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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 diatom test for drowning has proved to be a useful, reliable, and valid test for the postmortem diagnosis of drowning in hundreds of cases of drowning in Ontario, Canada. In Ontario, the test has been largely applied to the femoral bone marrow which has facilitated the referral of cases from sites outside of the Office of the Chief Coroner for Ontario. The diatom test has also provided key scientific evidence for the prosecution of homicidal drownings in Ontario, and other provinces. New frontiers for application of the diatom test include wider application in putative drowning cases where the cause of death is obscured by decomposition, burning of the body or other means. Application of molecular biological approaches to the diagnosis of drowning through polymerase chain reaction-based amplification of diatom DNA from human tissues may be the next step in the evolution of the diatom test for drowning.

Most polymers which comprise biological filaments assemble by two mechanisms: nucleation and elongation or a sequential, stepwise process involving a hierarchy of intermediate species. We report the application of atomic force microscopy (AFM) to the study of the early events in the sequential or stepwise mode of assembly of a macromolecular filament. Collagen monomers were assembled in vitro and the early structural intermediates of the assembly process were examined by AFM and correlated with turbidimetric alterations in the assembly mixture. The assembly of collagen involved a sequence of distinctive filamentous species which increased in both diameter and length over the time course of assembly. The first discrete population of collagen oligomers were 1-2 nm in diameter (300-500 nm in length); at later time points, filaments approximately 2-6 nm in diameter (> 10 microns in length) many with a conspicuous approximately 67-nm axial period were observed. Occasional mature collagen fibrils with a approximately 67-nm axial repeat were found late in the course of assembly. Our results are consistent with initial end-to-end axial association of monomers to form oligomers followed by lateral association into higher-order filaments. On this basis, there appears to be at least two distinctive types of structural interactions (axial and lateral) which are operative at different levels in the assembly hierarchy of collagen.

Eight cases of basal skull fracture with transverse fracture of the petrous temporal bone with medial extension to the internal carotid artery and lateral extension of the structures of the middle ear are described. Injuries in all cases were due to major blunt impact to the head usually occurring in a motor vehicle accident. General autopsy revealed major blood loss without any obvious external or internal site of hemorrhage suggesting that exsanguination was a complication of the head injury. The internal carotid arteries at the most medial extension of the fractures were lacerated or transected in all cases. In selected cases, the cervical internal carotid arteries were perfused and perfusate escaped rapidly from the ear(s) with the majority of fluid bypassing the cerebral venous system. Magnetic resonance image reconstruction of sequential sections of the fractured base of the skull confirmed the laceration of the internal carotid arteries and disruption of the middle ear. Based on this evidence, we propose that some displaced fractures of the base of the skull produce carotid-middle ear continuities which act as arterial shunts, resulting in rapid fatal exsanguination through the ear.

The mechanism for the preferential distribution of emboli to cerebral arterial bordcrzone regions, known to cause some watershed infarcts was studied. We hypothesized that emboli of a specific size range are selectively directed to the arterial borderzones due to the tendency of emboli to bypass the small arterial branches which emerge proximal to major borderzones. To test this hypothesis we perfused the brains of cadavers with suspensions of 90-210 µm glass microspheres and chemically extracted the particles from various arterial territories and a watershed zone. Particles in the 150-210 µm size range were found to be preferentially distributed to the watershed zone whereas particles less than 150 µm in size were randomly dispersed in leptomeningeal arteries of all vascular regions. To assess the role of branch size on the concentration of emboli at bifurcations, we perfused artificial analogs of evenly and unevenly branching bifurcations with suspensions of 90-150 µm and 150-210 µm particles. Branching cylinders with symmetrical branches contained the same concentration of particles, independent of particle size. In contrast, when one branch was one-quarter the size of the other, the concentration of 150-210 µm particles in the asymmetric branch was approximately 65% of the main trunk. Particles 90-150 µm in size were evenly distributed despite variation in branch size. These results indicate that emboli, of a limited range of size, may be selectively propagated to the distal ramifications of subarachnoid arteries located in the watershed zone rather than diverging into small calibre branches which arise along the way.