Cortical excitability in patients with essential tremor

We used transcranial magnetic stimulation in 10 patients with essential tremor and 8 matched healthy subjects. A round stimulating coil was placed over the vertex and electromyographic activity was recorded from the first dorsal interosseous muscle. Paired transcranial stimuli were delivered at interstimulus intervals of 3, 5, 20, 100, 150, and 200 ms. The intensity of the conditioning stimulus was 80% of motor threshold at short and 150% at long interstimulus intervals (ISIs). We also measured the silent period obtained after a single magnetic pulse delivered at 150% of motor threshold during a submaximal muscle contraction. Patients and controls had similar motor threshold and similar latencies. Paired magnetic stimuli given at short and long ISIs at rest, and during a voluntary muscle contraction, elicited similar responses in both groups. The silent period evoked by transcranial magnetic stimulation had a similar duration in patients with ET and controls. In conclusion, these findings suggest that patients with essential tremor have normal cortical motor area excitability.     

Medical treatment of essential tremor and Parkinson''s disease

Tremor is commonly the first neurologic sign of Parkinson's disease (PD) that leads patients to see a physician. Knowing how to differentiate the resting tremor of PD from essential tremor is an important diagnostic skill. Unlike patients with essential tremor, those with PD have other neurologic findings. A diagnosis of PD is likely if the patient has two of three major clinical features: resting tremor, bradykinesia, and rigidity. Minor signs may also be seen, including cognitive slowing, speech abnormalities, depression, dysautonomia, and sleep disturbances. The history and physical exam can determine if the patient has parkinsonism and whether the cause is Parkinson's disease.     

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.     

Unilateral thalamic deep brain stimulation for refractory essential tremor and Parkinson''s disease tremor

BACKGROUND: We hypothesized that endotoxin (LPS) would impair bradykinin (BK)-induced calcium (Ca2+) mobilization in aortic endothelial cells, perhaps due to cytotoxicity or via stimulation of nitric oxide (NO) synthesis. As well, we sought to define contributions of LPS-stimulated Ca2+ mobilization to these effects. METHODS: LPS- or BK-induced increments of intracellular Ca2+ were assessed by microspectrofluorimetry with fura-2 in passaged bovine aortic endothelial cells. Time- and dose-dependent effects of LPS exposure (+/- inhibitors of NO or prostaglandin synthesis) on subsequent BK-induced Ca2+ mobilization and on attached cell counts were determined. RESULTS: LPS (0.1 to 1.0 mg/ml) led to rapid increments of Ca2+, while Ca2+ responses were delayed following LPS (1 to 10 microg/ml) and lower doses were without effect. By contrast, LPS more potently (1.0 pg to 1.0 microg/ml) led to dose- and time-dependent impairment of subsequent BK-induced Ca2+ mobilization, with peak effect at four to six hours, persisting for at least 18 hours. This delayed effect on BK-response was unaltered by inhibition of either NO synthase or cyclooxygenase. The effect of LPS on BK-responsivity depended importantly on cell confluence, as it was not observed in subconfluent cells. By contrast, LPS-induced cell detachment, which was observed only at doses > or = 1.0 microg/ml, did not depend on confluence. CONCLUSIONS: Different mechanisms lead to endothelial cytotoxicity and to impaired BK-response following LPS. Only the former effect, occurring at higher doses, might depend on initial LPS-induced Ca2+ mobilization.     

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.     

A randomized study of the efficacy of the PROPATH Program for patients with Parkinson disease

By polymerase chain reaction (PCR) using a pair of primers specific for Salmonella phoE gene a 365-bp specific gene fragment could be amplified from yolk of infertile eggs and dead-in-shell chicken embryos, and from environmental samples. Out of 45 dead-in-shell embryo samples, 20 (44.4%) were found positive for Salmonella DNA by PCR compared to 11 (24.4%) by bacteria isolation. Salmonella DNA could also be detected from infertile eggs, chicken faeces, floor litter and chick fluff, which incidence was higher than that by bacteria isolation.     

Resetting of tremor by mechanical perturbations: a comparison of essential tremor and parkinsonian tremor

With the use of a computer-controlled torque motor, experiments were carried out on 11 patients with essential tremor and 13 with parkinsonian tremor to determine the effect of mechanical displacements at the wrist joint on the established pattern of tremor. Analysis of the timing of tremor bursts in electromyographic recordings before and following the stimuli revealed that the phase of essential tremor could be readily reset by external perturbations. In the majority of the parkinsonian patients the same type of stimuli had very little effect on the pattern of tremor. Differences between predicted and actual times of occurrence of tremor bursts following the stimuli were used to calculate a normalized resetting index, with 0 representing no resetting and 1, complete resetting. For the patients with essential tremor the mean resetting index was 0.64 +/- 0.14 (SD); for the parkinsonian patients the generation of essential tremor. Reflex mechanisms are less important in parkinsonian tremor, which is more likely dependent on oscillations originating in the central nervous system.     

Botulinum toxin restores presynaptic inhibition of group Ia afferents in patients with essential tremor

We studied the effect of botulinum toxin A injection on the abnormal presynaptic phase of reciprocal inhibition between forearm antagonist muscles in patients with essential tremor. Ten patients with essential tremor were investigated before and 1 month after botulinum injection. Reciprocal inhibition was studied by conditioning the H reflex in forearm flexors with a radial-nerve stimulus delivered at a range of time intervals. Botulinum toxin produced a significant functional improvement in tremor (about 20%). Before botulinum toxin injection, patients had a reduced presynaptic phase of reciprocal inhibition. After botulinum toxin this phase was significantly more pronounced. The normal early disynaptic phase of reciprocal inhibition was normal before and after botulinum treatment. Although botulinum treatment reduced the size of the H reflex and the M wave to a similar extent, it left the H/M ratio unchanged. These findings show that botulinum toxin treatment restores presynaptic inhibition between forearm antagonist muscles. The results are also consistent with botulinum toxin having a beneficial effect in patients with essential tremor. Both effects probably depend upon the toxin's concurrent action on the extrafusal and intrafusal motor end-plates, the latter resulting in decreased spindle afferent input to the spinal cord.     

Accuracy of the clinical diagnoses of Lewy body disease, Parkinson disease, and dementia with Lewy bodies: a clinicopathologic study

BACKGROUND: Whether Parkinson disease (PD) and dementia with Lewy bodies (DLB) represent 2 distinct nosologic entities or are diverse phenotypes of Lewy body disease is subject to debate. OBJECTIVES: To determine the accuracy of the diagnoses of Lewy body disease, PD, and DLB by validating the clinical diagnoses of 6 neurologists with the neuropathologic findings and to identify early predictors of the diagnoses. METHODS: Six raters who were unaware of the neuropathologic diagnoses analyzed 105 clinical vignettes corresponding to 29 cases of Lewy body disease (post hoc analysis of 15 patients with PD and 14 with DLB) and 76 patients without PD or DLB whose cases were confirmed through autopsy findings. MAIN OUTCOME MEASURES: Sensitivity and positive predictive value (PPV) were chosen as validity measures and the K statistic as a reliability measure. RESULTS: Interrater reliability for the diagnoses of Lewy body disease and PD was moderate for the first visit and substantial for the last, whereas agreement for diagnosis of DLB was fair for the first visit and slight for the last. Median sensitivity for diagnosis of Lewy body disease was 56.9% for the first visit and 67.2% for the last; median PPV was 60.0% and 77.4%, respectively. Median sensitivity for the diagnosis of PD was 73.3% for the first visit and 80.0% for the last; median PPV was 45.9% and 64.1%, respectively. Median sensitivity for the diagnosis of DLB was 17.8% for the first visit and 28.6% for the last; median PPV was 75.0% for the first visit and 55.8% for the last. The raters' results were similar to those of the primary neurologists. Several features differentiated PD from DLB, predicted each disorder, and could be used as clinical pointers. CONCLUSIONS: The low PPV with relatively high sensitivity for the diagnosis of PD suggests overdiagnosis. Conversely, the extremely low sensitivity for the diagnosis of DLB suggests underdiagnosis. Although the case mix included in the study may not reflect the frequency of these disorders in practice, limiting the clinical applicability of the validity measures, the raters' results were similar to those of the primary neurologists who were not exposed to such limitations. Overall, our study confirms features suggested to predict these disorders, except for the early presence of postural imbalance, which is not indicative of either disorder.     

How familial is familial tremor? The genetic epidemiology of essential tremor

BACKGROUND & AIMS: Dilated intercellular spaces are a sign of epithelial damage in acid-perfused rabbit esophagus, a change best identified by transmission electron microscopy. The aim of this study was to determine if this change is also a feature of acid damage to human esophageal epithelium. METHODS: Endoscopic esophageal biopsy specimens from patients with (n = 11) and without (n = 13) recurrent heartburn were examined using transmission electron microscopy. Of 11 patients with heartburn, 6 had erosive esophagitis and 5 had normal-appearing mucosa on endoscopy; 13 controls had no symptoms or signs of esophageal disease. Using a computer, intercellular space diameter was measured from transmission electron microscopy photomicrographs of the specimen from each patient. RESULTS: Intercellular space diameter was significantly greater in specimens from patients with heartburn than those from controls; this was true irrespective of whether the patient had erosive or nonerosive disease. Space diameters of > or = 2.4 microns were present in 8 of 11 patients with heartburn and in no controls. CONCLUSIONS: Dilated intercellular spaces are a feature of reflux damage to human esophageal epithelium. As a morphological marker of increased paracellular permeability, its presence in patients without endoscopic abnormalities may help explain their development of heartburn.     

Parkinson disease in twins: an etiologic study

CONTEXT: The cause of Parkinson disease (PD) is unknown. Genetic linkages have been identified in families with PD, but whether most PD is inherited has not been determined. OBJECTIVE: To assess genetic inheritance of PD by studying monozygotic (MZ) and dizygotic (DZ) twin pairs. DESIGN: Twin study comparing concordance rates of PD in MZ and DZ twin pairs. SETTING AND PARTICIPANTS: A total of 19842 white male twins enrolled in the National Academy of Sciences/National Research Council World War II Veteran Twins Registry were screened for PD and standard diagnostic criteria for PD were applied. Zygosity was determined by polymerase chain reaction or questionnaire. MAIN OUTCOME MEASURE: Parkinson disease concordance in twin pairs, stratified by zygosity and age at diagnosis. RESULTS: Of 268 twins with suspected parkinsonism and 250 presumed unaffected twin brothers, 193 twins with PD were identified (concordance-adjusted prevalence, 8.67/1000). In 71 MZ and 90 DZ pairs with complete diagnoses, pairwise concordance was similar (0.129 overall, 0.155 MZ, 0.111 DZ; relative risk, 1.39; 95% confidence interval, 0.63-3.1). In 16 pairs with diagnosis at or before age 50 years in at least 1 twin, MZ concordance was 1.0 (4 pairs), and DZ was 0.167 (relative risk, 6.0; 95% confidence interval, 1.69-21.26). CONCLUSIONS: The similarity in concordance overall indicates that genetic factors do not play a major role in causing typical PD. No genetic component is evident when the disease begins after age 50 years. However, genetic factors appear to be important when disease begins at or before age 50 years.     

Visual hallucinations associated with Parkinson disease

Lysophosphatidic acid (LPA, 1-acyl-sn-glycerol 3-phosphate), at a concentration of 1-40 microM, was found to induce the formation of [3H]inositol-labelled phosphatidylinositol-4-phosphate (PIP) without significantly altering the levels of either phosphatidylinositol (PI) or phosphatidylinositol bisphosphate (PIP2) in washed human platelets. Preincubation of platelets with the cyclooxygenase/lipoxygenase inhibitor, BW755C at 100 microM, did not alter the LPA-induced formation of PIP. Activation of platelets with the phorbol ester, phorbol 12-myristate 13-acetate (PMA), elicited a similar response (induction of PIP formation). The specific protein kinase C (PKC) inhibitor, GF109203X (10 microM), completely blocked the effect of PMA but not the LPA-induced generation of PIP. The present results indicate that LPA can induce PIP formation via PI-4-kinase activation, through processes which are independent of the eicosanoid/TxA2 pathway and are not PKC-dependent.     

Modulation of postural tremors at the wrist by supramaximal electrical median nerve shocks in essential tremor, Parkinson's disease and normal subjects mimicking tremor

The response of postural wrist tremors to supramaximal median nerve stimulation was examined in patients with hereditary essential tremor (n = 10) and Parkinson's disease (n = 9), and in normal subjects mimicking wrist tremor (n = 8). The average frequency of on-going tremor was the same in all three groups. Supramaximal peripheral nerve shocks inhibited and then synchronised the rhythmic electromyographic (EMG) activity of all types of tremor. The duration of inhibition ranged from 90 to 210ms, varying inversely with the frequency of on-going tremor. There was no significant difference in mean duration of inhibition or in the timing of the first peak after stimulation on the average rectified EMG records between the three groups. The degree to which supramaximal peripheral nerve shocks could modulate the timing of rhythmic EMG bursts in the forearm flexor muscles was also quantified by deriving a resetting index. No significant difference in mean resetting index of the three groups was found. These results suggest that such studies cannot be used to differentiate between the common causes of postural wrist tremors.     

The effect of ethanol on alcohol-responsive essential tremor: a positron emission tomography study

We used H2 15O positron emission tomography (PET) to investigate the effect of ethyl alcohol on regional cerebral blood flow in 6 patients with alcohol-responsive essential tremor and 6 age-matched control subjects. The patients were scanned while at rest and during involuntary postural tremor of the extended right arm. Normal control subjects were scanned at rest and during passive wrist oscillation of the right arm at tremor frequency. Regional cerebral blood flow associated with these conditions was measured before and after oral administration of 2 to 3 units of alcohol. The mean blood alcohol level was 35.3 +/- 20.0 mg/dl in the patient group and caused marked suppression of tremor; it was 33.9 +/- 12.9 mg/dl in the control group. Similar to previous PET studies on essential tremor patients, tremor compared with rest was associated with bilateral cerebellar activation including the cerebellar vermis. This pattern of activation differed from passive wrist oscillation where ipsilateral cerebellar activation was observed. Ethanol ingestion led to bilateral decreases of cerebellar blood flow in both tremor patients and normal subjects, and this was associated with suppression of tremor in the patients. Alcohol-associated increases of regional cerebral blood flow were observed in the inferior olivary nuclei in the patients but not in the control subjects. We conclude that alcohol-induced suppression of essential tremor is mediated via a reduction of cerebellar synaptic overactivity resulting in increased afferent input to the inferior olivary nuclei.     

Episodic memory and metamemory in Parkinson’s disease patients.

This study investigated episodic memory and metamemory for verbs and nouns in patients who have cognitive impairments associated with Parkinson’s disease (PD). PD patients and healthy control participants were asked to recall word pairs and provide feeling-of-knowing (FOK) judgments for the items they were unable to recall. This was followed by a 4-alternative recognition test. PD patients were impaired in both recall and recognition, compared with controls. In terms of metamemory, PD patients were less confident in their ability to recognize the unrecalled items in a future recognition test. Most important, accuracy of PD patients’ FOK judgments was not above chance and was lower than that of control participants. The PD group correctly recognized fewer verbs than nouns, but type of material (verb vs. noun) had no impact on recall or FOK judgments. In addition, contribution of executive functions to FOK accuracy was different in PD patients and controls. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Long-term results of continuous subcutaneous apomorphine pump therapy in patients with advanced Parkinson disease

Laser microprobe mass analysis (LAMMA) was used to study the composition of the brick-red crystalline material which had accumulated in the spleen of mice that had received the anti-leprosy drug Clofazimine in their diet for several months. The crystalline deposits light-microscopically resembled pure Clofazimine crystals. The presence of the drug in the crystals was indicated by LAMMA by the appearance of the chloride mass peaks in the negative mass spectra. More specific information was obtained from the positive mass spectra. A mass signal for the protonated molecule was present.     

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.