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Background: On-demand treatments can treat OFF episodes in Parkinson's disease, however, there is limited information regarding when to prescribe them., Objective: Develop expert consensus to determine appropriate clinical factors for considering on-demand treatments., Methods: Using a RAND/UCLA modified Delphi panel method, a panel developed consensus on the use of on-demand treatments for OFF episodes., Results: The panel agreed on-demand treatments were appropriate when OFF episodes were associated with greater functional impact and interfered with basic daily activities. The panel also agreed on-demand treatment may be appropriate for patients with morning akinesia and/or delayed ON of first levodopa dose and >1 type of OFF episode (eg, early morning OFF or wearing OFF regardless of frequency)., Conclusions: Experts agreed on-demand treatment is appropriate for many patients with OFF episodes. The greater the functional impact of OFF episodes, the more likely experts agreed that on-demand treatment is appropriate to prescribe., (© 2023 Sunovion Pharmaceuticals Inc. Movement Disorders Clinical Practice published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Background: Parkinson's disease psychosis (PDP) is a common, nonmotor symptom of Parkinson's disease (PD), which may affect up to 60% of patients and is associated with impaired quality of life, increased healthcare costs, and nursing home placement, among other adverse outcomes. Characteristic symptoms of PDP include illusions; visual, auditory, tactile, and olfactory hallucinations; and delusions. PDP symptoms typically progress over its course from being mild, infrequent, and often untroubling to complex, sometimes constant, and potentially highly disturbing. PDP has traditionally been treated with atypical antipsychotics (e.g., clozapine and quetiapine) although these are not approved for this indication and clozapine requires frequent white blood cell count monitoring due to the risk of agranulocytosis. Pimavanserin is a newer atypical antipsychotic with highly selective binding to serotonergic receptors, no evidence for worsening motor symptoms in PD, and no need for white blood cell count monitoring. It is currently the only approved medication indicated for PDP treatment. However, because it was approved relatively recently (2016), clinical experience with pimavanserin is limited. Case Presentations . A wide variety of representative clinical scenarios are presented, each with distinct variables and complications. Issues addressed include distinguishing PDP from similar symptoms caused by other disorders such as dementia, coordinating pimavanserin with other PD medications and with deep brain stimulation, adapting pimavanserin dosing for optimal benefit and tolerability, and recognizing variability of PDP symptoms due to patients' changing life circumstances., Conclusions: These scenarios provide multiple insights regarding PDP management and the role of pimavanserin. Effective treatment of PDP may reduce disturbing symptoms of psychosis, thus improving patient function and quality of life. In addition, effective pharmacotherapy for PDP may also facilitate the use of other medications needed to treat neurological symptoms of PD (e.g., tremor, bradykinesia, and dyskinesia), although they may also have adverse effects that contribute to symptoms of PDP., Competing Interests: Khashayar Dashtipour has received honoraria or payments for consulting, advisory services, or speaking over the past 12 months from AbbVie, Acadia, Adamas, Allergan, Impax, Ipsen, Lundbeck, Merocrine Biosciences, Merz, Sunovion, and Teva. Dr. Dashtipour's institution has received research support over the past 12 months from AbbVie, Acorda, Lundbeck, and US WorldMeds. Fiona Gupta has received honoraria or payments for consulting, advisory services, or speaking over the past 12 months from Abbott, Acadia, Acorda, and Kyowa. Robert A. Hauser has received honoraria or payments for consulting, advisory services, or speaking services over the past 12 months from AbbVie, Acadia, Allergan, AstraZeneca, Biotie Therapeutics, Ceregene, Chelsea Therapeutics, Cleveland Clinic, Eli Lilly, GE Healthcare, Impax Laboratories, Inc., Indus, Ipsen Biopharmaceuticals, Lundbeck, Merck/MSD, Neurocrine, Noven Pharmaceuticals, Pfizer, Straken Pharmaceuticals, Targacept, Teva Neuroscience, Teva Pharmaceutical Industries, Ltd., UCB, UCB Pharma SA, University of Houston, Upsher-Smith Laboratories, US WorldMeds, XenoPort, and Zambon Company SpA. Dr. Hauser's institution has received research support over the past 12 months from Abbott Laboratories, Addex Therapeutics, Allergan, AstraZeneca, Biotie Therapeutics, Chelsea Therapeutics, Civitas, GE Healthcare, Impax Laboratories, Inc., Ipsen Biopharmaceuticals, Merck/MSD, Merz, The Michael J. Fox Foundation for Parkinson's Research, NINDS, Parkinson Study Group, Schering-Plough, Teva Neuroscience, UCB, and Vita-Pharm. Dr. Hauser has received royalties in the past 12 months from the University of South Florida. Cherian A. Karunapuzha has received honoraria or payments for consulting, advisory services, or speaking over the past 12 months from Acadia, Acorda, Adamas, Amneal, Kyowa, Lundbeck, Neurocrine Biosciences, Teva, and US WorldMeds. John C. Morgan has received honoraria or payments for consulting, advisory services, or speaking over the past 12 months from AbbVie, Acadia, Acorda, Adamas, Amneal, Kirin, Kyowa, Lundbeck, Neurocrine Biosciences, and Teva. Dr. Morgan's institution has received research support over the past 12 months from AbbVie, Acorda, Kyowa, Lilly, Lundbeck, Parkinson's Foundation, Pharma2B, Prilenia, PSG, Roche, Sunovion, and US WorldMeds., (Copyright © 2021 Khashayar Dashtipour et al.)

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.

Background: Interventional magnetic resonance imaging (iMRI) guided deep brain stimulation (DBS) for Parkinson's disease (PD) has been shown to be effective. The costs of a dedicated intraoperative MRI may be prohibitive. The procedure can also be performed in a diagnostic scanner, however this presents challenges for utilization of time when the scanner is used both as a diagnostic and an interventional unit. This report outlines our novel methodology for patient selection for implantation in a diagnostic MR scanner, as an attempt to streamline the use of resources. A retrospective review of our outcomes is also presented., Methods: DBS candidacy evaluation included a PD questionnaire-39. Anxiety, age, difficulties in communication and body habitus were factors that were assessed in selecting patients for this technique. Eleven patients underwent iMRI-guided DBS implantation in the subthalamic nucleus. All patients were implanted bilaterally. Unified PD rating scale (UPDRS) part III and L-dopa dose were compared pre- and post-stimulation. A cohort of 11 DBS patients not selected for iMRI-guided DBS were also reported for comparison., Results: For the iMRI-guided patients, mean "Off" UPDRS III score was 47.6 (standard deviation [SD] 8.26). Postoperative "On" medication, "On" stimulation UPDRS III was 13.6 (SD 5.23). Mean preoperative L-dopa dose was 1060 mg (SD 474.3) and mean postoperative L-dopa dose was 320 (SD 298.3)., Conclusion: iMRI-guided DBS is a newly emerging technique for surgical treatment of patients with PD. We present a novel scoring system for patient selection assessing anxiety, age, ability to communicate, and body habitus to identify patients who will be benefited most from this technique.

Dysphagia is common in Parkinson's disease (PD) and causes significant morbidity and mortality. PD dysphagia has usually been explained as dysfunction of central motor control, much like other motor symptoms that are characteristic of the disease. However, PD dysphagia does not correlate with severity of motor symptoms nor does it respond to motor therapies. It is known that PD patients have sensory deficits in the pharynx, and that impaired sensation may contribute to dysphagia. However, the underlying cause of the pharyngeal sensory deficits in PD is not known. We hypothesized that PD dysphagia with sensory deficits may be due to degeneration of the sensory nerve terminals in the upper aerodigestive tract (UAT). We have previously shown that Lewy-type synucleinopathy (LTS) is present in the main pharyngeal sensory nerves of PD patients, but not in controls. In this study, the sensory terminals in UAT mucosa were studied to discern the presence and distribution of LTS. Whole-mount specimens (tongue-pharynx-larynx-upper esophagus) were obtained from 10 deceased human subjects with clinically diagnosed and neuropathologically confirmed PD (five with dysphagia and five without) and four age-matched healthy controls. Samples were taken from six sites and immunostained for phosphorylated α-synuclein (PAS). The results showed the presence of PAS-immunoreactive (PAS-ir) axons in all the PD subjects and in none of the controls. Notably, PD patients with dysphagia had more PAS-ir axons in the regions that are critical for initiating the swallowing reflex. These findings suggest that Lewy pathology affects mucosal sensory axons in specific regions of the UAT and may be related to PD dysphagia.

Data from studies examining lipid peroxidation as a mechanism involved with hyperhomocysteinemia (HHcy)-induced vascular remodeling in patients with occlusive vascular disease have been contradictory. It has not yet been studied in Indians within the context of atherogenesis. Therefore, we measured the levels of homocysteine (Hcy), malondialdehyde (MDA) as a measure of lipid peroxides (LPOs), and total antioxidant status (TAS) in the serum of 167 patients with occlusive vascular disease [coronary artery disease (CAD) = 43; cerebrovascular disease (CVD) = 82; peripheral vascular disease (PVD) = 42]. Each of these groups was further divided into groups of individuals with or without HHcy. In the case of CAD and CVD, patients with HHcy had significantly higher LPOs than those without HHcy (p = 0.009, 0.001, respectively). TAS was significantly lower in CVD patients with HHcy than in those without (p = 0.014). In patients with CAD or CVD, Hcy directly correlated with LPOs (p = 0.002, 0.001, respectively). Lipid peroxidation is a significant mechanism in HHcy-induced vascular remodeling in CAD and CVD, but not in PVD, probably because it is not relevant in thrombosis (38 of 42 patients of PVD had deep-vein thrombosis). To explain the significantly lower TAS in CVD, we hypothesized that CVD patients present very early with grave symptoms, whereas CAD and PVD occur over a longer period of time. Therefore, when CVD presents, TAS is still overwhelmed by HHcy-induced oxidative stress. Hence, adjuvant therapy with antioxidants would benefit patients with CVD.

Coronary artery disease (CAD) affects Indians 5-6 years earlier than in the west, is diffuse and malignant, and poses a heavy burden on India's developing economy. Traditional risk factors have failed to explain this high incidence of premature CAD and hence this study investigated the association of two novel risk biomarkers, cystatin C and small dense LDL (sdLDL) with the presence and severity of CAD. Cystatin C and sdLDL were estimated in 204 CAD patients ≤45 years of age and compared with 161 age-matched healthy controls. The traditional lipid profile parameters, i.e., cholesterol, LDL, HDL, triglycerides, apolipoproteins A1 and B, and Lp(a) were also measured in both groups. Cystatin C was significantly raised and mean LDL particle size significantly reduced in CAD patients as compared to controls. 62.7 % of CAD patients showed pattern B while 37.3 % patients showed pattern A. Of the traditional lipid tests, only HDL and apolipoprotein A1 showed a significant decrease in the CAD group. sdLDL was significantly associated with the severity of CAD, while cystatin C was not. Both cystatin C and sdLDL emerged as independent risk factors, however, of the two, sdLDL was a more sensitive predictor of CAD events. Cystatin C and mean LDL particle size are significantly and independently associated with the presence of CAD events in patients ≤45 years with normal kidney function. Hence, these novel risk biomarkers can be useful tools in reducing the morbidity and mortality associated with CAD in the productive Indian workforce.

A theoretical study of molybdenum and caesium solution in uranium dioxide is carried out. Calculations are performed using the density functional theory with the projector-augmented-wave method as implemented in the Vienna ab initio simulation package (VASP). Correlation effects are taken into account within the DFT+U approach. Molybdenum is preferentially inserted in uranium-oxygen divacancies for understoichiometric urania and uranium vacancies for overstoichiometric urania. The favourable sites for caesium solution are the Schottky defect for understoichiometric urania and U vacancies and U-O divacancies for overstoichiometric urania. Using the stability of many binary and ternary compounds in comparison to soluted atoms, we show that caesium and molybdenum are insoluble in uranium dioxide whatever the stoichiometric regime.

Neurobehavioral changes characterize the clinical presentation of bilateral caudate infarction. We describe an 82-year-old man who presented with a Parkinsonian gait disorder in the absence of behavioral abnormality whose diffusion-weighted imaging demonstrated infarction of the caudate nuclei.