Search Results (1,193)

Background: Iron plays a crucial role in neurotransmitter synthesis, myelination, and neuronal metabolism. Iron deficiency has been associated with a variety of neurodevelopmental disorders, particularly attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). However, the prevalence, clinical impact, and treatment implications differ between these conditions. Objective: To synthesize current evidence on the prevalence, neurobehavioral consequences, and therapeutic implications of iron deficiency in ADHD and ASD, highlighting convergences and disorder-specific findings. Results: In ADHD, studies using serum ferritin and related peripheral markers show inconsistent associations with core symptom severity, with reported ferritin thresholds for deficiency ranging widely. While some studies suggest links between low ferritin and hyperactivity, inattention, or stimulant response, others report null findings. In contrast, emerging neuroimaging evidence consistently demonstrates reduced brain iron in dopaminergic regions in children. In ASD, the strongest link is between low ferritin and sleep-related motor disturbances, and iron supplementation may improve sleep and motor symptoms. Conclusions: Screening for iron status and targeted supplementation may improve sleep and behavioral outcomes in ADHD and ASD, meriting integration into clinical practice and further randomized controlled trials. Full article

Background/Objectives: Speech difficulties are an early and disabling manifestation of Parkinson’s disease (PD), affecting communication and quality of life. This study aimed to examine demographic, clinical, dopaminergic imaging and cerebrospinal fluid (CSF) correlates of speech difficulties in early PD, comparing treatment-naïve and levodopa-treated patients. Methods: A cross-sectional analysis was conducted using data from the Parkinson’s Progression Markers Initiative (PPMI). The sample included 376 treatment-naïve and 133 levodopa-treated early PD participants. Speech difficulties were defined by Movement Disorder Society—Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part III, with Item 3.1 ≥ 1. Group comparisons and binary logistic regression identified predictors among demographic, clinical, dopaminergic and CSF biomarker variables, including [¹²³I]FP-CIT specific binding ratios (SBRs). All analyses were cross-sectional, and findings reflect associative relationships rather than treatment effects or causal mechanisms. Results: Speech difficulties were present in 44% of treatment-naïve and 57% of levodopa-treated participants. In both cohorts, higher MDS-UPDRS Part III ON scores—reflecting greater motor severity—and lower mean putamen SBR values were significant independent predictors of speech impairment. Age was an additional predictor in the treatment-naïve group. No significant differences were found in CSF biomarkers (α-synuclein, amyloid-β, tau, phosphorylated tau). These findings indicate that striatal dopaminergic loss, particularly in the putamen, and motor dysfunction relate to early PD-related speech difficulties, whereas CSF neurodegeneration markers do not differentiate affected patients. Conclusions: Speech difficulties in early PD are primarily linked to dopaminergic and motor dysfunction rather than global neurodegenerative biomarker changes. Longitudinal and multimodal studies integrating acoustic, neuroimaging, and cognitive measures are warranted to elucidate the neural basis of speech decline and inform targeted interventions. Full article

Background and objectives: Anterior cruciate ligament reconstruction (ACLR) is often associated with significant postoperative pain. Effective pain control is vital for early mobilization and reducing opioid use. While femoral nerve block (FNB) and adductor canal block (ACB) are common, they can cause motor weakness and incomplete analgesia. The genicular nerve block (GNB), typically used for chronic knee pain and arthroplasty, may offer a motor-sparing alternative for ACLR pain management. This review evaluates the evidence on GNB’s effectiveness for pain control, opioid reduction, and recovery after ACLR. Materials and Methods: A literature search (January 2014–May 2025) identified five studies involving adult ACLR patients receiving GNB. Data on demographics, techniques, pain scores, opioid use, and complications were analyzed. Results: Among 115 patients, GNB provided effective analgesia and reduced opioid needs. Randomized trials showed GNB was comparable to ACB and more effective when combined. Ultrasound, especially with Doppler, enhances precision and safety. No major motor deficits or adverse events were noted. Landmark-based approaches also showed utility in low-resource settings. Conclusions: GNB is a promising, motor-sparing option for postoperative pain in ACLR. Further high-quality trials are needed to confirm the benefits and standardize its use. The findings should be interpreted with caution, as the current evidence is of limited quality and lacks generalizability. Full article

Background/Objectives: Ischemic stroke is a leading cause of death and disability, and neuroprotection therapies, or those that increase recovery, are not available. While the garlic-derived bioactive compound S-allyl cysteine (SAC) has shown neuroprotective properties, its subacute long-term effects remain underexplored, particularly in females. Methods: We evaluated whether SAC supports functional recovery after ischemia/reperfusion (IR), focusing on neurotrophin signaling, tropomyosin receptor kinase B (TrkB), protein kinase B (AKT), and extracellular signal-regulated kinase (ERK). Adult female Wistar rats underwent 1 h of ischemia and 15 days of reperfusion. SAC (100 mg/kg, i.p.) was administered at the onset of reperfusion and daily for 15 days. Motor and cognitive deficit tests were performed. Infarct area, Ki67, brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), nerve growth factor (NGF), pTrkB, pAKT, and pERK levels were quantified in the cortex, striatum, and hippocampus. Results: MicroPET analysis revealed comparable glucose uptake between the IR and IR + SAC groups, indicating similar ischemic severity. SAC reduced infarct area (54.7%) and significantly improved motor deficits (53.9%), circling behavior (38.9%), and long-term memory compared with ischemia/reperfusion (IR) animals. SAC increased the proportion of Ki67-positive cells (4.3-fold in the cortex and 1.8-fold in the striatum) and enhanced neurotrophin levels, NGF (cortex), BDNF (cortex and striatum), VEGF (striatum), pTrkB, pAKT, and pERK (cortex and striatum). Conclusions: SAC supports post-ischemic recovery, improving motor performance and preserving long-term recognition memory, effects that could be associated with increased cell proliferation, neurotrophin levels, and activation of the TrkB, AKT, and ERK pathways. Full article

The sensory system plays a critical role in development, as it enables the processing and integration of internal and external stimuli. Dysfunctions in this system lead to sensory processing disorders (SPDs), which affect approximately 5–13% of children aged 4–6 years, impacting not only sensory responsiveness but also social interaction, emotional regulation, motor coordination, learning, attention, communication, and sleep. Although SPDs have been extensively investigated from molecular to behavioral levels, their underlying neurobiological mechanisms remain debated, and reliable biomarkers are still lacking. Moreover, due to overlapping behavioral manifestations, SPDs are frequently misdiagnosed as attention deficit hyperactivity disorder (ADHD), leading to challenges in accurate diagnosis and treatment planning. This narrative review aims to synthesize current evidence on the neurofunctional and molecular underpinnings of SPDs in relation to ADHD, providing an integrated perspective on their converging and diverging pathways. By comparing neuroimaging and neurophysiological findings across the two conditions, we seek to deepen understanding of their shared mechanisms, clarify diagnostic boundaries, and inform the development of targeted, evidence-based interventions to address a critical gap in the field. Full article

Background/Objectives: Holocord astrocytomas are exceptionally rare intramedullary tumors, especially in adults, and often present with extensive longitudinal growth. Because only a small number of cases have been described, management strategies remain insufficiently defined. This report presents an adult patient treated with a staged surgical approach and provides an updated review of the literature. Methods: A 31-year-old male presented with progressive paraparesis, sensory deficits, and sphincter dysfunction. MRI demonstrated an intramedullary tumor extending from T3 to the conus medullaris. The patient underwent a planned two-stage resection with intraoperative neurophysiological monitoring. Histopathological and DNA-methylation analyses were performed. Additionally, a systematic review of previously reported holocord astrocytoma cases was conducted. Results: The two-stage surgical strategy enabled extensive debulking across multiple spinal segments while preserving neurological function. The patient demonstrated marked postoperative improvement, including restoration of sphincter control, improved motor function, and better mobility. Histopathological analyses confirmed a high-grade astrocytoma with piloid features. The literature review identified 28 previously reported cases, including only 5 in adults. Reported neurological outcomes across adult cases are variable, reflecting the heterogeneity and rarity of this tumor entity. Conclusions: Holocord astrocytomas in adults are extremely rare and pose particular diagnostic and therapeutic challenges. This case demonstrates that a carefully planned, staged surgical approach can achieve meaningful neurological recovery, even in patients presenting with severe preoperative deficits. The report expands the limited body of evidence available for adult holocord astrocytomas and may support future management strategies. Full article

Parkinson’s disease (PD) is a common neurodegenerative disorder characterized by motor dysfunction and non-motor symptoms, including cognitive decline. Animal models that replicate PD’s clinical features are essential for therapeutic research. The widely used subacute 1-methyl-4-phenyl-1,2,3,6tetrahydropyridine (MPTP)-induced mouse model effectively mimics motor deficits but fails to fully represent aging-related non-motor symptoms. In this study, we established an aging-associated PD mouse model by combining MPTP with D-galactose treatment. Compared to mice treated with MPTP alone, MPTP + D-galactose-treated mice exhibited typical motor impairments alongside cognitive deficits in the Morris water maze and Y-maze tests. D-galactose alone induced cognitive impairment without motor dysfunction. Pathological analysis showed that the MPTP + D-galactose treatment caused tyrosine hydroxylase-positive neuron loss similar to MPTP, while D-galactose did not damage these neurons. Additionally, Micro-CT revealed bone loss in both the MPTP + D-galactose and D-galactose groups. This model recapitulates both the motor and aging-related non-motor symptoms of PD, including cognitive impairment and bone loss, providing a more comprehensive tool for studying PD pathogenesis and evaluating potential therapies. Full article

Parkinson’s disease is the second leading neurodegenerative disease of aging. For over five decades, oral levodopa has been used to manage the progressive motor deficits that are the hallmark of the disease. However, individual dose requirements are highly variable, and patients typically require increased levodopa dosage as the disease progresses, which can cause undesirable side effects. It has become increasingly apparent that the gut microbiome can have a major impact on the metabolism and efficacy of therapeutic drugs. In this Perspective, we examine recent studies highlighting the impact of metabolism by Enterococcus faecalis, a common commensal gut bacterium, on levodopa bioavailability. E. faecalis expresses a highly conserved tyrosine decarboxylase that promiscuously converts levodopa to dopamine in the gut, resulting in decreased neuronal uptake of levodopa and reduced dopamine formation in the brain. Mitochondria-targeted antioxidants conjugated to a triphenylphosphonium moiety have shown promise in transiently suppressing the growth of E. faecalis and decreasing microbial levodopa metabolism, providing an approach to modulating the microbiome that is less perturbing than conventional antibiotics. Thus, mitigating metabolism by the gut microbiota is an attractive therapeutic target to preserve and potentiate the efficacy of oral levodopa therapy in Parkinson’s disease. Full article

Background/Objectives: Chronic psychomotor and cognitive slowing after stroke can persist despite standard rehabilitation, especially in young adults with subcortical injuries. Innovative, integrated interventions are crucial for patients who have reached a plateau in their rehabilitation. We present a case of a 41-year-old male with chronic psychomotor and cognitive slowing following a left lenticulostriate infarction (NIHSS score = 5 at onset), who had plateaued after conventional rehabilitation. Methods: Over 4 weeks the patient underwent 20 sessions of a multimodal approach including high-frequency repetitive transcranial magnetic resonance stimulation over the supplementary motor area and bilateral temporo-parietal junctions and simultaneous computerized cognitive training targeting attention and executive function. Both motor and cognitive assessments, along with quantitative EEG (qEEG) evaluations, were conducted before and after the treatment. Results: At the end of treatment, the patient showed significant clinical improvement: speed and coordination in upper extremities (Finger Tapping Test) increased by 66% (dominant hand) and 74% (non-dominant hand), while finger dexterity (Nine-Hole Peg Test) increased by 25% (dominant hand) and 19% (non-dominant hand). Cognitive scores improved in alertness (58%), visual exploration (25%), and flexibility (24%), while divided attention remained stable. qEEG investigation showed increases in alpha (79%), gamma (33%), and beta (10%) power, with topographic shifts in the stimulated regions. Conclusions: These findings highlight the feasibility of combining targeted rTMS and cognitive training to enhance neuroplasticity in the chronic phase of stroke. Clinical recovery was accompanied by normalized cortical rhythms, suggesting qEEG biomarkers may be useful for tracking treatment response. Multimodal precision neurorehabilitation may offer a path forward for patients with persistent cognitive–motor deficits post-stroke. Full article

Traumatic brain injury (TBI) often leads to long-lasting motor deficits, but the underlying cellular mechanisms still remain poorly understood. In this study, we examined glial and neuronal responses after focal cortical aspiration injury of the right hindlimb sensorimotor cortex in adult male rats. This is a model we have previously shown induces persistent gait asymmetry and postural deficits. Immunohistochemical analysis of activated microglia/macrophages (CD11b, IBA-1), astrocytes (GFAP), and neurons (NeuN) was performed bilaterally in the peri-lesional cortex at 3, 7, 14, 21, and 28 days post-injury (n = 3–6 per time point). The injury induced an early, sharply localized increase in CD11b-positive myeloid cells in the injured hemisphere, suggesting an activation of both resident microglia and infiltrating monocyte-derived cell. This was followed by a more sustained IBA-1-positive microglial activation that gradually extended contralaterally. Astrocytic activation showed a delayed but prolonged profile, rising ipsilaterally within the first week, peaking around two weeks, and becoming bilaterally elevated by four weeks. Sham-operated animals showed only basal glial immunoreactivity without signs of hypertrophy or reactive morphology at any time point. NeuN immunoreactivity remained stable across timepoints, suggesting preservation of neuronal soma labeling without evidence of overt secondary neuronal loss. These findings reveal a staged and spatially distinct glial response to focal cortical injury, with early myeloid activation, prolonged microglial reactivity, and delayed bilateral astrogliosis. Together, these findings are consistent with the possibility that persistent motor deficits after focal TBI arise from both primary tissue loss within the lesion core and peri-lesional glial remodeling, highlighting glial–neuronal interactions as a potential therapeutic target. Full article

Vision is fundamental to the acquisition of motor, cognitive, and social skills, playing a crucial role in typical development. Early visual impairments are associated with various neurodevelopmental conditions, including Autism Spectrum Disorder (ASD). The (Brain-specific serine/threonine-protein kinase 2, BRSK2) gene has been identified as a high-risk gene for ASD. This study aims to investigate the role of brsk2 in retinal photoreceptor development and visual function in zebrafish. Using behavioral assays, histological analysis, and transcriptomic profiling, we assessed the impact of brsk2 deletion on retinal structure and function. The results showed that brsk2ab^−/− zebrafish larvae exhibited significantly enhanced light perception compared to wild-type (WT) controls. Structural analysis of the retina revealed disruptions in the layered organization, along with up-regulated rhodopsin expression in retinal cells. Additionally, transcriptomic analysis indicated that key opsins and genes involved in visual development and phototransduction pathways were markedly up-regulated following brsk2 deletion. This research highlights the importance of brsk2 in early retinal circuit development and its potential implications for understanding sensory processing deficits in neurodevelopmental disorders. By linking BRSK2 to specific sensory phenotypes, this study addresses a critical gap in knowledge regarding the mechanisms underlying sensory abnormalities in ASD and related conditions. Full article

Diffusion tensor imaging (DTI) tractography is routinely employed in neurosurgical planning; however, the prognostic significance of quantitative DTI metrics for postoperative functional outcomes remains unclear. We conducted a PRISMA-informed systematic review of PubMed (January 2005–1 December 2025), supplemented by additional indexed sources, to synthesize the evidence on quantitative DTI measures associated with postoperative motor, language, and cognitive outcomes following intracranial surgery. Thirty-seven studies were included, primarily single-center studies, and predominantly focused on glioma surgery. Motor outcomes exhibited the most consistent associations, with reduced corticospinal tract integrity and adverse postoperative diffusion changes correlating with muscle weakness and poorer recovery. Recovery from supplementary motor area syndrome was associated with interhemispheric callosal connectivity, with greater disconnection predicting a prolonged symptom duration. Language outcomes demonstrated reproducible structure–function relationships: higher preoperative integrity of the dorsal language pathways was associated with milder postoperative aphasia and better recovery, whereas postoperative tract disruption and diffusivity changes predicted persistent naming and fluency deficits, and ventral pathway alterations were specifically linked to lexico-semantic impairment. In epilepsy surgery, language performance correlated with contralateral and distributed network diffusion changes, consistent with reorganization. Evidence for cognition and gait outcomes was limited and mainly involved the association, limbic, and callosal pathways. Overall, quantitative DTI provides clinically relevant markers of tract and network disruption and postoperative remodeling; however, methodological heterogeneity and limited external validation currently preclude universal prognostic thresholds. Full article

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by age-dependent degeneration of dopaminergic neurons in the substantia nigra, a process mediated by α-synuclein aggregation, mitochondrial dysfunction, and impaired proteostasis. While BAP31—an endoplasmic reticulum protein critical for protein trafficking and degradation—has been implicated in neuronal processes, its role in PD pathogenesis remains poorly understood. To investigate the impact of BAP31 deficiency on PD progression, we generated dopamine neuron-specific BAP31 conditional knockout with DAT-Cre (cKO) mice (Slc6a3cre-BAP31^fl/fl) and subjected them to MPTP-lesioned Parkinsonian models. Compared to BAP31^fl/fl controls, Slc6a3cre-BAP31^fl/fl mice exhibited exacerbated motor deficits following MPTP treatment, including impaired rotarod performance, reduced balance beam traversal time, and diminished climbing and voluntary motor capacity abilities. BAP31 conditional deletion showed no baseline phenotype, with deficits emerging only after MPTP. Our results indicate that these behavioral impairments correlated with neuropathological hallmarks: decreased NeuN neuronal counts, elevated GFAP astrogliosis, reduced tyrosine hydroxylase levels in the substantia nigra, and aggravated dopaminergic neurodegeneration. Mechanistically, BAP31 deficiency disrupted mitochondrial homeostasis by suppressing the PINK1–Parkin mitophagy pathway. Further analysis revealed that BAP31 regulates PINK1 transcription via the transcription factor Engrailed Homeobox 1. Collectively, our findings identify BAP31 as a neuroprotective modulator that mitigates PD-associated motor dysfunction by preserving mitochondrial stability, underscoring its therapeutic potential as a target for neurodegenerative disorders. Full article

Total hip arthroplasty (THA) is a widely performed procedure that significantly enhances patients’ quality of life. However, nerve injury remains a concerning complication, with an incidence ranging from 0.6% to 3.7%, depending on patient and surgical variables. This narrative review provides a comprehensive overview of nerve injuries associated with THA, focusing on etiology, risk factors, clinical manifestations, prevention, and treatment strategies. The most affected nerves include the sciatic, femoral, lateral femoral cutaneous (LFCN), superior gluteal, and obturator nerves. Anatomical factors such as developmental hip dysplasia (DDH), limb length discrepancy, and aberrant nerve courses, along with patient-specific conditions like female sex, obesity, and pre-existing spinal disorders, increase the risk of nerve damage. Surgical complexity, revision procedures, and surgeon experience also influence injury likelihood. Clinical manifestations range from sensory disturbances to motor deficits including foot drop, Trendelenburg gait, or impaired knee extension, depending on the nerve involved. Diagnosis is primarily clinical, supported by electrophysiological studies and imaging when needed. Prevention hinges on careful preoperative planning, appropriate surgical approach selection, meticulous intraoperative technique, and attention to limb positioning. Treatment is typically conservative, involving pain control, physical therapy, and neurostimulation. In refractory or severe cases, interventions such as nerve decompression, repair, or tendon transfer may be considered. Pharmacological agents including vitamin B12, tacrolimus, and melatonin show potential in promoting nerve regeneration. Although most nerve injuries resolve spontaneously or with conservative measures, some cases may result in long-term deficits. Understanding the mechanisms, risk factors, and management strategies is essential to mitigating complications and optimizing functional outcomes in patients undergoing THA. Full article

Background: Alcohol use disorder (AUD) is associated with chronic heavy or repeated binge alcohol abuse, which can cause alcohol-related brain damage (ARBD) marked by neurobehavioral, cognitive, and motor deficits. The anterior frontal lobe and cerebellar vermis are two of the major targets of ARBD in humans with AUD and in experimental alcohol exposed models. Alcohol’s neurotoxic and neurodegenerative effects include impairments in signaling through insulin and insulin-like growth factor (IGF) pathways that regulate energy metabolism. This human AUD study was inspired by a recent report suggesting that dysfunction of the frontal lobe incretin network in experimental ARBD is linked to known impairments in brain insulin/IGF signaling. Objective: The overarching goal was to investigate whether AUD is associated with dysfunction of the brain’s incretin network, focusing on the cerebellum and frontal lobe. Methods: Fresh frozen postmortem cerebellar vermis and anterior frontal lobe tissues from adult male AUD (n = 6) and control (n = 6) donors were processed for protein extraction. Duplex enzyme-linked immunosorbent assays (ELISAs) were used to assess immunoreactivity to neurofilament light chain (NfL) as a marker of neurodegeneration. A multiplex ELISA was used to measure immunoreactivity to a panel of gut hormones, including incretin polypeptides. Results: AUD was associated with significantly increased NfL immunoreactivity in both the cerebellar vermis and anterior frontal lobe. However, the patterns of AUD-related alterations in gut hormone immunoreactivity differed regionally. AUD reduced pancreatic polypeptide immunoreactivity in the cerebellar vermis, and GIP, GLP-1, leptin, and ghrelin in the frontal lobe. Conclusions: (1) Increased NfL may serve as a useful biomarker of neurodegeneration in AUD. (2) AUD’s adverse effects on neuroendocrine signaling networks differ in the cerebellar vermis and anterior frontal region, although both are significant targets of ARBD. (3) The finding of AUD-associated reductions in frontal lobe GIP and GLP-1 suggests that therapeutic targeting with incretin receptor agonists may help restore energy metabolism and neurobehavioral and cognitive functions linked to their networks. Full article