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PubMed1995

Striatal dopamine depletion, tremors, and hypokinesia following the intracranial injection of S-adenosylmethionine: a possible role of hypermethylation in parkinsonism.

The major symptoms of Parkinson disease (PD) are tremors, hypokinesia, rigidity, and abnormal posture, caused by the degeneration of dopamine (DA) neurons in the substantia nigra (SN) and deficiency of DA in the neostriatal DA terminals. Norepinephrine (NE) and serotonin (5-HT) levels in the neostriatum and tyrosine hydroxylase and melanin pigments in the substantia nigra are also decreased, and brain cholinergic activity is increased. The cause of PD is unknown, but PD is an age-related disorder, suggesting that changes that occur during the aging process may help to precipitate PD. Methylation increases in aging animals. Increased methylation can deplete DA, NE, and 5-HT; increase acetylcholine; and cause hypokinesia and tremors. These effects are similar to changes seen in PD, and interestingly also, they are similar to some of the changes that are associated with the aging process. It is suggested, therefore, that increased methylation may be an inducing factor in parkinsonism. Accordingly, the effects of an increase in methylation in the brain of rats were studied. S-adenosylmethionine (AdoMet), the limiting factor in the methylation process, was injected into the lateral ventricle of rats. Specific behavioral changes that resemble changes seen in PD were investigated. The results showed that AdoMet caused tremors, rigidity, hypokinesia, and depleted DA. The hypokinetic effects of a single dose of AdoMet lasted for about 90 min. AdoMet has a dose-dependent hypokinetic effect. A dose of 9.4 nmol reduced movement time (MT) by 68.9% and increased rest time (RT) by 20.7%, and a dose of 400 nmol reduced MT by 92.4% and increased RT by 27.6%. The normethyl analog of AdoMet, S-adenosylhomocysteine, did not cause hypokinesia or tremors, but it blocked the AdoMet-induced motor effects. L-dopa, the precursor of DA, also blocked the AdoMet-induced motor effects. These data suggest that the methyl group of AdoMet as well as DA depletion are involved in the AdoMet-induced motor effects. A dose of 0.65 mumol of AdoMet depleted DA in the ipsilateral caudate nucleus (CN) or neostriatum by 50.1%, and DA in the contralateral CN was reduced by 9.3%. Double the dose of AdoMet did not increase the depletion of DA on the ipsilateral CN, but DA in the contralateral CN was decreased by 26.3%. Taken together, the results suggest that increased methylation may contribute to the symptoms of PD.

Animals↗
PubMed1997

Frequency peaks of tremor, muscle vibration and electromyographic activity at 10 Hz, 20 Hz and 40 Hz during human finger muscle contraction may reflect rhythmicities of central neural firing.

The output from the central nervous system to muscles may be rhythmic in nature. Previous recordings investigating peripheral manifestations of such rhythmic activity are conflicting. This study attempts to resolve these conflicts by employing a novel arrangement to measure and correlate rhythms in tremor, electromyographic (EMG) activity and muscle vibration sounds during steady index finger abduction. An elastic attachment of the index finger to a strain gauge allowed a strong but relatively unfixed abducting contraction of the first dorsal interosseous (1DI). An accelerometer attached to the end of the finger recorded tremor, surface electrodes over 1DI recorded EMG signals and a heart-sounds monitor placed over 1DI recorded vibration. This arrangement enabled maintenance of a constant overall muscle contraction strength while still allowing measurement of the occurrence of tremulous movements of the finger. Ten normal subjects were studied with the index finger first extended at rest and then contracting 1DI to abduct the index finger against three different steady forces up to 50% of maximal voluntary contraction (MVC). Power spectral analysis of tremor, EMG activity and muscle vibration signals each revealed three frequency peaks occurring together at around 10 Hz, 20 Hz and 40 Hz. Coherence analysis showed that the same three peaks were present in the three signals. Phase analysis indicated a fixed time lag of tremor behind EMG of around 6.5 ms. This is compared with previous measurements of electromechanical delay. Other experiments indicated that the three peaks were of central nervous origin. Introducing mechanical perturbations or extra loading to the finger and making recordings under partial anaesthesia of the hand and forearm demonstrated preservation of all the peaks, suggesting that they did not originate from mechanical resonances or peripheral feedback loop resonances. It is concluded that, at least for a small hand muscle, there exist not one but a number of separate peak frequencies of oscillation during active contraction, and that these oscillations reflect synchronization of motor units at frequencies determined within the central nervous system. It is proposed that the multiple oscillations may be a means of frequency coding of motor commands.

Adult↗
PubMed2006

Functional MRI for immediate monitoring stereotactic thalamotomy in a patient with essential tremor.

The effect of stereotactic thalamotomy was assessed with pre- and postoperative functional magnetic resonance imaging (fMRI) under motor stimulation. A patient with unilateral essential tremor (ET) of the left arm underwent stereotactically guided thalamotomy of the right ventral intermediate thalamic nucleus (VIM). FMRI was done directly before and after surgery on a 1.5-Tesla scanner. The stimulation paradigm was maintainance of the affected arm in an extended position and hand clenching being performed in a block design manner. Statistical analysis was done with Brain Voyager 2000. After thalamotomy the tremor diminished completely. As a difference between the pre- and postoperative fMRI, a significant activation was found in the VIM contralateral to the activation site, adjacent to the inferior olivary nucleus contralateral to the activation site and in the dorsal cingulum. In conclusion, fMRI can detect the functional effect of thalamotomy for tremor treatment. Direct postoperative fMRI provides a sufficient method for estimating the effect of thalamotomy immediately after intervention. The importance of the intermediate thalamic nucleus and the olivary nucleus in tremor generation is supported by our findings.

Essential Tremor↗
PubMed2004

How to treat tremor.

This paper presents an example of 18(th) century medical thinking. The author, Dr Georg Ernst Stahl (1659-1734) was the founder of the phlogiston theory in the field of chemistry, a medical professor, and a court physician in Saxony and Prussia. His description includes a definition of tremor, the internal and external causes of tremor, the types of tremor, the diagnostic and prognostic signs, and the treatment. From a present (contemporary) point of view, some compounds that were then used in treatment may have had a limited therapeutic effect on some kinds of tremor. Protopin has an anticholinergic and GABA-ergic effect, and rhoeadin (tetrahydrobenzazepin) may have had an effect similar to that of neuroleptics. Nevertheless, it is not clear whether the recommended quantity of these compounds was sufficient for a clinical effect. Most of the prescribed drugs could only have had a placebo effect.

Benzophenanthridines↗
PubMed2005

Assessment of movement time in patients with essential tremor.

BACKGROUND: We have observed mild bradykinesia in essential tremor (ET) patients, which do not satisfy the criteria of Parkinson's disease (PD). OBJECTIVE: To compare the mean movement time for repetitive movements around distal and proximal joints in ET patients with normal controls by using a simple test paradigm. PATIENTS AND METHODS: Seventeen patients with ET and 14 control subjects were instructed to tap with the index finger sequentially on push-button microswitches. Movement times around metacarpophalangeal, wrist, elbow, and shoulder joints of the right side were tested. The data collected were stored on a computer and the time elapsed between sequential taps on two keys (ms) and number of taps on the left key for 15 seconds were evaluated offline. RESULTS: Movement times of the patients with ET were not found to be significantly different from those of the controls at all joints tested despite slight prolongation for movements around the shoulder joint. CONCLUSION: The simple test paradigm we have used showed that there is no difference in the movement time for repetitive movements around four joints of the upper extremity between patients with ET and normal control subjects. The slightly prolonged movement time around the shoulder joint noted in patients with ET may be ascribed to tremor, not bradykinesia. Tremor may cause these patients to pay more attention to the performance of goal-directed finger movements and consequently prolong movement time slightly or it may simply delay the time elapsed to reach the goal in the absence of overt intention tremor.

Aged↗
PubMed1998

Cross-spectral analysis of physiological tremor and muscle activity. I. Theory and application to unsynchronized electromyogram.

We investigate the relationship between the extensor electromyogram (EMG) and tremor times series in physiological hand tremor by cross-spectral analysis. Special attention is directed to the phase spectrum and the effects of observational noise. We calculate the theoretical phase spectrum for a second-order linear stochastic process and compare the results to measured tremor data recorded from subjects who did not show a synchronized EMG activity in the corresponding extensor muscle. The results show that physiological tremor is well described by the proposed model and that the measured EMG represents a Newtonian force by which the muscle acts on the hand.

Biomechanical Phenomena↗
PubMed1998

Cross-spectral analysis of physiological tremor and muscle activity. II. Application to synchronized electromyogram.

We investigated the relationship between synchronized muscle activity and tremor time series in (enhanced) physiological tremor by cross-spectral analysis. Special attention was directed to the phase spectrum and its potential to clarify the contribution of reflex mechanisms to physiological tremor. The phase spectra are investigated assuming that the electromyogram (EMG) synchronization was caused by a reflex or a central oscillator. Comparing these results to phase spectra of measured data, we found a significant contribution of reflexes. But reflexes only modify existing peaks in the power spectrum. The main agents of physiological tremor are an efferent pace and the resonant behavior of the biomechanical system.

Biomechanical Phenomena↗
PubMed2001

Synchrony of rest tremor in multiple limbs in parkinson's disease: evidence for multiple oscillators.

Recent evidence points to involvement of central nervous system oscillators in Parkinson's disease (PD) rest tremor. It remains unknown whether one or multiple oscillators cause tremor in multiple limbs. Based on the prediction that multiple oscillators would cause low coherence even with similar average frequency, we studied 22 PD patients using accelerometers on multiple limbs. Records were digitized and spectral analysis was performed. Peak frequencies in the arms, legs, and chin were similar, indicating that biomechanical factors did not determine the frequency. Coherence between different axes of individual accelerometers and between different segments of the same limb was high. However, coherence between tremor in different limbs was low. There was no consistent pattern across patients of ipsi- vs. contralateral predominance of coherence. These data suggest that tremor in PD is generated by multiple oscillatory circuits, which operate on similar frequencies.

Aged↗
PubMed2000

Botulinum toxin treatment for functional disability induced by essential tremor.

This study aimed to improve botulinum toxin's (BTX) efficacy and to reduce its unwanted effects in the treatment of functional disability due to essential tremor (ET) of the hand. Twenty patients with disabling ET, not responding to conventional pharmacological therapy, were enrolled in this open-label study. Activities of daily living self-questionnaire (ADLS) and severity tremor scale (STS) were used to establish patients' functional disability and tremor severity. Accelerometry and surface electromyography were used to identify the arm muscles with tremorogenic activity during impaired positions. Global rating was used to measure treatment efficacy and unwanted effects. BTX type A was injected into the muscles principally responsible for impaired positions. After BTX treatment, there was a significant reduction in both severity and functional rating scales scores (ADLS and STS) and of tremor amplitude as measured with accelerometry and EMG. Adverse effects were limited to a slight third finger extension weakness in 15% of patients. BTX injections are effective and safe in reducing disability due to ET, if based on the criterion of functional selection.

Aged↗
PubMed2000

New alternative agents in essential tremor therapy: double-blind placebo-controlled study of alprazolam and acetazolamide.

Propranolol and primidone are widely used, effective agents in essential tremor although they are not tolerated by all patients. In the present study, the effectiveness of alprazolam, a triazole analog of benzodiazapine class, and acetazolamide, a carbonic anhydrase inhibitor, were investigated as symptomatic treatments for essential tremor. We studied 22 patients with essential tremor in a double-blind, cross-over, placebo-controlled design. The patients received in random order alprazolam, acetazolamide, primidone and placebo for four weeks, each separated by a two-week washout period. The study demonstrated that alprazolam was superior to placebo and equipotent to primidone, whereas there was no statistically significant difference between acetazolamide and placebo. The mean effective daily dose of alprazolam was 0.75 mg and there was not any troublesome side effect reported by the patients on alprazolam. Alprazolam can be used as an alternative agent in elderly essential tremor patients who can not tolerate primidone or propranolol.

Acetazolamide↗
PubMed1977

The indolaminergic innervation of the inferior olive. 2. Relation to harmaline induced tremor.

The possible involvement of serotoninergic mechanisms in the induction of harmaline generated tremor in the inferior olive has been investigated electrophysiologically in the cat and rat. Mass recordings of Purkinje cell activity in the cat showed that harmaline induces strong, synchronous and rhythmic activity in those parts of the climbing fibre system originating in the caudal part of the medial accessory olive and the caudolateral parts of the dorsal accessory nucleus. These are the areas of the cat olive shown to receive a dense serotoninergic innervation. In the rat, the selective removal of the serotoninergic innervation--produced by an intraventricular injection of 5,6-dihydroxytryptamine, or 5,7-dihydroxytryptamine in combination with desipramine--caused a significant attenuation of both the tremor and the climbing fibre activity induced by an intravenous harmaline injection. In the 5,6-dihydroxytryptamine-treated animals the reappearance of the harmaline tremor seemed to parallel the regrowth of new serotoninergic axon sprouts in the inferior olive. On the basis of the present results it is proposed that the serotoninergic afferents to the accessory olivary nuclei are of critical importance for the tremor induction of harmaline in the inferior olive. It is suggested that harmaline, rather than acting directly on the olivary neurones, exerts its effect through an interference with a serotoninergic (possibly inhibitory) innervation of these cells.

5,6-Dihydroxytryptamine↗
PubMed1993

Suppression of magnetic mu rhythm during parkinsonian tremor.

We recorded spontaneous magnetoencephalographic (MEG) activity and somatosensory-evoked fields (SEFs) with a 24-channel planar SQUIDgradiometer in five patients with hemiparkinsonism. The SEFs of the patients were within normal limits. During tremorless periods, the spontaneous activity over the somatomotor cortex had a frequency peak at approximately 10 Hz in all five patients and another at approximately 20 Hz in three. Tremor dampened the 10-Hz activity in all patients; in three the effect was bilateral. Tremor did not increase MEG activity at the tremor frequency. The suppression of the mu rhythm by the parkinsonian tremor resembled that occurring during voluntary movements in healthy subjects.

Adult↗
PubMed1976

The importance of 5-hydroxytryptamine for the induction of harmine tremor and its antagonism by dopaminergic agonists assessed by lesions of the midbrain raphe nuclei.

The brain lesion technique was used to destroy the ascending 5-hydroxytryptamine (5-HT) system at its cell bodies in the dorsal and medial raphe nuclei in order to assess the importance of 5-HT for the induction of harmine tremor and its antagonism by the dopaminergic agonists, L-DOPA, apomorphine and d-amphetamine. Lesions of the medial or dorsal raphe nucleus reduced the intensity of harmine tremor. The remaining tremor was generally resistant to further reduction by the dopaminergic agonists. 5-hydroxytryptophan was shown to enhance tremor: this effect was reduced both by the raphe lesions and by treatment with L-DOPA. The data are discussed in terms of the possible relationship between 5-HT and dopamine.

Alkaloids↗
PubMed1976

Non-hypertrophic familial neuropathy associated with intention tremor. A variety of Charcot-Marie-Tooth disease?

A family with an association of sensorimotor neuropathy and intention tremor is reported. Clinical examination of 3 affected family members showed in varying degrees areflexia, muscle wasting, impairment of deep sensation with an ataxic gait, pes cavus and disabling intention tremor. Motor nerve conduction velocities were moderately slowed. A superficial peroneal nerve biopsy showed axonal degeneration without segmental demyelination or onion bulb formation. Our observation seems to indicate an association of intention tremor with the non-hypertrophic variety of Charcot-Marie-Tooth disease. It can therefore be suggested that the two classical types of Charcot-Marie-Tooth syndrome possess variants which are associated with intention tremor. This association is well-known for the hypertrophic type; our report gives an example of the non-hypertrophic type.

Adult↗
PubMed1995

Efficacy of an adenosine antagonist, theophylline, in essential tremor: comparison with placebo and propranolol.

Propranolol, which has long been used as the standard treatment for essential tremor, has been compared with placebo and theophylline in ten newly diagnosed patients without other, prior drug treatments. Patients were treated for four weeks with one drug, followed by placebo for four weeks, and then the second drug for the same period, in a blind cross-over trial. Tremor was quantified using the volumetric method, and was decreased significantly after one week on propranolol, 80 mg/day. Theophylline 150 mg/day reduced tremor to the same extent, although the improvement was not significant until the second week. Three patients reported side effects on propranolol. It is suggested that theophylline may be a useful alternative agent in the treatment of essential tremor, probably due to a chronic up-regulation of adenosine receptors.

Adenosine↗
PubMed1984

Ethanol effects on harmaline-induced tremor and increase of cerebellar cyclic GMP.

The spectra of pharmacological effects of ethanol and the benzodiazepine show a degree of overlap. Neurophysiological and neurochemical evidence indicates that both ethanol and benzodiazepines facilitate inhibitory neurotransmission mediated by GABA. Diazepam has been reported to inhibit both the tremor and mechanism of cerebellar cyclic GMP caused by harmaline by a neurotransmission in the cerebellum. Because of the similarities between ethanol and benzodiazepines, the effects of ethanol on harmaline-induced tremor and increase of cerebellar cyclic GMP were studied. Ethanol inhibited harmaline-induced tremor at doses as low as 0.1 g/kg. At this low dose, however, a dissociation between inhibition of harmaline tremor and inhibition of the harmaline-induced increase of cerebellar cyclic GMP was observed.

Alkaloids↗
PubMed1986

Separation of the tremorous and muscular rigidity components of the ethanol withdrawal syndrome in the rat.

The alcohol withdrawal syndrome consists of a kinetic tremor, the tremorous component, and a peculiar abnormality of tone called asterixis, the muscular rigidity component. The severity of the ethanol withdrawal syndrome in the rat is generally assessed by the severity of the tremors. 3-Hydroxybutyrate suppresses the tremorous component but not the muscular rigidity component of the ethanol withdrawal syndrome, thus effectively differentiating the two components in the rat.

3-Hydroxybutyric Acid↗
PubMed1984

Effects of chlordecone exposure on brain neurotransmitters: possible involvement of the serotonin system in chlordecone-elicited tremor.

The purpose of this study was to correlate the chlordecone-elicited tremor activity with alterations of brain neurotransmitters. A single injection of chlordecone (80 mg/kg, ip) significantly increased the brain levels of 5-hydroxyindoleacetic acid (5-HIAA) but did not affect the concentrations of dopamine, dihydroxphenylacetic acid, aspartate, taurine, glutamate, glycine, and gamma-aminobutyric acid (GABA). There was a dose- and time-related correlation between the increases in striatal 5-HIAA levels and tremor after chlordecone treatment. A subsequent study with pargyline indicated that the increase in striatal 5-HIAA level represented an increase in the turnover of serotonin. This study plus the previous finding that pizotifen (BC-105), a serotonin receptor blocker, attenuated chlordecone-elicited tremor strongly suggests a possible involvement of the serotonin system in mediating the tremor elicited by this insecticide.

3,4-Dihydroxyphenylacetic Acid↗