Clinical and Translational Neuroscience doi: 10.3390/ctn10020017

Authors: Asmeret Demoz Zhanserik Shynykul Aijun Zhang Wenli Lyu Xusheng Wang Haewon Shin

Early diagnosis of post-traumatic epilepsy (PTE) is crucial for timely intervention. However, it is hampered by the lack of reliable biomarkers. In this review, we provide a comprehensive summary of current advances in PTE biomarker research, drawing primarily on evidence from human cohort studies, with selective support from experimental animal models where mechanistic insights are required. We cover (i) neuroimaging, including CT, MRI, and EEG/qEEG, which reveal structural and functional alterations associated with epileptogenesis; (ii) molecular biomarkers, including RNAs, proteins, metabolites, and extracellular vesicle (EV)-derived molecules that reflect neuroinflammation, blood–brain barrier (BBB) dysfunction, neuronal injury, and synaptic remodeling; and (iii) artificial intelligence (AI)-assisted approaches, which integrate multimodal datasets to identify complex predictive patterns. While individual modalities offer valuable but incomplete prognostic information, AI-driven analytics hold the greatest promise for early predictive power by combining multimodal data. Future progress will depend on the integration of high-resolution imaging, multi-omics profiling, and rigorous validation to deliver clinically actionable biomarker panels and ultimately reduce the burden of PTE.

Clinical and Translational Neuroscience doi: 10.3390/ctn10020016

Authors: Claudio L. A. Bassetti Urs Fischer

With the death of Prof [...]

Clinical and Translational Neuroscience doi: 10.3390/ctn10020015

Authors: Elisa Grana Victoria Saulnier Jocelyne Bloch Stefano Carda

Objective: Our objective was to report the successful in situ management of Staphylococcus epidermidis meningitis following intrathecal baclofen pump implantation without removing the device. Design: This was a single case report with clinical follow-up. Subjects/Patients: We discuss a 34-year-old tetraplegic patient with severe generalized spasticity due to cerebral anoxia at birth who developed meningitis six weeks after intrathecal baclofen pump implantation. Methods: We used a multidisciplinary management approach. This involved aggressive intravenous and intrathecal antibiotic therapy while preserving the intrathecal baclofen device. Treatment included intravenous Meropenem. This was followed by intravenous Vancomycin and oral Linezolid. Calculated intrathecal Vancomycin was administered through the implanted pump. Results: The treatment resulted in a complete resolution of infection with negative cerebrospinal fluid cultures and polymerase chain reaction analysis. The patient had significant functional improvement throughout treatment with intrathecal baclofen. Six months post-infection, the patient remained stable, with continued efficacy of intrathecal baclofen and no recurrence of infection. Conclusion: In carefully selected patients with intrathecal baclofen pump-associated Staphylococcus epidermidis meningitis, successful in situ management is possible without device removal, preserving functional benefits while achieving infection eradication through aggressive antibiotic therapy.

Clinical and Translational Neuroscience doi: 10.3390/ctn10020014

Authors: Wei Gong Zuodong Yuan Baiwei Zhang Chansachak Chea Chunlei Tian Fei Ye

Objective: CDCA8 is frequently overexpressed in malignant tumors and linked to poor prognosis. This study evaluated the prognostic significance of CDCA8 expression in glioma patients using the CGGA and TCGA datasets. Methods: Clinical and expression data of glioma patients from CGGA and TCGA were analyzed. CDCA8 expression was compared across subgroups based on tumor grade (GBM vs. LGG) and IDH mutation status, and meta-analyses were performed to assess inter-database differences. Results: This study included 1125 glioma patients from CGGA and TCGA. CDCA8 expression was higher in TCGA GBM (p < 0.001) but comparable between databases in LGG (p = 0.501). CGGA showed lower CDCA8 in IDH-mutant gliomas (p < 0.001), with no difference in IDH-wildtype cases (p = 0.154). CGGA patients had longer overall survival in all above subgroups. Meta-analysis found no significant prognostic association of CDCA8 in GBM, IDH-wildtype and IDH-mutant gliomas. In LGG, high CDCA8 was significantly linked to reduced adverse events (p < 0.001, OR = 0.22, 95% CI [0.11–0.43]). Conclusion: CDCA8 has grade-dependent prognostic roles in gliomas. Its overexpression correlates with poor prognosis in GBM but favorable outcomes in LGG. Inter-database variations support CDCA8 as a promising prognostic biomarker for LGG, and reflect the influences of regional, therapeutic and genetic factors.

Clinical and Translational Neuroscience doi: 10.3390/ctn10020013

Authors: Panagiotis Papamichail Maria Louiza Sagredaki Anna Christakou

(1) Background: Alzheimer’s disease is a common neurodegenerative disease which mainly affects the elderly. The aim of the study is to investigate the relationship between handgrip strength and cognitive ability in a geriatric population with early-stage dementia. There are only a few studies that associate handgrip strength with cognitive ability in a population with early-stage dementia. (2) Methods: The present study consists of a sample of 60 individuals with early-stage dementia and was conducted at the Alzheimer’s Association of Athens. Participants’ ages ranged from 65 to 93 years (M = 80 years, SD = 6.05). Specific inclusion and exclusion criteria of the sample were defined. Handgrip strength was assessed using a digital handheld dynamometer, while cognitive ability was measured using the Mini-Mental State Examination Test (MMSE). (3) Results: Descriptive statistics showed that the mean handgrip strength of the dominant upper limb was 144.45 ± 50.47 Newtons, and the mean cognitive score was M = 21.75 (SD = 1.97) (0–30 points). In a multivariable regression analysis adjusted for age, sex, and education, handgrip strength was not significantly associated with MMSE score (B = 0.056, 95% CI: −0.054 to 0.166, p = 0.314). (4) Discussion: There are few studies that correlate cognitive ability with handgrip strength in a population with early-stage dementia; thus, further studies are needed to investigate the present results, possibly with a larger sample size or using different cognitive function measurement tools. (5) Conclusions: Handgrip strength may appear not to be associated with cognitive ability when elderly patients are in early-stage dementia. More research should be conducted to confirm the present findings.

Clinical and Translational Neuroscience doi: 10.3390/ctn10020012

Authors: Jeffrey J. Parr Mary R. King Corbit Franks

Attention-deficit/hyperactivity disorder (ADHD) is a prevalent neurodevelopmental condition characterized by inattention, impulsivity, and executive dysfunction, which may influence both the risk and clinical course of sport-related concussion (SRC). This narrative review aimed to synthesize current evidence on the relationship between ADHD and SRC in athletic populations, with a focus on injury risk, symptom presentation, assessment challenges, and recovery trajectories. A targeted narrative review of the literature was conducted to synthesize current evidence on ADHD and sport-related concussion, with emphasis on literature published within the past 10 to 15 years. Studies were selected based on relevance to concussion risk, neurocognitive and symptom assessment, and recovery outcomes in athletes with ADHD, with priority given to methodologically rigorous research involving athletic populations. Available evidence suggests that athletes with ADHD are at an increased risk of SRC, with some studies reporting an approximately twofold increase, potentially due to impairments in inhibitory control and attention regulation. ADHD is also associated with elevated baseline symptom reporting, lower neurocognitive performance, and higher rates of invalid baseline testing, complicating post-injury assessment. Findings regarding recovery are mixed; however, emerging evidence indicates that ADHD may be associated with prolonged return-to-learn and return-to-sport timelines in some populations. Stimulant medication may influence risk and recovery, though results remain inconsistent. Overall, ADHD presents unique challenges in the clinical management of SRC, necessitating individualized, multidisciplinary approaches. Integrating neurocognitive and behavioral considerations into concussion protocols may improve diagnostic accuracy and optimize recovery in this population.

Clinical and Translational Neuroscience doi: 10.3390/ctn10020011

Authors: Jennifer Taun Elisa Costanza Dakota Hamilton Omid Ali Kharazmi Pam Larouche Terra Nevrencan Kya Collins

Background: Attention-Deficit Hyperactivity Disorder (ADHD) is a complex neurodevelopmental disorder affecting executive functions such as impulse control, focus, and organization. This study addresses three research questions: current models and gaps in ADHD interventions, ways to enhance strengths and address weaknesses, and program recommendations for various ages. The aim is to develop a comprehensive framework to improve ADHD interventions, with a particular focus on youth and addressing existing gaps to enhance effectiveness. Methods: The current study systematically reviews the literature to answer these research questions. Sources were examined to identify existing intervention models, documented strengths and weaknesses, and recommendations relevant to different developmental stages. Results: Findings show that interventions for ADHD are varied and include psychological or behavioural therapy, family-school issues and parent involvement, school-based approaches, and medication. Key challenges include a lack of evidence-based practices, gaps in translational research, and insufficient teacher training. Notable strengths are family-school conference and family input, though there is less emphasis on building problem-solving capacity and family agency. Conclusions: Program recommendations highlighted in the literature include the need for family involvement, matching intervention intensity to individual needs, and ensuring professional education for special education. Addressing these gaps is essential for strengthening ADHD interventions and improving outcomes for children and youth.

Clinical and Translational Neuroscience doi: 10.3390/ctn10020010

Authors: Allan Yukawa Schwartz Lucas da Silva Machado Francisco Gonzalez-Lima Farzad Salehpour Sérgio Gomes da Silva Rodrigo Álvaro Brandão Lopes-Martins Afonso Shiguemi Inoue Salgado Fabrizio dos Santos Cardoso

Background: Attention-Deficit/Hyperactivity Disorder (ADHD) is a prevalent neurodevelopmental condition characterized by impairments in attention, inhibitory control, working memory, and executive functions, largely associated with dysfunction of prefrontal and frontoparietal networks. Limitations and variable tolerability of pharmacological treatments have motivated interest in nonpharmacological neuromodulatory approaches. Methods: This narrative review was conducted based on a structured search of the PubMed database to identify preclinical and clinical studies investigating the cognitive and neurobiological effects of transcranial photobiomodulation. Studies were selected using predefined keywords related to photobiomodulation, cognition, and ADHD, and included investigations assessing cognitive or neurophysiological outcomes. Results: Across studies, photobiomodulation targeting prefrontal regions was associated with improvements in sustained and selective attention, inhibitory control, working memory, and broader executive functions, accompanied by increased cortical oxygenation, enhanced mitochondrial metabolism, and functional reorganization of prefrontal and frontoparietal networks; preliminary studies in ADHD populations also suggest beneficial effects on attention and working memory. Limitations: The current literature is constrained by the limited number of ADHD-specific clinical studies, heterogeneity in stimulation parameters, variability in cognitive outcome measures, relatively small sample sizes, and limited long-term follow-up. Conclusion: Transcranial photobiomodulation represents a promising, safe, and biologically plausible nonpharmacological strategy for modulating cognitive dysfunctions associated with ADHD; however, well-controlled randomized clinical trials are required to confirm efficacy, define optimal protocols, and establish long-term outcomes.

Clinical and Translational Neuroscience doi: 10.3390/ctn10020009

Authors: Robert K. Weissfeld

Non-organic (muscle) weakness (NOw) is proposed as a distinct pathological entity characterized by maladaptive neuroplasticity (learning) affecting motor control. Functional deficits are most directly revealed through the manual muscle testing (MMT) break test, which uniquely exposes a muscle’s ability to adapt to increasing external load, potentially serving as an index of motor control integrity. We advance the “muscle-motor-movement PTSD” (mPTSD) model in which learning during pain or stress (trauma) yields chronic avoidance (inhibition) of the associated muscles. In a second stage, compensatory synergies develop, overriding attempts at hypertrophy-oriented training. This non-systematic, integrative review synthesizes clinical reports, learning theories, motor control and pain literature, and objective tests of force and movement over time during MMT. Predictive processing and reinforcement learning offer complementary accounts of how hyper-precise priors and passive avoidance may maintain NOw beyond functional recovery. Unexplained muscle weakness is found in non-specific musculoskeletal disorders and functional motor disorder (functional weakness), but may also contribute to other conditions, such as kinesiophobia. Effective alternative treatments for NOw may act by updating or erasing maladaptive motor learning by disrupting memory reconsolidation, allowing immediate restoration of function. Analogous to psychoneuroimmunology’s role in immune function, we propose “psychoneurokinesiology”, the study of how maladaptive learning affects movement.

Clinical and Translational Neuroscience doi: 10.3390/ctn10010008

Authors: Boris Đurović Petar Vuleković Veljko Pantelić Jagoš Golubović

Mild traumatic brain injury (mTBI) in adults is extremely common worldwide, but only a small fraction of these patients harbor clinically significant intracranial injuries. Computed tomography (CT) of the head is the standard diagnostic tool to detect traumatic brain hemorrhages or lesions, yet indiscriminate CT scanning of all mTBI patients is inefficient, costly, and exposes patients to ionizing radiation. To optimize patient care, numerous clinical decision rules and guidelines have been developed internationally to identify which adult patients with mTBI should undergo head CT. This review provides a global perspective on the indications for head CT in adult mTBI, comparing key decision rules including the Canadian CT Head Rule, New Orleans Criteria, UK NICE Head Injury Guidelines, and others. Methods: We conducted a comprehensive analysis of major international guidelines and decision rules for head CT in adult mTBI, focusing on their inclusion criteria, risk factors, and diagnostic performance. Results: All the examined rules prioritize near-100% sensitivity for identifying patients who need neurosurgical intervention, but they differ greatly in specificity and recommended CT utilization rates. North American rules such as the New Orleans Criteria tend to favor higher sensitivity, scanning almost all patients with any symptom, whereas the Canadian CT Head Rule and certain European guidelines (NICE, Scandinavian) are more selective, significantly reducing CT usage while maintaining safety. Discussion: We discuss how these variations reflect different healthcare settings and risk tolerances, and we examine the implications for neurosurgical practice. We also highlight challenges in guideline implementation, the impact on global CT utilization, and emerging approaches (such as biomarker-assisted triage) that may further refine decision-making. In conclusion, appropriate use of clinical decision rules for head CT in mTBI can safely minimize unnecessary imaging, but local adaptation and clinician judgment remain crucial to ensure that no significant injuries are missed while avoiding over-scanning.

Clinical and Translational Neuroscience doi: 10.3390/ctn10010007

Authors: Gregorio Garcia-Aguilar Verónica Reyes-Meza

Electroencephalogram (EEG) methods for the diagnosis of Benign Epilepsy with Centrotemporal Spikes (BECTS) are reviewed. The focus is on procedures reported for EEG analysis and diagnosis in BECTS, since some recent and potential applications of artificial intelligence (AI) aim to enhance the diagnostic accuracy and time reduction process, thereby moving a step closer to advancing our knowledge of the electrical nuclei sources and dynamics of energy distribution through the scalp in patients with epilepsy. The advantages of AI classification techniques have an increasing publication rate in the specialist literature, with no clear agreement on methodology. Hence, a better understanding of the procedures, arguments, and achievements is needed. To achieve this goal, (1) we review the background knowledge of the clinical characteristics of BECTS, (2) we analyze the results and advantages of computational processing methods for source and connectivity analyses of EEG in BECTS, and finally, (3) we explore the AI methods published in specialized journals for BECTS analysis. In conclusion, we argue in favor of the combined use of a priori information, which is the basis of the clinical visual analysis of EEG, as a potential feature to be included in AI methods for the classification of epileptiform graphoelements in EEG in BECTS diagnosis.

Clinical and Translational Neuroscience doi: 10.3390/ctn10010006

Authors: Vinod Metta Huzaifa Ibrahim Shaikha Almazrouei Hani T. S. Benamer Tom Loney Prashanth Kukle Vinay Goyal Rukmini Mridula Guy Chung-Faye Merie Octavia Gloria Tanjung Hasna Hussain Afsal Nalarakettil Rupam Borgohain Rajinder K. Dhamija Kallol Ray Chaudhuri

Background: Parkinson’s disease (PD) is a progressive neurodegenerative disorder marked by both motor and non-motor symptoms. The home-based wearable sensor monitoring Parkinson’s KinetiGraph (PKG) evaluates clinical efficacy, caregiver satisfaction, and cost-effectiveness in the clinical management of Parkinson’s disease (PD) compared to prior usual standard care. Methods: We analyzed 50 patients with Parkinson’s disease, comparing baseline clinical outcomes, healthcare utilization, and caregiver burden without PKG to follow-up data after 12 months with PKG. We used IBM SPSS Statistics for the analysis. Statistical significance was set at p < 0.05 for hypothesis testing. We employed the Wilcoxon signed-rank test to evaluate differences between the two time points, while exploratory bivariate associations between caregiver burden (Zarit score) and various outcomes were examined using Spearman’s rank correlation. Results: Over a 12-month period following the implementation of PKG-guided care, significant improvements were observed in various clinical, functional, and economic areas for the patients. Key findings include the following: motor function improved, with UPDRS Part III scores showing a 20% median reduction (from 25 to 20); medication adjustments decreased by 40% (from 5 to 3); outpatient visits were reduced by 60% (from 5 to 2); hospital admissions decreased by 100% (from 1 to 0); caregiver burden, as measured using the Zarit caregiver burden score, declined by 37.5% (from 48 to 30); and total direct medical costs decreased by 17.9% (from AED 261,800 to AED 215,000). Conclusions: These findings indicate substantial reductions in healthcare utilization, costs, and caregiver burden following the integration of PKG monitoring into clinical practice.

Clinical and Translational Neuroscience doi: 10.3390/ctn10010005

Authors: Cuiping Yuan Hector Acosta-Rodriguez Nahla M. H. Elsaid Clara F. Weber Pratheek Bobba Anh T. Tran Ajay Malhotra Seyedmehdi Payabvash

The National Institutes of Health (NIH) Toolbox cognition battery and Trail Making Tests (TMT) are widely used to quantify cognitive aging and to detect early cognitive vulnerability in Alzheimer’s disease and related conditions. However, these tests are often treated as interchangeable markers of global cognition, despite likely differences in their dependence on specific brain systems, limiting interpretability across studies and clinical contexts. To address this gap, we examined associations between four commonly used cognitive measures—fluid cognition, crystallized cognition, TMT-A, and TMT-B—and multimodal MRI metrics in 725 healthy volunteers aged 36 to 100 years from the Human Connectome Project–Aging. Voxel-wise diffusion MRI and vertex-wise cortical thickness and volume analyses were adjusted for age, sex, and years of education. Higher crystallized and fluid cognition scores and faster TMT-A/B completion times were generally associated with greater white matter integrity. TMT-B showed the most extensive diffusion and cortical associations, involving major projection, commissural, and association pathways and frontoparietal and temporo-occipital cortices. TMT-A and crystallized cognition demonstrated intermediate, overlapping patterns, whereas fluid cognition showed only focal brainstem and limited cortical correlates. These findings demonstrate systematic differences in the neuroanatomical substrates underlying commonly used cognitive tests and provide normative structure–cognition reference maps that can improve test selection, mechanistic interpretation, and sensitivity to brain health in studies of aging, vascular risk, and preclinical neurodegenerative disease.

Clinical and Translational Neuroscience doi: 10.3390/ctn10010004

Authors: Seonghyuk Son Nina Sharp Dongwoo (Jason) Yeom

Background: Recent studies have highlighted the significant impact of combined thermal and lighting conditions on human comfort. However, there is limited understanding of how these factors influence cognitive performance in older adults. This study explored the effects of complex thermal and lighting conditions on various cognitive functions and physiological responses in older adults. Additionally, a predictive cognitive model was developed using physiological indicators as well as demographic factors. Methods: Twenty-two older adults participated in a within-subject design experiment under different thermal and lighting combinations. The study focused on two temperature conditions, 18 °C and 28 °C, and two lighting conditions, 480 nm with 5500 K and 644 nm with 3200 K. Conclusions: The finding showed that males significantly performed better at 18 °C under 480 nm lighting, while females excelled at 28 °C under 644 nm lighting. Electrodermal activity (EDA) increased in warmer conditions with warmer lighting, and pupil size expanded similarly but decreased under cooler conditions. Males’ EDA was negatively correlated with cognitive performance, while females’ pupil size and BMI were positively correlated. Using the classification and regression tree (CART) algorithm, predictive model demonstrated 89.7% accuracy. These findings emphasize the potential of optimizing thermal and lighting conditions to enhance cognitive functions and predict performance in older adults

Clinical and Translational Neuroscience doi: 10.3390/ctn10010003

Authors: Nazar S. Annanepesov Justina Phiri Gennady E. Chmutin Gerald Musa Nicola Montemurro

Background: The management of asymptomatic lumbosacral lipomas remains controversial, with studies reporting both prophylactic surgery and conservative management. This review compares conservative and surgical treatment approaches for asymptomatic lumbosacral lipomas in children, analyzing outcomes, complications and secondary treatment. Methods: A systematic literature review was conducted using PubMed, Cochrane, and Web of Science databases. Data were extracted and analyzed based on demographic characteristics, lipoma classification, treatment modality, complications and secondary treatment. Results: A total of 22 retrospective studies comprising 1215 patients were included. The mean age was 1.87 years, with a 1.12:1 female-to-male ratio. Dorsal lipomas were the most common subtype (31.6%). At first, a total of 1017 (83.7%) patients underwent surgery, whereas 198 (16.3%) patients had conservative management. Total resection was achieved in 422 (41.9%) patients, whereas subtotal resection and partial resections were performed in 261 (25.9%) and in 334 (33.29%) patients, respectively. Neurological worsening occurred in 17.2% of patients treated conservatively at first diagnosis, with urological dysfunction being the most common symptoms reported (15.2%), followed by neurological deficit to the lower limbs (12.6). Conservative management following prior surgical intervention was performed in 2.6% of cases. A favorable outcome was observed in 88.7% of patients following surgical resection and in 81.8% of patients who were not treated surgically. Conclusion: While surgical intervention is associated with operative risk, it provides a lower risk of long-term neurological deterioration compared to conservative management. The decision to operate should be individualized, considering patient age, anatomical complexity and based on risk of progression.

Clinical and Translational Neuroscience doi: 10.3390/ctn10010002

Authors: Aleksandra Ochneva Olga Abramova Yana Zorkina Irina Morozova Valeriya Ushakova Konstantin Pavlov Denis Andreyuk Eugene Zubkov Alisa Andryushchenko Anna Tsurina Karina Kalinina Olga Gurina Vladimir Chekhonin Georgy Kostyuk Anna Morozova

Objective: Alzheimer’s disease (AD) and other forms of dementia are a heterogeneous group of neurodegenerative diseases characterized by progressive cognitive decline. Differential diagnosis between AD and other dementias is crucial for choosing the optimal treatment strategy. Currently, cerebrospinal fluid (CSF) analysis remains the most accurate diagnostic method, but its invasiveness limits its use. In this regard, the search for reliable biomarkers in the blood is an urgent task. Methods: The study included 31 dementia patients (23 women and 8 men) diagnosed via interdisciplinary consultations and neuropsychological testing (MMSE ≤ 24). CSF and blood plasma samples were collected and analyzed using Luminex technology. Biomarker concentrations were measured, and statistical analyses (ANOVA, Kruskal–Wallis, and Pearson correlation) were performed to compare groups and assess correlations. Results: Levels of Aβ40 and Aβ42 in CSF were significantly lower in patients with AD compared with non-AD dementia (p = 0.02 and p < 0.001, respectively). The Aβ42/40 ratio in CSF was higher in patients with non-AD dementia (p = 0.048). The concentration of Aβ42 in blood plasma was increased in patients with AD (p = 0.001). Positive correlations were found between Aβ42 in CSF and TDP-43 in plasma in non-AD dementia (r = 0.97, p < 0.001), as well as between neurogranin and TDP-43 in plasma in AD (r = 0.845, p < 0.001). Conclusions: The study demonstrates the potential of blood biomarkers, in particular Aβ42, for the differential diagnosis of AD and other forms of dementia. The discovered correlations between CSF and plasma biomarkers deepen the understanding of neurodegenerative processes and contribute to the development of noninvasive diagnostic methods.

Clinical and Translational Neuroscience doi: 10.3390/ctn10010001

Authors: Gabriela N. F. Guimarães Farzad Salehpour Jordan Schwartz Douglas W. Barrett Francisco Gonzalez-Lima

Down Syndrome Regression Disorder (DSRD) is a rare but severe neuropsychiatric condition characterized by abrupt loss of speech, autonomy, and cognitive abilities in individuals with Down syndrome, often associated with immune dysregulation and gut–brain axis dysfunction. We report the case of an 11-year-old girl with Down syndrome who developed developmental regression at age five, in temporal proximity to a family transition (the birth of a younger sibling), with loss of continence, language, and comprehension, alongside persistent behavioral agitation and gastrointestinal symptoms. Laboratory assessment revealed Giardia duodenalis infection, elevated fecal calprotectin and secretory IgA, and microbial imbalance with overgrowth of Streptococcus anginosus and S. sobrinus. The patient received a single oral dose of tinidazole (2 g), daily folinic acid (1 mg/kg), and a 90-day course of transcranial and abdominal photobiomodulation (PBM) (1064 nm, 10 min per site). Post-treatment, stool analysis showed normalized inflammation markers and restoration of beneficial bacterial genera (Bacteroides, Bifidobacterium, Lactobacillus) with absence of Enterococcus growth. Behaviorally, she exhibited marked recovery: CARS-2-QPC decreased from 106 to 91, ABC from 63 to 31, and ATEC from 62 to 57, alongside regained continence, speech, and fine-motor coordination. These outcomes suggest that abdominal and transcranial PBM, by modulating mitochondrial metabolism, mucosal immunity, and microbiota composition, may facilitate systemic and neurobehavioral recovery in DSRD. This translational case supports further investigation of PBM as a non-invasive, multimodal therapy for neuroimmune regression in genetic and developmental disorders including validation through future randomized controlled clinical trials.

Clinical and Translational Neuroscience doi: 10.3390/ctn9040058

Authors: Vera Vladimirovna Kudelkina Alexandra Igorevna Bulava Alexander Georgievich Gorkin Yana Andreevna Venerina Yuri Iosifovich Alexandrov

The high attrition rates in glioblastoma (GB) therapeutic development stem largely from preclinical models that fail to adequately recapitulate the dynamic tumor–host ecosystem. Unlike previous reviews that characterize glioma cell lines in isolation, this article integrates tumor biology with the distinct neuro-immune–endocrine landscapes of major laboratory rat strains. We critically evaluate standard rat malignant glioma cell lines (C6, F98, RG2, 9L) alongside transplantable tissue models (GB 101.8, GB 15/47), which offer enhanced translational relevance, demonstrating that the predictive value of any model is contingent upon the specific “glioma model and host strain” pairing and the individual physiological characteristics of the host. We provide evidence that strain-specific hypothalamic–pituitary–adrenal (HPA) axis reactivity (e.g., hyper-reactive Fischer 344 versus normo-reactive Wistar) acts as a decisive, yet often overlooked, modulator of the tumor microenvironment and therapeutic response. The review delineates the utility and limitations of these models, specifically addressing the MHC incompatibilities of the widely used C6 model in immunotherapy research, while contrasting it with the immune-evasive phenotypes of RG2 and the GB 101.8 tissue model. Furthermore, we highlight the superiority of tissue transplants in preserving cellular polyclonality and diffuse infiltration patterns compared to the circumscribed growth often observed in cell line-derived tumors. Consequently, we propose a strategic selection paradigm wherein immunogenic models serve as bioindicators of host immunocompetence, while invasive, non-immunogenic systems (F98, RG2, and GB 101.8) are utilized to investigate therapeutic resistance and systemic host-tumor interactions.

Clinical and Translational Neuroscience doi: 10.3390/ctn9040057

Authors: Heiko Pohl

Considering the prevalence of migraine and its impact on everyday living, its evolutionary persistence remains puzzling. This essay reviews recent literature and conceptual perspectives that frame migraine attacks as a possible side-effect of prolonged stress and unmet needs. To illustrate this, the article compares the antithetical relationship of triggers and migraine symptoms: During the early phase of the attack, many eat, drink, rest and sleep more and tolerate less nuisance compared to the hours and days before; previously, however, there was too little time to eat, drink, rest, and sleep, and the nuisance had to be tolerated. A relevant characteristic of many migraineurs is that they are prone to stress, e.g., because of a character trait, an impaired adaptation to stress, the lack of habituation to sensory stimuli, and disturbances of the energy supply. In that way, the appearance of the attack during fading stress makes sense: the body seizes the opportunity and communicates its needs when circumstances permit. In this context, the concept of pain as an imperative—a signal designed to enforce behavioural change—provides an insightful framework. Understanding migraine in this way may help reframe its pathophysiology and its clinical and translational significance.

Clinical and Translational Neuroscience doi: 10.3390/ctn9040056

Authors: Tobias Monschein Iris-Katharina Penner Irina Filchenko Albrecht P. A. Vorster Hakan Sarikaya Gian Luca Di Tanna Mirjam R. Heldner Bogdan Draganski Kristina Adorjan Simon Jung Marcel Arnold Urs Fischer Claudio L. A. Bassetti

Brain Health has become a global public health priority, driven mainly by the rapid aging of populations and the increasing burden of neurological and psychiatric disorders. This report presents the first activities of the Bern Brain Health Working Group, established to implement the Swiss Brain Health Plan (SBHP), published in 2023. The aim is to describe the development and initial outcomes of regional initiatives promoting Brain Health in Switzerland. Specifically, we outline the structure and objectives of the Bern Brain Health Consultation, the development process and conceptual framework of the Swiss Brain Health Questionnaire, and additional educational and research activities supporting the SBHP. By summarizing these first steps, this report provides a model for regional implementation of a national Brain Health strategy and contributes to building a foundation for broader national and international Brain Health efforts.

Clinical and Translational Neuroscience doi: 10.3390/ctn9040055

Authors: Maha S. Alsaad Abeer F. Almarzouki Solafa H. Ghoneim Basma A. Al-Jabri Samraa Suliman

Working memory training (WMT) has promising effects on cognitive and clinical outcomes in children with attention deficit hyperactivity disorder (ADHD). However, few studies have explored the effectiveness of such programs in developing countries with different populations and sociocultural backgrounds. This study aimed to pilot Cogmed WMT (CWMT) and examine its impact on clinical and cognitive outcomes in children diagnosed with ADHD in Saudi Arabia. We assessed 34 children with ADHD assigned to either a CWMT or standard-of-care group. Both groups were evaluated at baseline and five weeks for ADHD symptoms and cognitive function, including working memory (WM), sustained attention, and impulsivity. Compared with the baseline and the control group, the intervention group demonstrated improved parent ratings of ADHD clinical symptoms and cognitive function scores, including WM, sustained attention, and impulsivity. CWMT improved cognitive and clinical measures in our sample of Saudi children with ADHD and is a promising non-pharmacological therapy for treating children with ADHD in developing countries.

Clinical and Translational Neuroscience doi: 10.3390/ctn9040054

Authors: Anas Zaman Yasmine Albalushi Hashim Alibrahim Sameh Almatroushi Mahmood Alnoufali Kawthar Almaknena Tariq D Al-Saadi

Background: Traumatic Brain Injury (TBI) represents a growing cause of medical emergencies globally. Objective: This study evaluates whether healthcare outcomes for TBI patients differ between daytime and on-call (after-hours) admissions. Methods: A retrospective analysis was conducted using data from a hospital database spanning January 2015 to December 2019. Of the 670 cases reviewed, 45 patients over the age of 65 were admitted with head trauma. Data were analyzed using SPSS. Results: Surgical interventions were significantly less frequent during on-call hours. Admission type (elective vs. emergent) showed a statistically significant difference (p < 0.05). Postoperative ICU length of stay (LOS) was markedly longer for on-call admissions (p = 0.002). Due to a controlled sample size, p-value interpretations would need some discretion. TBI patients admitted during on-call hours had a 9.9-fold increase in ICU stay, a 2.5-fold increase in total hospital LOS, and a 475% higher complication rate compared to daytime admissions. Complication rates were 20% for daytime admissions versus 92% for on-call admissions. Furthermore, patients treated during on-call hours were 11 times more likely to be discharged in an unconscious state (GCS < 8). Conclusions: TBI outcomes are significantly worse during on-call hours. Enhancing imaging availability and staffing during these periods may help improve patient outcomes.

Clinical and Translational Neuroscience doi: 10.3390/ctn9040053

Authors: Đula Đilvesi Teodora Tubić Sanja Maričić Prijić Jagoš Golubović

Background: Severe traumatic brain injury (TBI) often leads to elevated intracranial pressure (ICP) that requires aggressive management. Inducing burst suppression with deep sedation is an established therapy for refractory intracranial hypertension. Traditionally, barbiturate coma has been used to achieve burst-suppression EEG in TBI patients, but alternative sedative agents (propofol, midazolam, ketamine, dexmedetomidine) are increasingly utilized in modern neurocritical care. This review compares barbiturates with these alternatives for inducing burst suppression in adult TBI, focusing on protocols, mechanisms, efficacy in controlling ICP, safety profiles, and impacts on neurological outcomes. Methods: A search of the literature was performed, including clinical trials, observational studies, and guidelines on deep sedation for ICP control in adult TBI. Studies comparing high-dose barbiturates to other sedatives (propofol, midazolam, ketamine, dexmedetomidine) in the context of burst suppression or severe TBI management were included. Data on sedative protocols (dosing and EEG targets), mechanisms of action, ICP-lowering efficacy, complications, and patient outcomes were extracted and analyzed qualitatively. Results: High-dose barbiturates (e.g., pentobarbital or thiopental) and propofol are both effective at inducing burst-suppression EEG and reducing ICP via cerebral metabolic suppression. Barbiturate coma remains a third-tier intervention reserved for ICP refractory to other treatments. Propofol infusion has become first-line for routine ICP control due to rapid titratability and shorter half-life, though it can also achieve burst suppression at high doses. Midazolam infusions provide sedation and seizure prophylaxis but yield less metabolic suppression and ICP reduction compared to barbiturates or propofol, and are associated with longer ventilation duration and delirium. Ketamine, once avoided for fear of raising ICP, has shown neutral or lowering effects on ICP when used in ventilated TBI patients, thanks to its analgesic properties and maintenance of blood pressure; however, ketamine alone does not reliably produce burst-suppression patterns. Dexmedetomidine offers sedative and anti-delirium benefits with minimal respiratory depression, but it is generally insufficient for deep burst-suppressive sedation and has only a modest effect on ICP. In comparative clinical evidence, propofol and barbiturates both effectively lower ICP, but neither has demonstrated clear improvement in long-term neurological outcome when used prophylactically. Early routine use of barbiturate coma may increase complications (hypotension, immunosuppression), and thus, current practice restricts it to refractory cases. Modern sedation protocols emphasize using the minimal necessary sedation to maintain ICP < 22 mmHg, with continuous EEG monitoring to titrate therapy to a burst-suppression target (commonly 2–5 bursts per minute) when deep coma is employed. Conclusions: In adult TBI patients with intracranial hypertension, propofol-based sedation is favored for first-line ICP control and can achieve burst suppression if needed, whereas high-dose barbiturates are reserved for ICP crises unresponsive to standard measures. Compared to barbiturates, alternative agents (propofol, midazolam, ketamine, dexmedetomidine) offer differing advantages: propofol provides potent, fast-acting metabolic suppression; midazolam adds anticonvulsant sedation for prolonged use at the cost of slower wake-up; ketamine supports hemodynamics and analgesia; dexmedetomidine aids lighter sedation and delirium control. The choice of agent is guided by the clinical scenario, balancing ICP reduction needs against side effect profiles. While all sedatives can transiently reduce ICP, careful monitoring and a tiered therapy approach are essential, as no sedative has conclusively improved long-term neurological outcomes in TBI. EEG monitoring for burst suppression and meticulous titration is required when employing barbiturate or propofol coma. Ongoing research into optimal combinations and protocols may further refine sedation strategies to improve safety and outcomes in severe TBI.

Clinical and Translational Neuroscience doi: 10.3390/ctn9040052

Authors: Güven Gürsoy Beste Daltaban Gönül Güvenç

Background and Objectives: The mechanisms of traumatic brain injury (TBI), patient characteristics, and long-term outcomes in elderly patients differ from those in other age groups. This study aims to evaluate the effectiveness of the Elderly Traumatic Brain Injury (eTBI) Scoring System, recently described in the literature, in predicting mortality, prognosis, and surgical indication. Materials and Methods: Patients diagnosed with TBI over the age of 65 between January 2017 and December 2024 were retrospectively analyzed, and their eTBI scores were calculated. Statistical analyses were conducted to assess mortality, prognosis, and surgical indication or benefit from surgery across low-, medium-, and high-risk groups. Results: In this cohort of 236 patients, the mortality rate was higher in the high-risk group according to the eTBI scoring system, compared to the medium- and low-risk groups. However, the scoring system does not appear to be effective in determining surgical indications. While the medium-risk group was most predictive of mortality, the low-risk group demonstrated better accuracy in predicting prognosis. Conclusions: The eTBI scoring system appears to be an effective tool for assessing mortality risk and predicting prognosis in specific subgroups of elderly TBI patients.

Clinical and Translational Neuroscience doi: 10.3390/ctn9040051

Authors: Venkatraman Pitchaikannu Subramani Vellaiyan Shweta Kedia Vivek Tandon Rajinder Kumar Deepak Agarwal Manoj Phalak Satish Kumar Verma Dattaraj P. Sawarkar Kanwaljeet Garg Gopishankar Natanasabapathi

Neuroradiology and neuro-oncology are rapidly emerging fields in the diagnosis and treatment of central nervous system (CNS) diseases, including brain tumors. This review presents a comprehensive look at the current imaging techniques, clinical applications, and therapeutic strategies, with a focus on gliomas, metastases, and functional brain mapping. Conventional modalities such as CT and MRI, as well as sophisticated approaches including functional MRI (fMRI), diffusion tensor imaging (DTI), MR spectroscopy, PET, and hybrid techniques, are discussed. On the therapeutic front, high-precision radiotherapy modalities such as stereotactic radiosurgery (SRS), stereotactic radiotherapy (SRT), and proton therapy are discussed, with a focus on radiation biology, dose planning, and the impact on neurocognitive outcomes. The interlink between neuroradiology and radiotherapy is highlighted through advanced image-guided treatment planning.

Clinical and Translational Neuroscience doi: 10.3390/ctn9040050

Authors: Karsten Krakow Paolo Rossi Arseny A. Sokolov Matthias Elstner Rene M. Müri Daniel Zutter

Background: Neurorehabilitation plays a central role in restoring and maintaining brain health across lifespan. However, its contribution is often underestimated in public health policies. Aim: This paper aims to highlight the importance of neurorehabilitation within the brain health frameworks, advocating for its full integration into global and national health strategies. Main content: We discuss the unique characteristics of neurorehabilitation, including its interdisciplinary structure, long-term scope and role in prevention. We underline how the ICF model provides a bridge between clinical practice and public health policy. Key prevention strategies and the potential of digital technologies are also examined. Conclusion: A stronger integration of neurorehabilitation into brain health policy can yield individual and socio-economic benefits. We call for strategic political and structural efforts to expand its availability and recognition.

Clinical and Translational Neuroscience doi: 10.3390/ctn9040049

Authors: Yuxiang Yang Darryl Chen Sonu M. M. Bhaskar

Background: Deep vein thrombosis (DVT) is a serious thromboinflammatory complication of acute ischemic stroke (AIS). The true incidence, mechanistic risk factors, and optimal prophylactic strategies remain uncertain, particularly in the era of reperfusion therapy. Methods: This systematic review and meta-analysis (IRIS-DVT) searched PubMed, Embase, Cochrane, Scopus, and Web of Science for studies reporting DVT incidence, risk factors, or prophylaxis in AIS (2004–2025). Random-effects models were used to generate pooled prevalence and effect estimates, and the certainty of evidence was graded using the GRADE framework. Results: Forty-two studies (n = 6,051,729 patients) were included. The pooled prevalence of DVT was 7% (95% CI, 6–9%), approximately seventy-fold higher than in the general population, with wide heterogeneity influenced by screening timing and diagnostic modality. Pathophysiological risk factors included higher stroke severity (NIHSS; SMD 0.41; 95% CI, 0.38–0.43), older age (SMD 0.32; 95% CI, 0.18–0.46), elevated D-dimer (SMD 0.55; 95% CI, 0.38–0.72), female sex (OR 1.33; 95% CI, 1.19–1.50), and malignancy (OR 2.69; 95% CI, 1.56–5.22), supported by moderate-certainty evidence. Respiratory infection and admission hyperglycemia showed weaker, low-certainty associations. Traditional vascular risk factors (hypertension, diabetes, atrial fibrillation, dyslipidemia) were not significantly related to DVT risk. Evidence for prophylaxis with low-molecular-weight heparin, direct oral anticoagulants, or intermittent pneumatic compression was limited and graded very low certainty. Conclusions: DVT complicates approximately one in fourteen AIS cases, reflecting a distinct thromboinflammatory process driven more by acute neurological severity, systemic hypercoagulability, and malignancy than by conventional vascular risk factors. Early systematic screening (≤72 h) and consistent use of mechanical prophylaxis are warranted. Dedicated AIS-specific mechanistic and interventional trials are urgently needed to refine prevention strategies and improve post-stroke outcomes.

Clinical and Translational Neuroscience doi: 10.3390/ctn9040048

Authors: Calixto Machado Gerry Leisman

We here delve into the intricate and evolving concepts of brain death and consciousness, particularly at the end of life. We examine the historical and technological advancements that have influenced our understanding of death, such as mechanical ventilation and resuscitation techniques. These developments have challenged traditional definitions of death, leading to the concept of brain death, defined as the irreversible loss of all brain functions, including the brainstem. We emphasize that consciousness exists on a continuum, ranging from full alertness to deep coma and complete cessation of brain activity. It explores various disorders of consciousness, including coma, vegetative state, minimally conscious state, and locked-in syndrome, each with distinct characteristics and levels of awareness. Neuroimaging techniques, such as EEG, fMRI, and DTI, are highlighted for their crucial role in diagnosing and understanding disorders of consciousness. These techniques help to detect covert consciousness, assess brain activity, and predict recovery potential. The phenomenon of the “wave of death,” which includes a paradoxical surge in brain activity at the point of death, is also discussed. We address the challenges in defining and understanding both death and consciousness, calling for biologically grounded, ethically defensible, and culturally sensitive definitions. We advocate for standardized neuroimaging protocols, longitudinal studies, and the integration of artificial intelligence to improve diagnosis and treatment. In conclusion, the document underscores the importance of an integrated, evidence-based approach to understanding the gray zones between life and death, recognizing that consciousness and death are dynamic processes with both biological and experiential dimensions.

Clinical and Translational Neuroscience doi: 10.3390/ctn9040047

Authors: Merih Can Yilmaz Keramettin Aydin

Background/Objectives: This study presents a case of chronic internal carotid artery [ICA] occlusion initially misinterpreted as ICA agenesis on magnetic resonance angiography (MRA). The report underscores the importance of retrospective review of prior imaging, particularly computed tomography angiography [CTA], in establishing the correct diagnosis. Case Report: A 70-year-old man presented with persistent headache, pulsatile tinnitus, and intermittent dizziness. Neurological examination and laboratory results were unremarkable. Initial cranial MRA demonstrated absence of flow in the left ICA, raising suspicion of congenital agenesis. However, retrospective evaluation of a CTA performed nine years earlier revealed a well-formed left carotid canal without ICA opacification, confirming the diagnosis of chronic ICA occlusion. Results: Current imaging again showed lack of enhancement in the left ICA, with adequate cerebral perfusion supplied via the contralateral ICA and vertebrobasilar system. Recognition of the preserved carotid canal on earlier CTA clarified the diagnosis as chronic occlusion rather than agenesis. Although surgical or endovascular revascularization was recommended, the patient opted for conservative management. At three months of follow-up, symptoms had improved and clinical monitoring continues. Conclusions: This case underscores the importance of distinguishing ICA agenesis from chronic occlusion, particularly by evaluating the carotid canal on CT. The presence of a carotid canal strongly indicates prior patency of the ICA and supports a diagnosis of occlusion. Careful differentiation is critical to avoid misinterpretation and to guide appropriate clinical management. In addition, reviewing prior imaging can be valuable when current findings are inconclusive or potentially misleading. Since this is a single case report, these observations should be regarded as hypothesis-generating rather than definitive, and further studies are needed to validate their broader applicability.

Clinical and Translational Neuroscience doi: 10.3390/ctn9040046

Authors: Ananthapadmanabha Kotambail Yogananda Shamamandri Markandeya Raghavendra Mahima Ramya Sukrutha Madhura Milind Nimonkar Suravi Sasmita Dash Chandrajit Prasad Ghati Kasturirangan Chetan Pooja Mailankody Gautham Arunachal

Introduction: Genes in the endolysosome and autophagy pathways are major contributors to hereditary spastic paraplegia (HSP). A pathogenetic link between HSP and Alzheimer disease (AD) involving macroautophagy is well established. Sortilin-related receptor 1 (SORL1), an endosomal trafficking protein, plays a key role in glutamatergic neuron homeostasis and white matter tract integrity. Until now, SORL1 has only been associated with dominant AD and cerebral amyloid angiopathy. Methods: A case of HSP with cerebroretinal vasculopathy (CRV) negative on exome sequencing was further investigated using whole-genome sequencing. RNA-seq, Western blot, and immunofluorescence imaging were performed to explore a potential loss-of-function mechanism. Results: Sequencing revealed a biallelic SORL1 splice donor variant (c.1211 + 1G > A). Transcriptomics confirmed nonsense-mediated decay and aberrant splicing, predicting a disrupted reading frame. Reduced SORLA protein levels and significant enlargement of endolysosomes in patient-derived fibroblasts further cemented the pathogenicity of the variant. Conclusions: The probability that SORL1 acts as a recessive disease-causing gene gathers support from the following data: SORL1 genomic constraint score pRec = 1, high meiotic recombination rates on the locus, phenotype of Sorl1−/− mice reminiscent of HSP with CRV, and endolysosomal enlargement in SORL1−/− glutamatergic neurons in vitro. Taken together, SORL1 is probably a new candidate for a recessive form of complicated HSP.

Clinical and Translational Neuroscience doi: 10.3390/ctn9040045

Authors: Swiss Federation of Clinical Neuro-Societies (SFCNS) Swiss Federation of Clinical Neuro-Societies (SFCNS)

On behalf of the SFCNS, Swiss Federation of Clinical Neuro-Societies, we are pleased to present the Abstracts of the 6th SFCNS Congress, which will be held in Lausanne, Switzerland, 29–31 October 2025. In total, 182 abstracts were selected as ePosters, of which 60 abstracts are presented as short presentations during the ePoster Sessions and 2 abstracts are presented at the Neurosurgery Sessions. We congratulate all the presenters on their research work and contributions.

Clinical and Translational Neuroscience doi: 10.3390/ctn9040044

Authors: Claudio L. A. Bassetti

While the term mental health officially exists since the foundation of the WHO in 1948 and the related concept of «mental hygiene» was used in the literature already in 1843, the term brain health first appeared only in 1989 [...]

Clinical and Translational Neuroscience doi: 10.3390/ctn9030043

Authors: Umberto Nencha Friedhelm C. Hummel

The prevalence and the burden of neurodegenerative diseases is projected to increase in the future, but therapeutic options remain limited, relatively invasive, and not readily accessible. In this context, non-invasive brain stimulation (NIBS) techniques, mainly transcranial magnetic stimulation (TMS) and transcranial electrical stimulation (tES), are emerging as safe and reliable instruments to enhance cognitive performance in asymptomatic individuals and patients with cognitive decline. Nevertheless, these techniques face some limitations that delay their deployment in clinical practice. Here, we describe the current status in the development of these technologies for the treatment of neurodegenerative diseases, and we present a novel promising approach for focally and non-invasively target deep brain regions. In light of these technological advances, we then propose a stepwise research roadmap to achieve an effective clinical translation of these techniques. Firstly, the constitution of open-access multimodal databases will allow to inform future interventions and design a new generation of clinical trials. Secondly, research efforts targeting symptomatic patients will need to assess the impact of NIBS techniques in different forms of dementias and probe their efficacy as disease-modifying therapies. In a future step, randomized clinical trials could focus on highly characterized at-risk populations to probe the impact of NIBS in secondary prevention. Once validated on research grounds, these techniques could enter clinical practice, enhancing cognitive performance in asymptomatic individuals and slowing disease progression in symptomatic patients, ultimately lowering the burden of neurodegenerative diseases. Eventually, NIBS techniques could be integrated into clinical practice within the framework of national Brain Health programs to provide early non-invasive interventions against cognitive decline to patients and individuals at risk.

Clinical and Translational Neuroscience doi: 10.3390/ctn9030042

Authors: Basema Temehy Andrew Soundy Ahmad Sahely Sheeba Rosewilliam

Background: Continuity of care is critical for optimal stroke rehabilitation, yet gaps in post-stroke services in Saudi Arabia may undermine long-term patient outcomes and recovery. The therapists who care for people with stroke should be aware of patients’ needs post discharge and possess skills to address them. This study explored physiotherapists’ perspectives on gaps in care continuity for stroke patients in Saudi Arabia and identified the training needs required to address these gaps. Methods: An exploratory qualitative study situated within critical realism was conducted using nine semi-structured interviews and three focus groups. Twenty-six physiotherapists who were working in outpatient stroke rehabilitation services participated. Data was analysed using reflexive thematic analysis. Results: Three major themes emerged. Significant gaps in post-stroke care were identified, including the lack of specialised stroke rehabilitation centres and clinical practice guidelines. Participants described both facilitators and barriers to implementing continuity of care approaches, such as telerehabilitation, self-management and home care. Further, physiotherapists highlighted the need for comprehensive training in stroke assessment and management, along with the development of standardised patient and caregiver educational protocols to support care continuity. Conclusion: The study highlights the need for targeted training programmes to enhance physiotherapists’ competencies in stroke care. It also calls for systemic collaboration among healthcare organisations and policymakers to develop structured post-stroke services.

Clinical and Translational Neuroscience doi: 10.3390/ctn9030041

Authors: Alice Accorroni Davide Zani Iliya Petkov Peyneshki Umberto Nencha Valentina Basile Lukas Sveikata Katharina Jury Martina Göldlin Annaelle Zietz Violette Corre

The concept of Brain Health is transforming the neuroscientific landscape, promoting an integrative and preventive approach to care under a unifying vision. This position paper, developed by Swiss junior societies in neurology and psychiatry, presents a trainee perspective on how Brain Health should be addressed from the earliest stages of postgraduate training. It explores current gaps in postgraduate training, including the continued separation of neurology, psychiatry and other specialties involved in brain disorder care, limited interdisciplinary and interprofessional exposure, and gaps in leadership, public health, and advocacy skills. We highlight promising models such as Switzerland’s integrated training components and the proposed “brain medicine” framework, inspired by internal medicine. Additionally, we examine innovative initiatives from trainee associations that promote collaborative learning, advocacy, and Brain Health awareness through academic and creative channels. The paper also stresses the importance of equitable global access to training, the integration of research into clinical education, and the urgent need to address burnout and working conditions among early-career professionals. By reframing trainees not as passive learners but as active agents of change, we call for systemic reforms that support their role in advancing Brain Health. Ultimately, we advocate for the development of international core competencies, adaptable curricula, and structured interdisciplinary pathways that embed Brain Health into every level of medical training. Only through this comprehensive approach can we equip the next generation of clinicians to promote lifelong Brain Health across specialties, systems, and populations.

Clinical and Translational Neuroscience doi: 10.3390/ctn9030040

Authors: Igor Horvat Jagoš Golubović Djula Djilvesi Bojan Jelača Petar Vuleković

Introduction: Mild traumatic brain injury (mTBI) in older adults (≥65 years) is often underestimated, despite being associated with significant morbidity. Age-related vulnerability, comorbidities, and medication use may exacerbate outcomes. This study aimed to identify predictors of brain health and functional recovery in older adults following mTBI, focusing on acute symptoms, CT imaging findings, and sociodemographic factors. Methods: We analyzed a cohort of 93 older adult patients with mTBI (GCS 13–15) who were prospectively enrolled at a tertiary neurosurgical center. All patients underwent baseline CT, structured clinical assessment, and follow-up at six months with standardized instruments (Glasgow Outcome Scale–Extended-GOSE, 12-Item Short Form Health Survey (quality-of-life measure)-SF-12, Rivermead Post-Concussion Symptoms Questionnaire-RPQ, Patient Health Questionnaire-9 (depression measure)-PHQ-9, PTSD (Post Traumatics Stress Disorder) Checklist for DSM (Diagnostic and Statistical Manual for Mental Disorders)-PCL-5, Timed up and Go Test (mobility measure-TUG test). Multivariate regression was performed to identify independent predictors of recovery. Results: At six months, 94.9% of older adults achieved functional independence (GOSE ≥ 5), though only 43% attained complete recovery (GOSE = 8). Patients with acute intracranial lesions on CT had worse physical outcomes, including slower mobility (mean TUG 17.6 vs. 16.3 s, p = 0.012). Severe acute headache independently predicted poorer recovery (lower GOSE and SF-12 PCS). Lower educational attainment correlated with worse functional and quality-of-life outcomes, consistent with reduced cognitive reserve. Psychological outcomes (PTSD and depression rates) were not associated with CT findings but were influenced by social support and sex. Prompt anticoagulation reversal in patients on anticoagulants markedly reduced hemorrhagic complications. Discussion: Older adults with mTBI generally maintain independence but experience reduced physical health and mobility compared to younger patients. Predictors of poorer outcomes include severe acute symptoms, CT-detected lesions, advanced age, and lower educational levels. Psychosocial support mitigated mental health complications. Conclusions: mTBI in older adults is not benign. Clinical, imaging, and sociodemographic factors collectively shape recovery. Early identification of high-risk patients and targeted interventions are essential to preserve brain health and independence in this growing population.

Clinical and Translational Neuroscience doi: 10.3390/ctn9030039

Authors: Carlos Darcy Alves Bersot Lucas Ferreira Gomes Pereira Vitor Alves Felippe Matheus Reis Rocha Melo Barros Gustavo Fernandes Nunes José Eduardo Guimarães Pereira Luiz Fernando dos Reis Falcão

Introduction: Craniotomy, a common neurosurgical procedure, is frequently associated with substantial perioperative challenges and delayed recovery. While Enhanced Recovery After Surgery (ERAS) protocols have demonstrated clear benefits in multiple surgical fields, their application in neurosurgery, particularly elective craniotomy, remains emerging. Objective: This systematic review and meta-analysis aimed to evaluate the efficacy and safety of ERAS protocols in adult patients undergoing elective craniotomy, focusing on key outcomes such as length of hospital stay (LOS), postoperative pain, complications, and functional recovery. Methods: Following PRISMA guidelines, a comprehensive search was conducted in PubMed, Embase, Scopus, Web of Science, and the Cochrane Library up to June 2025. Eligible studies included adult patients (≥18 years) undergoing elective craniotomy and compared ERAS protocols to conventional perioperative care. Primary outcomes were LOS, postoperative complications, pain, early oral intake, and early mobilization. Data extraction and risk of bias assessment (RoB 2.0) were independently performed by two reviewers. Results: Nine randomized controlled trials (RCTs), totaling 1453 patients, were included. Meta-analysis showed that ERAS protocols significantly reduced length of hospital stay (mean difference: −2.17 days; 95% CI: −2.92 to −1.42; p < 0.00001) and decreased the incidence of postoperative nausea and vomiting (odds ratio [OR]: 0.29; 95% CI: 0.19 to 0.44; I2 = 0%). ERAS protocols were associated with higher odds of early mobilization (OR: 6.88; 95% CI: 3.46 to 13.68) and early oral intake (OR: 14.04; 95% CI: 7.80 to 25.26). Postoperative complications were significantly reduced in the ERAS group (OR: 0.49; 95% CI: 0.24 to 0.99; p = 0.048; I2 = 0%). While early urinary catheter removal showed a favorable trend (OR: 13.48), high heterogeneity (I2 = 95.7%) limits interpretability. Postoperative pain on day 1 did not differ significantly between groups (mean difference: −0.37; 95% CI: −2.38 to 1.63; p = 0.72). The overall risk of bias was rated low to moderate across studies. Conclusions: ERAS protocols in elective craniotomy are associated with shorter hospital stays, lower complication rates, reduced PONV, and earlier return to function, without increasing adverse events. These findings support broader implementation of ERAS in neurosurgical practice. Further multicenter RCTs are warranted to standardize and refine ERAS components for craniotomy.

Clinical and Translational Neuroscience doi: 10.3390/ctn9030038

Authors: Jagoš Golubović Igor Horvat Djula Djilvesi Bojan Jelača Petar Vuleković

Chronic subdural hematoma (cSDH) is a common neurosurgical condition in the elderly, often resulting from minor head trauma. Traditional surgical treatments such as burr-hole drainage carry recurrence rates of 10–20% and significant risks in older patients, especially those on anticoagulation therapy. Middle meningeal artery (MMA) embolization has emerged as a minimally invasive alternative, aiming to reduce blood flow to the dura and thereby promote hematoma resolution and lower recurrence. We conducted a bibliometric analysis of publications on MMA embolization for cSDH up to December 2023. The analysis shows a sharp increase in research activity over the past decade. North America, Japan, and Europe are leading contributors, with collaborative networks forming among major institutions. Key journals in neurosurgery and neurointervention have published much of this research, and author collaborations are extensive. Frequently used keywords such as “recurrence” and “treatment outcome” reflect an emphasis on reducing rebleeding and improving patient outcomes. In conclusion, MMA embolization is rapidly gaining attention as a promising treatment for cSDH. While early results are favorable and multi-center efforts are expanding the evidence base, further research is needed to establish long-term efficacy, optimize patient selection, and standardize techniques.

Clinical and Translational Neuroscience doi: 10.3390/ctn9030037

Authors: Lydia Maderthaner Mark J. Edwards

Physical and mental health are intrinsically linked. However, healthcare systems, training programs, and clinical practice often operate in silos, creating structural disincentives that exacerbate morbidity, mortality, and economic burden. Integrated care models have consistently demonstrated improved outcomes, enhanced quality of life, and greater cost-effectiveness across a range of neuropsychiatric and chronic disorders. With the launch of the World Health Organization Brain Health Framework (2022) and the Swiss Brain Health Plan (2023–2033), important progress has been made toward integrating mental and brain health. However, current brain health concepts could be further strengthened by more explicitly incorporating the role of the body and physical health, including psychosomatic and social aspects, particularly in terms of their dynamic, bidirectional interactions with the brain. This article further outlines the health-related and economic benefits of integrated care, key challenges to the systematic implementation of mind–body integration within healthcare systems, and proposes strategic directions for embedding body–brain dynamics into research, education, and policy. This includes interdisciplinary teaching, harmonized conceptual models, composite clinical metrics, transferable interventions, and the removal of systemic barriers to establish integrated care pathways and reduce stigma through patient-centered empowerment. Ultimately, the “no health without brain health” ethos demands the conceptual and practical integration of dynamic, bidirectional body–brain interactions.

Clinical and Translational Neuroscience doi: 10.3390/ctn9030036

Authors: Karl-Olof Lövblad Karl Schaller Raphael Guzman Claudio Bassetti Luca Regli

The Swiss Society of Clinical Neuro-Societies mourns the loss of the former director of the Clinic of Neurosurgery at the University Hospital of Zurich Switzerland. He has pioneered microneurosurgery for lesions of the central nervous system and has had an enormous impact not just on the development of neurosurgery but also on neighboring specialties of clinical neuroscience such as neurology and neuroradiology. He is considered one of the major innovators in his field and his impact is still felt in today’s practice, not only in neurosurgery but also in advanced techniques for the exploration of the central nervous system such as angiography.

Clinical and Translational Neuroscience doi: 10.3390/ctn9030035

Authors: Simon Jung David Tanner Jacques Reis Claudio Lino A. Bassetti

Background: Brain health is a growing public health priority due to the high global burden of neurological and mental disorders. Promoting brain health across the lifespan supports individual and societal well-being, creativity, and productivity. Objective: To address the need for specialized education in this field, the University of Bern developed a Certificate of Advanced Studies (CAS) in Brain Health. This article outlines the program’s rationale, structure, and goals. Program Description: The one-year, 15 ECTS-credit program is primarily online and consists of four modules: (1) Introduction to Brain Health, (2) Brain Disorders, (3) Risk Factors, Protective Factors and Interventions, and (4) Brain Health Implementation. It offers a multidisciplinary, interprofessional, life-course approach, integrating theory with practice through case studies and interactive sessions. Designed for healthcare and allied professionals, the CAS equips participants with skills to promote brain health in clinical, research, and public health contexts. Given the shortage of trained professionals in Europe and globally, the program seeks to build a new generation of brain health advocates. It aims to inspire action and initiatives that support the prevention, early detection, and management of brain disorders. Conclusions: The CAS in Brain Health is an innovative educational response to a pressing global need. By fostering interdisciplinary expertise and practical skills, it enhances professional development and supports improved brain health outcomes at individual and population levels.

Clinical and Translational Neuroscience doi: 10.3390/ctn9030034

Authors: Roberta Mulargia Federica Ribaldi Sophie Mutel Ozge Sayin Giorgi Khachvani Gabriele Volpara Giulia Remoli Umberto Nencha Stefano Gianonni-Luza Stefano Cappa Giovanni B. Frisoni Augusto J. Mendes

Dementia prevention is a global public health priority, and lifestyle interventions, including nutrition, have gained interest for their potential to maintain cognitive health. Among nutritional interventions, omega-3 polyunsaturated fatty acids (n-3 FA), particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have been widely studied for their potential to support cognitive health. This systematic review evaluated whether n-3 FA supplementation improves global cognition in cognitively unimpaired older adults. Nineteen randomized controlled trials (RCTs) met inclusion criteria, of which five reported significant improvements in global cognition. A random-effects meta-analysis of 11 placebo-controlled RCTs showed no significant effect (SMD = −0.02, 95% CI: −0.07 to 0.04). Heterogeneity in supplement type, dosage, duration, and outcome measures may have contributed to inconsistent findings and limited comparability. Furthermore, methodological quality of the trials was generally low. While current evidence does not demonstrate a significant effect of n-3 FA supplementation on global cognition, future research should prioritize well-powered, longer-duration RCTs that incorporate biomarker monitoring and more appropriate doses. Clarifying the role of n-3 FA in cognitive aging remains essential for informing nutrition-based dementia prevention strategies.

Clinical and Translational Neuroscience doi: 10.3390/ctn9030033

Authors: Juan C. Lopez-Alvarenga Jesus D. Melgarejo Jesus Rivera-Sanchez Lorena Velazquez-Alvarez Isabel Omaña-Guzmán Carlos Curtis-Lopez Rosa V. Pirela Luis J. Mena John Blangero Jose E. Cavazos Michael C. Mahaney Joseph D. Terwilliger Joseph H. Lee Gladys E. Maestre

The quality of life (QoL) perception has been studied in neurological diseases; however, there is limited information linking brain morphological characteristics, QoL, and cognition. Human behavior and perception are associated with specific brain areas that interact through diffuse electrochemical networking. We used magnetic resonance imaging (MRI) to analyze the brain region volume (BRV) correlation with the scores of Rand’s 36-item Short Form Survey (SF-36) and cognitive domains (memory and dementia status). We analyzed data from 420 adult participants in the Maracaibo Aging Study (MAS). Principal component analysis with oblimin axis rotation was used to gather redundant information from brain parcels and SF-36 domains. Canonical correlation was used to analyze the relationships between SF-36 domains and BRV (adjusted for intracranial cavity), as well as sex, age, education, obesity, and hypertension. The average age (±SD) of subjects was 56 ± 11.5 years; 71% were female; 39% were obese; 12% had diabetes, 52% hypertension, and 7% dementia. No sex-related differences were found in memory and orientation scores, but women had lower QoL scores. The 1st and 2nd canonical correlation roots support the association of SF-36 domains (except social functioning and role emotional) and total brain volume, frontal lobe volume, frontal pole, lateral orbital lobe, cerebellar, and entorhinal areas. Other variables, including age, dementia, memory score, and systolic blood pressure, had a significant influence. The results of this study demonstrate significant correlations between BRV and SF-36 components, adjusted for covariates. The frontal lobe and insula were associated with the mental health component; the lateral-orbital frontal lobe and entorhinal area were correlated with the physical component.

Clinical and Translational Neuroscience doi: 10.3390/ctn9030032

Authors: Sachin Sharma Vibhuti Joshi Vivek Kumar

Adeno-associated virus (AAV) vectors have emerged as powerful tools for in vivo gene therapy, enabling long-term transgene expression in targeted tissues with minimal pathogenicity. This review examines the AAV serotypes used in clinical gene therapy trials for neurodegenerative (central nervous system, CNS) diseases, highlighting their tropisms, engineering advances, and translational progress. We discuss how capsid modifications, cell-specific promoters, and novel delivery routes are enhancing AAV tropism and reducing immunogenicity to overcome current limitations. Key clinical trials in neurodegenerative disorders (such as Parkinson’s, Alzheimer’s, and Huntington’s disease) are summarized, including delivery methods (intravenous, intracoronary, intrathecal, etc.) and outcomes. We further outline the regulatory landscape with recent approvals of AAV-based therapies and ongoing efforts to address safety challenges like immune responses and vector dose toxicity. A more translational, forward-looking perspective is adopted to consider combination therapies (e.g., AAV with immune modulation or genome editing) and strategic directions to improve the next generation of AAV vectors. Overall, continued innovation in AAV vector design and delivery, alongside careful clinical evaluation, is accelerating the translation of gene therapies for neurodegenerative diseases.

Clinical and Translational Neuroscience doi: 10.3390/ctn9030031

Authors: Merih C. Yilmaz Keramettin Aydin

Background: Arteriovenous malformations (AVMs) are rare vascular anomalies that can cause intracerebral hemorrhage, particularly in pediatric patients. Low-flow AVMs may not be visualized on initial non-invasive imaging modalities such as MR angiography. Methods: We report a 6-year-old boy who presented with intracerebral hemorrhage and initially had no detectable vascular anomaly on MR angiography and MR venography. Two years later, he was re-admitted with a recurrent hemorrhage. Repeating MR angiography again failed to reveal any vascular pathology. Results: Digital subtraction angiography (DSA) performed later identified a grade 3 low-flow AVM in the left posterior temporal region. The patient underwent successful endovascular treatment with no subsequent neurological deficits. Conclusions: This case underscores the limitations of MR angiography in detecting low-flow AVMs and highlights the essential role of DSA in the definitive diagnosis and management of unexplained intracerebral hemorrhages in pediatric patients.

Clinical and Translational Neuroscience doi: 10.3390/ctn9030030

Authors: Claudio Giorlandino Katia Margiotti Marco Fabiani Alvaro Mesoraca

This report presents two cases of pregnant women positive for folate receptor alpha (FRα) autoantibodies who received folinic acid supplementation. Both had previously given birth to children diagnosed with autism spectrum disorder (ASD). In subsequent pregnancies, folinic acid was administered preconceptionally and continually throughout gestation. The resulting offspring, monitored up to three years of age, exhibited typical neurodevelopment with no signs of ASD. These cases suggest that folinic acid supplementation during pregnancy may mitigate the risk of ASD in children born to mothers with FRα autoantibodies.

Clinical and Translational Neuroscience doi: 10.3390/ctn9030029

Authors: Bethany C. Fitzmaurice James Carroll Asius T. A. Rayen Nicola R. Heneghan Andrew A. Soundy

(1) Background: There has been a recent growth in evidence regarding the use, value and impact of photobiomodulation therapy for individuals with fibromyalgia. However, the nature of the evidence has, to the best of the authors’ knowledge, not been presented within a scoping review. The objective of this work is to reveal the nature of the evidence, gaps in the evidence, and a map of the evidence considering photobiomodulation therapy against established policy guidelines; (2) Methods: A scoping review was undertaken considering all academic research that has examined the experiences and impact of photobiomodulation therapy on individuals with fibromyalgia; (3) Results: Our results highlight that, indeed, there is plentiful data available to address a high proportion of the concerns portrayed by the National Institute for Healthcare and Excellence. Outcome measures are wide-ranging, albeit demonstrating heterogeneity, and the results are extremely promising; (4) Conclusion: Based on the current evidence, the United Kingdom’s ‘standard of care’ for fibromyalgia needs to be ascertained, and stringent cost-effectiveness data needs to be collected and presented to governing bodies with the aim of integrating recommendations into future healthcare guidelines.

Clinical and Translational Neuroscience doi: 10.3390/ctn9020027

Authors: Rini Souren Balz Ronald Winteler Nina Bischoff Oliver Fluri Johannes Grolimund Adrian Scutelnic Konrad Streitberger David Beckwée Christoph J. Schankin

Migraine is a common disabling primary headache disorder with significant personal and socio-economic impacts. A combination of medication and non-pharmacological therapies is essential for migraine management. Outpatient multidisciplinary headache therapy has not yet been evaluated in Switzerland. This study evaluates the effectiveness of the headache management program at Inselspital, Bern University Hospital, in improving headache-related disability in migraine patients. This open-label pilot study used prospectively assessed routine data from our headache registry. Participants aged 18 years or older with a diagnosis of migraine, confirmed by a headache specialist, were included. The program consisted of seven weekly sessions, each with a 50 min educational lecture and a 30 min progressive muscle relaxation (PMR) exercise. Primary outcomes were headache-related impact and disability, measured by the Headache Impact Test 6 (HIT-6) and Migraine Disability Assessment (MIDAS). Secondary outcomes included symptoms of anxiety, measured by the Generalized Anxiety Disorder 7-item scale (GAD-7), and symptoms of depression, assessed using the eight-item Patient Health Questionnaire depression scale (PHQ-8). Data were analysed using paired t-test and Wilcoxon signed rank tests. Significant improvements were observed in HIT-6 scores (pre-program: 65.2; post-program: 61.9; p = 0.012) and MIDAS scores (pre-program: 38; post-program: 27; p = 0.011), while PHQ-8 also showed a statistically significant reduction. Although the GAD-7 scores improved numerically, this change was not statistically significant. These findings suggest that the headache management program may reduce headache burden and disability; however, further research with larger samples is needed to confirm these preliminary results.

Clinical and Translational Neuroscience doi: 10.3390/ctn9020028

Authors: Helaina Lehrer Ankit Bansal Nicki Mohammadi Anmol Mittal John Liang Alexandra S. Reynolds

Aneurysmal subarachnoid hemorrhage (aSAH) has high morbidity and mortality in part due to vasospasm and delayed cerebral ischemia (DCI). This retrospective, single-center, case–control study evaluates the accuracy of an attention test, counting backwards from twenty to one (TTO), for detecting vasospasm and DCI in patients admitted to the ICU with aSAH over one year. The odds of symptomatic vasospasm and hospital outcomes were compared between the inattention and control groups. A subgroup analysis included accuracy tests comparing TTO to radiographic vasospasm. Of 44 subjects, 24 had inattention during their ICU course. Compared to controls, the inattention group had increased odds of vasospasm (OR 72 [7.6–677.7], p = 0.001), with significantly longer ICU (5.9 days) and hospital (6.6 days) lengths of stay, and higher odds of discharge to other healthcare facilities (OR 11.4 [2.8 to 46.8], p < 0.001). Errors on TTO testing had a specificity and sensitivity of 78%, and a positive predictive value (PPV) of 91%, for radiographic vasospasm, primarily in the anterior circulation. This study provides support for future prospective research to help elucidate the utility of TTO testing for monitoring and treatment of patients with aSAH.

Clinical and Translational Neuroscience doi: 10.3390/ctn9020026

Authors: Constantinos Koutsojannis Dionysia Chrysanthakopoulou

Evoked potentials (EPs), including somatosensory evoked potentials (SSEPs) and motor evoked potentials (MEPs), are used to assess neural conduction in spinal cord injury (SCI) and multiple sclerosis (MS), conditions marked by demyelination, inflammation, and axonal damage. Machine learning (ML), using data-driven algorithms, enhances EPs’ prognostic utility, but evidence synthesis is limited. This meta-analysis evaluated the predictive performance of EP-based ML models for SCI recovery (ASIA scale) and MS progression (EDSS) using a random-effects model. Five studies (n = 583) were included, extracting accuracy and area under the curve (AUC). Pooled results showed high predictive accuracy of 77.7% (95% CI, 75.1–80.3%; I² = 57%) and AUC 0.82 (95% CI, 0.79–0.85; I² = 55%). Stratified analyses by disease type (SCI vs. MS) or injury severity were not feasible due to the limited number of studies (n = 5). Sensitivity analysis excluding a rat model (N = 551) showed stable results (accuracy 76.9%; AUC 0.81). SSEP latency and MEP time series were key predictors, with amplitude critical in SCI and multimodal approaches enhancing performance. Moderate heterogeneity (I² = 55–57%) and limited studies constrain generalizability. This meta-analysis highlights EPs’ prognostic potential in ML-driven precision neurology, advocating for further human studies to validate multimodal approaches.

Clinical and Translational Neuroscience doi: 10.3390/ctn9020025

Authors: Tarek Jebrini Michael Ruzicka Hans Stubbe Kristina Adorjan

Despite the increasing evidence of neurocognitive impairment (NCI) in patients suffering from post-COVID-19 conditions (PCC), the interplay between patient-reported symptoms and objective findings remains poorly characterized. Valid diagnostic tests and sufficient treatment strategies are lacking. We conducted a narrative perspective synthesis of current findings of NCI, standardized assessments (e.g., MoCA, PCCIS), and their association with inflammatory parameters. We highlighted findings on the discrepancy of subjective versus objectively measured neurocognitive impairment. The “subjectivity-objectivity-gap” may contribute to patient stigmatization, impair therapy adherence and be associated with a suboptimal clinical outcome. Although established multimodal interventions, such as cognitive rehabilitation, psychoeducation, group therapy, and pharmacotherapy—show preliminary efficacy, adherence may be compromised when subjective experiences of NCI are invalidated. We summarized the current state of the literature regarding demographic and clinical risk factors such as advanced age, lower education, neuropsychiatric comorbidities and evidence on the possible underlying role of persistent neuroinflammation in NCI in PCC. This perspective emphasizes the need for evidence-based diagnostic algorithms that integrate both subjective and objective NCI, explicitly addressing the risk of stigmatization. Future research should focus on addressing the neurobiological basis of NCI, discrepant NCI findings and associated stigmatization, and incorporate these findings in clinical guidelines.

Clinical and Translational Neuroscience doi: 10.3390/ctn9020024

Authors: Nikolaos C. Zygouris Irini Dermitzaki Panayiotis Patrikelis Lambros Messinis Eugenia I. Toki

Exploring cognitive abilities is necessary in educational contexts, where such insights shape decisions about student placement and teaching methods. Traditionally, educational assessments have been leaned on academic performance to guide decisions related to grading and student placement. This study examines the relationships among specific neuropsychological measures, namely the Event Related Potentials (ERPs), P300 waveform, reaction time, and fluid intelligence in children. Raven’s Standard Progressive Matrices (RSPM) was utilized to assess intelligence levels. Based on their RSPM scores, participants were grouped into two categories: those with “high mental abilities” and those with “average mental abilities”. It was hypothesized that children with higher RSPM scores might display reduced P300 latencies and quicker reaction times, potentially reflecting greater neural efficiency. Electrophysiological data collected using ERPs, focusing on the P300 component. The results suggest a possible association between higher intelligence scores and shorter P300 latencies and quicker reaction times, which could support the concept of neural efficiency and the significance of cognitive speed in understanding intelligence. This investigation into the neuropsychological foundations of cognitive ability in children is in the same line with studies supporting how brain activity, connectivity, and processing efficiency vary. These differences could help develop educational strategies that are more tailored to individual cognitive processing styles.

Clinical and Translational Neuroscience doi: 10.3390/ctn9020023

Authors: Melike Y. Celik Selver Güler

Background/Objectives: Social media addiction has increased among adolescents, and this addiction has negatively affected their health. It is necessary to investigate how this addiction brings negative effects to adolescents. This study aimed to examine the relationship between social media addiction and sleepiness in adolescents. Methods: Personal information form, Social Media Addiction Scale for Adolescents (SMAS), and Cleveland Adolescent Sleepiness Questionnaire (CASQ) were used as data collection tools. Prerequisites (correlation, linearity, continuous variable, normal distribution) for regression analysis were tested. The study sample consisted of adolescents between the ages of 10–18. The data were analyzed in the SPSS program. Results: It was determined that 37.9% of the adolescents had sleep problems. The increase in the use of social media significantly affects sleepiness rates (r = 0.61, p < 0.05). The increase in social media use can explain 37.5% of the increase in sleepiness rates (R2 = 0.375). It was observed that a 1-unit increase in social media use would increase the sleepiness rate by 0.79 (B = 0.79). Conclusions: A significant relationship was found between adolescents’ social media addiction and sleepiness. Social media addiction was seen as a predictor of sleepiness in adolescents.

Clinical and Translational Neuroscience doi: 10.3390/ctn9020022

Authors: Cécile Barras Michael Amiguet Joëlle Schwarz Patrik Michel Carole Clair

Backround: The aim is to analyze whether sex and gender are associated with missed acute ischemic stroke (M-AIS). Methods: We performed a nested case-control study, using data collected from March 2003 to December 2020 from ASTRAL (Acute STroke Registry and Analysis of Lausanne). M-AIS were compared with a randomly selected control sample of acute ischmemic stroke (AIS). We extracted six gender-related socioeconomic variables. A gendered socioeconomic position (SEP) score was constructed reflecting the level of correspondence with feminine characteristics. Associations between M-AIS and the gender-related socioeconomic variables and the gendered SEP score were investigated using logistic regression. Results: Of the 6007 AIS, 182 (3%) were M-AIS. 80 (44%) were women. No association between administrative sex and M-AIS was found (OR 1.25, 95% CI 0.78–2.00). Differences were found for gender-related socioeconomic variables, women in the middle professional category had higher odds of an M-AIS compared to women in the lower professional category (OR 3.93, 95% CI 1.19–13.03). Men with higher education had lower odds of an M-AIS compared to men with lower education (OR 0.31, 95% CI 0.10–0.92). For women, a 20-unit increase in the gendered SEP score was associated with lower odds of an M-AIS (OR 0.66, 95% CI 0.46–0.94). For men, the same increase in the score tended to higher the odds of an M-AIS (OR 1.52, 95% CI 1.00–2.32). Conclusions: The interaction of administrative sex with gender-related socioeconomic variables revealed different associations with M-AIS for women and men. Correspondence to expected gender norms may have a protective effect against M-AIS.

Clinical and Translational Neuroscience doi: 10.3390/ctn9020021

Authors: Afaf El-Ansary Altaf Alabdali Abir Ben Bacha Mona Alonazi Laila Y. Al-Ayadhi

Background: Autism spectrum disorders (ASDs) comprise a neurodevelopmental disease marked by impaired social communication and repetitive activities. An imbalance between excitatory and inhibitory neurotransmitters, such as glutamate and GABA, may play a significant function in ASDs. The neurophysiological process behind epilepsy is abnormal neuronal excitatory firing in particular brain regions brought on by a lack of GABAergic inhibition. The study of GABAergic dysfunction could explain the substantial comorbidity with epilepsy or increased susceptibility to seizures observed in people with autism. Objective: This study analyzes molecular indicators directly and indirectly related to GABAergic inhibitory signaling in individuals with autism and healthy controls, with the purpose of uncovering probable diagnoses. Methods: The study included 46 male autistic participants and 26 age- and gender-matched healthy controls. Plasma levels of two chloride co-transporters (KCC2, NKCC1), and vitamin D3 were evaluated using ELISA. Results: Autistic individuals showed a significant drop in all three examined variables when compared to healthy controls. Statistical methods such as correlation, combined receiver operating characteristic (ROC) curve analysis, and multiple regression modeling were used to assess the diagnostic value and interrelationships of these biomarkers. A significant increase in the area under the curve was seen using the combined ROC curve analysis. The combined variables also exhibited significantly higher sensitivity and specificity as an index of high predictiveness values. Measurement of plasma levels of vitamin D status and chloride co-transporters (KCC2, NKCC1) in children with ASD may help to better understand how sleep disturbances and epilepsy as comorbidities of ASD linked to vitamin D deficiency and peculiar inhibitory/excitatory effects of GABA.

Clinical and Translational Neuroscience doi: 10.3390/ctn9020020

Authors: Andrea Seiler Jimin Park Flavio Frohlich

Stimulation-induced sensations including the perception of flickering lights (phosphenes) and scalp tingling are commonly reported in studies on transcranial alternating current stimulation (tACS). So far, these sensations have been considered benign side-effects of stimulation that may interfere with the blinding of participants in trials. It remains unknown what shapes the susceptibility to such side-effects. We hypothesized that cortical excitability predicts their intensity. Hence, we investigated the relationship between sensations during tACS and the motor threshold measured by transcranial magnetic stimulation (TMS). Nine healthy participants aged 50 and older underwent two tACS sessions at 21 Hz and 40 Hz as part of a cross-over pilot study. The stimulation amplitude was individualized to tolerability. Sensations were assessed post-session to calculate correlation with TMS-determined motor thresholds. Stimulation sensations (a flickering light and tingling scalp sensation) correlated with brain excitability as determined by the TMS motor threshold (r = −0.51, p = 0.03, N = 9). The findings suggest a relationship between the intensity of tACS-induced sensations and cortical excitability. Tailoring tACS intensity to individual tolerability and excitability thresholds may enhance the efficacy of tACS by ensuring a more consistent and effective dose relative to endogenous cortical excitability.

Clinical and Translational Neuroscience doi: 10.3390/ctn9010019

Authors: Majed Alluqmani

Multiple sclerosis (MS) is a chronic autoimmune-mediated neurodegenerative disease that affects young adults. The diagnosis of MS currently based on the McDonald criteria, which based on four core principles: the presence of a symptomatic demyelinating syndrome, an objective neurologic finding, the dissemination in space (DIS), and the dissemination in time (DIT). In addition, the diagnosis of MS relies on the exclusion of any alternative diagnosis. This may implicate the absence of systemic non-neurological symptoms and signs, such as rheumatological, cutaneous, or ophthalmological findings. Nevertheless, the non-neurological symptoms are commonly observed in patients with MS either at the onset of MS, which therefore can delay the diagnosis and the incrementation of a disease-modifying therapy, or during the course of the disease progression. The purpose of our review is to highlight non-neurological symptoms of MS that frequently go undiagnosed or mistakenly linked to other conditions, aiming for the more accurate and earlier diagnosis of MS.

Clinical and Translational Neuroscience doi: 10.3390/ctn9010018

Authors: Alice Accorroni Umberto Nencha Indrit Bègue

The study of brain disorders has long been central to both neurology and psychiatry, with these two disciplines evolving as distinct yet deeply interconnected fields. In fact, these specialties often share overlapping symptoms, neural pathways, and treatment modalities, making interdisciplinary collaboration essential. Despite this, such collaborations remain sparse, particularly in clinical settings, research, training, and policy development. The increasing global burden of brain disorders has induced a paradigm shift, emphasizing the need for cooperative efforts to preserve brain health. Effective interdisciplinary collaborations between neurology and psychiatry as well as with other partners involved in brain health and other medical specialties is crucial to improving patient outcomes and societal well-being. Furthermore, the development of comprehensive training programs in brain health is vital, aligning with the recent rise in brain medicine as a unified field. This article reviews the historical evolution of neurology and psychiatry, explores current synergies, and identifies areas for future collaboration, particularly in enhancing research, education, and shared preventative strategies. Ultimately, fostering interdisciplinary collaboration between neurology and psychiatry along with other medical specialties and relevant partners will be key to advancing brain health and addressing the global burden of brain disorders.

Clinical and Translational Neuroscience doi: 10.3390/ctn9010017

Authors: Samuel Tell Gurary Daniela LaGrange Daniele Botta Paolo Machi Isabel Wanke Felix Tobias Kurz Karl-Olof Lovblad

Acute ischemic stroke (AIS) remains a critical concern in clinical practice, with significant implications for patient outcomes and healthcare costs. This review highlights the role of clot composition in AIS, emphasizing the clinical relevance of radiological characterization. Variations in thrombus composition, such as red blood cell (RBC)-rich and white blood cell (WBC)-dominant clots, influence the success of thrombolytic therapies and mechanical thrombectomy. Advanced radiological techniques, including non-contrast CT, CT angiography, and MRI, are essential for pre-interventional clot characterization, guiding optimal treatment decisions. Integrating artificial intelligence (AI) in radiology can enhance the precision of clot composition assessment, facilitating personalized treatment approaches and improving predictive accuracy. By combining histopathological insights with imaging and AI technologies, this review underscores the importance of comprehensive radiological evaluation in the management of AIS, ultimately aiming to enhance clinical outcomes and reduce the burden on healthcare systems.

Clinical and Translational Neuroscience doi: 10.3390/ctn9010016

Authors: Lukasz Kolakowski Katarina Alexandra Ebner Athina Papadopoulou

Headache and facial pain syndromes are frequently observed in people with multiple sclerosis (MS), often affecting young adults during pivotal stages of their lives. These conditions can disrupt their ability to work, maintain relationships, and engage in daily activities, leading to significant socio-economic and personal challenges. This narrative review summarizes key epidemiological data and diagnostic insights into headache and facial pain disorders in people with MS. It addresses the complexities of diagnosing these overlapping conditions and highlights specific therapeutic considerations.

Clinical and Translational Neuroscience doi: 10.3390/ctn9010015

Authors: Livia G. Fregolente Lara Diem Jan D. Warncke Julia van der Meer Anina Schwarzwald Carolin Schäfer Helly Hammer Andrew Chan Robert Hoepner Claudio L. A. Bassetti

Sleep–wake disturbances are common in post-COVID-19 syndrome but lack extensive objective characterization. This study evaluated sleep–wake patterns in 31 patients with post-COVID-19 syndrome referred for fatigue and excessive daytime sleepiness (EDS). Assessments included questionnaires (the fatigue severity scale, the Epworth sleepiness scale, and the Beck Depression Index-II), video polysomnography (V-PSG), the multiple sleep latency test (MSLT, n = 15), and actigraphy (n = 29). Patients (70% female, mean age 45 years) had mostly mild acute SARS-CoV-2 infections and were assessed a median of 31 weeks post-infection. Fatigue (fatigue severity scale, median 6.33), sleepiness (the Epworth sleepiness scale, median 15), and depression (Beck depression inventory-II, median 20) scores were elevated. V-PSG showed moderate sleep apnea in 35.5%, increased arousal index in 77.4%, and median sleep stage percentages of NREM1 (12%), NREM2 (37%), NREM3 (19%), and REM (15.8%). MSLT revealed only 13.3% with sleep latencies under 8 min and no sleep-onset REM periods. Actigraphy indicated increased inactivity index in 96.6%, with high variability in time in bed. These findings highlight a polysomnographic and actigraphic profile of increased arousal and clinophilia, alongside moderate sleep apnea and limited objective sleepiness on MSLT. Addressing these multifactorial sleep disturbances is crucial in managing post-COVID-19 syndrome.

Clinical and Translational Neuroscience doi: 10.3390/ctn9010014

Authors: Gabriel Urreola Omar Ortuno Jose Castillo

Background: Chronic renal pain secondary to urological pathology can severely affect a patient’s quality of life. Utero Pelvic Junction Obstruction (UPJO) and Loin Pain Hematuria Syndrome (LPHS) are two conditions known to cause chronic renal pain that can be refractory to conventional treatments. Recent publications demonstrate neuromodulation as an effective treatment option for refractory renal pain. The purpose of this review is to (1) provide evidence from a patient case demonstrating the expanding clinical application of spinal cord stimulation (SCS) for refractory renal pain; (2) provide a review of the literature surrounding UPJO/LPHS and SCS; and (3) express a call to action to investigate the clinical applications of neuromodulation and SCS to treatment-resistant genitourinary pathologies. Methods: We performed a search across PubMed and Web of Science databases to search for patients with UPJO/LPHS who had chronic renal/flank pain and were treated with SCS. Results: In our review, we included five case reports/series (including our own) of eight patients who had chronic flank pain secondary to the genitourinary pathologies UPJO and LPHS. Some patients have been having renal pain for up to 20 years, with all patients experiencing significant or complete alleviation of pain after SCS despite multiple failed attempts with other modalities. Five patients had complete resolution of pain and four patients were able to discontinue their pain medications entirely. Conclusions: SCS is gaining traction in its versatility in the management of various chronic pathologies beyond just CNS conditions. Specifically, UPJO and LPHS are examples of urogenital conditions that may benefit from using SCS. Our case shows an exciting opportunity for managing clinical symptoms in patients who have these conditions but have not undergone surgery for many reasons. Our review and clinical report suggest more research is needed in the application of SCS to genitourinary conditions and those experiencing refractory chronic pain.

Clinical and Translational Neuroscience doi: 10.3390/ctn9010013

Authors: Sophie De Beukelaer Antonia Klein Christoph J. Schankin

Neurobehavioral signatures, such as cortical hyperexcitability, thalamo-cortical dysrhythmia, and pulvinar dysfunction, appear to drive the persistent visual misperceptions in Visual Snow Syndrome (VSS). We propose that heightened perceptual uncertainty and impaired metacognitive monitoring perpetuate these disturbances and formalize these processes within different frameworks (predictive coding, signal detection theory, and attentional control). By clarifying these mechanisms, we aim to inform targeted interventions that could address this currently untreatable condition.

Clinical and Translational Neuroscience doi: 10.3390/ctn9010012

Authors: Andreas R. Gantenbein Susanne Wegener Christoph J. Schankin Andreas K. Kleinschmidt

Migraine affects around one billion individuals worldwide, many in their working life, leading to significant personal and societal burdens. As modern working environments continue to change, so do the expectations of new generations of employees. The importance of creating migraine-friendly workspaces is becoming increasingly pressing. The Swiss Headache Society’s migraine-friendly workspace (MFWS) proposal aims to reduce direct and indirect costs associated with migraines in the workspace and provides practical recommendations and interventions for designing environments that promote employee well-being and productivity.

Clinical and Translational Neuroscience doi: 10.3390/ctn9010011

Authors: Valerio Massimo Magro Andrea Sorbino Nicola Manocchio Concetta Ljoka Calogero Foti

Background: Disorders of Consciousness (DoC) following acute brain injuries, such as intracerebral hemorrhage, present significant clinical challenges in intensive care and rehabilitation settings. Early multidisciplinary interventions, including physiatric care, are critical in optimizing recovery trajectories. However, evidence regarding the timing and intensity of rehabilitation interventions remains limited. This case report highlights the role of physiatrists in managing a critically ill patient with a DoC in an Intensive Care Unit (ICU), focusing on early rehabilitation strategies and individualized care planning. Case presentation: A 63-year-old male with a history of hypertension and cardiac disease presented with a left hemispheric hemorrhage and quadriventricular intraventricular hemorrhage. The patient was admitted to the ICU in a comatose state (Glasgow Coma Scale [GCS] 5). Initial physiatric evaluation revealed a critical condition precluding immediate initiation of an Individual Rehabilitation Project (IRP). Over subsequent weeks, clinical improvements were observed, including an increased GCS and Coma Recovery Scale-Revised (CRS-R) score. A tailored IRP was implemented, emphasizing passive mobilization to prevent complications such as muscle atrophy, joint contractures, and pressure ulcers. The patient demonstrated gradual progress, transitioning to a Minimally Conscious State (MCS) and achieving improved joint mobility and reduced peripheral edema. Discussion and Conclusions: This case underscores the pivotal role of physiatrists in ICU settings, particularly for patients with DoC. Early physiatric interventions, even in critically ill patients, can prevent secondary complications and facilitate functional recovery. Close collaboration with ICU teams and infectious disease specialists ensured the safe implementation of rehabilitation strategies despite the patient’s severe condition. The observed clinical improvements highlight the potential benefits of early mobilization and individualized care plans, both in terms of survival (quoad vitam) and quality of life (quoad valetudinem). This report emphasizes the need for further research to refine rehabilitation practices for patients with DoC, bridging gaps between acute care and neurorehabilitation.

Clinical and Translational Neuroscience doi: 10.3390/ctn9010010

Authors: Joseph P. Antonios Nana Adenu-Mensah Brianna C. Theriault Miguel Millares-Chavez Anita Huttner Mariam Aboian Veronica L. Chiang

Radiosurgery (SRS) is a primary treatment for intracranial metastatic disease, but it can lead to cerebral radiation necrosis (RN) in approximately 25% of cases. Unlike tumor progression (TP), which indicates a lack of response to treatment, RN suggests an effective SRS response. Differentiating RN from TP is challenging using standard radiological imaging, often necessitating surgical biopsy. This study investigates the utility of the central vein sign (CVS), a novel MRI biomarker associated with immune infiltrate-rich perivascular spaces, to differentiate RN from TP. Overall, our findings suggest that pre-SRS CVS could serve as a non-invasive marker to distinguish RN from TP, aiding in treatment decisions. Further research is needed to validate CVS as a predictive marker in larger patient cohorts and explore its potential in guiding cancer therapy response.

Clinical and Translational Neuroscience doi: 10.3390/ctn9010009

Authors: Alexander A. Tarnutzer Fausto Romano Nina Feddermann-Demont Urs Scheifele Marco Piccirelli Giovanni Bertolini Jürg Kesselring Dominik Straumann

Purpose: Accurate and precise navigation in space and postural stability rely on the central integration of multisensory input (vestibular, proprioceptive, visual), weighted according to its reliability, to continuously update the internal estimate of the direction of gravity. In this study, we examined both peripheral and central vestibular functions in a world-renowned 53-year-old male tightrope walker and investigated the extent to which his exceptional performance was reflected in our findings. Methods: Comprehensive assessments were conducted, including semicircular canal function tests (caloric irrigation, rotatory-chair testing, video head impulse testing of all six canals, dynamic visual acuity) and otolith function evaluations (subjective visual vertical, fundus photography, ocular/cervical vestibular-evoked myogenic potentials [oVEMPs/cVEMPs]). Additionally, static and dynamic posturography, as well as video-oculography (smooth-pursuit eye movements, saccades, nystagmus testing), were performed. The participant’s results were compared to established normative values. High-resolution diffusion tensor magnetic resonance imaging (DT-MRI) was utilized to assess motor tract integrity. Results: Semicircular canal testing revealed normal results except for a slightly reduced response to right-sided caloric irrigation (26% asymmetry ratio; cut-off = 25%). Otolith testing, however, showed marked asymmetry in oVEMP amplitudes, confirmed with two devices (37% and 53% weaker on the left side; cut-off = 30%). Bone-conducted cVEMP amplitudes were mildly reduced bilaterally. Posturography, video-oculography, and subjective visual vertical testing were all within normal ranges. Diffusion tensor MRI revealed no structural abnormalities correlating with the observed functional asymmetry. Conclusions: This professional tightrope walker’s exceptional balance skills contrast starkly with significant peripheral vestibular (otolithic) deficits, while MR imaging, including diffusion tensor imaging, remained normal. These findings highlight the critical role of central computational mechanisms in optimizing multisensory input signals and fully compensating for vestibular asymmetries in this unique case.

Clinical and Translational Neuroscience doi: 10.3390/ctn9010008

Authors: Patrick Stancu Duarte Janela Samuel Gurary Lukas Sveikata Frédéric Assal

Background: Dementia with Lewy bodies (DLBs) often presents with neuropsychiatric symptoms (NPSs), yet the role of hyperglycemia, a common cause of delirium in older adults, as a contributing factor remains under-recognized. This article aims to explore the relationship between hyperglycemia and NPSs. Methods: We report the case of a 71-year-old male with DLBs and type 2 diabetes mellitus (T2DM) who experienced worsening NPSs closely associated with periods of hyperglycemia. Initial pharmacological and nonpharmacological interventions were insufficient, prompting adjustments to insulin therapy and dietary modifications to stabilize blood glucose levels. Results: Improved glycemic control resulted in a clinically significant reduction in NPSs. Conclusions: This case suggests a potential link between hyperglycemia and NPSs in DLB patients, emphasizing the importance of maintaining glycemic control in managing NPSs. Although the exact mechanisms remain incompletely understood, adopting a holistic framework for brain health could offer a comprehensive approach to cognitive care. Further studies are needed to elucidate the biological pathways involved, validate these findings in larger populations, and develop evidence-based clinical guidelines.

Clinical and Translational Neuroscience doi: 10.3390/ctn9010007

Authors: Sean W. Mulvaney Sanjay Mahadevan Kyle J. Dineen Roosevelt Desronvilles Kristine L. Rae Olmsted

Posttraumatic stress disorder (PTSD) is a common neuropsychiatric condition with a complex etiology. Stellate Ganglion Block (SGB) is a novel but well-observed procedure for treating the disorder. However, the long-term durability of SGB has yet to be established. The primary objective of this study was to determine if performing ultrasound-guided, bilateral, two-level cervical sympathetic chain block (2LCSB) is associated with PTSD symptom improvement across six months. A secondary objective was to characterize treatment effects between trauma types. A retrospective chart review was conducted, and 75 patients meeting inclusion and exclusion criteria were identified. Posttraumatic stress disorder checklist for DSM-5 (PCL-5) scores were collected throughout a six-month period post-procedure. In addition, patients were asked to identify the category of trauma associated with their PTSD diagnosis. Nearly all (96%) patients showed significant improvement in their PCL-5 scores between the baseline and six months, with an average improvement of 55.48%. This is the first study to be conducted that examines the effects associated with SGB over a time period of greater than one month. Bilateral 2LCSB may provide durable PTSD symptom improvement for six months. However, additional research is necessary to establish causality.

Clinical and Translational Neuroscience doi: 10.3390/ctn9010006

Authors: Ahmed Abualhasan Guglielmo Pero Luca Quilici Mariangela Piano Luca Valvassori Khaled Sobh Ossama Mansour Ahmed Elbassiony Omar El-Serafy Edoardo Boccardi Foad Abd-Allah

Background: Intracranial stenting is still feasible, but its effectiveness is still investigational. Our study investigated outcomes of endovascular treatment in high-volume and low-volume centres. Methods: We retrospectively recruited 36 patients with intracranial atherosclerosis who underwent endovascular treatment from January 2014 to June 2016 at three low-volume centres (n = 18), and a single high-volume centre (n = 18). Detailed periprocedural records, as well as clinical and radiological follow-up data, were revised through at least one-year post-procedure. The outcome parameters included successful revascularization, occurrence of any death, stroke, and/or Transient Ischaemic Attack (TIA) after intervention or during the follow-up period, and restenosis (≥50%). Results: The successful revascularization rate was 97.2%. The 30-day rate of any death, stroke, and/or TIA was 13.9%. At a median clinical follow-up of 18 months, the rate of any death, stroke, and/or TIA was 27.8%. Rates of any death, stroke, and/or TIA at 30 days and 18 months were higher among patients treated in low-volume centres versus those treated in high-volume centres but without reaching statistical significance (22.2% versus 5.6%, p = 0.188; and 38.9% versus 16.7%, p = 0.137, respectively). Conclusions: Although not statistically significant, our study showed a higher incidence of death, stroke and/or TIA among patients treated in the low-volume centre compared to those treated in the high-volume centre.

Clinical and Translational Neuroscience doi: 10.3390/ctn9010005

Authors: Ahmed Abualhasan Shereen Fathi Hala Gabr Abeer Mahmoud Diana Khedr

(1) Background: Persistent post-COVID-19 headaches are emerging as a significant post-infection symptom. This study investigates the clinical characteristics of persistent post-COVID-19 headaches and the potential role of pro-inflammatory cytokines. (2) Methods: We conducted a pilot case–control study involving 84 participants divided into three groups: post-COVID with headache (n = 28), post-COVID without headache (n = 28), and healthy controls (n = 28). The detailed headache characteristics, including pain intensity, were assessed using the Visual Analog Scale (VAS). The serum levels of inflammatory cytokines (IL-6 and TNF-α) were measured. (3) Results: Post-COVID headaches predominantly presented as bilateral (53.6%) and throbbing (60.7%) in nature, with a median of 12 headache days per month and high pain intensity (median VAS score = 80). The associated symptoms were phonophobia (85.7%), fatigue (78.6%), and photophobia (75%). The serum levels of IL-6 and TNF-α were significantly higher in post-COVID headache patients than in the post-COVID without headache and healthy control groups (p < 0.001). A Receiver Operating Characteristic analysis showed that the circulating levels of IL-6 and TNF-α could discriminate our study groups at cutoffs with variable sensitivity and specificity. (4) Conclusions: Persistent post-COVID-19 headaches have diverse clinical characteristics and are associated with elevated circulating levels of pro-inflammatory cytokines, suggesting a potential underlying neuroinflammation.

Clinical and Translational Neuroscience doi: 10.3390/ctn9010004

Authors: Rasit Dinc Nurittin Ardic

Intracerebral hemorrhage (ICH) is a significant health problem with high mortality and morbidity rates, partly due to limited treatment options. Hematoma after ICH causes neurological deficits due to the mass effect. Hemorrhage catalyzes secondary damage, resulting in increased neurological damage, poor prognosis, and treatment problems. This review evaluates the role of immunotherapeutic approaches in ICH based on original full-text and review articles on the pathophysiology and immunotherapy of ICH, with emphasis on the modulation of microglia/macrophage polarization to the M2 subtype. In this review, we concluded that the pathophysiology of injury progression after ICH is complex and multifaceted. Inflammation plays a dominant role in secondary injuries. Furthermore, cells involved in the inflammatory process have dual roles in pro-inflammatory/destructive and anti-inflammatory/healing. While the role of inflammation in the pathophysiology makes the immune system a therapeutic target in ICH, the dual role of cells makes them a therapeutic target that can modulate anti-inflammatory/healing. Resident microglia (and even macrophages migrating from a peripheral source) are important therapeutic targets for modulation because of their role in the initiation phase and in shaping immunity. Although clinical results remain poor, experimental and clinical trial data seem promising for deciphering the pathophysiology of ICH and providing treatment options.

Clinical and Translational Neuroscience doi: 10.3390/ctn9010003

Authors: Adrian Scutelnic Isabelle Dominique Stöckli Antonia Klein Franz Riederer Nedelina Slavova Christoph J. Schankin

Introduction: Cortical spreading depression (CSD) is thought to be the pathophysiologic correlate of migraine aura. In experimental animals, CSD was shown to cause an increase in oxyhemoglobin. Susceptibility weighted imaging (SWI) on magnetic resonance imaging (MRI) depicts cerebral veins according to their concentration in oxyhemoglobin. The aim of this study was to assess whether the distribution of SWI changes in people with migraine aura resembles the clinical presentation, with a focus on topology. Methods: In this retrospective single-center study, patients were included if they (i) had acute focal neurological symptoms beginning with visual symptoms, (ii) underwent head MRI including SWI within eight hours of symptom onset, (iii) SWI showed focal dilated veins, and (iv) they had a discharge diagnosis of migraine with aura. Eleven predefined cerebral regions of interest (ROIs) were assessed for prominent focal veins (PFVs) on SWI. We determined whether symptoms correlated with the topography of ROIs with PFVs. Results: We found a posterior to anterior gradient of SWI changes during acute migraine aura when visual symptoms were present. Conclusion: MRI with SWI might be able to detect traces of CSD. The posterior to anterior distribution of areas with SWI changes corresponds anatomically to the canonical succession of symptoms in migraine aura.

Clinical and Translational Neuroscience doi: 10.3390/ctn9010002

Authors: Serra Aksoy Pritika Dasgupta

Background/Objectives: Brain tumors are among the severe and life-threatening conditions, with timely and accurate detection being crucial for determining the appropriate course of treatment. These tumors can vary widely in their aggressiveness, location, and type, making early diagnosis and precise classification essential for improving patient outcomes and survival rates. The complexity of brain tumors, combined with the detailed nature of MRI scans, presents significant challenges in the diagnostic process, underscoring the need for advanced tools to support clinicians in making informed decisions. New Method: This study focuses on developing and evaluating a proposed model for brain tumor classification using MRI images. The model employs a transfer learning approach fine-tuned to the brain tumor dataset, explicitly utilizing the EfficientNetB0 architecture. Results: The proposed model achieved an outstanding overall accuracy of 0.99, with precision, recall, and F1 scores exceeding 0.98 across all tumor classes. Comparison with Existing Methods: These results demonstrate the model’s potential as a reliable tool for assisting clinicians in diagnosing and classifying brain tumors. Conclusions: This is particularly valuable in the early stages of tumor development, where detection can be challenging, and early intervention is critical for successful treatment.

Clinical and Translational Neuroscience doi: 10.3390/ctn9010001

Authors: Karl-Olof Lövblad Isabel Wanke Daniele Botta Felix T. Kurz Roland Wiest Daniel Rüfenacht Luca Remonda

Neuroradiology, as a modern branch of the neurosciences and radiological sciences, has an impact on global health, particularly on brain health. On the one hand, neuroradiology directly impacts diseases of the nervous system, such as stroke and inflammatory diseases, by providing an all-in-one package combining imaging, diagnosis, treatment, and follow-up. This has been impacted by the continuous evolution over the last decades of both diagnostic and interventional tools in parallel: this was the case in stroke, where the endovascular treatment was followed closely by developments in fast MRI techniques and multi-slice CT imaging. Additionally, inflammatory diseases of the brain, as well as tumors of the central nervous system, can be imaged and localized in order to set in place both an early diagnosis and initiate treatment. Neurodegenerative diseases such as Alzheimer’s disease, in which treatment options are appearing on the horizon, also benefit from the use of modern neuroimaging techniques. On the other hand, neuroradiology plays an important role in the prevention and prediction of brain diseases and helps in building up the so-called digital twin, often from birth till late in life. Additionally, the practice of neuroradiology itself is evolving to not only improve patient health but also the health of the practitioners of neuroradiology themselves. By improving the overall work environment also, neuroradiologists will be working under better conditions and will suffer less fatigue and burn-out, thereby providing better service to patients and population. By using less radiation for diagnostic tests and shifting to techniques that rely more and more on either magnetic resonance or ultra-sound techniques, the radiation load on the population and on the neuroradiologists will decrease. Furthermore, using less contrast, such as gadolinium, has been shown to result in fewer deposits in the brains of patients, as well as less pollution at the ocean level, thus contributing to general well-being. Additionally, the implementation and use of artificial intelligence at many levels of the diagnostic and treatment chain will be beneficial to patients and physicians. In this paper, we discuss the place and potential not just of the techniques but of neuroradiology and the neuroradiologist as promoters of brain health and thus global health.

Clinical and Translational Neuroscience doi: 10.3390/ctn8040031

Authors: Emilia Westarp Tim Jonas Hallenberger Karl-Olof Lövblad Thomas Mokrusch Claudio Bassetti Raphael Guzman

Background: Traumatic brain injury (TBI) is referred to as a “silent epidemic” due to its limited awareness in the general public. Nevertheless, it can cause chronic, lifelong physical and cognitive impairments with severe impact on quality of life, resulting in high healthcare costs and loss of employment. To evaluate the outcome after mild and moderate TBI, “return to work (RTW)” is a relevant parameter, reflecting the socio-economic consequences of TBI. Our study aims to summarize RTW-rates to raise awareness on the impact of non-severe TBI. Methods: We performed a systematic literature review screening the databases Medline, Embase and Web of Science for studies reporting RTW in mild to moderate TBI. Studies that reported on RTW after mild or moderate TBI (defined by GCS > 9) in adults, with a minimum follow-up of six months were included. Risk of bias was assessed using the QUIPS tool. Results: We included 13 studies with a total 22,550 patients. The overall RTW rate after at least six months, varies between 37% and 98%. Full RTW is reported in six of the included 13 studies and varies between 12% and 67%. In six studies (46%) the RTW-rate by the end of follow-up was ≤60%, with four studies being from high-income countries. Conclusion: Mild and moderate TBI have a high impact on employment rates with diverging rates for RTW even between high-income countries. Increasing the societal awareness of this silent epidemic is of utmost importance and is one of the missions of the Swiss Brain Health Plan.

Clinical and Translational Neuroscience doi: 10.3390/ctn8040030

Authors: Sebastian Finkener Arkady Ovchinnikov Ronald Bauer Michael Diepers Markus Gschwind

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) is a rare mitochondrial disorder primarily presenting in pediatric patients, with onset after 40 years being exceptionally rare (1–6%). Here, we report a complex diagnostic journey of a 47-year-old male presenting with new-onset seizures, hemiparesis, and neurocognitive deficits. Initial work-up, including MRI, CSF analysis, and extensive antibody screening, yielded inconclusive results, prompting differential considerations such as autoimmune encephalitis and neoplastic conditions. Finally muscle biopsy findings, coupled with genetic confirmation of the m.3243A>G mutation in the MT-TL1 gene, ultimately established the diagnosis of MELAS. This case depicts the atypical presentation of adult-onset MELAS without initial lactic acidemia, diabetes, or hearing impairment. The prolonged diagnostic process underscores the challenges of identifying rare diseases under today’s financial and administrative constraints. Still ee emphasize the importance of comprehensive diagnostics in rare cases to advance generall understanding and improve future patient outcomes, also amidst resource limitations.

Clinical and Translational Neuroscience doi: 10.3390/ctn8040029

Authors: Evgenii Nuzhnyi Natalia Abramycheva Arina Protsenko Alexandra Belyakova-Bodina Ekaterina Larina Ekaterina Fedotova Sergey Klyushnikov Sergey Illarioshkin

An intronic GAA repeat expansion in the FGF14 gene was recently identified as a common cause of autosomal dominant GAA-FGF14 ataxia (SCA27B). We aimed to characterize in detail the clinical and video-oculographic features in our cohort of SCA27B patients. We genotyped the FGF14 GAA repeat expansion in 52 patients with unsolved late-onset cerebellar ataxia. Brain MRI and nerve conduction study, as well as video-oculographic (VOG) assessment, were performed. Eight patients (15.4%) with pathogenic GAA repeat expansion in the FGF14 gene were found. The median age at onset was 51 years (range—23–63 years). Sensory axonal neuropathy was found in 5/8 patients. Cerebellar atrophy was observed in 5/8 patients, and in one case, pontocerebellar atrophy was found. All tested patients had impaired smooth pursuit, 5/6 patients had impaired vestibulo-ocular reflex suppression, nystagmus, and an increased number of square wave jerks, 4/6 patients had horizontal gaze-evoked nystagmus, 3/6 had spontaneous downbeat nystagmus, and 1/6 had an upbeat one. Video head impulse test gain was lower than 0.8 on both sides in 2/4 patients, along with the presence of overt saccades. Further studies in different cohorts are needed to complete the phenotype of the FGF14-related disorders.

Clinical and Translational Neuroscience doi: 10.3390/ctn8040028

Authors: Roaa Alsharif Salsabil Abo Al-Azayem Nimah Alsomali Wjoud Alsaeed Nawal Alshammari Abdulaziz Alwatban Yaseen Alrabae Razan Orfali Faisal Alqarni Ahmad Alrasheedi

The Glasgow Coma Scale (GCS) is essential for assessing traumatic brain injury and predicting patient outcomes, yet studies indicate that nurses often have only a basic understanding of the GCS. In Saudi Arabia, research on this topic is limited, suggesting a need for improvement in nurses’ GCS knowledge. This study aimed to evaluate the knowledge and proficiency of 199 staff nurses at King Fahd Medical City in Riyadh, Saudi Arabia, regarding GCS usage and to identify the factors impacting their competence. A descriptive, cross-sectional survey was conducted, and the data were analyzed using SPSS version 23.0. The results showed that 81.4% of nurses had an average level of GCS knowledge, with a mean score of 8.8 ± 1.826. Only 13.6% demonstrated good knowledge, while 5% had poor knowledge. A significant correlation was found between GCS knowledge and nurses’ departments (χ2(2) = 19.184, p < 0.001). The study concludes that GCS knowledge among nurses in this Saudi Arabian center is moderate, highlighting the need for continuous education programs to enhance their competence in GCS assessment.

Clinical and Translational Neuroscience doi: 10.3390/ctn8030027

Authors: Keith J. Yoder Geoffrey Brookshire Ryan M. Glatt David A. Merrill Spencer Gerrol Colin Quirk Ché Lucero

Across many resting-state electroencephalography (EEG) studies, dementia is associated with changes to the power spectrum and fractal dimension. Here, we describe a novel method to examine changes in the fractal dimension over time and within frequency bands. This method, which we call fractal dimension distributions (FDD), combines spectral and complexity information. In this study, we illustrate this new method by applying it to resting-state EEG data recorded from patients with subjective cognitive impairment (SCI) or dementia. We compared the performance of FDD with the performance of standard fractal dimension metrics (Higuchi and Katz FD). FDD revealed larger group differences detectable at greater numbers of EEG recording sites. Moreover, linear models using FDD features had lower AIC and higher R2 than models using standard full time-course measures of the fractal dimension. FDD metrics also outperformed the full time-course metrics when comparing SCI with a subset of dementia patients diagnosed with Alzheimer’s disease. FDD offers unique information beyond traditional full time-course fractal analyses and may help to identify dementia caused by Alzheimer’s disease and dementia from other causes.

Clinical and Translational Neuroscience doi: 10.3390/ctn8030026

Authors: Michael Graber Alice Panchaud Helene Legardeur Tobias Derfuss Christoph Friedli Claudio Gobbi Chiara Zecca Cristina Granziera Ilijas Jelcic Helly Noemi Hammer Sandra Bigi Lara Diem Nicole Kamber Veronika Kana Jens Kuhle Stefanie Müller Anke Salmen Robert Hoepner Philipp Do Canto Marie Théaudin Daniel Surbek Caroline Pot Andrew Chan

A large number of disease-modifying immunotherapies are available for the treatment of people with multiple sclerosis. Many disease-modifying immunotherapies show scarce or no safety data in pregnancy and breastfeeding and are labeled as being contraindicated during these periods in the Swiss summary of product characteristics. Some disease-modifying immunotherapies also have restrictions for male patients. Hence, family planning should always be considered in treatment decisions. If clinically necessary, the continuation of immunotherapy during pregnancy can be considered for some substances. In these situations, the “Good Off-Label Use Practice”, careful consideration of the benefit–risk profile, and interprofessional cooperation between the treating neurologist, obstetrician–gynecologist, and pharmacist/pharmacologist, ideally with the involvement of experienced centers, is necessary. Here, we present an update on disease-modifying immunotherapies in multiple sclerosis with a focus on family planning, pregnancy, and breastfeeding and provide consensus recommendations of the Medico-Scientific Advisory Board of the Swiss Multiple Sclerosis Society, the Swiss Neurological Society, and the Swiss Society for Gynecology and Obstetrics (represented by the Academy of Fetomaternal Medicine). These unified national recommendations are necessary, as guidelines from other countries differ and because of separate approval/reimbursement situations in Switzerland.

Clinical and Translational Neuroscience doi: 10.3390/ctn8030025

Authors: Valentina Baldini Francesco Biscarini Giorgia Varallo Fabio Pizza Giuseppe Plazzi

Narcolepsy is a chronic central disorder of hypersomnolence most frequently arising during childhood/adolescence. This review article examined the literature concerning the etiology, prevalence, clinical course, and treatment of children with type 1 narcolepsy (NT1). Core symptoms of pediatric NT1 include excessive daytime sleepiness (EDS) and cataplexy, together with disrupted night sleep, sleep paralysis, and hypnagogic and hypnopompic hallucinations that can also occur. This disease frequently presents several comorbidities, such as obesity and precocious puberty, conditions ranging from psychological distress to psychiatric disorders, and cognitive aspects that further worsen the clinical picture. NT1 impairs the quality of life of children, thus calling for an early diagnosis and adequate treatment. To date, pharmacological treatments have been registered for childhood NT1 and can improve symptoms. Non-pharmacological approaches are also essential to improve patients’ well-being, ranging from behavioral treatments (e.g., planned napping) to psychosocial interventions (e.g., school programs). Multidisciplinary treatment management and early diagnosis are key factors in order to allow for adequate quality of life and development in children with NT1.

Clinical and Translational Neuroscience doi: 10.3390/ctn8020024

Authors: Swiss Society of Neurosurgery (SSNS) Swiss Society of Neurosurgery (SSNS) Swiss Society of Neuroradiology (SSNR) Swiss Society of Neuroradiology (SSNR)

Main Topic: Artificial Intelligence and Digitalization: Applications to Neurosurgery and Neuroradiology. On behalf of the SSNS and SSNR, we are pleased to present the Abstracts of the Joint Annual Meeting, which is held at the Congress Kursaal Interlaken, Switzerland, 20–21 June 2024. In total, 62 abstracts were selected, of which 19 abstracts are oral presentations and 43 abstracts are for ePoster. We congratulate all the presenters on their research work and contribution.

Clinical and Translational Neuroscience doi: 10.3390/ctn8020023

Authors: Luigi Ferini-Strambi Maria Salsone

Robust evidence suggests that the glymphatic system plays a key role in preserving brain health. Indeed, its activity in maintaining homeostasis by clearing neurotoxic proteins such as beta-amyloid from the human brain is essential. Sleep represents the factor that mainly influences this system, since it is selectively active during the night, in particular during non-rapid eye movement (NREM) sleep. This is true, since the sleep head position, in particular the supine position for its relationship to the status of opening/closing of the jugular veins, appears to be determinant for the development of future neurodegeneration. Growing evidence from human and animal models highlights the neurobiological link between sleep, glymphatic dysfunction and neurodegeneration. On the other hand, several modifiable factors have been recently identified modulating (improve/reduce) glymphatic system activity, such as Omega-3 polyunsaturated fatty acids, stress, hypertension, physical activity, alcohol, gender and genetic predisposition, in particular variants of aquaporin-4 (AQP4). From this viewpoint, our ambition is to discuss how the glymphatic system works in the brain, what factors mainly impact on this activity and its strict relation with the neurodegeneration. Future directions might include the analysis of factors modulating glymphatic system activity and a personalized glymphatic profile, “glymphatom”, as a natural target for preventive neurodegenerative treatment.

Clinical and Translational Neuroscience doi: 10.3390/ctn8020022

Authors: Swiss Neurological Society (SNS) Swiss Neurological Society (SNS)

On behalf of the SNS, we are pleased to present the Abstracts of the Annual Meeting which is held at the Congress Center in Basel, Switzerland, from 6–7 June 2024. In total, 83 abstracts were selected, whereof we include 8 abstracts for the Plenary Sessions, 6 abstracts for the SAYN GemSession, 30 abstracts for Poster flash presentations, and 39 abstracts as ePosters. We congratulate all the presenters on their research work and contributions.

Clinical and Translational Neuroscience doi: 10.3390/ctn8020021

Authors: Nicolas Deperrois Mihai Petrovici Jakob Jordan Lukas Huber Walter Senn

The importance of sleep for healthy brain function is widely acknowledged. However, it remains unclear how the internal generation of dreams might facilitate cognitive processes. In this perspective, we review a computational approach inspired by artificial intelligence that proposes a framework for how dreams occurring during rapid-eye-movement (REM) sleep can contribute to learning and creativity. In this framework, REM dreams are characterized by an adversarial process that, against the dream reality, tells a discriminator network to classify the internally created sensory activity as real. Such an adversarial dreaming process is shown to facilitate the emergence of real-world semantic representations in higher cortical areas. We further discuss the potential contributions of adversarial dreaming beyond learning, such as balancing fantastic and realistic dream elements and facilitating the occurrence of creative insights. We characterize non-REM (NREM) dreams, where a single hippocampal memory is replayed at a time, as serving the complementary role of improving the robustness of cortical representations to environmental perturbations. We finally explain how subjects can become aware of the adversarial REM dreams, but less of the NREM dreams, and how content- and state-awareness in wake, dream, and lucid dreaming may appear.

Clinical and Translational Neuroscience doi: 10.3390/ctn8020020

Authors: Riccardo Bortoletto Marta Basaldella Anna Candolo Marco Garzitto Carla Comacchio Francesco Curcio Martina Fabris Stefano Fornasaro Fabiana Piscitelli Orietta Sepulcri Matteo Balestrieri Marco Colizzi

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by impaired social communication and restricted or repetitive behavior and interests. Psychic distress is common among individuals with ASD, especially in its milder form (level 1), with anxiety and depression being the most common types. Recent research has identified neuroinflammation and gut dysbiosis as potential neurobiological mechanisms underlying ASD. Palmitoylethanolamide (PEA), an endocannabinoid (eCB)-like compound, has shown promise in modulating such mechanisms and may thus have therapeutic implications for ASD. To date, no clinical trial has evaluated the efficacy of PEA in adults with ASD. This 12-week open-label study will assess the feasibility, tolerability, safety, and efficacy of ultramicronized PEA (um-PEA) in treating symptoms of psychic distress, such as anxiety and depression, in adults with level 1 ASD. Secondary research endpoints will include um-PEA’s effects on levels of personal autonomy and neurocognitive and interpersonal function. From a biological point of view, this study will assess um-PEA’s effects on inflammatory markers, the metabolic profile, eCB system modulation, and microbial composition as potential mechanisms of action for its therapeutic effect. In conclusion, this study will investigate a novel approach to the treatment of adults presenting with psychic distress in the context of level 1 ASD. The results may provide valuable insight into the use of um-PEA as a treatment option for ASD adults, addressing a significant unmet clinical need.

Clinical and Translational Neuroscience doi: 10.3390/ctn8020019

Authors: Claudio L. A. Bassetti Felicitas Sohm Antoine Adamantidis Kaspar Schindler Fabrizio Barazzoni Mauro Manconi

Introduction: Sleep–wake circadian disorders (SWCDs) are very frequent and linked to major negative effects on the body, mental health, the brain, and on occupational and societal health. The prevention, diagnosis, and treatment of SWCDs and the promotion of sleep health require the sufficient education of general practitioners, specialists, and other health professionals. Unfortunately, education at pre- and postgraduate level is insufficient in most countries across the world. Aims and methods: This article describes the historical context, basic considerations, and methodological approach for the creation of the International Postgraduate Sleep Master by the University of Bern and Svizzera Italiana. Results: The postgraduate Master, which was launched in 2017, is a part-time, flexible course, taken over 2 ½ years, which targets health professionals, scientists, and technicians. After an initial introduction, which is the same for everybody (“common trunk”), the course can be individualized. The 12 modules of the Master include online lectures, schools, internships in a sleep center (in one of our 15 partner universities), case discussions and interactive sessions with students and internationally recognized experts from over 20 countries across the world, and culminates with a Master thesis. The program covers sleep–wake circadian biology; the management of SWCDs; disturbances of consciousness and sleep-related epilepsies; novel approaches in sleep medicine (e.g., clinical trials, telemedicine, data science, artificial intelligence); and topics of increasing relevance (e.g., neurodegenerative disorders, gender and diversity, sleep health, new technologies, artificial intelligence, professional and societal implications). Students are encouraged to also take “crash courses” in preparation for the national, European, and World sleep examinations. Conclusion: The Postgraduate University Sleep Master of the Universities of Bern and Svizzera Italiana offers a unique part-time, (mainly) virtual opportunity to acquire state-of the art knowledge, skills, and professional experiences to prepare for a clinical or scientific career in sleep medicine for physicians, scientists, and other health professionals.

Clinical and Translational Neuroscience doi: 10.3390/ctn8020018

Authors: Valentin K. Steinsiepe Hakan Sarikaya Pasquale R. Mordasini Susanne Wegener Corinne Inauen Philipp Baumgartner Simon Jung Kateryna Antonenko Urs Fischer Jan Gralla Roza M. Umarova Barbara Goeggel Simonetti Constance J. H. C. M. van Laarhoven Gert J. de Borst Hugues Chabriat Mirjam R. Heldner Marcel Arnold

Dissecting aneurysms in patients with spontaneous cervical artery dissections have, so far, been reported as “benign”, but more specific information is scarce. We aimed to elucidate (1) vascular risk factors, (2) local and ischemic symptoms, and (3) long-term prognosis compared to non-aneurysmal dissections. This case–control study included consecutive patients with spontaneous cervical artery dissection from three university hospitals in Switzerland and France, evaluated at baseline and at 3 months. In addition, further follow-ups were performed at the discretion of the treating physician. Dissecting aneurysms were diagnosed with duplex sonography, magnetic resonance angiography, and/or digital subtraction angiography. Of 1012 patients, 151 (14.9%) presented with 167 dissecting aneurysms at baseline (n = 103) or follow-up (n = 64). The median follow-up was 24.9 months (IQR: 6.8–60.8). Compared to patients without a dissecting aneurysm there were no significant differences in the vascular risk factors or local symptoms (91.4 vs. 89.8%). Ischemic strokes at baseline were less common (29.1% vs. 54.4%; OR: 0.41; 95% CI: 0.28–0.60) in patients with a dissecting aneurysm, even after correction for the degree of stenosis of the dissected arteries (OR: 0.53; 95% CI: 0.34–0.81). Patients with a dissecting aneurysm more often had a favorable clinical outcome (modified Rankin Scale Score of 0–1) at 3 months (80.6% vs. 54.5%). There was no significant difference in recurrent cerebrovascular events at 3 months or overall. The lower rate of ischemic strokes at baseline may reflect a different pathogenic mechanism, such as a smaller initial tear in the vessel wall or an increased vessel caliber from an early or primary intramural hematoma with a different shape.

Clinical and Translational Neuroscience doi: 10.3390/ctn8020017

Authors: Fabrizio Giammello Antonio Ciacciarelli Domenico Cosenza Santi Galletta Valeria Barresi Paolino La Spina Maria Carolina Fazio Jolanda De Caro Masina Cotroneo Cristina Dell’Aera Francesco Grillo Serena Ammendola Agostino Tessitore Sergio Lucio Vinci Rosa Fortunata Musolino Carmela Casella Antonio Toscano

Background: In atherothrombotic acute ischemic stroke (AIS), when the atheroma breaks down, the clot can incorporate foam cells (FCs). The identification of the correct etiology is paramount for secondary stroke prevention. This study aims to evaluate the presence of the FC in the arterial clot, and to determine whether patients with FCs and patients without FCs (NFCs) had different cerebrovascular risk factors, haemato-chemical parameters, and atherosclerotic disease incidence, in order to predict the etiological diagnosis. Methods: We collected 100 clots retrieved by mechanical thrombectomy from 495 consecutive AIS patients with large vessel occlusion. An expert pathologist evaluated the FC presence by histological examination stained with hematoxylin and eosin. Results: We observed FCs in 29/100 (29%) of retrieved clots and divided the patients into two groups, with/without FCs. The two groups had similar clinical and laboratory features, with a discrepancy between the FC presence in the clot and the clinical etiological diagnosis, even if not statistically significant. Conclusions: Our study showed the presence of FCs in approximately one-third of the retrieved clots, but the identification of the clot that presumably comes from the atheromatous plaque rupture tended to disagree with the clinical diagnosis. Future studies may reveal their potential to disclose clot origin or specific patient characteristics, guiding treatment options.

Clinical and Translational Neuroscience doi: 10.3390/ctn8020016

Authors: Elisa Colaizzo Luca Prosperini Antonio Petrucci Alessia Perna

Several recent studies reported on some patients developing Creutzfeldt–Jakob disease (CJD) following coronavirus disease 2019, but, to the best of our knowledge, this case is the first reported in Italy on an onset of a CJD genetic form (gCJD) immediately after COVID-19 infection. We present a 51-year-old woman with a positive family history for CJD, who, two months after a mild SARS-CoV-2 infection, presented a rapidly progressing dementia diagnosed as CJD through clinical features, imaging, electroencephalography, and cerebrospinal fluid analysis. Genetic testing revealed the E200K mutation (p.Glu200Lys) c.598G>A, with homozygosity for methionine (MET) at codon 129, thus confirming the diagnosis of Creutzfeldt–Jakob disease. She passed away two months later. Interestingly, our case confirms that homozygous E200K gCJD patients are characterized by a relatively younger age of onset; moreover, it also sheds light on the neurodegeneration underlying both prion diseases and COVID-19 infection. In our opinion, the rising global prevalence of neurodegenerative complications following COVID-19 disease adds urgency to the study of this potential relationship, mostly in elderly patients who may experience worse long-lasting outcomes systemically and within the nervous system.

Clinical and Translational Neuroscience doi: 10.3390/ctn8010015

Authors: Papitha Saravanamuthu Susanne Wegener Heiko Pohl

Many patients with cluster headaches report that their relatives do not understand what they are going through. This qualitative study aimed to collect patients’ recommendations and wishes on how others should respond to those suffering from cluster headaches. We recruited 22 patients with episodic or chronic cluster headaches for this cross-sectional study. They responded to seven questions that assessed the disease’s impact on their relationships with relatives and their wishes for others’ behaviour towards them. Seven recommendations for relatives emerged: (i) withdraw during attacks, (ii) respect post-ictal exhaustion, (iii) do not insist on discussing the disorder, (iv) help the patient to lead a “normal” life, (v) support preserving social contacts, (vi) show being aware of the disease severity, and (vii) expect the disease to take up space in patients’ lives and minds. Two recommendations for the interictal period indicate avoidance, which is considered a negative coping strategy. Conversely, the suggestion to support preserving social contacts might mean confronting the disease, which is likely associated with more favourable outcomes. Still, adhering to all patients’ requests might increase suffering instead of reducing it. Thus, further research is needed to develop strategies suited to improve well-being.

Clinical and Translational Neuroscience doi: 10.3390/ctn8010014

Authors: Simone B. Duss Albrecht P. A. Vorster Antoine Urech Wolfgang J. Schmitt Jonas Beck Daniella Hilt Oriella Gnarra Julia van der Meer Marina Tüzün Thomas Berger Carolin Schäfer Anne-Kathrin Brill Markus H. Schmidt Kaspar A. Schindler Claudio L. A. Bassetti

Sleep is essential for health, well-being, creativity, and productivity. Sleep loss and sleep–wake circadian disorders (SWCDs) affect at least one in three individuals but are underdiagnosed and undertreated for different reasons: First, the importance of sleep health and, second, the burden of sleep loss and SWCDs are underestimated. Third, education in sleep medicine is insufficient and health care-related sleep research is underdeveloped. Fourth, the validation and implementation of tele-sleep medicine approaches and novel devices to monitor SWCDs are still insufficient. Fifth, the reimbursement of sleep medicine in most countries is inadequate and the availability of specialized care is limited to a few centers. The Swiss Sleep House Bern (SSHB) was founded in 2022 to address these challenges and eventually promote better care for patients with SWCDs and improve sleep health for the broader population. The interdisciplinary and interprofessional team of the SSHB, which is integrated in the Bernese Interdisciplinary Sleep-Wake-Epilepsy Center, links sleep specialists with primary care providers to offer a rapid and accessible triage and first-level management of sleep complaints and SWCDs. The SSHB also promotes awareness and offers educational programs on sleep health and SWCDs, performs health care research, and fosters the implementation of new technologies, data science, and telemedicine into clinical routine.

Clinical and Translational Neuroscience doi: 10.3390/ctn8010013

Authors: Pinar Göktepe-Kavis Florence M. Aellen Sigurd L. Alnes Athina Tzovara

The field of sleep research is both broad and rapidly evolving. It spans from the diagnosis of sleep-related disorders to investigations of how sleep supports memory consolidation. The study of sleep includes a variety of approaches, starting with the sole focus on the visual interpretation of polysomnography characteristics and extending to the emergent use of advanced signal processing tools. Insights gained using artificial intelligence (AI) are rapidly reshaping the understanding of sleep-related disorders, enabling new approaches to basic neuroscientific studies. In this opinion article, we explore the emergent role of AI in sleep research, along two different axes: one clinical and one fundamental. In clinical research, we emphasize the use of AI for automated sleep scoring, diagnosing sleep-wake disorders and assessing measurements from wearable devices. In fundamental research, we highlight the use of AI to better understand the functional role of sleep in consolidating memories. While AI is likely to facilitate new advances in the field of sleep research, we also address challenges, such as bridging the gap between AI innovation and the clinic and mitigating inherent biases in AI models. AI has already contributed to major advances in the field of sleep research, and mindful deployment has the potential to enable further progress in the understanding of the neuropsychological benefits and functions of sleep.

Clinical and Translational Neuroscience doi: 10.3390/ctn8010012

Authors: Raffaele Ferri

The burden of sleep disorders is a global health concern that affects millions of people worldwide [...]

Clinical and Translational Neuroscience doi: 10.3390/ctn8010011

Authors: Abubaker Ibrahim Birgit Högl Ambra Stefani

Recently, it has become increasingly clear that there is a bidirectional relationship between sleep/circadian rhythms and neurodegeneration. Knowledge about this topic further improved after the description of the glymphatic system, which is mainly active during sleep. Changes in sleep and circadian rhythms are present not only in overt neurodegenerative diseases but also in their early, prodromal, and preclinical phases, supporting that they precede (and contribute to) the development of neurodegeneration. This narrative review provides a brief overview of sleep and circadian rhythm disruption in neurodegeneration, highlights the bidirectional relationship between sleep changes and neurodegeneration, and addresses future perspectives, in particular, whether sleep changes are able to predict neurodegeneration and the potential sleep actionability to prevent or modulate the development of neurodegenerative diseases.

Clinical and Translational Neuroscience doi: 10.3390/ctn8010010

Authors: Dieter Riemann Raphael J. Dressle Kai Spiegelhalder

The last ten years have seen the development and publication of numerous national and international guidelines devoted to the diagnosis and treatment of insomnia. These include guidelines by the American College of Physicians (ACP), the American Academy of Sleep Medicine (AASM), the British Sleep Society (BSS), the German Sleep Society (GSS), and the European Sleep Research Society (ESRS). Though coming from very diverse authors and backgrounds, these guidelines by and large agree concerning the therapeutic recommendations: cognitive behavioral treatment of insomnia (CBT-I), a multicomponent psychotherapeutic intervention, is unequivocally recommended as a first-line treatment. In this report, we will focus on the most recent guideline update from the ESRS, which was published in November 2023. After suggesting a careful diagnostic procedure, CBT-I, both applied face to face (F2F) or digitally (dCBT-I), is again recommended as a first-line treatment based on the available evidence. Hypnotic medications like benzodiazepines (BZ), benzodiazepine receptor agonists (BZRA), sedating antidepressants, and others are approved for short-term-treatment of up to four weeks. Orexin receptor antagonists (i.e., daridorexant) and prolonged release melatonin are considered as options for longer-term treatment when carefully considering the advantages and disadvantages. Both light therapy and exercise regimens were viewed as promising; however, they still lack convincing evidence for the time being. Given the fact that not every patient responds satisfactorily or even remits following CBT-I or other treatment options, the research agenda calls for the development and evaluation of new therapeutic avenues and combination therapies.

Clinical and Translational Neuroscience doi: 10.3390/ctn8010009

Authors: Chiara Cirelli Giulio Tononi

When we are asleep, we lose the ability to promptly respond to external stimuli, and yet we spend many hours every day in this inherently risky behavioral state. This simple fact strongly suggests that sleep must serve essential functions that rely on the brain going offline, on a daily basis, and for long periods of time. If these functions did not require partial sensory disconnection, it would be difficult to explain why they are not performed during waking. Paradoxically, despite its central role in defining sleep and what sleep does, sensory disconnection during sleep remains a mystery. We have a limited understanding of how it is implemented along the sensory pathways; we do not know whether the same mechanisms apply to all sensory modalities, nor do we know to what extent these mechanisms are shared between non-rapid eye movement (NREM) sleep and REM sleep. The main goal of this contribution is to review some knowns and unknowns about sensory disconnection during sleep as a first step to fill this gap.

Clinical and Translational Neuroscience doi: 10.3390/ctn8010008

Authors: Albrecht P. A. Vorster Eus J. W. van Someren Allan I. Pack Reto Huber Markus H. Schmidt Claudio L. A. Bassetti

Together with (physical and mental) exercise, diet, and social activities, sleep is a key health behavior that occupies one third of our lives, yet remains neglected. In the first part of this review, we present the current knowledge on how sleep promotes body, brain, mental, occupational, and social health as well as creativity, productivity, and well-being. In the second part, we discuss how good sleep and screening for sleep–wake disorders may improve health and reduce the burden of brain, mental, cardiovascular, metabolic disorders and cancer. We also review the literature on measurements of sleep health and present the Bernese Sleep Health Questionnaire, a new and simple tool to assess sleep health and screen for sleep–wake circadian disorders in clinical practice.

Clinical and Translational Neuroscience doi: 10.3390/ctn8010007

Authors: Clinical and Translational Neuroscience Editorial Office

The Clinical and Translational Neuroscience Editorial Office would like to make the following correction to the Academic Editor listed on this published paper [...]