Age-matched Healthy Control Subjects Research Articles

Altered brain function during movement programming is linked with motor deficits after stroke: a high temporal resolution study.

Stroke leads to motor deficits, requiring rehabilitation therapy that targets mechanisms underlying movement generation. Cortical activity during the planning and execution of motor tasks can be studied using EEG, particularly via the Event Related Desynchronization (ERD). ERD is altered by stroke in a manner that varies with extent of motor deficits. Despite this consensus in the literature, defining precisely the temporality of these alterations during movement preparation and performance may be helpful to better understand motor system pathophysiology and might also inform development of novel therapies that benefit from temporal resolution. Patients with chronic hemiparetic post-stroke (n = 27; age 59 ± 14 years) and age-matched healthy right-handed control subjects (n = 23; 59 ± 12 years) were included. They performed a shoulder rotation task following the onset of a stimulus. Cortical activity was recorded using a 256-electrode EEG cap. ERD was calculated in the beta frequency band (15-30 Hz) in ipsilesional sensorimotor cortex, contralateral to movement. The ERD was compared over time between stroke and control subjects using permutation tests. The correlation between upper extremity motor deficits (assessed by the Fugl-Meyer scale) and ERD over time was studied in stroke patients using Spearman and permutation tests. Patients with stroke showed on average less beta ERD amplitude than control subjects in the time window of -350 to 50 ms relative to movement onset (t(46) = 2.8, p = 0.007, Cohen's d = 0.31, 95% CI [0.22: 1.40]). Beta-ERD values correlated negatively with the Fugl-Meyer score during the time window -200 to 400 ms relative to movement onset (Spearman's r = -0.54, p = 0.003, 95% CI [-0.77 to -0.18]). Our results provide new insights into the precise temporal changes of ERD after hemiparetic stroke and the associations they have with motor deficits. After stroke, the average amplitude of cortical activity is reduced as compared to age-matched controls, and the extent of this decrease is correlated with the severity of motor deficits; both were true during motor programming and during motor performance. Understanding how stroke affects the temporal dynamics of cortical preparation and execution of movement paves the way for more precise restorative therapies. Studying the temporal dynamics of the EEG also strengthens the promising interest of ERD as a biomarker of post-stroke motor function.

Stepwise Functional Brain Architecture Correlates with Atrophy in Progressive Supranuclear Palsy.

Stepwise functional connectivity (SFC) detects whole-brain functional couplings of a selected region of interest at increasing link-step topological distances. This study applied SFC to test the hypothesis that stepwise architecture propagating from the disease epicenter would shape patterns of brain atrophy in patients with progressive supranuclear palsy-Richardson's syndrome (PSP-RS). Thirty-six patients with PSP-RS and 44 age-matched healthy control subjects underwent brain magnetic resonance imaging on a 3-T scanner. The disease epicenter was defined as the peak of atrophy observed in an independent cohort of 13 cases with postmortem confirmation of PSP pathology and used as seed region for SFC analysis. First, we explored SFC rearrangements in patients with PSP-RS, as compared with age-matched control subjects. Subsequently, we tested SFC architecture propagating from the disease epicenter as a determinant of brain atrophy distribution. The disease epicenter was identified in the left midbrain tegmental region. Compared with age-matched control subjects, patients with PSP-RS showed progressively widespread decreased SFC of the midbrain with striatal and cerebellar regions through direct connections and sensorimotor cortical regions through indirect connections. A correlation was found between average link-step distance from the left midbrain in healthy subjects and brain volumes in patients with PSP-RS (r = 0.38, P < 0.001). This study provides comprehensive insights into the topology of functional network rearrangements in PSP-RS and demonstrates that the brain architectural topology, as described by SFC propagating from the disease epicenter, shapes the pattern of atrophic changes in PSP-RS. Our findings support the view of a network-based pathology propagation in this primary tauopathy. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Postural motion perception during vestibular stimulation depends on the motion perception threshold in persistent postural-perceptual dizziness

Patients with persistent postural-perceptual dizziness (PPPD) perceive postural instability larger than the observed sway. It is unknown whether the concept of postural misperception prevails during vestibular stimulation and whether it may account for the unsteadiness patients complain during body movements. We tested the hypothesis of an abnormal sensory-perceptual scaling mechanism in PPPD by recording objective, perceived, and the reproduced postural sway under various standing conditions, modulating visual and proprioceptive input, by binaural galvanic vestibular stimulation (GVS). We related postural sway speed to individual vestibular motion perceptional thresholds and disease-related PPPD questionnaires in 32 patients and 28 age-matched healthy control subjects (HC). All participants showed normal vestibular function tests on quantitative testing at the time of enrollment. The perception threshold of GVS was lower in patients. Compared to HC, patients showed and perceived larger sway on the firm platform. With GVS, posturo-perceptual ratios did not show group differences. The ratio of reproduced to real postural sway showed no group differences indicating normal postural sway perception during vestibular stimulation. Noticeably, only in patients, reproduced postural instability became larger with lower individual thresholds of vestibular motion detection. We conclude that posturo-perceptual (metacognitive) scaling of postural control seems to be largely preserved in PPPD during GVS. Vestibular stimulation does not destabilize patients more than HC, even in challenging postural conditions. Low individual thresholds of vestibular motion perception seem to facilitate instability and postural misperception on solid grounds. This conclusion is important for an effective physical therapy with vestibular exercises in PPPD.

Effects of acute whole-body and lower limb heating on hemodynamic responses to walking in patients with peripheral artery disease

Background: The exercise pressor reflex is exaggerated in patients with peripheral artery disease (PAD). There has been speculation regarding cardiovascular benefits of heating therapy for patients with PAD. The impact of acute leg heating and whole-body heating on hemodynamic responses during walking remains incompletely understood. The purpose of this study was to evaluate the effects of acute whole-body and lower leg heating on hemodynamic responses to walking in both patients with PAD and healthy control subjects. Hypothesis: We hypothesized that both acute whole-body and lower leg heating would attenuate the pressor response to walking in patients with PAD. Methods: 10 PAD patients (68 ± 7 yrs; Male/Female, N = 7/3) and 8 age-matched healthy control subjects (64 ± 5 yrs, Male/Female, N = 5/3) participated in this study. The treadmill walking test followed the Gardner protocol, involving a constant speed of 2 mph with a 2%-grade increment every 2 minutes. The study encompassed 3 trials/visits: 1) non-heating (control), 2) post leg heating, and 3) post whole-body heating. The order of these visits was randomized. During the leg heating visit, the subjects' lower limbs (below the knees) were immersed in warm water (40-42℃) for 30 minutes. Whole-body heating was administered by outfitting the subjects in a tube-lined heating suit until their internal temperature increased by 0.3℃ (~ 45 min). Hemodynamic responses were assessed by comparing the average systolic blood pressure (SBP) and heart rate (HR) during the last 3 stages of treadmill walking with baseline values. Results: Resting SBP and HR did not exhibit significant differences between groups (all P &gt; 0.05). During the control visit, the increase in SBP due to treadmill walking was significantly (P = 0.04) higher in patients with PAD than in healthy subjects. No group differences were observed in the increase in HR by treadmill walking. The responses in SBP and HR to treadmill walking, following leg heating, were comparable to those observed in the control visit for both groups (all P &gt; 0.05). Compared to the control visit, whole-body heating significantly attenuated the SBP (ΔSBP%, 32.9 ± 13.5 vs. 21.3 ± 9.5 %, P = 0.02) and HR responses (ΔHR%, 61.6 ± 24.3 vs. 42.7 ± 15.6 %, P = 0.03) to treadmill walking in PAD. However, in healthy subjects after whole-body heating, these responses were not different from the control visit (both P &gt; 0.05). Neither whole-body nor leg heating had any impact on the walking distance in patients with PAD. Discussion and Conclusion: Acute whole-body heating significantly attenuated the pressor response to walking in patients with PAD, while lower leg heating exhibited no such impact. These findings suggest potential benefits of acute whole-body heating for patients with PAD. We speculate that the comprehensive systemic adjustments by whole-body heat exposure play a pivotal role in improving the exaggerated pressor response to exercise in PAD. Conversely, local lower leg heating, as observed in our study, seems insuffcient to change the hemodynamic response to exercise in patients with PAD. This study was supported by NIH R01 HL141198 and R01 HL144781. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Cerebral palsy risk in relation to parental age: insights from a matched case-control study

BackgroundCerebral palsy, a prevalent childhood physical disability, exhibits complex multifactorial causes. This case-control study explores the role of parental age in cerebral palsy risk and associated patterns.MethodsA case-control study comparing children with cerebral palsy at ages 3 months to 3 years with age-matched healthy control subjects was conducted between January 2022 and August 2023 at Federal Medical Centre, Abeokuta, Nigeria. Cases were recruited from the pediatric physiotherapy outpatient clinic, while controls were selected from pediatric and children emergency wards. Data were collected retrospectively from electronic medical records. Risk factors were evaluated using conditional logistic regression models.ResultsWe studied 134 subjects with cerebral palsy and 134 age-matched control subjects. Significant risk factors for cerebral palsy included the maternal age 35–39 years (odds ratio 2.16, P < 0.005), maternal age ≥ 40 years (odds ratio 3.83, P < 0.005), paternal age 41–45 (odds ratio 2.00, P < 0.05), paternal age ≥ 46 (odds ratio 6.80, P < 0.05), primiparous (odds ratio 2.2, P < 0.05), paternal low income (odds ratio 2.49, P < 0.05), paternal primary education (odds ratio 24.61, P < 0.05), and maternal primary education (odds ratio 2.39, P < 0.05).ConclusionsThis research contributes to our understanding of parental age as risk factors associated with cerebral palsy in children. The results also underscore the importance of demographic and socioeconomic factors, especially father’s level of income, maternal parity, and parental education. These findings can guide future research and public health interventions aimed at reducing the burden of cerebral palsy.

Effects of Susac syndrome on the central vascular structure of the retina-An optical coherence tomography angiography study

Susac syndrome (SS)describes an endotheliopathy of vessels in the central nervous system. Retinal involvement plays acentral role in the manifestation of the disease. This case-control study investigated the macular microvasculature in patients with chronic SS compared to controls using optical coherence tomography angiography (OCTA). 12eyes of 12patients with SS were compared with age-matched healthy control subjects with regard to their OCT angiographic parameters. The flow density (FD) of different macular layers, foveal avascular zone (FAZ) parameters and central retinal thickness and volume values were compared between the two groups. The FD of the choriocapillaris was reduced in Susac patients compared to healthy controls. The FD values of the superficial and deep capillary plexus of the inner retina, parameters of the FAZ as well as central retinal thickness and volume showed no significant differences between the two groups. Treated chronic SS does not appear to significantly affect the vascular and structural composition of the central inner retina; however, differences in the choriocapillaris indicate changes in deeper, highly vascularized capillary layers.

Visual and vestibular motion perception in persistent postural-perceptual dizziness (PPPD)

Persistent postural-perceptual dizziness (PPPD) is a chronic disorder of perceived unsteadiness. Symptoms can be exacerbated in visually complex stationary or moving environment. Visual dependence and increased motion sensitivity are predictors for PPPD but its pathophysiology remains unknown. We hypothesized an abnormal sensory–perceptual scaling mechanism in PPPD and tested visual- and vestibular perceptional thresholds in 32 patients and 28 age-matched healthy control subjects (HC). All participants showed normal vestibular function tests on quantitative testing. Visual motion coherence thresholds were assessed by random dot kinetomatograms. Vestibular perceptional thresholds of egomotion were assessed by binaural galvanic vestibular stimulation (GVS) and passive chair rotation around an earth-vertical axis. Chair rotation trials were contrasted with no-motion (sham) stimulus trials. Mean thresholds of visual motion perception were higher in patients compared to HC. The perception threshold of GVS was lower in patients but the threshold of correctly perceived egomotion during chair rotation did not differ. Interestingly, the number of trials with correct perception in the no-motion condition increased with the threshold of correct responses for rotatory egomotion in patients. Unlike expected, PPPD patients required more coherently moving random dots than HC to perceive visual motion. A poorer complex visual motion recognition, e.g., traffic visual stimuli, may increase anxiety and levels of uncertainty as visuomotor reactions might occur delayed. The vestibular rotatory perception threshold predicted the probability of making false assignments in the sham condition in PPPD, i.e., patients who readily recognize the correct egomotion direction are prone to perceive egomotion in the no-motion condition. As this relation was not found in healthy subjects, it may reflect an abnormal sensory–perceptual scaling feature of PPPD.

Severity of COVID-19 Infectious and Immune-Based Profile

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes immune system dysregulation and a systemic cytokine storm. Under healthy conditions, T helper cells protect against intracellular pathogens, extracellular parasites, and extracellular bacteria. Objectives: For the novelty of our study, little is known regarding the balance of T cell subtypes and responses in two forms of COVID-19 in our country. We investigated whether there was a relationship between T cell subtype frequency and cytokines by COVID-19 severity. Methods: Forty-six PCR-confirmed severe (n = 30) and moderate (n = 16) COVID-19 patients and 13 sex- and age-matched healthy control (HC) subjects were enrolled. Immunophenotyping of T cell subsets and related serum cytokines was performed using flow cytometry and ELISA, respectively. Results: There was a significantly lower frequency of CD8+Tbet+ (P &lt; 0.01) T cells in the severe group compared to HC. Also, there was a significantly lower frequency of CD4+GATA3+ (P &lt; 0.001) and CD8+Tbet+ (P &lt; 0.001) T cells in the severe group compared to the moderate group. Moreover, receiver-operating characteristic (ROC) curve analysis revealed a considerable correlation between CTL (CD8+T-bet+) subtypes and the severity of the disease. Severe COVID-19 disease was associated with reduced interferon-gamma (IFN-γ) and interleukin (IL)-2 concentration and increased IL-5 and IL-6 concentration. Conclusions: Reduced systemic levels of IL-2 can trigger decreased numbers of Th1 and Th2 cells, and in contrast to elevated IL-5 and IL-6, the numbers of Th2 cells did not increase in these cases.

Do intravitreal anti-VEGF injections have an effect on corneal endothelial remodeling in children with premature retinopathy?

This study was carried out to investigate the effects of retinopathy of prematurity (ROP) and intravitreal antivascular endothelial growth factor (VEGF) injections on the corneal endothelium in the childhood period of patients who have had ROP. The material of comparative case-control clinical study consisted of patients followed up with ROP between February 2013 and February 2023. The eyes in the study group were divided into two subgroups consisting of those who received intravitreal anti-VEGF injections (subgroup 1) and those who were followed up only (subgroup 2). Central corneal endothelial cell density (ECD), coefficient of variation (CV), central corneal thickness (CCT), and pleomorphism parameters in the childhood period were evaluated by corneal specular microscopy and compared with age-matched healthy control subjects. There were 84 eyes of 42 patients with ROP in the study group and 80 eyes of 40 healthy children in the control group. Mean CCT was significantly higher in subgroup 1 and the control group than in subgroup 2 (p = 0.037), and mean ECD was significantly higher in subgroup 2 than in subgroup 1 and the control group (p < 0.001). There was no significant difference between subgroup 1 and the control group in mean ECD and CCT values (p = 1.000 for both cases). Considering that ROP patients who received intravitreal anti-VEGF injections had more advanced-stage ROP than ROP patients who were followed up only, these findings suggest that intravitreal anti-VEGF applications in ROP cases may lead to corneal endothelial parameters similar to those of healthy eyes.

Secondary Data Analysis of Inflammation-Related mRNAs in Conjunctival Impression Cytology Samples of Aniridia Patients.

Aniridia is a rare corneal disease that is often associated with aniridia-associated keratopathy (AAK). In AAK, the conjunctival tissue crosses the limbal border, forming a corneal pannus that extends into the corneal center. With increasing AAK severity, corneal pannus formation, vascularization, and ocular surface inflammation increase. The purpose of this study was to investigate inflammation-related mRNA expression in conjunctival epithelial cells in AAK and its relationship with AAK severity. Using impression cytology, bulbar conjunctival cells were sampled from 20 subjects with congenital aniridia and 20 age-matched and sex-matched healthy control subjects. RNA was extracted, and mRNA analyses were performed using microarray, which was evaluated for inflammatory markers. In the analyzed aniridia subjects, 70 deregulated mRNAs encoding proinflammatory or antiinflammatory cytokines or factors associated with chronic inflammation, including increased IL-1, IL-8, and MIP3A/CCL20 mRNA. The most downregulated mRNA was TIMP3, and the most upregulated mRNA was Protein c-Fos.Of the 70 mRNAs, 14 inflammation-related genes were altered only in the mild AAK forms, whereas only 2 mRNAs were altered only in the severe AAK forms (TLR4 and PPARG). The expression of numerous proinflammatory and antiinflammatory cytokines is deregulated at the ocular surface of aniridia subjects with mild AAK. Thus, early antiinflammatory treatment may prevent or slow down corneal scarring and pannus formation in aniridia subjects.

Stress-Mediated Abnormalities in Regional Myocardial Wall Motion in Young Women with a History of Psychological Trauma.

Psychosocial stress has been associated with the development and progression of atherosclerotic cardiovascular disease (CVD). Previously, we reported subtle differences in global longitudinal strain in somatically healthy women with a psychiatric diagnosis of borderline personality disorder (BPD). This study aimed to investigate the impact of BPD on segmental myocardial wall motion using speckle tracking echocardiography (STE) analysis. A total of 100 women aged between 18 and 38 years were included in this study. Fifty patients meeting the diagnostic criteria for BPD were recruited from the Department of Psychiatry (LWL-University Hospital Bochum) and compared with fifty age-matched healthy control subjects without previous cardiac disease. Laboratory tests and STE were performed with segmental wall motion analysis. The BPD group had a higher prevalence of risk factors for CVD, with smoking and obesity being predominant, when compared with the control group. Other cardiovascular parameters such as blood pressure, glucose, and cholesterol levels were also elevated, even though not to pathological values. Moreover, in the STE analysis, the BPD group consistently exhibited decreased deformation in nine myocardial wall regions compared with the control group, along with a shift toward higher values in the distribution of peak pathological segments. Additionally, significantly higher values of free thyroxine concentration and thyroid's secretory capacity were observed in the BPD group, despite falling within the (high-) normal range. BPD is associated with chronic stress, classical risk factors, and myocardial wall motion abnormalities. Further exploration is warranted to investigate the relationship between high-normal thyroid metabolism, these risk factors, and myocardial function in BPD patients. Long-term follow-up studies would be valuable in confirming the potential for predicting adverse events.

MicroRNAs as a Tool for Differential Diagnosis of Neuromuscular Disorders

Neuromuscular disorders (NMD) are a class of progressive disorders that are characterized by wasting of the muscles. Some of the disorders like Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), congenital muscular dystrophies (CMDs), limb-girdle muscular dystrophies (LGMD), and mild spinal muscular atrophy (SMA) type III share several presenting clinical features, and hence, diagnosis is usually a challenging task. In this study, the diagnostic potential of some species of microRNAs (miRNAs) that are known to play roles in normal and pathological contexts of myocytes (myomiRs) were evaluated to assess their potential in differential diagnosis of NMDs. In this study, seventy-four patients with different neuromuscular disorders along with thirty age-matched healthy control subjects were enrolled. Peripheral blood samples were collected from enrolled subjects followed by miRNA extraction and reverse transcription followed by quantification of the circulating levels of the studied miRNAs (miR-499, miR-206, miR-208a, miR-223, miR-191, miR-103a-3p, miR-103a-5p), by real-time PCR and statistical analysis. The data indicated that miR-499 level showed high circulating levels in DMD patients as well as in patients with other related disorders such as BMD. However, the levels of miR-499 were much higher in DMD patients and it can be used to diagnose DMD. In addition, miR-206 can selectively differentiate between DMD and all other disorders. The results also revealed that miR-208a and miR-223 were significantly dysregulated in SMA patients, and miR-103a-3p could distinguish DMD from BMD. The expression levels of some miRNA species can be utilized in the process of differential diagnosis of NMDs and can serve as a diagnostic biomarker, and such findings will pave the way towards generating targeted therapies.

Higher angiotensin-converting enzyme 2 (ACE2) levels in the brain of individuals with Alzheimer’s disease

Cognitive decline due to Alzheimer’s disease (AD) is frequent in the geriatric population, which has been disproportionately affected by the COVID-19 pandemic. In this study, we investigated the levels of angiotensin-converting enzyme 2 (ACE2), a regulator of the renin-angiotensin system and the main entry receptor of SARS-CoV-2 in host cells, in postmortem parietal cortex samples from two independent AD cohorts, totalling 142 persons. Higher concentrations of ACE2 protein (p < 0.01) and mRNA (p < 0.01) were found in individuals with a neuropathological diagnosis of AD compared to age-matched healthy control subjects. Brain levels of soluble ACE2 were inversely associated with cognitive scores (p = 0.02) and markers of pericytes (PDGFRβ, p = 0.02 and ANPEP, p = 0.007), but positively correlated with concentrations of soluble amyloid-β peptides (Aβ) (p = 0.01) and insoluble phospho-tau (S396/404, p = 0.002). However, no significant differences in ACE2 were observed in the 3xTg-AD mouse model of tau and Aβ neuropathology. Results from immunofluorescence and Western blots showed that ACE2 protein is predominantly localized in microvessels in the mouse brain whereas it is more frequently found in neurons in the human brain. The present data suggest that higher levels of soluble ACE2 in the human brain may contribute to AD, but their role in CNS infection by SARS-CoV-2 remains unclear.

Chemotherapy effect on myocardial fibrosis markers in patients with gynecologic cancer and low cardiovascular risk.

Patients with gynecologic cancers experience side effects of chemotherapy cardiotoxicity. We aimed to quantify cardiac magnetic resonance (CMR) markers of myocardial fibrosis in patients with gynecologic cancer and low cardiovascular risk who undergo chemotherapy. This study is part of a registered clinical research. CMR T1 mapping was performed in patients with gynecologic cancer and low cardiovascular risk undergoing chemotherapy. The results were compared with those of age-matched healthy control subjects. 68 patients (median age = 50 years) and 30 control subjects were included. The median number of chemotherapy cycles of patients was 9.0 (interquartile range [IQR] 3.3-17.0). Extracellular volume fraction (ECV) (27.2% ± 2.7% vs. 24.5% ± 1.7%, P < 0.001) and global longitudinal strain (-16.2% ± 2.8% vs. -17.4% ± 2.0%, P = 0.040) were higher in patients compared with controls. Patients with higher chemotherapy cycles (>6 cycles) (n=41) had significantly lower intracellular mass indexed (ICMi) compared with both patients with lower chemotherapy cycles (≤6 cycles) (n=27) (median 27.44 g/m2 [IQR 24.03-31.15 g/m2] vs. median 34.30 g/m2 [IQR 29.93-39.79 g/m2]; P = 0.002) and the control group (median 27.44 g/m2 [IQR 24.03-31.15 g/m2] vs. median 32.79 g/m2 [IQR 27.74-35.76 g/m2]; P = 0.002). Patients with two or more chemotherapy regimens had significantly lower ICMi compared with both patients with one chemotherapy regimen (27.45 ± 5.16 g/m2 vs. 33.32 ± 6.42 g/m2; P< 0.001) and the control group (27.45 ± 5.16 g/m2 vs. 33.02 ± 5.52 g/m2; P < 0.001). The number of chemotherapy cycles was associated with an increase in the ECV (Standard regression coefficient [β] = 0.383, P = 0.014) and a decrease in the ICMi (β = -0.349, P = 0.009). Patients with gynecologic cancer and low cardiovascular risk who undergo chemotherapy have diffuse extracellular volume expansion, which is obvious with the increase of chemotherapy cycles. Myocyte loss may be part of the mechanism in patients with a higher chemotherapy load. http://www.chictr.org.cn, identifier ChiCTR-DDD-17013450.

Validity and reliability measures of the Swedish Karolinska version of the Edinburgh Cognitive and Behavioral ALS Screen (SK-ECAS)

Objective Cognitive and behavioral impairment is observed in up to 50% of patients with amyotrophic lateral sclerosis (ALS). The Edinburgh Cognitive and Behavioral ALS Screen (ECAS) is a 5-domain screening tool customized for quick cognitive screening in patients with ALS. Although the ECAS is available in Swedish at the Karolinska University Hospital (SK-ECAS), it has not yet been validated in Sweden stressing the need to assess validity and reliability of the SK-ECAS Version A. Methods The study included 176 patients with ALS or other motor neuron disease diagnosed between September 2017 and October 2021 at the Karolinska ALS Clinical Research Center in Stockholm, Sweden, and 35 age-matched healthy control subjects. SK-ECAS was validated against the Montreal Cognitive Assessment (MoCA) and optimal cutoffs, receiver operating characteristic (ROC) curve and area under the curve (AUC) were calculated. Results We identified an optimal cutoff of 108 for the SK-ECAS total score and 82 for the SK-ECAS ALS-specific score to detect cognitive impairment. The SK-ECAS showed good performance in indicating abnormal cognition with an AUC of 0.73 for SK-ECAS ALS-specific score and 0.77 for SK-ECAS total score. There was good internal consistency with a Cronbach’s alpha of 0.79. Conclusions This study demonstrates good validity and reliability indices for SK-ECAS Version A for the detection of cognitive impairment in newly diagnosed ALS patients.

Neural Regeneration in Dry Eye Secondary to Systemic Lupus Erythematosus Is Also Disrupted like in Rheumatoid Arthritis, but in a Progressive Fashion.

Our objective in this study was to analyze the aberrant neural regeneration activity in the cornea by means of in vivo confocal microscopy in systemic lupus erythematosus patients with concurrent dry eye disease. We examined 29 systemic lupus erythematosus patients and 29 age-matched healthy control subjects. Corneal nerve fiber density (CNFD, the number of fibers/mm2) and peripheral Langerhans cell morphology were lower (p < 0.05) in systemic lupus erythematosus patients compared to the control group. Interestingly, corneal nerve branch density, corneal nerve fiber length, corneal nerve fiber total branch density, and corneal nerve fiber area showed a negative correlation with disease duration. A negative correlation was also demonstrated between average corneal nerve fiber density and central Langerhans cell density. This is in line with our hypothesis that corneal somatosensory terminal Piezo2 channelopathy-induced impaired Piezo2-Piezo1 crosstalk not only disrupts regeneration and keeps transcription activated, but could lead to Piezo1 downregulation and cell activation on Langerhans cells when we consider a chronic path. Hence, Piezo2 containing mechanosensory corneal nerves and dendritic Langerhans cells could also be regarded as central players in shaping the ocular surface neuroimmune homeostasis through the Piezo system. Moreover, lost autoimmune neuroinflammation compensation, lost phagocytic self-eating capacity, and lost transcription regulation, not to mention autoantibodies against vascular heparin sulfate proteoglycans and phospholipids, could all contribute to the progressive fashion of dry eye disease in systemic lupus erythematosus.

Preserved autophagy in cognitively intact non-demented individuals with Alzheimer's neuropathology.

Growing evidence supports that dysfunctional autophagy, the major cell mechanism responsible for removing protein aggregates and a route of clearance for Tau in healthy neurons, is a major finding in demented Alzheimer's disease (AD) patients. However, the association of autophagy with maintenance of cognitive integrity in resilient individuals who have AD neuropathology but remain non-demented (NDAN) has not been evaluated. Using post mortem brain samples from age-matched healthy control, AD, and NDAN subjects, we evaluated autophagy in relation to Tau pathology using Western blot, immunofluorescence and RNA-seq. Compared to AD patients, NDAN subjects had preserved autophagy and reduced tauopathy. Furthermore, expression of autophagy genes and AD-related proteins were significantly associated in NDAN compared to AD and control subjects. Our results suggest preserved autophagy is a protective mechanism that maintains cognitive integrity in NDAN individuals. This novel observation supports the potential of autophagy-inducing strategies in AD therapeutics. NDAN subjects have preserved autophagic protein levels comparable with control subjects. Compared to control subjects, NDAN subjects have significantly reduced Tau oligomers and PHF Tau phosphorylation at synapses that negatively correlate with autophagy markers. Transcription of autophagy genes strongly associates with AD-related proteins in NDAN donors.

Factual and counterfactual learning in major adolescent depressive disorder, evidence from an instrumental learning study.

The incidence of adolescent depressive disorder is globally skyrocketing in recent decades, albeit the causes and the decision deficits depression incurs has yet to be well-examined. With an instrumental learning task, the aim of the current study is to investigate the extent to which learning behavior deviates from that observed in healthy adolescent controls and track the underlying mechanistic channel for such a deviation. We recruited a group of adolescents with major depression and age-matched healthy control subjects to carry out the learning task with either gain or loss outcome and applied a reinforcement learning model that dissociates valence (positive v. negative) of reward prediction error and selection (chosen v. unchosen). The results demonstrated that adolescent depressive patients performed significantly less well than the control group. Learning rates suggested that the optimistic bias that overall characterizes healthy adolescent subjects was absent for the depressive adolescent patients. Moreover, depressed adolescents exhibited an increased pessimistic bias for the counterfactual outcome. Lastly, individual difference analysis suggested that these observed biases, which significantly deviated from that observed in normal controls, were linked with the severity of depressive symoptoms as measured by HAMD scores. By leveraging an incentivized instrumental learning task with computational modeling within a reinforcement learning framework, the current study reveals a mechanistic decision-making deficit in adolescent depressive disorder. These findings, which have implications for the identification of behavioral markers in depression, could support the clinical evaluation, including both diagnosis and prognosis of this disorder.

Corneal confocal microscopy identifies corneal nerve fiber loss in patients with migraine.

Migraine affects >1 billion people but its pathophysiology remains poorly understood. Alterations in the trigeminovascular system play an important role. We have compared corneal nerve morphology in patients with migraine to healthy controls. Sixty patients with episodic (n = 32) or chronic (n = 28) migraine and 20 age-matched healthy control subjects were studied cross-sectionally. Their migraine characteristics and signs and symptoms of dry eyes were assessed. Manual and automated quantification of corneal nerves was undertaken by corneal confocal microscopy. In patients with migraine compared to controls, manual corneal nerve fiber density (P < 0.001), branch density (P = 0.015) and length (P < 0.001); and automated corneal nerve fiber density (P < 0.001), branch density (P < 0.001), length (P < 0.001), total branch density (P < 0.001), nerve fiber area (P < 0.001), nerve fiber width (P = 0.045) and fractal dimension (P < 0.001) were lower. Automated corneal nerve fiber density was higher in patients with episodic migraine and aura (P = 0.010); and fractal dimension (P = 0.029) was lower in patients with more headache days in the last three months. Automated corneal nerve fiber density predicted a significant amount of the observed variance in pain intensity (adjusted r2 = 0.14, partial r = -0.37, P = 0.004) in patients with migraine. Corneal confocal microscopy reveals corneal nerve loss in patients with migraine. It may serve as an objective imaging biomarker of neurodegeneration in migraine.

Muscle synergies in Parkinson’s disease before and after the deep brain stimulation of the bilateral subthalamic nucleus

The aim of this study is to quantitatively assess motor control changes in Parkinson’s disease (PD) patients after bilateral deep brain stimulation of the subthalamic nucleus (STN-DBS), based on a novel muscle synergy evaluation approach. A group of 20 PD patients evaluated at baseline (before surgery, T0), at 3 months (T1), and at 12 months (T2) after STN-DBS surgery, as well as a group of 20 age-matched healthy control subjects, underwent an instrumented gait analysis, including surface electromyography recordings from 12 muscles. A smaller number of muscle synergies was found in PD patients (4 muscle synergies, at each time point) compared to control subjects (5 muscle synergies). The neuromuscular robustness of PD patients—that at T0 was smaller with respect to controls (PD T0: 69.3 ± 2.2% vs. Controls: 77.6 ± 1.8%, p = 0.004)—increased at T1 (75.8 ± 1.8%), becoming not different from that of controls at T2 (77.5 ± 1.9%). The muscle synergies analysis may offer clinicians new knowledge on the neuromuscular structure underlying PD motor types of behavior and how they can improve after electroceutical STN-DBS therapy.