PATHOLOGY OF PERIMACULAR FOLDS DUE TO VITREORETINAL TRACTION IN ABUSIVE HEAD TRAUMA.

PURPOSE: To demonstrate vitreoretinal traction as a mechanism for perimacular folds in abusive head trauma. METHODS: We performed gross and histopathologic examination of eyes of children with suspected abusive head trauma and identified those with typical perimacular folds. Information was collected regarding the incident that led to the child's death and systemic manifestations noted at autopsy. Eyes were prepared in a fashion that allowed for demonstration of the vitreoretinal interface. RESULTS: Ten eyes of five patients (2-13 months) were examined. All patients had systemic manifestations of abusive trauma including intracranial injury. All cases provided evidence of vitreoretinal traction producing perimacular folds. Condensed vitreous was seen attached to the apices of the retinal folds, and the detached internal limiting membrane comprising the inner surfaces of the schisis cavity. Four cases showed severe bilateral multilayered symmetric retinal hemorrhages extending to the ora serrata. All cases showed optic nerve sheath subdural hemorrhage and subarachnoid hemorrhage. Orbital hemorrhage was unilateral in two cases and bilateral in three cases. Four cases showed orbital fat hemorrhage. One case showed extraocular muscle sheath and cranial nerve sheath hemorrhage. Two cases showed juxtapapillary intrascleral hemorrhage. CONCLUSION: Vitreoretinal traction is the likely mechanism of perimacular folds in abusive head trauma.

The doublecortin-related gene zyg-8 is a microtubule organizer in Caenorhabditis elegans neurons.

Doublecortin-domain containing (DCDC) genes play key roles in the normal and pathological development of the human brain cortex. The origin of the cellular specialisation and the functional redundancy of these microtubule (MT)-associated proteins (MAPs), especially those of Doublecortin (DCX) and Doublecortin-like kinase (DCLKs) genes, is still unclear. The DCX domain has the ability to control MT architecture and bundling. However, the physiological significance of such properties is not fully understood. To address these issues, we sought post-mitotic roles for zyg-8, the sole representative of the DCX-DCLK subfamily of genes in C. elegans. Previously, zyg-8 has been shown to control anaphase-spindle positioning in one-cell stage embryos, but functions of the gene later in development have not been investigated. Here we show that wild-type zyg-8 is required beyond early embryonic divisions for proper development, spontaneous locomotion and touch sensitivity of adult worms. Consistently, we find zyg-8 expression in the six touch receptor neurons (TRNs), as well as in a subset of other neuronal and non-neuronal cells. In TRNs and motoneurons, zyg-8 controls cell body shape/polarity and process outgrowth and morphology. Ultrastructural analysis of mutant animals reveals that zyg-8 promotes structural integrity, length and number of individual MTs, as well as their bundled organisation in TRNs, with no impact on MT architecture.

Motor neuron synapse and axon defects in a C. elegans alpha-tubulin mutant.

Regulation of microtubule dynamics underlies many fundamental cellular mechanisms including cell division, cell motility, and transport. In neurons, microtubules play key roles in cell migration, axon outgrowth, control of axon and synapse growth, and the regulated transport of vesicles and structural components of synapses. Loss of synapse and axon integrity and disruption of axon transport characterize many neurodegenerative diseases. Recently, mutations that specifically alter the assembly or stability of microtubules have been found to directly cause neurodevelopmental defects or neurodegeneration in vertebrates. We report here the characterization of a missense mutation in the C-terminal domain of C. elegans alpha-tubulin, tba-1(ju89), that disrupts motor neuron synapse and axon development. Mutant ju89 animals exhibit reduction in the number and size of neuromuscular synapses, altered locomotion, and defects in axon extension. Although null mutations of tba-1 show a nearly wild-type pattern, similar axon outgrowth defects were observed in animals lacking the beta-tubulin TBB-2. Genetic analysis reveals that tba-1(ju89) affects synapse development independent of its role in axon outgrowth. tba-1(ju89) is an altered function allele that most likely perturbs interactions between TBA-1 and specific microtubule-associated proteins that control microtubule dynamics and transport of components needed for synapse and axon growth.