Relating caregiver experiences to personalized "push" content in mobile applications among caregivers of pediatric patients with oncology conditions.

OBJECTIVE: With the evolution of data algorithms and personalized push systems in mobile applications, patients who have searched for disease-related information may repeatedly receive similar content on app homepages or through notifications. This study aims to assess the influence of health-related content delivered through mobile applications on the anxiety and depression levels of caregivers of pediatric oncology patients. METHODS: A survey consisting of 16 questions was conducted among 91 caregivers of pediatric oncology patients at the Children's Hospital affiliated with Chongqing Medical University. The questionnaire was designed by oncologists and the Hospital Anxiety and Depression Scale was used to assess the caregivers' psychological states. RESULTS: The study found that 31.5% of caregivers exhibited borderline anxiety symptoms, while 20.2% displayed borderline depression symptoms. Caregivers who noticed changes in homepage recommendations reported higher levels of anxiety (p = .004) and depression (p = .034). Additionally, 50.6% occasionally felt anxious or uneasy due to personalized notifications and 19.1% frequently felt this way. Moreover, 53.9% of the caregivers reported a negative impact on their emotions or daily life. SIGNIFICANCE: Personalized push notifications related to disease information in mobile applications can impose a significant psychological burden on patients and their caregivers. Mobile application developers and healthcare providers must strengthen their support in the digital health domain to enhance the emotional well-being of cancer patients and their caregivers.

Early antiseizure medication withdrawal and risk of seizure recurrence in children after epilepsy surgery: A retrospective study.

OBJECTIVE: The timing of antiseizure medication (ASM) withdrawal in children after epilepsy surgery remains controversial and lacks recognized standards. Given the various negative effects of ASM on development in children, this study aimed to evaluate the safety and feasibility of early ASM withdrawal after epileptic resection surgery. METHODS: We retrospectively assessed the seizure outcomes and ASM profiles of children who had undergone epileptic resection surgery between August 2015 and August 2020 and attempted ASM reduction in the early postoperative phase. Tapering the dose of ASM was attempted when children were seizure-free with no interictal epileptiform discharges (IEDs) on electroencephalogram (EEG) for at least 6 months postoperatively. RESULTS: This study included 145 children with a median follow-up duration of 40 months. Early ASM tapering was attempted postoperatively in 99 (68.3 %) children. Postoperative ASM discontinuation was attempted in 87 (60.0 %) children. Nine (9.1 %) children experienced seizure recurrence during the ASM reduction stage, and 10 (11.5 %) experienced recurrence after ASM discontinuation. Incomplete resection (P = 0.003) and postoperative seizures before ASM tapering (P = 0.003) were independent predictors of seizure recurrence during and after early ASM withdrawal. SIGNIFICANCE: ASM withdrawal is viable and safe to be initiated in children who are seizure-free postoperatively and have no IEDs on the scalp EEG for at least 6 months. Children with incomplete resection and postoperative seizures before ASM withdrawal are at a higher risk of seizure recurrence and may need to continue ASM for a longer period.

Evaluating the performance of the language model ChatGPT in responding to common questions of people with epilepsy.

OBJECTIVE: People with epilepsy desire to acquire accurate information about epilepsy and actively engage in its management throughout the long journey of living with seizures. ChatGPT is a large language model and we aimed to assess the accuracy and consistency of ChatGPT in responding to the common concerns of people with epilepsy and to evaluate its ability to provide emotional support. METHODS: Questions were collected from the International League against Epilepsy and the China Association against Epilepsy. The responses were independently assessed by two board-certified epileptologists from the China Association against Epilepsy, and a third reviewer resolved disagreements. The reviewers assessed its ability to provide emotional support subjectively. RESULTS: A total of 378 questions related to epilepsy and 5 questions related to emotional support were included. ChatGPT provided "correct and comprehensive" answers to 68.4% of the questions. The model provided reproducible answers for 82.3% questions. The model performed poorly in answering prognostic questions, with only 46.8% of the answers rated as comprehensive. When faced with questions requiring emotional support, the model can generate natural and understandable responses. SIGNIFICANCE: ChatGPT provides accurate and reliable answers to patients with epilepsy and is a valuable source of information. It also provides partial emotional support, potentially assisting those experiencing emotional distress. However, ChatGPT may provide incorrect responses, leading users to inadvertently accept incorrect and potentially dangerous advice. Therefore, the direct use of ChatGPT for medical guidance is not recommended and its primary use at present is in patients education.

Epilepsy and childhood psychiatric disorders: a two-sample bidirectional Mendelian randomization study.

BACKGROUND: Observational studies have indicated that psychiatric disorders are the most common comorbidities in pediatric epilepsy. However, the existence and direction of a causal relationship between the two remains controversial. This study aims to investigate the association between common childhood psychiatric disorders and epilepsy using a two-sample, bidirectional Mendelian randomization (MR) approach. METHODS: Genetic instruments were obtained from the most recent and largest genome-wide association studies (GWAS), including datasets for epilepsy (N_case = 29,994, N_control = 52,538), attention deficit hyperactivity disorder (ADHD) (N_case = 38,691, N_control = 186,843), autism spectrum disorder (ASD) (N_case = 18,381, N_control = 27,969), and Tourette syndrome (TS) (N_case = 4,819, N_control = 9488). MR analyses were conducted using the inverse variance weighted (IVW) method, weighted median method, and MR-Egger regression. RESULTS: No reliable evidence was found to suggest a causal effect of ADHD, ASD, or TS on epilepsy, nor was there any reliable evidence indicating that epilepsy increases the risk of these three psychiatric disorders. These findings remained consistent across various sensitivity analyses. CONCLUSION: Although observational studies have highlighted a high comorbidity rate between pediatric epilepsy and psychiatric disorders like ADHD and ASD, the MR analysis did not confirm a causal relationship between them. This suggests that previous studies might have been influenced by confounding biases or other biases, potentially overestimating the true relationship. A deeper understanding of the mechanisms underlying these comorbidities is crucial for refining the treatment of pediatric epilepsy.

Neurosurgical short-term outcomes for pediatric medulloblastoma patients and molecular correlations: a 10-year single-center observation cohort study.

This study examined the risk factors for short-term outcomes, focusing particularly on the associations among molecular subgroups. The analysis focused on the data of pediatric patients with medulloblastoma between 2013 and 2023, as well as operative complications, length of stay from surgery to adjuvant treatment, 30-day unplanned reoperation, unplanned readmission, and mortality. 148 patients were included. Patients with the SHH TP53-wildtype exhibited a lower incidence of complications (45.2% vs. 66.0%, odds ratio [OR] 0.358, 95% confidence interval [CI] 0.160 - 0.802). Female sex (0.437, 0.207 - 0.919) was identified as an independent protective factor for complications, and brainstem involvement (1.900, 1.297 - 2.784) was identified as a risk factor. Surgical time was associated with an increased risk of complications (1.004, 1.001 - 1.008), duration of hospitalization (1.006, 1.003 - 1.010), and reoperation (1.003, 1.001 - 1.006). Age was found to be a predictor of improved outcomes, as each additional year was associated with a 14.1% decrease in the likelihood of experiencing a prolonged length of stay (0.859, 0.772 - 0.956). Patients without metastasis exhibited a reduced risk of reoperation (0.322, 0.133 - 0.784) and readmission (0.208, 0.074 - 0.581). There is a significant degree of variability in the occurrence of operative complications in pediatric patients with medulloblastoma. SHH TP53-wildtype medulloblastoma is commonly correlated with a decreased incidence of complications. The short-term outcomes of patients are influenced by various unmodifiable endogenous factors. These findings could enhance the knowledge of onconeurosurgeons and alleviate the challenges associated with patient/parent education through personalized risk communication. However, the importance of a dedicated center with expertise surgical team and experienced neurosurgeon in improving neurosurgical outcomes appears self-evident.

TonEBP: A Key Transcription Factor in Microglia Following Intracerebral Hemorrhage Induced-Neuroinflammation.

Transcription factors within microglia contribute to the inflammatory response following intracerebral hemorrhage (ICH). Therefore, we employed bioinformatics screening to identify the potential transcription factor tonicity-responsive enhancer-binding protein (TonEBP) within microglia. Inflammatory stimuli can provoke an elevated expression of TonEBP in microglia. Nevertheless, the expression and function of microglial TonEBP in ICH-induced neuroinflammation remain ambiguous. In our recent research, we discovered that ICH instigated an increased TonEBP in microglia in both human and mouse peri-hematoma brain tissues. Furthermore, our results indicated that TonEBP knockdown mitigates lipopolysaccharide (LPS)-induced inflammation and the activation of NF-κB signaling in microglia. In order to more deeply comprehend the underlying molecular mechanisms of how TonEBP modulates the inflammatory response, we sequenced the transcriptomes of TonEBP-deficient cells and sought potential downstream target genes of TonEBP, such as Pellino-1 (PELI1). PELI has been previously reported to mediate nuclear factor-κB (NF-κB) signaling. Through the utilization of CUT & RUN, a dual-luciferase reporter, and qPCR, we confirmed that TonEBP is the transcription factor of Peli1, binding to the Peli1 promoter. In summary, TonEBP may enhance the LPS-induced inflammation and activation of NF-κB signaling via PELI1.

Embolization of midbrain arteriovenous malformation fed by the artery of Percheron in a child, the first case report and literature review.

BACKGROUND: Artery of Percheron (AOP) as main feeder artery of arteriovenous malformation (AVM) is extremely rare. Two cases of thalamic AVM fed by AOP have been reported to date and only one AVM been removed by microsurgery when attempt of intervention embolization failed. Midbrain AVM fed by AOP has not been reported yet. CASE PRESENTATION: Here, we presented the first successful embolized case of midbrain AVM supplied by the AOP in a 10-year-old boy, who suffered dual oculomotor nerve palsy and secondary hemorrhage before embolization. During endovascular embolization, selective angiography by 1.2 Fr. Magic microcatheter showed an intranidal aneurysm located on the distal AOP. Two injections of a 1:4 ratio mixture of NBCA-MS completely occlude the nidus and intranidal aneurysm with no complications occurred. The child recovered well and the oculomotor deficits improved. CONCLUSION: This case highlighted that AOP is a clinically significant branch associated with AVM in midbrain and thalamus. Moreover, intervention embolization of midbrain AVM fed by AOP is a considerable therapeutic strategy.

Neurodevelopmental outcomes of neonatal posthemorrhagic hydrocephalus and psychological effects on the parents.

BACKGROUND: Neonatal posthemorrhagic hydrocephalus remains a common complication in preterm infants, with high rates of mortality and morbidity, placing parents at high risk of anxiety and depression. We sought to investigate the neurodevelopmental outcomes of infants with posthemorrhagic hydrocephalus who underwent surgery and the psychological effect on their parents. METHODS: We retrospectively analysed all infants with posthemorrhagic hydrocephalus born between 2014 and 2020 in the Children's Hospital of Chongqing Medical University, China. The neurodevelopmental outcomes of 28 patients were evaluated by the Pediatric Stroke Outcome Measure score, and the psychological states of the parents of survivors were assessed by the Hospital Anxiety and Depression Scale. RESULTS: The families of the 28 patients were followed up for a median duration of 3 years; 6 (21.4%) patients died within 6 months after discharge, 12 (42.9%) patients had moderate to severe dysfunction, and only 10 (35.7%) patients had good outcomes. Regarding the 22 parents of the survivors, 5 (22.7%) and 4 (18.2%) had borderline anxiety and depression symptoms, respectively. Two (9.1%) caregivers had exact anxiety and depression symptoms. Leukomalacia after intraventricular haemorrhage was associated with adverse neurological outcomes. The infants' histories of epileptic seizures during the neonatal period were associated with the anxiety of their parents. CONCLUSION: The overall outcome of posthemorrhagic hydrocephalus patients is unsatisfactory, and children with leukomalacia after haemorrhage tend to have poor outcomes. A history of epileptic seizures during the course of the disease may exacerbate the anxiety of the caregivers.

The insertion and management of an external ventricular drain in pediatric patients with hydrocephalus associated with medulloblastoma.

An external ventricular drain (EVD) is used to facilitate cerebrospinal fluid (CSF) removal in medulloblastoma patients suffering from hydrocephalus. It is essential to recognize that EVD management plays a crucial role in influencing the incidence of drain-related complications. However, the ideal method for EVD management remains undetermined. Our research sought to examine the safety of EVD placement and the impact of EVD on the incidences of intracranial infections, postresection hydrocephalus, and posterior fossa syndrome (PFS). We conducted a single-center observational study involving a cohort of 120 pediatric medulloblastoma patients who were treated from 2017 to 2020. The rates of intracranial infection, postresection hydrocephalus, and PFS were 9.2%, 18.3%, and 16.7%, respectively. EVD did not influence the occurrence of intracranial infection (p = 0.466), postresection hydrocephalus (p = 0.298), or PFS (p = 0.212). A gradual EVD weaning protocol correlated with an elevated incidence of postresection hydrocephalus (p = 0.033), whereas a rapid weaning approach resulted in 4.09 ± 0.44 fewer drainage days (p < 0.001) than the gradual weaning strategy. EVD placement (p = 0.010) and intracranial infection (p = 0.002) were linked to delayed speech return, whereas a longer duration of drainage was conducive to the recovery of language function (p = 0.010). EVD insertion was not correlated with the incidence of intracranial infection, postoperative hydrocephalus, or PFS. The optimal EVD management method should encompass a rapid EVD weaning strategy, followed by prompt drain closure. We have presented additional evidence to improve the safety of EVD insertion and management in neurosurgical patients to ultimately facilitate the establishment of standardized institutional/national implementation and management protocols.

NPAS4 Exacerbates Pyroptosis via Transcriptionally Regulating NLRP6 in the Acute Phase of Intracerebral Hemorrhage in Mice.

Intracerebral hemorrhage (ICH) is a severe cerebrovascular disease with a high disability rate and high mortality, and pyroptosis is a type of programmed cell death in the acute phase of ICH. Neuronal Per-Arnt-Sim domain protein 4 (Npas4) is a specific transcription factor highly expressed in the nervous system, yet the role of NPAS4 in ICH-induced pyroptosis is not fully understood. NLR family Pyrin-domain-containing 6 (NLRP6), a new member of the Nod-like receptor family, aggravates pyroptosis via activating cysteine protease-1 (Caspase-1) and Caspase-11. In this study, we found that NPAS4 was upregulated in human and mouse peri-hematoma brain tissues and peaked at approximately 24 h after ICH modeling. Additionally, NPAS4 knockdown improved neurologic dysfunction and brain damage induced by ICH in mice after 24 h. Meanwhile, inhibiting NPAS4 expression reduced the levels of myeloperoxidase (MPO)-positive cells and Caspase-1/TUNEL-double-positive cells and decreased cleaved Caspase-1, cleaved Caspase-11, and N-terminal GSDMD levels. Consistently, NPAS4 overexpression reversed the above alternations after ICH in the mice. Moreover, NPAS4 could interact with the Nlrp6 promoter region (-400--391 bp and -33--24 bp) and activate the transcription of Nlrp6. Altogether, our study demonstrated that NPAS4, as a transcription factor, can exacerbate pyroptosis and transcriptionally activate NLRP6 in the acute phase of intracerebral hemorrhage in mice.

Research Progress on Chemical Constituents and Pharmacological Activities of Menispermi Rhizoma.

Menispermi Rhizoma, the rhizome of Menispermum dauricum DC., is a traditional Chinese medicine, which has the effect of clearing away heat and detoxification, dispelling wind, and relieving pain. It is often used in the treatment of sore throat, enteritis, dysentery, and rheumatism. The chemical constituents of M. Rhizoma mainly include alkaloids, phenolic acids, quinones, cardiotonic glycosides, and so on. Modern pharmacological studies have proved that M. Rhizoma has the effects of anti-tumour, anti-inflammation, anti-oxidation, bacteriostasis, cardio-cerebrovascular protection, anti-depression and anti-Alzheimer's disease. In recent years, the chemical constituents of M. Rhizoma have been found continuously, and the pharmacological studies have deepened gradually. This paper reviews the research progress on the chemical composition and pharmacological effects of M. Rhizoma, to provide a basis for further research and development of its medicinal value.

Does Adjustment of Antiseizure Medication Regimen after Failed Epilepsy Surgery Improve Outcomes?

Background and Objectives: After failed epilepsy surgery, patients often revert to an antiseizure medication (ASM) ASM regimen, which can be adjusted or optimized in three ways: increasing the dose, alternative therapy, and combination therapy. It is unclear which type of antiseizure medication adjustment method can improve outcomes. Materials and Methods: Children who underwent failed epileptic resection surgery at the Department of Neurosurgery, Children's Hospital of Chongqing Medical University between January 2015 and December 2021 were included in this cohort, who were reviewed for whether they underwent adjustment of ASM with increased dose, alternative therapy, or combination therapy. The seizure outcome and quality of life (QoL) were assessed. Two-tailed Fisher exact test and Mann-Whitney U test were used for statistical analysis. Results: Sixty-three children with failed surgery were included for further analysis, with a median follow-up time of 53 months. The median seizure recurrence time was 4 months. At the last follow-up, 36.5% (n = 23) of patients achieved seizure freedom, 41.3% (n = 26) achieved seizure remission, and 61.9% (n = 39) had a good QoL. None of the three types of ASM adjustment improved children's outcomes, whether considered in terms of seizure-free rate, seizure remission rate, or QoL. Early recurrences were significantly associated with decreased probability of seizure freedom (p = 0.02), seizure remission (p = 0.02), and a good QoL (p = 0.01). Conclusions: Children who underwent failed epilepsy surgery remains some potential for late seizure remission from ASM. Yet adjusting ASM regimen does not increase the probability of seizure remission nor does it improve the QoL. Clinicians should complete evaluations and consider the need for other antiepileptic treatment as soon as possible after surgery failed, especially when dealing with children with an early recurrence.

ACTL6A deficiency induces apoptosis through impairing DNA replication and inhibiting the ATR-Chk1 signaling in glioblastoma cells.

Actin-like 6A (ACTL6A) is a core subunit of the SWI/SNF chromatin remodeling complex and is highly expressed in several types of human cancers including glioblastoma. Recent studies verified that ACTL6A regulates the proliferation, differentiation, and migration of cancer cells. In this study, we identified ACTL6A as an important regulator of DNA replication. ACTL6A knockdown could impair the DNA replication initiation in glioblastoma cells. The regulation of DNA replication by ACTL6A was mediated through regulating the expression of the CDC45-MCM-GINS (CMG) complex genes. Further investigation revealed that ACTL6A transcriptionally regulates MCM5 expression. Furthermore, ACTL6A knockdown induced DNA damage and diminished the activity of the ATR-Chk1 pathway, which ultimately led glioblastoma cells to apoptosis and death. Taken together, our findings highlight the critical role of ACTL6A in DNA replication and ATR-Chk1 pathway, and reveal a potential target for therapeutic intervention in glioblastoma.

Endovascular management of pediatric pial arteriovenous fistulas with hereditary GDF2 mutation: illustrative case.

BACKGROUND: Intracranial pial arteriovenous fistulas (PAVFs) are uncommon neurovascular anomalies that primarily affect the pediatric population. PAVFs are often linked to hereditary hemorrhagic telangiectasia, yet the specific genetic mutations remain unidentified. While endovascular embolization is the preferred treatment for PAVFs, complications like hydrocephalus and sinus thrombosis pose challenges in management. OBSERVATIONS: The authors present a rare case of PAVF in a 6-month-old male neonate with a hereditary GDF2 mutation, where the fistula was supplied by the posterior inferior cerebellar artery and drained directly into the sigmoid sinus. The PAVF was effectively treated with endovascular embolization using coils and Onyx. Furthermore, the authors describe the successful use of rivaroxaban in managing subsequent sinus thrombosis after the embolization of PAVFs. Additionally, the authors review treatment strategies and complications following fistula disconnection. LESSONS: Endovascular embolization is the primary treatment choice for the majority of pediatric PAVFs, while a hereditary GDF2 mutation is considered a potential contributing factor to the formation of these malformations in children. Rivaroxaban has shown promise as an effective therapeutic option for pediatric sinus thrombosis, supported by its established safety profile. https://thejns.org/doi/10.3171/CASE24182.

Long Noncoding RNA GAS5-Involved Progression of Neonatal Hydrocephalus and Inflammatory Responses.

Intraventricular hemorrhage results in posthemorrhagic hydrocephalus (PHH). Neonatal hydrocephalus remains a challenging disease due to the high failure rate of all management strategies. We evaluated long noncoding RNA growth arrest-specific 5 (GAS5)-mediated network in neonatal hydrocephalus, providing a new direction for the treatment of hydrocephalus. The PHH model was constructed in neonatal rats after intracerebroventricular injection with GAS5, miR-325-3p, and chaperonin containing T-complex protein 1, subunit 8 (CCT8) plasmids, or oligonucleotides. Next, behavioral tests, measurement of serum inflammation, observation of brain tissue pathology, and calculation of hemoglobin and brain water contents were implemented. GAS5, miR-325-3p, and CCT8 expression, in combination with their interactions, was checked. As the results reported, collagenase infusion induced hydrocephalus, impairing neurological function, enhancing inflammation and neuronal apoptosis, and increasing hemoglobin and brain water contents. GAS5 and CCT8 were up-regulated, while miR-325-3p was down-regulated in hydrocephalic rats. Downregulating GAS5/CCT8 or upregulating miR-325-3p could inhibit inflammatory response and improve neurological function in young hydrocephalic rats. GAS5 promotes CCT8 expression through sponge adsorption of miR-325-3p. GAS5 silencing-mediated protections against hydrocephalus were counteracted by CCT8 overexpression. In summary, GAS5 aggravates neonatal hydrocephalus and inflammatory responses in a way of leasing miR-325-3p-involved regulation of CCT8.

Pediatric WNT medulloblastoma predisposition in intraoperative blood loss: a retrospective observational cohort study.

Introduction: Molecular subgroups influence the vascular architecture within medulloblastomas, particularly the wingless (WNT) subgroup, which contributes to its propensity for primary tumor hemorrhage. Whether this mechanism affects intraoperative blood loss remains unknown. This study aimed to assess the association between WNT medulloblastoma and the predisposition for blood loss. Methods: This was a retrospective observational study using data from a neuro-oncology center comprising molecular data on patients treated between December 31, 2014, and April 30, 2023. Differences between WNT and other subgroups in the risk of primary outcome-intraoperative blood loss were assessed using multivariable-adjusted linear regression. Results: Of the 148 patients included in the analysis, 18 patients (12.2%) had WNT, 42 (28.4%) had sonic hedgehog (SHH) TP53-wildtype, 7 (4.7%) had SHH TP53-mutant, and 81 (54.7%) were non-WNT/ non-SHH. The WNT subgroup more frequently underwent primary intratumoral hemorrhage (22% vs. 3.8%; p = 0.011). The median intraoperative blood loss was 400.00 (interquartile range [IQR] 250, 500) mL for WNT and 300.00 [200, 400] mL for the other subgroups (p = 0.136), with an adjusted ß of 135.264 (95% confidence intervals [CI], 11.701-258.827; p = 0.032). Similar results were observed in both midline and noninfiltrative margin medulloblastoma. Discussion: WNT medulloblastoma is typically associated with primary intratumoral hemorrhage and intraoperative blood loss. The validity of determining the surgical approach based on predicted molecular subtypes from imaging data is questionable. However, attempting to engage in risk communication with patients in a molecular-specific way is worthwhile to validate.

Postoperative interictal epileptiform discharges predict seizure recurrence after antiepileptic drug withdrawal regardless of concordance with surgical site.

Objective: The study aimed to explore the association between the site of interictal epileptic discharges (IEDs) on postoperative electroencephalogram (EEG) and seizure recurrence after antiepileptic drug (AED) withdrawal. The study hypothesizes that the concordance of IED sites with surgical sites indicates incomplete resection of epileptic focus, while non-concordance of IED sites with surgical sites indicates postoperative changes or cortical stimulation. The former has a higher risk of seizure recurrence. Methods: We retrospectively analyzed the postoperative EEG pattern of 182 consecutive children who underwent resection surgery. To identify the risk factors for seizure recurrence, we compared the attributes of seizure recurred and seizure-free groups by univariate and multivariate analyses. AED tapering was standardized, involving a 25% reduction in the dose of a single type of AED every 2 weeks, independent of the presurgical AED load. Results: We attempted AED withdrawal in 116 (63.7%) children. Twenty-eight (24.1%) children experienced seizure recurrence during or after AED withdrawal. A greater number of AEDs used at the time of surgery (p=0.005), incomplete resection (p=0.001), and presence of IED on postoperative EEG (p=0.011) are predictors of seizure recurrence. The completeness of resection and seizure recurrence after AED withdrawal were related to the presence of IED on the EEG, but not to the concordance of IED with surgical sites. Conclusion: For children with abnormal EEG, the decision to discontinue AED should be made more cautiously, regardless of the relative location of the discharge site and the surgical site.

Pathophysiological mechanisms underlying the development of focal cortical dysplasia and their association with epilepsy: Experimental models as a research approach.

Focal cortical dysplasia (FCD) is a structural lesion that is the most common anatomical lesion identified in children, and the second most common in adults with drug-resistant focal-onset epilepsy. These lesions vary in size, location, and histopathological manifestations. FCDs are classified into three subtypes associated with loss-of-function mutations in PI3K/AKT, TSC1/TSC2, RHEB, and DEPDC/NPRL2/NPRL3. During the decades of research into FCD, experimental models have played an irreplaceable role in the research design of studies investigating disease pathogenesis, pathophysiology, and treatment. Further, the establishment of FCD experimental models has moved the field forward by (1) revealing the cellular processes and signaling pathways underlying FCD pathogenesis and (2) varying the methods and materials to study the function of FCD proteins. Currently, FCD experimental models are predominantly murine, with each model providing unique insights into FCD lesions. This review briefly summarizes the pathology and molecular functions of FCD, further comparing the available modeling methods and indexes, as well as the utilization of models, followed by an analysis of the similarities, advantages, and disadvantages between these models and human FCD.

TYROBP serve as potential immune-related signature genes in the acute phase of intracerebral hemorrhage.

The development of intracerebral hemorrhage (ICH) is a dynamic process and intervention during the acute phase of ICH is critical for subsequent recovery. Therefore, it is crucial to screen potential signature genes and therapeutic target genes in the acute phase of ICH. In this study, based on the results of mRNA sequencing in mouse ICH and mRNA sequencing of human ICH from online databases, top five potential signature genes after ICH, Tyrobp, Itgb2, Tlr2, Ptprc and Itgam, were screened. Quantitative PCR results showed higher mRNA expression of Tyrobp, Itgb2, Tlr2, Ptprc, and Itgam in the 1-, 3- and 5-day mouse ICH groups compared to the sham-operated group. Immune infiltration correlation analysis shows that the top-ranked signature gene, Tyrobp, is negatively correlated with M2 macrophages and plasma cells, and Western blot analysis shows higher expression of the Tyrobp protein in the 1-, 3-, and 5-day mouse ICH groups compared to the sham-operated group. Furthermore, immunohistochemistry revealed that TYROBP protein expression was significantly higher in human ICH tissues than in normal brain tissues. Our results suggest that Tyrobp is a signature gene in the acute phase of ICH and may be a potential target for the treatment of the acute phase of ICH.

Seizure, Motor, and Cognitive Outcomes After Epilepsy Surgery for Patients With Sturge-Weber Syndrome: Results From a Multicenter Study.

BACKGROUND AND OBJECTIVES: Surgery is widely performed for refractory epilepsy in patients with Sturge-Weber syndrome (SWS), but reports on its effectiveness are limited. This study aimed to analyze seizure, motor, and cognitive outcomes of surgery in these patients and to identify factors associated with the outcomes. METHODS: This was a multicenter retrospective observational study using data from patients with SWS and refractory epilepsy who underwent epilepsy surgery between 2000 and 2020 at 16 centers throughout China. Longitudinal postoperative seizures were classified by Engel class, and Engel class I was regarded as seizure-free outcome. Functional (motor and cognitive) outcomes were evaluated using the SWS neurologic score, and improved or unchanged scores between baseline and follow-up were considered to have stable outcomes. Outcomes were analyzed using Kaplan-Meier analyses. Multivariate Cox regression was used to identify factors associated with outcomes. RESULTS: A total of 214 patients with a median age of 2.0 (interquartile range 1.2-4.6) years underwent surgery (focal resection, FR [n = 87]; hemisphere surgery, HS [n = 127]) and completed a median of 3.5 (1.7-5.0) years of follow-up. The overall estimated probability for being seizure-free postoperatively at 1, 2, and 5 years was 86.9% (95% CI 82.5-91.6), 81.4% (95% CI 76.1-87.1), and 70.7% (95% CI 63.3-79.0), respectively. The overall estimated probability of being motor stable at the same time post operatively was 65.4% (95% CI 58.4-71.2), 80.2% (95% CI 73.8-85.0), and 85.7% (95% CI 79.5-90.1), respectively. The overall probability for being cognition stable at 1, 2, and 5 years was 80.8% (95% CI 74.8-85.5), 85.1% (95% CI 79.3-89.2), and 89.5% (95% CI 83.8-93.2), respectively. Both FR and HS were effective at ensuring seizure control. For different HS techniques, modified hemispherotomy had comparable outcomes but improved safety compared with anatomical hemispherectomy. Regarding FR, partial resection (adjusted hazard ratio [aHR] 11.50, 95% CI 4.44-29.76), acute postoperative seizure (APOS, within 30 days of surgery; aHR 10.33, 95% CI 3.94-27.12), and generalized seizure (aHR 3.09, 95% CI 1.37-6.94) were associated with seizure persistence. For HS, seizure persistence was associated with APOS (aHR 27.61, 9.92-76.89), generalized seizure (aHR 7.95, 2.74-23.05), seizure frequency ≥30 times/month (aHR 4.76, 1.27-17.87), and surgical age ≥2 years (aHR 3.78, 1.51-9.47); motor stability was associated with severe motor defects (aHR 5.23, 2.27-12.05) and postoperative seizure-free status (aHR 3.09, 1.49-6.45); and cognition stability was associated with postoperative seizure-free status (aHR 2.84, 1.39-5.78) and surgical age <2 years (aHR 1.76, 1.13-2.75). DISCUSSION: FR is a valid option for refractory epilepsy in patients with SWS and has similar outcomes to those of HS, with less morbidity associated with refractory epilepsy. Early surgical treatment (under the age of 2 years) leads to better outcomes after HS, but there is insufficient evidence that surgical age affects FR outcomes. These findings warrant future prospective multicenter cohorts with international cooperation and prolonged follow-up in better exploring more precise outcomes and developing prognostic predictive models. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that in children with SWS and refractory seizures, surgical resection-focal, hemispherectomy, or modified hemispherotomy-leads to improved outcomes.