Prevalence of Dyskinesia and OFF by 30-Minute Intervals Through the Day and Assessment of Daily Episodes of Dyskinesia and OFF: Novel Analyses of Diary Data from Gocovri Pivotal Trials.

BACKGROUND: Parkinson\u27s disease (PD) patients using levodopa commonly develop dyskinesia and OFF episodes that reduce quality of life. OBJECTIVE: Evaluate prevalence of troublesome dyskinesia and OFF through the day, assessed by 30-minute intervals, as well as the mean number and duration of troublesome dyskinesia and OFF episodes, transitions between PD states, and effects of Gocovri® (amantadine) extended release capsules on these episodes. METHODS: Evaluate diary data from pooled Gocovri phase 3, placebo-controlled trials-analyzed for 17 hours following wake-up-at baseline and week 12. RESULTS: Diaries were evaluable for 162 patients. At baseline, 67% of patients woke up OFF, with prevalence decreasing to 13% at 2 hours and then remaining relatively steady at ∼12% (range, 6-17%) across half-hour intervals thereafter. Troublesome dyskinesia prevalence rose steadily from 5% to 24% over the first 2 hours, then fluctuated between 20% and 44% through the rest of the waking day. At baseline, patients experienced a mean of 3.0 daily episodes of troublesome dyskinesia (average duration 2.0 hours each), and 2.2 daily episodes of OFF (average duration 1.1 hour each). At week 12, Gocovri-treated patients showed greater reductions than placebo in troublesome dyskinesia and OFF episodes per day (treatment difference: -1.0 episodes and -0.4 episodes, respectively) and average episode duration (treatment difference: -0.6 hours and -0.3 hours, respectively). Mean duration of individual episodes of ON without troublesome dyskinesia (Good ON) increased by 5.0 hours for Gocovri, compared with 2.0 hours for placebo. Patients taking Gocovri experienced 2.2 fewer transitions between states than patients taking placebo. CONCLUSIONS: Troublesome dyskinesia and OFF occurred in the morning and throughout the waking day. Gocovri-treated patients experienced fewer, shorter episodes of both troublesome dyskinesia and OFF, thereby increasing the duration of continuous Good ON episodes and reducing the frequency of transitions between motor states

How to Manage the Initiation of Apomorphine Therapy Without Antiemetic Pretreatment: A Review of the Literature

Introduction Pretreatment with the antiemetic trimethobenzamide has been recommended practice in the United States (US) to address the risk of nausea and vomiting during initiation of apomorphine treatment. However, trimethobenzamide is no longer being manufactured in the US, and despite the recent update to the US prescribing information, there may be uncertainty regarding how to initiate apomorphine. Methods To better understand why antiemetic pretreatment was recommended and if it is necessary when initiating apomorphine therapy, we performed a literature review of subcutaneous apomorphine therapy initiation with and without antiemetic pretreatment in patients with PD. Results Three studies were identified as providing relevant information on antiemetic prophylaxis with initiation of injectable apomorphine. The first study demonstrated that nausea was significantly more common in patients who received 3-days of trimethobenzamide pretreatment compared with those who did not, while the primary endpoint of second study found no significant effect on the binary incidence of nausea and/or vomiting on Day 1 of apomorphine treatment. In the third study, which used a slow titration scheme for apomorphine, transient nausea was reported in just 23.1% of the antiemetic nonusers. Conclusions Based on the reviewed trials and our clinical experience, we suggest that subcutaneous apomorphine therapy can be initiated using a slow titration scheme without antiemetic pretreatment

Network Influence of the Cerebellum for Predicting DBS Response in Patients with Advanced Parkinson’s Disease

Introduction: Deep brain stimulation (DBS) is a treatment option for reducing motor symptoms in patients with Parkinson’s Disease (PD) when first-line medication becomes ineffective. Existing literature has hypothesized that the clinical outcome of DBS may depend on brain connectivity profiles of the stimulation site to distant brain regions. However, the potential of brain connectivity profiles to predict response to DBS in PD remains unclear. Objective: This study aimed to investigate how changes in structural and functional connectivity may relate to patient response to DBS, through the examination of brain network changes using graph theory. Methods: Ten patients with advanced PD were included in this study. Diffusion tensor imaging (DTI) and resting-state fMRI scans were acquired prior to DBS implantation. Pre-DBS and post-DBS UPDRS-III scores were obtained. Network analysis of the DTI and fMRI scans was performed using GRETNA to compute structural and functional graph theory metrics, respectively. Metrics were correlated with UPDRS-III improvement to identify significant correlations to UPDRS improvement due to DBS. Results: Combined structural and functional graph theory metrics highlighted 32 structures to be significantly correlated with UPDRS-III improvement. Mainly, connections to the cerebellum were found to be significantly correlated with UPDRS-III improvement across several metrics for both structural and functional connectivity. Discussion: This work combined DTI, fMRI, and graph theory analysis to evaluate improvement with DBS. Several imaging biomarkers were identified that are robust predictors for UPDRS-III improvement. This work warrants investigation into the compensatory effect of the cerebellum and other potential biomarkers for identifying DBS candidates

Capturing Initial Understanding and Impressions of Surgical Therapy for Parkinson\u27s Disease

Background: Deep Brain Stimulation (DBS) is an underutilized surgical therapy for Parkinson\u27s Disease (PD). Both physician and patient hesitancies have been described as potential barriers to DBS, but the specifics of patient perceptions of DBS have not been well-characterized in the general PD population. Objective: To characterize the understanding and impressions of surgical therapy in PD patients prior to formal surgical evaluation. Methods: A 30-question survey assessing impressions of surgical therapy for PD and understanding of DBS for PD was administered to PD patients seen at an urban movement disorders clinic. Results: One hundred and two patients completed the survey. When asked if they would undergo a hypothetical risk-free, curative brain surgery for PD, 98 patients responded “yes.” Patients were more agreeable to “reversible,” “minimally-invasive,” and “incisionless” surgery. 51.2% thought DBS is an “effective” treatment for PD, 76.6% thought it was “invasive,” and 18.3% thought it was “reversible.” 45.2% reported fear of being awake during DBS surgery. Regarding costs, 52.4% were concerned that DBS was “very expensive” or “not covered by insurance.” Initial source of information and perceived treatment effectiveness were not associated with concerns about DBS effectiveness or threats to normality. Negative perceptions of past surgery were associated with concerns about DBS altering mood and personality. Conclusion: Overall, patients expressed concerns regarding procedural efficacy, invasiveness, cost, and irreversibility—independent of the original source of information. Future studies are required to allow us to better understand the impact of these initial findings on DBS hesitancy and underutilization

N-Acetyl Cysteine May Support Dopamine Neurons in Parkinson\u27s Disease: Preliminary Clinical and Cell Line Data.

BACKGOUND: The purpose of this study was to assess the biological and clinical effects of n-acetyl-cysteine (NAC) in Parkinson\u27s disease (PD). METHODS: The overarching goal of this pilot study was to generate additional data about potentially protective properties of NAC in PD, using an in vitro and in vivo approach. In preparation for the clinical study we performed a cell tissue culture study with human embryonic stem cell (hESC)-derived midbrain dopamine (mDA) neurons that were treated with rotenone as a model for PD. The primary outcome in the cell tissue cultures was the number of cells that survived the insult with the neurotoxin rotenone. In the clinical study, patients continued their standard of care and were randomized to receive either daily NAC or were a waitlist control. Patients were evaluated before and after 3 months of receiving the NAC with DaTscan to measure dopamine transporter (DAT) binding and the Unified Parkinson\u27s Disease Rating Scale (UPDRS) to measure clinical symptoms. RESULTS: The cell line study showed that NAC exposure resulted in significantly more mDA neurons surviving after exposure to rotenone compared to no NAC, consistent with the protective effects of NAC previously observed. The clinical study showed significantly increased DAT binding in the caudate and putamen (mean increase ranging from 4.4% to 7.8%; p CONCLUSIONS: The results of this preliminary study demonstrate for the first time a potential direct effect of NAC on the dopamine system in PD patients, and this observation may be associated with positive clinical effects. A large-scale clinical trial to test the therapeutic efficacy of NAC in this population and to better elucidate the mechanism of action is warranted. TRIAL REGISTRATION: ClinicalTrials.gov NCT02445651

Victoria's Secret

Vertigo with accompanying unsteady gaitA 34-year old male with acute onset of vertigo accompanied by dizziness and unsteady gait.Bilateral horizontal end-gaze jerk nystagmusScattered, large necrotizing granulomas composed of eosinophils, histiocytes, giant cells within the cerebellum.Surgery; Corticosteroids1. http://www.cdc.gov/ncidod/dpd/parasites/schistosomiasis/factsht_schistosomiasis. 2. Strickland GT, ed. Hunter's Tropical Medicine, 7th ed. Strickland GT and Abdel-Wahab MF. Schistosomiasis. 781-807. Philadelphia: 1991. 3. Ropper AH, Stemmer-Rachamimov A. 31-year-old man with an apparent seizure and a mass in the right parietal lobe. NEJM, 2001: 126-31. 4. Pitella, JEH et al., Tumoral form of cerebral schistosomiasis mansoni. A report of four cases and a review of the literature. Clin Neurology and Neurosurgery, 1996: 15-20. 5. Miller, N., Newman, N., eds. Walsh & Hoyt's Clinical Neuro-Ophthalmology, 5th ed, Vol. 4, Odel J. and Moazami G., Diseases Caused by Helminths, 4485-4492. Baltimore: 1998

Tardive Dyskinesia in Older Persons Taking Antipsychotics

Tardive dyskinesia (TD) is a hyperkinetic movement disorder caused by the use of dopamine receptor-blocking agents (DRBAs), a category of medications that includes first-and second-generation antipsychotics (APs) and agents such as metoclopramide that are used for the treatment of nausea and gastrointestinal dysmotility. While TD can affect people of all ages, older age is associated with increased risk of TD and also with the emergence of TD occurring after shorter treatment durations and lower dosages of DRBAs. TD is characterized by involuntary movements that include the face, limbs, and trunk, and is associated with increased comorbidities, social stigmatization, and impaired physical and mental health. Once present, TD tends to persist despite AP dose adjustment or discontinuation. Even with the use of US Food and Drug Administration (FDA)-approved medications for TD, symptoms may persist. Because the leading hypothesis for the pathophysiology of TD has been dysregulation of dopamine transmission due to treatment with DRBAs, APs that avoid postsynaptic dopamine receptor blockade may provide an alternative therapeutic approach for patients who require an AP. In this review, we discuss the risks, burdens, prevention, and management of TD, with a focus on older people

How to manage the initiation of apomorphine therapy without antiemetic pretreatment: A review of the literature

Introduction: Pretreatment with the antiemetic trimethobenzamide has been recommended practice in the United States (US) to address the risk of nausea and vomiting during initiation of apomorphine treatment. However, trimethobenzamide is no longer being manufactured in the US, and despite the recent update to the US prescribing information, there may be uncertainty regarding how to initiate apomorphine. Methods: To better understand why antiemetic pretreatment was recommended and if it is necessary when initiating apomorphine therapy, we performed a literature review of subcutaneous apomorphine therapy initiation with and without antiemetic pretreatment in patients with PD. Results: Three studies were identified as providing relevant information on antiemetic prophylaxis with initiation of injectable apomorphine. The first study demonstrated that nausea was significantly more common in patients who received 3-days of trimethobenzamide pretreatment compared with those who did not, while the primary endpoint of second study found no significant effect on the binary incidence of nausea and/or vomiting on Day 1 of apomorphine treatment. In the third study, which used a slow titration scheme for apomorphine, transient nausea was reported in just 23.1% of the antiemetic nonusers. Conclusions: Based on the reviewed trials and our clinical experience, we suggest that subcutaneous apomorphine therapy can be initiated using a slow titration scheme without antiemetic pretreatment