Atlanto-occipital assimilation (AOA), also known as atlas occipitalization, is a rare congenital craniovertebral junction anomaly characterized by partial or complete fusion of the atlas with the occipital bone. It often remains asymptomatic until adulthood, and presentation in childhood is rare. We report a nine-year-old boy with partial AOA who developed early-onset neurological symptoms. He presented with a one-year history of intermittent neck pain and transient right-hand clumsiness and numbness, which were provoked by neck extension. Imaging demonstrated a C1 hemiring, partial right-sided AOA, mild basilar invagination with the odontoid tip extending 6 mm above Chamberlain's line, mild occiput-C1 instability, and dynamic C1-C2 instability. MRI showed ventral cervicomedullary indentation without associated medullary signal abnormality, and the clivo-axial angle (CXA) was reduced to approximately 117°. No other associated congenital anomalies were identified. Given the early neurological involvement, dynamic instability, and pathological clivo-axial angulation, occipitocervical fusion was performed using an occipital plate, C2 pedicle screws, and an autologous rib graft, without significant donor-site morbidity. The patient recovered uneventfully, with complete symptom resolution and preserved functional neck mobility. Six-month follow-up imaging confirmed stable instrumentation. This case highlights that neurological symptoms may occur in children with AOA even without marked static cord compression when dynamic instability and pathological clivo-axial angulation are present. Early stabilization may help prevent irreversible neurological deterioration in carefully selected pediatric patients.
Bismuth subsalicylate is a widely available over-the-counter medication commonly used for gastrointestinal symptoms. Although generally considered safe, prolonged use can result in systemic toxicity, including severe neurological manifestations that are often underrecognized. We report the case of a 77-year-old man with microscopic colitis, lymphocytic subtype, who developed progressive encephalopathy, proximal muscle weakness, tremor, and gait instability after more than two years of daily bismuth subsalicylate use. His clinical course was marked by fluctuating neurological symptoms, multiple hospitalizations, extensive negative diagnostic evaluations, and an initial misdiagnosis of a Parkinsonian disorder. Serum testing ultimately revealed markedly elevated bismuth levels. Discontinuation of bismuth subsalicylate and supportive care resulted in gradual clinical improvement, with normalization of serum bismuth levels and gradual neurological recovery over several months. This case highlights the diagnostic challenges associated with bismuth-induced neurotoxicity and underscores the importance of thorough medication reconciliation, including over-the-counter agents. Increased clinician awareness is critical, as prompt recognition and discontinuation of bismuth-containing products can lead to substantial neurological recovery and prevent unnecessary diagnostic interventions.
This study investigated changes in neurological grades and plasma biomarker levels, including hypoxia-inducible factor-1α (HIF-1α), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and total plasma NAD(H) levels, in dogs with thoracolumbar intervertebral disc disease (TL-IVDD) undergoing acupuncture treatment. A total of 46 treatment episodes from 36 dogs with TL-IVDD were included in the neurological assessment. Plasma biomarker analyses were performed using available paired samples after exclusion of missing values and incomplete paired observations. Neurological grades improved after acupuncture treatment, with significant reductions observed in dogs treated with electroacupuncture during both the acute and preventive phases. Plasma TNF-α concentrations showed significant treatment period-, disease phase-, and treatment method-dependent changes, with significant Pre-Post differences observed in the electroacupuncture group during both phases. Plasma IL-6 concentrations showed more limited changes, with a significant Pre-Post difference detected only in the classical needle acupuncture group during the acute phase. In contrast, total plasma NAD(H) levels and plasma HIF-1α concentrations did not show significant treatment-related changes. These findings suggest that acupuncture treatment, particularly electroacupuncture, was associated with neurological improvement in dogs with TL-IVDD, and that TNF-α may reflect phase- and method-dependent inflammatory responses after acupuncture treatment. Plasma IL-6, total plasma NAD(H) levels, and HIF-1α should be interpreted as exploratory biomarkers in this clinical setting.
Cardiac disease is a leading cause of arterial ischaemic stroke (AIS) in children, yet data on paediatric cardioembolic stroke remain limited. This study investigated the incidence rate, underlying cardiac diseases and outcome of paediatric cardioembolic stroke in Denmark. In a nationwide registry, we identified all children with a stroke or stroke-related diagnosis (2013-2020). Arterial ischaemic stroke events were confirmed by medical record review and classified using the Childhood AIS Standardized Classification and Diagnostic Evaluation (CASCADE) criteria as definite cardioembolic, probable cardioembolic or non-cardioembolic. Neuroimaging and neurological outcomes were extracted from medical records. Follow-up time was 2 years. Cardioembolic stroke was identified in 31 (24.6%) of 126 children with AIS, corresponding to an incidence rate of 0.28 (95% CI, 0.20-0.40) per 100,000 person-years. Congenital heart diseases were the most common underlying conditions (n = 26, 83.9%). Among children undergoing angiography, LVOs were present in 41.2% of the cardioembolic group and in 18.5% of the non-cardioembolic group (P-value .060). The frequency of neurological impairments was similar between cardioembolic and non-cardioembolic AIS (48.4% vs 43.6%, P = .681). When limiting analysis to definite cardioembolic stroke, neurological impairment was more common in the cardioembolic than the non-cardioembolic group (73.3% vs 43.6%, P = .050), though this association was non-significant after adjusting for stroke severity. Cardioembolic stroke accounted for nearly one-quarter of paediatric AIS events. While clinical outcomes were similar between cardioembolic and non-cardioembolic AIS, definite cardioembolic stroke was associated with a higher risk of incomplete neurological recovery, highlighting the need for improved preventive strategies.
Pregabalin is FDA-approved for the treatment of neuropathic pain associated with diabetes, postherpetic neuralgia, spinal cord injury, and as an adjunctive treatment for partial seizures and thus is a commonly prescribed agent in the primary care, neurological, and pain management settings. Adverse effects of pregabalin include dizziness, somnolence, diplopia, blurry vision, and respiratory depression, as well as delayed dermatological hypersensitivity reactions and weight gain. Pregabalin dosing is influenced by renal function, and dose adjustment should be considered in all patients. A much rarer but serious adverse effect of pregabalin is myoclonus. There have been a few case reports of negative myoclonus in patients treated with both pregabalin and gabapentin; however, these patients tend to have renal dysfunction and typically present with altered mentation. Furthermore, these patients are often treated in the context of refractory epilepsy and are treated with other antiepileptic drugs, some of which can also result in myoclonus. Brief episodes of confusion, diplopia, word-finding difficulty, or other transient neurological deficits, which could be concerning for acute ischemic events in the setting of pregabalin use, have never been described. Here, we present a case report of a patient on long-term pregabalin without renal dysfunction who initially presented as a stroke alert for transient neurological deficits followed by jerking movements consistent with positive myoclonus, which is much less commonly reported than negative myoclonus in the setting of pregabalin usage.
This present work focuses on designing and identifying a probable nanocarrier for neurological drug-delivery applications. Silicon-doped graphdiyne (Si-GDY), exhibiting notable modulation in its electronic structure, was functionalized with amino acid derivatives (dopamine, octopamine, and tyramine) to evaluate molecular interactions. A systematic investigation of these nanocarriers was performed by using quantum chemical density functional theory (DFT). To explore the adsorption prospective of pristine and Si-TA-GDY nanocarriers toward the loading of levodopa (L-Dopa), an anti-Parkinson drug, through two different configurations (A and B). The adsorption (-26.811 kcal/mol) energy confirms stable equilibrium of L-Dopa on Si-TA-GDY (B). The lowest deformation energy (0.04892 kcal/mol) reveals minimal lattice strain. Si-TA-GDY@L-Dopa (A) shows energetically favorable adsorption via solvation stabilization (ΔEadsorp,solv) in both water (-27.720 kcal/mol) and ethanol (-23.164 kcal/mol), indicating potential drug-carrier binding affinity. High solvation stabilization energies ΔEsolv in water (-49.462 kcal/mol) and ethanol (-75.905 kcal/mol) demonstrate effective dielectric screening. Additionally, temperature-dependent thermochemical parameter analysis reveals spontaneous and exothermic adsorption dominated by enthalpic stabilization (-25.400 kcal/mol) and shows the highest firmness (ΔG = -13.783 kcal/mol) in Si-TA-GDY@L-Dopa (B). For the same system, the longer recovery time correlates with the higher NEB-derived desorption barrier (∼0.29 eV), enabling controlled drug release. Among all investigated complex structures, Si-doped GDY functionalized with tyramine exhibits the most favorable system toward L-Dopa at both configurations, suggesting that tyramine-functionalized Si-doped GDY serves as a promising candidate for future L-Dopa drug-delivery investigations for neurological disorder.
The pathological features of cerebral ischemia-reperfusion (CIR) include necroptosis activation. This study investigated how healthy fecal microbiota transplantation (H-FMT) improves CIR and intestinal barrier damage. Rats subjected to middle cerebral artery occlusion and reperfusion (MCAO/R) were treated with H-FMT and/or a Cysteine-aspartic acid protease-8 (Caspase-8) inhibitor. Survival and body weight were monitored throughout the experiment. Neurological function, tissue damage, inflammatory cytokines, and Caspase-8/Receptor-interacting protein kinase 1 (RIPK1)-Receptor-interacting protein kinase 3 (RIPK3)-Mixed lineage kinase domain-like protein (MLKL) expression were assessed. Ultrastructural changes were examined by transmission electron microscopy (TEM), p-RIPK1/p-RIPK3 expression by immunohistochemistry (IHC), and gut microbiota by 16 S sequencing. H-FMT significantly ameliorated neurological deficits and intestinal barrier disruption, reduced infarct volume and neuronal loss, and attenuated mitochondrial damage. These effects were accompanied by reduced apoptosis and inflammation, increased Caspase-8 activation, and suppressed RIPK1-RIPK3-MLKL phosphorylation. IHC confirmed reduced p-RIPK1/p-RIPK3 signals after H-FMT. 16 S sequencing revealed that H-FMT restored microbial diversity, reduced pathogenic Proteobacteria, and enriched beneficial Lactobacillus, which positively correlated with Caspase-8 activation. Our findings suggest that H-FMT alleviates CIR injury by activating Caspase-8 and suppressing necroptosis. However, due to the small sample size, these results should be considered preliminary.
The benefits and risks of intravenous thrombolysis (IVT) with alteplase for acute ischemic stroke (AIS) beyond 4.5 h are unclear. Decision-making is further limited by the lack of comparisons between imaging strategies used for patient selection, including magnetic resonance imaging with diffusion-weighted imaging (MRI/DWI) and perfusion-guided approaches such as MRI with perfusion-weighted imaging (MRI/PWI) or computed tomography perfusion (CTP). This study aims to evaluate the efficacy and safety of alteplase administered beyond 4.5 h and to compare MRI/DWI- and perfusion-guided IVT. Databases were searched for RCTs enrolling AIS patients treated with alteplase beyond 4.5 h. Efficacy outcomes included excellent (mRS 0-1) and favorable (mRS 0-2) functional outcomes at 90 days, and major neurological improvement up to 72 h. Safety outcomes included any intracranial hemorrhage (aICH), symptomatic ICH (sICH), parenchymal hemorrhage (PH), and 90-day mortality. Seven RCTs comprising 1685 patients were included. There were no differences between imaging strategies in any efficacy or safety outcome. Alteplase administered beyond 4.5 h was associated with higher rates of excellent (RR 1.24; 95% CI 1.12-1.38) and favorable (RR 1.17; 95% CI 1.09-1.26) functional outcomes, and increased major neurological improvement (RR 1.28; 95% CI 1.11-1.49). The risks of aICH (RR, 2.82; 95% CI 1.17-6.80), sICH (RR, 3.31; 95% CI 1.42-7.74), and PH (RR, 2.95; CI 95% 1.33-6.53) were higher in the alteplase group, while mortality showed no difference (RR 1.27; 95% CI 0.91-1.76). This network meta-analysis did not detect a statistically significant difference between perfusion-guided and DWI/FLAIR mismatch-guided selection; however, this comparison was indirect, based on a limited number of trials, and not powered to demonstrate equivalence, and should not be interpreted as evidence that the two paradigms are interchangeable.
Infective endocarditis (IE) is a serious infection of the endocardial surface of the heart that is associated with significant morbidity due to systemic embolic complications. Neurological involvement is well recognized but most commonly manifests as ischemic stroke or intracranial hemorrhage due to embolic events. Complete spinal cord infarction as an initial presentation of IE is rare and may mimic acute myelopathy or longitudinally extensive transverse myelitis (LETM), leading to diagnostic challenges. We describe a patient who presented with an acute-onset motor weakness and sensory deficits suggestive of LETM. Initial neuroimaging findings were consistent with LETM. However, further evaluation with blood cultures and echocardiography revealed IE with valvular vegetations, indicating an embolic source and explaining the neurological presentation as spinal cord ischemia secondary to IE. The patient was managed with the timely initiation of appropriate intravenous antimicrobial therapy along with supportive care. This case highlights the importance of considering an underlying embolic etiology in patients presenting with LETM-like acute myelopathy and emphasizes the role of early recognition and timely treatment in improving outcomes and preventing further complications.
Spinocerebellar ataxia type 27B is a recently described autosomal dominant, late-onset cerebellar ataxia caused by an intronic GAA repeat expansion in the fibroblast growth factor 14 (FGF14) gene. Despite being recognized as a frequent adult-onset ataxia, its full clinical spectrum remains incompletely understood. To characterize the neurological, cognitive, and paraclinical phenotype of patients with heterozygous FGF14 repeat expansions (>200) and expand the currently known motor and non-motor features, as well as to assess the co-occurrence of other repeat expansions. In this cross-sectional single-center study, patients with heterozygous FGF14 repeat expansions underwent standardized neurological examination and cognitive screening. Paraclinical data were reviewed when available. 18 patients were included in the study (mean age at onset: 64 [37-79], at examination: 76 [61-94]). They all presented with gait ataxia, most commonly a lateral veering gait with corrective sidesteps. In addition to the core known cerebellar phenotype, we identified other movement-disorder manifestations, including myokymia, myoclonus, dystonia, and parkinsonism, with nigrostriatal degeneration confirmed in one patient. Cognitive impairment was common, with two-thirds of patients fulfilling criteria for cerebellar cognitive-affective syndrome (mean MoCA: 25 [21-29], CCAS: 86.9/120 [62-108]). Worse CCAS and MoCA performance was associated with increasing ataxia severity. FGF14 repeat expansions ranged from 210 to 520, and co-occurrence with heterozygous expansions in RFC1 or ATXN8/ATXN8OS were identified in three patients. Earlier diagnostic misclassification as transient ischemic attack was reported in 33%. These findings expand the known phenotype of spinocerebellar ataxia type 27B, emphasizing it as a multisystem movement disorder.
The anterior intrapelvic approach (AIP) is increasingly used for pelvic ring and acetabular fractures, yet its learning curve during structured implementation remains poorly defined. This study evaluated the learning curve associated with AIP introduction in a trauma center. A retrospective analysis of a prospectively maintained database was conducted at a level-1 trauma center. Eighty-six consecutive patients treated with AIP by a single senior surgeon (2015-2019) were included. Patients were divided chronologically into two equal groups (first 43 vs. last 43 cases). The primary outcome was operative time. Secondary outcomes included blood loss, reduction quality assessed on postoperative CT (Matta and Matta-Tornetta criteria), and complications. Multivariable analyses were performed to identify independent predictors of operative time and reduction quality. Operative time decreased significantly from 226 ± 93 to 187 ± 83 min (p = 0.04) and remained independently associated with case sequence (p < 0.01). Blood loss decreased by 31% (897 ± 694 vs. 620 ± 436 mL, p = 0.01). Reduction quality remained stable, with anatomical or satisfactory reduction achieved in 86% of cases, without intergroup differences. The overall complication rate was 8%. Early postoperative neurological deficits were more frequent in the initial phase but decreased significantly over time (p = 0.04). No implant failures or loss of reduction were observed. AIP implementation was associated with improved operative efficiency without compromising reduction quality or increasing complications, suggesting a progressive learning curve with an acceptable and improving neurological morbidity profile in a trauma center setting.
Intracranial aneurysms caused by trauma are rare, and occlusion of the carotid vessels caused by trauma is also uncommon. The authors report on the case of a patient who had an internal carotid artery (ICA) aneurysm accompanied by occlusion because of a car accident. A 37-year-old man presented after a motor vehicle accident with severe traumatic brain injury (TBI), subarachnoid hemorrhage, intraventricular hemorrhage, multiple skull fractures, and right ICA occlusion. Initial CT angiography and digital subtraction angiography showed no aneurysm, and emergency external ventricular drainage was performed. One month later, repeat angiography demonstrated a right C7 ICA aneurysm. CT perfusion showed mild hypoperfusion in the right hemisphere. The patient underwent craniotomy with aneurysm trapping and superficial temporal artery-middle cerebral artery bypass. He later required ventriculoperitoneal shunt insertion for hydrocephalus. Follow-up imaging showed improved perfusion, but marked neurological deficits remained at discharge. In selected patients with traumatic aneurysm and carotid occlusion, microsurgical trapping combined with extracranial-intracranial bypass can be a practical treatment option when endovascular therapy is not suitable. In high-risk TBI, repeat vascular imaging is important even when initial studies are negative. https://thejns.org/doi/10.3171/CASE26241.
Although intraluminal shunt insertion during carotid endarterectomy (CEA) is widely used to maintain cerebral perfusion, distal intimal injury of the internal carotid artery (ICA) can occur as a rare yet consequential complication. An 82-year-old man with an elongated styloid process who underwent CEA for left ICA stenosis at the C2 vertebral level developed a new progressive high-grade stenosis immediately distal to the endarterectomy site, likely associated with shunt manipulation. Preoperative images demonstrated that the distal ICA segment at the C1 vertebral level was positioned between the styloid process anterolaterally and the transverse process of C1 posteromedially, in closer proximity to these osseous structures than on the right side. The dissected segment corresponded to the region of closest proximity between the ICA and the transverse process of C1. The patient underwent carotid artery stent placement for the distal dissected stenosis without neurological sequelae. This case suggests that an Eagle syndrome-like osseous-vascular configuration may predispose the artery to shunt-related injury during CEA. Meticulous preoperative assessment of the relationship between the ICA and both the transverse process of C1 and the styloid process may help mitigate the risk of distal ICA dissection in high cervical lesions with an elongated styloid process. https://thejns.org/doi/10.3171/CASE26320.
Acute vertebrobasilar occlusion is most commonly thromboembolic and requires emergency endovascular therapy (EVT). However, upper cervical instability may rarely cause neck motion-dependent dynamic vertebral artery (VA) occlusion. Os odontoideum is a recognized cause of atlantoaxial instability that has been associated with bow hunter syndrome; however, acute bilateral VA occlusion mimicking basilar artery occlusion (BAO) is exceedingly uncommon. A 73-year-old man with recurrent posterior circulation infarctions collapsed while golfing and rapidly progressed to coma with respiratory failure and quadriparesis. CT angiography demonstrated bilateral VA occlusion at the vertebrobasilar junction, and EVT was initiated for presumed BAO. Angiography revealed left VA occlusion at C1-2. After micro-guidewire passage, contrast stagnation at the lesion demonstrated to-and-fro flow extending to the left posterior inferior cerebellar artery. Full stent expansion with preserved aspiration backflow and repeated failure to retrieve the thrombus suggested a dynamic, nonthrombotic mechanism. Bone-window CT angiography identified os odontoideum with displacement and extension-dependent bilateral VA compromise. Durable VA patency was restored by cervical immobilization followed by occipitocervical fusion. Persistent to-and-fro flow during EVT should raise the suspicion of dynamic occlusion. Disproportionate neurological decline, including hypoventilation, warrants evaluation for cervical instability requiring surgical stabilization. https://thejns.org/doi/10.3171/CASE26267.
An angiogram-negative subarachnoid hemorrhage (SAH) with a high Hunt-Hess grade and atypical radiographic features warrants evaluation for occult lesions. Cervicomedullary spinal arteriovenous malformations (AVMs) are rare causes frequently missed on initial imaging. A 54-year-old male presented with a Hunt-Hess grade V SAH, and initial multimodal angiography findings were negative. Neurological status improved following external ventricular drain (EVD) placement. Imaging clues included a focal ventral cervicomedullary spot sign, disproportionate prepontine blood accumulation with inferior tracking, and an intraventricular hemorrhage. Angiography performed on day 10 revealed a 3-mm ruptured anterior spinal artery (ASA) aneurysm with cervicomedullary AVM. Endovascular treatment was high risk given the proximity of the ASA. Resection via far-lateral transcondylar approach was performed. Neuromonitoring demonstrated bilateral motor evoked potential (MEP) decline with preserved D-wave amplitude, prompting reinspection, revealing an inadvertent ASA trunk clipping, and enabling correction and complete MEP recovery. The lesion was obliterated without deficits. In a high-grade, angiogram-negative SAH, ventral blood distribution and spot signs should prompt targeted spinal angiography at 7-14 days. EVD placement can reverse herniation and coma in high-grade presentations. The far-lateral approach and cord rotation provide direct visualization for ventral spinal pathology when endovascular access is restricted. D-wave monitoring with transcranial MEPs enables real-time distinction between reversible ischemic changes and irreversible mechanical injury, guiding intraoperative decision-making. https://thejns.org/doi/10.3171/CASE26229.
Neurological disorders severely impair the daily life of patients, necessitating precise assessments of neural conduction pathway damage to guide effective diagnosis and treatment. However, current clinical neurodiagnostic equipment is expensive, bulky, and restricted to hospital settings. Furthermore, the rigid nature and low adhesion of conventional electrodes lead to the acquisition of low-quality neurophysiological signals. Here, we develop a soft hybrid electronic system assembled with printed responsive hydrogel electrodes. By synthesizing thermoresponsive hydrogel microsphere inks, we achieve rapid direct-printed patterning of interface layers. Based on a thermally triggered hydration-dehydration strategy of hydrogel microspheres, the hydrogel electrodes demonstrate customizable adhesion, enabling intimate integration with skin for high-fidelity signal acquisition and gentle detachment after monitoring. Through hydrogel interface modification, on-skin electrodes also show excellent charge injection capability for stimulation and improved signal-to-noise ratio (SNR). The integration of hydrogel patches with the hybrid electronic system enables high-frequency and high-fidelity acquisition of subtle neural conduction signals. We further apply this system to assess injuries to the median and ulnar nerves in clinical cases, realizing accurate diagnosis of neural impairment while ensuring customized adhesion regulation. This user-friendly system holds great promise as a low-cost and portable diagnostic platform for telemedicine, home-based care, and clinical settings.
Head and neck cancer (HNC) presents a significant challenge in oncology. It has high prevalence rates, especially in India, where 30-40% of cancer cases are attributed to HNC. While chemotherapy and radiation therapy are essential components of treatment, they often lead to significant sleep disturbances that negatively impact patients' quality of life and the effectiveness of their treatment. These sleep disturbances are frequently associated with disruptions in the circadian rhythm, which are commonly seen in cancer survivors. This study aimed to evaluate the effect of an exercise oncology program on sleep quality and circadian rhythm in patients with HNC undergoing chemo-radiation therapy. Patients with HNC (stage III, IVa, or IVb) undergoing chemo-radiation therapy, aged 18 years or above, of any gender, and with an Eastern Cooperative Oncology Group score < 2 were included. Patients with severe orthopedic or neurological conditions, hemoglobin < 8 g/dL, platelet count < 30,000/µL, or unfit for exercise were excluded. Seventy HNC patients were randomized to exercise oncology and control group. The exercise oncology group received 15-20-minute sessions of aerobic (brisk walking) and resistance training (upper and lower limb exercises). Participants in the control group were asked to follow the walking protocol recommended by National Comprehensive Cancer Network guidelines, five days a week for seven weeks. Pittsburgh Sleep Quality Index (PSQI) was used to assess overall sleep quality, while melatonin excretion in urine, quantified using ELISA, was used to evaluate the circadian rhythm. Between-group comparisons were analyzed using mixed analysis of variance for PSQI and analysis of covariance for urinary melatonin. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic accuracy of PSQI scores and melatonin levels. PSQI significantly improved in the exercise group (13.97 ± 2.29 to 7.09 ± 1.15), and significantly worsened in controls, (13.06 ± 1.73 to 14.14 ± 2.64) (both p < 0.001). Although urinary melatonin levels increased in the exercise group (284.16 ± 85.29 ng/L to 369.75 ± 91.61 ng/L) and decreased in controls (368.00 ± 100.62 ng/L to 304.39 ± 99.50 ng/L), the between-group difference was not significant after adjusting for baseline values (p = 0.372). Furthermore, ROC curve analysis demonstrated that post-intervention PSQI exhibited excellent diagnostic accuracy for distinguishing between good and poor sleep quality. An exercise oncology program has potential benefits in improving quality of sleep and regulating the circadian rhythm in HNC patients undergoing chemo-radiation therapy.
Chikungunya virus, a mosquito-borne alphavirus, causes fever, rash, arthritis, and neurological disorders. Its non-structural protein 3 harbors a macrodomain, a key neurovirulence factor that removes adenosine diphosphate ribose from ADP-ribosylated substrates. Notably, chikungunya virus infection results in distinct ADP-ribosylation patterns and non-structural protein 3 macrodomain-mediated replication dynamics in astrocytes and neurons. Understanding the connection between ADP-ribosylation and the activation of innate immunity, particularly interferon release, is key to elucidating how the cellular immunological state influences ADP-ribosylation, an understudied post-translational modification during viral infection. Here, murine astrocytic (C8-D1A) and neuronal (NSC-34) cells were infected with chikungunya virus to profile transcript and protein expression of innate immune mediators and type I IFNs. The role of PARP1 in global ADP-ribosylation patterns was assessed using PARP-specific inhibitors and genetic depletion approaches. Our investigations revealed that neuronal chikungunya virus infection induces ADP-ribosylation through PARP1 activation, driven by caspase-3-mediated apoptosis, without transcriptionally activating PARPs. In contrast, astrocytic infections showed minimal ADP-ribosylation despite transcriptional activation of interferon-stimulated PARPs. Neurons exhibited limited innate immune response gene transcriptional activity, whereas astrocytes demonstrated strong upregulation of genes essential for pattern recognition receptor activation, thus enhancing double-stranded RNA sensing and increasing type I interferon production during infection. We posit that PARP1 activation and type I IFN response differentially regulate ADP-ribosylation in chikungunya virus-infected neural cells in a cell type-dependent manner.IMPORTANCEChikungunya virus is an emergent mosquito-borne alphavirus increasingly associated with neurological infection and subsequent long-term disabilities. Its continued global spread and recurrent outbreaks underscore its significant pandemic potential and the urgent need for effective countermeasures. Chikungunya virus showcases distinct, cell-type dependent replication dynamics within astrocytes and neurons, two major permissive cerebral cell types. However, understanding of the immunological basis of such cell type-specific infection dynamics remains limited, yet is necessary to elucidate virus pathogenesis within the brain and thus identification of downstream drug targets. Our study characterized two distinctly activated innate immunological pathways in chikungunya virus-infected astrocytes versus neurons, thus significantly contributing to molecular understanding cell type-specific chikungunya virus neurovirulence on a molecular level.
Spinal extradural meningeal cysts are rare spinal lesions, and the optimal surgical strategy remains debated, particularly regarding the relative importance of complete cyst wall excision and closure of the dural communication. We retrospectively reviewed 10 patients (5 male and 5 female; mean age, 38.5 years) who underwent surgical treatment for Nabors Type IA spinal extradural meningeal cysts at a single institution between 1987 and 2023. The median symptom duration was 5.5 months. All lesions showed cerebrospinal fluid-equivalent signal intensity on magnetic resonance imaging. Surgical approaches included total or subtotal laminectomy, hemilaminectomy, and osteoplastic laminotomy. The mean clinical follow-up period was 121.6 months. Nine patients underwent partial cyst wall resection or fenestration with primary dural defect closure; among the seven patients in this group with available postoperative radiological follow-up, no radiological recurrence was observed. The single patient in whom primary dural closure was not achieved showed a persistent residual or recurrent cystic lesion on follow-up imaging but remained clinically improved. No neurological complications were observed. These findings suggest that identifying and closing the dural communication may be an important component of durable spinal extradural meningeal cyst management, whereas complete cyst wall excision may not always be necessary. Because this was a small retrospective case series with incomplete imaging follow-up in some patients, these findings should be interpreted as supportive clinical observations rather than definitive evidence of causality.
The interplay between gut microbiota and mitochondria represents a dynamic relationship that profoundly impacts host physiology, ranging from maintaining intestinal homeostasis to regulating systemic metabolic and neurological functions. Microbial metabolites such as short-chain-fatty-acids, bile acids, and amino acid derivatives serve as pivotal modulators of mitochondrial bioenergetics, oxidative stress management, and fission-fusion processes. These interactions are vital for preserving epithelial integrity, supporting energy metabolism, shaping immune responses, and managing inflammatory signaling pathways. Disruptions within this microbiota-mitochondria axis are associated with various pathologies, including non-alcoholic fatty liver disease, obesity, type 2 diabetes, and chronic inflammatory conditions like inflammatory bowel disease. Additionally, growing evidence connects gut dysbiosis and mitochondrial dysfunction to neurodegenerative disorders such as Parkinson's disease and Alzheimer's disease, highlighting the importance of this bidirectional relationship in maintaining neuronal health. On a mechanistic level, pathways involving AMPK, sirtuins, and PGC-1α govern mitochondrial biogenesis and adaptive responses to microbial signals. Dysregulation of these pathways can heighten oxidative stress, hinder mitophagy, and contribute to systemic inflammation. Emerging therapeutic strategies aim to target this axis through dietary modifications, probiotics and engineered microbes, FMT, and mitochondria-specific pharmacological treatments. These interventions focus on restoring metabolic stability, enhance resilience against oxidative damage, and slowing disease progression. By integrating insights from fields such as metabolism, immunology, and neuroscience, this review positions the microbiota-mitochondria axis as a critical area of focus in biomedical research. A deeper understanding of this communication network offers promising opportunities for precision therapies aimed at addressing metabolic, inflammatory, and neurodegenerative diseases.