Who will remain tremor dominant? The possible role of cognitive reserve in the time course of two common Parkinson's disease motor subtypes.

In a prospective 5-year study among Parkinson's disease (PD) tremor-dominant (TD) patients, we investigated who will remain TD and who will later convert into the postural instability gait difficulty (PIGD) phenotype. At follow-up, 38% were still considered TD. At baseline the TD non-convertors had more years of education and better cognitive function than the convertors and significantly smaller deterioration in gait, balance, cognitive function and other non-motor symptoms. These results highlight the potential role of cognition in protecting against the development of PIGD symptoms.

Rapid accumulation of genome rearrangements in liver but not in brain of old mice.

Somatic mutations have long been considered a possible cause of ageing. To directly study mutational events in organs and tissues of ageing mammals, a transgenic mouse model has been generated that harbours lacZ reporter genes as part of chromosomally integrated plasmids. Using this model, we determined spontaneous mutant frequencies and spectra in mouse liver and brain as a function of age. In the liver, mutant frequencies increased with age from birth to 34 months; in the brain, an increase was observed only between birth and 4-6 months. Molecular characterization of the mutations showed that a substantial portion involved genome rearrangement events, with one breakpoint in a reporter gene and the other in the mouse flanking sequence. In the liver, these genome rearrangements did not increase with age until after 27 months, when they increased rapidly. In brain, the frequency of genome rearrangements was lower than in liver and did not increase with age.

Disease severity and prefrontal cortex activation during obstacle negotiation among patients with Parkinson's disease: Is it all as expected?

BACKGROUND: Previous reports indicate that patients with Parkinson's disease (PD) activate the prefrontal cortex (PFC) during complex activities such as obstacle negotiation to compensate for impaired motor function. However, the influence of disease severity on PFC activation has not been systematically evaluated. Here, we examined the effects of disease severity on PFC activation during obstacle negotiation. METHODS: 74 patients with PD (age 68.26 ± 7.54 yrs; 62.2% men) were divided into three groups based on Hoehn and Yahr stages. All patients walked along an obstacle course while negotiating anticipated and unanticipated obstacles (long/low available response time) at heights of 50 mm and 100 mm. PFC activation was measured using functional near-infrared spectroscopy (fNIRS) and was compared between groups and tasks using mixed model analyses. RESULTS: Participants with more advanced PD (i.e., Hoehn & Yahr 3) had higher PFC activation levels when negotiating anticipated obstacles, compared to participants with milder PD (i.e., Hoehn & Yahr 1, 2) (p < 0.001). Moreover, higher LEDD correlated with higher prefrontal activation during the higher anticipated obstacle. In contrast, during the negotiation of unanticipated obstacles, the differences in PFC activation were not associated with disease severity in a linear manner. CONCLUSIONS: The present study suggests that with increased disease severity, patients with PD rely more on the PFC when negotiating anticipated obstacles, perhaps to compensate for attention and motor deficits. These findings support the role of cognition in fall risk and the need to improve attention and cognition in fall prevention programs, especially among patients with more advanced disease.

Which obstacle attributes place additional demands on higher-level cognitive function in patients with Parkinson's disease?

BACKGROUND: Previous reports show that patients with Parkinson's disease (PD) rely on prefrontal activation to compensate for impaired motor function during complex activities such as obstacle negotiation. However, the influence of the properties of the obstacles on prefrontal activation has not been systematically evaluated. Here, we examined the effects of obstacle height and anticipation time on prefrontal activation in patients with PD and older adults. METHODS: 34 patients with PD (age: 67.4 ± 5.7 years; 14 women) and 26 older adults (age: 71.3 ± 8.9 years; 11 women) walked in an obstacle course while negotiating anticipated and unanticipated obstacles (long/short available time response, ART) at heights of 50 mm and 100 mm. Prefrontal activation was measured using functional Near-Infrared Spectroscopy (fNIRS); obstacle negotiation performance was measured using Kinect cameras. RESULTS: PD patients showed greater increases in prefrontal activation during and after obstacle crossing compared to the older adults (p < 0.001). Obstacle height affected prefrontal activity only when crossing anticipated obstacles (ARTxheight interaction, p = 0.011), in which case higher obstacles were accompanied by higher prefrontal activity. PD patients showed higher levels of activation during unanticipated obstacles, compared to older adults (groupXART: p = 0.015). Different correlations between prefrontal activation and obstacle negotiation strategies were observed in patients and controls. CONCLUSIONS: These results point to the use of prefrontal activation as a compensatory mechanism in PD. Moreover, the higher activation observed when negotiating more challenging obstacles suggests that there is greater reliance on cognitive resources in these demanding situations that may contribute to the higher risk of falls in PD patients.

A multi-modal virtual reality treadmill intervention for enhancing mobility and cognitive function in people with multiple sclerosis: Protocol for a randomized controlled trial.

BACKGROUND: Gait and cognitive impairments are common in individuals with Multiple Sclerosis (MS) and can interfere with everyday function. Those with MS have difficulties executing cognitive tasks and walking simultaneously, a reflection of dual-task interference. Therefore, dual-task training may improve functional ambulation. Additionally, using technology such as virtual reality can provide personalized rehabilitation while mimicking real-world environments. The purpose of this randomized controlled trial is to establish the benefits of a combined cognitive-motor virtual reality training on MS symptoms compared to conventional treadmill training. METHODS: This study will be a single-blinded, two arm RCT with a six-week intervention period. 144 people with MS will be randomized into a treadmill training alone group or treadmill training with virtual reality group. Both groups will receive 18 sessions of training while walking on a treadmill, with the virtual reality group receiving feedback from the virtual system. Primary outcome measures include dual-task gait speed and information processing speed, which will be measured prior to training, one-week post-training, and three months following training. DISCUSSION: This study will provide insight into the ability of a multi-modal cognitive-motor intervention to reduce dual-task cost and to enhance information processing speed in those with MS. This is one of the first studies that is powered to understand whether targeted dual-task training can improve MS symptoms and increase functional ambulation. We anticipate that those in the virtual reality group will have a significantly greater increase in dual-task gait speed and information processing speed than those achieved via treadmill training alone.

Bilateral coordination of gait and Parkinson's disease: the effects of dual tasking.

The aetiology of gait disturbances in Parkinson's disease (PD) is not fully understood. Recently, it was shown that in patients with PD, bilateral coordination of gait is impaired and that walking while being simultaneously engaged in a cognitive task is detrimental to their gait. To assess whether cognitive function influences the bilateral coordination of gait in PD, this study quantified left-right stepping coordination using a phase coordination index (PCI) that evaluates both the variability and inaccuracy of the left-right stepping phase (phi) generation (where the ideal phi value between left and right stepping is 180 degrees ). This report calculated PCI values from data obtained from force sensitive insoles embedded in subjects' shoes during 2 min of walking in a group of patients with PD (n = 21) and in an age matched control group (n = 13). All subjects walked under two walking conditions: usual walking and dual tasking (DT) (ie, cognitive loading) condition. For patients with PD, PCI values were significantly higher (ie, poorer coordination) during the DT walking condition compared with usual walking (p<0.001). In contrast, DT did not significantly affect the PCI of the healthy controls (p = 0.29). PCI changes caused by DT were significantly correlated with changes in gait variability but not with changes in gait asymmetry that resulted from the DT condition. These changes were also associated with performance on a test of executive function. The present findings suggest that in patients with PD, cognitive resources are used in order to maintain consistent and accurate alternations in left-right stepping.

Treadmill training for the treatment of gait disturbances in people with Parkinson's disease: a mini-review.

This report reviews recent investigations of the effects of treadmill training (TT) on the gait of patients with Parkinson's disease. A literature search identified 14 relevant studies. Three studies reported on the immediate effects of TT; over-ground walking improved (e.g., increased speed and stride length) after one treadmill session. Effects persisted even 15 min later. Eleven longer-term trials demonstrated feasibility, safety and efficacy, reporting positive benefits in gait speed, stride length and other measures such as disease severity (e.g., Unified Parkinson's Disease Rating Scale) and health-related quality of life, even several weeks after cessation of the TT. Long-term carryover effects also raise the possibility that TT may elicit positive neural plastic changes. While encouraging, the work to date is preliminary; none of the identified studies received a quality rating of Gold or level Ia. Additional high quality randomized controlled studies are needed before TT can be recommended with evidence-based support.

A new approach to quantifying the EEG during walking: Initial evidence of gait related potentials and their changes with aging and dual tasking.

BACKGROUND: The electroencephalogram (EEG) can be a useful tool to investigate the neurophysiology of gait during walking. Our aims were to develop an approach that identify and quantify event related potentials (ERPs) during a gait cycle and to examine the effects of aging and dual tasking on these gait related potentials (GRPs). METHODS: 10 young and 10 older adults walked on a treadmill while wearing a wireless 20-channels EEG and accelerometers on the ankles. Each heel strike extracted from the accelerometers was used as an event to which the electrical brain activity pattern was locked. The subjects performed usual and dual task walking that included an auditory oddball task. GRPs amplitude and latency were computed, and a new measure referred to as Amplitude Pattern Consistency (APC) was developed to quantify the consistency of these GRP amplitudes within a gait cycle. The results were compared between and within groups using linear mixed model analysis. RESULTS: The electrical pattern during a gait cycle consisted of two main positive GRPs. Differences in these GRPs between young and older adults were observed in Pz and Cz. In Pz, older adults had higher GRPs amplitude (p = 0.006, p = 0.010), and in Cz lower APC (p = 0.025). Alterations were also observed between the walking tasks. Both groups showed shorter latency during oddball walking compared to usual walking in Cz (p = 0.040). In addition, the APC in Cz was correlated with gait speed (r = 0.599, p = 0.011) in all subjects and with stride time variability in the older adults (r = -0.703, p = 0.023). CONCLUSIONS: This study is the first to define specific gait related potentials within a gait cycle using novel methods for quantifying waveforms. Our findings show the potential of this approach to be applied broadly to study the EEG during gait in a variety of contexts. The observed changes in GRPs with aging and walking task and the relationship between GRPs and gait may suggest the neurophysiologic foundation for studying walking and for developing new approaches for improving gait.

Do you see what I see? Mobile eye-tracker contextual analysis and inter-rater reliability.

Mobile eye-trackers are currently used during real-world tasks (e.g. gait) to monitor visual and cognitive processes, particularly in ageing and Parkinson's disease (PD). However, contextual analysis involving fixation locations during such tasks is rarely performed due to its complexity. This study adapted a validated algorithm and developed a classification method to semi-automate contextual analysis of mobile eye-tracking data. We further assessed inter-rater reliability of the proposed classification method. A mobile eye-tracker recorded eye-movements during walking in five healthy older adult controls (HC) and five people with PD. Fixations were identified using a previously validated algorithm, which was adapted to provide still images of fixation locations (n = 116). The fixation location was manually identified by two raters (DH, JN), who classified the locations. Cohen's kappa correlation coefficients determined the inter-rater reliability. The algorithm successfully provided still images for each fixation, allowing manual contextual analysis to be performed. The inter-rater reliability for classifying the fixation location was high for both PD (kappa = 0.80, 95% agreement) and HC groups (kappa = 0.80, 91% agreement), which indicated a reliable classification method. This study developed a reliable semi-automated contextual analysis method for gait studies in HC and PD. Future studies could adapt this methodology for various gait-related eye-tracking studies.

Age-associated changes in obstacle negotiation strategies: Does size and timing matter?

INTRODUCTION: Tripping over an obstacle is one of the most common causes of falls among older adults. However, the effects of aging, obstacle height and anticipation time on negotiation strategies have not been systematically evaluated. METHODS: Twenty older adults (ages: 77.7±3.4years; 50% women) and twenty young adults (age: 29.3±3.8years; 50% women) walked through an obstacle course while negotiating anticipated and unanticipated obstacles at heights of 25mm and 75mm. Kinect cameras captured the: (1) distance of the subject's trailing foot before the obstacles, (2) distance of the leading foot after the obstacles, (3) clearance of the leading foot above the obstacles, and (4) clearance of the trailing foot above the obstacles. Linear-mix models assessed changes between groups and conditions. RESULTS: Older adults placed their leading foot closer to the obstacle after landing, compared to young adults (p<0.001). This pattern was enhanced in high obstacles (group*height interaction, p=0.033). Older adults had lower clearance over the obstacles, compared to young adults (p=0.007). This was more pronounced during unanticipated obstacles (group*ART interaction, p=0.003). The distance of the leading foot and clearance of the trailing foot after the obstacles were correlated with motor, cognitive, and functional abilities. CONCLUSIONS: These findings suggest that there are age-related changes in obstacle crossing strategies that are dependent on the specific characteristics of the obstacle. The results have important implications for clinical practice, suggesting that functional exercise should include obstacle negotiation training with variable practice of height and available response times. Further studies are needed to better understand the effects of motor and cognitive abilities.

Do cognition and other non-motor symptoms decline similarly among patients with Parkinson's disease motor subtypes? Findings from a 5-year prospective study.

Among patients with Parkinson's disease (PD), a wide range of motor and non-motor symptoms (NMS) are evident. PD is often divided into tremor dominant (TD) and postural instability gait difficulty (PIGD) motor subtypes. We evaluated the effect of disease duration and aimed to characterize whether there are differences in the deterioration of cognitive function and other NMS between the PIGD and TD subtypes. Sixty-three subjects were re-evaluated at the follow-up visit about 5 years after baseline examination. Cognitive function and other NMS were assessed. At follow-up, the PIGD and TD groups were similar with respect to medications, comorbidities and disease-related symptoms. There was a significant time effect for all measures, indicating deterioration and worsening in both groups. However, cognitive scores, particularly those related to executive function, became significantly worse in the PIGD with a more moderate decrease in the TD group. For example, the computerized global cognitive score declined in the PIGD group from 94.21 ± 11.88 to 83.91 ± 13.76, p < 0.001. This decline was significantly larger (p = 0.03) than the decrease observed in the TD group (96.56 ± 10.29 to 92.21 ± 14.20, p = 0.047). A significant group × time interaction effect was found for the change in global cognitive score (p = 0.047), the executive function index (p = 0.002) and accuracy on a motor-cognitive catch game (p = 0.008). In contrast, several NMS including depression, health-related quality of life and fear of falling deteriorated in parallel in both subtypes, with no interaction effect. The present findings highlight the difference in the natural history of the disease between the two PD "motor" subtypes. While the PIGD group demonstrated a significant cognitive decline, especially in executive functions, a more favorable course was observed in the TD subtype. This behavior was not seen in regards to the other NMS.

The impact of Tai Chi and Qigong mind-body exercises on motor and non-motor function and quality of life in Parkinson's disease: A systematic review and meta-analysis.

PURPOSE: To systematically evaluate and quantify the effects of Tai Chi/Qigong (TCQ) on motor (UPDRS III, balance, falls, Timed-Up-and-Go, and 6-Minute Walk) and non-motor (depression and cognition) function, and quality of life (QOL) in patients with Parkinson's disease (PD). METHODS: A systematic search in 7 electronic databases targeted clinical studies evaluating TCQ for individuals with PD published through August 2016. Meta-analysis was used to estimate effect sizes (Hedges's g) and publication bias for randomized controlled trials (RCTs). Methodological bias in RCTs was assessed by two raters. RESULTS: Our search identified 21 studies, 15 of which were RCTs with a total of 735 subjects. For RCTs, comparison groups included no treatment (n = 7, 47%) and active interventions (n = 8, 53%). Duration of TCQ ranged from 2 to 6 months. Methodological bias was low in 6 studies, moderate in 7, and high in 2. Fixed-effect models showed that TCQ was associated with significant improvement on most motor outcomes (UPDRS III [ES = -0.444, p < 0.001], balance [ES = 0.544, p < 0.001], Timed-Up-and-Go [ES = -0.341, p = 0.005], 6 MW [ES = -0.293, p = 0.06], falls [ES = -0.403, p = 0.004], as well as depression [ES = -0.457, p = 0.008] and QOL [ES = -0.393, p < 0.001], but not cognition [ES = -0.225, p = 0.477]). I2 indicated limited heterogeneity. Funnel plots suggested some degree of publication bias. CONCLUSION: Evidence to date supports a potential benefit of TCQ for improving motor function, depression and QOL for individuals with PD, and validates the need for additional large-scale trials.

Altered brain activation in complex walking conditions in patients with Parkinson's disease.

INTRODUCTION: Behavioral studies suggest that deficits in cognitive domains and sensory-motor processes associated with Parkinson's disease (PD) impair the ability to walk in complex environments. However, the neural correlates of locomotion in complex environments are still unclear. METHODS: Twenty healthy older adults (mean age 69.7 ± 1.3 yrs) and 20 patients with PD (mean age 72.9 ± 1.6 yrs; disease duration: 6.8 ± 1.3 yrs; UPDRSIII: 29.8 ± 2.4) were asked to imagine themselves walking while in the MRI scanner. Three imagined walking tasks, i.e., usual walking, obstacle negotiation, and navigation were performed. Watching the same virtual scenes without imagining walking served as control tasks. Whole brain analyses were used. RESULTS: Compared to usual walking, both groups had increased activation during obstacle negotiation in middle occipital gyrus (MOG) (pFWEcorr<0.001), middle frontal gyrus (MFG) (pFWEcorr<0.005), and cerebellum (pFWEcorr<0.001). Healthy older adults had higher activation in precuneus and MOG (pFWEcorr<0.023) during navigation, while no differences were observed in patients with PD. Between group comparisons revealed that patients with PD had a significantly higher activation in usual walking and obstacle negotiation (pFWEcorr<0.039) while during navigation task, healthy older adults had higher activation (pFWEcorr<0.047). CONCLUSIONS: Patients with PD require greater activation during imagined usual walking and obstacle negotiation than healthy older adults. This increased activation may reflect a compensatory attempt to overcome inefficient neural activation in patients with PD. This increased activation may reduce the functional reserve needed during more demanding tasks such as during navigation which may contribute to the high prevalence of falls and dual tasking difficulties among patients with PD.

PhysioBank, PhysioToolkit, and PhysioNet: components of a new research resource for complex physiologic signals.

The newly inaugurated Research Resource for Complex Physiologic Signals, which was created under the auspices of the National Center for Research Resources of the National Institutes of Health, is intended to stimulate current research and new investigations in the study of cardiovascular and other complex biomedical signals. The resource has 3 interdependent components. PhysioBank is a large and growing archive of well-characterized digital recordings of physiological signals and related data for use by the biomedical research community. It currently includes databases of multiparameter cardiopulmonary, neural, and other biomedical signals from healthy subjects and from patients with a variety of conditions with major public health implications, including life-threatening arrhythmias, congestive heart failure, sleep apnea, neurological disorders, and aging. PhysioToolkit is a library of open-source software for physiological signal processing and analysis, the detection of physiologically significant events using both classic techniques and novel methods based on statistical physics and nonlinear dynamics, the interactive display and characterization of signals, the creation of new databases, the simulation of physiological and other signals, the quantitative evaluation and comparison of analysis methods, and the analysis of nonstationary processes. PhysioNet is an on-line forum for the dissemination and exchange of recorded biomedical signals and open-source software for analyzing them. It provides facilities for the cooperative analysis of data and the evaluation of proposed new algorithms. In addition to providing free electronic access to PhysioBank data and PhysioToolkit software via the World Wide Web (http://www.physionet. org), PhysioNet offers services and training via on-line tutorials to assist users with varying levels of expertise.

Falls in outpatients with Parkinson's disease: frequency, impact and identifying factors.

Falls are one of the most serious complications of gait disturbances in patients with Parkinson's disease (PD). Among previous reports, the percentage of patients with PD who fall varies between 38% to 68%. We sought to determine the frequency of falls and the factors associated with falls in a group of patients with idiopathic PD who attended an outpatient, tertiary movement disorders clinic. 350 ambulatory, non-demented patients (230 males) were studied. Mean age was 69.7+/-10.6 years (range: 43-97 yrs) and mean duration of PD symptoms was 8.6+/- 6.2 years (range: 1-33 yrs). Assessments included characterization of demographics, disease duration, disease severity as measured by the Hoehn and Yahr Scale (H&Y), co-morbidities, the presence of depressive symptoms, the presence of urinary incontinence, use of anti-parkinsonian medications, and two performance-based tests of balance and gait (tandem standing and Timed Up & Go). Fall history was determined during three time periods: previous week, previous month, and previous year. Univariate and multivariate logistic regression models were applied to evaluate the relationship between the above-mentioned factors and falls. 46% of the subjects reported at least one fall in the previous year and 33% reported 2 or more falls and were classified as Fallers. Fallers had significantly more prolonged and advanced PD compared with Non-fallers (p=0.001 and p<0.001, respectively). Urinary incontinence was the factor most closely associated with falls (crude and adjusted OR were 1.95 and 5.89, respectively). Other factors significantly associated with fall status included increased Timed Up & Go times and increased PD duration. These findings confirm that falls are a common problem among patients with advanced PD and suggest easily measurable features that may be used to prospectively identify those PD patients with the greatest risk of falls.

Clinical characteristics of elderly patients with a cautious gait of unknown origin.

OBJECTIVE: To evaluate and systematically characterize a group of older adults with disturbed gait of unknown origin. DESIGN: Cross-sectional study. SETTING: Outpatient clinic in a movement disorders unit. PARTICIPANTS: Twenty-five patients (mean age 78.4 years) with a disturbed gait of unknown origin were compared with twenty-eight age matched "healthy" controls (mean age 78.2). MEASUREMENT: Detailed medical history, geriatric and neurological assessments. RESULTS: Patients walked more slowly (P<0.0001) and with shorter strides (P<0.0001) compared with controls. Muscle strength was lower, and static and dynamic balance and gait performance were worse among the patients (P<0.0001). The patients also tended to be more depressed (P<0.0001),more anxious (P<0.002), had a greater fear of falling (P<0.0001) and had lower scores on the Mini-Mental State Examination (P<0.005). There was no difference in the frequency of cerebellar or pyramidal signs in the two groups. However, neurological testing revealed that extrapyramidal (P<0.0001) and frontal release signs (P<0.0001) were more common among the patients. Neuroradiological findings were rare among the patients and they did not explain the changes in gait speed or fear of falling. CONCLUSIONS: Older adults with a disturbed gait of unknown origin appear to share common characteristics. They walk more slowly than "healthy" controls with increased unsteadiness and with excessive fear of falling. The extrapyramidal, frontal lobe, and limbic systems apparently play an important role, to different degrees, in what can be viewed as a multisystem neurodegenerative syndrome clearly different from "aging."

A phase I trial of doxorubicin, paclitaxel, and valspodar (PSC 833), a modulator of multidrug resistance.

PURPOSE: P-glycoprotein is an efflux pump for many drugs including doxorubicin and paclitaxel. This study evaluated the coadministration of these drugs with the P-glycoprotein inhibitor valspodar (PSC 833) with the aim of determining: (a) maximum tolerated doses (MTDs) of doxorubicin followed by paclitaxel (DP); (b) the MTD of DP combined with PSC 833 (DPV), without and with filgrastim (G-CSF); and (c) the pharmacokinetic interactions of PSC 833 with doxorubicin and paclitaxel. EXPERIMENTAL DESIGN: For the first cycle, patients received doxorubicin as a 15-min infusion followed by paclitaxel as a 1-h infusion. For the second cycle, patients received reduced doses of DP with PSC 833 at 5 mg/kg p.o., four times a day for 12 doses. RESULTS: Thirty-three patients with various refractory malignancies were enrolled and assessable. The MTD of DP without PSC 833 was 35 mg/m(2) doxorubicin and 150 mg/m(2) paclitaxel. The MTD of DPV without G-CSF was 12.5 mg/m(2) doxorubicin and 70 mg/m(2) paclitaxel. The dose-limiting toxicity for both DP and DPV was neutropenia without thrombocytopenia. With G-CSF, the MTD for DPV was 20 mg/m(2) doxorubicin and 90 mg/m(2) paclitaxel. No grade 4 nonhematological toxicities were observed. Five partial and two minor tumor remissions were observed. Paired pharmacokinetics with and without PSC 833 revealed substantial drug interactions with both doxorubicin and paclitaxel. CONCLUSIONS: PSC 833 can be administered safely with doxorubicin and paclitaxel. The pharmacokinetic profiles of these drugs are significantly affected by PSC 833, requiring approximately 60% dose reductions for equivalent degrees of myelosuppression.

Gait instability and fractal dynamics of older adults with a "cautious" gait: why do certain older adults walk fearfully?

Many older adults walk with a cautious and impaired gait of unknown origin, however, the relationship between fear of falling and the observed gait changes is not well understood. To better understand the "cautious" gait of the elderly, we tested the hypothesis that temporal gait variability, putatively a marker of intrinsic walking unsteadiness, is increased among older adults with a cautious gait and a higher-level gait disorder (HLGD), an altered gait that cannot be attributed to a well-defined cause. Twenty-five older adults (mean age: 78 years) with a HLGD were compared to healthy controls of similar age and sex (n=28). The clinical characteristics (e.g., neurological status, fear of falling), the magnitude of the stride-to-stride variations in gait cycle timing (a measure of temporal gait variability), and a fractal index of gait (a measure of the stride dynamics independent of the magnitude of the variability) were studied in both groups. Gait variability was significantly increased (P<0.0001) in HLGD subjects (52+/-26 ms) compared to controls (27+/-9 ms). Changes in frontal lobe and extra-pyramidal function were also found in the patient group. Among HLGD subjects, gait variability was not associated (P>0.05) with age, gender, MMSE score, muscle strength, # of co-morbidities, balance, cerebellar signs, or pyramidal signs, but was significantly associated with scores on the Geriatric Depression Scale (r=0.46, P<0.02) and fear of falling (r=0.69, P<0.0001). Among HLGD subjects, only a fractal index was significantly different in fallers and non-fallers. These findings underscore the idea that the gait changes in older adults who walk with fear may be an appropriate response to unsteadiness, are likely a marker of underlying pathology, and are not simply a physiological or psychological consequence of normal aging.

Postictal heart rate oscillations in partial epilepsy.

We report postictal heart rate oscillations in a heterogeneous group of patients with partial epilepsy. This pattern is marked by the appearance of transient but prominent low-frequency heart rate oscillations (0.01 to 0.1 Hz) immediately after 5 of 11 seizures recorded in 5 patients. This finding may be a marker of neuroautonomic instability and, therefore, may have implications for understanding perturbations of heart rate control associated with partial seizures.

A new technique for simultaneous monitoring of electrocardiogram and walking cadence.

A new technique for simultaneously recording continuous electrocardiographic (ECG) data and walking step rate (cadence) is described. The ECG and gait signals are recorded on 2 channels of an ambulatory Holter monitor. Footfall is detected using ultrathin, force-sensitive foot switches and is frequency modulated. The footfall signal provides an indication of the subject's activity (walking or standing), as well as the instantaneous walking rate. Twenty-three young and elderly subjects were studied to demonstrate the use of this ECG and gait recorder. High-quality gait signals were obtained in all subjects, and the effects of walking on the electrocardiogram were assessed. Initial investigation revealed the following findings: (1) Although walking rates were similar in young and elderly subjects, the elderly had both decreased heart rate (HR) variability (p < 0.005) and increased cadence variability (p < 0.0001). (2) Overall, there was an inverse relation between HR and cadence variability (r = -0.73). Three elderly subjects with no known cardiac disease had HR and cadence variability similar to those of the young, whereas elderly subjects with history of congestive heart failure were among those with the lowest HR variability and the highest cadence variability. (3) Low-frequency (approximately equal to 0.1 Hz) HR oscillations (frequently observed during standing) persisted during walking in all young subjects. (4) In some subjects, both step rate and HR oscillated at the same low frequency (approximately equal to 0.1 Hz) previously identified with autonomic control of the baroreflex.(ABSTRACT TRUNCATED AT 250 WORDS)