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Neurodegenerative Disease Parkinson’s Disease


Advances in Therapeutic Options for Gait and Balance in Parkinson’s Disease Nicolaas I Bohnen, MD, PhD,1


Roger L Albin, MD,2 Martijn LTM Müller, PhD3 and Kelvin L Chou, MD4


1. Professor, Functional Neuroimaging, Cognitive and Mobility Laboratory, Departments of Radiology and Neurology, University of Michigan, and Veterans Administration, Ann Arbor; 2. Professor, Department of Neurology, University of Michigan, and Veterans Administration, Ann Arbor; 3. Research Investigator, Department of Radiology, University of Michigan; 4. Clinical Associate Professor, Departments of Neurology and Neurosurgery, University of Michigan


Abstract


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.


Keywords


Acetylcholine, dopamine, noradrenergic, deep brain stimulation, exercise, falls, mobility, Parkinson’s disease, pedunculopontine nucleus, striatum, substantia nigra


Disclosure: The authors have no conflicts of interest to declare. Acknowledgments: 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. Received: August 31, 2011 Accepted: October 10, 2011 Citation: US Neurology, 2011;7(2):100–108 Correspondence: Nicolaas I Bohnen, MD, PhD, 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. E: nbohnen@umich.edu


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


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


Falls are common in PD.


Because of the primary basal ganglia involvement in PD, it is often asserted that postural control impairments are mainly attributable to the dopaminergic deficits. The majority of postural control and gait impairments associated with falls are resistant to dopaminergic treatment.17


With disease progression, stooped posture, short steps, and shuffling (the latter associated with reduced ground clearance and festination) become more prominent features.7–9


Unlike falls in the general population, which result generally from slipping 100


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


or tripping incidents, the majority of falls in PD occur during routine walking, stopping, turning, and standing up or bending down maneuvers.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


other features, including temporal parameters (e.g. cadence, swing and stance duration), kinetic abnormalities, and gait variability, are treatment resistant.20,22,23


There is an increasing research effort in exploring non-dopaminergic correlates of gait impairment in PD. © TOUCH BRIEFINGS 2011


While some gait parameters, including stride length, gait velocity, and movement amplitudes, improve with dopaminergic treatment,6,18–21


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