NeuroSci

Background/Objectives: The glymphatic system is a recently characterized glial-dependent waste clearance pathway in the brain, which makes use of perivascular spaces for cerebrospinal fluid exchange. Diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) offers a non-invasive method for estimating perivascular flow, but its biological specificity and susceptibility to methodological variation, particularly head position during MRI acquisition, remain as threats to the validity of this technique. This study aimed to assess the prevalence of current DTI-ALPS practices, evaluate the impact of head orientation on ALPS index calculation, and propose a novel computational approach to improve measurement validity. Methods: We briefly reviewed DTI-ALPS literature to determine the use of head-orientation correction strategies. We then analyzed diffusion MRI data from 172 participants in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) to quantify the influence of head orientation on ALPS indices computed using the conventional Unrotated-ALPS, a vecrec-corrected ALPS, and the new LD-ALPS method proposed within. Results: A majority of studies employed Unrotated-ALPS, which does not correct for head orientation. In our sample, Unrotated-ALPS values were significantly associated with absolute head pitch (r₁₆₉ = −0.513, p < 0.001), indicating systematic bias. This relationship was eliminated using either vecreg or LD-ALPS. Additionally, LD-ALPS showed more sensitivity to cognitive status as measured by Mini-Mental State Examination scores. Conclusions: Correcting for head orientation is essential in DTI-ALPS studies. The LD-ALPS method, while computationally more demanding, improves the reliability and sensitivity of perivascular fluid estimates, supporting its use in future research on aging and neurodegeneration. Full article

Background: The Coma Recovery Scale–Revised (CRS-R) is the gold standard for diagnosing chronic disorders of consciousness (DoC); however, its clinical utility is limited by lengthy administration and the need for specialized training. The Simplified Evaluation of Disorders of Consciousness (SECONDs) provides a faster and more user-friendly alternative. Objective: This study aims to evaluate the validity and reliability of the Argentine adaptation of the SECONDs scale in adults with chronic DoC due to acquired brain injury. Methods: Twenty-nine patients were evaluated over two consecutive days by three blinded raters. On day one, rater A administered the SECONDs (A1) and rater B administered the CRS-R (B) to assess concurrent validity. On day two, rater A repeated the SECONDs (A2), and rater C performed an additional SECONDs assessment (C), permitting evaluation of intra-rater (A1 vs. A2) and inter-rater (A vs. C) reliability. Results: The SECONDs demonstrated excellent intra-rater (ICC = 0.98) and inter-rater (ICC = 0.86) reliability. Concurrent validity with the CRS-R was strong (r = 0.73, p < 0.001). Diagnostic agreement was high between A1 and B (κ = 0.75) and between both A1-A2 and A1-C (κ = 0.82). The median administration time was significantly shorter for the SECONDs (10 vs. 15 min; p < 0.001). Conclusion: The Argentine SECONDs is a valid, reliable, and efficient tool for the clinical assessment of DoC patients in rehabilitation settings. Full article

Until recently, research on the pathobiological substrate of psychosis has been focused on neurotransmitter perturbations. However, this scope has expanded to include new fields, such as the immune/redox/metabolic/neuroendocrine/stress systems. Indeed, basic research in the stress field showed that the systems above can represent components of a general inflammatory process as tightly interconnected as a Gordian knot. Based on the inflammatory hypothesis concerning the psychosis etiopathology, the findings from psychotic cohort studies on each one of the immune/redox/metabolic/neuroendocrine/stress systems have started to accumulate. The evidence favors the involvement of these systems in the formation of the pathobiological psychotic substrate, yet little is known concerning their interplay. This review attempts to establish a frame of reference for the evidence concerning intersystemic interactions, starting with the basic research on the stress field and expanding to clinical studies with psychosis cohorts, hoping to instigate new avenues of research. Full article

This study aims to investigate whether a combined action observation–motor imagery practice may enhance the effects of conventional physical rehabilitation in a stroke survivor population. A total of 8 (7 male, 1 female) post-stroke patients with upper limb hemiparesis were enrolled into a single-blinded, randomised, study. Five times per week for three weeks, four patients experienced 60’ conventional physical therapy, while the other 4 experienced 30’ conventional physical therapy and 30’ action observation–motor imagery practice. The Fugl-Meyer Assessment-Upper Extremity and the Wolf Motor Function Test scores from the baseline and post-physiotherapy were used to evaluate upper extremity motor function. Patients who received the AO + MI alongside conventional physical rehabilitation benefitted more than those who received only conventional physical rehabilitation. However, the sample size was very small (only eight participants), which reduces both the statistical power and the ability to generalise the results. Moreover, there was no follow-up; therefore, it is unclear whether the observed improvements lasted over time. Finally, some potentially confounding factors, such as stroke type or lesion site, were not statistically controlled. Notwithstanding these limitations, our findings may serve as a basis for future large-scale, well-controlled studies on AO + MI in stroke rehabilitation. Full article

Background: attention-deficit/hyperactivity disorder (ADHD) and Alzheimer’s disease (AD) are distinct neurological conditions that may share genetic and molecular underpinnings. ADHD, a neurodevelopmental disorder, affects approximately 5% of children and 3% of adults globally, while AD, a neurodegenerative disorder, is the leading cause of dementia in older adults. Emerging evidence suggests potential overlapping contributors, including pathways related to synaptic plasticity, neuroinflammation, and oxidative stress. Methods: this systematic review investigated potential genetic predispositions linking Attention-Deficit/Hyperactivity Disorder (ADHD) and Alzheimer’s Disease (AD). Following PRISMA guidelines, a search was conducted in Web of Science, Embase, PsycINFO, and PubMed using keywords related to ADHD, AD, and genetic factors. Studies included were original human studies utilizing genetic analyses and ADHD polygenic risk scores (PRS), with AD confirmed using established diagnostic criteria. Exclusion criteria comprised non-original studies, animal research, and articles not addressing genetic links between ADHD and AD. Screening was conducted with Rayyan software, assessing relevance based on titles, abstracts, and full texts. Results:. The search identified 1450 records, of which 1092 were screened after duplicates were removed. Following exclusions, two studies met inclusion criteria. One study analyzed ADHD-PRS in 212 cognitively unimpaired older adults using amyloid-beta (Aβ) PET imaging and tau biomarkers. The findings revealed that ADHD-PRS was associated with progressive cognitive decline, increased tau pathology, and frontoparietal atrophy in Aβ-positive individuals, suggesting that ADHD genetic liability may exacerbate AD pathology. Another study assessed ADHD-PRS in a cohort of 10,645 Swedish twins, examining its association with 16 somatic conditions. The results showed modest risk increases for cardiometabolic, autoimmune, and neurological conditions, with mediation effects through BMI, education, tobacco use, and alcohol misuse, but no direct link between ADHD-PRS and dementia. Discussion and conclusion: this review highlights preliminary but conflicting evidence for a genetic intersection between ADHD and AD. One study suggests that ADHD genetic liability may exacerbate AD-related pathology in Aβ-positive individuals, whereas another large registry-based study finds no direct link to dementia, with associations largely mediated by lifestyle factors. The potential ADHD–AD relationship is likely complex and context-dependent, influenced by biomarker status and environmental confounders. Longitudinal studies integrating genetics, biomarkers, and detailed lifestyle data are needed to clarify this relationship. Full article

The extracranial–intracranial (EC–IC) bypass is a complex neurosurgical procedure performed for cerebral flow augmentation or flow replacement. Anesthetic management of these patients poses significant challenges due to the delicate balance required to maintain cerebral perfusion, often complicated by extensive cardiovascular comorbidities. Despite the complexity of these cases, current literature offers limited guidance on optimal anesthetic strategies. At our high-volume academic institution, we developed a standardized multimodal anesthetic protocol aimed at achieving intraoperative hemodynamic stability and facilitating timely postoperative emergence. A dedicated team of neuroanesthesiologists manages these cases in constant communication with the surgical team, ensuring real-time adjustments aligned with surgical needs and patient physiology. Our experience highlights the importance of individualized anesthetic planning and interdisciplinary coordination. Given the scarcity of published data and the specialized nature of EC–IC bypass procedures, we believe our institutional approach may serve as a useful reference for other centers, particularly those with limited exposure to this complex patient population, and lay the foundation for future prospective trials on optimal anesthetic care for this patient population. Full article

Background: Sciatic nerve schwannomas are rare benign tumors that can develop along the nerve’s course, from the pelvis to the thigh. Giant schwannomas, defined as those exceeding 5 cm, are particularly rare and may alter the tumor’s anatomical relationship with the nerve, impacting surgical strategy. Methods: A PRISMA 2020-compliant systematic review was conducted using the terms (“sciatic” AND “schwannoma”) for publications from 2000 to October 2024. Of 166 identified articles, we excluded those lacking giant schwannoma cases or involving syndromic associations. We also report a novel case from our center. Results: Our patient, a 35-year-old woman, presented with tingling and discomfort while sitting, localized to the left thigh, without radicular pain or motor deficits. MRI revealed a 14 × 7 cm mass. This is, to our knowledge, the first reported case of a giant solitary sciatic schwannoma of these dimensions located exclusively in the thigh, resected via intracapsular dissection with nerve monitoring, that was fully documented and reported. The review yielded 22 relevant articles, most involving pelvic or pelvic–thigh junction locations, with low recurrence rates. Conclusions: Giant sciatic schwannomas may be asymptomatic and slow-growing. This case is notable for tumor’s location, large size, and successful nerve-sparing surgical outcome. Full article

Background: The consequences of median nerve compression at the carpal tunnel level require a precise diagnostic evaluation before a frequently applied surgical intervention. Positive Tinel or Phalen signs are not always related to abnormal results in electroneurographic examinations of sensory and motor nerve fibers, which are intended to confirm final diagnoses, thereby confusing both surgeons and neurophysiologists. In the face of contradictory data, this study aims to reinvestigate these correlations in a randomly chosen population of patients with a primary diagnosis of carpal tunnel syndrome (CTS). Methods: Seventy-five randomly chosen patients with clinically detected CTS underwent neurophysiological studies of median nerve sensory (SNAP) and motor (CMAP) fibers conduction at the wrist. Both the median and ulnar nerves were assessed to reduce the risk of misinterpretation related to anatomical variations. Results: This study provides evidence on the relatively high utility of Phalen’s test in the early clinical detection of CTS within a general population of patients, whose positive results moderately correlate (rho = −0.327) with abnormalities in amplitudes rather than the distal latency parameters of SNAP recordings. The axonal injury type is more distinct than slowing-down impulses at the wrist following compression of the sensory nerve fibers in the early course of CTS. Positive Tinel’s test results are useful in diagnosing CTS patients with advanced axonal and demyelinating changes in the motor fibers at the wrist, which weakly correlate with prolonged latency and decreased amplitude in SNAP recordings (rho = −0.214 and rho = −0.235, respectively), but not with abnormalities in recordings of both amplitudes and latencies in CMAP electroneurography. Conclusions: The correlations between clinical signs and neurophysiological findings in CTS indicate that provocative tests, such as Phalen’s and Tinel’s, have limited diagnostic value, demonstrating only weak-to-moderate associations with neural conduction parameters. A positive Tinel’s sign should be regarded mainly as a marker of severe or chronic sensory impairment, often accompanied by motor fibers involvement in advanced pathological stages, rather than as an indicator of motor damage alone. Nerve conduction studies remain essential for confirming CTS, assessing its severity, and guiding treatment decisions, including surgical qualification. The presented correlation of clinical and functional neurophysiological results in CTS diagnosis allows us not only to specify the source and severity of the pathology of the median nerve fibers but also may influence the personalization of physiotherapeutic and surgical treatments. Full article

Patients with Parkinson’s disease frequently suffer from complicated anxiety disorders that are entwined with their attitudes and behaviors. In regard to this population, cognitive behavioral therapy (CBT) has been attracting an increasing amount of attention as a potentially effective treatment for mental health issues like anxiety. CBT helps patients manage stress and improve their psychological well being through behavioral, relaxation, and cognitive techniques. Even though there is already evidence that cognitive behavioral therapy (CBT) can dramatically reduce psychological symptoms in Parkinson’s patients, more thorough research is required to determine its exact role in comprehensive anxiety treatment and prove its long-term efficacy. The purpose of this study is to examine the body of research on the use of cognitive behavioral therapy (CBT) to treat anxiety in patients with Parkinson’s disease, looking at its limitations and challenges as well as clinical characteristics, advantages, and possible behavioral and psychological impacts. Full article

Traumatic brain injury (TBI), even when mild, has been associated with the presence of depression. Depression is a mood disorder characterized by persistent negative thoughts and sadness and is challenging to treat due to the multiple mechanisms involved in its pathophysiology, including increased nitric oxide (NO) levels. There are no completely safe and effective pharmacological strategies to treat this disorder. Mucuna pruriens (MP) has been shown to possess neuroprotective properties by regulating inflammatory responses and nitric oxide synthase activity. In this study, we evaluated the antidepressant-like effect of MP in male Wistar rats with induced mild traumatic brain injury (mTBI). MP extract (50 mg/kg i.p.) was administered immediately after mTBI and every 24 h for five days. We used the rats’ preference for sucrose consumption to assess the presence of depression-like behavior and analyzed the nitrite and nitrate levels in their cerebral cortex, striatum, midbrain, and nucleus accumbens. Untreated animals with mTBI showed a reduced preference for sucrose than those treated with MP, whose preference for sucrose was similar to that of sham animals. Increased nitrite and nitrate levels were observed in different brain regions in the TBI subjects; however, this increase was not observed in MP-treated animals. MP reduces behavior associated with depression and the brain NO levels in rats with mTBI. Full article

The antipsychotic drug haloperidol is found on the WHO list of essential drugs. In vitro, haloperidol demonstrates binding affinity for various receptors, including histamine H₂ receptors (H₂Rs). Several cardiac effects of haloperidol are known, but it remains unclear whether H₂Rs are involved. Here, the hypothesis was tested that haloperidol has the potential to act as either an agonist or an antagonist of human cardiac H₂Rs. The contractile effects of haloperidol were studied in isolated left and right atrial preparations from transgenic mice overexpressing human H₂Rs in the heart (H₂-TG), and compared to human atrial preparations from adult patients. Haloperidol reduced the histamine-stimulated force of contraction in the human atrial preparations as well as the histamine-stimulated force of contraction and beating rate in the left and right atrial preparations from the H₂-TG, respectively. Moreover, haloperidol reduced the isoprenaline-stimulated force of contraction in the human atrial preparations. In the wild-type mouse preparations, haloperidol only reduced the isoprenaline-stimulated beating rate in the right atria, but not the force in the left atria. Principally, haloperidol is capable of acting as an antagonist of both H₂Rs and β-adrenoceptors in the human heart. However, the effects are only relevant at very high doses of haloperidol, which are never or seldom achieved in practice. Full article

Background: Systemic lupus erythematosus (SLE) is reported to be the most common rheumatological disorder associated with catatonia. To date, reports on catatonia manifestations in SLE patients are uncommon in published literature, which has often favored a fragmented vision. We performed a narrative review with the aim of identifying all published reports of catatonia in SLE patients to ascertain—in a comprehensive view—its clinical characteristics and to provide useful insights for daily clinical practice. Methods: Comprehensive literature searches were carried out on 10 March 2025 (subsequently repeated ahead of draft on 6 June) in all main bibliographic databases: MEDLINE and EMBASE (OVID interface); PsycINFO (ProQuest); and PubMed, to capture within-text references. All searches combined controlled (MESH, Entree, and APA Headings) and free-text elements for both areas under observation: systemic lupus erythematosus (SLE) AND catatonia, with primary focus on case reports and series. Sets of findings were reviewed separately by the authors, and the full text of selected items was sourced. Further useful references were retrieved through citation lists. Results: 39 cases of patients with SLE and catatonia were identified (35 females and 4 males), with a mean age of 22.64 years (range 11–46). Only three patients were over the age of 40; a total of 10 had catatonia at the same time of SLE onset and 5 within a month of SLE diagnosis. Antiphospholipid and anti-ribosomal P protein antibodies were rarely identified. Almost all the patients improved following treatment with lorazepam and/or electroconvulsive therapy. Only one case of malignant catatonia was reported. Finally, a large number of patients were Asian or Afro-American, at least in the reports where ethnicity was specified. Conclusions: Catatonia can occur in patients with SLE, and it may be its first clinical manifestation, especially in young patients. Its prognosis is mostly favorable. Full article

Advanced glycation end products (AGEs) are reactive compounds formed through non-enzymatic glycation in a process known as the Maillard reaction. While humans produce AGEs endogenously, these compounds can also enter the body through dietary sources, food preparation methods, and exposure to agricultural and food-related chemicals. AGEs can accumulate within cells and impair cellular function. In addition, when AGEs bind to receptors for advanced glycation end products (RAGE), they activate intracellular signaling pathways that promote the generation of reactive oxygen species (ROS), mitochondrial dysfunction, and inflammation. Sustained AGE-RAGE signaling drives chronic inflammation contributing to the development of various ailments, including neurodegenerative diseases. This review examines AGE formation, metabolism, and accumulation, with an emphasis on dietary sources as modifiable contributors to AGE-RAGE mediated pathology. We highlight the need for further research on dietary AGE restriction as a potential strategy to prevent or slow the progression of neurodegenerative and neuroinflammatory disorders. Full article

This study examines changes in frailty among patients hospitalized for acute ischemic stroke (AIS) in a nationwide hospital cohort in Germany. Data from AIS patients were compared between the period before the corona virus disease 2019 (COVID-19)-pandemic (1 January 2016 to 31 December 2019) vs the pandemic phase (1 January 2020 to 31 December 2022). Frailty was categorized using the Hospital Frailty Risk Score (HFRS). Inferential statistics were conducted using generalized linear mixed models. Among the 101,124 included AIS patients, the median HFRS decreased from 9.3 (interquartile range [IQR]: 5.2–15.5) in pre-pandemic years to 8.4 (IQR: 4.4–14.2) during the pandemic (p < 0.01). Among high frailty AIS patients, length of stay rose from 15.7 (±14.9) to 16.0 (±15.0) days, differing significantly from the decrease observed among low frailty patients from 5.9 (±3.7) to 5.0 (±3.5; p < 0.01) days. Compared to pre-pandemic levels, among low frailty patients, there was a significant increase in rates of thrombolysis (odds ratio [OR] 1.14 [95% CI 1.02–1.28; p = 0.020]) and thrombectomy (OR 1.35 [1.32–1.48; p = 0.047]). In this nationwide study in Germany, there was a longitudinal decrease in frailty among patients hospitalized for AIS which was accompanied by increased rates of thrombolysis and thrombectomy. Full article

Accessible, dependable cognitive assessment is integral to patient care of people with multiple sclerosis (PwMS). Traditional neuropsychological tests are well validated in the multiple sclerosis (MS) population, but not without limitations, such as the time and financial cost associated with traditional in person administration. Recent endeavors have sought to refine assessment, with particular attention to psychometric properties, accessibility, efficiency, and other practical considerations. One approach has been to streamline neuropsychological batteries to brief measures of essential domains, such as the Brief International Cognitive Assessment for MS (BICAMS). Another approach is the use of computerized neuropsychological assessment devices (CNADs). A systematic review of CNADs in PwMS was published in 2019. However, research has continued to expand in the years since. Here, we present an updated review of the BICAMS and further development of CNADs in MS. Tests with strong psychometric foundations are highlighted. Full article

Early detection of cognitive decline in older adults is essential for implementing timely interventions. This study aimed to compare the diagnostic accuracy of the Mini-Mental State Examination (MMSE^®) and the Montreal Cognitive Assessment (MoCA©) in identifying cognitive impairment among community-dwelling older adults, while considering the effect of educational level. A cross-sectional, analytical study was conducted with 90 individuals aged 60 years or older, classified into cognitively preserved and cognitively impaired groups using the Clinical Dementia Rating (CDR) scale. Cognitive performance was assessed using the MMSE and MoCA, with results analyzed using both standard and education-adjusted cut-off scores. Diagnostic accuracy was evaluated using Receiver Operating Characteristic (ROC) curves. The MoCA demonstrated superior discriminative ability compared to the MMSE, with a significantly larger area under the ROC curve (AUC = 0.943 vs. 0.826; p < 0.001), higher sensitivity (90.2% vs. 78.4%), and higher specificity (87.2% vs. 76.9%). When education-adjusted cut-off scores were applied, the MoCA achieved markedly improved diagnostic accuracy (87.8%) compared to the MMSE (71.1%), with stronger agreement with CDR classifications (κ = 0.746 vs. κ = −0.132). These findings demonstrate that the MoCA is more sensitive in detecting cognitive impairment and should be considered the preferred screening tool in clinical and research settings, particularly when appropriate educational adjustments are applied. Full article

The static orientation of the eyes during visual fixation is determined by the simultaneous operation of multiple equilibria. This phenomenon is collectively referred to as poly-equilibrium, which involves multiple systems that work together to cancel each other out and establish gaze direction. While other systems, such as audio- and cervico-ocular systems, may also contribute to gaze direction, this review focuses primarily on the commands issued by the vestibulo- and visuo-oculomotor systems that determine gaze direction, as they play a key role in the poly-equilibrium process. From the visual and vestibular activities accompanying the appearance of an object in the central visual field to the recruitment of premotor neurons responsible for the generation of slow and saccadic eye movements, a delicate balance is maintained. As long as the recruited channels convey commands that counterbalance each other, no movement is initiated. This alternative viewpoint leads to reconsidering the nature of saccadic and pursuit eye movements. Rather than viewing them as the dynamic reduction in brain signals encoding kinematic parameters such as position or velocity, they can be seen as the physical expression of intracerebral processes restoring balanced activities between sensorimotor channels whose recruitment leads to mutually opposed movements. Full article

Autism Spectrum Disorder presents one of the most complex challenges in contemporary neuroscience. This review adopts an unconventional narrative structure, drawing inspiration from song titles by The Beatles to explore the multifaceted biological, developmental, and social dimensions of autism. Spanning historical perspectives to embryonic origins and adult cognition, we examine critical topics including cortical folding, sensory processing, and the contributions of various brain regions such as the cerebellum and brainstem. The role of mirror neurons and other neural systems in shaping social behavior is discussed, alongside insights from animal models that have advanced our understanding of autism’s underlying mechanisms. Ultimately, this manuscript argues that autism is not merely a biomedical challenge, but a broader societal issue intersecting with education, human rights, and identity. Following the long and winding road of scientific discovery, we advocate for a more empathetic, interdisciplinary, and human-centered approach to autism research. Though the path ahead remains uncertain, every step informed by evidence and driven by collaboration brings us closer to deeper understanding, greater inclusion, and more effective support. Full article

Interest in ketamine as a novel treatment for substance use disorders (SUDs) has been increasing due to its N-methyl-D-aspartate (NMDA) glutamate receptor antagonism and mounting evidence that glutamate neurotransmission is involved in the pathogenesis of both depression and addictions. This narrative review provides an outline of clinical evidence reported in the literature from the 1970s to 2025 that examines the efficacy of ketamine for the treatment of SUDs, focusing primarily on randomized blinded controlled trials (RBCTs). Key cohort studies, retrospective studies, secondary analyses, case reports, and relevant basic neuroscience studies are reviewed to complement the more rigorous human controlled trial data. Thus far, ketamine has been tested in nine RBCTs targeting cocaine (three studies), alcohol (three studies), opioid use disorder (two studies), and nicotine (one study), suggesting efficacy for addiction in combination with psychotherapies, and often when doses produce subjectively reported mystical or psychedelic experiences. This review highlights promising preliminary evidence, and the need for more rigorous studies to elucidate the scope of drug addictions ketamine may target, its optimal dosing or route of administration, the importance of concurrent psychotherapies, professional supervision and safety monitoring, and which psychiatric comorbidities or contexts may contraindicate its use for SUDs. Full article