Diagnosis Of Idiopathic Parkinson's Disease Research Articles

Associations between cerebrovascular risk factors and parkinson disease.

To determine whether cerebrovascular risk factors are associated with subsequent diagnoses of Parkinson disease, and whether these associations are similar in magnitude to those with subsequent diagnoses of Alzheimer disease. This was a retrospective cohort study using claims data from a 5% random sample of Medicare beneficiaries from 2008 to 2015. The exposures were stroke, atrial fibrillation, coronary disease, hyperlipidemia, hypertension, sleep apnea, diabetes mellitus, heart failure, peripheral vascular disease, chronic kidney disease, chronic obstructive pulmonary disease, valvular heart disease, tobacco use, and alcohol abuse. The primary outcome was a new diagnosis of idiopathic Parkinson disease. The secondary outcome was a new diagnosis of Alzheimer disease. Marginal structural Cox models adjusting for time-dependent confounding were used to characterize the association between exposures and outcomes. We also evaluated the association between cerebrovascular risk factors and subsequent renal colic (negative control). Among 1,035,536 Medicare beneficiaries followed for a mean of 5.2 years, 15,531 (1.5%) participants were diagnosed with Parkinson disease and 81,974 (7.9%) were diagnosed with Alzheimer disease. Most evaluated cerebrovascular risk factors, including prior stroke (hazard ratio = 1.55; 95% confidence interval = 1.39-1.72), were associated with the subsequent diagnosis of Parkinson disease. The magnitudes of these associations were similar, but attenuated, to the associations between cerebrovascular risk factors and Alzheimer disease. Confirming the validity of our analytical model, most cerebrovascular risk factors were not associated with the subsequent diagnosis of renal colic. Cerebrovascular risk factors are associated with Parkinson disease, an effect comparable to their association with Alzheimer disease. ANN NEUROL 2019;86:572-581.

Quantitative autonomic function test in differentiation of multiple system atrophy from idiopathic Parkinson disease.

Differential diagnosis of idiopathic Parkinson disease (IPD) and multiple system atrophy-Parkinson type (MSA-P) is challenging since they share clinical features with parkinsonism and autonomic dysfunction. To distinguish MSA-P from IPD when the symptoms are relatively mild, we investigated the usefulness of the quantitative fractionalized autonomic indexes and evaluated the correlations of autonomic test indexes and functional status. Thirty-six patients with parkinsonism (22 with IPD and 14 with MSA-P) in Soonchunhyang University Bucheon Hospital from February 2014 to June 2015 were prospectively enrolled in the study. We compared fractionalized autonomic indexes and composite autonomic scoring scale between patients with IPD and MSA-P with Hoehn and Yahr (H&Y) score ≤3. Parasympathetic indexes included expiratory/inspiratory ratio during deep breathing, Valsalva ratio (VR), and regression slope of systolic blood pressure (BP) in early phase II (vagal baroreflex sensitivity) during Valsalva maneuver. Sympathetic adrenergic indexes were pressure recovery time (PRT) and adrenergic baroreflex sensitivity (BRSa) (BP decrement associated with phase 3 divided by the PRT), sympathetic index 1, sympathetic index 3, early phase II mean BP drop, and pulse pressure reduction rate. Additionally, we compared the unified multiple system atrophy rating scale (UMSARS) and H&Y scores and the autonomic indexes in all patients. PRT was significantly different between the IPD and MSA-P groups (P = 0.004) despite the similar BP drop during tilt. Cut-off value of PRT was 5.5 s (sensitivity, 71.4%; specificity, 72.7%). VR (r = -0.455, P = 0.009) and BRSa (r = -0.356, P = 0.036) demonstrated a significant correlation with UMSARS and H&Y scores. Among the cardiovascular autonomic indexes, PRT can be a useful parameter in differentiating the early stage of MSA-P from that of IPD. Moreover, VR, and BRSa may be the optimal indexes in determining functional symptom severity.

What Predicts Hospital Admissions in Community-Dwelling People With Parkinsonism?

Previous studies have looked at the reasons for hospital admission in people with parkinsonism (PwP), yet few have looked at factors that precipitate admission. People with parkinsonism with a diagnosis of idiopathic Parkinson disease of Hoehn and Yahr stage III-V and those with Parkinson plus syndromes were assessed for motor and nonmotor symptoms, quality of life, and functional performance. Logistic regression was used to investigate predictors of hospital admission over the subsequent 2 years. Overall, 162 patients consented to be part of the study. Seventy-one PwP (43.8%) had at least 1 hospital admission, and 17 (10.5%) patients had 3 or more admissions to hospital. Poorer cognition, more nonmotor symptoms, poorer quality of life, slower timed-up-and-go test scores, and abnormal swallow predicted a subsequent hospital admission. Our study emphasizes the importance of nonmotor symptoms in predicting admission. A cost-benefit analysis of early intervention to prevent admission should be considered.

Radiomic Features of the Nigrosome-1 Region of the Substantia Nigra: Using Quantitative Susceptibility Mapping to Assist the Diagnosis of Idiopathic Parkinson's Disease.

Introduction: The loss of nigrosome-1, which is also referred to as the swallow tail sign (STS) in T2*-weighted iron-sensitive magnetic resonance imaging (MRI), has recently emerged as a new biomarker for idiopathic Parkinson's disease (IPD). However, consistent recognition of the STS is difficult due to individual variations and different imaging parameters. Radiomics might have the potential to overcome these shortcomings. Therefore, we chose to explore whether radiomic features of nigrosome-1 of substantia nigra (SN) based on quantitative susceptibility mapping (QSM) could help to differentiate IPD patients from healthy controls (HCs).Methods: Three-dimensional multi-echo gradient-recalled echo images (0.86 × 0.86 × 1.00 mm3) were obtained at 3.0-T MRI for QSM in 87 IPD patients and 77 HCs. Regions of interest (ROIs) of the SN below the red nucleus were manually drawn on both sides, and subsequently, volumes of interest (VOIs) were segmented (these ROIs included four 1-mm slices). Then, 105 radiomic features (including 18 first-order features, 13 shape features, and 74 texture features) of bilateral VOIs in the two groups were extracted. Forty features were selected according to the ensemble feature selection method, which combined analysis of variance, random forest, and recursive feature elimination. The selected features were further utilized to distinguish IPD patients from HC using the SVM classifier with 10 rounds of 3-fold cross-validation. Finally, the representative features were analyzed using an unpaired t-test with Bonferroni correction and correlated with the UPDRS-III scores.Results: The classification results from SVM were as follows: area under curve (AUC): 0.96 ± 0.02; accuracy: 0.88 ± 0.03; sensitivity: 0.89 ± 0.06; and specificity: 0.87 ± 0.07. Five representative features were selected to show their detailed difference between IPD patients and HCs: 10th percentile and median in IPD patients were higher than those in HCs (all p < 0.00125), while Gray Level Run Length Matrix (GLRLM)-Long Run Low Gray Level Emphasis, Gray Level Size Zone Matrix (GLSZM)–Gray Level Non-Uniformity, and volume (all p < 0.00125) in IPD patients were lower than those in HCs. The 10th percentile was positively correlated with UPDRS-III score (r = 0.35, p = 0.001).Conclusion: Radiomic features of the nigrosome-1 region of SN based on QSM could be useful in the diagnosis of IPD and could serve as a surrogate marker for the STS.

Grand Total EEG Score Can Differentiate Parkinson's Disease From Parkinson-Related Disorders.

Background: Semi-quantitative electroencephalogram (EEG) analysis is easy to perform and has been used to differentiate dementias, as well as idiopathic and vascular Parkinson's disease.Purpose: To study whether a semi-quantitative EEG analysis can aid in distinguishing idiopathic Parkinson's disease (IPD) from atypical parkinsonian disorders (APDs), and furthermore, whether it can help to distinguish between APDs.Materials and Methods: A comprehensive retrospective review of charts was performed to include patients with parkinsonian disorders who had at least one EEG recording available. A modified grand total EEG (GTE) score evaluating the posterior background activity, and diffuse and focal slow wave activities was used in further analyses.Results: We analyzed data from 76 patients with a final diagnosis of either IPD, probable corticobasal degeneration (CBD), multiple system atrophy (MSA), or progressive supra-nuclear palsy (PSP). IPD patients had the lowest mean GTE score, followed those with CBD or MSA, while PSP patients scored the highest. However, none of these differences were statistically significant. A GTE score of ≤9 distinguished IPD patients from those with APD (p < 0.01) with a sensitivity of 100% and a specificity of 33.3%.Conclusion: The modified GTE score can distinguish patients with IPD from those with CBD, PSP or MSA at a cut-off score of 9 with excellent sensitivity but poor specificity. However, this score is not able to distinguish a particular form of APD from other forms of the disorder.

Serum inflammation biomarkers are associated with stages of Parkinson's disease

Aim: The aim was to identify serum neutrophil/lymphocyte ratio (NLR), monocyte/lymphocyte ratio (MLR), platelet/lymphocyte ratio (PLR) and C - reactive protein (CRP)/albumin ratio (CAR) according to disease stage in patients with idiopathic Parkinson disease (IPD). Material and Methods: The study included 211 patients IPD diagnosis and 200 healthy individuals abiding by the exclusion criteria. Patients with Stage 4 and 5 IPD according to Modified Hoehn and Yahr (H&Y) staging were not included in the study. The control group comprised individuals in the same age interval as IPD patients, with normal neurological examinations, Mental State Examination (MMSE) score above 24 and Geriatric Depression Rating Scale (GDRS) score below 11 who abided by the exclusion criteria. Results: For males and females in the IPD group, serum MLR, NLR and CAR were found to be high (p

Circulating miRNAs as Diagnostic Biomarkers for Parkinson's Disease.

Parkinson’s disease (PD) is the second most common neurodegenerative disorder worldwide. Its main neuropathological hallmarks are the degeneration of dopaminergic neurons in the substantia nigra and alpha-synuclein containing protein inclusions, called Lewy Bodies. The diagnosis of idiopathic PD is still based on the assessment of clinical criteria, leading to an insufficient diagnostic accuracy. Additionally, there is no biomarker available allowing the prediction of the disease course or monitoring the response to therapeutic approaches. So far, protein biomarker candidates such as alpha-synuclein have failed to improve diagnosis of PD. Circulating microRNAs (miRNAs) in body fluids are promising biomarker candidates for PD, as they are easily accessible by non- or minimally-invasive procedures and changes in their expression are associated with pathophysiological processes relevant for PD. Advances in miRNA analysis methods resulted in numerous recent publications on miRNAs as putative biomarkers. Here, we discuss the applicability of different body fluids as sources for miRNA biomarkers, highlight technical aspects of miRNA analysis and give an overview on published studies investigating circulating miRNAs as biomarker candidates for diagnosis of PD and other Parkinsonian syndromes.

Access to End-of Life Parkinson's Disease Patients Through Patient-Centered Integrated Healthcare.

Background: Palliative care in Parkinson's Disease (PD) patients considerably differs from palliative care in oncology patients. Integrated care models are a concept to support patients and improve management of PD symptoms. However, it is not known if the access to PD patients at the end of life can be achieved through integrated care models.Aim: To analyze an integrated model of care for PD patients with the aim to identify if this integrated model of care has access to PD patients at the end of life.Material and Methods: The Cologne Parkinson's network was designed as a randomized, controlled prospective clinical trial in order to increase quality of life of PD patients. This innovative model of care integrated a neurologist in private practice, a movement disorder specialist of the University Hospital and a PD nurse. Mortality rates of PD patients during the study period of 6 months were registered and compared with mortality rates of the general population of Germany according to the Federal Statistical Office of Germany. The retrospective post-hoc analysis was conducted after completion of the initial study at the University Hospital and neurologists' practices in the greater area of Cologne, Germany. Eligible patients had a diagnosis of idiopathic PD and were aged 25–85 years.Results: Parkinson's Disease patients in this trial had an even slightly lower mortality rate as the general population (1.66 v. 2.1%). These results are contradictory and speak for a substantial proportion of late-stage disease patients, who have not been adequately included in this study or have been better treated within this trial. The mean disease duration of patients in this study was around 6 years which resembles the lower range of the mean disease duration at death of PD patients in general.Conclusions: The results of our post-hoc analysis show, that accessing PD patients in the last phase of their disease is extremely difficult and nearly fails in spite of an integrated care approach. Reasons for poor access and loss of follow-up at the end of life have to be identified and care models for PD patients until the end of life should be developed urgently.

Voice Quality and Orofacial Strength as Outcome of Levodopa Effectiveness in Patients with Early Idiopathic Parkinson Disease: A Preliminary Report

Sixty to 90% of patients with idiopathic Parkinson disease (IPD) developed early dysphonia and subtle speech impairment, which is usually related to orofacial muscular dysfunctions. The aim of this preliminary study is to assess the usefulness of voice quality and orofacial strength (involved in speech) as outcome of levodopa challenge test used for the IPD diagnosis. A total of 20 patients with early IPD were recruited and evaluated for clinical findings (Hoehn and Yahr scale), voice handicap index, maximal phonation time, phonation quotient, percent jitter, percent shimmer, noise-to-harmonic ratio, and orofacial muscular strength (Iowa Oral Performance Instrument) at baseline, throughout the levodopa challenge test and after therapeutic stabilization. The intake of a standardized dose of levodopa (levodopa challenge test) significantly improved phonation quotient and percent shimmer. We did not find similar improvement after medical stabilization of patients (based on levodopa medication) despite an improvement of Hoehn and Yahr mean score. The intake of levodopa significantly improved cheeks and lips strength involved in speech quality both along the challenge test and after the therapeutic stabilization. These preliminary findings support a differential impact of levodopa on voice and speech functions in early diagnosed IPD and a mismatch between the clinical examination, orofacial strength, and voice quality improvements once the patient is medically stabilized.

Voice quality outcomes of idiopathic Parkinson's disease medical treatment: A systematic review.

To investigate voice quality (VQ) impairments in idiopathic Parkinson's disease (IPD) and to explore the impact of medical treatments and L-Dopa challenge testing on voice. Relevant studies published between January 1980 and June 2017 describing VQ evaluations in IPD were retrieved using PubMed, Scopus, Biological Abstracts, BioMed Central and Cochrane databases. Issues of clinical relevance, including IPD treatment efficiency and voice quality outcomes, were evaluated for each study. The grade of recommendation for each publication was determined according to the Oxford Centre for Evidence-Based Medicine evidence levels. The database research yielded 106 relevant publications, of which 33 studies met the inclusion criteria, for a total of 964 patients with IPD. Data were extracted by 3 independent physicians who identified 21, 11 and 1 trials with IIIb, IIb and IIa evidence levels, respectively. The main VQ assessment tools used were acoustic testing (N=27), aerodynamic testing (N=10), subjective measurements (N=8) and videolaryngostroboscopy (N=3). The majority of trials (N=32/33) identified subjective or objective VQ improvements after medical treatment (N=10) or better VQ evaluations in healthy subjects compared to patients with IPD (N=22). Especially, our analysis supports that VQ overall improves during the L-Dopa challenge testing, making the VQ evaluation an additional tool for the IPD diagnosis. The methodology used to assess subjective and objective VQ substantially varied from 1 study to another. All of the included studies took into consideration the patient's clinical profile in the VQ analysis. The majority of studies supported that VQ assessments remain useful as outcome measures of the effectiveness of medical treatment and could be helpful for the IPD diagnosis based on L-Dopa challenge testing. Further controlled studies using standardised and transparent methodology for measuring acoustic parameters are necessary to confirm the place of each tool in both IPD diagnosis and treatment evaluation.

Increased risk of overactive bladder in patients with idiopathic Parkinson's disease: Insight from a nationwide population-based cohort study.

BackgroundIdiopathic Parkinson’s disease (IPD) is a progressive neurodegenerative disorder characterized by typical motor impairment. However, lower urinary tract symptoms, including urinary urgency or frequency, which are non-motor phenomena, occur frequently among patients with IPD. In this study, we assess the risk of overactive bladder (OAB) in patients with IPD.MethodsThe National Health Insurance Research Database of Taiwan was used to identify patients with IPD (IPD cohort) and four-fold controls (non-IPD cohort) from 2000 to 2010. The non-IPD cohort was matched according to age, sex, and baseline comorbidities, including benign prostate hyperplasia, stress incontinence, diabetes, and cerebrovascular diseases. The occurrence of OAB was monitored until the end of 2011. Hazard ratios of OAB were estimated using Cox proportional hazards regression models.ResultsIn total, 4,571 and 18,255 patients were included in IPD and non-IPD cohorts, respectively. Results showed a significantly higher overall incidence rate of OAB in the IPD cohort compared with the non-IPD cohort (14.5 vs. 6.37 per 10,000 person-years), with a 2.3-fold increased risk of OAB (95% confidence interval [CI] = 1.51–3.51) after controlling for benign prostate hyperplasia and stress incontinence. The mean follow-up period for the IPD cohort was 5.0 years. This cohort study showed that the cumulative incidence of OAB was 0.65% at the fifth year and 1.54% at the tenth year after IPD diagnosis; this risk was highest in the age group 65–74 years.ConclusionThis study reveals that IPD is independently associated with an increased risk of OAB in patients with IPD. The probability of OAB was 1.54% over a 10-year period after IPD diagnosis; the risk of OAB is considered to be age-dependent and most substantial in patients aged 65–74 years.

10 Screening of neuropsychiatric symptoms in patients with parkinson’s disease in a uk general practice

Objective Neuropsychiatric symptoms are common in Parkinson’s disease (PD) and have important consequences for quality of life and daily functioning. Amongst the most frequent are dementia, depression, anxiety and psychosis. By contrast with the motor symptoms of PD, these problems are often poorly recognised and inadequately treated. The first step towards their management is identification. Therefore, a service evaluation was undertaken, at a UK general practice, with the aim to identify the proportion of patients who are screened for the common neuropsychiatric manifestations of PD. Method The electronic medical records of 12 915 registered patients at one UK general practice were searched for read codes relating to PD and dopaminergic drug use. This identified twelve patients with a diagnosis of idiopathic PD. The notes of these patients were then reviewed to determine whether any form of screening had taken place in the last year regarding dementia/cognitive impairment, depression, anxiety, sleep disturbance and hallucinations. Results In the last year, 83% (n=10) of identified patients had seen a GP. For these patients, the average number of visits was 5.4 range 2–11). Screening in relation to dementia was documented in 1 patient, to depression in 2 patients, to anxiety in patients, to sleep in 2 patients and to hallucinations in 1 patient. Conclusion In patients who had visited their GP in the last year, there was a low proportion of documented screening for the common neuropsychiatric symptoms occurring in PD. Although these patients may not be consulting about issues relating to PD, given the significance of neuropsychiatric symptoms, opportunistic screening should be considered. A presentation of these results has been delivered to the GPs at this practice and a service evaluation will be performed again next year.

Abstract TP165: Associations Between Parkinson Disease and Stroke

Introduction: Cerebral ischemia and vascular risk factors are associated with the development of Alzheimer disease (AD). While Parkinson disease (PD) is also a common neurodegenerative condition, the relationship between ischemic stroke and PD remains unclear. Some evidence suggests a shared pathogenic pathway between both diseases. Methods: We used inpatient and outpatient claims data from 2008-2014 in a 5% sample of Medicare beneficiaries ≥66 years of age. Our variables of interest were: 1) a hospital-based diagnosis of ischemic stroke and 2) an outpatient or hospital-based diagnosis of idiopathic PD. Previously validated ICD-9-CM code algorithms were used to identify all diagnoses. We used Cox proportional hazards modeling to characterize the relationship between ischemic stroke and PD, while adjusting for demographics and vascular risk factors. We assessed both the association between PD and subsequent stroke, as well as stroke and subsequent PD. In a separate but identically designed set of analyses, we characterized the relationship between ischemic stroke and AD as a point of comparison. Results: Our analysis encompassed nearly 1.6 million patients with a mean age of 73(+/- 8) years, of whom 57% were female. The annual incidence of ischemic stroke was 1.75% (95% confidence interval [CI], 1.67-1.85%) after a diagnosis of PD versus 0.96% (95% CI, 0.96-0.97%) in those without PD (adjusted hazard ratio [aHR], 1.25; 95% CI, 1.19-1.32). In contrast, the annual incidence of ischemic stroke was 1.96% (95% CI, 1.89-2.03%) after a diagnosis of AD versus 0.96% (95% CI, 0.96-0.97%) in those without AD (aHR, 0.98; 95% CI, 0.95-1.02). The annual incidence of PD was 0.97% (95% CI, 0.92-1.03%) after ischemic stroke versus 0.39% (95% CI, 0.38-0.39%) in those without ischemic stroke (aHR, 1.62; 95% CI, 1.53-1.72). In contrast, the annual incidence of AD was 3.66% (95% CI, 3.56-3.78%) after a diagnosis of ischemic stroke versus 1.17% (95% CI, 1.16-1.17%) in those without ischemic stroke (aHR, 1.67; 95% CI, 1.61-1.72). Conclusions: Among Medicare beneficiaries, the relationships between stroke and PD were similar to those between stroke and AD. As in AD, a link may exist between cerebrovascular disease and PD.

Using 'swallow-tail' sign and putaminal hypointensity as biomarkers to distinguish multiple system atrophy from idiopathic Parkinson's disease: A susceptibility-weighted imaging study.

To investigate the value of 'swallow-tail' sign and putaminal hypointensity on 3T susceptibility-weighted imaging (SWI) for distinguishing multiple system atrophy (MSA) from idiopathic Parkinson's disease (IPD). Three groups - 39 MSA patients, 18 IPD patients,and 31 healthy controls (HCs) - were administered a 3T SWI sequence to evaluate 'swallow-tail' sign and putaminal hypointensity using visual scales from 0 to 2 and 0 to 3 scores, respectively. The diagnostic accuracy of the two signs separately and combined was calculated using a receiver operating characteristic curve, with clinical diagnosis as the gold standard. The scores of 'swallow-tail' sign were lower in IPD than in MSA or in HCs, as well as for putaminal hypointensity in IPD or HCs than in MSA (p < 0.05). The sensitivity and specificity of 'swallow-tail' sign and putaminal hypointensity were 87.9% and 83.3%, and 35.9% and 100%, respectively, in the respective patient groups. The area under the curve of combined signs was increased from 0.85 ('swallow tail') or 0.68 (putaminal hypointensity) to 0.93. The combination of 'swallow-tail' sign and putaminal hypointensity can increase the accuracy of discriminating between MSA and IPD. • Differential diagnosis of MSA and IPD is still challenging in clinical practice. • Absence of 'swallow-tail' sign is a valuable biomarker for IPD on SWI. • Putaminal hypointensity is a valuable biomarker for MSA on SWI. • Combined 'swallow- tail' sign and putaminal hypointensity increase diagnostic accuracy.

Acupuncture as Adjuvant Therapy for Sleep Disorders in Parkinson’s Disease

There are few studies which attest the efficacy of acupuncture on treatment of sleep disturbs in Parkinson disease. The aimed of this randomized clinical trial was to evaluate the effects of acupuncture on sleep disturbs of 22 patients with diagnosis of idiopathic Parkinson disease (Hoehn–Yahr 1 to 3) who have assistance on the Pro-Parkinson Program of Clinical Hospital at Federal University of Pernambuco in Brazil. All participants were evaluated by Parkinson Disease Sleep Scale (PDSS) before and after 8 weeks. The experimental group was submitted to 8 sections (once a week) which had duration of 30 minutes. The control group had no intervention. The intervention was executed using the acupuncture points LR3 (Taichong), SP6 (Sanyinjiao), LI4 (Hegu), TE5 (Wai-Guan), HT7 (Shenmen), PC6 (Neiguan), LI11 (Quchi), GB20 (Fengchi). Paired analyses were obtained by Wilcoxon test and independent analyses were made according to Mann–Whitney test. This study presented a potential therapeutic benefit of acupuncture on sleep disturbs of Parkinson's disease patients. This study showed a possible therapeutic benefit through acupuncture in sleep disorders in patients with PD. However, we propose new studies related to the effects of acupuncture on the clinical symptoms and evolution of the disease.

The key points for treatment of Parkinsonism in older persons

Signs and symptoms of Parkinsonism have a high prevalence in older persons. Parkinsonism is associated with negative outcomes in the elderly and there is still uncertainty about when and how to start levodopa in these conditions. The diagnosis of idiopathic Parkinson disease is often not pursued in the oldest old. The coexistence of both motor and cognitive impairment is the strongest factor limiting the initiation of treatment with levodopa and/or dopamine agonists in a geriatric setting, given the possibility of producing psychotic symptoms, such as visual hallucinations. It seems reasonable to perform at least one attempt to administer levodopa in older persons with parkinsonism, especially when symptoms and motility disorders are evident, in order to try to obtain an improvement in walking speed and balance. Important signs that should guide treatment for Parkinsonism in older persons are the presence of &lt;em&gt;line-pipe&lt;/em&gt; rigidity and &lt;em&gt;cogwheel&lt;/em&gt; rigidity.

A door-to-door survey to estimate the prevalence of Parkinsonism in Pakistan.

IntroductionParkinson’s disease (PD) occurs in all races and cultures, and population-related differences in frequency may provide etiological clues. The present study was designed to explore the prevalence of PD and Parkinsonism in Pakistan, the world’s sixth most populous country, for which no published prevalence data are available.MethodsWe conducted a three-phase door-to-door survey in two districts of the Khyber Pakhtunkhwa province of Pakistan, to assess the prevalence of PD and Parkinsonism in a sample of 4,000 individuals aged 50 years and above.ResultsWe identified 14 cases of Parkinsonism, eleven with a diagnosis of idiopathic PD. The overall prevalence estimates were 1.7/100 (95% confidence interval [CI]: 0.9–2.46) for Parkinsonism and 1.28/100 (95% CI: 0.6–1.94) for PD in persons aged 65 years and above. The age-standardized prevalence of PD (aged 65 years and above), normalized to the USA population in 2000, was 1.33/100, which is similar to that observed in other human populations. Of the total 14 cases, five were newly diagnosed and four had a family history of PD.ConclusionThe estimated prevalence rates in Pakistan are similar to those observed in other human populations. The frequency of familial Parkinsonism is also equivalent to previous estimates.

Sarcopenia and Dynapenia in Patients With Parkinsonism

ObjectivesTo estimate prevalence of sarcopenia and dynapenia in outpatients with Parkinson disease (PD) and to investigate their association with the features of the disease. DesignCross-sectional study. SettingA specialized tertiary care center. ParticipantsConsecutive patients (n = 364) aged 65 years or older, affected by parkinsonian syndromes. MeasurementsSkeletal muscle mass (SMM), as well as strength and gait speed (GS) were assessed by bioimpedence analysis, handgrip dynamometry, and the 4-meter walking test, respectively. Based on these assessments, sarcopenia was diagnosed using the European Working Group on Sarcopenia in Older People criteria. Dynapenia was defined as handgrip strength less than 30 kg in men and less than 20 kg in women. ResultsIn total, 235 patients (64.6%) had a diagnosis of idiopathic PD. Low SMM index was recorded in 27 patients. Due to gait disturbances and postural instability, GS could not be measured in 98 patients and was found to be reduced in 61.3% of those assessed. Prevalence of sarcopenia and dynapenia was 6.6% (95% confidence interval [CI] 4.3–9.7) and 75.5% (95% CI 70.8–79.9), respectively. Sarcopenia tended to be higher in patients unable to perform GS assessment and was unrelated to the type of parkinsonian syndrome. It was associated with older age, longer disease duration, more severe disease, and higher disability in activities of daily living, as assessed by disease-specific clinical rating scale. Dynapenia was directly associated with parkinsonism other than PD, older age, and disability, whereas regular physical therapy appeared to be a preventive factor. However, it was unrelated to disease duration and severity. Finally, the disability score of activities of daily living was inversely correlated with handgrip strength and GS, whereas no association was found with SMM index. ConclusionBeing primarily motor disorders, parkinsonian syndromes are characterized by progressive disability in performing activities of daily living. Impaired functional status is a prominent feature of this patient population, independently of disease duration and severity. Sarcopenia is mainly related to advancing disease and, due to a significant sparing of SMM, is an infrequent condition, likely to play a minor role in disability. Several factors could be responsible for this favorable body composition (eg, motor symptoms, levodopa therapy) and deserve further investigation. The prognostic impact of sarcopenia also needs to be addressed.

Impact of current antipsychotic medications on comparative mortality and adverse events in people with Parkinson’s disease psychosis (PDP)

Objectives: To establish the mortality risk and adverse events associated with the use of atypical antipsychotic medications in people with Parkinson disease psychosis (PDP) in a clinically defined trial cohort. Design: Post hoc analysis of data from a multicenter, open-label extension study of pimavanserin comparing people taking and not taking current antipsychotics. Setting: Primary and secondary care medical centers in the United States, Canada, Europe, and India. Participants: A total of 459 people with PDP enrolled in the extension study. Participants were between ages 30 and 80 years, and had an established diagnosis of idiopathic Parkinson disease and moderate to severe psychosis. Interventions: Participants were categorized into 2 groups: those receiving concomitant antipsychotic medications (“concurrent APD”) and those who did not take antipsychotic medications at any time during the study (“no APD”). Participants were receiving 40 mg pimavanserin daily in addition to concurrent antipsychotics and Parkinson disease medications. Main Outcome Measures: Safety assessments at 2 weeks; 1, 3, 6, 9, and 12 months; and every 6 months thereafter, including evaluation of adverse events (AEs), vital signs, weight, physical examinations, 12lead electrocardiograms, clinical laboratory tests (serum chemistry, hematology, and urinalysis), and the Unified Parkinson’s Disease Rating Scale Parts II and III (UPDRS-IIþIII, activities of daily living and motor impairment, respectively). Differences between participants taking and not taking current antipsychotics were evaluated using incidence rate ratios (IRRs) with 95% confidence intervals (CIs). Results: There was significant increase in the mortality rate for participants taking concurrent antipsychotics compared with the group not taking antipsychotic medications (IRR 4.20, 95% CI 2.13e7.96). Participants who received a concurrent antipsychotic were also significantly more likely to experience overall a serious AE (IRR 2.95, 95% CI 2.02e4.24), any antipsychotic-related event (IRR 1.66, 95% CI 1.18 e2.29), cognition-related events (IRR 2.70, 95% CI 1.19e5.58), infections (IRR 1.97, 95% CI 1.17e3.16), and edema (IRR 2.61, 95% CI 1.09e5.59). The risk of falls, stroke, sedation, orthostatic hypotension, and thromboembolic events was also increased in these individuals but this was not significant. Conclusions: This study highlights a significant risk of mortality, and severe AEs in patients with Parkinson disease receiving atypical antipsychotics. This is similar to or greater than the risks seen in people

The role of skin biopsy in differentiating idiopathic Parkinson's disease from other types of parkinsonism.

Parkinson’s disease is one of the most common neurodegenerative disorders with a worldwide distribution. It has variable and complex phenotype with motor and non-motor manifestations, causes considerable psychosocial morbidity and consumes significant health care resources. Changing population demographics, and in particular, an ageing population in western societies is likely to result in gradually increasing prevalence. Despite significant advances in the understanding of disease pathology, the diagnosis of idiopathic Parkinson’s disease (IPD) remains largely clinical, with discriminatory investigations such as Ioflupane (123I)-labelled single-photon emission computed tomography (DaTSCAN) being used only in the minority of patients. However, postmortem studies have historically demonstrated the fallibility of relying on clinical phenotype and in differentiating IPD from ‘Parkinson’s plus’ conditions such as multiple system atrophy (MSA). An in vivo accessible peripheral biomarker for IPD and MSA would, therefore, be of great value to direct therapy and more accurate patient counselling. The three papers discussed below assess the value of one of the most promising of the available candidate biomarkers in this context; phosphorylated alpha-synuclein (p-α-Syn) which has recently been identified within dermal nerve fibres in IPD. In the first paper, the authors examine the utility of p-α-Syn as a biomarker for diagnosis of IPD, the second looks at p-α-Syn as a biomarker for MSA and the third at using p-α-Syn to differentiate IPD from MSA.