

Lack of association between essential tremor and Parkinson's disease

Four aspects of a possible association between essential tremor (ET) and Parkinson's disease (PD) were investigated: (1) the frequency of extrapyramidal signs in ET; (2) the frequency of concurrent ET and PD (i.e., monosymptomatic postural tremor for 5 or more years prior to onset of PD); (3) the frequency of ET in the families of PD patients; and (4) the frequency of PD in families of ET patients. Two hundred and thirty-seven ET patients (137 in London and 100 in Chicago) were evaluated. One hundred patients with PD and 100 normal control subjects were also investigated. Mild extrapyramidal signs occurred in only 4.5% of ET patients and were consistent with those found in normal aging. Only 3% of PD patients gave a history of uncomplicated ET. There was no difference in the frequency of a family history of PD between ET patients, a group of PD patients, and control subjects. Frequency of a family history of ET was higher among PD patients than control subjects, although the difference was not statistically significant. These data indicate that there is no association or genetic link between ET and PD.     

Subclinical tremor in normal controls with versus without a family history of essential tremor: data from the United States and Turkey

Background and purpose: Mild action tremor is very common in the population. One fundamental question is whether this tremor is related to the neurological disease essential tremor (ET), which occurs in a much smaller segment of the population? ET is often genetic, and variable phenotypic expression is well‐documented in the literature. We determined whether normal controls who report a family history of ET have greater action tremor than normal controls who do not report such a history. Methods: Controls, enrolled in two epidemiological studies (New York and Turkey), were examined in detail and action tremor was rated using a valid and reliable clinical rating scale, resulting in a total tremor score (range 0–36). Results: In New York, the total tremor score was higher in 44/406 (10.8%) controls who reported a family history of ET than in 362/406 controls with no such history (4.25 ± 2.51 vs. 3.78 ± 2.93, P = 0.02). Controls who reported a first‐degree relative with ET had the highest total tremor scores. In Turkey, the total tremor score was higher in 7/89 (7.9%) controls with a family history than in 82/89 controls with no family history (3.43 ± 4.54 vs. 1.13 ± 2.54, P = 0.048). All affected relatives in Turkey were first‐degree. Conclusions: These data suggest that some of the normal tremor exhibited by people in the population is likely to be subclinical, partially expressed ET and that the sphere of ET is wider than is apparent from a consideration of clinically diagnosed cases.