Neurological Morbidity Research Articles (Page 1)

Diagnosis of central nervous system (CNS) lymphoma has historically required CNS tissue biopsy, which often leads to delays in diagnosis and carries risk of neurological morbidity. MYD88 L265P is a prevalent recurrent mutation in CNS lymphoma that can be effectively detected by polymerase chain reaction (PCR) of cell-free DNA. We sought to determine whether detection of MYD88 L265P is a viable method for diagnosis of CNS lymphoma. We developed and implemented a Clinical Laboratory Improvement Amendments-certified rapid PCR assay for the detection of circulating MYD88 L265P variant in cerebrospinal fluid. Testing was conducted across a multi-institutional prospective cohort, and diagnostic yield, clinical course, and treatment outcomes were analyzed. Our assay was implemented in 184 patients from 19 hospitals over the course of 16 months. A positive result (N = 14 patients with clinical data) facilitated rapid initiation of CNS lymphoma-targeted treatment with clinical response. There was 100% diagnostic concordance with CNS tissue biopsy (N = 8) and multiple cases (N = 6) for whom treatment was initiated without the need for CNS tissue confirmation. Time to treatment was faster in patients who underwent cerebrospinal fluid analysis for MYD88 L265P without CNS biopsy (P = .048). These findings support the utilization of rapid PCR of cell-free DNA as a diagnostic method that may obviate tissue biopsy in the diagnosis of CNS lymphoma. Liquid biopsy to detect the MYD88 L265P variant is a rapid, feasible, and safe method for diagnosing CNS lymphoma.

Traumatic brain injury has a high neurological morbidity, it is characterized by structural and physiological damage to brain function caused by external forces. Extensive and sustained damage mediated by neuroimmune and neuroinflammation may be closely associated with the prolonged course of TBI and the worsening of its prognosis. Tumor necrosis factor-alpha, one of the pro-inflammatory mediators, has been identified as a key regulator of the inflammatory response. It has attracted attention for binding to two different receptors, thereby initiating distinct signal transduction pathways. It has been found that there is a lack of relevant summaries of the different factors that make the pro-inflammatory or anti-inflammatory effects of TNF-α in TBI vary significantly. Therefore, this review examines the fundamental signaling pathways that regulate TNF-α in TBI in both the neuroimmune and inflammatory responses. It also reviews the progress of research on the pharmacological and physical technologies that target TNF-α for the treatment of TBI. The review emphasizes the biological effects of TNF-α as a receptor and ligand, as well as current difficulties and challenges.

Brain arteriovenous malformations (bAVMs) consist of a tangled nidus of abnormal dilated vessels characterized by direct connections between arteries and veins that lack an intervening capillary bed, creating a high-to-low flow pressure system that is predisposed to spontaneous hemorrhage with significant associated neurologic morbidity and mortality. Treatment options for bAVMs include the following: surgical resection, intravascular embolization to obliterate blood flow through the AVM, and radiosurgery. Understanding the molecular mechanisms of bAVM formation and factors that predispose it to hemorrhage can lead to novel treatments that can improve the prognosis for patients. This review summarizes emerging insights into the complex and dynamic molecular mechanisms of bAVMs. Dysregulation in key VEGF, TGF-β/BMP9/10–ENG–ALK1–SMAD4, Notch, and MAPK/ERK signaling pathways drive abnormal angiogenesis in both syndromic and sporadic forms, with KRAS/BRAF/MAPK21 mutations specifically linked to the latter. Advances in bAVM-induced animal models have corroborated many of the genetic profiles found in humans, and they continue to provide novel insights into bAVM mechanisms. Collectively, these mechanistic findings are guiding translational advances, with targeted therapies and liquid biopsy approaches emerging as avenues for precision treatment and improved patient outcomes.

IntroductionNeonatal aortic arch surgery is associated with neurological morbidity of varying severity which is detected and potentially limited through neuroprotective strategies. We conducted a survey of healthcare professionals at all neonatal cardiac surgery centres in the United Kingdom and Ireland to determine current intraoperative neuromonitoring and neuroprotection practice.MethodsAn online cross-sectional survey was sent to congenital cardiac surgeons, cardiac anaesthetists, clinical perfusion scientists, and clinical neurophysiology professionals in all 12 level 1 paediatric cardiac surgical centres. Information was sought on their current clinical practice in neonates undergoing aortic arch surgery, including pharmacological management, cardiopulmonary bypass, acid-base and blood pressure management, neuromonitoring, and hypothermic circulatory arrest, and the feasibility and willingness to participate in a future clinical trial of neuroprotective strategies in these patients.ResultsWe received 55 (34%) responses, including representatives of all four clinical disciplines in 9 (75%) centres. Cooling to a nasopharyngeal temperature of 18°C before hypothermic circulatory arrest, selective antegrade cerebral perfusion, and near-infrared spectroscopy (NIRS) monitoring are common practice, whereas pharmacology, acid-base management, blood pressure and flow parameters, and NIRS-based interventions vary. In 7 (58%) centres, respondents from all four disciplines were willing to consider participation in a future clinical trial on neuroprotection.ConclusionsAspects of intraoperative neuroprotection and neuromonitoring are common across centres, although key areas of practice differ between practitioners and institutions. Most respondents were willing to participate in a future multi-centre clinical trial, which suggests clinical equipoise in the optimal strategy to protect the neonatal brain during aortic arch surgery.

High-grade gliomas (HGG) are aggressive primary brain tumors associated with substantial neurological and functional morbidity. While previous research has shown no significant differences in self-reported quality of life between patients undergoing first-time resection (FTR) and those undergoing repeat surgical resection (RSR), the impact of repeated surgical resections on objective cognitive outcomes remains unclear. This study compared pre- and postoperative neuropsychological performance in these two patient groups. Sixty-seven adults with HGG (FTR: n = 39; RSR: n = 28) completed comprehensive neuropsychological evaluations both pre- and approximately 2 weeks postoperatively. Cognitive domains assessed included attention/working memory, processing speed, executive functioning, language, and learning/memory. Standardized Z-scores were used to compute composite domain scores, and both composite-score and individual-test approaches were applied to classify cognitive impairment and postoperative decline. There were no group differences in any of the cognitive domains at baseline. Four to 28% of the surgical sample showed single domain cognitive impairment while 33 to 71% showed multidomain impairment depending on the classification method used. Further, no significant differences were seen between the FTR and RSR groups in cognitive outcome or change following surgery. Most patients showed no decline in cognitive performance. Across classification schemes, 18 to 36% declined in a single domain and 4 to 26% declined in multiple domains. In a carefully selected, high-functioning surgical cohort, repeat surgical resection was not associated with increased risk of early postoperative cognitive decline compared to first-time resection. These findings support the consideration of RSR as a viable treatment option for recurrent HGG when aiming to balance oncologic control with preservation of cognitive function.

IntroductionCompare outcomes of very preterm infants (VPIs) with a birth weight<1,500 g based on delivery mode and propensity score matching (PSM).MethodsThis was a retrospective study (2016–2021) of 1,375 VPIs (692 vaginal and 683 cesarean deliveries). PSM created 390 matched pairs. Outcomes included respiratory and neurological morbidity and mortality.ResultsPSM revealed no significant difference between the two groups at baseline or after antenatal corticosteroids administration. The incidence rates of birth asphyxia, delivery room resuscitation, neonatal respiratory distress syndrome, use of pulmonary surfactants, pulmonary hemorrhage, and use of invasive ventilation in the vaginal delivery group after PSM were 42.3, 68.2, 65.9, 59.2, 7.2, and 36.7%, respectively. These rates were significantly lower than those in the cesarean delivery group (52.3, 83.3, 79.5, 70.8, 14.4, and 51.8%, respectively) (p < 0.05). The difference was more significant in infants with a gestational age of 28–31+6 weeks (p < 0.05). There were no significant differences in the incidence rates of intraventricular hemorrhage (IVH), severe IVH, periventricular leukomalacia, bronchopulmonary dysplasia, necrotizing enterocolitis (NEC), NEC surgery, premature infant retinopathy (ROP), severe ROP, late-onset neonatal sepsis, or mortality between the two groups. The mortality rate within 3 days in the vaginal delivery group was 7.7%, which was higher than that in the cesarean delivery group (3.3%), primarily in infants with a gestational age < 28 weeks (p < 0.05).ConclusionCesarean section reduced early mortality in VPIs <28 weeks but increased respiratory morbidity at 28–31+6 weeks, with no impact on other outcomes. Since 52.1% of the cesarean sections were emergency procedures, this may have biased the results.

Cerebral ischemia/reperfusion (I/R) injury remains a significant contributor to adult neurological morbidity, primarily due to exacerbated neuroinflammation and cell apoptosis. These processes amplify brain damage through the release of various pro-inflammatory cytokines and pro-apoptotic mediators. Although long non-coding RNAs (lncRNAs) are increasingly recognized for their involvement in regulating diverse biological pathways, their precise role in cerebral I/R injury has not been fully elucidated. In the current study, transcriptomic profiling was conducted using a rat model of focal cerebral I/R, leading to the identification of lncRNA-1810026B05Rik-also referred to as CHASERR-as a novel lncRNA responsive to ischemic conditions. The elevated expression of this lncRNA was observed in mouse brain tissues subjected to middle cerebral artery occlusion followed by reperfusion (MCAO/R), as well as in primary cortical neurons derived from rats exposed to oxygen-glucose deprivation and subsequent reoxygenation (OGD/R). The results suggested that lncRNA-1810026B05RiK mediates the activation of the nuclear factor-kappaB (NF-κB) signaling pathway by physically binding to NF-kappa-B inhibitor alpha (IκBα) and promoting its phosphorylation, thus leading to neuroinflammation and neuronal apoptosis during cerebral ischemia/reperfusion. In addition, lncRNA-1810026B05Rik knockdown acts as an NF-κB inhibitor in the OGD/R and MCAO/R pathological processes, suggesting that lncRNA-1810026B05Rik downregulation exerts a protective effect on cerebral I/R injury. In summary, the lncRNA-1810026B05Rik has been identified as a critical regulator of neuronal apoptosis and inflammation through the activation of the NF-κB signaling cascade. This discovery uncovers a previously unrecognized role of 1810026B05Rik in the molecular mechanisms underlying ischemic stroke, offering valuable insights into disease pathology. Moreover, its involvement highlights its potential as a novel therapeutic target, paving the way for innovative treatment strategies for stroke patients.

Maternal risk stratification and planned birth improve pregnancy outcomes at term: A population-based cohort study.

Contralateral Transfalcine Approach for Recurrent Glioblastoma: A Technical Note on Multimodal Planning, Fluorescence-guided Resection, and Re-Irradiation Strategy.

Evolving treatment paradigms for melanoma brain metastases: A systematic review of current modalities.

For patients with language-eloquent brain tumors, surgeons must maximize the extent of resection while minimizing neurological morbidity. Despite the extensive use of noninvasive brain mapping techniques, it remains unclear how to preoperatively localize brain regions essential for sustaining language function in a data-driven manner. Here the authors investigate the clinical utility and functional relevance of regions mapped by functional MRI (fMRI), transcranial magnetic stimulation (TMS), and diffusion tensor imaging (DTI). This study included 71 consecutive patients undergoing resection of language-eloquent gliomas from July 1, 2017, to August 1, 2023. A nonlinear coregistration algorithm was used to overlay the postoperative resection cavity onto the preoperative MRI. The resection of preoperative cortical and subcortical localizations was correlated with long-term linguistic outcomes. Fiber tracts were localized by seeding DTI tractography with different cortical features: TMS points (TMS tracts), the fMRI blood oxygen level-dependent (BOLD) signal (fMRI tracts), and a peritumoral 1-cm grid (grid tracts). Multiple fractional anisotropy (FA) thresholds were used for each cortical seed structure. Fiber tracts were normalized to Montreal Neurological Institute space to identify group-level characteristics. The majority of patients were male (n = 42, 59%) and younger than 60 years of age (n = 46, 65%). Forty-one patients (58%) had high-grade gliomas, while 30 patients (42%) had low-grade gliomas. The authors found that the resection of preoperatively identified cortical language regions does not predict long-term aphasic decline. However, the resection of tracts localized by the TMS points and grid at the 75% normalized FA threshold significantly predicted language outcomes (OR 51, p < 0.001 and OR 5.0, p = 0.04, respectively). Tracts localized by the fMRI BOLD signal did not predict language outcomes at any FA threshold (OR 0.29-5.32, p = 0.42-0.94). Tracts localized by all three cortical seed structures recapitulated normative patterns of subcortical connectivity by colocalizing with and sharing group-level features with language-associated normative tracts derived from the Human Connectome Project. Functional tracts that predicted linguistic outcomes (TMS and grid tracts) demonstrated shared features at a group-level distinct from the nonpredictive fMRI tracts. The resection of cortical language regions mapped preoperatively by fMRI and TMS did not predict aphasic surgical deficits. In contrast, resecting white matter tracts localized by cortical TMS points and a peritumoral cortical grid significantly predicted aphasic decline, while resecting tracts localized by the fMRI BOLD signal as seeds did not predict linguistic outcomes.

Spinal metastases pose a significant challenge in oncology, with incidence rates increasing alongside improved survival rates. Radiation therapy (RT) has played a crucial role in managing spinal disease progression and reducing associated neurological morbidity. However, management of spinal metastases for which prior RT failed is challenging, and there are limited data regarding the safety and efficacy of stereotactic body radiotherapy (SBRT) for reirradiation. The authors present the largest series to date of patients undergoing SBRT for reirradiation of spinal metastases. The medical records of patients treated with spine SBRT for reirradiation at a target that overlapped or abutted a previous radiation field between 2010 and 2021 were retrospectively reviewed. The cumulative constraint to the neural avoidance structures was a biologically effective dose with an α/β value of 3 of 75 Gy (above the conus) or 106 Gy (below the conus), accounting for 25% repair at 6 months and 50% repair at 1 year following the first course of RT. Radiographic local recurrence was defined according to Spine Response Assessment in Neuro-Oncology criteria as progressive disease in the treatment volume or at the margin of the treatment field on CT or MRI compared with imaging studies before SBRT. Cumulative incidence of local recurrence was reported with death as a competing event, and overall survival was estimated using Kaplan-Meier analysis. Toxicity grades were determined according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. A total of 224 vertebral segments from 89 lesions treated with SBRT reirradiation in 83 patients were included in this analysis. The median age at SBRT reirradiation was 63 years, with a median follow-up of 8.0 months. The most common primary cancer types were non-small cell lung cancer (18%), gastrointestinal cancer (16%), renal cell carcinoma (15%), and prostate cancer (15%). Lesions predominantly occurred in the thoracic spine (52%). The median time between initial RT and SBRT reirradiation was 15.4 months. Prior radiation techniques included 3D or 2D conformal RT (52%), SBRT (43%), and intensity-modulated radiotherapy (4%). Reirradiation SBRT prescription doses varied by fractionation, with a median planning target volume of 179.1 cm3. Immunotherapy use was associated with improved local control and, notably, no increase in toxicity. No cases of radiation myelopathy were observed. SBRT reirradiation for progressive or recurrent spinal metastases appears to be a safe and effective treatment option, offering durable local control and pain relief with low toxicity. Future prospective and multi-institutional studies are warranted to validate these findings.

Carotid Blowout Syndrome in Head and Neck Cancer Patients after Free Flap Reconstruction.

Despite a current overall survival (OS) > 20 years in patients undergoing surgery for diffuse low-grade glioma (LGG), there is no study focusing on functional status in long-term survivors. Here, a unique cohort of LGG patients followed for at least 15 years after mapping-guided resection is reported with analysis of long-lasting outcomes, especially the ability to work. Inclusion criteria were LGG patients operated on by the author using intraoperative mapping and follow-up ≥ 15 years after surgery. Long-term functional results were studied by assessing the Karnofsky Performance Scale (KPS) score and professional activity until the last evaluation. Two groups were compared: group 1 comprising patients who continued to work after surgery until the last follow-up, including those who eventually retired because of age; and group 2 comprising patients who did not return to work (RTW) after surgery or who stopped working because of their disease during follow-up. This consecutive cohort included 103 patients (54 men [52.4%], 49 women [47.6%], mean ± SD age 37.8 ± 7.6 years), including 96 (93.2%) who experienced seizures (and 7 with incidentalomas [6.8%]). The mean preoperative tumor volume was 46.7 ± 35.6 cm3. Three patients (2.9%) had postoperative hemianopia deliberately generated. The mean postoperative KPS score was 94.8 ± 5.7, with 81 patients able to RTW (90%). The mean extent of resection (EOR) was 93.4% ± 7.4%, with 40 supratotal/total resections (38.8%). The mean residual tumor volume was 3.6 ± 5.6 cm3. There were 22 isocitrate dehydrogenase-mutated astrocytomas (21.4%) and 48 oligodendrogliomas (46.6%) (33 gliomas not otherwise specified [32%]). Ten patients (9.7%) received early radiotherapy, which was correlated to a lower rate of RTW (p = 0.05). Sixty-three patients (61.2%) underwent reoperation(s), with a total rate of neurological morbidity of 1.5% after 205 resections. The mean follow-up was 18.2 ± 2.9 years with an OS rate of 83.5%. Among the 86 patients who were still alive at final evaluation, 78 (90.7%) had KPS score ≥ 80. The proportion of patients with KPS score ≥ 80 at last follow-up was lower among irradiated patients (p = 0.005). The mean KPS score was lower before (p = 0.003) and 3 months after (p < 0.00001) surgery in group 2. In group 1, the preoperative (p = 0.046) and postoperative (p = 0.047) tumor volumes were smaller, with greater extent of resection (p = 0.03). This is the first series of LGG patients who lived ≥ 15 years after mapping-based surgery. These original data show long-term preservation of functional status, including professional activities, particularly in patients with early supratotal/total resection and without radiation therapy.

Foix-Alajouanine syndrome: A systematic review and meta-analysis of presentation, management, and outcomes.

BACKGROUNDVestibular schwannomas (VS) represent the fourth most common type of intracranial tumor. While the majority of these benign lesions are non-growing or slow-growing with the potential to be managed through active surveillance, a subset progress rapidly between scans, posing a substantial threat of neurologic morbidity. At present, patient demographic, clinical, and radiographic characteristics have failed to reliably identify these high-risk tumors. There is growing interest in the use of fluid-based biomarkers to predict tumor growth, hearing loss, and response to surgical or radiotherapeutic treatment. METHODSWe conducted a systematic review summarizing the current evidence for the utility of fluid-based biomarkers in predicting tumor progression and hearing outcomes in VS. Ovid MEDLINE, Embase, Web of Science, and Scopus were searched for primary source articles using keywords for fluid-based biomarkers and outcomes in adult (≥ 18 years) patients with de novo diagnoses of sporadic vestibular schwannoma. RESULTSTen studies conducted from 2011–2024 were included. Five studies measured biomarkers in blood, two in CSF, and two in perilymph. Three studies evaluated immune-related biomarkers, one analyzed protease enzymes, three performed proteomics, and a final study performed microRNA profiling. Perilymph AHSG and CFHR2, cerebrospinal fluid FN1 and fibrinogen, and plasma MMP-14, were identified as biomarkers of hearing loss. Blood neutrophil-to-lymphocyte ratio, serum TGF-β1 and CSF of ABCA3, KLF11, SCG1, BASP1, CA2D1 and PRDX2 were associated with tumor growth. CONCLUSIONBiomarkers involved in inflammation and extracellular matrix remodeling show promise for risk stratification in sporadic VS. More work is needed to validate these preliminary findings.

Neonatal hypoxic-ischemic brain injury (HIBI) caused by perinatal asphyxia is a primary cause of long-term neurological morbidity. Hypothermia is the sole available clinical intervention despite its limited efficacy. Intranasal mesenchymal stem cells (MSCs) show promise for the treatment of HIBI. This study explores the efficacy, migration, treatment window, and therapeutic mechanisms of intranasally applied Wharton's jelly-derived MSCs (WJ-MSCs) in a neonatal HIBI mouse model, and assesses its therapeutic benefit in conjunction with hypothermia. Nine-day-old C57BL/6 mice underwent hypoxia-ischemia (HI), with or without hypothermia, and were intranasally dosed with 0.1 to 2.0 × 106 WJ-MSCs, at 3 or 10 days post-HI. WJ-MSCs were traced using different techniques. Neurogenesis was examined 2 days post-treatment. Neuroinflammation, sensorimqotor outcome, and neuronal tissue loss was assessed 28 days post-HI. Additionally, anti-inflammatory and neuroregenerative properties of WJ-MSCs were investigated in non-contact co-cultures with microglia and neural stem cells, and by secretome profiling. Intranasally delivered WJ-MSCs reduced HI-induced lesion size and sensorimotor impairments. WJ-MSCs expressed multiple receptors for upregulated chemokines in the HI-lesion, and migrated from the nasal cavity into the meninges and brain parenchyma. WJ-MSCs secreted a broad spectrum of immunomodulatory and neuroregenerative proteins, and inhibited neuroinflammation and boosted neuroregeneration in vivo and in vitro. WJ-MSC potency was sustained across different donors. Importantly, intranasal WJ-MSCs augmented the therapeutic benefits of hypothermia following neonatal HIBI in mice. This study provides new translational evidence that intranasal WJ-MSCs, either alone or in combination with hypothermia, mitigate the consequences of neonatal HIBI by resolving inflammation and boosting neurorepair through their secretome. ANN NEUROL 2025.

Spinal cord hemangioblastomas are rare, benign, intradural tumors that, despite their nonmalignant histopathology, can lead to substantial neurological morbidity. While disparities in outcomes based on race and socioeconomic status have been well-documented in other spinal tumor populations, their role in spinal cord hemangioblastoma remains poorly understood. In this study, we utilize the National Cancer Database (NCDB) to evaluate the influence of race, socioeconomic factors, and healthcare access on survival outcomes in patients with spinal cord hemangioblastoma. Additionally, we explore the utility of machine learning-based survival models to improve individualized risk prediction and to identify key clinical and sociodemographic determinants of long-term survival. Patients diagnosed with spinal cord hemangioblastoma were identified from the National Cancer Database (NCDB) using ICD-O-3 histology and topography codes. Demographic, socioeconomic, and clinical variables were compared across racial groups (White, Black and Asian). Long-term overall survival (OS) was defined as survival beyond 10years. Kaplan-Meier and multivariable Cox regression analyses were used to evaluate survival outcomes and identify independent predictors of mortality. Tumor size was stratified using the cohort-wide mean (62.2mm) for interpretability. Temporal trends in racial distribution and surgical technique (open vs. MIS) were assessed using Mann-Kendall trend testing. Gradient Boosting Survival, Cox proportional hazards, and Random Survival Forest models were developed and validated for mortality prediction. The best-performing model was interpreted using SHAP analysis. A total of 716 adult patients with spinal cord hemangioblastoma were analyzed, with the majority being White (83.7%), followed by Black (12.3%) and Asian (4%). Significant differences were observed across racial groups in age, insurance status, income quartiles, and comorbidity scores, though sex distribution and facility type utilization were comparable. Most patients were treated at academic centers, and surgery alone was the predominant treatment modality, with no racial disparities in extent of resection or use of radiation. Kaplan-Meier analysis showed significantly higher 10-year and long-term mortality in White patients; however, race was not an independent predictor in multivariable Cox regression, where increased age, higher CDCC scores, urban residence, and treatment at comprehensive community cancer centers were associated with worse survival. Surgery, with or without radiation, was protective compared to radiation alone. Temporal analysis showed stable racial distribution and minimal uptake of minimally invasive surgery from 2010 to 2017. The Gradient Boosting Survival model achieved the highest predictive performance (AUC = 0.8214; C-index = 0.7817), with age, facility type, and comorbidity burden identified as the strongest predictors of mortality in SHAP analysis. A publicly available web-based calculator was developed based on this model to provide individualized survival estimates. Racial and socioeconomic disparities were associated with differences in clinical outcomes on univariate analysis. However, race and insurance status were not independent predictors of mortality in multivariable-adjusted models. This suggests that the observed survival differences may be explained by confounding factors, such as comorbidity burden, treatment modality, or access to specialized care. Notably, poorer survival was independently associated with treatment at Comprehensive Community Cancer Programs and with higher comorbidity scores, underscoring the importance of ensuring equitable access to high-volume, specialized centers. Lastly, the Gradient Boosting Survival model enhanced mortality risk prediction by incorporating both clinical and socioeconomic variables, supporting its potential utility in guiding targeted interventions to improve long-term outcomes.

Neurological disorders acquired during the perinatal period are a leading cause of long-term childhood disability and constitute a significant portion of the global disease burden. Despite progress in reducing neonatal mortality, neurological morbidity remains a major challenge. Neonatal neurology, a relatively new subspecialty, aims to improve outcomes for affected infants through advances in understanding neurological injury mechanisms, developing assessment tools, and implementing preventive and therapeutic strategies. In Spain, neonatal neurology has significantly progressed over the past three decades, largely due to the contributions of Dr. Alfredo García-Alix. Recognized as a pioneer in the field, he played a crucial role in establishing neonatal neurological care services and fostering education and research. After training at Washington University in St. Louis, he introduced comprehensive neonatal neurology programs in Spain and co-founded the NeNe Foundation to advance education in the field. He also led the creation of the 'Spanish Neonatal Brain Group' and contributed extensively to neonatal neurology research. Dr. García-Alix was an advocate for holistic, multidisciplinary neonatal care, emphasizing early intervention, neuroprotective strategies, and parental involvement. His work significantly influenced neonatal care models in Spain and Latin America, and his legacy continues to shape the field through his teachings, research, and clinical contributions.

Developmental and Epileptic Encephalopathies: Progress in Understanding and Clinical Implications