Treatment of HIV-related inflammatory cerebral cryptococcoma with adalimumab.

Cryptococcomas have been described in AIDS patients in the setting of immune reconstitution inflammatory syndrome. We report the first case of human immunodeficiency virus-related inflammatory cerebral cryptococcoma to be treated with a recombinant human monoclonal tumor necrosis factor antagonist.

A morphometric analysis of the infant calvarium and dura.

Literature addressing the anatomic development of the dura and calvarium during childhood is limited. Nevertheless, histological features of a subdural neomembrane (NM), including its thickness and vascularity, developing in response to an acute subdural hematoma (SDH) have been compared to the dura of adults to estimate when an injury occurred. Therefore, we measured the morphometric growth of the calvarium and dura and the vascular density within the dura during infancy. The mean thicknesses of the calvarium and dura as a function of occipitofrontal circumference (OFC), as well as the mean number of vessels per 25 × field, were determined from the right parasagittal midparietal bone lateral to the sagittal suture of 128 infants without a history of head trauma. Our results showed that as OFC increased, the mean thicknesses of the calvarium and dura increased while the vascular density within the dura decreased. Our morphometric data may assist in the interpretation of subdural NM occurring during infancy. We recommend future investigations to confirm and extend our present data, especially by evaluating cases during later infancy and beyond as well as by sampling other anatomic sites from the calvarium. We also recommend morphometric evaluation of subdural NM associated with SDH in infancy and childhood.

Myocardial inflammation, cellular death, and viral detection in sudden infant death caused by SIDS, suffocation, or myocarditis.

The significance of minor myocardial inflammatory infiltrates and viral detection in SIDS is controversial. We retrospectively compared the demographic profiles, myocardial inflammation, cardiomyocyte necrosis, and myocardial virus detection in infants who died of SIDS in a safe sleep environment, accidental suffocation, or myocarditis. Formalin-fixed, paraffin-embedded myocardial sections were semiquantitatively assessed for CD3 lymphocytes and CD68 macrophages using immunohistochemistry and for cardiomyocyte cell death in H&E-stained sections. Enteroviruses and adenoviruses were searched for using PCR technology. The means of lymphocytes, macrophages, and necrotic cardiomyocytes were not statistically different in SIDS and suffocation cases. Enterovirus, not otherwise specified, was detected in one suffocation case and was the only virus detected in the three groups. Very mild myocardial lymphocyte and macrophage infiltration and scattered necrotic cardiomyocytes in SIDS are not pathologic, but may occur after the developing heart is exposed to environmental pathogens, including viruses.

Aspiration of gastric contents in sudden infant death syndrome without cardiopulmonary resuscitation.

OBJECTIVES: (1) To compare demographic profiles among sudden infant death syndrome (SIDS) infants with or without gastric aspiration, for whom cardiopulmonary resuscitation (CPR) had not been attempted; (2) to review the severity and potential significance of aspiration in those SIDS cases; and (3) to assess the risk of supine sleep position with regard to gastric aspiration. STUDY DESIGN: Retrospective review of records and microscopic slides for all postneonatal SIDS cases (29 to 365 days of age) accessioned by the San Diego County Medical Examiner from 1991 to 2004. RESULTS: Ten (14%) of 69 cases of SIDS infants who had not undergone CPR before autopsy revealed microscopic evidence of gastric aspiration into the distal lung; this group was not otherwise clinically or pathologically different from cases of SIDS infants without aspiration. Similar proportions of infants were found supine or prone, regardless of gastric aspiration. CONCLUSIONS: Gastric aspiration is not uncommon in infants dying of SIDS, and supine sleep position does not increase its risk. Gastric aspiration may be a terminal event that some infants, representing a subset of SIDS cases, cannot overcome.

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 death in a toddler with laryngotracheitis caused by human parainfluenza virus-1.

Laryngotracheitis caused by human parainfluenza virus (HPIV) and not complicated by bacterial superinfection rarely causes sudden unexpected death in infants and toddlers, especially in the absence of stridor and a barking cough. We therefore describe a 15-month-old white male who died suddenly and unexpectedly with clinical and pathological features of laryngotracheitis caused by culture-proven HPIV-1 infection. Given the presence of mucosal inflammation extending into the vocalis muscle of the larynx without associated significant narrowing of the laryngotracheal airway lumen, we propose his death was a result of a laryngospasm, perhaps mediated by immune responses.

Delayed death in sudden infant death syndrome: a San Diego SIDS/SUDC Research Project 15-year population-based report.

A fraction of SIDS cases have death delayed by successful CPR, yet they have not been compared to SIDS cases which were found dead or not successfully resuscitated. Our aims were to: (1) determine the percent of SIDS cases in the San Diego SIDS Research Project database for whom death was delayed by CPR and subsequent life support; (2) compare demographics, circumstances of death and autopsy findings of delayed death SIDS cases (delayed SIDS) with those whose deaths were not delayed (non-delayed SIDS); (3) examine the evolution of pathologic changes in delayed SIDS as a function of survival interval. A retrospective 15-year population-based study of 454 infant deaths attributed to SIDS revealed 29 delayed SIDS cases (Group I) and 425 non-delayed SIDS cases (Group II). Group I cases were significantly older than Group II cases (mean age 132 days vs. 102 days and p<0.0001). Eighty-nine percent of the Group I cases were discovered between 08.00 and 19.59 h; none were found between 00.00 and 07.59 h, compared to 38% of the Group II cases. Group I infants were found significantly more often away from home (at daycare, or at the home of a relative, friend, or baby sitter) than Group II infants (45% vs. 25%, p<0.05). There were no differences between groups with regard to gender, gestational age, type of delivery, bed sharing, URI within 48 h of death, ALTEs, a history of referral to child protective services, body position when placed or found, or face position when found. Pathologic changes were semiquantitatively evaluated; findings were characteristic of anoxic-ischemic injury that generally became more severe with increasing survival intervals. Anoxic-ischemic brain injury was the immediate cause of death in all delayed SIDS cases. Aspiration of gastric contents was identified in Group I cases surviving less than 48 h and was the likely etiology of acute bronchopneumonia occurring in 83% of the Group I cases. We did not identify factors that would reliably predict which SIDS cases might be discovered soon enough to allow earlier and more effective CPR and survival without permanent brain injury.

Intrathoracic petechiae in SIDS: a retrospective population-based 15-year study.

Intrathoracic petechiae (IP), the most common gross finding in sudden infant death syndrome (SIDS) cases at autopsy, suggest upper airway obstruction (UAO) occurs during the terminal event. If true, IP would be expected more frequently among SIDS cases found face down compared to other face positions. We compare the rates of IP in SIDS cases found face down versus other face positions. A retrospective 15-year review of IP among all cases of SIDS occurring from 1991 through 2005 accessioned by the San Diego County Medical Examiner's Office was conducted. The presence or absence of IP was based on both gross and microscopic observations of the thoracic organs. The severity of thymic petechiae was scored semiquantitatively from microscopic observations. There were 489 SIDS cases during the study period. Sixteen of these were excluded because their deaths had been delayed by initially successful cardiopulmonary resuscitation. Among the remaining 473 SIDS cases, face position when found was specifically described for 332 (70%). Of 122 cases found face down, 112 (92%) had IP, compared to 85% (179) of 210 infants found with the face up or to the side (P = 0.06). The groups were not different with respect to age or gender, but the racial distribution was significantly different (P = 0.004). African-American infants comprised 28% of the found face down group compared to only 12% of the face up or side group. Our data do not support a role for external UAO caused by face positioning directly into the sleep surface in SIDS, but are consistent with internal UAO associated with apnea or gasping before dying of SIDS.

Sudden infant death while awake.

Epidemiologic data suggest that SIDS is related to the sleep state, but exiguous literature has addressed infants who had been awake at the time of sudden catastrophic deterioration and subsequent death. The aims of this study are to: (1) Report five infants who were awake at the onset of the lethal event, and (2) Discuss potential lethal pathophysiological events that may lead to these circumstances. The demographic and pathologic profiles of these cases are similar to SIDS. Altered responses to severe hypotension, bradycardia, and apnea, perhaps elicited by aspiration and mediated by cerebellar and vestibular structures, might be involved in the pathogenesis of these deaths. Comprehensive medical history review, investigation of the circumstances of death, thorough postmortem examination with ancillary studies, and preservation of tissues for gene testing, are crucial to explaining these deaths. Careful attention should be given to the awake or sleep state immediately prior to the sudden clinical collapse, and death of infants; those who were awake should be reported to enhance understanding of this phenomenon.

Unclassified sudden infant death associated with pulmonary intra-alveolar hemosiderosis and hemorrhage.

The significance of severe pulmonary intra-alveolar hemosiderosis in sudden infant death is controversial in forensic pathology. We report a previously healthy 9-month-old female infant who died suddenly and unexpectedly after being placed and then found prone in her crib. Her gestation and delivery were uncomplicated, and she had no history of anemia, hemoptysis, chest trauma, or chronic lung disease. Autopsy revealed diffuse severe pulmonary congestion and severe multifocal intra-alvedar hemorrhage. Metabolic and toxicological screening, microbiologic cultures, and vitreous chemistry were noncontributory. A diagnosis of SIDS had been made by the medical examiner. Subsequent semiquantitative assessment of the severity of pulmonary intra-alveolar hemosiderosis prompted consideration of other disorders, including a heretofore undescribed lethal infantile variant of idiopathic pulmonary hemosiderosis, but none could be confirmed. Therefore, we assigned a study diagnosis of unclassified sudden infant death. We recommend that a diagnosis of SIDS not be made in cases with unexplained large numbers of intra-alveolar PS. We also recommend that quantitative assessment of lung sections stained for iron be undertaken in cases with numerous intra-alveolar macrophages in order to accumulate data that might allow diagnostic correlations with the circumstances of death and autopsy findings.

Hemoglobin F in sudden infant death syndrome: a San Diego SIDS/SUDC Research Project report.

Whether levels of fetal hemoglobin (HbF), a possible marker of antecedent hypoxemia, are increased in sudden infant death syndrome (SIDS) compared to controls is unresolved. Our aims are to: (1) Compare percent fetal hemoglobin (%HbF) levels in SIDS and control cases, and (2) compare our findings with those reported in previous studies. Using Triton-acid-urea gel electrophoresis and quantitative densitometry, %HbF was determined in whole blood specimens obtained at autopsy from SIDS and control cases accessioned into the San Diego SIDS/SUDC Research Project database. The SIDS and control cases were not different with respect to mean age, gender, gestational age, method of delivery, birth weight, or mean autopsy interval; %HbF levels in SIDS and control cases were not significantly different. Given that our results were obtained using optimal methods in well-defined SIDS and control cases, we concur with others that %HbF is not elevated in SIDS.

Congenital cerebellar malignant rhabdoid tumor in an infant with junctional epidermolysis bullosa.

Epidermolysis bullosa (EB), a hereditary blistering condition of the skin, is divided into simplex, hemidesmosomal, junctional, and dystrophic types. It may be complicated by the development of squamous cell carcinoma of the skin, but other neoplasms, especially those separate from involved skin, are distinctly rare. We report a male infant with junctional EB who died of Pseudomonas sepsis and was found at autopsy to have a clinically unrecognized cerebellar malignant rhabdoid tumor (MRT). This is the first reported case of an infant with EB and a coincident extracutaneous neoplasm. It is also the first known case of EB associated with a pathologically confirmed malignant brain tumor. Cytogenetic results from the infant and his tumor and both of his parents suggest the infant's EB and MRT were not genetically linked.

A comparison of pulmonary intra-alveolar hemorrhage in cases of sudden infant death due to SIDS in a safe sleep environment or to suffocation.

The differentiation of SIDS from accidental or inflicted suffocation may be impossible without corroborating findings from the death scene or autopsy or in the absence of a confession from a perpetrator. Pulmonary intra-alveolar hemorrhage (PH) has been proposed as a potential clue to suffocation, but none of the previous studies on this topic have limited SIDS cases to those who were in a safe sleep environment, in which all were found supine and alone on a firm surface with their heads uncovered. Our aims are to: (1) compare PH in SIDS cases found in a safe sleep environment to a control group comprised of infants whose deaths were attributed to accidental or inflicted suffocation and (2) assess the effect of age, CPR, and postmortem interval (PMI), with regard to the severity of PH in this subset of safe-sleeping SIDS cases. We conducted a retrospective study of all postneonatal cases accessioned by the Office of the Medical Examiner in San Diego County, California who died of SIDS or suffocation between 1999 and 2004. A total of 74 cases of sudden infant death caused by SIDS (34 cases as defined above, comprising 8% of the total SIDS cases), accidental suffocation (37), and inflicted suffocation (3) from the San Diego SIDS/SUDC Research Project database were compared using a semiquantitative measure of pulmonary intra-alveolar hemorrhage. The most severe (grade 3 or 4) PH occurred in 35% of deaths attributed to suffocation, but in only 9% of the SIDS cases. Age, duration of CPR attempts and PMI had no effect on the severity of PH in SIDS. Our results indicate that the severity of PH cannot be used independently to differentiate SIDS from suffocation deaths. Each case must be evaluated on its own merits after thorough review of the medical history, circumstances of death, and postmortem findings.

Sudden unexpected death in childhood associated with cardiac rhabdomyoma, involuting adrenal ganglioneuroma, and megalencephaly: another expression of tuberous sclerosis?

We report a 9-year-old, previously healthy girl who died suddenly and unexpectedly and was found at postmortem examination to have a cardiac rhabdomyoma, megalencephaly, and an involuting adrenal ganglioneuroma. Her death was possibly caused by a fatal cardiac arrhythmia resulting from interference of the ventricular septal rhabdomyoma with the cardiac conduction fibers. Her extended family history included a variety of disorders, including cleft lip and palate and ill-defined cardiac and neurologic diseases. The constellation of her autopsy findings suggested a diagnosis of tuberous sclerosis, for which there are gene defects that can be identified in surviving family members.