Impact of falls and fear of falling on health-related quality of life in patients with Parkinson's disease.

Postural instability, recurrent falls and fear of falling are common in advanced Parkinson's disease (PD). We examined the impact of fall frequency, fear of falling, balance confidence and objectively measured balance impairment (using Tinetti's Mobility Index) on health-related quality of life (HrQoL) in PD. In 74 subjects HrQoL was assessed using the 39-item Parkinson's disease Quality of Life Questionnaire [PDQ-39]. Patients were interviewed using a validated falls questionnaire, addressing fall history, consequences of falls and fear of falling. Neurological examination included Hoehn and Yahr scale, the Unified Parkinson's disease Rating Scale and Tinetti's Mobility Index. Disease severity, age and gender explained 43% of the differences in HrQoL across patients (R2 = 0.43). The combination of these factors and each of the factors fear of falling, balance confidence and fall frequency lead to 55%, 50% and 45% of explained variation, respectively. The standardised regression coefficients of these risk factors were 0.34 (fear of falling), 0.28 (balance confidence) and 0.13 (fall frequency). This suggests that fear of falling is a more important determinant of HrQoL than actual falling. These results emphasise the importance of addressing fear of falling in the clinical management of PD, and the need for development of strategies to reduce fear of falling in intervention programs.

Postural instability in Parkinson's disease: the adrenergic hypothesis and the locus coeruleus.

Parkinson's disease (PD) is traditionally viewed as a mainly hypodopaminergic syndrome, with symptoms resulting predominantly from loss of dopamine-producing neurons in the substantia nigra. However, while most of the cardinal motor features of PD respond well to dopaminergic therapy, many other features of the disease do not. Balance impairment and the associated risk of falling represent one of the most prominent and potentially disabling features that are typically refractory to dopaminergic treatment. Therefore, it is possible that lesions in nondopaminergic systems contribute to the pathophysiology of postural instability in PD. Such nondopaminergic lesions are well recognized, certainly in advanced stages of PD where postural instability and falls dominate the clinical presentation. However, it remains unclear which of the identified nondopaminergic lesions is specifically responsible for postural instability and balance impairment. In this review, we argue that cell loss in the locus coeruleus and a resultant central norepinephrine deficit are intimately involved in the pathophysiology of postural instability in PD. If proven to be correct, this link between defective noradrenergic neurotransmission and postural instability could have important implications for the future development of new symptomatic treatments aimed to correct postural instability and preventing falls. Studies in the next 5 years could test this hypothesis, using a battery of complementary research techniques, including advanced neuroimaging (structural, functional imaging and nuclear), neurochemical studies of cerebrospinal fluid, post-mortem clinicopathological analyses and detailed clinical balance evaluations supplemented by posturography studies.

Falls and gait disturbances in Huntington's disease.

Falls are common in patients with Huntington's disease, but the incidence, falling circumstances and contributing factors have never been examined. We recorded falls in 45 early to midstage Huntington's disease patients, both retrospectively (12 months) and prospectively (3 months). Fall rates were related to relevant baseline measures, including the Unified Huntington's Disease Rating Scale (UHDRS) and quantitative measures of balance (using angular velocity sensors) and gait (using a pressure-sensitive walkway). Balance and gait measures were compared between patients and 27 healthy age-matched controls. Twenty-seven patients (60%) reported two or more falls in the previous year and were classified as fallers. During prospective follow-up 40% reported at least one fall. A high proportion of falls (72.5%) caused minor injuries. Compared to nonfallers, fallers showed significantly higher scores for chorea, bradykinesia and aggression, as well as lower cognitive scores. Compared to controls, Huntington patients had a decreased gait velocity (1.15 m/s versus 1.45 m/s, P < 0.001) and a decreased stride length (1.29 m versus 1.52 m, P < 0.001). These abnormalities were all significantly greater in fallers compared to nonfallers. In addition, fallers had an increased stride length variability and a significantly greater trunk sway in medio-lateral direction compared to nonfallers. We conclude that falls are common in Huntington's disease. Contributing factors include a combination of "motor" deficits (mainly gait bradykinesia, stride variability and chorea, leading to excessive trunk sway), as well as cognitive decline and perhaps behavioral changes. These factors should be considered as future targets for therapies that aim to reduce falls in Huntington's disease.

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

Recurrent falls are a disabling feature of Parkinson's 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.

The "posture second" strategy: a review of wrong priorities in Parkinson's disease.

Falls are common in Parkinson's disease. It remains difficult to predict these falls, presumably because clinical balance tests assess single components of postural control, whereas everyday fall mechanisms are typically more complicated. A substantial proportion of everyday falls appears to occur while Parkinson patients attempt to perform multiple tasks at the same time. Furthermore, little attention is generally paid to the possible contribution of cognitive impairments to falls. The importance of mental dysfunction is supported by the fact that cognitive loading while walking or balancing can lead to marked deteriorations in postural performance, and there is some evidence to suggest that such "dual tasking" is particularly difficult for elderly persons with dementia or depression. We examined what strategies Parkinson patients used when a basic walking task became increasingly challenging by adding additional tasks (both motor and cognitive). Most patients could perform a simple "dual task" test: simultaneously walking and answering simple questions. However, as the walking task became more complex, patients' performance began to deteriorate. Interestingly, this was reflected not only by failure to answer questions, but also by an increasing number of blocks in motor performance (walking and balancing). This behaviour was different from that of both young and elderly controls, who appeared to sacrifice performance on the cognitive task in order to optimise their gait and balance ("posture first" strategy). Preliminary evidence suggest that impaired multiple task performance is associated with a two-fold increased risk of sustaining falls in daily life. We conclude that Parkinson patients are less inclined than healthy persons to maintain a safe gait. Instead, Parkinson patients use a "posture second" strategy and treat all elements of a complex task with equal priority, which in daily life may go at the expense of maintaining balance and lead to falls.

Falls in Parkinson's disease.

PURPOSE OF REVIEW: To summarize the latest insights into the clinical significance, assessment, pathophysiology and treatment of falls in Parkinson's disease. RECENT FINDINGS: Recent studies have shown that falls are common in Parkinson's disease, even when compared with other fall-prone populations. The clinical impact of falls is considerable, often leading to an incapacitating fear of renewed falls. The associated costs for society are substantial. Clinical assessment often includes the retropulsion test, and recent studies have offered practical recommendations regarding the execution and scoring of this test. Insights into the pathophysiology underlying falls are growing and point to an important role for the loss of inter-segmental flexibility ('stiffness'), which predisposes patients to falls in a backward or medial-lateral direction. New evidence has clarified why Parkinson's disease patients commonly fall during transfers and under 'dual tasking' circumstances. The absence of adequately directed arm movements may explain the relatively high proportion of hip fractures in Parkinson's disease. The importance of freezing of gait as a cause of falls is recognized, and we are beginning to understand the different manifestations of gait freezing. Recent work has defined the contributions of pharmacotherapy, stereotactic neurosurgery, physiotherapy and multidisciplinary interventions in the treatment of postural instability to prevent falls in Parkinson's disease. SUMMARY: No dramatic breakthroughs have occurred during the review period, but new information in various areas may be useful for practising clinicians. Interesting new questions have been raised that should fuel studies of pathophysiological mechanisms, which could help in the development of improved treatment strategies to reduce falls in Parkinson's disease.

Therapeutic options for Huntington's disease.

Huntington's disease (HD) is an autosomal dominant, progressive neurodegenerative disorder. The genetic defect lies in the expansion of a CAG repeat on chromosome 4 and neuropathologically it is characterized by neuronal loss in the striatum. Clinical signs are chorea, impaired voluntary movement, behavioral changes and dementia. Present therapies are limited to these symptoms without any influence on the course of the disease, whereas current pharmacological developments mainly focus on delaying disease progression. This review discusses the present symptomatic treatments and focuses on recent developments of new therapeutic approaches for HD.