Cranial Ultrasonography

1. Luis H. Ospina, MD* 1. *Assistant Professor, Pediatric Ophthalmology and Neuro-ophthalmology, Ste-Justine Hospital, University de Montreal, Montreal, Quebec, Canada After completing this article, readers should be able to: 1. Recognize cortical visual impairment (CVI) as an important cause of pediatric visual loss. 2. Identify the most frequent causes of pediatric CVI and, more specifically, understand the role of hypoxia as a cause of central visual damage. 3. Describe the different patterns and implications for future vision of hypoxic central visual damage occurring in preterm compared with term babies. 4. Know the clinical signs suggestive of CVI in children. 5. Discuss the involvement of visual functions other than visual acuity (ie, cognitive visual aspects) in CVI and correlate them with the likely affected neuroanatomic substrates. 6. Explain the value of using a multidisciplinary approach in rehabilitating children who have CVI early in their development. Vision loss caused by central nervous system damage often is referred to as CVI but also may be referred to as cerebral visual impairment or neurologic visual impairment. These terms refer to the fact that the primary defect may not necessarily be limited to the striate (primary visual) cortex and may affect other areas subserving vision, such as the visual associative cortex, optic radiations, and visual attention pathways. Although it is not yet certain which of these three terms best describes the visual deficit, it is clear that use of the label cortical blindness must be abandoned. That term not only evokes negative connotations for the child and the family but is inaccurate because in almost every instance, some degree of residual vision remains, and visual improvement can occur. CVI has become the greatest cause of pediatric visual impairment in developed countries (1)(2)(3)(4)(5) and is becoming increasingly prevalent in developing nations. CVI is a problem of increasing frequency for two primary reasons. First, the progress in neonatal care has resulted in improved survival of …

Review of Neonatal and Infant Cranial US.

Magnetic Resonance and Cranial Ultrasound Characteristics of Periventricular White Matter Abnormalities in Newborn Infants

To assess symmetrical increased echogenicity of bilateral caudothalamic grooves (SIEBCG) detected on newborn cranial ultrasonography (CUS) using magnetic resonance susceptibility-weighted imaging (SWI). A total of 14 newborns (8 girls; 12 premature with mean gestational age of 30weeks and 5days, 2 mature) who were detected to have SIEBCG on routine serial CUS and underwent cranial magnetic resonance imaging (MRI) were recruited for the study. The cranial MRI examinations including SWI acquired on the same day of SIEBCG detection and serial CUS to assess the progress of SIEBCG lesions in the following 6month period were retrospectively evaluated and compared for the presence of germinal matrix hemorrhage. On SWI, solely one patient (7, 1%) had signal alteration on caudothalamic groove compatible with grade 1 germinal matrix hemorrhage. Two patients (14, 2%) had parenchymal (on cerebellar and parietal white matter) millimetric hemorrhagic foci. Seven patients (50%) had signs of presumptive hypoxic insult including hyperintense dots on centrum semiovale and periventricular white matter in five, and increased signal intensity on the globus pallidi in two, on T1-weighted images. Four patients (28, 6%) had normal findings. Of these, 10 patients became normal on follow-up CUS at postterm-equivalent age, whereas four were missing. Symmetrical increased echogenicity of bilateral caudothalamic grooves seen on newborn CUS may be the indicator of other pathologies as ischemic insult or focal parenchymal hemorrhage. In the presence of SIEBCG, further examination with SWI should be performed.

To the Editor.—The first classification strategy for intraventricular hemorrhage (IVH grade I–IV) was developed by Papile et al1 for computed tomography (CT) scan studies in 1978. It is still widely used by most cranial ultrasonographers, radiologists, and neonatologists. Volpe,2 based on neuropathologic findings, has suggested that the presence of parenchymal lesions (IVH grade IV) should be noted separately. Still, the grading systems imply, to a different extent, that IVH (presence of blood within the ventricular system) is the expansion of a germinal matrix hemorrhage (GMH), and also, in grade III IVH, the ventricular dilation is posthemorrhagic. However, this is not always the case.The choroid plexus can be a source of bleeding and may be the exclusive site of origin of IVH.3,4 IVH may lead to acute or progressive ventricular dilation as a neuropathologic consequence, but other, more global or diffused brain injury such as ischemic white matter injury and periventricular leukomalacia may accompany IVH.5,6 Based on routine ultrasonography, it is difficult to distinguish between IVH grade III, subacute-chronic hydrocephalus, and ventriculomegaly.Furthermore, grading IVH is often not well standardized. The determination of the ventricular area occupied with blood is not always applicable. In many cases, ventricular dilation is observed only with moderate presence of blood in the lateral ventricles. Parenchymal hemorrhage can be caused by periventricular hemorrhage infarction (PVH), but the etiology and association with IVH is not always certain.2,7Most importantly, many developmental follow-up studies use the variables of low-grade (I and II) and high-grade (III and IV) IVH.7–10 Based on the pathophysiology or the outcome, this grouping is not justified. In IVH grade III (with no persistent ventriculomegaly), the known pathology is the same with grade I and II, and it is the GMH and destruction. From the outcome point of view, studies have shown that, apart from high-grade IVH, low-grade IVH is also associated with a relatively increased risk of impaired outcome.9,10These issues, plus the fact that the timing of scanning is crucial in staging IVH, make the grading systems complex and in some cases may be misleading. In that direction, a suggestion would be to use GMH, IVH, ventricular dilation (VD, the progress would provide information on whether it is posthemorrhagic or ventriculomegaly due to different pathology), and PVH. The hemorrhage could be described as a possible combination (eg, GMH and IVH and VD or GMH and VD). This system would reflect most of the known variations of IVH. The diagnosis could follow the evolution of IVH and also allow better consideration of IVH attendant but different brain pathology. This suggestion might be a more descriptive system with no grades, more informative, and more flexible and precise.In Reply.—We were delighted to read the comments of Dr Vasileiadis, who underscores many of the limitations, for both clinicians and researchers, that are inherent in using a cranial ultrasound grading system as a shorthand means of communicating results. Since 1984, we and our colleagues have advocated describing the findings rather than using a grading system.1–3For the clinician, use of a 4-grade system has a number of limitations, both practically and conceptually. First, this classification does not lend itself to classifying infants who have significant echoabnormalities without intraventricular hemorrhage (IVH). Cerebral white matter echolucency, the most powerful ultrasonographic predictor of adverse outcomes,4,5 can occur with minimal or no IVH and no ventriculomegaly, although both of these latter findings increase the risk of white matter abnormalities.6Similarly, the 4-grade system also does not have a place for infants who have isolated ventriculomegaly. Persistently enlarged ventricles, regardless of the severity or degree of hemorrhage even in the absence of recognizable sonographic white matter echoabnormality, also strongly predict later neurologic abnormalities.7,8Second, this classification implies that grade IV hemorrhage is generally an extension of subependymal hemorrhage. This concept has virtually no pathologic support.9 The suggestion that parenchymal lesions be considered separately10 is commendable, but it is built on acceptance of a 4-grade system. Once again, we suggest that the 4-grade system has long passed its time of usefulness.For the researcher, creating a single nomenclature oversimplifies the complex nature of several disorders that have heterogeneous risk factors and different pathophysiologies, most of which have not been fully elucidated yet. Separating distinct disorders from each other rather than grouping heterogeneous imaging outcomes together enables investigators to make better sense of factors that may contribute to each of the underlying disorders as well as to the interrelationships of the several disorders to each other.

Clinical neuroimaging in the preterm infant: Diagnosis and prognosis.

Traditionally, descriptions of germinal matrix hemorrhage (GMH), derived from observations in preterm and very preterm infants, indicate its location at the caudothalamic grooves. However, before the germinal matrix begins to recede at approximately 28weeks' gestational age (GA), it extends along the floor of the lateral ventricles far posterior to the caudothalamic grooves. Germinal matrix-intraventricular hemorrhage (GMH-IVH) can occur along any site from which the germinal matrix has not yet involuted. Therefore, as current advances in neonatology have allowed the routine survival of extremely preterm infants as young as 23weeks' GA, postnatal GMH-IVH can occur in previously undescribed locations. Hemorrhage in the more posterior GMH on head ultrasound, if unrecognized, may lead to errors in diagnosis and mislocalization of this injury to the periventricular white matter or lateral walls of the lateral ventricles instead of to the subependyma, where it is in fact located. Our aim is to describe posterior GMH in extremely premature infants, including its characteristic imaging appearance and potential pitfalls in diagnosis. Over a 5-year period, all consecutive extremely preterm infants of 27weeks' GA or less who developed GMH-IVH of any grade were included. A consecutive group of 100 very preterm infants of 31weeks' GA with a GMH-IVH of any grade served as controls. In 106 extremely preterm neonates (mean GA: 25weeks, range: 23.1-26.6weeks) with 212 potential lateral ventricular germinal matrix bleeding sites, 159 sites had bleeds. In 70/159 (44%), the GMH-IVH was located posterior to the caudothalamic grooves and the foramina of Monro, 52 (32.7%) were both anterior and posterior and 21 (13.2%) were exclusively anterior. In 16 ventricles with intraventricular hemorrhage, an origin site in the germinal matrix could not be determined. In the control population of very preterm infants, all hemorrhages were at the anterior caudothalamic grooves and 95% were grade I. Unlike the older very preterm and moderately preterm infants that form the basis of our GMH-IVH description and classification, the extremely preterm infants now routinely surviving have a more fetal pattern of germinal matrix distribution, which is reflected in a different distribution and size of germinal matrix injury. We report the postnatal occurrence of subependymal GMH-IVH in extremely preterm infants in these more primitive, posterior locations, its potential imaging pitfalls and sonographic findings.

Sonographic patterns of brain injury in the term and near-term infant are quite different from those in the premature infant. Although periventricular leukomalacia and germinal matrix hemorrhage are rarely seen in term infants, selective neuronal injury, parasagittal infarction, focal stroke, diffuse hypoxic-ischemic injury, and deep parenchymal hemorrhages are more common lesions. In addition, congenital brain tumors, hamartomatous lesions, such as hemimegalencephaly, and tuberous sclerosis can mimic ischemic and hemorrhagic injury. Sonography remains an important tool in the initial evaluation of intracranial abnormalities in critically ill term and near-term infants. An understanding of the differences in etiology, sonographic patterns, and limitations of sonography in the term infant is essential for accurate and effective diagnoses in this age group.

Hypoxic-ischemic injury to the periventricular cerebral white matter [periventricular leukomalacia (PVL)] results in cerebral palsy and is the leading cause of brain injury in premature infants. The principal feature of PVL is a chronic disturbance of myelination and suggests that oligodendrocyte (OL) lineage progression is disrupted by ischemic injury. We determined the OL lineage stages at risk for injury during the developmental window of vulnerability for PVL (23-32 weeks, postconceptional age). In 26 normal control autopsy human brains, OL lineage progression was defined in parietal white matter, a region of predilection for PVL. Three successive OL stages, the late OL progenitor, the immature OL, and the mature OL, were characterized between 18 and 41 weeks with anti-NG2 proteoglycan, O4, O1, and anti-myelin basic protein (anti-MBP) antibodies. NG2+O4+ late OL progenitors were the predominant stage throughout the latter half of gestation. Between 18 and 27 weeks, O4+O1+ immature OLs were a minor population (9.9 +/- 2.1% of total OLs; n = 9). Between 28 and 41 weeks, an increase in immature OLs to 30.9 +/- 2.1% of total OLs (n = 9) was accompanied by a progressive increase in MBP+ myelin sheaths that were restricted to the periventricular white matter. The developmental window of high risk for PVL thus precedes the onset of myelination and identifies the late OL progenitor as the major potential target. Moreover, the decline in incidence of PVL at approximately 32 weeks coincides with the onset of myelination in the periventricular white matter and suggests that the risk for PVL is related to the presence of late OL progenitors in the periventricular white matter.

The pathogenesis of injury to the developing brain encompasses low oxygen tension and decreased perfusion, often termed hypoxia-ischemia. Factors playing key roles in this setting include (1) inherent vulnerability of immature cells to conditions such as oxidative stress, cytokines, and excitotoxicity; (2) imperfect autoregulation of cerebral blood flow in the face of fluctuations in systemic perfusion pressure, especially in prematurity; (3) presence of blood products in direct contact with developing brain regions, such as the germinal matrix and cerebellum; (4) frequent co-occurrence of other serious illnesses, such as lung disease in the premature infant, or congenital heart disease in the term infant; and (5) significant antenatal conditions, for example, maternal pre-eclampsia with chronic placental hypoperfusion, or acute chorioamnionitis precipitating preterm delivery. The totality of neuropathology experienced by an infant is a summation over time of all of the above circumstances, which may be singular, intermittent, or continuous, or, most likely, a combination thereof. This article will attempt to shed light on the spectrum of injury seen in the perinatal brain and will comprise lesions encountered in the stillborn, the premature, and the term infant through the presentation of 4 illustrative case studies. These include a term stillbirth with diffuse white matter gliosis and selective neuronal vulnerability (pontosubicular necrosis); a 3-week-old premature infant with periventricular leukomalacia and thalamic/basal ganglionic injury; a premature infant with germinal matrix hemorrhage, complicated by periventricular hemorrhagic infarction; and a term infant with congenital heart disease requiring extracorporeal membrane oxygenation therapy, and global hypoxic-ischemic encephalopathy.

Cranial ultrasound (CUS) findings are routinely used to identify preterm infants at risk for impaired neurodevelopment, and neurobehavioral examinations provide information about early brain function. The associations of abnormal findings on early and late CUS with neurobehavior at neonatal intensive care unit (NICU) discharge have not been reported. To examine the associations between early and late CUS findings and infant neurobehavior at NICU discharge. This prospective cohort study included infants enrolled in the Neonatal Neurobehavior and Outcomes in Very Preterm Infants Study between April 2014 and June 2016. Infants born before 30 weeks' gestational age were included. Exclusion criteria were maternal age younger than 18 years, maternal cognitive impairment, maternal inability to read or speak English or Spanish, maternal death, and major congenital anomalies. Overall, 704 infants were enrolled. The study was conducted at 9 university-affiliated NICUs in Providence, Rhode Island; Grand Rapids, Michigan; Kansas City, Missouri; Honolulu, Hawaii; Winston-Salem, North Carolina; and Torrance and Long Beach, California. Data were analyzed from September 2019 to September 2021. Early CUS was performed at 3 to 14 days after birth and late CUS at 36 weeks' postmenstrual age or NICU discharge. Abnormal findings were identified by consensus of standardized radiologists' readings. Neurobehavioral examination was performed using the NICU Network Neurobehavioral Scale (NNNS). Among the 704 infants enrolled, 675 had both CUS and NNNS data (135 [20.0%] Black; 368 [54.5%] minority race or ethnicity; 339 [50.2%] White; 376 [55.7%] male; mean [SD] postmenstrual age, 27.0 [1.9] weeks). After covariate adjustment, lower attention (adjusted mean difference, -0.346; 95% CI, -0.609 to -0.083), hypotonicity (mean difference, 0.358; 95% CI, 0.055 to 0.662), and poorer quality of movement (mean difference, -0.344; 95% CI, -0.572 to -0.116) were observed in infants with white matter damage (WMD). Lower attention (mean difference, -0.233; 95% CI, -0.423 to -0.044) and hypotonicity (mean difference, 0.240; 95% CI, 0.014 to 0.465) were observed in infants with early CUS lesions. In this cohort study of preterm infants, certain early CUS lesions were associated with hypotonicity and lower attention around term-equivalent age. WMD was associated with poor attention, hypotonicity, and poor quality of movement. Infants with these CUS lesions might benefit from targeted interventions to improve neurobehavioral outcomes during their NICU hospitalization.

Subventricular echodensities medioventral to the caudate nucleus near the caudothalamic groove are regular ultrasonographic findings in preterm infants with germinal matrix hemorrhages. The transformation into pseudocysts is termed germinolysis. Interestingly, identical ultrasonographic findings are rarely even reported for near-term infants. We examined 5 cases of near-term infants presenting with various localized subventricular echodensities after various noncerebral infections (intra-amniotic infection, gastroenteritis of unidentified pathogens, septic wound, and a twin pair with rotavirus gastroenteritis), suggesting an inflammatory or ischemic rather than a hemorrhagic etiology. With high-resolution ultrasonography, these lesions showed similar characteristics: all were space-occupying, homogeneous, echodense, and ultimately transformed into pseudocysts. Additionally, Doppler ultrasonography showed linear perivascular echodensities in the basal ganglia of one infant. All infants were also examined by cerebral magnetic resonance imaging (MRI) including T2*-weighted gradient-echo sequences so that subventricular hemorrhages could be excluded in 4 infants. One of these 4 infants died unexpectedly at home. Brain autopsy revealed nonhemorrhagic germinal matrix pseudocysts with gliotic walls. Based on our findings and the original literature, we favored an ischemic infarction of the strongly vascularized and highly metabolic germinal matrix as cause of this germinolysis and gliosis. We postulated that the infarction was the result of an obstructive and possibly mineralizing, or even fossilizing vasculopathy due to an inflammatory response. The precise pathogenesis of the suspected immune-mediated vasculitis remains unknown. We concluded that cerebral ultrasonography should be performed in infants with noncerebral infection and that it should be complemented by MRI in cases of subventricular echodensities to prove or to exclude a germinal matrix hemorrhage.

The evaluation and characterization of germinal matrix hemorrhages have been predominantly described on postnatal head sonography in premature neonates. However, germinal matrix hemorrhages that are seen in premature neonates can be also seen in fetuses of the same postconceptual age and are now more frequently encountered in the era of fetal MR imaging. Our aim was to examine and describe the MR imaging findings of fetuses with intracranial hemorrhage. A retrospective review of diagnostic-quality fetal MRIs showing intracranial hemorrhage from January 2004 to May 2020 was performed. Images were reviewed by 2 radiologists, and imaging characteristics of fetal intracranial hemorrhages were documented. Corresponding postnatal imaging and clinical parameters were reviewed. One hundred seventy-seven fetuses with a mean gestational age of 25.73 (SD, 5.01) weeks were included. Germinal matrix hemorrhage was identified in 60.5% (107/177) and nongerminal matrix hemorrhage in 39.5% (70/177) of patients. Significantly increased ventricular size correlated with higher germinal matrix hemorrhage grade (P < .001). Fetal growth restriction was present in 21.3% (20/94) of our population, and there was no significant correlation with germinal matrix grade or type of intracranial hemorrhage. An increased incidence of neonatal death with grade III germinal matrix hemorrhages (P = .069) compared with other grades was identified; 23.2% (16/69) of the neonates required ventriculoperitoneal shunts, with an increased incidence in the nongerminal matrix hemorrhage group (P = .026). MR imaging has become a key tool in the diagnosis and characterization of intracranial hemorrhage in the fetus. Appropriate characterization is important for optimizing work-up, therapeutic approach, and prenatal counseling.

Introduction/Objective. Implementing cranial ultrasound (CUS) into daily clinical practice represents a major advance in the diagnosis and treatment of newborns. Preterm birth is considered a risk factor for abnormal neurological development. The study aimed to evaluate the significance of CUS in preterm infants as a complementary method to the General Movements Assessment for predicting neurological outcomes. The study focused on a cohort of infants without significant neonatal morbidity. Methods. The study included 160 preterm infants and was designed as a prospective clinical study. Statistical analysis included cranial ultrasound findings and the assessment of spontaneous motor activity in the first five days after birth (?Writhing? period), perinatal data, and pregnancy data. Results. There was a statistically significant association between abnormal CUS findings and cerebral palsy in the final neurological outcome (p &lt; 0.001). Pathological CUS findings were significantly more frequent in preterm infants born before 30 weeks of gestation (p &lt; 0.001), those delivered by cesarean section (p &lt; 0.001), and infants with an Apgar score &lt; 8 at one and five minutes (p &lt; 0.001). The specificity of a normal CUS was 86% but increased to 100% when combined with a normal General Movements Assessment. Conclusion. This research confirms that CUS can be a valuable tool for predicting neurological outcomes in preterm infants. It can provide data that can guide the judicious use of different monitoring methods and rationalize their examinations.

We have encountered bilateral hyperechoic foci in the region of the germinal matrix on cranial sonograms in neonates that have an appearance similar to germinal matrix hemorrhage (GMH), but are unusual either due to the age of the patient at presentation or to the evolution of the foci on follow-up. We believe that these findings represent hyperechoic caudate nuclei (HCN) rather than GMH. To demonstrate that bilateral HCN can be seen on cranial sonography in neonates and can mimic bilateral GMH. The cranial sonograms were reviewed in nine neonates (three term and six premature) who had HCN identified on at least one sonographic examination. CT (two patients) and MR (one patient) studies were also reviewed, as well as the neuropathological examination in one patient who died and had an autopsy. The patients' medical records were reviewed to identify any clinical markers for significant risk of perinatal ischemia. There was clinical evidence for risk of ischemia in five of the nine neonates. All nine patients had bilateral HCN on the initial or follow-up studies. Small cysts were seen sonographically in two patients. CT was normal in one patient and revealed a small unilateral focus of increased attenuation in one infant (very small compared to the bilateral HCN). MR was normal in one patient. Histopathological examination of the brain was normal in the one patient who died and had an autopsy. Hyperechoic caudate nuclei can occur in neonates either as a normal finding, or possibly related to ischemia, and should not always be attributed to GMH.