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Advances in Therapeutic Options for Gait and Balance in Parkinson’s Disease Conclusions

Gait disorders and postural instability are common in patients with PD and respond poorly to dopaminergic agents effective for other features of PD. Gait and balance impairments in PD probably result from an intricate interplay of multisystem degenerations and neurotransmitter deficiencies extending beyond loss of dopaminergic nigral neurons. We showed recently that cholinergic denervation, especially of the thalamus, rather than the degree of nigrostriatal dopaminergic denervation, is associated with falls in PD. Our results are consistent with a key role for the PPN in the maintenance of balance in humans and with PPN dysfunction/degeneration as a cause of impaired postural control and gait in PD. Other recent evidence suggests that PPN degeneration is associated with akinesia, including gait ignition failure and gait freezing, in PD. Degeneration of cholinergic corticopetal afferents from the basal forebrain complex may play in a role in executive function and attentional deficits contributing to gait and balance dysfunction in PD. Although

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STN DBS in PD patients produces sustained benefits for tremor and bradykinesia, axial motor function continues to decline. Low-frequency DBS of the PPN is emerging as a treatment for postural and gait disorders in PD, although the PPN is a technically challenging target. New lines of research are emerging exploring non-dopaminergic pharmacologic treatments of gait and balance problems in PD. Cholinergic therapies may benefit frequently falling PD patients. Contrary to open-label experiences, a recent placebo-controlled study did not find gait improvements with methylphenidate therapy in PD. Non-pharmacologic and non-surgical approaches to treating mobility problems in PD emphasize the increasing importance of exercise and physical fitness in PD. As comorbid white matter disease is associated with impaired axial symptoms and increased stooped posture in PD, it is possible that aggressive management of vascular or inflammatory risk factors, especially when initiated early in the disease course, could reduce the severity of axial motor dysfunction in PD. n

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