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Abnormal vibration induced illusion of movement in essential tremor: evidence for abnormal muscle spindle afferent function.

OBJECTIVES: Vibration induced illusion of movement (VIIM) is abnormal in patients with idiopathic focal dystonia, an abnormality which corrects with fatigue of the vibrated muscle. Since dystonia and essential tremor sometimes coexist in families, we investigated the perception of VIIM and the effect of fatigue on VIIM in patients with essential tremor. METHODS: VIIM in 18 patients with essential tremor was compared with VIIM in 18 healthy control participants before and after volitional fatigue of the vibrated muscles. RESULTS: Vibration of the immobilised biceps produced a subnormal VIIM in patients with essential tremor (12.81 degrees (SEM 2.15)) compared with healthy control subjects (28.55 degrees (1.66)). The perception increased following volitional fatigue of the vibrated arm in patients with essential tremor (16.23 degrees (2.50)) but not in healthy controls (27.55 degrees (1.66)). No difference was observed in patients with alcohol or non-alcohol responsive tremor. CONCLUSIONS: The VIIM decreased with increasing age in healthy control subjects. Abnormal VIIM implies abnormal sensorimotor processing in patients with essential tremor, similar to that found in idiopathic focal dystonia, and the change of the perception with age could explain the age related onset of the disorder.

Afferent Pathways↗

Variability in amplitude of untreated essential tremor.

Tremor amplitude was monitored in untreated patients with essential tremor by a procedure designed to minimise fluctuations due to factors known to influence tremor. Tremor was measured hourly for 6 hours in 14 patients and on five to seven occasions (separated by at least a week) in 22 patients. A wide range of within-patient variability was found, with some patients showing little and others showing considerable fluctuations in amplitude over the series of recordings. There was no simple relationship between variability and mean amplitude, frequency, age, duration of tremor or response to a single oral dose of propranolol. Variability did not differ between males and females or between patients with and without a family history of tremor. Diurnal fluctuations showed no consistent pattern. Long-term assessment revealed a significant trend towards lower amplitudes on successive occasions. To overcome systematic bias in data collection, clinical trials in essential tremor should employ large numbers of patients and rigorous randomisation of treatments in cross-over designs.

Adolescent↗

Stability and tremor in the fingers associated with cerebellar hemisphere and cerebellar tract lesions in man.

Stability and tremor in the fingers were assessed by a new technique in patients with unilateral cerebellar syndromes. In 11 patients with unilateral cerebellar hemisphere lesions tremor was observed with either clear tremor at 5-7 Hz or prolongation of the tremor profile out to 11 Hz. In 10 patients with unilateral cerebellar lesions associated with ipsilateral past-pointing there was an asymmetry in finger stability. Compared with normal subjects there was a significant decrease in stability contralateral to the lesion, while the ipsilateral side's stability was not different from normal. In patients with high brain stem lesions at the level of cranial nerves VII and above, tremor had frequencies of 5-7 Hz. In those with lower brain stem lesions, often with long tract signs as well, the frequencies of tremor were faster, 8-11 Hz, which may reflect damage to cerebellar inflow tracts. A broad if not specific correlation was found between clinical condition, site of lesion and finger stability and tremor.

Adolescent↗

Parkinson's disease and essential tremor in families of patients with early-onset Parkinson's disease.

The occurrence of Parkinson's disease and of essential tremor was examined in the parents and siblings of 52 Parkinson's disease patients with onset before the age of 45 years. The expected numbers of cases with Parkinson's disease or essential tremor were calculated according to the age and sex specific incidence rates of Parkinson's disease and essential tremor in the general population. Among the parents, there was one case of Parkinson's disease (expected 1.2), and 10 cases of essential tremor (expected 5.4); among the siblings there were two cases of Parkinson's disease (expected 0.7), and three cases of essential tremor (expected 5.3). The observed and expected incidence of Parkinson's disease or essential tremor were not significantly different. This does not support the inheritance of early-onset Parkinson's disease, or the association of Parkinson's disease with essential tremor.

Adult↗

Diurnal variation of essential and physiological tremor.

Evaluations were made of the diurnal variations of tremor power at rest, after fatigue and after mass loading, and plasma norepinephrine in patients with familial essential tremor and normal subjects. Diurnal tremor power rhythms for both essential and physiological tremor pursued identical temporal profiles. Plasma norepinephrine levels followed a congruent diurnal pattern with later peak values than the peak values of tremor power. Sympathetic nervous system activity is unlikely to be the cause of diurnal tremor power variation. The consistent diurnal rhythm of tremor power may affect dosage schemes of tremorolytic drugs.

Adult↗

Modulation of primary orthostatic tremor by magnetic stimulation over the motor cortex.

OBJECTIVES: To study the role of corticomotor neuronal pathways in primary orthostatic tremor. METHODS: Transcranial magnetic stimuli at an intensity 10% above the resting motor threshold were delivered over the leg motor cortex in two patients with primary orthostatic tremor while standing still. Electromyographic responses in both tibialis anterior muscles were recorded after 20 stimuli given randomly at intervals of 120 to 180 seconds. Differences between predicted and actual times of occurrence of tremor bursts after the stimuli were used to calculate a resetting index, with a value of 0 representing no resetting and a value of 1 representing complete resetting. RESULTS: Transcranial magnetic stimulation evoked EMG responses in both tibialis anterior muscles, followed by transient suppression of tremor before reappearance of rhythmic EMG activity. Analysis of the timing of tremor bursts from EMG recordings before and after the magnetic stimuli disclosed that the phase of orthostatic tremor could be reset by brain stimulation (mean resetting indices 0.93 and 0.82). CONCLUSION: The results suggest that a central oscillator, involving the motor cortex, has a crucial role in either the generation or modulation of orthostatic tremor.

Electromyography↗

Differential diagnosis of common tremor syndromes.

Tremor is one of the most common involuntary movement disorders seen in clinical practice. In addition to the detailed history, the differential diagnosis is mainly clinical based on the distinction at rest, postural and intention, activation condition, frequency, and topographical distribution. The causes of tremor are heterogeneous and it can present alone (for example, essential tremor) or as a part of a neurological syndrome (for example, multiple sclerosis). Essential tremor and the tremor of Parkinson's disease are the most common tremors encountered in clinical practice. This article focuses on a practical approach to these different forms of tremor and how to distinguish them clinically. Evidence supporting various strategies used in the differentiation is then presented, followed by a review of formal guidelines or recommendations when they exist.

Brain Diseases↗

Tremor and somatosensory studies during chamber He-O2 compressions to 13.1, 25.2, 37.3, and 49.4 ATA.

Comparison was made between intentional and postural tremor amplitudes with a 2-to 50-Hz bandwidth in four men rapidly compressed from surface to 13.1, 25.2, and 37.3 ATA in 4 h while breathing helium-oxygen mixtures (Predictive Studies IV, University of Pennsylvania). Excursions with compression rates of 20 and 40 ft/min were then made to 49.4 ATA on exposure days 2 and 3, returning to saturation at 37.3 ATA for 6 additional days. During compression from 25.2 to 37.3 ATA, there were increases in tremor amplitudes for both intentional and postural tremor in the 3-to 7-Hz and 8- to 12-Hz ranges. Both types of tremor showed increases in amplitudes at 49.4 ATA on exposure days 2 and 3. Amplitude changes in postural tremor, which occurred only on the fastest compression to 49.4 ATA, were less evident than those in intentional tremor during the remaining dive profile, and adaptation to pressure exposure could be defined by day 8. Intentional tremors did not show adaptation at pressure.

Adult↗

Parallel neuronal mechanisms underlying physiological force tremor in steady muscle contractions of humans.

We present results from a study of the 6-to 12-Hz force tremor in relation to motor unit (MU) firing synchrony. Our experimental observations from 32 subjects, 321 contractions, and 427 recorded MUs reveal that tremor is accompanied by corresponding, in-phase MU rhythms that are additional to the ones at the MU intrinsic firing rates. This rhythmical synchrony is widespread and has a uniform strength that ranges from near zero to very large (MU/MU coherence > 0.50) in different contractions. Both the synchrony and the tremor are suppressed during ischemia, and this strongly suggests an involvement of spindle feedback in their generation. Furthermore, in the presence of substantial synchrony, the tremor enhancement, relative to the minimal tremor of ischemia, reflects the strength of the synchrony. Theoretical considerations based on these observations indicate that the muscle force signal is expected to show 1) frequency components in the band of the firing rates of the last-recruited, large MUs, and 2) because of the synchronized MU rhythms, an additional, distinct component with a size reflecting the strength of synchrony. Furthermore, synchronized MU rhythms, with frequencies in the 6- to 12-Hz range, are expected to arise from self-oscillations in the monosynaptic stretch reflex loop, due primarily to the associated muscle delay (several tens of milliseconds). Our results therefore reveal the parallel action of two tremor mechanisms, one of which involves MU synchrony probably caused by loop action. Clearly, the results on the synchrony and its impact also apply to other possible generators of tremor synchrony, including supraspinal ones.

Action Potentials↗

Voxel-based morphometry shows no decreases in cerebellar gray matter volume in essential tremor.

OBJECTIVE: To investigate cerebellar gray matter volume in patients with essential tremor (ET). METHODS: We used voxel-based morphometry (VBM) based on high-resolution T1-weighted MRI to compare gray and white matter density between 27 patients with ET and 27 age- and sex-matched healthy control subjects. Fourteen patients had only postural tremor, whereas 13 patients showed additional intention tremor. RESULTS: VBM failed to demonstrate regional decreases in gray and white matter volume in patients with ET. There was, however, an expansion in gray matter depending on the type of tremor. Compared with age-matched control groups, patients with intention tremor showed a relative expansion of gray matter bilaterally in the region of the temporoparietal junction and the right middle occipital cortex. CONCLUSIONS: The lack of a consistent decrease in gray and white matter density argues against a progressive neurodegenerative process in essential tremor that leads to a substantial decrease in cerebellar gray matter volume. Patients with predominant intention tremor show a relative expansion of gray matter areas involved in higher order visuospatial processing, which might represent a long-term result of adaptive reorganization compensating the higher demands on the visuospatial control of skilled movements in case of trembling.

Adult↗

Blinded evaluation confirms long-term asymmetric effect of unilateral thalamotomy or subthalamotomy on tremor in Parkinson's disease.

In the past, stereotactic surgery was a regular treatment for prominent unilateral tremor in Parkinson's disease (PD), but follow-up studies were usually short-term and always unblinded. We examined 17 PD patients in long-term follow-up (mean, 10.9 years after surgery) and used videotapes and the Unified Parkinson's Disease Rating Scale to blindly compare tremor ipsilateral and contralateral to the side of surgery. Since the patients were specifically selected for stereotactic surgery because of asymmetric tremor, and the surgical side chosen was contralateral to the predominant tremor, a sign of long-term efficacy would be current postoperative reversal of tremor side predominance. Upper extremity tremor was significantly better contralateral to the surgery compared with the ipsilateral side. We conclude that stereotactic surgery improved the absolute magnitude of tremor or ameliorated its rate of progression. Since asymmetric bradykinesia and dyskinesia were not a prerequisite for the choice of surgical side, we cannot make any conclusion about long-term impact of surgery on these features.

Aged↗

A positron emission tomography study of primary orthostatic tremor.

Primary orthostatic tremor (OT), a clinical syndrome in which a rapid (14 to 16 Hz), regular lower limb tremor causes unsteadiness on standing, may be associated with a postural upper limb tremor of similar frequency. We used H2 15O PET to analyze the abnormal pattern of cerebral activation associated with the postural upper limb tremor in four patients with primary OT. Patients had regional cerebral bloodflow (rCBF) measured during involuntary tremor while maintaining a posture with their outstretched right upper limb and again at rest. Tremor was associated with abnormal bilateral cerebellar and contralateral lentiform and thalamic activation. These findings were evident on group analysis of pooled PET data after transformation into standard stereotactic space and in single subjects when PET images were coregistered with structural MRI of the brain. At rest, cerebellar blood flow was significantly increased bilaterally in OT when compared with age- and sex-matched controls. We have previously demonstrated similar abnormal bilateral cerebellar activation in essential and writing tremors and conclude that abnormal bilateral overactivity of cerebellar connections is a common feature of tremulous disorders.

Aged↗

Does a screening questionnaire for essential tremor agree with the physician's examination?

In research studies of essential tremor (ET), monetary and geographic factors often necessitate diagnosis by interview rather than by examination. Few attempts have been made to determine the validity of a screening instrument for ET. A total of 242 subjects (33 definite or probable ET, 54 possible ET, and 155 normal) were part of a community-based family study of ET in northern Manhattan. Subjects underwent a tremor interview and videotaped tremor examination. The interview included 12 screening questions for ET. Two neurologists rated the severity of tremor on videotape and assigned diagnoses. The subjects' responses to the 12 screening questions were compared with the neurologic examination and the neurologists' diagnoses. There was an association between the number of affirmative responses on the 12-item screen and the severity of tremor during the videotaped tremor examination (r = 0.66, p < 0.01). Including those with probable and definite ET and defining a positive screen result as an affirmative response to at least 1 of 12 screening questions, the sensitivity of the screening questionnaire was 73%, the specificity was 96%, and the positive predictive value was 80%. The responses to the questionnaire closely correlated with the severity of tremor on neurologic examination. The questionnaire had moderate validity for subjects with probable or definite ET; subjects with mild ET often screened negative. Hence, in population-based studies and family studies of ET, it is important to examine all subjects for the presence of mild asymptomatic ET.

Adolescent↗

A randomized, double masked, controlled trial of botulinum toxin type A in essential hand tremor.

OBJECTIVE: To evaluate the safety and efficacy of botulinum toxin type A injection in essential tremor of the hand. BACKGROUND: Botulinum toxin type A is an effective treatment for dystonia, spasticity, and other movement disorders and has been found to be useful in open-label studies and one double-masked study of essential hand tremor. METHODS: One hundred thirty-three patients with essential tremor were randomized to low-dose (50 U) or high-dose (100 U) botulinum toxin type A (Botox) or vehicle placebo treatment. Injections were made into the wrist flexors and extensors. Patients were followed for 16 weeks. The effect of treatment was assessed by clinical rating scales, measures of motor tasks and functional disability, and global assessment of treatment. Hand strength was evaluated by clinical rating and by a dynamometer. RESULTS: Both doses of botulinum toxin type A significantly reduced postural tremor on the clinical rating scales after 4 to 16 weeks. However, kinetic tremor was significantly reduced only at the 6-week examination. Measures of motor tasks and functional disability were not consistently improved with botulinum toxin type A treatment. Grip strength was reduced for the low- and high-dose botulinum toxin type A groups as compared with the placebo group. Adverse reactions consisted mainly of dose-dependent hand weakness. CONCLUSION: Botulinum toxin type A injections for essential tremor of the hands resulted in significant improvement of postural, but not kinetic, hand tremors and resulted in limited functional efficacy. Hand weakness is a dose-dependent significant side effect of treatment at the doses used in this study.

Aged↗

Surgical therapy for tremor in multiple sclerosis: an evaluation of outcome measures.

OBJECTIVE: To assess the reliability, validity, and sensitivity of outcome measures that might be used in a clinical trial of surgery for the treatment of severe tremor associated with MS (MS tremor). METHODS: Nine patients with MS tremor were evaluated before and 3 and 12 months after thalamic surgery (six thalamotomy, three deep brain stimulation). A clinical tremor rating scale (CTRS), a novel quantitative movement analysis technique (QMA), and a variety of measures of disability, neurologic impairment, and quality of life was utilized. RESULTS: Both the CTRS and QMA were reliable measures of tremor and both were sensitive to the improvement in tremor following surgery. However, QMA correlated with disability measures and corresponded better to patient and examiner assessment of surgical results. The disability scales used were insensitive to functional improvements that may follow surgery. The box and blocks test clearly separated three patients who had excellent results from three who had poor results. Baseline QMA values predicted improvement on the box and blocks test. CONCLUSIONS: 1) QMA is a reliable, objective and valid measure of MS tremor that could be used in a clinical trial. 2) The box and blocks test can detect the improvement in prehensile function that follows surgery, but standard disability scales are poorly responsive to this change. 3) Preoperative QMA values may predict which patients are most amenable to functional improvement after surgery.

Adult↗

[Inhibition of harmaline induced tremor by L-threo-3, 4-dihydroxyphenylserine, an L-norepinephrine precursor].

Effect of 3, 4-dihydroxyphenylserine (DOPS), a norepinephrine precurosr, on harmaline tremor was investigated in mice to elucidate the role of norepinephrine in the genesis of tremor. 1) Spontaneous motor activity was inhibited by L-threo-DOPS (200 mg/kg i.p.). 2) Tremor induced by harmaline (5 and 7 mg/kg i.p.) was enhanced by alpha-methyl-p-tyrosone (200 mg/kg i.p.). 3) The development and duration of tremor induced by harmaline (10 mg/kg i.p.) were inhibited significantly in a dose dependent manner by L-threo-DOPS (50, 70, 100, 150 and 200 mg/kg i.p.), but neither by D-threo-DOPS (200 mg/kg i.p.) nor DL-erythro-DOPS (200 mg/kg i.p.). 4) L-threo-DOPS (200 mg/kg i.-.) had no effect on the development of tremor induced by tremorine (5 and 10 mg/kg i.p.), while lacrimation and diarrhea caused by tremorine was markedly inhibited. 5) Administration of harmaline (10 mg/kg i.p.) produced an increase in brain 5-hydroxytryptamine content but not in that of norepinephrine. Administration of L-threo-DOPS (100 mg/kg i.p.) increased the norepinephrine content but not the 5-hydroxytryptamine content in the brain. Inhibition of harmaline tremor induced by L-threo-DOPS is attributed to the L-norepinephrine converted from L-threo-DOPS and the involvement of a noradrenergic mechanism in harmaline tremor has to be considered.

Alkaloids↗

Depression of drug-induced tremor by a new isoxazol derivative in mice.

The effects of a newly synthesized compound, MLV-208, on drug-induced tremor were investigated in mice. The study involved a power spectral analysis of the random current induced by movement of a magnet attached to the mouse on a wire coil. To induce tremor, tremorine and harmaline were subcutaneously injected. The power spectral density function defined the frequency composition of the tremor, and its severity was determined quantitatively in terms of the mean square value of the data in any frequency range of concern. MLV-208 depressed the power spectral density of both the tremorine- and harmaline-induced tremors, but reduced more effectively the former than the latter. The peak frequency of the tremorine-induced tremor did not change in the presence of MLV-208, while MLV-208 sometimes developed a new peak of the power spectral densities of the harmaline-induced tremor in the low frequency side, in addition to the original tremor component.

Animals↗

Effects of beta-blockers and nicardipine on oxotremorine-induced tremor in common marmosets.

Effects of beta-blockers (propranolol, arotinolol and nipradilol) and a Ca2+ channel blocker (nicardipine) on oxotremorine-induced tremor were studied in common marmosets. Generalized tremor was elicited by an intraperitoneal administration of 0.25 mg/kg oxotremorine. Intensity of the tremor was classified into 7 degrees, and it was evaluated every 10 min. The total intensity of oxotremorine-induced tremor for each drug was expressed as "points", which were the sum of tremor intensity scores evaluated every 10 min up to 190 min following the administration of oxotremorine. Beta-blockers significantly suppressed the tremor. On the other hand, the Ca2+ channel blocker exacerbated the tremor.

Adrenergic beta-Antagonists↗