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PubMed1995

Resting tremor only: a variant of Parkinson's disease or of essential tremor.

Resting tremor is one of the characteristic features of Parkinson's disease. However, there are a number of patients who typically have resting tremor alone for at least 5 years without development of other parkinsonian signs or symptoms. The etiology of an isolated resting tremor is still obscure. Recently, positron emission tomography was used to study these patients with isolated resting tremor, and demonstrated a markedly decreased striatal uptake of fluoro-dopa to the range of Parkinson's disease. These findings suggested the existence of a separate subtype, namely, tremulous Parkinson's disease with a manifestation of resting tremor alone. In order to confirm the existence of this subgroup of tremulous Parkinson's disease and further investigate its morphological changes and the usefulness of magnetic resonance imaging, we collected 5 patients who typically have resting tremor for at least 8 years in the absence of other features of Parkinson's disease. MRI was performed and the results of the images showed typical findings of Parkinson's disease with smudging or decreased distance between substantia nigra and red nucleus. Quantitative analysis also demonstrated a significant decrease of the above-noted distance when the resting tremor group was compared to the essential tremor group. Therefore, patients with an isolated resting tremor can have morphological abnormalities in addition to functional disturbances shown by positron emission tomography. To our knowledge, this is the first paper to report that resting tremor is a variant of Parkinson's disease rather than essential tremor, by using a double-blind method, with magnetic resonance imaging to support.

Aged↗

PubMed2002

Peripheral silent periods in essential tremor.

BACKGROUND: Pathophysiology of essential tremor (ET) is controversial. In the present study, peripherally induced silent period (SP) in ET patients is studied. AIMS AND OBJECTIVES: To study if the peripherally induced SP was different in ET patients as compared to age matched healthy controls. MATERIAL AND METHODS: 24 patients of ET diagnosed according to diagnostic criteria of Louis et al. [Neurology 50 (1998) 1351] (mean age 45.37+/-14.86 years) and an equal number of healthy controls (mean age 36.21+/-15.72 years) were recruited for the study. Peripherally induced SP was recorded according to the methods already described. Student's t-test and Wilcoxon sign rank test were used for statistical analysis. RESULTS: The peripheral SP was 50.29+/-50.15 and 93.04+/-35.93 ms (p=0.0014) in ET patients and controls respectively. CONCLUSION: Our study shows that peripheral silent period is shorter in patients of ET as compared to normal individuals.

Adult↗

PubMed2003

Cortical silent period in essential tremor.

BACKGROUND: Pathophysiology of essential tremor (ET) is controversial, current evidence indicating its genesis through a central oscillator and modulation by a peripheral component. Since transcranial magnetic stimulation induced silent period (SP) has been attributed mainly to intracortical inhibitory mechanisms, it has been found useful in assessing central motor disturbances. AIMS AND OBJECTIVES: To assess if the cortically induced SP was different in ET patients as compared to age matched healthy controls. MATERIAL AND METHODS: Twenty-four patients of ET (mean age 45.4 +/- 14.9 years) diagnosed according to criteria of Louis et al (1998) and an equal number of healthy controls (mean age 36.2 +/- 15.7 years) were recruited in the study. Cortically induced (magnetic) SP were recorded according to the standard methods described. Student's "t" test and Wilcoxon sign rank test were used for statistical analysis. RESULTS: The mean +/- SD cortical SP in ET patients (180.75 +/- 57.11 msec) in ET patients and in controls (163.83 +/- 35.65 msec) were statistically similar (p = 0.22). CONCLUSION: Our study shows that there is no significant difference in mean cortical SPs in patients with ET as compared to controls.

Adult↗

PubMed2000

Clinical subtypes of essential tremor.

BACKGROUND: There is clinical variability in essential tremor (ET), but it is not clear whether this variability is because of the existence of distinct clinical subtypes of ET (ie, forms of ET that may differ in their etiology, rate of progression, or response to treatment). OBJECTIVES: To examine in a group of ET cases the age of onset, anatomic distribution, and rate of progression of tremor, and to look for associations between these factors. METHODS: Cases of ET were ascertained from a community (n = 60) and a tertiary referral clinic (n = 55) in northern Manhattan, New York, NY. All subjects underwent an interview and videotaped tremor examination. Rate of progression was estimated based on the tremor severity and reported disease duration at the time of evaluation. RESULTS: Age of onset was bimodally distributed in clinic cases. There were differences in the anatomic distribution of the tremor (arm tremor only vs head and arm tremor vs isolated head tremor). Rate of progression was distributed exponentially; there was a large cluster of subjects with slower rates of progression, and a smaller number who had faster rates. There was an association between age of onset and rate of progression (r = 0.46-0.50, P<.002); cases with older age of onset (>60 years) progressed more rapidly (P<.001). In addition, upper limb tremor progressed more slowly among those with concomitant head tremor (P =.03). CONCLUSIONS: Essential tremor is not a homogeneous condition. There are differences in age of onset, anatomic distribution of tremor, and rate of progression. The ET in several groups of patients in this study (those with age of onset >60 years and those without head tremor) progressed more rapidly, suggesting that these ET cases may define distinct clinical subtypes. These subtypes should be further assessed for etiologic and genetic heterogeneity as well as differences in responsiveness to therapeutic agents. Arch Neurol. 2000;57:1194-1198

Age of Onset↗

PubMed2006

Population-based case-control study of cognitive function in essential tremor.

OBJECTIVES: To determine whether patients with essential tremor (ET) have cognitive deficits when compared with controls and whether the types of cognitive deficits reported previously are also found in this large sampling of patients with ET. METHODS: A total of 232 patients with ET and 696 matched controls age 65 years or older (median 75 years) living in central Spain (the Neurologic Diseases in Central Spain study) underwent a neuropsychological assessment, including tests of global cognitive performance, frontal executive function, verbal fluency, and memory. Subjects also were asked whether they had forgetfulness. RESULTS: Fifty-six patients with ET were previously undiagnosed; only 14 (6%) were taking medication for tremor. Adjusted for age, gender, education, premorbid intelligence, medications, and depressive symptoms, cases performed less well on most neuropsychological tests and especially tests of global cognitive performance (37-item Mini-Mental State Examination = 27.0 +/- 6.7 in cases vs 28.9 +/- 5.9 in controls, p < 0.001) and frontal executive function (Trail Making Test number of errors = 8.7 +/- 11.0 in cases vs 3.8 +/- 7.6 in controls, p < 0.001). Forgetfulness was reported in 117 (50.4%) patients with ET vs 300 (43.1%) controls (p = 0.05). CONCLUSIONS: In a population-based sample of largely untreated patients with essential tremor, cases performed more poorly on formal neuropsychological testing than did their counterparts without tremor. A complaint of forgetfulness was also marginally more common in patients with essential tremor.

Age Factors↗

PubMed2003

A multicenter randomized crossover multiple-dose comparison study of arotinolol and propranolol in essential tremor.

BACKGROUND: A new medication is needed to treat essential tremor. Preliminary evidence suggests that arotinolol may be effective in the treatment of this disorder. OBJECTIVE: To study the effect of arotinolol and propranolol in a crossover, multiple dose comparative trial of patients with essential tremor. PATIENTS AND METHODS: One hundred and seventy-five outpatients, with essential tremor were included in the study; 161 patients completed the study. Patients were identically evaluated at eight consecutive visits. The study consisted of two treatments, which were arranged according to a crossover design that evaluated the dose of each (arotinolol 10 mg per day and propranolol 40 mg per day, arotinolol 20 mg per day and propranolol 80 mg per day, arotinolol 30 mg per day and propranolol 160 mg per day). Each course of treatment lasted 6 weeks. Major outcome evaluations consisted of a self-reported disability scale, and motor performance score obtained before drug intake and 14 days after each treatment. The treatment effects were evaluated by analysis of variance using the Hills-Armitage test. RESULTS: Arotinolol was found to be as effective as propranolol at reducing tremor. Drug effects as evaluated using motor-task performance scores revealed that arotinolol had a more significant effect than propranolol. CONCLUSIONS: Arotinolol may be more useful than propranolol for the treatment of essential tremor.

Adrenergic beta-Antagonists↗

PubMed2005

Genetic essential tremor in gamma-aminobutyric acidA receptor alpha1 subunit knockout mice.

Essential tremor is the most common movement disorder and has an unknown etiology. Here we report that gamma-aminobutyric acidA (GABA(A)) receptor alpha1-/- mice exhibit postural and kinetic tremor and motor incoordination that is characteristic of essential tremor disease. We tested mice with essential-like tremor using current drug therapies that alleviate symptoms in essential tremor patients (primidone, propranolol, and gabapentin) and several candidates hypothesized to reduce tremor, including ethanol; the noncompetitive N-methyl-D-aspartate receptor antagonist MK-801; the adenosine A1 receptor agonist 2-chloro-N6-cyclopentyladenosine (CCPA); the GABA(A) receptor modulators diazepam, allopregnanolone, and Ro15-4513; and the L-type Ca2+ channel antagonist nitrendipine. Primidone, propranolol, and gabapentin reduced the amplitude (power) of the pathologic tremor. Nonsedative doses of ethanol eliminated tremor in mice. Diazepam, allopregnanolone, Ro15-4513, and nitrendipine had no effect or enhanced tremor, whereas MK-801 and CCPA reduced tremor. To understand the etiology of tremor in these mice, we studied the electrophysiological properties of cerebellar Purkinje cells. Cerebellar Purkinje cells in GABA(A) receptor alpha1-/- mice exhibited a profound loss of all responses to synaptic or exogenous GABA, but no differences in abundance, gross morphology, or spontaneous synaptic activity were observed. This genetic animal model elucidates a mechanism of GABAergic dysfunction in the major motor pathway and potential targets for pharmacotherapy of essential tremor.

Adrenergic beta-Antagonists↗

PubMed1993

A positron emission tomography study of essential tremor: evidence for overactivity of cerebellar connections.

The origin of essential tremor is unknown. Animal models have suggested that the inferior olivary nucleus may act as a tremor generator. We used positron emission tomography to study changes in regional cerebral blood flow associated with involuntary postural tremor and passive wrist oscillation in patients with essential tremor. Activation due to voluntary wrist oscillation and arm extension without tremor was studied in normal control subjects. The essential tremor group had bilaterally increased cerebellar blood flow at rest (without tremor) compared with the control group. Involuntary postural tremor was associated with further bilateral cerebellar activation, and also contralateral striatal, thalamic, and sensorimotor cortex activation. Voluntary wrist oscillation, maintained arm extension without tremor, and passive wrist oscillation were all associated with significant ipsilateral rather than bilateral cerebellar activation. We conclude that essential tremor is associated with increased bilateral cerebellar activity both at rest and during tremor.

Adult↗

PubMed2003

Electrophysiological approach to the study of essential tremor in children and adolescents.

Surface electromyography and accelerometry provide essential information on the neurophysiological characteristics of essential tremor. There are many reports on neurophysiological features in adult-onset essential tremor, but to our knowledge there have been no similar investigations of essential tremor in children. We conducted a neurophysiological study of nine children, six males and three females, with definite essential tremor. They were subdivided into two groups according to age: a 'children's group', consisting of four patients aged from 7 to 12 years, and an 'adolescent group', consisting of five patients aged from 14 to 16 years. Finger tremor as opposed to hand tremor was studied. In children the mean tremor frequency was 5.3 Hz (SD 0.5) with arms extended, which increased to 8.2 Hz (SD 1.5) when we added a mass of 300 g. In adolescents the mean tremor frequency was 9.0 Hz (SD 1.4) with arms extended, and 7.2 Hz (SD 1.8) with added mass. We discuss several hypotheses to find an explanation for these results.

Adolescent↗

PubMed2005

Harmaline-induced tremor as a potential preclinical screening method for essential tremor medications.

No preclinical method to evaluate potential new medications for essential tremor (ET) is available currently. Although harmaline tremor is a well known animal model of ET, it has not found utility as a preclinical drug screen and has not been validated with anti-ET medications. We measured harmaline tremor in rats (10 mg/kg s.c.) and mice (20 mg/kg s.c.) with a load sensor under the cage floor and performed spectral analysis on 20-minute epochs. The motion power over the tremor frequency bandwidth (8-12 Hz in rats; 10-16 Hz in mice) was divided by the motion power over the full motion frequency range (0-15 Hz in rats; 0-34 Hz in mice). The use of these measures greatly reduced data variability, permitting experiments with small sample sizes. Three drugs that suppress ET (propranolol, ethanol, and octanol) all significantly suppressed harmaline-induced tremor. We propose that, with this methodology, harmaline-induced tremor may be useful as a preclinical method to identify potential medications for ET.

Animals↗

PubMed2006

CYP2C19 polymorphism and risk for essential tremor.

Many patients with essential tremor (ET) develop acute adverse effects to primidone. We investigated the association between CYP2C19 polymorphism (possibly related to primidone metabolism) and the risk for developing essential ET and acute adverse effects to primidone. Leukocytary DNA from 200 ET patients and 300 healthy controls was studied for the genotype CYP2C19 and the occurrence of CYP2C19 allelic variants by using allele-specific PCR amplification and Sma I and BamH I RFLP analyses. The frequencies of the genotype CYP2C19*1/CYP2C19*2 and of the allelic variant CYP2C19*2 were significantly higher in ET patients than in controls. The mean age at onset of ET did not differ significantly between patients with genotypes CYP2C19*1/CYP2C19*2andCYP2C19*1/CYP2C19*1. The frequencies of the genotype CYP2C19*1/CYP2C19*2 and the allelic variant CYP2C19*2 were similar in ET patients who developed acute adverse effects to primidone, in those who tolerated primidone and in controls; the frequencies were also similar in patients with head, voice, tongue and chin tremor compared with controls. These results suggest that heterozygosis CYP2C19*1/CYP2C19*2 is associated with the risk for ET, but not with the age at onset of ET, the presentation of acute side effects of primidone, or the existence of head, voice, tongue or chin tremor.

Adult↗

PubMed2006

[Social phobia in essential tremor].

OBJECTIVES: This study is aimed to determine the frequency of social phobia among a group of subjects with essential tremor, to compare subject groups with and without social phobia with regard to the level of social phobia and disability, and to study the effect of the severity of social phobia on disability in essential tremor. METHOD: 45 subjects, diagnosed with essential tremor were included in the study, and their severity of tremor and essential tremor-related functional impairment were determined. Subjects were evaluated in 2 groups; those with a social phobia diagnosis and those without, as determined with the SCID-I interview. Additionally, the Liebowitz Social Anxiety Scale (LSAS) and the Sheehan Disability Scale (SDS) were administered to both groups and the findings were statistically compared. RESULTS: Social phobia was observed in 19 subjects (42.2%) with essential tremor. While no difference was found between the groups in terms of tremor severity scores, the mean score of tremor-related functional disability in the social phobia group was found to be higher. Among subjects with social phobia, the mean fear and avoidance scores on LSAS were higher, whereas social lives and leisure activities of the same group were observed to have been affected more, according to SDS scores. Social avoidance and tremor severity were predictive for the difference on SDS. A significant and positive correlation between fear and avoidance, and disability in the group with social phobia was established. CONCLUSION: It was concluded that essential tremor patients diagnosed with social phobia demonstrated higher social anxiety and disability compared to those without social phobia, and that social avoidance contributed to disability. Identifying social phobia in essential tremor patients and diagnosing these patients with social phobia, contrary to DSM's restrictive approach, would be appropriate and beneficial in terms of providing sufficient treatment.

Adult↗

PubMed2002

Clinical and electromyographic assessment of essential tremor treatment.

It is a matter of debate whether beta-blockers or primidone have a better influence on essential tremor. It is also controversial whether essential tremor with synchronous electromyographic activity is influenced by the administration beta-blockers, while tremor with alternating electromyographic activity is influenced by primidone. The aim of this study was to reevaluate the effects of beta-blockers and primidone on essential tremor. We also aimed to evaluate the differential effects of beta-blockers and primidone on tremor with synchronous or alternating electromyographic activity and on tremor in different limb positions. One hundred patients (57 female, 43 male) with essential tremor were included in this study. According to the electromyographic pattern recorded from the antagonistic muscles, the patients were subdivided into group with synchronous (SYN) and group with alternating (ALT) activity. After the initial clinical and electromyographic examinations the patients were randomly assigned first to treatment with propranolol (180 mg daily), or to treatment with primidone (500 mg daily) for 30 days. After a washout period of 20 days the patients were assigned to the other treatment. Our results revealed that the effects of propranolol and primidone on essential tremor and on SYN or ALT tremor were similar. Differences between both drugs existed as regards to better primidone influence on the kinetic and intention tremors and to tremor localized outside the limbs. In conclusion it is better to treat patients with kinetic and intention essential tremor and tremor localized outside the limbs with primidone.

Adrenergic beta-Antagonists↗

PubMed2006

Topiramate in essential tremor: a double-blind, placebo-controlled trial.

BACKGROUND: Essential tremor is most prevalent and most disabling in older patients. Additional therapies are required for patients with an inadequate response or intolerable side effects. In small trials, topiramate appeared to be beneficial in essential tremor. METHODS: In this multicenter, double-blind, placebo-controlled, parallel-design trial, patients with moderate to severe essential tremor of the upper limbs were randomized to 24 weeks of treatment with placebo or topiramate (target dose, 400 mg/day) as monotherapy or as an adjunct to one antitremor medication. The primary efficacy variable was the final visit tremor score based on the Fahn-Tolosa-Marin Tremor Rating Scale (TRS). RESULTS: The intent-to-treat population was 208 patients (topiramate, 108; placebo, 100). The final visit score (last observation carried forward) was lower in the topiramate group than with placebo (p < 0.001). Mean percentage improvement in overall TRS scores was 29% with topiramate at a mean final dose of 292 mg/day and 16% with placebo (p < 0.001). Topiramate was associated with greater improvement in function and disability (p = 0.001). A between-group difference (p < 0.001) was observed at the first on-treatment visit at 4 weeks when the target topiramate dose was 100 mg/day (mean achieved dose, 62 +/- 9 mg/day). The most common treatment-limiting adverse events in topiramate-treated patients were paresthesia (5%), nausea (3%), concentration/attention difficulty (3%), and somnolence (3%). Adverse events were treatment limiting in 31.9% of topiramate patients and 9.5% of placebo patients. CONCLUSIONS: Topiramate was effective in the treatment of moderate to severe essential tremor. Tremor reduction was accompanied by functional improvements, such as in motor tasks, writing, and speaking.

Adult↗

PubMed1984

Propranolol therapy for essential tremor of the head.

The effect of propranolol on essential tremor affecting the head was studied in a placebo-controlled trial. Clinical tremor scores and tremor amplitude as measured by an accelerometer were significantly decreased for both head and hand tremor by 160-mg/d and 320-mg/d doses of propranolol. Placebo and 80 mg/d were without effect. In individual patients, the responsiveness of head tremor tended to parallel that of hand tremor. The head tremor of essential tremor can be treated successfully with propranolol therapy.

Clinical Trials as Topic↗

PubMed1994

Essential tremor entrains rapid voluntary movements.

The effect of essential tremor on the timing of rapid wrist flexion was examined in 10 patients with moderate to severe disability. The mean reaction time and motor time of the patients did not differ from the mean values of 10 healthy age- and sex-matched controls. The latencies of the triphasic agonist and antagonist EMG bursts did not differ between patients and controls. The initiation of movement was time-locked to the tremor cycle in all patients. The initial agonist muscle activation occurred in phase with the rhythmic bursts of EMG, but the onset of rapid wrist flexion occurred when the momentum of essential tremor opposed the volitional movement. Essential tremor has subtle effects on motor control that transcend oscillation per se. These effects probably contribute to the impaired performance of fine motor tasks in patients with advanced disease.

Aged↗

PubMed2006

[Complex tremor analysis for the differential diagnosis of essential tremor and Parkinson's disease].

OBJECTIVE: Tremor is the most common movement disorder which is most often either essential or caused by Parkinson's disease. The differentiation of these disorders at the initial stage may be difficult. Objective assessment of the efficacy of tremor medications is only possible by instrumental measurements. The aim of this study was to determine whether the computer assisted tremor analysis system CATSYS 2000 can help in the differentiation of parkinsonian from essential tremor. METHODS: The rhythmicity and maximal frequency of fast alternating hand and finger movements, simple reaction time and postural instability were recorded in healthy controls (n = 18), patients with Parkinson's disease (n = 39) and essential tremor (n = 37). Data were digitally converted and statistically analyzed. RESULTS: Tremor intensity, median frequency and frequency distribution showed characteristic differences in the three groups. Performance in fast alternating movements of hands and fingers were significantly worse in both tremor groups compared to the healthy controls. CONCLUSIONS: The data also indicated that quantitative measurements of tremor parameters must be performed on both sides, because the presence of significant side differences support the diagnosis of Parkinson's disease. The method presented can be used to objectively analyze tremor and performance in rhythmic movements. The results show that it helps to differentiate parkinsonian from essential tremor as well as to predict disease course and the effectiveness of therapy. Multivariate statistical analysis of tremor and movement performance also provides an opportunity to study the pathogenesis of human tremor.

Adult↗

PubMed2002

The contribution of tremor studies to diagnosis of parkinsonian and essential tremor: a statistical evaluation.

This study statistically evaluated a set of commonly measured tremor parameters to determine their individual and combined ability to discriminate between essential tremor (ET) and Parkinsonian tremor (PT). Accelerometer and surface electromyographic (EMG) records of moderate to severe upper limb tremor in 20 patients with ET and 22 patients with PT were used to quantitatively compare tremor amplitude, frequency and pattern of muscle bursting in two resting and three non resting postures. The group statistics showed significant differences between ET and PT with respect to tremor frequency in all five postures, tremor amplitude at rest and muscle bursting patterns. Discriminant function analysis showed that no single parameter or combination of parameters was able to correctly classify all patients. Frequency was much more discriminating than amplitude or muscle bursting patterns in all limb postures. The best amplitude discrimination was obtained when the hand and forearm were both fully supported. Muscle bursting patterns were poorly discriminating and did not assist in correct classification of single patients. Group statistics confirmed a highly significant biological difference between the two tremor types. Optimal classification of single PT (86% correct) and ET (95% correct) patients was obtained using frequency and two selected amplitude parameters from the resting limb. Limb posture was an important variable in optimising the discriminative ability of tremor studies. The implications for routine tremor studies are summarised.

Adult↗