Non-Motor Fluctuations in Parkinson's Disease: Validation of the Non-Motor Fluctuation Assessment Questionnaire.

BACKGROUND: In patients with Parkinson's disease (PD), sleep, mood, cognitive, autonomic, and other non-motor symptoms may fluctuate in a manner similar to motor symptoms. OBJECTIVES: To validate a final version of a patient-rated questionnaire that captures the presence and severity of non-motor fluctuations in levodopa-treated PD patients (NoMoFA). METHODS: We recruited PD subjects from five movement disorders centers across the US and Canada. We assessed the internal consistency, floor and ceiling effects, test-retest reliability, and concurrent validity of NoMoFA. Classical test theory and item response theory methods informed item reduction and Delphi process yielded a final questionnaire. RESULTS: Two hundred subjects and their care-partners participated in the study (age: 66.4 ± 9.6 years; disease duration: 9 ± 5.5 years; median Hoehn and Yahr [H&Y] OFF: 3 [range 1-5]; mean Unified Parkinson's Disease Rating Scale (UPDRS) III ON score: 27.4 ± 14.9). Acceptability of the scale was adequate. There were floor effects in 8/28 items. Cronbach's alpha was 0.894. While eight items had "item-to-total" correlations below the cutoff of 0.4, removing these items did not improve Cronbach's alpha. Test-retest reliability was acceptable (intraclass correlation coefficient [ICC] 0.73; 95% confidence interval, 0.64-0.80). Concurrent validity was adequate with all Spearman's rho values comparing NoMoFA score to other measures of parkinsonian severity showing significance and in the expected direction. A final Delphi panel eliminated one item to avoid redundancy. CONCLUSIONS: The final 27-item self-administered NoMoFA is a valid and reliable questionnaire, capturing both static and fluctuating non-motor symptoms in PD. © 2021 International Parkinson and Movement Disorder Society.

Tardive Dyskinesia: Treatment Update.

PURPOSE OF REVIEW: Tardive dyskinesia (TD) is caused by exposure to medications with dopamine antagonism, mainly antipsychotics. It often distresses individuals, physically and emotionally and affects their quality of life. We evaluated peer-reviewed recently published articles with a goal of providing a critically appraised update on the latest advancements in this field. RECENT FINDINGS: In 2017, FDA approved VMAT2 inhibitors, deutetrabenazine and valbenazine. They have demonstrated efficacy in several class 1 studies. Also there have been update in the evidence-based guidelines for treatment for tardive dyskinesia. Various medication classes are being used for treatment of TD with VMAT2 inhibitors to be first FDA-approved medications. Their use should be tailored to the individual patient. Long-term studies will further guide us in how to optimize treatment, especially in the real-world setting. As clinicians, we need to take into consideration all aspects of symptomatology, etiology, potential side effects of the medications, to find the best possible "match" for our patients.

Adopting a palliative care mindset is an unmet need in Parkinson's disease.

Introduction: Parkinson's disease (PD) affects multiple facets of patients' lives, many of which may not be recognized or addressed by their healthcare team. A growing body of evidence has shown that palliative care improves patients' quality of life with PD; however, little is currently known about how patients with PD perceive palliative care. Methods: An 8-question multiple choice survey was created and given to patients with established care for PD at a movement disorders clinic in a quaternary care center. Patients with less than two years of follow-up or that had atypical features of PD were excluded from the survey. Results: There were 106 respondents to the survey. A third of patients reported having never heard of palliative care and an additional 25% had heard of it but did not know what it was. Eighty-eight percent reported being familiar with or very knowledgeable about hospice, though 50% of respondents did not know the difference between hospice and palliative care. 93% had never been offered either service. 37.7% thought their neurologist should discuss advance care planning early in the course of their disease. Conclusion: Even among established patients with Parkinson's disease in a quaternary center, over half were not familiar with palliative care, and the majority had never been offered palliative or hospice services despite growing evidence that it could improve their quality of life. Additionally, patients would like to be introduced to advanced care planning early in the course of their disease.

End of life care of hospitalized patients with Parkinson disease: a retrospective analysis and brief review.

Background: Towards the end of life (EOL), persons with parkinsonism (PwP) have complex needs and can present with unique palliative care (PC) challenges. There are no widely accepted guidelines to aid neurologists, hospitalists, or PC clinicians in managing the symptoms of PwP at EOL. We examined a population of PwP at EOL, aiming to describe trends of in-hospital management and utilization of PC services. Methods: All PwP admitted to two hospitals during 2018 (N = 727) were examined retrospectively, assessing those who died in hospital or were discharged with hospice (EOL group, N = 35) and comparing them to the main cohort. Their demographics, clinical data, engagement of multidisciplinary and palliative services, code status changes, invasive care, frequency of admissions, and medication administration were assessed. Results: Among the EOL group, 8 expired in hospital, and 27 were discharged to hospice. Forty-six percent of EOL patients received a PC consultation during their admission. The median interval from admission to death was 37 days. Seventy-seven percent had a full code status on admission. Compared to hospice patients, those who expired in hospital had higher rates of invasive procedures and intensive care unit transfers (41% vs. 75%, in both variables), and lower rates of PC involvement (52% vs. 25%). The transition of code status change for the EOL group from Full code to Do Not Resuscitate (DNR) occurred at a median 4-5 days from admission. For patients that passed in the hospital, the median days from transition of code status to death was 0(IQR 0-1). Levodopa dose deviations were frequent in both EOL and non-EOL group, but contraindicated medications were infrequently administered (11% in EOL group vs. 9% in non-EOL group). Conclusion: Our data suggest a low utilization of PC services and delayed discussions of goals of care. More work is needed to raise awareness of inpatient teams managing PwP regarding the unique but common challenges facing PwP with advanced disease. A brief narrative review summarizing the suggested management of symptoms common to hospitalized PwP near EOL is provided.

Delivery models of neuropalliative care.

Drawing its beginnings from end-of-life care, palliative care has developed into a specialized interdisciplinary effort aiming to alleviate distress in all its form, and spanning the whole serious illness trajectory. With this evolution came the inevitable expansion to different sites and modes of care delivery. This section discusses the various models of bringing palliative care to patients with neurologic illness. It begins by distinguishing primary from specialist palliative care, then examines various models of inpatient and outpatient care. Hospital-based models include consultation service and dedicated inpatient units, while outpatient care mainly consists of palliative care specialists embedded in disease-specific clinics. Home-based palliative care and services provided through telemedicine are discussed. Hospice, a model of care often associated with end-of-life palliative care is detailed, together with suggestions on when to consider transitioning to hospice care. It is worth noting that there is not a single best model of palliative care delivery for persons living with neurologic illness. The models discussed in this chapter are complementary not competing and should be adopted by clinicians to fit the needs of patients and caregivers, the resources available in the healthcare system, and based on where patients are in the spectrum of their illness.

Impact of behavioral side effects on the management of Parkinson patients treated with dopamine agonists.

Dopamine agonists are one of the main stay of treatment option for Parkinson disease (PD). Side effects that develop from their use are generally categorized into behavioral and non-behavioral. Behavioral side effects include: impulse control behavior disorder (ICD), psychosis and cognitive impairment. Non-behavioral side effects include: nausea/vomiting, "sleep attacks", leg swelling, weight gain and orthostasis. The aim of this study is to evaluate the clinicians' response to PD patients who developed behavioral side effects from dopamine agonists, in comparison to those patients who developed only non-behavioral side effects. We performed a retrospective chart review of all patients diagnosed with PD over a two year period. Among 313 patients who were on a dopamine agonist, 156 reported side effects. Sixty-five patients reported behavioral (with or without non-behavioral) side effects, while 91 experienced only non-behavioral side effects. Forty-nine out of the 65 patients (75.3%) who experienced behavioral side effects had their dopamine agonist dose decreased compared to 53 out of 91patients (58.2%) who experienced only non-behavioral side effects (Chi square = 4.92, p < 0.05). Patients with behavioral side effects were 3 times more likely have their dose decreased (OR = 3.3; 95%CI = 1.442-7.551; P = 0.005). However, neither taper speed nor the occurrence of dopamine agonist withdrawal syndrome (DAWS) differed between the two groups. Amongst PD patients treated with dopamine agonists, the presence of behavioral side effects independently increased the chance of dopamine agonist dose reduction. Prospective studies are needed to confirm these findings.

Current treatment of tardive dyskinesia.

Tardive dyskinesia (TD) is a common, iatrogenic movement disorder affecting many individuals treated with dopamine-receptor blocking agents (DRBAs). Studying treatment of TD can be complex, as the symptoms can be affected by changes in either dosage or type of DRBA, as well as by the variable natural course of the disease. Historically many pharmacological therapies have been studied in TD, finding varying degrees of treatment success. Most recently, the VMAT2 inhibitors valbenazine and deutetrabenazine were rigorously studied in TD in large, phase III clinical trials, and were shown to be beneficial in this population. In this article, we will review various treatments of TD, including manipulation of the offending agent, VMAT2 inhibitors, other non-VMAT2-inhibiting medications, and non-pharmacological approaches.

Predictors of clinically meaningful change in PDQ-39 in Parkinson's disease.

OBJECTIVE: To determine predictors of clinically meaningful change in Health-Related Quality of Life (HRQL) in patients with Parkinson's disease (PD). BACKGROUND: There is limited literature on longitudinal predictors of change in HRQL in PD. METHODS: Data were collected from the National Parkinson Foundation Quality Improvement Initiative (NPF-QII) registry, a multicenter, longitudinal observational study. HRQL is measured by the Parkinson's Disease Questionnaire-39 (PDQ-39). We calculated the PDQ-39 change between every two consecutive visits and generated binary outcomes using the threshold for clinically meaningful change (previously determined to be 1.6). We used chi-squared tests for discrete and t-test for continuous variables for baseline characteristic comparison between patient groups of interest. Generalized linear mixed models with repeated measures were used for identifying the predictors of whether PDQ-39 outcomes worsen over time. RESULTS: Of 8041 subjects enrolled, 5250 had at least one follow-up visit and were included in the analysis. Subjects were separated into two groups, "worse" and "not worse" based on PDQ-39 change >1.6 across consecutive visits. The "worse" group was more likely to be older (p = 0.001), to have motor fluctuations (p = 0.011), be on cognitive enhancers (p = 0.01), and to have more impaired immediate five-word recall (p = 0.04). The "non-worse" group was more likely to have rest tremor (p = 0.003), and to utilize social work/counseling (p = 0.046). CONCLUSIONS: The majority of predictors of worsening of HRQL are baseline disease and demographic characteristics that are difficult to modify. The positive effect of social service/counseling is intriguing and important to further explore in controlled interventional studies.