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At least 55 records · Page 3Linked to original sources
PubMed2006

Carbenoxolone and mefloquine suppress tremor in the harmaline mouse model of essential tremor.

Excessive olivo-cerebellar synchrony is implicated in essential tremor. Because synchrony in some networks is mediated by gap junctions, we examined whether the gap junction blockers heptanol, octanol, carbenoxolone, and mefloquine suppress tremor in the mouse harmaline model, and performed an open-treatment clinical study of mefloquine for essential tremor. Digitized motion was used to quantify tremor in mice administered harmaline, 20 mg/kg s.c. In mice the broad-spectrum gap junction blockers heptanol, octanol (350 mg/kg i.p. each), and carbenoxolone (20 mg/kg) suppressed harmaline tremor. Mefloquine (50 mg/kg), which blocks gap junctions containing connexin 36, robustly suppressed harmaline tremor. Glycyrrhizic acid (related to carbenoxolone) and chloroquine (related to mefloquine), which do not block gap junctions, failed to suppress harmaline tremor in mice. Clinically, tremor was assessed with standard rating scales, and subjects asked to take 62.5, 125, and 250 mg mefloquine weekly for 12 weeks at each dose. None of the four human subjects showed a meaningful tremor reduction with mefloquine, likely because clinical levels were below those required for efficacy. In view of recent genetic evidence, the anti-tremor mechanism of these compounds is uncertain but may represent a novel therapeutic target, possibly involving gap junctions other than those containing connexin 36.

1-Octanol↗
PubMed1990

Limb positioning and magnitude of essential tremor and other pathological tremors.

We examined the influence of maintaining different postural configurations of the upper extremity on the magnitude of tremor in patients with essential tremor and with postural tremor from a variety of other neurological disorders. Patients maintained postures requiring different angles of forward flexion in the sagittal plane, of horizontal flexion, and of elbow extension. The tremor of patients diagnosed with essential tremor was either unaffected or affected only little by changes in limb position. In contrast, patients with pathological tremors, of the cerebellar postural, parkinsonian, and other types, exhibited positional dependence of their tremor. When there was positional dependence of tremor, it was always largest when the hands were near the nose or chin. These observations suggest a practical method for assistance with the clinical discrimination of essential tremor from other postural tremors.

Adult↗
PubMed1985

Further studies on quantification of drug-induced tremor in mice: effects of antitremorgenic agents on tremor frequency.

The effects of diazepam, dantrolene and atropine on drug-induced tremors were investigated in mice from the point of view of the tremor frequency. The study involved a power spectral analysis of the random current induced by movement of a magnet (attached to the mouse) on a wire coil. To induce tremor, tremorine and harmaline were subcutaneously injected. The power spectral density function defined the frequency composition of the tremor and its severity was determined quantitatively in terms of the mean square value of the data in any frequency range of concern. Diazepam markedly depressed the power spectral density of the tremorine- and harmaline-induced tremor and reduced the tremor frequency. With higher doses of diazepam, the peak frequency of the tremorine-induced tremor shifted to the lower frequency side as if the tremor components were taken into the component of the spontaneous motor activity. Dantrolene and atropine suppressed the power spectral density without affecting tremor frequency. The relationship between the change of tremor frequency and the site of action of antitremorgenic agents are discussed.

Animals↗
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↗
PubMed1992

Orthostatic tremor associated with voice tremor.

We report a 67-year-old female with orthostatic and voice tremor. Her orthostatic tremor mainly affected her lower extremities, alternating between antagonist muscle groups at a frequency of 4.4-4.8 Hz. The voice tremor ranged between 4.8 and 8.8 Hz. In this case, the frequency of voice tremor was same as that of orthostatic tremor, suggesting a common origin from a tremor-generating mechanism. These tremors were diagnosed as 'forme fruste' of the essential tremor, not the incipient stage of Parkinson's disease. Medications including clonazepam, perphenazine, Dopa and trihexyphenidyl hydrochloride had no effect on both the orthostatic and voice tremors, but propranolol was somewhat beneficial on voice tremor.

Aged↗
PubMed1997

[Clinicophysiological study of tremor in Parkinson's disease: quantitative tremor-based assessment of motor count using actigraphy].

In Parkinson's disease, resting tremor is often the initial symptom. This report focuses on the mechanism underlying tremor in Parkinson's disease and quantitative assessment of tremor. Central factors including Vim (nucleus ventralis intermedius) in the thalamus, and peripheral factors, such as acceleration of input pathways from muscle spindles via muscle tonus, are important aspects of the tremor mechanism in Parkinson's disease. It has also been suggested that tremor in Parkinson's disease is associated with parasympathetic and sympathetic dysfunctions. Objective assessments of tremor, such as the application of surface electromyography, are useful in the diagnosis and treatment of Parkinson's disease. Actigraph, as introduced herein, is a three dimensional motor sensing apparatus. Therefore, motor counts over 0.01 G can be detected by actigraphy. To date, this device has been used for evaluating akinesia in Parkinson's disease and insomnia. In this study, actigraphy was used in Parkinson patients with tremor, and it reflected motor activity in the wrist and was associated with the severity of hand tremor. Activities of daily living (ADL) are disturbed by hyperkinesia of the hand for Parkinson patients with hand tremor. We demonstrated that actigraphy is a simple and quantitative method of assessing motor activity in Parkinson patients with tremor.

Aged↗
PubMed2004

Increased risk of head tremor in women with essential tremor: longitudinal data from the Rochester Epidemiology Project.

In one cross-sectional study of a community in northern Manhattan, women with essential tremor (ET) were more likely to have head tremor than were men. In that study, patients were seen at one point in time, rather than followed longitudinally. Head tremor often develops after arm tremor, and its appearance in patients with ET may therefore be a function of duration of follow-up. In a second epidemiological study utilizing the Rochester Epidemiology Project, in which ET subjects were followed from disease diagnosis to death, we determined whether there was an association between female gender and head tremor. We utilized the records-linkage system of the Rochester Epidemiology Project to identify ET cases. Records were reviewed and clinical data abstracted by a neurologist specializing in movement disorders. A second neurologist reviewed a subsample of records. There were 107 ET cases (69 women, 38 men) followed for 10.1 +/- 9.1 years from ET diagnosis to death. Head tremor was present in 37 (53.6%) women and 5 (13.2%) men (odds ratio [OR] = 7.6, 95% confidence interval [CI] = 2.7-21.9, P < 0.001). In a multivariate linear regression analysis, women remained at high risk for head tremor (OR = 6.5, 95% CI = 2.2-19.0, P = 0.001) independent of disease duration. We found in this longitudinal epidemiological study that women with ET were six times more likely to develop head tremor over the course of their illness than were men. The reason for the association between gender and head tremor, which has now been demonstrated in several studies, is not known, but it could reflect gender differences in the distribution of disease pathology within the brain.

Aged↗
PubMed1999

Function of the cerebellum in Parkinsonian rest tremor and Holmes' tremor.

We describe a patient who developed Parkinson's disease (PD) 17 years after resection of his right cerebellum because of a Lindau tumor. He showed a classic 4.3-Hz resting tremor on the left side but a 3.1-Hz resting, postural, and intention tremor on the right side compatible with midbrain tremor (Holmes' tremor). We conclude that the generator of the tremor in PD cannot be located within the olivocerebellar loop. The cerebellum, however, seems to modulate the tremor frequency of parkinsonian rest tremor and may prevent the rest tremor from transforming into a postural and goal-directed tremor.

Adult↗
PubMed1988

Orthostatic tremor: an essential tremor variant?

Three patients with a clear-cut history of essential tremor of the upper limbs presented with the clinical features reported by Heilman as orthostatic tremor. Electromyographic findings included 6-8 Hz postural tremor in all four limbs. Highly synchronized 16 Hz rhythmic discharges were found in the legs upon standing. This peculiar pattern of discharge was also observed in the upper limbs and spinal muscles. High frequency rhythmic bursts, either alternating or co-contracting were present in specific postures not necessarily related to standing. An additional group of 12 patients with postural tremor of the legs was studied; seven of these showed modification in the frequency and synchronization of the muscle discharges upon standing. Although none of them had the full-blown clinical syndrome of orthostatic tremor, they complained of mild unsteadiness upon standing, together with a vague sensation of stiffness in the lower limbs. The present findings induce us to think that there might be a link between essential tremor and the so-called orthostatic tremor. Orthostatic tremor might be an essential-tremor-related entity that may be caused by a derangement in the central mechanism in charge of the organization of certain motor activities, not necessarily controlling the standing position.

Aged↗
PubMed1991

Orthostatic tremor: an association with essential tremor.

Orthostatic tremor is characterized by tremor of the trunk and legs while standing. Rapid frequency has been emphasized as an important criterion for the diagnosis of this tremor. We observed five patients who had the typical findings of orthostatic tremor but had a wide range of frequencies. All five also had postural hand tremor and a family history of essential tremor, suggesting a relationship between orthostatic tremor and essential tremor. This report also emphasizes the association of orthostatic tremor with painful cramps and a relatively consistent improvement with clonazepam.

Aged↗
PubMed2004

Muscle loading as a method to isolate the underlying tremor components in essential tremor and Parkinson's disease.

Tremor is clinically evaluated and classified on the basis of its response to limb posture (resting, postural, and kinetic tremor), but the mechanisms underlying this powerful influence remain unclear and no satisfactory method exists to identify or quantify underlying tremor subtypes. Postural change is closely linked to changes in gravitational load. We therefore assessed the effect of changes in muscle load on essential tremor (ET) and parkinsonian tremor (PT) independently of postural change. A motor accurately delivered a series of constant (0.2-1.2 Nm) flexion and extension torques about the affected wrist while subjects maintained a constant wrist angle by isometrically contracting wrist flexors or extensors against the applied loads. Linear regression of tremulous electromyogram (EMG) spectral peak amplitude against the applied loads estimated the magnitudes of the load-dependent (LDT) and load-independent (LIT) tremor components. The amplitude of ET was linearly related to increase in gravitational load. It thus contained a large LDT component and a small or absent LIT component. Muscle loading revealed significant LDT and LIT components in PT. LIT was dominant at zero load (classic rest tremor) but both components were present during loading (classic postural tremor). Muscle loading more clearly identifies tremor subtypes than postural effects alone. The method could be applied in clinical and pathophysiological studies.

Analysis of Variance↗
PubMed2003

Localization of thalamic cells with tremor-frequency activity in Parkinson's disease and essential tremor.

It has been reported that parkinsonian and essential tremor can be controlled by deep brain stimulation or radiofrequency lesion within the cluster of cells with a tremor-frequency activity in the ventral thalamic nuclei. However, there have been very few reports about the exact localization of cells with tremor-frequency activity in the ventral thalamic nuclei. In the present study, we investigated the localization of cells with tremor-frequency activity in the ventral thalamic nuclei employing autopower spectrum and coherence analysis. Activity of a total of 130 cells, 63 in patients with parkinsonian tremor and 67 in patients with essential tremor, were recorded from the area anterior to the nucleus ventralis caudalis. Among these cells, 31 cells showed a coherence of greater than 0.4 to the electromyographic activity of both agonist and antagonist muscles. The proportion of cells exhibiting tremor-frequency activity were 26.8% in the nucleus ventralis intermedius (Vim) and 25.0% in the nuclei ventralis oralis posterior et anterior (Vop + Voa). There were no significant differences in proportion by nuclear location or disease. The present study demonstrated that cells with tremor-frequency activity are widely distributed over the area extending from the Vim to the Vop + Voa. This indicates that the best location for placing electrodes for deep brain stimulation or a radiofrequency lesion cannot be defined by identification of cells with tremor-frequency activity alone.

Action Potentials↗
PubMed1987

Primidone and propranolol in essential tremor: a study based on quantitative tremor recording and plasma anticonvulsant levels.

Primidone was compared to the unselective beta adrenoceptor antagonist propranolol in the suppression of essential tremor. In a 4-week single-blind placebo-controlled study primidone was given in increasing doses from 62.5 mg X 1 up to 250 mg X 3 daily and propranolol 20 mg X 3 daily. The drugs produced a similar reduction in the degree of tremor after 2 and 1 weeks' medication respectively. This indicates that primidone can be an alternative to propranolol when beta-blockers are contraindicated. However, primidone was significantly even more effective in the beginning after only 2 doses, when at the same time 10 of 13 patients showed a maximum of acute toxic side-effects producing nausea, vomiting, giddiness and/or sedation. Correlation analysis between the individual tremor amplitude reductions and plasma primidone concentrations showed on the second day a tendency towards a greater reduction in tremor in those patients with the highest primidone plasma concentration. By the fourteenth day tremor had increased compared with the second day and correlation analysis between individual increase in tremor amplitude and plasma phenobarbital concentrations showed the highest degree of tremor increase in those patients who had the highest levels of phenobarbital. These and other data suggest that after the first doses, tremor suppression and acute toxicity is related to the initial exposure to primidone and the plasma level of the drug itself rather than its metabolites phenobarbital and phenylethylmalanomide. The individual tremor frequency spectrums did not change significantly during the placebo and propranolol periods, whereas the frequency tended to decrease during the primidone period.

Adrenergic beta-Antagonists↗
PubMed1993

Is parkinsonian arm tremor a resting tremor?

Arm tremor in Parkinson's disease occurs during rest which has been explained by a specific tremulous mechanism activated during rest. During action or posture maintenance, the tremor may persist or recur, but with reduced amplitude. We present 2 patients with idiopathic Parkinson's disease who showed persisting arm tremor which was most marked during action rather than during rest. The patterns of upper limb tremor were investigated during rest, maintenance of fixed posture, and slow movement, using an advanced computerized movement-monitoring system (Coda 3). Four parkinsonian patients showing tremor under all conditions were studied, comparing 2 patients whose tremor was most marked during rest with 2 whose tremor was most marked during action. All showed intermediate amplitudes during posture maintenance. Patterns of tremor frequency were very similar between patients, irrespective of amplitude characteristics. These features suggest that tremors in all patients originate in a single, complex mechanism which may involve both central and peripheral mechanisms.

Aged↗
PubMed2002

[Speech-related tremor of lips: a focal task-specific tremor].

We report a 66-year-old Japanese woman in whom tremor of lips appeared during speech. Her past and family histories were unremarkable. On neurological examination, there was no abnormal finding except the lip tremor. Results of laboratory findings were all within normal levels. Her MRI and EEG were normal. Surface EMG studies revealed that regular grouped discharges at a frequency of about 4-5 Hz appeared in the orbicularis oris muscle only during voluntary speaking. The tremor was not observed under conditions of a purposeless phonation or a vocalization of a simple word, suggesting that the tremor was not a vocal tremor but a task-specific tremor related to speaking. Administration of a beta-blocker and consumption of small amount of alcohol could effectively improve the tremor, possibly suggesting that this type of tremor might be a clinical variant of essential tremor.

Aged↗