Fluctuations in tremor at rest and eye movements during ocular fixation in subjects with Parkinson's disease

This exploratory study investigates possible relationships between fluctuations in tremor at rest (TR) and fluctuations in eye movement amplitude during ocular fixation. TR of the hand and eye movements were analyzed in five subjects with Parkinson's disease (PD) and five age-matched controls. TR was recorded using a position laser system and eye movements were recorded using an infrared reflectometry technique (Ober2). TR amplitudes were significantly larger in the group of subjects with PD than in the control group (p/=0.05). Changes in TR amplitude were not systematically correlated with modifications of eye movement amplitude in either group. However, occasional but distinct monocular oscillations were found in subjects with PD. Coherence values between frequencies of TR from the tested hand (3.5-7Hz) and frequencies of oscillatory eye movements (within the same frequency band) were clearly higher for the eye ipsilateral to the side of the body most affected by the disease in three subjects with PD. It is believed that these monocular oscillations may be a consequence of PD. Results from two previously published exploratory studies are integrated with the present results and new avenues of research are proposed.     

Diurnal motor variations to repeated doses of levodopa in Parkinson's disease

Patients with Parkinson's disease (PD) in long-term levodopa therapy often complain of worsening of motor symptoms in the afternoon and evening. The pathophysiology of this phenomenon is not known. We evaluated the motor response to repeated doses of levodopa during a 12-hour period in 52 parkinsonian patients (19 de novo, 20 stable, and 13 wearing-off). On the day of the study, all patients received standard doses of levodopa/carbidopa at 8:00 a.m., 12:00 noon, and 4:00 p.m. Motor measurements such as tapping test, walking time, and tremor score, and blood samples for levodopa and 3-O-methyldopa (3OMD) plasma analysis, were performed hourly. Mean motor scores and pharmacokinetic data, evaluated for a period of 3 hours after each levodopa dose, were compared. In de novo patients, we did not observe diurnal changes in motor score, whereas a progressive daytime worsening was visible in stable and wearing-off patients. No significant difference in levodopa pharmacokinetics after each levodopa dose was observed within each patient group, whereas 3OMD plasma levels significant increased with repeated levodopa administrations. However, no significant correlation between motor scores and 3OMD plasma levels was observed, suggesting that the diminishing motor response to afternoon and evening doses of levodopa in patients in long-term levodopa therapy does not relate to the pharmacokinetics of the drug. It is possible that this phenomenon may be an expression of the occurrence of tolerance to repeated doses of levodopa.     

Eyelid movements during blinking in patients with Parkinson's disease.

We examined eyelid movements during spontaneous, voluntary, and trigeminal reflex blinks in 16 patients with mild to moderate Parkinson's disease (PD) off medication and 14 controls. Voluntary and reflex blink amplitudes tended to be smaller than normal for PD patients, whereas eyelid kinematics (amplitude-maximum velocity relationship) for all three blink types were normal. Spontaneous blink rate was less than normal for 10 patients and abnormally high for 6 patients. A significant positive correlation between spontaneous blink amplitude and blink rate was found. These observations suggest that PD modifies the gain of a premotor blink circuit shared by spontaneous, voluntary, and reflex blinks.     

Kinetic tremor during tracking movements in patients with Parkinson's disease

This study was undertaken to analyse kinetic tremor during a compensatory tracking task performed with the index fingers. Patients with Parkinson's disease (PD) (n=21) and control subjects (n=30) were tested using a laser system transducing displacement. All participants underwent a clinical examination. Nine characteristics quantifying the tracking task and tremor were applied to the processed displacement or velocity signal. The discriminating power of each characteristic was evaluated using differences between group means (p values), maximum percentage discrimination, and number of outliers in the patient group. All nine characteristics showed significant differences between means of the two groups using Welch-modified t-tests for unequal variances. The most discriminating characteristics reflected differences in the frequency distribution of the movement (proportional power in the 3-4Hz range, harmonicity and median frequency). These differences were rarely visible and did not correlate highly with tremor amplitude or with clinical ratings of tremor. Control subjects had residual spectral power from the tracking oscillations leaking above 3Hz, while most patients had a small 'kinetic tremor' in the 7-12Hz range. The maximum discrimination was moderate, 63% in the best case. Combining representative information about proportional power during posture (recorded in the same subjects) and tracking gave a much higher discrimination (90%) with respect to the 96.7th percentile of the control group. These results suggest that information coming from postural and kinetic tremors can be combined to isolate a subclinical feature of PD symptomatology. This feature could be used to re-evaluate the classic distinction made between the akineto-rigid and tremulous forms of PD and is independent of tremor amplitude.     

Blood pressure changes associated with periodic leg movements during sleep in healthy subjects

Background and objectivesPeriodic leg movements during sleep (PLMS) are associated with important blood pressure (BP) increases in restless legs syndrome (RLS) patients. These movements also are highly prevalent in the healthy elderly population. The aims of our study were to evaluate if heart rate (HR) and BP changes associated with PLMS are present in healthy subjects with no report of health concerns and to compare the amplitude of cardiovascular changes in healthy subjects to that of RLS subjects.MethodsFourteen healthy subjects (six men, eight women; 46.6 ± 9.7 y) and 14 RLS subjects (six men, eight women; 47.6 ± 11.8 y) matched for age and gender participated in our study. Beat-to-beat noninvasive BP was continuously recorded during one night of polysomnography. HR, systolic BP (SBP) and diastolic BP (DBP) were measured for 10 beats before and 15 beats after onset of PLMS with and without microarousals (MA).ResultsPLMS were associated with sudden and significant increases of HR, SBP and DBP in both groups; however, cardiovascular increases were more pronounced in RLS subjects than in healthy subjects.ConclusionsBecause PLMS index increases with age in healthy subjects and aging is associated with higher cardiovascular risk, further studies should investigate the impact of PLMS-related BP changes on the development of cardiovascular diseases in healthy elderly populations.     

Mirror movements in patients with Parkinson's disease

Mirror movements (MM) refer to ipsilateral involuntary movements that appear during voluntary activity in contralateral homologous body regions. This study aimed to compare the frequency and distribution of MM in an unselected sample of 274 patients with Parkinson's disease (PD) and 100 healthy subjects, and to check a possible relationship between MM and parkinsonian features. MM of the hand were scored according to the Woods and Teuber scale. The frequency of MM was lower in PD patients than in healthy subjects (29% vs. 71%, P < 0.0001). The distribution of MM also differed in the two groups being often bilateral in healthy subjects, invariably unilateral in PD patients. When parkinsonian signs were unilateral, MM always manifested on the unaffected side; when parkinsonian signs were bilateral, MM manifested on the less affected side. PD patients manifesting MM scored significantly lower on Hohen and Yahr staging than patients without MM. Likewise, there was a significant inverse correlation between the intensity of MM as rated by the Woods and Teuber score and HY staging (r = ?0.16, P < 0.01). The low frequency of MM in PD probably relates to the complex interactions between the pathophysiological mechanisms leading to parkinsonian signs and the mechanisms responsible for movement lateralization. © 2007 Movement Disorder Society     

Effect of medication and STN-DBS on postural control in subjects with Parkinson's disease

Aims and objectivesTo assess the effect of disease severity, dopaminergic medication (med) and STN-DBS on postural stability in Parkinson’s disease (PD).MethodsPostural sway in quiet stance, and the Unified Parkinson’s Disease Rating Scale (motor) (UPDRS III) were evaluated in 129 subjects in the off-med state. A subgroup of 28 subjects was studied on-med and after STN-DBS. Postural sway was measured using center of pressure (CoP) root mean square displacement (RMS_CoP) and mean velocity (V_CoP) in the anterior-posterior (AP) and medial-lateral (ML) directions.ResultsAll CoP parameters were larger in moderate/advanced subjects vs controls (P < 0.001) and early subjects. Only RMS_CoPML was larger in early subjects vs controls (P < 0.05). Med, DBS and DBS + med decreased UPDRS III compared to off-med (P < 0.001). RMS_CoPML and V_CoPML were larger on-med vs off-med and vs DBS (P < 0.001). Compared to controls and PD subjects with normal CoP sway off-med, med increased all CoP parameters (P < 0.01) but DBS returned V_CoPML to normal values. For ‘abnormal’ PD subjects, STN-DBS improved the excessive V_CoP in ML compared to off and on-med pre-DBS (P < 0.05).ConclusionsPostural sway in quiet stance increased with disease severity. Only ML CoP displacement was abnormal in early stage PD, and this may be a compensatory mechanism. Medication increased ML postural sway. In ‘normal’ PD subjects, STN-DBS reversed medication induced postural instability. Subjects with abnormal balance in quiet stance did not benefit from medication or DBS, except for improvement in ML CoP velocity from DBS. This may serve to reduce postural instability and falling.     

Body movements during night sleep in healthy elderly subjects and their relationships with sleep stages

In order to enlighten the profile of body movements during sleep at old age, the night sleep of twelve elderly subjects was polygraphically investigated; seven young healthy subjects were the control group. Significantly less body movements during sleep were found in the elderly compared to young subjects, meaning that the decrease in the number of body movements observed from infancy to childhood up to adulthood also continues at later ages. Differently from young adult, whose sleep body movements mainly occur in stage REM, no specific sleep state and/or stage was preferentially associated with the occurrence of body movements in the elderly. These data may point to an age-related modification in the interaction between motor cortex control and subcortical circuits. Furthermore, when body movements occur in elderly individuals, they are significantly more often followed in the next 60 s by a sleep stage change or by a spontaneous behavioural awakening. This might reflect a peculiar inability of elderly subjects to sustain stable states, and could also suggest that body movements may act as a co-factor in a process, comprising other physiological changes, leading to state shifts.     

Effects of increased stroke number on sequential arm movements in Parkinson's disease subjects

To examine whether multiple-component movements performed by Parkinson's disease (PD) patients are impaired differentially depending on the number of strokes, 10 PD patients and 10 age-matched control subjects performed sequential arm movements with one, two or three strokes on a digitizer. The patients were slower than the controls in executing the movement sequences and showed prolonged delays between strokes. These slowing characteristics were accentuated as stroke number increased from two to three. These results suggest that PD patients have a reduced capacity to process information rapidly, thereby limiting their ability to perform complex movements.     

Depressive symptoms in Parkinson's disease: a comparison with disabled control subjects

A high incidence of depressive symptoms has been observed in patients with Parkinson's disease (PD). PD involves a loss of central monoamines, and a decrease of monoamines has been implicated in depression; therefore, it is possible that depressive symptoms in PD result from the loss of endogenous neurotransmitters. However, it is equally possible that depressive symptoms represent a reaction to the chronic disabling course of PD. By comparing depressive symptoms in PD patients to those in matched patients with other chronic disabling diseases not involving a loss of central monoamines, it may be possible to decide between these alternatives. Thus, depressive symptoms were assessed in 45 patients with PD and 24 disabled controls that did not differ from the PD subjects on a measure of functional disability. Results showed that PD subjects obtained significantly higher total scores on the Beck Depression Inventory (BDI) than controls. PD subjects scored significantly higher than controls on BDI items grouped to reflect cognitive-affective and somatic depressive symptoms. The BDI scores of PD subjects were not reliably related to age, sex, duration of PD, or clinical ratings of PD symptom severity or functional disability. Self-rated disability and the number of recent medical problems were the greatest predictors of depressive symptoms. These findings supported the hypothesis that depressive symptoms in PD may not represent solely a reaction to disability.     

Platelet alpha- and gamma-synucleins in Parkinson's disease and normal control subjects

Alpha-synuclein (alphaSN) has been implicated in Parkinson's Disease (PD) and alphaSN is a major component of Lewy bodies (LBs). This study explored platelets as a model system for study of alphaSN metabolism and platelet alphaSN as a diagnostic marker for PD. We used Western blot analysis to characterize and compare platelet and brain alpha-, beta- and gammaSN; and to quantitate alphaSN levels in platelets from PD and age-matched controls. We found that platelets contain full-length alphaSN and 6 and 12 kDa fragments, and gammaSN-like protein. alphaSN and gammaSN were not secreted by thrombin-activated platelets. Furthermore, we also found that the alphaSN and gammaSN levels in sporadic PD patients and age-matched normal controls were not significantly different. This indicates that platelet alphaSN or gammaSN is not a suitable peripheral diagnostic marker for PD. Platelets may be used for study of alphaSN and gammaSN metabolism, and may give some broad insight into the normal functions of alphaSN and gammaSN.     

Calpastatin immunoreactivity in the monkey and human brain of control subjects and patients with Parkinson's disease

Parkinson's disease is characterized by a selective loss of dopaminergic neurons in the nigrostriatal pathway. However, not all dopaminergic neurons degenerate in this disease, and calcium has been suspected of playing a role in this differential vulnerability. An overexpression of the calcium-dependent protease calpain II has recently been reported in the parkinsonian substantia nigra, suggesting that a rise in intracellular calcium concentrations may be involved in the mechanism leading to cell death. The proteasic activity of calpain is regulated by an endogenous inhibitory protein called calpastatin. Because little is known about the distribution of calpastatin in the primate brain, we first analyzed immunohistochemically the calpastatin expression in normal human and monkey brain. A ubiquitous distribution of calpastatin immunostaining was observed in both cases, but its expression was variable from one region to another. In the basal ganglia, staining was intense in the striatum, in the pallidal complex, and in some nuclei of the thalamus. The cerebellum was stained intensely, particularly in the granular and Purkinje cell layers. A dense, heterogeneous staining was observed in the hippocampal formation, mostly in the pyramidal and granular layers. The distribution of staining was similar in the different cerebral cortices studied, and it was most intense in layer V. In the brainstem, staining was particularly prominent in the substantia nigra pars reticulata and compacta, the central gray substance, the superior colliculus, and the cuneiform nucleus, and staining was moderate in the tegmenti pedonculopontinus nucleus and the griseum pontis. In the second part of the study, the authors compared calpastatin expression in the mesencephalon between patients with Parkinson's disease and control subjects. Sequential double staining revealed that some dopaminergic neurons coexpress calpastatin, the proportion of double-stained neurons ranging between 52% and 76% among the different dopaminergic cell groups. Quantitative analysis of the number of calpastatin-stained neurons evidenced a loss of both calpastatin-positive and calpastatin-negative neurons in the substantia nigra of patients with Parkinson's disease. These data suggest that calpain II overexpression in Parkinson's disease is not compensated for by a concomitant increase in calpastatin expression.     

Levodopa-induced modulation of subthalamic beta oscillations during self-paced movements in patients with Parkinson's disease

Excessive synchronization of neural activity in the beta frequency band ( approximately 20 Hz) within basal ganglia circuits might contribute to the paucity and slowness of movement in Parkinson's disease (PD). Treatment with dopaminergic drugs reduces the background level of beta frequency band synchronization in the subthalamic nucleus (STN), but has not been shown to increase the proportion of beta activity that is suppressed before voluntary movement in PD. We assessed changes in the event-related desynchronization (ERD) in the beta frequency band of local field potential signals from the region of the STN in 14 patients with PD as they performed self-paced movements of a joystick before and after levodopa administration. The dopamine precursor, levodopa, increased the duration and magnitude of the premovement beta ERD, but did not alter postmovement synchronization in the beta band. Both the latency and magnitude of the beta ERD inversely correlated with the degree of motor impairment. These findings suggest that the beta ERD recorded in the STN area reflects motor-preparative processes that are at least partly dependent on dopaminergic activity within the basal ganglia.     

Influence of thoracoabdominal movement on pulmonary function in patients with Parkinson's disease: comparison with healthy subjects

Patients with Parkinson's disease (PD) may develop pulmonary dysfunction, but the pathogenesis remains unclear. We investigated a correlation between thoracoabdominal movements and pulmonary function in seven patients with PD and 14 healthy controls. We measured vital capacity (VC) and forced vital capacity (FVC) using an autospirometer, and measured chest and abdominal movements using a respiratory inductance plethysmography by fixing transducers on the rib cage and umbilicus. Patients with PD had significantly decreased % VC (90.3 +/- 17.1 vs 105.8 +/- 13.9%), chest movement (271.3 +/- 79.6 vs. 375.2 +/- 126.7% VT) and abdominal movement (217.6 +/- 93.5 vs. 247.4 +/- 100.2% VT) with 100% VT being an average volume of chest and abdomen at rest during measurement of VC. Patients with PD also had significantly decreased % FVC (74.4 +/- 20.6 vs. 97.6 +/- 14.1%), chest movement (246.2 +/- 115.2 vs. 344.5 +/- 126.4% VT) and abdominal movement (160.3 +/- 105.6 vs 207.6 +/- 104.7% VT) with 100% VT being an average volume of chest and abdomen at rest during forced maximal inspiration. Based on the results, we conclude that a reduction of % VC in patients with PD correlated with chest movements, while a reduction of % FVC correlated with abdominal movement in patients with PD.     

Inhibitory control during smooth pursuit in Parkinson's disease and Huntington's disease

The basal ganglia are involved in the preferential selection and suppression of competing responses. Parkinson's disease and Huntington's disease are 2 prototypical basal ganglia disorders that feature impaired inhibitory control, a function of poor conflict resolution. Previous saccadic studies showed that individuals with Parkinson's disease experience difficulty suppressing unwanted ocular motor responses, whereas evidence for a similar difficulty in Huntington's disease is more equivocal. Relative to saccades, few research studies have examined inhibitory control processes in the context of an ongoing smooth pursuit task. In this study, we examined the ability of 16 patients with Parkinson's disease and 12 patients with Huntington's disease to suppress automatic responses to irrelevant distracters that transiently appeared during the tracking of a moving visual stimulus. Compared with an equivalent number of age‐matched controls, patients with Parkinson's disease generated proportionately more saccades to distracter stimuli. This was particularly evident for distracters appearing far away from the target. Conversely, whereas individuals with early‐stage Huntington's disease and healthy controls made a comparable number of errors toward distracter stimuli, those in a more advanced clinical stage demonstrated significantly poorer inhibitory control. The current findings in parkinsonian patients replicate those previously reported in the saccadic and manual response literature, demonstrating difficulty inhibiting a competing motor response. However, in Huntington's disease we demonstrate for the first time that inhibitory control declines in more advanced‐disease stages. This suggests that ocular motility may provide a sensitive marker of clinical disease progression in Huntington's disease. © 2011 Movement Disorder Society     

Direction-specific postural instability in subjects with Parkinson's disease

The purpose of this study was to determine whether and why subjects with Parkinson's disease (PD) have greater instability in response to specific directions of perturbations than do age-matched control subjects and how instability is affected by stance width. This study compared postural responses to 8 directions of surface translations in PD subjects and age-matched control subjects while standing in a narrow and wide stance. PD subjects were tested in their practical OFF state. A postural stability margin was quantified as the difference between peak center of pressure (CoP) and peak center of mass (CoM) displacement in response to surface translations. The control subjects maintained a consistent stability margin across directions of translations and for both narrow and wide stance by modifying rate of rise of CoP responses. PD subjects had smaller than normal postural stability margins in all directions, but, especially for backwards sway in both stance widths and for lateral sway in narrow stance width. The reduced stability margin in PD subjects was due to a slower rise and smaller peak of CoP in the PD subjects than in control subjects. Lateral postural stability was compromised in PD subjects by lack of trunk flexibility and backwards postural stability was compromised by lack of knee flexion, resulting in excessive displacements of the body CoM. Stability margins in PD subjects were related to their response on the pull test in the Unified Parkinson's Disease Rating Scale. Thus, PD patients have directionally specific postural instability due to an ineffective stiffening response and inability to modify their postural responses for changing postural demands related to direction of perturbation and initial stance posture. These results suggest that the basal ganglia, in addition to regulating muscle tone and energizing postural muscle activation, also are critical for adapting postural response patterns for specific biomechanical conditions.     

Programming of single movements in Parkinson's disease: Comparison with huntington's disease

Abstract

The preparation of individual finger movements was examined in Parkinson's disease (PD), in comparison with a similar study of Huntington's disease (HD). Motor programming was varied by increasing the amount of information available in advance of each movement. PD patients had particular difficulty when there was no cue light in advance of the movement, and when two upcoming movements were cued ahead of the current movement. Such difficulties suggest that PD patients may have difficulty in performing movements without sensory cuing, and in maintaining and organising a future sequence of movements. HD patients had been previously shown to have similar deficits. Commonalities in these once contrasted disorders probably arise from disruption of common mechanisms.     

Kinematic analysis of handwriting movements in patients with Alzheimer's disease,mild cognitive impairment,depression and healthy subjects

A variety of studies have demonstrated that motor disorders, parkinsonism and extrapyramidal motor symptoms (EPMS) are common in patients with Alzheimer's disease (AD). Several studies have reported an association of EPMS with severity, progression and poor prognosis of AD. The majority of these studies used clinical assessments for the rating of EPMS. In this study, kinematic handwriting analysis was used to quantify differences in fine hand motor function in patients with probable AD and mild cognitive impairment (MCI, as an assumed initial stage of AD) compared to depressed patients and healthy controls. Both patients with MCI and patients with probable AD exhibited loss of fine motor performance. Movements of AD patients were significantly less regular than those of healthy controls.     

Postural control of the trunk during unstable sitting in Parkinson's disease

Postural instability and falls, both common in Parkinson's disease (PD), have been related to altered trunk control. In this study, we investigated dynamic trunk control with subjects balancing on a seat mounted on a hemisphere, for up to 15 s in five trials. We compared eight PD patients with a fall-history, eight without a fall-history, and eight matched healthy subjects. The number of trials completed without balance loss and the time to balance loss were significantly lower in PD patients as compared to healthy controls, whereas the PD patients with a fall-history did not perform significantly less than the patients without a fall-history. Multivariate analysis of variance showed significant effects of group on movements of the center of pressure (CoP) under the seat with the largest amplitudes among the PD fallers and the smallest amplitudes among the healthy controls. Univariate analyses revealed that this effect was mainly based on a significantly larger root mean square CoP displacement in the medio-lateral direction, with significant post hoc differences between all three groups. Trunk angular deviations were significantly smaller among PD patients than controls. Finally, both CoP movements and trunk movements had a significantly lower frequency content and were thus slower in PD patients than in controls, except for anterior–posterior CoP movements. The results show that trunk control is affected in PD and suggest that these changes may be related to postural instability and fall risk.