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Unrecognized Tourette syndrome in adult patients referred for psychogenic tremor.

BACKGROUND: The diagnosis of Tourette syndrome may be overlooked in patients with severe psychopathologic disorder but mild motor manifestations of Tourette syndrome. OBJECTIVE: To describe 4 patients with long-lasting general psychopathologic disorder and previously unrecognized mild motor and phonic tics exacerbated during adulthood by the onset of tremor; all of the patients had been referred for the evaluation of psychogenic tremor. SUBJECTS: Four adult patients, with previous psychiatric diagnoses of depression (2 cases), generalized anxiety disorder (3 cases), malingering (1 case), and conversion disorder (3 cases). METHODS: Single case studies. RESULTS: Clinical interviews disclosed that the 4 patients had positive family histories of Tourette syndrome, and all had mild motor and phonic tics that had started before the age of 18 years. On neurologic examination, 2 patients had bilateral postural tremor of the hands that varied in frequency, rhythmicity, and amplitude, and the other 2 had resting tremor mimicking parkinsonism. All 4 patients described involuntary somatic sensations of the affected limbs, which they attempted to alleviate by executing movements. No consistent positive placebo response was observed, but in all patients tremoric movements improved with haloperidol. CONCLUSIONS: These cases illustrate an unusual movement disorder (tremor as a "tic equivalent") in adults with Tourette syndrome and emphasize that cases of the syndrome with mild tics often go unrecognized, precluding adequate treatment.

Adult↗

A lesion of the anterior thalamus producing dystonic tremor of the hand.

BACKGROUND: Thalamic tremor is typically characterized by resting and intention components; a postural element is often present as well. Previously reported cases of acquired thalamic tremor have demonstrated lesions in the posterior thalamus or dentatorubrothalamic tract. OBJECTIVES: To report a case of dystonic-postural tremor of the upper extremity that occurred after a contralateral anterior thalamic infarct, and to discuss potential tremorigenic mechanisms. DESIGN: Case report. SETTING: Municipal hospital neurology clinic. PATIENT: A 65-year-old right-handed woman suddenly developed a dystonic tremor in her left hand after undergoing coronary bypass surgery. The tremor persisted unchanged for 8 months, at which time she was evaluated by us. Cranial magnetic resonance imaging scans demonstrated a right anterior thalamic infarct. CONCLUSION: To our knowledge, this is the first report of focal tremor caused by a lesion of the anterior thalamus.

Aged↗

Transcranial magnetic stimulation of the cerebellum in essential tremor: a controlled study.

BACKGROUND: Growing evidence implicates an overactivity of the cerebellum in the pathophysiology of essential tremor. In a small series of patients, we explored the acute effects and therapeutic possibilities of low-frequency repetitive transcranial magnetic stimulation (rTMS) of the cerebellum in patients with essential tremor in a double-blind, crossover, placebo-controlled design. METHODS: Ten patients with essential tremor underwent an active and a sham rTMS session, at a 1-week interval. The rTMS was performed with a focal double 70-mm butterfly coil (maximum peak field of 2.2 T) applied 2 cm below the inion. Each session consisted of 30 trains of 10-second duration separated by 30-second pauses, at 100% of the maximum output intensity and at 1-Hz frequency. Major evaluation outcomes were the score on the Tremor Clinical Rating Scale and accelerometric recordings obtained before (-5 minutes), immediately after (+5 minutes), and 1 hour after (+60 minutes) each rTMS session. Both clinical and accelerometric measurements were obtained by a blinded neurologist. RESULTS: On the +5-minute assessment, active rTMS produced a notable tremor improvement compared with sham rTMS, as evidenced by a significant reduction in scores on the clinical rating scale and accelerometric values. At +60 minutes, no clinical or accelerometric benefit was evidenced. No adverse effects of rTMS were observed. CONCLUSIONS: This exploratory study of the potential therapeutic properties of rTMS on essential tremor showed an acute antitremor effect. Further investigation in search of a more lasting benefit is warranted.

Aged↗

Essential tremor associated with focal nonnigral Lewy bodies: a clinicopathologic study.

BACKGROUND: Essential tremor is one of the most common neurological diseases. Its links with Parkinson disease (PD) are often debated. There have been few published postmortem studies. OBJECTIVE: To study our first case of essential tremor through the recently established Essential Tremor Centralized Brain Repository. DESIGN: Report of a case of a patient with a diagnosis of severe essential tremor for 46 years who exhibited no signs of parkinsonism. RESULTS: On postmortem examination, gross brain sections showed no abnormalities. Results of microscopic examination of hematoxylin-eosin-stained sections revealed that the locus coeruleus contained multiple Lewy bodies (LBs), although none were found in the substantia nigra, dorsal vagal nuclei, thalamus, substantia innominata, inferior olivary nucleus, or cerebellum. Immunochemical staining using antibodies directed against alpha-synuclein confirmed the presence of many LBs in the locus ceruleus and showed rare LBs in the substantia innominata and dorsal vagal nuclei. There were no LBs in the substantia nigra. CONCLUSIONS: Our patient had a very focal presence of LBs in the locus ceruleus, an anatomically restricted form of LB disease. This study provides support for the link between essential tremor and LB disease and raises the question as to what proportion of patients with essential tremor might have unusual forms of LB disease.

Aged↗

Synchrony of laryngeal muscle activity in persons with vocal tremor.

OBJECTIVE: To determine if the tremor activity in laryngeal muscles is synchronous, which would indicate a single central source of tremor. DESIGN: Six persons with vocal tremor participated in this study. Laryngeal muscle activity was recorded from 2 intrinsic and 2 extrinsic laryngeal muscles during production of a sustained \i\ sound. Correlations were computed between electromyographic activity in pairs of laryngeal muscles to measure the degree to which electromyographic activity in one muscle was synchronous with electromyographic activity in another laryngeal muscle. In addition, correlations were computed between each of the 4 laryngeal muscles and the voice signal to determine which muscle had activity that was most highly related to amplitude modulations in the voice. Multiple samples from each subject were analyzed to obtain measures of the consistency and strength of the correlations. RESULTS: In most subjects, the bursts of electromyographic activity in one muscle were not consistently related to tremor activity in other affected muscles. Half the subjects exhibited moderate to strong correlations between thyroarytenoid muscle activity and the amplitude of the voice signal. Although the thyroarytenoid and cricothyroid muscles were always active during sustained phonation, half of the subjects did not activate either the thyrohyoid or the sternothyroid muscle during this task. CONCLUSIONS: The results of this study did not support the hypothesis that essential voice tremor is generated by a single central oscillator. Differences in the presence and timing of modulations in laryngeal muscle activity, as described in this study, may reflect clinically in the variable regularity and severity of vocal tremor.

Aged↗

Validity of family history data on essential tremor.

BACKGROUND: In family studies of essential tremor (ET), valid data on the presence of ET in relatives of probands with ET is important. The family history method uses information obtained by interviewing probands with ET to identify ET in their relatives. The validation of this method by direct examination of the relatives has not been performed. OBJECTIVE: To determine the validity of family history data on ET in families in which the proband has ET. METHODS: ET cases (probands) and their respective relatives were enrolled in a genetic study of ET in Washington Heights-Inwood, New York. Each underwent a tremor interview and videotaped examination. Two neurologists rated the severity of tremor and assigned diagnoses (ET versus normal). Probands were asked to identify their relatives who had ET. The validity of the probands' responses was tested against the neurologists' diagnoses. RESULTS: There were 206 subjects: 46 ET cases and 160 relatives. Twelve (7.5%) of 160 relatives were diagnosed with ET (four definite ET and eight probable ET). Probands with ET reported that two of these 12 had tremor (sensitivity of probands' report = 16.7%). Six of the 12 affected relatives (50.0%) reported their own tremor. The probands reported that one of 136 of their unaffected relatives had tremor (specificity of probands' report = 99.3%). CONCLUSIONS: For family studies of ET, information on reportedly unaffected relatives is of limited use given the low sensitivity of family history data. The neurologic examination remains the only valid means of ascertaining cases of ET among relatives.

Aged↗

Inter- and intralimb oscillator coupling in parkinsonian tremor.

This study reports the findings of an analysis of temporal correlation between tremor of different muscles of the same and different limbs in four patients with Parkinson's disease. Spectral coherence methods were used for determining whether simultaneously occurring oscillations in the electromyograms of different muscles are statistically coupled. The incidence of significant coherence was considerably higher for muscle pairs in the same limb than for pairs in different limbs; Parkinson's disease tremor is coupled within but not between limbs. Because the characteristics of tremor are known to vary under different behavioral situations, the intralimb coupling was examined for different tasks. A mental arithmetic task resulted in an increase in the coherence between muscles of the same limb, whereas the finger-to-nose task decreased the coherence. No significant change in coherence was found for a postural task. The amplitude and regularity of tremor electromyography showed changes analogous to those in coherence. These results support the hypothesis that tremor in different limbs results from the activity of several neural circuits oscillating independently. The results also emphasize the value of these methods for rigorously characterizing tremor, in relation to disease state, behavioral conditions, and the selection of treatment strategies.

Aged↗

Tremor and ataxia in fragile X premutation carriers: blinded videotape study.

Fragile X premutation carriers do not have typical fragile X syndrome (FXS) although late-onset progressive action tremor and gait disorder with CNS atrophy was recently reported in male carriers. We compared tremor, gait disorder and parkinsonian signs in FXS premutation subjects (age 50 or more) and a similar control population, using a standardized videotaping protocol. Videotapes were rated using standard scales for tremor (CRST), ataxia (ICARS), and parkinsonian signs (UPDRS) by an investigator blinded to premutation status. Compared to all other groups pooled (n = 30), the male premutation carrier group (n = 7) had significantly higher scores on the CRST (p = 0.0008), ICARS (p = 0.001), and UPDRS (p = 0.0094). On the CRST, rest, postural and kinetic tremor scores were all higher in the male carriers. The elevated total UPDRS and ICARS scores mainly resulted from markedly higher scores for tremor and limb ataxia, respectively. The female carrier (n = 14) and control groups (n = 8) did not differ on any measure. The FMR1 premutation is associated with increased levels of CGG repeat-containing FMR1 mRNA, which may predispose to these symptoms by interfering with nuclear mechanisms. Given the relatively high population frequency of the FMR1 premutation, this mutation may be a significant cause of late-onset "idiopathic" progressive tremor.

Aged↗

Association between essential tremor and Parkinson's disease.

To examine a possible relationship of essential tremor to Parkinson's disease (PD), 130 patients with essential tremor were studied. Twenty-five patients had both essential tremor and PD. These 25 patients were matched for age and duration of PD symptoms with 25 patients who had idiopathic PD. Bradykinesia, postural instability, and gait difficulty were more severe in the patients with idiopathic PD. Degree of tremor, rigidity, and functional disability did not differ in the two groups. The prevalence of PD in the population with essential tremor was 24 times greater than expected. This study suggests that some patients with essential tremor have a genetically increased risk for PD.

Adolescent↗

Motor unit synchronization in physiologic, enhanced physiologic, and voluntary tremor in man.

Synchronization between pairs of single motor units simultaneously recorded from wrist extensor muscles was quantitated in 3 normal subjects during physiologic tremor (PT), beta-adrenergically enhanced physiologic tremor (EPT), and fast voluntary wrist flexion-extension movements mimicking tremor (VT). Cross-correlation histograms generated from the two spike trains of each motor unit pair demonstrated central or paracentral peaks in 13/19 recordings during PT, 22/36 during EPT, and 6/7 during VT. Relative peak area was used as a quantitative index of synchronization between the two motor units of each pair. It was lowest in PT, progressively increased in EPT as tremor amplitude increased, and highest in VT. In PT and lower amplitude EPT, the synchronization indexes were higher between motor units that discharged at the same or nearly the same frequency. In contrast, in higher amplitude EPT and VT, motor units with different firing frequencies were sometimes strongly synchronized as a consequence of double discharges in faster-firing motor units that had burst repetition rates in the range of slower-firing motor units discharging as singlets. Greater motor unit synchronization with increasing tremor amplitude in EPT may be secondary to a simultaneous increase in muscle spindle afferent activity from the tremulous muscle. Greatest synchronization in VT presumably reflects near maximal supraspinal and segmental common synaptic input onto motoneurons that generate VT. These results support a longstanding hypothesis that synchronization of motor units is the physiological basis for higher amplitude tremor.

Electromyography↗

Red nuclear and cerebellar but no olivary activation associated with essential tremor: a positron emission tomographic study.

There has been debate as to whether essential tremor has a central origin and over the possible role of the inferior olivary nucleus in its genesis. We used positron emission tomography with radioactive water (H2(15)O) to detect abnormal patterns of cerebral activity associated with this condition, at rest, without tremor, and on posture when the tremor was present. At rest, cerebellar blood flow was significantly increased bilaterally in the group with essential tremor (30-40%) but no increased olivary activity was evident. Essential tremor during arm extension was associated with further abnormal increases in bilateral cerebellar and abnormal red nuclear activation. Again, no olivary overactivity was evident. Voluntary wrist oscillation in control subjects caused only ipsilateral cerebellar activation. We conclude that essential tremor is associated with abnormal bilateral overactivity of cerebellar and red nuclear connections but found no evidence of intrinsic overactivity of the inferior olivary nucleus, as evidenced by raised blood flow.

Adult↗

Double-blind, single-dose, cross-over study of the effects of pramipexole, pergolide, and placebo on rest tremor and UPDRS part III in Parkinson's disease.

Tremor is one of the cardinal signs of Parkinson's disease (PD) but its response to antiparkinsonian medication is variable. It has been postulated that pramipexole may have a stronger antiparkinsonian tremor effect than pergolide, another direct acting dopamine agonist medication, possibly because the former has preferential affinity for the dopamine D3 receptor. The purpose of this pilot study was to compare the effects of a single oral dose of either pramipexole (Pr) or pergolide (Pe) or placebo (Pl) on parkinsonian tremor and the motor (part III) subsection of the UPDRS. Ten patients (6 men, 4 women), mean age 65.3 years, mean duration from diagnosis of 2.6 years, with tremor dominant PD were recruited. On three separate occasions a single dose of pramipexole (salt) 500 microg, pergolide 500 microg or placebo were administered in random order to each patient, who were pretreated with domperidone and had their antiparkinsonian medication withheld from midnight before study. After each medication patients were assessed at baseline and then every 30 min for 4 hr using a 0 to 10 tremor rating scale and the UPDRS (part III) in a double-blind protocol. Adverse effects were systematically recorded. The results demonstrate that 500 microg of either pramipexole or pergolide reduced PD rest tremor scores to a similar degree, which at peak effect was significantly greater than placebo (respectively Pe v Pl: P < 0.006, Pr v Pl: P < 0.033). The two active drugs also had weaker beneficial effects on the UPDRS part III. Pergolide, however, was significantly more likely than pramipexole to cause nausea (P = 0.005) or vomiting (P = 0.014).

Aged↗

Orthostatic tremor arises from an oscillator in the posterior fossa.

We tested the hypotheses that orthostatic tremor is generated by a central oscillator and that the tremor is expressed through spinal Ib interneurons. Six patients with orthostatic tremor were examined. The tremor was reset by electrical stimulation over the posterior fossa at intensities that were below the threshold for a motor evoked potential (MEP) but was not reset by transcranial magnetic stimulation over the motor cortex that did produce an MEP. It is argued that the oscillator involves the cerebellum or brainstem. The inhibition of voluntary EMG produced by stimulation over tendons, which has been attributed to effects from Golgi tendon organs (GTO), was not modulated in synchrony with the tremor. We were unable to demonstrate, therefore, that the tremor is expressed through GTO interneurons with this method.

Aged↗

Effect of ethanol on the central oscillator in essential tremor.

We investigated the effects of ethanol and diazepam on the central, mechanical, and mechanical reflex components of tremor in patients with essential tremor (ET). A double-blind crossover study (ethanol or diazepam) was conducted on 2 separate days. Dose of ethanol or diazepam was calculated in each individual according to height, weight, and age in 10 patients with ET. The postural tremor amplitude at the wrist was recorded using a three-dimensional accelerometer placed on the dorsum of the hand. Electromyogram (EMG) was recorded with surface electrodes placed on the forearm extensors and flexors. To separate central and mechanical (reflex) components, a 500-g weight was placed on the dorsum of the hand during a second tremor measurement. Tremor recordings were done at baseline and 30, 60, 90, and 120 minutes after drug ingestion. Ethanol and diazepam blood levels were measured at baseline and after 20, 40, 80, and 120 minutes. Blood ethanol and diazepam levels were highest after 40 and 80 minutes. The amplitude of the central component 60 minutes after ingestion of ethanol was decreased significantly (P = 0.029) compared with diazepam. Our findings suggest that the improvement in tremor after ethanol ingestion was due, at least in part, to an effect on a central oscillator.

Biological Clocks↗

Late-life action tremor in a southern sea otter (enhydris lutris nereis).

Although tremor is highly prevalent in human beings, there are few reports of tremor occurring in other mammals. Such tremor can further our insight into the mechanisms and anatomical basis of human tremor disorders. We report on a southern sea otter with a slowly progressive 6.5 to 8.5 Hz action tremor of late life that shared several clinical characteristics with essential tremor. The main pathological finding was in the cerebellum, where there was extensive vacuolation of Purkinje cells.

Age Factors↗

Semiquantitative study of current coffee, caffeine, and ethanol intake in essential tremor cases and controls.

There are several reasons to study caffeine, coffee, and ethanol intake in essential tremor (ET) patients. ET patients also might modify their use of these beverages because of their effects on tremor. Intake of caffeine, coffee, and ethanol has not been quantified in a group of ET patients. Our objective is to use a semiquantitative food frequency questionnaire to compare current daily intake of coffee, caffeine, and ethanol in ET patients and controls. A total of 130 ET cases were patients at the Neurological Institute of New York, and 175 controls were ascertained by random digit dialing. Caffeine (in milligrams) and ethanol (in grams) intake were calculated from a semiquantitative food-frequency questionnaire. Mean daily caffeine intake in patients was 138.4 versus 246.6 mg in controls; medians were 101.1 versus 175.5 mg (P < 0.001). Mean daily ethanol intake in patients was 8.2 versus 6.2 gm in controls; medians were 2.4 versus 1.9 gm (P = 0.89). Cases drank less coffee than controls, but drank similar amounts of tea, soft drinks, fruit juices, and milk. Daily caffeine intake was not correlated with tremor severity or duration. ET patients consumed less caffeine than did controls, which is likely to be a dietary modification in response to tremor. The observation that caffeine consumption was not correlated with tremor severity raises the additional possibility that lower caffeine consumption in ET patients may not exclusively be a response to tremor. A prospective study is needed to explore whether decreased caffeine consumption is a risk factor for ET.

Aged↗

Pilot efficacy and tolerability: a randomized, placebo-controlled trial of levetiracetam for essential tremor.

The purpose of this pilot single-site study was to assess efficacy and safety of levetiracetam for essential tremor, using a placebo-controlled, double-blind, randomized crossover design with an interim analysis planned after completion of the first 10 to 15 subjects. The study was designed to detect a mean 30% reduction in composite tremor score, comparable to that of primidone or propranolol, which can be demonstrated with 30 or fewer subjects. Each treatment arm included baseline tremor assessments, a 4-week medication titration, 2 weeks of stable dose, and treatment tremor assessments. Levetiracetam was titrated to 3,000 mg/day or to a lower maximal tolerated dose. The median age was 72 years, with 28 years median tremor duration. There was no statistically significant difference in response between placebo and levetiracetam on any tremor rating scale or accelerometry measure. The 95% confidence interval for the true mean difference between placebo and levetiracetam treatments was +18.5 to -22.5%, which excludes the minimum 30% drop required to consider levetiracetam clinically effective to a degree comparable to primidone or propranolol. Whether levetiracetam has lesser-degree antitremor efficacy was not addressed in this pilot study.

Aged↗

Association of the C677T and A1298C polymorphisms of methylenetetrahydrofolate reductase gene in patients with essential tremor in Turkey.

Essential tremor (ET) is a most common human movement disorder of unknown etiology. Previous reports have shown that the C677T polymorphism of methylenetetrahydrofolate reductase gene has been associated with neurodegenerative disorders. To investigate the role of methylenetetrahydrofolate reductase gene polymorphisms in essential tremor, we analyzed the alleles and genotypes of methylenetetrahydrofolate reductase (MTHFR) C677T and MTHFR A1298C in a total of 158 unrelated essential tremor patients and compared them with those of 246 unrelated healthy control subjects, using a polymerase chain reaction restriction fragment length polymorphism method. The allele frequency of MTHFR 677T was 35.76% in the essential tremor cases and 30.08% in the controls. We obtained statistically significant results for MTHFR677 and also for MTHFR1298. The MTHFR T677T genotype was overrepresented and was statistically significant. The T677T/A1298A and C677C/C1298C compound genotypes were similarly statistically significant. The C677C/A1298A compound genotype provided protection for essential tremor. In conclusion, the MTHFR 677T, 1298C alleles and MTHFR T677T genotype and T677T/A1298A, and C677C/C1298C compound genotypes are genetic risk factors for essential tremor in Turkey.

Adult↗