Pathology/Biology __ 2018 H1 A Rare Presentation of Alexander Disease Edana D. Stroberg, DO*, Office of the Chief Medical Examiner, 901 N Stonewall Avenue, Oklahoma City, OK 73117; Kenneth D. Hutchins, MD, Miami-Dade County, Medical Examiner Department, Number One on Bob Hope Road, Miami, FL 33136; and E.O. Lew, MD, Miami-Dade County, Medical Examiner Department, Number One on Bob Hope Road, Miami, FL 33136-1133 After attending this presentation, attendees will better understand Alexander disease, a rare leukodystrophy, and its presentation. This presentation will impact the forensic science community by increasing attendees’ understanding of Alexander disease and the importance of a thorough neuropathologic evaluation in cases of anoxic encephalopathy. Introduction: Alexander disease is an extremely rare, usually progressive and fatal, neurological disorder.1 Initially, it was detected most often during infancy or early childhood, but as better diagnostic tools have become available, it has been found to occur with similar frequency at all stages of life.1 Approximately 95% of Alexander disease cases are caused by mutations in a gene named GFAP for a structural protein called glial fibrillary acidic protein that is found exclusively in astrocytes in the central nervous system.1 Alexander disease has been estimated to occur at a frequency of approximately one in one million births.1 There are three forms of Alexander disease: infantile, juvenile, and adult. Juvenile Alexander disease is characterized by difficulty in talking and swallowing and the inability to cough.2 There can also be weakness and spasticity of the extremities, particularly the legs.2 Unlike the infantile form of the disease, mental ability and head size may be normal.2 Survival can extend several years following the onset of symptoms, with occasional longer survival into middle age.2 The course of the disease may involve signs of swallowing or speech difficulty, vomiting, ataxia, and/or spasticity and kyphoscoliosis can occur.2 The most striking neuropathological feature is the diffuse presence of eosinophilic fibrinoid bodies in the cytoplasm of fibrillary astrocytes. Material and Methods: The decedent was a 14-year-old girl with a history of narcolepsy, sleep apnea, and scoliosis. Eighteen months prior to her death, the decedent and several others were playing in a backyard pool. When the decedent did not resurface, one of the children notified the supervising adult, who pulled her out of the pool. She was transported to a local hospital and recovered; however, she began to display signs of global developmental delay with onset of impulse control issues, anxiety, depression, self-mutilating behaviors, dysphagia with bouts of aspiration pneumonia, and ataxia. Two weeks prior to her death, she was hospitalized for self-mutilation and her condition progressed to her refusing to eat, talk, or get out of bed. She was also found to be bradycardic and hypothermic. She became unresponsive and was found to have worsening cerebral edema with cerebellar tonsillar herniation. Results: At autopsy, she was found to have cerebral edema and scoliosis of the thoracic spine. Neuropathologic consultation revealed a non- perfused, respirator-type, macerated brain and spinal cord with diffuse collections of eosinophilic fibrinoid bodies (Rosenthal fibers) in all sections. Conclusion: The decedent experienced a near-drowning episode and was diagnosed with anoxic encephalopathy when she was 12 years old. Afterward, she experienced a myriad of psychiatric and neurologic issues that were determined to be sequelae of anoxic encephalopathy. A Magnetic Resonance Imaging (MRI) of her brain revealed atrophy of the cervical spinal cord and periventricular white matter changes, which can be seen in both Alexander disease and anoxic encephalopathy. She became unresponsive in the hospital and care was withdrawn after the girl had been on a respirator for multiple days. At autopsy, she had a non-perfused, macerated brain and spinal cord, which is a known complication of being on a respirator. Her brain and spinal cord were submitted for neuropathologic evaluation, which revealed Alexander disease. The decedent experienced onset of the disease at approximately 12 years of age, which unfortunately coincided with a near-drowning event with resultant anoxic encephalopathy, thus confounding her clinical course. This case highlights the importance of performing a thorough neuropathologic evaluation when necessary, even when it is presumed to be of little informative value because of autolytic changes in the brain. Reference(s): 1. Goldman, James E. Alexander Disease. NORD (National Organization for Rare Disorders). n.d. Web. 14, June 2017. 2. Alexander Disease. United Leukodystrophy Foundation. n.d. Web. 14 June 2017. Alexander, Leukodystrophy, Anoxic Copyright 2018 by the AAFS. Permission to reprint, publish, or otherwise reproduce such material in any form other than photocopying must be obtained by the AAFS. ______________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ *Presenting Author - 657 - Pathology/Biology __ 2018 H2 Adrenal Gland Changes in Relation to the Cause of Death Cristina Mondello, MD*, Department BIOMORF, University of Messina, via Consolare Valeria, 1, Messina 98123, ITALY; Elvira Ventura Spagnolo, MD*, University of Palermo, Via Del Vespro, 129, Palermo 90127, ITALY; Letteria Minutoli, MD, University of Messina, Via Consolare Valeria, 1, Messina 98125, ITALY; Domenico Puzzolo, MD, University of Messina, Via Consolare Valeria, 1, Messina 98125, ITALY; Vincenzo Macaione, MD, University of Messina, Via Consolare Valeria, 1, Messina 98125, ITALY; Consuelo Malta, BS, University of Messina, Via Consolare Valeria, 1, Messina 98125, ITALY; Mariagrazia Rinaldi, BS, University of Messina, Via Consolare Valeria, 1, Messina 98125, ITALY; and Antonio Micali, MD, University of Messina, Via Consolare Valeria, 1, Messina 98125, ITALY After attending this presentation, attendees will understand the importance of improving knowledge regarding adrenal gland involvement in response to stress related to the death process and their changes in relation to cause of death. This presentation will impact the forensic science community by highlighting: (1) whether the adrenal gland is undergoing structural and/or molecular changes in relation to different causes of death; (2) if these changes have significant differences; and, (3) if it is possible to create a timeline of the death process resulting in more or less prolonged pain. The adrenal response to stress occurs in a syndrome that reflects activation of the sympathoadrenal system and the Hypothalamic-Pituitary- Adrenocortical (HPA) axis, and a “stress syndrome” maintains homeostasis in emergencies, such as “fight or flight” situations. One of the principal tissues involved in the stress response is the adrenal gland; in fact, there is clear evidence of fasciculata activation with the release of cortisol and the release of adrenaline from the medulla. The literature suggests that the biochemical analyses of catecholamines may be useful markers for investigating various stress responses in the process of death involving bleeding, burns, cold exposure, physical hyperactivity, or drug abuse; this is possible when these markers can be used in combination with other chemical and immunohistochemical markers; however, in postmortem investigation, catecholamines have been considered rather unstable markers for investigating the cause or process of death due to pain, terminal medical care, and postmortem interference.1 This study sought an adrenal tissue marker that was involved in the stress response process with special reference to activated/stimulated receptors by the activation of the sympatho-adrenal system and HPA. The β2-AR (adrenergic receptor) was chosen because stress promotes the release of epinephrine, a catecholamine stress hormone that binds to β(2)-adrenergic receptors (β(2)ARs) with high affinity. Cases with several causes of death were selected in order to conduct an immunohistochemical analysis by the β2-AR antibody. Several causes of death were drowning, sudden cardiac death, sepsis, hanging, strangulation, traffic accident, and fire. This study revealed a different expression of β2-AR immunopositivity in relation to the cause of death; highlighted was the fact that the positive staining varied both for localization (fasciculate and/or glomerulosa and/or reticularis zone and/or medulla) and quantity. The results were then analyzed in relation to factors such as sex, age, and timing of the death process. Reference(s): 1. Zhu B.L., Ishikawa T., Michiue T., Li D.R., Zhao D., Quan L., Oritani S., Bessho Y., Maeda H. Postmortem serum catecholamine levels in relation to the cause of death. Forensic Sci Int. 2007;173(2-3):122-9. Adrenal Gland, Medicolegal Autopsy, Immunohistochemistry Copyright 2018 by the AAFS. Permission to reprint, publish, or otherwise reproduce such material in any form other than photocopying must be obtained by the AAFS. ______________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ *Presenting Author