Graham K. Kerr

A meta-analysis of six prospective studies of falling in Parkinson's disease

Recurrent falls are a disabling feature of Parkinsons disease (PD). We have estimated the incidence of falling over a prospective 3 month follow‐up from a large sample size, identified predictors for falling for PD patients repeated this analysis for patients without prior falls, and examined the risk of falling with increasing disease severity. We pooled six prospective studies of falling in PD (n = 473), and examined the predictive power of variables that were common to most studies. The 3‐month fall rate was 46% (95% confidence interval: 38–54%). Interestingly, even among subjects without prior falls, this fall rate was 21% (12–35%). The best predictor of falling was two or more falls in the previous year (sensitivity 68%; specificity 81%). The risk of falling rose as UPDRS increased, to about a 60% chance of falling for UPDRS values 25 to 35, but remained at this level thereafter with a tendency to taper off towards later disease stages. These results confirm the high frequency of falling in PD, as almost 50% of patients fell during a short period of only 3 months. The strongest predictor of falling was prior falls in the preceding year, but even subjects without any prior falls had a considerable risk of sustaining future falls. Disease severity was not a good predictor of falls, possibly due to the complex U‐shaped relation with falls. Early identification of the very first fall therefore remains difficult, and new prediction methods must be developed.

Autologous olfactory ensheathing cell transplantation in human paraplegia: a 3-year clinical trial

Olfactory ensheathing cells show promise in preclinical animal models as a cell transplantation therapy for repair of the injured spinal cord. This is a report of a clinical trial of autologous transplantation of olfactory ensheathing cells into the spinal cord in six patients with complete, thoracic paraplegia. We previously reported on the methods of surgery and transplantation and the safety aspects of the trial 1 year after transplantation. Here we address the overall design of the trial and the safety of the procedure, assessed during a period of 3 years following the transplantation surgery. All patients were assessed at entry into the trial and regularly during the period of the trial. Clinical assessments included medical, psychosocial, radiological and neurological, as well as specialized tests of neurological and functional deficits (standard American Spinal Injury Association and Functional Independence Measure assessments). Quantitative test included neurophysiological tests of sensory and motor function below the level of injury. The trial was a Phase I/IIa design whose main aim was to test the feasibility and safety of transplantation of autologous olfactory ensheathing cells into the injured spinal cord in human paraplegia. The design included a control group who did not receive surgery, otherwise closely matched to the transplant recipient group. This group acted as a control for the assessors, who were blind to the treatment status of the patients. The control group also provided the opportunity for preliminary assessment of the efficacy of the transplantation. There were no adverse findings 3 years after autologous transplantation of olfactory ensheathing cells into spinal cords injured at least 2 years prior to transplantation. The magnetic resonance images (MRIs) at 3 years showed no change from preoperative MRIs or intervening MRIs at 1 and 2 years, with no evidence of any tumour of introduced cells and no development of post-traumatic syringomyelia or other adverse radiological findings. There were no significant functional changes in any patients and no neuropathic pain. In one transplant recipient, there was an improvement over 3 segments in light touch and pin prick sensitivity bilaterally, anteriorly and posteriorly. We conclude that transplantation of autologous olfactory ensheathing cells into the injured spinal cord is feasible and is safe up to 3 years of post-implantation, however, this conclusion should be considered preliminary because of the small number of trial patients.

Quantitative assessment of driving performance in Parkinson’s disease

Objectives: The primary aim of this study was to determine how Parkinson’s disease (PD) affects driving performance. It also examined whether changes in driver safety were related to specific clinical disease markers or an individual’s self rating of driving ability. Methods: The driving performance of 25 patients with idiopathic PD and 21 age matched controls was assessed on a standardised open road route by an occupational therapist and driving instructor, to provide overall safety ratings and specific driving error scores. Results: The drivers with PD were rated as significantly less safe (p<0.05) than controls, and more than half of the drivers with PD would not have passed a state based driving test. The driver safety ratings were more strongly related to disease duration (r = −0.60) than to their on time Unified Parkinson’s Disease Rating Scale (r = −0.24). Drivers with PD made significantly more errors than the control group during manoeuvres that involved changing lanes and lane keeping, monitoring their blind spot, reversing, car parking, and traffic light controlled intersections. The driving instructor also had to intervene to avoid an incident significantly more often for drivers with PD than for controls. Interestingly, driver safety ratings were unrelated to an individual’s rating of their own driving performance, and this was the case for all participants. Conclusions: As a group, drivers with PD are less safe to drive than age matched controls. Standard clinical markers cannot reliably predict driver safety. Further studies are required to ascertain whether the identified driving difficulties can be ameliorated.

A multidomain approach for predicting older driver safety under in-traffic road conditions

OBJECTIVES: To identify a battery of tests that predicts safe and unsafe performance on an on‐road assessment of driving.

Pedunculopontine nucleus stimulation improves gait freezing in Parkinson disease.

BACKGROUND Pedunculopontine nucleus (PPN) stimulation is a novel therapy for Parkinson disease. However, controversies remain regarding the clinical application of this new therapy, including patient selection, electrode positioning, and how best to assess outcomes. OBJECTIVE To clarify the clinical application of PPN stimulation in Parkinson disease. METHODS Five consecutive patients with Parkinson disease complicated by severe gait freezing, postural instability, and frequent falls (all persisting even while the patient was on medication) received bilateral stimulation of the mid-lower PPN without costimulation of other brain targets. Outcomes were assessed prospectively over 2 years with gait-specific questionnaires and the Unified Parkinson Disease Rating Scale (part III). RESULTS The primary outcome, the Gait and Falls Questionnaire score, improved significantly with stimulation. Benefits were maintained over 2 years. Unified Parkinson Disease Rating Scale (part III) items assessing gait and posture were relatively insensitive to these treatment effects. Beneficial effects often appeared to outlast stimulation for hours or longer. Thus, single-session on- vs off-stimulation assessments may be susceptible to “delayed washout effects.” Stimulation of the PPN did not change akinesia scores or dopaminergic medication requirements. CONCLUSION Bilateral stimulation of the mid-lower PPN (more caudal than previous reports) without costimulation of other brain targets may be beneficial for the subgroup of patients with Parkinson disease who experience severe gait freezing and postural instability with frequent falls, which persist even while on medication. Choosing appropriate outcome measures and accounting for the possibility of prolonged stimulation washout effects appear to be important for detecting the clinical benefits.

A spatiotemporal analysis of gait freezing and the impact of pedunculopontine nucleus stimulation.

Gait freezing is an episodic arrest of locomotion due to an inability to take normal steps. Pedunculopontine nucleus stimulation is an emerging therapy proposed to improve gait freezing, even where refractory to medication. However, the efficacy and precise effects of pedunculopontine nucleus stimulation on Parkinsonian gait disturbance are not established. The clinical application of this new therapy is controversial and it is unknown if bilateral stimulation is more effective than unilateral. Here, in a double-blinded study using objective spatiotemporal gait analysis, we assessed the impact of unilateral and bilateral pedunculopontine nucleus stimulation on triggered episodes of gait freezing and on background deficits of unconstrained gait in Parkinson’s disease. Under experimental conditions, while OFF medication, Parkinsonian patients with severe gait freezing implanted with pedunculopontine nucleus stimulators below the pontomesencephalic junction were assessed during three conditions; off stimulation, unilateral stimulation and bilateral stimulation. Results were compared to Parkinsonian patients without gait freezing matched for disease severity and healthy controls. Pedunculopontine nucleus stimulation improved objective measures of gait freezing, with bilateral stimulation more effective than unilateral. During unconstrained walking, Parkinsonian patients who experience gait freezing had reduced step length and increased step length variability compared to patients without gait freezing; however, these deficits were unchanged by pedunculopontine nucleus stimulation. Chronic pedunculopontine nucleus stimulation improved Freezing of Gait Questionnaire scores, reflecting a reduction of the freezing encountered in patients’ usual environments and medication states. This study provides objective, double-blinded evidence that in a specific subgroup of Parkinsonian patients, stimulation of a caudal pedunculopontine nucleus region selectively improves gait freezing but not background deficits in step length. Bilateral stimulation was more effective than unilateral.

Risk of Falls, Injurious Falls, and Other Injuries Resulting from Visual Impairment among Older Adults with Age-Related Macular Degeneration

PURPOSE Age-related macular degeneration (AMD) is the leading cause of irreversible visual impairment among older adults. This study explored the relationship between AMD, fall risk, and other injuries and identified visual risk factors for these adverse events. METHODS Participants included 76 community-dwelling individuals with a range of severity of AMD (mean age, 77.0 ± 6.9 years). Baseline assessment included binocular visual acuity, contrast sensitivity, and merged visual fields. Participants completed monthly falls and injury diaries for 1 year after the baseline assessment. RESULTS Overall, 74% of participants reported having either a fall or a non-fall-related injury. Fifty-four percent of participants reported a fall and 30% reported more than one fall; of the 102 falls reported, 63% resulted in an injury. Most occurred outdoors (52%), between late morning and late afternoon (61%) and when navigating on level ground (62%). The most common non-fall-related injuries were lacerations (36%) and collisions with an object (35%). Reduced contrast sensitivity and visual acuity were associated with increased fall rate, after controlling for age, sex, cognitive function, cataract severity, and self-reported physical function. Reduced contrast sensitivity was the only significant predictor of non-fall-related injuries. CONCLUSIONS Among older adults with AMD, increased visual impairment was significantly associated with an increased incidence of falls and other injuries. Reduced contrast sensitivity was significantly associated with both increased rates of falls and other injuries, while reduced visual acuity was only associated with increased fall rate. These findings have important implications for the assessment of visually impaired older adults.

Different cognitive profiles for single compared with recurrent fallers without dementia.

Relationships between self-reported retrospective falls and cognitive measures (executive function, reaction time [RT], processing speed, working memory, visual attention) were examined in a population based sample of older adults (n = 658). Two of the choice RT tests involved inhibiting responses to either targets of a specific color or location with hand and foot responses. Potentially confounding demographic variables, medical conditions, and postural sway were controlled for in logistic regression models, excluding participants with possible cognitive impairment. A factor analysis of cognitive measures extracted factors measuring RT, accuracy and inhibition, and visual search. Single fallers did not differ from nonfallers in terms of health, sway or cognitive function, except that they performed worse on accuracy and inhibition. In contrast, recurrent fallers performed worse than nonfallers on all measures. Results suggest that occasional falls in late life may be associated with subtle age-related changes in the prefrontal cortex leading to failures of executive control, whereas recurrent falling may result from more advanced brain ageing that is associated with generalized cognitive decline.

Predictors of driving assessment outcome in Parkinson's disease

This study evaluated selected clinical and functional tests as predictors of driving safety outcomes in Parkinsons disease (PD) patients. A total of 25 PD patients and 21 age‐matched controls, all regular drivers, underwent neurological evaluation and assessment of cognitive, visual, and motor function and a standardized, on‐road driving assessment. The capacity of the tests to predict pass/fail driving outcomes was determined by selecting a subset with the highest predictive value from each domain and then subjecting these subsets to discriminant function analysis. Accuracy, sensitivity, specificity, and positive and negative predictive values were determined. Three relatively simple tests from the larger battery predicted passes with relatively high sensitivity (PD, 72.7%; controls, 93.8%; both combined, 85.2%); and moderate specificity (PD, 64.3%; controls, 60.0%; both combined. 63.2%). These tests assessed motor performance (Purdue Pegboard test), contrast sensitivity (Pelli–Robson test), and cognitive function (verbal version of Symbol Digit Modalities test). Adding time since diagnosis for the PD group increased sensitivity to 90.9% and specificity to 71.4%. These simple tests confer more objectivity and predictive power to clinical recommendations for driving, they reflect distinct functions that are necessary for safe driving, and they may be especially useful when on‐road assessments are not feasible.

Postural stability and gait among older adults with age-related maculopathy

PURPOSE To assess the postural stability and gait characteristics of adults with age-related maculopathy (ARM) and to identify the visual factors associated with postural stability and gait in this clinical population. METHODS Participants included 80 individuals with a range of severity of ARM (mean age, 77.2 years). Binocular visual function measures included visual acuity, contrast sensitivity, and merged binocular visual fields. Postural stability was assessed on both a firm and a foam surface using center-of-pressure measures derived from a force platform. Forty three of the participants underwent a three-dimensional motion analysis to quantify gait characteristics, including walking velocity, proportion of time spent with both feet in contact with the ground (double-support time), stride length, and step width. RESULTS After adjustment for age, sex, self-reported physical function, and cataract severity, all the vision measures were significantly associated with postural stability on the foam surface, with contrast sensitivity being the strongest correlate. In the analysis of the gait measures, only contrast sensitivity was significantly associated with walking velocity, step width, or stride length, whereas contrast sensitivity and visual field loss were both significantly associated with double-support time. CONCLUSIONS Impaired contrast sensitivity was associated with postural instability, slower walking velocity, increased step width, and reduced stride length. Impairments in either contrast sensitivity or visual fields were associated with increased double-support time. This result suggests that loss of contrast sensitivity and visual fields in patients with ARM can lead to balance and mobility problems.