Retinodural haemorrhage of infancy, abusive head trauma, shaken baby syndrome: The continuing quest for evidence.

The shaken baby syndrome was originally proposed in the 1970s without any formal scientific basis. Once data generated by scientific research was available, the hypothesis became controversial. There developed essentially two sides in the debate. One side claimed that the clinical triad of subdural haemorrhage, retinal haemorrhage, and encephalopathy, or its components, is evidence that an infant has been shaken. The other side stated this is not a scientifically valid proposal and that alternative causes, such as low falls and natural diseases, should be considered. The controversy continues, but the contours have shifted. During the last 15 years, research has shown that the triad is not sufficient to infer shaking or abuse and the shaking hypothesis does not meet the standards of evidence-based medicine. This raises the issue of whether it is fit for either clinical practice or for the courtroom; evidence presented to the courts must be unassailable. WHAT THIS PAPER ADDS: There is insufficient scientific evidence to assume that an infant with the triad of subdural haemorrhage (SDH), retinal haemorrhage, and encephalopathy must have been shaken. Biomechanical and animal studies have failed to support the hypothesis that shaking can cause SDH and retinal haemorrhage. Patterns of retinal haemorrhage cannot distinguish abuse. Retinal haemorrhages are commonly associated with extracerebral fluid collections (including SDH) but not with shaking. Infants can develop SDH, retinal haemorrhage, and encephalopathy from natural diseases and falls as low as 1 foot. The shaking hypothesis and the literature on which it depends do not meet the standards of evidence-based medicine.

Normative spatiotemporal fetal brain maturation with satisfactory development at 2 years.

Maturation of the human fetal brain should follow precisely scheduled structural growth and folding of the cerebral cortex for optimal postnatal function1. We present a normative digital atlas of fetal brain maturation based on a prospective international cohort of healthy pregnant women2, selected using World Health Organization recommendations for growth standards3. Their fetuses were accurately dated in the first trimester, with satisfactory growth and neurodevelopment from early pregnancy to 2 years of age4,5. The atlas was produced using 1,059 optimal quality, three-dimensional ultrasound brain volumes from 899 of the fetuses and an automated analysis pipeline6-8. The atlas corresponds structurally to published magnetic resonance images9, but with finer anatomical details in deep grey matter. The between-study site variability represented less than 8.0% of the total variance of all brain measures, supporting pooling data from the eight study sites to produce patterns of normative maturation. We have thereby generated an average representation of each cerebral hemisphere between 14 and 31 weeks' gestation with quantification of intracranial volume variability and growth patterns. Emergent asymmetries were detectable from as early as 14 weeks, with peak asymmetries in regions associated with language development and functional lateralization between 20 and 26 weeks' gestation. These patterns were validated in 1,487 three-dimensional brain volumes from 1,295 different fetuses in the same cohort. We provide a unique spatiotemporal benchmark of fetal brain maturation from a large cohort with normative postnatal growth and neurodevelopment.

Thrombosis is not a marker of bridging vein rupture in infants with alleged abusive head trauma.

AIM: Thrombosis of bridging veins has been suggested to be a marker of bridging vein rupture, and thus AHT, in infants with subdural haematoma. METHODS: This is a non-systematic review based on Pubmed search, secondary reference tracking and authors' own article collections. RESULTS: Radiological studies asserting that imaging signs of cortical vein thrombosis were indicative of traumatic bridging vein rupture were unreliable as they lacked pathological verification of either thrombosis or rupture, and paid little regard to medical conditions other than trauma. Autopsy attempts at confirmation of ruptured bridging veins as the origin of SDH were fraught with difficulty. Moreover, microscopic anatomy demonstrated alternative non-traumatic sources of a clot in or around bridging veins. Objective pathological observations did not support the hypothesis that a radiological finding of bridging vein thrombosis was the result of traumatic rupture by AHT. No biomechanical models have produced reliable and reproducible data to demonstrate that shaking alone can be a cause of bridging vein rupture. CONCLUSION: There is no conclusive evidence supporting the hypothesis that diagnostic imaging showing thrombosed bridging veins in infants correlates with bridging vein rupture. Hence, there is no literature support for the use of thrombosis as a marker for AHT.

The pathology and aetiology of subcortical clefts in infants.

In infants, traumatic surface contusions of the brain are rare but subcortical clefts or cysts, variously labelled "contusional tears", "contusional clefts", "cortical tears" or "parenchymal lacerations" have been ascribed to trauma, and are even said to be characteristic of shaking and abuse. We describe the pathology of subcortical clefts or haemorrhages in seven infants. In none were the axonal swellings characteristic of traumatic axonal injury seen in relation to the clefts. Subpial bleeding was associated with clefts in all the cases of recent onset. We hypothesize that subcortical clefts are not due to direct mechanical forces of trauma but are part of a secondary cascade caused by impaired venous drainage which may or may not follow trauma. The finding of subcortical and subpial haemorrhages should prompt a search for CVT. We consider the term "contusion" is not accurate and is misleading.

Epidemiology of subdural haemorrhage during infancy: A population-based register study.

OBJECTIVES: To analyse subdural haemorrhage (SDH) during infancy in Sweden by incidence, SDH category, diagnostic distribution, age, co-morbidity, mortality, and maternal and perinatal risk factors; and its association with accidents and diagnosis of abuse. METHODS: A Swedish population-based register study comprising infants born between 1997 and 2014, 0-1 years of age, diagnosed with SDH-diagnoses according to the (International Classification of Diseases, 10th version (ICD10), retrieved from the National Patient Register and linked to the Medical Birth Register and the Death Cause Register. Outcome measures were: 1) Incidence and distribution, 2) co-morbidity, 3) fall accidents by SDH category, 4) risk factors for all SDHs in the two age groups, 0-6 and 7-365 days, and for ICD10 SDH subgroups: S06.5 (traumatic SDH), I62.0 (acute nontraumatic), SDH and abuse diagnosis. RESULTS: Incidence of SDH was 16·5 per 100 000 infants (n = 306). Median age was 2·5 months. For infants older than one week, the median age was 3·5 months. Case fatality was 6·5%. Male sex was overrepresented for all SDH subgroups. Accidental falls were reported in 1/3 of the cases. One-fourth occurred within 0-6 days, having a perinatal risk profile. For infants aged 7-365 days, acute nontraumatic SDH was associated with multiple birth, preterm birth, and small-for-gestational age. Fourteen percent also had an abuse diagnosis, having increased odds of being born preterm, and being small-for-gestational age. CONCLUSIONS: The incidence was in the range previously reported. SDH among newborns was associated with difficult birth and neonatal morbidity. Acute nontraumatic SDH and SDH with abuse diagnosis had similar perinatal risk profiles. The increased odds for acute nontraumatic SDH in twins, preterm births, neonatal convulsions or small-for-gestational age indicate a perinatal vulnerability for SDH beyond 1st week of life. The association between prematurity/small-for-gestational age and abuse diagnosis is intriguing and not easily understood.

Neonatal subcortical bruising.

A specific type of acute brain injury can occur during birth, presenting on ultrasound examination with focal, unilateral, or asymmetrical change in the core of the superior frontal gyri. Ultrasound inspection of the superior gyri near the convexity of the frontal lobe is warranted following mechanically difficult delivery.

Infants dying suddenly and unexpectedly share demographic features with infants who die with retinal and dural bleeding: a review of neural mechanisms.

The cause of death in infants who die suddenly and unexpectedly (sudden unexpected death in infancy [SUDI]) remains a diagnostic challenge. Some infants have identified diseases (explained SUDI); those without explanation are called sudden infant death syndrome (SIDS). Demographic data indicate subgroups among SUDI and SIDS cases, such as unsafe sleeping and apparent life-threatening events. Infants dying suddenly with retinal and dural bleeding are often classified as abused, but in many there is no evidence of trauma. Demographic features suggest that they may represent a further subgroup of SUDI. This review examines the neuropathological hypotheses to explain SIDS and highlights the interaction of infant oxygen-conserving reflexes with the brainstem networks considered responsible for SIDS. We consider sex- and age-specific vulnerabilities related to dural bleeding and how sensitization of the dural innervation by bleeding may influence these reflexes, potentially leading to collapse or even death after otherwise trivial insults.

The histopathology of polymicrogyria: a series of 71 brain autopsy studies.

AIM: Polymicrogyria (PMG) is one of the most common forms of cortical malformation yet the mechanism of its development remains unknown. This study describes the histopathological aspects of PMG in a large series including a significant proportion of fetal cases. METHOD: We have reviewed the neuropathology and medical records of 44 fetuses and 27 children and adults in whom the cortical architecture was focally or diffusely replaced by one or more festooning bands of neurons. RESULTS: The pial surface of the brain overlying the polymicrogyric cortex was abnormal in almost 90% of cases irrespective of the aetiology. This accords with animal studies indicating the importance of the leptomeninges in cortical development. The aetiology of PMG was highly heterogeneous and there was no correlation between cortical layering patterns and aetiology. PMG was almost always associated with other brain malformations. INTERPRETATION: The inclusion of many fetal cases has allowed us to examine the early developmental stages of PMG. The study indicates the significance of surface signals responsible for human corticogenesis and the complex interaction between genetic and environmental factors leading to this common endpoint of cortical maldevelopment.

Mechanics of the brain: perspectives, challenges, and opportunities.

The human brain is the continuous subject of extensive investigation aimed at understanding its behavior and function. Despite a clear evidence that mechanical factors play an important role in regulating brain activity, current research efforts focus mainly on the biochemical or electrophysiological activity of the brain. Here, we show that classical mechanical concepts including deformations, stretch, strain, strain rate, pressure, and stress play a crucial role in modulating both brain form and brain function. This opinion piece synthesizes expertise in applied mathematics, solid and fluid mechanics, biomechanics, experimentation, material sciences, neuropathology, and neurosurgery to address today's open questions at the forefront of neuromechanics. We critically review the current literature and discuss challenges related to neurodevelopment, cerebral edema, lissencephaly, polymicrogyria, hydrocephaly, craniectomy, spinal cord injury, tumor growth, traumatic brain injury, and shaken baby syndrome. The multi-disciplinary analysis of these various phenomena and pathologies presents new opportunities and suggests that mechanical modeling is a central tool to bridge the scales by synthesizing information from the molecular via the cellular and tissue all the way to the organ level.

H1N1 triggered recurrent acute necrotizing encephalopathy in a family with a T653I mutation in the RANBP2 gene.

A 28-month-old infant presented with fever, vomiting and encephalopathy. Magnetic resonance imaging findings and family history confirmed a diagnosis of recurrent familial acute necrotizing encephalopathy (ANE1). We believe that this is the first description implicating the H1N1 viral strain as a trigger and the second report of a T653I mutation in the RANBP2 gene described in relation to ANE1.