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Efficacy of primidone in essential tremor.

Primidone, 50 to 1,000 mg/d, reduced the amplitude of essential tremor in both untreated and propranolol-treated patients. Low doses were as effective as high doses. Primidone decreased tremor more than propranolol. There was no correlation between therapeutic response and serum levels. Acute reactions to the initial dose and side effects of higher doses caused drug intolerance. A single oral dose (250 mg) decreased tremor by 60% 1 to 7 hours after ingestion, with stable serum primidone levels but no detectable phenobarbital levels. Tremor control was lost when phenobarbital was substituted for primidone. Primidone is an effective agent for the treatment of essential tremor.

Dose-Response Relationship, Drug↗

Focal task-specific tremor and dystonia: categorization of occupational movement disorders.

We studied 28 patients with focal task-specific disorders. Three groups were identified, according to the occurrence of focal tremor alone (group I, n = 10), dystonia alone (group II, n = 8), and tremor-dystonia combination (group III, n = 10). Four of six patients in groups I and III showed improvement with beta blocking agents alone, and another patient improved with primidone and metoprolol. Four of seven patients in groups II and III improved at least moderately with only anticholinergic medication. The coexistence of focal tremor and focal dystonia in the same limb in 10 patients (group III) suggests a link between these focal disorders. We conclude that focal tremor and focal dystonia are related to generalized essential tremor and generalized dystonia. A scheme which conceptualizes these interrelationships is proposed.

Adolescent↗

Treatment of essential tremor with arotinolol.

We investigated the effect of arotinolol, a new peripherally acting beta-adrenergic blocker, in 15 patients with essential tremor. The patients received 30 mg per day of arotinolol for 8 weeks. Accelerometer readings showed a significant reduction in amplitude of postural tremor after treatment. Action tremor also improved to essentially the same degree as postural tremor. The present findings support the view that the therapeutic effect of beta-blockers in essential tremor is mediated by peripheral beta-adrenergic receptors.

Adrenergic beta-Antagonists↗

Psychogenic tremors.

We diagnosed 24 patients, 9 men and 15 women ranging in age from 15 to 78 years, with clinically established or documented psychogenic tremors. Clinical presentations were unique, with complex tremors (often resting, postural, and kinetic), unusual temporal profiles (abrupt onset with a variable course), absence of other neurologic signs, inconsistent and incongruous symptomatology, selective disability with ability to perform some functions despite severe tremors, distractibility that lessens or abolishes tremor, atypical tremorgraphic recordings with changing amplitude and frequency, unusual handwriting and drawing specimens, presence of multiple undiagnosed somatizations, unresponsiveness to all treatments, absence of documented disease by laboratory or radiographic tests, presence of psychiatric disease, spontaneous remissions, or recovery with psychotherapy. We present criteria for the diagnosis of psychogenic tremor.

Adolescent↗

The effect of mechanical damping loads on disabling action tremor.

Patients with severe action tremor have uncontrollable, relatively rapid oscillatory motion super-imposed on otherwise useable slower voluntary motor activity. Because a mechanical damper produces an opposing force proportional to velocity, applying damping loads to tremorous limbs should attenuate the (high-velocity) tremor component of movement while permitting the slower purposeful portion to proceed relatively unopposed. In this study, the effect of upper extremity damping in three degrees of freedom was examined in 10 patients with cerebellar action tremor due to multiple sclerosis or traumatic brain injury. Variable amounts of damping were applied by prototype energy-dissipating orthoses which generated resistive viscous loads by means of computer-controlled magnetic particle brakes. All patients experienced statistically and functionally significant tremor reduction with the application of damping.

Adult↗

Central motor loop oscillations in parkinsonian resting tremor revealed by magnetoencephalography.

A variety of clinical and experimental findings suggest that parkinsonian resting tremor results from the involuntary activation of a central mechanism normally used for the production of rapid voluntary alternating movements. However, such central motor loop oscillations have never been directly demonstrated in parkinsonian patients. Using magnetoencephalography, we recorded synchronized and tremor-related neuromagnetic activity over wide areas of the frontal and parietal cortex. The spatial and temporal organization of this activity was studied in seven patients suffering from early-stage idiopathic Parkinson's disease (PD). Single equivalent current dipole (ECD) analysis and fully three-dimensional distributed source solutions (magnetic field tomography, MFT) were used in this analysis. ECD and MFT solutions were superimposed on high-resolution MRI. The findings indicate that 3 to 6 Hz tremor in PD is accompanied by rhythmic subsequent electrical activation at the diencephalic level and in lateral premotor, somatomotor, and somatosensory cortex. Tremor-evoked magnetic activity can be attributed to source generators that were previously described for voluntary movements. The interference of such slow central motor loop oscillations with voluntary motor activity may therefore constitute a pathophysiologic link between tremor and bradykinesia in PD.

Aged↗

Reduction in voice tremor under thalamic stimulation.

We studied the effect of deep brain stimulation (DBS) of the ventral intermediate thalamic nucleus on voice symptoms in seven patients with essential tremor. All had undergone DBS for management of hand tremor. Five of the patients had received unilateral implants; two were treated bilaterally. Each reported improvement in hand tremor with thalamic stimulation (a 1-to-3-point change on a 5-point severity scale). Voice tremor was evaluated with and without stimulation using patient and clinician severity ratings, and acoustic measures (rate and amplitude). Four of the seven patients showed reductions in voice symptoms in at least two of these measures, although degree of change differed (e.g., from 1 to 3 points on the 5-point severity scale). Voice gains typically were restricted to those patients with the more severe symptoms and did not parallel improvements in the upper extremities. It appears that reduced voice tremor may be an additional benefit of DBS for some individuals.

Aged↗

Thalamic stimulation reduces essential tremor but not the delayed antagonist muscle timing.

BACKGROUND: Electrical stimulation of the thalamus dramatically reduces essential tremor (ET). It has been hypothesized that the cerebellum and inferior olive are involved in the generation of ET, and thalamic stimulation is presumed to dampen ET through interactions with cerebellar output to the thalamus. Evidence suggests that abnormal timing of agonist and antagonist muscle responses contribute to cerebellar tremor (CbT); however, this relationship has not been investigated for ET. The mechanisms of the tremor and improvement are unknown. OBJECTIVE: To measure the effect of ventral intermediate thalamic stimulation in controlling the ET response to sudden stretch of an agonist muscle and to determine whether, in ET, the timing relationships between the initial agonist and antagonist electromyography (EMG) responses show abnormalities similar to those seen in CbT. METHODS: The authors studied ET subjects (with implanted thalamic stimulators turned off and on) and normal controls as they responded to mechanical torque pulses given at the wrist joint. The wrist joint angle, wrist agonist, and antagonist EMG were recorded. RESULTS: Like CbT, patients with ET showed delayed onsets of antagonist EMG and excessive rebound. Thalamic stimulation reduced the tremor but did not alter the antagonist delay or the rebound. CONCLUSIONS: In ET, antagonist muscle responses to a torque pulse are similar to that in CbT. However, benefit from thalamic stimulation did not alter these EMG responses; therefore, suppression of tremor must be caused by mechanisms other than the re-establishment of normal agonist-antagonist timing.

Aged↗

A new model of petit mal epilepsy: spontaneous spike and wave discharges in tremor rats.

A mutant rat, which was found in a colony of Kyoto:Wistar rats and genetically defined as a tremor rat (tm/tm), developed tremor of the whole body at 2 weeks of age but the tremor gradually disappeared between 6 and 8 weeks of age. The electroencephalogram (EEG) recorded using chronically implanted electrodes showed a 5-7 Hz (mostly 6 Hz) spike and wave complex synchronously in the cerebral cortex and hippocampus accompanied by absence-like seizure in all six tremor rats examined. The spike and wave complex appeared 0.8-1.9 times per minute and lasted for 1-17 s. However, normal EEG activity was observed in the intervening periods, free of absence-like seizure. Thus the tremor rat is considered to be a possible model for studying the pathogenesis and therapy of petit mal epilepsy in humans.

Animals↗

Basic aspects of action tremors in the human M. brachioradialis.

Since the first measurements of tremors it was obvious that the tremor signal originates from very complicated and continuously changing nervous and mechanical factors. However, the tremors originate in the beginning from the action tremors of the skeletal muscles. In this study the basic structure of the action tremors, regular 13-Hz oscillations, was revealed (measured by an accelerometer fixed on the distal end of the muscle belly of the m. brachioradialis). The mechanical oscillations measured with this technique had a linear relationship to the electrical oscillations of the EMG. Further, harmonic interference of isometric contraction with faradic contraction was observed. During simultaneous contraction of neighbouring muscles, completely synchronous but exactly out-of-phase oscillations were observed.

Adult↗

Interactions between ethanol and pantothenic acid on tremor and behavior in squirrel monkeys.

Ethanol consumption alters the levels and distribution of pantothenic acid and its metabolic products, an effect that can be counteracted by preloading with pantothenic acid. Ethanol also produces significant disturbances in motor function and has a potent tremorolytic activity when administered acutely. To investigate the interaction of pantothenic acid and ethanol, the two substances were administered alone and in combination to three squirrel monkeys trained to perform a response-initiated positioning task that enabled the detection of tremor. Tremor was evaluated using spectral analytical techniques. Ethanol at 1.0 gm/kg produced a tenfold reduction in tremor over control sessions while pantothenic acid alone had no effect on tremor. Pantothenic acid (200 mg/kg, IP or IV) administered before ethanol intubation completely counteracted the tremor-reducing action of ethanol in two monkeys and partially counteracted it in a third. The interaction between pantothenic acid and ethanol was limited to these motor effects; the rate-reducing effect of ethanol was unaffected by pantothenic acid.

Animals↗

Involvement of the central catecholaminergic system in nicotine-induced tail-tremor in rats.

The effect of 6-hydroxydopamine on repeated nicotine-induced tail-tremor was investigated in rats. Tail-tremor induced by nicotine (0.5 mg/kg/day, subcutaneously) became more pronounced in intensity with daily administration for 9 days. Rats pretreated with 6-hydroxydopamine (250 micrograms, intracerebroventricularly) showed almost the maximum degree of tail-tremor during the whole experimental period. However, in rats pretreated with 6-hydroxydopamine plus desipramine, enhancement of tail-tremor was slight in the beginning but increased with the daily nicotine administration. Fourteen-day administration of nicotine did not result in significant changes in noradrenaline and dopamine levels in the cortex, hypothalamus, striatum and nucleus accumbens. These results suggest that nicotine-induced tail-tremor is associated with the supersensitivity of postsynaptic catecholaminergic receptors in the central nervous system, and that the noradrenergic system may be more important than the dopaminergic system in this phenomenon.

Animals↗

Physiological tremor under pseudo-fraction gravity.

The effect of pseudo-fraction gravity on physiological tremor of the human finger (finger tremor) has been examined experimentally by immersing an index finger into water at different immersion levels. The pseudo-fraction gravity, gamma G, was established by water buoyancy at immersion level omega, G being gravitation acceleration and gamma between zero and unit. The nature of variations of finger tremor under the influence of gamma G is estimated based on FFT spectral analysis. It is illustrated that with a decrease in gamma, or equivalently an increase in omega, two dominant peaks remaining approximately constant in frequencies around 10Hz and 20Hz are found, while peak amplitude is decreased rapidly for higher peak and slowly for lower one. Theoretically the effect of pseudo-fraction gravity is analyzed in terms of a specific model for finger tremor. The experimental results presented in this paper are predicted rather well by two resonant modes which occurred in our model system. It is possible to conclude that the model, which is characterized by a pair of antagonistic muscles and two reflex pathways, provides an adequate quantitative description of finger tremor.

Adult↗

Lithium-induced tremor treated with vitamin B6: a preliminary case series.

OBJECTIVE: The occurrence of tremor in patients receiving lithium is well known, but the management of this side effect is a significant problem both for patients and physicians. Although some reports have suggested that beta-blockers may be useful in treating lithium-induced tremor (LT), these agents have different side effects which limit the possibility of their use. Vitamin B6 has been reported to be effective in treatment of patients suffering from different kinds of neuroleptic-induced movement disorders including parkinsonism and tardive dyskinesia. METHODS: This report presents the results of a preliminary four-week open-label clinical trial of five patients who suffered from LT and who were treated with vitamin B6 (900-1200 mg/d). The severity of tremor was assessed using the tremor subscale from the Simpson-Angus Scale (SAS) and Subjective Clinical Improvement Impression scale (SCII). RESULTS: After the addition of vitamin B6 to their treatment, according to the SAS scores four patients showed an impressive improvement until total disappearance of tremor. The subjective scale, on which the patients' scored their impression of clinical improvement, showed similar results. None of the patients suffered from any side effects attributable to vitamin B6. CONCLUSIONS: The results suggest that vitamin B6 may alleviate LT, double-blind controlled trials are needed to establish this effect.

Adult↗

Tremor-bursts induced by a combined application of chlorpromazine and pentobarbital in guinea pigs are asymmetrically influenced by right- and left-brain lesions.

The effect of right- and left-brain lesions on pentobarbitone-chlorpromazine induced tremor-bursts was studied in guinea pigs. The left-brain transections did not affect these tremor bursts except post-thalamic sections, which caused a complete disappearance of extensor jerks with coinciding tremors at four legs. These tremor bursts simultaneously occurring at four legs completely disappeared after a right-forebrain transection at the level of the rostral striatum. Extensor jerks without tremors continued to occur, however. It is concluded that the postural system is asymmetrically controlled and the rostral right brain is responsible for the tonic postural activity in guinea pigs.

Animals↗

Control of tremor and involuntary movement disorders by chronic stereotactic stimulation of the ventral intermediate thalamic nucleus.

The authors report on the long-term results of chronic stereotactic stimulation of the ventralis intermedius thalamic nucleus performed in 14 cases of disabling and intractable tremor. There were 10 patients with parkinsonian tremor and four with essential tremor. Three of the 10 parkinsonian patients had previously undergone contralateral thalamotomy. Tremor was assessed by clinical evaluation, surface electromyography, accelerometer, and videotape recordings before and after stimulation. The deep-brain electrode was implanted in the ventralis intermedius nucleus according to stereotactic procedure and connected to a subcutaneous pulse generator after a stimulation test period. Tremor suppression or reduction was obtained in all cases with high-frequency (130 Hz) stimulation. Marked functional improvement was maintained in 11 patients with a mean follow-up interval of 17 months. Levodopa-induced dyskinesias observed in five parkinsonian patients prior to surgery were improved or suppressed in four cases by thalamic stimulation. Stimulation was continued during the day and stopped at night in eight cases. Six patients were stimulated night and day to avoid a rebound effect which appeared as soon as the pulse generator was stopped. The only side effects were hand tonic posture in one case and persistent paresthesia in another case. The mechanism of action of this attractive treatment may be a functional alteration of the thalamic discharging area. The authors conclude that this technique is a good alternative to thalamotomy, especially when the risks of high-frequency coagulation are severe in frail and older patients.

Adult↗

Optimal location of thalamotomy lesions for tremor associated with Parkinson disease: a probabilistic analysis based on postoperative magnetic resonance imaging and an integrated digital atlas.

OBJECT: Renewed interest in stereotactic neurosurgery for movement disorders has led to numerous reports of clinical outcomes associated with different treatment strategies. Nevertheless, there is a paucity of autopsy and imaging data that can be used to describe the optimal size and location of lesions or the location of implantable stimulators. In this study the authors correlated the clinical efficacy of stereotactic thalamotomy for tremor with precise anatomical localization by using postoperative magnetic resonance (MR) imaging and an integrated deformable digital atlas of subcortical structures. METHODS: Thirty-one lesions were created by stereotactic thalamotomy in 25 patients with tremor-dominant Parkinson disease. Lesion volume and configuration were evaluated by reviewing early postoperative MR images and were correlated with excellent, good, or fair tremor outcome categories. To allow valid comparisons of configurations of lesions with respect to cytoarchitectonic thalamic boundaries, the MR image obtained in each patient was nonlinearly deformed into a standardized MR imaging space, which included an integrated atlas of the basal ganglia and thalamus. The volume and precise location of lesions associated with different clinical outcomes were compared using nonparametric statistical methods. Probabilistic maps of lesions in each tremor outcome category were generated and compared. Statistically significant differences in lesion location between excellent and good. and excellent and fair outcome categories were demonstrated. On average, lesions associated with excellent outcomes involved thalamic areas located more posteriorly than sites affected by lesions in the other two outcome groups. Subtraction analysis revealed that lesions correlated with excellent outcomes necessarily involved the interface of the nucleus ventralis intermedius (Vim; also known as the ventral lateral posterior nucleus [VLp]) and the nucleus ventrocaudalis (Vc; also known as the ventral posterior [VP] nucleus). Differences in lesion volume among outcome groups did not achieve statistical significance. CONCLUSIONS: Anatomical evaluation of lesions within a standardized MR image-atlas integrated reference space is a useful method for determining optimal lesion localization. The results of an analysis of probabilistic maps indicates that optimal relief of tremor is associated with lesions involving the Vim (VLp) and the anterior Vc (VP).

Aged↗

Thalamic deep brain stimulation for disabling tremor after excision of a midbrain cavernous angioma. Case report.

Thalamic deep brain stimulation (DBS) has been demonstrated to be effective for the treatment of parkinsonian or essential tremor. To date, however, few data exist to support the application of this method to treat midbrain tremor. A 24-year-old right-handed man underwent radiosurgery and subsequent resection of a recurrently hemorrhaging cavernous angioma located in the left side of the midbrain. The surgery exacerbated severe choreoathetotic resting and action tremors of his right extremities and trunk. The patient underwent placement of a deep brain stimulator into the left ventral intermediate nucleus of the thalamus (Vim). Postoperatively, decreased truncal ataxia and right-sided choreoathetotic tremor were demonstrated, with a 57% increase in dexterity as measured by task testing. The authors demonstrate that DBS can be an effective treatment modality for disabling tremor after resection of a midbrain cavernous angioma.

Adult↗