Infusion of levodopa-carbidopa intestinal gel (LCIG; also designated carbidopa-levodopa enteral suspension) for 16 hours is a standard treatment for patients with advanced Parkinson's disease, and clinical observations suggest that 24-hour LCIG infusion may further reduce symptoms. This review provides practical advice on the management of patients transitioning to 24-hour LCIG infusion. We review available clinical data for 24-hour infusion and discuss adjustments to dosing, recommendations for monitoring, and management of patient concerns, based on our clinical experience. Data from multiple studies suggest that LCIG may improve non-motor symptoms. Although few studies have examined 24-hour LCIG infusion, available data indicate that certain patients may benefit from around-the-clock treatment. Studies of 24-hour LCIG infusion are limited by small sample sizes and open-label study designs, which may hamper translation to clinical practice. In our experience, we have found that patients may benefit from 24-hour infusion when reductions in nocturnal symptoms and improvements to quality of sleep are needed. Levodopa-unresponsive freezing of gait or poorly controlled troublesome dyskinesias may also indicate a patient may benefit from 24-hour infusion. Dose adjustments, especially of the nocturnal rate, are typically necessary and, as with 16-hour infusion, patients should be monitored for autonomic dysfunction; overnight wearing off symptoms; weight changes; fluctuations in plasma levels of vitamins B 6 /B 12 , folate, and homocysteine; changes in sleep patterns; or worsening of hallucinations, delusions, and/or nightmares. Available data and our clinical experience suggest that 24-hour LCIG may be warranted among selected patients who have poorly controlled nocturnal fluctuations or early morning "off" symptoms.

Screening consecutive patients with ischemic stroke with routine Holter monitoring will identify new atrial fibrillation/flutter in approximately one in 17 patients. Older age and type of stroke are strongly associated with increased risk. By carefully selecting the patients, the detection rates could be further increased.

Deep brain stimulation (DBS) surgery has become increasingly utilized in the treatment of advanced Parkinson’s disease. Over the past decade, a number of studies have demonstrated that DBS is superior to best medical management in appropriately selected patients. The primary targets for DBS in Parkinson’s disease include the subthalamic nucleus and the internal segment of the globus pallidus, both of which improve the cardinal motor features in Parkinson’s disease. Recent randomized studies have revealed that both targets are similarly effective in treating the motor symptoms of Parkinson’s disease, but emerging evidence suggests that the globus pallidus may be the preferred target in many patients, based on differences in nonmotor outcomes. Here, we review appropriate patient selection, and the efficacy and safety of DBS therapy in Parkinson’s disease. Best outcomes are achieved if the problems of the individual patient are considered when evaluating surgical candidates and considering whether the subthalamic nucleus or the globus pallidus internus should be targeted.

Background: In advanced Parkinson’s disease (PD), dyskinesias and non-motor symptoms such as sleep dysfunction can significantly impair quality of life, and high-quality management is an unmet need. Objective: To analyze changes in dyskinesia and non-motor symptoms (including sleep) among studies with levodopa-carbidopa intestinal gel (LCIG) in patients with advanced PD. Methods: A comprehensive literature review identified relevant studies examining LCIG efficacy. Outcomes of interest were dyskinesia (UDysRS, UPDRS IV item 32), overall non-motor symptoms (NMSS), mentation/behavior/mood (UPDRS I), and sleep/daytime sleepiness (PDSS-2, ESS). The pooled mean (95% confidence interval) change from baseline per outcome was estimated for each 3-month interval with sufficient data (i.e., reported by≥3 studies) up to 24 months using a random-effects model. Results: Seventeen open-label studies evaluating 1,243 patients with advanced PD were included. All outcomes of interest with sufficient data for meta-analysis showed statistically significant improvement within 6 months of starting LCIG. There were statistically significant improvements in dyskinesia duration as measured by UPDRS IV item 32 at 6 months (–1.10 [–1.69, –0.51] h/day) and 12 months (–1.35 [–2.07, –0.62] h/day). There were statistically and clinically significant improvements in non-motor symptoms as measured by NMSS scores at 3 months (–28.71 [–40.26, –17.15] points). Significant reduction of NMSS burden was maintained through 24 months (–17.61 [–21.52, –13.70] points). UPDRS I scores significantly improved at 3 months (–0.39 [–0.55, –0.22] points). Clinically significant improvements in PDSS-2 and ESS scores were observed at 6 and 12 months in individual studies. Conclusion: Patients with advanced PD receiving LCIG showed significant sustained improvements in the burden of dyskinesia and non-motor symptoms up to 24 months after initiation.

To estimate the impact of carbidopa/levodopa enteral suspension (CLES) on key patient-centered outcomes in patients with advanced Parkinson's disease (PD). Methods: A comprehensive literature review identified relevant studies, from which data were meta-analyzed over 3-month intervals up to 24 months. Patient-centered outcomes of interest included mean (95% CI) changes from baseline (Δ) in quality of life (QoL), measured using PD-specific (PDQ-8, PDQ-39) and generic (EQ-5D) instruments; activities of daily living (ADL), measured in On and Off states using UPDRS Part II; and motor symptoms (i.e., Off time/day and motor examination [measured in On and Off states using UPDRS Part III]). Results: The pooled meta-analysis included data from 26 studies evaluating 1556 patients on CLES. At 3 months, all outcomes showed significant improvement: QoL (ΔPDQ-39 = − 10.26 [-11.54, − 8.97], ΔEQ-5D VAS = 15.42 [12.58, 18.26]); ADL (ΔUPDRS II ON = − 4.32 [-5.63, − 3.01]); motor symptoms (ΔOff time hours/day = − 3.48 [-4.15, − 2.82], ΔUPDRS III ON = − 6.20 [-9.88, − 2.51]). At 24 months, there were statistically significant mean improvements in QoL (ΔPDQ-39 = − 7.74 [-12.40, − 3.07], ΔEQ-5D VAS = 11.18 [6.90, 15.45]) and ADL (ΔUPDRS II OFF = − 3.88 [-5.34, − 2.42]), and Off time (− 4.21 [-5.16, − 3.26] hours/day).Conclusions: Impact of CLES on significantly reducing Off time/day was observed to be rapid and durable (i.e., remained consistent across 24 months). Most QoL and ADL measures showed a consistent pattern of improvement with initiation of treatment and remained significantly improved from baseline at 24 months.