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To assess the association between cerebral saturation (crSOsub2/sub) using Near-Infrared Spectroscopy (NIRS) and brain injury in extremely preterm infants.This retrospective study includes 62 infants (lt;28 weeks gestation) who underwent continuous NIRS monitoring in the first 5 days after birth. Median crSOsub2/subwere compared in 12 h increments between infants with and without germinal matrix/intraventricular hemorrhage (GM/IVH). crSOsub2/subwas also compared by IVH severity, onset, and by grade of injury on term equivalent MRI.After 48 h of life (HOL), infants with GM/IVH had significantly lower crSOsub2/subthan those without GM/IVH in analysis adjusted for potential confounding e.g., at 49-60 HOL (69.5 (66.2, 72.8) vs. 74.7 (71.8, 77.6), p = 0.023). There were no significant differences in crSOsub2/subby IVH subcategory or injury severity on MRI.Clinical use of NIRS has the potential to identify crSOsub2/subpatterns associated with development of GM/IVH.

BACKGROUND: Risdiplam is an oral small molecule approved for the treatment of patients with spinal muscular atrophy, with approval for use in patients with type 2 and type 3 spinal muscular atrophy granted on the basis of unpublished data. The drug modifies pre-mRNA splicing of the SMN2 gene to increase production of functional SMN. We aimed to investigate the safety and efficacy of risdiplam in patients with type 2 or non-ambulant type 3 spinal muscular atrophy. METHODS: In this phase 3, randomised, double-blind, placebo-controlled study, patients aged 2-25 years with confirmed 5q autosomal recessive type 2 or type 3 spinal muscular atrophy were recruited from 42 hospitals in 14 countries across Europe, North America, South America, and Asia. Participants were eligible if they were non-ambulant, could sit independently, and had a score of at least 2 in entry item A of the Revised Upper Limb Module. Patients were stratified by age and randomly assigned (2:1) to receive either daily oral risdiplam, at a dose of 5·00 mg (for individuals weighing =20 kg) or 0·25 mg/kg (for individuals weighing

To correlate arterial umbilical cord gas (aUCG) and infant blood gas with severity of neurological injury. Retrospective single-site study of infants evaluated for therapeutic hypothermia. Clinical neurological examination and a validated MRI scoring system were used to assess injury severity. Sixty-eight infants were included. aUCG base deficit (BD) and lactate correlated with infant blood gas counterparts (r = 0.43 and r = 0.56, respectively). aUCG and infant pH did not correlate. Infant blood gas lactate (RADJ2 = 0.40), infant BD (RADJ2 = 0.26), infant pH (RADJ2 = 0.17), aUCG base deficit (RADJ2 = 0.08), and aUCG lactate (RADJ2 = 0.11) were associated with clinical neurological examination severity. aUCG and infant blood gas measures were not correlated with MRI score. Metabolic measures from initial infant blood gases were most associated with the clinical neurological examination severity and can be used to evaluate hypoxic-ischemic cerebral injury risk.

To assess the association of cerebral oxygen saturation (CrSO2) collected by near infrared spectroscopy (NIRS) during therapeutic hypothermia (TH) and rewarming with evidence of brain injury on post-rewarming MRI. This retrospective cohort study included 49 infants, who received TH for mild to severe neonatal encephalopathy. Of those, 26 presented with brain injury assessed by a novel MRI grading system, whereas 23 had normal MRI scans. CrSO2 increased significantly from the first to the second day of TH in infants with brain injury, whereas it remained stable in patients with normal MRI. Increasing mean CrSO2 values during rewarming was associated with brain injury (aOR 1.14; 95% CI 1.00–1.28), specifically with gray matter (GM) injury (aOR 1.23; 95% CI 1.02–1.49). The area under the ROC curve showed an excellent discrimination for GM involvement. Clinically applied NIRS during TH and rewarming can assist in identifying the risk for brain injury.

Background: Risdiplam is an orally administered therapy that modifies pre-mRNA splicing of the survival of motor neuron 2 (SMN2) gene and is approved for the treatment of spinal muscular atrophy. The FIREFISH study is investigating the safety and efficacy of risdiplam in treated infants with type 1 spinal muscular atrophy versus historical controls. The primary endpoint of part 2 of the FIREFISH study showed that infants with type 1 spinal muscular atrophy attained the ability to sit without support for at least 5 s after 12 months of treatment. Here, we report on the safety and efficacy of risdiplam in FIREFISH part 2 over 24 months of treatment. Methods: FIREFISH is an ongoing, multicentre, open-label, two-part study. In FIREFISH part 2, eligible infants (aged 1-7 months at enrolment, with a genetically confirmed diagnosis of spinal muscular atrophy, and two SMN2 gene copies) were enrolled in 14 hospitals in ten countries across Europe, North America, South America, and Asia. Risdiplam was orally administered once daily at 0·2 mg/kg for infants between 5 months and 2 years of age; once an infant reached 2 years of age, the dose was increased to 0·25 mg/kg. Infants younger than 5 months started at 0·04 mg/kg (infants between 1 month and 3 months old) or 0·08 mg/kg (infants between 3 months and 5 months old), and this starting dose was adjusted to 0·2 mg/kg once pharmacokinetic data were available for each infant. The primary and secondary endpoints included in the statistical hierarchy and assessed at month 12 have been reported previously. Here we present the remainder of the secondary efficacy endpoints that were included in the statistical hierarchy at month 24: the ability to sit without support for at least 30 s, to stand alone, and to walk alone, as assessed by the Bayley Scales of Infant and Toddler Development, third edition gross motor subscale. These three endpoints were compared with a performance criterion of 5% that was defined based on the natural history of type 1 spinal muscular atrophy; the results were considered statistically significant if the lower limit of the two-sided 90% CI was above the 5% threshold. FIREFISH is registered with ClinicalTrials.gov, NCT02913482. Recruitment is closed; the 36-month extension period of the study is ongoing. Findings: Between March 13 and Nov 19, 2018, 41 infants were enrolled in FIREFISH part 2. After 24 months of treatment, 38 infants were ongoing in the study and 18 infants (44% [90% CI 31-58]) were able to sit without support for at least 30 s (p

Background Subgaleal hemorrhage (SGH) is reported to be associated with severe hemodynamic instability, coagulopathy, and even mortality. The importance of the presence or absence of neonatal encephalopathy in predicting SGH outcomes has not been explored. The aim of this study was to determine the relationship of clinical encephalopathy to short-term outcomes in neonates with SGH. Methods Neonates ≥35 weeks gestation, diagnosed radiologically with SGH between 2010 and 2017, were included. Cases were divided into encephalopathic and non-encephalopathic. Demographic, clinical, and outcome data were compared between groups. Results Of 54,048 live births, 56 had SGH, of them 13 (23%) had encephalopathy. When compared to the non-encephalopathic neonates, encephalopathic neonates had lower Apgar scores, lower hemoglobin, lower platelet count, longer neonatal intensive care unit stay, two (15%) deaths, and four (31%) required blood transfusion. No non-encephalopathic infant with SGH died or required blood transfusion. Notably, on magnetic resonance imaging (MRI), a majority of subgaleal collections had either no or minimal blood products. Conclusions In the absence of encephalopathy, SGH is not associated with adverse short-term outcome. Neurological assessment is likely to identify infants at higher risk for adverse outcome. The absence of MRI signal consistent with blood in subgaleal collection warrants further research.

BACKGROUND Type 1 spinal muscular atrophy (SMA) is a progressive neuromuscular disease characterized by an onset at 6 months of age or younger, an inability to sit without support, and deficient levels of survival of motor neuron (SMN) protein. Risdiplam is an orally administered small molecule that modifies SMN2 pre-messenger RNA splicing and increases levels of functional SMN protein in blood. METHODS We conducted an open-label study of risdiplam in infants with type 1 SMA who were 1 to 7 months of age at enrollment. Part 1 of the study (published previously) determined the dose to be used in part 2 (reported here), which assessed the efficacy and safety of daily risdiplam as compared with no treatment in historical controls. The primary end point was the ability to sit without support for at least 5 seconds after 12 months of treatment. Key secondary end points were a score of 40 or higher on the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND; range, 0 to 64, with higher scores indicating better motor function), an increase of at least 4 points from baseline in the CHOP-INTEND score, a motor-milestone response as measured by Section 2 of the Hammersmith Infant Neurological Examination (HINE-2), and survival without permanent ventilation. For the secondary end points, comparisons were made with the upper boundary of 90% confidence intervals for natural-history data from 40 infants with type 1 SMA. RESULTS A total of 41 infants were enrolled. After 12 months of treatment, 12 infants (29%) were able to sit without support for at least 5 seconds, a milestone not attained in this disorder. The percentages of infants in whom the key secondary end points were met as compared with the upper boundary of confidence intervals from historical controls were 56% as compared with 17% for a CHOP-INTEND score of 40 or higher, 90% as compared with 17% for an increase of at least 4 points from baseline in the CHOP-INTEND score, 78% as compared with 12% for a HINE-2 motor-milestone response, and 85% as compared with 42% for survival without permanent ventilation (P

Background: Type 1 spinal muscular atrophy is a rare, progressive neuromuscular disease that is caused by low levels of functional survival of motor neuron (SMN) protein. Risdiplam is an orally administered, small molecule that modifies SMN2 pre-messenger RNA splicing and increases levels of functional SMN protein. Methods: We report the results of part 1 of a two-part, phase 2-3, open-label study of risdiplam in infants 1 to 7 months of age who had type 1 spinal muscular atrophy, which is characterized by the infant not attaining the ability to sit without support. Primary outcomes were safety, pharmacokinetics, pharmacodynamics (including the blood SMN protein concentration), and the selection of the risdiplam dose for part 2 of the study. Exploratory outcomes included the ability to sit without support for at least 5 seconds. Results: A total of 21 infants were enrolled. Four infants were in a low-dose cohort and were treated with a final dose at month 12 of 0.08 mg of risdiplam per kilogram of body weight per day, and 17 were in a high-dose cohort and were treated with a final dose at month 12 of 0.2 mg per kilogram per day. The baseline median SMN protein concentrations in blood were 1.31 ng per milliliter in the low-dose cohort and 2.54 ng per milliliter in the high-dose cohort; at 12 months, the median values increased to 3.05 ng per milliliter and 5.66 ng per milliliter, respectively, which represented a median of 3.0 times and 1.9 times the baseline values in the low-dose and high-dose cohorts, respectively. Serious adverse events included pneumonia, respiratory tract infection, and acute respiratory failure. At the time of this publication, 4 infants had died of respiratory complications. Seven infants in the high-dose cohort and no infants in the low-dose cohort were able to sit without support for at least 5 seconds. The higher dose of risdiplam (0.2 mg per kilogram per day) was selected for part 2 of the study. Conclusions: In infants with type 1 spinal muscular atrophy, treatment with oral risdiplam led to an increased expression of functional SMN protein in the blood. (Funded by F. Hoffmann-La Roche; ClinicalTrials.gov number, NCT02913482.).

The purpose of this Commentary is to discuss recent evidence that primary impairment of neuronal maturation of gray matter structures in the human preterm infant is common, important and likely modifiable. The major cellular element of gray matter structures in the human brain is the neuron. The principal gray matter structures, especially the cerebral cortex, basal ganglia, and thalamus, are crucial determinants of cognitive and related higher functions, developing subsequent to the newborn period. Impaired cognitive functions, including overall intellect, language, behavior, and socialization, occur in at least 50% of survivors of very preterm birth [1]. In the last trimester of human gestation, development of the cerebral cortex is especially prominent [2]. The principal anatomic features are development of a complex dendritic arbor, elaboration of axonal ramifications, onset of synaptogenesis and establishment of connectivity between cortical regions and deep nuclear structures. A variety of imaging studies in survivors of preterm birth have shown disturbances in maturation of gray matter structures [1], manifested by deficits in volumetric growth, microstructure and functional connectivity. The prevailing concept has been that injury to the vulnerable developing cerebral white matter leads secondarily to neuronal dysmaturation [3]. This secondary neuronal dysmaturation results because the pre-oligodendrocyte fails to ensheath axons, thereby causing, by anterograde and retrograde mechanisms, impairment of neuronal maturation. Recent experimental studies, however, suggest that impaired neuronal maturation also may be a primary event (see later), not related to white matter injury. Moreover, studies of very preterm human infants have shown impaired cognitive functions in the absence of definite white matter injury (see later). The occurrence of primary neuronal dysmaturation has important implications for elucidating the anatomic substrate for the cognitive deficits observed in survivors of preterm birth, and, critically for interventions to restore normal maturation and improve outcome. The following will review the principal experimental and human studies supportive of primary neuronal dysmaturation in the very preterm infant and of potential restorative interventions

Severe germinal matrix-intraventricular hemorrhage (IVH) is a major problem in preterm infants [1]. “Severe IVH” generally refers to lesions with large amounts of intraventricular blood, distending the lateral ventricular (Grade III), or a comparable degree of IVH with an associated periventricular hemorrhagic infarction (Grade IV) [2]. The incidence of severe IVH among very preterm infants (

To assess the association of cerebral oxygen saturation (CrSOThis retrospective cohort study included 49 infants, who received TH for mild to severe neonatal encephalopathy. Of those, 26 presented with brain injury assessed by a novel MRI grading system, whereas 23 had normal MRI scans.CrSOClinically applied NIRS during TH and rewarming can assist in identifying the risk for brain injury.

To assess outcomes following post-hemorrhagic ventricular dilatation (PHVD) among infants born at ≤26 weeks of gestation.Observational study of infants born April 1, 2011, to December 31, 2015, in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network and categorized into 3 groups: PHVD, intracranial hemorrhage without ventricular dilatation, or normal head ultrasound. PHVD was treated per center practice. Neurodevelopmental impairment at 18-26 months was defined by cerebral palsy, Bayley Scales of Infant and Toddler Development, 3rd edition, cognitive or motor score70, blindness, or deafness. Multivariable logistic regression examined the association of death or impairment, adjusting for neonatal course, center, maternal education, and parenchymal hemorrhage.Of 4216 infants, 815 had PHVD, 769 had hemorrhage without ventricular dilatation, and 2632 had normal head ultrasounds. Progressive dilatation occurred among 119 of 815 infants; the initial intervention in 66 infants was reservoir placement and 53 had ventriculoperitoneal shunt placement. Death or impairment occurred among 68%, 39%, and 28% of infants with PHVD, hemorrhage without dilatation, and normal head ultrasound, respectively; aOR (95% CI) were 4.6 (3.8-5.7) PHVD vs normal head ultrasound scan and 2.98 (2.3-3.8) for PHVD vs hemorrhage without dilatation. Death or impairment was more frequent with intervention for progressive dilatation vs no intervention (80% vs 65%; aOR 2.2 [1.38-3.8]). Death or impairment increased with parenchymal hemorrhage, intervention for PHVD, male sex, and surgery for retinopathy; odds decreased with each additional gestational week.PHVD was associated with high rates of death or impairment among infants with gestational ages ≤26 weeks; risk was further increased among those with progressive ventricular dilation requiring intervention.

To correlate arterial umbilical cord gas (aUCG) and infant blood gas with severity of neurological injury.Retrospective single-site study of infants evaluated for therapeutic hypothermia. Clinical neurological examination and a validated MRI scoring system were used to assess injury severity.Sixty-eight infants were included. aUCG base deficit (BD) and lactate correlated with infant blood gas counterparts (r = 0.43 and r = 0.56, respectively). aUCG and infant pH did not correlate. Infant blood gas lactate (RMetabolic measures from initial infant blood gases were most associated with the clinical neurological examination severity and can be used to evaluate hypoxic-ischemic cerebral injury risk.

Background and purposeThe anatomy of the deep venous system plays an important role in the pathogenesis of brain lesions in the preterm brain as shown by different histological studies. The aims of this study were to compare the subependymal vein anatomy of preterm neonates with germinal matrix haemorrhage–intraventricular haemorrhage (GMH–IVH), as evaluated by susceptibility-weighted imaging (SWI) venography, with a group of age-matched controls with normal brain MRI, and to explore the relationship between the anatomical features of subependymal veins and clinical risk factors for GMH–IVH.MethodsSWI venographies of 48 neonates with GMH–IVH and 130 neonates with normal brain MRI were retrospectively evaluated. Subependymal vein anatomy was classified into six different patterns: type 1 represented the classic pattern and types 2–6 were considered anatomic variants. A quantitative analysis of the venous curvature index was performed. Variables were analysed by using Mann-Whitney U and χ2 tests, and a multiple logistic regression analysis was performed to evaluate the association between anatomical features, clinical factors and GMH–IVH.ResultsA significant difference was noticed among the six anatomical patterns according to the presence of GMH–IVH (χ2=14.242, p=0.014). Anatomic variants were observed with higher frequency in neonates with GMH–IVH than in controls (62.2% and 49.6%, respectively). Neonates with GMH–IVH presented a narrower curvature of the terminal portion of subependymal veins (pConclusionPreterm neonates with GMH–IVH show higher variability of subependymal veins anatomy confirming a potential role as predisposing factor for GMH–IVH.

Microglia, the resident immune cells of the brain, rapidly change states in response to their environment, but we lack molecular and functional signatures of different microglial populations. Here, we analyzed the RNA expression patterns of more than 76,000 individual microglia in mice during development, old age and after brain injury. Our analysis uncovered at least nine transcriptionally distinct microglial states, which expressed unique sets of genes and were localized in the brain using specific markers. The greatest microglial heterogeneity was found at young ages; however, several states – including chemokine-enriched inflammatory microglia – persisted throughout the lifespan or increased in the aged brain. Multiple reactive microglial subtypes were also found following demyelinating injury in mice, at least one of which was also found in human multiple sclerosis lesions. These distinct microglia signatures can be used to better understand microglia function and to identify and manipulate specific subpopulations in health and disease.

Prematurity, especially preterm birth (less than 32 weeks' gestation), is common and associated with high rates of both survival and neurodevelopmental disability, especially apparent in cognitive spheres. The neuropathological substrate of this disability is now recognized to be related to a variety of dysmaturational disturbances of the brain. These disturbances follow initial brain injury, particularly cerebral white matter injury, and involve many of the extraordinary array of developmental events active in cerebral white and gray matter structures during the premature period. This review delineates these developmental events and the dysmaturational disturbances that occur in premature infants. The cellular mechanisms involved in the genesis of the dysmaturation are emphasized, with particular focus on the preoligodendrocyte. A central role for the diffusely distributed activated microglia and reactive astrocytes in the dysmaturation is now apparent. As these dysmaturational cellular mechanisms appear to occur over a relatively long time window, interventions to prevent or ameliorate the dysmaturation, that is, neurorestorative interventions, seem possible. Such interventions include pharmacologic agents, especially erythropoietin, and particular attention has also been paid to such nutritional factors as quality and source of milk, breastfeeding, polyunsaturated fatty acids, iron, and zinc. Recent studies also suggest a potent role for interventions directed at various experiential factors in the neonatal period and infancy, i.e., provision of optimal auditory and visual exposures, minimization of pain and stress, and a variety of other means of environmental behavioral enrichment, in enhancing brain development.

Subgaleal hemorrhage (SGH) is reported to be associated with severe hemodynamic instability, coagulopathy, and even mortality. The importance of the presence or absence of neonatal encephalopathy in predicting SGH outcomes has not been explored. The aim of this study was to determine the relationship of clinical encephalopathy to short-term outcomes in neonates with SGH.Neonates ≥35 weeks gestation, diagnosed radiologically with SGH between 2010 and 2017, were included. Cases were divided into encephalopathic and non-encephalopathic. Demographic, clinical, and outcome data were compared between groups.Of 54,048 live births, 56 had SGH, of them 13 (23%) had encephalopathy. When compared to the non-encephalopathic neonates, encephalopathic neonates had lower Apgar scores, lower hemoglobin, lower platelet count, longer neonatal intensive care unit stay, two (15%) deaths, and four (31%) required blood transfusion. No non-encephalopathic infant with SGH died or required blood transfusion. Notably, on magnetic resonance imaging (MRI), a majority of subgaleal collections had either no or minimal blood products.In the absence of encephalopathy, SGH is not associated with adverse short-term outcome. Neurological assessment is likely to identify infants at higher risk for adverse outcome. The absence of MRI signal consistent with blood in subgaleal collection warrants further research.

The central neuroaxis develops from a streak of ectodermal cells on the dorsal surface of the embryo that specialize into neuroepithelium, starting as a plate of cells that develops into the neural tube. Midline neural tube closure (raphism) starts around the level of the future foramen magnum and proceeds anteriorly forming the future prosencephalon and caudally (primary neurulation) forming the spinal cord above the sacral level. Secondary neurulation follows and results in formation of the conus medullaris, cauda equina, and elements of the hindgut and genitourinary system. Arrested or disturbed development of these neural events are intimately connected to disturbances in formation of overlying mesodermal (muscle, bone, dura) and nonneural ectoderm (cutaneous) structures. The resulting spectrum of malformations includes those due to craniocerebral dysraphism (craniorachischisis, anencephaly, encephaloceles) and those due to spinal dysraphism resulting from disturbances in primary neurulation (myelomeningocele, myeloschisis) and secondary neurulation (meningoceles, lipomeningoceles, tethered cord, other). In recent years, preventive (nutritional) public health strategies and fetal diagnostic advances have significantly reduced the number of live-born infants with spinal dysraphism, while fetal surgical approaches have decreased the rate and severity of complications in live-born infants with these lesions.

Neonatal encephalopathy occurs in 2 to 5/1000 live births and is principally related to hypoxic-ischemic injury to the newborn brain in the immediate peripartum period. In the last decade, there have been significant advances in neuroprotection that have been successful in reducing the risk of death and disability in infants who have suffered from a potential hypoxic-ischemic cerebral injury. The advent of therapeutic hypothermia has led to a major focus on the early clinical recognition of infants that may benefit from such therapies. In addition, optimal recognition and therapeutic targeting of neonatal seizures, with other neuroprotective approaches, have been emphasized. This chapter will summarize the clinical presentation, neuropathological correlates, neurodiagnostic evaluation, prognosis, and management of this condition.

The major unifying clinical manifestations of disorders of the neonatal motor system are hypotonia and weakness, which do not necessarily occur with similar severity. In this chapter, all disorders, except those related to the involvement of muscle, are reviewed, principally in terms of clinical features, results of pertinent laboratory studies, pathological features, pathogenesis and etiology, and management.

Drugs can exert major effects on the developing central nervous system (CNS). In the broadest sense, drugs may disturb specific developmental events in the brain and, in turn, produce teratogenic effects. In addition, maternal ingestion of certain drugs can result in passive addiction of the fetus and postnatally lead to a neonatal withdrawal or abstinence syndrome. Although some effects may be transient, most are likely to persist in some form into childhood and adolescence with multiple systems affected spanning cognition, motor function, language, and behavior. This chapter provides a comprehensive overview of the neurological effects of a range of licit and illicit drugs on the infant and growing child. Drugs reviewed include fetal exposure to alcohol, antiepileptic drugs, stimulants, opioids, selective serotonin reuptake inhibitors (SSRIs), sedatives, anesthetics, and marijuana. Clinical considerations in the evaluation and care of the drug-exposed neonate are also discussed.

Intracranial hemorrhage in the neonatal period is an important clinical problem. Its importance relates to a relatively high frequency of occurrence, accompanied at times by serious neurological sequelae. Over the last decade there have been changes in the relative frequency of intracranial hemorrhage owing to changes in obstetric practice, such as increased vacuum-assisted delivery and reduced rotational forceps, as well as the improved survival of preterm infants with complex intracranial hemorrhagic lesions. Moreover, systematic neuroimaging studies in otherwise asymptomatic term infants have led to a new awareness of the incidence of more clinically benign forms of intracranial hemorrhage. In this chapter, an overview of neonatal intracranial hemorrhage and the basic elements of recognition are presented. Detailed discussion is devoted to subdural hemorrhage, primary subarachnoid hemorrhage, intraventricular hemorrhage of the full-term infant, and certain unusual, miscellaneous examples of neonatal intracranial hemorrhage.

The central nervous system (CNS) and its covering membranes may become involved with a variety of infectious processes in the newborn infant. These infections may occur either in the intrauterine period or within days or weeks after birth with devastating effects on structure and function. In this chapter, infections of the CNS by viruses together with protozoan infections and related organisms are reviewed. Infections recently gaining interest, such as Zika virus, and some rare causes including mosquito-borne alphaviruses are also discussed. The emphasis is on the neuropathological, clinical, and neuroimaging features.

The neuropathology of the encephalopathy of prematurity (see Chapter 14 ) includes injury to cerebral white matter and, in a major proportion of infants, a variety of neuronal-axonal disturbances. The encephalopathy includes a broad spectrum of initiating destructive events or disturbances in cellular maturation that are followed by widespread disruptions in cerebral white and gray matter growth and neuronal connectivity. This chapter emphasizes the pathophysiology of the most consistent and well-defined feature of the encephalopathy, injury to the cerebral white matter.

This chapter is focused on injuries of extracranial, cranial, intracranial, spinal cord, and peripheral nervous system structures, with emphasis on those disorders that appear to be related primarily to mechanical trauma. Extracranial hemorrhage consists of three major lesions: caput succedaneum, subgaleal hemorrhage, and cephalhematoma. These lesions are generally not serious, except for several uncommon complications. Skull fracture, the principal bony lesion of the newborn, may be linear, be depressed, or consist of occipital osteodiastasis. Intracranial hemorrhage, not unexpectedly, may result from mechanical factors, although among all types of intracranial hemorrhage, trauma per se is a prominent pathogenetic factor principally only for epidural and some cases of subdural hemorrhage. Subdural hemorrhage is discussed in Chapter 22 . Spinal cord injury is the most serious CNS parenchymal lesion related primarily to mechanical factors. Two major sites of injury are upper to mid-cervical, occurring mainly in cephalic deliveries and relating primarily to torsional factors, and lower cervical to upper thoracic, occurring mainly in breech deliveries and relating primarily to longitudinal or lateral tractional factors. MRI has proven valuable for both diagnosis and prognosis. Improvements in obstetrical practice have led to declines in incidence. Management is difficult, but new pharmacological, cellular, and rehabilitative interventions are on the horizon. Traumatic injury to peripheral nervous system structures is particularly dominated by brachial plexus injury. The mechanical forces underlying most cases are usually some combination of exogenous factors, such as downward lateral traction involving delivery of the head in a breech delivery or of the shoulder in cephalic deliveries and endogenous factors, such as very strong maternal expulsion forces. Other injuries to peripheral nervous system structures individually are uncommon but collectively are relatively common.