Clinical and Translational Neuroscience

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

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. Full article

(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. Full article

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. Full article