Setting the clinical context to non-motor symptoms reflected by Park-pain, Park-sleep, and Park-autonomic subtypes of Parkinson's disease.

Non-motor symptoms (NMS) of Parkinson's disease (PD) are well described in both clinical practice and the literature, enabling their management and enhancing our understanding of PD. NMS can dominate the clinical pictures and NMS subtypes have recently been proposed, initially based on clinical observations, and later confirmed in data driven analyses of large datasets and in biomarker-based studies. In this chapter, we provide an update on what is known about three common subtypes of NMS in PD. The pain (Park-pain), sleep dysfunction (Park-sleep), and autonomic dysfunction (Park-autonomic), providing an overview of their individual classification, clinical manifestation, pathophysiology, diagnosis, and potential treatments.

SARS-CoV-2 and Parkinson's Disease: A Review of Where We Are Now.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), has been discussed in the context of Parkinson's disease (PD) over the last three years. Now that we are entering the long-term phase of this pandemic, we are intrigued to look back and see how and why the community of patients with PD was impacted and what knowledge we have collected so far. The relationship between COVID-19 and PD is likely multifactorial in nature. Similar to other systemic infections, a probable worsening of PD symptoms secondary to COVID-19, either transient or persistent (long COVID), has been demonstrated, while the COVID-19-related mortality of PD patients may be increased compared to the general population. These observations could be attributed to direct or indirect damage from SARS-CoV-2 in the central nervous system (CNS) or could result from general infection-related parameters (e.g., hospitalization or drugs) and the sequelae of the COVID-19 pandemic (e.g., quarantine). A growing number of cases of new-onset parkinsonism or PD following SARS-CoV-2 infection have been reported, either closely (post-infectious) or remotely (para-infectious) after a COVID-19 diagnosis, although such a link remains hypothetical. The pathophysiological substrate of these phenomena remains elusive; however, research studies, particularly pathology studies, have suggested various COVID-19-induced degenerative changes with potential associations with PD/parkinsonism. We review the literature to date for answers considering the relationship between SARS-CoV-2 infection and PD/parkinsonism, examining pathophysiology, clinical manifestations, vaccination, and future directions.

The Park Sleep subtype in Parkinson's disease: from concept to clinic.

INTRODUCTION: The heterogeneity of Parkinson's disease (PD) is evident from descriptions of non-motor (NMS) subtypes and Park Sleep, originally identified by Sauerbier et al. 2016, is one such clinical subtype associated with the predominant clinical presentation of sleep dysfunctions including excessive daytime sleepiness (EDS), along with insomnia. AREAS COVERED: A literature search was conducted using the PubMed, Medline, Embase, and Web of Science databases, accessed between 1 February 2023 and 28 March 2023. In this review, we describe the clinical subtype of Park Sleep and related 'tests' ranging from polysomnography to investigational neuromelanin MRI brain scans and some tissue-based biological markers. EXPERT OPINION: Cholinergic, noradrenergic, and serotonergic systems are dominantly affected in PD. Park Sleep subtype is hypothesized to be associated primarily with serotonergic deficit, clinically manifesting as somnolence and narcoleptic events (sleep attacks), with or without rapid eye movement behavior disorder (RBD). In clinic, Park Sleep recognition may drive lifestyle changes (e.g. driving) along with therapy adjustments as Park Sleep patients may be sensitive to dopamine D3 active agonists, such as ropinirole and pramipexole. Specific dashboard scores based personalized management options need to be implemented and include pharmacological, non-pharmacological, and lifestyle linked advice.

Chaudhuri's Dashboard of Vitals in Parkinson's syndrome: an unmet need underpinned by real life clinical tests.

We have recently published the notion of the "vitals" of Parkinson's, a conglomeration of signs and symptoms, largely nonmotor, that must not be missed and yet often not considered in neurological consultations, with considerable societal and personal detrimental consequences. This "dashboard," termed the Chaudhuri's vitals of Parkinson's, are summarized as 5 key vital symptoms or signs and comprise of (a) motor, (b) nonmotor, (c) visual, gut, and oral health, (d) bone health and falls, and finally (e) comorbidities, comedication, and dopamine agonist side effects, such as impulse control disorders. Additionally, not addressing the vitals also may reflect inadequate management strategies, leading to worsening quality of life and diminished wellness, a new concept for people with Parkinson's. In this paper, we discuss possible, simple to use, and clinically relevant tests that can be used to monitor the status of these vitals, so that these can be incorporated into clinical practice. We also use the term Parkinson's syndrome to describe Parkinson's disease, as the term "disease" is now abandoned in many countries, such as the U.K., reflecting the heterogeneity of Parkinson's, which is now considered by many as a syndrome.

The Dashboard Vitals of Parkinson's: Not to Be Missed Yet an Unmet Need.

The vitals of Parkinson's disease (PD) address the often-ignored symptoms, which are considered either peripheral to the central core of motor symptoms of PD or secondary symptoms, which, nevertheless, have a key role in the quality of life (QoL) and wellness of people with Parkinson's (PwP) [...].

Improving the Delivery of Levodopa in Parkinson's Disease: A Review of Approved and Emerging Therapies.

Levodopa is the most effective drug for the treatment of Parkinson's disease, but its use as an oral medication is complicated by its erratic absorption, extensive metabolism and short plasma half-life. On long-term use and with disease progression, there is a high incidence of motor and non-motor complications, which remain a major clinical and research challenge. It is widely accepted that levodopa needs to be administered using formulations that result in good and consistent bioavailability and the physiologically relevant and continuous formation of dopamine in the brain to maximise its efficacy while avoiding and reversing 'wearing off' and dyskinesia. However, the physicochemical properties of levodopa along with its pharmacokinetic and pharmacodynamic profile make it difficult to deliver the drug in a manner that fulfils these criteria. In this review, we examine the problems associated with the administration of levodopa in Parkinson's disease and how the use of novel technologies and delivery devices is leading to a more consistent and sustained levodopa delivery with the aim of controlling motor function as well as non-motor symptoms.

Do medical students studying in the United Kingdom have an adequate factual knowledge of basic life support?

BACKGROUND: Healthcare professionals have a duty to maintain basic life support (BLS) skills. This study aims to evaluate medical students' factual knowledge of BLS and the training they receive. METHODS: A cross-sectional, closed-response questionnaire was distributed to the first- and fourth-year students studying at institutions in the United Kingdom. The paper questionnaire sought to quantify respondent's previous BLS training, factual knowledge of the BLS algorithm using five multiple choice questions (MCQs), and valuate their desire for further BLS training. Students received 1 point for each correctly identified answer to the 5 MCQ's. RESULTS: A total of 3,732 complete responses were received from 21 medical schools. Eighty percent (n=2,999) of students completed a BLS course as part of their undergraduate medical studies. There was a significant difference (P<0.001) in the percentage of the fourth-year students selecting the correct answer in all the MCQ's compared to the first-year students except in identifying the correct depth of compressions required during CPR (P=0.095). Overall 10.3% (95% CI 9.9% to 10.7%) of respondents correctly identified the answer to 5 MCQ's on BLS 9% of the first-year students (n=194) and 12% of the fourth-year students (n=190). On an institutional level the proportion of students answering all MCQ's correctly ranged from 2% to 54% at different universities. Eighty-one percent of students (n=3,031) wished for more BLS training in their curriculum. CONCLUSION: Factual knowledge of BLS is poor among medical students in the UK. There is a disparity in standards of knowledge across institutions and respondents indicating that they would like more training.

Rotigotine transdermal patch and sleep in Parkinson's disease: where are we now?

A wide range of sleep dysfunction complicates Parkinson's disease during its course from prodromal to palliative stage. It is now increasingly acknowledged that sleep disturbances are thus integral to the disease and pose a significant burden impacting on quality of life of patients. Sleep fragmentation, restless legs syndrome, nocturia, and nocturnal pain are regarded as one of the main components of night-time sleep dysfunction with possible secondary impact on cognition and well-being. The role of dopaminergic therapies, particularly using a continuous drug delivery strategy in managing some of these sleep issues, have been reported but the overall concept remains unclear. This review provides an overview of several aspects of night-time sleep dysfunction in Parkinson's disease and describes all available published open-label and blinded studies that investigated the use of rotigotine transdermal patch targeting sleep. Blinded studies have suggested beneficial effects of rotigotine transdermal patch on maintenance insomnia and restless legs syndrome in Parkinson's disease patients. Open-label studies support these observations and also suggest beneficial effects on nocturia and nocturnal pain.

Nonmotor Subtyping in Parkinson's Disease.

Nonmotor symptoms are integral to Parkinson's disease. Several subtypes dominated by specific nonmotor symptoms have emerged. In this chapter, the rationale behind nonmotor subtyping and currently proposed nonmotor subgroups within Parkinson's disease based on data-driven cluster analysis and clinical observations will be summarized. Furthermore, the concept of seven clinical nonmotor subtypes will be discussed in detail including the clinical presentation, potential biomarkers, and the clinical relevance. In future, nonmotor subtypes will possibly play a major role within the aim to achieve personalized medicine.

Nonmotor Symptoms in Experimental Models of Parkinson's Disease.

Nonmotor symptoms of Parkinson's disease (PD) range from neuropsychiatric, cognitive to sleep and sensory disorders and can arise from the disease process as well as from drug treatment. The clinical heterogeneity of nonmotor symptoms of PD is underpinned by a wide range of neuropathological and molecular pathology, affecting almost the entire range of neurotransmitters present in brain and the periphery. Understanding the neurobiology and pathology of nonmotor symptoms is crucial to the effective treatment of PD and currently a key unmet need. This bench-to-bedside translational concept can only be successful if robust animal models of PD charting the genesis and natural history of nonmotor symptoms can be devised. Toxin-based and transgenic rodent and primate models of PD have given us important clues to the underlying basis of motor symptomatology and in addition, can provide a snapshot of some nonmotor aspects of PD, although the data are far from complete. In this chapter, we discuss some of the nonmotor aspects of the available experimental models of PD and how the development of robust animal models to understand and treat nonmotor symptoms needs to become a research priority.

Biomarkers of Parkinson's Disease: An Introduction.

The development of biomarkers is of great importance in Parkinson's disease (PD) as it may contribute to confirmation and support of the diagnosis, tracking of progression, and prediction of the natural history of PD. Biomarkers also help in the identification of targets for treatment and measuring the efficacy of interventions. Biomarkers are, therefore, crucial to understanding the pathophysiology of PD, the second commonest neurodegenerative disorder in the world. Modern understanding of PD suggests that it is a multipeptide, multiorgan disorder presenting with a heterogeneous clinical condition, both motor and nonmotor. Biomarkers need to reflect this neuropathological and clinical heterogeneity of PD. In this review, we outline some key advances in the field of clinical, genetic, neuroimaging, and tissue-based biomarkers proposed or used for PD. The individual sections will be covered in relevant chapters and our review is largely a primer aimed to alert readers to the current state of the various biomarkers proposed for PD. In doing so, we have also underlined the important role multimodal rather than single biomarkers could play in our future understanding of PD.

The Nonmotor Features of Parkinson's Disease.

Nonmotor symptoms (NMS) of Parkinson's disease (PD) were recognized by the great James Parkinson himself who mentioned symptoms such as sleep dysfunction, delirium, dementia, and dysautonomia, in his seminal 1817 essay, "An Essay on the Shaking Palsy" (Parkinson, 1817). In spite of the key impact of PD NMS on quality of life, there was little holistic research and awareness till the validation and use of comprehensive tools such as the NMS questionnaire, scale, and the revised version of the unified PD rating scale. Research studies using these tools highlighted the key impact of the burden of NMS on quality of life of PD patients and the need for NMS to be routinely assessed in clinic. We now define PD as a motor and nonmotor disorder, and the natural history includes a long prodromal phase of PD dominated by a range of NMS. The prodromal phase is the subject of much research particularly in relation to neuroprotection and identifying subjects at risk. Use of NMS tools has also validated burden grading of NMS with cutoff values, which can be used as outcome measure in clinical trials. Finally, the complex multineurotransmitter dysfunction that is seen in PD has been shown to manifest clinically as nonmotor subtypes. Recognition of such subtypes is likely to lead to the emergence of personalized and precision medicine in PD.

Multidisciplinary Care in Parkinson's Disease.

Parkinson's disease (PD) is now known to be a multisystemic and multipeptide neurodegenerative disorder, whereby patients have an array of symptoms both motor and nonmotor. Nonmotor features of PD have been shown to arise almost 15-20 years prior to motor symptoms and, as such, are also a key determinant to the quality of life of a patient. Therefore, there is increasing evidence that a PD patient's management must encompass a multidisciplinary approach to effectively manage and treat the patient's PD and also their individual symptoms. Therefore, the notion that a PD nurse specialist and a neurologist are the only key players, is no longer the case. Rather, the involvement of speech and language therapist, physiotherapists, palliative care, and others is vital for a patient's recovery and their effective management. Here we discuss a few professions who should ideally be present for each PD patient.

The efficacy of apomorphine - A non-motor perspective.

Non-motor features have a great impact on progression and quality of life in individuals with Parkinson's disease. Current treatments for PD are limited and apomorphine is one of the advanced therapies available with advantageous effects on motor complications. Several studies have suggested that apomorphine has potential benefits in PD patients beyond its established role in the treatment of motor fluctuations and levodopa-induced dyskinesia. This review examines the efficacy of apomorphine in the treatment of non-motor symptoms (NMS), describing recent studies that highlight its possible effect on cognition. Despite a limited number of studies, the available evidence shows that apomorphine has an overall beneficial effect on NMS of PD patients, including neuropsychiatric symptoms, sleep disturbances, pain, urinary dysfunction, and impulse control disorders. If the effects of apomorphine on amyloid deposition are confirmed in the future, its place in the armamentarium of PD treatment could see a shift towards younger and non-demented PD patients.

New concepts in the pathogenesis and presentation of Parkinson's disease.

Parkinson's disease (PD) was first described by James Parkinson in 1817. He noted the complex nature of this condition and that non-motor symptoms (NMS) underpinned the classic motor symptoms of PD. The concept of what PD is has therefore undergone substantial changes and it is now recognised that PD is a combined motor and non-motor syndrome and NMS are present during the prodromal phase of PD, starting up to 20 years before the first clinical motor signs emerge. PD may originate from pathology in the gut, olfactory bulb and lower brainstem rather than in the substantia nigra. Complex phenotypes of PD may exist where clinical NMS overshadow motor features. Therapy needs to be adjusted based on motor and non-motor loads, ideally using validated tools. Recently, a multimodal biomarker battery in PD has emerged and might play an important role in the future.

Non-oral dopaminergic therapies for Parkinson's disease: current treatments and the future.

Dysfunction of the gastrointestinal tract has now been recognized to affect all stages of Parkinson's disease (PD). The consequences lead to problems with absorption of oral medication, erratic treatment response, as well as silent aspiration, which is one of the key risk factors in developing pneumonia. The issue is further complicated by other gut abnormalities, such as small intestinal bacterial overgrowth (SIBO) and an altered gut microbiota, which occur in PD with variable frequency. Clinically, these gastrointestinal abnormalities might be associated with symptoms such as nausea, early-morning "off", and frequent motor and non-motor fluctuations. Therefore, non-oral therapies that avoid the gastrointestinal system seem a rational option to overcome the problems of oral therapies in PD. Hence, several non-oral strategies have now been actively investigated and developed. The transdermal rotigotine patch, infusion therapies with apomorphine, intrajejunal levodopa, and the apomorphine pen strategy are currently in clinical use with a few others in development. In this review, we discuss and summarize the most recent developments in this field with a focus on non-oral dopaminergic strategies (excluding surgical interventions such as deep brain stimulation) in development or to be licensed for management of PD.