There is a need to explore non-dopaminergic approaches to treating balance and gait problems in Parkinson’s disease (PD). There is emerging evidence on the role of cholinergic denervation of the pedunculopontine nucleus (PPN) thalamus system and falls in PD. Preliminary clinical trial data suggest that the subgroup of PD patients with frequent falls may be suitable candidates for future cholinergic augmentation clinical trials. Recent controlled clinical trials using methylphenidate have been unable to confirm earlier reports of improved gait in PD. Although progressive deterioration of axial motor symptoms occur with deep brain stimulation of the subthalamic nucleus or globus pallidus interna, new preliminary research suggests that other surgical stimulation sites, such as the PPN, may have a potential benefit on gait and balance impairments in PD. Continuing vigorous exercise and physical fitness should be highly encouraged to patients with PD who are at risk of physical deconditioning and fear of falling, but effective antifall physical therapy interventions remain an unmet clinical need.
Acetylcholine, dopamine, noradrenergic, deep brain stimulation, exercise, falls, mobility, Parkinson’s disease, pedunculopontine nucleus, striatum, substantia nigra
Parkinson’s disease (PD) is a clinical syndrome consisting of a variable combination of the four cardinal features of resting tremor, rigidity, bradykinesia and postural instability.1 Akinesia, defined as inability to initiate movement (e.g. gait ignition failure) or sustain movement (e.g. sudden freezes), is considered by some to be the fifth cardinal feature of PD.2 Most motor features of PD are believed to result mainly from loss of striatal dopamine secondary to the degeneration of dopaminergic neurons of the substantia nigra pars compacta (SNpc).3 The greater the neuronal loss in the SNpc, the lower the striatal dopamine concentration and the more severe the parkinsonian symptoms, particularly bradykinesia.4 The rate of disease progression is highly variable among PD patients. Patients with tremor-predominant disease at onset, for example, tend to progress more slowly than patients with early prominent postural instability and gait disturbances (PIGD).5
Clinical characteristics of parkinsonian locomotor patterns include slow gait and reduced angular excursion of joints such as shoulder, knee and trunk joints.6,7 With disease progression, stooped posture, short steps and shuffling (the latter associated with reduced ground clearance and festination) become more prominent features.7–9 Falls are common in PD. Unlike falls in the general population, which result generally from slipping or tripping incidents, the majority of falls in PD occur during routine walking, stopping, turning and standing up or bending down manoeuvres.10,11 One prospective survey of relatively mildly affected PD patients found that 60 % fell during a six-month period and 33 % had multiple falls in this period.12 Fall risk in PD is a bell-shaped function of disease severity,13 reaching a maximum during Hoehn and Yahr stage 3 and decreasing in later stages as patients become less mobile.14,15 The emergence of postural instability marks the onset of increased risk for severe disability in PD patients as up to 40 % of patients with postural instability have multiple falls which may result in injury, including potentially crippling hip and wrist fractures.16
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The authors have no conflicts of interest to declare.
Nicolaas I Bohnen, Functional Neuroimaging, Cognitive and Mobility Laboratory, Departments of Radiology and Neurology, University of Michigan, 24 Frank Lloyd Wright Drive, Box 362, Ann Arbor, MI 48105-9755, US. E: firstname.lastname@example.org
The authors gratefully acknowledge research support from the National Institutes of Health (NIH) (National Institute of Neurological Disorders and Stroke [NINDS]), the Department of Veterans Affairs, and the Michael J Fox Foundation.
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