Browsing by Subject "Autopsy"

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    Comorbidities in Early-Onset Sporadic versus Presenilin-1 Mutation-Associated Alzheimer’s Disease Dementia: Evidence for Dependency on Alzheimer’s Disease Neuropathological Changes
    (medRxiv, 2023-08-16) Sepulveda-Falla, Diego; Lanau, Carlos Andrés Villegas; White, Charles, III; Serrano, Geidy E.; Acosta-Uribe, Juliana; Mejía-Cupajita, Barbara; Villalba-Moreno, Nelson David; Lu, Pinzhang; Glatzel, Markus; Kofler, Julia K.; Ghetti, Bernardino; Frosch, Matthew P.; Restrepo, Francisco Lopera; Kosik, Kenneth S.; Beach, Thomas G.; Pathology and Laboratory Medicine, School of Medicine
    Autopsy studies have demonstrated that comorbid neurodegenerative and cerebrovascular disease occur in the great majority of subjects with Alzheimer disease dementia (ADD), and are likely to additively alter the rate of decline or severity of cognitive impairment. The most important of these are Lewy body disease (LBD), TDP-43 proteinopathy and cerebrovascular disease, including white matter rarefaction (WMR) and cerebral infarcts. Comorbidities may interfere with ADD therapeutic trials evaluation of ADD clinical trials as they may not respond to AD-specific molecular therapeutics. It is possible, however, that at least some comorbidities may be, to some degree, secondary consequences of AD pathology, and if this were true then effective AD-specific therapeutics might also reduce the extent or severity of comorbid pathology. Comorbidities in ADD caused by autosomal dominant mutations such as those in the presenilin-1 (PSEN1) gene may provide an advantageous perspective on their pathogenesis, and deserve attention because these subjects are increasingly being entered into clinical trials. As ADD associated with PSEN1 mutations has a presumed single-cause etiology, and the average age at death is under 60, any comorbidities in this setting may be considered as at least partially secondary to the causative AD mechanisms rather than aging, and thus indicate whether effective ADD therapeutics may also be effective for comorbidities. In this study, we sought to compare the rates and types of ADD comorbidities between subjects with early-onset sporadic ADD (EOSADD; subjects dying under age 60) versus ADD associated with different types of PSEN1 mutations, the most common cause of early-onset autosomal dominant ADD. In particular, we were able to ascertain, for the first time, the prevalences of a fairly complete set of ADD comorbidities in United States (US) PSEN1 cases as well as the Colombian E280A PSEN1 kindred. Data for EOSADD and US PSEN1 subjects (with multiple different mutation types) was obtained from the National Alzheimer Coordinating Center (NACC). Colombian cases all had the E280A mutation and had a set of neuropathological observations classified, like the US cases according to the NACC NP10 definitions. Confirmatory of earlier reports, NACC-defined Alzheimer Disease Neuropathological Changes (ADNC) were consistently very severe in early-onset cases, whether sporadic or in PSEN1 cases, but were slightly less severe in EOSADD. Amyloid angiopathy was the only AD-associated pathology type with widely-differing severity scores between the 3 groups, with median scores of 3, 2 and 1 in the PSEN1 Colombia, PSEN1 US and EOSADD cases, respectively. Apoliprotein E genotype did not show significant proportional group differences for the possession of an E-4 or E-2 allele. Of ADD comorbidities, LBD was most common, being present in more than half of all cases in all 3 groups. For TDP-43 co-pathology, the Colombian PSEN1 group was the most affected, at about 27%, vs 16% and 11% for the US PSEN1 and sporadic US cases, respectively. Notably, hippocampal sclerosis and non-AD tau pathological conditions were not present in any of the US or Colombian PSEN1 cases, and was seen in only 3% of the EOSADD cases. Significant large-vessel atherosclerosis was present in a much larger percentage of Colombian PSEN1 cases, at almost 20% as compared to 0% and 3% of the US PSEN1 and EOSADD cases, respectively. Small-vessel disease, or arteriolosclerosis, was much more common than large vessel disease, being present in all groups between 18% and 37%. Gross and microscopic infarcts, however, as well as gross or microscopic hemorrhages, were generally absent or present at very low percentages in all groups. White matter rarefaction (WMR) was remarkably common, at almost 60%, in the US PSEN1 group, as compared to about 18% in the EOSADD cases, a significant difference. White matter rarefaction was not assessed in the Colombian PSEN1 cases. The results presented here, as well as other evidence, indicates that LBD, TDP-43 pathology and WMR, as common comorbidities with autosomal dominant and early-onset sporadic ADD, should be considered when planning clinical trials with such subjects as they may increase variability in response rates. However, they may be at least partially dependent on ADNC and thus potentially addressable by anti-amyloid or and/anti-tau therapies.
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    Concordance of Solid Organ Biopsy Diagnoses With Hospital Autopsy and the Contribution of Biopsies to Death
    (Springer Nature, 2023-01-17) Priemer, David S.; Curran, Joseph M.; Phillips, Carrie L.; Cummings, Oscar W.; Saxena, Romil; Pathology and Laboratory Medicine, School of Medicine
    Biopsies of the liver, lung, and kidney are performed for many indications, including organ dysfunction, mass lesions, and allograft monitoring. The diagnosis depends on the sample, which may or may not be representative of the lesion or pathology in question. Further, biopsies are not without risk of complications. Autopsies are a resource for assessing the accuracy of biopsy diagnoses and evaluating possible complications. Herein, we aimed to compare liver, lung, and kidney biopsy diagnoses with those from autopsies conducted soon after the procedure and to assess the contribution of biopsy to mortality. A 28-year search of our database identified 147 patients who were autopsied after dying within 30 days of a liver, lung, or kidney biopsy. The concordance of the biopsy diagnosis with the autopsy findings was determined. Finally, medical records were reviewed to determine the likelihood that a biopsy contributed to the patient's death. The contribution of the biopsy to death was categorized as "unlikely," "possible," or "probable." Overall concordance between biopsy and autopsy diagnoses was 87% (128/147), including 95% (87/92), 71% (32/45), and 90% (9/10) for liver, lung, and kidney biopsies, respectively. Concordance was lower for biopsies of suspected neoplasms versus non-neoplastic diseases. Lung biopsy concordance was higher for wedge biopsy versus needle or forceps biopsy. A biopsy was determined to at least "possibly" contribute to death in 23 cases (16%). In conclusion, an autopsy is an important tool to validate liver, lung, or kidney biopsy diagnoses. Confirmation of biopsy diagnoses via post-mortem examination may be particularly valuable when patients die soon after the biopsy procedure. Furthermore, an autopsy is especially useful when patients die soon after a biopsy in order to determine what role, if any, the procedure played in their deaths. Though biopsy complications are uncommon, a biopsy may still contribute to or precipitate death in a small number of patients.
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    Death Resulting from Pneumocephalus Complicating Endoscopic Food Bolus Retrieval in a Patient with Eosinophilic Esophagitis
    (Sage, 2016-12) Fuhs, Amy K.; Prahlow, Joseph A.; IU School of Medicine
    Pneumocephalus is a rare complication of esophagogastroduodenoscopy (EGD), but existing literature does not discuss pneumocephalus surrounding endoscopic food bolus retrieval. We present a death involving pneumocephalus complicating endoscopic food removal from the esophagus. A 40-year-old man presented with dysphagia and suprasternal discomfort 12 hours following chicken ingestion. On flexible endoscopy, chicken was visualized in the distal esophagus. After successful retrieval, a mucosal laceration was noted where the chicken had been lodged. He was unarousable following the procedure and was emergently transported to a hospital, where computed tomography scanning showed pneumocephalus. He was later declared brain dead. The case was referred for medicolegal autopsy. The brain was examined first, revealing rare air bubbles within meningeal vessels and numerous, diffuse petechiae-like hemorrhages within the brain parenchyma. The esophageal mucosa had focal discoloration and a partial thickness laceration; microscopic examination revealed eosinophilic esophagitis. Eosinophilic esophagitis is a known risk factor for food bolus impaction and should be suspected in such patients. Pneumocephalus is a rare possible complication of EGD for food bolus retrieval. In patients unresponsive after endoscopy, radiographic detection of potential pneumocephalus should be encouraged to enable timely therapy and improved outcomes, or to supplement autopsy in the event of patient death. Forensic pathologists should understand that pneumocephalus is a potential mechanism of injury/death in patients experiencing esophageal trauma, including injury incurred during EGD.
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    Differential diagnosis of amnestic dementia patients based on an FDG-PET signature of autopsy-confirmed LATE-NC
    (Wiley, 2023) Grothe, Michel J.; Moscoso, Alexis; Silva-Rodríguez, Jesús; Lange, Catharina; Nho, Kwangsik; Saykin, Andrew J.; Nelson, Peter T.; Schöll, Michael; Buchert, Ralph; Teipel, Stefan; Alzheimer’s Disease Neuroimaging Initiative; Radiology and Imaging Sciences, School of Medicine
    Introduction: Limbic age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) is common in advanced age and can underlie a clinical presentation mimicking Alzheimer's disease (AD). We studied whether an autopsy-derived fluorodeoxyglucose positron emission tomography (FDG-PET) signature of LATE-NC provides clinical utility for differential diagnosis of amnestic dementia patients. Methods: Ante mortem FDG-PET patterns from autopsy-confirmed LATE-NC (N = 7) and AD (N = 23) patients were used to stratify an independent cohort of clinically diagnosed AD dementia patients (N = 242) based on individual FDG-PET profiles. Results: Autopsy-confirmed LATE-NC and AD groups showed markedly distinct temporo-limbic and temporo-parietal FDG-PET patterns, respectively. Clinically diagnosed AD dementia patients showing a LATE-NC-like FDG-PET pattern (N = 25, 10%) were significantly older, showed less abnormal AD biomarker levels, lower APOE ε4, and higher TMEM106B risk allele load. Clinically, they exhibited a more memory-predominant profile and a generally slower disease course. Discussion: An autopsy-derived temporo-limbic FDG-PET signature identifies older amnestic patients whose clinical, genetic, and molecular biomarker features are consistent with underlying LATE-NC.
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    Fatal eosinophilic myocarditis and submassive hepatic necrosis in lamotrigine induced DRESS syndrome
    (BMC, 2023-10-25) Doan, Khanh Duy; Akinsanya, Adeyinka; Kuhar, Matthew; Mesa, Hector; Pathology and Laboratory Medicine, School of Medicine
    Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome is a rare but severe and sometimes fatal adverse drug reaction that is known to occur with a number of antiepileptic drugs. It often follows a prolonged clinical course, which can worsen even after discontinuing the causative drug and administering steroid treatment. Failure to promptly identify the delayed involvement of vital organs, such as the heart and liver, may result in irreversible organ failure and death. We report a case of a presumed sudden death of a young woman who had a documented history of a protracted intermittent hypersensitivity reaction to lamotrigine. Postmortem examination revealed the presence of eosinophilic myocarditis and submassive hepatic necrosis diagnostic of fatal DRESS syndrome that progressed despite early discontinuation of the medication and improvement of dermatologic and hematologic symptoms following steroid therapy.
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    The man who revolutionized our knowledge of the human body
    (The Conversation US, Inc., 2014-12-31) Gunderman, Richard; Radiology and Imaging Sciences, School of Medicine
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    Williams Syndrome With Rare Ureteric Abnormality
    (Cureus, 2021-08-16) Khan, Jaffar; Al-Obaidy, Khaleel I.; Fan, Rong; Pathology and Laboratory Medicine, School of Medicine
    Williams syndrome (WS), also known as Williams-Beuren syndrome, is a rare genetic disorder characterized by infantile hypercalcemia, short stature, a varying degree of mental retardation, elfin-like facial features, and cardiovascular abnormalities, including systemic hypertension, aortic hypoplasia, coarctation of the aorta, and valvular heart disease (aortic and pulmonic stenosis, mitral valve prolapsed or bicuspid aortic valve). It is also characterized by friendly and outgoing personality. The majority of WS cases are sporadic, while few are familial. Both sporadic and familial cases are due to deletion of chromosome 7 (7q11.23). Herein, we present an autopsy case of a 16-day-old male infant born to a 25-year-old mother with a history of William syndrome. Prenatal echocardiogram showed supravalvular aortic stenosis and pulmonary stenosis. The postnatal course was complicated by feeding difficulties and desaturation. Gross autopsy findings included generalized edema, macrocephaly with short neck, and multiple facial anomalies (mandibular hypoplasia, depressed nasal bridge, long philtrum, ear malformation, and wide mouth). The heart was hypertrophied with obstructed ventricles and rudimentary, hypoplastic aortic root. An enlarged, dilated, and tortuous left ureter was a unique finding to this case, in addition to variation in the renal arteries' size and an small bowel outpouching located 33 cm from the ileocecal valve. Cytogenetic analysis revealed deletion of chromosome 7 (7q11.23). In conclusion, majority of WS cases are sporadic, and few are familial and are inherited as autosomal dominant.