Periadventitial extracranial vertebral artery hemorrhage in a case of shaken baby syndrome.

We report a case of a two-month-old boy who became unresponsive in the sole custody of his father. Resuscitation efforts on route to the hospital were able to restore the infant's heart beat. However, neurologic function never recovered. Autopsy revealed massive cerebral edema, recent subdural, and subarachnoid hemorrhages, bilateral retinal hemorrhages, and cervical spine ligament hemorrhages. Separation of individual cervical vertebrae showed extensive, bilateral, periadventitial vertebral artery hemorrhages between C1 and C4, with corresponding luminal compression of the vertebral arteries. The importance of this previously unreported phenomena of periadventitial vertebral artery hemorrhage in the setting of shaken baby syndrome is discussed.

Optic nerve damage in shaken baby syndrome: detection by beta-amyloid precursor protein immunohistochemistry.

BACKGROUND: Rapid acceleration-deceleration of an infant's head during intentional shaking should in theory exert stretch or shear forces upon the optic nerves sufficient to cause axonal injury. beta-Amyloid precursor protein (beta-APP) immunohistochemistry recently has been shown to be a highly effective method for identifying diffuse axonal injury in the brains of infants with shaken baby syndrome. In this study, we investigated the utility of beta-APP in identifying optic nerve damage in infants who have sustained fatal whiplash shaking. MATERIALS AND METHODS: beta-Amyloid precursor protein immunohistochemistry was performed on formalin-fixed, paraffin-embedded sections of eyes (including optic disc and distal optic nerve) from infants less than 1 year of age with shaken baby syndrome (5 cases), combined shaken baby syndrome/blunt head trauma (3 cases), and "pure" blunt head trauma (1 case). Nontraumatic control cases included infants who died of suffocation (1 case), sudden infant death syndrome (1 case), and positional asphyxia (1 case) and an enucleation from a child with a retinoblastoma (1 case). Matched hematoxylin-eosin-and neurofilament-stained sections were used for comparison. RESULTS: Three of the 5 shaken baby cases and all 3 combined shaken baby/blunt head trauma cases had optic nerve axonal injury identified by the presence of strongly beta-APP-immunoreactive beaded or swollen axonal segments. Axonal injury could not be detected in the corresponding hematoxylin-eosin-or neurofilament-stained sections. Optic nerve axonal injury was not seen in the case involving pure blunt head trauma or in the nontraumatic control cases. CONCLUSIONS: Optic nerve axonal injury is a prominent feature of intentional fatal whiplash head trauma in infants less than 1 year of age. beta-Amyloid protein precursor immunohistochemistry appears to be the most effective method for demonstrating axonal damage in the optic nerve.

Neuronal and glial DNA fragmentation in Pick's disease.

Pick's disease (PD) is characterized by severe neuronal loss and gliosis in a frontotemporal lobar distribution, often associated with Pick bodies and ballooned neurons. Abnormal tau metabolism has been implicated in the pathogenesis of PD; however, the underlying mechanism of neuronal degeneration remains poorly understood. Evidence from other neurodegenerative diseases has suggested that DNA damage and apoptosis may play a major role in cellular degeneration and death. In the present study, an in situ nucleotidyl transferase assay (ISNTA) was used to identify DNA fragmentation in three cases of classical PD with Pick bodies and ballooned neurons, and two PD "variants", one with ballooned neurons only and the other without Pick bodies or ballooned neurons. In all cases large numbers of ISNTA-positive neurons were present in anatomic regions having obvious degenerative changes (neuronal atrophy and loss, gliosis, cytoplasmic inclusions) by conventional histology. There was no clear association between neuronal DNA fragmentation and the presence of structural abnormalities such as Pick bodies or ballooned cytoplasm. ISNTA-positive glia were present in both cortex and subcortical white matter. Morphologic evidence of apoptosis was not detected in either neurons or glial cells. We suggest that DNA fragmentation in PD and probably other neurodegenerative disorders most likely specifies a population of potentially vulnerable cells in which both cell death and repair mechanisms have been activated. It is likely that only a very small number of these vulnerable cells at a given time will proceed to cell death; however, it is uncertain whether this occurs by apoptosis or some other mechanism.

Diffuse axonal injury in infants with nonaccidental craniocerebral trauma: enhanced detection by beta-amyloid precursor protein immunohistochemical staining.

OBJECTIVE: Accurate identification of diffuse axonal injury is important in the forensic investigation of infants who have died from traumatic brain injury. beta-Amyloid precursor protein (beta-APP) immunohistochemical staining is highly sensitive in identifying diffuse axonal injury. However, the effectiveness of this method in brain-injured infants has not been well established. The present study was undertaken to assess the utility of beta-APP immunohistochemistry in detecting diffuse axonal injury in infants with either shaken baby syndrome or blunt head trauma. MATERIALS AND METHODS: Archival formalin-fixed, paraffin-embedded blocks from infants (<1 year old) with shaken baby syndrome (7 cases) and blunt head trauma (3) and blocks from 7 control cases that included nontraumatic cerebral edema (1), acute hypoxic-ischemic encephalopathy (1), and normal brain (5) were immunostained for beta-APP. A semiquantitative assessment of the severity of axonal staining was made. Corresponding hematoxylin-eosin-stained sections were examined for the presence of axonal swellings. RESULTS: Immunostaining for beta-APP identified diffuse axonal injury in 5 of 7 infants with shaken baby syndrome and 2 of 3 infants with blunt head trauma. Immunoreactive axons were easily identified and were present in the majority of the sections examined. By contrast, hematoxylineosin staining revealed axonal swellings in only 3 of 7 infants with shaken baby syndrome and 1 of 3 infants with blunt head trauma. Most of these sections had few if any visible axonal swellings, which were often overlooked on initial review of the slides. No beta-APP immunoreactivity was observed in any of the 7 control cases. CONCLUSIONS: Immunostaining for beta-APP can easily and reliably identify diffuse axonal injury in infants younger than 1 year and is considerably more sensitive than routine hematoxylin-eosin staining. We recommend its use in the forensic evaluation of infants with fatal craniocerebral trauma.

Sudden unexpected death from primary posterior fossa tumors.

We report 2 cases of sudden death in which hospital autopsies revealed unsuspected primary posterior fossa neoplasms. The first case was a 3-year-old girl who was found apneic and pulseless in bed and was brought to the hospital moribund and could not be resuscitated. Autopsy revealed a 3-cm ganglioglioma that infiltrated nearly the entire medulla. The second case involved a 39-year-old man who was found asystolic and unresponsive in bed. He was resuscitated and maintained on a ventilator for a few hours, after which life support was withdrawn. Autopsy showed a 5-cm pilocytic astrocytoma arising from the ventral cerebellum and extending into the fourth ventricle and compressing the brain stem. Previously reported cases of clinically unsuspected primary posterior fossa tumors presenting with sudden death are reviewed. Hypotheses for the mechanism of sudden death are presented.