Search Results (36)

Background/Objectives: Severe brain injury (SBI) in very preterm infants includes heterogeneous lesions with distinct timing, burden and outcomes. We used cranial ultrasound (CUS) to describe SBI entity, documented timing, three-domain burden, deaths following documented withdrawal, withholding or non-escalation of life-sustaining treatment for poor neurological prognosis (neuro-WWLST), and survivor outcomes. Methods: Retrospective single-center cohort (1991–2020) of 2841 very preterm infants (<32 weeks’ gestation and/or birth weight ≤ 1500 g) with complete CUS within 48 h after birth. CUS was summarized by four windows, three domains—parenchymal lesion, intraventricular hemorrhage (IVH) and ventriculomegaly—and three mutually exclusive entities: periventricular hemorrhagic infarction (PVHI), cystic periventricular leukomalacia (cPVL and grade 3 IVH without PVHI/cPVL (IVH3 entity). Cross-outcome analyses used common maximal-burden CUS. Results: SBI occurred in 286/2841 infants (10.1%) and neuro-WWLST death in 45/2841 infants (1.6%); 43/45 occurred within SBI, and 43/89 SBI deaths (48.3%) followed documented neuro-WWLST. Using common maximal-burden CUS, severe three-domain involvement was more frequent among neuro-WWLST deaths than survivors (37.2% vs. 8.6%). Among SBI survivors with follow-up, cerebral palsy (CP) occurred in 87/176 (49.4%) and clinically classified school-age cognitive sequelae in 50/155 (32.3%). Outcomes varied by entity, with mainly ambulatory unilateral CP after PVHI, more frequent non-ambulatory bilateral CP after cPVL, and a heterogeneous IVH3 profile. Severe three-domain involvement identified a small subgroup with higher outcome burden, but outcomes were not deterministic. Conclusions: A structured, descriptive CUS approach separating lesion entity, documented timing and multidomain burden may support transparent cohort-level description of SBI trajectories, documented neuro-WWLST deaths and survivor outcomes. Full article

Background/Objectives: Multiple sclerosis (MS) remains challenging to diagnose due to clinical and radiological overlap with mimicking conditions. The 2024 revisions of the McDonald criteria have incorporated the central vein sign (CVS) and paramagnetic rim lesions (PRLs) as magnetic resonance imaging (MRI) biomarkers to improve diagnostic specificity. This study assessed the prevalence and anatomical distribution of CVS and PRLs in patients with relapsing–remitting MS (RRMS). Methods: This cross-sectional study included 91 patients with RRMS diagnosed according to the 2017 McDonald criteria. MRI scans were obtained using 3T scanners, and T2-FLAIR and susceptibility-weighted angiography (SWAN) sequences were analyzed. CVS and PRLs were identified using established criteria. Patients were stratified by lesion count (<5, 5–9, ≥10), and lesions were categorized by anatomical location. Descriptive statistics, chi-square tests, and multivariable logistic regression adjusted for covariates were performed. Results: CVS was present in 69.2% of patients, while PRLs were identified in 29.7%. Both markers were more frequent in patients with higher lesion burden in univariate analysis. CVS prevalence increased significantly with lesion count (p < 0.001) and remained an independent predictor in multivariable logistic regression. PRL presence was associated with lesion count in univariate analysis but not after adjustment. Most CVS- and PRL-positive lesions were supratentorial and predominantly periventricular. No significant association was observed between CVS and PRL presence. Conclusions: CVS is a highly prevalent MRI feature in RRMS and independently associated with lesion burden, supporting its role as a diagnostically relevant imaging marker. PRLs were less prevalent and showed weaker independent associations. Full article

Background/Objectives: Ventricular enlargement is a common finding on non-contrast computed tomography (CT) in acute neurological presentations, occurring in hydrocephalus, stroke, and traumatic brain injury. This study evaluated whether routinely available CT-based ventricular morphometric parameters can distinguish hydrocephalus from stroke and traumatic brain injury using initial imaging examinations. Methods: This retrospective observational study included 186 adults (68 with hydrocephalus, 64 with stroke, and 54 with TBI) who underwent index non-contrast cranial CT. Quantitative ventricular parameters included Evans index and third ventricle width, alongside temporal horn dilation and periventricular edema. Multivariable logistic regression models were developed to assess diagnostic performance. A primary morphometric model and a distortion-controlled model incorporating midline shift, mass lesions, and hemorrhage burden were analyzed. Discrimination was evaluated using receiver operating characteristic (ROC) curves. Results: Patients with hydrocephalus showed significantly greater ventricular enlargement, with higher Evans index and third ventricle width compared with stroke and traumatic brain injury groups. The primary model demonstrated moderate discrimination (AUC 0.71). After adjustment for intracranial distortion variables, model performance improved substantially (AUC 0.91), with balanced sensitivity and specificity at optimized thresholds. Evans index and third ventricle width were the strongest independent predictors. Conclusions: CT-derived ventricular morphometrics provide a practical and reproducible approach for differentiating hydrocephalus from stroke and traumatic brain injury on first-presentation CT, supporting objective interpretation in routine neuroimaging practice. Full article

Background and Clinical Significance: Deep thalamic and periventricular lesions are uncommon in adults but can result in significant loss of function because of their convergence on three interdependent processes: thalamocortical state regulation, throughput of periventricular long association systems, and ventricular compartmental compliance. The resulting combination of executive control collapse, retrieval-weighted language fragility, and load-sensitive gait instability may occur early after a lesion forms an atrial/posterior horn interface, and pressure-linked autonomic symptoms may be late to develop. Screening deficits will likely be minimal and therefore underreported. Objective/Aim: To present a thalamic–atrial/posterior horn tumor case with quantified load-sensitive cognitive–language–gait dysfunction and to detail a physiology-guided, sequence-driven decompression approach emphasizing ventricular relaxation and perforator-preserving, interface-limited thalamic resection. Case Presentation: A 56-year-old female patient experienced a 3-month, rapidly progressive decline in her cognitive and language abilities. The clinical progression was not stepwise or punctuated by a single “sentinel” event. She had a moderate level of cognitive impairment consistent with both Broca’s and Wernicke’s aphasias (MoCA: 22/30) and suffered from significant interference effects and increased cost of task-switching. Her ability to generate novel responses and name objects was significantly impaired; however, she was able to repeat words and phrases appropriately. In addition, she exhibited a severe sustained attention signature and a high error rate during dual-task performance, indicating severe gait instability, although her overall global anchors were nearly neutral (GCS 15; FOUR 15/16; NIHSS 2). Nausea and vomiting occurred simultaneously with the cognitive and language decline, suggesting decreased intracranial compliance. MRI revealed a heterogeneous left-sided thalamic tumor extending into the posterior horn of the lateral ventricle. The tumor caused deformation of the lateral ventricle and midline displacement. The patient underwent microsurgical intervention using a physiology-conscious sequence of graded cerebrospinal fluid (CSF) equilibration and primary mechanical removal of the tumor from the ventricular system. Additionally, decompression of the thalamus was performed in a manner that was cognizant of the boundaries formed by the perforating arteries of the thalamus. Early resolution of pressure symptoms was noted postoperatively. Objective measures demonstrated significant improvement in the patient’s executive functioning, language skills, attentional errors, and dual-task performance stability. The patient remained functionally independent at discharge and at subsequent follow-up visits. Surveillance imaging did not demonstrate any evidence of tumor recurrence. Conclusions: The clinical presentation described above is supportive of a model in which the synergy between deep network damage and distortion of the posterior ventricular compartment amplifies network dysfunction. Additionally, the use of quantitative stress-phenotyping makes it possible to identify deep network pathology early in its course. Finally, the physiology-guided decompression approach that was used in this case has the potential to increase functional reserve in patients with pathology that requires millimeter transitions. Full article

Background and Objectives: Endoscopic biopsy of brain lesions plays an important role in the management of intra- and periventricular lesions. While the diagnostic yield of this technique has been reported with varying success across studies, its outcome is likely influenced by specific technical nuances of the procedure. However, the relationship between these technical factors and diagnostic accuracy remains understudied in the current literature. We aim to describe the procedural rationale, key anatomical considerations, and technical nuances of the endoscopic biopsy of intra- and paraventricular brain lesions, comparing standard tissue forceps with a side-cutting biopsy needle technique. Materials and Methods: We conducted a ten-year single-center, retrospective study of patients who underwent endoscopic biopsy for intra- and paraventricular brain lesions between January 2014 and December 2024. Patients were divided based on the biopsy technique used: the first group of 11 patients was treated using a side-cutting biopsy needle from the center of the lesion, while the second group of five patients underwent tissue sampling with standard endoscopic tissue cup forceps. The study evaluates and compares both approaches in terms of safety and diagnostic accuracy. Results: Endoscopic visualization enabled direct assessment of the biopsy site in both groups. Histopathological diagnoses were successfully obtained in all cases with a side-cutting biopsy needle (11/11, 100.0%), and in almost all cases with the cup forceps technique (4/5, 80.0%). In patients with obstructive hydrocephalus, an endoscopic third ventriculostomy (ETV) was performed as the first and therapeutic step in all procedures and two patients required a shunt procedure. Conclusions: Endoscopic biopsies utilizing a side-cutting biopsy needle strategy offer a promising adjunctive approach for selected intra- and paraventricular brain lesions. This method allows for direct visualization of the intraventricular surface, while the use of a needle biopsy can enhance the likelihood of obtaining diagnostically representative tissue with a high degree of reliability. Full article

Background and objectives. White matter hyperintensities (WMHs) on brain magnetic resonance imaging (MRI) are linked to cognitive decline, but clinical assessment still relies mainly on visual grading (Fazekas), which is coarse and rater-dependent. We described the lesion volume of WMHs and the association of the anatomical distribution with the severity of cognitive impairment using automated lesion analysis. In addition, we evaluated whether automated volumetric quantification is more strongly associated with cognitive performance than visual grading. Materials and Methods. In a retrospective cross-sectional study, forty-one adults referred for cognitive concerns underwent standardised 3.0 tesla MRI. White matter hyperintensities were automatically segmented using Icometrix software to obtain total and regional volumes (periventricular, subcortical, brainstem, cerebellum). Visual grading used the Fazekas scale separately for periventricular and deep white matter, with a combined grade defined by the higher of the two. Cognitive performance was grouped based on the Montreal Cognitive Assessment (MoCA) into high (≥26), moderate (18–25), and low (≤17). Statistics included Spearman’s correlation and the Kruskal–Wallis test with Dunn’s post hoc test where applicable. Results. Higher total white matter hyperintensity volume was associated with lower Montreal Cognitive Assessment scores and showed significant differences across cognitive groups. The Fazekas combined grade correlated more weakly with the MoCA score. Regional volumetric differences showed trends, but were not statistically significant. Total volumetric burden increased stepwise across combined Fazekas categories, supporting convergent validity between methods. Conclusions. Our study found that automated volumetric quantification provides a more objective, sensitive, and scalable measure of white matter hyperintensity burden than visual grading, aligns more closely with cognitive status, and is better suited for longitudinal monitoring and research endpoints. Full article

Background/Objectives: Despite multimodal therapeutic concepts, treatment of recurrent malignant gliomas remains challenging. Stereotactic radiosurgery (SRS) may be a possible safe and effective non-invasive salvage treatment. In this study, we aim to investigate the SRS treatment outcomes using partly 18F-Fluorethylthyrosine (FET)-PET-imaging sequences for SRS treatment planning focusing on overall survival, event-free survival, and the incidence and factors influencing radiation necrosis (RN) occurrence. Additionally, we evaluated the potential application of AI-based tumor segmentation. Methods: We conducted a retrospective analysis of patients with recurrent malignant glioma treated with single-fraction or hypofractionated SRS at our institution. The outcomes assessed included local control, overall survival (OS), and local event-free survival (LEFS, defined as the interval until tumor recurrence or the onset of RN). We also performed a simulation analysis to assess the potential of AI-based tumor segmentation. Results: The study included 27 patients with a median age of 57 years and 41 lesions. The median OS post-SRS was 9.6 months and an LEFS of 5.2 months. Factors positively influencing OS and LEFS included the gross tumor volume (GTV) of the lesions before SRS therapy, presence of an IDH mutation, and lomustine treatment post-SRS. The incidence of RN post-SRS was 31.7%. RN was confirmed histopathologically in 15.4%, based on MRI in 46.2% and by FET-PET in 38.5% of lesions. In a simulation analysis, AI-based tumor segmentation reliably delineated all lesions, requiring only minimal manual adjustments to define target volumes. Conclusions: High-dose SRS is a feasible salvage treatment for small-volume recurrent high-grade gliomas, achieving local control and survival outcomes comparable to other re-irradiation strategies. IDH mutation, smaller tumor volume, and lomustine therapy were associated with improved survival. RN occurred frequently, particularly in periventricular lesions. AI-based tumor segmentation showed promise in well-defined satellite recurrences, but remains limited in cavity-adjacent lesions, underlining the need for expert review and ¹⁸FET-PET imaging. Full article

Background/Objectives: Multiple sclerosis (MS) is a chronic demyelinating disease where early identification of patients at risk of conversion from clinically isolated syndrome (CIS) to clinically definite MS remains a critical unmet clinical need. Existing machine learning approaches often lack interpretability, limiting clinical trust and adoption. The objective of this research was to develop a novel two-stage machine learning framework with comprehensive explainability to predict CIS-to-MS conversion while addressing demographic bias and interpretability limitations. Methods: A cohort of 177 CIS patients from the National Institute of Neurology and Neurosurgery in Mexico City was analyzed using SeruNet-MS, a two-stage framework that separates demographic baseline risk from clinical risk modification. Stage 1 applied logistic regression to demographic features, while Stage 2 incorporated 25 clinical and symptom features, including MRI lesions, cerebrospinal fluid biomarkers, electrophysiological tests, and symptom characteristics. Patient-level interpretability was achieved through SHAP (SHapley Additive exPlanations) analysis, providing transparent attribution of each factor’s contribution to risk assessment. Results: The two-stage model achieved a ROC-AUC of 0.909, accuracy of 0.806, precision of 0.842, and recall of 0.800, outperforming baseline machine learning methods. Cross-validation confirmed stable performance (0.838 ± 0.095 AUC) with appropriate generalization. SHAP analysis identified periventricular lesions, oligoclonal bands, and symptom complexity as the strongest predictors, with clinical examples illustrating transparent patient-specific risk communication. Conclusions: The two-stage approach effectively mitigates demographic bias by separating non-modifiable factors from actionable clinical findings. SHAP explanations provide clinicians with clear, individualized insights into prediction drivers, enhancing trust and supporting decision making. This framework demonstrates that high predictive performance can be achieved without sacrificing interpretability, representing a significant step forward for explainable AI in MS risk stratification and real-world clinical adoption. Full article

Background: Vascular risk factors (VRFs) are known to influence cerebral small vessel disease (cSVD) burden and progression. However, their specific impact on the presence and distribution of each cSVD imaging marker (white matter hyperintensity [WMH], perivascular spaces [PVSs], lacunes, and cerebral microbleeds [CMBs]) and their spatial distribution remains unclear. Methods: We conducted a retrospective analysis of 93 patients with lacunar stroke with a standardized investigational magnetic resonance imaging protocol using a 3T scanner. WMH and PVSs were segmented semi-automatically, and lacunes and CMBs were manually segmented. We assessed the univariable associations of four common VRFs (hypertension, hyperlipidemia, diabetes, and smoking) with the load of each cSVD marker. Then, we assessed the independent associations of these VRFs in multivariable regression models adjusted for age and sex. Spatial lesion patterns were explored with regional volumetric comparisons using Pearson’s coefficient analysis, which was adjusted for multiple comparisons, and by visually examining heatmap lesion distributions. Results: Hypertension was the VRF that exhibited stronger associations with the cSVD markers in the univariable analysis. In the multivariable analysis, only lacunes (p = 0.009) and PVSs in the basal ganglia (p = 0.014) and white matter (p = 0.016) were still associated with hypertension. In the regional analysis, hypertension showed a higher WMH load in deep structures and white matter, particularly in the posterior periventricular regions. In patients with hyperlipidemia, WMH was preferentially found in hippocampal regions. Conclusions: Hypertension was confirmed to be the VRF with the most impact on cSVD load, especially for lacunes and PVSs, while the lesion topography was variable for each VRF. These findings shed light on the complexity of cSVD expression in relation to factors detrimental to vascular health. Full article

Background: Unilateral basal ganglia calcinosis (BGC) is a rare radiological finding that can be diagnosed on computed tomography (CT) and magnetic resonance imaging (MRI) but often presents challenges for clinicians and radiologists in determining its underlying cause. So far, only a few potential causes that could explain unilateral BGC have been described in the literature. Case Report: A 54-year-old Caucasian male was admitted to a tertiary university hospital due to the sudden onset of speech impairment and right-sided weakness. The patient had no significant medical history prior to this event. Non-enhanced computed tomography (NECT) of the brain revealed no evidence of acute ischemia; CT angiography (CTA) showed acute left middle cerebral artery (MCA) M2 segment occlusion. CT perfusion (CTP) maps revealed an extensive penumbra-like lesion, which is potentially reversible upon achieving successful recanalization. However, a primary neoplastic tumor with calcifications in the basal ganglia was initially interpreted as the potential cause; therefore, acute stroke treatment with intravenous thrombolysis was contraindicated. A follow-up CT examination at 24 h revealed an ischemic lesion localized to the left insula, predominantly involving the left parietal lobe and the superior gyrus of the left temporal lobe. Subsequent gadolinium-enhanced brain MRI revealed small blood vessels draining into the subependymal periventricular veins on the left basal ganglia. Digital subtraction angiography was conducted, confirming the diagnosis of venous angioma. Conclusions: Unilateral BGC caused by venous angioma is a rare entity with unclear pathophysiological mechanisms and heterogeneous clinical presentation. It may mimic conditions such as intracerebral hemorrhage or hemorrhagic brain tumors, complicating acute stroke management, as demonstrated in this case. Surrounding tissue calcification may provide a valuable radiological clue in diagnosing venous angiomas DVAs and vascular malformations. Full article

Background/Objectives: Radiotherapy (RT) remains crucial in treating both primary and metastatic central nervous system cancer. Despite advancements in modern techniques that mitigate some toxic adverse effects, magnetic resonance imaging (MRI) scans still reveal a wide range of radiation-induced changes. Radiation can adversely affect neuroglial cells and their precursors, potentially triggering a demyelinating pattern similar to multiple sclerosis (MS). The aim of the current review is to investigate the occurrence and characteristics of such cases presented in the literature. Methods: We present the case of a 37-year-old female patient with multiple white matter lesions on a brain MRI, mimicking MS, after the completion of RT sessions. Additionally, a systematic review of the literature (PROSPERO id: CRD42024624053) was performed on 4 January 2024. The databases of MEDLINE and SCOPUS were searched. Case reports or case series of adult patients with white matter lesions in a brain MRI, consistent with the MAGNIMS criteria for MS plaques, after RT, were included in our final synthesis. The PRISMA guidelines were applied. Results: The systematic search of the literature revealed 1723 studies, 7 of which conformed to our inclusion criteria, including seven patients in our final analysis. Four of them were female and the mean age was 39 ± 11 years. Several intracranial and extracranial RT types were performed. The symptoms occurred 3 ± 0.8 months after the completion of RT. Lesions were revealed in infratentorial, periventricular and subcortical white matter regions, but not in the spinal cord. All patients who received corticosteroids (83%) showed clinical improvement. Clinical and radiological recurrence occurred in two of the patients during the follow-up period. Fingolimod and Interferon beta-1a were administered to these two patients. Conclusions: Radiation-induced demyelination is a critical clinical and radiological entity that requires attention from both oncologists and neurologists. Comprehensive follow-up is essential to identify patients who may benefit from disease-modifying therapies and to distinguish them from those with pre-existing demyelinating conditions. Full article

Hypoxic-ischemic brain damage presents a significant neurological challenge, often manifesting during the perinatal period. Specifically, periventricular leukomalacia (PVL) is emerging as a notable contributor to cerebral palsy and intellectual disabilities. It compromises cerebral microcirculation, resulting in insufficient oxygen or blood flow to the periventricular region of the brain. As widely documented, these pathological conditions can be caused by several factors encompassing preterm birth (4–5% of the total cases), as well single cotwin abortion and genetic variants such as those associated with GTPase pathways. Whole exome sequencing (WES) analysis identified a de novo causative variant within the pleckstrin homology domain-containing family G member 1 (PLEKHG1) gene in a patient presenting with PVL. The PLEKHG1 gene is ubiquitously expressed, showing high expression patterns in brain tissues. PLEKHG1 is part of a family of Rho guanine nucleotide exchange factors, and the protein is essential for cell division control protein 42 (CDC42) activation in the GTPase pathway. CDC42 is a key small GTPase of the Rho-subfamily, regulating various cellular functions such as cell morphology, migration, endocytosis, and cell cycle progression. The molecular mechanism involving PLEKHG1 and CDC42 has an intriguing role in the reorientation of cells in the vascular endothelium, thus suggesting that disruption responses to mechanical stress in endothelial cells may be involved in the formation of white matter lesions. Significantly, CDC42 association with white matter abnormalities is underscored by its MIM phenotype number. In contrast, although PLEKHG1 has been recently associated with patients showing white matter hyperintensities, it currently lacks a MIM phenotype number. Additionally, in silico analyses classified the identified variant as pathogenic. Although the patient was born prematurely and subsequently to dichorionic gestation, during which its cotwin died, we suggest that the variant described can strongly contribute to PVL. The aim of the current study is to establish a plausible association between the PLEKHG1 gene and PVL. Full article

The effects of exposure to environmental pollutants on neurological processes are of increasing concern due to their potential to induce oxidative stress and neurotoxicity. Considering that many industries are currently using different types of plastics as raw materials, packaging, or distribution pipes, microplastics (MPs) have become one of the biggest threats to the environment and human health. These consequences have led to the need to raise the awareness regarding MPs negative neurological effects and implication in neuropsychiatric pathologies, such as schizophrenia. The study aims to use three zebrafish models of schizophrenia obtained by exposure to ketamine (Ket), methionine (Met), and their combination to investigate the effects of MP exposure on various nervous system structures and the possible interactions with oxidative stress. The results showed that MPs can interact with ketamine and methionine, increasing the severity and frequency of optic tectum lesions, while co-exposure (MP+Met+Ket) resulted in attenuated effects. Regarding oxidative status, we found that all exposure formulations led to oxidative stress, changes in antioxidant defense mechanisms, or compensatory responses to oxidative damage. Met exposure induced structural changes such as necrosis and edema, while paradoxically activating periventricular cell proliferation. Taken together, these findings highlight the complex interplay between environmental pollutants and neurotoxicants in modulating neurotoxicity. Full article

Background: The origin of pre-existing cognitive impairment in stroke patients remains controversial, with a vascular or a degenerative hypothesis. Objective: To determine whether endothelial dysfunction is associated with pre-existing cognitive problems, lesion load and biological anomalies in stroke patients. Methods: Patients originated from the prospective STROKDEM study. The baseline cognitive state, assessed using the IQ-CODE, and risk factors for stroke were recorded at inclusion. Patients with an IQ-CODE score >64 were excluded. Endothelial function was determined 72 h after stroke symptom onset by non-invasive digital measurement of endothelium-dependent flow-mediated dilation and calculation of the reactive hyperemia index (RHI). RHI ≤ 1.67 indicated endothelial dysfunction. Different biomarkers of endothelial dysfunction were analysed in blood or plasma. All patients underwent MRI 72 h after stroke symptom onset. Results: A total of 86 patients were included (52 males; mean age 63.5 ± 11.5 years). Patients with abnormal RHI have hypertension or antihypertensive treatment more often. The baseline IQ-CODE was abnormal in 33 (38.4%) patients, indicating a pre-existing cognitive problem. Baseline IQ-CODE > 48 was observed in 15 patients (28.3%) with normal RHI and in 18 patients (54.6%) with abnormal RHI (p = 0.016). The RHI median was significantly lower in patients with abnormal IQ-CODE. Abnormal RHI was associated with a significantly higher median FAZEKAS score (2.5 vs. 2; p = 0.008), a significantly higher frequency of periventricular lesions (p = 0.015), more white matter lesions (p = 0.007) and a significantly higher cerebral atrophy score (p < 0.001) on MRI. Vascular biomarkers significantly associated with abnormal RHI were MCP-1 (p = 0.009), MIP_1a (p = 0.042), and homocysteinemia (p < 0.05). Conclusions: A vascular mechanism may be responsible for cognitive problems pre-existing stroke. The measurement of endothelial dysfunction after stroke could become an important element of follow-up, providing an indication of the functional and cognitive prognosis of stroke patients. Full article

Background: Improvements in perinatal care have substantially decreased mortality rates among preterm infants, yet their neurodevelopmental outcomes and quality of life persist as a pertinent public health concern. Family-centered care has emerged as a holistic philosophy that promotes effective alliances among patients, families, and healthcare providers to improve the quality of care. Aims: This longitudinal prospective study aims to evaluate the neurodevelopmental outcomes and brain MRI findings in a cohort of preterm newborns admitted to a neonatal intensive care unit (NICU) adopting a family-centered care model. Methods: Very low birth weight (VLBW) infants admitted to the NICU of Modena between 2015 and 2020 were enrolled. Infants who underwent conventional brain magnetic resonance imaging (MRI) at term-equivalent age were included. Neurodevelopmental follow-up was performed until the age of 24 months by a multidisciplinary team using the Amiel-Tison neurological assessment and the Griffiths Mental Developmental Scales (GMDS-R). Neurodevelopmental outcomes were classified as major sequelae (cerebral palsy, DQ ≤ 70, severe sensory impairment), minor sequelae (minor neurological signs such as clumsiness or DQ between 71 and 85), and normal outcomes (no neurological signs and DQ > 85). Risk factors for severe outcomes were assessed. Results: In total, 49 of the 356 infants (13.8%) died before hospital discharge, and 2 were excluded because of congenital disorders. Of the remaining 305 infants, 222 (72.8%) completed the 24 month follow-up and were included in the study. Neurodevelopmental outcomes were classified as normal (n = 173, 77.9%), minor (n = 34, 15.3%), and major sequelae (n = 15, 6.8%). Among 221 infants undergoing brain MRI, 76 (34.4%) had major lesions (intraventricular hemorrhage, hemorrhagic parenchymal infarction, periventricular leukomalacia, and large cerebellar hemorrhage). In the multivariate regression model, the retinopathy of prematurity (OR 1.8; p value 0.016) and periventricular–intraventricular hemorrhage (OR 5.6; p value < 0.004) were associated with major sequelae. Conclusions: We reported low rates of severe neurodevelopmental outcomes in VLBW infants born in an Italian NICU with FCC. Identifying the risk factors for severe outcomes can assist in tailoring and optimizing early interventions on an individual basis, both within the NICU and after discharge. Full article