Search Results (288)

Brain metastases are the third most common metastatic site in melanoma patients, with 40% of melanoma patients developing melanoma brain metastasis (MBM). Symptomology of MBM ranges from headaches, neurological deficits, cognitive changes, and seizures, resulting from MBM embedding in areas of highest blood flow following the breakdown of the blood–brain barrier (BBB) via genetic, cytokine, and molecular processes. The BBB is highly restrictive, making MBM difficult to treat. Challenges in MBM treatment are evident in adverse therapeutic effects, such as neurocognitive decline with whole-brain radiation therapy (WBRT), increased risk of radiation necrosis with stereotactic radiosurgery (SRS), and reduced penetration into the brain, which can lead to drug resistance with prolonged use of MAPK inhibitors. This review investigates current and novel treatments against MBM, including radiotherapy, chemotherapy, targeted therapies such as BRAF/MAPK inhibitors, and immunotherapy. Full article

Over the past years, burn care has evolved from a discipline focused on survival to one centered on restoring long-term health, function, and quality of life. Significant advances in critical care, early excision and grafting, infection control, and metabolic support have transformed survival outcomes for even the most severe injuries. As a result, the field now faces a new frontier: understanding and managing the long-term physical, psychological, and systemic sequelae of survival. This review traces the evolution of burn care over the last century and outlines the challenges and priorities for the next 25 years. The first era of progress, defined by innovations in resuscitation, surgery, and critical care, has given rise to a growing cohort of long-term survivors. Research over the past decade has revealed that major burns induce chronic multisystem alterations, including metabolic, cardiovascular, neurocognitive, and immunological dysfunctions. Emerging concepts such as burn-associated heart failure exemplify this shift from acute to chronic disease understanding. Looking ahead, the future of burn medicine lies in personalized and lifelong care, supported by translational research, digital health, regenerative therapies, and interdisciplinary collaboration. Overall, burn care stands at a pivotal crossroads. By integrating precision medicine, rehabilitation science, and psychosocial care, we aim to move the field from survival toward sustained, holistic recovery over the next 25 years. Full article

Heavy metals including mercury (Hg), lead (Pb), cadmium (Cd), and arsenic (As) remain significant global toxins due to their environmental persistence, widespread anthropogenic release, and serious biological effects. This review consolidates current understanding of their natural and industrial sources, environmental cycling, human exposure routes, and population-level vulnerabilities. It covers their toxicokinetics and toxicodynamics, emphasizing species-specific absorption, distribution, and injury mechanisms, including oxidative stress, thiol binding, mitochondrial dysfunction, endocrine disruption, and cancer risk. Clinical signs range from subtle neurocognitive impairment and kidney damage to severe acute poisoning. The review evaluates evidence-based approaches to risk assessment and biomonitoring, such as blood, urine, hair, and speciation tests, noting issues, including unvalidated provoked testing. Treatment focuses on removing exposure, providing nutritional support, and offering supportive care, with chelation therapy reserved for specific cases. It explains the chemistry, pharmacology, and roles of chelating agents—ALA, DMSA, DMPS, Cys, GSH, and physiologic thiols, comparing their effectiveness, limitations, and costs for various metals. Emerging therapies, precision toxicology, and public health strategies are discussed within a prevention-focused context. Unlike prior reviews focused primarily on toxic mechanisms or isolated clinical management, this review integrates mechanistic toxicology, biomarker interpretation and speciation, evidence-based clinical care, and ethical, cost-conscious decision-making within a single translational framework. This narrative review synthesizes foundational and contemporary literature published through 2025, with particular emphasis on studies published since 2000 that inform toxicokinetics, biomarker interpretation, diagnostics, clinical management, and prevention. Full article

Introduction: Chronic non-cancer pain represents a major global health challenge because of its high prevalence, functional impact, and limited response to conventional therapies, highlighting the need for alternative approaches. In this context, subanesthetic-dose ketamine has emerged as a promising therapeutic option because of its ability to modulate central sensitization and enhance analgesia through NMDA receptor antagonism. However, current evidence regarding its long-term efficacy and safety remains limited and heterogeneous. Objective: To evaluate the efficacy and safety of subanesthetic ketamine for the management of chronic non-cancer pain in adults, based on randomized controlled trials published between 2005 and 2025. Methods: A systematic review was conducted in accordance with the PRISMA 2020 guidelines. Randomized controlled trials involving adults with chronic non-cancer pain were included, comparing ketamine with placebo or other active agents. The databases searched were PubMed, ScienceDirect, and the Cochrane Library. Risk of bias was assessed using the Cochrane RoB-2 tool, and the certainty of evidence was evaluated using GRADE. Results: Five trials met the inclusion criteria. All included studies evaluated intravenous ketamine at doses ranging from 0.3 to 0.5 mg/kg. Overall, ketamine demonstrated significant short-term pain relief (p < 0.05), particularly in neuropathic conditions; however, the magnitude of this effect decreased progressively after the infusion ended. Reported adverse effects were mild and transient, with no evidence of severe toxicity. Heterogeneity in dosing protocols, pain phenotypes, comparator strategies, and follow-up duration limited cross-study comparability. Conclusions: Current evidence supports the short-term efficacy and safety of subanesthetic-dose ketamine as an analgesic option for chronic non-cancer pain, especially in neuropathic syndromes. However, the transient nature of its effects and the heterogeneity among studies underscore the need for standardized protocols and longer follow-up periods. Despite its generally favorable short-term safety profile, subanesthetic ketamine should be used with caution under strict clinical supervision, as the potential for long-term neurocognitive, urological, and hepatic adverse effects remains insufficiently defined. Full article

Cognitive impairment persists in people with HIV (PWH) despite effective combination antiretroviral therapy, possibly as a result of persistent alterations in white matter microstructural abnormalities in the brain. Noninvasive tensor-valued diffusion MRI (dMRI) is sensitive to microstructural integrity; thus, it may contribute to the understanding of HIV-associated cognitive impairment. In this exploratory cross-sectional study, 31 healthy controls (HCs) and 24 PWH underwent 3T MRI and neurocognitive assessment. Tensor-valued dMRI metrics, including microscopic fractional anisotropy (µFA) and isotropic, anisotropic, and total mean kurtosis (MKi, MKa, MKt), and conventional DTI and DKI metrics (FA, MD, and MK) were evaluated across six functionally defined brain networks. Compared with HCs, PWH exhibited reduced FA, µFA, and MKa in the dorsal default mode and anterior salience networks, along with increased MKi in the salience network and decreased MKi in the executive control network, with moderate effect sizes. Compared with HCs, PWH performed significantly worse on measures of learning, memory, and language, but showed no differences in executive function, attention, or processing speed. Additionally, significant associations and interactions between dMRI metrics and HIV status were observed, particularly for MKi and attention, executive function, and processing speed across the default mode, salience, and executive control networks. These preliminary findings underscore tensor-valued dMRI as a sensitive biomarker of network-specific neurocognitive vulnerability in HIV. Full article

HIV-associated neurocognitive disorders (HAND) persist despite combination antiretroviral therapy (cART) and can be exacerbated by repeated cocaine (COC) exposure. Because COC, HAND, and cART independently disrupt medial prefrontal cortex (mPFC) function, their combined neurotoxic impact is a critical clinical concern. Using patch-clamp electrophysiology in HIV-1 transgenic (Tg) and non-Tg rats, we examined mPFC pyramidal neuron activity following repeated exposure to COC and/or cART. In non-Tg rats, COC and cART independently increased neuronal firing, trending toward an additive hyperactive effect when combined. Conversely, HIV-1 Tg rat neurons exhibited plateaued excitability, with no further firing elevations induced by COC or cART. Under intense depolarizing stimuli, treated neurons displayed overactivation-induced firing declines. These findings indicate that while COC and cART additively disrupt mPFC function in non-Tg rats, excitability mechanisms appear saturated in the HIV-1 Tg model. This restricted experimental context highlights the overlapping neurobiological impacts of cART and stimulant use, providing foundational insights into the comorbidity of COC use disorder and HAND. Full article

Background/Objective: Advances in intensive care medicine have substantially improved the survival of critically ill patients; however, they have also revealed the growing burden of neurological complications that affect both short-term outcomes and long-term functioning. Neurological complications in the intensive care unit (ICU) include a wide spectrum of disorders, ranging from acute brain dysfunction such as delirium, coma, and encephalopathy to persistent cognitive impairment after discharge, which represents a key component of Post-Intensive Care Syndrome (PICS). Delirium affects approximately one-third of ICU patients and is independently associated with increased mortality, prolonged hospitalization, and worse long-term neurocognitive outcomes. Due to the limited effectiveness of pharmacological therapies, current clinical approaches emphasize prevention, early diagnosis, and non-pharmacological strategies in line with PADIS guidelines. This narrative review aims to provide a clinically relevant synthesis of neurological complications in adult ICU patients, conceptualized as a continuum from acute brain dysfunction to long-term cognitive impairment. Methods: A narrative review of the literature was conducted, focusing on studies addressing epidemiology, pathophysiology, risk factors, diagnostic strategies, and prevention of neurological complications in critically ill adults. Attention was given to delirium, ICU-acquired cognitive impairment, and their association with PICS, as well as to current guideline-based and non-pharmacological interventions. Results: Available evidence indicates that neurological complications in the ICU are multifactorial and result from the interaction between patient vulnerability, severity of illness, systemic inflammation, sedative exposure, and environmental factors. Delirium remains the most common manifestation of acute brain dysfunction and is strongly associated with adverse outcomes. Increasing evidence supports the effectiveness of structured screening, early mobilization, sleep optimization, and multidisciplinary care bundles in reducing delirium incidence and duration. Moreover, growing attention is directed toward post-ICU follow-up and rehabilitation to reduce long-term cognitive decline. Conclusions: Neurological complications should be considered a central component of critical illness and a continuum extending beyond ICU discharge. Early identification of high-risk patients, implementation of preventive strategies, and integration of acute and post-ICU care are essential to improve survival and long-term cognitive outcomes. Further research should focus on personalized preventive and neuroprotective approaches in critically ill patients. Full article

Chronic migraine (CM) is a debilitating neurological disorder characterized not only by persistent and severe pain, but also by substantial cognitive dysfunction that affects attention, working memory, processing speed, and executive functions. These neuropsychological disturbances are likely influenced by overall disease burden and are further modulated by affective comorbidities, sleep disturbances, and medication overuse. OnabotulinumtoxinA (BoNT-A) is an established preventive therapy for CM, supported by strong evidence of both efficacy and safety. This narrative review synthesizes findings from studies examining the relationship between BoNT-A treatment and domain-specific cognitive improvements in CM. It also outlines the potential pathophysiological mechanisms underlying these effects, summarizes the limitations of the existing literature, and highlights priorities for future research. Current evidence suggests that BoNT-A may confer neurocognitive benefits, particularly in working memory and processing speed, and that these improvements may occur partly independently of reductions in headache frequency. These favorable cognitive effects appear to be plausibly linked to decreased nociceptive “noise” and improved cortical inhibition, potentially mediated through modulation of central sensitization, nociceptive signaling, and affective states. Full article

Background/Objectives: Obstructive sleep apnea (OSA) is a prevalent disorder in adults, characterized by recurrent upper airway obstruction during sleep, resulting in intermittent hypoxia, sympathetic activation, and sleep fragmentation. It is linked to significant cardiovascular, metabolic, neurocognitive, and psychosocial morbidity. There is increasing evidence that continuous positive airway pressure (CPAP) adherence remains suboptimal in many patients, and in those patients, surgery is often indicated. Methods: This protocol report presents an updated and protocol-driven surgical approach grounded in clinical evidence and experience, highlighting the role of drug-induced sleep endoscopy (DISE) and personalized multi-level interventions for adult patients with OSA. The integration of anatomical phenotyping and DISE-directed planning enables precise surgical targeting. The protocol emphasizes patient selection, individualized treatment based on obstruction patterns, and perioperative optimization. This surgical algorithm improves the success rates and long-term outcomes in patients who are intolerant of CPAP therapy. Results: A DISE-guided and multi-level surgical approach includes uvulopalatoplasty, septoplasty, tongue base reduction, palatoplasty, and maxillomandibular advancement (MMA). Preoperative assessments include BMI and the STOP-BANG and Epworth Sleepiness scales, while postoperative care emphasizes follow-up polysomnography and adjunctive therapies only when necessary. Regional experiences in Saudi Arabia and Canada underscore the importance of standardized evidence-based surgical care. Conclusions: The purpose of this article is to establish a clear protocol for managing patients diagnosed with OSA, drawing on a review of the existing literature and the insights of experienced surgeons in the field of sleep apnea, and to update current protocols with modern evidence. Full article

Cognitive impairments are a core feature of psychotic disorders and are strongly associated with long-term functional disability. Although Cognitive Remediation Therapy (CRT) is an evidence-based intervention for improving cognition in psychosis, its feasibility and preliminary effects in acute inpatient settings—particularly using web-based platforms—remain underexplored. This single-arm, pre–post pilot study evaluated the feasibility of delivering a web-based CRT program and examined preliminary cognitive outcomes in a secure psychiatric inpatient facility. Thirteen inpatients with psychotic and non-psychotic diagnoses completed a 15-week intervention comprising twice-weekly sessions that included adaptive computerized CRT exercises (Happy Neuron Pro) and therapist-led bridging discussions focused on metacognitive reflection and functional application. Cognitive performance was assessed pre- and post-intervention using the MATRICS Consensus Cognitive Battery. All participants completed the study with no withdrawals or adverse events, attending a mean of 27.77 of 30 sessions (93.0%). Pre–post improvements were observed in processing speed, verbal learning, and overall composite cognition, with large within-sample effect sizes that remained robust in sensitivity analyses. Exploratory analyses suggested potential associations between sex, history of self-harm, and cognitive change, though these findings require cautious interpretation. Findings support the feasibility of inpatient web-based CRT and provide preliminary cognitive effect-size estimates. Given the single-arm design and absence of systematic medication monitoring, results should be interpreted as exploratory signals warranting controlled validation. Overall, findings support the feasibility of inpatient web-based CRT and provide preliminary signals of cognitive benefit, warranting evaluation in larger controlled studies. Full article

Background: Pediatric kidney failure, whether acute or chronic, constitutes a major public health issue because of its impact on survival, linear growth, neurocognitive development, and long-term quality of life. While high-income countries have markedly improved outcomes through early diagnosis, advanced dialysis technologies, and kidney transplantation, management remains limited in low- and middle-income countries, particularly in the Maghreb region. Objective: This review aims to provide an updated synthesis of pediatric kidney failure, with emphasis on renal replacement therapy modalities and the specific challenges encountered in resource-limited contexts, particularly in Algeria. Methods and Content: We successively address the pathophysiological and clinical bases of pediatric acute kidney injury and chronic kidney disease, followed by a discussion of available therapeutic strategies: peritoneal dialysis, intermittent hemodialysis, continuous renal replacement therapy, and pediatric kidney transplantation. Particular attention is given to organizational constraints, actual availability of modalities, limited access to consumables and immunosuppressive therapies, and the specificities of pediatric kidney care in the Maghreb region in comparison with international recommendations. Perspectives: Improving outcomes for children with kidney failure in Maghreb countries requires a multidimensional approach integrating early screening, strengthening peritoneal dialysis programs, structured development of pediatric kidney transplantation, and enhanced regional and international collaboration. Reinforcing local research capacity and participation in international registries are essential steps toward reducing disparities in care and adapting global guidelines to local realities. Full article

Background: Moyamoya disease (MMD) is a rare, progressive cerebrovascular arteriopathy characterized by stenosis and occlusion of the distal internal carotid arteries with the development of compensatory collateral networks. In children, MMD is a major cause of ischemic stroke; however, neurological morbidity frequently extends beyond cerebrovascular events to include epilepsy, headache, cognitive impairment, and psychiatric manifestations. Data regarding the long-term evolution of these complications in Caucasian pediatric patients remains limited. Case Report: We present the longitudinal case of a Caucasian female diagnosed with advanced MMD after an ischemic stroke at the age of 7 years, followed by indirect surgical revascularization (encephalo-duro-arterio-synangiosis) and chronic antiplatelet therapy. Four years later, she developed recurrent focal aware sensory–motor seizures associated with chronic post-ischemic cortical injury. Despite stable vascular imaging and absence of recurrent infarction, the patient experienced persistent neurological sequelae, including residual spastic hemiparesis, episodic tension-type headaches, and evolving neuropsychological complications. Cognitive assessment initially suggested mild neurocognitive impairment, with subsequent improvement during adolescence. In late follow-up, prominent anxiety symptoms emerged, and psychiatric evaluation confirmed panic disorder requiring psychological and pharmacological support. The patient remained neurologically stable into adulthood under continued multidisciplinary care. This case illustrates the broad spectrum of neurological and psychiatric complications that may accompany pediatric MMD, even in the absence of new ischemic events. The accompanying literature review emphasizes that epilepsy, headache, cognitive dysfunction, and psychiatric disorders represent clinically significant components of the long-term disease burden in children with MMD. Conclusions: Pediatric moyamoya disease should be regarded not only as a cause of childhood stroke, but also as a chronic condition with long-term epileptic, cognitive, and psychiatric sequelae that may evolve independently of recurrent ischemic injury. By providing longitudinal follow-up from childhood into adulthood in a Caucasian patient, this report underscores the importance of integrating neuropsychological and psychiatric surveillance into standard care pathways, alongside vascular and surgical management, to better address the full spectrum of morbidity and improve quality of life. Full article

HIV-associated neurocognitive impairment persists despite combination antiretroviral therapy, largely driven by chronic microglial activation that sustains neuroinflammation and neuronal injury. Activated microglia contribute to HIV-associated brain pathology by releasing proinflammatory mediators that disrupt synaptic integrity and impair cognition. N-acetylaspartylglutamate (NAAG), an abundant neuropeptide that maintains glutamatergic homeostasis, is hydrolyzed by glutamate carboxypeptidase II (GCPII) to glutamate. We previously demonstrated that reduced brain and cerebrospinal fluid NAAG levels in people living with HIV correlate with cognitive impairment, and that pharmacological GCPII inhibition with 2-(phosphonomethyl)-pentanedioic acid (2-PMPA) elevates brain NAAG and improves cognition in EcoHIV-infected mice. To enhance brain delivery and preferentially target activated microglia, we conjugated 2-PMPA to a generation 4 hydroxyl poly(amidoamine) (PAMAM) dendrimer (D-2-PMPA). Our findings demonstrate that D-2-PMPA achieves preferential microglial drug delivery, resulting in a >600% increase in cerebrospinal fluid NAAG levels. At doses 8.3-fold lower than free 2-PMPA, this formulation reversed EcoHIV-induced deficits in social interaction, novel object recognition, and fear-conditioned memory without altering locomotor activity or anxiety-like behavior. D-2-PMPA also restored prefrontal cortex synaptic density and preserved dendritic architecture. Together, these findings demonstrate that microglia-targeted GCPII inhibition represents a potent nanotherapeutic strategy to restore synaptic integrity and cognitive function in HIV-associated neurocognitive impairment. Full article

Background: Cancer-related cognitive impairment (CRCI) affects quality of life, daily functioning and return-to-work. However, CRCI remains under-addressed in cancer care. Since cognitive complaints often co-occur with fatigue and psychological distress, a multimodal approach is warranted. We developed Integrative Neuro-Cognitive Remediation Therapy (INCRT), a multidisciplinary survivorship program combining personalized cognitive function and strategy training with group-based psychoeducation, cognitive–behavioral therapy and Acceptance and Commitment Therapy, and onco-yoga. Methods: Cancer survivors suffering from CRCI were eligible. Assessments included neuropsychological testing, patient-reported outcomes, and daily functioning at baseline (T0), post-intervention (T1), and 6-month follow-up (T2). Primary outcomes were objective and subjective neurocognitive functioning (NCF); secondary outcomes were psychological distress, fatigue, metacognition, and daily functioning. Changes were analyzed using linear mixed models. Results: Between November 2022 and January 2025, 44 of 56 eligible survivors enrolled; 38 completed the program (71.1% female; median age 53.5). Objective and subjective NCF improved significantly at T1 and T2 (ps < 0.001). Psychological distress, fatigue, and unhelpful metacognitions decreased over time (ps < 0.05). Participants reported greater emotional and cognitive insight and improved daily functioning. Conclusions: INCRT improves cognitive functioning, reduces psychological distress and fatigue, and enhances daily functioning, with benefits maintained at follow-up. The integrative design supports sustained effects by promoting internalization and daily application of learned strategies. Full article

HIV infection remains a major global health challenge due to its complex pathogenesis and lifelong persistence in people living with HIV (PLWH). A central barrier to eradication is the virus’s ability to establish long-lived latent reservoirs in different tissues, including the central nervous system (CNS), where it evades immune clearance and antiretroviral therapy (ART). These reservoirs, seeded early during infection, fuel viral rebound if ART is interrupted, requiring lifelong treatment. In the CNS, HIV persists despite systemic viral suppression because of limited ART penetration across the blood–brain barrier (BBB), and infection of long-lived cells such as microglia and perivascular macrophages. Although modern ART regimens significantly reduce viral burden and HIV-related morbidity, they do not eliminate neurocognitive complications. Suboptimal CNS drug penetration and certain ART-associated toxicities contribute to CNS dysfunction, persistent neuroinflammation, and accelerated aging of the brain. As PLWH now experience increased life expectancy, prolonged exposure to ART and persistent low-level viral activity exacerbate chronic inflammation, immune activation, and metabolic dysregulation, collectively accelerating neurobiological aging. These pathological processes contribute to the development of HIV-associated neurocognitive disorders (HAND), which affect nearly half of virally suppressed PLWH. This review examines HIV-associated inflammation, neurotoxic pathways, and accelerated aging in PLWH in the modern ART era. Full article