Limb amputations in fixed dystonia: a form of body integrity identity disorder?

Fixed dystonia is a disabling disorder mainly affecting young women who develop fixed abnormal limb postures and pain after apparently minor peripheral injury. There is continued debate regarding its pathophysiology and management. We report 5 cases of fixed dystonia in patients who sought amputation of the affected limb. We place these cases in the context of previous reports of patients with healthy limbs and patients with chronic regional pain syndrome who have sought amputation. Our cases, combined with recent data regarding disorders of mental rotation in patients with fixed dystonia, as well as previous data regarding body integrity identity disorder and amputations sought by patients with chronic regional pain syndrome, raise the possibility that patients with fixed dystonia might have a deficit in body schema that predisposes them to developing fixed dystonia and drives some to seek amputation. The outcome of amputation in fixed dystonia is invariably unfavorable

Pancreatic lipases: evolutionary intermediates in a positional change of catalytic carboxylates?

Comparison of the fold of lipases from Geotrichum candidum and from human pancreas identified a high degree of similarity which was not expected on the basis of their amino acid sequences. Although both enzymes utilize a serine protease-like catalytic triad, they differ in the topological position of the acid. We speculate that these proteins are evolutionarily related and that the pancreatic lipase is an evolutionary intermediate in the pathway of migration of the catalytic acid to a new position within the fold

Identification of prodromal presentations of Parkinson's disease among primary care outpatients in Germany

Background: This study aimed to identify clinical features that predate the diagnosis of PD in a primary care setting. Methods: This retrospective case-control study was based on data from the Disease Analyzer database (IQVIA) and included 17,702 patients with Parkinson's disease and 17,702 non-PD controls matched for age, sex, and index year. We analyzed the prevalence of 15 defined diagnoses and symptoms documented within 2 years, ≥2 to <5, and ≥5 to <10 years prior to the index date in patients with and without PD. Logistic regression analyses were conducted to assess the association between PD and the predefined diagnoses. Results: The prevalence of motor, neuropsychiatric and autonomic features was higher in those with a later diagnosis of Parkinson's disease than controls for all three periods except for rigidity in the ≥2 to <5 and ≥5 to <10-year periods and erectile dysfunction in the most recent period before diagnosis. The clinical presentation recorded in the greatest percentage of patients was depression, followed by dizziness, insomnia, and constipation, but these were also common in the control population. The odds ratios were highest for increase in tremor, followed by balance impairment and memory problems, particularly in the latest period before diagnosis, and by constipation particularly in the earliest period examined. Conclusion: The prodromal features of PD could be identified in this large primary care database in Germany with similar results to those found in previous database studies despite differences in methodologies and systems

Prediagnostic presentations of Parkinson's disease in primary care: a case-control study

Background: Parkinson’s disease (PD) has an insidious onset and is diagnosed when typical motor features occur. A number of motor and non-motor features may occur during a “pre-diagnostic” phase, reflecting the early disease process. Previously there has been no comprehensive analysis in the general population of the relative magnitude and timing of their association with PD diagnosis. Aim: To assess the association of first presentation of several pre-diagnostic features in primary care with a subsequent diagnosis of PD, and to chart the timeline of these first presentations before diagnosis of PD. Methods: 8,166 individuals with a first diagnosis of PD and 46,755 individuals without PD were identified from 1st January 1996 to 31st December 2012 from The Health Improvement Network, United Kingdom primary care database. Codes were extracted for a wide range of possible pre-diagnostic or early symptoms comprising motor features (tremor, rigidity, balance impairment, neck pain and shoulder pain), autonomic features (constipation, hypotension, dizziness, erectile dysfunction, urinary dysfunction), mental disturbances (memory problems, depression, anxiety) and additional features (fatigue, insomnia) in the years prior to diagnosis. Incidence rates for symptoms recorded in more than 1% of cases per 1000 person years and incidence risk ratio (RR) were calculated and compared for individuals with and without PD at two, five and ten years before diagnosis. Findings: At two years before PD diagnosis the incidence of all examined pre-diagnostic features except neck pain was higher in patients (n=7,232) than in controls (n=40,541). At five years before diagnosis, patients with PD (n=4,769) had higher incidence rates of tremor (RR 13.70 (95%CI 7.82-24.31), balance impairment (RR, 2.19 (95%CI 1.09-4.16), depression (RR 1.76 (95%CI 1.41-2.17), anxiety (RR 1.41 (95%CI 1.09-1.79), constipation (RR 2.24 (95%CI 2.04-2.46), postural hypotension (RR 3.23 (95%CI 1.85-5.52), dizziness (RR 1.99 (95%CI 1.67-2.37), erectile dysfunction (RR 1.30 (95%CI 1.11-1.51), fatigue (RR 1.56 (95%CI 1.27-1.91), and urinary dysfunction (RR 1.96 (95%CI 1.34-2.80) than controls (n=25,544). At ten years before diagnosis of PD the incidence of constipation (RR 2.01 (95%CI 1.62-2.49) and tremor (RR 7.59 (95%CI 1.1-44.8) was already higher in those with later diagnosis with PD (n=1,680) than in controls (n=8,305). Interpretation: This study for the first time provides evidence for a range of pre-diagnostic features that can be detected several years before diagnosis of PD in primary care, estimating the comparative magnitude of risk for each and where they fit in the prodromal timeline. These data on the pre-diagnostic symptoms of PD can be incorporated into ongoing efforts to identify individuals at the earliest stages of the disease in future trials and help understand progression in the earliest phase of PD

Orthostatic Hypotension and Antiparkinsonian Drugs: A Systematic Review and Meta-analysis

BACKGROUND: Orthostatic hypotension (OH) is multifactorial in Parkinson's disease (PD). Antiparkinsonian medication can contribute to OH, leading to increased risk of falls, weakness and fatigue. METHODS: We conducted a systematic review and meta-analysis of randomised controlled trials (RCTs) of antiparkinsonian drugs associated with OH as an adverse effect, compared to placebo. We searched EMBASE, MEDLINE and Web of Science databases until November 2020. Analysis used fixed-effects models and the GRADE tool to rate quality of evidence. Meta-analysis was performed if 3 or more studies of a drug group were available. RESULTS: Twenty-one RCTs including 3783 patients were included comparing 6 PD drug groups to placebo (MAO-B inhibitors, dopamine agonists, levodopa, COMT inhibitors, levodopa and adenosine receptor antagonists). OH was recorded as an adverse event or measurement of vital signs, without further specification on how this was defined or operationalised. Meta-analysis was performed for MAO-B inhibitors and dopamine agonists, as there were 3 or more studies for these drug groups. In this analysis, compared with placebo, neither MAO-B inhibitors or dopamine agonists were associated with increased risk of OH, (OR 2.28 [95% CI:0.81-6.46]), (OR 1.39 [95% CI:0.97-1.98]). CONCLUSIONS: Most studies did not specifically report OH, or reporting of OH was limited, including how and when it was measured. Furthermore, studies specifically reporting OH included participants that were younger than typical PD populations without multimorbidity. Future trials should address this, for example,, by including individuals over the age of 75, to improve estimations of how antiparkinsonian medications affect risk of OH

Mortality of People with Parkinson's Disease in a Large UK-Based Cohort Study: Time Trends and Relationship to Disease Duration

BACKGROUND: Parkinson's disease (PD) is associated with increased mortality, but little is known about changes over time, and relationship to disease progression. OBJECTIVES: To explore how PD mortality rates have changed over time and their relationship to disease duration and demographics using a large population-based cohort in the UK. METHODS: We included individuals aged 50+ years with a first recording of PD diagnosis and at least two prescriptions of any antiparkinsonian drug actively registered within a general practice from 2006 to 2016 and up to six frequency-matched controls from The Health Improvement Network (THIN) database. We estimated adjusted mortality rates using multivariable Poisson regression. RESULTS: A total of 10,104 people with a diagnosis of PD and 55,664 people without PD were included. Overall, PD was associated with slightly increased mortality compared to non-PD controls (adjusted mortality rate ratio: 1.14; 95% CI: 1.03 to 1.19). Adjusted mortality rates per 1000 person-years at risk for people with PD approximately doubled in the 5 years following diagnosis from 43 (95% CI: 38 to 48) to 75 (95% CI: 64 to 85). Following adjustments for age, gender, and time since diagnosis, mortality rates between 2007 and 2016 declined more slowly for people with PD (2% per year; 95% CI: 0%–4%) compared to people without PD (5% per year; 95% CI: 3%–6%). CONCLUSIONS: Whilst mortality in PD is only slightly increased overall, it gradually increases with advancing disease. There has been a decline in mortality in PD over time, but this decrease was less pronounced than that in the general population. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society

Systematic review and meta-analysis of clinical effectiveness of self-management interventions in Parkinson’s disease

BACKGROUND: Parkinson's disease is a complex neurodegenerative condition with significant impact on quality of life (QoL), wellbeing and function. The objective of this review is to evaluate the clinical effectiveness of self-management interventions for people with Parkinson's disease, taking a broad view of self-management and considering effects on QoL, wellbeing and function. METHODS: Systematic searches of four databases (MEDLINE, Embase, PsycINFO, Web of Science) were conducted for studies evaluating self-management interventions for people with Parkinson's disease published up to 16th November 2020. Original quantitative studies of adults with idiopathic Parkinson's disease were included, whilst studies of atypical Parkinsonism were excluded. Full-text articles were independently assessed by two reviewers, with data extracted by one reviewer and reliability checked by a second reviewer, then synthesised through a narrative approach and, for sufficiently similar studies, a meta-analysis of effect size was conducted (using a random-effects meta-analysis with restricted maximum likelihood method pooled estimate). Interventions were subdivided into self-management components according to PRISMS Taxonomy. Risk of bias was examined with the Cochrane Risk of Bias 2 (RoB2) tool or ROBIN-I tool as appropriate. RESULTS: Thirty-six studies were included, evaluating a diverse array of interventions and encompassing a range of study designs (RCT n = 19; non-randomised CT n = five; within subject pre- and post-intervention comparisons n = 12). A total of 2884 participants were assessed in studies across ten countries, with greatest output from North America (14 studies) and UK (six studies). Risk of bias was moderate to high for the majority of studies, mostly due to lack of participant blinding, which is not often practical for interventions of this nature. Only four studies reported statistically significant improvements in QoL, wellbeing or functional outcomes for the intervention compared to controls. These interventions were group-based self-management education and training programmes, either alone, combined with multi-disciplinary rehabilitation, or combined with Cognitive Behaviour Therapy; and a self-guided community-based exercise programme. Four of the RCTs evaluated sufficiently similar interventions and outcomes for meta-analysis: these were studies of self-management education and training programmes evaluating QoL (n = 478). Meta-analysis demonstrated no significant difference between the self-management and the control groups with a standardised mean difference (Hedges g) of - 0.17 (- 0.56, 0.21) p = 0.38. By the GRADE approach, the quality of this evidence was deemed "very low" and the effect of the intervention is therefore uncertain. Components more frequently observed in effective interventions, as per PRISMS taxonomy analysis, were: information about resources; training or rehearsing psychological strategies; social support; and lifestyle advice and support. The applicability of these findings is weakened by the ambiguous and at times overlapping nature of self-management components. CONCLUSION: Approaches and outcomes to self-management interventions in Parkinson's disease are heterogenous. There are insufficient high quality RCTs in this field to show effectiveness of self-management interventions in Parkinson's disease. Whilst it is not possible to draw conclusions on specific intervention components that convey effectiveness, there are promising findings from some studies, which could be targeted in future evaluations

The experience of Anxiety for people with Parkinson’s disease

Anxiety is a common non-motor symptom of Parkinson's disease (PD) associated with increased disability and reduced quality of life. However, anxiety is poorly understood, underdiagnosed, and undertreated. To date, little research has explored how anxiety is experienced by patients themselves. This study explored the experience of anxiety for people with Parkinson's (PWP) to inform future research and interventions. Semi-structured interviews with 22 PWP (aged 43-80, 50% female) were conducted and analysed using inductive thematic analysis. Four main themes were extracted: conceptualising anxiety; anxiety and the body; anxiety and social identity; and coping with anxiety. Sub-themes revealed inconsistent perceptions: anxiety was in body and mind, part of disease and human nature, part of self-identity and a threat to it. The symptoms described were diverse. Many perceived their anxiety as more incapacitating than motor symptoms or capable of amplifying them, and described that anxiety restricted their lifestyle. All perceived anxiety as connected to PD, and ultimately persistent: dominant aspirations were coping and acceptance rather than cures, with medications strongly resisted. Findings highlight the complexity and high importance of anxiety for PWP. Implications for therapeutic approaches are discussed

Factors associated with hospitalisation among people with Parkinson's disease – A systematic review and meta-analysis

INTRODUCTION: Parkinson's disease (PD) is associated with an increased risk of admission to hospital, however data on the main reasons for admission is lacking. Our objective was to determine the pooled prevalence of the most common factors leading to admissions among people with Parkinson's disease. METHODOLOGY: MA systematic literature search was conducted in 11 electronic databases. We included all studies providing reasons for admissions among PD patients without restrictions to diagnostic criteria of PD, language or year of study. In the included studies, methodological quality, publication bias and heterogeneity were assessed. Meta-analysis was performed using random-effects models to calculate the pooled estimates of the identified top factors that lead to admission among people with PD. RESULTS: A total of 7283 studies were identified of which nine studies including 7162 people with PD were included in this review. There was a high degree of heterogeneity between studies regarding reasons for hospitalisation. The pooled prevalence of the topmost reasons for hospitalisation among people with PD was 22%(95%CI 16.0%-30.0%) for infections (mainly urinary tract infections and pneumonia); 19%(95%CI 13.0%-27.0%) for worsening motor manifestations of PD; 18%(95%CI 14.0%-21.0%) for falls/fractures; 13%(95%CI 9.0%-18%) for cardiovascular co-morbidities; 8%(95%CI 4.0%-13.0%) for neuropsychiatric and 7%(95%CI 4.0%-11.0%) gastrointestinal complications. CONCLUSION: The main reasons for hospitalisation among people with PD are infections, worsening motor features, falls/fractures, cardiovascular co-morbidities, neuropsychiatric and gastrointestinal complications. Further research is needed in targeting and implementing preventative strategies