Implication of nutrition in severity of symptoms and treatments in quality of life in Parkinson's disease: a systematic review.

Parkinson's disease (PD) is characterized by motor and non-motor symptoms. Nutritional alterations are one of the non-motor symptoms that most influence the quality of life (QoL) in PD. Objective: Therefore, this review aims to evaluate whether nutritional alterations are related either to the severity of motor and non-motor symptoms through the gut-brain axis or to the different treatments for PD and whether all of this, in turn, impacts the QoL of patients. Methods: A systematic review was carried out in MEDLINE and EMBASE databases, and Mendeley from 2000 to June 2024, searching for articles related to nutritional alterations in PD that alter patients' QoL. A total of 14 articles (2,187 participants) of 924 records were included. Results: Among the 14 studies examined, two investigated the relationship between nutritional status and QoL in patients with PD. Poor nutritional status was associated with lower QoL scores. Four studies explored the connection between nutritional status and its impact on both motor and non-motor symptoms (psychiatric disturbances, cognitive impairment, and fatigue), revealing a link between nutritional status, activities of daily living, and the severity of motor symptoms. Three studies identified changes in body weight associated with the severity of symptoms related to mobility issues in PD patients. Three studies investigated the relationship between different PD treatments and their interaction with changes in weight and energy metabolism, highlighting that weight loss in the early stages of PD needs adequate monitoring of different treatments, as well as the interaction between the central and peripheral nervous systems in regulating these processes. Finally, two studies investigated how gastrointestinal alterations and changes in the microbiota were related to cognitive status, thus identifying them as risk factors and early signs of PD. Discussion: The systematic review highlighted the significant relationship between nutritional status and QoL in patients with PD, as well as how the PD treatments influenced their weight. An association was also observed in the gut-brain axis, where adequate nutritional status influenced the balance of intestinal microbiota, slowing cognitive decline, improving activities of daily living, and the QoL of PD patients. It is confirmed that the nutritional status of patients influenced both motor and non-motor symptoms of the disease, and therefore their QoL.

Invasive procedures and surgery following etranacogene dezaparvovec gene therapy in people with hemophilia B.

BACKGROUND: Little information regarding the management of invasive procedures in people with hemophilia B (HB) after undergoing gene therapy is available. Here, we report the management of invasive procedures in people with severe or moderately severe HB who had previously been treated with etranacogene dezaparvovec in the phase 2b and phase 3 Health Outcomes with Padua Gene; Evaluation in Hemophilia B clinical trials (NCT03489291 and NCT03569891). OBJECTIVES: The objective of this study was to describe the use of exogenous FIX, endogenous FIX activity prior to invasive procedures, and peri- and postoperative bleeds in participants who underwent invasive procedures after receiving etranacogene dezaparvovec gene therapy. METHODS: This retrospective analysis included invasive procedures performed within 3 and 2 years following a single infusion of 2 × 1013 gc/kg of etranacogene dezaparvovec in participants in the phase 2b and Health Outcomes with Padua Gene; Evaluation in Hemophilia B trials, respectively. Data for factor (F)IX dosing, duration of postoperative FIX use, FIX activity prior to invasive procedures, and postoperative bleeds were collected and analyzed. RESULTS: The analysis included 64 procedures in 29 participants: 9 major surgeries, 24 minor surgeries, 11 endoscopies, 3 endoscopies with biopsy/polypectomy, and 17 dental procedures. Uncontaminated endogenous FIX activity corresponded to mild hemophilia or normal levels prior to 98% of all procedures, with a median endogenous FIX activity of 43.8 IU/dL (range, 3.1-113 IU/dL). All major surgeries were managed with exogenous FIX, 67% with ≤4 days of FIX infusion. Most minor surgeries (88%), endoscopies (82%), and dental procedures (94%) were managed with no or a single FIX infusion. Postoperative bleeds occurred after 1 minor surgery and 4 dental procedures. There were no symptomatic thrombotic events or FIX inhibitor developments. CONCLUSION: Etranacogene dezaparvovec has the potential to facilitate perioperative management in people with HB by reducing the need for perioperative exogenous FIX and its associated risks.

Virtual Coaching for Home Rehabilitation - Evidence of an Empirical Study.

Older individuals often face disabilities or diseases that lower their quality of life (QoL). While inpatient rehabilitation can initially enhance QoL, there is often a lack of continuation at home. Virtual coaches (VCs) as specific embodied conversational agents promise appropriate support for home rehabilitation. They emerge as complementary digital aids to ensure care continuity. This paper presents the results of implementing a full-featured VC for older patients' home rehabilitation in a multi-stage study, summarizing the main results regarding QoL outcomes and user experience tests. The study confirms the intervention as an engaging means for rehabilitation (mostly above user experience thresholds) and improvements of QoL (>10% between experimental and control groups).

Rapid iPSC inclusionopathy models shed light on formation, consequence, and molecular subtype of α-synuclein inclusions.

The heterogeneity of protein-rich inclusions and its significance in neurodegeneration is poorly understood. Standard patient-derived iPSC models develop inclusions neither reproducibly nor in a reasonable time frame. Here, we developed screenable iPSC "inclusionopathy" models utilizing piggyBac or targeted transgenes to rapidly induce CNS cells that express aggregation-prone proteins at brain-like levels. Inclusions and their effects on cell survival were trackable at single-inclusion resolution. Exemplar cortical neuron α-synuclein inclusionopathy models were engineered through transgenic expression of α-synuclein mutant forms or exogenous seeding with fibrils. We identified multiple inclusion classes, including neuroprotective p62-positive inclusions versus dynamic and neurotoxic lipid-rich inclusions, both identified in patient brains. Fusion events between these inclusion subtypes altered neuronal survival. Proteome-scale α-synuclein genetic- and physical-interaction screens pinpointed candidate RNA-processing and actin-cytoskeleton-modulator proteins like RhoA whose sequestration into inclusions could enhance toxicity. These tractable CNS models should prove useful in functional genomic analysis and drug development for proteinopathies.

Plasma Neurofilament Light Chain: A Potential Biomarker for Neurological Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex disorder characterized by heterogeneous symptoms, which lack specific biomarkers for its diagnosis. This study aimed to investigate plasma neurofilament light chain (NfL) levels as a potential biomarker for ME/CFS and explore associations with cognitive, autonomic, and neuropathic symptoms. Here, 67 ME/CFS patients and 43 healthy controls (HCs) underwent comprehensive assessments, including neuropsychological evaluation, autonomic nervous system (ANS) testing, and plasma NfL level analysis. ME/CFS patients exhibited significantly higher plasma NfL levels compared to HC (F = 4.30, p < 0.05). Correlations were observed between NfL levels and cognitive impairment, particularly in visuospatial perception (r = -0.42; p ≤ 0.001), verbal memory (r = -0.35, p ≤ 0.005), and visual memory (r = -0.26; p < 0.05) in ME/CFS. Additionally, higher NfL levels were associated with worsened autonomic dysfunction in these patients, specifically in parasympathetic function (F = 9.48, p ≤ 0.003). In ME/CFS patients, NfL levels explained up to 17.2% of the results in cognitive tests. Unlike ME/CFS, in HC, NfL levels did not predict cognitive performance. Elevated plasma NfL levels in ME/CFS patients reflect neuroaxonal damage, contributing to cognitive dysfunction and autonomic impairment. These findings support the potential role of NfL as a biomarker for neurological dysfunction in ME/CFS. Further research is warranted to elucidate underlying mechanisms and clinical implications.

Caracterización epidemiológica de pacientes con síndrome posterior a resección anterior baja de recto y aproximación de su relación con aspectos demográficos, patológicos y quirúrgicos, en un centro de referencia en Medellín, entre 2016-2022 / Epidemiological characterization of patients with post-low anterior rectal resection syndrome and approximation of its relationship with demographic, pathological, and surgical aspects, in a referral center in Medellin, between 2016-2022

Introducción. El cáncer colorrectal es uno de los tipos de cáncer más comunes y mortales a nivel mundial. Aunque los avances médicos han mejorado el manejo, la cirugía sigue siendo fundamental. La resección anterior baja (RAB) de recto ha ganado relevancia, a pesar de que puede llevar al síndrome de resección anterior baja de recto (LARS, por sus siglas en inglés), afectando la calidad de vida. Métodos. Estudio de corte transversal con intención analítica en un centro de referencia en Medellín, Colombia. Los pacientes con cáncer de recto sometidos a RAB entre enero de 2016 y diciembre de 2022 completaron el cuestionario LARS para evaluar disfunción intestinal. Se evaluaron factores relacionados con la presencia de LARS por medio de un análisis bivariado. Resultados. De 234 pacientes elegibles, 110 (47 %) respondieron la encuesta, predominantemente mujeres (58,2 %). La edad promedio fue 62 años. Dos tercios de los pacientes recibieron neoadyuvancia y el 69 % requirieron ileostomía. La prevalencia de LARS fue 47,3 %. El 80,9 % llevaban más de 12 meses desde la cirugía o el cierre del estoma. Factores estadísticamente significativos asociados a LARS fueron edad mayor de 65 años (p=0,03), estadío patológico avanzado (p=0,02) y requerimiento de estoma (p=0,03). Conclusiones. El LARS afecta a casi la mitad de los pacientes en diferentes etapas posquirúrgicas. El LARS scorees una herramienta práctica para evaluar la función intestinal en el seguimiento del paciente. La prevalencia y los factores de riesgo identificados contribuyen a la comprensión del impacto de la cirugía conservadora del esfínter en la calidad de vida de los pacientes.

Introduction. Colorectal cancer is one of the most common and deadly types of cancer worldwide, with a high incidence of rectal cancer. Although medical advances have improved management, surgery remains crucial. Low anterior resection of the rectum (LAR) has gained significance, despite its potential to lead to low anterior resection syndrome (LARS), affecting quality of life. Methods. A cross-sectional study with analytical intent was conducted at a referral center in Medellín, Colombia. Patients with rectal cancer who underwent LAR between January 2016 and December 2022 completed the LARS questionnaire to assess intestinal dysfunction. Factors related to the presence of LARS were analyzed using bivariate analysis. Results. Of 234 eligible patients, 110 (47%) responded, predominantly women (58.2%). The average age was 62 years. Two-thirds of patients received neoadjuvant therapy and 69% required ileostomy. The prevalence of LARS was 47.3%. 80.9% had been more than 12 months post-surgery or stoma closure. Statistically significant factors associated with LARS included age over 65 years (p=0.03), advanced pathological stage (p=0.02), and stoma requirement (p=0.03). Conclusions. LARS affects almost half of the patients in various post-surgical stages. The LARS score is a practical tool for assessing intestinal function in patient follow-up. The prevalence and risk factors identified contribute to the understanding of the impact of sphincter-conserving surgery on patients' quality of life.

Understanding the olfactory role in post-COVID cognitive and neuropsychiatric manifestations.

Introduction: Olfactory dysfunction (OD) is frequent after SARS-CoV-2 infection. The aim of this study was to examine if long-term OD is common in post-COVID condition, and the relationship between olfaction, cognition, neuropsychiatric symptoms, and disease duration in these patients. Methods: This study included 121 participants with post-COVID condition and 51 healthy controls (HC). A comprehensive neuropsychological and neuropsychiatric assessment was conducted, encompassing various domains, including general cognition, processing speed, verbal fluency, attention, verbal memory, visual memory, visuoconstructive ability, visuospatial ability, abstraction, executive functions, anxious-depressive symptoms, general health perception, fatigue level, sleep quality, and olfaction. Statistical analyses were carried out to understand the relationship of OD with cognition, and its role as moderator variable. Results: In total, 25% of the post-covid patients had a reduced smell capacity, while only 9.3% of HC presented OD. Post-COVID patients had statistically significantly worse cognitive performance and clinical status than HC. Verbal fluency (AUC = 0.85, p < 0.001), and attention (AUC = 0.82, p < 0.001) were the variables that best discriminate between groups. OD seemed to be a moderator between fatigue and cognition, and between disease duration and attention (ß = -0.04; p = 0.014). Discussion: The study highlights marked cognitive and neuropsychiatric sequelae in individuals post-COVID relative to HC. Olfactory impairment exhibits correlations with both cognitive performance and general health. Olfaction emerges as a potential prognostic marker owing to its moderating influence on disease severity indicators.

The endocannabinoid anandamide activates pro-resolving pathways in human primary macrophages by engaging both CB2 and GPR18 receptors.

Resolution of inflammation is the cellular and molecular process that protects from widespread and uncontrolled inflammation and restores tissue function in the aftermath of acute immune events. This process is orchestrated by specialized pro-resolving mediators (SPM), a class of bioactive lipids able to reduce immune activation and promote removal of tissue debris and apoptotic cells by macrophages. Although SPMs are the lipid class that has been best studied for its role in facilitating the resolution of self-limited inflammation, a number of other lipid signals, including endocannabinoids, also exert protective immunomodulatory effects on immune cells, including macrophages. These observations suggest that endocannabinoids may also display pro-resolving actions. Interestingly, the endocannabinoid anandamide (AEA) is not only known to bind canonical type 1 and type 2 cannabinoid receptors (CB1 and CB2) but also to engage SPM-binding receptors such as GPR18. This suggests that AEA may also contribute to the governing of resolution processes. In order to interrogate this hypothesis, we investigated the ability of AEA to induce pro-resolving responses by classically-activated primary human monocyte-derived macrophages (MoDM). We found that AEA, at nanomolar concentration, enhances efferocytosis in MoDMs in a CB2- and GPR18-dependent manner. Using lipid mediator profiling, we also observed that AEA modulates SPM profiles in these cells, including levels of resolvin (Rv)D1, RvD6, maresin (MaR)2, and RvE1 in a CB2-dependent manner. AEA treatment also modulated the gene expression of SPM enzymes involved in both the formation and further metabolism of SPM such as 5-lipoxygenase and 15-Prostaglandin dehydrogenase. Our findings show, for the first time, a direct effect of AEA on the regulation of pro-resolving pathways in human macrophages. They also provide new insights into the complex interactions between different lipid pathways in activation of pro-resolving responses contributing to the reestablishment of homeostasis in the aftermath of acute inflammation.

An LGR6 frameshift variant abrogates receptor expression on select leukocyte subsets and is associated with viral infections.

ABSTRACT: The leucine-rich repeat-containing G-protein-coupled receptor 6 (LGR6) was recently identified as the cognate receptor for the proresolving mediator maresin 1 (MaR1). To address the biological role of LGR6 in humans, we investigated the functional impact of a genetic variant in the gene encoding for LGR6, which is predicted to lead to a frameshift mutation in one of the receptor isoforms, on both receptor expression and immune cell responses. In neutrophils, monocytes, and natural killer (NK) cells from volunteers homozygous for this variant, we found a significant downregulation in the expression of LGR6 when compared with controls without the variant; whereas the LGR6 expression was essentially similar in monocyte-derived macrophages and CD8+ T cells. Functionally, loss of LGR6 expression was linked with a decreased ability of neutrophils and monocytes to phagocytose bacteria. We observed an increase in neutrophil chemotaxis and leukotriene B4 production and increased expression of activation markers, including markers for platelet-leukocyte phagocyte heterotypic aggregates, such as CD41, in neutrophils and monocytes from the variant group. Using data from the UK Biobank, we found that at a population level the rs4266947 variant, which is in high linkage disequilibrium with rs74355478, was associated with a higher incidence of viral infections. Intriguingly, neutrophils, NK cells, and CD8+ T cells from volunteers with the LGR6 variant displayed altered viral responses when stimulated with Toll-like receptor 3 (TLR3), TLR7/TLR8, and TLR9 agonists. Together, these findings shed new light on the cell type-specific regulation of LGR6 expression and the role of this receptor in directing host immune responses.

Stomach Cancer and Postendoscopy Colorectal Cancer: Parallel Lives / Cáncer gástrico y cáncer colorrectal posendoscopia: vidas paralelas

Abstract Background and objectives: The rates of (interval) stomach cancer (SC) or postendoscopy (PECRC) or postcolonoscopy (PCCRC) colorectal cancer (CRC) have been little studied in our setting. Data from overseas studies reported PECRC and PCCRC rates of 7-26%. We aim to determine and compare local PECRC and PCCRC rates and characteristics. Patients and methods: With data from three quaternary-care cancer centers, we ambispectively identified patients diagnosed with SC and CRC between 2012 and 2021, in whom a history of endoscopies or colonoscopies in the previous three years was investigated. Cancers diagnosed between 6 and 36 months after an endoscopic study reported as normal were defined as interval cancers. This study compares the clinical, endoscopic, and survival characteristics of both PECRC and PCCRC cohorts. Results: Of 828 patients diagnosed with SC, 66 had PECRC (rate: 7.3%), while in 919 patients with CRC, 68 had PCCRC (rate: 6.9%). There were no significant differences in age or sex, although males predominated (2:1) in the PECRC (0.09). The finding of premalignant lesions was similar in both groups (p = 0.260). The anatomical location was shown to be more proximal (right colon) in the PCCRC than in the PECRC (cardia/fundus) (p = 0.002). Gastric neoplasms were more poorly differentiated (58%) than colon neoplasms (26%) (p = 0.001). There were no differences in early cancers, but tumor status was more advanced in PECRC (p < 0.01). The Kaplan-Meier showed a worse survival for PCCRC than for detected CRC, with no differences in SC and PECRC, suggesting poor survival. Conclusions: The rate of interval cancers is 7.3% and 6.9%, and differences were found between PECRC and PCCRC, proximal locations of the lesions, degree of differentiation, tumor status, and poor survival for the PCCRC. Establishing measures to achieve the World Endoscopy Organization's goal of <5% is necessary.

Resumen Antecedentes y objetivos: Las tasas de cáncer gástrico (CG) o cáncer colorrectal (CCR) posendoscopia (CGPE) o poscolonoscopia (CCRPC) (de intervalo) han sido poco estudiadas en nuestro medio. Los datos de estudios en el exterior informaron tasas de CGPE y CCRPC de 7%-26%. Nuestro objetivo fue determinar y comparar las tasas y características del CGPE y CCRPC locales. Pacientes y métodos: Con datos de tres centros oncológicos de cuarto nivel se identificaron, de forma ambispectiva, pacientes diagnosticados con CG y CCR entre 2012 y 2021, en quienes se investigó el antecedente de endoscopias o colonoscopias en los tres años previos. Los cánceres diagnosticados entre 6 y 36 meses después de un estudio endoscópico reportado como normal se definieron como cánceres de intervalo. En este estudio se comparan las características clínicas, endoscópicas y de sobrevida entre ambas cohortes de cánceres posendoscopia y poscolonoscopia. Resultados: De 828 pacientes diagnosticados con CG, 66 tuvieron CGPE (tasa: 7,3%), mientras que en 919 pacientes con CCR, 68 pacientes presentaron CCRPC (tasa: 6,9%). No hubo diferencias significativas en la edad o el sexo, aunque predominó el masculino (2:1) en el CGPE (0,09). El hallazgo de lesiones premalignas fue similar en ambos grupos (p = 0,260). La ubicación anatómica mostró ser más proximal (colon derecho) en el CCRPC que en el CGPE (cardias/fondo) (p = 0,002). Las neoplasias gástricas fueron más mal diferenciadas (58%) que las de colon (26%) (p = 0,001). No hubo diferencias en los cánceres tempranos, pero el estado tumoral fue más avanzado en el CGPE (p < 0,01). El Kaplan-Meier mostró una peor sobrevida para el CCRPC que para el CCR detectado, sin diferencias en el CG y el CGPE, que mostraron una pobre sobrevida. Conclusiones: La tasa de cánceres de intervalo es de 7,3% y 6,9%, y se encontraron diferencias entre los CGPE y el CCRPC, ubicaciones proximales de las lesiones, grado de diferenciación, estado del tumor y una pobre sobrevida para el CCRPC. Se hace necesario establecer medidas para lograr la meta de la Organización Mundial de Endoscopia de <5%.

Association of retinal neurodegeneration with the progression of cognitive decline in Parkinson's disease.

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 (ß [SE] = -0.58 [0.06]) than in controls (ß [SE] = -0.29 [0.06], p < 0.001). In PD, the progression pattern of pfGCIPL atrophy depended on baseline thickness, with slower thinning rates observed in PD patients with pfGCIPL below 89.8 µm. This result was validated with an external dataset from Moorfields Eye Hospital NHS Foundation Trust (AlzEye study). Slow pfGCIPL progressors, characterized by older at baseline, longer disease duration, and worse cognitive and disease stage scores, showed a threefold increase in the rate of cognitive decline (ß [SE] = -0.45 [0.19] points/year, p = 0.021) compared to faster progressors. Furthermore, temporal sector pRNFL thinning was accelerated in PD (ßtime x group [SE] = -0.67 [0.26] µm/year, p = 0.009), demonstrating a close association with cognitive score changes (ß [SE] = 0.11 [0.05], p = 0.052). This study suggests that a slower pattern of pfGCIPL tissue loss in PD is linked to more rapid cognitive decline, whereas changes in temporal pRNFL could track cognitive deterioration.

Prognostic factors for falls in Parkinson's disease: a systematic review.

BACKGROUND: Falls represent a critical concern in Parkinson's disease (PD), contributing to increased morbidity and reduced quality of life. PURPOSE: We conducted a systematic review to assess the prognostic factors associated with falls in PD, aiming to provide a comprehensive overview of relevant demographic and clinical parameters, and aid neurologists in identifying subsets of PD patients most susceptible to falls and associated injuries. METHODS: PubMed and Web of Science databases were searched for prospective studies assessing factors associated with falls in ambulatory PD patients across different settings, from inception to August 2023. Data extraction was conducted using CHARMS-PF checklist and risk of bias was assessed with QUIPS tool. PRISMA guidelines were followed. RESULTS: The initial search yielded 155 references. Thirty-four studies, involving a total of 3454 PD patients, were included in the final analysis. The mean pooled age was 67.6 years, and 45.1% were women. PD patients presented mild motor impairment (UPDRS III score 27.8) with mean pooled disease duration of 5.7 years. Gait and balance disorders and history of prior falls emerged as the most consistent predictors of falls across studies. Disease duration, disease severity, dysautonomic symptoms, freezing of gait, frontal cognitive functions, and PD medication dosages yielded inconsistent findings. Conversely, dyskinesias, age, sex, and depression were unrelated to future falls in PD. Logistic regression models were most commonly employed to identify factors significantly associated with falls in PD. Substantial heterogeneity prevailed in the inclusion of confounding factors. CONCLUSION: The evidence suggests that previous history of falls, gait disorders, and poor balance are robust prognostic markers for falls in PD.

Dysautonomia and small fiber neuropathy in post-COVID condition and Chronic Fatigue Syndrome.

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.

Multiple system atrophy: Clinical, evolutive and histopathological characteristics of a series of cases.

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.

SYNAPSES. A European observational study to evaluate the safety and the effectiveness of safinamide in routine clinical practice: post-hoc analysis of the Spanish study population. / SYNAPSES. Estudio observacional europeo para evaluar la seguridad y la efectividad de la safinamida en la práctica clínica habitual: análisis post hoc de la población española del estudio.

INTRODUCTION: Parkinson's Disease (PD) is a progressive age-related neurodegenerative condition requiring new therapeutic alternatives. Safinamide, a novel levodopa add-on therapy, positively affects disease fluctuations by modulating both dopaminergic and glutamatergic systems. To further investigate the use of safinamide in European routine clinical practice, the present post-hoc analysis aimed to understand safinamide's safety profile within the Spanish study population. PATIENTS AND METHODS: Five hundred eleven Spanish patients with PD were evaluated at baseline, four (±1), eight (±1), and 12 (±1) months after initiating safinamide treatment. Unified Parkinson's Disease Rating Scale (UPDRS) total score and UPDRS part III score during on time were used to measure the overall severity of PD and motor complications, respectively, while the severity of adverse events was evaluated following the investigators' criteria. RESULTS: Safinamide showed a favourable safety profile within the Spanish study population, although prescription to patients with psychiatric conditions and off-label use were more frequent than in the European study population. In Spain, clinically meaningful improvements were observed in UPDRS scores when safinamide was used as the only add-on therapy to levodopa (57.4% and 53.7% of patients) and when switching from rasagiline (55.1% of patients). Motor complications were reduced from 83.2% to 63.3% after the study period. Increased safety concerns were undetected in any patient subgroup, although patients with cognitive impairment showed a slightly higher frequency of adverse events. CONCLUSIONS: This subanalysis further supports safinamide use as a safe and efficacious option for the management of motor fluctuations in different subgroups of levodopa-treated patients. However, safinamide should be used with caution in patients with cognitive impairment.

TITLE: SYNAPSES. Estudio observacional europeo para evaluar la seguridad y la efectividad de la safinamida en la práctica clínica habitual: análisis post hoc de la población española del estudio.Introducción. La enfermedad de Parkinson (EP) es una enfermedad neurodegenerativa progresiva relacionada con la edad que requiere nuevas alternativas terapéuticas. La safinamida, un nuevo tratamiento add-on a la levodopa, afecta positivamente a las fluctuaciones de esta enfermedad al modular los sistemas dopaminérgico y glutamatérgico. Para investigar más a fondo el uso de la safinamida en la práctica clínica rutinaria europea, el presente análisis post hoc tiene como objetivo comprender el perfil de seguridad de la safinamida dentro de la población española del estudio. Pacientes y métodos. Se evaluó a 511 pacientes españoles con EP al inicio, cuatro (±1), ocho (±1) y 12 (±1) meses después de iniciar el tratamiento con safinamida. Se utilizaron la puntuación total de la escala unificada de puntuación de la enfermedad de Parkinson (UPDRS) y la puntuación de la UPDRS III, durante el tiempo en on para medir la gravedad general de la EP y las complicaciones motoras, respectivamente, mientras que la gravedad de los acontecimientos adversos se evaluó siguiendo los criterios de los investigadores. Resultados. La safinamida mostró un perfil de seguridad favorable en la población española del estudio, aunque la prescripción a pacientes con enfermedades psiquiátricas y el uso para indicaciones no autorizadas fueron más frecuentes que en la población europea del estudio. En España se observaron mejoras clínicamente significativas en las puntuaciones de la UPDRS cuando se utilizó la safinamida como único tratamiento add-on a la levodopa (el 57,4 y el 53,7% de los pacientes) y cuando se venía de administrar rasagilina (el 55,1% de los pacientes). Las complicaciones motoras se redujeron del 83,2 al 63,3% tras el período de estudio. No se detectaron mayores problemas de seguridad en ningún subgrupo de pacientes, aunque los pacientes con deterioro cognitivo mostraron una frecuencia algo superior de acontecimientos adversos. Conclusiones. Este subanálisis respalda el uso de la safinamida como opción segura y eficaz para el tratamiento de las fluctuaciones motoras en diferentes subgrupos de pacientes tratados con levodopa. Sin embargo, la safinamida debe utilizarse con precaución en pacientes con deterioro cognitivo.

Usefulness of thermography in the diagnosis and classification of complex regional pain syndrome.

INTRODUCTION: We propose a protocol for study of complex regional pain syndrome (CRPS) based on a battery of quantitative measures (skin thermography, electrochemical skin conductance and sensory thresholds) and apply such protocol to 5 representative cases of CRPS. PATIENTS AND METHODS: 5 CPRS cases (2 women/3 men) that met the Budapest criteria for the diagnosis of CRPS. RESULTS: All patients showed spontaneous pain and allodynia. Two cases correspond to a stage I, in both the resting basal temperature was increased in the affected limb. Three cases reflect more advanced stages with a decrease in resting temperature and a delay in the recovery of the temperature when compared to contralateral limb. DISCUSSION: These non-invasive quantitative functional tests not only improve the diagnostic accuracy of CRPS but also, they help us to stratify and understand the pathological processes of the disease.

Optimal High-Dimensional Entanglement Concentration for Pure Bipartite Systems.

Considering pure quantum states, entanglement concentration is the procedure where, from N copies of a partially entangled state, a single state with higher entanglement can be obtained. Obtaining a maximally entangled state is possible for N=1. However, the associated success probability can be extremely low when increasing the system's dimensionality. In this work, we study two methods to achieve a probabilistic entanglement concentration for bipartite quantum systems with a large dimensionality for N=1, regarding a reasonably good probability of success at the expense of having a non-maximal entanglement. Firstly, we define an efficiency function Q considering a tradeoff between the amount of entanglement (quantified by the I-Concurrence) of the final state after the concentration procedure and its success probability, which leads to solving a quadratic optimization problem. We found an analytical solution, ensuring that an optimal scheme for entanglement concentration can always be found in terms of Q. Finally, a second method was explored, which is based on fixing the success probability and searching for the maximum amount of entanglement attainable. Both ways resemble the Procrustean method applied to a subset of the most significant Schmidt coefficients but obtaining non-maximally entangled states.

Retinal thickness as a biomarker of cognitive impairment in manifest Huntington's disease.

BACKGROUND: Cognitive decline has been reported in premanifest and manifest Huntington's disease but reliable biomarkers are lacking. Inner retinal layer thickness seems to be a good biomarker of cognition in other neurodegenerative diseases. OBJECTIVE: To explore the relationship between optical coherence tomography-derived metrics and global cognition in Huntington's Disease. METHODS: Thirty-six patients with Huntington's disease (16 premanifest and 20 manifest) and 36 controls matched by age, sex, smoking status, and hypertension status underwent macular volumetric and peripapillary optical coherence tomography scans. Disease duration, motor status, global cognition and CAG repeats were recorded in patients. Group differences in imaging parameters and their association with clinical outcomes were analyzed using linear mixed-effect models. RESULTS: Premanifest and manifest Huntington's disease patients presented thinner retinal external limiting membrane-Bruch's membrane complex, and manifest patients had thinner temporal peripapillary retinal nerve fiber layer compared to controls. In manifest Huntington's disease, macular thickness was significantly associated with MoCA scores, inner nuclear layer showing the largest regression coefficients. This relationship was consistent after adjusting for age, sex, and education and p-value correction with False Discovery Rate. None of the retinal variables were related to Unified Huntington's Disease Rating Scale score, disease duration, or disease burden. Premanifest patients did not show a significant association between OCT-derived parameters and clinical outcomes in corrected models. CONCLUSIONS: In line with other neurodegenerative diseases, OCT is a potential biomarker of cognitive status in manifest HD. Future prospective studies are needed to evaluate OCT as a potential surrogate marker of cognitive decline in HD.

Staging Parkinson's Disease According to the MNCD (Motor/Non-motor/Cognition/Dependency) Classification Correlates with Disease Severity and Quality of Life.

BACKGROUND: Recently, a novel simple classification called MNCD, based on 4 axes (Motor; Non-motor; Cognition; Dependency) and 5 stages, has been proposed to classify Parkinson's disease (PD). OBJECTIVE: Our aim was to apply the MNCD classification in a cohort of PD patients for the first time and also to analyze the correlation with quality of life (QoL) and disease severity. METHODS: Data from the baseline visit of PD patients recruited from 35 centers in Spain from the COPPADIS cohort fromJanuary 2016 to November 2017 were used to apply the MNCD classification. Three instruments were used to assess QoL:1) the 39-item Parkinson's disease Questionnaire [PDQ-39]); PQ-10; the EUROHIS-QOL 8-item index (EUROHIS-QOL8). RESULTS: Four hundred and thirty-nine PD patients (62.05±7.84 years old; 59% males) were included. MNCD stage was:stage 1, 8.4% (N = 37); stage 2, 62% (N = 272); stage 3, 28.2% (N = 124); stage 4-5, 1.4% (N = 6). A more advancedMNCD stage was associated with a higher score on the PDQ39SI (p < 0.0001) and a lower score on the PQ-10 (p< 0.0001) and EUROHIS-QOL8 (p< 0.0001). In many other aspects of the disease, such as disease duration, levodopa equivalent daily dose, motor symptoms, non-motor symptoms, and autonomy for activities of daily living, an association between the stage and severity was observed, with data indicating a progressive worsening related to disease progression throughout the proposed stages. CONCLUSION: Staging PD according to the MNCD classification correlated with QoL and disease severity. The MNCD could be a proper tool to monitor the progression of PD.