White Matter Abnormalities in Traumatic Subarachnoid Hemorrhage: A Tract-Based Spatial Statistics Study.

BACKGROUND The pathophysiology of traumatic subarachnoid hemorrhage and brain injury has not been fully elucidated. In this study, we examined abnormalities of white matter in isolated traumatic subarachnoid hemorrhage patients by applying tract-based spatial statistics. MATERIAL AND METHODS For this study, 10 isolated traumatic subarachnoid hemorrhage patients and 10 age- and sex-matched healthy control subjects were recruited. Fractional anisotropy data voxel-wise statistical analyses were conducted through the tract-based spatial statistics as implemented in the FMRIB Software Library. Depending on the intersection between the fractional anisotropy skeleton and the probabilistic white matter atlases of Johns Hopkins University, we calculated mean fractional anisotropy values within the entire tract skeleton and 48 regions of interest. RESULTS The fractional anisotropy values for 19 of 48 regions of interest showed significant divergences (P<0.05) between the patient group and control group. The regions showing significant differences included the corpus callosum and its adjacent neural structures, the brainstem and its adjacent neural structures, and the subcortical white matter that passes the long neural tract. CONCLUSIONS The results demonstrated abnormalities of white matter in traumatic subarachnoid hemorrhage patients, and the abnormality locations are compatible with areas that are vulnerable to diffuse axonal injury. Based on these results, traumatic subarachnoid hemorrhage patients also exhibit diffuse axonal injuries; thus, traumatic subarachnoid hemorrhage could be an indicator of the presence of severe brain injuries associated with acute or excessive mechanical forces.

Impaired meningeal lymphatic vessels exacerbate early brain injury after experimental subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Blood that enters the subarachnoid space (SAS) and its breakdown products are neurotoxic and are the principal inducers of brain injury after subarachnoid hemorrhage (SAH). Recently, meningeal lymphatic vessels (MLVs) have been proven to play an important role in clearing erythrocytes that arise from SAH, as well as other macromolecular solutes. However, evidence demonstrating the relationship between MLVs and brain injury after SAH is still limited. Therefore, we performed this study to observe the effects of meningeal lymphatic impairment on early brain injury (EBI) after experimental SAH. METHODS: The MLVs of C57BL/6 male adult mice were ablated by injecting Visudyne into the cisterna magna and transcranially photoconverting it with laser light. The MLVs were then examined by immunofluorescence staining for lyve-1. Next, both the MLV-ablated group and the control group (normal mice) underwent filament perforation to model SAH or sham operation. We assessed the cortical perfusion of all the mice before SAH induction, 5 min after SAH and 24 h after SAH. In addition, we evaluated neurological function deficits by Garcia scores and measured brain water content at 24 h post SAH. Then, neuroinflammation and neural apoptosis in the mouse brain were also examined. RESULTS: Visudyne and transcranial photoconversion treatment notably ablated mouse MLVs. Five minutes after SAH induction, cortical perfusion was significantly impaired, and after 24 h, this impairment was ameliorated considerably in the control group but ameliorated only slightly or worsened in the MLV-ablated group. Additionally, the MLVablated group presented worse neurological function deficits and more severe brain edema than the control group. More notably, neuroinflammation and neural apoptosis were also observed. CONCLUSION: Ablation of MLVs by Visudyne treatment exacerbated EBI after experimental SAH in mice. The worsening of EBI may have arisen from limited drainage of blood and other breakdown products, which are thought to cause brain edema, neuroinflammation, neuronal apoptosis and other pathological processes.

An autopsy case of death due to AC compressor blast - A rare case illustrating primary, secondary, tertiary & quaternary blast injuries.

Blast injuries seen in various accidents involving pressurized containers like gas cylinders, tires, et cetera, and acts of terrorism. The associated factors can vary from poor handling of equipment to inadequate safety precautions. These injuries include a variety of injuries, such as, injuries due to shock wave, burns, fractures, et cetera, involving multi-organ systems, especially lungs and hollow organs, due to the high-pressurized shock wave. The presented case is of the death of a 24-years-old male as a result of a blast of the compressor present in the AC outdoor unit during the filling of the gas. Here, the body showed injuries due to shock wave, secondary impact, tertiary impact because of fall on the ground, and quaternary injuries due to burns. The cause of death was Blast lung associated with Subarachnoid hemorrhage.

Mechanism of brain swelling in cases of brain evisceration due to catastrophic craniocerebral injury - an autopsy study.

Some previously reported cases of brain evisceration in catastrophic craniocerebral injuries showed the presence of brain swelling. The aim of this study was to observe the occurrence of focal or diffuse brain swelling in such cases in order to explain the underlying mechanism. An observational autopsy study included 23 adults, 18 males and 5 females, whose average age was 48 ± 22 years (range: 19-89 years) and who died as the result of catastrophic craniocerebral injury with brain evisceration. In all the examined cases, either focal (12 cases) or diffuse (11 cases) brain swelling was present. Grossly visible brain contusions (either cortical or deep) were rarely present - only in 6 out of 23 cases, while microscopic brain contusions were observed in 22 out of 23 cases, with 1 remaining case of microscopic subarachnoid bleeding. Blood aspiration in the lungs, as a vital reaction, was noted in 20 out of 23 cases. Microscopic examination showed absence of edema in 20 cases and mild edema in only 3 cases, while microscopic signs of moderate or severe edema were absent. Brain swelling in cases of brain evisceration likely represents a biomechanical reaction (i.e. decompression) due to a sudden decrease in intracranial pressure. The rapidity of death, together with marked absence of microscopic signs of edema, suggests that this is not a form of biological response to injury, but rather a pure physical phenomenon, strictly in a living person. In such cases, the occurrence of brain swelling and parenchymal microbleeding should be considered vital reactions.

Exosomes from Bone Marrow Mesenchymal Stem Cells Can Alleviate Early Brain Injury After Subarachnoid Hemorrhage Through miRNA129-5p-HMGB1 Pathway.

In this study, the roles of exosomes (Exo) from bone marrow mesenchymal stem cells (BMSCs) in attenuating early brain injury (EBI) in rat brain after subarachnoid hemorrhage (SAH) had been investigated. The male Sprague-Dawley rats (300-350 g) were used to establish the SAH model using endovascular perforation method. The animals were randomly divided into three groups: sham (n = 25), SAH+PBS (n = 42), and SAH+Exo groups (n = 33). At 1 h after SAH, Exo or phosphate-buffered saline (PBS) was administered by femoral vein injection. The effects of Exo on the mortality, neurological function, brain water content, and blood-brain barrier (BBB) were explored. Furthermore, the expressions of miRNA129-5p and high-mobility group box 1 protein (HMGB1) after Exo treatment were also detected. In addition, immunohistochemistry and western blot were applied to investigate the mechanism of Exo's effects. The results indicated that Exo could improve the neurological functions, reduce brain water content and maintain BBB integrity after SAH. After Exo treatment, the expression of miRNA129-5p was significantly increased, whereas the RNA level of HMGB1 was decreased. The protein levels of proinflammatory and proapoptosis factors, such as HMGB1, Toll-like receptor-4 (TLR4), tumor necrosis factor-α, and p53, were increased after SAH, which were significantly declined after Exo application. The results indicated that Exo from BMSCs could alleviate EBI after SAH through miRNA129-5p's anti-inflammation and antiapoptosis effects through quenching the activity of HMGB1-TLR4 pathway.

Neurostereologic Lesion Volumes and Spreading Depolarizations in Severe Traumatic Brain Injury Patients: A Pilot Study.

BACKGROUND: Spreading depolarizations (SDs) occur in 50-60% of patients after surgical treatment of severe traumatic brain injury (TBI) and are independently associated with unfavorable outcomes. Here we performed a pilot study to examine the relationship between SDs and various types of intracranial lesions, progression of parenchymal damage, and outcomes. METHODS: In a multicenter study, fifty patients (76% male; median age 40) were monitored for SD by continuous electrocorticography (ECoG; median duration 79 h) following surgical treatment of severe TBI. Volumes of hemorrhage and parenchymal damage were estimated using unbiased stereologic assessment of preoperative, postoperative, and post-ECoG serial computed tomography (CT) studies. Neurologic outcomes were assessed at 6 months by the Glasgow Outcome Scale-Extended. RESULTS: Preoperative volumes of subdural and subarachnoid hemorrhage, but not parenchymal damage, were significantly associated with the occurrence of SDs (P's < 0.05). Parenchymal damage increased significantly (median 34 ml [Interquartile range (IQR) - 2, 74]) over 7 (5, 8) days from preoperative to post-ECoG CT studies. Patients with and without SDs did not differ in extent of parenchymal damage increase [47 ml (3, 101) vs. 30 ml (- 2, 50), P = 0.27], but those exhibiting the isoelectric subtype of SDs had greater initial parenchymal damage and greater increases than other patients (P's < 0.05). Patients with temporal clusters of SDs (≥ 3 in 2 h; n = 10 patients), which included those with isoelectric SDs, had worse outcomes than those without clusters (P = 0.03), and parenchymal damage expansion also correlated with worse outcomes (P = 0.01). In multivariate regression with imputation, both clusters and lesion expansion were significant outcome predictors. CONCLUSIONS: These results suggest that subarachnoid and subdural blood are important primary injury factors in provoking SDs and that clustered SDs and parenchymal lesion expansion contribute independently to worse patient outcomes. These results warrant future prospective studies using detailed quantification of TBI lesion types to better understand the relationship between anatomic and physiologic measures of secondary injury.

Cervical Spine Involvement in a Challenging Case of Accidental Strangulation.

Although strangulation is generally homicidal, the scientific literature reports several cases in which it is suicidal or even accidental. The former eventuality is particularly interesting because extremely atypical ligatures (such as locks of hair), complex dynamics, and uncommon findings can be involved. Only a meticulous evaluation of the body and of both direct and circumstantial evidence can help in the complex differential diagnosis that includes murder, suicide, and accident. In accidental strangulation, the number and severity of injuries depend on the magnitude of applied force. This implies that high-energy strangulation (in our case, caused by the entanglement of a scarf in an electrical generator) can produce a complex polytrauma. In this case, accidental self-strangulation caused widespread, posttraumatic subarachnoid hemorrhaging, laceration of the larynx, and fracture-dislocation of the C2/C3 vertebrae. We believe that all these events contributed to the death of the victim, but the complexity of the polytrauma and the lack of direct evidence did not allow us to determine a univocal cause-effect chain.

Fatal subarachnoid hemorrhage caused by rupture of variant anterior communicating artery: a case report and literature review.

Fatal subarachnoid hemorrhage (SAH) caused by anterior communicating artery (ACoA) rupture is a rare event in medicolegal practice. Anatomical variations of the ACoA tend to make its anatomical structure, and as a result, blood flow through it, more complicated, which may increase hemodynamic stress and cause weak spots in the affected blood vessels. Variant ACoAs are prone to rupture in the event of a blunt-force trauma. Here, we report a fatal case of SAH caused by the rupture of a variant ACoA when the victim's head was struck from behind, causing the head to rotate and the victim to fall forward onto the ground. A medicolegal autopsy revealed diffuse basal SAH and ACoA duplication. The smaller of the two variant ACoA branches had ruptured near its junction with the right anterior cerebral artery. No basal aneurysms or other fatal diseases or injuries were found. This case highlights the significance of anatomical variation in forensic pathology.

Delayed rupture of a vertebral artery laceration: a case report and challenges for the forensic pathologist.

Vertebral artery laceration/dissection (VALD) resulting in fatal subarachnoid hemorrhage (SAH) is a rare, but well-known phenomenon encountered in the forensic setting. Delayed ruptures are exceptionally rare, and pose several challenges to the forensic pathologist. In this paper we present a case of a 47-year-old male who collapsed suddenly following recent complaints of a headache and a reported seizure. He had a reported history of potential head trauma that occurred several days prior. Attempts at resuscitation were unsuccessful, and an autopsy examination was ordered. Computer tomography (CT), autopsy, histological and ancillary studies were performed. External examination showed mild, healing trauma to the head and upper limbs, and pre-autopsy CT demonstrated a SAH. Examination of the brain showed basally oriented SAH, and there was a laceration of the left vertebral artery. Histological examination demonstrated a delayed rupture, and there was no significant blood vessel abnormality. Molecular testing was negative for collagen vascular disorders. Delayed rupture of the vertebral arteries following head trauma is rare. The presence of remote and/or mild trauma may be difficult to establish at autopsy, and it is important to identify underlying aortopathies. Several autopsy techniques and ancillary studies should be performed in these cases.

Atorvastatin ameliorates early brain injury through inhibition of apoptosis and ER stress in a rat model of subarachnoid hemorrhage.

Aneurysmal subarachnoid hemorrhage (SAH) is a severe cerebrovascular disease with very poor prognosis. The aim of the present study was to evaluate the protective effects of atorvastatin on early brain injury (EBI) after SAH using a perforation SAH model. Male Sprague-Dawley rats were randomly divided into four groups: the sham group, the SAH group (model group), SAH + 10 mg.kg-1day-1 atorvastatin (low atorvastatin group), and SAH + 20 mg.kg-1day-1 atorvastatin (high atorvastatin group). Atorvastatin was administered orally by gastric gavage for 15 days before operation. At 24 h after SAH, we evaluated the effects of atorvastatin on brain water content, apoptosis by TUNEL assay and scanning electron microscope (SEM), and the expression of apoptosis-related proteins by immunofluorescence and Western blotting analysis. Compared with the sham group, we observed increased brain water content, significant apoptosis, and elevated levels of apoptosis-related proteins including caspase-3, CCAAT enhancer-binding protein homologous protein (CHOP), the 78-kDa glucose-regulated protein (GRP78), and aquaporin-4 (AQP4) in the SAH group. Atorvastatin administration under all doses could significantly reduce brain water content, apoptosis, and the expression levels of caspase-3, CHOP, GRP78, and AQP4 at 24 h after SAH. Our data show that early treatment with atorvastatin effectively ameliorates EBI after SAH through anti-apoptotic effects and the effects might be associated inhibition of caspase-3 and endoplasmic reticulum (ER) stress related proteins CHOP and GRP78.

Traumatic subarachnoid hemorrhage related to ophthalmic artery avulsion: a case report.

We present a case of ophthalmic artery (OA) traumatic avulsion, leading to a post-traumatic subarachnoid hemorrhage (SAH) with ventricular blood invasion and hydrocephalus, mimicking an internal carotid aneurysm rupture. This is the third case of such an event reported in literature and the first without orbital fractures and optic nerve avulsion. Conservative treatment was sufficient for the avulsion, but surgery was needed for the coexisting eye luxation. Traumatic OA avulsion is a rare but possible event and should be suspected in case of basal cisterns SAH, evidence of orbital trauma and CT angiogram or angiographic absence of opacification of the OA.

A case of intrauterine lethal fetal injury after attempted suicide of the mother.

Traumatic injuries in pregnancy such as abdominal trauma, pelvic fractures and penetrating trauma are major causes of maternal and neonatal morbidity and mortality. The most common causes of trauma during pregnancy are motor vehicle accidents, falls, assaults, gunshots, and burns. Pregnancy itself has been identified as a risk factor for trauma, together with a younger age, drug use, alcohol use, and domestic violence. We report the case of a 46-year-old woman, 34 weeks pregnant, who attempted suicide by jumping from a flyover, immediately after a probably deliberate traffic collision with the guardrail. She had fractures of five lumbar vertebrae and three ribs with pulmonary contusions, but was without other injuries. Following the mother's stabilization, the fetal heart tones were detected as abnormal and the patient had an emergency caesarean section delivering a still-born male infant. Neither alcohol nor drugs were found in the mother who had been diagnosed with an unspecified episodic mood disorder. She recovered completely from her injuries. At autopsy of the newborn, a massive subarachnoid hemorrhage with deformity of the skull was found, caused by maternal blunt abdominal trauma following car accident and fall. This case is an outstanding example of fetal head trauma which occurred with no life-threatening maternal injury due to attempted suicide. It is important for clinicians and forensic pathologists to have adequate knowledge and practical experience of these cases, because pregnancy is a special risk factor for self-inflicted injuries among females, with significant adverse effects on the fetus even with minor injuries to the mother.

The importance of optic nerve sheath hemorrhage as a postmortem finding in cases of fatal abusive head trauma: A 13-year study in a tertiary hospital.

Fatal abusive head trauma is a major cause of death in children and toddlers who suffer from cruel physical abuse. Postmortem differentiation of fatal abusive head trauma from accidental head trauma can be a complicated process. This consecutive case series study aimed to determine the role of subdural optic nerve sheath hemorrhage (ONSH) in 70 autopsy cases of children ≤3 years old in making this differentiation. The study took place over a 13 year period (between August 1st 2003 and July 31st 2016) at a tertiary hospital in Thailand. Eleven cases were diagnosed with fatal abusive head trauma and 10 were identified as being accidental closed head trauma cases. Bilateral retinal hemorrhage was noted in antemortem medical records in every hospitalized abusive head trauma case (n=10). Upon autopsy, ONSH was observed in all 11 fatal cases of abusive head trauma (bilateral=10 and unilateral=1) but not in any cases of accidental head trauma (0/5). Subdural hemorrhage was found in 10 out of 11 abusive head trauma victims but not in any of the 10 with accidental head trauma. Other postmortem findings in abusive head trauma included subarachnoid hemorrhage (5/11), marked brain swelling (3/11), skull fracture (4/11) and brain contusion (1/11). This study suggests that ONSH, together with subdural hemorrhage, plays an essential role in an accurate postmortem diagnosis of fatal abusive head trauma. Therefore, an ocular investigation should be performed in all autopsy cases where child abuse is suspected and where there is no reliable history/witnesses, confession or antemortem ophthalmologic examination.

Sudden Death From Ruptured Intracranial Vascular Malformations During Mechanical Asphyxia: A Domestic Violence Case Report.

Smothering and manual strangulation are not uncommon in domestic violence against women; however, no report on the combination of mechanical asphyxia and intracranial vascular malformations has been previously published. We report a middle-aged woman who was smothered and manually strangled by her husband and subsequently died from subarachnoid hemorrhage due to ruptured intracranial vascular malformations, rather than direct mechanical asphyxiation. Smothering and manual strangulation are considered provocative conditions for rupture and contributory causes of death. In this case study, we underline the importance of meticulous autopsy in cases of mechanical asphyxia and intracranial hemorrhage. Exclusion of underlying diseases that may have caused or contributed to death is also required, despite serious asphyxiation signs and neck injuries. Postmortem angiography is a valuable complement to autopsy to detect vascular pathology, with good prospects for further development in China.

An unusual case of murder-suicide: The importance of studying knots.

An atypical murder-suicide that involved a married couple over 80 years of age was investigated at the Institute of Legal Medicine of the University of Chieti-Pescara and is presented and discussed here. The whole story allows us to confront the difficulties involved in the discovery of a dead body in water when the circumstantial evidence does not allow any unique interpretation of the facts. The atypical and misleading element appeared to be how the body of the man was tied, with the interpretation inclined towards a homicidal manner of death. It was only by combining the contributions of each of the findings that emerged during the course of the autopsy with the circumstantial evidence from the site inspection that it was possible to reach resolution of this case, which was then identified as a murder-suicide.

The clinical significance of small subarachnoid hemorrhages.

With advancing technology, the sensitivity of computed tomography (CT) for the detection of traumatic subarachnoid hemorrhage (tSAH) continues to improve. Increased resolution has allowed for the detection of hemorrhage that is limited to one or two images of the CT exam. At our institution, all patients with a SAH require intensive care unit (ICU) admission, regardless of size. It was our hypothesis that patients with small subarachnoid hemorrhage experience favorable outcomes, and may not require the intensive monitoring offered in the ICU. This retrospective study evaluated 62 patients between 2011 and 2014 who presented to our Level I trauma center emergency room for acute traumatic injuries, and found to have subarachnoid hemorrhages on CT examination. The grade of subarachnoid hemorrhage was determined using previously utilized scoring systems, such as the Fisher, Modified Fisher, and Claassen grading systems. Electronic medical records were used to evaluate for medical decline, neurological decline, neurosurgical intervention, and overall hospital course. Admitting co-morbidities were noted, as were the presence of patient intoxication and use of anticoagulants. Patient outcomes were based on discharge summaries upon which the neurological status of the patient was assessed. Each patient was given a score based on the Glasgow outcome scale. The clinical and imaging profile of 62 patients with traumatic SAH were studied. Of the 62 patients, 0 % underwent neurosurgical intervention, 6.5 % had calvarial fractures, 25.8 % had additional intracranial hemorrhages, 27.4 % of the patients had significant co-morbidities, and 1.6 % of the patients expired. Patients with low-grade tSAH spent less time in the ICU, demonstrated neurological and medical stability during hospitalization. None of the patients with low-grade SAH experienced seizure during their admission. In our study, patients with low-grade tSAH demonstrated favorable clinical outcomes. This suggests that patients may not require as aggressive monitoring as is currently provided for those with tSAH.

Traumatic basal subarachnoid haemorrhage or ruptured brain aneurysm in 16-year-old boy? - case report

Traumatic basal subarachnoid haemorrhage (TBSAH) represents only 1.8% of all subarachnoid haemorrhage cases diagnosed during autopsy. This report presents such a case from the current practice of the authors. Sixteen-year-old boy was beaten by the aggressors. Suddenly he lost his consciousness and fall after he received a single blow in the neck. He was resuscitated immediately, but died at the scene. During the external examination we did not find any significant external injuries. Autopsy revealed large contusion of right sternocleidomastoid muscle. In the cranial cavity we found extensive subarachnoid haemorrhage, located mainly on brain basis, in the posterior cranial fossa and covering the subtentorial structures. During the preparation of blood vessels we noticed a slight change of morphology suggesting damaged vessel or aneurysm, or vascular malformation located in the basilar artery bifurcation, which was taken to detailed microscopic evaluation using the special stainings. Histological examination showed vital interruption of the basilar artery wall with massive haemorrhage, without the presence of general microscopic pathology. From the medico-legal viewpoint, to determine traumatic background of haemorrhage it is necessary to find the coexistence of the following circumstances: a sustained trauma, post-mortem findings consistent with a time of injury, the presence of temporal relationship between injury and death, and morphological vital injury of the brain vessel, as well as the absence of prior vascular malformations. For this purpose Verhoeff-van Gieson's, Masson's, Turnbull's and Gomori' histological stainings may be successfully used.

Suicide by blunt head trauma - Two cases with striking similarities.

There have been several forensic pathological studies on the distinction between falls from height and homicidal blows in blunt head trauma, but few studies have focused on suicidal blows. Self-inflicted blunt head trauma is usually a part of a complex suicide with more than one suicidal method applied. Actually, no reports on suicide indicate blunt head trauma to be the singular cause of death in recent publications. Cases with self-inflicted blunt trauma are often challenging for those involved in the investigation because they are confronted with findings that are also found in homicides. A refined guideline to differentiate suicidal blows from homicidal blows in blunt head trauma allows for a more accurate representation of the events surrounding death. This paper presents two cases of suicide by self-inflicted blunt head trauma in which blunt head trauma from repeatedly hitting the decedent's head with a hammer was considered to be the only cause of death.