Neuropathologic Examination in Sudden Unexpected Deaths in Infancy and Childhood: Recommendations for Highest Diagnostic Yield and Cost-Effectiveness in Forensic Settings

Abstract

In infants and toddlers (less than four years of age), determination of cause and manner of death often requires a complete autopsy. Few evidence-based guidelines exist regarding optimum nervous system sectioning in this population. Over a six-month interval and using a comprehensive section protocol, we categorized cases having neuropathological findings that were critical (Class A), contributory (Class B), or noncontributory (Class C) to the final cause and manner of death. We further evaluated which sections helped make this determination. Among 53 cases (44 infants, 9 toddlers; 26 girls, 27 boys), Class A neuropathology was noted in nine (16.9%). Seven infants had meningoencephalitis (2/7, 28.6%), craniospinal trauma (3/7, 42.8%), brainstem necrosis suggesting Leigh Disease (1/7, 14.3%), and hydrocephalus in Dandy-Walker malformation (1/7, 14.3%); two toddlers had inflicted craniospinal trauma (2/2, 100%). Class B factors were identified in 11/53 (20.8%), including recent hypoxic-ischemic lesions (2/11, 18.2%), meningitis or dural venous sinus thrombosis in systemic sepsis (2/11, 18.2%), multicystic encephalopathy following peripartum asphyxia (2/11, 18.2%), and microcephaly and delayed myelination (Cri-du-Chat Syndrome) (1/11, 9.09%). Class B also included three toddlers (3/11, 27.2%) with features of hippocampal dysgenesis, two in the setting of febrile seizures. Class C comprised normal brains (3/53, 5.7%), and those with findings of uncertain significance, such as white matter and brainstem gliosis (30/53, 56.6%). The sections most valuable for detection of relevant pathology, and thus recommended for routine sampling, were: 1) bilateral hippocampus; 2) cerebral cortex and leptomeninges; and 3) pons or medulla.