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Abstract Retinal thickness may serve as a biomarker in Parkinson’s disease (PD). In this prospective longitudinal study, we aimed to determine if PD patients present accelerated thinning rate in the parafoveal ganglion cell-inner plexiform layer (pfGCIPL) and peripapillary retinal nerve fiber layer (pRNFL) compared to controls. Additionally, we evaluated the relationship between retinal neurodegeneration and clinical progression in PD. A cohort of 156 PD patients and 72 controls underwent retinal optical coherence tomography, visual, and cognitive assessments between February 2015 and December 2021 in two Spanish tertiary hospitals. The pfGCIPL thinning rate was twice as high in PD (β [SE] = −0.58 [0.06]) than in controls (β [SE] = −0.29 [0.06], p

Parkinson’s disease (PD) is a neurodegenerative disorder marked by motor and cognitive impairments. The early prediction of cognitive deterioration in PD is crucial. This work aims to predict the change in the Montreal Cognitive Assessment (MoCA) at years 4 and 5 from baseline in the Parkinson’s Progression Markers Initiative database. The predictors included demographic and clinical variables: motor and non-motor symptoms from the baseline visit and change scores from baseline to the first-year follow-up. Various regression models were compared, and SHAP (SHapley Additive exPlanations) values were used to assess domain importance, while model coefficients evaluated variable importance. The LASSOLARS algorithm outperforms other models, achieving lowest the MAE, 1.55±0.23 and 1.56±0.19, for the fourth- and fifth-year predictions, respectively. Moreover, when trained to predict the average MoCA score change across both time points, its performance improved, reducing its MAE by 19%. Baseline MoCA scores and MoCA deterioration over the first-year were the most influential predictors of PD (highest model coefficients). However, the cumulative effect of other cognitive variables also contributed significantly. This study demonstrates that mid-term cognitive deterioration in PD can be accurately predicted from patients’ baseline cognitive performance and short-term cognitive deterioration, along with a few easily measurable clinical measurements.

Background and objective: Multiple system atrophy is a rare and fatal neurodegenerative disorder, characterized by autonomic dysfunction in association with either parkinsonism or cerebellar signs. The pathologic hallmark is the presence of alpha-synuclein aggregates in oligodendrocytes, forming glial cytoplasmic inclusions. Clinically, it may be difficult to distinguish form other parkinsonisms or ataxias, particularly in the early stages of the disease. In this case series we aim to describe in detail the features of MSA patients. Material and methods: Unified MSA Rating Scale (UMSARS) score, structural and functional imaging and cardiovascular autonomic testing, are summarized since early stages of the disease. Results: UMSARS proved to be useful to perform a follow-up being longitudinal examination essential to stratify risk of poor outcome. Neuropathological diagnosis showed an overlap between parkinsonian and cerebellar subtypes, with some peculiarities that could help to distinguish from other subtypes. Conclusion: A better description of MSA features with standardized test confirmed by means of neuropathological studies could help to increase sensitivity. Resumen: Antecedentes y objetivo: La atrofia multisistémica es un trastorno neurodegenerativo raro y letal que se caracteriza por una disfunción autonómica en asociación con parkinsonismo o signos cerebelosos. La marca anatomopatológica es la presencia de agregados de α-sinucleína en los oligodendrocitos, que forman inclusiones citoplasmáticas gliales. Desde un punto de vista clínico, puede ser difícil de distinguir de otros parkinsonismos o ataxias, particularmente en las primeras etapas de la enfermedad. En esta serie de casos, nuestro objetivo es describir en detalle las características de los pacientes con atrofia multisistémica. Material y métodos: Se resumen los datos objetidos de la puntuación de la Escala de calificación unificada de la atrofia multisistémica (UMSARS), imágenes estructurales y funcionales y las pruebas autonómicas cardiovasculares realizadas desde las primeras etapas de la enfermedad. Resultados: La escala UMSAR demostró ser útil para hacer un seguimiento: el examen longitudinal esencial fue para estratificar el riesgo de peor evolución. El diagnóstico neuropatológico mostró un solapamiento entre los subtipos parkinsoniano y cerebeloso, con algunas peculiaridades que podrían ayudar a distinguir los subtipos. Conclusión: Una mejor descripción de las características de la atrofia multisistémica en casos confirmados mediante neuropatología podría ayudar a aumentar la sensibilidad del diagnóstico.

Abstract Background Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and post-COVID condition can present similarities such as fatigue, brain fog, autonomic and neuropathic symptoms. Methods The study included 87 patients with post-COVID condition, 50 patients with ME/CFS, and 50 healthy controls (HC). The hemodynamic autonomic function was evaluated using the deep breathing technique, Valsalva maneuver, and Tilt test. The presence of autonomic and sensory small fiber neuropathy (SFN) was assessed with the Sudoscan and with heat and cold evoked potentials, respectively. Finally, a complete neuropsychological evaluation was performed. The objective of this study was to analyze and compare the autonomic and neuropathic symptoms in post-COVID condition with ME/CFS, and HC, as well as, analyze the relationship of these symptoms with cognition and fatigue. Results Statistically significant differences were found between groups in heart rate using the Kruskal–Wallis test (H), with ME/CFS group presenting the highest (H = 18.3; p ≤ .001). The Postural Orthostatic Tachycardia Syndrome (POTS), and pathological values in palms on the Sudoscan were found in 31% and 34% of ME/CFS, and 13.8% and 19.5% of post-COVID patients, respectively. Concerning evoked potentials, statistically significant differences were found in response latency to heat stimuli between groups (H = 23.6; p ≤ .01). Latency was highest in ME/CFS, and lowest in HC. Regarding cognition, lower parasympathetic activation was associated with worse cognitive performance. Conclusions Both syndromes were characterized by inappropriate tachycardia at rest, with a high percentage of patients with POTS. The prolonged latencies for heat stimuli suggested damage to unmyelinated fibers. The higher proportion of patients with pathological results for upper extremities on the Sudoscan suggested a non-length-dependent SFN.

Abstract Background Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is characterized by persistent physical and mental fatigue. The post-COVID-19 condition patients refer physical fatigue and cognitive impairment sequelae. Given the similarity between both conditions, could it be the same pathology with a different precipitating factor? Objective To describe the cognitive impairment, neuropsychiatric symptoms, and general symptomatology in both groups, to find out if it is the same pathology. As well as verify if the affectation of smell is related to cognitive deterioration in patients with post-COVID-19 condition. Methods The sample included 42 ME/CFS and 73 post-COVID-19 condition patients. Fatigue, sleep quality, anxiety and depressive symptoms, the frequency and severity of different symptoms, olfactory function and a wide range of cognitive domains were evaluated. Results Both syndromes are characterized by excessive physical fatigue, sleep problems and myalgia. Sustained attention and processing speed were impaired in 83.3% and 52.4% of ME/CFS patients while in post-COVID-19 condition were impaired in 56.2% and 41.4% of patients, respectively. Statistically significant differences were found in sustained attention and visuospatial ability, being the ME/CFS group who presented the worst performance. Physical problems and mood issues were the main variables correlating with cognitive performance in post-COVID-19 patients, while in ME/CFS it was anxiety symptoms and physical fatigue. Conclusions The symptomatology and cognitive patterns were similar in both groups, with greater impairment in ME/CFS. This disease is characterized by greater physical and neuropsychiatric problems compared to post-COVID-19 condition. Likewise, we also propose the relevance of prolonged hyposmia as a possible marker of cognitive deterioration in patients with post-COVID-19.

Abstract Heart rate variability (HRV) abnormalities are potential early biomarkers in Parkinson’s disease (PD) but their relationship with central autonomic network (CAN) activity is not fully understood. We analyzed the synchronization between HRV and brain activity in 31 PD patients and 21 age-matched healthy controls using blood-oxygen-level-dependent (BOLD) signals from resting-state functional brain MRI and HRV metrics from finger plethysmography recorded for 7.40 min. We additionally quantified autonomic symptoms (SCOPA-AUT) and objective autonomic cardiovascular parameters (blood pressure and heart rate) during deep breathing, Valsalva, and head-up tilt, which were used to classify the clinical severity of dysautonomia. We evaluated HRV and BOLD signals synchronization (HRV-BOLD-sync) with Pearson lagged cross-correlations and Fisher’s statistics for combining window-length-dependent HRV-BOLD-Sync Maps and assessed their association with clinical dysautonomia. HRV-BOLD-sync was lower significantly in PD than in controls in various brain regions within CAN or in networks involved in autonomic modulation. Moreover, heart-brain synchronization index (HBSI), which quantifies heart-brain synchronization at a single-subject level, showed an inverse exposure–response relationship with dysautonomia severity, finding the lowest HBSI in patients with severe dysautonomia, followed by moderate, mild, and, lastly, controls. Importantly, HBSI was associated in PD, but not in controls, with Valsalva pressure recovery time (sympathetic), deep breathing E/I ratio (cardiovagal), and SCOPA-AUT. Our findings support the existence of heart-brain de-synchronization in PD with an impact on clinically relevant autonomic outcomes.

Parkinson's disease (PD) is a neurodegenerative disorder marked by motor and cognitive impairments. The early prediction of cognitive deterioration in PD is crucial. This work aims to predict the change in the Montreal Cognitive Assessment (MoCA) at years 4 and 5 from baseline in the Parkinson's Progression Markers Initiative database. The predictors included demographic and clinical variables: motor and non-motor symptoms from the baseline visit and change scores from baseline to the first-year follow-up. Various regression models were compared, and SHAP (SHapley Additive exPlanations) values were used to assess domain importance, while model coefficients evaluated variable importance. The LASSOLARS algorithm outperforms other models, achieving lowest the MAE, 1.55 ± 0.23 and 1.56 ± 0.19 , for the fourth- and fifth-year predictions, respectively. Moreover, when trained to predict the average MoCA score change across both time points, its performance improved, reducing its MAE by 19%. Baseline MoCA scores and MoCA deterioration over the first-year were the most influential predictors of PD (highest model coefficients). However, the cumulative effect of other cognitive variables also contributed significantly. This study demonstrates that mid-term cognitive deterioration in PD can be accurately predicted from patients' baseline cognitive performance and short-term cognitive deterioration, along with a few easily measurable clinical measurements. [ABSTRACT FROM AUTHOR]

Characterizing the effect of age and sex on macular retinal layer thicknesses and foveal pit morphology is crucial to differentiating between natural and disease-related changes. We applied advanced image analysis techniques to optical coherence tomography (OCT) to: 1) enhance the spatial description of age and sex effects, and 2) create a detailed open database of normative retinal layer thickness maps and foveal pit shapes. The maculae of 444 healthy subjects (age range 21–88) were imaged with OCT. Using computational spatial data analysis, thickness maps were obtained for retinal layers and averaged into 400 (20 x 20) sectors. Additionally, the geometry of the foveal pit was radially analyzed by computing the central foveal thickness, rim height, rim radius, and mean slope. The effect of age and sex on these parameters was analyzed with multiple regression mixed-effects models. We observed that the overall age-related decrease of the total retinal thickness (TRT) (-1.1% per 10 years) was mainly driven by the ganglion cell-inner plexiform layer (GCIPL) (-2.4% per 10 years). Both TRT and GCIPL thinning patterns were homogeneous across the macula when using percentual measurements. Although the male retina was 4.1 μm thicker on average, the greatest differences were mainly present for the inner retinal layers in the inner macular ring (up to 4% higher TRT than in the central macula). There was an age-related decrease in the rim height (1.0% per 10 years) and males had a higher rim height, shorter rim radius, and steeper mean slope. Importantly, the radial analysis revealed that these changes are present and relatively uniform across angular directions. These findings demonstrate the capacity of advanced analysis of OCT images to enhance the description of the macula. This, together with the created dataset, could aid the development of more accurate diagnosis models for macular pathologies.

Background: We aimed to characterize subtypes of synucleinopathies using a clustering approach based on cognitive and other nonmotor data and to explore structural and functional magnetic resonance imaging (MRI) brain differences between identified clusters. Methods: Sixty-two patients (n = 6 E46K-SNCA, n = 8 dementia with Lewy bodies (DLB) and n = 48 idiopathic Parkinson’s disease (PD)) and 37 normal controls underwent nonmotor evaluation with extensive cognitive assessment. Hierarchical cluster analysis (HCA) was performed on patients’ samples based on nonmotor variables. T1, diffusion-weighted, and resting-state functional MRI data were acquired. Whole-brain comparisons were performed. Results: HCA revealed two subtypes, the mild subtype (n = 29) and the severe subtype (n = 33). The mild subtype patients were slightly impaired in some nonmotor domains (fatigue, depression, olfaction, and orthostatic hypotension) with no detectable cognitive impairment; the severe subtype patients (PD patients, all DLB, and the symptomatic E46K-SNCA carriers) were severely impaired in motor and nonmotor domains with marked cognitive, visual and bradykinesia alterations. Multimodal MRI analyses suggested that the severe subtype exhibits widespread brain alterations in both structure and function, whereas the mild subtype shows relatively mild disruptions in occipital brain structure and function. Conclusions: These findings support the potential value of incorporating an extensive nonmotor evaluation to characterize specific clinical patterns and brain degeneration patterns of synucleinopathies.

BackgroundRetinal microvascular alterations have been previously described in Parkinson’s disease (PD) patients using optical coherence tomography angiography (OCT-A). However, an extensive description of retinal vascular morphological features, their association with PD-related clinical variables and their potential use as diagnostic biomarkers has not been explored.MethodsWe performed a cross-sectional study including 49 PD patients (87 eyes) and 40 controls (73 eyes). Retinal microvasculature was evaluated with Spectralis OCT-A and cognitive status with Montreal Cognitive Assessment. Unified PD Rating Scale and disease duration were recorded in patients. We extracted microvascular parameters from superficial and deep vascular plexuses of the macula, including the area and circularity of foveal avascular zone (FAZ), skeleton density, perfusion density, vessel perimeter index, vessel mean diameter, fractal dimension (FD) and lacunarity using Python and MATLAB. We compared the microvascular parameters between groups and explored their association with thickness of macular layers and clinical outcomes. Data were analyzed with General Estimating Equations (GEE) and adjusted for age, sex, and hypertension. Logistic regression GEE models were fitted to predict diagnosis of PD versus controls from microvascular, demographic, and clinical data. The discrimination ability of models was tested with receiver operating characteristic curves.ResultsFAZ area was significantly smaller in patients compared to controls in superficial and deep plexuses, whereas perfusion density, skeleton density, FD and lacunarity of capillaries were increased in the foveal zone of PD. In the parafovea, microvascular parameters of superficial plexus were associated with ganglion cell-inner plexiform layer thickness, but this was mainly driven by PD with mild cognitive impairment. No such associations were observed in controls. FAZ area was negatively associated with cognition in PD (non-adjusted models). Foveal lacunarity, combined with demographic and clinical confounding factors, yielded an outstanding diagnostic accuracy for discriminating PD patients from controls.ConclusionParkinson’s disease patients displayed foveal microvascular alterations causing an enlargement of the vascular bed surrounding FAZ. Parafoveal microvascular alterations were less pronounced but were related to inner retinal layer thinning. Retinal microvascular abnormalities helped discriminating PD from controls. All this supports OCT-A as a potential non-invasive biomarker to reveal vascular pathophysiology and improve diagnostic accuracy in PD.

ObjectiveTo prospectively evaluate nocturnal sleep problems and excessive daytime sleepiness (EDS) in Parkinson's disease (PD) patients, and analyze the influence of motor symptoms, treatment, and sex differences on sleep problems in PD.MethodsSleep disturbances of 103 PD patients were assessed with Parkinson's Disease Sleep Scale (PDSS) and the Epworth Sleepiness Scale (ESS). Student's t-test for related samples, one-way ANOVA with Tukey's HSD post hoc test were used to assess group differences. Bivariate correlations and mixed-effects linear regression models were used to analyze the association between clinical aspects and sleep disturbances over time.ResultsAt baseline, 48.5% of PD patients presented nocturnal problems and 40% of patients presented EDS. The PDSS and ESS total score slightly improve over time. Nocturnal problems were associated with age and motor impartment, explaining the 51% of the variance of the PDSS model. Males presented less nocturnal disturbances and more EDS than females. Higher motor impairment and combined treatment (L-dopa and agonist) were related to more EDS, while disease duration and L-dopa in monotherapy were related to lower scores, explaining the 59% of the model.ConclusionsSleep disturbances changed over time and age, diseases duration, motor impairment, treatment and sex were associated with nocturnal sleep problems and EDS. Agonist treatment alone or in combination with L-dopa might predict worse daytime sleepiness, while L-dopa in monotherapy is related to lower EDS, which significantly affects the quality of life of PD patients.

Parkinson’s disease (PD) is the second most common neurodegenerative disease after Alzheimer’s disease. In this study, the tear proteome profile of patients with idiopathic PD (iPD, n = 24), carriers of the E46K-SNCA mutation (n = 3) and healthy control (CT, n = 27) subjects was analyzed to identify candidate biomarkers for the diagnosis of PD. An observational, prospective and case-control pilot study was carried out, analyzing the participants tear samples by nano-liquid chromatography–mass spectrometry (nLC–MS/MS) and assessing their neurological impairment. The proteomic data obtained are available at ProteomeXchange with identifier 10.6019/PXD028811. These analyses led to the identification of 560 tear proteins, some of which were deregulated in PD patients and that have been implicated in immune responses, inflammation, apoptosis, collagen degradation, protein synthesis, defense, lipid transport and altered lysosomal function. Of these proteins, six were related to neurodegenerative processes and showed a good capacity to classify patients and controls. These findings revealed that certain proteins were upregulated in the tears of PD patients, mainly proteins involved in lysosomal function. Thus, in this study, tear proteins were identified that are implicated in neurodegeneration and that may be related to an aggressive disease phenotype in PD patients.

Corneal refractive surgery procedures are widely performed to permanently correct refractive errors. Overall, refractive surgeries are safe, predictable and present high rates of satisfaction. Nevertheless, the induced epithelial, stromal and nerve damage alters corneal integrity and function, triggering a regenerative response. Complications that arise from corneal wound healing process might directly impact on visual outcomes of keratorefractive procedures. Most of these complications can be prevented or effectively treated with minimal consequences and minor impact on optical quality. Nevertheless, it is crucial to accurately and timely identify these corneal regeneration-related complications for successful counseling and management. Optometrists, as primary eye care providers, play an essential role in detecting anatomic and functional alterations in vision. It is therefore of great interest for optometrists to be familiar with the principal postoperative complications derived from alterations in regenerative process after corneal laser refractive surgeries. This review aims to provide a basis for optometrists to better understand, identify and manage the main wound healing-related complications after refractive surgery. Resumen: La cirugía refractiva corneal se lleva a cabo a menudo para corregir de manera permanente los errores refractivos. En general, la cirugía refractiva es segura y predecible, y presenta altos índices de satisfacción. Sin embargo, el daño inducido a nivel epitelial, estromal y nervioso altera la integridad y la función de la córnea, y desencadena una respuesta regenerativa. Las complicaciones que surgen del proceso de cicatrización de la herida corneal podrían tener un impacto directo sobre los resultados visuales de los procedimientos queratorefractivos. La mayoría de estas complicaciones pueden prevenirse, o tratarse de manera efectiva con mínimas consecuencias y un menor impacto sobre la calidad óptica. Sin embargo, es esencial identificar de manera precisa y oportuna dichas complicaciones relacionadas con la regeneración de la córnea, en aras de llegar a un asesoramiento y tratamiento satisfactorios. Los optometristas, al ser profesionales sanitarios de atención ocular primaria, juegan un papel esencial a la hora de detectar las alteraciones anatómicas y funcionales de la visión. Por tanto, es muy interesante que los optometristas estén familiarizados con las complicaciones postoperatorias principales derivadas de las alteraciones del proceso regenerativo tras cirugía refractiva corneal láser. Esta revisión tiene como objetivo proporcionar una base a los optometristas para la mejor comprensión, identificación y tratamiento de las principales complicaciones relacionadas con el proceso de cicatrización tras una cirugía refractiva. Keywords: Refractive surgery, Corneal regeneration, Complications, Visual outcomes, Palabras clave: Cirugía refractiva, Regeneración de la córnea, Complicaciones, Resultados visuales

Disentangling the cellular anatomy that gives rise to human visual perception is one of the main challenges of ophthalmology. Of particular interest is the foveal pit, a concave depression located at the center of the retina that captures light from the gaze center. In recent years, there has been a growing interest in studying the morphology of the foveal pit by extracting geometrical features from optical coherence tomography (OCT) images. Despite this, research has devoted little attention to comparing existing approaches for two key methodological steps: the location of the foveal center and the mathematical modelling of the foveal pit. Building upon a dataset of 185 healthy subjects imaged twice, in the present paper the image alignment accuracy of four different foveal center location methods is studied in the first place. Secondly, state-of-the-art foveal pit mathematical models are compared in terms of fitting error, repeatability, and bias. The results indicate the importance of using a robust foveal center location method to align images. Moreover, we show that foveal pit models can improve the agreement between different acquisition protocols. Nevertheless, they can also introduce important biases in the parameter estimates that should be considered.