Epidemiology and Functional Impact of Early Peripheral Neuropathy Signs in Older Adults from a General Population.

INTRODUCTION: Peripheral neuropathy (PN) becomes more common with increasing life expectancy, but general population prevalence estimates are lacking. We investigated an epidemiological distribution of signs of PN among 2,996 community-dwelling participants in Good Aging in Skåne Study, age 60-97, and their impact on physical and autonomic function. METHODS: Signs of PN were measured with Utah Early Neuropathy Scale (UENS). Associations between UENS and physical tests, pain, and dysautonomic phenomena were calculated for each sex, adjusted for age, with estimated marginal means (EMM) and odds ratios (ORs) in four UENS quantiles (Q1-Q4). RESULTS: Participants in Q4 had worse EMM for: time to complete Timed Up and Go test (Q4-Q1: male 10.8-9.6 s; female 11.7-10.2 s), 15 m Walk test (Q4-Q1: male 11.1-9.9 s; female 11.2-10.4 s), and fewer repetitions in Step test (Q4-Q1: male 15.2-17.0 steps; female 14.5-15.8 steps). Higher OR of failing one-leg balance 60 s test {male 2.5 (confidence interval [CI] 95%: 1.7-3.8); female 2.1 (1.1-3.2)}, Foam Pad Balance test (male 4.6 [CI 95%: 3.2-6.7]; female 1.8 [1.3-2.6]), and lower physical quality of life were seen in Q4 compared to Q1. Participants in Q4 had higher OR for walking aid usage, falls, fear of falling, pain, and urinary incontinence, while in males, higher OR for orthostatic intolerance, fecal incontinence, and constipation. CONCLUSIONS: In a general population, 20-25% of older adults who have highest UENS scores, a sensitive measure of early PN, express slower gait, worse balance, lower quality of life, pain, falls and fear of falling, and autonomic symptoms.

Dyskinesia and FAB score predict future falling in Parkinson's disease.

A growing body of research highlights the importance of cognition for prediction of falls in Parkinson's disease (PD). However, a previously proposed prediction model for future near falls and falls in PD, which includes history of near falls, tandem gait, and retropulsion, was developed without considering cognitive impairment. Therefore, by using a sample of 64 individuals with relatively mild PD and not excluding those with impaired cognition we aimed to externally validate the previously proposed model as well as to explore the value of additional predictors that also consider cognitive impairment. Since this validation study failed to support the proposed model in a PD sample including individuals with impaired global cognition, extended analyses generated a new model including dyskinesia (item 32 of Unified PD Rating Scale) and frontal lobe impairment (Frontal Assessment Battery-FAB) as significant independent predictors for future near falls and falls in PD. The discriminant ability of this new model was acceptable (AUC, 0. 80; 95% CI 0.68-0.91). Replacing the continuous FAB scores by a dichotomized version of FAB with a cut-off score ≤14 yielded slightly lower but still acceptable discriminant ability (AUC, 0. 79; 95% CI 0.68-0.91). Further studies are needed to test our new model and the proposed cut-off score of FAB in additional samples. Taken together, our observations suggest potentially important additions to the evidence base for clinical fall prediction in PD with concomitant cognitive impairment.

Factors associated with fear of falling in people with Parkinson's disease.

BACKGROUND: This study aimed to comprehensibly investigate potential contributing factors to fear of falling (FOF) among people with idiopathic Parkinson's disease (PD). METHODS: The study included 104 people with PD. Mean (SD) age and PD-duration were 68 (9.4) and 5 (4.2) years, respectively, and the participants' PD-symptoms were relatively mild. FOF (the dependent variable) was investigated with the Swedish version of the Falls Efficacy Scale, i.e. FES(S). The first multiple linear regression model replicated a previous study and independent variables targeted: walking difficulties in daily life; freezing of gait; dyskinesia; fatigue; need of help in daily activities; age; PD-duration; history of falls/near falls and pain. Model II included also the following clinically assessed variables: motor symptoms, cognitive functions, gait speed, dual-task difficulties and functional balance performance as well as reactive postural responses. RESULTS: Both regression models showed that the strongest contributing factor to FOF was walking difficulties, i.e. explaining 60% and 64% of the variance in FOF-scores, respectively. Other significant independent variables in both models were needing help from others in daily activities and fatigue. Functional balance was the only clinical variable contributing additional significant information to model I, increasing the explained variance from 66% to 73%. CONCLUSIONS: The results imply that one should primarily target walking difficulties in daily life in order to reduce FOF in people mildly affected by PD. This finding applies even when considering a broad variety of aspects not previously considered in PD-studies targeting FOF. Functional balance performance, dependence in daily activities, and fatigue were also independently associated with FOF, but to a lesser extent. Longitudinal studies are warranted to gain an increased understanding of predictors of FOF in PD and who is at risk of developing a FOF.

Gait Speed Reserve in the general population-based 'Good Aging in Skåne' cohort study-distribution and associated factors.

Gait Speed Reserve (GSR) expresses a difference between fast and comfortable gait speed and may have an impact on everyday functioning. It was also hypothesized as a useful proxy measure of physiological reserve. However, height-normalizing values of GSR and its associated factors have not been evaluated in a general population of older adults. Therefore, we aimed to investigate the distribution of height-normalized GSR (HN-GSR) in an elderly population-based cohort from urban and rural areas (n = 4342) aged 60-93 years and evaluate associated physiological and lifestyle factors. Using linear mixed models, we identified gender and nine modifiable factors as significantly associated with HN-GSR across four age groups. Better handgrip strength, cognition and standing balance, higher physical activity level, larger calf circumference, and less smoking had positive associations with HN-GSR, while female gender, more leg pain, higher weight and, alcohol consumption had opposite effects. The Marginal R2 imply that this model explained 26% of the variance in HN-GSR. Physical activity and handgrip strength varied across age groups in impact on HN-GSR. The differences were however comparatively minor. In this large cohort study of older adults, we proposed for the first time that factors associated with HN-GSR represented multi-domain features that are in line with previous findings reported for GSR. Measuring HN-GSR/GSR may help clinicians identify early physiological impairments or unhealthy lifestyle habits, especially among older women, and may also have safety implications in daily life. Further work is needed to find out if measuring HN-GSR/GSR may be useful in identifying adverse health outcomes and overall physiological reserve.

Diabetic Neuropathy Assessed with Multifrequency Vibrometry Develops Earlier than Nephropathy but Later than Retinopathy.

BACKGROUND: Diabetes is associated with systemic complications. Prevalence of diabetic nephropathy, and retinopathy, in type 1 diabetes mellitus (T1DM) is declining, but it is not known if this is true also for diabetic neuropathy. AIM: To investigate the relationship between large fibre diabetic neuropathy and other diabetic complications. MATERIALS AND METHODS: Neuropathy, defined here as large fibre neuropathy, was assessed by measuring vibration perception thresholds at four different frequencies on the sole of the foot, using a standard VibroSense Meter and/or neuropathic symptoms, in 599 individuals with T1DM. Retinopathy status was graded using the International Clinical Disease Severity Scale. Grade of albuminuria and previous history of any macrovascular complications were registered. RESULTS: Diabetic individuals without retinopathy had similar vibration thresholds as age- and gender-matched control participants without diabetes, whereas those without microalbuminuria had higher thresholds than controls. Two individuals out of 599 (0.3%) had microalbuminuria, but not retinopathy or neuropathy, and 12/134 (9%) without retinopathy had signs of neuropathy. Totally 119/536 (22%) of the patients without microalbuminuria had neuropathy. Vibration thresholds increased with the rising severity of retinopathy and grade of albuminuria. In a multinomial logistic regression analysis, neuropathy was associated with retinopathy (OR 2.96 [1.35-6.49], p=0.007), nephropathy (OR 6.25 [3.21-12.15]; p=6.7×10-8) and macrovascular disease (OR 2.72 [1.50-4.93], p=0.001). CONCLUSIONS: Despite recent changes in the incidence of diabetic complications, the onset of large fibre neuropathy follows that of retinopathy but precedes the onset of nephropathy in T1DM.

Striatal Hand Deformities in Parkinson's Disease: Hand Surgical Perspectives.

Background: The knowledge about striatal hand deformities (SHD) in Parkinson's disease (PD), has recently increased but need more attention due to their early impact on dexterity. The focus of clinical studies has been on the staging of SHD severity and neurological features. However, a hand surgical perspective has not been considered. Objectives: Our purpose was to examine SHD in patients with PD using hand surgical assessment methods and the recommended staging of SHD. Methods: In this observational study, a specialist in neurological physiotherapy examined 100 consecutive PD patients and identified 35 with suspected SHD, who were then examined by two hand surgeons. Their hands were clinically evaluated for severity of SHD, according to a previous proposed staging, focusing on metacarpophalangeal (MCP) joint flexion, presence of intrinsic and extrinsic tightness, as well as other hand deformities. Results: Three kinds of deformities were identified among 35 included patients: surgical diagnoses unrelated to PD (n = 5), SHD (n = 23), and PD related hand deformities with increased extrinsic tightness (n = 10); three of these 10 patients had also contralateral SHD, thus are included in SHD group. In addition to previously described MCP joint flexion, swan neck deformity and z-thumb deformity, we found in most hands finger "clefting," abduction of the little finger and/or an increased intrinsic tightness, indicating pathology of intrinsic muscles of the hand involved in SHD. Conclusions: SHD diagnosed with a modified staging method, including features of intrinsic and extrinsic hand deformities, should be considered in PD to implement early and more accurate treatment.

Longitudinal prediction of falls and near falls frequencies in Parkinson's disease: a prospective cohort study.

INTRODUCTION AND OBJECTIVE: Several prediction models for falls/near falls in Parkinson's disease (PD) have been proposed. However, longitudinal predictors of frequency of falls/near falls are poorly investigated. Therefore, we aimed to identify short- and long-term predictors of the number of falls/near falls in PD. METHODS: A prospective cohort of 58 persons with PD was assessed at baseline (mean age and PD duration, 65 and 3.2 years, respectively) and 3.5 years later. Potential predictors were history of falls and near falls, comfortable gait speed, freezing of gate, dyskinesia, retropulsion, tandem gait (TG), pain, and cognition (Mini-Mental State Exam, MMSE). After each assessment, the participants registered a number of falls/near falls during the following 6 months. Multivariate Poisson regression was used to identify short- and long-term predictors of a number of falls/near falls. RESULTS: Baseline median (q1-q3) motor (UPDRS) and MMSE scores were 10 (6.75-14) and 28.5 (27-29), respectively. History of falls was the only significant short-time predictor [incidence rate ratio (IRR), 15.17] for the number of falls/near falls during 6 months following baseline. Abnormal TG (IRR, 3.77) and lower MMSE scores (IRR, 1.17) were short-term predictors 3.5 years later. Abnormal TG (IRR, 7.79) and lower MMSE scores (IRR, 1.49) at baseline were long-term predictors of the number of falls/near falls 3.5 years later. CONCLUSION: Abnormal TG and MMSE scores predict the number of falls/near falls in short and long term, and may be indicative of disease progression. Our observations provide important additions to the evidence base for clinical fall prediction in PD.

Clinical Usefulness of Retropulsion Tests in Persons with Mild to Moderate Parkinson's Disease.

People with Parkinson's disease (PwPD) have an increased risk for falls and near falls. They have particular difficulties with maintaining balance against an external perturbation, and several retropulsion tests exist. The Unified PD Rating Scale item 30 (UPDRS30) is the most common, involving an expected shoulder pull. Others recommend using an unexpected shoulder pull, e.g., the Nutt Retropulsion Test (NRT). We aimed to evaluate the clinical usefulness of these tests for detecting future fallers. By using two different golden standards related to self-reported prospective falls and near falls over 6 months following two different time points with 3.5 years between, we estimated sensitivity/specificity, Youden index, predictive values, and likelihood ratios for each test. The different time points yielded a different prevalence of falls and near falls, as well as different predictive values. When comparing the performance of the NRT and UPDRS30 for detecting future fallers, we found that the NRT consistently performed better than UPDRS30. However, neither test exhibited optimal performance in terms of predictive values and associated likelihood ratios. Our findings speak against using either of these tests as a single assessment for this purpose and support previous recommendations of using a multifactorial approach when targeting balance problems in PwPD.

The clinical significance of 10-m walk test standardizations in Parkinson's disease.

BACKGROUND: The 10-m walk test (10MWT) is a widely used measure of gait speed in Parkinson's disease (PD). However, it is unclear if different standardizations of its conduct impact test results. AIM OF THE STUDY: We examined the clinical significance of two aspects of the standardization of the 10MWT in mild PD: static vs. dynamic start, and a single vs. repeated trials. Implications for fall prediction were also explored. METHODS: 151 people with PD (mean age and PD duration, 68 and 4 years, respectively) completed the 10MWT in comfortable gait speed with static and dynamic start (two trials each), and gait speed (m/s) was recorded. Participants then registered all prospective falls for 6 months. RESULTS: Absolute mean differences between outcomes from the various test conditions ranged between 0.016 and 0.040 m/s (effect sizes, 0.06-0.14) with high levels of agreement (intra-class correlation coefficients, 0.932-0.987) and small standard errors of measurement (0.032-0.076 m/s). Receiver operating characteristic curves showed similar discriminate abilities for prediction of future falls across conditions (areas under curves, 0.70-0.73). Cut-off points were estimated at 1.1-1.2 m/s. CONCLUSIONS: Different 10MWT standardizations yield very similar results, suggesting that there is no practical need for an acceleration distance or repeated trials when conducting this test in mild PD.

Outcome on Balance and Gait Following Botulinum Toxin Treatment for Striatal Foot in Parkinson's Disease.

BACKGROUND: Striatal foot deformity can shorten the stance phase of gait and impair the ability to stand and walk. Botulinum neurotoxin type A (BoNT A) is a treatment option. However, no previous study has included clinical balance testing in the evaluation of treatment effects. The aim of this study was to evaluate gait and balance in patients with striatal foot deformities and Parkinson's disease (PD) before and after treatment with BoNT A injections. METHOD: The study included 10 patients with PD and striatal foot deformity who visited a neurological clinic. The mean ± standard deviation age and PD-duration was 62.8 ± 8.8 years and 4.9 ± 3.6 years, respectively. Clinical assessment was made before and 4 and 16 weeks after injection and included 5 clinical gait and balance tests. The intensity of distress due to deformities was investigated with a visual analogue scale. Parkinsonian motor status was assessed with the Unified Parkinson's Disease Rating Scale part III (motor part). Based on ordinary clinical examination, electromyography-guided BoNT A injection was given in affected muscles. Clinically effective doses of BoNT A were used. RESULTS: Improvements were observed regarding functional, dynamic, and standing balance as well as intensity of distress at 4 weeks but not at 16 weeks compared with baseline. CONCLUSIONS: BoNT A injection treatment improved gait and balance in patients with PD and striatal foot deformities. Multicenter trials are needed; and, to achieve increased power, a randomized, double-blind controlled design is needed and should focus on the ability of tests to capture subtle changes in gait and balance.

External validation of a 3-step falls prediction model in mild Parkinson's disease.

The 3-step falls prediction model (3-step model) that include history of falls, history of freezing of gait and comfortable gait speed <1.1 m/s was suggested as a clinical fall prediction tool in Parkinson's disease (PD). We aimed to externally validate this model as well as to explore the value of additional predictors in 138 individuals with relatively mild PD. We found the discriminative ability of the 3-step model in identifying fallers to be comparable to previously studies [area under curve (AUC), 0.74; 95 % CI 0.65-0.84] and to be better than that of single predictors (AUC, 0.61-0.69). Extended analyses generated a new model for prediction of falls and near falls (AUC, 0.82; 95 % CI 0.75-0.89) including history of near falls, retropulsion according to the Nutt Retropulsion test (NRT) and tandem gait (TG). This study confirms the value of the 3-step model as a clinical falls prediction tool in relatively mild PD and illustrates that it outperforms the use of single predictors. However, to improve future outcomes, further studies are needed to firmly establish a scoring system and risk categories based on this model. The influence of methodological aspects of data collection also needs to be scrutinized. A new model for prediction of falls and near falls, including history of near falls, TG and retropulsion (NRT) may be considered as an alternative to the 3-step model, but needs to be tested in additional samples before being recommended. Taken together, our observations provide important additions to the evidence base for clinical fall prediction in PD.

Prediction of falls and/or near falls in people with mild Parkinson's disease.

OBJECTIVE: To determine factors associated with future falls and/or near falls in people with mild PD. METHODS: The study included 141 participants with PD. Mean (SD) age and PD-duration were 68 (9.7) and 4 years (3.9), respectively. Their median (q1-q3) UPDRS III score was 13 (8-18). Those >80 years of age, requiring support in standing or unable to understand instructions were excluded. Self-administered questionnaires targeted freezing of gait, turning hesitations, walking difficulties in daily life, fatigue, fear of falling, independence in activities of daily living, dyskinesia, demographics, falls/near falls history, balance problems while dual tasking and pain. Clinical assessments addressed functional balance performance, retropulsion, comfortable gait speed, motor symptoms and cognition. All falls and near falls were subsequently registered in a diary during a six-month period. Risk factors for prospective falls and/or near falls were determined using logistic regression. RESULTS: Sixty-three participants (45%) experienced ≥ 1 fall and/or near fall. Three factors were independent predictors of falls and/or near falls: fear of falling (OR = 1.032, p<0.001) history of near falls (OR = 3.475, p = 0.009) and retropulsion (OR = 2.813, p = 0.035). The strongest contributing factor was fear of falling, followed by a history of near falls and retropulsion. CONCLUSIONS: Fear of falling seems to be an important issue to address already in mild PD as well as asking about prior near falls.