Brain water content in sudden unexpected infant death.

The extensive and rapid development of the human brain during the first years of life complicates the postmortem diagnosis of brain edema in infancy. The aim of this study was to describe brain water content, the brain weight/body weight ratio, and the brain weight/head circumference ratio throughout the first years of life. Furthermore, we examined the relationship between these parameters and rs2075575 in the AQP4 gene. Our hypothesis was that dysregulated water homeostasis might be a risk factor for sudden infant death syndrome (SIDS), which may be reflected by increased water content in the brain. The study included 90 subjects with sudden unexpected death < 4 years of age: 22 cases of sudden infant death syndrome, 11 cases of sudden unexplained death in childhood, 47 cases of death due to disease, and 10 cases of accident/violent death. Brain water content, brain weight/body weight ratio, and brain weight/head circumference ratio were investigated according to corrected age, diagnosis group, attempt to resuscitate, and presence of brain edema. We found that brain water content and brain weight/body weight ratio were significantly reduced with increasing age, while brain weight/head circumference were increased. Brain weight/head circumference was correlated with brain water content. Cases with brain edema had a significantly higher brain weight/head circumference than the non-edematous cases. No differences were found between the diagnosis groups for any of the investigated parameters. In summary, the findings contribute to the current body of knowledge regarding brain growth during the first months of life.

Young adults in motor vehicle collisions in Norway: user safety errors observed in majority of cases with severe or fatal injuries.

PURPOSE: We performed a multidisciplinary investigation of young adults involved in motor vehicle collisions (MVCs) to elucidate injury mechanisms and the role of passive safety equipment such as seat belts and airbags. METHODS: MVCs resulting in death or serious injuries to the driver or passengers aged 16-24 years in southeastern Norway during 2013-2016 were investigated upon informed consent. We assessed the crash scene, the motor vehicle (MV) interior and exterior, and analyzed data from medical records, forensic autopsies and reports from police and civil road authorities. RESULTS: This study included 229 young adult occupants involved in 212 MVCs. The Maximum Abbreviated Injury Scale (MAIS) score was ≥2 in 111 occupants, of which 22 were fatalities. In 59% (65/111) of the cases with MAIS score ≥2 injuries, safety errors and occupant protection inadequacies were considered to have contributed to the injury outcome. Common errors were seatbelt non-use and misuse, carrying insecure luggage, and the seat back being too reclined. MAIS score ≥2 head/neck injuries were observed in side impacts despite correct seatbelt use, related to older MVs lacking side airbag curtains. The independent risk factors for MAIS score ≥2 injuries included not using a seatbelt, driving under the influence of alcohol or drugs, nighttime driving, side impacts, heavy collision partner, and MV deformation. CONCLUSION: User safety errors (not using a seatbelt, seatbelt misuse, excessive seat-back reclining, and insecure cargo) and a lack of occupant protection in older MVs resulted in young adults sustaining severe or fatal injuries in MVCs.

Aquaporin-1 and aquaporin-9 gene variations in sudden infant death syndrome.

Several studies have indicated that a vulnerability in the development and regulation of brain function is involved in sudden infant death syndrome (SIDS). The aim of this study was to investigate the genes encoding the brain aquaporins (AQPs) AQP1 and AQP9 in SIDS. The hypothesis was that specific variants of these genes are part of the genetic vulnerability predisposing infants to sudden unexpected death. The study included 168 SIDS cases with a median age of 15.5 (range 2-52) weeks and 372 adolescent/adult deceased controls with a median age of 44 (range 11-91) years. In the AQP1 gene, the rs17159702 CC/CT genotypes were found to be associated with SIDS (p = 0.02). In the AQP9 gene, the combination of a TT genotype of rs8042354, rs2292711 and rs13329178 was more frequent in SIDS cases than in controls (p = 0.03). In the SIDS group, an association was found between genetic variations in the AQP1 gene and maternal smoking and between the 3xTT combination in the AQP9 gene and being found lifeless in a prone position. In conclusion, this study adds further evidence to the involvement of brain aquaporins in SIDS, suggesting that specific variants of AQP genes constitute a genetic predisposition, making the infant vulnerable to sudden death together with external risk factors and probably other genetic factors.

Norwegian parents avoid placing infants in prone sleeping positions but frequently share beds in hazardous ways.

AIM: Campaigns to prevent prone sleeping and other modifiable risk factors have greatly reduced the incidence of sudden infant death syndrome in Norway. Sleep-related infant deaths still occur sporadically and may be preventable. We studied infants' sleeping environments and whether parents followed safe sleep recommendations. METHODS: Parents with infants up to 12 months of age were invited to complete an online questionnaire from May to December 2018. It was publicised by health centres and on websites and social media. RESULTS: We received 4886 responses and 4150 met the age criteria and were included. Just under two-thirds (62.7%) reported routine bed-sharing, and this practice was associated with increased nocturnal breastfeeding, single parents and having more than one child. A small number of infants under six months were occasionally placed prone when they were laid down to sleep (2.1%) and 29.7% were placed on their side. Nearly three-quarters (72.6%) of the 2330 parents with infants under six months of age reported previous high-risk behaviour, such as sleeping together on a sofa or bed-sharing after smoking or drinking. CONCLUSION: Norwegian parents rarely used prone sleeping positions for infants. However, bed-sharing was common, including high-risk scenarios such as smoking, alcohol use and sofas.

Amongst Norwegian paediatricians there is little agreement in management of cases of suspected child maltreatment.

AIM: Child maltreatment is not unusual in our society but little is known about the medical management of cases in the Nordic countries. This study investigated physician knowledge and practice in cases of suspected physical and sexual abuse and neglect. METHODS: Using a patient vignette questionnaire, we assessed paediatrician knowledge and clinical decision-making on paediatric wards at 17 hospitals in Norway. Experts and non-experts in child maltreatment responded to the survey which described six potential cases of physical and sexual abuse and neglect. RESULTS: A total of 156 paediatricians, 67% of whom were female and with a mean age of 40, responded. There was a high level of unanimity in recognition of abuse, but wide variation and little consensus in clinical decision-making and adherence to national guidelines, with Fleiss kappa ranging from -0.002 to 0.468. In cases involving physical abuse concerns in infants and toddlers, less than half of all paediatricians reported they would order a full radiologic skeletal survey and head MRI/CT imaging, and less than 30% would plan follow-up consultations. CONCLUSION: This study shows little agreement in the paediatric management of child maltreatment cases. These findings suggest the need for a national plan ensuring appropriate paediatric care for maltreated children.

Autopsy findings in drivers and passengers from fatal motor vehicle collisions: limited differences in injury patterns and toxicological test results.

We performed a retrospective study of the injuries and characteristics of occupant fatalities in motor vehicle collisions in southeast Norway. The goal was to provide updated knowledge of injuries sustained in modern vehicles and detect possible differences in injury pattern between drivers and passengers. Forensic autopsy reports, police, and collision investigation reports from 2000 to 2014 were studied, data extracted and analyzed.A total of 284 drivers, 80 front-seat passengers, and 37 rear-seat passengers were included, of which 67.3% died in front collisions, 13.7% in near-side impacts, 13.5% in rollovers and 5.5% in other/combined collisions. Overall, 80.5% died within one hour after the crash. The presence of fatal injuries to the head, neck, thorax and abdomen were observed in 63.6%, 10.7%, 61.6% and 27.4% respectively. All occupants with severe injuries to the head or neck had signs of direct impact with contact point injuries to the skin or skull. Injuries to the heart and spleen were less common in front-seat passengers compared to drivers. Seat belt abrasions were more common and lower extremity fractures less common in both front-seat and rear-seat passengers compared to drivers. Blood alcohol and/or drug concentrations suggestive of impairment were present in 30% of all occupants, with alcohol more often detected among front-seat passengers compared to drivers.Few driver-specific and passenger-specific patterns of injury could be identified. When attempting to assess an occupant's seating position within a vehicle, autopsy findings should be interpreted with caution and only in conjunction with documentation from the crash scene.

Death-scene investigations contribute to legal protection in unexpected child deaths in Norway.

AIM: This study reviewed cases of sudden unexpected child deaths in Norway to determine the significance of death-scene investigations (DSIs) in establishing cause and manner of death, and thereby it is relevance to legal protection. METHODS: Data from forensic autopsy reports and DSIs were collected and analysed for cases of unexpected deaths in children below 4 years of age in Norway during 2010-2016. RESULTS: Out of 141 cases, the death scene was investigated as a voluntary procedure in 75 cases and by the police in 41 cases. The cause of death remained unexplained in 81/141 (57%) of the cases, of which 46/141 (33%) met the criteria for sudden infant death syndrome (SIDS) or sudden unexplained death in early childhood (SUDC). The manner of death was determined in 102/141 (72%). Voluntary DSI increased the ability to rule out accidental suffocation, facilitated evaluations of environmental risk factors and enabled detection of possible neglect. CONCLUSION: Death-scene investigations illuminate uncertainty about the cause of death, especially in grey-area cases where accidental suffocation, neglect or abuse is suspected. Knowledge about the course of events and the cause of death enhances both the child's and the caregiver's legal protection. Death-scene investigations should therefore be mandatory.

The significance of preexisting medical conditions, alcohol/drug use and suicidal behavior for drivers in fatal motor vehicle crashes: a retrospective autopsy study.

Driver fatalities in motor vehicle collisions (MVCs) encompass accidents, suicides, and natural deaths when driving. The objective of this study was to determine the significance of pathology and other autopsy findings for drivers in fatal MVCs. Forensic autopsy records of driver fatalities in southeast Norway between 2000 and 2014 were studied retrospectively. Data from individual police and collision investigation reports were also collected and analyzed. In 406 driver fatalities, the male/female ratio was 340/66; 9% died from natural causes, 9% were suicides, 65% were culpable accidental deaths, 14% were nonculpable deaths, and 3% were undetermined deaths. Head injuries and thoracic injuries were the most common causes of death. A seatbelt had been worn in 50% of the fatalities, and its prevalence did not differ between accidental deaths and suicides. Blood levels of alcohol and/or drugs that indicated impairment at the time of the collision were found in 40% (105/262) of all culpable accidental deaths but in 50% (64/127) of drivers aged up to 35 years. Pathology (most often cardiovascular disease) suggestive of sudden incapacitation before the collision was present in 24% (62/264) of drivers who were culpable in the accident and in 70% (46/66) of culpable drivers older than 55 years. A substantial proportion of drivers are killed in accidental collisions that may have occurred as a result of either alcohol/drug impairment or preexisting disease. Suicides and natural deaths both constitute significant proportions of MVC fatalities and may be misclassified unless a full inquest including an autopsy is performed.

How Different Iterative and Filtered Back Projection Kernels Affect Computed Tomography Numbers and Low Contrast Detectability.

OBJECTIVE: The aim of this study was to evaluate how different iterative and filtered back projection kernels affect the computed tomography (CT) numbers and low contrast detectability. METHODS: Five different scans were performed at 6 different tube potentials on the same Catphan 600 phantom using approximately the same dose level and otherwise identical settings. The scans were reconstructed using all available filtered back projection body kernels and with iterative reconstruction techniques. RESULTS: The CT numbers and the contrast-to-noise ratios were reported and how they are affected by the kernel choice and strength of iterative reconstruction. CONCLUSIONS: Iterative reconstruction improved contrast-to-noise ratio in most cases, but in certain situations, it decreased it. Variations in CT numbers can be large between kernels with similar sharpness for certain densities.

The gene encoding the inwardly rectifying potassium channel Kir4.1 may be involved in sudden infant death syndrome.

AIM: Disturbances in brain function and development may play a role in sudden infant death syndrome (SIDS). This Norwegian study aimed to test the hypothesis that specific variants of genes involved in water transport and potassium homeostasis would be predisposing factors for SIDS. METHODS: Genetic variation in the genes encoding aquaporin-4 (AQP4), Kir4.1 (KCNJ10) and α-syntrophin was analysed in 171 SIDS cases (62.6% male) with a median age of 15.5 (2-52) weeks and 398 adult controls (70.6% male) with a median age of 44 (11-91) years. All the subjects were Caucasians who were autopsied from 1988 to 2013. RESULTS: The CC genotype of rs72878794 in the AQP4 gene and a combination of the CC genotype in rs17375748, rs1130183, rs12133079 and rs1186688 in KCNJ10 (4xCC) were found to be associated with SIDS. The SIDS cases with the 4xCC SNP combination were younger than the SIDS cases with other genotype combinations (p = 0.006). CONCLUSION: This study indicates that genetic variations in KCNJ10 and AQP4 may be predisposing factors for SIDS. Alterations in the expression of the AQP4/Kir4.1 complex can disrupt water and ion homeostasis, which may influence brain development and facilitate brain oedema formation This may be especially unfavourable during the first weeks of life.

Injuries associated with mechanical chest compressions and active decompressions after out-of-hospital cardiac arrest: A subgroup analysis of non-survivors from a randomized study.

Background: Both skeletal and visceral injuries are reported after cardiopulmonary resuscitation (CPR). This subgroup analysis of a randomized clinical study describes/compares autopsy documented injury patterns caused by two mechanical, piston-based chest compression devices: standard LUCAS® 2 (control) and LUCAS® 2 with active decompression (AD, intervention) in non-survivors with out-of-hospital cardiac arrest (CA). Method: We compared injuries documented by autopsies (medical/forensic) after control and intervention CPR based on written relatives consent to use patients' data. The pathologists were blinded for the device used. The cause of CA and injuries reported were based on a prespecified study autopsy template. We used Pearson's chi-squared test and logistic regression analysis with an alpha level of 0.05. Results: 221 patients were included in the main study (April 2015-April 2017) and 207 did not survive. Of these, 114 (55%, 64 control and 50 intervention) underwent medical (N = 73) or forensic (N = 41) autopsy. The cause of CA was cardiac 53%, respiratory 17%, overdose/intoxication 14%, ruptured aorta 10%, neurological 1%, and other 5%. There were no differences between control and intervention in the incidence of rib fractures (67% vs 72%; p-value = 0.58), or sternal fractures (44% vs 48%; p-value = 0.65), respectively. The most frequent non-skeletal complication was bleeding (26% of all patients) and intrathoracic was the most common location. Ten of the 114 patients had internal organ injuries, where lungs were most affected. Conclusion: In non-survivors of OHCA patients, the most frequent cause of cardiac arrest was cardiogenic. Skeletal and non-skeletal fractures/injuries were found in both control and intervention groups. Bleeding was the most common non-skeletal complication. Internal organ injuries were rare.

An infant with subdural hematoma and retinal hemorrhages: does von Willebrand disease explain the findings?

An 11-month-old girl presented to hospital with a massive subdural haematoma and bilateral retinal haemorrhages following an allegedly minor fall. There were no external signs of bruising and no prior bleeding tendency was reported. Although initial analyses were normal, repeated testing of the coagulation-fibrinolysis system led to a diagnosis of mild von Willebrand disease (vWD) Type 1. It was concluded that minor head trauma as described by the parents, in the presence of such a coagulation disorder, could explain the findings. Police charges against the parents, initially accused of child abuse, were withdrawn. Retinal haemorrhages in infants with vWD have not been previously reported. This case highlights the importance of considering vWD as a possible contributory factor in cases of infant head injury.

Violent Infant Surrogate Shaking: Continuous High-Magnitude Centripetal Force and Abrupt Shift in Tangential Acceleration May Explain High Risk of Subdural Hemorrhage.

Violent shaking is believed to be a common mechanism of injury in pediatric abusive head trauma. Typical intracranial injuries include subdural and retinal hemorrhages. Using a laboratory surrogate model we conducted experiments evaluating the head motion patterns that may occur in violent shaking. An anthropomorphic test device (ATD; Q0 dummy) matching an infant of 3.5 kg was assembled. The head interior was equipped with accelerometers enabling assessment of three-axial accelerations. Fifteen volunteers were asked to shake the surrogate vigorously holding a firm grip around the torso. We observed the volunteers performing manual shaking of the surrogate at a median duration of 15.5 sec (range 5-54 sec). Typical acceleration/deceleration patterns were produced after 2-3 shakes with a steady-state shaking motion at a pace of 4-6 cycles (back and forth) per second. Mean peak sagittal tangential accelerations at the vertex were 45.7g (range 14.2-105.1g). The acceleration component in the orthogonal direction, the radial acceleration, fluctuated around a negative mean of more than 4g showing that the surrogate head was continuously subjected to centripetal forces caused by rotations. This surrogate experiment showed that violent shaking may induce high peak tangential accelerations and concomitantly a continuous high-magnitude centripetal force. We hypothesize that the latter component may cause increased pressure in the subdural compartment in the cranial roof and may cause constant compression of the brain and possibly increased stretching or shearing of the bridging veins. This may contribute to the mechanism accountable for subdural hematoma in abusive head trauma.

Aquaporin 4 expression in the hippocampus in sudden infant death syndrome and sudden unexplained death in childhood.

Aquaporin 4 (AQP4) is the main membrane water channel in the brain involved in regulating water homeostasis. The water distribution in neural tissue is often dysregulated after hypoxic neural injury. Previous research has indicated that victims of sudden infant death syndrome (SIDS) and sudden unexplained death in childhood (SUDC) have an underlying brain dysfunction that impairs their critical arousal response to hypoxic stress during sleep. The aim of this study was to determine the expression levels of AQP4 in the hippocampus in SIDS/SUDC cases and controls, and compare the findings with AQP4 genotypes that previously have been shown to be associated with SIDS. Immunochemical staining and morphometry were used to evaluate the density of AQP4-positive astrocytes in 30 SIDS/SUDC cases and 26 controls. AQP4-positive cells were counted in grids covering three layers in the hippocampus, which revealed that their count in any of the layers did not differ significantly between cases and controls. A decline in AQP4 expression was observed for infants older than 12 weeks. The AQP4 expression was lower in infants and children with the rs2075575 CT/TT genotype than in those with the CC genotype. This study indicates that AQP4 expression may be influenced by both age and genotype in infants. The role of AQP4 in the pathogenesis of SIDS remains to be elucidated.

Iterative reconstruction improves image quality and reduces radiation dose in trauma protocols; A human cadaver study.

BACKGROUND: Radiation-related cancer risk is an object of concern in CT of trauma patients, as these represent a young population. Different radiation reducing methods, including iterative reconstruction (IR), and spilt bolus techniques have been introduced in the recent years in different large scale trauma centers. PURPOSE: To compare image quality in human cadaver exposed to thoracoabdominal computed tomography using IR and standard filtered back-projection (FBP) at different dose levels. MATERIAL AND METHODS: Ten cadavers were scanned at full dose and a dose reduction in CTDIvol of 5 mGy (low dose 1) and 7.5 mGy (low dose 2) on a Siemens Definition Flash 128-slice computed tomography scanner. Low dose images were reconstructed with FBP and Sinogram affirmed iterative reconstruction (SAFIRE) level 2 and 4. Quantitative image quality was analyzed by comparison of contrast-to-noise ratio (CNR) and signal-to-noise ratio (SNR). Qualitative image quality was evaluated by use of visual grading regression (VGR) by four radiologists. RESULTS: Readers preferred SAFIRE reconstructed images over FBP at a dose reduction of 40% (low dose 1) and 56% (low dose 2), with significant difference in overall impression of image quality. CNR and SNR showed significant improvement for images reconstructed with SAFIRE 2 and 4 compared to FBP at both low dose levels. CONCLUSIONS: Iterative image reconstruction, SAFIRE 2 and 4, resulted in equal or improved image quality at a dose reduction of up to 56% compared to full dose FBP and may be used a strong radiation reduction tool in the young trauma population.

Vaccine Induced Immune Thrombotic Thrombocytopenia Causing a Severe Form of Cerebral Venous Thrombosis With High Fatality Rate: A Case Series.

During a 2-week period, we have encountered five cases presenting with the combination of cerebral venous thrombosis (CVT), intracerebral hemorrhage and thrombocytopenia. A clinical hallmark was the rapid and severe progression of disease in spite of maximum treatment efforts, resulting in fatal outcome in for 4 out of 5 patients. All cases had received ChAdOx1 nCov-19 vaccine 1-2 weeks earlier and developed a characteristic syndrome thereafter. The rapid progressive clinical course and high fatality rate of CVT in combination with thrombocytopenia in such a cluster and in otherwise healthy adults is a recent phenomenon. Cerebral autopsy findings were those of venous hemorrhagic infarctions and thrombi in dural venous sinuses, including thrombus material apparently rich in thrombocytes, leukocytes and fibrin. Vessel walls were free of inflammation. Extra-cerebral manifestations included leech-like thrombi in large veins, fibrin clots in small venules and scattered hemorrhages on skin and membranes. CVT with thrombocytopenia after adenovirus vectored COVID-19 vaccination is a new clinical syndrome that needs to be recognized by clinicians, is challenging to treat and seems associated with a high mortality rate.

Aquaporin-4 gene variation and sudden infant death syndrome.

The purpose of this study was to investigate the aquaporin-4 (AQP4) gene in cases of sudden infant death syndrome (SIDS) and controls and to elucidate the hypothesis that a genetically determined disturbed water homeostasis in the brain is involved as a predisposing factor in SIDS. The single nucleotide polymorphisms (SNPs) rs2075575, rs4800773, rs162004, and rs3763043 in the AQP4 gene were investigated in 141 SIDS cases and 179 controls. For each SIDS case, a brain/body weight ratio was calculated. The study revealed an association between the T allele and the CT/TT genotypes of rs2075575 and SIDS (C versus T, p < 0.01; CC versus CT/TT, p = 0.03). For the other three investigated SNPs, there were no differences in genotype frequencies between SIDS cases and controls. For the SNP rs2075575, it was also found an association between brain/body weight ratio and genotype in the SIDS cases aged 0.3-12 wk (p = 0.014, median ratio CC 10.6, CT/TT 12.1). In conclusion, this study indicates that rs2075575 may be of significance as a predisposing factor for SIDS, and that the CT/TT genotypes are associated with an increased brain/body weight ratio in infants dying from SIDS during the vulnerable period from birth up to 3 mo of age.