Tremor Duration Research Articles

Effects of Kangpa bolus on behaviors and dopamine concentration of striatum in Parkinson's disease model animals

Objective To investigate the effects of Kangpa bolus on behaviors, dopamine and its metabolites of striatum in animals with Parkinson' s disease (PD). Methods The mice models of muscle tremor and rigor were established to observe the antagonism of Kangpa bolus. Step-down and step-through tests were used to evaluate the effects of Kangpa bolus on learning and memory function in mice. The rat model of PD was established to observe the effects of Kangpa bolus on rotation behaviors. The contents of DA and homovanillic acid( HVA) in the injured side of striatum were detected by ELISA. Results Compared with model group(723. 1 ±79.3) s,the duration of tremor in mice shortened significantly (P < 0. 01) in Kangpa bolus high dose and middle dose group ((548.0±27.0)s,(590.9 ±28.7)s). Compared with model group(3194.5 ±251.7)s,the duration of rigor in mice shortened significantly(P<0.01) in Kangpa bolus all dose group((2300.1 ±352.5)s,(2478.2 ±276.6)s, (2559.3 ±207.6) s). In step-down test, compared with model group (3. 10 ±0.74), the number of errors decreased significantly(P<0.01) in Kangpa bolus high dose and middle dose group (1.60 ±0. 97,1. 80 ±0.63). In step-through test, compared with model group( 2.30 ± 0. 68), the number of errors decreased significantly (P < 0.01) in Kangpa bolus high dose and middle dose group(0.80 ±0.79,1.10 ±0.74). Compared with model group (340.6 ±18.8) , the number of rotations of PD rats in thirty minutes reduced significantly (P< 0.01) in Kangpa bolus high dose and middle dose group(286.5 ± 12.1,296.6 ± 12.7) after three weeks treatment. Compared with model group(9.43 ±1.79,0. 87 ±0.12) nmol/L,the contents of DA and HVA in the injured side of striatum increased significantly(P<0. 01 ) in Kangpa bolus high dose( 18. 9 ±4. 01,1. 50 ± 1. 39) nmol/L and middle dose group (17.3±3.01,1.39±0.53)nmol/L Conclusion Kangpa bolus has some therapeutic effects on the animals of PD. Key words: Parkinson disease; Kangpa bolus; Step-down test; Step-through test; Rotation test

Striations, duration, migration and tidal response in deep tremor

Deep tremor in subduction zones is thought to be caused by small repeating shear slip events on the plate interface with significant slow components. It occurs at a depth of about 30 kilometres and provides valuable information on deep plate motion and shallow stress accumulation on the fault plane of megathrust earthquakes. Tremor has been suggested to repeat at a regular interval, migrate at various velocities and be modulated by tidal stress. Here I show that some time-invariant interface property controls tremor behaviour, using precise location of tremor sources with event duration in western Shikoku in the Nankai subduction zone, Japan. In areas where tremor duration is short, tremor is more strongly affected by tidal stress and migration is inhibited. Where tremor lasts longer, diffusive migration occurs with a constant diffusivity of 10(4) m(2) s(-1). The control property may be the ratio of brittle to ductile areas, perhaps determined by the influence of mantle wedge serpentinization on the plate interface. The spatial variation of the controlling property seems to be characterized by striations in tremor source distribution, which follows either the current or previous plate subduction directions. This suggests that the striations and corresponding interface properties are formed through the subduction of inhomogeneous structure, such as seamounts, for periods as long as ten million years.

Mirror movements in patients with essential tremor

Mirror movements (MM), which occur in age-related neurodegenerative diseases such as Parkinson's disease (PD), have never been studied in essential tremor (ET). The objective of this work is to study the prevalence and clinical correlates of MM in ET cases and controls. In a clinical-epidemiological study in New York, participants performed repetitive motor tasks; MM (hands and feet) were rated. MM occurred in 35/107 (32.7%) ET cases versus 23/97 (23.7%) controls (OR 1.56, P = 0.16). Total MM score was 2x higher in cases (3.9 +/- 7.7 vs. 1.9 +/- 3.9, P = 0.02). MM (hands) occurred in 16 (15.0%) cases versus 5 (5.2%) controls (OR 3.24, P = 0.03) and total hand MM score was three to four times higher in ET cases (1.4 +/- 4.5 vs. 0.4 +/- 2.0, P = 0.03). MMs were not correlated with age, tremor duration, or severity and were most severe in cases with rest tremor. Thus, it was concluded that MM occurred in 1/3 of ET cases. These results further expand the spectrum of nontremor, motor phenomenology seen in ET. Whether, as in PD, MMs in ET represent a failure of subcortical structures to support the cortical network involved with the initiation of unilateral motor activity, requires future neurophysiological investigation.

Tremor patches in Cascadia revealed by seismic array analysis

Episodic tremor and slip (ETS) events in Cascadia have recently been observed, illuminating the general area that radiates seismic energy in the form of non‐volcanic tremor (NVT). However, the picture of the ETS zone remains fuzzy because of difficulties in tremor detection and location. To observe the intimate details of tremor, we deployed a dense 84‐element small‐aperture seismic array on the Olympic Peninsula, Washington, above the tremor migration path. It recorded the main ETS event in May 2008, as well as a weaker tremor episode two months earlier. Using a beamforming technique, we are able to capture and track tremor activity with an unprecedented resolution from southern Puget Sound to the Strait of Juan de Fuca. The array technique reveals up to four times more duration of tremor compared to the conventional envelope cross‐correlation method. Our findings suggest that NVT is not uniformly distributed on the subduction interface, and unveils several distinct patches that release much of the tremor moment. The patches appear to be devoid of ordinary earthquakes, and may indicate the heterogeneity in fault strength that affects the modes of stress release within the ETS zone.

Features of Central Neurotransmission in Animals in Conditions of Dietary Magnesium Deficiency and After Its Correction

Magnesium is important in the regulation of neurotransmitter metabolism and the modulation of receptor function in the CNS, including neurotransmitters and receptors involved in the pathogenesis of many mental disorders. The aim of the present work was to perform a pharmacological evaluation of the central mechanisms of action of magnesium salts in the clofelin, phenamine, arecoline, nicotine, apomorphine, and 5-hydroxytryptophan tests in conditions of dietary magnesium deficiency. After reaching the magnesium deficiency state, animals were given oral (via tube) magnesium L-asparaginate and magnesium chloride lone and in combination with vitamin B(6), as well as the reference agent Magne B6. Our assessments of phenamine stereotypy in magnesium-deficient animals showed reductions in the latent period by an average of 14.89% and a significant increase in the duration of phenamine stereotypy by an average of 19.44% (from 268.23 +/- 8.17 to 320.36 +/- 19.90 min) as compared with intact rats. Studies of hyperkinesia induced by 5-hydroxytryptophan showed a two-fold reduction in its extent in the magnesium-deficient group (p </= 0.05). Administration of arecoline to magnesium-deficient animals resulted in a statistically significant increase in the latent period from a mean of 92.75 +/- 19.35 to 245.17 +/- 121.86 sec, with a reduction in the duration of tremor from an average of 1175.58 +/- 127.87 to 703.83 +/- 89.33 sec (p </= 0.05) as compared with intact rats. In terms of its influence on the hypothermic effects of clofelin and apomorphine and the convulsive effect of nicotine, there were no significant differences between the intact group and the magnesium-deficiency animals. Administration of magnesium salts compensated for the magnesium deficiency in plasma and erythrocytes, which was accompanied by recovery of measures in the phenamine, arecoline, and 5-HT tests to levels typical of intact controls. There was a tendency for magnesium L-asparaginate and magnesium chloride combined with pyridoxine to have greater activity, and the efficacies of these treatments was no less than that of reference agent Magne B6. Thus, dietary magnesium deficiency led to impairment of neurotransmission in central serotoninergic, M-cholinergic, and noradrenergic structures and administration of magnesium salts reversed these changes.

Moment release rate of Cascadia tremor constrained by GPS

A comparison of GPS and seismic analyses of 23 distinct episodic tremor and slip events, located throughout the Cascadia subduction zone over an 11‐year period, yields a highly linear relationship between moment release, as estimated from GPS, and total duration of nonvolcanic tremor, as summed from regional seismic arrays. The events last 1–5 weeks, typically produce ∼5 mm of static forearc deformation, and show cumulative totals of tremor that range from 40 to 280 h. Moment released by each event is estimated by inverting GPS‐measured deformation, which is sensitive to all rates of tremor‐synchronous faulting, including aseismic creep, for total slip along the North American‐Juan de Fuca plate interface. Tremor, which is shown to be largely invariant in amplitude and frequency content both between events and with respect to its duration, is quantified using several different parameterizations that agree to within 10%. All known Cascadia events detected since 1997, which collectively span the Cascadia arc from northern California to Vancouver Island, Canada, release moment during tremor at a rate of 5.2 ± 0.4 × 1016 N m per hour of recorded tremor. This relationship enables estimation of moment dissipation, via seismic monitoring of tremor, along the deeper Cascadia subduction zone that poses the greatest threat to its major metropolitan centers.

Factor Analysis of Motor and Nonmotor Signs in Essential Tremor: Are These Signs All Part of the Same Underlying Pathogenic Process?

Essential tremor (ET) has traditionally been viewed as monosymptomatic. However, there is an emerging appreciation of an expanded number of motor manifestations as well as a new awareness of nonmotor manifestations. The current goal, through factor analyses, was to determine how these diverse signs relate to one another and shed light on their pathogenic bases. One hundred and thirty-eight ET patients had detailed neurological examinations. In these analyses, three separate factors emerged, explaining 58.7% of the variance. Factor I was comprised of the hallmark feature of ET, action tremor. It also included intention tremor, which is generally viewed as a sign of cerebellar dysfunction, and tremor duration. Factor II was comprised of cognitive test scores and age, and factor III, of rest tremor. Cognitive test scores did not fall into the same domain as motor features or tremor duration. These results suggest that: (1) the process that underlies cognitive dysfunction in ET is distinct from that which is responsible for action and intention tremors and their progression over time, and (2) cognitive dysfunction in ET is not likely due to cerebellar degeneration. Age loaded with cognitive test scores, further raising the possibility that age-related processes (e.g. Alzheimer-type changes) could underlie cognitive changes in ET.

Prevalence of unilateral tremor in autosomal dominant essential tremor

The presence of bilateral arm tremor is a key diagnostic feature of essential tremor (ET). We analyzed the presence of unilateral arm tremor in familial ET cohort of 133 autosomal dominant ET kindreds with 412 affected individuals. Inclusion criteria in patients with unilateral arm postural and/or kinetic tremor required the duration of tremor for at least 5 years, without hypokinetic-rigid syndrome, dystonic posturing, or history of sudden onset of tremor. Only subjects with at least one living first degree relative who met diagnostic criteria for definite ET were included. Eighteen subjects met the inclusion criteria and five had postural tremor only, while the majority (13/18) had a combination of postural and kinetic tremor. Our data shows that unilateral tremor associated with ET is relatively rare and can be identified in 4.4% patients in a cohort of familial ET.

Effect of Cabergoline on Parkinsonian Tremor Assessed by Long-Term Actigraphy

Background: Tremor is one of the cardinal symptoms in Parkinson’s disease, but only few clinical studies have focussed on its therapy as the primary endpoint. One reason is the substantial fluctuation of tremor severity over time, which is difficult to capture and may render momentary clinical assessments unreliable. Methods: We evaluated the usefulness of a novel wrist-worn actigraph allowing long-term recordings of tremor in a pilot study, in which we assessed the therapeutic effect of cabergoline on tremor in 10 patients with tremor-dominant Parkinson’s disease. Clinical data were obtained by using the Unified Parkinson’s Disease Rating Scale (UPDRS Part III, item 20) and simultaneously a patient’s tremor diary. Results: We found a significant reduction in UPDRS motor and tremor scores, in tremor duration and tremor amplitude by actigraphy and diaries. Furthermore, we found significant correlations between actigraphy measurements and patient ratings of tremor intensity and occurrence in diaries. Conclusion: Long-term actigraphy is a reliable method to assess tremor occurrence and severity and may be used to document antitremor effects in clinical studies.

Dopamine receptor D3 gene and essential tremor in large series of German, Danish and French patients

The genetic causes of essential tremor (ET) seem to be heterogeneous. Recently, ET has been found associated with a functional variant (Ser9Gly) of the dopamine D(3) receptor (DRD3), located in the ETM1 locus on chromosome 3q13.3 described for the first time in 1997. We examined this variant in three different populations from Germany, Denmark and France. We undertook an association study of the Ser9Gly variant in 202 cases with a familial history from unrelated families with ET, 97 cases with isolated non-familial ET and 528 healthy controls. In addition, linkage and segregation analyses were carried out in 22 ET families. The distribution of genotypes and allele frequencies showed no significant differences in the whole sample and in a subanalysis of familial and sporadic cases. Age at onset of tremor, tremor duration and tremor severity did not show an association with the genotype. In addition, the DRD3 variant was not found linked to the disease in a subset of informative ET families. We did not find a significant association of the DRD3 variant with ET nor linkage to the DRD3 receptor in German, Danish and French ET patients and families, suggesting that it is unlikely to be a causal factor for ET.

123I]FP‐CIT SPET imaging in drug‐induced Parkinsonism

We assessed the status of dopamine nerve terminals in patients treated with dopamine receptor blocking agents (DRBAs) who had developed drug-induced parkinsonism (DIP). We performed [(123)I]FP-CIT SPET in 32 consecutive patients who were on DRBAs for at least 6 months and developed extrapyramidal signs. The UPDRS-III was used to assess clinical severity. Twenty-six age- and sex-matched healthy subjects served as control group. Putamen [(123)I]FP-CIT SPET binding was reduced in 14 and normal in the remaining 18 patients. There was no difference between the two groups for age, duration of DRBAs treatment, UPDRS III, tremor, rigidity, and bradykinesia subscores for upper and lower limbs. Conversely, symmetry of parkinsonian signs and presence bucco-linguo-masticatory dyskinesias were more frequent in individuals with normal tracer binding. Imaging of the dopamine transporter may help to identify subjects with DIP secondary to a loss of dopamine nerve terminals.

Poster Abstract #4: Development of Long-Duration Accelerometry for Use in Clinical Trials of Essential Tremor

Background Essential tremor (ET) is a common movement disorder affecting 0.4% of the general population and 14% of people 65 years and older. Current therapies provide modest tremor suppression and are often accompanied by intolerable side effects. Key to the success of future studies is the development of objective biomarkers to assess tremor in a sensitive and unbiased manner. Numerous subjective and objective tremor measures are available, including laboratory-based accelerometry, electromyography, spirography, and surveys assessing quality of life or impact on activities of daily living. The utility of objective measures are limited by time and expense, and subjective measures lack sensitivity and rely heavily on standardization of ratings or patient responses. Furthermore, all these methods are temporally biased, in that they reflect only brief time intervals. We hypothesized that portable uniaxial monitoring devices could be used to reliably measure tremor over long durations in patients with ET. Methods The study population consisted of adults with ET who underwent an ethanol challenge to assess tremor response, prior to enrollment in a clinical trial at NIH. Wrist-based accelerometers were used (Cambridge Neurotechnology, Cambridge, UK) to record the intensity and duration of tremor and nontremor movements. We developed an algorithm to calculate a Tremor Severity Score (TSS) characterizing tremor patterns over extended time periods. To assess individual subject changes, we normalized the TSS at each timepoint by each subject's own baseline TSS. The primary outcome measures were TSS at baseline, 0–30, 30–60, and 60–90 minutes after ethanol challenge. Results Thirteen patients were included in the analysis. Mean percent reduction in tremors from baseline TSS was 165%, 408%, and 423% at 0–30, 30–60, and 60–90 minutes after ethanol challenge, respectively. A post hoc linear regression of the TSS total score and baseline TSS revealed high correlation ( R 2 = 0.77). Conclusions Our results show that the TSS, based on long-duration accelerometry data, provides a sensitive and reliable method for objectively measuring ET outcomes. This method could serve as a model for the development of low-cost, high-throughput clinical trials. Further work is needed to validate this method with tremor measures in current use.

Pathologic findings in prospectively ascertained essential tremor subjects

To assess pathologic changes in prospectively characterized subjects with essential tremor (ET). Subjects enrolled in the Sun Health Research Institute Brain and Body Donation Program were examined annually by a movement disorders neurologist, and semiannually by a behavioral neurologist and neuropsychologist. Twenty-four subjects without a prior diagnosis of dementia or other major movement disorder met clinical criteria for ET and came to autopsy. Subjects with mild cognitive impairment (n = 3) were included. These subjects were compared with 21 controls. Brains were examined postmortem according to standardized protocols for assessment of age-related changes and specific pathologic conditions (e.g., Parkinson disease, Alzheimer disease). Subjects had a mean age of 86.2 years and a mean duration of tremor of 11.1 years. Seven subjects had evidence for cerebellar pathology (Purkinje cell loss, cerebellar cortical sclerosis, and proliferation of Bergmann glia). Pigmented neurons were qualitatively depleted in the locus ceruleus in eight subjects and in the substantia nigra in five subjects. Of these, three had Lewy bodies, one subject had brainstem predominant disease, and two had limbic stage. Three subjects had a nonspecific cerebral tauopathy and another met pathologic criteria for progressive supranuclear palsy. However, when compared with controls, only changes in the locus ceruleus and gliosis of the cerebellum remained significant findings. This study supports previous findings of heterogenous pathology in essential tremor (ET). There is an increased frequency of cerebellar gliosis and locus ceruleus depletion. We did not find an increased incidence of Lewy bodies in subjects with ET.

Volcanic tremor during eruptions: Temporal characteristics, scaling and constraints on conduit size and processes

We investigated characteristics of eruption tremor observed for 24 eruptions at 18 volcanoes based on published reports. In particular, we computed reduced displacements ( D R) to normalize the data and examined tremor time histories. We observed: (a) maximum D R is approximately proportional to the square root of the cross sectional area of the vent, however, with lower than expected slope; (b) about one half of the cases show approximately exponential increases in D R at the beginnings of eruptions, on a scale of minutes to hours; (c) one half of the cases show a sustained maximum level of tremor; (d) more than 90% of the cases show approximately exponential decay at the ends of eruptions, also on a scale of minutes to hours; and (e) exponential increases, if they occur, are commonly associated with the first large stage of eruptions. We estimate the radii of the vents using several methods and reconcile the topographic estimates, which are systematically too large, with those obtained from D R itself and theoretical considerations. We compare scaling of tremor D R with that for explosions and find that explosions have large absolute pressures and scale with vent radius squared, whereas tremor consists of pressure fluctuations that have lower amplitudes than the absolute pressure of explosions, and the scaling is different. We explore several methods to determine the appropriate scaling. This characteristic helps us to distinguish the type of eruptions: explosive (Vulcanian or Strombolian) eruptions versus sustained or continuous ash (e.g. Plinian) eruptions. Average eruption discharge, estimated from the total volume of tephra and the total duration of eruption tremor, is well correlated with peak discharge calculated from cross sectional area of the vent and velocity of volcanic ejecta. These results suggest similar scaling between different eruption types and the overall usefulness of monitoring tremor for evaluating volcanic activity.

Quantitative assessment of neuromotor function in workers with current low exposure to mercury vapor

Evaluation of neuromotor function has been used in several epidemiological studies of workers with long-term exposure to mercury vapor (Hg 0). Some recent studies indicate adverse effects at relatively low exposure levels. In the present study, we used sensitive quantitative methods, developed specifically to detect subtle effects of exposure to toxins on motor function. After exclusion of individuals with neurological diseases or other conditions that may affect performance, 43 chloralkali workers with current low exposure to Hg 0, and 22 age-matched referents remained for further analysis. The median urinary mercury concentration in exposed workers was 5.9 μg/g (range 1.3–25) creatinine (μg/gC), while that in referents was 0.7 μg/gC (range 0.2–4.1). The mean exposure time was 15 years, and the median cumulative mercury index was 161 years × μg/gC in exposed workers. A eurythmokinesimeter (EKM) was used to quantify eye–hand coordination, and a diadochokinesimeter, to measure rapid alternating rotation of the forearms. In general, the differences in performance between the exposed workers and the referents were small. Age was associated with a decrease in speed, more tremor, and longer contact duration between the stylus and the metal targets in performance of rapid pointing movements. Smokers had significantly more tremor, and more contacts per event in the EKM test, than nonsmokers. Taking age, shift work, and smoking habits into account, no significant associations with current or cumulative mercury exposure were found for the majority of the outcome variables from the quantitative tests. In general, this study indicates no significant adverse effects of Hg 0 on neuromotor function at the exposure levels studied.

Quantitative Assessment of Neuromotor Function in Workers With Current Low Exposure to Mercury Vapor

Evaluation of neuromotor function has been used in several epidemiological studies of workers with long-term exposure to mercury vapor (Hg 0). Some recent studies indicate adverse effects at relatively low exposure levels. In the present study, we used sensitive quantitative methods, developed specifically to detect subtle effects of exposure to toxins on motor function. After exclusion of individuals with neurological diseases or other conditions that may affect performance, 43 chloralkali workers with current low exposure to Hg 0, and 22 age-matched referents remained for further analysis. The median urinary mercury concentration in exposed workers was 5.9 microg/g (range 1.3-25) creatinine (microg/gC), while that in referents was 0.7 microg/gC (range 0.2-4.1). The mean exposure time was 15 years, and the median cumulative mercury index was 161 years x microg/gC in exposed workers. A eurythmokinesimeter (EKM) was used to quantify eye-hand coordination, and a diadochokinesimeter, to measure rapid alternating rotation of the forearms. In general, the differences in performance between the exposed workers and the referents were small. Age was associated with a decrease in speed, more tremor, and longer contact duration between the stylus and the metal targets in performance of rapid pointing movements. Smokers had significantly more tremor, and more contacts per event in the EKM test, than nonsmokers. Taking age, shift work, and smoking habits into account, no significant associations with current or cumulative mercury exposure were found for the majority of the outcome variables from the quantitative tests. In general, this study indicates no significant adverse effects of Hg 0 on neuromotor function at the exposure levels studied.

Distinguishing psychogenic and essential tremor

In contrast to essential tremor (ET), psychogenic tremor (PT) is often manifested by shaking with variable amplitude and frequency, distractibility, suggestibility, and entrainment. The sensitivity and specificity of these findings in differentiating PT and ET have not been systematically examined. In order to determine clinical features that reliably distinguish PT from ET, we collected patient information regarding tremor onset, spontaneous remissions, family history, and employment history. A "blinded" rater evaluated video segments of subjects using a standardized protocol with special attention to distractibility, suggestibility, or entrainment. A total of 45 subjects with ET or PT were enrolled in this study: 33 met clinical criteria for ET with a mean age of 56.8+/-17.0 years and 12 met clinical criteria for PT with a mean age of 42.5+/-11.0 years. PT subjects were significantly more likely to relay a history of sudden onset (p=0.03), spontaneous remissions (p=0.03), and shorter duration of tremor (p=0.001). Family history of tremor was significantly more common in the ET group (p=0.001). A moderate-to-marked degree of distraction with alternate finger tapping (p=0.01) and mental concentration on serial 7 s (p=0.01) was more common in PT. Furthermore, suggestibility with a tuning fork (p=0.04) and exacerbation with hyperventilation (p=0.06) seemed predictive of PT. Entrainment was not different in the two groups. In conclusion, a history of tremor with sudden onset and spontaneous remissions along with distractibility and suggestibility on examination are good predictors of PT and help differentiate it from ET.

Effects of AIT-082, a Purine Derivative, on Tremor Induced by Arecoline or Oxotremorine in Mice

The effects of AIT-082, a hypoxanthine derivative, on tremor in mice were investigated. The mice received intragastric administration of AIT-082 for consecutive 60 days at doses of 150, 300 and 600 mg·kg^–1. The results showed that AIT-082 not only effectively inhibited the tremor induced by arecoline or oxotremorine, but also alleviated the tremor intensity and significantly shortened the tremor durations. The inhibition of tremor was perhaps associated with the central cholinergic nerve depressant effects as well as the stimulation of proliferation and differentiation of nerve cells.

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.

The range and nature of sleep dysfunction in untreated Parkinson's disease (PD). A comparative controlled clinical study using the Parkinson's disease sleep scale and selective polysomnography

In this study we have explored the nature and range of sleep dysfunction that occurs in untreated Parkinson's disease (PD) comparing data obtained from the use of the Parkinson's disease sleep scale (PDSS) in an untreated PD patient group compared to advanced PD and healthy controls. 25 untreated (drug-naive, DNPD) PD patients (mean age 66.9 years, range 53–80, 18 males) completed the validated Parkinson's disease sleep scale (PDSS), mean duration of PD was 2.1 years (1–10, up to 4 years in all except one patient with tremulous PD reporting tremor duration of 10 years) and mean Hoehn and Yahr score 1.9 (1–3). Data were compared to 34 advanced PD (mean age 70.2 years, range 51–88, 23 male), mean duration of PD 11 years (range 4–22), mean Hoehn and Yahr score 3.4 (3–5) and PDSS data obtained from 131 healthy controls (mean age 66.6 years, range 50–93, 56 males). Total PDSS scores and PDSS sub-items, except PDSS item 2, were highly significantly different ( p < 0.001) between DNPD, advanced PD and controls. Controls reported higher mean PDSS scores than both groups of patients, and advanced cases reported lower (mean ± S.D.) PDSS scores (86.95 ± 20.78) than drug-naive (105.72 ± 21.5) ( p < 0.001). Logistic regression analysis showed that items PDSS8 (nocturia), PDSS11 (cramps), PDSS12 (dystonia), PDSS13 (tremor), and PDSS15 (daytime somnolence) were significantly impaired in DNPD compared to controls while PDSS7 (nighttime hallucinations) additionally separated advanced PD from DNPD. In a subgroup of 11 advanced PD cases (mean age 62 years, range = 49–84 years, mean Hoehn and Yahr score 2.5, range = 1–3) with high Epworth Sleepiness Scale (ESS) scores (mean 14.5), low item 15 PDSS score (mean 4.7) and complaints of severe daytime sleepiness, underwent detailed overnight polysomnography (PSG) studies, all showing abnormal sleep patterns. We conclude that nocturia, nighttime cramps, dystonia, tremor and daytime somnolence seem to be the important nocturnal disabilities in DNPD and some of these symptoms may be reminiscent of “off” period related symptoms even though patients are untreated. Furthermore, polysomnography in “sleepy” PD patients may help diagnose unrecognised conditions such as periodic limb movement of sleep (PLMS), obstructive sleep apnoea (OSA) and REM Sleep Behaviour Disorder.