Corneal Confocal Microscopy Identifies Parkinson's Disease with More Rapid Motor Progression

From Wiley via Jisc Publications RouterHistory: received 2020-12-15, rev-recd 2021-03-11, accepted 2021-03-12, pub-electronic 2021-04-07, pub-print 2021-08Article version: VoRPublication status: PublishedFunder: Michael J Fox Foundation Trust (Grant ID 12059); Id: http://dx.doi.org/10.13039/100010269ABSTRACT: Background: Corneal confocal microscopy (CCM) is a noninvasive, reproducible ophthalmic technique to quantify corneal small nerve fiber degeneration. CCM demonstrates small nerve fiber damage in Parkinson's disease (PD), but its role as a longitudinal biomarker of PD progression has not been explored. Objective: The aim of this study was to assess corneal nerve morphology using CCM in relation to disease progression in PD. Methods: Sixty‐four participants with PD were assessed at baseline and at 12‐month follow‐up. Participants underwent CCM with automated corneal nerve quantification and assessment of Movement Disorder Society Unified Parkinson's Disease Rating Scale, Hoehn and Yahr stage, and Montreal Cognitive Assessment. Results: Corneal nerve fiber density (CNFD), corneal nerve branch density, corneal nerve fiber length, corneal total branch density, and corneal nerve fiber area were significantly lower in participants with PD compared with healthy control subjects. Worsening of Movement Disorder Society Unified Parkinson's Disease Rating Scale part III score over 12 months was significantly greater in participants with a CNFD in the lowest compared with the highest quartile at baseline (mean difference: 6.0; 95% CI: 1.0–10.9; P = 0.019). There were no significant changes in CNFD, corneal nerve branch density, corneal nerve fiber length, corneal total branch density, corneal nerve fiber area, or corneal nerve fiber width between baseline and 12‐month follow‐up. Conclusions: CCM identifies neurodegeneration in patients with PD, especially those who show the greatest progression in neurological disability. CCM may be a useful tool to help enrich clinical trials with those likely to exhibit more rapid progression and reduce required sample size and cost of studies. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Societ

Validating differential volatilome profiles in Parkinson’s disease

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Corneal Confocal Microscopy to Image Small Nerve Fiber Degeneration: Ophthalmology Meets Neurology.

Neuropathic pain has multiple etiologies, but a major feature is small fiber dysfunction or damage. Corneal confocal microscopy (CCM) is a rapid non-invasive ophthalmic imaging technique that can image small nerve fibers in the cornea and has been utilized to show small nerve fiber loss in patients with diabetic and other neuropathies. CCM has comparable diagnostic utility to intraepidermal nerve fiber density for diabetic neuropathy, fibromyalgia and amyloid neuropathy and predicts the development of diabetic neuropathy. Moreover, in clinical intervention trials of patients with diabetic and sarcoid neuropathy, corneal nerve regeneration occurs early and precedes an improvement in symptoms and neurophysiology. Corneal nerve fiber loss also occurs and is associated with disease progression in multiple sclerosis, Parkinson's disease and dementia. We conclude that corneal confocal microscopy has good diagnostic and prognostic capability and fulfills the FDA criteria as a surrogate end point for clinical trials in peripheral and central neurodegenerative diseases

Mindful gratitude journaling: psychological distress, quality of life and suffering in advanced cancer: a randomised controlled trial

Context Numerous studies have shown that gratitude can reduce stress and improve quality of life. Objective Our study aimed to examine the effect of mindful gratitude journaling on suffering, psychological distress and quality of life of patients with advanced cancer. Methods We conducted a parallel-group, blinded, randomised controlled trial at the University of Malaya Medical Centre, Malaysia. Ninety-two adult patients with advanced cancer, and an overall suffering score ≥4/10 based on the Suffering Pictogram were recruited and randomly assigned to either a mindful gratitude journaling group (N=49) or a routine journaling group (N=43). Results After 1 week, there were significant reductions in the overall suffering score from the baseline in both the intervention group (mean difference in overall suffering score=−2.0, 95% CI=−2.7 to −1.4, t=−6.125, p=0.000) and the control group (mean difference in overall suffering score=−1.6, 95% CI=−2.3 to −0.8, t=−4.106, p=0.037). There were also significant improvements in the total Hospital Anxiety and Depression Scale score (mean difference=−3.4, 95% CI=−5.3 to −1.5, t=−3.525, p=0.000) and the total Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being score (mean difference=7.3, 95% CI=1.5 to 13.1, t=2.460, p=0.014) in the intervention group after 7 days, but not in the control group. Conclusion The results provide evidence that 7 days of mindful gratitude journaling could positively affect the state of suffering, psychological distress and quality of life of patients with advanced cancer

Effectiveness and safety of opicapone in Parkinson’s disease patients with motor fluctuations: the OPTIPARK open-label study

Background The efficacy and safety of opicapone, a once-daily catechol-O-methyltransferase inhibitor, have been established in two large randomized, placebo-controlled, multinational pivotal trials. Still, clinical evidence from routine practice is needed to complement the data from the pivotal trials. Methods OPTIPARK (NCT02847442) was a prospective, open-label, single-arm trial conducted in Germany and the UK under clinical practice conditions. Patients with Parkinson’s disease and motor fluctuations were treated with opicapone 50 mg for 3 (Germany) or 6 (UK) months in addition to their current levodopa and other antiparkinsonian treatments. The primary endpoint was the Clinician’s Global Impression of Change (CGI-C) after 3 months. Secondary assessments included Patient Global Impressions of Change (PGI-C), the Unified Parkinson’s Disease Rating Scale (UPDRS), Parkinson’s Disease Questionnaire (PDQ-8), and the Non-Motor Symptoms Scale (NMSS). Safety assessments included evaluation of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). Results Of the 506 patients enrolled, 495 (97.8%) took at least one dose of opicapone. Of these, 393 (79.4%) patients completed 3 months of treatment. Overall, 71.3 and 76.9% of patients experienced any improvement on CGI-C and PGI-C after 3 months, respectively (full analysis set). At 6 months, for UK subgroup only (n = 95), 85.3% of patients were judged by investigators as improved since commencing treatment. UPDRS scores at 3 months showed statistically significant improvements in activities of daily living during OFF (mean ± SD change from baseline: − 3.0 ± 4.6, p < 0.0001) and motor scores during ON (− 4.6 ± 8.1, p < 0.0001). The mean ± SD improvements of − 3.4 ± 12.8 points for PDQ-8 and -6.8 ± 19.7 points for NMSS were statistically significant versus baseline (both p < 0.0001). Most of TEAEs (94.8% of events) were of mild or moderate intensity. TEAEs considered to be at least possibly related to opicapone were reported for 45.1% of patients, with dyskinesia (11.5%) and dry mouth (6.5%) being the most frequently reported. Serious TEAEs considered at least possibly related to opicapone were reported for 1.4% of patients. Conclusions Opicapone 50 mg was effective and generally well-tolerated in PD patients with motor fluctuations treated in clinical practice. Trial registration Registered in July 2016 at clinicaltrials.gov (NCT02847442)

Paper Spray Ionization Ion Mobility Mass Spectrometry of Sebum Classifies Biomarker Classes for the Diagnosis of Parkinson's Disease

[Image: see text] Parkinson’s disease (PD) is the second most common neurodegenerative disorder, and identification of robust biomarkers to complement clinical diagnosis will accelerate treatment options. Here, we demonstrate the use of direct infusion of sebum from skin swabs using paper spray ionization coupled with ion mobility mass spectrometry (PS-IM-MS) to determine the regulation of molecular classes of lipids in sebum that are diagnostic of PD. A PS-IM-MS method for sebum samples that takes 3 min per swab was developed and optimized. The method was applied to skin swabs collected from 150 people and elucidates ∼4200 features from each subject, which were independently analyzed. The data included high molecular weight lipids (>600 Da) that differ significantly in the sebum of people with PD. Putative metabolite annotations of several lipid classes, predominantly triglycerides and larger acyl glycerides, were obtained using accurate mass, tandem mass spectrometry, and collision cross section measurements

Tau associated peripheral and central neurodegeneration: Identification of an early imaging marker for tauopathy

Pathological hyperphosphorylated tau is a key feature of Alzheimer’s disease (AD) and Frontotemporal dementia (FTD). Using transgenic mice overexpressing human non-mutated tau (htau mice), we assessed the contribution of tau to peripheral and central neurodegeneration. Indices of peripheral small and large fiber neuropathy and learning and memory performances were assessed at 3 and 6 months of age. Overexpression of human tau is associated with peripheral neuropathy at 6 months of age. Our study also provides evidence that non-mutated tau hyperphosphorylation plays a critical role in memory deficits. In addition, htau mice had reduced stromal corneal nerve length with preservation of sub-basal corneal nerves, consistent with a somatofugal degeneration. Corneal nerve degeneration occurred prior to any cognitive deficits and peripheral neuropathy. Stromal corneal nerve loss was observed in patients with FTD but not AD. Corneal confocal microscopy may be used to identify early neurodegeneration and differentiate FTD from AD