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PubMed1983

The correlation between tremor characteristics and the predicted volume of effective lesions in stereotaxic nucleus ventralis intermedius thalamotomy.

In 51 cases (6 cases with bilateral operations) with various kinds of tremor, stereotaxic ventralis intermedius (Vim) thalamotomies were performed using Leksell's apparatus and the results of operation evaluated. Several characteristics of the tremor, including clinical features and EMG, were correlated with the assumed location and volume of the coagulative lesion. In 54 of the 57 operations, the thalamic Vim nucleus was identified physiologically and a therapeutic lesion placed at a site that included the Vim neurons. In all these cases, except one in which the lesion was estimated to be too small, tremor was immediately abolished by a relatively small lesion. The estimated volume of the lesion was about 40 to 200 mm3 and the effect persisted over a long follow-up period (maximum ten years). The size of the lesion that was necessary apparently depended on several features of the tremor. A larger lesion was required in cases of movement type tremor, tremor with a low rate (less than 4 Hz), tremor of high amplitude (more than 600 microV), and tremor involving proximal muscles or with a wide distribution. Tremor following a cerebrovascular lesion and post-traumatic tremor were characterized by coarse oscillation (high amplitude and low frequency) involving proximal muscles. A relatively larger coagulative lesion was therefore necessary to relieve this type of tremor. In contrast, parkinsonian and essential tremor were usually of low amplitude and distal in distribution. For the relief of such tremor, the lesion could be very small: if aided by electrophysiological methods to identify Vim neurons, the minimal effective volume of the lesion was estimated as about 40 mm3 and restricted to the Vim nucleus. Based on these results, the importance of the Vim nucleus in tremor mechanisms is discussed.

Adult↗
PubMed1987

Essential tremor variants: effect of treatment.

Essential tremor may not represent a single condition. Subclassifications include kinetic predominant tremor; combined resting-postural tremor; primary writing tremor; isolated voice, chin, or tongue tremor; and orthostatic truncal tremor. We report patients with these disorders. An association of these conditions with essential tremor is suggested by a high occurrence of a family history of essential tremor, frequent presence of a mild postural tremor, and tremor reduction with alcohol ingestion. Pharmacologic responsiveness is different for these disorders. Propranolol and primidone often have beneficial effects but clonazepam was the only drug effective in some cases of kinetic predominant tremor and in orthostatic truncal tremor. Combined resting-postural tremor and voice tremor were often unresponsive to treatment.

Adult↗
PubMed2004

Postural hand tremor before and following liver transplantation and immunosuppression with cyclosporine or tacrolimus in patients without clinical signs of hepatic encephalopathy.

OBJECTIVE: To assess tremor characteristics and severity in patients with severe liver disease without hepatic encephalopathy and following orthotopic liver transplantation (LTX) and immunosuppression (IS) with cyclosporin A (CsA) or tacrolimus (FK 506). METHODS: A total of 35 consecutive patients were included into the prospective study and serum levels of CsA (n = 29) or FK 506 (n = 6) were monitored following LTX. Tremor characteristics and severity were assessed by two-blinded raters before and following LTX. In addition, accelerometric recordings were taken before and after LTX, and compared with 16 normal controls without tremor and without clinical signs of hepatic encephalopathy or liver disease. Accelerometry was performed while sitting in a comfortable chair with the forearms supported and included rest and postural condition with and without weight load (500 g) on each hand. Kolmogorov-Smirnov test, paired t-test and t-test for independent samples were used for statistical analysis. RESULTS: The clinical rating revealed no rest but a mild postural hand tremor before LTX with a significant increase following LTX (p < 0.001). After LTX the mean score of postural tremor was significantly (p < 0.05) higher in patients with plasma levels of >850 ng CsA/ml compared with patients with lower levels. Patients and normal controls showed comparable mean peak frequencies of rest and postural hand tremor. The mean amplitude of postural hand tremor was significantly higher in patients before and after LTX compared with controls. In the majority of patients (89%) and controls (88%), the dominant tremor frequency decreased significantly (>1.5 Hz) when applying a weight load on each hand. CONCLUSION: The present study is the first to describe hand tremor characteristics in patients with severe liver disease without clinical signs of hepatic encephalopathy and in patients following LTX and IS. Compared with normal controls the patients showed a significant postural hand tremor prior and post-LTX and an increase of mean tremor amplitude following LTX and CsA/FK 506 treatment. The decrease of the dominant tremor frequency with weight load and an increase of tremor amplitude with higher plasma levels of CsA are both indicative of an enhanced physiological or toxic tremor.

Adult↗
PubMed2001

Evidence for familial aggregation of tremor in normal individuals.

BACKGROUND: Tremor occurs in most normal individuals, and this tremor may offer basic clues about the mechanisms of neuromuscular control. It is not known whether genetic factors influence the magnitude of tremor in normal families. OBJECTIVE: To assess the familial aggregation of tremor in normal families. METHODS: Control subjects from the Washington Heights-Inwood community in northern Manhattan, NY, were enrolled in a family study. These subjects and their first- and second-degree relatives underwent a videotaped tremor examination. Two neurologists rated the severity of tremor on the videotaped examination, assigning a total tremor score (0 to 36 [maximum]). Associations between the control subjects' and their relatives' total tremor scores were assessed using correlation coefficients and linear regression analysis. In addition, maximum likelihood methods were used to fit a linear mixed-effects model to the total tremor scores of probands and their siblings, after excluding any relatives with essential tremor. RESULTS: There were 56 control subjects and 226 relatives. Tremor was clinically detectable in 221 (97.8%) of 226 relatives. There was an association between the control subjects' total tremor scores and those of their siblings (r = 0.40; p = 0.018), those of all of their first-degree relatives (siblings and children combined, r = 0.20; p = 0.037), but not those of their second-degree relatives (r = 0.002; p = 0.99). In analyses of probands and normal siblings, the estimate of the variance of the family-specific component of the age-adjusted total tremor score was different from zero (p < 0.005), and the family specific component was estimated to account for 52% of the variability in the scores. CONCLUSIONS: Tremor aggregates in normal families, suggesting that genetic factors may contribute to its etiology. Other studies might be designed by investigators to identify these genes through genetic linkage or association analysis. Identification of such genes would help to elucidate the mechanisms underlying this ubiquitous condition.

Adult↗
PubMed2001

[Assessment of anti-tremorogenic drugs using nicotine-induced tail-tremor model and elucidation of the mechanism].

Repeated administration of nicotine causes a tremor only in the tail (tail-tremor) of rats. The tremor is accompanied with locomotor hyperactivity without rigidity and immobility of the whole body, suggesting the involvement of the mechanism associated with the movement. The tail-tremor induced by nicotine was suppressed by nicotinic acethylcholine (nACh) receptor antagonists, but not by muscarinic acethylcholine (mACh) receptor antagonists. Moreover, the tail-tremor was suppressed by beta-adrenoceptor antagonists and benzodizepines. The tremor at rest is observed only in Parkinson's disease, which is improved by the use of mACh receptor antagonists. An essential tremor is one of the typical tremor connected with the movement (postural tremor) and improved with beta-adrenoceptor antagonists. These findings and results suggest that the nicotine-induced tail-tremor is useful for the study of the essential tremor as an animal model. On the other hand, daily administration of nicotine resulted in an augmentation of the tail-tremor. The development of the tail-tremor was suppressed by nACh receptor antagonists, N-methyl-D-aspartate (NMDA) receptor antagonists and nitric oxide (NO) synthase inhibitors. These results suggest that central nACh receptors are essential for the onset and further development of the tail-tremor induced by repeated administration of nicotine, and that NO formation mediated by NMDA receptors is involved in the developmental mechanisms.

Adrenergic beta-Antagonists↗
PubMed2002

Bilateral thalamic deep brain stimulation for the treatment of head tremor. Report of two cases.

Isolated head tremor is rare, but can be disabling. The authors' experience with the treatment of limb tremor due to essential tremor led them to consider using bilateral thalamic deep brain stimulation (DBS) in two patients presenting only with disabling head tremor. One patient exhibited no peripheral tremor and the other displayed only a slight upper-limb tremor. Both patients underwent placement of units that apply simultaneous bilateral thalamic DBS. Surgical targets were verified by using intraoperative macrostimulation, and the stimulators were implanted during the same surgery. Patients were videotaped preoperatively and at 2, 4, 6, and 9 months postoperatively during periods in which the stimulators were turned on and off. Videotapes were randomized and rated for resting, postural, and action tremors according to the Fahn clinical rating scale for tremor. Because this scale is not designed for head tremor, the patients were also evaluated on the basis of a functional scale that reflected their quality of life and the amount of disability caused by head tremor. Both patients experienced no tremor after their stimulators were turned on and properly adjusted at the 6th postoperative week. The patients were followed for a total of 9 months and results remained stable throughout this period. No complications were encountered. Bilateral thalamic DBS appears to be an effective and safe treatment for isolated head tremor in patients with essential tremor. The authors present a scale for the functional assessment of head tremor.

Adult↗
PubMed1999

Classification of tremor and update on treatment.

Tremor is a symptom of many disorders, including Parkinson's disease, essential tremor, orthostatic tremor, cerebellar disease, peripheral neuropathy and alcohol withdrawal. Tremors may be classified as postural, rest or action tremors. Symptomatic treatment is tailored to the tremor type. Combination therapy with carbidopa and levodopa remains the first-line approach for parkinsonian tremor. Essential tremor may be amenable to propranolol or primidone. Propranolol may be useful in treating alcohol withdrawal tremor, and isoniazid may control the cerebellar tremor associated with multiple sclerosis. Clonazepam may relieve orthostatic tremor. Other agents are also available for the treatment of tremor. When medical therapy fails to control the tremor, surgical options such as thalamotomy, pallidotomy and thalamic stimulation should be considered in severe cases. Thalamic stimulation, the most recent of these surgical approaches, offers the advantage over ablative procedures of alleviating tremor without the creation of a permanent lesion.

Diagnosis, Differential↗
PubMed1987

[Orthostatic tremor: clinical aspects, pathophysiology and therapy].

Orthostatic tremor is characterized by its isolated occurrence in leg and trunk muscles during standing with undisturbed sitting, lying and walking. In a female patient with this tremor syndrome the basic electrophysiological feature of muscle activity was a 16 Hz, highly synchronized tremor in all leg muscles and sometimes in the arm muscles. This rhythmic EMG activity however, was not restricted to stance but occurred during all kinds of muscle activation in sitting, lying or standing positions, despite only standing was accompanied by a subjective sensation of unsteadiness and falling to the ground. Mechanical tremor analysis at the patella revealed an additional 8 Hz tremor caused by alternating large and small amplitudes of the 16 Hz tremor bursts. The occurrence of the 8 Hz tremor was much more related to the feeling of unsteadiness than the 16 Hz tremor. Single motor units mostly fired at a frequency of 8 Hz, but only at the time of tremor bursts. Hence the 16 Hz-pattern may not be explained as the result of a pure motoneuronal abnormality. There were no indications for abnormal reflexes contributing to tremor genesis. A fixed time relation of the tremor bursts in different muscles has been found suggesting a common generator within the CNS for the tremor. After successfully treatment with Primidon the pattern of muscle activation was normalized during sitting and lying, however, during standing and walking the 16 Hz tremor was still present. We believe that an unknown central oscillator is causing the tremor and central structures which are involved in stance regulation have a predominant access to switch on this oscillator.

Diagnosis, Differential↗
PubMedDate not supplied

Alcohol withdrawal tremor.

It is well known that during the withdrawal period after chronic alcohol intake, tremor is one of the symptoms that disturb patients. Alcohol withdrawal tremor might be a variant of enhanced physiological tremor, most often caused by anxiety or emotional stress. The aim of this investigation was to establish the EMG pattern of alcoholic tremor and to compare it with the well known pattern of enhanced physiological tremor caused by anxiety or emotional stress. Forty patients 20-43 years old were investigated by a neurologist and psychiatrist 1-10 days after acute alcohol withdrawal. They all met the criteria for chronic alcoholism. Thirty three patients 26-43 years old with the complaint of tremor and anxiety or emotional stress were also investigated. An electromyographic investigation was performed to evaluate the pattern, frequency and amplitude of tremor. Results revealed that both groups of patients had 8-12 Hz low amplitude postural tremor with synchronous activity in antagonist muscles. Patients with alcohol withdrawal tremor had significantly higher amplitude tremor compared with patients with anxiety and emotional stress. No other clinical or electromyographic differences existed between both groups. In conclusion alcohol withdrawal tremor is a variant of enhanced physiological tremor. Both types of tremor could be distinguished only by the circumstances responsible for tremor occurrence.

Adult↗
PubMed1997

[Assessment of anti-tremorogenic drugs--nicotine-induced tail-tremor model].

The repeated administration of nicotine at small doses, which do not produce whole body tremor or convulsion, causes tremor only in the tail (tail-tremor) of rats. The tremor is accompanied by locomotor hyperactivity without rigidity and immobility of the whole body, suggesting that the nicotine-induced tail-tremor model is useful for studying the mechanism underlying tremor associated with movement. The tail-tremor induced by nicotine was suppressed by mecamylamine, a nicotinic antagonist, but not by atropine or scopolamine, muscalinic antagonists. Moreover, the tail-tremor was suppressed by the beta-blockers propranolol and pindolol, as well as the benzodiazepines diazepam and clonazepam. Tremor at rest is observed only in Parkinson's disease, which is improved with anti-muscalinic drugs. Essential tremor is one of the typical tremors connected with movement (postural and kinetic tremor) and is improved with beta-blocker. These findings and results suggest that nicotine-induced tail-tremor is useful for the study of essential tremor in animal models.

Adrenergic beta-Antagonists↗
PubMed1982

A normative study of postural tremor of the hand.

In a normative study of amplitude, frequency, and variability of postural tremor of the hand in 97 normal subjects, 15 to 80 years old, tremor was transduced using accelerometers and characterized by power spectral analysis. Tremor amplitude ranged from a 0.0015- to 0.035-g peak at the dominant frequency. The modal tremor amplitude was 0.01-g peak, and the threshold for "visible tremor" was 0.007-g peak. The modal tremor frequency was constant at about 7 Hz in those subjects up to 70 years old and thereafter decreased to about 6 Hz. The mean range of variability of the dominant frequency was 2.5 Hz. The tremor pattern, characterized by the shape of spectra, varied greatly from a single finely tuned peak to multiple broad peaks. More than two thirds of normal subjects showed complex spectral patterns with more than one peak of significance. Passive resonance of the hand tissues was an important factor in determining dominant tremor frequencies in most subjects. Many subjects showed a strong, albeit variable , cardioballistic component. The results provide baseline data for studies of the effects of drugs on tremor, particularly in cases of "essential" tremor, and provide warnings that such studies require objective recording methods for adequate evaluation and need recourse to measurement of several factors of the tremor to elucidate the component of tremor affected by a drug. A scaling of tremor can be used in terms of reference to the strength of gravitational acceleration (1.0 g), which provides simple numerical relationships.

Adolescent↗
PubMed2000

Ethnic differences in essential tremor.

BACKGROUND: Ethnic differences in the clinical characteristics (severity and distribution) of essential tumor (ET) have not been studied. The presence of these differences suggests that ET is not a homogeneous disease and that there is variability in disease expression under different circumstances. As part of a community-based study, we evaluated a multiethnic group of cases. OBJECTIVE: To assess whether there are ethnic differences in the clinical characteristics of ET. METHODS: Elderly residents of Washington Heights-Inwood, New York, were enrolled in a community-based health study (N = 2117). Participants underwent a medical interview and a neurological examination conducted by a neurologist, and subjects with ET were identified. These subjects with ET were then enrolled in a community-based study of ET and underwent a tremor interview, a videotaped tremor examination, and in some cases, a performance-based test of function and quantitative computerized tremor analysis. A total tremor score (range, 0-36, with 0 indicating no tremor and 36 indicating maximum tremor) was assigned to each subject based on 2 neurologists' ratings of the tremor examination. RESULTS: Among 62 subjects with ET (white [n = 16], African American [n = 18], and Hispanic [n = 28]), there were ethnic differences in the total tremor score (F = 3.68, P = .03). In a multiple regression model adjusting for age, white subjects had a mean total tremor score that was 5.3 points lower than that of nonwhite subjects (P = .008). We divided the nonwhite group into African American and Hispanic subgroups. In a regression model adjusting for age and duration, the white group had a mean total tremor score that was 6.1 points lower than that of the Hispanic group (P = .07) and 7.2 points lower than that of the African American group (P = .05). The mean performance-based test score was 1.7 times higher in the African American group and 2.1 times higher in the Hispanic group compared with the white group (P = .38). No subjects in the African American group had head tremor, while 4 subjects in the white group (25%) and 8 subjects in the Hispanic group (29%) did have head tremor (chi2 = 6.17, P = .05). CONCLUSIONS: There are ethnic differences in the expression of ET, suggesting that ET is not a homogeneous disorder. These differences may reflect phenotypic variability caused by genotypic differences or differences in exposure to environmental factors that influence tremor.

Black or African American↗
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↗
PubMed2000

Validation of a portable instrument for assessing tremor severity in epidemiologic field studies.

BACKGROUND: An important part of epidemiologic and genetic studies of essential tremor (ET) is an assessment of tremor severity. Clinical rating scales are semiquantitative and computerized tremor analysis, available at tertiary medical centers, is not transportable into the field. As part of an epidemiologic study, we modified the Klove-Matthews Motor Steadiness Battery, collecting objective quantitative data on tremor severity in patients with ET and control subjects. OBJECTIVE: To describe the modified Klove-Matthews Motor Steadiness Battery, validate this test battery against several other measures of tremor severity, demonstrate test-retest reliability, and provide standard reference values for normal control subjects and patients with ET who undergo this test battery. METHODS: Patients with ET and control subjects, ascertained from both a clinic and a community, underwent a standardized evaluation including a demographic and medical questionnaire, tremor disability questionnaire, videotaped tremor examination, performance-based test, modified Klove-Matthews Motor Steadiness Battery (Groove-Type Steadiness Tester [GTST] and Nine-Hole Steadiness Tester [NHST]), and quantitative computerized tremor analysis. RESULTS: There were 19 patients with ET and 28 control subjects. NHST and GTST total scores were correlated significantly with the tremor disability questionnaire score (r = 0.63, p = 0.001 and r = 0.49, p = 0.016), total tremor score (tremor examination, r = 0.68, p<0.001 and r = 0.41, p = 0.005), performance-based test score (r = 0.81, p<0.001 and r = 0.65, p = 0.001), and quantitative computerized tremor analysis results (for example, spiral drawing, r = 0.62, p = 0.01 and r = 0.58, p = 0.019). Test-retest reliability was generally high (r = 0.79-0.94, p<0.001). CONCLUSION: The modified Klove-Matthews Motor Steadiness Battery provides a reliable and valid means to collect objective quantitative data on tremor severity. Rapidity of administration and ease of transport make it a potentially useful tool in epidemiologic and genetic field studies.

Adult↗
PubMed2005

Olfaction testing in patients with tremor-dominant Parkinson's disease: is this a distinct condition?

There is considerable controversy regarding the relationship between essential tremor (ET) and Parkinson's disease (PD), especially when tremor is the dominant feature of PD or there is a family history of tremor. Reduced olfaction function is one of the initial signs of PD. In contrast, ET has relatively preserved olfaction. To infer whether the tremor-dominant subgroup of PD is intrinsically different from mainstream PD, we tested olfaction using the University of Pennsylvania Smell Identification Test-40 (UPSIT) in this group and compared the findings with those of patients with non-tremor-dominant "regular" PD. We then evaluated predictors of reduced UPSIT scores within the tremor-dominant group. Overall, olfaction did not differ between tremor-dominant PD and regular PD; however, the subgroup of tremor-dominant PD with a family history of tremor had less olfaction loss than those without a family history (P = 0.0007) or those with regular PD (P = 0.0350). Other clinical features of this tremor-dominant PD with a family history of tremor group mostly resembled those without a family history. This finding suggests that patients with a family history of tremor may represent a different disease process even though, aside from differences in olfaction, they are clinically similar to other patients with tremor-dominant parkinsonism. It additionally suggests phenotypic overlap between PD and ET.

Aged↗
PubMed2006

Uniform qualitative electrophysiological changes in postoperative rest tremor.

Ablation and deep brain stimulation (DBS) can treat pharmacologically uncontrollable tremor. Here, we compared the postoperative electrophysiological changes in resting hand tremor after 32 ablations and 12 DBS implantations in patients with severe tremor-dominant idiopathic Parkinson's disease (PD) and essential tremor (ET). Short- and long-term accelerometric data were acquired after surgery and were compared to the preoperative tremor. After effective surgical treatments, significant rest tremor reduction and increase in both frequency and approximate entropy (ApEn) were detected in all PD cases, irrespective of the type and target of intervention. However, the long-term effect of DBS implantation on tremor reduction was significantly better compared to that after ablative treatments. In cases of thalamotomy, the postoperative increase in frequency and ApEn was significantly larger in essential tremor compared to PD, suggesting that the etiology of tremor may influence the size of the similar changes. However, cases where clinical tremor re-emerged 6 to 12 months after the surgery, no change in frequency and ApEn was detected on the second postoperative day, despite an initial tremor reduction and clinical improvement similar to the effective operations. Our results suggest that uniform postoperative changes in rest tremor and the increase in frequency and ApEn could be due to attenuation of pathological oscillators and might be immediate indicators of the effectiveness of neurosurgical treatments relieving tremor.

Cautery↗
PubMed1996

Quantification of essential tremor in writing and drawing.

Eighty-seven patients, aged 15-84 years (mean, 61.8 +/- 16.2 SD), with essential tremor wrote two series of cursive e's and cursive l's on a standard sheet of ruled paper that was mounted on a commercially available digitizing tablet. Forty patients also drew an Archimedes spiral. Postural wrist tremor was measured with a triaxial accelerometer on the dorsum of the horizontally extended hand. The digitizing tablet was sufficiently sensitive to measure sustained visible tremor. Very severe tremor could not be recorded when it prevented a patient from keeping the ballpoint pen on the tablet. The intertrial variability of the handwriting data was such that a 36.0% change in mean acceleration amplitude (cm/s2) and an 8.3% change in mean tremor frequency (Hz) could be detected in the hypothetical population of 30 patients (paired-sample t test, p = 0.01, power = 90%). The intertrial changes detectable with accelerometry were 35.9% (amplitude) and 7.8% (frequency). The correlations between wrist tremor and writing tremor were < 0.60 for amplitude and < 0.25 for frequency. Significant correlations between patient age and tremor frequency and between tremor amplitude and frequency existed for postural tremor but not for writing or drawing tremor. Standard digitizing tablets for personal computers are useful in the quantitative assessment of writing tremor. The amplitude and frequency characteristics of tremor in posture, writing, and drawing may differ significantly.

Adolescent↗
PubMed2001

Concurrent quantification of tremor and depression of locomotor activity induced in rats by harmaline and physostigmine.

RATIONALE: Both harmaline and physostigmine are known to produce whole-body tremors in rodents, yet there is little quantitative information on the differential frequency characteristics of these tremors or on other possible motor effects of these drugs. In addition, the degree to which tolerance develops to their tremorogenic effects is uncertain. OBJECTIVES: The purpose of this work was to use a new kind of instrument (the force-plate actometer) to describe quantitatively the frequency characteristics of tremor induced by the two drugs and simultaneously to measure locomotor activity effects. Another aim was to detect any tolerance effects on the tremor or locomotor measurements. METHODS: Sprague-Dawley rats in four separate groups received harmaline (0, 4.0, 8.0, and 16.0 mg/kg) while another four groups received physostigmine (0, 0.10, 0.25, and 0.50 mg/kg). Dosing continued for 4 consecutive days. Each day, every rat's whole-body tremor and locomotor activity were recorded for 30 min. Fourier analysis of the force-plate recordings was used to quantify tremor and characterize its frequency components. RESULTS: Harmaline induced a dose-related tremor that peaked in the 10 Hz region of the spectrum, while the dose related-tremor of physostigmine was demonstrably of a broader-band frequency composition. While harmaline tremor exhibited pronounced tolerance, physostigmine tremor remained substantial across the 4 days of dosing. Both drugs suppressed locomotor activity, and there was no tolerance on this measure for either drug. CONCLUSIONS: In regard to tremor, harmaline and physostigmine induced quantitatively different kinds of tremor, and these differences probably reflect the drugs' different sites of action in the brain (harmaline: inferior olive; physostigmine: basal ganglia). For harmaline, tolerance to the tremorogenic effect was concurrent with a lack of tolerance to locomotor suppression, and this finding suggested the presence of a strong motor effect of harmaline that continued to be expressed despite the absence of tremor.

Animals↗