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Tremor disorders. Diagnosis and management.

Tremor is commonly encountered in medical practice, but can be difficult to diagnose and manage. It is an involuntary rhythmic oscillation of a body part produced by reciprocally innervated antagonist muscles. Tremors vary in frequency and amplitude and are influenced by physiologic and psychological factors and drugs. Categorization is based on position, posture, and the movement necessary to elicit the tremor. A resting tremor occurs when the body part is in repose. A postural tremor occurs with maintained posture and kinetic tremor with movement. Various pathologic conditions are associated with tremors. Essential tremor, which is the most common, is postural and kinetic, with a frequency between 4 and 8 Hz, and involves mainly the upper extremities and head. Essential tremor responds to treatment with primidone, beta-blockers, and benzodiazepines. Parkinson's disease causes a 4- to 6-Hz resting tremor in the arms and legs that responds to the use of anticholinergics and a combination of carbidopa and levodopa. Tremor can also be a manifestation of Wilson's disease, lesions of the cerebellum and midbrain, peripheral neuropathy, trauma, alcohol, and conversion disorders. Treatment should be directed to the underlying condition. Stereotactic thalamotomy of thalamic stimulation is a last resort.

Humans↗

Lesion of dentatothalamic pathways in severe post-traumatic tremor.

The present study investigates evidence of dentatothalamic pathway lesions in nineteen patients with severe kinetic post-traumatic tremor respectively by magnetic resonance imaging (MRI). Kinetic tremor is thought to be characteristic of lesions of the cerebellar outflow. While this hypothesis is supported by experimental data, neuropathological and neuroradiological findings have been limited. The appendicular tremors were unilateral in 13 patients and bilateral in 6, accounting for 25 instances of tremor. The tremor developed after severe head trauma in 18 patients. These patients had evidence of diffuse axonal injury on MRI. Postural and kinetic tremor was present in all patients, and was accompanied by tremor also present at rest in 14 instances. Multiplanar MRI studies were performed on a high-field MRI system operating at 2.0 T in 13 patients and on intermediate-field strength MRI systems in 6 patients according to a standardized protocol. To detect small deposits of hemosiderin after post-traumatic lesions, the protocol included a heavily T2-weighted spin-echo pulse sequence. Lesions of the dentatothalamic pathways were found in 22 instances. The lesions were classified into different types of according to their distribution. A lesion of the dentate nucleus ipsilateral to the tremor (type 1) was found in one instance (4%), lesions involving the ipsilateral predecussational dentatothalamic pathway (type II and III) were found in 14 instances (56%), and lesions involving the contralateral post-decussational course (type IV) in 7 instances (28%). One patient with a mild head trauma had a lesion of the contralateral thalamus. The lesions appeared as hypointense, hyperintense or mixed. Two of three patients with a parkinsonian-like rest tremor had type IV lesions involving the substantia nigra. The nosological concepts of tremors are discussed. 'Midbrain' tremor may have distinct pathoanatomical lesion sites.

Adult↗

Levetiracetam for cerebellar tremor in multiple sclerosis: an open-label pilot tolerability and efficacy study.

PURPOSE: Disabling tremor is frequent in multiple sclerosis (MS) and its treatment remains challenging. We conducted an open-label trial to evaluate the effect of levetiracetam (LEV) to treat cerebellar tremor in MS patients. PATIENTS AND METHODS: Fourteen MS patients, aged 27 to 57 years, with cerebellar tremor. Tremor duration ranged from 3 to 14 years. The tremor clinical rating scale, the spiral drawings scale, and ataxia clinical scale were used to assess the severity of tremor. Data about the tremor-induced disability were obtained by using the specific Activities of Daily Living Questionnaire (ADL). LEV was orally administered at a starting dose of 500 mg twice daily for one week followed by increments of 500 mg twice daily each week up to the target dose of 50 mg/Kg/day. Patients were evaluated at baseline and two weeks after the end of titration phase. The Wilcoxon matched-pairs test was used for statistical analysis. RESULTS: Eleven patients completed the trial. LEV administration was associated with subjective and objective improvement of the tremor, with significant lowering of all tremor measurements' sum of scores as well as of ADL mean score between the baseline and follow-up. No correlation was found between the degree of improvement of the tremor and the disease duration or progression. LEV was well tolerated by subjects who completed the study. CONCLUSIONS: LEV could be useful for the management of cerebellar tremor in MS and the good tolerability makes it easy to test. LEV long-term efficacy should be confirmed in extended studies.

Activities of Daily Living↗

Clinical and electromyographic characteristics of tremor in patients with depression.

The aim of this investigation was to establish the clinical and electromyographic pattern of tremor in patients with depression.Twenty-eight patients with depression and tremor and 30 patients with tremor and generalized anxiety disorder were investigated. Tremor was scored clinically by the Webster Tremor Scale. Electromyographic examination of tremor activity from antagonistic hand muscles was performed.Our results revealed in both groups of patients a postural and kinetic tremor with characteristics of an enhanced physiological tremor. Tremor involved only both upper limbs and no other body parts in all patients.In conclusion tremor in depression and generalized anxiety disorder is an enhanced physiological tremor.

Journal Article↗

Tremor.

PURPOSE OF REVIEW: Tremors can be encountered in a variety of disease states but the most common causes are Parkinson disease and essential tremor. This review was undertaken to highlight advances in the field during the last 12 months. RECENT FINDINGS: Kinetic tremor may be more prominent in essential tremor than postural tremor. Clinically Parkinson disease and essential tremor may be confused with each other but it may be possible to distinguish between these two nitrites using sophisticated electrophysiology. Monosymptomatic rest tremor has recently been shown to be associated with decreased fluorodopa uptake on the positron emission tomography scan suggesting its relationship to Parkinson disease. SUMMARY: Significant advances have been made in the understanding of the pathophysiology, genetics and therapy of tremor disorders during the last 12 months. This review will consider Parkinson disease, essential tremor and other tremors and highlight advances in the field.

Acetates↗

Tremor at onset. Predictor of cognitive and motor outcome in Parkinson's disease?

We examined 46 male patients with idiopathic Parkinson's disease to see whether tremor at onset was as useful a predictor of benign clinical outcome as tremor predominance after several years. When we compared patients with tremor at onset (n = 27) with those whose disease began with brady-kinesia/rigidity (n = 9), or gait disorder (n = 10), we found no significant differences after a mean of 7 years in motor, cognitive, or affective status. Sixteen of the tremor-onset patients continued to have tremor predominance with minimal gait disorder after about 7 years. These tremor-predominant patients had significantly better motor outcome and somewhat better cognitive outcome than either tremor-onset patients who subsequently developed gait disorder (n = 11) or patients without tremor at onset (n = 19). Tremor predominance after several years appears to be a better predictor of a benign clinical course of Parkinson's disease than tremor at onset.

Cognition↗

19th-century American contributions to the recording of tremors.

Studies of tremor in the 19th century were based initially on simple observation and later on the use of crude graphic recording devices that had been modified from instruments developed for other purposes. Like several European contemporaries, American investigators studying tremor used and adapted various existing instruments, including tambours and sphygmographs. A tambour used a drum-shaped pneumatic mechanism to transmit movements to a recording instrument, whereas the sphygmograph was a nonpneumatic mechanical device initially used to record the pulse. 19th-century American neurologists who used such devices included Frederick Peterson, Hobart Amory Hare, Charles Loomis Dana, and Augustus A. Eshner. Their measurements of tremor frequency were generally consistent with modern estimates for various types of tremor. Eshner, in particular, was frustrated by the overlap of frequency domains for tremors in different diseases, because this precluded use of tremor frequency alone as a differentiating feature for diagnosis. Peterson and Dana recognized the variation in tremor frequency in different body parts resulting from different natural resonance frequencies of these parts as a function of weight and elastic properties. Peterson, Dana, and Eshner also recognized that tremor amplitude and frequency are inversely related. Finally, these 19th-century investigators recognized that the tremor of Parkinson's disease is a relatively low-frequency rest tremor, suppressed by action, and generally synchronous in symmetric body parts, but varying in amplitude and frequency in different body parts or over time.

History, 19th Century↗

A teaching videotape for the assessment of essential tremor.

UNLABELLED: Teaching videotapes, developed to aid in the evaluation of several movement disorders, have not been used in essential tremor research. As part of the Washington Heights-Inwood Genetic Study of Essential Tremor (WHIGET), we developed a reliable and valid tremor rating scale. Because this rating scale is currently being used by investigators at other centers, we developed a teaching videotape to aid in the consistent application of this scale. OBJECTIVE: To develop a teaching videotape for a revised version of the WHIGET Tremor Rating Scale and to assess the interrater agreement among raters who used this videotape to rate tremor. METHODS: The revised WHIGET Tremor Rating Scale was used to rate action tremor from 0 to 4 during six tests: arm extension, pouring, drinking, using a spoon, finger-to-nose, and drawing spirals. A 22-minute teaching videotape was developed that includes a 29-item educational section and a self-assessment section consisting of 20 examples of tremor ratings chosen by the two WHIGET study neurologists. Eight raters, including senior movement disorder specialists, movement disorder fellows, general neurologists, and a movement disorder nurse practitioner, independently viewed the videotape and rated tremor during the self-assessment section. Interobserver reliability was assessed with weighted kappa statistics (kappa(w)). RESULTS: Eight raters each rated 20 items (160 ratings total). Total kappa(w) was 0.97 (nearly perfect agreement). Interrater reliability was as follows: kappa(w) = 0.99 (movement disorder specialists), kappa(w) = 0.98 (movement disorder fellows), and kappa(w) = 0.97 (general neurologists); all kappa(w) were nearly perfect. CONCLUSIONS: This teaching videotape may be used to improve the uniform application of the revised WHIGET Tremor Rating Scale by raters with various levels of experience in movement disorders.

Essential Tremor↗

The tremor in fatigue.

After a maximal voluntary effort made for about 2 min, tremor of the muscles concerned is increased in amplitude by up to one order of magnitude for a period of several hours afterwards. Spectral analysis reveals that all frequencies of tremor show this increase. Maximal electrical stimulation of the motor nerve to the muscle does not result in any change in tremor so it is inferred that the increase is due to the operation of spinal or supra-spinal mechanisms. A sub-maximal voluntary effort, maintained for about 1 h, leads to the development of large amplitude, low frequency tremor (4-6 Hz) in addition to increased physiological tremor (8-12 Hz). It is generally accepted that physiological tremor originates as an oscillation in the reflex arc servo loop. The 4-6 Hz slow tremor of this type of fatigue also appears to arise as servo loop oscillation, the feedback delays being longer than in physiological tremor. The spectrum of the slow tremor resembles that found in Parkinsonism and it may be useful model for the tremor of that condition.

Electric Stimulation↗

Effect of a single oral dose of propranolol on essential tremor: a double-blind controlled study.

The effect of a single oral dose of propranolol (120 mg) on essential tremor was investigated in a double-blind, placebo-controlled study in 26 patients. Hand tremor was recorded by means of accelerometers, and its frequency and amplitude calculated by using spectrum analysis. Recordings were made before and 1 1/2 hours after drug or placebo administration. Pretreatment tremor ranged from 4.2 to 9.6 Hz (median, 6.9 Hz) in frequency and from 0.002 to 1.33 cm (median, 0.014 cm) in amplitude. Neither propranolol nor placebo affected the frequency of the underlying tremor. The amplitude of tremor was reduced by 43 +/- 11% (SEM) after propranolol (p less than 0.01) and by 12 +/- 8% after placebo (NS). The reduction observed after propranolol was significantly greater than that observed after placebo. The tremor response after propranolol correlated negatively with baseline frequency and positively with pretreatment amplitude, duration of tremor, and age of the patient. No significant relationships could be found between tremor response, serum propranolol levels, and degree of cardiac beta blockade as assessed by the inhibition of standing tachycardia. There was a clear tendency for patients with small tremor amplitude (less than 0.006 cm hand displacement) to show the least satisfactory response to propranolol. These results indicate that a single oral dose of propranolol is effective in producing a rapid and marked reduction of essential tremor. Measurement of pretreatment amplitude and frequency might be useful in predicting the therapeutic outcome in these patients.

Adult↗

Characterization of subclinical tremor in Parkinson's disease.

The physiological or pathological nature of subclinical tremor amplitude in Parkinson's disease (PD) is not well established. We analyzed characteristics of resting and postural tremors of subclinical amplitude in 17 patients with idiopathic PD without visible resting tremor, having a postural tremor in their least-affected hand rated 0 (12 subjects) or 1 (5 subjects) on Item 21 of the Unified Parkinson's Disease Rating Scale, compared to 17 control subjects matched for age, sex, and handedness. Tremor was recorded at the tip of the index finger using a displacement laser transducer. Overall results show that subclinical resting tremor in PD is significantly different from physiological tremor in terms of amplitude fluctuation, frequency dispersion, harmonic index, and proportional power in 4 to 6 Hz. No significant differences were found for postural tremor. These differences appear to originate mainly from patients with the mixed form of the disease. This study also confirms the preservation of physiological tremor likely originating from a distinct central oscillator in PD. The use of this method in the early and detailed characterization of PD tremors when amplitude is still within normal limits is proposed.

Adult↗

Corticomuscular coherence is increased in the small postural tremor of Parkinson's disease.

The mechanisms and electrophysiological characteristics of the postural tremor in Parkinson's disease (PD) have not been defined. We hypothesized that PD subjects with small amplitude postural tremor would show increased corticomuscular coherence at certain frequencies compared to PD subjects without visible tremor. Four groups of participants were studied: (1) Control without postural tremor, (2) Control with small amplitude postural tremor, (3) PD without postural tremor, and (4) PD with small amplitude postural tremor. Accelerometry and electroencephalography-electromyography fast-fourier transform and corticomuscular coherence spectra were generated. Findings showed (1) elevated corticomuscular coherence centered at 12-18 Hz in PD with small amplitude postural tremor; (2) 5-12 Hz accelerometer frequency peaks that did not shift with increasing weight loads in some individuals; and (3) 5-8 Hz accelerometer peaks that shifted frequency with increasing weight loads, consistent with a peripheral-mechanical oscillator in all groups. The small amplitude postural tremor in PD arises from heterogeneous oscillator mechanisms. The discovery of increased corticomuscular coupling shows cortical involvement in the small amplitude postural tremor of PD.

Aged↗

Primary writing tremor. A form of focal dystonia?

Five patients exhibited severe tremor in the upper extremity, primarily when attempting to write or draw. Electromyography was performed to determine the patterns of muscle activity that were responsible for this tremor. Tremor was measured with an accelerometer and with a digitizing tablet. Two patients had postural tremor that was indistinguishable from mild, high-frequency essential tremor. All patients exhibited a severe 5-7-Hz tremor during the acts of writing and drawing. Muscles throughout the affected extremity exhibited rhythmic 5-7-Hz bursts of motor unit discharge, and the average level of motor unit activity was tonically increased in antagonistic muscles. This abnormal coactivation of antagonistic muscles produced subtle dystonic posturing of the affected limb that was overshadowed by severe tremor. Electromyography was useful in confirming the coexistence of tremor and dystonia in our patients. The nonspecificity of dystonia and postural tremor must be considered when discussing the nosology and pathophysiology of primary writing tremor.

Adult↗

Factors influencing the amplitude and frequency of essential tremor.

Quantitative electromyography (EMG) and triaxial accelerometry were used to measure hand tremor, finger tremor, and forearm motor unit activity in 36 men and 23 women with essential tremor. Hand tremor was studied with and without 300-g mass loading. Tremor and EMG were recorded twice, with a 3-min rest interval, to assess the spontaneous intertrial variability in tremor amplitude, frequency, and motor unit entrainment. In general, the minimum detectable differences in tremor amplitude, frequency, and motor unit entrainment were roughly 30%, 5%, and 10% of the initial sample means, respectively, assuming a sample size of 30 patients, a statistical power of 0.9, and a significance level of 0.05. Linear regression analyses were performed to test the hypotheses that (a) there is an age-associated decrease in tremor frequency that is independent of symptom duration and (b) tremor frequency and motor unit entrainment make independent contributions to tremor amplitude. Our data supported both hypotheses.

Adolescent↗

Treatment of tremor in Parkinson's disease by subthalamic nucleus stimulation.

The recent resurgent interest in functional surgery for the treatment of Parkinson's disease (PD) has focused on the effects on akinesia and levodopa-induced dyskinesia. Stimulation of the subthalamic nucleus (STN) improves akinesia and rigidity but its effects on tremor have not been studied. The objective of this study was to assess the efficacy of STN stimulation on tremor in patients with the complete parkinsonian triad with motor fluctuations. Of 27 consecutive patients with STN stimulation (26 bilateral), 15 exhibited tremor rated at least 2/4 according to item 20 (rest tremor) of the Unified Parkinson's Disease Rating Scale (UPDRS) in at least one limb. The mean preoperative tremor score was 11.3+/-5.6 in off-drug and 1.2+/-2.4 in on-drug conditions. The postoperative tremor scores at the last follow up (from 1-12 months) were 2.2+/-2.2 off-drug/on-stimulation and 0.2+/-0.4 on-drug/on-stimulation. Both rest and action tremors were improved in all patients. The UPDRS tremor score was reduced by 80%, rigidity score by 65%, and akinesia score by 51% on average. For the three symptoms, the stimulation effect was close to that induced before surgery by a suprathreshold dose of levodopa given in the morning. STN stimulation can be considered an interesting alternative to thalamic or internal pallidal surgery even in PD patients with severe high-amplitude tremor. In keeping with electrophysiological data in monkeys rendered parkinsonian by MPTP injections, our results emphasize the importance of the oscillation of a neuronal loop involving the STN in the pathophysiology of parkinsonian tremor.

Adult↗

Characteristics of hand tremor time series.

Tremor is classified into physiological, essential, and parkinsonian tremor by means of clinical criteria. The aim of our work was to extract quantitative features from the measurements of the acceleration of human postural hand tremor. Different mathematical methods were adopted and modified in order to separate these three types of tremor. Best discrimination between physiological and pathological tremors has been achieved by methods distinguishing nonlinear from linear behavior. On the other hand, methods separating different forms of nonlinear behavior have been found to be superior in discriminating parkinsonian and essential tremor. By these methods physiological and pathological tremors can be separated with an error rate below 20% and essential and parkinsonian tremor with an error rate below 10%. This may help to classify tremor time series by objective mathematical criteria and may increase the understanding of the pathophysiological differences underlying these kinds of tremor.

Cybernetics↗

Primary orthostatic tremor: further observations in six cases.

The clinical and physiological features of six new patients with primary orthostatic tremor are described. We suggest that use of the term primary orthostatic tremor be confined to the clinical syndrome in which unsteadiness when standing is the predominant complaint and accompanied by characteristic electrophysiological findings of a rapid (frequency around 16 Hz), regular leg tremor which is not influenced by peripheral feedback, is synchronous between homologous leg muscles, and in certain postures of the upper limbs, between muscles of the arm and leg. The fast frequency of muscle activity in primary orthostatic tremor of the legs causes unsteadiness when standing (presumably due to partially fused muscle contraction) but only a fine ripple of muscle activity is visible. In contrast, the slower frequency of other leg tremors, for example essential tremor, results in obvious leg movement which is evident in many leg postures, is variable over time and can be reset by a peripheral nerve stimulus. Essential tremor and orthostatic tremor do not respond to the same therapies, suggesting differences in the pharmacological profiles of the two conditions. Accordingly, there are clinical, physiological and pharmacological differences between primary orthostatic and essential tremor. Whether these factors are sufficient to regard these tremors as separate conditions is discussed.

Adult↗

Attenuation of pathological tremors by functional electrical stimulation. II: Clinical evaluation.

In this study we evaluated a technique for tremor suppression with functional electrical stimulation (FES), the technical details of which were described in the previous paper. Three groups of patients were investigated: those with essential tremor, parkinsonian tremor, and cerebellar tremor associated with multiple sclerosis. In each group, tremor was attenuated by significant amounts (essential tremor: 73%; parkinsonian tremor: 62%; cerebellar tremor: 38%). These attenuations were in good accord with predictions based on the dynamic analyses and filter designs derived in the previous paper. With filters "tuned" to the lower mean tremor frequency encountered in the cerebellar patients, more attenuation was possible in this group as well. We identified some practical limitations in the clinical application of the technique in its present form. The most important was that in daily use, only one antagonist pair of muscles can realistically be controlled. At first sight, this restricts the usefulness of the system to patients with single-joint tremors. However, the concomitant use of mechanical orthoses may broaden the scope of application.

Adult↗