There is limited evidence for the treatment of orthostatic hypotension in idiopathic Parkinson's disease. The objective of this study was to determine the efficacy of three treatments (nonpharmacological therapy, fludrocortisone, and domperidone). Phase I assessed the compliance, safety, and efficacy of nonpharmacological measures. Phase II was a double-blind randomized controlled crossover trial of the two medications. Primary outcome measures consisted of the orthostatic domain of the Composite Autonomic Symptom Scale (COMPASS-OD), a clinical global impression of change (CGI), and postural blood pressure testing via bedside sphygmomanometry (Phase I) or tilt table testing (Phase II). For the 17 patients studied, nonpharmacological therapy did not significantly alter any outcome measure. Both medications improved the CGI and COMPASS-OD scores. There was a trend towards reduced blood pressure drop on tilt table testing, with domperidone having a greater effect.

The results suggest anteromedial globus pallidus interna DBS for Tourette's syndrome is an effective and well-tolerated treatment for a subgroup of patients with severe Tourette's syndrome.

We are gradually becoming aware that there is more to Parkinson's disease (PD) than meets the eye. Accumulating evidence has unveiled a disease complexity that has not (yet) been incorporated into ongoing efforts aimed at slowing, halting or reversing the course of PD, likely underlying their lack of success. There is a substantial latency between the actual onset of PD pathology and our ability to confirm diagnosis, during which accumulating structural and functional damage might be too advanced for effective modification or protection. Identification at the earliest stages of the disease course in the absence of Parkinsonism is crucial if we are to intervene when it matters most. Prognostic and therapeutic inferences can only be successful if we are able to accurately predict who is at risk for developing PD and if we can differentiate amongst the considerable clinicopathologic diversity. Biomarkers can greatly improve our identification and differentiation abilities if we are able to disentangle cause and effect.

Background Some people with Parkinson’s disease (PD) report poorer dynamic postural stability following high-frequency deep brain stimulation of the subthalamic nucleus (STN-DBS), which may contribute to an increased falls risk. However, some studies have shown low-frequency (60 Hz) STN-DBS improves clinical measures of postural stability, potentially providing support for this treatment. This double-blind randomised crossover study aimed to investigate the effects of low-frequency STN-DBS compared to high-frequency stimulation on objective measures of gait rhythmicity in people with PD. Methods During high- and low-frequency STN-DBS and while off-medication, participants completed assessments of symptom severity and walking (e.g., Timed Up-and-Go). During comfortable walking, the harmonic ratio, an objective measures of gait rhythmicity, was derived from head- and trunk-mounted accelerometers to provide insight in dynamic postural stability. Lower harmonic ratios represent less rhythmic walking and have discriminated people with PD who experience falls. Linear mixed model analyses were performed on fourteen participants. Results Low-frequency STN-DBS significantly improved medial–lateral and vertical trunk rhythmicity compared to high-frequency. Improvements were independent of electrode location and total electrical energy delivered. No differences were noted between stimulation conditions for temporal gait measures, clinical mobility measures, motor symptom severity or the presence of gait retropulsion. Conclusions This study provides evidence for the acute benefits of low-frequency stimulation for gait outcomes in STN-DBS PD patients, independent of electrode location. However, the perceived benefits of this therapy may be diminished for people who experienced significant tremor pre-operatively, as lower frequencies may cause these symptoms to re-emerge. Trial registration: This study was prospectively registered with the Australian and New Zealand Clinical Trials Registry on 5 June 2018 (ACTRN12618000944235).

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