Impact of Isolation During the COVID-19 Pandemic on the Patient Burden of Parkinson's Disease: A PMD Alliance Survey.

Purpose: As the COVID-19 pandemic resulted in social restrictions around the globe, this cross-sectional survey aimed to assess the impact of social isolation on self- or proxy-reported symptoms of Parkinson's disease (PD) during the pandemic. Patients and Methods: The survey was distributed among 7109 subscribers of the Parkinson and Movement Disorders Alliance (PMD Alliance) News and Information list and was open only to people with PD (PwP) and care partners (CP, defined as main caregivers of PwP and serving as proxy respondents). No attempt was made to identify PwP and CP pairs. The survey was distributed online using Survey Monkey between 01/06/2021 and 02/27/2021. Respondents were grouped by level of social support from outside of their household during the pandemic (decreased or maintained [ie, the same as pre-pandemic or increased]). Results: Of 7109 invited participants, 718 responded to the survey (response rate 10.1%). PwP (self-reports) accounted for 70.6% of respondents and CP (proxy reports) for 29.4%. Decreased social support from outside of the household during the COVID-19 pandemic (58.5% of all responses) was significantly associated with increases in sadness/depression and anxiety, compared with maintained levels of social support (p < 0.0001 for both comparisons). It was also associated with increased burden of several non-motor (decline in memory, problem solving, or communication, p = 0.0009; new or worsening confusion, p < 0.0001; new or worsening delusions, p = 0.018) and motor PD symptoms. Conclusion: Decline in social support from outside of the household during the COVID-19 pandemic showed a statistically significant and negative association with the burden of mood and non-motor symptoms of PD. These results call for increased vigilance towards non-motor symptoms in PwP experiencing social isolation and highlight the need for stronger provider focus on encouraging PwP and their CPs to build and maintain social connections and engagements.

Adult Abdominal Migraine Improved by OnabotulinumtoxinA Injections.

Abdominal migraine is often regarded as a childhood disorder and less commonly described in adults. However, gastrointestinal symptoms are known to occur to adult migraine patients, and recognition of adult abdominal migraine may facilitate treatment of the recurrent abdominal symptoms and avoidance of unproductive and sometimes invasive therapies. Here, I describe a patient with chronic migraine headaches and recurrent abdominal pain both of which showed sustained improvement after treatment with onabotulinumtoxinA injections.

Fosmetpantotenate Randomized Controlled Trial in Pantothenate Kinase-Associated Neurodegeneration.

BACKGROUND: Pantothenate kinase-associated neurodegeneration (PKAN) currently has no approved treatments. OBJECTIVES: The Fosmetpantotenate Replacement Therapy pivotal trial examined whether treatment with fosmetpantotenate improves PKAN symptoms and stabilizes disease progression. METHODS: This randomized, double-blind, placebo-controlled, multicenter study evaluated fosmetpantotenate, 300 mg oral dose three times daily, versus placebo over a 24-week double-blind period. Patients with pathogenic variants of PANK2, aged 6 to 65 years, with a score ≥6 on the PKAN-Activities of Daily Living (PKAN-ADL) scale were enrolled. Patients were randomized to active (fosmetpantotenate) or placebo treatment, stratified by weight and age. The primary efficacy endpoint was change from baseline at week 24 in PKAN-ADL. RESULTS: Between July 23, 2017, and December 18, 2018, 84 patients were randomized (fosmetpantotenate: n = 41; placebo: n = 43); all 84 patients were included in the analyses. Six patients in the placebo group discontinued treatment; two had worsening dystonia, two had poor compliance, and two died of PKAN-related complications (aspiration during feeding and disease progression with respiratory failure, respectively). Fosmetpantotenate and placebo group PKAN-ADL mean (standard deviation) scores were 28.2 (11.4) and 27.4 (11.5) at baseline, respectively, and were 26.9 (12.5) and 24.5 (11.8) at week 24, respectively. The difference in least square mean (95% confidence interval) at week 24 between fosmetpantotenate and placebo was -0.09 (-1.69 to 1.51; P = 0.9115). The overall incidence of treatment-emergent serious adverse events was similar in the fosmetpantotenate (8/41; 19.5%) and placebo (6/43; 14.0%) groups. CONCLUSIONS: Treatment with fosmetpantotenate was safe but did not improve function assessed by the PKAN-ADL in patients with PKAN. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Two-year clinical outcomes associated with robotic-assisted subthalamic lead implantation in patients with Parkinson's disease.

Few centers have routinely implemented robotic stereotactic systems for deep brain stimulator (DBS) placement. The present study compares clinical outcomes associated with robotic-assisted subthalamic nucleus (STN)-targeted DBS surgery in patients with Parkinson's disease (PD) to those of the traditional frame-based method. A retrospective chart review was performed (February 2013-June 2017). Thirty-three patients were implanted using the Cosman-Roberts-Wells (CRW) frame and 27 patients were implanted using the ROSA robot. Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) or UPDRS part III motor scores and levodopa equivalent daily doses (LEDD) were examined preoperatively and at 6, 12, and 24 months of follow-up. Operative times and complication rates were recorded. For the frame-based group, the reduction in the mean MDS-UPDRS part III motor score compared to baseline was 27% both at 6 and 12 months, and 36.7% at 24 months. For the robotic-assisted group, the reduction in the mean motor score from baseline was 17.6% at 6 months, 19% at 12 months and 21.4% at 24 months. The mean LEDD for the frame-based group decreased by 48.7% at 6 months, 56.7% at 12 months, and 29.7% at 24 months. For the robotic-assisted group, the mean LEDD decreased by 42% at 6 months, 45% at 12 months and 50% at 24 months. There were no significant differences in the mean motor scores and the LEDD reduction between the two groups. Operative times tended to be longer for robotic-assisted DBS surgery. Clinical outcomes associated with robotic-assisted surgery are comparable to those with frame-based surgery.

Assessing and addressing footwear needs in Parkinson's disease-design thinking in neurology.

BACKGROUND: Parkinson's disease (PD) is a neurodegenerative movement disorder that results in a variety of motor deficits such as unsteady gait, bradykinesia, resting tremor, and rigidity. OBJECTIVE: The objective of this study was to quantify and assess the challenges and preferences Parkinson's disease patients have regarding footwear. METHODS: A 13-question survey was designed to assess footwear challenges and preferences among PD patients. A total of 89 PD patients, both male and female, were surveyed in the outpatient setting at UC Irvine during their appointments with the senior author. RESULTS: A majority of the PD patients in our cohort (64%) reported experiencing difficulties wearing shoes on their own. Patients who experienced difficulties wearing shoes were significantly more likely to report having been forced to make changes to their desired outfits (p = 0.0011), choosing not to wear dress shoes due to their discomfort (p = 0.0175), and preferring shoes without laces (p = 0.0 048). CONCLUSIONS: The present study is the first attempt to use a survey to quantify the challenges and preferences reported by PD patients in regard to their usage of footwear. Inspired by our findings, the study team designed a novel dress shoe prototype that may address some of the difficulties and concerns gathered through our survey.

PKG Movement Recording System Use Shows Promise in Routine Clinical Care of Patients With Parkinson's Disease.

Parkinson's disease (PD) is a debilitating, neurodegenerative disorder that affects nearly one million people. It's hallmark signs and symptoms include slow movements, rigidity, tremor, and unstable posture. Additionally, non-motor symptoms such as sleeplessness, depression, cognitive impairment, impulse control behaviors (ICB) have been reported. Today, treatment regimens to modify disease progression do not exist and as such, treatment is focused on symptom relief. Additionally, physicians are challenged to base their diagnoses and treatment plans on unreliable self-reported symptoms, even when used in conjunction to validated assessments such as the Unified Parkinson's Disease Rating Scale (UPDRS) and clinical exams. Wearable technology may provide clinicians objective measures of motor problems to supplement current subjective methods. Global Kinetics Corporation (GKC) has developed a watch-device called the Personal KinetiGraph (PKG) that records movements and provides patients medication dosing reminders. A separate clinician-use report supplies longitudinal motor and event data. The PKG was FDA-cleared in September 2016. We studied 63 PD patients during 85 routine care visits in 2 US academic institutions, evaluating the clinical utility of the PKG. Patients wore a PKG for 6 continuous days before their visit. Next, PKG data was uploaded to produce a report. In clinic, physicians discussed PD symptoms with patients and conducted a motor examination prior to reviewing the PKG report and comparing it to their initial assessments. Lastly, patient, caregiver and physician satisfaction surveys were conducted by each user. Across all visits when patients did not report bradykinesia or dyskinesia, the PKG reported these symptoms (50 and 33% of the time, respectively). The PKG provided insights for treatment plans in 50 (79%) patients across 71 (84%) visits. Physicians found improved patient dialogue in 50 (59%) visits, improved ability to assess treatment impact in 32 (38%) visits, and improved motor assessment in 28 (33%) visits. Patients stated in 82% of responses that they agreed or strongly agreed in PKG training, usability, performance, and satisfaction. In 39% of responses, they also reported a very valuable impact on their care. PKG use in 63 PD patients within our clinical practice showed clinically relevant utility in many areas.

Impact of non-motor symptoms in Parkinson's disease: a PMDAlliance survey.

PURPOSE: Parkinson's disease (PD) is associated with non-motor symptoms (NMS) that can cause progressive disability and impact quality of life of people with PD (PwP) and increase burden on care partners. This survey was designed to evaluate the prevalence, impact, and educational preferences regarding NMS on PwP and their care partners. PATIENTS AND METHODS: A 17-question survey was sent to the total membership of PMDAlliance, a nonprofit organization reaching 3,685 households of PwP. Care partners and other interested individuals could also respond. The survey was conducted using Survey Monkey, an online survey platform, and included distinct questions for respondents with and without NMS. RESULTS: A total of 700 individuals responded to the survey. Of the respondents, 378 (54%) were care partners and 287 (41%) were PwP. About 90% of the respondents reported having experience with NMS in PwP, including sleep problems (84%), cognitive symptoms (76%), anxiety (65%), depression (56%), hallucinations (40%), and delusions (23%). NMS in PwP were reported by more care partners (97%) than PwP (80%). NMS had at least some impact on quality of life for 84% of the respondents; 48% indicated that NMS represented a greater challenge than motor symptoms. Care partners were more likely than PwP to report that NMS were more challenging than motor symptoms (58% vs 32%). Respondents with and without NMS indicated a desire for NMS education. CONCLUSION: This survey underscores the significant impact of NMS on the quality of life of PwP and highlights the need for improved recognition and education about its effects.

Patient and physician perceptions of disease management in Parkinson's disease: results from a US-based multicenter survey.

Background: Clinical care for patients with Parkinson's disease (PD) is complex, and disconnect may exist between patient and physician perceptions of treatment, disease awareness, and impact on quality of life (QoL). Relatively few studies have analyzed patient and physician perspectives of disease management concurrently, and even fewer have compared responses between corresponding patients and their physicians. This study aimed to characterize these aspects and identify opportunities to improve alignment. Methods: This cross-sectional study used an online survey and chart review. Participating physicians completed a profiling survey, followed by patient record forms (PRFs) for their next five patients with PD. Patients completed paper questionnaires. PRFs were matched with patient questionnaires, and patient and physician responses compared. Results: Of 107 participating physicians, 70 completed 350 PRFs. Patients completed 71 questionnaires; 66 were matched to PRFs. From a physician perspective, there was alignment between the motor symptoms that were most bothersome for patients and those that were most discussed (physicians felt tremor was most bothersome for most patients [71%]; 77% of physicians included tremor among top three most discussed), but disconnect between the most bothersome and most discussed nonmotor symptoms (physicians felt fatigue was most bothersome for most patients [35%]; cognitive impairment was the most discussed nonmotor symptom, with 52% of physicians including it in top three most discussed). Patients and physicians reported moderate satisfaction with current PD medication. Patients considered form of delivery more important than did physicians. Physicians showed a strong level of awareness of PD's impact on patient QoL, although validated QoL instruments were not widely used. Physicians were more confident than patients about patients' awareness of support resources for patients with PD. Conclusion: Nonmotor symptoms, form of medication delivery, and awareness of support services are areas where PD physician and patient alignment could be increased to improve outcomes.

Changing the treatment paradigm for Parkinson's disease psychosis with pimavanserin.

Introduction: Parkinson's disease psychosis (PDP) may affect up to 60% of patients with Parkinson's disease over the course of their disease, and is associated with poor prognosis, including increased risks of mortality and nursing home placement. PDP treatments have been limited to off-label use of atypical antipsychotics, most of which pose risks of worsened motor symptoms and other potential adverse events (AEs) due to their dopamine receptor blockade and additional off-target receptor affinities. Pimavanserin is a highly selective 5-HT2A inverse agonist and poses no known risks for worsening of parkinsonism or other off-target receptor AEs. Pimavanserin is the first and only medication approved for PDP treatment. Areas covered: This review covers estimated prevalence, clinical characteristics, diagnostic criteria, and risk factors for PDP; the hypothetical progression of PDP; management of PDP including use of antipsychotics; pharmacology and clinical trial data on pimavanserin; and expert opinion on PDP treatment. The NLM/PubMed database was searched for papers using the search terms of "PDP" AND "treatment" AND "pimavanserin" for the last 10 years. Expert opinion: The recent insights into PDP pathophysiology and approval of the only medication specifically to treat PDP are key advances that should improve the recognition, diagnosis, and management of PDP.

Neurological commentary addressing the article titled "Guidance for switching from off-label antipsychotics to pimavanserin for Parkinson's disease psychosis: an expert consensus".

Parkinson's disease psychosis (PDP) occurs commonly and can comprise the most troubling symptoms among the many that occur with this illness. Prior treatment options for PDP have been limited and unsatisfactory due to uneven efficacy data, burdensome monitoring, and lack of a specific FDA indication coupled with warnings of increased mortality. Pimavanserin, approved for the treatment of PDP by the FDA in 2016, overcomes some of these obstacles, with data proven efficacy and without the frequent monitoring required for clozapine. This presents an opportunity to transition patients with PDP to pimavanserin from older therapies. Black and colleagues provide their thoughtful recommendations on how to achieve this transition to pimavanserin while maintaining symptom control and minimizing disruptions that might occur with a medication change.

Delusional misidentification in Parkinson's disease: report of two cases and a review.

Syndromes of delusional misidentification consist of disordered familiarity and have been reported in diverse diagnoses, including Parkinson's disease. Although the most common delusional misidentification is Capgras syndrome, in which the sufferer believes a familiar person has been replaced by an identical imposter, other forms have been also described. The pathogenesis of delusions of misidentification appears to require dysfunction of or connection to a left cerebral cortical area involved in recognition of familiarity, and also right frontal cortex serving belief evaluation. Two cases of Parkinson's disease with an unusual delusional misidentification, intermetamorphosis, are presented, along with their improvement with pimavanserin, a novel atypical antipsychotic medication.

The Emerging Role of Pimavanserin in the Management of Parkinson's Disease Psychosis.

A panel of experts drawn from neurology, psychiatry, geropsychiatry, geriatrics, and pharmacy representatives of 3 health plans convened in New York City on July 30, 2016, with the objective of sharing opinions, ideas, and information regarding the optimal management of Parkinson's disease psychosis (PDP). Three key points emerged from the discussion: (1) Because of the nature of Parkinson's disease and PDP, finding appropriate treatment can prove challenging; (2) emerging therapies may present an opportunity for effective disease management; and (3) moving forward, provider and patient education regarding PDP and available treatment options is essential for well-managed symptoms and better quality of life. The panel reviewed current practices and formulated recommendations on moving forward in the treatment of PDP. DISCLOSURES: This project and manuscript was funded by ACADIA Pharmaceuticals and developed by Magellan Rx Management. Lopes and Farnum are employees of Magellan Rx Management. Kremens has received consulting/speaker fees from Teva Pharmaceuticals, UCB, Sunovion, Impax, Lundbeck, ACADIA, USWorldMeds, Merz, Acorda, Kyowa, Neurocrine, and GE Healthcare. Pagan reports consulting/speaker fees from Teva Nanoscience, AbbVie, Impax, ACADIA, Medtronic, USWorldMeds, Merz, and Cynapsus and research and educational grants from USWorldMeds, Teva, and Medtronic. Patel has received consultant/speaker fees from ACADIA, Allergen, and Avanir. Alva reports research support from Accera, Allergan, Axovant, Eisai, Neurotrope, Genentech, Intra Cellular, Janssen, Lundbeck, Neurim, Novartis, Otsuka, Roche, Suven, and Trans Tech and consultant/speaker fees from ACADIA, Alkermes, Allergan, Avanir, Janssen, Lundbeck, Merck, Nestle, Otsuka, Sunovion, Takeda, and Vanda. The other authors report no potential conflicts of interest, financial or otherwise.

Frameless Stereotactic Robot-Assisted Subthalamic Nucleus Deep Brain Stimulation: Case Report.

BACKGROUND: Electrode implantation for deep brain stimulation (DBS) can be performed in numerous ways, but the current "gold standard" is the use of frame-based systems for accuracy. Robotic stereotactic procedures, however, have gained increased interest because of their ease of use and reliability, but there could be concern about their safety in the United States as the result of recent lawsuits (e.g., the da Vinci Surgical System). We report the first DBS implantation performed using a robot (ROSA robotic device) approved by Food and Drug Administration for use in North America. CASE DESCRIPTION: A 56-year-old, right-handed woman with a 12-year history of Parkinson disease is described. She was offered bilateral subthalamic nucleus DBS placement to address motor fluctuations and dyskinesias. DBS electrode implantation was implemented successfully with ROSA robotic stereotactic assistance. Using preoperative magnetic resonance imaging scan acquisitions, we targeted the patient's subthalamic nucleus bilaterally. Bone fiducials were placed and intraoperative computed tomography (CT) imaging was obtained. The magnetic resonance imaging and CT were fused, and the patient was registered to the ROSA software. Trajectories were obtained and a microdrive device was fixed to the robotic arm to advance the electrode to the correct location. Electrodes were then placed bilaterally. Intraoperative CT showed good placement with no complications encountered. CONCLUSIONS: The advantages of robotic assistance in stereotactic procedures are as follows: 1) improved accuracy, 2) "arc-less" approach, and 3) minor adjustments can be made in multiple planes to the entry point without adjustment of a frame. The case demonstrates robotic stereotactic assistance viability as an alternative to traditional frame-based or frameless systems in U.S. hospitals.

Clinical utility of DaTscan™ imaging in the evaluation of patients with parkinsonism: a US perspective.

INTRODUCTION: Single photon emission computed tomography (SPECT) with Ioflupane I123 injection (DaTscan™) was approved by the Food and Drug Administration in 2011 for striatal dopamine transporter visualization to assist in the evaluation of adult patients with suspected parkinsonian syndromes. While brain SPECT imaging using DaTscan is a covered service under Medicare policy, there is a lack of consensus on its role in routine clinical practice in the US. Areas covered: To address this issue, an expert group of US-based movement disorders neurologists convened to discuss the clinical utility of DaTscan in movement disorders practices within the US. The group identified and discussed routine clinical scenarios where imaging with DaTscan can provide useful information that may impact management and/or clarify clinical diagnoses. This paper summarizes a consensus reached by the expert group at this meeting. Expert commentary: The major utility of DaTscan imaging is the assistance it provides in distinguishing between nigrostriatal dopaminergic degeneration and non-nigrostriatal degeneration in patients displaying equivocal signs and symptoms of parkinsonism.

The Effect of Gabapentin Enacarbil on Pain Associated with Moderate-to-Severe Primary Restless Legs Syndrome in Adults: Pooled Analyses from Three Randomized Controlled Trials.

BACKGROUND: Adults with moderate-to-severe primary restless legs syndrome (RLS) often experience painful dysesthesias, which may lead to impaired quality of life. OBJECTIVES: The aim of this study was to assess the effects of gabapentin enacarbil (GEn) on pain associated with moderate-to-severe primary RLS in adults. METHODS: Data were pooled from three double-blind, randomized, placebo-controlled, 12-week trials (NCT00298623, NCT00365352, NCT01332305) for adults receiving GEn or placebo once daily. Change in average daily RLS pain score and a combined International Restless Legs Scale (IRLS)-pain response were examined. RESULTS: The modified intention-to-treat population included 671 adults (placebo, n = 244; GEn 600 mg, n = 161; GEn 1200 mg, n = 266). Both GEn doses significantly improved average daily RLS pain score at week 12 (p < 0.001 for GEn 600 mg vs. placebo and GEn 1200 mg vs. placebo). The combined IRLS-pain response subanalysis included 366 patients with a baseline IRLS total score ≥15 and pain score ≥4 (placebo, n = 133; GEn 600 mg, n = 86; GEn 1200 mg, n = 147). Most patients were both IRLS and pain responders (placebo, 40 %; GEn 600 mg, 70 %; GEn 1200 mg, 67 %). Spearman rank correlations between IRLS total and pain score (change from baseline to week 12) were moderate or strong. The most frequent treatment-emergent adverse events were somnolence (placebo, 5 %; GEn 600 mg, 20 %; GEn 1200 mg, 23 %) and dizziness (placebo, 4 %; GEn 600 mg, 13 %; GEn 1200 mg, 22 %). CONCLUSIONS: This post hoc pooled analysis suggests that GEn (600 and 1200 mg) once daily significantly improved pain associated with moderate-to-severe primary RLS in adults; however, the analysis was not powered to detect statistical differences between the two GEn doses. Numerically, more GEn-treated patients had a combined IRLS-pain response than placebo-treated patients.

The safety, tolerability and efficacy of pimavanserin tartrate in the treatment of psychosis in Parkinson's disease.

Parkinson's disease psychosis (PDP) is a common and often very disturbing component of Parkinson's disease (PD). PDP consists of hallucinations that are mainly visual and delusions that are often of a paranoid nature. These symptoms can be the most troubling and disruptive of all the manifestations of Parkinson's disease. Current treatment methods include the reduction of anti-Parkinson's medications, a strategy that may worsen the motor problems the medications are prescribed to alleviate, and the introduction of selected antipsychotic medications that carry with them the potential for troubling side effects and serious consequences. Pimavanserin has been developed and studied in clinical trials to specifically address Parkinson's disease psychosis and has been submitted to the U.S. Food and Drug Administration for its approval for this purpose. If this is granted, we believe the evidence of Pimavanserin efficacy, safety and tolerability will position this medication as the first choice for treatment of Parkinson's disease psychosis.

Parkinson's disease psychosis: symptoms, management, and economic burden.

Parkinson's disease psychosis (PDP) is a costly,debilitating condition that generally develops several years after diagnosis of Parkinson's disease (PD).PD is the second-most common neurodegenerative disease, and it imposes a significant burden on the healthcare system. Non-motor symptoms commonly manifest in PD, contributing to the severity of a patient's disability. The neuropsychiatric symptoms that are common in PD can be a significant source of distress to patients and caregivers. Recent studies have shown that more than 50% of patients with PD will develop psychosis at some time over the course of the disease. The responsibility for caring for a person with PDP frequently falls on family members. Caregiver distress is frequently predicted when patients with PD have symptoms of psychosis.Hallucinations and delusions are independent predictors of nursing home placement for patients with PDP. The authors sought to examine total healthcare expenditures among patients with PDP compared with patients with PD without psychosis.All costs were higher for patients with PDP than for those with PD without psychosis and all-Medicare cohorts, with the highest cost differentials found in long-term care costs ($31,178 for PDP vs $14,461 forPD without psychosis), skilled nursing facility costs($6601 for PDP vs $2067 for PD without psychosis),and inpatient costs ($10,125 for PDP vs $6024 for PD without psychosis). Patients with PDP spent an average of 179 days in long-term care, compared with 83 days for patients with PD without psychosis. As expected, long-term care utilization and expenditures were significantly higher for patients with PDP than for patients with PD without psychosis. Reducing long-term care utilization by patients with PDP may significantly lower the overall economic burden associated with PDP.

Colorectal surgery in Parkinson's disease--outcomes and predictors of mortality.

PURPOSE: Although diseases of the lower gastrointestinal tract are common in patients with Parkinson's disease, there is a paucity of data regarding postoperative outcomes after colorectal surgery. METHODS: The Nationwide Inpatient Sample database (2007-2011) was utilized to analyze outcomes in patients with Parkinson's disease (PD) undergoing colorectal surgery. Main outcomes were risk-adjusted inpatient morbidity, mortality, hospital charge, and length of hospital stay. RESULTS: A total of 6490 patients were identified. Utilization of laparoscopic surgery in Parkinson's patients has progressively increased in frequency over the latest 5 years analyzed. The most common diagnoses were colorectal malignancy (39 %) and intestinal obstruction (20 %). Right hemicolectomy (37 %) and sigmoidectomy (30 %) were the most common operations. Laparoscopy was used in 18 % of Parkinson's patients and most commonly in the elective setting. 54.3 % of Parkinson's patients had emergency surgery compared to 38.6 % in non-Parkinson's. Overall morbidity and mortality were significantly lower after laparoscopic surgery compared to open (20 vs. 25 % and 2.1 vs. 6.6 %, respectively). Length of stay was significantly shorter (OR -1.86; p < 0.01) for laparoscopic operations, but there were no significant differences in risk-adjusted outcomes between laparoscopic and open groups. CONCLUSION: PD patients have high rates of morbidity and mortality after colorectal surgery; this may be because more than half of all patients in this population undergo emergent surgery. The laparoscopic approach appears to have short-term benefits in this patient population.

Effect of prior exposure to dopamine agonists on treatment with gabapentin enacarbil in adults with moderate-to-severe primary restless legs syndrome: pooled analyses from 3 randomized trials.

BACKGROUND: Dopamine agonists (DAs) are a first-line therapy for moderate-to-severe restless legs syndrome (RLS), but these treatments may lead to complications, such as augmentation and impulse control disorders, requiring switching to another therapeutic class. Here we assess efficacy and tolerability of gabapentin enacarbil (GEn) in adults with moderate-to-severe primary RLS, with or without prior DA exposure. METHODS: Data from 3 trials were pooled. Patients were identified as DA-naive or DA-exposed, based on prior treatment with ropinirole, pramipexole, rotigotine, or pergolide mesylate, and the dopamine precursor levodopa. Details on prior treatment duration and dose were unavailable. Patients with a history of augmentation were excluded. Within DA-naive/DA-exposed patients we investigated the co-primary end points from the pivotal trials: mean change from baseline to week 12 in International RLS (IRLS) Rating Scale total score and proportion of responders ("much"/"very much" improved) on the investigator-rated Clinical Global Impression-Improvement (CGI-I) scale. Safety was also assessed. RESULTS: 671 patients were randomized (DA-naive: placebo, n = 194; GEn 600 mg, n = 131; GEn 1200 mg, n = 214; DA-exposed: placebo, n = 50; GEn 600 mg, n = 30; GEn 1200 mg, n = 52). Across treatment arms, no significant differences between DA-naive and DA-exposed subgroups in IRLS Rating Scale total score change from baseline at any visit were seen, except week 1 in the placebo group (-6.1 DA-naive vs -3.4 DA-exposed, P = .020). No significant differences in the odds of CGI-I response at week 12 between DA-naive vs DA-exposed patients in any treatment group were seen; however, with placebo there was a nonsignificant trend toward fewer responders among DA-exposed (34.0%) vs DA-naive (44.3%) patients. Both GEn doses significantly improved the IRLS Rating Scale total score change from baseline and CGI-I response vs placebo, regardless of prior DA exposure. The most common treatment-emergent adverse events were dizziness and somnolence. CONCLUSIONS: Prior DA exposure had no significant effect on efficacy or tolerability of GEn (600 or 1200 mg) in this pooled analysis of adults with moderate-to-severe primary RLS. These data support the use of GEn in DA-exposed and DA-naive patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT00298623, NCT00365352, and NCT01332305.

A synthetic cannabinoid agonist promotes oligodendrogliogenesis during viral encephalitis in rats.

Chronic CNS infection by several families of viruses can produce deficits in prefrontal cortex (PFC) and striatal function. Cannabinoid drugs have been long known for their anti-inflammatory properties and their ability to modulate adult neuro and gliogenesis. Therefore, we explored the effects of systemic administration of the cannabinoid agonist WIN55,212-2(WIN) on prefrontal cortex (PFC) and striatal cytogenesis in a viral model of CNS injury and inflammation based on Borna Disease (BD) virus encephalitis. Active BrdU(+) progenitor populations were significantly decreased 1 week after BrdU labeling in BD rats [p<0.001 compared to uninfected (NL) controls] while less than 5% of BrdU(+) cells colabeled for BDV protein. Systemic WIN (1mg/kg i.p. twice daily×7 days) increased the survival of BrdU(+) cells in striatum (p<0.001) and PFC of BD rats, with differential regulation of labeled oligodendroglia precursors vs microglia/macrophages. WIN increased the percentage of BrdU(+) oligodendrocyte precursor cells and decreased BrdU(+) ED-1-labeled phagocytic cells, without producing pro- or antiviral effects. BDV infection decreased the levels of the endocannabinoid anandamide (AEA) in striatum (p<0.05 compared to NL rats), whereas 2-AG levels were unchanged. Our findings indicate that: 1) viral infection is accompanied by alterations of AEA transmission in the striatum, but new cell protection by WIN appears independent of its effect on endocannabinoid levels; and 2) chronic WIN treatment alters the gliogenic cascades associated with CNS injury, promoting oligodendrocyte survival. Limiting reactive gliogenesis and macrophage activity in favor of oliogodendroglia development has significance for demyelinating diseases. Moreover, the ability of cannabinoids to promote the development of biologically supportive or symbiotic oligodendroglia may generalize to other microglia-driven neurodegenerative syndromes including NeuroAIDS and diseases of aging.