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Clinical analysis in familial cortical myoclonic tremor allows differential diagnosis with essential tremor.

Familial cortical myoclonic tremor (FCMT) is a rare disorder often leading to a wrong clinical diagnosis of essential tremor. Electrophysiological data are usually considered to allow a correct diagnosis. We describe a FCMT French family with previously unreported clinical features such as sensitivity to glucose deprivation, vibration, repetitive visual patterns, and intense visual or auditory stimulation and contrasts. Electrophysiological studies of the propositus confirm the cortical reflex myoclonus elicited by photic stimulation and the absence of epileptic electroencephalographic discharges. We emphasize that a precise clinical analysis can lead to a correct diagnosis before electrophysiological confirmation. This is also the first-ever report of efficacy of levetiracetam in FCMT.

Adult↗

Essential tremor: diagnosis and treatment.

Essential tremor is a common movement disorder in adults that interferes with the performance of functional and social activities. Differentiation of essential tremor from other tremor syndromes is important in order to provide appropriate patient education and therapy. The mainstays of pharmacotherapy are propranolol and primidone; however, in selected patients, agents such as alcohol, benzodiazepines, botulinum toxin, and gabapentin may provide symptomatic benefits. Advances in surgical interventions, such as stereotactic thalamotomy and thalamic deep brain stimulation, offer patients an alternative treatment modality when pharmacotherapy is inadequate. A treatment algorithm is provided to guide clinicians in the management of patients with essential tremor.

Acetates↗

Pilot trial of 1-octanol in essential tremor.

1-Octanol (an 8-C alcohol currently used as a food-flavoring agent) is known to inhibit tremor in essential tremor (ET) animal models at a much lower dose than ethyl alcohol. The authors conducted a randomized, placebo-controlled pilot trial of a single oral dose of 1 mg/kg of 1-octanol in 12 patients with ET. No significant side effects or signs of intoxication were observed. 1-Octanol significantly decreased tremor amplitude for up to 90 minutes. The results suggest 1-octanol as a well-tolerated and safe potential treatment for ET. Further trials are warranted.

1-Octanol↗

Essential tremor: occupational exposures to manganese and organic solvents.

Occupational exposures to manganese and organic solvents cause parkinsonism as well as prominent action tremor, resembling essential tremor (ET), yet their association with ET has not been studied. These chemicals cause cerebellar pathology. Cerebellar changes have been linked with ET. Using lifetime occupational histories, the authors demonstrated that occupational exposures were similar in cases and controls, which does not support an etiologic link between occupational exposures to these chemicals and ET.

Aged↗

The effect of alcohol on essential tremor.

Five patients with essential tremor had a dramatic diminution in tremor amplitude within 15 minutes of ingesting small doses of ethyl alcohol. The same patients were given equivalent amounts of ethyl alcohol infused into a brachial artery, and there was no decrease in tremor amplitude in the perfused limb. It is concluded that, in patients with essential tremor, ethanol acts in a specific fashion on sensitive structures within the central nervous system and has no effect on peripheral tremorogenic mechanisms. This provides additional evidence for a central mechanism in essential tremor, distinguishing it from other tremors arising primarily from oscillation in peripheral servo-loops.

Administration, Oral↗

Carbenoxolone and mefloquine suppress tremor in the harmaline mouse model of essential tremor.

Excessive olivo-cerebellar synchrony is implicated in essential tremor. Because synchrony in some networks is mediated by gap junctions, we examined whether the gap junction blockers heptanol, octanol, carbenoxolone, and mefloquine suppress tremor in the mouse harmaline model, and performed an open-treatment clinical study of mefloquine for essential tremor. Digitized motion was used to quantify tremor in mice administered harmaline, 20 mg/kg s.c. In mice the broad-spectrum gap junction blockers heptanol, octanol (350 mg/kg i.p. each), and carbenoxolone (20 mg/kg) suppressed harmaline tremor. Mefloquine (50 mg/kg), which blocks gap junctions containing connexin 36, robustly suppressed harmaline tremor. Glycyrrhizic acid (related to carbenoxolone) and chloroquine (related to mefloquine), which do not block gap junctions, failed to suppress harmaline tremor in mice. Clinically, tremor was assessed with standard rating scales, and subjects asked to take 62.5, 125, and 250 mg mefloquine weekly for 12 weeks at each dose. None of the four human subjects showed a meaningful tremor reduction with mefloquine, likely because clinical levels were below those required for efficacy. In view of recent genetic evidence, the anti-tremor mechanism of these compounds is uncertain but may represent a novel therapeutic target, possibly involving gap junctions other than those containing connexin 36.

1-Octanol↗

Stimulation of the ventral intermediate thalamic nucleus in tremor dominated Parkinson's disease and essential tremor.

Based on Benabid's experimental and clinical findings that low-frequency (50 Hz) electrical stimulation of the ventral intermediate thalamic nucleus may increase tremor, while higher frequencies (> 100 Hz) lead to suppression of the tremor, we implanted a stimulation electrode in 33 thalami among 27 patients. Six patients were implanted bilaterally. 23 suffered from Parkinson's disease, 4 from essential tremor. All patients had a drug-resistant tremor. The Vim target was calculated based on stereotactic ventriculography. An intra-operative neurophysiological target control was performed on all patients. After a monopolar (12 thalami) or quadripolar (21 thalami) lead was implanted we then connected it to a percutaneous extension lead. In the days following the surgery a test stimulation was performed. In all but one patient stimulation resulted in a suppression of the tremor. In a second procedure, a pulse generator (ITREL II; MEDTRONIC) was implanted and connected subcutaneously to the thalamic lead. After implantation of the pulse generator all patients stimulate chronically while some turn off the stimulator at night. In 21 thalami total suppression of tremor was observed, 6 showed major improvement, 4 only minor improvement. There was no significant effect on any other existing symptom of Parkinson's disease. Due to the proximity of Vim to the sensory thalamus the majority of the patients (27 thalami) report slight temporary paraesthesias when the pulse generator is turned on. Two report permanent paraesthesias when stimulation is on. In 4 cases a slight dysarthria occurs under stimulation. In 2 the dysarthria is marked. In one case dysequilibrium occurs under stimulation. All these side effects are reversible when stimulation is turned off. In 3 patients, the lead was displaced due to an insufficient lead fixation, thus making a second procedure necessary to correct the electrode position. We had one complication due to bleeding at the burr hole side. Follow-up ranges from 3 to 48 months. So far in no cases has the effect of stimulation worn off. In conclusion we regard Vim neurostimulation as an effective and safe alternative to conventional thalamotomy and recommend that it should be considered in cases in which drug therapy has failed to affect Parkinsonian or essential tremor. Moreover, we believe that this procedure is a less invasive and equally efficient alternative to classic thalamotomy and thus should be given preference.

Adult↗

Delayed beta synchronization after movement of the more affected hand in essential tremor.

To investigate the pathomechanism of parkinsonian tremor (PT) and essential tremor (ET) by studying the correlation between tremor asymmetry and post-movement beta synchronization (PMBS) of the human EEG. We recorded the EEG of 10 patients with ET, 10 patients with Parkinson's disease and 10 controls. Subjects pressed an on-off switch in a self-paced manner with the thumb of their less (T+) and more (T++) tremulous hand. After digitalization of the EEG from the Cz, C3, C4 electrodes the movement reactive beta frequency, its maximum peak power value and its latency triggered to movement offset were determined. In ET tremor intensity did not influence the power of PMBS, however it was significantly delayed after the movement of the more tremulous hand. In Parkinson's disease after the movement of the more tremulous hand PMBS power was decreased, but it was not delayed. In controls the side of movement had no effect on the power and latency of the PMBS. The neuronal mechanisms underlying PMBS generation are differently affected in essential tremor and Parkinson's disease. The increase of PMBS latency after movement of the more affected hand in ET indicates possible cortical mechanisms in essential tremor generation.

Adult↗

Eye-hand coordination in essential tremor.

Patients with essential tremor (ET) or with cerebellar lesions have in common oculomotor abnormalities, with the exception of saccadic eye movements, which do not seem to be involved in ET. Since grasping is prolonged in ET and might be related to saccadic dysmetria, we tested whether simultaneous hand pointing could unmask it. Twelve ET patients and 14 controls performed saccades with and without simultaneous pointing movements to the same targets, and with and without a gap between the disappearance of the fixation point and the appearance of the target. Eye movements were recorded with the magnetic search-coil method, hand movements with an ultrasound-emitting probe. ET patients did not have saccadic dysmetria, and contrary to normal subjects their saccadic latency did not decrease during combined eye-hand movements compared with saccades performed in isolation. Hand movements had a longer duration in ET patients, with decreased peak acceleration, an increased latency of the peak velocity, and peak deceleration. In conclusion, this first study on eye-hand coordination in ET revealed abnormal kinematic changes in the early phase of pointing movements. These changes might be related to cerebellar disease but they are independent of the intention tremor component and saccade performance.

Adult↗

Clinical features of childhood onset essential tremor.

Childhood onset essential tremor (ET) is uncommon. It is not clear as to whether ethnicity-specific differences may influence the phenotypic features. To determine the frequency and clinical characteristics of childhood ET in a tertiary referral center. In a prospective evaluation of 120 consecutive ET patients in a movement disorders clinic, we found a 15.5% (19) frequency of childhood onset ET patients. The mean age of onset and mean age was 10.8 +/- 4.1 (6-16) years and 25.7 +/- 15.0 (16-73) years consisting of 73.6% (14/19) men and 26.4% (5/19) women. A positive family history of ET was present in 11 of 19 (52.6%). Presence of a head tremor was observed in 2/19 (10.5%). We highlighted a relatively high frequency (15,5%) of childhood ET in our Asian cohort. In addition, we drew attention to the male preponderance and the low frequency of head tremor in childhood ET corroborating study findings in white ET patients. These observations appear to transcend ethnic and cultural differences and lend further support that gender difference may play a role in the pathogenesis and expression of ET.

Adolescent↗

Interest in participating in clinical research: A study of essential tremor patients.

Enrolling essential tremor (ET) patients in clinical research can be challenging. Investigators can maximize recruitment by targeting patient subgroups with greater interest in participation. Nothing has been published on factors that are associated with higher levels of interest in participation. The objective of this study was to identify factors associated with higher levels of interest in participating in clinical research on ET. A total of 149 ET patients were questioned about level of interest in participating in future research. Two questions were used, although one was of primary interest. Interest was rated from 0 to 10 (maximal). Data were collected on demographic factors, family history, and tremor-related disability. Tremor severity was assessed. The mean level of interest was 8.0 +/- 2.3. Level of interest was not related to age of tremor onset, tremor duration, tremor severity, extent of tremor-related disability, or use of tremor medication. Level of interest was related to family history of tremor (P < 0.05), concern that other family members might develop tremor (P < 0.05), >2 versus 0 live births in women (P < 0.05), the view that the tremor worsens with age (P < 0.05), and presence of head tremor (P = 0.05). A variety of factors were identified that were associated with greater interest in participating in clinical research. These observations should be assessed in additional patient samples. Investigators may use our observations to identify and target patients for clinical trials and other research.

Biomedical Research↗

Intention tremor of the head in patients with essential tremor.

Patients with essential tremor (ET) have kinetic arm tremor; this tremor can also have an intentional component. We are unaware of reports of intention tremor of the head in ET. Our aims were to describe, provide electrophysiological data and video documentation of, and estimate the prevalence of intention tremor of the head in our sample. Ten (9.0%; 95% confidence interval = 4.7%-14.3%) of 111 patients had intention tremor of the head; in 7 it involved the neck and in 3 the chin. These patients trended toward having more severe kinetic arm tremor and they had more severe intention tremor of the arms. These observations provide further support for the evolving view that the cerebellum may be involved in ET.

Aged↗

Essential tremor: clinical characteristics.

Essential tremor (ET) is the most common movement disorder. However, only a small percentage of people affected by this genetically transmitted neurologic disorder seek medical attention. Lack of consensus on the diagnostic criteria for ET is an impediment to accurate diagnosis and leads to difficulty in accessing accurate prevalence data. Although a positive family history, alcohol sensitivity, and propranolol responsiveness are characteristic of ET, these factors should not be considered necessary for the diagnosis of ET. ET can produce substantial physical and psychosocial disabilities. The occasional coexistence of ET and Parkinson's disease (PD) in the same individual may present a diagnostic challenge.

Adult↗

Frequent sequence variation at the ETM2 locus and its association with sporadic essential tremor in Korea.

Essential tremor (ET) is the most common but a complex neurological movement disorder. ET usually affects hands, but it may also affect head, neck, face, jaw, tongue, voice, trunk and, rarely, legs and feet. Although two susceptibility loci were identified on chromosome 2p24 (ETM2) and 3q13 (ETM1 or FET1), the exact transcript(s) has not been cloned. We analyzed unrelated Korean individuals with ET for a genetic association with three reported polymorphic loci (STS-etm1240, STS-etm1231, and STS-etm1234) in a candidate region on chromosome 2p24.1. We investigated sequence polymorphisms at these three loci in 30 ET patients and 30 controls using polymerase chain reaction (PCR) amplification followed by sequence analysis. Eight different sequence variants (5 at etm1234, 2 at etm1240, and 1 at etm1231) were detected from 7 patients. Of interest, sequence variants were found only in classic ET patients but not in nonclassic ET patients and healthy individuals. Additionally, we also observed that a decrease in the number of short tandem repeats within etm1234 locus is more frequent in ET patients compared to controls. Our data thus support that ET development would be linked with the ETM2 locus and will facilitate the search for the ETM2 gene transcript.

Aged↗

Writing tremor: its relationship to benign essential tremor.

Nine patients with tremor on writing and one patient with tremor only on swinging a golf club were investigated. None of the patients had any other neurological symptoms or signs. The frequency of the tremor ranged from 5 to 6 Hz. Rapid passive supination or pronation of the forearm by a torque motor evoked a short burst of alternating tremor in seven patients. The tremor was improved by alcohol or propranolol in six patients. These characteristics of writing tremor (and of other isolated action tremors) suggest that it is a variant of benign essential tremor.

Adult↗

Risk of tremor and impairment from tremor in relatives of patients with essential tremor: a community-based family study.

Essential tremor (ET) is a common condition that is present in as many as 23% of elderly individuals. Our objective was to determine the risk of ET and to study the impairment resulting from ET among relatives of ET cases compared to relatives of controls. ET cases and matched controls from the Washington Heights-Inwood community, New York, and their first- and second-degree relatives underwent a standardized tremor examination. The risk of having ET in relatives of cases vs relatives of controls was compared using Cox proportional hazards models. Five hundred ninety-one subjects were examined (59 ET cases, 72 controls, 234 case relatives, and 226 control relatives). ET was present in 25 (22.5%) of the 111 first-degree relatives of cases compared to 6 (5.6%) of 107 first-degree relatives of controls [relative risk (RR) = 4.67, 95% confidence interval (CI) = 1.90-11.49, p = 0.0008]. RRs were higher in relatives of cases with onset < or =50 years than in those with later onset (RR = 10.38 vs 4.82). Sixteen (64%) of twenty-five affected first-degree case relatives exhibited moderate tremor while performing tasks such as writing, drinking, or pouring. Relatives of ET patients are five times more likely to develop the disease than are members of the population and ten times more likely if the proband's tremor began at an early age. The majority of the affected relatives can expect to experience impairment resulting from tremor.

Adolescent↗