Clinical presentation of spinal cord concussion

Spinal cord concussion is a transient disturbance of spinal cord function, with or without vertebral damage and no demonstrable pathologic changes, that results from a rapid change in velocity following trauma, and resolves within 48 hours. In a retrospective review of patients with spinal injury referred to a tertiary care center, spinal cord concussion was observed in 3.7% of patients. Thirteen cases are presented. A variety of clinical presentations may occur, all of which can be explained on the basis of the magnitude or direction of acceleration of the spinal cord. The cervical cord is most commonly affected, but concussion can occur at any level of the spinal cord. Spinal cord concussion is often associated with pre-existing vertebral abnormalities that result in narrowing of the spinal canal or areas of hypermobility.     

Confocal light absorption and scattering spectroscopic microscopy monitors organelles in live cells with no exogenous labels

This article reports the development of an optical imaging technique, confocal light absorption and scattering spectroscopic (CLASS) microscopy, capable of noninvasively determining the dimensions and other physical properties of single subcellular organelles. CLASS microscopy combines the principles of light-scattering spectroscopy (LSS) with confocal microscopy. LSS is an optical technique that relates the spectroscopic properties of light elastically scattered by small particles to their size, refractive index, and shape. The multispectral nature of LSS enables it to measure internal cell structures much smaller than the diffraction limit without damaging the cell or requiring exogenous markers, which could affect cell function. Scanning the confocal volume across the sample creates an image. CLASS microscopy approaches the accuracy of electron microscopy but is nondestructive and does not require the contrast agents common to optical microscopy. It provides unique capabilities to study functions of viable cells, which are beyond the capabilities of other techniques.     

Phosphorylation and cleavage of tau in non-AD tauopathies

The tau protein, well known as the primary component of neurofibrillary tangles, also comprises the Pick bodies found in Pick’s disease (PiD) and the glial lesions associated with progressive supranuclear palsy (PSP) and cortico-basal ganglionic degeneration (CBD). Many of the tau alterations that are characteristic of Alzheimer’s disease have also been identified in PSP and CBD. In this report, we examine three non-AD tauopathies (PSP, CBD, and PiD) for the presence of two specific tau alterations, phosphorylation at Ser422 and truncation at Asp421. We find that truncation at Asp421 is an alteration that is unique to neuronal lesions, occurring in Pick bodies as well as in neurofibrillary tangles, but not in lesions associated with glia. Conversely, phosphorylation at Ser422 is not only present in all these lesions, but identifies additional glial and neuronal pathology in disease-susceptible cortical regions. These results suggest that the molecular alterations of tau that occur during the initial process of tangle formation in AD are similar in non-AD tauopathies, but the middle and later changes are not common to all diseases. This work is supported by grants AG021184 and AG09466 from the NIH.     

Characterization of juvenile and young adult mice following induction of hydrocephalus with kaolin

Hydrocephalus is a common neurological problem in humans, usually caused by an impairment of cerebrospinal fluid (CSF) flow or absorption. A reliable induced model of chronic hydrocephalus in mice would be useful to test hypotheses using genetic mutants. Our goal was to characterize behavioral and histological changes in juvenile and young adult mice with kaolin (aluminum silicate)-induced hydrocephalus. Seven-day old and 7–8 week old mice received injection of kaolin into the cisterna magna. Behavior was assessed repeatedly. Seven or 14 days following kaolin, magnetic resonance (MR) imaging was used to assess ventricle size. In hydrocephalic mice, body weight was significantly lower than in age-matched saline-injected sham controls and the gait and posture score were impaired. Juvenile mice developed severe ventriculomegaly and had reduced corpus callosum thickness with gross white matter destruction by 14 days. Reactive astroglial change in white matter and cortex and reduced cellular proliferation in the subependymal zone were also apparent. Young adult mice developed only moderate ventricular enlargement without overt white matter destruction, although there was corpus callosum atrophy and mild astroglial reaction in white matter. Glial fibrillary acidic protein content was significantly higher in juvenile and young adult hydrocephalic mice at 7 and 14 days, but myelin basic protein content was not significantly altered. In conclusion, hydrocephalus induced by percutaneous injection of kaolin in juvenile and young adult mice is feasible. The associated periventricular alterations are essentially the same as those reported in rats of comparable ages.     

Update on recent molecular and genetic advances in frontotemporal lobar degeneration

Great strides have been made in the last 2 years in the field of frontotemporal lobar degeneration (FTLD), particularly with respect to the genetics and molecular biology of FTLD with ubiquitinated inclusions. It is now clear that most cases of familial FTLD with ubiquitinated inclusions have mutations in the progranulin gene, located on chromosome 17. It is also clear that most ubiquitinated inclusions in FTLD with ubiquitinated inclusions are composed primarily of TAR DNA-binding protein-43. Thus, FTLDs can be separated into 2 major groups (i.e. tauopathies and ubiquitinopathies), and most of the ubiquitinopathies can now be defined as TAR DNA-binding protein-43 proteinopathies. Many of the familial FTLDs are linked to chromosome 17, including both the familial tauopathies and the familial TAR DNA-binding protein-43 proteinopathies with progranulin mutations. This review highlights the neuropathologic features and the most important discoveries of the last 2 years and places these findings into the historical context of FTLD.