Motor Portion Research Articles

Myosins pull together to move cargo

Two kinds of myosin motors depend on teamwork to keep their cellular cargos rolling, as Dunn et al. show. The finding explains how the molecules, which previous work suggested couldn't move forward, work as haulers. Figure 1 Myo4p concentrates labeled mRNA in a yeast bud (left), but the cargo remains dispersed if the cell lacks the myosin (right). When a yeast cell sprouts a bud, two myosin proteins help furnish the new structure with necessities. Myo2p trucks in organelles and vesicles essential for growth, whereas Myo4p hauls mRNA that helps the bud differentiate from the mother cell. Running on tracks of actin, the proteins seem to keep their cargos moving continuously. That presents a mystery, however, because evidence suggests that the individual myosins are nonprocessive—they let go of the tracks after every power stroke, instead of remaining attached and sliding along. To resolve that apparent contradiction, Dunn et al. isolated the two myosins and determined that they move differently. Molecules of Myo2p didn't always detach after the power stroke, the researchers found. They were “weakly processive.” Several Myo2p molecules latched onto each cargo. At any time, most of them might not be attached to the tracks, but one Myo2p probably will be and can nudge the cargo along. The method makes sense for what Myo2p transports. The vesicles and organelles it totes are large and have room for multiple myosins to hook on. An individual Myo4p was nonprocessive, but the molecules formed clusters that were processive. A single cluster was able to ferry one molecule of mRNA. Again, the strategy matches the cargo: mRNA has few attachment points for myosins. The researchers also wanted to determine what accounts for the differences between the two myosins. They created hybrid molecules that carried the tail end of one protein—which attaches to the cargo—fused to the motor portion of the other. A hybrid with the motor of Myo4p and the tail of Myo2p worked like Myo2p, and vice versa. The tail thus dictates myosin's behavior. The researchers now want to investigate how cells integrate pulling by separate motors. Reference: Dunn, B.D., et al. 2007. J. Cell Biol. 178:1193–1206. [PubMed]

Restricted ablative lesions in motor portions of GPi in primates produce extensive loss of motor-related neurons and degeneration of the lenticular fasciculus

Deep brain stimulation (DBS) of the internal pallidum (GPi) and the subthalamic nucleus and to a lesser extent, ablative lesioning, are broadly utilized to treat patients with medically intractable Parkinson's disease and other movement disorders. Beneficial outcomes however are not uniform and adverse cognitive and behavioral are significant risks. Surgical outcomes of GPi surgeries might be improved by approaches that better account for the course of motor and non-motor pallidothalamic projections. Although several studies, including our own tracer investigations, suggest that motor projections from GPi principally form the lenticular fasciculus and non-motor projections primarily contribute to the ansa lenticularis, other schemes have perpetuated. Presently, to corroborate the course of pallidothalamic projections and to assess the feasibility of selectively targeting the motor circuit of GPi, radiofrequency lesions were placed in the motor portion of GPi in monkeys. Degenerating pallidothalamic fibers were visualized with amino cupric staining techniques and regional cell counts in GPi were compared with control hemispheres. Lesions restricted to posterior motor portions of GPi produced selective degeneration of LF and only damaged AL if the lesions extended more anteriorly. Marked secondary neuronal loss occurred well beyond the principal lesions but was mainly confined to the posterolateral motor region of GPi. These findings corroborate the original pallidothalamic outflow scheme proposed by Ranson and Ranson. Conceivably, a restrictive lesion or a DBS probe could be placed in the centroposterior portion of GPi to selectively target both local motor-related neurons and traversing pallidothalamic fibers originating from more posterior and lateral motor regions.

Behavioral Therapy for Treatment of Stereotypic Movements in Nonautistic Children

Although typically described in autistic, mentally retarded, and sensory-deprived individuals, motor stereotypies also occur in normal children. In this preliminary report, the behavior modification techniques of habit reversal and differential reinforcement of other behavior were evaluated as a therapeutic modality for the suppression of stereotypic movements in nonautistic subjects. Twelve children, ages 6 to 14 years, with physiologic stereotypies were treated using a standardized treatment protocol. Clinical outcomes were based on differences between assessments obtained at baseline and on telephone follow-up. Evaluation scales included measures of the frequency, intensity, interference, and number of stereotypies (Stereotypy Severity Scale motor portion and Stereotypy Linear Analog Scale) and assessment of global function (Child Global Assessment Scale and Stereotypy Severity Scale global portion). The results were correlated with the child's level of motivation and the number of treatment sessions. After a mean follow-up of 12.1 months, motor stereotypies showed significant improvement on the Stereotypy Linear Analog Scale and Stereotypy Severity Scale total score, P = .009 and P = .046, respectively. Both scales showed a relationship between the number of treatment sessions attended and a reduction in movements. The Child Global Assessment Scale also improved with therapy, but there was no correlation with the number of treatment sessions. Highly motivated patients had greater improvement on the Stereotypy Linear Analog Scale and Stereotypy Severity Scale scales compared with less motivated patients, but motivation had no impact on the Child Global Assessment Scale. The combined use of habit reversal and differential reinforcement of other behavior is beneficial in reducing motor stereotypies in nonautistic children.

Electrophysiological characteristics of limbic and motor globus pallidus internus (GPI) neurons in two cases of Lesch–Nyhan syndrome

Objective. – Lesch–Nyhan syndrome is a rare and debilitating condition characterized by dystonia and self-mutilating behavior. In order to shed light on the pathophysiology of dystonia, we report the pallidal electrophysiological activity recorded in two patients during deep brain stimulation surgery (DBS). Methods. – Microrecordings were performed on 162 neurons along four tracks aimed at the right and left anterior (limbic) and posterior (motor) globus pallidus internus (GPI). Results. – Regardless of the anesthetic agent used (propofol or sevoflurane), both patients showed similar neurons firing rates in the four regions studied, namely the limbic and motor portions of the globus pallidus externus (GPE) or GPI. In both patients, firing rates were similar in the GPE (12.2 ± 1.8 Hz, N = 38) and GPI (13.2 ± 1.0 Hz, N = 83) portions of the limbic track, while the motor GPE fired at a higher frequency (23.8 ± 2.7 Hz, N = 18) than the motor GPI (12.5 ± 1.4 Hz, N = 23). Conclusions. – These results demonstrate that light propofol or sevoflurane anesthesia influences pallidal activity in a similar way. Electrophysiological recordings suggest that Lesch–Nyhan syndrome might be characterized by analogous firing frequencies in the limbic GPE and GPI while motor GPE would tend to fire at higher rate than the motor GPI. It is therefore tempting to suggest that the symptoms that are observed in Lesch–Nyhan syndrome might result from motor GPI inhibition. Significance. – This observation may confirm the Albin and Delong's model of the basal nuclei in hypokinetic and hyperkinetic disorders.

Alteration of central motor excitability in a patient with hemimasticatory spasm after treatment with botulinum toxin injections

Hemimasticatory spasm (HMS) is a condition characterized by paroxysmal involuntary contraction of masticatory muscles. We performed an electrophysiological investigation of a single patient with HMS to identify any pathophysiological changes associated with the condition. We identified a delayed M wave and jaw jerk on the affected side and an absent masseteric silent period during spasm. Botulinum toxin injections successfully treated the clinical symptoms and resulted in a significant reduction in the excitability of the blink reflex recovery cycle. These data suggest that HMS may be due to ectopic activity in the motor portion of the trigeminal nerve that is capable of inducing changes in the excitability of central reflex pathways. These changes can be altered by successful treatment with botulinum toxin.

Is the functional decline of Parkinson's disease similar to the functional decline of Alzheimer's disease?

Since many Parkinson’s disease (PD) subjects develop dementia, we determined whether the correlation between functional and cognitive decline seen in Alzheimer's disease (AD) is seen in PD. Seventy-five PD subjects with and without dementia and 103 AD/MCI subjects underwent the Functional Assessment Staging (FAST), the Global Deterioration Scale (GDS), the UPDRS motor portion, and the MMSE. In AD/MCI subjects, changes in FAST and GDS scores correlated with MMSE ( ρ=−0.814, P<0.001; ρ=−0.840, P<0.001, respectively). In PD subjects, the FAST and GDS also correlated with MMSE ( ρ=−0.675, P<0.001; ρ=−0.647, P<0.001, respectively). The UPDRS correlated with the GDS and FAST more closely in PD than in AD. Similar to AD, functional declines in PD correlates with cognitive decline and may be influenced by motor disability in PD.

Association between mild parkinsonian signs and mild cognitive impairment in a community

Mild parkinsonian signs (MPS) are associated with prevalent and incident dementia but it is not known whether they are associated with mild cognitive impairment (MCI). To determine whether MPS and specific MPS (changes in axial function, rigidity, tremor) are associated with MCI in nondemented community-dwelling older people in northern Manhattan, NY. Participants underwent neurologic assessment, including a modified motor portion of the Unified Parkinson Disease Rating Scale. MCI was diagnosed in nondemented participants who had cognitive impairment based on neuropsychological testing and no functional impairment. Participants with MCI were classified as having MCI with memory impairment (MCI+M) vs MCI without memory impairment (MCI-M). MCI was present in 608 (27.3%) of 2,230 participants, including 255 participants with MCI+M and 353 with MCI-M; 1,622 participants did not have MCI. MPS were present in 369 (16.5%) of 2,230 participants. In a univariate logistic regression model, odds of MCI+M (vs no MCI) were 51% higher in participants with MPS compared to those with no MPS (OR = 1.51, 95% CI = 1.09 to 2.09, p = 0.01). Multivariate models yielded similar results (OR = 1.45, 95% CI = 1.03 to 2.05, p = 0.03). Rigidity was present in a higher proportion of participants with MCI+M compared to participants without MCI. Mild parkinsonian signs, especially rigidity, are associated with amnestic mild cognitive impairment. Mild parkinsonian signs and mild cognitive impairment may share similar pathogeneses. Whether this involves Alzheimer-type pathology, Lewy bodies, or vascular changes in the basal ganglia or basal ganglia circuitry deserves further investigation in postmortem studies.

Functional Correlates and Prevalence of Mild Parkinsonian Signs in a Community Population of Older People

Mild parkinsonian signs (MPS) are associated with incident dementia and an increased risk of mortality. To our knowledge, the functional correlates of MPS have not been studied. To study the functional correlates of MPS, including self-reported and performance-based measures of function, and to determine the prevalence of MPS in a cohort of community-dwelling older people (aged >or=65 years). Participants (N = 1866) in the Washington Heights-Inwood Columbia Aging Project underwent a neurological assessment that included a modified motor portion of the Unified Parkinson's Disease Rating Scale, which yielded a parkinsonian sign score (range, 0-40) and parkinsonian sign subscores (axial function, rigidity, and tremor). A functional assessment included 3 self-reported measures of function and 2 performance-based tests. Participants with Parkinson disease were excluded. Mild parkinsonian signs were present in 469 (25.1%) of the 1866 participants. The parkinsonian sign score was correlated with functional and performance-based test scores (r = 0.24-0.32, P<.001). The axial function and rigidity subscores correlated to a greater extent with functional and performance-based test scores than did the tremor subscore. In analysis of covariance models, excluding participants with dementia and adjusting for age, sex, ethnicity, education, depressive symptoms, and medical illnesses (eg, arthritis), the parkinsonian sign score and age were strongly and independently associated with functional scores. Mild parkinsonian signs, and particularly axial dysfunction, were associated with functional disability, including self-reported and performance-based measures of functional difficulty. Given the high prevalence of these signs in elderly persons, MPS may be a significant indicator of disability in elderly persons.

Diabetes mellitus and progression of rigidity and gait disturbance in older persons.

Parkinsonian-like signs, including rigidity, gait disturbance, and bradykinesia, are common and progressive in old age and are associated with morbidity and mortality. Few risk factors for these signs have been identified. Diabetes mellitus, also a common chronic condition in old age and known to be associated with physical and neurologic disability, may be associated with parkinsonian-like signs. To examine the relation of diabetes to four parkinsonian-like signs. Participants were 822 older Catholic clergymen and women who were without clinically diagnosed Parkinson disease or dementia at baseline. For up to 9 years, they had uniform annual evaluations, which included a modified version of the motor portion of the Unified Parkinson's Disease Rating Scale, from which previously established measures of four specific parkinsonian-like signs were derived. Participants were evaluated for the presence of diabetes, based on direct medication inspection and history. Diabetes was present in 128 (15.6%) participants. In random effects models controlling for age, sex, and education, diabetes was associated with worsening rigidity (p < 0.01) and gait (p < 0.05), over an average of 5.6 years of follow-up, but not with change in bradykinesia or tremor. The presence of stroke did not substantially affect the association of diabetes with rigidity but reduced the association of diabetes with gait to a trend (p = 0.08). Diabetes may be a previously unrecognized risk factor for progression of parkinsonian-like signs in older persons.

Factor structure of parkinsonian signs in the community-dwelling elderly.

Parkinsonian signs are present in 40% of older people. Factor analysis of the motor section of the Unified Parkinson's Disease Rating Scale (UPDRS) in patients with Parkinson's disease (PD) has identified several principal domains, including rigidity, axial function, and rest tremor. We hypothesized that if Parkinsonian signs in the elderly were due to basal ganglia dysfunction that this same constellation of factors (rigidity, axial function, rest tremor) would emerge in a factor analysis. We carried out factor analysis, using the principal component method with orthogonal (varimax) rotation, on motor UPDRS scores in community-dwelling elderly without PD. A modified (10-item) version of the motor portion of the UPDRS was administered to 1,339 older adults living in the Washington Heights-Inwood community and it was found that Parkinsonian signs were present in 537 (40.1%). Three factors (rigidity, axial function. and rest tremor) were obtained from the factor analysis and, together, explained 67.4% of the variance. A second factor analysis was carried out excluding the 26 participants with rest tremor, and two factors (rigidity, axial function) emerged. These data support the view that Parkinsonian signs in older adults might be due to basal ganglia dysfunction, a possibility that requires further exploration.

Blood supply of the trigeminal ganglion and nerve root

Great surgical significance and lack of relevant anatomic data were the reasons for this study. Twenty-five trigeminal nerve roots and ganglia were examined under the stereoscopic microscope. The nerve root received between two and six vascular twigs from two or three of the following arteries: the superolateral pontine (92%), anterior inferior cerebellar (88%), inferolateral or posterolateral pontine, superior cerebellar, basilar and trigeminocerebellar. The trigeminal twigs measured from 110 to 520 μm in diameter. A single trigeminal artery may supply either the motor portion of the nerve root or the sensory portion, or both. The superolateral pontine artery (88%) usually perfused the motor root. The same artery often supplied (64%) the ophthalmic part of the sensory root. The maxillary part was most often irrigated by the superolateral and inferolateral pontine arteries, and the mandibular part by the anterior inferior cerebellar artery (AICA). The trigeminal ganglion received the vascular twigs from the middle meningeal artery (92%), accessory middle meningeal artery (8%), inferolateral trunk (90%) and tentorial branch (8%). The obtained data in the trigeminal vasculature can be the anatomic basis for decompressive neurovascular operations and surgery of the cavernous sinus.

Predictors of personal care assistance for people with spinal cord injury

Weitzenkamp DA, Whiteneck GG, Lammertse DP. Predictors of personal care assistance for people with spinal cord injury. Arch Phys Med Rehabil 2002;83:1399-405. Objective: To assess the predictors of personal care assistance (PCA) use in people with spinal cord injury (SCI). Design: Cross-sectional. Setting: Follow-up of individuals crossing their 1st, 5th, 10th, 15th, 20th, or 25th anniversary of injury who underwent their initial rehabilitation at a Spinal Cord Injury Model Systems center. Participants: A total of 2154 participants (2547 records) who met the inclusion criteria for the National Spinal Cord Injury Database and had valid values for the main outcome measures. Interventions: Not applicable. Main Outcome Measures: Daily hours of paid, unpaid, and occasional PCA services. Results: Differences in an interval version of the motor portion of the FIM™ instrument accounted for 26.3% of the variance in total PCA hours, Model Systems differences accounted for 9.3%, and no other predictor accounted for more than 2.1% of the variance. Conclusion: Activities of daily living functioning, as measured by the motor portion of the FIM, was the strongest predictor of PCA use among people with SCI. © 2002 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation

Progression of gait disorder and rigidity and risk of death in older persons.

Bradykinesia, gait disturbance, rigidity, and tremor are common motor signs in old age. All of these signs are associated with increased morbidity and mortality, but the extent to which they are progressive is unknown. Study participants were 787 older Catholic clergy members without clinically diagnosed PD, related conditions, or dementia at baseline. They were evaluated annually for up to 7 years, with >95% follow-up participation by survivors. Evaluations included administration of a modified version of the motor portion of the Unified PD Rating Scale (UPDRS), from which previously established measures of the global UPDRS and four specific motor signs were derived. Scores represent the percent of the total possible UPDRS score obtained. At baseline, the global UPDRS score ranged from 0 to 36.3 (mean +/- SD, 7.3 +/- 6.4). It increased by an average of 0.69 unit per year during follow-up, with more rapid progression in older persons, but there was wide variability with no progression in 21% of subjects and annual increases of up to 8.23 units in the remaining 79%. Of 129 persons who died, 106 had follow-up UPDRS data. In a proportional hazards model, risk of death was associated with both the level of the global UPDRS score at baseline and the annual rate of progression (both p < 0.001). Overall, risk of death in subjects who had some worsening of the global UPDRS score was 2.93 times the rate among those without progression (95% CI, 1.32-6.50). Gait disorder/postural reflex impairment and rigidity worsened, but bradykinesia and tremor did not. Risk of death was associated with worsening of gait/posture but not with the other signs. Gait disorder and rigidity, as assessed with the modified UPDRS, are usually progressive in old age. Both the severity of the gait disorder and its rate of progression are strongly associated with risk of death.

Acute effects of thalamotomy and pallidotomy on regional cerebral metabolism, evaluated by PET

The subacute effect of thalamotomy and pallidotomy on regional cerebral metabolism was studied by means of Positron Emission Tomography (PET). In this way we aimed to identify the pattern of functional deafferentiation following a specific lesion in the basal ganglia. The cerebral distribution of 2-[18F]fluoro 2-deoxy- d-glucose (FDG) uptake at 1–2 weeks after operation was compared with the uptake before operation. Analysis of the changes was done by statistical parametric mapping (SPM). Thalamotomy resulted in a reduction of FDG uptake in predominantly the lateral prefrontal- and the parietal cortex, whereas pallidotomy affected only uptake in the (pre)frontal cortex. The absence of change in the primary sensory-motor cortex after either surgical procedure may suggest that, in man, the motor portions of the thalamus exert a predominantly indirect influence on the human motor cortex.

Progression of parkinsonian signs in Alzheimer's disease.

To describe the progression of parkinsonian signs in persons with AD. Parkinsonian signs are common in AD and appear to be related to morbidity and mortality. However, little is known about individual patterns of progression of parkinsonian signs. A cohort of 410 people with clinically diagnosed AD underwent annual clinical evaluations over a 4-year period, with over 90% of survivors participating in follow-up. The entire motor portion of the Unified Parkinson's Disease Rating Scale (UPDRS) was administered at each evaluation. Previously established measures of four parkinsonian signs were derived from the UPDRS. Scores ranged from 0 to 100 and represented the percent obtained of the total possible item score. A growth curve approach was used to estimate individual paths of change. Rates of change in bradykinesia (4.5% increase per year), rigidity (6.0% increase per year), and gait disorder/postural reflex impairment (8.9% increase per year) were substantial and positively correlated (median r = 0.69). Change in tremor was minimal, mostly confined to postural tremor, and weakly correlated with change in other signs (median r = 0.16). The rate of progression in each sign was highly variable across individuals and not strongly related to demographic factors or use of neuroleptic medications. Parkinsonian signs other than tremor progress rapidly in AD but at widely differing rates.

Course of motor and associative pallidothalamic projections in monkeys

As a result of the frequent performance of lesioning and electrical stimulation procedures targeting the globus pallidus internus (GPi) to treat medically intractable hypokinetic and hyperkinetic movement disorders, the course of the pallidothalamic projections originating, in particular, from the motor territory of GPi has important clinical relevancy. To assess the organization of pallidothalamic projections originating from motor and associative portions of GPi, small quantities of the anterograde/ retrograde tracer, biotinylated dextran amine (BDA) were injected into localized regions of the caudal GPi in squirrel monkeys. The localization to motor and associative territories in GPi was confirmed by examining the corresponding regions of retrograde labeling in the striatum and subthalamic nucleus (STN). The labeled pallidothalamic fibers projected principally medially across the inferior edge of the internal capsule. The fiber bundle ventral to the caudal GPi was mainly devoid of labeling. Fibers labeled along the medial and inferior borders of GPi at centrorostral levels were traceable to the medial edge of the injections. The densest fiber labeling at rostral levels was produced by those injections with the greatest extent of rostral labeling of neurons. In opposition to generally accepted schemes, the findings from this study suggest that the pallidothalamic fibers originating from the caudal portions of GPi, including the motor territory, do not course ventromedially to form the ansa lenticularis, but rather, travel predominately medially through the lenticular fasciculus en route to the thalamus. Thus, proposed surgical schemes to target fibers ventral to the caudal GPi or at the rostral pole of GPi appear to be misguided.

Stereotactic Pallidotomy for Parkinson's Disease: Long Term Results

Introduction: The optimal surgical technique and long term effectiveness of pallidotomy remain subjects of debate. We present the three year follow-up results of a prospective series of 97 pallidotomies in 75 patients with idiopathic Parkinson's Disease (PD). Methods: All patients were evaluated preoperatively using the Unified Parkinson's Disease Rating Scale (UPDRS) and brain MRI. Only patients with idiopathic PD were considered candidates for pallidotomy. Intraoperative macrostimulation was used to optimize lesion placement and avoid injury to nearby structures. Postoperatively, patients were evaluated with clinical examinations at 3, 6, 12, 24, and 36 months. Results: Seventy-five patients (mean age 60 years, range 38–79) underwent unilateral pallidotomies with 16 patients undergoing bilateral pallidotomies and 6 patients undergoing repeat pallidotomies. Most patients were improved on both global and specific clinical measures. Significant improvements were observed in the “OFF” period scores of the activities of daily living and motor portions of the UPDRS, total...

Comparison of MPTP-induced changes in spontaneous neuronal discharge in the internal pallidal segment and in the substantia nigra pars reticulata in primates.

The basal ganglia are currently viewed as components of segregated corticosubcortical reentrant circuits. One of these circuits, the "motor" circuit, is critically involved in the development of parkinsonian motor signs. Current pathophysiologic models postulate that parkinsonism is associated with increased activity in the basal ganglia output nuclei. The neuronal activity in the motor portion of one of these output nuclei, the internal segment of the globus pallidus (GPi), has been characterized in detail in intact and parkinsonian animals, but the neuronal activity in the second major basal ganglia output nucleus, the substantia nigra pars reticulata (SNr), has received far less attention. This study in primates represents a comparison of the effects of parkinsonism, induced by injections of the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), on the neuronal discharge in the GPi and SNr. These electrophysiologic recording experiments were carried out in three African green and two rhesus monkeys. One hundred and twenty-four neurons were recorded in the GPi before treatment with MPTP, and 93 neurons thereafter. In the SNr, 55 cells were recorded before treatment with MPTP, and 41 cells thereafter. MPTP induced a non-significant increase in the average discharge rate and a significant decrease in the median interspike interval length (ISI) in the GPi (by 13%), whereas no changes were detected in either parameter in the SNr. The average ISI distributions were markedly asymmetric in both structures, and could be modeled by a logarithmic normal distribution. With the MPTP treatment, the mode of the ISI distribution fell by 24% in the GPi (P< or =0.01), whereas it did not change significantly in the SNr. An algorithm that detects burst discharges in the raw ISI data (based on the method by Legendy and Salcman) detected a significant increase in the proportion of action potentials that participated in bursts of discharge in both structures (increase by 257% in the GPi, and by 67% in the SNr). Power spectral and autocorrelation analysis revealed that treatment with MPTP increased the proportion of cells with oscillatory burst patterns at 3-8 Hz in both structures (from 0.8% to 27% of all neurons in the GPi, and from none to 10% in the SNr). The results show that neuronal discharge in the SNr is affected in parkinsonism, but that the changes in the SNr are less pronounced then those seen in the GPi.

Progression of parkinsonian signs in Parkinson disease.

Current knowledge about the rate of progression of extrapyramidal signs (EPSs) in Parkinson disease (PD) is derived largely from cross-sectional studies comparing subjects at various stages of illness rather than longitudinal studies in which the subjects were followed up over time. To longitudinally study the progression of EPSs in PD by quantifying the rate of change of EPSs and by examining each EPS (rigidity, bradykinesia, tremor, and postural instability) separately. A community-based cohort of 237 patients with PD living in Washington Heights-Inwood in Manhattan, NY, was evaluated at baseline and at yearly intervals. The EPSs were rated using the motor portion of the Unified Parkinson's Disease Rating Scale Motor Examination. Analyses of longitudinal data were performed by applying generalized estimating equations to regression analyses. The total EPS score increased at an annual rate of 1.5 points (1.5%), but, among those who died, the total EPS score increased at an annual rate of 3.6 points (3.6%). Bradykinesia, rigidity, and gait and balance subscores worsened at similar annual rates of 2.0% to 3.1%, whereas the tremor subscore did not clearly worsen with time. Patients with a shorter disease duration (< or =3 years) may have progressed more rapidly than patients with longer disease duration (annual rate of change, 1.9% vs 1.4%, respectively), although this did not reach statistical significance. A high total EPS score was independently associated with dementia, low Activities of Daily Living score, and long disease duration at baseline. In this cohort, the progression of EPSs in PD occurred at a rate of 1.5% per year and at twice that rate among those who died. Bradykinesia, rigidity, and gait and balance impairment worsened at similar rates, whereas tremor did not, suggesting that tremor may be relatively independent of these other cardinal manifestations of PD.

The capabilities of upper extremity instrument: reliability and validity of a measure of functional limitation in tetraplegia

Objective: To evaluate the reliability and validity of the Capabilities of Upper Extremity (CUE) instrument, designed to measure upper extremity functional limitations in individuals with tetraplegia. Functional limitations are actions such as reaching or grasping and are a link between the domains of impairment and disability. Design: Survey of people with chronic spinal cord injury. Setting: Regional spinal cord injury center. Subjects: One hundred fifty-four individuals (140 male) with tetraplegia at least 1 year after injury and followed by the center. Mean age was 36.7 years (SD = 11.1). Sixty-eight percent were motor complete. Methods: The 32-item CUE was administered by telephone interview twice about 2 weeks apart. The motor portion of the Functional Independence Measure (FIM sm) was collected during the first interview. Upper extremity motor scores and motor levels were obtained from the most recent assessment in the outpatient chart. The instrument was evaluated for internal consistency, reliability, and validity. Exploratory factor analysis was performed to examine scale structure. Results: Homogeneity of the scale was excellent. Cronbach's α was .96, and item-total correlations ranged from .49 to .78. Test-retest reliability was high (ICC = .94). All but three items had desired levels of agreement (κ > .60). Analysis of variance indicated that the CUE distinguished between motor levels of tetraplegia more than one level apart. The CUE was correlated highly with both motor scores and FIM. Regression analysis indicated that the CUE was better than upper extremity motor scores for predicting FIM scores. The model containing the CUE explained 73% of the variance in FIM and was not enhanced by the addition of motor scores. Factor analysis suggested four potential subscales: arm function (bilateral), right hand function, left hand function, and reaching down. Conclusion: The CUE exhibits good homogeneity, reliability, and validity; further work is needed to determine its sensitivity to change in function.