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High-frequency stimulation of the subthalamic nucleus suppresses experimental resting tremor in the monkey.

The effect of high-frequency stimulation of the subthalamic nucleus on parkinsonian-like resting tremor was investigated in two monkeys (Macaca fascicularis). Unilateral tremor of the arm and leg was induced by electrical coagulation of the brainstem area including the substantia nigra and the red nucleus. The tremor was only seen at rest condition with a very stable frequency of 4.46+/-0.59 Hz (mean+/-S.D.). Apomorphine (0.10-0.4 mg/kg, s.c.) completely blocked the tremor, suggesting that it was a dopaminergic-dependent symptom just like the parkinsonian tremor. When the stimulating frequency varied from 20 to 1000 Hz, both mono- and bipolar stimulation (square pulses, 0-5 mA, 0.06 ms) of the subthalamic nucleus suppressed resting tremor in a frequency-dependent manner but monopolar stimulation was more effective. These effects remained stable for more than two years. The present results suggest that the subthalamic nucleus is involved in the control and mechanism of resting tremor and that the high-frequency stimulation of the subthalamic nucleus can be used as an alternative therapy in parkinsonian patients with akinesia, rigidity and resting tremor.

Animals↗

Sensitivity and specificity of a portable system measuring postural tremor.

A portable, accelerometric system measuring tremor was evaluated. That is, the validity and consistency of measurements as well as its ability to discriminate pathologic from physiological tremor were investigated. Control subjects and patients with Parkinson's disease were tested with this portable system and with an independent system that gave precise displacement data using lasers. It was found that amplitude of postural tremor as measured by the two systems differed significantly, but further investigation revealed that this difference was due 1) to the difference between amplitude of acceleration and amplitude of displacement, and 2) to changes in tremor over the time between tests, rather than to any inaccuracy or unreliability in the portable system. The other characteristics of tremor reported by the portable system were also valid and reasonably reliable in test-retest experiments, with the exception of the "harmonic index," which proved less stable. Most of the reported characteristics were distributed differently for the control group and for the patients with Parkinson's disease, but the large overlaps between distributions would make diagnosis difficult when tremor is not very pronounced. These results suggest that until better discriminating measures of tremor are available, tremor tests should be repeated and combined with other tests of motor function.

Humans↗

Effect of electrical stimulation of the thalamic Vim nucleus on hand tremor during stereotactic thalamotomy.

OBJECTIVE: The aim of this study was to analyze the correlation between neuronal responses in the thalamic ventralis intermedius (Vim) nucleus to peripheral, natural stimulation and the modulation of tremor by electrical stimulation during stereotactic thalamotomy. DESIGN AND METHODS: The authors studied 36 patients with hand tremor using a microelectrode. The responses of tremor to electrical stimulation were analysed electromyographically. Sixty stimulation sites were divided into three groups. RESULTS: Group A (20 sites) where responses to stretching of the contralateral forearm muscles were recorded. Group B (26 sites) where responses to stretching of the other muscles of the upper extremity were recorded. Electrical stimulation at sites in groups A and B temporarily suppressed the contralateral tremor, but the minimum current intensity to suppress tremor at sites in group A was less than that in group B. Electrical stimulation in group C (14 sites), where kinesthetic responses of contralateral lower extremity were recorded, resulted in increased amplitude of hand tremor. Selective coagulation including the area of tremor suppression resulted in abolition of the tremor in all patients. CONCLUSIONS: These results suggest that the most effective site for thalamotomy may also be suitable for chronic stimulation in the Vim nucleus.

Electric Stimulation↗

Classification of normal and pathological tremors using a multidimensional electromagnetic system.

A new multidimensional movement analysis system was used to record limb tremor over six degrees-of-freedom, and signal processing techniques were explored to develop a suitable classification method to distinguish between different types of tremor. The specific aims were to investigate the ability of the system to screen for differences between normal subjects and a group of neurological patients, and then to differentiate between three diagnostic groups of patients. Postural tremor at the hand was recorded in normal subjects (n=24) and patients with essential tremor (n=21), multiple sclerosis (n=17) and parkinsonism (n=19). Data were collected using a 3Space Fastrak((R)) (Polhemus, Inc.) over six degrees-of-freedom (three translational directions and three rotations). Spectral estimates produced measures of tremor frequency and amplitude. Mathematical models of the data, using autoregressive modelling and K-nearest neighbour classification, produced parameters used to classify, (1) the normal subjects and 24 patients (using the three rotational movements), and (2) the three patient groups (using all six movement directions). Results were given in terms of the probability of each subject belonging to the groups being classified. 70%). The diagnostic classification produced clear differences between the patient groups (60% for essential tremor, 80% for multiple sclerosis and 60% for parkinsonism). The ability of this assessment technique to distinguish between postural tremor in normal subjects and neurological patients suggests that it could be developed as a screening tool. Classification of tremors between the patients groups, with a high degree of sensitivity, indicates the potential for further development of the system as a diagnostic aid.

Adult↗

Characteristics of physiologic tremor in young and elderly adults.

OBJECTIVE: To determine the prevalence of tremor-related motor-unit entrainment in young and elderly adults. METHODS: Postural hand tremor in neurologically healthy people, age ranges 20-42 (59 women and 41 men) and 70-92 (50 women and 50 men) years, was studied with accelerometry and forearm electromyogram (EMG). Tremor was recorded with and without a 300 g load distributed over the distal half of the horizontally extended hand and was analyzed with Fourier spectral techniques. RESULTS: No tremor-related spectral peak was found in the EMG of 59 young and 65 elderly controls, and inconsistent EMG peaks were observed in 29 young and 21 elderly. Twelve young and 14 elderly people exhibited a well-defined tremor-coherent EMG peak with and without 300 g loading, and the frequency of the EMG peak decreased less than 1 Hz in 8 young and 7 elderly. The EMG peak frequency was 9-12 Hz during mass loading in all 8 young adults but in only two elderly adults. The other 5 elderly people had peak frequencies at 5-7 Hz. Age had no significant effect on the frequency and amplitude of the mechanical-resonant component of hand tremor. CONCLUSIONS: Approximately 8% of young and elderly adult controls have an EMG-acceleration pattern that is indistinguishable from mild essential tremor. SIGNIFICANCE: These results provide a framework for the interpretation of electrophysiologic studies in patients with suspected essential tremor.

Adult↗

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↗

Thalamic deep brain stimulation for essential tremor: recommendations for long-term outcome analysis.

OBJECTIVES: Determine the efficacy of thalamic deep brain stimulation (DBS) for tremor control among individuals with essential tremor (ET). METHODS: A clinical series of 52 consecutive individuals undergoing placement of a DBS system for treatment of ET completed an unblinded battery of subjective and objective measures at postoperative intervals of one, three, and 12 months, and annually thereafter up to three years. The assessment battery included measures of tremor and activities of daily living. RESULTS: Both subjective and objective measures showed that stimulation was associated with significant improvement at nearly every postoperative interval as compared to pre-operative and stimulation 'off' ratings of activities of daily living functioning, midline tremor, contralateral upper extremity tremor, and contralateral lower extremity tremor. Ipsilateral tremor showed some improvement with stimulation, but only within the first three months. Trend analysis showed stable tremor control. Stimulation settings remained largely unchanged after the first three months. Dysarthria was more common among those with bilateral stimulation. A range of missing data estimation methods were performed, and subsequent analyses corroborated the main findings of the study. CONCLUSION: Thalamic DBS is generally a well-tolerated and effective treatment for ET. Methodological and analytical recommendations are provided for the evaluation of long-term outcome.

Aged↗

Relative efficacy of alcohol and propranolol in action tremor.

Thirty-nine patients with a variety of diseases, including essential tremor, Parkinson's Disease, olivopontocerebellar degeneration, ataxia telangiectasia, and cervical cord injury with action tremor, were evaluated for the effect of one ounce of absolute alcohol ingestion. Tremor significantly subsided in 61.9% of E.T.; 46.6% of P.D.; one patient with A.T.; and one patient with C6 lesion. The tremor became worse in one patient with O.P.C.D. Twenty of these patients were treated with propranolol, an average dose of 92 mgm. per day, and re-evaluated three to six months later. All those who improved on alcohol improved on propranolol and the one whose tremor accentuated with alcohol had a similar response to propranolol. It is concluded that the tremorilytic effect of alcohol is neither specific for, nor limited to, essential tremor and is of no value in differentiating various neurological disorders which manifest as action tremor. It is recommended that one ounce of absolute alcohol by mouth be used as an office procedure to predict the response of patients' tremor to propranolol.

Adult↗

Ropinirole for the treatment of tremor in early Parkinson's disease.

The effect of Ropinirole on tremor in early Parkinson's disease (PD) was assessed. The results of three multicentre, randomized, double-blind trials comparing ropinirole monotherapy with levodopa, bromocriptine and placebo treatment were analysed retrospectively with respect to improvement of resting tremor and postural/action tremor as measured by items 20 and 21 of the motor section of the Unified Parkinson's Disease Rating Scale (UPDRS). Improvements in resting tremor were significantly better with ropinirole than placebo. There were no significant differences between the effect of ropinirole and those of levodopa (L-dopa) or bromocriptine on resting tremor. Postural/action tremor was mild in these early therapy studies, and there were no significant differences between treatment groups. These results suggest that ropinirole monotherapy is effective in treating resting tremor in early PD. On the other hand, response of postural/action tremor to dopaminergic treatment in early PD was not significantly better than to placebo at the dosages used in these trials.

Aged↗

Intention tremor rated according to different finger-to-nose test protocols: a survey.

OBJECTIVES: To investigate the dependence of intention tremor rating scores on different finger-to-nose test (FNT) protocols, varying in arm position and the time the finger has to be kept on the nose, and to examine their relevance to function. DESIGN: Observational survey. Video recordings were made while patients performed the FNTs and functional tasks such as pouring water. SETTING: Three European rehabilitation centers in Belgium, Finland, and England. PARTICIPANTS: Twenty-six multiple sclerosis patients with intention tremor (avg age, 44.1y). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Six examiners rated the degree of intention tremor by using the Fahn Tremor Rating Scale. RESULTS: Interrater reliability for rating intention tremor during the FNTs was high (kappa=.65-.74). Both the required arm position and time constraints affected the magnitude of intention tremor rating scores (mean rank, 2.27-2.95) and their functional relevance (rho=.70-.84). Intention tremor was scored the highest when the arm was lifted to 90 degrees of abduction at the shoulder and the subject was required to stabilize the finger on the nose. However, its functional relevance was lower compared with a more "functionally" executed FNT. CONCLUSIONS: The rating of intention tremor during the FNT depends on test instructions. A standardized protocol is needed.

Adult↗

The role of reflexes in the resting tremor of Parkinson's disease.

Forces and electromyograms were recorded from patients with Parkinson's disease during imposed joint movements. Muscles which were stretched by 3 to 5 Hz sinusoidally alternating movements often showed vigorous bursts of EMG activity whose timing established that it was a reflex response to the movement. The same movements provoke no stretch reflex response from normal subjects. When resting tremor was present the driven movements sometimes entrained it, and the bursts of EMG activity then became locked to the imposed movement. On other occasions the tremor activity continued at its own rate; EMG bursts then occurred at times unrelated to the movement, and the irregular force records reflected a conflict between the movement and the muscle activity. Tremor was most consistently entrained when a large mass of muscle was driven through a large movement at a frequency that was close to the usual tremor frequency. Tremor which involved synchronous contractions of muscles at different joints was often resistant to the effects of our imposed movements, but it could sometimes also be entrained by large movements of a single joint. When tremor was entrained by a driving movement, the EMG discharge was indistinguishable from a reflex response, and the limb exerted forces on the machinery which had the timing and magnitude that would be expected of a reflex response. Spontaneous tremor in the same subjects had frequencies which altered in the predicted way with changes of mechanical load. We conclude that peripheral reflexes are more important in parkinsonian tremor than has often been supposed, although afferent activity from the moving limb probably interacts with other potentially oscillatory mechanisms.

Aged↗

Primary writing tremor.

Primary writing tremor (PWT) is considered to be a type of task-specific tremor in which tremor predominantly occurs and interferes with handwriting. We describe the clinical and neurophysiological features of 21 patients (20 male and one female) with PWT. Mean age at tremor onset was 50.1 years. A family history of PWT was obtained from seven patients. Ten patients obtained benefit from drug treatment (mainly propranalol or primidone) and seven responded to alcohol. The writing speeds of the patients (mean +/- SEM: 73.1 +/- 6.6 letters per minute) when using their preferred hand were significantly reduced (Student's t test: P < 0.001) compared with those of healthy control subjects (mean +/- SEM: 127.7 +/- 6.4). Surface polymyography performed during writing showed 4.1-7.3 Hz rhythmic activity predominantly in the intrinsic hand and forearm muscles. Alternating, extensor activation alone, skipping from alternating to extensor activation, and co-contracting EMG patterns were recorded from the flexor and extensor muscles of the forearm. There was no evidence for excessive 'overflow' of this rhythmic EMG activity, as similar activity was detected in comparable muscle groups of healthy control subjects. Accelerometry confirmed that the frequency of PWT ranged from 4.1-7.3 Hz (median 5.5 Hz) and that normal subjects wrote with a 4.0-7.7 Hz oscillation (median 4.6 Hz). Forearm reciprocal inhibition was normal in PWT (n = 13), and thus patients with PWT can be distinguished from those with writer's cramp in whom decreased presynaptic inhibition has been found. Patients were sub-classified as having either type A (n = 11) or B (n = 10) PWT depending on whether tremor appeared during writing (type A: task induced tremor) or whilst writing and adopting the hand position used in writing (type B: positionally sensitive tremor). However, the only differences between these two groups were that a co-contracting EMG pattern and tremor induced by tendon taps to the volar aspect of the wrist were present in type B but not type A cases.

Adult↗

Physiological and pathological tremors and rhythmic central motor control.

In recent years there has been increasing interest in oscillatory neural activity in the CNS and in the role that such activity may have in motor control. It is thought that physiological tremor may be a manifestation in the periphery of such central oscillatory activity and that some pathological tremors are the result of derangement of these oscillators. This review re-evaluates both early and recent studies on physiological and pathological tremors and other peripheral oscillations in order to gain a new perspective on the nature and function of their central progenitors. This approach, namely using tremor as a 'window' into the function of central oscillations, is particularly suited to human investigations because of the obvious limitations of direct central recording. It is argued that physiological tremor is likely to be multifactorial in origin, with contributions not only from CNS 10-Hz range oscillatory activity, but also from motor unit firing properties, mechanical resonances and reflex loop resonances. Different origins are likely to dominate under different conditions. While some pathological tremors appear to arise as a distortion of central or peripheral components of physiological tremor, others arise de novo, such as the pathological oscillation of 3- to 6-Hz parkinsonian tremor. CNS oscillations outside the 10-Hz range are also found to modulate limb activity in normal individuals, and oscillatory activity exists in other motor systems such as eye movements. Finally, it is shown how studies of peripheral oscillations may help develop hypotheses on the role of CNS oscillations in motor control, including the proposed 'binding' function of synchronized oscillations and the possibility that motor signals could be coded by frequency of modulating oscillation as well as by synaptic connectivity.

Animals↗

Classification of essential tremor.

Classification of essential tremor was attempted using tremor frequency; tremor duration; family history of tremor; responsiveness to alcohol, propranolol, and primidone; muscle contraction pattern; and long-latency reflexes. Sixty-one patients were evaluated. The majority of patients had a tremor frequency less than 7.0 Hz, a positive family history, and a positive response to alcohol. Approximately 46% of patients had a beneficial response with propranolol and 71% with primidone. Tremor frequency was inversely correlated with age and directly correlated with an antagonist pattern of muscle contraction. Enhanced long-latency reflexes were not found. Other characteristics of essential tremor were not significantly correlated. It is concluded that essential tremor can not be classified into subtypes.

Aged↗

Postural tremor of Parkinson's disease.

Previous studies have reported the resting tremor (RT) of Parkinson's disease to occur at frequencies between 3-7 Hz and to be characterised by an alternating pattern of electromyographic (EMG) bursting activity between opposing muscles. A postural tremor (PT), of higher frequency (> 6 Hz) and with a synchronous pattern of EMG activity, has also been previously described in Parkinson's disease. We investigated the electrophysiological and pharmacological properties of both the RT and PT of 11 patients with Parkinson's disease and 10 patients with essential tremor in a double-blind, placebo-controlled study of L-Dopa/benserazide and propranolol. Tremor amplitude and frequency were assessed via bidirectional accelerometry, and the pattern of activation of the antagonist muscles of the forearm was determined with use of surface EMG. In the Parkinson's disease group studied, the frequency, EMG pattern of bursts, and response to L-Dopa were similar for the two tremors (median improvement of RT by 70% and PT by 61%). Despite some overlap between the Parkinson's disease and essential tremor groups in the electrophysiology of the tremor, there was no such dramatic pharmacological response in the latter group. These results suggest that the RT and PT of Parkinson's disease share a common pathophysiology and are distinct from essential tremor.

Adult↗

Relationship between multiple sclerosis intention tremor severity and lesion load in the brainstem.

Intention tremor due to multiple sclerosis is clinically similar to cerebellar tremor. This study investigated, in 14 multiple sclerosis patients, the relationship between intention tremor severity and the lesion load in different infratentorial regions. Tremor amplitude was quantified during step-tracking tasks. The lesion load was measured on magnetic resonance images using an automated segmentation method. Intention tremor amplitude was significantly related to lesion load in the brainstem but not in the cerebellum. Specifically, tremor amplitude correlated with the lesion load in the contralateral pons, and patients with more severe tremor in both arms had a greater lesion load bilaterally in the pons. These results support the view that multiple sclerosis intention tremor is related to dysfunction of cerebellar inflow and/or outflow pathways.

Brain Stem↗

The tremorolytic action of beta-adrenoceptor blockers in essential, physiological and isoprenaline-induced tremor is mediated by beta-adrenoceptors located in a deep peripheral compartment.

The effects of intravenous propranolol 100 micrograms kg-1, sotalol 500 micrograms kg-1, timolol 7.8 micrograms kg-1, atenolol 125 micrograms kg-1 and placebo on essential, physiological and isoprenaline-induced tremor were studied. These beta-adrenoceptor blocker doses produced equal reduction of standing-induced tachycardia in essential tremor patients. Atenolol produced significantly less reduction of essential and isoprenaline-induced tremor than the non-selective drugs, confirming the importance of beta 2-adrenoceptor blockade in these effects. Propranolol and sotalol produced equal maximal inhibition of isoprenaline-induced tremor but propranolol was significantly more effective in reducing essential tremor. The rate of development of the tremorolytic effect was similar in essential, physiological and isoprenaline-induced tremors but all tremor responses developed significantly more slowly than the heart rate responses. It is proposed that these results indicate that the tremorolytic activity of beta-adrenoceptor blockers in essential, physiological and isoprenaline-induced tremor is exerted via the same beta 2-adrenoceptors located in a deep peripheral compartment which is thought to be in the muscle spindles.

Adrenergic beta-Antagonists↗

Tremor in patients with migraine.

BACKGROUND: It has been suggested that patients with migraine are at a higher risk of developing essential tremor (ET). In addition, it was shown that patients with migraine are at higher risk of subclinical vascular infarcts in the cerebellum, a structure believed to be implicated in ET. OBJECTIVE: Determine whether patients with migraine who do not show clinically detectable ET have subtle alteration in their physiological tremor characteristics that may serve as a predictor for the eventual appearance of ET. METHODS: The physiological tremor of 30 patients with migraine (25 women, mean age: 41 +/- 8 years) was examined using a laser displacement sensor. Tremor was recorded in 5 conditions: hand-rest, hand-postural, finger-rest, finger-postural, and finger-loading (70 g). We also recorded tremor in healthy controls who never experienced migraine. Amplitude, median power frequency, power dispersion (width of a frequency band containing 68% of the power), and power distribution within 3 predetermined frequency bands of interest (3.5 to 7.5, 7.5 to 12.5, and 16 to 30 Hz) were assessed in each condition. RESULTS: All tremor characteristics described above were very similar between the migraine group and controls. These results were supported by the lack of correlation between tremor characteristics and the number of years of experiencing migraine (ranging from 3 to 41 years; mean: 20 +/- 10). Patients with aura (N = 21) had tremor characteristics similar to that of patients without aura (N = 9) and controls. CONCLUSION: These results suggest that, if a link exists between migraine and ET, the latter might be the result of an "acute event" (eg, stroke) rather than a progressive alteration of tremorogenic mechanisms.

Adult↗