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Effects of p-chlorophenylalanine on striatal acetylcholinesterase activity and on biogenic amine levels in nuclei raphe and caudate-putamen during physostigmine-induced tremor in rats.

The biochemical mechanism underlying tremor is unknown. We investigated the effects of p-chlorophenylalanine (pCPA), a serotonin (5-HT) depletor, on the neurochemical processes in nuclei raphe dorsalis (NRD) and caudatus putamen (NCP) paralleling physostigmine-induced tremor in rats. Peak of physostigmine tremor correlated with increase in 5-HT in NRD and NCP, and a decrease in striatal dopamine (DA), as assayed employing high pressure liquid chromotography-electrochemistry. Administration of pCPA caused significant decrease in DA, norepinephrine (NE) and 5-HT levels in both the nuclei, without affecting striatal NE content and acetylcholinesterase activity. pCPA pretreatment significantly inhibited physostigmine-induced tremor and blocked corresponding increase in the levels of 5-HT in NRD and NCP. These results indicate involvement of central 5-HT, but not DA or NE, in the genesis of physostigmine tremor.

Acetylcholinesterase↗

Hypermetabolism in the ventrolateral thalamus in unilateral Parkinsonian resting tremor: a positron emission tomography study.

Tremorogenesis in Parkinson's disease (PD) is assumed to involve a cerebral network including the thalamus. An imaging study was performed on eight PD patients with strictly unilateral resting tremor using fluorodeoxyglucose positron emission tomography coregistered to 3-dimensional magnetic resonance imaging. Increased metabolic activity of high statistical significance (P<0.001) was found in the anterior ventrolateral nuclear group of the thalamus located contralateral to the tremor side. The metabolic changes significantly covaried with tremor amplitudes. For the first time, it could be demonstrated that thalamic metabolic changes associated with tremor in PD are localized in the ventral lateral anterior nucleus (VLa). The results are discussed with respect to previous studies on tremor generation.

Aged↗

Load compensation tasks evoke tremor in cerebellar patients: the possible role of long latency stretch reflexes.

'Tremor' is one of the clinical signs of cerebellar dysfunction. Its nature remains subject to debate, one hypothesis being that of a predominant role of peripheral afferences in its genesis. This study was designed to study whether load compensating tasks, evoking sudden stretch, and thus stimulation of peripheral afferences induced tremor in cerebellar patients. We study the kinematics and EMG pattern of a load compensating task which consists of maintaining a constant elbow position despite the onset and cessation of a 2 Nm torque loading the elbow flexors in eight cerebellar patients and six controls. Angular position and velocity, and EMG of the biceps and triceps are recorded at a sampling rate of 1 kHz. In normal subjects, trajectories are simple with little overshoot of the aimed position. EMG analysis shows a long latency stretch response (LLSR) which initiates a phasic and then tonic voluntary activity. In cerebellar patients, the two prominent cinematic features are hypermetria and tremor. The stretch response is of the same latency, but the EMG pattern is modified with bursts of activity related to the tremor. These results show severe perturbations of load compensating tasks in cerebellar patients. We discuss the possible role of the exaggeration of LLSR in both hypermetria and tremor.

Case-Control Studies↗

The treatment of essential voice tremor with botulinum toxin A: a longitudinal case report.

The purpose of this study was to evaluate the effects of bilateral botulinum toxin injection into the thyroarytenoid (TA) muscles of a patient with essential voice tremor. Acoustic and aerodynamic data were collected weekly over a 16-week period. Flexible nasolaryngoscopy was performed prior to injection and 2, 6, 10, and 16 weeks postinjection. Perceptual analyses of the acoustic and nasolaryngoscopic data were performed. A reduction in frequency tremor and, to a lesser extent, amplitude tremor was observed during the 1-10 week period. Estimated laryngeal resistance decreased after injection and was accompanied in perceptual measures by a reduction in vocal effort, laryngeal tremor, and supraglottic hyperfunction. Essential voice tremor can be successfully attenuated with bilateral percutaneous injection of botulinum toxin A into the vocalis muscle.

Aged↗

The effect of temperature on hand function in patients with tremor.

Hand therapists may notice a patient's tremor when treating another diagnostic problem, such as arthritis or a fracture. In these instances, the tremor may become apparent as the patient attempts to don or doff a splint or to practice a home exercise program, or it may be reported in terms of difficulty with dressing or eating. The authors hypothesized that limb cooling would temporarily improve hand function among patients with essential tremor (ET) and that limb warming would temporarily improve hand function among patients with resting tremor secondary to Parkinson disease (PD). Twenty patients with ET and 20 patients with PD completed this single-blind randomized crossover study. Scores following exposure to cold water were compared with scores following exposure to warm water. For patients with ET, subtest scores for the Archimedes spiral, simulated feeding, and checkers were, statistically, significantly lower (i.e., improved) following exposure to cold water than following exposure to warm water; scores for Archimedes spiral card turning, simulated feeding, and checkers were significantly lower following exposure to cold water than at baseline. Scores for Archimedes spiral and card turning were also significantly lower following exposure to warm water than at baseline. For patients with PD, no statistically significant differences were noted between treatments or from baseline except the score for small common objects, which was lower (improved) following exposure to warm water than at baseline. The significant findings from this study support the therapeutic use of cooling to temporarily decrease tremor, thereby improving hand function among patients with ET.

Aged↗

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↗

Amplitude changes in the 8-12, 20-25, and 40 Hz oscillations in finger tremor.

OBJECTIVE: The study examined the amplitude and frequency modulation of the 8-12, 20-25, and 40 Hz frequencies of tremor to determine the degree to which increments of load affect the amplitude of these neural rhythms. METHODS: Finger acceleration from the middle phalange and electromyographic (EMG) activity of the extensor digitorum communis (EDC) muscle were recorded on 10 normal adult subjects. Two experiments are reported that manipulated loads ranging from 0 to 40 and 0 to 200 g that were attached to the distal portion of the outstretched middle phalange. RESULTS: There were 8-12, 20-25, and 40 Hz oscillations in the EMG recording but only the 8-12 and 20-25 Hz rhythms were present in the tremor and tremor-EMG coherence. Adding load to the finger reliably decreased the 20-25 Hz band of acceleration, reduced the relative power within the 20-25 Hz EMG band, increased the relative power of the 40 Hz band, but had no effect on the relative power within the 8-12 Hz EMG frequency band. The tremor-EMG coherence in the 8-12 and 40 Hz regions was independent of load, but was markedly reduced with load in the 20-25 Hz band. CONCLUSIONS: The 8-12, 20-25, and 40 Hz neural rhythms of physiological tremor have a stable frequency consistent with central oscillations. There is an increase in the relative power of the 40 Hz EMG band with force, but only the amplitude of the 20-25 Hz band is modulated by mechanical-reflex feedback.

Adolescent↗

The nature of primary vocal tremor.

Three elderly women with marked progressive voice tremor, without other neurological symptoms, and negative family histories were investigated. All had a 4-5 Hz respiratory tremor in expiration and, to a lesser degree, in inspiration; and all had vocal tremulousness synchronous with their respiratory irregularity. Articulation of phonemes was normal. In two cases the neurological examination was otherwise normal; in the third case there was a minimal 71/2 Hz tremor in the left thumb and index finger. Simultaneous speech and vocal air pressure recordings, as well as cinematographic studies of the vocal apparatus and diaphragm were carried out. It is suggested that these cases represent primarily an action tremor of respiration, that they belong in the spectrum of essential tremor, and hence may be amenable to treatment with propranolol.

Aged↗

Head tremor in dentatorubral-pallidoluysian atrophy.

Dentatorubral-pallidoluysian atrophy (DRPLA) is a rare autosomal-dominant neurodegenerative disorder characterized by variable combination of clinical manifestations including ataxia, myoclonus, seizures, dementia, and choreic movements. Head tremor has been rarely reported. We report a 66-year-old-woman with genetically determined DRPLA who presented with head tremor. A "no-no" type head tremor was the initial and the most prominent symptom, and mild cerebellar signs and choreic movements were also observed later. Neither hand tremor nor dystonia was noted. The patient did not show dementia, myoclonus, or seizures. Surface electromyogram (EMG) revealed 3.5-4 Hz rhythmic EMG bursts in both sternocleidomastoid muscles. DNA analysis disclosed expanded trinucleotide repeats (n = 54) in the DRPLA gene. We suggest that isolated head tremor can be a clinical manifestation of DRPLA.

Aged↗

Metoprolol and alpha-hydroxymetoprolol concentrations and reduction in essential tremor.

The relationship between reductions in essential tremor and concentrations of metoprolol and alpha-hydroxymetoprolol was examined in five patients with essential tremor after treatment with 0, 25, 50, and 75 mg metoprolol twice daily for 7 to 10 days. Serum concentrations of metoprolol and alpha-hydroxymetoprolol were measured simultaneous to serial accelerometry measurements of tremor over 8-hr periods. There was a relationship between degree of tremor reduction and steady-state metoprolol concentration. Time course of the drug and metabolite concentration correlated better with the time course of effect than with the time course of metoprolol concentration alone. Data suggest that the alpha-hydroxymetabolite of metoprolol may contribute to the reduction in essential tremor.

Adolescent↗

Essential tremor: emerging views of a common disorder.

Essential tremor (ET) is the most prevalent tremor disorder. ET has traditionally been viewed as a monosymptomatic disorder characterized by a kinetic arm tremor, but this definition is gradually being replaced. The clinical spectrum has come to include several motor features, including tremor and ataxia, and several non-motor features, including possible cognitive impairment and personality disturbances. Postmortem studies are revealing several different patterns of pathology. The emerging view is that ET might be a family of diseases, unified by the presence of kinetic tremor, but further characterized by etiological, clinical and pathological heterogeneity. Effective pharmacological treatments for the disorder remain limited, although new insights into disease mechanisms might result in more-effective therapies. In addition, recent investigations of environmental toxicants that might be linked to ET open the way towards primary disease prevention through a reduction in exposure to these factors.

Essential Tremor↗

Five common tremors. Classification, key to therapy.

Tremor is the most common movement disorder seen in clinical practice, encountered frequently by primary care physicians as well as neurologists. Most tremors can be classified as physiologic, enhanced physiologic, essential, cerebellar, or parkinsonian on the basis of careful clinical observation. Sometimes, electrophysiologic studies are helpful. With correct classification, effective treatment can usually be provided. Beta-blocking drugs are effective in both enhanced physiologic tremor and essential tremor, although at widely varying dosages, and a levodopa combination often relieves parkinsonian rest tremor.

Adrenergic beta-Antagonists↗

Rapid wrist movements in patients with essential tremor. The critical role of the second agonist burst.

Ballistic wrist flexion movements towards 15, 30 and 60 degrees visual targets were studied in a group of 17 patients with hereditary essential tremor. Compared with age-matched normal subjects (n = 16), there were three main kinematic differences: patients overshot the target a little more; the kinematic profile of their movements was more 'asymmetric' due to higher peak decelerations; and their movements initiated tremor. Ballistic movements performed by patients with essential tremor were associated with a triphasic pattern of agonist-antagonist-agonist muscle activity similar to that of normal subjects. The duration and size of each EMG burst was normal. The onset latency of the antagonist EMG burst was also normal, but the onset of the second agonist EMG burst was delayed. The delay in the onset of the second agonist EMG activity resulted in unopposed action of the antagonist muscle in the second half of each movement. As a result, deceleration occurred too rapidly as the hand returned past the target leading to a series of damped oscillations around the point of aim. The onset latency of the second agonist EMG burst correlated significantly with the tremor period; the longer the period the later the burst. We speculate that the delay in the second agonist burst reflects an abnormality in the timing of anticipatory muscle activity in essential tremor and that this may involve cerebellar mechanisms.

Adult↗

Therapeutic effects of arotinolol, a beta-adrenergic blocker, on tremor in MPTP-induced parkinsonian monkeys.

The effect of arotinolol, a peripherally acting beta-adrenergic-blocking agent, on postural or kinetic tremor was studied in monkeys with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism. Male cynomolgus monkeys (Macaca fascicularis) were treated with three injections of MPTP hydrochloride (0.3 mg/kg, i.v.) at an interval of 3-4 days, followed by several injections of the same dose every 7 days. Four monkeys with persistent parkinsonian symptoms manifested for greater than 1 year were used. The animals developed mild to moderate degrees of postural or kinetic tremor, and their motor activity was reduced. Arotinolol (20-30 mg/kg, s.c.) significantly suppressed postural tremor in a dose-dependent manner. Propranolol (20-30 mg/kg) was also effective in suppressing the tremor. However, the application of propranolol induced emesis, whereas arotinolol had no adverse effects. These results suggest that arotinolol is a useful adjunct to dopaminergic therapy for tremor in Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Central mechanisms of tremor.

Physiologic and pathologic tremors are mechanistically classified into two broad groups: (1) those produced by oscillation in sensorimotor loops, so-called mechanical-reflex tremors, and (2) those produced by the oscillatory properties of central neuronal networks. This review provides a contemporary perspective of tremor pathophysiology while acknowledging that no form of tremor is understood completely. Indeed, the origin of oscillation in most forms of tremor is undefined, and in many instances the underlying pathology is unknown.

Basal Ganglia↗

Gabapentin for treatment of pain and tremor: a large case series.

BACKGROUND: Several anticonvulsant agents, including carbamazepine, phenytoin, and valproate, are effective in some patients for the treatment of pain and tremor. This study reports on a trial of the newly introduced anticonvulsant, gabapentin, for pain and tremor control. METHODS: A large case series of patients with centrally mediated pain, peripherally mediated pain, migraine, and tremor were treated in an open-label study with gabapentin (maximum of 2,700 mg/day). RESULTS: Thirty-nine patients (65%) had moderate-to-excellent improvement in symptoms, with the best responses occurring in patients with peripherally mediated neuropathic pain. The other conditions treated that showed some improvement were benign essential/familial tremor, restless legs syndrome, centrally mediated pain, and periodic nighttime leg movements. CONCLUSIONS: Gabapentin offers an effective, safe alternative therapy or co-therapy for the listed painful conditions and tremor; it does not affect the metabolism of other medications and is well tolerated.

Acetates↗

Optimal digital filtering for tremor suppression.

Remote manually operated tasks such as those found in teleoperation, virtual reality, or joystick-based computer access, require the generation of an intermediate electrical signal which is transmitted to the controlled subsystem (robot arm, virtual environment, or a cursor in a computer screen). When human movements are distorted, for instance, by tremor, performance can be improved by digitally filtering the intermediate signal before it reaches the controlled device. This paper introduces a novel tremor filtering framework in which digital equalizers are optimally designed through pursuit tracking task experiments. Due to inherent properties of the man-machine system, the design of tremor suppression equalizers presents two serious problems: 1) performance criteria leading to optimizations that minimize mean-squared error are not efficient for tremor elimination and 2) movement signals show ill-conditioned autocorrelation matrices, which often result in useless or unstable solutions. To address these problems, a new performance indicator in the context of tremor is introduced, and the optimal equalizer according to this new criterion is developed. Ill-conditioning of the autocorrelation matrix is overcome using a novel method which we call pulled-optimization. Experiments performed with artificially induced vibrations and a subject with Parkinson's disease show significant improvement in performance. Additional results, along with MATLAB source code of the algorithms, and a customizable demo for PC joysticks, are available on the Internet at http:¿tremor-suppression.com.

Algorithms↗

Tremor suppression through impedance control.

This paper presents a method for designing tremor suppression systems that achieve a specified reduction in pathological tremor power through controlling the impedance of the human-machine interface. Position, rate, and acceleration feedback are examined and two techniques for the selection of feedback coefficients are discussed. Both techniques seek a desired closed-loop human-machine frequency response and require the development of open-loop human-machine models through system identification. The design techniques were used to develop a tremor suppression system that was subsequently evaluated using human subjects. It is concluded that nonadaptive tremor suppression systems that utilize impedance control to achieve a specified reduction in tremor power can be successfully designed when accurate open-loop human-machine models are available.

Acceleration↗