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Objective: To assess the efficacy of 10% formalin perfusion fixation as a method of rapid fixation to examine the human brain immediately following autopsy., Design: Compare the histology and immunohistochemistry from human brains in which one hemisphere undergoes perfusion fixation using 10% buffered formalin, and the contralateral nonperfused hemisphere undergoes standard 14-day immersion fixation in 8 L of 10% buffered formalin., Setting: Autopsy material in a general medical-surgical university hospital., Participants: Pathologists, neuropathologists, resident pathologists, and pathology assistants., Intervention: Immediately following brain removal, a single hemisphere was perfused with 1 L 10% buffered formalin over a 15- to 20-minute period. The contralateral nonperfused hemisphere served as a control, undergoing standard immersion fixation for 2 weeks in 10% formalin. The perfusion-fixation hemisphere was immediately available for neuropathologic examination, and histologic sections of the brain were processed immediately with the other necropsy tissue sections. This allows completion of a final autopsy neuropathology report within 3 to 5 days in concert with the systemic section of the report., Main Outcome Measure: Perfusion-fixation brain sections were compared with immersion-fixation brain sections from the same brain. The effects on hematoxylin-eosin, Bielschowsky's silver, and immunohistochemical staining were evaluated by an experienced neuropathologist and a general pathologist with no prior knowledge of the fixation technique., Results: Perfusion fixation revealed equal and occasionally superior histologic sections compared with traditional immersion fixation in terms of (1) technical preparation of section, (2) quality and intensity of staining with both hematoxylin-eosin and silver, and (3) immunoreactivity localization with a variety of immunohistochemical reactions., Conclusions: Immediate perfusion of the brain is an easily performed fixation technique that yields comparable or superior fixation to prolonged immersion fixation and allows an immediate complete neuropathologic examination and report within 3 to 5 days of performance of the autopsy.

Objective: To develop a system for enhancing the performance and reporting of autopsies in an effective and clinically useful manner., Design: Twelve steps were defined as essential for the completion of the autopsy. Each step of the process was evaluated for usefulness and effectiveness., Setting: Autopsies performed in a university hospital from 1992 through 1994., Participants: Pathology residents and staff, clinicians, and clinical team house staff., Intervention: Participants followed the 12-step process, with emphasis on involving the clinical team in the interview, prosection, and final rounds. The final rounds conference was designated a working conference, where the perfused-fixed brain was cut, histologic sections of the case were submitted, and the provisional diagnosis was written with the clinicians. A next-day microscopic slide review session was scheduled to "sign out" the case. Establishing a philosophy of status equal to all other department functions facilitated implementation., Main Outcome Measure: All autopsies performed for a period of 3 years (2 retrospective and 1 prospective) were included., Results: The autopsy completion time was reduced from a mean of 57 days (range 7 to 174) in 1992 to 4.8 days (range 1 to 16) in 1994., Conclusion: The autopsy completion time was reduced, increasing its usefulness for teaching and quality assurance. Relationships with the clinical staff were enhanced with consultation-style final reports. Enthusiasm for, and satisfaction with, the new process was expressed by clinicians, pathology staff, residents, and technical support staff.

Three of six siblings presented with sleep apnea between 18 and 26 months of age. Twin females and a male had normal growth and development without antecedent neurologic or apparent metabolic disorder. The females presented at 25 and 27 months respectively with irregular respiration and episodes of apnea. Twin A succumbed to an apneic episode while sleeping. Central sleep apnea was diagnosed in twin B at the Stanford Sleep Clinic. She died following an apneic episode three months after evaluation. The male presented at 18 months with fatal sleep apnea. A fourth child was evaluated for sleep apnea at 7 weeks of age with several hospitalizations before her death at 31 months. She and remaining family members were extensively studied for inherited neurologic disorders including subacute necrotizing encephalomyopathy (SANE, Leigh disease). This family with lethal sleep apnea presents an association with SANE with minimal neurologic signs and symptoms and neuropathologic involvement. Lesions were confined to the respiratory centers of the lower brain stem, making sleep apnea explicable. This child and family members tested positive or borderline for inhibitor substance thiamine triphosphate (TTP). All testing for TTP inhibitor substance was performed in Professor Jack R. Cooper's laboratory, Department of Pharmacology, Yale University School of Medicine, New Haven, Conn. These cases present an interesting and instructive lesson emphasizing the need for extensive evaluation of children with unsuspected sleep apnea with early demise.