Bastiaan R. Bloem

Prospective assessment of falls in Parkinson's disease.

Abstract We studied prospectively the epidemiology, clinical impact and prediction of falls in 59 moderately affected patients with Parkinsons disease (PD) (mean UPDRS motor score 31.5; mean age 61 years) and 55 controls (mean age 60 years). At baseline, balance and gait were evaluated extensively. The retropulsion test (response to sudden shoulder pull) was executed first unexpectedly and five more times following prior warning. All persons used standardised scoring forms to document their falls during six months. Thirty patients (50.8 %) and eight controls (14.5 %) fell at least once (relative risk [RR] 6.1; 95 % confidence interval [CI] 2.5–15.1, p < 0.001). Recurrent (≥ 2) falls occurred in 15 patients (25.4 %), but in only two controls (RR 9.0; 95 % CI 2.0–41.7; p=0.001). Recurrent falls were more common among persons taking benzodiazepines (RR 5.0; 95 % CI 1.6–15.5; p < 0.01). Sixty-two percent of the falls in patients caused soft tissue injuries, but no fractures occurred. A fear of future falls was common (45.8 % of patients) and was accompanied by restriction of daily activities (44.1 % of patients). Seventy percent of falls reported by patients were ‘intrinsic’ (due to patient-related factors), but falls in controls were mainly (50 %) ‘extrinsic’ (due to environmental factors). None of the baseline posture and gait variables predicted falls adequately. The first ‘unexpected’ retropulsion test was more often abnormal than all subsequent (predictable) tests. Irrespective of its method of execution, the retropulsion test did not predict falls. A combination of asking for prior falls, disease severity and the Romberg test yielded the best overall diagnostic utility (sensitivity 65 % and specificity 98 %). Recurrent fallers were best predicted by disease severity (RR for Hoehn and Yahr stage 3 was > 100; 95 % CI 3.1–585) and asking for prior falls (RR 5.0; 95 % CI 1.2–20.9). We conclude that falls are common and disabling, even in relatively early stage PD. Recurrent fallers were best predicted by disease severity and presence of prior falls. Strategies to prevent falls in PD should particularly focus at intrinsic (patient-related) factors, such as minimising the use of benzodiazepines.

Freezing of gait: moving forward on a mysterious clinical phenomenon

Freezing of gait (FoG) is a unique and disabling clinical phenomenon characterised by brief episodes of inability to step or by extremely short steps that typically occur on initiating gait or on turning while walking. Patients with FoG, which is a feature of parkinsonian syndromes, show variability in gait metrics between FoG episodes and a substantial reduction in step length with frequent trembling of the legs during FoG episodes. Physiological, functional imaging, and clinical-pathological studies point to disturbances in frontal cortical regions, the basal ganglia, and the midbrain locomotor region as the probable origins of FoG. Medications, deep brain stimulation, and rehabilitation techniques can alleviate symptoms of FoG in some patients, but these treatments lack efficacy in patients with advanced FoG. A better understanding of the phenomenon is needed to aid the development of effective therapeutic strategies.

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.

Evidence-based analysis of physical therapy in Parkinson's disease with recommendations for practice and research†

Physical therapy is often prescribed in Parkinsons disease. To facilitate the uniformity and efficacy of this intervention, we analyzed current evidence and developed practice recommendations. We carried out an evidence‐based literature review. The results were supplemented with clinical expertise and patient values and translated into practice recommendations, developed according to international standards for guideline development. A systematic literature search yielded 6 systematic reviews and 23 randomized controlled trials of moderate methodological quality with sufficient data. Six specific core areas for physical therapy were identified: transfers, posture, reaching and grasping, balance, gait, and physical capacity. We extracted four specific treatment recommendations that were based on evidence from more than two controlled trials: cueing strategies to improve gait; cognitive movement strategies to improve transfers; exercises to improve balance; and training of joint mobility and muscle power to improve physical capacity. These practice recommendations provide a basis for current physical therapy in Parkinsons disease in everyday clinical practice, as well as for future research in this field.

Gender differences in Parkinson's disease

Objective: To investigate gender differences in basic disease characteristics, motor deterioration and nigrostriatal degeneration in Parkinson’s disease (PD). Methods: We studied 253 consecutive PD patients who were not receiving levodopa or dopamine agonists (disease duration ⩽10 years). We investigated the influence of gender and oestrogen status on: (1) age at onset, (2) presenting symptom, (3) severity and progression of motor symptoms (Unified Parkinson’s Disease Rating Scale III (UPDRS-III) scores) and (4) amount and progression of nigrostriatal degeneration ([123I]FP-CIT single photon emission computed tomography measurements). Results: Age at onset was 2.1 years later in women (53.4 years) than in men (51.3 years). In women, age at onset correlated positively with parity, age at menopause and fertile life span. Women more often presented with tremor (67%) than men (48%). Overall, patients presenting with tremor had a 3.6 year higher age at onset and a 38% slower UPDRS-III deterioration. Mean UPDRS-III scores at disease onset were equal for both genders, as was the rate of deterioration. Women had a 16% higher striatal [123I]FP-CIT binding than men at symptom onset and throughout the course of PD. Conclusions: Our results suggest that, in women, the development of symptomatic PD may be delayed by higher physiological striatal dopamine levels, possibly due to the activity of oestrogens. This could explain the epidemiological observations of a lower incidence and higher age at onset in women. Women also presented more often with tremor which, in turn, is associated with milder motor deterioration and striatal degeneration. Taken together, these findings suggest a more benign phenotype in women with PD.

Spatial Remapping of Cortico-striatal Connectivity in Parkinson's Disease

Parkinsons disease (PD) is characterized by striatal dopamine depletion, especially in the posterior putamen. The dense connectivity profile of the striatum suggests that these local impairments may propagate throughout the whole cortico-striatal network. Here we test the effect of striatal dopamine depletion on cortico-striatal network properties by comparing the functional connectivity profile of the posterior putamen, the anterior putamen, and the caudate nucleus between 41 PD patients and 36 matched controls. We used multiple regression analyses of resting-state functional magnetic resonance imaging data to quantify functional connectivity across different networks. Each region had a distinct connectivity profile that was similarly expressed in patients and controls: the posterior putamen was uniquely coupled to cortical motor areas, the anterior putamen to the pre-supplementary motor area and anterior cingulate cortex, and the caudate nucleus to the dorsal prefrontal cortex. Differences between groups were specific to the putamen: although PD patients showed decreased coupling between the posterior putamen and the inferior parietal cortex, this region showed increased functional connectivity with the anterior putamen. We conclude that dopamine depletion in PD leads to a remapping of cerebral connectivity that reduces the spatial segregation between different cortico-striatal loops. These alterations of network properties may underlie abnormal sensorimotor integration in PD.

Neurological gait disorders in elderly people: clinical approach and classification

Gait disorders are common and often devastating companions of ageing, leading to reductions in quality of life and increased mortality. Here, we present a clinically oriented approach to neurological gait disorders in the elderly population. We also draw attention to several exciting scientific developments in this specialty. Our first focus is on the complex and typically multifactorial pathophysiology underlying geriatric gait disorders. An important new insight is the recognition of gait as a complex higher order form of motor behaviour, with prominent and varied effects of mental processes. Another relevant message is that gait disorders are not an unpreventable consequence of ageing, but implicate the presence of underlying diseases that warrant specific diagnostic tests. We next discuss the core clinical features of common geriatric gait disorders and review some bedside tests to assess gait and balance. We conclude by proposing a practical three-step approach to categorise gait disorders and we present a simplified classification system based on clinical signs and symptoms.

Age-dependent variations in the directional sensitivity of balance corrections and compensatory arm movements in man

We investigated the effects of ageing on balance corrections induced by sudden stance perturbations in different directions. Effects were examined in biomechanical and electromyographic (EMG) recordings from a total of 36 healthy subjects divided equally into three age groups (20–34, 35–55 and 60–75 years old). Perturbations consisted of six combinations of support‐surface roll (laterally) and pitch (forward‐backward) each with 7.5 deg amplitude (2 pure pitch, and 4 roll and pitch) delivered randomly. To reduce stimulus predictability further and to investigate scaling effects, perturbations were at either 30 or 60 deg s−1. In the legs, trunk and arms we observed age‐related changes in balance corrections. The changes that appeared in the lower leg responses included smaller stretch reflexes in soleus and larger reflexes in tibialis anterior of the elderly compared with the young. For all perturbation directions, onsets of balance correcting responses in these ankle muscles were delayed by 20–30 ms and initially had smaller amplitudes (between 120–220 ms) in the elderly. This reduced early activity was compensated by increased lower leg activity after 240 ms. These EMG changes were paralleled by comparable differences in ankle torque responses, which were initially (after 160 ms) smaller in the elderly, but subsequently greater (after 280 ms). Findings in the middle‐aged group were generally intermediate between the young and the elderly groups. Comparable results were obtained for the two different stimulus velocities. Stimulus‐induced trunk roll, but not trunk pitch, changed dramatically with increasing age. Young subjects responded with early large roll movements of the trunk in the opposite direction to platform roll. A similarly directed but reduced amplitude of trunk roll was observed in the middle‐aged. The elderly had very little initial roll modulation and also had smaller stretch reflexes in paraspinals. Balance‐correcting responses (over 120–220 ms) in gluteus medius and paraspinals were equally well tuned to roll in the elderly, as in the young, but were reduced in amplitude. Onset latencies were delayed with age in gluteus medius muscles. Following the onset of trunk and hip balance corrections, trunk roll was in the same direction as support‐surface motion for all age groups and resulted in overall trunk roll towards the fall side in the elderly, but not in the young. Protective arm movements also changed with age. Initial arm roll movements were largest in the young, smaller in the middle aged, and smallest in the elderly. Initial arm roll movements were in the same direction as initial trunk motion in the young and middle aged. Thus initial roll arm movements in the elderly were directed oppositely to those in the young. Initial pitch motion of the arms was similar across age groups. Subsequent arm movements were related to the amplitude of deltoid muscle responses which commenced at 100 ms in the young and 20–30 ms later in the elderly. These deltoid muscle responses preceded additional arm roll motion which left the arms directed ‘downhill’ (in the direction of the fall) in the elderly, but ‘uphill’ (to counterbalance motion of the pelvis) in the young. We conclude that increased trunk roll stiffness is a key biomechanical change with age. This interferes with early compensatory trunk movements and leads to trunk displacements in the direction of the impending fall. The reversal of protective arm movements in the elderly may reflect an adaptive strategy to cushion the fall. The uniform delay and amplitude reduction of balance‐correcting responses across many segments (legs, hips and arms) suggests a neurally based alteration in processing times and response modulation with age. Interestingly, the elderly compensated for these ‘early abnormalities’ with enlarged later responses in the legs, but no similar adaptation was noted in the arms and trunk. These changes with age provide an insight into possible mechanisms underlying falls in the elderly.

The clinical utility of posturography.

Postural instability and falls are common and devastating features of ageing and many neurological, visual, vestibular or orthopedic disorders. Current management of these problems is hampered by the subjective and variable nature of the available clinical balance measures. In this narrative review, we discuss the clinical utility of posturography as a more objective and quantitative measure of balance and postural instability, focusing on several areas where clinicians presently experience the greatest difficulties in managing their patients: (a) to make an appropriate differential diagnosis in patients presenting with falls or balance impairment; (b) to reliably identify those subjects who are at risk of falling; (c) to objectively and quantitatively document the outcome of therapeutic interventions; and (d) to gain a better pathophysiological understanding of postural instability and falls, as a basis for the development of improved treatment strategies to prevent falling. In each of these fields, posturography offers several theoretical advantages and, when applied correctly, provides a useful tool to gain a better understanding of pathophysiological mechanisms in patients with balance disorders, at the group level. However, based on the available evidence, none of the existing techniques is currently able to significantly influence the clinical decision making in individual patients. We critically review the shortcomings of posturography as it is presently used, and conclude with several recommendations for future research.

Falls in Parkinson's disease.

Purpose of reviewTo summarize the latest insights into the clinical significance, assessment, pathophysiology and treatment of falls in Parkinsons disease. Recent findingsRecent studies have shown that falls are common in Parkinsons 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 Parkinsons 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 Parkinsons 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 Parkinsons disease. SummaryNo 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 Parkinsons disease.