Low-frequency STN-DBS provides acute gait improvements in Parkinson's disease: a double-blinded randomised cross-over feasibility trial.

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).

Perspective: Current Pitfalls in the Search for Future Treatments and Prevention of Parkinson's Disease.

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.

Deep brain stimulation of anteromedial globus pallidus interna for severe Tourette's syndrome.

OBJECTIVE: Multiple anatomical targets for deep brain stimulation (DBS) have been proposed for the treatment of severe Tourette's syndrome. In this open study, the authors evaluated the effectiveness of DBS of the anteromedial globus pallidus interna on tic severity and common comorbidities. METHOD: Eleven patients (eight of them men, mean age=39 years) with severe and medically intractable Tourette's syndrome underwent implantation of Medtronic quadripolar electrodes in the globus pallidus interna bilaterally. The primary outcome measure was the Yale Global Tic Severity Scale. Secondary outcome measures included the Yale-Brown Obsessive Compulsive Scale, the Hamilton Depression Rating Scale, the Gilles de la Tourette Syndrome-Quality of Life Scale, and the Global Assessment of Functioning Scale. Follow-up occurred at 1 month and then at a mean of 14 months after surgery (range=4-30 months). RESULTS: Ten patients (91%) reported improvement in tic severity soon after DBS. Overall, there was a 48% reduction in motor tics and a 56.5% reduction in phonic tics at final follow-up. Six patients (54.5%) had a more than 50% reduction, sustained for at least 3 months, in Yale Global Tic Severity Scale score. Only two patients required ongoing pharmacotherapy for tics after surgery, and patients improved significantly on all secondary measures. One patient did not tolerate DBS and discontinued treatment after 3 months. Greater anxiety in two patients and hardware malfunction in three patients were noteworthy adverse outcomes. CONCLUSIONS: 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.

Nonpharmacological treatment, fludrocortisone, and domperidone for orthostatic hypotension in Parkinson's disease.

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.

Development and utilization of the patient knowledge questionnaire on botulinum toxin use in movement disorders.

Following a pilot study, the 28-item Patient Knowledge Questionnaire on Botulinum Toxin Use in Movement Disorders (PKQ-BMD) was utilized to assess efficacy of current educational tools by comparing scoring of patients to that of the general population, as well as to identify information resources, target demographics for education, and key counseling topics. Of the 109 participants, the number of correct answers was higher in the patient group, while the number of incorrect answers was low in both groups. Education was the only demographic factor which affected the total score. The primary source of patient information was their neurologist, and "adverse effects" was perceived as the most important educational topic. We conclude that the PKQ-BMD is a valuable instrument for knowledge assessment, as well as a tool for developing more effective patient resources.

Teaching people with Parkinson's disease about their medication.

PD is a progressive neurodegenerative disorder affecting an estimated 78,000 Australians. Predominantly it affects older people, although or younger. Medications to treat PD are aimed at controlling symptoms as there is no known cure. A regime of PD medications may involve taking doses at frequent intervals and adverse reactions are common. Education of the person with PD, their close carers and family that covers medications, observational techniques and dealing with side effects, along with unpredictable worsening of PD symptoms, may result in improvement in quality of life. When the person with PD has realistic expectations about PD drug therapy then the ability to cope with the physical disability caused by symptoms may be improved. It is important to educate about any possible interaction with commonly taken drugs including dietary supplements and over-the-counter medication. Before a medication education session, nurse activities should include assessment of the person with PD and their support network, development of an appropriate education plan and subsequent implementation, followed by evaluation. Ongoing nursing support at each clinic visit can provide opportunity for evaluation. An individualised session guided by the principles of adult learning theory may provide a successful tool for use in the education of people with PD as well as healthcare professionals. A large amount of available information and untested educational material does not address the educational needs of people with PD with regard to their medications. There is a need for further research in this area. The effectiveness of a one-on-one educational session about PD medication supported by printed, individualised PD medication information may provide more appropriate education and lead to improved quality of life. It is the focus of a planned research study.