The changing pattern of HIV neuropathology in the HAART era

Highly active antiretroviral treatment (HAART), which has been available for most AIDS patients in France since 1996, has resulted in a dramatic improvement of the progression of the disease. From the survey of our series of 343 brains with acquired immunodeficiency syndrome (AIDS) from patients who died between 1985 and 2002, we found both quantitative and qualitative changes in the pattern of human immunodeficiency virus (HIV) neuropathology. Quantitatively, despite a dramatic decrease in the number of autopsies, brain involvement remained a major cause of death. There was an overall decrease in incidence of cerebral toxoplasmosis, cytomegalovirus encephalitis (CMVE), and HIV encephalitis (HIVE), for which successful treatment is available. This contrasted with the unchanged incidence of progressive multifocal leukoencephalopathy (PML) and malignant non-Hodgkin lymphomas (MNHL). However, when looking closer at the 3 last years, the incidence of diseases affecting patients with severe immunodepression (CMVE, PML, and MNHL) decreased between 2000 and 2002, whereas infections occurring in patients with milder immunodeficiency, toxoplasmosis, varicella-zoster encephalitis (VZVE), or herpes simplex virus encephalitis (HSVE) became more frequent. In addition, we found uncommon types of brain infection such as BK virus encephalitis or general paresis. Finally, we described new variants of HIVE: severe leukoencephalopathy with intense perivascular macrophage and lymphocyte infiltration, possibly due to an exaggerated response from a newly reconstituted immune system, and chronic "burnt out" forms of HIVE as VZVE, toxoplasmosis, or PML, possibly associated with prolonged survival, in which neither inflammation nor organisms could be detected. These findings are compared with those reported in other neuropathological studies from different developed countries.     

Comparison of multi-lineage cells from human adipose tissue and bone marrow

Our laboratory has recently characterized a population of cells from adipose tissue, termed processed lipoaspirate (PLA) cells, which have multi-lineage potential similar to bone-marrow-derived mesenchymal stem cells (MSCs). This study is the first comparison of PLA cells and MSCs isolated from the same patient. No significant differences were observed for yield of adherent stromal cells, growth kinetics, cell senescence, multi-lineage differentiation capacity, and gene transduction efficiency. Adipose tissue is an abundant and easily procured source of PLA cells, which have a potential like MSCs for use in tissue-engineering applications and as gene delivery vehicles.     

Developmental molecular switches regulating breathing patterns in CNS

The present paper presents some of the molecular switches that may operate at early embryonic stages to make development of the brainstem respiratory rhythm generator a robust and irreversible process. We concentrate on the role of transient Hox-related gene expression patterns in register with the regionalisation of the rhombencephalic neural tube along the antero-posterior axis. Using different recording and isolation procedures in chick embryos, we show that the hindbrain is subdivided at E1 into developmental units (rhombomeres) intrinsically able to produce rhythm generating neuronal circuits active at E5. At E6, intrinsic cues also allow a progressive maturation of episodic rhythm generators that persists after isolation of the hindbrain in vitro and requires odd/even rhombomeric interactions at E1. From these results and from respiratory pathologies observed in transgenic mice, we are beginning to understand that, despite diversity of breathing patterns and adaptations, there are links between developmental control genes and adult respiration.     

Automatic change detection in multimodal serial MRI: application to multiple sclerosis lesion evolution

The automatic analysis of subtle changes between MRI scans is an important tool for assessing disease evolution over time. Manual labeling of evolutions in 3D data sets is tedious and error prone. Automatic change detection, however, remains a challenging image processing problem. A variety of MRI artifacts introduce a wide range of unrepresentative changes between images, making standard change detection methods unreliable. In this study we describe an automatic image processing system that addresses these issues. Registration errors and undesired anatomical deformations are compensated using a versatile multiresolution deformable image matching method that preserves significant changes at a given scale. A nonlinear intensity normalization method is associated with statistical hypothesis test methods to provide reliable change detection. Multimodal data is optionally exploited to reduce the false detection rate. The performance of the system was evaluated on a large database of 3D multimodal, MR images of patients suffering from relapsing remitting multiple sclerosis (MS). The method was assessed using receiver operating characteristics (ROC) analysis, and validated in a protocol involving two neurologists. The automatic system outperforms the human expert, detecting many lesion evolutions that are missed by the expert, including small, subtle changes.     

Prenatal exposure of rats to Ginkgo biloba extract (EGb 761) increases neuronal survival/growth and alters gene expression in the developing fetal hippocampus

Hippocampal neuron survival/growth and gene expression have been examined after prenatal (in utero) exposure of rats to EGb 761, a leaf extract of Ginkgo biloba. Oral administration of EGb 761 (100 or 300 mg/kg/day) to pregnant dams for 5 days increased the number of hippocampal neurons (maintained in culture) of their fetuses, indicating a neurotrophic effect of the extract. Using large-scale oligonucleotide microarrays containing over 8000 combined rat genes and expressed sequence tag clusters, it was shown that treatment of pregnant dams with EGb 761 (25, 50 or 100 mg/kg/day for 5 days) altered the expression of 187 genes in the hippocampi of male fetuses and 160 genes in those of female fetuses. Using gene-cluster analysis, these genes were grouped into 18 distinct clusters for males and 17 distinct clusters for females. Among these clusters, 35 genes shared a common expression pattern in male and female hippocampal development. Of these genes, the changes observed in insulin growth factor II, insulin growth factor binding protein 2, testosterone repressed prostate message-2, glutathione-dependent dehydroascorbate reductase, lipoprotein lipase, guanylate cyclase and DNA binding protein Brn-2 were confirmed by real-time quantitative polymerase chain reaction. These findings, which have provided the first genetic profile of the effects of EGb 761 on the developing rat hippocampus, increase our understanding of the molecular and genetic programs that are activated by the extract. These effects of EGb 761 may underlie its neuroprotective properties.     

Cavernous sinus dural fistulae treated by transvenous approach through the facial vein: report of seven cases and review of the literature

BACKGROUND AND PURPOSE: Dural Carotid Cavernous Fistulas (CCFs) can be treated by transarterial and/or transvenous endovascular techniques. The venous route usually goes through the internal jugular vein (IJV) and the inferior petrosal sinus (IPS) up to the pathologic shunts of the cavernous sinus. In case a thrombosed IPS, catheterization through the obstructed sinus is not always possible and a puncture of the superior ophthalmic vein (SOV) can be performed often after a surgical approach. We report our results in the endovascular transvenous treatment of dural CCFs through the facial vein (retrograde catheterization of the IJV, facial vein, angular vein, SOV, and cavernous sinus). METHODS: A retrospective study of seven patients with a dural CCF treated with transvenous embolization via the facial vein was performed. In five patients, the IPS was thrombosed. In one patient, the IPS was patent, but there was not communication between the cavernous sinus compartment in which the CCF shunts were located and the IPS itself. In the only patient with the CCF draining through permeable IPS, the transvenous route through the IPS permitted the occlusion of the posterior CCF shunts and a second session was performed through the facial vein in order to occlude the shunts of the anterior compartment of the cavernous sinus. The other six patients underwent one embolization session only. RESULTS: In all seven cases, it was possible to navigate through the tortuous junction of the angular vein and the SOV. In one patient with a thrombosed SOV, the venous procedure was interrupted because the catheterization through the occluded SOV failed. In the other six patients, after transvenous catheterization of the cavernous sinus via the facial vein, placement of coils resulted in complete occlusion of the dural CCF with clinical cure in four patients and improvement in two. CONCLUSION: In the endovascular treatment of the dural CCFs, the transfemoral approach via the facial vein provides a valuable alternative to other transvenous routes. Catheterization of the cavernous sinus via the facial vein is usually successful. Although this technique requires caution, it allows a safe and effective treatment of these lesions.     

Foot,hand, face and eye representation in the human striatum

The present study aimed at determining the three-dimensional organization of striatal activation during foot, hand, face and eye movements. Seven right-handed, healthy volunteers were studied at 1.5 T using blood oxygen level dependent (BOLD) contrast. The tasks consisted of self-paced flexion/extension of the right and left fingers and right toes, contraction of the lips and saccadic eye movements. For foot, hand and face movements, striatal activation was mainly found in the putamen with a somatotopical organization, the foot area being dorsal, the face area more ventral and medial, the hand area in between. Overlap between somatotopic territories was present, more prominent for hand-face than for foot-face or foot-hand areas. In the putamen, the activated areas of the ipsi- and contralateral hand areas were not identical, suggesting a partial segregation of the ipsi- and contralateral striatal sensorimotor projections. For saccadic eye movements, bilateral activation was observed at the junction between the body and the head of the caudate nucleus and in the right putamen. These data present evidence for a somatotopic organization of the human striatum which corresponds with the topography of corticostriatal projections described in the non-human primates.