Pseudo-TORCH syndrome (PTS) is characterized by microcephaly, enlarged ventricles, cerebral calcification, and, occasionally, by systemic features at birth resembling the sequelae of congenital infection but in the absence of an infectious agent. Genetic defects resulting in activation of type 1 interferon (IFN) responses have been documented to cause Aicardi-Goutières syndrome, which is a cause of PTS. Ubiquitin-specific peptidase 18 (USP18) is a key negative regulator of type I IFN signaling. In this study, we identified loss-of-function recessive mutations of USP18 in five PTS patients from two unrelated families. Ex vivo brain autopsy material demonstrated innate immune inflammation with calcification and polymicrogyria. In vitro, patient fibroblasts displayed severely enhanced IFN-induced inflammation, which was completely rescued by lentiviral transduction of USP18. These findings add USP18 deficiency to the list of genetic disorders collectively termed type I interferonopathies. Moreover, USP18 deficiency represents the first genetic disorder of PTS caused by dysregulation of the response to type I IFNs. Therapeutically, this places USP18 as a promising target not only for genetic but also acquired IFN-mediated CNS disorders.

In the past three decades, cerebral ultrasound (CUS) has become a trusted technique to study the neonatal brain. It is a relatively cheap, non-invasive, bedside neuroimaging method available in nearly every hospital. Traditionally, CUS was used to detect major abnormalities, such as intraventricular hemorrhage (IVH), periventricular hemorrhagic infarction, post-hemorrhagic ventricular dilatation, and (cystic) periventricular leukomalacia (cPVL). The use of different acoustic windows, such as the mastoid and posterior fontanel, and ongoing technological developments, allows for recognizing other lesion patterns (e.g., cerebellar hemorrhage, perforator stroke, developmental venous anomaly). The CUS technique is still being improved with the use of higher transducer frequencies (7.5–18 MHz), 3D applications, advances in vascular imaging (e.g. ultrafast plane wave imaging), and improved B-mode image processing. Nevertheless, the helpfulness of CUS still highly depends on observer skills, knowledge, and experience. In this special article, we discuss how to perform a dedicated state-of-the-art neonatal CUS, and we provide suggestions for structured reporting and quality assessment.

Understanding the links between sleep and brain development is important, as rapid eye movement (REM) sleep and non‐REM (NREM) sleep seem to contribute to different aspects of brain maturation. If children have sleep problems, REM sleep and NREM sleep are likely to have different consequences for their developing brain, depending on their age. We highlight important discoveries from human and animal research on the role sleep plays in brain development. A hypothetical model is presented to explain the dynamic relationship of REM sleep and NREM sleep with different processes of brain maturation, with implications for current neonatal care and future research.

BACKGROUND AND PURPOSE: Knowledge of the sequence of signal-intensity (SI) changes on conventional and diffusion-weighted MR imaging (DWI) following perinatal arterial ischemic stroke (PAIS) is limited, adding to the difficulty in timing the onset of PAIS. We hypothesized that SI changes seen on early sequential MR imaging following PAIS should follow a similar time course. The aim of this study was to evaluate the time course of SI changes by using a simple classification that could be assessed visually from conventional imaging and DWI in term-born neonates with symptomatic unilateral PAIS.

CONTEXT: The effect of neonatal cerebellar hemorrhage on neurodevelopmental outcome (NDO) in the absence of supratentorial injury is still largely unknown. OBJECTIVE: To evaluate the influence of isolated neonatal cerebellar hemorrhage on cognitive, motor, language, and behavioral NDOs and assess the effect of location and size on outcome. DATA SOURCES: Embase, Medline, and Scopus were searched from inception to September 30, 2017. STUDY SELECTION: Studies in which a diagnosis of isolated cerebellar hemorrhage was reported in preterm infants (<32 weeks’ gestation) with a standardized NDO at ≥12 months of age were included. DATA EXTRACTION: Patient characteristics, location, and size of bleeding and NDO (defined as severe [yes or no] on the basis of given cutoff points) in 4 domains were extracted. RESULTS: Of the 1519 studies identified, 8 were included in final analyses. Of infants with isolated cerebellar hemorrhage, 128 were described (cumulative incidence: 2.3%). The incidence of severe delay in cognition, motor, language, and behavioral development was 38%, 39%, 41%, and 38%, respectively. The overall incidence of severe neurodevelopmental delay in ≥1 domain ranged from 43% to 75% and was most seen in infants with vermis involvement (87%–93%) and with large bleeds (46%–82%). LIMITATIONS: Different neurodevelopmental scales lead to data heterogeneity, and reporting of data on a group level limited possibilities for an outcome description on an individual level. CONCLUSIONS: Of infants with isolated cerebellar hemorrhage, 43% to 75% were severely delayed in cognition, motor, language, and/or behavioral development, with the highest incidence with vermis involvement and with large bleeds.