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Holmes-like tremor of the lower extremity following brainstem hemorrhage.

Holmes tremor is an arrhythmic, 2- to 5-Hz resting, postural, and kinetic upper extremity movement disorder that occurs weeks to months after acute mesencephalic pathology. We present a patient who developed tremor in three body parts postbrainstem hemorrhage with subsequent hypertrophic olivary degeneration and discuss the relevant clinical evolution. Our case is unique because in addition to expected upper extremity and cervical dystonic head tremors, the patient also developed a severe lower extremity movement disorder, which we believe to be a form of Holmes tremor. Tremor involving the lower extremity in this setting has not been previously reported.

Acute Disease↗

A double-blind placebo-controlled trial of zonisamide (zonegran) in the treatment of essential tremor.

Medical therapy for essential tremor (ET), a common movement disorder, is often inadequate. We performed a double-blind placebo-controlled randomized trial to evaluate the efficacy and tolerability of zonisamide (ZNS), an antiepileptic agent, in treating ET. Twenty patients (mean age, 60 +/- 15 years) with ET were randomized to receive ZNS or placebo. ZNS was initiated at a dosage of 100 mg/day and escalated to 200 mg/day at day 14. Patients were evaluated by accelerometry and the Fahn-Tolosa-Marin (FTM) rating scale at baseline and days 14 and 28, as well as the Clinical Global Impression (CGI-C) scale at day 28. At endpoint, subjects assigned to ZNS were taking a mean dosage of 160 +/- 50 mg/day. There were no significant improvements in the FTM total score or its subsections. Tremor amplitude as assessed by accelerometry significantly improved in the ZNS group compared to the placebo group at endpoint relative to baseline (-0.50 +/- 0.72 vs. 0.30 +/- 0.79 m/s(2); P = 0.03). On the CGI-C, 60% (n = 6) of patients in the ZNS group felt that their tremor was unchanged, while the remaining patients felt that their tremor was "minimally improved." Thirty percent (n = 3) of patients taking ZNS discontinued the study due to side effects (fatigue, headache, paresthesias) while taking 100 mg per day. ZNS did not provide significant improvements in clinical rating scales at study endpoint compared to placebo and was only modestly well tolerated. ZNS was effective in reducing tremor amplitude as measured by accelerometry.

Anticonvulsants↗

Dystonia and tremor following exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin.

Forty-seven railroad workers who were exposed to polychlorinated phenols, including dioxin (TCDD), during 1979 while cleaning up the chemical spillage following damage to a tank car filled with these chemicals were followed medically for the subsequent 6 years. Two committed suicide. The initial neurological complaints included a sense of fatigue and muscle aching, both of which have been reported in other individuals following dioxin exposure. On detailed neurological examination in December, 1985, 24 of 45 had dystonic writer's cramp and/or other action dystonias of the hands. None of the involved individuals had a family history of dystonia, and all 24 dated the onset of the dystonia to the first 2 to 3 years subsequent to their toxic exposure. The dystonias varied in severity but were usually mild. No other types of dystonic involvement were recognized. Thirty-five of the 45 individuals also manifested postural and terminal intention tremor which resembled benign essential tremor. None of the involved individuals had a family history of tremor, and all 35 of those affected dated the onset of the tremor to some time subsequent to their toxic exposure. Forty-three of 45 patients had histories and findings suggestive of peripheral neuropathy. This is the first report relating any type of dystonia to prior dioxin exposure and the first report relating action dystonia, such as dystonic writer's cramp, and postural/terminal intention tremor, to toxic exposure of any type.

Adult↗

Tremor and idiopathic dystonia.

The clinical and electromyographic characteristics of tremor were studied in 45 patients presenting with various forms of idiopathic dystonia. Dystonic tremor was shown to be postural, localized, and irregular in amplitude and periodicity, absent during muscle relaxation, exacerbated by smooth muscle contraction, and associated frequently with myoclonus. Although it resembles essential tremor, dystonic tremor seems to be a distinct entity: it is more irregular with a broader range of frequencies; it is asymmetric and remains localized; myoclonus is sometimes associated. This type of tremor is most often seen in the presence of dystonia, but may be observed without evident dystonic symptoms.

Adolescent↗

Tardive tremor.

A variety of hyperkinetic movement disorders has been associated with the use of neuroleptics (dopamine receptor blocking drugs), but tardive tremor has not been previously documented. We describe five patients in whom tremor occurred after chronic treatment with neuroleptics, was aggravated by and persisted after neuroleptic withdrawal, and improved after treatment with the dopamine depleting drug tetrabenazine. This involuntary oscillatory movement, with a frequency range of 3-5 Hz, was most prominent during maintenance of a posture, but was also present at rest and during a goal-directed movement. The tremor was accompanied by other tardive movement disorders, including akathisia, chorea, dystonia, myoclonus, and stereotypy. There was no family history or other explanation for tremor in these patients. We suggest that this hitherto unreported movement disorder is best termed "tardive tremor."

Aged↗

Focal task-specific tremors.

Focal task-specific tremors besides primary writing tremor have rarely been reported in the literature. We describe nine cases of focal tremors induced by different specific tasks, involving a repetitive and frequently performed movement. Only one of these patients had a family history of any similar disorders. There was no overt dystonia in any of the cases, but these tremors may be forms of focal dystonia, rather than a manifestation of essential tremor.

Adult↗

Assessment of ability/disability in patients treated with chronic thalamic stimulation for tremor.

Chronic thalamic stimulation (CTS) has a documented good effect on tremor in patients with Parkinson's disease (PD) and essential tremor (ET). This study evaluates whether the alleviation of impairment, i.e., tremor, translates into improvement of the patient's ability in performing instrumental activities of daily living (IADL). Thirteen patients were assessed with an occupational therapy tool called Assessment of Motor and Process Skills (AMPS). This observation-based scale rates the patient's motor and process skills needed to perform a given task. The evaluations were done at a mean of 13 months after surgery in the patient's home, and included assessments of IADL with the CTS activated and switched off, respectively. The results showed that most patients improved to variable degrees in their IADL ability when the thalamic stimulation was on. The improvement was more marked in patients operated on for tremor of their dominant hand. The improvement concerned mainly the skill items related to the patients' abilities of coordination, calibration, endurance, and accommodation during IADL task performance. The authors concluded that for some patients with tremor, CTS can improve independence in domestic activities of daily living.

Activities of Daily Living↗

Pharmacologic treatment of tremor.

Tremor is a common neurologic symptom that can also be incapacitating to the patient, so effective therapy is needed. The causes of tremor are heterogeneous. Essential tremor (ET) and the tremor associated with Parkinson's disease (PD) are the most common encountered in clinical practice. Beta-adrenergic blockers and primidone remain the mainstay of treatment for ET, whereas carbidopa/levodopa and anticholinergics are most beneficial in PD. However, the efficacy of various other medications has been studied in ET and PD, and also in patients with tremor resulting from other conditions, with varying results.

Humans↗

Effect of exercise on microsurgical hand tremor.

This study investigated the effects of upper-body and aerobic/lower-body-only (nonupper-body) exercise on microsurgical hand tremor. Subjects were given a task of holding a microsurgical needle tip over a small target, with video-microscopic documentation immediately before and 0, 2, 4, 8, and 24 h after either upper-body or nonupper-body (aerobic) exercise. Tremor was quantified by the amount of time the needle was maintained within a 100 x 100-microm target zone and the number of times the needle extruded from the zone. Both upper-body and aerobic-only exercise groups had significant increases in tremor immediately after exercise (P < 0.02), with a return to baseline tremor 2 h after exercise in the aerobic group and only a slightly prolonged return to baseline (by 4 h) in the majority of upper-body exercise subjects. These findings demonstrate that microsurgical hand tremor increases following exercise, but returns to baseline within 4 h in the majority of individuals, particularly after aerobic-only workouts.

Exercise↗

Physiologic tremor and microsurgery.

Physiologic tremor hampers the ability of students to learn microsurgical technique. An understanding of normal tremor both as to origin and methods of control would be of help. Physiological tremor arises from both mechanical and neuromuscular sources and is made worse by a number of factors. The "size principle of motoneuron recruitment" is an important physiologic consideration, and the use of biofeedback techniques enables the student to confirm his understanding of the principle. Knowledge of the factors which aggravate physiological tremor allows the microsurgeon to control his own tremor both in the laboratory and in the operating room.

Biomechanical Phenomena↗

Loss of reflex inhibition following muscle tendon stimulation in essential tremor.

Electrical stimulation of human upper limb muscle tendons produces a reflex inhibition (I(1)) in the same muscles. This inhibition is reduced in Parkinson's disease (PD), prompting a similar study of essential tremor (ET). In essential tremor, two of eight subjects had no discernible inhibition, even following supramaximal stimulation (< 80 mA) of the tendons from extensor digitorum communis and extensor pollicis brevis. In the remaining six subjects, the mean thresholds for I(1) in these muscles were increased by 270 and 320%, respectively, relative to controls. The maximal amplitude of the inhibition was significantly reduced in the ET group, as was the following excitation (E(1)). The latency and duration of I(1) were not different in ET subjects and controls. The maximal duration of I(1) was correlated with tremor frequency in individuals, and tendon stimulation was effective in initiating ongoing tremor cycles. These results disclose a peripheral reflex abnormality in ET that is mediated by tendon afferents and can be linked to the coexistent tremor. The response in ET was distinguished from that in PD by its different time-course and by failure of the response to appear in the antagonist muscle. The abnormality may prove a useful marker for ET, which currently lacks a definitive pathological or neurophysiological marker to support objective clinical diagnosis.

Electric Stimulation↗

Isometric features of orthostatic tremor: an electromyographic analysis.

A patient is described with "orthostatic" tremor. Electromyography revealed tremor bursts of 15 Hz in the lower extremities while standing and with isometric activation of the muscles, but the bursts disappeared with isotonic activation of muscles. Similar tremor was recorded in the arms with isometric, but not isotonic activation. Review of previously reported cases confirms these findings. The clinical and electrophysiologic features of this tremor distinguish it from other recognized forms of tremor.

Aged↗

Deep brain stimulation and thalamotomy for tremor compared.

Deep brain stimulation (DBS) and thalamotomy are both capable of abolishing tremor. However, no technique is perfect and if thalamotomy proves inadequate so that tremor recurs, presumably because of suboptimal lesion location, the only option is to repeat the thalamotomy. With DBS all that has been necessary to date is to change the parameters of stimulation. Similarly with complications such as the "cerebellar" ones and paraesthesiae. If these occur after thalamotomy one can only wait and hope that they will subside and they do not always do so. With DBS, changing the parameters in the authors' patients has so far been successful in eliminating them. DBS, like thalamotomy is very effective for controlling tremor in Parkinson's disease (PD) and essential tremor (ET) and for improving dexterity in ET, but both techniques are less useful for the control of dopa dyskinesia, Parkinsonian rigidity, or impaired dexterity in PD, though DBS may be better than thalamotomy for the latter condition. On the other hand, both DBS and thalamotomy are very effective in improving dexterity in PD and ET may depend upon the fact that in PD bradykinesia is a major component, whereas in ET only the tremor is. The advantages of DBS over thalamotomy have to be weighed against the peculiar risks of DBS and of course, its cost.

Adult↗

Inter- and intra-limb coordination in arm tremor.

Inter- and intra-limb coordination in arm tremor was examined in adult subjects under vision and no vision conditions using accelerometery techniques. The accelerometer data were analyzed using standard time and frequency domain analyses and the regularity of the acceleration time series was determined using an approximate entropy (Ap En) measure. The data analysis was structured to examine the hypothesis that there is a functional compensatory relation between the motion (tremor) of the limb segments in the arm coordination postural pointing task. The results showed that the level of acceleration increased in a proximal to distal direction within a single arm and was symmetrical across homologous arm segments. The frequency analysis showed the established power spectral profiles for each limb segment in postural tremor tasks, but the finger motion included (beyond the normal 8-12 Hz and 20 Hz tremor) a third slower peak at around 2-3 Hz, due possibly to the reactive forces of the other arm links. There was no effect of vision on the level or frequency patterns of accleration in the limb segments. The coordination analysis showed that there was no linkage between the arms in either the time or frequency domain in the execution of this postural task. This result would tend to suggest that the neuronal commands underlying normal tremor are not derived from a common central oscillator within the central nervous system but are organized in a parallel fashion. The strength of the coupling of intra-limb coordination varied according to the particular adjacent limb links. There were significant correlations in the time domain and coherence in the frequency domain in the acceleration signals between upper arm and forearm, and between hand and finger. The phase lag of the arm units within each of these respective segment pairs was close to in phase or 0 deg. Significant coherence in the frequency domain was also evident between upper arm and hand motion, with the phase lag between these segments being close to 180 deg out of phase. The Ap En analysis of the acceleration signals revealed that there was more regularity to the upper arm and hand accelerometer signals than the forearm and finger signals. The findings show that the intra-limb coordination of the arm links in a two-limb postural pointing task is effected by a compensatory synergy organized about the action of the wrist and shoulder joints. This compensatory synergy reduces the coordination of the 4 within-limb degrees of freedom (arm links) to, in effect, a single degree of freedom arm control task that is not coupled in organization to the motion of the other limb or the torso. It is proposed that this coordination solution reduces the degrees of freedom independently regulated for realization of the task goal but preserves independent body segment control in critical degrees of freedom for potential adaptation to postural perturbations.

Adaptation, Physiological↗

Influence of handedness on motor unit discharge properties and force tremor.

Discharge properties of motor units (MUs) in the first dorsal interosseous muscle (FDI) were studied in the dominant and non-dominant hands of six right-handed (RH) and six left-handed (LH) individuals. MU discharge rates and variability were similar in each hand in RH (186 MUs) and LH (160 MUs) subjects. MU synchronization was less prominent in the dominant hand of RH subjects, with 51% (45/88) of cross-correlograms of MU discharge having significant central peaks, compared with 81% (90/111) for the non-dominant hand. The strength of MU synchronization (expressed as the frequency of extra synchronous discharges above chance) was weaker in the dominant hand of right-handers (0.23 +/- 0.03 s-1 vs 0.39 +/- 0.03 s-1), and synchronous peaks from that hand were slightly broader. Four of six RH subjects had significant differences in synchronization between hands (weaker in dominant hand). In contrast, left-handers had similar incidence (80 vs 82%, n = 161) and strength (0.41 +/- 0.03 s-1 vs 0.37 +/- 0.03 s-1) of MU synchrony in dominant and non-dominant hands. No LH subject had a significant difference in synchronization between hands. Force tremor was quantified in each hand in the same subjects during isometric abduction of FDI at 0.5 N and 3.5 N, and directly correlated with the extent of MU synchronization in the muscle. Tremor root mean square amplitude was similar in dominant and non-dominant hands. Power spectral analysis of the tremor force revealed that the peak frequency in the power spectrum was not influenced by handedness, but power at the peak frequency was higher in the non-dominant hand of RH subjects. Correlations between MU discharge variability and synchrony with measures of tremor amplitude were weak. The reduced MU synchronization in the dominant hand of right-handers may reflect a more restricted distribution of direct projections from motor cortical neurons within the FDI motoneuron pool, or reduced excitability of the cortical neurons during the task. These differences in MU synchronization, however, had an insignificant influence on the magnitude of physiological tremor in the FDI.

Adult↗

Change in the concentrations of amino acids in CSF and serum of patients with essential tremor.

The concentrations of amino acids in the cerebrospinal fluid (CSF) (n = 20) and serum (n = 20) taken from patients with essential tremor were measured by HPLC and compared with those of controls (n = 10). Reduced concentrations of some amino acids (asparagine, glutamine, glycine, threonine, isoleucine, leucine) were observed in serum taken from patients with tremor. Significant increases were detected in the concentrations of glutamate (p < 0.001) and aspartate (p < 0.01). The general tendency of the changes in CSF and serum was similar; although the highest differences were observed in amino acid concentrations in the serum of patients with essential tremor. Opposite shifts of some amino acids were detected, in the concentrations of aspartate, serine, tyrosine, leucine, and isoleucine, which may indicate the independence of the changes in the serum from those in the CSF. This study raises the possibility that a genetically determined metabolic disorder is involved in the etiology of essential tremor that appears peripherally and, partly, centrally. The slight increase in the concentration of glutamate together with the reduced levels of GABA, glycine, and serine in CSF may form the neurochemical basis of the central oscillation observed in essential tremor.

Adolescent↗

Behavioral relaxation training for tremor disorders in older adults.

Two adult men, aged 86 and 63, with essential tremor and Parkinson's-disease-related tremor, respectively, were provided Behavioral Relaxation Training in reclined and upright seated positions. Multiple measures were recorded, including the Behavioral Relaxation Scale (BRS), clinical and self-rated tremor severity, informant ratings, ratings of disability in activities of daily living (ADL), and forearm EMG. Results showed increased relaxation skills on the BRS, with reductions in EMG, tremor ratings, and some ADL disabilities. Upright BRS scores did not change during reclined training, but improved rapidly during upright training. The second man was found to suffer from dyskinesia when he relaxed during baseline, which declined markedly during training. A two-week follow-up indicated that most improvements were maintained by both men. Statistical analyses of data for each man showed significant changes. These results suggest that relaxation may be useful in the treatment of idiopathic and pathologic tremor disorders in older adults.

Aged↗

Assessment of the amplitude of oscillations associated with high-frequency components of physiological tremor: impact of loading and signal differentiation.

The goal of this study was accurate quantification of the amplitude of high-frequency components of physiological tremor (PT) in units of displacement, velocity, and acceleration. In addition, changes of amplitude with finger loading were compared within specific frequency bands. Index finger tremor was measured for 20 healthy subjects using a high-resolution laser, simultaneously with an accelerometer, under two conditions, unloaded and loaded (70 g). By use of an accurate filtering technique, oscillations within six predetermined frequency bands were isolated. Results showed that overall mean tremor amplitude under the unloaded condition was 0.0973 mm in displacement units, 4.525 mm s(-1) in velocity units, and 301.526 mm s(-2) in acceleration units. Although the mean amplitude of oscillations located within the 16.5-30 Hz band was 0.009 mm and represented only 10% of total tremor amplitude, amplitude of acceleration within the 16.5-30 Hz band was 191 mm s(-2) and represented 60% of total acceleration amplitude. Mean amplitude increased significantly with loading (displacement, t=-2.67, P=0.015; velocity, t=-4.33, P=0.000; acceleration, t=-3.48, P=0.002) but the magnitude of that change was different in each frequency band and its relative importance depended on the level of signal differentiation. Velocity was the only measure that retained sensitivity to changes in amplitude with loading in the low and high-frequency components of PT. In conclusion, this study provides, for the first time, accurate quantification of the amplitude of oscillation of high-frequency components of PT. In addition, it provides clear evidence that the velocity of tremor oscillation is more suitable for detection of the impact of finger loading because it enables detection of amplitude changes in both the low and high-frequency components of PT.

Adolescent↗