Sarcoidosis and mechanisms of unexpected death

Sarcoidosis is a multisystem disease of uncertain etiology characterized by multifocal areas of discrete and confluent granulomatous inflammation that may rarely be responsible for sudden and unexpected death. Two cases are reported to demonstrate disparate pathological features in fatal cases, one involving cardiac sarcoidosis, and the other neurosarcoidosis with hypothalamic infiltration. Sarcoidosis in individuals dying suddenly may be completely unrelated to the death, contributory or causal. Cardiovascular causes of sudden death in sarcoidosis include arrhythmias associated with cardiomyopathy and ischemia, ventricular rupture, and cor pulmonale due to pulmonary hypertension; respiratory causes include hemorrhage and upper airway obstruction; central nervous system causes include arrhythmias from infiltration of autonomic centers, epilepsy, and obstructive hydrocephalus from brainstem involvement; and gastrointestinal deaths may be due to hemorrhage from esophageal varices associated with portal hypertension. The diagnosis relies on the demonstration of typical noncaseating granulomas and the exclusion of other infective and environmental diseases with similar histopathological findings.     

Sudden unexpected death in infancy and childhood due to undiagnosed neoplasia: an autopsy study

Sudden unexpected death due to clinically undiagnosed neoplasia in infancy and childhood (SUDNIC) is a rare phenomenon, with only small numbers of cases reported in the literature. In the majority of instances, the tumors involve critical structures within the heart or central nervous system and include gliomas, medulloblastomas, rhabdomyomas, and neoplasms of stromal elements. A 20-year retrospective review of autopsy records from the Hospital for Sick Children, Toronto, was performed (1984-2003, n = 4926), and 7 cases of SUDNIC were identified (0.14%). In addition, 1 case was obtained from the files of the Children's and Women's Health Centre of British Columbia, Vancouver. Diagnoses included 2 cases of acute leukemia (1 myelogenous, 1 lymphoblastic), 2 cases of mediastinal lymphoblastic lymphoma (pre-T cell type), 1 papillary fibroelastoma of the mitral valve prolapsing into and totally occluding the left anterior descending coronary artery, 1 medulloblastoma, 1 Wilms tumor associated with fatal intraperitoneal hemorrhage, and 1 widely disseminated gastric carcinoma. These cases demonstrate that infants and children may have minimal or no symptoms in the presence of significant disease and highlight the need for a thorough autopsy examination in cases of sudden unexpected death in infancy and childhood.     

Lethal Epistaxis

Epistaxis or nosebleed refers to bleeding from the nostrils, nasal cavity, or nasopharynx. Occasional cases may present with torrential lethal hemorrhage. Three cases are reported to demonstrate particular features: Case 1: A 51‐year‐old woman with lethal epistaxis with no obvious bleeding source; Case 2: A 77‐year‐old man with treated nasopharyngeal carcinoma who died from epistaxis arising from a markedly neovascularized tumor bed; Case 3: A 2‐year‐old boy with hemophilia B who died from epistaxis with airway obstruction in addition to gastrointestinal bleeding. Epistaxis may be associated with trauma, tumors, vascular malformations, bleeding diatheses, infections, pregnancy, endometriosis, and a variety of different drugs. Careful dissection of the nasal cavity is required to locate the site of hemorrhage and to identify any predisposing conditions. This may be guided by postmortem computerized tomographic angiography (PCTA). Despite careful dissection, however, a source of bleeding may never be identified.     

Hemorrhagic Retinopathy and Optic Nerve Sheath Hemorrhage Associated With Fatal Subarachnoid Hemorrhage from a Ruptured Intracranial Aneurysm Due to Segmental Fibromuscular Dysplasia

Fibromuscular dysplasia is an idiopathic, nonatheromatous, and noninflammatory arterial disease that most commonly affects the renal and carotid arteries. We report a child with subarachnoid and ocular hemorrhage associated with an aneurysm due to fibromuscular dysplasia. Computed tomography following a witnessed collapse revealed diffuse subarachnoid hemorrhage and severe cerebral edema. An autopsy confirmed the radiographic findings and detected bilateral retinal hemorrhages, optic nerve sheath hemorrhages, and a ruptured saccular aneurysm due to focal fibromuscular dysplasia involving the intracranial right vertebral artery. This case documents a fatal subarachnoid hemorrhage in a child with an intracranial saccular aneurysm caused by fibromuscular dysplasia. The associated retinal hemorrhages are easily detected by postmortem monocular indirect ophthalmoscopy.     

Sudden death due to primary diffuse leptomeningeal gliomatosis

Tumors of the central nervous system are an unusual cause of sudden death. This report describes the sudden death of a presumed healthy 28-year-old woman from primary diffuse leptomeningeal gliomatosis. She presented to an emergency room with headache and vomiting, subsequently became unresponsive and was pronounced dead 14 h later. Autopsy revealed a diffuse extensive infiltrate of well-differentiated astrocytoma in the leptomeninges of the brain and spinal cord without an underlying parenchymal tumor. Primary diffuse leptomeningeal gliomatosis is a rare tumor that arises within the leptomeninges from small neuroglial heterotopic rests that undergo neoplastic transformation. Grossly. this tumor can mimic leptomeningeal carcinomatosis, pachymeningitis, tuberculosis, sarcoidosis, and fungal infections. However, the histologic features of primary diffuse leptomeningeal gliomatosis should allow it to be readily distinguished from grossly similar conditions. The mechanism of death in this case is most likely tumor obstruction of cerebrospinal fluid outflow resulting in the usual complications seen with increased intracranial pressure. Although this tumor is aggressive and is associated with a rapidly progressive fatal course, it has not been previously associated with sudden death.     

Sudden Death Due to Primary Intraventricular Hemorrhage: Report of Two Cases

Primary intraventricular hemorrhage (PIVH) is a rare type of stroke defined as bleeding within the ventricles of the brain without any associated parenchymal hemorrhage. Here, we reported two cases of sudden death due to PIVH. One of the patients was found dead under a highway bridge without witnesses, and the other patient was hospitalized with hemorrhage in the ventricular system, as revealed by a head computed tomography scan. In these two patients, autopsy and macroscopic examination only showed hemorrhages in the ventricular system without any traumatic brain injury or other intraparenchymal hemorrhage. The sources of bleeding for both patients were ultimately confirmed as ruptured brain arteriovenous malformations located in the subventricular zone. We reported these cases to broaden our understanding of sudden death associated with PIVH, especially when caused by brain arteriovenous malformation. We also summarized the essential details of the diagnoses and available technical methods for PIVH cases.     

Forensic considerations in cases of neurofibromatosis--an overview

Neurofibromatosis types 1 and 2 are inherited neurocutaneous disorders characterized by a variety of manifestations that involve the circulatory system, the central and peripheral nervous systems, the skin, and the skeleton. Significant reduction in lifespan occurs in both conditions often related to complications of malignancy and hypertension. Individuals with these conditions may also be the subject of medicolegal autopsy investigation if sudden death occurs. Unexpected lethal events may be associated with intracranial neoplasia and hemorrhage or brainstem compression. Vasculopathy with fibrointimal proliferation may result in critical reduction in blood flow within the coronary or cerebral circulations, and aneurysmal dilatation may be associated with rupture and life-threatening hemorrhage. An autopsy approach to potential cases should include review of the history/hospital record, liaison with a clinical geneticist (to include family follow-up), a full external examination with careful documentation of skin lesions and nodules, measurement of the head circumference in children, photography, possible radiologic examination, a standard internal autopsy examination, documentation of the effects of previous surgery and/or chemo/radiotherapy, examination for specific tumors, specific examination and sampling of vasculature (renal, cerebral, and cardiac), formal neuropathologic examination of brain and spinal cord, possible examination of the eyeballs, examination of the gastrointestinal tract, histology to include tumors, vessels, gut, and bone marrow, toxicological testing for anticonvulsants, and sampling of blood and tissue for possible cytogenetic/molecular evaluation if required.     

Vertebral artery laceration mimicking elder abuse

Elder abuse was first described almost 30 years ago. Today, approximately 1 in 25 elders is abused each year in the United States. A newly described form of domestic violence, the incidence of elder abuse will surely increase as the elderly population grows. Physical abuse/inflicted trauma is generally considered the most extreme form of elder mistreatment and includes blunt trauma, sexual assault, traumatic alopecia, and burns. Elder homicide is usually due to gunshot wounds, blunt trauma, stab wounds, or asphyxia. However, the difficult aspect of assessing the possible elder abuse homicide victim is delineating such inflicted trauma from accidental trauma. We report the case of a 94-year-old "demented" male, who reportedly fell out of his wheelchair. He was transported to a local emergency room, where he became unresponsive during examination. He experienced respiratory distress and was pronounced dead shortly thereafter. At autopsy, he had periorbital contusions and a midline abrasion between the eyes, with underlying supraorbital contusion. The skull, brain, and spinal cord were unremarkable for signs of trauma. The major traumatic finding was in the neck region. Neck dissection revealed hemorrhage extending from the base of the skull to the level of T-1 and anteriorly about the soft tissues, strap muscles, and vasculature. The strap muscles were individually examined and were free of hemorrhage. The carotid arteries and jugular veins were unremarkable. The larynx, hyoid, and thyroid were intact, with only surrounding hemorrhage. Further examination revealed a horizontal fracture of the C5 vertebral body and a medial laceration of the left vertebral artery at the C5 level; subarachnoid hemorrhage was absent. What initially appeared to be trauma to the neck, worrisome for strangulation or blunt force trauma, was a large retropharyngeal hematoma from the left vertebral artery laceration. Traumatic rupture of the vertebral artery usually occurs at the C1 and C2 levels, with resultant subarachnoid hemorrhage. This is an especially vulnerable location since it is where the artery turns and then enters the skull. Associated injuries include spinal cord transection or contusion, brachial plexus injury, pharyngoesophageal injury, and vertebral fractures. Retropharyngeal hemorrhage may result from deep neck infection, tumor, and trauma. Hemorrhage associated with trauma often involves flexion of the cervical spine, followed by hyperextension. The accumulation of blood slowly impinges on the pharynx/larynx and vasculature structures. The exact injuries and etiology of the hemorrhage must be determined to distinguish strangulation from blunt force trauma. The presentation of signs and symptoms can be helpful in assessing the decedent; however, in the practice of forensic pathology such a history is more often lacking.     

A case of sudden infant death due to massive hemorrhage in primitive neuroectodermal tumor.

A case of the sudden death of a 14-month-old girl due to massive hemorrhage in a primitive neuroectodermal tumor (PNET) is presented along with a review of the relevant literature. PNET is a rare, malignant brain neoplasm occurring predominantly in children.     

Giant berry aneurysms in a forensic setting: a series of 14 cases

This is a series reviewing 14 cases of giant saccular aneurysms diagnosed at the Office of the Chief Medical Examiner of New York City collected over an 11-year period. Data collected on all 14 cases included neuropathological findings, comorbidities, and toxicological findings. Of these 14 cases, 8 were in women, and the ages ranged from 3 to 79 years, with a mean and a median of 50 years. Women were overrepresented in the sixth through eighth decades. Of the 14 cases described, 11 presented with a subarachnoid hemorrhage; 3, no hemorrhage; 2, subdural hemorrhage; 8, intraventricular hemorrhage; 2, intracerebral hemorrhage; and 8, more than 1 hemorrhage type. Location of the aneurysms varied with 6 in the left side of the brain, 6 present in the right side of the brain, and 2 at the midline. We described the clinical, pathological, and toxicological findings associated with these giant aneurysms.     

Sudden death from massive pulmonary tumor embolism due to hepatocellular carcinoma

Massive pulmonary embolism in cancer patients can be due to detached thrombi or tumor. Pulmonary tumor embolism is often undiagnosed antemortem. We report a 52-year-old Chinese man admitted for management of hepatocellular carcinoma (HCC). Computerized tomography showed tumor involvement of hepatic vein and inferior vena cava. He died suddenly on the day of admission. At autopsy the main pulmonary arteries of both lungs were blocked by large tumor emboli, the immediate cause of death. Although rapid death in patients with HCC is usually caused by intraperitoneal hemorrhage from spontaneous rupture of tumor, massive pulmonary tumor embolism should also be considered in these patients, especially when antemortem evidence of hepatic vein and/or inferior vena cava invasion is present.     

Spontaneous acute subdural hematoma complicating arachnoid cyst

The overwhelming majority of cases of acute subdural hematoma in the forensic setting occur as a result of head trauma. We report a case of sudden unexpected death in a middle-aged woman with a history of arachnoid cyst who had sudden spontaneous onset of severe headache that was rapidly followed by collapse and death. A postmortem multiple-slice computed tomographic scan showed a large acute subdural hematoma associated with hemorrhage into an arachnoid cyst. Subdural hemorrhage is an uncommon but well-described complication of an arachnoid cyst.     

Cocaine‐Induced Intracerebral Hemorrhage in a Patient with Cerebral Amyloid Angiopathy*

Abstract: Intracerebral hemorrhage (ICH) is a well‐recognized complication of recreational cocaine use. The precise mechanism of the cocaine‐induced hemorrhagic event is unclear, although multiple factors have been implicated. We report a case of a 62‐year‐old woman who suffered left parieto‐occipital ICH with herniation and death, following a cocaine binge. Microscopic examination also revealed extensive cerebral amyloid angiopathy (CAA) in the vicinity of the hemorrhage. We additionally studied brain tissue in eight subjects between ages of 60 and 80 who were positive for cocaine metabolites at autopsy; of these, none had vascular amyloid‐β deposits by immunohistochemistry. Whereas we found no evidence that chronic cocaine use is a risk factor for CAA, given the age‐associated nature of CAA and the aging population using cocaine, CAA‐induced hemorrhage in the setting of cocaine use may be more common than recognized. This is the first reported case of CAA‐associated ICH precipitated by cocaine.     

Severe Retinal Hemorrhages with Retinoschisis in Infants are Not Pathognomonic for Abusive Head Trauma

The combination of subdural hemorrhage (SDH), retinal hemorrhage (RH), and encephalopathy, or the presence of severe retinal hemorrhages alone in infants, is often attributed to and has been stated to be pathognomonic for abusive head trauma (AHT) or shaken baby syndrome. These beliefs have been challenged, because the same constellation of findings has been identified in accidental head injuries and natural diseases, and most if not all of the studies that support the concept of diagnostic specificity have serious flaws in their methodology. Presented here are two cases of severe retinal hemorrhages with retinoschisis associated with subdural hemorrhage in a natural disease and with severe cerebral edema in an accidental head injury. These cases challenge the dogma that severe retinal hemorrhages with retinoschisis are pathognomonic for AHT.     

Sudden and unexpected death from pituitary tumor apoplexy

Pituitary tumor apoplexy refers to a clinical syndrome precipitated by the expansion of a pituitary adenoma by hemorrhage or infarction. Individuals may present with myriad signs, including sudden onset of severe headache, visual changes, altered mental status, cranial nerve palsies, and hormonal dysfunction. This disorder constitutes a medical emergency and warrants an expedited evaluation, diagnosis, and treatment to prevent the potential sequelae of permanent visual loss, endocrine abnormalities, or death. We report a case of sudden death from undiagnosed pituitary tumor apoplexy. The decedent was evaluated by medical personnel on three occasions in the week prior to her death for severe headache, nausea, vomiting, and photophobia. Postmortem examination demonstrated a hemorrhagic infarction of a pituitary adenoma with necrosis and expansion out of the sella turcica. The recognition of and treatment for a patient with pituitary tumor apoplexy requires a rapid multidisciplinary effort. Failure of prompt diagnosis may be fatal and require a medico-legal death investigation for sudden and unexpected death.     

Cerebral massive hemorrhage in congophilic angiopathy and its medicolegal significance

The principles of a special type of senile cerebromeningeal angiopathy, these days usually named “congophilic angiopathy”, are demonstrated on the basis of eight cases, complicated by spontaneous massive intracranial hemorrhages in seven and late traumatic hemorrhage in one of them. The occurrence of massive hemorrhages associated with congophilic angiopathy has until now only rarely been reported. The medicolegal significance of this vascular disease is emphasized by the eighth, traumatic, case, which became forensically relevant; the late massive hemorrhage had to be regarded as significantly favoured by amyloid angionecrosis, which is the main feature of congophilic angiopathy.     

Hemorrhage of the head and neck in death by burning

The 202 deaths connected with burns in 1976-1986 included 134 in which death occurred during the fire. In 49 cases the face was so badly charred that it was not possible to judge whether hemorrhage had occurred in the eyelids and/or conjuctivae. Such blood extravasation was seen in 14 of the remaining 85 cases, taking the form of petechiae in some cases and in others the form associated with more extensive extravasation, in some cases hemolytic. No other features known to cause such hemorrhages were present, so that they are attributed to the burning process itself. Signs of extensive pronounced burns were found in 13 of these cases, and it seemed that high-degree burns on the neck and trunk with less severe burns on the head were particularly likely to be associated with such hemorrhages. In most cases the flames had quickly come into direct contact with the body (clothing, bed or chair had caught fire), leading to rapid death, as documented by the fact that usually very little or no soot at all had been aspirated and by the low level of carbon monoxide intoxication (max. COHb 22%). One plausible explanation for the development of hemorrhage is the supposition first expressed over 20 years ago that when the circulation is maintained rapid burn-induced shrinkage of the skin of the neck has the effect of strangulating the victim; hemorrhage of eyelids and/or conjunctivae in such cases be could regarded as a vital reaction to the effect of fire. This is particularly significant, insofar as evidence of hemorrhage of this kind was found predominantly in bodies in which other vital signs indicative of the effects of burning were sparse and slight or even totally absent. In addition, specific examination of the laryngeal area revealed congestion-induced extravasation at various points, as well as petechial hemorrhage in the mucous membrane.     

Fatal pediatric head injuries caused by short-distance falls.

Physicians disagree on several issues regarding head injury in infants and children, including the potential lethality of a short-distance fall, a lucid interval in an ultimately fatal head injury, and the specificity of retinal hemorrhage for inflicted trauma. There is scant objective evidence to resolve these questions, and more information is needed. The objective of this study was to determine whether there are witnessed or investigated fatal short-distance falls that were concluded to be accidental. The author reviewed the January 1, 1988 through June 30, 1999 United States Consumer Product Safety Commission database for head injury associated with the use of playground equipment. The author obtained and reviewed the primary source data (hospital and emergency medical services' records, law enforcement reports, and coroner or medical examiner records) for all fatalities involving a fall. The results revealed 18 fall-related head injury fatalities in the database. The youngest child was 12 months old, the oldest 13 years. The falls were from 0.6 to 3 meters (2-10 feet). A noncaretaker witnessed 12 of the 18, and 12 had a lucid interval. Four of the six children in whom funduscopic examination was documented in the medical record had bilateral retinal hemorrhage. The author concludes that an infant or child may suffer a fatal head injury from a fall of less than 3 meters (10 feet). The injury may be associated with a lucid interval and bilateral retinal hemorrhage.     

Could Intra‐alveolar Hemosiderin Deposition in Adults be Used as a Marker for Previous Asphyxial Episodes in Cases of Autoerotic Death?

Intra-alveolar hemorrhage and hemosiderin have been cited as possible markers of recent and remote asphyxial events. Little study has been undertaken of the potential significance of intra-alveolar hemosiderin in adults as a potential marker of previous sublethal asphyxial episodes. Ten cases of lethal sexual asphyxia (an entity known to be associated with repetitive sublethal asphyxial episodes) and 20 randomly selected, age- and sex-matched controls had sections of lung stained for hemosiderin. Subsequently, intra-alveolar, iron-containing macrophages were counted. All cases were men (ages 15-50 years; mean 31.8). No significant increase in hemosiderin was found in victims of sexual asphyxia, indicating that asphyxial episodes in sublethal sexual asphyxial activities may not be sufficiently intense or prolonged to cause intra-alveolar hemorrhage or that intra-alveolar hemorrhage in adults is a relatively nonspecific finding. These results do not support intra-alveolar hemosiderin deposition as a marker for previous sublethal asphyxial events in autoerotic asphyxia.     

Sudden unexpected death resulting from previously nonsymptomatic subependymoma

A 34-year-old, previously healthy man died suddenly and unexpectedly. The autopsy showed brain and pulmonary edema, numerous small meningeal meningiomas, bilateral and symmetrical juxtaventricular meningiomas, and a well-demarcated gray tan tumor in the medulla oblongata and upper cervical spinal cord. The latter tumor was a subependymoma with features of ependymoma in places. The authors describe and discuss the characteristics of this rare central nervous system tumor, its histogenesis, and its coexistence with other intracranial tumors. The possible mechanisms of death in the present case include compression of vital centers and acute obstruction of the cerebrospinal fluid flow.