Localizing imbalance in progressive supranuclear palsy

Gait imbalance and falls present a major challenge in neurologic care. Current therapeutics have little to offer for most problems of balance, especially in neurodegenerative disorders like progressive supranuclear palsy (PSP). Frequent falling, a hallmark of PSP, typically develops early and with greater disability than in idiopathic Parkinson disease (PD), in which imbalance is primarily retropulsive rather than multidirectional. The pathologic changes in PSP are intraneuronal aggregates of tau protein (predominantly the H1 haplotype1), but there is little known about the circuitry and neurochemistry of specific motor impairments.2 Fortunately, new insight into the functional anatomy of PSP comes from a report by Zwergal et al.3 in this issue of Neurology ®. Their findings argue for thalamic localization of postural imbalance and falling in PSP. Using controlled multimodal studies to characterize a group of 16 patients with PSP, this report brings together data from the patients' reported frequency of falls, posturography, brain [18F]fluorodeoxyglucose PET scanning, and fMRI. The sophisticated analysis was based primarily on functional connectivity, without evidence from neurotransmitter or electrophysiologic studies. The conclusions should be regarded as tentative, therefore, although suggestive of where therapeutic interventions should be targeted. Next to PD, PSP is the most common parkinsonian syndrome; although clinically heterogeneous, it is …