Ischemic stroke causes severe neurological disability, with some patients still presenting with residual neurological dysfunction. Aerobic exercise shows potential for post-stroke recovery. However, the mechanism behind its beneficial effects on the brain remains to be further explored. This study aimed to explore aerobic exercise's role in the neurological recovery of ischemic stroke mice and to clarify the specific protective mechanisms involved. A mouse model of ischemic stroke was employed in this study. Mice were subjected to aerobic exercise intervention, with additional exogenous lactate administration and RNA-sequencing (RNA-seq) analysis conducted to explore the molecular mechanisms. Results demonstrated that aerobic exercise significantly elevated protein lactylation levels in ischemic stroke mice and facilitated neurological recovery. In addition, aerobic exercise attenuated neuroinflammation in the ischemic penumbra and promoted neural cell proliferation in the subventricular zone. Mechanistically, aerobic exercise-induced lactylation of α-tubulin may enhance the dynamic properties of microtubules, thereby facilitating neural repair. Exogenous lactate intervention was found to augment α-tubulin lactylation, promote hippocampal neurogenesis, and increase dendritic spine density as well as synaptic plasticity in both the ischemic penumbra and hippocampus. Consistent with these findings, exogenous lactate administration improved neurological function in ischemic stroke mice. RNA-seq analysis further revealed that elevated lactate levels exerted a promotive effect on neural repair. Aerobic exercise promotes post-ischemic stroke neurological recovery via elevating protein lactylation (α-tubulin lactylation), attenuating neuroinflammation, and enhancing neural repair. These findings highlight the potential of targeting lactate metabolism and protein lactylation as therapeutic strategies for facilitating neural repair and improving neurological outcomes following ischemic stroke.
Climate change's impact on global health is increasingly recognized, with growing focus on its effects on the developing brain and on children with neurological disorders. This scoping review aims to update the evidence on climate change's effects on paediatric neurological disorders. A PRISMA-ScR-based protocol guided a systematic search across major databases (PubMed, Scopus, WoS, ClinicalTrials.gov, WHO ICTRP). We included all study types published in English up to September 2025 examining the impact of any climate-change related factor in children (0-18 years) with neurological disorders. Data extraction included study design, population, exposure/intervention and outcome variables. Out of 482 records, 17 studies met the inclusion criteria, involving over 340,000 children (54.6% male, in studies reporting sex distribution) across Asia, Africa, North America, and Europe. A total of 15 out of 17 studies were observational (OCEBM level 3-4). Epilepsy and seizures were the most frequently investigated conditions (8/17 studies). Extreme heat triggered immediate increases in hospitalisations, while cold exposure showed delayed but prolonged effects (up to 21 days). Temperature variability and air pollution further amplified seizure risk. Winter storms disrupted medication access which led to seizure worsening. Other studies (5/17 studies) linked meningitis and encephalitis incidence to high temperatures, humidity, and seasonal variability, particularly in low-resource settings. Sunlight and humidity were common migraine triggers, and cold-related illness was differentially co-diagnosed across behavioural health disorders groups. Prenatal and early childhood exposure to temperature extremes was associated with altered white matter development on MRI in one study. Across conditions, children in socioeconomically disadvantaged settings consistently emerged as the most vulnerable. Current evidence suggests that climate change-related exposures, particularly extreme temperatures, temperature variability, and natural disasters, negatively affect paediatric neurological health directly (increased seizure risk, impaired myelination) and indirectly (disrupted treatment access, emotional stress). Neuroinfectious diseases were also strongly associated with climatic variability, disproportionately affecting children in low-income areas. However, findings remain fragmented, heterogeneous, and largely context-specific, underscoring the urgent need for multicentric studies with harmonised methodologies and stronger longitudinal designs to clarify causal pathways and guide preventive strategies.
Infection is a significant complication of CSF shunt surgery, with most infections occurring early in the postoperative course. While standardized perioperative protocols have successfully reduced early infections, the epidemiology, risk factors, and clinical patterns of late shunt infections are poorly characterized. This study aimed to determine the incidence, risk factors, clinical features, and outcomes of late shunt infections in a large, multicenter pediatric cohort. The Hydrocephalus Clinical Research Network (HCRN) Core Data Project was queried for all CSF shunt procedures performed between November 2016 and June 2023 in patients younger than 18 years. Each shunt surgery was treated as an index surgery, defined as the starting point for subsequent infection surveillance. Shunt surgeries were assigned to one of the following categories: no infection, early infection (≤ 6 months after the surgery), or late infection (> 6 months after the surgery). Demographic, operative, and clinical features of early versus late infections were compared, and Cox proportional hazards models were developed to assess shunt survival following early versus late infections. Of 6698 shunt procedures, 285 (4.3%) were followed by early infections and 58 (0.9%) by late infections. Late infections accounted for 16.9% of all shunt infections. Late infections were significantly more likely than early infections to be associated with abdominal pseudocysts (24.1% vs 3.5%, p < 0.001) and less likely to be diagnosed via CSF culture (53.4% vs 78.6%, p < 0.001). Clinical events that took place between the shunt surgery and the late infection included abdominal surgeries (21.4%), shunt taps (23.2%), bacteremia (9.1%), and nonoperative abdominal processes requiring hospitalization (19.6%). Vancomycin was administered less frequently in the late infection group (62.1% vs 85.3%, p < 0.001), and shunts were less likely to be initially treated with complete shunt removal (65.5% vs 88.4%, p < 0.001) and more likely to be initially managed with externalization of the distal catheter alone (34.5% vs 11.6%, p < 0.001). Shunt survival after infection did not differ significantly between early and late infections. Late CSF shunt infections are uncommon but clinically distinct from early infections and are often associated with heterogeneous secondary exposures not addressed by perioperative protocols. These findings highlight the need for long-term surveillance in patients with shunts, tailored diagnostic strategies, and expanded infection tracking efforts.
Cerebral hemangioma is a recognized cause of acute onset of epileptic seizures with interictal neurological abnormalities in dogs, although the number of cases reported is limited. Hemangiomas can affect dogs of all age groups, but there is an increasing risk with age, peaking at nine years. This case report describes a 5-month-old female Chow Chow dog with an acute onset of epileptic seizures and interictal neurological deficits indicative of a right forebrain lesion due to a cerebral hemangioma and associated hemorrhage. Initially, extracranial causes were excluded, and magnetic resonance imaging of the head was performed, revealing a large well-delineated hemorrhagic mixed intra- and extra axial lobular mass in the right frontal lobe, generalized ventriculomegaly, and two intraventricular smaller, well-defined cyst-like structures in the right cerebellopontine angle and fourth ventricle. The dog was euthanized due to the severity of neurological deficits combined with imaging findings, suggesting a poor prognosis. Post-mortem gross examination, histopathology, and immunohistochemistry identified the larger structure as a hemangioma accompanied by extensive hemorrhage. The significant hemorrhage likely explained the acute onset of neurological signs. It is probable that the hemangioma might have remained subclinical, had this hemorrhage not occurred. The smaller cyst-like structures were identified as multilocular ependymal diverticula originating from the fourth ventricle. This case report underlines the importance of considering cerebral hemangiomas accompanied by acute hemorrhage as a possible differential diagnosis in cases with an acute onset of epileptic cluster seizures with accompanying interictal neurological signs, here found in a juvenile dog.
Traumatic brain injury (TBI) can result in prolonged post-concussive syndrome and chronic hypoxic-ischemic brain injury (HIBI) sequelae remains therapeutically challenging with the persistence of significant neurological and cognitive impairments. While conventional treatments often provide limited relief, emerging research explores alternative therapeutic interventions, including psychedelic compounds combined with therapeutic interventions. This naturalistic case series examines clinical observations following an integrative, participant-directed iboga-containing microdosing protocol paired with Accelerated Experiential Dynamic Psychotherapy (AEDP) in three individuals with persistent neurologic symptoms after traumatic brain injury (TBI) or hypoxic-ischemic brain injury. Three participants completed a 6 week protocol using Tabernanthe iboga root bark biomass (participant-directed titration 0.1-1.0 g/day, 4 days-on/3 days-off). Quantitative qNMR/HPLC analysis (University of Cape Town) demonstrated approximately 3.845% ibogaine content by mass, yielding estimated ibogaine-equivalent exposure of 3.8-38.5 mg/day. All administration utilized whole root bark biomass only. Weekly AEDP psychotherapy and supportive nutraceuticals were provided concurrently. A 43 year-old man with TBI sustained in a motorcycle accident. Patient Two: A 40-year-old woman with chronic hypoxic brain injury sustained during an avalanche burial event. Patient Three: A 19 year old woman with TBI sustained in a motor vehicle accident. All three patients demonstrated progressive neurological recovery over the 6-week microdosing iboga protocol with two of the patients declaring complete symptom remission at a long term follow up assessment. Initial reported symptoms included a constellation of daily headaches, episodic migraines, disequilibrium, irritability, mood swings, fatigue, brain fog, sleep disruptions, and loss of interest in typical life activities. At the conclusion of the protocol, and at long term follow-up visits, patients felt able to discontinue all prescription medications for symptomatic treatment, reporting absence of severe migraine headaches, resolution of brain fog, fatigue, irritability, and stabilized mood, with the ability to return all regular activities with a renewed enthusiasm for life. All patients provided consent to share their significant clinical and therapeutic improvement journey in this publication. The microdosing protocol was carefully implemented with rigorous screening to mitigate potential cardiac and neurological risks associated with iboga administration, including medical background screening for potential drug interactions, and past medical history contraindications including heart conditions and/or the concomitant administration of selective serotonin reuptake inhibitors (SSRIs). This naturalistic case series provides hypothesis-generating observations regarding possible clinical improvement following an integrative iboga-containing intervention paired with psychotherapeutic and supportive care. The findings do not establish causality or iboga-specific efficacy and should be interpreted within the context of multimodal therapeutic exposure and substantial methodological limitations. These preliminary observations suggest that an integrative iboga microdosing protocol, in association with psychotherapeutic and supportive care, may be linked to meaningful improvements in prolonged post-concussive symptoms. As a hypothesis-generating case series, these findings warrant further investigation in controlled trials to establish causality and specificity.
The purpose of this study was to review the assessment of residual tumor, analyze surgical factors associated with incomplete resection, determine the risk of neurological sequelae for reoperation, and assess the impact of second surgeries on survival. Patients 0-21 years old with nonmetastatic intracranial ependymoma treated within the prospective multicenter E-HIT2000 trial were included. Prospective central neuroradiological review of pre- and postoperative imaging was performed. The 291 patients included in the E-HIT2000 trial underwent surgery at 71 centers in Germany, Austria, and Switzerland. Timely central review of postoperative imaging of sufficient quality was performed in 206 patients, and extent of resection was classified as gross-total resection (GTR) in 137 (67%) patients and incomplete with residual disease (RD) in 69 (33%) patients. Surgeons erroneously reported GTR in 11/40 patients with RD and available surgical reports; adhesions in the rhomboid fossa and/or brainstem were the most common reasons for intentional RD. Twenty-three of the 69 patients with RD underwent a second surgery as part of their primary treatment, 11 before and 12 after the start of adjuvant therapy; in 11/23 patients, GTR was achieved after a maximum of 3 procedures. The frequency of postoperative neurological deficits in the patients with second surgery did not differ from that in patients with primary GTR. Ten-year overall survival with GTR was 69.8% ± 4.4% versus 51.2% ± 7.1% with RD (p = 0.002). A second surgery significantly improved progression-free survival (42.4% ± 11.5% vs 22.2% ± 6.5% without second surgery, p = 0.004). Second surgery was not associated with an increased frequency of neurological sequelae and conferred an advantage in survival overall. The authors strongly recommend early central neuroradiological review to evaluate postoperative residual tumor and discuss reoperation. Further studies are needed to outline a tailored risk assessment for each patient based on molecular and clinical aspects.
Neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are rare autoimmune disorders. Their true prevalence in Germany is unknown and can only be estimated from heterogeneous international data. Assuming 1-3 cases per 100,000 people for each disease suggests several thousand affected individuals nationwide, yet the German Neuromyelitis Optica Study Group (NEMOS) registry currently holds records of only about 1,300 patients seen in specialised centres. Numbers and care structures outside such facilities remain largely unknown. This survey aimed to assess the current state of NMOSD and MOGAD care in Germany, identify gaps, and inform future care strategies. An online questionnaire aimed at neurologists and neuropaediatricians was distributed via NEMOS, the German Neurological Society (DGN), the Professional Association of German Neurologists (BVDN), and the German Network for Research on Autoimmune Encephalitis (GENERATE) from March to May 2025. Questions addressed care structures, diagnostics, coding, treatment, guideline use, and practitioners' needs. A total of 104 physicians from all German federal states participated. Half worked in university hospitals, the remainder in other clinics and outpatient settings. Most were specialised in neuroimmunology (70.2%). Many reported an increase in patient numbers for NMOSD (55.8%) and MOGAD (77.4%). Diagnostic practices revealed significant inconsistencies: almost half of the respondents were unaware of their referral laboratory's antibody assays, and ELISA remained in use despite clear recommendations for cell-based assays. ICD-10 coding varied widely. Off-label rituximab was most frequently used for first-line therapy of AQP4-antibody-positive NMOSD (69.6%), compared to satralizumab (57.1%), ravulizumab (55.4%) and inebilizumab (50.0%). AQP4-antibody-negative NMOSD was mainly treated with rituximab (87.0%). Also in MOGAD, rituximab was frequently used (by 58.9%), yet paediatricians preferred glucocorticoids and intravenous immunoglobulins. 69.6% initiated treatment for MOGAD after the first attack. Notably, 41.8% of physicians reported untreated NMOSD and 64.6% untreated MOGAD patients. Most respondents relied on national guidelines; 43.2% expressed a need for further education and patient information. Our findings highlight substantial heterogeneity in the diagnosis and treatment of NMOSD and MOGAD in Germany with potential implications for patient outcomes. This underscores the need for harmonised procedures and targeted educational resources to improve diagnostic reliability, treatment equity, and overall quality of care.
Sophisticated hand movements are essential for daily activities, but central neurological impairments often compromise them. Since full recovery through conventional physiotherapy is rare, assistance is crucial. While neural implants show promise, clinical use remains distant, urging immediate assistive alternatives. Current exoskeletons and neurostimulation garments lack sufficient motor support and sensory feedback, limiting dexterity. We developed a neurorobotic system combining portable exoskeletons with targeted neurostimulation via custom-made e-sleeve and tested it in 14 individuals with central neural injuries. We provide evidence of restored finger mobility and tactile perception, even in patients with clinically complete sensory loss, by recruiting residual peripheral pathways. Eight participants completed functional assessments, in which they exploited neurostimulation to improve grasp precision and enhance strength. This enabled manipulation of fragile and cumbersome objects, essential for everyday activities. Personalized assistive technologies have clinical potential to promote independence and support the reintegration of people with neurological impairments into society.
Benzothiadiazine derivatives are an important class of sulfur-nitrogen heterocycles widely recognized in medicinal chemistry for their structural flexibility and varied biological effects. This review highlights recent developments in the synthesis of benzothiadiazine-derived compounds, including 1-oxides, 1,1-dioxides, and newly explored 1-imines. It focuses on contemporary synthetic methods, including transition-metal catalysis, cascade reactions, heterogeneous catalysis (polyoxometalates and metal-organic frameworks), and environmentally friendly metal-free approaches. The review discusses the scope, effectiveness, and limitations of these techniques, alongside their key biological applications in cardiovascular, anticancer, antiviral, and neurological fields. Additionally, it underscores existing challenges and future research directions to foster the development of more efficient and sustainable synthetic strategies.
Soft robotic systems have become a promising technology in the biomedical field due to their higher safety, dexterity and adaptability compared to traditional rigid robotic systems. This review focuses on recent advances in soft robotic systems applied to surgical assistance and rehabilitation. In surgery, soft grippers and flexible endoscopes show better adaptability, dexterity, and miniaturization, enabling safer and more precise manipulation of delicate tissues. In rehabilitation, wearable soft devices show great potential to help patients with neurological injuries to regain movement. Key innovations in actuation technology are examined, along with recent advances in multifunctional, self-healing, and environmentally responsive materials. Meanwhile, sensing systems are evolving from unimodal sensing to multimodal fusion, self-perception, and sense-drive integration, enabling robots to sense the body state and external environment with higher accuracy and realize closed-loop control. Finally, this paper points out that soft robots still face key challenges such as material durability, biosafety, and stability during clinical translation. In the future, the focus should be on the construction of systems with self-diagnosis, self-adaptive adjustment and closed-loop control, and promote the efficient landing and personalized application of soft robots from experimental research to real medical scenarios.
Emerging evidence indicates that early-life lung injuries-including bronchopulmonary dysplasia, childhood asthma, recurrent respiratory infections, and environmental tobacco smoke exposure-are significantly associated with an increased risk of neurodevelopmental disorders such as cognitive impairment, autism spectrum disorder, attention-deficit/hyperactivity disorder, and emotional or behavioral affections. The developing brain is particularly vulnerable during infancy and childhood, and pulmonary insults during this critical window may disrupt normal neurodevelopment through multiple interconnected mechanisms along the lung-brain axis. These mechanisms include the hypoxia-oxidative stress axis, which impairs oligodendrocyte maturation and myelination; pulmonary microvascular injury leading to neuronal energy metabolism dysregulation; systemic inflammation-mediated disruption of the blood-brain barrier; and a cascade from pulmonary inflammation to neuroinflammation, characterized by microglial activation, synaptic dysfunction, and impaired myelination. Together, these pathways converge to produce long-lasting neurodevelopmental consequences. Understanding the lung-brain axis provides a novel theoretical framework for explaining this comorbidity and highlights the need to integrate neurodevelopmental risk assessment and early intervention into the clinical management of early-life lung diseases. Future research should focus on longitudinal cohorts, identification of critical developmental windows, and targeted therapeutic strategies that address both pulmonary and neurological health.
Inborn errors of metabolism (IEM) are a diverse group of inherited disorders resulting from defects in enzymes, transporters, or cofactors involved in essential metabolic pathways. These defects disrupt normal biochemical processes, leading to the accumulation of toxic metabolites, deficiency of vital compounds, or impaired energy production. Although individually rare, IEM collectively contribute significantly to morbidity and mortality, particularly in neonates and children. The clinical presentation is highly variable, ranging from acute metabolic crises in the neonatal period to chronic or late-onset manifestations. Common features include developmental delay, neurological impairment, metabolic acidosis, hypoglycemia, hyperammonemia, and dysfunction of organs such as the liver, heart, and muscles. Due to their nonspecific presentation, early diagnosis remains challenging and requires a high index of clinical suspicion. Advancements in diagnostic techniques, including plasma amino acid analysis; urine organic acid profiling; acylcarnitine analysis; and molecular genetic testing, have improved the accuracy of diagnosis. Expanded newborn screening using tandem mass spectrometry has enabled early detection and timely intervention, significantly improving outcomes. Management of IEM is disorder-specific and includes dietary modifications, pharmacological therapy, and enzyme replacement. Emerging therapies such as gene therapy offer promising future prospects. Despite these advances, challenges in diagnosis, treatment accessibility, and long-term care persist, highlighting the need for continued research and improved healthcare strategies. RésuméLes erreurs innées du métabolisme (EIM) constituent un groupe hétérogène de maladies héréditaires dues à des anomalies enzymatiques, de transporteurs ou de cofacteurs impliqués dans les voies métaboliques essentielles. Ces anomalies perturbent les processus biochimiques normaux, entraînant l’accumulation de métabolites toxiques, des carences en composés vitaux ou une production d’énergie altérée. Bien que rares individuellement, les EIM contribuent collectivement de manière significative à la morbidité et à la mortalité, en particulier chez les nouveau-nés et les enfants. Le tableau clinique est très variable, allant de crises métaboliques aiguës en période néonatale à des manifestations chroniques ou d’apparition tardive. Les symptômes fréquents comprennent un retard de développement, des troubles neurologiques, une acidose métabolique, une hypoglycémie, une hyperammoniémie et des dysfonctionnements d’organes tels que le foie, le cœur et les muscles. En raison de leur présentation non spécifique, le diagnostic précoce demeure complexe et exige une forte suspicion clinique. Les progrès des techniques diagnostiques, notamment l’analyse des acides aminés plasmatiques, le profilage des acides organiques urinaires, l’analyse des acylcarnitines et les tests de génétique moléculaire, ont amélioré la précision du diagnostic. L’élargissement du dépistage néonatal par spectrométrie de masse en tandem a permis une détection précoce et une intervention rapide, améliorant significativement le pronostic. La prise en charge des erreurs innées du métabolisme (EIM) est spécifique à chaque maladie et comprend des modifications alimentaires, un traitement pharmacologique et une enzymothérapie substitutive. Les thérapies émergentes, telles que la thérapie génique, offrent des perspectives d’avenir prometteuses. Malgré ces progrès, des difficultés persistent en matière de diagnostic, d’accès aux traitements et de suivi à long terme, soulignant la nécessité de poursuivre les recherches et d’améliorer les stratégies de soins de santé.
Introduction  Recurrent neurological symptoms following thrombolysis in acute ischemic stroke (AIS) pose treatment challenges due to limited evidence guiding antiplatelet therapy. Current practices vary across institutions, reflecting a lack of standardized recommendations. This study uses the TriNetX US Collaborative Network to compare the safety and efficacy of dual antiplatelet therapy (DAPT) versus aspirin monotherapy (AM) in this patient population. Materials and methods  This retrospective study analyzed de-identified electronic health records from the TriNetX US Collaborative Network, comprising over 66 hospitals. Adult patients aged ≥18 years with AIS who underwent thrombolysis within 4.5 hours of symptom onset between January 2015 and December 2023 were identified. Patients who developed recurrent neurological symptoms between one and 30 days post-thrombolysis and were subsequently treated with either aspirin alone or DAPT (aspirin plus clopidogrel) were included. The following two treatment groups were compared: AM and DAPT. Propensity score matching was performed to balance baseline characteristics between groups. The primary efficacy endpoint was recurrent ischemic stroke between 30 and 90 days, and primary safety endpoints were symptomatic intracranial hemorrhage (SICH) and 90-day all-cause mortality. Outcomes were evaluated using odds ratios and adjusted odds ratios, with statistical significance set at two-sided p<0.05. Results In this study, 2,502 patients met the inclusion criteria. After propensity-score matching, 889 patients were included in each treatment group. The incidence of recurrent ischemic stroke was similar between both groups (12.2% in the AM group and 12.6% in the DAPT group). The SICH rate was identical in both cohorts (1.1%). The DAPT cohort had a minor reduction in 90-day mortality compared to the AM cohort (1.6% vs 2.5%), although it was non-significant. Conclusion In AIS patients who develop recurrent symptoms after thrombolysis, DAPT did not demonstrate a significant advantage compared to AM in reducing recurrent stroke, SICH, or 90-day mortality. These findings support no observed benefit of routine DAPT escalation in this clinical context and support the need for prospective studies to guide management.
Yolk sac tumors (YSTs) are highly malignant germ cell neoplasms, most commonly arising in the gonads. Intracranial involvement is exceptionally rare and typically affects the pineal or suprasellar regions. Metastatic YST presenting as a hemorrhagic brain lesion is an exceedingly unusual occurrence that poses significant diagnostic and therapeutic challenges. We report the case of a 26-year-old male who presented with rapidly progressive left-sided weakness and headache. Imaging revealed a right frontoparietal hemorrhagic mass with marked vasogenic edema and midline shift. The patient underwent urgent right frontal craniotomy and near-total tumor excision via a transsulcal approach. Postoperatively, neurological recovery was rapid, with near-complete motor improvement within days. Systemic evaluation revealed multiple pulmonary and para-aortic metastases and an enlarged right testis. Serum α-fetoprotein (AFP) was markedly elevated, and histopathological examination confirmed the diagnosis of YST. The patient received adjuvant chemotherapy, followed by radical orchidectomy and lymph node dissection, achieving normalization of AFP and full functional recovery at one year of follow-up. This case underscores the importance of considering germ cell tumors in the differential diagnosis of hemorrhagic brain lesions, particularly in young males. Early surgical intervention, combined with systemic chemotherapy, can lead to favorable neurological and oncologic outcomes even in such rare and aggressive presentations.
Degenerative cervical myelopathy (DCM) is a leading cause of nontraumatic spinal cord dysfunction. While posterior cervical decompression and fusion (PCDF) effectively improves neurological symptoms, persistent axial neck pain remains a common postoperative challenge. This prospective study evaluated the impact of postoperative cervical sagittal alignment on achieving the minimal clinically important difference (MCID) for axial neck pain eighteen months following PCDF for DCM. We conducted a single-center prospective cohort study including adult patients undergoing primary PCDF for DCM. Comprehensive clinical and radiographic data were collected preoperatively and at multiple postoperative intervals up to eighteen months. Key radiographic parameters evaluated included C2-C7 sagittal vertical axis (SVA), cervical lordosis (CL), and T1 slope minus cervical lordosis (TS-CL) mismatch. Multivariable logistic regression was utilized to identify independent predictors for achieving MCID. Fifty-five patients were included, with a mean follow-up of 20.4 months. Twenty-four patients (43.6%) successfully achieved MCID for axial neck pain. The MCID cohort exhibited significantly lower postoperative C2-C7 SVA, greater CL, and a smaller TS-CL mismatch. Multivariable analysis demonstrated that increased postoperative SVA and active opium addiction independently reduced the odds of achieving MCID. Furthermore, patients with "balanced" postoperative alignment (C2-C7 SVA < 40 mm and TS-CL < 15°) demonstrated significantly superior improvements in Visual Analog Scale (VAS) pain, Neck Disability Index (NDI), and modified Japanese Orthopedic Association (mJOA) scores. Postoperative cervical sagittal balance is a critical determinant of patient-reported outcomes and neurological recovery after PCDF. Minimizing postoperative SVA and addressing TS-CL mismatch significantly increases the likelihood of achieving clinically meaningful relief of axial neck pain and improves overall functional recovery.
Cervical dumbbell tumors present surgical challenges due to their proximity to critical structures, including the facet joints and vertebral artery (VA). Conventional posterior approaches often require facet joint resection and fusion, risking spinal instability. This study summarizes the authors' experience with a lateral foraminal approach that preserves facet integrity through a minimally invasive corridor. The lateral foraminal approach begins with an incision along the lateral border of the sternocleidomastoid, proceeding obliquely "outside-in" through the interscalene space between the scalene muscles. Depending on the specific spinal level and corresponding orientation of the intervertebral foramen, this surgical concept incorporates both the anterolateral approach (C2-3 to C7-T1) and the posterolateral approach (C1-2 and occasionally C2-3). The study comprised 30 males and 25 females with a median (range) age of 45 (11-69) years. The tumors were located from C1-2 to C7-T1 intervertebral foramina. Gross-total resection with preserved facet joint integrity was achieved in all cases, with visualization safeguarding brachial plexus and VA integrity during resection. Surgery resulted in significant improvements in neurological function and pain, with mean Japanese Orthopaedic Association (JOA) scores increasing from 13.3 to 15.1 (p < 0.001) and mean visual analog scale (VAS) scores decreasing from 4.3 to 2.4 (p < 0.001). The lateral foraminal approach is a minimally invasive technique for resecting cervical dumbbell tumors via an anatomical corridor. It preserves the facet joint entirely, eliminating the need for internal fixation or fusion. Under direct visualization, the brachial plexus and VA are microsurgically protected throughout dissection.
Sjögren disease (SjD) is a chronic systemic autoimmune disorder characterized by immune-mediated destruction of moisture-producing glands (e.g. tears/saliva), leading to dryness. It also affects organs outside the glands, reflecting its systemic nature. Neurologic involvement is a common complication of SjD that can occur in up to 20% of SjD patients. Neurological manifestations in SjD span the central, peripheral, and autonomic systems, with the highest incidence of involvement occurring within the peripheral nervous system (PNS). The heterogeneity of neurologic manifestations in SjD complicates the diagnosis and treatment, which should be directed toward the underlying neuropathologic mechanism which is often unclear. Optimizing the diagnosis, evaluation, and management of these manifestations is essential to prevent severe disability and to design more effective clinical trials. In this review, we summarize the current understanding of SjD-related peripheral neuropathies. By detailing their specific pathogenetic mechanisms, we advocate for a targeted diagnostic and therapeutic framework designed to improve long-term patient outcomes.
Whether differences in sex hormones influence cancer risk in men remains uncertain. We aimed to clarify the association of circulating testosterone, sex hormone-binding globulin (SHBG), and related hormones with risks of cancer death, incident cancer, and incident prostate cancer by means of individual participant data (IPD) meta-analyses. A systematic review of the literature using MEDLINE, Embase, OpenGrey, and Mednar was conducted from date of database inception till July 22, 2019, with bridge searches using MEDLINE till Jan 21, 2026. Prospective cohort studies comprising 1000 or more community-dwelling men with testosterone concentrations measured using mass spectrometry and a follow-up of 5 years or more were included. Two-stage random-effects meta-analyses were performed, controlling for baseline age, previous cancer, BMI, marital status, alcohol consumption, smoking status, physical activity, hypertension status, and diabetes status. Risk of bias was assessed using the Newcastle-Ottawa method. This study was prospectively registered with PROSPERO (CRD42019139668). Ten studies provided IPD (24 510 men; 276 931 participant-years; 2847 cancer deaths), and one provided aggregate data (1535 men; 184 cancer deaths). Five studies provided IPD for incident prostate cancer (12 280 men; 151 373 participant-years; 918 events). Lower total testosterone concentrations were associated with higher risk of cancer death (median of first vs median of fifth quintile [Q1:Q5] hazard ratio [HR] 1·18, 95% CI 1·04-1·34), as were lower dihydrotestosterone concentrations (Q1:Q5 1·21, 1·06-1·38), the risk increasing with testosterone concentrations less than 8.6 nmol/L. SHBG and luteinising hormone concentrations were non-linearly associated with risk of cancer death (lowest risk: SHBG Q3:Q5 HR 0·81, 95% CI 0·68-0·97; luteinising hormone Q2:Q5 0·73, 0·59-0·90). Men with very low baseline testosterone concentrations had a higher risk of incident cancer, the risk increasing with concentrations less than 7.3 nmol/L. Lower SHBG or lower luteinising hormone concentrations were associated with higher risk of incident prostate cancer (Q1:Q5 HR 1·28, 95% CI 1·07-1·54; Q1:Q5 1·45, 1·13-1·86); testosterone was not associated with this outcome. Estimates of I2 indicated negligible to moderate heterogeneity across most analyses. Lower total testosterone or dihydrotestosterone concentrations in men were associated with a higher risk of cancer death, and mid-range SHBG or luteinising hormone concentrations were associated with a lower risk. Men with lower SHBG or luteinising hormone concentrations had an associated higher risk of incident prostate cancer. Sex hormones could serve as biomarkers for cancer risk, warranting further investigation of these observed associations. Medical Research Future Fund; Government of Western Australia; Lawley Pharmaceuticals.
Post-stroke cognitive impairment (PSCI) significantly impacts patients' quality of life following a stroke. Its effects on white matter functional networks remain unclear. This study used resting-state functional MRI to examine alterations in white matter functional connectivity and spontaneous activity in this condition. Resting-state functional MRI data were acquired from PSCI (n = 21), non-PSCI (PSNCI, n = 16), and healthy subjects (HSs, n = 29). A clustering analysis was employed to identify white matter functional networks. Functional connectivity and the amplitude of low-frequency fluctuation within these networks were compared across groups. Correlation analyses assessed their relationships with neuropsychological scores. Sixteen stable white matter networks were identified. Both patient groups showed reduced functional connectivity between the inferior longitudinal fasciculus and anterior cingulum compared to HSs. PSCI patients also exhibited decreased functional connectivity between the anterior and posterior cingulum compared to HSs. Furthermore, the amplitude of low-frequency fluctuation in the posterior cingulum was lower in PSCI group than in PSNCI group. These altered metrics showed correlations with neuropsychological performance across multiple cognitive domains. This study identified alterations in functional connectivity and spontaneous activity within specific WM networks in PSCI, which were associated with cognitive performance. These findings suggest that white matter functional abnormalities may be involved in the neural mechanisms underlying PSCI and could inform future research on early identification.
Mucolipidosis II (MLII) is a severe lysosomal disorder caused by loss of GlcNAc-1-phosphotransferase activity, leading to defective mannose-6-phosphate (M6P) tagging and subsequently misrouting of M6P-dependent lysosomal hydrolases, and progressive multi-organ pathology. We generated a Gnptab p.R364X knock-in mouse model of MLII, which recapitulated the biochemical, skeletal, visceral, and neurological features of human MLII. Proteomic analysis of lysosomes isolated from MLII fibroblasts by LysoIP showed depletion or decrease of M6P-dependent hydrolases, upregulation of M6P-independent enzymes, and increased abundance of lysosomal membrane proteins. Zoledronic acid treatment increased both M6P-dependent and M6P-independent luminal hydrolases, and reduced glycosaminoglycan storage in MLII skin fibroblasts. Besides skeletal density improvement, Zoledronic acid, administered from 4 to 24 weeks to MLII mice, ameliorated multiple system manifestations, including articular cartilage degeneration, motor impairment, hepatomegaly, along with decreased urinary heparan sulfate and brain neuroinflammation. Our findings demonstrate that zoledronic acid ameliorates multiple system pathologies in MLII mice, which may be mediated, at least in part, through partial restoration of M6P-dependent proteins within lysosomes.