A Case of Postmortem Canine Depredation.

We report the case of postmortem animal depredation that produced initial confusion for investigators who responded to the scene. A decomposing elderly woman was found in her presumed home with bilateral upper extremity amputations and craniocerebral trauma. This raised suspicion of foul play. Subsequent investigations together with autopsy led the medical examiner to conclude that the cause of death was natural disease and that those injuries found on her body were produced by at least one of the dogs who shared the premises. We linked the canine culprit to the postmortem trauma and positively identified the remains by collecting material defecated by the animal and by using radiologic and dental comparison techniques.

Massive ovarian cyst and sudden death.

Massive enlargement of an ovarian cyst is an uncommon cause of morbidity and a rare cause of mortality due in large to part to noninvasive imaging techniques that usually permit early detection. When an ovarian cyst reaches giant proportions, it produces abdominal enlargement often with a fluid wave resulting in a condition that mimics ascites, called pseudoascites. Despite their impressive appearances, such cysts often are operable for cure. We describe a case of a middle-aged woman who presented 3 years before her death with symptoms from an undiagnosed giant cyst and given a diagnosis of ascites of undetermined etiology. She subsequently died at home unexpectedly, and at autopsy, she was found to have a massively enlarged but otherwise benign mucinous cystadenoma.

Autopsy findings after intracranial thrombectomy for acute ischemic stroke: a clinicopathologic study of 5 patients.

BACKGROUND AND PURPOSE: Endovascular thrombectomy is an increasingly used treatment for arterial occlusion in acute stroke. Various devices (including most extensively the Mechanical Embolus Removal in Cerebral Ischemia [MERCI] Retriever device) have been used for this. METHODS: We review the neuropathologic findings in 5 patients (age range, 59 to 87 years) who died acutely or as late as 38 days after procedures using the MERCI (4 patients) and Penumbra (1 patient) devices were carried out to remove thromboemboli from the middle cerebral artery. Partial recanalization was achieved by thrombectomy in all 5 patients. RESULTS: All patients showed extensive cerebral infarcts, 3 of 5 with clinical hemorrhagic transformations of the infarct or frank intraparenchymal hemorrhage after thrombectomy; in 1 case, this was judged to be at least partly on the basis of concomitant hypertensive microvascular disease. With 1 exception, basal arteries examined in detail by immunohistochemistry showed prominent, although usually nonocclusive (and generally nonulcerated), atheromata, often with significant luminal stenosis. One patient showed a subintimal dissection with resultant occlusion of the middle cerebral artery. CONCLUSIONS: In this highly selected group of patients, the vascular pathological abnormalities affecting basal arteries were variable, but complicated atherosclerosis was a common finding. Extensive irreversible brain necrosis before therapeutic procedures may have contributed to deaths.

Angiocentric systemic granulomatosis.

As part of a review of substance abuse deaths in Dutchess County, New York, the Dutchess County Medical Examiner's Office identified 3 cases of angiocentric systemic foreign-body granulomatosis discovered at autopsy. Our investigation disclosed that in all 3 cases patients surreptitiously injected crushed oral prescription medication. Of the patients, 2 obtained intravenous access through central venous lines, the other patient was found to have injected herself intramuscularly. Autopsy demonstrated lung abnormalities due to diffuse deposits of foreign material within and around vessels, associated with foreign-body granulomatous reaction. We also identified a systemic distribution of this foreign material deposited beyond the lungs in the brain, heart, kidneys, and spleen. We present these cases along with a review of the literature of systemic embolization of foreign material in previously documented cases of deaths due to parenteral abuse of oral medications.

Infantile perineal protrusion: case report.

Infantile perineal protrusion is a recently described dermatologic entity that resembles a skin tag and can be confused with evidence of sexual child abuse. Although well-described by the pediatric and dermatologic community in small case series and case reports, we found little reference to this abnormality in the forensic literature despite its medicolegal significance. Therefore, we present a case of a 3-month-old infant who had a representative example of this lesion.

Spontaneous rupture of urinary bladder associated with massive fecal impaction (fecaloma).

We report a case of sudden death due to a catastrophic spontaneous rupture of a urinary bladder associated with megacolon due to a fecal impaction (fecaloma). The massively distended rectum and sigmoid colon filled the pelvic cavity and pressed up against the posterior aspects of the uterus, vagina, and urinary bladder. This produced bladder outlet obstruction, followed by massive dilatation and rupture of the urinary bladder, bilateral hydronephrosis, and a 3.5 liter collection of urinary fluid within the abdominal cavity. Complications of chronic constipation, fecalomas, and rupture of the urinary bladder are reviewed.

Molecular determinants of the response of glioblastomas to EGFR kinase inhibitors.

BACKGROUND: The epidermal growth factor receptor (EGFR) is frequently amplified, overexpressed, or mutated in glioblastomas, but only 10 to 20 percent of patients have a response to EGFR kinase inhibitors. The mechanism of responsiveness of glioblastomas to these inhibitors is unknown. METHODS: We sequenced kinase domains in the EGFR and human EGFR type 2 (Her2/neu) genes and analyzed the expression of EGFR, EGFR deletion mutant variant III (EGFRvIII), and the tumor-suppressor protein PTEN in recurrent malignant gliomas from patients who had received EGFR kinase inhibitors. We determined the molecular correlates of clinical response, validated them in an independent data set, and identified effects of the molecular abnormalities in vitro. RESULTS: Of 49 patients with recurrent malignant glioma who were treated with EGFR kinase inhibitors, 9 had tumor shrinkage of at least 25 percent. Pretreatment tissue was available for molecular analysis from 26 patients, 7 of whom had had a response and 19 of whom had rapid progression during therapy. No mutations in EGFR or Her2/neu kinase domains were detected in the tumors. Coexpression of EGFRvIII and PTEN was significantly associated with a clinical response (P<0.001; odds ratio, 51; 95 percent confidence interval, 4 to 669). These findings were validated in 33 patients who received similar treatment for glioblastoma at a different institution (P=0.001; odds ratio, 40; 95 percent confidence interval, 3 to 468). In vitro, coexpression of EGFRvIII and PTEN sensitized glioblastoma cells to erlotinib. CONCLUSIONS: Coexpression of EGFRvIII and PTEN by glioblastoma cells is associated with responsiveness to EGFR kinase inhibitors.

Traumatic dissection and rupture of the abdominal aorta as a complication of the Heimlich maneuver.

Although the Heimlich maneuver is considered the best intervention for relieving acute upper airway obstruction, several complications have been reported in the literature. These complications can occur as a result of an increase in abdominal pressure leading to a variety of well-documented visceral injuries, including the great vessels. Acute abdominal aortic thrombosis after the Heimlich maneuver is a rare but recognized event; however, to date no case of traumatic dissection and rupture of the abdominal aorta has been described. We report the first known case, to our knowledge, of a traumatic dissection and rupture of the abdominal aorta after a forcefully applied Heimlich maneuver.

Three unusual neuropathologic-related causes of sudden death.

We discuss the autopsy findings of three medico-legal cases of sudden death associated with uncommon neuropathologic findings of which the general forensic pathologist may not be familiar. Case 1 was a 43-year-old man who died of a seizure due to malignant melanoma of the temporal lobe associated with neurocutaneous melanosis (NCM). Case 2 was a 57-year-old woman with a history of mental retardation and incoordination because of chronic lead poisoning, who died of a pulmonary thromboembolism due to deep venous thrombosis status post left leg fracture after a fall down a staircase. Autopsy revealed atrophy and gliosis of her cerebellum as a result of childhood lead poisoning. The third patient was a 75-year-old woman who died as a result of acute bacterial leptomeningitis at the cervico-medullary junction with acute inflammation of the connective tissue of her upper cervical spinal column associated with subluxation of her atlantoaxial (AA) joint, also known as Grisel's syndrome.

Systemic distribution of West Nile virus infection: postmortem immunohistochemical study of six cases.

Rare cases of West Nile virus (WNV)-associated inflammation outside the central nervous system (CNS) have been reported. We evaluated the systemic distribution of WNV in postmortem tissues during encephalitis in six patients using immunohistochemistry. WNV antigens were detected in neurons of CNS (all 6 cases), kidney (4 cases), lungs (2 cases), pancreas (2 cases), thyroid (2 cases), intestine (2 cases), stomach (1 case), esophagus (1 case), bile duct (1 case), skin (1 case), prostate (1 case) and testis (1 case). In systemic organs epithelial cells were infected. In none of the six cases were viral antigens identified in hepatocytes, heart, adrenal gland, nerves, skeletal muscles, bone, vessels and fat. All cases in which viral antigens were identified in systemic organs in addition to CNS were severely immunocompromised transplant recipients. With the exception of testis and brain, most foci of infection were not associated with inflammation. While the absence of inflammation may in part be due to patient immunosuppression or to possible transient nature of any host response, compartmentalization of viral antigen to the luminal region of epithelial cells may sequester WNV from immune recognition. Comparison of our findings with previous reports suggests that patients with WNV encephalitis can have widespread systemic infection.

Contralateral hemimicrencephaly and clinical-pathological correlations in children with hemimegalencephaly.

In paediatric epilepsy surgery patients with hemimegalencephaly (HME; n = 23), this study compared clinical, neuroimaging and pathologic features to discern potential mechanisms for suboptimal post-hemispherectomy developmental outcomes and structural pathogenesis. MRI measured affected and non-affected cerebral hemisphere volumes for HME and non-HME cases, including monozygotic twins where one sibling had HME. Staining against neuronal nuclei (NeuN) determined grey and white matter cell densities and sizes in HME and autopsy cases, including the non-affected side of a HME surgical/autopsy case. By MRI, the affected hemisphere was larger and the non-affected side smaller in HME compared with non-HME children. The affected HME side showed enlarged abnormal deep grey and white matter structures and/or T2-weighted hypointensity in the subcortical white matter in 75% of cases, suggestive of excessive pre-natal neurogenesis and heterotopias. Histopathological examination of the affected HME side revealed immature-appearing neurons in 70%, polymicrogyria (PMG) in 61% and balloon cells in 45% of cases. Compared with autopsy cases, in HME children NeuN cell densities on the affected side were increased in the molecular layer and upper cortex (+244 to +18%), decreased in lower cortical layers (-35%) and increased in the white matter (+139 to +149%). Deep grey matter MRI abnormalities and/or T2-weighted white matter hypointensity correlated with the presence of immature-appearing neurons and PMG on histopathology, decreased NeuN cell densities in lower cortical layers and a positive history of infantile spasms. Post-surgery seizure control was associated with decreased NeuN densities in the molecular layer. In young children with HME and epilepsy, these findings indicate that there are bilateral cerebral hemispheric abnormalities and contralateral hemimicrencephaly is a likely explanation for poorer post-surgery seizure control and cognitive outcomes. In addition, our findings support the hypothesis that HME pathogenesis probably involves somatic mutations that affect each developing cerebral hemisphere differently with more neurons than expected on the HME side.

A Ten-year Study of Suicides from a Rural/Suburban County.

This study will discuss trends in suicide data compiled over 10 years in Dutchess County, NY, from 2004 to 2013. These data were based on reporting and examination standards recommended by the National Association of Medical Examiners and Department of Justice death investigation standards. Almost 300 cases were analyzed in terms of the deceased's gender, age, race, method of suicide, and weapon used. Results from this study agree with other reports showing significant differences for method of death both in terms of age and gender, with men more likely to choose firearms and women more likely to choose overdose. Furthermore, older persons were more likely to commit suicide by firearms, and the younger persons were more likely to commit suicide by overdose. However, other areas, such as method of suicide, differ from national statistics.

Case Report of a Migrating Bullet: An Unusual Cause of Postmortem Confusion.

Migrating bullets are rare sequelae of penetrating gunshot wounds. Such cases have been described in the neurosurgical literature because they can produce complications in the management of patients such as decline in neurologic status, delays in rehabilitation, and difficulties in bullet removal. In contrast, few postmortem reports have described this phenomenon. We report a case of a gunshot wound in which the projectile entered the left side of the head and traversed to the right frontal area as documented by CT scan on hospital admission. At autopsy, the bullet was noted to have migrated back to the left side of the head from where it was recovered. Medical examiners need to be aware of this unusual phenomenon of retained intracranial projectiles.

Analysis of thrombi retrieved from cerebral arteries of patients with acute ischemic stroke.

BACKGROUND AND PURPOSE: Information regarding the histological structure of thromboemboli that cause acute stroke provides insight into pathogenesis and clinical management. METHODS: This report describes the histological analysis of thromboemboli retrieved by endovascular mechanical extraction from the middle cerebral artery (MCA) and intracranial carotid artery (ICA) of 25 patients with acute ischemic stroke. RESULTS: The large majority (75%) of thromboemboli shared architectural features of random fibrin:platelet deposits interspersed with linear collections of nucleated cells (monocytes and neutrophils) and confined erythrocyte-rich regions. This histology was prevalent with both cardioembolic and atherosclerotic sources of embolism. "Red" clots composed uniquely of erythrocytes were uncommon and observed only with incomplete extractions, and cholesterol crystals were notably absent. The histology of thromboemboli that could not be retrieved from 29 concurrent patients may be different. No thrombus >3 mm wide caused stroke limited to the MCA, and no thrombus >5 mm wide was removed from the ICA. A mycotic embolus was successfully removed in 1 case, and a small atheroma and attached intima were removed without clinical consequence from another. CONCLUSIONS: Thromboemboli retrieved from the MCA or intracranial ICA of patients with acute ischemic stroke have similar histological components, whether derived from cardiac or arterial sources. Embolus size determines ultimate destination, those >5 mm wide likely bypassing the cerebral vessels entirely. The fibrin:platelet pattern that dominates thromboembolic structure provides a foundation for both antiplatelet and anticoagulant treatment strategies in stroke prevention.

Dendritic cell vaccination in glioblastoma patients induces systemic and intracranial T-cell responses modulated by the local central nervous system tumor microenvironment.

PURPOSE: We previously reported that autologous dendritic cells pulsed with acid-eluted tumor peptides can stimulate T cell-mediated antitumor immune responses against brain tumors in animal models. As a next step in vaccine development, a phase I clinical trial was established to evaluate this strategy for its feasibility, safety, and induction of systemic and intracranial T-cell responses in patients with glioblastoma multiforme. EXPERIMENTAL DESIGN: Twelve patients were enrolled into a multicohort dose-escalation study and treated with 1, 5, or 10 million autologous dendritic cells pulsed with constant amounts (100 mug per injection) of acid-eluted autologous tumor peptides. All patients had histologically proven glioblastoma multiforme. Three biweekly intradermal vaccinations were given; and patients were monitored for adverse events, survival, and immune responses. The follow-up period for this trial was almost 5 years. RESULTS: Dendritic cell vaccinations were not associated with any evidence of dose-limiting toxicity or serious adverse effects. One patient had an objective clinical response documented by magnetic resonance imaging. Six patients developed measurable systemic antitumor CTL responses. However, the induction of systemic effector cells did not necessarily translate into objective clinical responses or increased survival, particularly for patients with actively progressing tumors and/or those with tumors expressing high levels of transforming growth factor beta(2) (TGF-beta(2)). Increased intratumoral infiltration by cytotoxic T cells was detected in four of eight patients who underwent reoperation after vaccination. The magnitude of the T-cell infiltration was inversely correlated with TGF-beta(2) expression within the tumors and positively correlated with clinical survival (P = 0.047). CONCLUSIONS: Together, our results suggest that the absence of bulky, actively progressing tumor, coupled with low TGF-beta(2) expression, may identify a subgroup of glioma patients to target as potential responders in future clinical investigations of dendritic cell-based vaccines.

Frontotemporal lobar degeneration: demographic characteristics of 353 patients.

BACKGROUND: Until recently, frontotemporal lobar degeneration (FTLD) was considered a rare neurodegenerative disorder that was difficult to diagnose. The publication of consensus criteria for FTLD, however, prompted systematic studies. The criteria categorize FTLD into 3 subgroups: frontotemporal dementia, semantic dementia, and progressive nonfluent aphasia. OBJECTIVE: To compare demographic characteristics of patients in the 3 FTLD subgroups. DESIGN: We compared diagnostic breakdown, age at onset, sex, Mini-Mental State Examination score at first visit, education, and neuropathological diagnoses in a large sample of FTLD patients from 3 different university dementia clinics, including 2 neurologic clinics in the United States and 1 psychiatric clinic in Germany. RESULTS: The frontotemporal dementia subgroup represented approximately half of all FTLD diagnoses. Patients diagnosed as having frontotemporal dementia (mean age, 57.5 years) and semantic dementia (mean age, 59.3 years) had an earlier age at onset than patients diagnosed as having progressive nonfluent aphasia (mean age, 63.0 years). There were significantly more men diagnosed as having frontotemporal dementia (63.5%) and semantic dementia (66.7%) when compared with progressive nonfluent aphasia (39.1%) (P = .005 for frontotemporal dementia vs progressive nonfluent aphasia and P = .002 for semantic dementia vs progressive nonfluent aphasia). Generally, the demographic features and diagnostic categories of the patient populations across the 3 sites were comparable. There were 68 deaths and 37 autopsies. Frontotemporal lobar degeneration with ubiquitin-positive tau-negative inclusions (48.5%), dementia lacking distinctive histopathological features (18.2%), and Pick disease (15.2%) were the most common neuropathological diagnoses. CONCLUSIONS: These findings show that cohorts of patients can be combined using new research criteria for FTLD and demonstrate striking demographic differences among FTLD subgroups. The sex and age-at-onset differences suggest that there may be biological differences among FTLD subgroups. In this sample, FTLD with ubiquitin-positive inclusions accounted for half of all neuropathological diagnoses.

Moderate and severe traumatic brain injury: epidemiologic, imaging and neuropathologic perspectives.

This article examines 3 contexts in which moderate or severe traumatic brain injury can be approached. The epidemiologic background of moderate and severe traumatic brain injury is presented, with particular attention paid to new findings from the study of a national hospital inpatient database. We review aspects of neuroimaging and how new imaging modalities can reveal fine detail about traumatic brain injury. Finally we examine the current state of neuropathologic evaluation of, and recent developments in, understanding of the neural disruptions that occur following traumatic brain injury, together with cellular reactions to these disruptions.

Pseudo-subarachnoid hemorrhage of the head diagnosed by computerized axial tomography: a postmortem study of ten medical examiner cases.

In this report, we describe ten cases of pseudo-subarachnoid hemorrhage on computer axial tomography (CT) scan of the head. A pseudo-subarachnoid hemorrhage is a false positive finding by CT of the head in which the scan is interpreted as being positive for a subarachnoid hemorrhage not substantiated by subsequent neuropathologic findings. This study is a retrospective review of postmortem cases brought into the Office of the Chief Medical Examiner for the State of Maryland over a three-year period (from 1997 to 2000). We compared the clinician's impression of the CT scan with the postmortem neuropathology. The clinical diagnosis of subarachnoid hemorrhage was based on misinterpretation of non-contrast CT scans of the head. In six of the ten cases, the reading was performed by a radiologist and in four cases by nonradiologist physicians (emergency room physician, neurologist, or neurosurgeon). All the patients survived between a few hours to a few days after being admitted to the hospital. For most of the cases (80%), the neuropathology showed hypoxic/ischemic encephalopathy. The most common cause of death (four out of ten cases) was narcotic intoxication. This report is submitted so that clinicians and pathologist become more familiar with this entity.

Sudden unexpected death due to hemophagocytic lymphohistiocytosis syndrome.

The hemophagocytic lymphohistiocytosis (HLH) syndrome is a hyperimmune disorder characterized by lymphohistiocytic infiltrations, elevated cytokine levels in the blood, macrophage activation, and hemophagocytosis, frequently presenting with a febrile septic picture. This unusual disease is more common in infancy and childhood than adulthood. It is classified as primary or familial when a genetic defect is identified and secondary or acquired when triggered by certain infections, autoimmune disorders, or malignancies. If or when such patients expire, they typically do so within a hospital or under a physician's care and so such cases rarely come to the attention of forensic pathologists. We report on the unexpected deaths of two hospitalized adult cases of HLH brought to autopsy without a premortem diagnosis. Postmortem examination demonstrated marked hepatosplenomegaly and lymphadenopathy in association with hemophagocytosis. Although very uncommon HLH must be considered in infants, children, or adults who die unexpectedly with an undiagnosed septic presentation.

Improving MRI differentiation of gray and white matter in epileptogenic lesions based on nonlinear feedback.

A new method for enhancing MRI contrast between gray matter (GM) and white matter (WM) in epilepsy surgery patients with symptomatic lesions is presented. This method uses the radiation damping feedback interaction in high-field MRI to amplify contrast due to small differences in resonance frequency in GM and WM corresponding to variations in tissue susceptibility. High-resolution radiation damping-enhanced (RD) images of in vitro brain tissue from five patients were acquired at 14 T and compared with corresponding conventional T(1)-, T(2) (*)-, and proton density (PD)-weighted images. The RD images yielded a six times better contrast-to-noise ratio (CNR = 44.8) on average than the best optimized T(1)-weighted (CNR = 7.92), T(2) (*)-weighted (CNR = 4.20), and PD-weighted images (CNR = 2.52). Regional analysis of the signal as a function of evolution time and initial pulse flip angle, and comparison with numerical simulations confirmed that radiation damping was responsible for the observed signal growth. The time evolution of the signal in different tissue regions was also used to identify subtle changes in tissue composition that were not revealed in conventional MR images. RD contrast is compared with conventional MR methods for separating different tissue types, and its value and limitations are discussed.