Nodding syndrome phenotypes.

Nodding syndrome (NS) is a progressive encephalopathy of children and adolescents characterized by seizures, including periodic vertical head nodding. Epidemic NS, which has affected parts of East Africa, appears to have clinical overlap with sub-Saharan Nakalanga syndrome (NLS), a brain disorder associated with pituitary dwarfism that appears to have a patchy distribution across sub-Sahara. Clinical stages of NS include inattention and blank stares, vertical head nodding, convulsive seizures, multiple impairments, and severe cognitive and motorsystem disability, including features suggesting parkinsonism. Head nodding episodes occur in clusters with an electrographic correlate of diffuse high-amplitude slow waves followed by an electrodecremental pattern with superimposed diffuse fast activity. Brain imaging reveals differing degrees of cerebral cortical and cerebellar atrophy. Brains of NS-affected children with mild frontotemporal cortical atrophy display neurofibrillary pathology and dystrophic neurites immunopositive for tau, consistent with a progressive neurodegenerative disorder. The etiology of NS and NLS appears to be dominated by environmental factors, including malnutrition, displacement, and nematode infection, but the specific cause is unknown.

The Rise of Forensic Pathology in Human Medicine: Lessons for Veterinary Forensic Pathology.

The rise of forensic pathology in human medicine has greatly contributed to the administration of justice, public safety and security, and medical knowledge. However, the evolution of human forensic pathology has been challenging. Veterinary forensic pathologists can learn from some of the lessons that have informed the growth and development of human forensic pathology. Three main observations have emerged in the past decade. First, wrongful convictions tell us to use a truth-seeking stance rather than an a priori "think dirty" stance when investigating obscure death. Second, missed homicides and concealed homicides tell us that training and certification are the beginning of reliable forensic pathology. Third, failure of a sustainable institutional arrangement that fosters a combination of service, research, and teaching will lead to stagnation of knowledge. Forensic pathology of humans and animals will flourish, help protect society, and support justice if we embrace a modern biomedical scientific model for our practice. We must build training programs, contribute to the published literature, and forge strong collaborative institutions.

Fatal hemorrhage following trans--sphenoidal resection of a pituitary adenoma: a case report and review of the literature.

A 58-year-old woman with acromegaly developed massive epistaxis 7 days following trans-sphenoidal resection of a growth hormone-secreting pituitary adenoma. At autopsy, it was determined that the source of the hemorrhage was a rupture of the intracavernous segment of the internal carotid artery secondary to a bacterial arteritis. We describe the gross dissection and histologic examination undertaken in this unusual case, discuss the possible etiology of the infection and review the potential complications of this surgical approach with a view to improving forensic examination of these patients.

Subtle fatal manual neck compression.

A critical analysis of the postmortem diagnostic criteria for asphyxia leads to a difficulty that has significant implications for the forensic pathologist. The difficulty is that there are no universally recognized pathognomic signs of asphyxia, but pathologists frequently make this diagnosis based on observations that individually have indeterminate significance but combined together, in the appropriate context, have diagnostic value. This leads to the question: if asphyxia has no recognizable signs at autopsy how are we able to diagnose this entity in the latter circumstances? This problem can be solved by defining the minimally adequate diagnostic criteria for compressive neck injury. These criteria are potentially well-defined but currently lacking, in part, due to incomplete morphological characterization of the injuries that frequently occur in strangulation. The problem is especially challenging because the signs of strangulation form a spectrum of degree from minimal to marked and there is no consensus as to the minimal number and nature of lesions that is required to make the diagnosis of strangulation. In the present review of lesions that are commonly encountered in strangulation, intracartilaginous laryngeal haemorrhages and laryngeal cartilage microfractures are considered to have unrecognized diagnostic value, and these lesions are described in detail. A triad of haemorrhages (subepithelial laryngeal haemorrhage, intralaryngeal muscular haemorrhage, and intracartilaginous laryngeal haemorrhage) is discussed in the context of developing a definition of strangulation based on morphological criteria in the absence of overt mechanical injuries to the neck. Although definitive criteria for cases with minimal findings are still lacking, several lesions have putative diagnostic value.

Limbs found in water: investigation using anthropological analysis and the diatom test.

We report the investigation, using a multi-disciplinary approach, of five cases of dismembered limbs which were recovered from Lake Ontario, Lake Erie and the Niagara River, and examined at the Office of the Chief Coroner for Ontario. In all cases, postmortem examination revealed that the limbs had been disarticulated in the postmortem period, by non-human taphonomic processes. In addition to routine gross examination, the femur and/or tibia were assessed using anthropological methods to give estimates of the sex, age, race and stature of the individual. The anthropologic data facilitated the identification of one of the cases. In all cases, nitric acid extracts of the femoral bone marrow were prepared and examined for the presence of diatoms. In all instances, diatom frustules were recovered from marrow extracts, indicating that drowning was the cause of death or at least a significant contributing factor in the cause of death. The use of the diatom test was helpful in excluding the possibility that the limbs were dismembered from individuals who had died by means other than drowning, and had been subsequently 'dumped' into water. The application of anthropological methods and the diatom test for drowning may significantly enhance the medico-legal investigation of body parts recovered from water, and we present an overview of useful techniques here. Anthropological data may facilitate identification, and the diatom test may establish a cause of death.

A triad of laryngeal hemorrhages in strangulation: a report of eight cases.

The results of histological studies on larynges from eight cases of manual strangulation, all that had intracartilaginous laryngeal hemorrhages, a recently described and under-recognized lesion associated with strangulation, are reported. Formalin-fixed larynges were examined in serial section using a standardized protocol. In all cases, intracartilaginous laryngeal hemorrhages were associated with subepithelial laryngeal hemorrhages, and intralaryngeal muscular hemorrhages forming a "triad of hemorrhages." In five cases, the triad was found in the presence of laryngeal cartilage microfractures. Since cartilage microfractures can be causally related to mechanical injury to the neck, it is likely that the triad of hemorrhages has diagnostic value as an independent morphological criterion for the postmortem diagnosis of strangulation. Since a proportion of cases of strangulation lack characteristics that are self-evidently due to violent application of pressure on the neck, recognition of the triad may have important implications for the postmortem diagnosis of strangulation.

Modeling of a periodic instability in paired helical filaments reveals an axial repeat.

Ultrastructural studies of paired helical filaments (PHF) have been facilitated by the ability to isolate enriched fractions of detergent-insoluble forms of PHF. These fractions are composed of a relatively homogeneous population of short (usually < 400 nm) highly fragmented PHF. A small proportion of isolated PHF have highly stereotyped angled profiles that represent deformations due to structural instability. These distorted PHF can be characterized quantitatively using a simple numerical procedure that reveals that the axial instabilities occur with predictable regularity over the length of the PHF. Using a structural model of PHF, it is shown that the periodicity of the axial instability can be correlated to an axially repeated subunit of uniform size. The upper limit for the axial extent of the repeated segment was calculated to be 80 nm, similar to the size of a single one-half twist in the PHF ribbon. It is proposed that this segment may represent one type of particle in the hierarchy of structural subunits in the PHF ribbon, or an oligomeric intermediate species in PHF assembly.

Unexpected death related to restraint for excited delirium: a retrospective study of deaths in police custody and in the community.

BACKGROUND: Some people in states of excited delirium die while in police custody. Emerging evidence suggests that physical restraint in certain positions may contribute to such deaths. In this study the authors determined the frequency of physical restraint among people in a state of excited delirium who died unexpectedly. METHODS: The authors reviewed the records of 21 cases of unexpected death in people with excited delirium, which were investigated by the Office of the Chief Coroner for Ontario between 1988 and 1995. Eyewitness testimony, findings during postmortem examinations, clinical history, toxicological data and other official documents describing the events surrounding the deaths were analyzed. Specific reference was made to documented eyewitness testimony of restraint method, body position and use of capsicum oleoresin (pepper) spray. Because cocaine was detected in the blood of some of these people during the postmortem examination, the role of cocaine in excited delirium was examined by comparing the cocaine levels in these cases with levels in 2 control groups: 19 people who died from acute cocaine intoxication and 21 people who had used cocaine shortly before they died but who had died from other causes. RESULTS: In all 21 cases of unexpected death associated with excited delirium, the deaths were associated with restraint (for violent agitation and hyperactivity), with the person either in a prone position (18 people [86%]) or subjected to pressure on the neck (3 [14%]). All of those who died had suddenly lapsed into tranquillity shortly after being restrained. The excited delirium was caused by a psychiatric disorder in 12 people (57%) and by cocaine-induced psychosis in 8 (38%). Eighteen people (86%) were in police custody when they died. Four (19%) had been sprayed with capsicum oleoresin, and heart disease was found in another 4 at autopsy. The blood level of cocaine in those whose excited delirium was cocaine induced was similar to levels found in recreational cocaine users and lower than levels found in people who died from cocaine intoxication. INTERPRETATION: Restraint may contribute to the death of people in states of excited delirium, and further studies to test this hypothesis are recommended. Meanwhile, law enforcement authorities and others should bear in mind the potential for the unexpected death of people in states of excited delirium who are restrained in the prone position or with a neck hold.

Intra-cartilaginous laryngeal haemorrhages and strangulation.

A previously unrecognized laryngeal injury in young female victims of manual strangulation is described. Twelve larynges that were retrospectively and prospectively collected at the Office of the Chief Coroner for Ontario (1982-1997) were used for this study. In all instances, the larynges were from cases of strangulation (mean age 27 +/- 10 years, range 20-46) with classical postmortem findings of asphyxia and either manual or combined manual and ligature strangulation. None of the larynges had fractures of the lamina of the thyroid cartilage, superior cornua, or cricoid cartilages. However, in 9 of the 12 cases (75%), sagittal sections revealed multifocal acute haemorrhages into the base of the superior cornua of the thyroid cartilage at the point of origin from the laminae. The presence of acute intra-cartilaginous haemorrhage into the larynx likely represents the disruption of small blood vessels due to elastic deformation of the flexible larynx during strangulation. The recognition of this form of laryngeal injuries broadens the pathological findings in cases of asphyxia associated with pressure on the neck.

Diatoms and homicide.

Six illustrative cases of homicidal drowning are reported in which the diatom test for drowning was a useful adjunct to the medicolegal investigation of death. In all six cases, diatom frustules were recovered from the femoral bone marrow. In five cases, diatoms extracted from the bone marrow were compared with diatoms obtained from samples of putative drowning medium. In all of these case, the same types of diatoms were observed in both the water samples and the marrow. In an additional case, watery fluid from the maxillary sinus contained the same diatom types as were present in the femoral bone marrow. Four of the six cases were found submerged in water and had autopsy findings consistent with drowning. In the remaining two cases, the bodies were found on land; one case was grossly decomposed and one body was extensively burned since the body was set afire on dry land after death. In some of the case drowning was associated with blunt force head injury (one case), sharp force injuries of the chest (one case), or strangulation (three cases). These results indicate that the diatom test for drowning is an important adjunct to the medicolegal investigation of homicidal drowning, particularly in those cases were autopsy and scene findings do not imply drowning as a cause of death.

Forensic significance of the polymorphism of hyoid bone shape.

The reasons why some hyoids fracture in strangulation and others do not may relate to anatomic features of the hyoid bone. On this basis, we studied the dimensions and shape of hyoid bones (n = 100) originating from the Terry collection, National Museum of Natural History, Smithsonian Institution. The hyoid bones were extensively polymorphic in both dimensions studied, the span or breadth, and the length of the cornua. There was no linear relationship between the breadth and length dimensions of the bone. Based on qualitative assessment, hyoid bones could be classed as either hyperbolic (55%) or parabolic (45%) in shape. Hyperbolic hyoid bones could be distinguished from hyoid bones with a parabolic configuration on the basis of the metric data although there was considerable overlap in the dimensions of hyoid bones of both configurations. Female hyoid bones tended to be smaller in both dimensions than male hyoid bones. The metric parameters of fractured hyoid bones from 10 cases (8 female, 2 male) of strangulation were compared with the dimensions of hyoid bones in this study. The metric features of the fractured hyoid bones were attributable to the predominance of females in the group of fractured hyoid bones studied, an observation that is anticipated because the majority of strangulations involve female decedents. On this basis, we conclude that variables other than the shape and dimensions of the hyoid bone are more relevant in determining if hyoid fracture occurs during strangulation.

Cortical degeneration in progressive supranuclear palsy. A comparison with cortical-basal ganglionic degeneration.

We report 3 patients with progressive supranuclear palsy (PSP) who developed limb apraxia, focal dystonia, and arm levitation late in the course of the disease. Neuropathological examination revealed cortical degeneration in addition to the characteristic pathological findings of PSP. Semiquantitative comparative histological and immunohistological studies of the neocortex of these patients as well as 5 cases of classical PSP and 4 cases of cortical-basal ganglionic degeneration (CBGD) revealed a distinctive form of cortical degeneration in PSP. The cortical degeneration was often circumscribed and confined to premotor and motor cortex. It was characterized by neuronal loss and gliosis. Swollen neurons were only rarely observed in neocortex of PSP cases in contrast with CBGD, where they were abundant. Neuronal and glial tau as well as tau immunoreactive threads were seen in both PSP and CBGD, but were more abundant in CBGD. The appearance of tau reactive astrocytes also differed in both disorders; tufted astrocytes were seen exclusively in PSP, while typical annular astrocytic plaques were confined to CBGD. These observations indicate that cortical degeneration occurs in PSP and may be associated with atypical clinical manifestations that lead to diagnostic difficulties.

The diagnostic value of the diatom test for drowning, I. Utility: a retrospective analysis of 771 cases of drowning in Ontario, Canada.

The utility and validity of the diatom test for drowning was studied using a retrospective analysis of 771 cases of drowning mostly from Ontario, Canada, over the period 1977 to 1993. In this article (part one), the utility of the test was assessed using an analysis of test outcomes. In the companion article (part two), the validity of the test was assessed by analyzing the relationship between test outcome and characteristics of diatoms in the bone marrow and samples of putative drowning medium. In the present study, freshwater drownings accounted for 738 of the cases and 33 cases were drownings in bathtubs, pools, or toilets. Diatoms were recovered from the femoral bone marrow of 205 cases (28%) of freshwater drowning and four cases (12%) of domestic water drowning. There was a monthly variation in the frequency of positive test outcomes that could not be explained by seasonal differences in the total number of drownings. However, the monthly variation was strongly correlated with the periodic cycle of diatom blooms that occurs in freshwater. Positive diatom tests were characterized by a limited number of distinctive diatom species per case, and a restricted quantity and size range of diatom frustules. These results indicate that the diatom test for drowning will identify approximately one in three victims of freshwater drowning and may be useful in the assessment of deaths occurring in bathtubs. The correlation of the outcome of the diatom test for drowning with diatom blooms provides further evidence for the reliability of the test.

The diagnostic value of the diatom test for drowning, II. Validity: analysis of diatoms in bone marrow and drowning medium.

In part two of this series, we investigated the characteristics of diatom frustules recovered from bone marrow and samples of putative drowning medium in case of freshwater drownings. A total of 52 cases of freshwater drowning with diatoms in the femoral bone marrow in which a sample of the putative drowning medium was also collected were available for analysis. The same types of diatoms were found in the bone marrow and putative drowning medium in 47 cases (90%) indicating that the water samples were representative of the site of drowning in at least 90% of freshwater drownings. In the remaining 5 cases (10%), the diatoms in the water samples did not match those in the bone marrow indicating that the site of body and water sample recovery were likely geographically remote from the site of drowning. In cases with matching diatoms in the bone marrow and drowning medium, the diatoms were consistently the smallest and most abundant types represented in the water samples. In addition, there were highly stereotyped physical characteristics of typical "drowning-associated" diatoms with small pennate diatoms representing the most common type of frustule found in the bone marrow. In an additional 34 cases of putative drowning in water that lacked detectable diatoms, 29 cases (85%) lacked diatoms in the bone marrow. Analysis of the diatom content of samples of putative drowning medium by month revealed that winter months had the highest frequency of samples devoid of diatoms. These data indicate that the true positive rate of the diatom test for drowning is at least 90% and that small pennate frustules are most commonly associated with drowning, particular in non winter months.

Paired helical filaments are twisted ribbons composed of two parallel and aligned components: image reconstruction and modeling of filament structure using atomic force microscopy.

To study the structure of Alzheimer paired helical filaments (PHF) we examined isolated detergent-insoluble PHF using atomic force microscopy with image reconstruction. The reconstructed AFM images of Alzheimer PHF most closely resembled ribbon-like helices with thin edges. The presence of a conspicuous furrow in the PHF midline indicated that PHF were composed of two distinctive strands. Our present conception of the overall configuration of PHF is consistent with that proposed by Crowther and Wischik in 1985 but includes an essential component of the prevailing model: the presence of two strands. Thus, our new model of PHF structure, based on atomic force microscopy-derived data, indicates that the true structure of PHF is actually a hybrid of the prevailing PHF model and a thin helical ribbon.

Unusual clinical presentations of cortical-basal ganglionic degeneration.

Cortical-basal ganglionic degeneration classically presents predominantly as a motor disorder with a unique constellation of histological alterations characterized by the presence of neuronal loss and gliosis in a selective distribution, swollen achromasic neurons, and extensive deposition of abnormal tau in neurons and glia. We now report 3 patients with this distinctive pathology who presented with cognitive changes and only mild or delayed motor symptoms. In 2 patients with severe dementia, pathological changes were extensive in the anterior frontal lobe, amygdala, and hippocampus. In a third patient who had an isolated speech disturbance for 5 years before developing the more typical motor features of cortical-basal ganglionic degeneration, the most severe changes were observed in the left motor cortex and adjacent Broca's area. It is therefore apparent that the histological changes of cortical-basal ganglionic degeneration result in a variety of clinical presentations depending on the topography of the lesions. On this basis we conclude that cortical-basal ganglionic degeneration should be considered in the differential diagnosis of language disturbances and dementia, particularly when the latter is accompanied by frontal lobe symptomatology, early speech alterations, or parkinsonism.

Sudden unexplained death in Asian immigrants: recognition of a syndrome in metropolitan Toronto.

OBJECTIVE: To determine the number of Southeast Asians in Ontario who died of the sudden unexplained death syndrome in Asian immigrants. DESIGN: Retrospective review. SETTING: Ontario. CASES: All deaths reported to the Office of the Chief Coroner for Ontario from 1992 to 1995. OUTCOME MEASURES: Age, residence and country of origin of people who died of sudden unexplained death syndrome in Asian immigrants, as defined by standard criteria, autopsy findings and social history of cases. RESULTS: Eight cases of sudden unexplained death in Asian immigrants were reported during the study period. All involved men, and the mean age at death was 34 (standard error of the mean 7) years (range 23 to 44 years). All of the people were residents of metropolitan Toronto. Four were from Vietnam, three from China and one from the Philippines. Seven people lived with family members; the eighth was unemployed and lived alone. Death occurred during sleep or in the waking hours of the morning in six cases; in two of these cases the person's spouse was awakened by loud, laboured breathing. Two men experienced chest pain, and one of them also had sudden-onset dyspnea. There was no prodromal illness in any case. The only consistent autopsy finding was acute nonspecific pulmonary edema and congestion. Analysis of heart weights failed to reveal signs of significant cardiomegaly. CONCLUSION: Men from Southeast Asia aged 20 to 45 years are at risk of sudden unexplained death, which usually occurs during sleep. No specific factors have been found that could be used to identify people at risk.

Injury of the tunica media in fatal rupture of the vertebral artery.

The histologic findings in seven cases of traumatic basal subarachnoid hemorrhage from rupture of a vertebral artery are reported. In all cases, blows to the head or neck resulted in minor injury to the cranial or cervical soft tissues but the ipsilateral intracranial segment of the vertebral artery was the site of a longitudinal transmural tear. In addition to rupture, the arterial wall proximal and distal to the site of rupture showed evidence of distortional injury of the tunica media. These traumatic lesions appeared as patchy anuclear regions of the media with distinctive pallor of smooth muscle staining. We propose that the forces which cause vertebral artery rupture stretch the artery along its long axis, thereby distorting the artery leading to this characteristic histologic change.

Altered neurofilament expression does not contribute to Lewy body formation.

Lewy bodies (LBs) are cytoskeletal alterations found in several neurodegenerative disorders. Although neurofilaments are the main constituent of the LB, the precise mechanisms that underlie their formation remain speculative. To examine the pathogenesis of this inclusion, we measured the mRNA level of the low molecular weight neurofilament subunit in the nigral dopaminergic neurons of patients with LB disorders and neurologically normal controls. We found a small but significant decrease in the mean mRNA values in the LB group as compared with controls. However, a comparison of LB-bearing and non-LB-bearing neurons on the same section showed no significant difference between these two neuronal populations. We conclude that altered neurofilament expression is not a major contributory event in the pathogenesis of the LB. The decrease in neurofilament mRNA expression observed in the overall nigral dopaminergic neuronal population of LB disorders probably represents a nonspecific response to neuronal injury independent of LB formation.