Drugs to the Rescue: Comparison of On-Demand Therapies for OFF Symptoms in Parkinson's Disease.

Patients with Parkinson's disease often suffer from OFF symptoms disrupting their daily routines and adding to disabilities. Despite polypharmacy and adjustments to medication schedules, they often do not experience consistent relief from their motor symptoms. As the disease progresses, impaired gastric emptying may evolve, making it even more challenging for dopaminergic drugs to provide consistent results. This review focuses on a group of drugs that have the pharmacokinetic advantage of a much earlier onset of action by virtue of their non-oral routes of absorption. We compare the current marketed options: subcutaneous apomorphine, sublingual apomorphine, and inhaled levodopa. Subcutaneous apomorphine is the speediest to take effect, whereas sublingual apomorphine offers the longest clinical effect. Inhaled levodopa has the most favorable side effect profile among the three options. An inhaled form of apomorphine is currently under development, having passed safety and efficacy studies. Each of these drugs has unique characteristics for the user, including different side effect profiles and onset of action. The best choice for a patient will depend on individual needs and circumstances. In this review, we explore those nuances to allow clinicians to select the best option for their patients.

Hyposmia and apathy in early, de novo Parkinson's disease: Lessons from structural brain connectivity.

INTRODUCTION: The neuroanatomical structures implicated in olfactory and emotional processing overlap significantly. Our understanding of the relationship between hyposmia and apathy, common manifestations of early Parkinson's disease (PD), is inadequate. MATERIALS AND METHODS: We analyzed data on 40 patients with early de-novo idiopathic PD enrolled within 2 years of motor symptom onset in the Parkinson's Progression Markers Initiative (PPMI) study. To be included in the analysis, patients must have smell dysfunction but no apathy at the baseline visit and had completed a diffusion MRI (dMRI) at the baseline visit and at the 48-month follow-up visit. We used the FMRIB Software Library's diffusion tool kit to measure fractional anisotropy (FA) in six regions of interest on dMRI: bilateral anterior corona radiata, left cingulum, left superior corona radiata, genu and body of the corpus callosum. We compared the FA in each region from the dMRI done at the beginning of the study with the follow up studies at 4 years. RESULTS: We found a significant decrease of FA at the bilateral anterior corona radiata, and the genu and body of the corpus callosum comparing baseline scans with follow up images at 4-years after starting the study. CONCLUSION: Structural connectivity changes associated with apathy can be seen early in PD patients with smell dysfunction.

The Effects of Deep Brain Stimulation on Mood and Quality of Life in Parkinson's Disease: A Systematic Review and Meta-Analysis.

Deep brain stimulation (DBS) is extensively used to treat motor and non-motor symptoms in Parkinson's disease (PD). The aim of this study was to investigate the difference between subthalamic (STN) and globus pallidus internus (GPi) DBS on mood and quality of life with reference to minimal clinically important differences (MCID). A systematic literature search for articles published until November 2022 yielded 14 studies meeting the eligibility criteria, with a total of 1,088 patients undergoing STN (n=571) or GPi (n=517) stimulation. Baseline patient and clinical characteristics were comparable between the two groups. Results showed that GPi stimulation demonstrated a greater reduction in the Beck depression inventory (mean difference (MD)=1.68) than STN stimulation (MD=0.84). Hospital anxiety and depression scale showed a 2.69- and 3.48-point decrease by the GPi group in the depression and anxiety categories, respectively. The summary index (SI) of the PD questionnaire depicted a greater improvement in the GPi group from baseline (mean=41.01, 95% CI 34.89, 47.13) to follow-up (mean=30.85, 95% CI 22.08, 39.63) when compared to the STN group (baseline mean=42.43, 95% CI 34.50, 50.37; follow-up mean=34.21, 95% CI 25.43, 42.99). The emotions category also demonstrated a similar trend. However, STN stimulation showed greater reductions in motor symptoms and medication than GPi stimulation. This meta-analysis demonstrated that GPi stimulation seems to offer an advantage over STN stimulation in improving mood and quality of life in PD, but those effects must be further validated by larger studies.

Olfaction and apathy in early idiopathic Parkinson's disease.

BACKGROUND: Apathy remains a disabling symptom in Parkinson's disease (PD) with limited therapeutic success. Processing of emotions and smell share neuroanatomical and evolutionary pathways. OBJECTIVES: To explore the association of apathy with smell dysfunction (SD) in early PD. METHODS: We analyzed patients with de-novo PD, with follow-up of at least 5 years from the Parkinson's Progression Markers Initiative. SD and apathy were defined using University of Pennsylvania Smell Identification Test and MDS-UPDRS part 1A. Odds ratios were calculated between apathy and olfaction groups. Kaplan-Meier survival analysis was grouped by presence/ absence of smell dysfunction. The Log Rank test was used to compare time to apathy. RESULTS: We found no association between presence of apathy in patients with and without SD (OR 1.01 [0.49-2.08]). There was no significant difference between PD patients with and without SD in time to apathy (p = 0.72). CONCLUSIONS: SD does not portend greater risk of apathy in PD.

Adjuvant medical therapy in cervical dystonia after deep brain stimulation: A retrospective analysis.

Background: There is limited information on optimization of symptomatic management of cervical dystonia (CD) after implantation of pallidal deep brain stimulation (DBS). Objectives: To describe the long-term, "real-world" management of CD patients after DBS implantation and the role of reintroduction of pharmacologic and botulinum toxin (BoNT) therapy. Methods: A retrospective analysis of patients with focal cervical or segmental craniocervical dystonia implanted with DBS was conducted. Results: Nine patients were identified with a mean follow-up of 41.7 ± 15.7 months. All patients continued adjuvant oral medication(s) to optimize symptom control post-operatively. Three stopped BoNT and four reduced BoNT dose by an average of 22%. All patients remained on at least one medication used to treat dystonia post-operatively. Conclusion: Optimal symptom control was achieved with DBS combined with either BoNT and/or medication. We suggest utilization of adjuvant therapies such as BoNT and/or medications if DBS monotherapy does not achieve optimal symptom control.

Under pressure: pressure-dependent pontine compression by a dolichoectasia basilar artery, a case report.

Basilar artery dolichoectasia can lead to ischemic stroke through thrombosis of small perforating vessels of the brainstem. Here we report the case of a patient with transient paramedian pontine syndrome in the setting of a hypertensive crisis, finding a dolichoectasia basilar artery compressing on the ventral surface of the pons. The outcome was near-complete resolution of deficits after blood pressure control. We propose increased basilar artery pulse pressure as a novel mechanism of transient compression of the brainstem by a dolichoectasia artery.