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Postmortem computed tomography (PMCT) is integrated into the evaluation of decedents in several American medical examiner offices and medicolegal death investigative centers in many other countries. We retrospectively investigated the value of PMCT in a series of firearm homicide cases from a statewide centralized medical examiner’s office that occurred during 2016. Autopsies were performed or supervised by board‐certified forensic pathologists who reviewed the PMCT scans prior to autopsy. PMCT scans were re‐evaluated by a forensic radiologist blinded to the autopsy findings and scored by body region (head–neck, thoracoabdominal, and extremities). Injury discrepancies were scored using a modified Goldman classification and analyzed with McNemar’s test. We included 60 males and 20 females (median age 31 years, range 3–73). Based on PMCT, 56 (79.1%) cases had injuries relevant to the cause of death in a single body region (24 head–neck region, 32 thoracoabdominal region). Out of these 56 cases, 9 had a missed major diagnosis by PMCT outside that region, including 6 extremity injuries visible during standard external examination. Yet all had evident lethal firearm injury. We showed that PMCT identifies major firearm injuries in homicide victims and excludes injuries related to the cause of death in other regions when a single body region is injured. Although PMCT has a known limited sensitivity for soft tissue and vascular pathology, it can be combined with external examination to potentially reduce or focus dissections in some of these cases depending on the circumstances and medicolegal needs.

Background: Dementia with Lewy bodies (DLB) is a common form of dementia. The presence of Alzheimer’s disease (AD) pathology modifies the clinical features of DLB, making it harder to distinguish DLB from AD clinically during life. Clinical diagnostic criteria for DLB applied at presentation can fail to identify up to 50% of cases. Our aim was to determine, in a series of patients with dementia in whom autopsy confirmation of diagnosis was available, whether functional imaging of the nigrostriatal pathway improves the accuracy of diagnosis compared with diagnosis by means of clinical criteria alone. Methods: A single photon emission computed tomography (SPECT) scan was carried out with a dopaminergic presynaptic ligand [ 123 I]-2beta-carbometoxy-3beta-(4-iodophenyl)-N-(3-fluoropropyl) nortropane (FP-CIT; ioflupane) on a group of patients with a clinical diagnosis of DLB or other dementia. An abnormal scan was defined as one in which right and left posterior putamen binding, measured semiquantitatively, was more than 2 SDs below the mean of the controls. Results: Over a 10 year period it was possible to collect 20 patients who had been followed from the time of first assessment and time of scan through to death and subsequent detailed neuropathological autopsy. Eight patients fulfilled neuropathological diagnostic criteria for DLB. Nine patients had AD, mostly with coexisting cerebrovascular disease. Three patients had other diagnoses. The sensitivity of an initial clinical diagnosis of DLB was 75% and specificity was 42%. The sensitivity of the FP-CIT scan for the diagnosis of DLB was 88% and specificity was 100%. Conclusion: FP-CIT SPECT scans substantially enhanced the accuracy of diagnosis of DLB by comparison with clinical criteria alone.

Background: The neurobiological changes underlying the association of the apolipoprotein E (APOE) e4 allele with level of cognition are poorly understood. Objective: To test the hypothesis that amyloid load can account for (mediate) the association of the APOE e4 allele with level of cognition assessed proximate to death. Methods: There were 44 subjects with clinically diagnosed Alzheimer's disease and 50 without dementia, who had participated in the Religious Orders Study. They underwent determination of APOE allele status, had comprehensive cognitive testing in the last year of life, and brain autopsy at death. The percentage area of cortex occupied by amyloid beta and the density of tau positive neurofibrillary tangles were quantified from six brain regions and averaged to yield summary measures of amyloid load and neurofibrillary tangles. Multiple regression analyses were used to examine whether amyloid load could account for the effect of allele status on level of cognition, controlling for age, sex, and education. Results: Possession of at least one APOE e4 allele was associated with lower level of cognitive function proximate to death (p = 0.04). The effect of the e4 allele was reduced by nearly 60% and was no longer significant after controlling for the effect of amyloid load, whereas there was a robust inverse association between amyloid and cognition (p = 0.001). Because prior work had suggested that neurofibrillary tangles could account for the association of amyloid on cognition, we next examined whether amyloid could account for the effect of allele status on tangles. In a series of regression analyses, e4 was associated with density of tangles (p = 0.002), but the effect of the e4 allele was reduced by more than 50% and was no longer significant after controlling for the effect of amyloid load. Conclusion: These findings are consistent with a sequence of events whereby the e4 allele works through amyloid deposition and subsequent tangle formation to cause cognitive impairment.

Background: Intravascular lymphoma (IVL) is a rare non-Hodgkin's lymphoma with relative predilection for the central nervous system. In the absence of extraneural manifestations, the disease is not recognised until autopsy in the majority of cases underlining the need for new clinical markers. Methods: This is a retrospective series of five patients with IVL seen at a single institution over three years. An advanced magnetic resonance imaging (MRI) protocol was performed at various time points prior to diagnosis and during treatment. Results: MRI revealed multiple lesions scattered throughout the cerebral hemispheres; the brainstem, cerebellum, and spinal cord were less frequently involved. On initial presentation, hyperintense lesions were seen on diffusion weighted images suggestive of ischaemia in three of four patients in whom the images were obtained at that time point. In four patients lesions were also identifiable as hyperintense areas on fluid attenuated inversion recovery (FLAIR) sequences. Initial contrast enhancement was encountered in three cases. Diffusion weighted imaging lesions either vanished or followed the typical pattern of an ischaemic small vessel stroke with evolution of abnormal FLAIR signal followed by enhancement with gadolinium in the subacute stage and tissue loss in the chronic stage. Diffusion weighted imaging and FLAIR abnormalities proved to be partially reversible, correlating with the response to chemotherapy. Conclusion: We provide the first detailed description of the dynamic pattern of diffusion weighted MRI in IVL. These patterns in combination with systemic findings may facilitate early diagnosis and serve as a new tool to monitor treatment response.

Objective: To investigate abnormal prion protein (PrP) deposition in the peripheral nervous system (PNS) in human prion diseases. Methods: Eight patients with prion diseases were examined: three with sporadic Creutzfeldt–Jakob disease (sCJD), two with dural graft associated CJD (dCJD), one with Gerstmann–Straussler–Scheinker disease (GSS) with a PrP P102L mutation (GSS102), and two with a P105L mutation (GSS105). An atypical case of sCJD with PrP plaques in the brain presented clinically with peripheral neuropathy, and showed demyelination in 12% of the teased fibres of the sural nerve. The PNS was investigated by immunohistochemical and western blotting analyses of PrP. Results: In immunohistochemical studies, granular PrP deposits were detected in some neurones of dorsal root ganglia and a few fibres of peripheral nerves and spinal posterior roots in one sCJD and two dCJD patients, but not in GSS102 or GSS105 patients. The atypical case of sCJD with peripheral neuropathy showed no obvious PrP deposition in the nerves. Western blotting analysis of the PNS from the dCJD patients revealed a small amount of protease K resistant PrP in the dorsal root ganglia and peripheral nerves. Conclusions: Abnormal PrP deposition occurs in the dorsal root ganglia and peripheral nerves in sCJD and dCJD. The PrP deposits in the PNS are not correlated with clinical manifestation of peripheral neuropathy in CJD.

Objective: In view of the association of the apolipoprotein E ( APOE ) e4 allele with poor outcome after traumatic brain injury we determined the frequency of cerebral amyloid angiopathy (CAA) and the extent of haemorrhagic pathology in relation to APOE genotype in an autopsy series of 88 head injured cases. Methods: Tissue sections from the frontal and temporal lobes were immunostained for amyloid-β peptide (Aβ) and stained for Congo red to identify vascular amyloid pathology. A semiquantitative assessment of contusions, the total contusion index, was used to estimate the severity of the haemorrhagic pathology. APOE genotypes were determined by polymerase chain reaction of genomic DNA extracted from paraffin embedded tissue sections. Results: CAA was present in 7/40 (18%) e4 carriers compared with 1/48 (2%) non-e4 carriers (p = 0.021, 95% confidence interval (CI) for difference in proportions with CAA 3% to 29%) with 6/40 (4 with CAA) e4 carriers being homozygotes. Thus the risk of having CAA for e4 carriers was 8.4 times that for the non-e4 carriers. However, there was no clear tendency for patients with CAA to have more severe or more numerous contusions (median contusion index 19 (CAA) v 14.5, p = 0.23, 95% CI for difference in medians −5 to 14). Conclusions: Presence of CAA in head injured cases was significantly associated with possession of an APOE e4 allele but not with the severity of contusions.

Background: The presence of Lewy bodies (LB) in the neocortex and limbic system in patients with Parkinson's disease (PD) is commonly thought to be linked with cognitive impairment. The authors present here a series of patients with diagnosis of PD in life and no significant cognitive impairment who, at necropsy, satisfied the current neuropathological criteria for dementia with Lewy bodies (DLB). Methods: Two hundred and seventy six brains with PD pathology were examined at the Queen Square Brain Bank in London between 1993 and 1999. The neuropathological diagnosis was PD, but 117 patients also had sufficient LB involvement above the brain stem to satisfy the current neuropathological criteria for DLB (50 patients had a neuropathological picture consistent with the limbic category of DLB and 67 with neocortical DLB). Forty eight cases were excluded who developed early cognitive impairment together with motor features of parkinsonism, 12 cases for lack of detailed clinical history, and 19 cases with coexistent features of advanced Alzheimer's disease changes. Thirty eight patients (13.8% of the total with PD pathology and 32.5 % of the total with DLB pathology) were found where there was no or very late cognitive impairment reported in the clinical records. Results: Selected cases were 24 men and 14 women, with a mean (SD) age at onset of parkinsonian symptoms of 60.1 (10.1) years and a mean disease duration of 15.3 (5.5) years. At some time during the evolution of the disease 21 patients developed different degrees of cognitive impairment (after a mean disease duration of 12.2 (4.8) years). Clinical diagnosis at death was PD in 10 cases and PD with dementia in 11. In the remaining 17 patients no history of cognitive impairment was ever recorded in life and all of them had a clinical diagnosis of PD at death; in this subgroup, nine patients later revealed a neuropathological picture consistent with limbic (or transitional) category of DLB and eight with neocortical DLB. Interestingly, in all these patients the parkinsonian features including the response to dopaminergic drugs were indistinguishable from classic brain stem PD. Conclusions: The authors demonstrate that the classic pathology of DLB can commonly be seen outside the generally accepted clinical spectrum for DLB and that important factors other than the absolute number of LB in the neocortex and limbic system influence the development of cognitive impairment in PD. Furthermore, the pathology of PD may be indistinguishable from that reported in DLB, suggesting that the two clinicopathological syndromes may be attributable to the same biological abnormality.

Background: Many patients diagnosed with Parkinson's disease are later found to have an erroneous diagnosis, often only when they come to necropsy; conversely, many patients with Parkinson's disease in the community remain undiagnosed. Objective: To assess the validity of a clinical diagnosis of parkinsonism in the general population according to strict published criteria. Methods: As part of a population based study on the prevalence of Parkinson's disease in London, all patients were identified with a diagnosis of parkinsonism, tremor with onset over age 50 years, or who had ever received antiparkinsonian drugs. All patients who agreed to participate were diagnosed according to strict clinical diagnostic criteria, after a detailed neurological interview and examination and discussion of the findings with examination of their video recordings. Follow up information was obtained over a period of at least one year, and atypical cases were reviewed at the end of the study. Results: A diagnosis of probable Parkinson's disease was confirmed in 83% of patients with this diagnosis, including three (2%) in whom atypical features were found that were insufficient to discard a diagnosis of Parkinson's disease. Two additional patients (2%) were found to have possible Parkinson's disease. However, in 15% of patients the diagnosis was unequivocally rejected. Conversely, 13 patients who had previously not been diagnosed with Parkinson's disease (19%) were found to have this disorder. Conclusions: At least 15% of patients with a diagnosis of Parkinson's disease in the population do not fulfil strict clinical criteria for the disease, and approximately 20% of patients with Parkinson's disease who have already come to medical attention have not been diagnosed as such.

A review of autopsy reports in cases in which cocaine featured in the cause of death in Northern Ireland revealed that there were 18 deaths between 1(st) January 1999 and 31(st) December 2007. Analysis revealed an increasing incidence of these deaths during the study period and this is compared to national statistics and those published by local drug addiction services and police.

Background: A recent study showed that transforming growth factor-β1 (TGF-β1) induces amyloid-β deposition in cerebral blood vessels and meninges of a transgenic mouse model of Alzheimer’s disease (AD), and that TGF-β1 mRNA levels are correlated with cerebral amyloid angiopathy (CAA) in human AD brains. A T/C polymorphism at codon 10 in exon 1 of the TGF-β1 gene has been reported to be associated with the serum TGF-β1 concentration. We investigated whether the TGF-β1 polymorphism is associated with the risk of CAA. Methods: The association between the severity of CAA and the T/C polymorphism at codon 10 in exon 1 of the TGF-β1 was investigated in 167 elderly Japanese autopsy cases, including 73 patients with AD. The apolipoprotein E ( APOE ) genotype was also determined. Results: The genotypes (TT/ TC/ CC) were associated with the severity of CAA significantly in all patients (p = 0.0026), in non-AD patients (p = 0.011), and APOE non-e4 carriers (p = 0.0099), but not in AD patients or APOE e4 carriers. The number of the T alleles positively correlated with the severity of CAA in all patients (p = 0.0011), non-AD patients (p = 0.0026), and APOE non-e4 carriers (p = 0.0028), but not in AD patients or APOE e4 carriers. The polymorphism was not significantly associated with AD. Conclusions: Our results suggest that the polymorphism in TGF-β1 is associated with the severity of CAA, especially in non-AD patients and APOE non-e4 carriers.

Objective: To estimate the mortality of progressive supranuclear palsy (PSP) and to assess the quality of death certification in patients with PSP who died in England and Wales. Methods: An analysis was conducted of ICD-9 (International Classification of Diseases, version 9) coded deaths obtained through the Office of National Statistics over an eight year period. Results: The crude annual mortality rate was 1.77 (95% confidence interval, 1.64 to 1.90) cases per million, using the mid-1996 population estimate for England and Wales. Annual mortality increased over time, possibly as a result of increased incidence or increased awareness of the disorder. Forty nine death certificates from deceased patients previously diagnosed clinically showed that the commonest proximate cause of death was pneumonia, occurring in 45% of cases (22/49). The underlying cause of death was cited as pneumonia in 14% of cases (7/49). PSP was mentioned in only 65% of death certificates (32/49). Eight of the 49 cases (16%) underwent necropsy and results were available for five of these cases. PSP was confirmed pathologically in four; the remaining case was diagnosed as Parkinson's disease. Conclusions: Further research is needed to establish the reasons for the observed increase in mortality. Determining the population mortality rate for PSP using the ICD-9 coding system is problematic but is likely to improve following the introduction of ICD-10 updated codes and coding rules.

Clostridium perfringens type C and type D toxins were absorbed on filter paper, dried and stored at room temperature (18-20 degrees C), at 37 degrees C, at 4 degrees C and at -20 degrees C. Type specific toxin was correctly identified in the EIA for 74 days. Absorption on filter paper may offer a simple method for conservation and transport of post mortem samples from cases of suspected enterotoxaemia.

A detailed account is given of a method of preparing giant paper sections of lung for the day following necropsy or, better and more easily, for the subsequent day. This method represents minor modifications to the highly successful Gough-Wentworth technique by challenging the need for lengthy fixation and embedding procedures, but producing results which are thought to be comparable.

DURING the past 10 years, we have observed that anisotropic intra-arterial fibers, similar to cotton or cellulose libers, are a common incidental finding in pathological specimens, found almost exclusively in post-mortem examination of patients who have undergone cardiac operations or catheterization. This report was prompted by the recent occurrence in two patients of thrombosis and infarction that were associated with these fibers, indicating that the presence of the foreign material is neither artifact nor innocuous. Method The minimum incidence and the site of fiber embolization were determined by review of the autopsy records from 1964 to 1973 of all patients . . .