Ana Alarcón

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.

Antenatal destructive events affecting the central nervous system of the foetus lead to disruptive brain lesions that are often associated with impaired neurodevelopment. The pathogenesis of these lesions encompasses a range of causes, including haemorrhagic, embolic, or other vascular events; exposure to teratogens, such as drugs or substance abuse; congenital brain infections; genetic conditions; and metabolic disorders. Cranial ultrasonography is the first‐line imaging modality to diagnose these antepartum brain lesions in the newborn infant; it is often complemented by brain magnetic resonance imaging to detect associated neuronal dysmigration and dysplasia. Using a pictorial approach, a differential diagnosis of foetal disruptive brain lesions and common findings related to antenatal brain damage can be made, including antenatal haemorrhagic and ischaemic brain injuries, porencephaly, schizencephaly, multicystic encephalomalacia, and hydranencephaly, as well as germinolytic cysts and lenticulostriate vasculopathy. The main conditions associated with foetal brain disruption, such as genetic cerebral vascular diseases, monochorionic twin pregnancies, congenital heart disease, maternal drug use, congenital infections, and inborn errors of metabolism can be used to illustrate typical imaging patterns that, when combined with clinical presentation, can assist in identifying the underlying mechanisms and causes, thus supporting individualized patient management.

Infection of the neonatal central nervous system (CNS) can cause irreversible brain damage. Cranial ultrasound is an important neuroimaging modality in the neonatal period for detecting brain injury. Several types of organism can cause neonatal CNS infection. The aim of this narrative review is to provide an overview of the most common and typical ultrasonographic features of neonatal CNS infections and their evolution over time. Different microorganisms cause characteristic brain injury patterns. Using numerous imaging examples, we explain the different injury patterns caused by several Gram‐positive and Gram‐negative microorganisms, fungi, and viruses. This can guide the clinician to appropriate diagnosis and treatment.

Purpose Perinatal hypoxic-ischemic encephalopathy (HIE) is a significant cause of neonatal brain injury. Therapeutic hypothermia (TH) is the standard treatment for term neonates, but its safety and efficacy in neonates < 36 weeks gestational age (GA) remains unclear. This case series aimed to evaluate the outcomes of preterm infants with HIE treated with TH. Methods Retrospective analysis of preterm infants (< 36w GA) treated with TH (01/2019–06/2024). Data on demographics, clinical complications, coagulation profiles, brain magnetic resonance imaging (MRI), and neurodevelopment outcomes were analyzed. Results Seventeen patients were included (range 32.5–35.5w, median 34.4; birthweight range 1556-2493 g, median 2300 g), 58.8% were male. Placental abruption was identified in 7 cases (41.2%), and 8 (47.1%) required advanced resuscitation. Thirteen patients (76.5%) presented anemia, 12 (70.6%) coagulopathy, 9 (52.9%) thrombocytopenia, and 9 (52.9%) acute liver failure. Hypofibrinogenemia (< 1 g/L) was significantly associated with severe intracranial hemorrhage (ICH), defined as extracerebral, intraventricular or parenchymal hemorrhage causing mass effect. MRI findings were classified based on the predominant lesion: I- hypoxic-ischemic injury, II- severe ICH, or III- normal/mild findings. Severe ICH was the predominant lesion in 4 cases (23.5%). White matter injury was seen in 12 (76%). Death occurred in 8 cases (47.1%). Of the 9 surviving patients, at 2 years, 6 (66.7%) had normal neurodevelopment, while 1 (11.1%) had severe disability. Conclusion Coagulation abnormalities, particularly hypofibrinogenemia, significantly increase the risk of severe ICH in < 36w infants treated with TH. The safety and efficacy of TH in this population require further investigation.

We examined behavior (Child Behavior Checklist) and family functioning (Family Impact Questionnaire) in 65 children with congenital cytomegalovirus. Behavioral problems were present in 30.8%. Parents of children with moderate/severe outcomes reported strain on all areas of family functioning. Behavioral problems were associated with negative impact on parental feelings and marital/partnership relationship. Our findings inform planning support services.

Objective: To evaluate the association between neuroimaging and outcome in infants with congenital cytomegalovirus (cCMV), focusing on qualitative MRI and quantitative diffusion-weighted imaging of white matter abnormalities (WMAs). Methods: Multicentre retrospective cohort study of 160 infants with cCMV (103 symptomatic). A four-grade neuroimaging scoring system was applied to cranial ultrasonography and MRI acquired at ≤3 months. WMAs were categorised as multifocal or diffuse. Temporal-pole WMAs (TPWMAs) consisted of swollen or cystic appearance. Apparent diffusion coefficient (ADC) values were obtained from frontal, parieto-occipital and temporal white matter regions. Available follow-up MRI at ≥6 months (N=14) was additionally reviewed. Neurodevelopmental assessment included motor function, cognition, behaviour, hearing, vision and epilepsy. Adverse outcome was defined as death or moderate/severe disability. Results: Neuroimaging scoring was associated with outcome (p<0.001, area under the curve 0.89±0.03). Isolated WMAs (IWMAs) were present in 61 infants, and WMAs associated with other lesions in 30. Although TPWMAs and diffuse pattern often coexisted in infants with IWMAs (p<0.001), only TPWMAs were associated with adverse outcomes (OR 7.8; 95% CI 1.4 to 42.8), including severe hearing loss in 20% and hearing loss combined with other moderate/severe disabilities in 15%. Increased ADC values were associated with higher neuroimaging scores, WMAs based on visual assessment and IWMAs with TPWMAs. ADC values were not associated with outcome in infants with IWMAs. Findings suggestive of progression of WMAs on follow-up MRI included gliosis and malacia. Conclusions: Categorisation of neuroimaging severity correlates with outcome in cCMV. In infants with IWMAs, TPWMAs provide a guide to prognosis.