Unusual case of corticobasal degeneration with tau/Gallyas-positive neuronal and glial tangles

A 74-year-old woman with corticobasal degeneration (CBD) had a 9-year history of progressive loss of strength and rigidity of her right hand and then arm, followed by speech difficulties, dyskinesia, rigidity, spasticity and weakness of the ipsilateral lower limb, ultimately also involving the apposite side. She later developed supranuclear gaze palsy. Her memory remained intact during most of the duration of her disease. Laboratory tests and anti-Parkinsonian medications were not helpful. At autopsy, frontal lobe atrophy, discoloration of putamen (Pt) and pallor of substantia nigra (Sn) were observed. Neuronal loss and gliosis were extensive in motor cortex and milder in frontal cortex, abruptly ending at the central sulcus and junction of cingulate gyrus. Achromatic neurons were present. Neuronal loss and gliosis were seen in Pt and Sn and corticobasal inclusions in Sn. Numerous Gallyas/tau-positive, Bielschowsky/ubiquitin-negative coil, sickle, or coma-shaped tangles and thread-like processes were found in affected cortex, Pt and Sn. Some of the tangles were in neurons, but most occurred in astroglia, and their processes. The presence of Gallyas/tau-positive glia in CBD may have the same diagnostic significance as in progressive supranuclear palsy, analogous to the argyrophilic ubiquinated inclusions in oligodendroglia in multisystem atrophy. We suggest that in CBD: (1) cytoskeletal protein metabolism in neurons and glia can simultaneously be perturbed in certain neurodegenerative diseases, and (2) the astrocytosis in CBD may not be simply a reactive process but an integral part of the disease.     

Pure midbrain ischemia and hypoplastic vertebrobasilar circulation

Isolated midbrain infarction is rare and little is known about etiology and patient’s long-term follow up. We aimed to describe the clinical features, the causative diseases and the outcome of patients with isolated midbrain infarction who were admitted to our center, focusing on vascular abnormalities of posterior circulation. All patients with first acute ischemic stroke limited to the midbrain were included and their demographic features, neurological symptoms, neuroimaging data, and cardiovascular risk factors were recorded. Functional outcome, using modified Rankin scale, was assessed at discharge and at the 3 month follow up evaluation. We found nine patients with acute isolated midbrain infarction, representing 0.61 % of all ischemic stroke admitted to our center. The most common cause of stroke was small-vessel disease (88.8 %). At stroke onset, none of the patients had consciousness disturbances, and four patients (44.4 %) had gait impairment, five patients (55.5 %) presented with diplopia due to involvement of the third nerve or fascicular type of third-nerve palsy, seven patients (77.7 %) had vascular anomalies of vertebrobasilar circulation: the most frequent was vertebral artery hypoplasia [four patients (44.4 %)]. At follow up evaluation, seven patients (77.7 %) had a good functional outcome and no patients experienced recurrence of cerebrovascular events. As isolated midbrain infarction is uncommon, specific ocular motor signs, mainly third-nerve palsy, may help to identify and localize the mesencephalic infarct. Abnormalities in vertebrobasilar circulation, such as hypoplastic basilar or vertebral artery, are frequently associated with isolated midbrain ischemia. The hypoplastic vertebrobasilar system may predispose to posterior ischemic stroke.     

Paired helical filaments in neurovisceral lipidosis (juvenile dystonic lipidosis)

Paired helical filaments, the ultrastructural substrate of Alzheimer neurofibrillary change, were found in great number in a 29-year-old patient with neurovisceral lipidosis. The abnormal filaments were frequently present in the distended neurons and axons. The clinical, pathological, and ultrastructural findings were consistent with juvenile dystonic lipidosis, which is considered to be a variant of type C Niemann-Pick disease. The association of Alzheimer neurofibrillary change and central nervous system lipidosis is reviewed.     

The fate of synaptic membranes of degenerating optic nerve terminals, and their role in the mechanism of trans-synaptic changes

Summary The fate of synaptic membranes of degenerating optic nerve terminals has been studied in the lateral geniculate nucleus of Rhesus monkey after eye enucleation. It was shown that pre-synaptic and post-synaptic membranes remain in close apposition to each other during all stages of degeneration and phagocytosis of affected terminals. As a result of this, fragments of presynaptic terminals were engulfed within glial processes, together with synaptic thickenings and parts of post-synaptic dendrites. On occasion small pieces of the degenerating terminals together with the synaptic membranes were engulfed by the post-synaptic dendrite. It is proposed that this pattern of removal of degenerating optic terminals results in injury to the post-synaptic cells, and triggers the transneuronal degeneration.     

Primitive pineal tumor with retinoblastomatous and retinal/ciliary epithelial differentiation: an immunohistochemical study

A one year old boy was found to have a large tumor encompassing the pineal region and extending towards the third and lateral ventricles and quadrigeminal plate. The tumor was composed mostly of small, undifferentiated cells. Some small cells were arranged in Flexner-Wintersteiner rosettes and a few displayed fleurettes. The tumor contained immature cartilage and skeletal muscle and numerous clusters of pigmented epithelial-like cells which, histologically, resembled those found in melanotic neuroectodermal tumors of infancy (retinal anlage tumors) and retinal or ciliary epithelium. Immunologic stains demonstrated neurofilaments, synaptophysin and retinal S-antigen in some of the small cells and transthyretin in some of the epithelial-like cells. The findings indicate that certain primary pineal parenchymal tumors have features in common with tumors of the ocular medullary epithelium.     

Bielschowsky bodies (Lafora bodies of Bielschowsky type): report of a case associated with Rosenthal fibers in the brain stem

Bielschowsky bodies are an uncommon type of polyglucosan body. Similar to Lafora bodies, they are characteristically identified within neuronal perikarya and neurites. However, they lack the diffuse distribution of Lafora bodies, and instead are typically restricted to the external pallidum, often in association with status marmoratus or atrophy of the putamen. Fewer numbers of Bielschowsky bodies have also been identified in other areas such as the substantia nigra, putamen and inner globus pallidus. We report an additional case with Bielschowsky bodies in an 18-year old female with cerebral palsy. This case demonstrated multifocal Bielschowsky bodies and abundant Rosenthal fibers in the midbrain and pons. To our knowledge the association of Bielschowsky bodies with this peculiar distribution of Rosenthal fibers has not previously been reported.     

Publication ethics from the ground up

It is relatively easy to begin policy documents with a general assertion that ethics will be followed. Less obvious is how to ensure that day‐to‐day activities are consonant with ethical standards. We suggest that using day‐to‐day publication activities as the driver for building policies and procedures can promote ethical practices from the ground up. Although basic principles of ethical publication practice may seem straightforward to some, for others this information may require explanation, interpretation and context. Effective policy development includes big‐picture items as well as more day‐to‐day tactical responsibilities such as those discussed below. Research questions, disciplinary practices, applications and team structures may vary. Thus, no single publication plan or policy solution is right for all teams. It is up to team members to review guidelines for best practices and find the optimal implementation for their situations. Experts in publication management, planning and writing can help large teams manage publication activities. These experts have an obligation to maintain and enhance their skills continually. A strong acumen in publication best practices will allow these publication professionals to better address any possible ethical dilemmas in the future.     

Serum ferritin levels and other indicators of organic iron as risk factors or markers in coronary artery disease.

BACKGROUND: Several international studies have discussed whether serum ferritin is a risk marker in coronary heart disease. The objective of this study was to evaluate the importance of serum ferritin levels and other indicators of organic iron as possible risk factors or markers in coronary artery disease. Secondly, the classical factors were studied in order to identify possible associations with organic iron markers. METHODS AND RESULTS: In a medical institution, 1263 patients underwent cinecoronary arteriography from December 1997 to May 1998. A sample of 400 patients was separated, at random, to establish a comparative clinical study between two groups: group A, comprising 200 individuals with coronary atherosclerosis and group B, comprising 200 patients without coronary atherosclerosis, as confirmed by cinecoronary arteriography. From group A, 182 patients (130 males) and from group B, 157 (96 females) did not show any exclusion criteria and were considered eligible. All women were in the postmenopausal period. The blood samples were collected by a biologist, between 8.30 and 9.0 a.m., after a 12-hour fast and a 36-hour non-smoking period. In order to analyze all results, univariate analysis, the logistic regression technique and the interactive forward stepwise method were used in order to optimize the model and to predict the chances of coronary atherosclerosis. The results of the logistic regression with all the variables analyzed showed that male gender, age, smoking, triglycerides/VLDL interaction, increased serum LDL-C levels and decreased serum HDL-C levels are important to predict the chances of coronary atherogenesis. CONCLUSION: Serum levels of ferritin and of other organic iron indicators--transferrin saturation, total iron-binding capacity, hemoglobin and hematocrit--were neither risk factors nor risk markers for coronary atherosclerosis. Paradoxically, serum iron levels were higher in the group without atherosclerosis. In this study, variables classically considered as risk factors were similar to those in the literature.