Pseudo-Central Pontine Myelinolysis.

ABSTRACT: Central pontine myelinolysis is most commonly associated with rapid correction of hyponatremia and has historically been associated with alcoholism. In this case report, 2 deaths with gross findings of central pontine lesions led to the possibility that CPM may have been a potential mechanism of death. Subsequent analysis revealed that these lesions were incidental findings. This case report discusses the importance of appropriate microscopic and immunohistochemical analysis of suspected CPM cases.

Accidental Carbon Monoxide Poisoning While Driving: A Case Report With Review of the Literature.

Carbon monoxide (CO) is the cause of a significant percentage of fatal poisonings in many countries. It is known that fatalities resulting from CO poisoning are underreported and/or misclassified. Carbon monoxide exposure while driving can occur due to faulty exhaust systems, defective ventilation systems, emission from other vehicles, and even cigarette smoking. We report the case of a 23-year-old woman who was involved in a low-speed motor vehicle collision and was found unresponsive in her vehicle due to CO poisoning. A review of the literature revealed rare vehicle-related accidental CO poisonings.

Post-Mortem evaluation of amyloid-dopamine terminal positron emission tomography dementia classifications.

Clinical classification of early dementia and mild cognitive impairment (MCI) is imprecise. We reported previously that molecular imaging classification of early dementia and MCI with dual amyloid and dopamine terminal positron emission tomography differs significantly from expert clinical classification. We now report pathological diagnoses in a substantial subset of our previously imaged subjects. Among 36 subjects coming to autopsy, imaging classifications and pathological diagnosis were concordant in 33 cases (κ = 0.85). This approach enhanced specificity of Alzheimer's disease diagnosis. The strong concordance of imaging-based classifications and pathological diagnoses suggests that this imaging approach will be useful in establishing more accurate and convenient classification biomarkers for dementia research.

Opsoclonus-Myoclonus Syndrome in Primary Central Nervous System Lymphoma.

Adult-onset opsoclonus-myoclonus syndrome (OMS) has been associated with multiple cancers, most commonly small-cell lung carcinoma and breast adenocarcinoma. A 53-year-old woman who presented with OMS was found to have primary central nervous system (CNS) diffuse large B-cell lymphoma. OMS has been described in only 5 cases with non-Hodgkin lymphoma (NHL), and this is only the third reported case of OMS in NHL limited to the CNS. Although the paraneoplastic antibody panel was negative, we presume that the OMS was a paraneoplastic manifestation. Antineoplastic and anti-immune therapy had no effect on the neurologic manifestations.

Lethal Complications of Meningiomas: A Case Series.

Background: Meningiomas are the most prevalent type of primary intracranial tumor in adults, comprising nearly one-third of all intracranial tumors. They are typically benign, slow-growing, and asymptomatic but may cause neurological symptoms as they expand due to mass effect. Classification is determined by World Health Organization (WHO) grades 1 to 3 following pathological examination corresponding to benign, atypical, and anaplastic (malignant), respectively, reflecting their rate of growth and risk of recurrence. The vast majority are WHO grade 1 and their slow growth permits timely presentation for elective resection; however, meningiomas in vulnerable locations and coexisting morbidities can result in sudden death. Objectives: We present a series of four adult patients with meningiomas which resulted in death, including a case of fatal seizure, midline hemorrhagic meningioma, postresection meningitis, and compression of the cerebellum. Research design: Retrospective review of the authors' cases was conducted. Available pathology, medical, and autopsy records including gross images were reviewed in each case. The inclusion criteria were adult patients (>18 years old) and that the cause of death had to include meningioma. Subjects: The four patients included a 61-year-old male, an 84-year-old female, a 62-year-old male, and a 37-year-old female. Measures: Qualitative; autopsy reports describing cause of death and pathology report findings including gross and microscopic analysis. Conclusions: Meningiomas are often benign in nature but can rarely result in death. Size and location of the tumor and risk factors are contributory. Autopsy examination can be instrumental in identifying the cause and mechanism of deaths associated with meningiomas.

Chronic traumatic encephalopathy neuropathologic change is uncommon in men who played amateur American football.

Introduction: We examined postmortem brain tissue from men, over the age of 50, for chronic traumatic encephalopathy neuropathologic change (CTE-NC). We hypothesized that (i) a small percentage would have CTE-NC, (ii) those who played American football during their youth would be more likely to have CTE-NC than those who did not play contact or collision sports, and (iii) there would be no association between CTE-NC and suicide as a manner of death. Methods: Brain tissue from 186 men and accompanying clinical information were obtained from the Lieber Institute for Brain Development. Manner of death was determined by a board-certified forensic pathologist. Information was obtained from next of kin telephone interviews, including medical, social, demographic, family, and psychiatric history. The 2016 and 2021 consensus definitions were used for CTE-NC. Two authors screened all cases, using liberal criteria for identifying "possible" CTE-NC, and five authors examined the 15 selected cases. Results: The median age at the time of death was 65 years (interquartile range = 57-75; range = 50-96). There were 25.8% with a history of playing American football and 36.0% who had suicide as their manner of death. No case was rated as definitively having "features" of CTE-NC by all five authors. Ten cases were rated as having features of CTE-NC by three or more authors (5.4% of the sample), including 8.3% of those with a personal history of playing American football and 3.9% of those who did not play contact or collision sports. Of those with mood disorders during life, 5.5% had features of CTE-NC compared to 6.0% of those who did not have a reported mood disorder. Of those with suicide as a manner of death, 6.0% had features of CTE-NC compared to 5.0% of those who did not have suicide as a manner of death. Discussion: We did not identify a single definitive case of CTE-NC, from the perspective of all raters, and only 5.4% of cases were identified as having possible features of CTE-NC by some raters. CTE-NC was very uncommon in men who played amateur American football, those with mood disorders during life, and those with suicide as a manner of death.

Clinical Characteristics of the 2019 Eastern Equine Encephalitis Outbreak in Michigan.

Background: Eastern equine encephalitis virus is a mosquito-borne alphavirus responsible for unpredictable outbreaks of severe neurologic disease in animals and humans. While most human infections are asymptomatic or clinically nonspecific, a minority of patients develops encephalitic disease, a devastating illness with a mortality rate of ≥30%. No treatments are known to be effective. Eastern equine encephalitis virus infection is rare in the United States, with an annual average nationwide incidence of 7 cases between 2009 and 2018. However, in 2019, 38 cases were confirmed nationwide, including 10 in Michigan. Methods: Data from 8 cases identified by a regional network of physicians in southwest Michigan were abstracted from clinical records. Clinical imaging and histopathology were aggregated and reviewed. Results: Patients were predominantly older adults (median age, 64 years), and all were male. Results of initial arboviral cerebrospinal fluid serology were frequently negative, and diagnosis was not made until a median of 24.5 days (range, 13-38 days) after presentation, despite prompt lumbar punctures in all patients. Imaging findings were dynamic and heterogeneous, with abnormalities of the thalamus and/or basal ganglia, and prominent pons and midbrain abnormalities were displayed in 1 patient. Six patients died, 1 survived the acute illness with severe neurologic sequelae, and 1 recovered with mild sequelae. A limited postmortem examination revealed diffuse meningoencephalitis, neuronophagia, and focal vascular necrosis. Conclusions: Eastern equine encephalitis is a frequently fatal condition whose diagnosis is often delayed, and for which no effective treatments are known. Improved diagnostics are needed to facilitate patient care and encourage the development of treatments.

A comparison of three decalcification agents for assessments of cranial fracture histomorphology.

The extraction of mineral calcium from bone by decalcification is a critical step in the preparation of histological samples for light microscopy. This study assessed the time required for complete decalcification and the resultant histomorphological preservation of bone histomorphology by three decalcification agents: 7% hydrochloric acid (HCl), 5% nitric acid, and 10% ethylenediaminetetraacetic acid (EDTA). The goal of this study was to identify which decalcification agent provides the optimal combination of expedient processing and quality histological outcomes of cranial fracture samples. HCl provided the most rapid decalcification ( X ¯  = 3.57 days), nitric acid followed closely ( X ¯  = 10.35 days), while EDTA took significantly longer on average ( X ¯  = 78.97 days) but encompassed a broader range of times. Decalcification agent, sample thickness, sample width, and decedent age are significant predictors of decalcification time. Sample visualization quality, measured for tissues, cells, and nuclei on a five-point Likert scale, was highest for samples decalcified in 10% EDTA, second highest using 5% nitric acid, and lowest for 7% HCl. The quality difference between EDTA and nitric acid was not highly significant for any of the three features. For basic assessments of bone histomorphology, the study results indicate 5% nitric acid is suitable for the decalcification of adult specimens and samples thicker than 3 mm. EDTA is a suitable agent for thin samples of the cranial vault (<3 mm) from infants and young children less than three years old, decalcifying samples in a timeframe comparable to nitric acid while providing the best quality and clarity of samples.

Suicide in Older Adult Men Is Not Related to a Personal History of Participation in Football.

Introduction: It is reasonable to estimate that tens of millions of men in the United States played high school football. There is societal concern that participation in football confers risk for later-in-life mental health problems. The purpose of this study is to examine whether there is an association between a personal history of playing high school football and death by suicide. Methods: The subjects were obtained from the Lieber Institute for Brain Development (LIBD) brain donation program in collaboration with the Office of the Medical Examiner at Western Michigan University Homer Stryker MD School of Medicine. Donor history was documented via medical records, mental health records, and telephone interviews with the next-of-kin. Results: The sample included 198 men aged 50 or older (median = 65.0 years, interquartile range = 57-75). There were 34.8% who participated in contact sports during high school (including football), and 29.8% participated in high school football. Approximately one-third of the sample had suicide as their manner of death (34.8%). There was no statistically significant difference in the proportions of suicide as a manner of death among those men with a personal history of playing football compared to men who did not play football or who did not play sports (p = 0.070, Odds Ratio, OR = 0.537). Those who played football were significantly less likely to have a lifetime history of a suicide attempt (p = 0.012, OR = 0.352). Men with mood disorders (p < 0.001, OR = 10.712), substance use disorders (p < 0.020, OR = 2.075), and those with a history of suicide ideation (p < 0.001, OR = 8.038) or attempts (p < 0.001, OR = 40.634) were more likely to have suicide as a manner of death. Moreover, those men with a family history of suicide were more likely to have prior suicide attempts (p = 0.031, OR = 2.153) and to have completed suicide (p = 0.001, OR = 2.927). Discussion: Suicide was related to well-established risk factors such as a personal history of a mood disorder, substance abuse disorder, prior suicide ideation, suicide attempts, and a family history of suicide attempts. This study adds to a steadily growing body of evidence suggesting that playing high school football is not associated with increased risk for suicidality or suicide during adulthood.

Multiple system atrophy pathology is associated with primary Sjögren's syndrome.

BACKGROUNDOur objective was to investigate whether primary Sjögren's syndrome (pSS) is associated with multiple system atrophy (MSA).METHODSWe performed a retrospective cohort study assessing (a) rates of MSA in a cohort of patients with pSS and (b) rates of pSS in a cohort of patients with MSA. These data were compared with rates in respective control groups. We additionally reviewed the neuropathologic findings in 2 patients with pSS, cerebellar degeneration, parkinsonism, and autonomic dysfunction.RESULTSOur cohort of 308 patients with pSS had a greater incidence of MSA compared with 4 large population-based studies and had a significantly higher prevalence of at least probable MSA (1% vs. 0%, P = 0.02) compared with 776 patients in a control cohort of patients with other autoimmune disorders. Our cohort of 26 autopsy-proven patients with MSA had a significantly higher prevalence of pSS compared with a cohort of 115 patients with other autopsy-proven neurodegenerative disorders (8% vs. 0%, P = 0.03). The 2 patients we described with pSS and progressive neurodegenerative disease showed classic MSA pathology at autopsy.CONCLUSIONOur findings provide evidence for an association between MSA and pSS that is specific to both pSS, among autoimmune disorders, and MSA, among neurodegenerative disorders. The 2 cases we describe of autopsy-proven MSA support that MSA pathology can explain neurologic disease in a subset of patients with pSS. These findings together support the hypothesis that systemic autoimmune disease plays a role in neurodegeneration.FUNDINGThe Michigan Brain Bank is supported in part through NIH grant P30AG053760.

Primary diffuse leptomeningeal melanomatosis: Description and recommendations.

Primary melanocytic disease of the central nervous system is a rarely encountered condition currently without consensus on treatment and lacking major guidelines for management. Understanding the nature of the disease and differentiating primary melanocytic disease from the much more commonly encountered secondary (metastatic) melanoma is important in identifying the condition and pursuing appropriate treatment.

Hyperthermia, Thermal Injuries, and Death from a Forced Convection Heat Source: A Case Report and Experimental Model.

Heat-related deaths of children are most often encountered in the context of enclosed vehicles in summer months. Deviating from this, a 16-month-old boy was found unresponsive in a stroller that was placed adjacent to a space heater during mid-winter. The cause of death was hyperthermia and thermal injuries. Manner of death determination was difficult due to alleged surrounding circumstances. To understand the time-course of this child's injuries, a child death scene investigation was performed; the stroller and space heater were recovered. In a re-enactment of the events, a slaughtered pig approximating the child's size was warmed using a water bath and placed in the stroller beside the space heater. Cutaneous temperature measurements showed rapid initial temperature rise with subsequent steady increases. Tanning of the skin was seen on periodic direct observations. Internal temperature monitoring illustrated steady increases. This experiment was essential in classifying the manner of death as homicide.

Rapid intraoperative histology of unprocessed surgical specimens via fibre-laser-based stimulated Raman scattering microscopy.

Conventional methods for intraoperative histopathologic diagnosis are labour- and time-intensive, and may delay decision-making during brain-tumour surgery. Stimulated Raman scattering (SRS) microscopy, a label-free optical process, has been shown to rapidly detect brain-tumour infiltration in fresh, unprocessed human tissues. Here, we demonstrate the first application of SRS microscopy in the operating room by using a portable fibre-laser-based microscope and unprocessed specimens from 101 neurosurgical patients. We also introduce an image-processing method - stimulated Raman histology (SRH) - which leverages SRS images to create virtual haematoxylin-and-eosin-stained slides, revealing essential diagnostic features. In a simulation of intraoperative pathologic consultation in 30 patients, we found a remarkable concordance of SRH and conventional histology for predicting diagnosis (Cohen's kappa, κ > 0.89), with accuracy exceeding 92%. We also built and validated a multilayer perceptron based on quantified SRH image attributes that predicts brain-tumour subtype with 90% accuracy. Our findings provide insight into how SRH can now be used to improve the surgical care of brain tumour patients.

Commode Cardia-Death by Valsalva Maneuver: A Case Series.

The Valsalva maneuver is used in clinical medicine for the diagnosis and/or treatment of various cardiovascular conditions. It can also be used in activities of daily living, such as defecation. Due to the cardiovascular effects produced during the Valsalva maneuver, it may be contraindicated in certain medical conditions and could be a trigger of sudden cardiac death. The incidence and prevalence of death following Valsalva maneuver in the presence of underlying cardiovascular disease, or "commode cardia," has not been examined. In 2012, the Wayne County Medical Examiner's Office (Detroit, MI) investigated 21 deaths that occurred on the toilet, fourteen of which were due to cardiovascular disease. In another 31 deaths in the bathroom due to cardiovascular disease, the possibility that the decedent defecated immediately prior to death could not be excluded. Hence, the incidence of commode cardia in this population ranges from 2.3 to 7.4% of all cardiovascular-related deaths.

Neuropathology of Autosomal Dominant Alzheimer Disease in the National Alzheimer Coordinating Center Database.

Alzheimer disease (AD) represents a genetically heterogeneous entity. To elucidate neuropathologic features of autosomal dominant AD ([ADAD] due to PSEN1, APP, or PSEN2 mutations), we compared hallmark AD pathologic findings in 60 cases of ADAD and 120 cases of sporadic AD matched for sex, race, ethnicity, and disease duration. Greater degrees of neuritic plaque and neurofibrillary tangle formation and cerebral amyloid angiopathy (CAA) were found in ADAD (p values < 0.01). Moderate to severe CAA was more prevalent in ADAD (63.3% vs. 39.2%, p = 0.003), and persons with PSEN1 mutations beyond codon 200 had higher average Braak scores and severity and prevalence of CAA than those with mutations before codon 200. Lewy body pathology was less extensive in ADAD but was present in 27.1% of cases. We also describe a novel pathogenic PSEN1 mutation (P267A). The finding of more severe neurofibrillary pathology and CAA in ADAD, particularly in carriers of PSEN1 mutations beyond codon 200, warrants consideration when designing trials to treat or prevent ADAD. The finding of Lewy body pathology in a substantial minority of ADAD cases supports the assertion that development of Lewy bodies may be in part driven by abnormal ß-amyloid protein precursor processing.

Detection of human brain tumor infiltration with quantitative stimulated Raman scattering microscopy.

Differentiating tumor from normal brain is a major barrier to achieving optimal outcome in brain tumor surgery. New imaging techniques for visualizing tumor margins during surgery are needed to improve surgical results. We recently demonstrated the ability of stimulated Raman scattering (SRS) microscopy, a nondestructive, label-free optical method, to reveal glioma infiltration in animal models. We show that SRS reveals human brain tumor infiltration in fresh, unprocessed surgical specimens from 22 neurosurgical patients. SRS detects tumor infiltration in near-perfect agreement with standard hematoxylin and eosin light microscopy (κ = 0.86). The unique chemical contrast specific to SRS microscopy enables tumor detection by revealing quantifiable alterations in tissue cellularity, axonal density, and protein/lipid ratio in tumor-infiltrated tissues. To ensure that SRS microscopic data can be easily used in brain tumor surgery, without the need for expert interpretation, we created a classifier based on cellularity, axonal density, and protein/lipid ratio in SRS images capable of detecting tumor infiltration with 97.5% sensitivity and 98.5% specificity. Quantitative SRS microscopy detects the spread of tumor cells, even in brain tissue surrounding a tumor that appears grossly normal. By accurately revealing tumor infiltration, quantitative SRS microscopy holds potential for improving the accuracy of brain tumor surgery.

Autopsy findings in eight patients with fatal H1N1 influenza.

A novel H1N1 influenza A virus emerged in April 2009, and rapidly reached pandemic proportions. We report a retrospective observational case study of pathologic findings in 8 patients with fatal novel H1N1 infection at the University of Michigan Health Systems (Ann Arbor) compared with 8 age-, sex-, body mass index-, and treatment-matched control subjects. Diffuse alveolar damage (DAD) in acute and organizing phases affected all patients with influenza and was accompanied by acute bronchopneumonia in 6 patients. Organizing DAD with established fibrosis was present in 1 patient with preexisting granulomatous lung disease. Only 50% of control subjects had DAD. Peripheral pulmonary vascular thrombosis occurred in 5 of 8 patients with influenza and 3 of 8 control subjects. Cytophagocytosis was seen in all influenza-related cases. The autopsy findings in our patients with novel H1N1 influenza resemble other influenza virus infections with the exception of prominent thrombosis and hemophagocytosis. The possibility of hemophagocytic syndrome should be investigated in severely ill patients with H1N1 infection.