Surgical interventions in the treatment of Parkinson's disease (PD) and essential tremor (ET): medial pallidotomy in PD and chronic deep brain stimulation (DBS) in PD and ET

Surgical treatments for PD and ET are promising. Medial Pallidotomy, the surgical lesioning of the pallidum, often improves symptoms of long-standing PD. We enrolled twenty-seven late stage PD patients for unilateral medial pallidotomy who were then assessed by the Core Assessment Program for Intracranial Transplantation (CAPIT) protocol. One year after surgery persistent improvement was seen contralateral to the lesion in the following features: drug-induced dyskinesias (92%), akinesia (38%), rigidity (51%), and tremor (42%). Complications included transient dysarthria (7 patients), facial weakness (9 patients), limb weakness (1 patient), swallowing problems (4 patients) and intracerebral haemorrhage (1 patient). Thalamic DBS may improve tremor in PD and ET patients. Therefore, we enrolled fifteen patients (9 PD and 6 ET patients) with disabling tremor, unresponsive to medication. They were assessed by the United Parkinson's Disease Rating Scale (UPDRS) and the Tremor Rating Scale (for PD and ET patients, respectively). Three months after surgery, limb tremor contralateral to stimulation improved by 71% in PD patients and 76% in ET patients. Complications included transient paresthesias (all), confusional state (1 patient) and intracerebral bleed (1 patient). Unilateral medial pallidotomy safely improves some Parkinsonian symptoms contralateral to the lesion. Thalamic DBS may effectively and safely improve contralateral limb tremor in PD and ET.     

Improvements in daily functioning after deep brain stimulation of the thalamus for intractable tremor

Deep brain stimulation (DBS) of the thalamus reduces tremor in patients with essential tremor (ET). However, few studies have determined the degree of improvement in daily functioning associated with DBS. We developed a self-report Tremor Activities of Daily Living Scale (TADLS) to compare daily functioning with the stimulator turned on and off. Patients rated their performance on the 30 items of the TADLS with the stimulator turned off and then on. They also performed 10 activities under the supervision of a clinician who rated their functional ability with stimulation off and then on. There was a 58% improvement in self-rated TADLS scores in patients with DBS with the stimulator on compared with stimulation off. When activities were rated by the clinician, the average improvement in functioning with the stimulator on was 54%. There were reasonably high correlations between patient and clinician ratings of functioning. ET patients have a marked improvement in daily functioning with thalamic DBS.     

Is essential tremor symmetric? Observational data from a community-based study of essential tremor

BACKGROUND: Essential tremor (ET) has been variably portrayed in the literature both as a symmetric arm tremor and as an asymmetric arm tremor. Few quantitative clinical or neurophysiological data specifically address the issue of tremor asymmetry in ET. OBJECTIVES: To examine a community-dwelling cohort of subjects with ET to (1) estimate the prevalence of tremor asymmetry and (2) quantify the magnitude of tremor asymmetry. METHODS: Fifty-four subjects with ET, identified in a community-based study of ET in New York City, underwent a Tremor Interview and a videotaped Tremor Examination. The examination included 6 tasks: sustained arm extension, pouring water, drinking water, using a spoon, finger-to-nose movements, and drawing spirals with each arm. Two neurologists rated the severity of tremor using a 0 to 3 clinical rating scale and a total tremor score was calculated (range, 0-36). Fourteen (25%) of 54 subjects also underwent quantitative computerized tremor analysis. RESULTS: The prevalence of asymmetry depended on the definition of asymmetry; small to moderate differences between sides were common. The mean side-to-side difference in clinical ratings for each of the 6 tasks was 0.54 of 3 points, which represented a 1.32-fold difference between sides. Clinical rating scores were higher in the nondominant arm in 39 subjects (72%), higher in the dominant arm in 9 (17%), and equal in 6 (11%). The 2 left-handed subjects had higher clinical ratings on the right. During quantitative computerized tremor analysis, there was a 1.71-fold mean difference between tremor amplitudes in the dominant and nondominant sides, and in 12 subjects (86%), the maximum tremor amplitude was in the nondominant arm. CONCLUSIONS: Small to moderate differences between sides were common in ET. In most community-dwelling subjects, tremor amplitude was greatest in the nondominant arm. In contrast, clinic-based studies have reported greater tremor in the dominant arm; those with ET who seek medical attention are more likely to exhibit severe tremor in their dominant arms. This study documents that mild asymmetry is a fundamental property of ET and that tremor is more severe in the nondominant arm.     

Functional expression of green fluorescent protein derivatives in Halobacterium salinarum

Protocols with demonstrated reliability have been established for the diagnosis of numerous movement disorders. whereas in the essential tremor (ET) literature, there is no discussion about the reliability of diagnostic protocols. Lack of knowledge of the reliability of diagnostic protocols in ET limits the use of these protocols because reliability is an essential requirement for scientific quality in data management. The objective of this study was to determine the reliability of a protocol for diagnosing ET. The protocol consists of a Tremor Interview, a videotaped Tremor Examination, and a diagnostic algorithm. Eighty-three subjects with ET, identified in a community-based health study in Washington Heights-Inwood, New York, were matched with 83 control subjects from the same community. These subjects and their relatives are being recruited to participate in the Washington Heights-Inwood Genetic Study of ET. Two hundred twenty-six subjects have been evaluated to date (35 ET cases, 40 controls, 151 relatives). All 226 underwent an 84-item Tremor Interview and 26-item videotaped Tremor Examination. Diagnoses (normal, possible ET, probable ET, definite ET) were independently assigned by two blinded neurologists specializing in movement disorders. The kappa statistic, k, was used to determine diagnostic agreement between these two neurologists. The concordance rate between two raters using diagnostic categories definite ET, probable ET. possible ET, and normal was 80%; kw = 0.84 (near perfect to perfect agreement). The concordance rate between two raters using two diagnostic categories (definite ET and normal) was 100%; k = 1.00 (perfect agreement). There was high correlation between the two raters' total tremor scores (r = 0.89, p < 0.00001). This diagnostic protocol is highly reliable. Research in ET would greatly benefit from diagnostic protocols with demonstrated reliability.     

Effect of nicardipine on essential tremor: brief report

The effects of nicardipine, a calcium channel blocker (CCB), were investigated in 11 patients with essential tremor (ET). In a placebo controlled study, a single oral dose of 30 mg of nicardipine was administered, followed by 1 month of sustained treatment (60 mg/day). Tremor was assessed by accelerometric recording. A single oral dose of nicardipine reduced the tremor amplitude respect baseline (p = 0.003) and placebo (p = 0.008). After 1 month of chronic treatment, nicardipine still reduced the tremor amplitude (30.78% +/- 17.13 SE from baseline), but failed to sustain the initial statistical improvement. A single oral dose of nicardipine is effective in reducing ET.     

Tremor in ostensibly normal elderly people

Tremor in ostensibly normal people, aged 70-91, was assessed clinically and electrophysiologically with the goal of estimating the prevalence of abnormal tremor. Fifty men and 50 women, mean age 76.0 +/- 4.7 yrs, were recruited through advertisements for healthy volunteers (n = 50 "biased" control subjects) and from the spouses of patients referred to us for dementia or Parkinson's disease (n = 50 "unbiased" control subjects). All participants were interviewed and examined by the author. Tremor was assessed quantitatively with rating scales, triaxial accelerometry, electromyography, a digitizing tablet, and spectral analysis. Twenty-three people (23%) were judged clinically to have mildly abnormal tremor resembling mild essential tremor. Twelve people with abnormal tremor belonged to the biased group and 11 were in the unbiased group. The clinical diagnosis of abnormal hand tremor correlated well with the presence of motor unit entrainment in the forearm EMG and with writing or drawing tremor that was measurable with a digitizing tablet. Only 10 of 23 people with abnormal tremor were aware of their tremor, and none had been diagnosed previously by a physician. Nine of 77 people (11.7%) with normal tremor had a parent or sibling with possible essential tremor, and five of the 23 people (21.7%) with abnormal tremor had this family history. Mild undiagnosed tremor, resembling essential tremor, is common in this age group.     

Levodopa does not aggravate postural tremor in Parkinson's disease

Characterization of postural tremor in Parkinson's disease (PD) is incomplete. It was suggested to be an exaggerated physiological tremor and to be enhanced by the action of levodopa. We compared the magnitude of postural tremor to the magnitude of rest tremor and to plasma levodopa levels in 20 PD patients, 10 with stable motor response to oral levodopa, and 10 with the wearing-off phenomenon. Tremor assessment included motor scores of the Unified Parkinson's Disease Rating Scale and accelerometric measurements. Accelerometric data showed that the absolute power of both rest and postural basal dominant tremor frequencies significantly diminished with the increase in plasma levodopa levels and increased with their decrease. Tremor frequencies were also significantly changed by levodopa, which slowed rest tremor and increased postural tremor dominant frequency. This latter, however, did not reach the 8- to 12-Hz frequency band said to be typical of exaggerated physiological tremor. No significant differences between groups were found in their tremor response to levodopa. This study shows that the net postural tremor exhibited by PD patients is improved by levodopa, that levodopa does not augment tremor in the 8- to 12-Hz range, and that this effect is independent of the patient's motor response pattern of oral levodopa.     

Disclosure of trauma and immune response to a hepatitis B vaccination program.

This study investigated whether emotional expression of traumatic experiences influenced the immune response to a hepatitis B vaccination program. Forty medical students who tested negative for hepatitis B antibodies were randomly assigned to write about personal traumatic events or control topics during 4 consecutive daily sessions. The day after completion of the writing, participants were given their first hepatitis B vaccination, with booster injections at 1 and 4 months after the writing. Blood was collected before each vaccination and at a 6-month follow-up. Compared with the control group, participants in the emotional expression group showed significantly higher antibody levels against hepatitis B at the 4 and 6-month follow-up periods. Other immune changes evident immediately after writing were significantly lower numbers of circulating T helper lymphocytes and basophils in the treatment group. The finding that a writing intervention influences immune response provides further support for a link between emotional disclosure and health. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Orthostatic tremor: an electrophysiological analysis

Orthostatic tremor (OT) is a clinically defined syndrome of leg tremor while standing. Controversy surrounds whether OT is a distinct syndrome or is an essential tremor (ET) variant. We report two patients with OT. Electrophysiological testing included polymyography, accelerometry, nerve conduction, and evoked potential studies. The effects of various maneuvers and body positions on the tremor were assessed. The findings included rapid (15-17 Hz) lower-extremity tremor burst frequency evoked by standing but not by walking or swaying; rapid upper-extremity burst pattern synchronous with lower-extremity bursts; and failure of electrical stimulation or mental concentration to "reset" the tremor. Additionally, there was the novel finding of accelerometric recordings in the legs revealing the same rapid frequency (16-17 Hz) as the electromyographic tremor bursts. Some prior reports have suggested that OT is related to ET by emphasizing a considerable disparity and variability between the accelerometric tremor frequency and the electromyographic burst frequency. In our patients, however, the rapid (15-17 Hz) accelerometer-recorded tremor synchronous with the electromyographic bursts, and also the clinical improvement with clonazepam but not beta blockers or mysoline, and the lack of a family history of ET provide support that OT is distinct from ET.     

Serotonin synthesis inhibition in olivo-cerebellar system attenuates harmaline-induced tremor in Swiss albino mice

Recent experimental evidences point to the active role of central serotonin (5-HT) elicited mechanisms in the pathogenesis of tremor. The present study was undertaken to investigate the effects of p-chlorophenylalanine (pCPA), a specific tryptophan hydroxylase inhibitor and a central 5-HT depletor, on the neurochemical processes that occur synchronously in olivary nucleus (ON) and cerebellum during harmaline-induced tremor in mice. Tremor appeared by 3-4 min following harmaline administration, and reached its peak by 25 min for the doses (10-30 mg/kg) studied. Peak of harmaline-tremor coincided with increases in 5-HT in ON and cerebellum, as assayed employing HPLC-electrochemistry. Administration of pCPA caused significant depletion in 5-HT level in both the regions analyzed, and also significantly inhibited harmaline-induced tremor. Our present results support the earlier electrophysiological evidences that harmaline-induced tremor originates from ON, and confirm the role of 5-HT in the genesis of this motor neuronal dysfunction.     

123I]beta-CIT and SPECT in essential tremor and Parkinson's disease

Resting and postural tremor may occur in essential tremor (ET) and Parkinson's disease (PD). The aim of the present study was to investigate the cocaine derivative [123I]beta-CIT, which labels striatal dopamine transporters, and SPECT in differentiating these diseases. METHODS: 30 healthy volunteers, 32 patients with ET and 29 patients with idiopathic PD of Hoehn/Yahr stage I were investigated. Specific over nondisplaceable binding ratios (target/cerebellum-1) were calculated for the striatum, the caudate nucleus and the putamen separately as well as a ratio putamen/caudate and the percent deviation of each patient's ratio from age-expected control values. RESULTS: Striatal [123I]beta-CIT binding ratios in ET were within normal ranges and showed only a discrete elevation to age-expected control values (+14.6%). In PD significantly reduced specific binding was evident not only contralaterally to the clinically affected side (putamen: -62%, caudate nucleus: -35%), but also ipsilaterally (putamen: -45%, caudate nucleus: -22%). All investigated parameters differed significantly between PD and controls and ET respectively. CONCLUSION: Imaging striatal dopamine transporters with [123I]beta-CIT and SPECT could clearly distinguish between ET and PD in an early stage of the disease. Findings do not suggest a subclinical involvement of dopaminergic nigrostriatal neurons in ET.     

Dissonance and healthy weight eating disorder prevention programs: A randomized efficacy trial.

In this trial, adolescent girls with body dissatisfaction (N = 481, M age = 17 years) were randomized to an eating disorder prevention program involving dissonance-inducing activities that reduce thin-ideal internalization, a prevention program promoting healthy weight management, an expressive writing control condition, or an assessment-only control condition. Dissonance participants showed significantly greater reductions in eating disorder risk factors and bulimic symptoms than healthy weight, expressive writing, and assessment-only participants, and healthy weight participants showed significantly greater reductions in risk factors and symptoms than expressive writing and assessment-only participants from pretest to posttest. Although these effects faded over 6-month and 12-month follow-ups, dissonance and healthy weight participants showed significantly lower binge eating and obesity onset and reduced service utilization through 12-month follow-up, suggesting that both interventions have public health potential. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Writing tremor after discrete cortical infarction

BACKGROUND: Hand tremor is a rare manifestation of stroke, and writing tremor has not been reported to be produced by stroke. We describe a patient who developed a unilateral hand tremor mimicking primary writing tremor after discrete cerebral cortical infarction. CASE DESCRIPTION: A 67-year-old man developed mild right hemiparesis. Brain magnetic resonance imaging showed a discrete cortical infarct in the left frontal area. After recovery of motor power, the patient showed significant right hand tremor exclusively during writing or similar motor activities including tooth brushing or shaving. The tremor was temporarily alleviated by clonazepam but persisted until 7 months of follow-up. Medical history suggested that the patient had mild essential tremor, but he did not experience tremor on writing before the onset of stroke. CONCLUSIONS: This observation suggests that unilateral hand tremor mimicking primary writing tremor may be produced by cortical infarction. It remains unclear whether the patient's previous essential tremor played an additional role in the development of this symptom.     

Female Wistar-Kyoto and SHR/y rats have the same genotype but different patterns of expression of renin and angiotensinogen genes

BACKGROUND: Prevalence estimates vary 2750-fold among the 20 studies of essential tremor (ET). It is not clear how the choice of diagnostic criteria affects research results. OBJECTIVE: To determine the impact of alternative sets of diagnostic criteria on the diagnosis of ET. METHODS: As part of the Washington Heights-Inwood Genetic Study of ET (WHIGET), a population-based study of ET, 285 subjects who include 36 case subjects with probable or definite ET, 34 case subjects with possible ET, and 215 normal subjects were interviewed and examined. All diagnoses in WHIGET were assigned by 2 neurologists. Ten of the 20 published prevalence studies of ET provided diagnostic criteria for ET. Criteria differed in terms of requirements for the distribution, duration, and severity of tremor. These 10 sets of criteria were then each separately applied to the subjects in the WHIGET cohort to determine their impact on the diagnosis of ET. RESULTS: Depending on which diagnostic criteria were applied to the WHIGET cohort, the proportion of WHIGET case subjects with definite or probable ET who would have been diagnosed as having ET was as low as 14% and the proportion of WHIGET normal subjects who would have been diagnosed as having ET was as high as 51%. Diagnostic criteria that included a positive family history of ET or a lengthy duration of tremor would have classified many WHIGET case subjects with ET as normal, whereas criteria that did not specify a minimal tremor severity would have classified many WHIGET normal subjects as having ET. CONCLUSIONS: Alternative sets of diagnostic criteria for ET greatly impact on the diagnosis of ET. For population-based studies, information on tremor type and severity rather than family history should be included in diagnostic criteria.     

Comparison of operant behavioral and cognitive-behavioral group treatment for chronic low back pain.

To evaluate and compare the efficacy of two widely used behavioral approaches for the treatment of chronic pain, 81 mildly dysfunctional chronic low back pain patients were randomly assigned to operant behavioral (OB) treatment, cognitive-behavioral (CB) treatment, or a waiting-list (WL) control condition. Both treatments, which were conducted in eight-session outpatient groups, resulted in decreased physical and psychosocial disability. The OB patients showed greater pre- to posttreatment improvement as rated by patients and their spouses than did the CB patients. Generally, the OB patients showed a leveling off in improvement at 6- and 12-month follow-ups, whereas the CB patients generally continued to improve over the 12 months following treatment. At 12-month follow-up, patients in both treatments remained significantly improved, with no significant differences between conditions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Metastatic squamous cell carcinoma in a liver graft. Report of a case diagnosed by fine needle aspiration

We studied the effect of deep brain stimulation (DBS) of the ventral intermediate thalamic nucleus on voice symptoms in seven patients with essential tremor. All had undergone DBS for management of hand tremor. Five of the patients had received unilateral implants; two were treated bilaterally. Each reported improvement in hand tremor with thalamic stimulation (a 1-to-3-point change on a 5-point severity scale). Voice tremor was evaluated with and without stimulation using patient and clinician severity ratings, and acoustic measures (rate and amplitude). Four of the seven patients showed reductions in voice symptoms in at least two of these measures, although degree of change differed (e.g., from 1 to 3 points on the 5-point severity scale). Voice gains typically were restricted to those patients with the more severe symptoms and did not parallel improvements in the upper extremities. It appears that reduced voice tremor may be an additional benefit of DBS for some individuals.     

Motor-unit activity responsible for 8- to 12-Hz component of human physiological finger tremor

Tremor of the extended third digit and bipolar surface and needle electromyograms of the extensor digitorum were recorded from six healthy volunteers for the purpose of elucidating the motor-unit activity responsible for the 8- to 12-Hz component of physiological finger tremor. Tremor was measured with a force transducer during steady voluntary contractions of approximately 200-250 g. The surface EMGs were full-wave rectified and low-pass filtered (-3 dB at 21 Hz), producing the envelope of the surface EMG (the demodulated EMG). Spectral analyses of simultaneous tremor and demodulated EMG records were performed. In four of six subjects, a pronounced 8- to 12-Hz amplitude modulation in the surface EMG was present, and coherency analysis demonstrated that this modulation was strongly correlated with the well-known 8- to 12-Hz tremor. In two subjects this amplitude modulation and tremor were barely detectable, despite the sensitive recording and analysis techniques used in this study. Spectral analysis was performed on 43 motor-unit spike trains. Twenty-two spike trains, having mean firing frequencies in the range of 10-22 spikes/s, produced statistically significant spectral peaks at 8-12 Hz, in addition to the expected spectral peaks at the mean firing frequencies. Of the 22 8- to 12-Hz-producing motor units, 12 had mean firing frequencies in the range of 17-22 spikes/s and exhibited the greatest 8- to 12-Hz activities of all motor units recorded. These motor units displayed transient sequences of double discharges in which interspike intervals (ISIS) of approximately 8-30 ms alternated with ISIS of 60-90 ms, thus producing an 8- to 12-Hz spectral peak. Adjacent ISIS of these motor units were correlated in the range of -0.5 to -0.9. Coherency analyses demonstrated that the 8- to 12-Hz activities of these motor units were correlated with the 8- to 12-Hz finger tremor and surface EMG modulation. The remaining 10 8- to 12-Hz-producing motor units had mean firing frequencies in the range of 10-17 spike/s. Although these motor units did not display the intense double-discharge firing pattern of the more rapidly firing motor units, a tendency toward action potential grouping was present and resulted in 8- to 12-Hz spectral activities which were correlated with the tremor and surface EMG modulation. .. ..     

Essential tremor: a review of pathogenic mechanisms

INTRODUCTION: Essential tremor (ET) is the commonest involuntary movement observed and is seen when a given posture is maintained. Although it does not affect life expectancy, it may cause considerable functional disability and serious psychological effects in the affected person. DEVELOPMENT: ET is a heterogeneous clinical condition. Its physiopathology is still not known, is very complex and involves many mechanisms, both structural and biochemical, although as yet there is no theory to include them all. In view of what is known at present, it may be accepted that there is a central oscillator at olive-cerebellar-thalamic-cortical-spinal level, which is the primary generator of ET, modulated by a peripheral component. The tremor results from interaction between increased central excitability and peripheral regulation, which in turn reinforces the central overactivity. It may also be that the monoaminergic system (catecholaminergic and serotoninergic), adrenoreceptors (especially the B2 muscular adreno-receptors) and the bodily structure itself, amongst other factors, may influence the pathogenic mechanism of ET. It is likely that there is a multifactorial genetic disorder which predetermines this physiopathogenic process, although this has not yet been determined. CONCLUSIONS: In this paper we review the various hypotheses and existing knowledge related to the aetiopathogenesis of TE.     

Comparative clinical study of patients with Parkinson disease and essential tremor

INTRODUCTION AND OBJECTIVE: Some studies have shown that essential tremor (ET) occurs more frequently in Parkinson disease (PD) patients and opposite, suggesting these disorders are pathogenically related. To evaluate this relationship, we have compared some clinical features between patients with ET and with PD. PATIENTS AND METHODS: PD patients (N = 134) and patients with ET (N = 46), were collected from Bajo Aragon district. A diagnosis of PD was taken according to the United Kingdom Parkinson's Disease Society Brain Bank criteria. A diagnosis of ET was confirmed on the basis of Rajput et al criteria. RESULTS: A statistically significant higher number of females with ET were founded (p < 0.05). An earlier mean age at tremor onset was observed in ET patients (p < 0.0001). More than half ET patients had a positive had a positive family history of ET (p < 0.0001). Interval period between tremor onset and first medical consulting was higher in ET patients (p < 0.01). Depression was more common in PD patients (p < 0.05). CONCLUSIONS: A statistically significant differences about mean age at tremor onset, duration of illness, positive family history of ET, one side or bilateral tremor onset and frequency of depression were observed between these two disorders. The differences found in clinical features and others described previously about necropsy findings and TEP with 18F-Dopa studies, don't support the possibility that PD and ET are pathogenically related.     

Abdominal non-Hodgkin''s lymphoma in childhood

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.