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Essential tremor prevalence is low in Arabic villages in Israel: door-to-door neurological examinations.

OBJECTIVE: To estimate the prevalence of essential tremor (ET) in Arabic villages of Wadi Ara. BACKGROUND: The prevalence ET which is higher than Parkinson's disease in North America and Europe, differs according to study population and methodology. Since hospital record based epidemiology carries referral bias and might provide low estimates of ET prevalence, we carried a population based survey. METHODS: This door-to-door survey comprised the Arabic villages of Wadi Ara in Northern Israel. Consecutive residents who agreed to participate in the study and were older than 64 years at prevalence day, underwent neurological examination. Medical and family history, medication and response to medication were recorded. RESULTS: Of the 444 subjects that were approached, 428 agreed to participate in the study (refusal rate 3.6%). Four were excluded owing to severe systemic disease. The study population consisted of 424 subjects (54% men, mean age 74+/-7 years). A clearly oscillatory action tremor of moderate amplitude was observed in 8 patients (age 75+/-7 years). Six patients had another possible cause of tremor. The prevalence of ET was calculated as 1.89% (95% CI 1.76-2.0) when all tremor cases were accepted as possible ET and 0.47% (95 CI 0.43-0.52) when patients with other causes of tremor were excluded. CONCLUSIONS: The prevalence of ET in Arabic villages of Wadi Ara is low.

Aged↗

Thalamic stimulation for primary writing tremor.

We report a patient with primary writing tremor whose tremor was treated with thalamic stimulation. He had undergone trials of multiple oral medications with no benefit for his tremor. An electrode lead was implanted in the thalamic nucleus ventralis intermedius with nearly complete control of his tremor and no postoperative complications. We conclude that nucleus ventralis intermedius thalamic stimulation is safe and effective for primary writing tremor.

Electric Stimulation Therapy↗

Behr syndrome variant with tremor treated by VIM stimulation.

Behr syndrome was first described in 1909 as a syndrome of heredofamilial optic atrophy, visual disturbances, nystagmus, and variable pyramidal tract signs. The syndrome has been reported in both sexes. So far, tremor has not been reported to be part of Behr Syndrome. We present the case of a 51-year-old man with a rare complicated dominant inherited cerebellar ataxia with accompanying visual loss and tremor (CICALVT) resembling a Behr Syndrome variant who suffered from advanced visual deterioration since childhood and progressive spastic paraparesis for 15 years. Furthermore, the patient presented increasing tremor of both hands for 5 years. The successful treatment of the tremor using deep brain stimulation (DBS) of the ventral intermediate thalamic nucleus (VIM) is reported. Our case indicates that deep brain stimulation of the ventral intermediate nucleus is an adequate operative intervention that can help to reduce tremor even in patients with complicated movement disorders.

Deep Brain Stimulation↗

Evidence for a common network of brain structures involved in parkinsonian tremor and voluntary repetitive movement.

Repeated measurements of regional cerebral blood flow (rCBF) were obtained in 7 patients who underwent a stereotactic thalamic electrode implantation in the nucleus ventralis intermedius (nVIM) of the thalamus for severe hemi-parkinsonian tremor. Using positron emission tomography and oxygen-15 labelled water, rCBF was studied in each patient in two conditions: in absence of tremor, e.g. under nVIM electrical stimulation, and in presence of tremor. X-ray tomograms permitted individual definition of anatomical regions of interest. In presence of tremor, normalized rCBF increases were observed in the following regions: postcentral (13.6 +/- 8.4%, P = 0.0003), precentral (7.7 +/- 8.8%, P = 0.016), paracentral (7.7 +/- 8.4%), supplementary motor (8.2 +/- 10.4%, P = 0.025), caudate nucleus (5.7 +/- 7.6%, P = 0.03), vermis (9.7 +/- 7.3%, P = 0.007), cerebellar grey nuclei (9 +/- 6%, P = 0.016) on the electrode side and on the contralateral vermis (17.8 +/- 7.5%, P = 0.0003) and cerebellar grey nuclei (22 +/- 6.3%, P = 0.0004). These results clearly indicate an activation of the sensory-motor cortex, as well as an involvement of the supplementary motor area and the cortico-cerebellar pathways in Parkinsonian resting tremor (PRT). They demonstrate that PRT shares common network of brain structures with repetitive voluntary movement.

Aged↗

Convergence of finger tremor and EEG rhythm at the alpha frequency induced by rhythmical photic stimulation.

The frequencies of EEG alpha rhythm and physiological finger tremor overlap at 9-10 c/sec, suggesting a functional relationship between the two mechanisms. We measured the correlation between the two rhythms when they occurred spontaneously and when rhythmical photic stimulation was applied. Rhythmical physiological finger tremor (9.7 c/sec +/- 1.06 S.D.) was accompanied by an alpha rhythm (10.3 c/sec +/- 0.51 S.D.) spontaneously, showing a one-to-one relationship at times. When photic stimulation was provided at a frequency (11 Hz) close to the subject's spontaneous alpha rhythm, a frequency-convergence occurred between finger tremor (10.3 c/sec +/- 0.68 S.D.) and the EEG (10.6 c/sec +/- 0.35 S.D.). The correlation coefficient between the two rhythms under photic stimulation was significantly higher (0.49 +/- 0.14 S.D.) than under the spontaneous condition (0.13 +/- 0.16; P less than 0.05). Consistent with this, the mean difference between finger tremor and EEG frequencies was significantly lower during photic stimulation (0.83 c/sec +/- 0.46 S.D.) than during the spontaneous condition (1.23 c/sec +/- 0.82 S.D.) (t = 2.54; P less than 0.05, t-test for correlated means). These findings indicate that the EEG and physiological finger tremor tend toward synchrony with each other in an environment of photic stimulation, supporting our hypothesis of a functional relationship between the two mechanisms.

Adult↗

Contrasting local effects of MAO inhibitors on caudate tremor activities.

Hindlimb tremor was produced in chronic cats by intracaudate microinjection of the monoamine oxidase (MAO) inhibitors tranylcypromine and harmaline throughout a range of doses (150-385 mug). Pargyline, however, was non-tremorgenic within the same range, suggesting that interference with MAO is not sufficient in itself to elicit tremor. Tranylcypromine tremors differed from those of harmaline by exhibiting a slower onset, longer duration and susceptibility to antagonism by hemicholinium. In contrast, ongoing cholinergic tremors following intracaudate physostigmine were variably suppressed by all three MAO inhibitors at comparable dose levels (175-200 mug); pargyline produced the most complete suppression. These results indicate that MAO inhibitors can modify tremor activities in a differential manner dependent both on the functional state of the caudate nucleus and on the ability of cartain MAO inhibitors to exert other local actions.

Alkaloids↗

Amantadin e tremor, a 5-hydroxytryptamine-mediated response?

Amantadine-induced tremor has been investigated using mice. Experiments with, mebanazine, reserpine, diethyldithiocarbamate, and p-chlorophenylalanine suggest that the tremorgenic action of amantadine is influenced by a balance between three putative central nervous system (CNS) transmitters: noradrenaline, dopamine and 5-hydroxytryptamine (5-HT). Drugs which reduce the concentration of the catecholamines in brain increase amantadine induced tremor. p-Chlorophenylalanine, which specifically depletes brain 5-HT, antagonises amantadine-induced tremor. An ED50 (tremor) dose of amantadine decreases the concentration of 5-hydroxy-indoleacetic acid (5-HIAA) in rat brain, particularly when this elevated due to pretreatment with 5-hydroxytryptophan. Neither inhibition of monoamine oxidase nor reduction of 5-HT-reuptake appear to be responsible for this decrease. Experiments on rat fundus suggest that amantadine increased the sensitivity of receptors to 5-HT. A similar mechanism of action in the CNS could explain both the tremor and the decrease in brain 5-HIAA. The possible relevance of these findings is discussed with respect to the known anti-Parkinson action of amantadine.

Amantadine↗

Isoelectric focusing and electrophoresis of the CSF proteins in tremor of different origins.

The CSF proteins have previously been very little investigated in the cerebellar syndrome of chronic alcoholism and in essential tremor. Such studies have been carried out more thoroughly by electrophoretic methods in Parkinson's disease but generally with normal results. In the present investigation the CSF proteins were examined by isoelectric focusing and quantitative paper electrophoresis in 10 patients with the cerebellar syndrome of chronic alcoholsm, 12 patients with Parkinson's disease and 16 subjects with essential tremor. Abnormal CSF proteins of very similar appearance were found on isoelectric focusing in the acidic pH interval 5.6-5.8 in 80% of the patients with the cerebellar syndrome of chronic alcoholism. In Parkinson's disease the most common aberration was evidence of nonspecific blood-CSF-barrier damage which occurred in half of the patients. In only 17% of these cases did other alterations appear, situated in the pH range alkaline to pH 5.8. Abnormal CSF proteins were found in 94% of the patients with essential tremor. The aberrant proteins appeared in both the acidic and alkaline pH regions, most frequently with anisoelectric point at pH 5.9, 7.2 and 9.3. There was a considerably higher frequency of CSF protein abnormalities in different pH ranges in patients with tremor of more pronounced degree as compared to those with only mild symptoms. The electrophoretic examinations failed to show any conclusive alterations. Barrier-damage patterns of mild or moderate degree or slightly increased levels of CSF beta1-globulin were occasionally found in all 3 diseases. The results indicate that isoelectric focusing of the CSF proteins may be of diagnostic value in the cerebellar syndrome of chronic alcoholism and in essential tremor but does not reveal any characteristic abnormalities in Parkinson's disease.

Adult↗

Studies on the possible sites of chlordecone-induced tremor in rats.

A series of psychopharmacological agents were administered to adult male Fischer-344 rats pretreated with a tremorigenic dose of chlordecone in an attempt to elucidate the involvement of spinal and supraspinal processes in the mediation and/or expression of chlordecone-induced tremor. Agents effective in attenuating the frequency of tremor were chlordiazepoxide, muscimol, and mecamylamine; quipazine exacerbated the tremor. Catecholaminergic agents including yohimbine, clonidine, propranolol, and haloperidol did not affect the frequency of chlordecone-induced tremor. Disinhibition of postsynaptic inhibitory sites in the spinal cord with strychnine and antagonism of spinal and supraspinal polysynaptic pathways with mephenesin exacerbated and attenuated the effects of chlordecone, respectively. Destruction of the climbing fibers with 3-acetylpyridine effectively blocked harmine, but not chlordecone-induced tremor, suggesting that chlordecone does not act through this pathway.

Animals↗

Quantification of tremor with a digitizing tablet.

Handwriting and drawing are commonly employed in the clinical assessment of tremor. These tasks have been quantified heretofore by subjective rating schemes, which are incapable of providing precise measures of the amplitude and frequency of tremor. A commercially-available digitizing tablet and personal computer can be interfaced so as to reliably record any pathologic tremor that is induced by writing or drawing. Numerical differentiation and spectral analysis can be used to conveniently quantify the amplitude and frequency of tremor. However, digitizing tablets lack sufficient sensitivity to measure physiologic tremor.

Handwriting↗

A special role of the parvocellular red nucleus in lesion-induced spontaneous tremor in monkeys.

The neural mechanisms underlying spontaneous tremor were investigated in monkeys. Tremor-producing ventromedial tegmental (VMT) lesions involve at least three major neural elements. (1) Parvocellular division of the red nucleus (RNpc); (2) cerebellothalamic fibers passing through the red nucleus, and, (3) nigrostriatal fibers. These three elements were destroyed stereotaxically in areas remote from the VMT area separately and/or in various combinations, and correlation between the site of lesions and tremor was made. Lesion-induced tremor appeared only when the three elements were destroyed. A possible, particular role of the RNpc in the production of the spontaneous tremor is discussed.

Animals↗

Citalopram-induced jaw tremor.

A variety of medications can induce or enhance a tremor. Tremors most commonly affect the limbs, especially the arms. We report a patient who presented with a 5-6 Hz jaw tremor with a temporal association with the administration of citalopram. To our knowledge, this is the first report in literature, of a transient jaw tremor associated with citalopram. According to the current data, citalopram-induced jaw tremor can be explained by an indirect inhibitory effect on central dopaminergic activity.

Citalopram↗

Stimulation of the motor cortex for disabling essential tremor.

OBJECTIVE: To examine the safety and efficacy of targeted stimulation of the motor cortex as a treatment for essential tremor (ET). PATIENTS AND METHODS: At the University of Kansas Medical Center, two patients with essential tremor received stimulation of the (contralateral) motor cortex using an investigational implantable pulse generator (IPG). Patients were evaluated with the Fahn Tolosa Marin tremor rating scale (TRS) at baseline, 1 week and 4 weeks after surgery, both with stimulation turned on and turned off. Both patients also received neuropsychological assessments at baseline and again after surgery. RESULTS: Patient 1 was a 75-year-old male with tremor for 20 years. His baseline total TRS score was 61 and his TRS 1 month after surgery was 57. His IPG was set at 30 Hz, 3 mA and 250 micros pulse width. Patient 2 was a 60-year-old male with tremor for over 10 years. His baseline total TRS was 47 and it was 43, 1 month after surgery. His IPG was set at 50 Hz, 5 mA and 250 micros pulse width. There were no adverse effects. CONCLUSION: Cortical stimulation of the primary hand motor cortex contralateral to the dominant hand was ineffective for the treatment of ET with the stimulation parameters used in this study. Future research examining other stimulation parameters is necessary to determine if there is a role for cortical stimulation in the treatment of ET.

Aged↗

Parkinsonian action tremor: interference with object manipulation and lacking levodopa response.

It has been postulated that Parkinsonian action tremor is distinct from classical resting tremor and that it may contribute to a loss of manual dexterity in Parkinson's disease. We analyzed pinch grip coordination in 20 patients with Parkinson's disease. An object with and without an additional 500 g weight was grasped, lifted and held for a short time with opposed thumb and index finger. Force sensors recorded the force exerted by both fingers. Spectral analysis of the force traces was performed. Transition times between grasping and lifting the object were measured. 18 age matched normal volunteers served as a control group. While holding the object, there were force oscillations in the 3.5-6.5 Hz band indicating (reemerging) classical Parkinsonian tremor in 65% of the patients. This was reduced to 15-20% under levodopa. Oscillations in the 6-15 Hz band were found in 30% (50% with weight) of the patients, remaining unchanged under levodopa, and in 10% (20% with weight) of the normal controls. During lift initiation, 6-15 Hz oscillations were found in all patients and the majority of controls. The band power was positively correlated with the movement transition times in the severely akinetic patients and was significantly higher than in controls. It remained unchanged under levodopa. Our data confirm that Parkinsonian action tremor activated during complex voluntary movements is distinct from classical resting tremor. It does not show a clear levodopa response but affects dextrous movement coordination when associated with clinically severe overall akinesia.

Adult↗

Quantifying the contribution of arm postural tremor to the outcome of goal-directed pointing task by displacement measures.

A method for quantifying the outcome of goal-directed postural pointing was presented and used for relating the tremor output to the oscillations of single arm landmarks. The displacement of reflective markers placed on shoulder, upper arm, forearm, and hand were measured by an optoelectronic motion capture system in nine subjects holding a laser penlight pointed at a target. The high signal-to-noise ratio of the measured displacement series (from 7:1 for shoulder marker to 30:1 for hand marker) demonstrated the feasibility of the proposed system to carry out tremor analysis. The track of the laser emission on the target, reconstructed from penlight displacements, was studied as the outcome of the pointing task. By measuring the length and the dispersion of the path covered by the target track in 30 s, a significant and comparable tremor amplitude was found in vertical and lateral directions. The correlation between target track and arm tremor was stronger for distal than for proximal markers. Spectral and cross-spectral analyses evidenced the presence of a dominant low frequency oscillation (1.5 Hz), along with a high frequency one (5-7 Hz), in the displacement of the target track. These two components were significantly linked to the oscillations of the hand, the forearm and the upper arm but not to those of the shoulder, suggesting that the oscillations in the overall tremor output during the pointing task are mainly generated by the arm segments.

Adult↗

Effect of zonisamide on essential tremor: a pilot crossover study in comparison with arotinolol.

We performed a pilot, crossover trial of zonisamide (ZNS) on essential tremor patients. Patients were randomly selected to start either ZNS or arotinolol treatment for 2 weeks. After a washout period, the patients were switched to an alternative drug. The assessment of tremor was carried out using the Fahn-Tolosa-Marin's clinical rating scale for tremor at baseline and 2 weeks after administration of each drug. There was a significant improvement after ZNS and arotinolol administration compared with the baseline. There was no significant difference in the antitremor effect between ZNS and arotinolol; however, ZNS was more effective for tremors of cranial nerve areas. Although the number of enrolled patients was limited in the present study, this open-label pilot study suggests that ZNS may have a therapeutic potential for essential tremor. A controlled trial of this drug in the future would be valuable.

Adrenergic alpha-Antagonists↗

Treatment of essential tremor with methazolamide.

We treated 28 patients (16 women and 12 men) who had essential tremor with methazolamide. Their median age was 69 years (range, 34 to 89 years), and the median duration of tremor was 16 years (range, less than 1 to 69 years). Fifteen cases were familial and 13 were sporadic. Improvement in 10 patients who continued taking the drug ranged from moderate to complete relief. In addition, four patients had marked improvement and two had moderate improvement but discontinued use of the drug because of side effects. Five patients with a mild response and seven with no response also discontinued methazolamide therapy. The maximal mean daily dose was 203 mg for all patients and 129 mg (maintenance dose) for the patients who continued taking the drug. Side effects consisted primarily of somnolence, nausea, epigastric discomfort, anorexia, paresthesias, and numbness. No aplastic anemia was noted in any of the patients. The median duration of follow-up was 6 months (range, 10 weeks to 29 months). The therapeutic effect seemed unrelated to a family history of tremor, the effect of alcohol, or the responsiveness to propranolol or primidone. Methazolamide may be an effective drug in the treatment of some patients with essential tremor, particularly those with head and voice tremor.

Adult↗

A software for recording and analysis of human tremor.

For many diseases various methods for the diagnosis and treatment monitoring are available. Presently, such methods are not established for an investigation of tremor diseases, although the different forms of tremor are common neurological symptoms and occur frequently in various neurological diseases and also other conditions. We developed an easy-to-use application for tremor-analysis and recording, running under MS-Windows, that allows us to investigate different forms of tremor by advanced mathematical methods of time series analysis. The application is also applicable for users who are not familiar with these kind of advanced data analysis methods. It provides tools for the diagnosis and treatment monitoring under laboratory conditions, based on previously developed and established methods of spectral and cross spectral analysis of tremor and electromyographic time series.

Electronic Data Processing↗