Neuropathological Autopsy Research Articles

On the regional distribution of cerebral microvascular 'raspberries' and their association with cerebral atherosclerosis and acute circulatory failure.

In this follow-up study, cerebral microvascular formations termed 'raspberries' were quantified according to cerebral atherosclerosis (C-ASCL) and acute circulatory failure (ACF). We also examined the regional distribution of raspberries throughout the brain. The study population consisted of adult individuals who had undergone a diagnostic neuropathological autopsy. Groups were formed to examine the association between raspberries, C-ASCL and ACF (control group, C-ASCL group, C-ASCL+ACF group [n=47 per group] and a combined C-ASCL-tot group [n=94]). To examine the regional distribution, additional groups were formed based on previously known raspberry densities of the frontal cortex (high-, medium- and low-density group [n=6 per group]). Raspberries were quantified on scanned haematoxylin-eosin-stained sections. Cortical raspberry density did not differ at a statistically significant level between the control group, the C-ASCL group and the C-ASCL+ACF group (P=0.10) but did so between the control group and the C-ASCL-tot group (P=0.033). The total raspberry density of the high-, medium- and low-density groups differed at a statistically significant level (P=0.005), which remained in group-to-group comparisons of the high- and medium-density groups (P=0.015) and the high- and low-density groups (P=0.002). Raspberries were rare in cerebral white matter and in the cerebellum. An association between raspberry density and C-ASCL is supported but is weaker than previously indicated. An association with ACF is not indicated. The raspberry density of the frontal cortex provides an approximation of the brain's total raspberry density.

Neuropathological autopsy findings in an individual with Alzheimer’s disease who received long‐term treatment with lecanemab (BAN2401)

AbstractBackgroundAnti‐amyloid antibodies administered to patients with Alzheimer’s disease can result in marked reduction of brain amyloid as measured by neuroimaging with amyloid PET ligands. However, there is a lack of pathological data. Here we present neuropathological findings in a patient who received ∼173 weeks of (interrupted) treatment with lecanemab (BAN2401), a humanized IgG1 monoclonal antibody that preferentially targets soluble aggregated β‐amyloid species (protofibrils) and insoluble fibrils, in a Phase 2 study (NCT01767311, Alz Res Therapy 2021;13:80).MethodBrain autopsy was performed on an ∼85 year old whose lecanemab treatment history over 6 years was: 79 weeks 10mg/kg monthly in the double‐blind (DB) phase, then 98 weeks without treatment, then 94 weeks at 10mg/kg biweekly in the open‐label extension (OLE) phase, followed by ∼12 weeks of treatment discontinuation prior to death.ResultClinically, memory symptoms started age ∼77. Study entry was at age ∼80, with mild dementia, CDR 0.5, CDR‐SB 3, and MMSE 24. Florbetapir PET scan was positive at baseline, and negative after 53 weeks DB treatment and at start of OLE. These findings and clinical measures are shown in Table 1. ARIA was not observed during the study. Autopsy showed low brain weight (1052g) with diffuse atrophy, including hippocampi, consistent with atrophy seen on clinical MRI scans. Microscopic findings showed tau pathology including tangles and threads (by AT8 antibody and Bielschowsky staining) throughout neocortex (Braak NF stage VI; B3). Beta‐amyloid immunohistochemical stain (6E10) showed only modest amyloid load (Thal phase 2; A1), with near‐absence of diffuse amyloid deposits and only scattered clusters of neuritic plaques (CERAD stage B; C2).ConclusionIn this autopsy of an individual with Alzheimer’s disease treated with lecanemab, neuropathological changes showed tau and β‐amyloid deposits. However, the pattern of significant tau pathology, accompanied by only a mild degree of β‐amyloid deposits, (A1B3C2), is uncommon in typical (untreated) Alzheimer’s disease. For example, in the NACC neuropathology dataset, only 2% of brains with Braak B2 or B3 show Thal stage A0 or A1. This pattern suggests that lecanemab treatment resulted in a reduction in brain amyloid, consistent with the amyloid PET scanning results in this patient.

Update on collaborative autopsy-based research in German pathology, neuropathology, and forensic medicine

HintergrundObduktionen sind ein wichtiges Instrument zum Verständnis von Krankheiten, einschließlich COVID-19.Material und MethodenDas im April 2020 eingerichtete und gestartete Deutsche Register für COVID-19-Obduktionen (DeRegCOVID) dient als elektronisches Rückgrat des Nationalen Obduktionsnetzwerks (NATON), das Anfang 2022 im Anschluss an DEFEAT PANDEMIcs gestartet worden ist.ErgebnisseDie vernetzte, kollaborative Obduktionsforschung des NATON-Konsortiums wird durch eine beispiellose Zusammenarbeit von 138 Personen an mehr als 35 universitären und nichtuniversitären Obduktionszentren ermöglicht, durch die Daten, einschließlich Daten zu Biomaterialien aus Pathologie, Neuropathologie und Rechtsmedizin, im DeRegCOVID gesammelt sowie gewebebasierte Forschung und Methodenentwicklung betrieben werden. Aus den teilnehmenden Obduktionszentren sind inzwischen mehr als 145 Publikationen hervorgegangen, die verschiedene grundlagenwissenschaftliche und klinische Aspekte von COVID-19 beleuchten, z. B. thromboembolische Ereignisse, Organtropismus, Nachweismethoden von SARS-CoV‑2 oder die Infektiosität von SARS-CoV‑2 bei der Obduktion.SchlussfolgerungenDie teilnehmenden Zentren haben den hohen Wert der Autopsie und der aus der Autopsie gewonnenen Daten und Biomaterialien für die moderne Medizin unter Beweis gestellt. Die geplante langfristige Fortführung und Weiterentwicklung des Registers und Netzwerks und die offene und partizipative Gestaltung ermöglichen es, alle interessierten Partner miteinzubeziehen.

Central nervous system autopsy - a neuropathological procedure based on multidisciplinary pathoclinical cooperation.

Neuropathological brain and spinal cord post mortem examination is a distinct procedure that still plays an important role in modern medicine. In front of increasing amounts of clinical and genetic data, together with important developments in the field of neuroimaging, the Polish Association of Neuropathologists have updated their recommendations regarding central nervous system (CNS) examination. These guidelines are aimed at neuropathologists, pathologists and clinicians. Presentation of the outlined recommendations as their goal is to improve the quality, informativity, and cost effectiveness of CNS post mortem examinations. A comprehensive study of the literature was conducted to provide a clinical background of neuropathological autopsy. There are numerous open questions in neuroscience, and new strategies are required to foster research in CNS diseases. These include the challenge of organizing brain banks tasked with managing and protecting detailed multidisciplinary information about their resources. Complex neuropathological analyses of post mortem series are also important to assess the effectiveness of diagnostics and therapy, identify environmental impact on the development of neurological disorders, and improve public health policy. The recommendations outline the need for collaboration between multiple specialists to establish the proper diagnosis and to broaden knowledge of neurological disorders.

Autopsy Human Brain Dissection Protocol for Common Age-Related Neurodegenerative Disorders.

Age-related neurodegenerative disorders are common causes of dementia-associated morbidity and mortality in populations throughout the world. Standardized, protocol-based methods for the examination and diagnosis of these disorders allow direct comparison between human cohorts and play a key role in understanding how these disorders impact our population. Further understanding of these protocols and harmonization with animal and in vitro investigative techniques is imperative to demonstrate relevance to human disease. The following is a concise protocol for the examination of human whole brain autopsy samples, with and without spinal cord, for the examination of neurodegenerative disorders. The following protocol is designed to provide samples appropriate for most neurodegenerative diseases. The collection of both fresh-frozen and formalin-fixed tissues is described.This guide presumes general knowledge of neuroanatomy of the human central nervous system. Tissue processing, detailed histological techniques and complete diagnostic examination of the brain is beyond the scope of this chapter; however, a limited evaluation appropriate for the evaluation of neurodegenerative disease is described here. Diagnostic protocols for the most common causes of dementia-associated, age-related neurodegenerative disorders are also summarized.

Traumatic brain injury and age at onset of cognitive decline in corticobasal degeneration, corticobasal syndrome, and progressive supranuclear palsy

AbstractBackgroundTraumatic brain injury (TBI) has been repeatedly shown to be a risk factor for several neurodegenerative diseases. However, no studies have yet examined TBI as a risk factor for corticobasal degeneration (CBD) or corticobasal syndrome (CBS), and few have examined progressive supranuclear palsy (PSP) in relation to TBI.MethodThis is a retrospective observational study using the National Alzheimer’s Coordinating Centers (NACC) database. TBI status was assessed based on self‐reported history. Clinicians estimate was used for determining age at onset (AAO) of cognitive decline and autopsy examination was used for neuropathological diagnosis of CBD and PSP. The most recent assessment of participants was used as of June 2018, including participant visits which occurred between 2005 and 2018. The NACC dataset includes a total of 38,249 participants. 101 (14 TBI+) participants were included with clinical (antemortem) diagnoses of PSP and 137 (16 TBI+) with CBS. 2,743 autopsy samples were also included, including 120 (14 TBI+), 58 (7 TBI+), and 11 (1 TBI+) with neuropathological (autopsy) diagnoses of PSP, CBD, or both, respectively. 181 (21 TBI+) of the participants with autopsy diagnosed PSP or CBD had antemortem cognitive decline.ResultTBI is associated with a significant 4‐year earlier AAO of cognitive decline among participants with an antemortem diagnosis of CBS and a 6‐year earlier AAO in participants with autopsy diagnosed PSP. Additionally, TBI among participants with autopsy diagnosed CBD without concomitant Alzheimer’s disease (AD) neuropathology was associated with a 7‐year earlier AAO of cognitive decline (p=.066). History of TBI was not significantly associated with the prevalence of PSP and/or CBD pathology postmortem.ConclusionThis is the first report linking TBI with an earlier onset of cognitive decline in CBS and in neuropathologically defined PSP.

Association of neighborhood-level disadvantage with neurofibrillary tangles.

Neighborhood disadvantage, a social exposome measure reflecting income, education, employment, and housing in a census-block group, is associated with markers of Alzheimer's disease brain health such as brain volume and amyloid plaque presence. Yet it is not known whether this association extends to neurofibrillary degeneration, signaling a stronger link to neuropathology confirmed Alzheimer's disease. A cross sectional analysis was conducted using a sample of decedents from two Alzheimer's Disease Research Center brain banks with known Braak stage and neighborhood disadvantage ranking from 1990-2016 (n=428). Neurofibrillary tangle Braak stage was abstracted from data collected via the Neuropathology Data Set form or autopsy reports for earlier donations. The main exposure was neighborhood-level disadvantage measured by the Area Deprivation Index. Generalized ordered logistic regression with site-level clustered standards errors was used to model the ordinal neurofibrillary B score adjusting for age, sex, rurality, geographic proximity to the Alzheimer center, and year of death. Living in a disadvantaged neighborhood at the time of death was associated with more severe neurofibrillary degeneration: for every decile increase in neighborhood disadvantage, there was a 2% increase in the odds of having a more severe B score (OR=1.02, 95% CI, 1.01-1.03) after adjustment. This 2% increase was proportional when comparing the odds at each increasing level of the neurofibrillary tangle B score-when comparing the odds of B score (1,2,3,) vs (0), B score (2,3) vs (0,1), and B score (3) vs (0,1,2). With these new findings, neighborhood disadvantage has been associated with both of the hallmarks signs of Alzheimer's disease neuropathology. Given that Alzheimer's is a life course problem with neuropathologic changes accumulating over decades, future work should apply a life course approach to understand how lifetime exposure accumulation impacts brain health. Taking such a perspective can move the field closer to uncovering and disrupting the social-to-biological pathways impacting Alzheimer's disease brain health and related disparities.

Neuropathologic Findings in Chronic Kidney Disease (CKD)

Studying the neuropathologic autopsy findings in subjects with chronic kidney disease (CKD) or chronic renal failure (CRF) is difficult for several reasons: etiology of the CKD may be heterogeneous, affected patients may have one or more major co-morbidities that themselves can cause significant neurologic disease, and agonal events may result in significant findings that were of minimal significance earlier in a patient's life. We studied the constellation of neuropathologic abnormalities in 40 autopsy brains originating from subjects of ages 34-95 years (no children in the study). The most common pathologic change was that of ischemic infarcts (cystic, lacunar and/or microinfarcts), which were seen in over half of subjects. These were associated with both large artery atherosclerosis and arteriolosclerosis (A/S), the latter finding being present in 29/40 subjects. Charcot-Bouchard microaneurysms were present in the brains of three subjects, in one case associated with severe amyloid angiopathy. Microvascular calcinosis (medial sclerosis in the case of arterioles) was seen in the basal ganglia (n=8) and/or endplate region of the hippocampus (n=7) and occasional ischemic infarcts in one brain showed severe calcification. Sequelae of cerebrovascular disease (especially A/S or microvascular disease) are a common neuropathologic substrate for neurologic disability and brain lesions in this complex group of patients. Regulation of calcium metabolism within brain microvessel walls may be worthy of further research in both human brain specimens and animal models.

Meningomyeloencephalitis secondary to Mycobacterium haemophilum infection in AIDS

Infections by opportunistic non-tuberculous mycobacteria (NTM) are rising in global incidence. One emerging, slowly growing NTM is Mycobacterium haemophilum, which can cause skin, lung, bone, and soft tissue infections in immunocompromised patients as well as lymphadenitis in immunocompetent individuals. Detection of this microorganism is difficult using conventional culture-based methods and few reports have documented involvement of this pathogen within the central nervous system (CNS).We describe the neuropathologic autopsy findings of a 39-year-old man with AIDS who died secondary to M. haemophilum CNS infection. He initially presented with repeated bouts of pyrexia, nausea and vomiting, and altered mental status that required numerous hospitalizations. CSF infectious workups were consistently negative. His most recent admission identified hyperintensities within the brainstem by MRI and despite antibiotic therapies for suspected CNS infection, he died. Autopsy revealed a swollen brain with marked widening of the brainstem. Microscopic examination of the brain and spinal cord showed focal lymphohistiocytic infiltrates, gliosis and neuronal loss that were associated with acid-fast bacilli (AFB). The brainstem was the most severely damaged and AFB were found to congregate along arterial territories lending support to the notion of hematogenous spread as a mechanism for the organisms’ dissemination. 16S rRNA sequencing on formalin-fixed paraffin-embedded tissue enabled post-mortem identification of M. haemophilum. This sequencing methodology may permit diagnosis on CSF intra-vitam.

Epilepsy Related Death: the London Health Sciences Center Experience

Premature mortality among epilepsy patients is well recognized. Except a few identifiable causes of unnatural death, more than half of the epilepsy related death remains unexplained after extensive workup. These cases are classified as sudden unexpected death in epilepsy (SUDEP). SUDEP incidence varies significantly depending on the population, the methods documenting cause of death and the availability of Neuropathological examination. An accurate diagnosis of the cause of death is needed for epilepsy related death. The goal of this study is to present the relevant clinical data, the general autopsy and Neuropathology findings of epilepsy related death investigated in London Health Sciences Center during the period of 2000 to 2011. We identified 71 cases with known history of chronic epilepsy. In the 29 cases of epilepsy associated death, the causes of death have been classified as cardiac, pulmonary, accidental (e.g. drowning), toxic (e.g. drug overdose) and non-related causes. Forty two cases are considered to be SUDEP, and were categorized according to the recently proposed SUDEP Definition and Classification. Half of the SUDEP cases have no specific Neuropathological findings. The most common identifiable lesions in SUDEP cases are perinatal/neonatal destructive lesions (29%), hippocampal sclerosis (24%), and focal cortical dysplasia (20%). These are followed by neuronal heterotopia (9%), previous head trauma (9%), and cavernoma (5%).LEARNING OBJECTIVESThis presentation will enable the learner to:1.Review cause of death in epilepsy related deaths2.Discuss the practice guideline in neuropathology autopsy of epilepsy related deaths

CNS findings in chronic fatigue syndrome and a neuropathological case report

Chronic fatigue syndrome (CFS) is characterized as a persistent, debilitating complex disorder of unknown etiology, whereby patients suffer from extreme fatigue, which often presents with symptoms that include chronic pain,...

CHCHD10 variant p.(Gly66Val) causes axonal Charcot-Marie-Tooth disease.

Objective:We describe the phenotype consistent with axonal Charcot-Marie-Tooth disease type 2 (CMT2) in 4 families with a c.197G>T (p.(Gly66Val)) variant in CHCHD10.Methods:We sequenced the CHCHD10 gene in a cohort of 107 families with CMT2 of unknown etiology. The patients were characterized by clinical examination and electroneuromyography. Muscle MRI and biopsy of the muscle or nerve were performed in selected cases. Neuropathologic autopsy was performed in 1 case.Results:The c.197G>T variant in CHCHD10 was found in 6 families, 4 of which included multiple individuals available for detailed clinical study. Variants in this gene have recently been associated with amyotrophic lateral sclerosis-frontotemporal dementia, mitochondrial myopathy, or spinal muscular atrophy Jokela type (SMAJ), but not with CMT2. Our patients had a late-onset distal axonal neuropathy with motor predominance, progressing to involve sensory nerves. Neurophysiologic and neuropathologic studies confirmed the diagnosis of sensorimotor axonal neuropathy with no loss of anterior horn neurons. Muscle biopsies showed occasional cytochrome c oxidase–negative fibers, combined with small amounts of mitochondrial DNA deletions.Conclusions:CHCHD10 c.197G>T (p.(Gly66Val)) is a cause of sensorimotor axonal neuropathy. This gene should be considered in patients presenting with a pure CMT2 phenotype, particularly when motor symptoms predominate.

Proteinase-activated receptor 2 and disease biomarkers in cerebrospinal fluid in cases with autopsy-confirmed prion diseases and other neurodegenerative diseases.

BackgroundProteinase-activated receptor 2 (PAR-2) has been shown to promote both neurotoxic and neuroprotective effects. Similarly, other routinely used nonspecific markers of neuronal damage can be found in cerebrospinal fluid (CSF) and can be used as biomarkers for different neurodegenerative disorders.MethodsUsing enzyme-linked immunosorbent assays and western blotting we assessed PAR-2, total-tau, phospho-tau, beta-amyloid levels, and protein 14-3-3 in the CSF of former patients who had undergone a neuropathological autopsy after death and who had been definitively diagnosed with a prion or other neurodegenerative disease.ResultsWe did not find any significant correlation between levels of PAR-2 and other biomarkers, nor did we find any differences in PAR-2 levels between prion diseases and other neurodegenerative conditions. However, we confirmed that very high total-tau levels were significantly associated with definitive prion diagnoses and exhibited greater sensitivity and specificity than protein 14-3-3, which is routinely used as a marker.ConclusionsOur study showed that PAR-2, in CSF, was not specifically altered in prion diseases compared to other neurodegenerative conditions. Our results also confirmed that very high total-tau protein CSF levels were significantly associated with a definitive Creutzfeldt-Jakob disease (CJD) diagnosis and should be routinely tested as a diagnostic marker. Observed individual variability in CSF biomarkers provide invaluable feedback from neuropathological examinations even in “clinically certain” cases.Electronic supplementary materialThe online version of this article (doi:10.1186/s12883-015-0300-x) contains supplementary material, which is available to authorized users.

Changing times - changing diseases. Review of the neuropathological autopsy documentations at the Markusovszky University Teaching Hospital (1964-2014)

Nearly 6000 autoptic studies were carried out during the last 50 years at the Laboratory of Neuropathology, Markusovszky University Teaching Hospital, Hungary. The aim of the authors was to present those previously frequent and often fatal conditions that can be prevented or treated today. Retrospective analyses of the neuropathological documentations. Measles-related subacute sclerosing panencephalitis caused death in 13 cases, the last occurred in 1991. The mandatory vaccination against the causative virus has eliminated this severe neurological complication. Fourteen lives were lost due to herpes simplex encephalitis, including the last case seen in 1999. Feasibility of early diagnosis and the availability of acyclovir therapy resulted in better outcome without fatality. Tuberculous meningitis still occurred in most recent years, although only sporadically. Recognition of this condition is not straightforward due to its rarity, and considerations for this disease are often omitted from the routine differential diagnosis. The generally low mortality rates in tick borne encephalitis further dropped after the introduction of vaccination. Altogether only 8 such cases were documented. The last fatal cases of neurolues were seen in the 1990s. However, syphilis itself has not disappeared, and the number of cases with newly acquired infection continues to rise. The introduction of intrathecal methotrexate and radiotherapy made possible the prevention or effective treatment of meningeal leukosis. A careful coordination of these treatment modalities, however, is important as nervous system complications may develop in the form of disseminated necrotizing leukoencephalopathy that is also reflected in the records. The 50-year neuropathology documentation reflects changes in the occurrence of diseases, and it calls attention to those disorders which can be prevented or treated today, but may represent diagnostic challenges.

An evaluation of overnight fixation to facilitate neuropathological examination in Coroner's autopsies: our experience of over 200 cases

AimsFollowing recent changes in Coroner's Rules, there has been a desire to examine brains at the time of autopsy, rather than after a prolonged period of immersion fixation. Examination of...

Neuropathology and general autopsy findings in nondemented aged subjects

A retrospective study of the essential general pathology and neuropathological features in 100 nondemented individuals aged 65 years or older (mean 81.23 ± 5.47 y) was performed using semiquantitative methods. 91% of the patients had a history of hypertension, 31% malignancies, 24% COPD, 18% myocardial infarction, and 4% stroke. Major causes of death were cardiovascular decompensation, pneumonia, acute myocardial infarction, and malignancies. General autopsy revealed severe systemic and coronary atherosclerosis in 86 and 90%, respectively, renal angioangiolosclerosis in 82%, acute or recurrent myocardial infarction in 65%, and other diseases. Neuropathology showed average brain weight of 1,163 ± 113 g, mild to moderate brain atrophy, absent to mild atherosclerosis of large cerebral arteries in 46%, mild, moderate and severe one in 31, 17, and 6%, respectively. There were considerable discrepancies in the severity between generalized/ aortic and intracranial atherosclerosis, only less than one-third being comparable. Negative Khachaturian criteria and CERAD Stage 0 were observed in 83 and 86%, respectively, only 13% with CERAD Stage A, and 1% Stage B. Braak neuritic stages ranged from 0 to II (53%), II - III (29%) to III - IV (18%), none scoring Grade V or VI. The average Braak score was 2.3 ± 0.8. Vascular pathologies were common; CAA was absent in 61%, mild or moderate in 36% and severe in 3%. Mild to severe lacunar state in basal ganglia and/or white matter was seen in 73%, hippocampal sclerosis in 3 cases, while only 9% were free of cerebrovascular lesions. Lewy bodies were observed in 5 brains involving substantia nigra (n = 3), cerebral cortex (n = 1) and medulla oblongata (n = 1), 1 case representing incidental Lewy body disease. τ pathology in brainstem was observed in 60 cases (60%). Mixed cerebral pathologies (cerebrovascular lesions and moderate neuritic Braak stages) were observed in 6 cases (mean age 89.6 y). The importance of mixed pathologies in nondemented elderly, being less frequent than in other studies, remains to be elucidated.

The critically ill patient with ataxia–telangiectasia

To describe the presentation, clinical course, and outcomes of critically ill patients with ataxia-telangiectasia. Retrospective case series. Adult and pediatric intensive care units at an urban tertiary academic center. Seven consecutive patients with confirmed diagnosis of ataxia-telangiectasia had nine intensive care admissions between January 1995 and December 2009. None. Mean age at time of admission 15.9 yrs (median, 13.9 yrs; range, 7.3-33.9 yrs). Mean duration of intensive care unit stay was 17 days (median, 9 days; range, 2-39 days). The most common admitting diagnosis was respiratory distress (six of seven patients). There was no difference in ventilator settings or duration of intensive care unit stay between survivors and nonsurvivors (p > .05). Forty-three percent (three of seven patients) survived to intensive care unit discharge with a 3-yr survival that was 14% (one of seven patients). Critically ill patients with ataxia-telangiectasia have complex, multisystem diseases. In this case series, the most common intensive care unit admission diagnosis was respiratory failure. Suspected or confirmed bacterial infections were prevalent. Neuropathologic autopsy findings were similar to those previously reported. Special considerations for the critical care of patients with ataxia-telangiectasia are discussed.

Regional neuropathology referral practice before and after new organ retention legislation

Previous organ retention controversies in the United Kingdom have resulted in public concern in relation to the retention of organs following post mortem examination. Therefore, protocols were devised and implemented to facilitate adequate sampling for diagnostic purposes for neuropathology autopsy referrals, without the need for organ retention. We have examined various aspects of referral practice before and after the introduction of these new sampling protocols. All neuropathology autopsy referral cases were reviewed between 1993 and 1995, and 2003 and 2005 and data such as: referral source, nature of samples (whether whole organ or limited sampling) and final diagnosis were recorded. Overall, the number of autopsy cases referred for neuropathology opinion reduced, particularly those originating from hospital consented autopsies. Forensic referrals also reduced, with a shift in practice from referrals of whole fixed brains, to both whole brains and sampled brain slices. Within the referrals from forensic practice, whilst cases of 'natural deaths' and head injury cases secondary to road traffic accidents or falls reduced, cases involving inflicted, traumatic head injury and sudden unexpected death in epilepsy and infancy remained static. The introduction of protocols to facilitate sampling of brains at autopsy, so minimising organ retention, proved successful and, whilst there has been a reduction in neuropathology referrals, cases in which neuropathology input is deemed best practice remained static.

Immunohistochemistry utilization in autopsy pathology: A Canadian experience

Immunohistochemistry (IHC) is an important part of the diagnostic work-up in surgical pathology, but the use of IHC in autopsy pathology is poorly defined. We measured IHC utilization by pathologists performing 609 consecutive non-medicolegal, hospital-based, adult autopsies over a three-year period. IHC requests on non-neurologic and neurologic material were analyzed separately. Total stains, number of tissue blocks, specific antibody requests, resident trainee involvement, and ordering pathologist were recorded. For all autopsies on which IHC was requested, the final autopsy report was reviewed. IHC was requested on 345 cases (57%), and a total of 4612 stains were performed (mean 13.5 per autopsy). For non-neurologic autopsy tissues, IHC was used most commonly for the accurate diagnosis of malignancy. For neuropathologic autopsy examinations, IHC was employed most commonly to exclude neurodegenerative conditions and correlate ante-mortem clinical neurologic findings. Resident involvement did not significantly impact utilization. Individual pathologists demonstrated a wide variation in IHC utilization. We conclude that IHC is used extensively in Canadian non-medicolegal autopsy pathology reflecting the complexity, extent, and severity of disease in patients dying in a tertiary-care, academic hospital setting. Utilization is strongly influenced by the neuropathology component of these autopsies. The results provide a point of reference for IHC utilization in autopsy pathology.

Cause of death and clinical grading criteria in a cohort of amyotrophic lateral sclerosis cases undergoing autopsy from the Scottish Motor Neurone Disease Register

Background: The Scottish Motor Neurone Disease Register is a population based register of amyotrophic lateral sclerosis/motor neurone disease (ALS/MND) in Scotland, with high case ascertainment levels. Objective: To investigate the...