Added Value of Spectroscopy to Perfusion MRI in the Differential Diagnostic Performance of Common Malignant Brain Tumors.

BACKGROUND AND PURPOSE: Perfusion and spectroscopic MR imaging provide noninvasive physiologic and metabolic characterization of tissues, which can help in differentiating brain tumors. We investigated the diagnostic role of perfusion and spectroscopic MR imaging using individual and combined classifiers of these modalities and assessed the added performance value that spectroscopy can provide to perfusion using optimal combined classifiers that have the highest differential diagnostic performance to discriminate lymphomas, glioblastomas, and metastases. MATERIALS AND METHODS: From January 2013 to January 2016, fifty-five consecutive patients with histopathologically proved lymphomas, glioblastomas, and metastases were included after undergoing MR imaging. The perfusion parameters (maximum relative CBV, maximum percentage of signal intensity recovery) and spectroscopic concentration ratios (lactate/Cr, Cho/NAA, Cho/Cr, and lipids/Cr) were analyzed individually and in optimal combinations. Differences among tumor groups, differential diagnostic performance, and differences in discriminatory performance of models with quantification of the added performance value of spectroscopy to perfusion were tested using 1-way ANOVA models, receiver operating characteristic analysis, and comparisons between receiver operating characteristic analysis curves using a bivariate χ2, respectively. RESULTS: The highest differential diagnostic performance was obtained with the following combined classifiers: maximum percentage of signal intensity recovery-Cho/NAA to discriminate lymphomas from glioblastomas and metastases, significantly increasing the sensitivity from 82.1% to 95.7%; relative CBV-Cho/NAA to discriminate glioblastomas from lymphomas and metastases, significantly increasing the specificity from 92.7% to 100%; and maximum percentage of signal intensity recovery-lactate/Cr and maximum percentage of signal intensity recovery-Cho/Cr to discriminate metastases from lymphomas and glioblastomas, significantly increasing the specificity from 83.3% to 97.0% and 100%, respectively. CONCLUSIONS: Spectroscopy yielded an added performance value to perfusion using optimal combined classifiers of these modalities, significantly increasing the differential diagnostic performances for these common brain tumors.

Complex fractures of the acetabulum: Should the enlarged iliofemoral approach be abandoned? Results at 20 years' follow-up.

INTRODUCTION: Among the various options for internal fixation of acetabular fractures, the enlarged iliofemoral approach is less often used, being more invasive, although providing greater exposure enabling control of all components in complex fractures. Even so, the impact of its invasiveness has not been confirmed, and long-term results are not known. We therefore performed a retrospective study, aiming: to assess long-term functional outcome, and; to assess associated morbidity. HYPOTHESIS: The enlarged iliofemoral approach allows precise reduction, with favorable long-term outcome. MATERIAL AND METHODS: Between 1992 and 1997, 15 patients were operated on for complex acetabular fracture by a single surgeon using an enlarged iliofemoral approach. Two patients were excluded due to lack of follow-up data, leaving 13 patients for analysis: 3 simple transverse fractures, 4 transverse+posterior wall fractures, 4 anterior column+posterior hemi-transverse fractures, one T-shaped fracture and one 2-column fracture. There were 4 cases of posterior dislocation of the hip, and 8 of intrapelvic protrusion. Surgical morbidity was assessed in terms of operative time, number of packed red blood cell transfusions, iatrogenic lesions or postoperative complications, rehabilitation time, and hospital stay. Functional assessment at follow-up used the WOMAC index and Harris score; radiologic assessment used the Kellgren-Lawrence score for osteoarthritis and Brooker score for ossification. RESULTS: Reduction was in all cases anatomic. There were no intra- or post-operative complications. Median number of packed red blood cell transfusions was 5 [range, 3-10]. Median operative time was 4hours [3-6]. Median hospital stay was 6 weeks [6-8], to allow systematic traction with early postoperative mobilization. Weight-bearing was resumed at a median 8 weeks [8-12]. At a median 22 years' follow-up [20-24], median Harris score was 83.5 [63-92] and median WOMAC index 24.5 [1-52]. All patients showed Brooker 1 or 2 ectopic ossification and moderate osteoarthritis. Two underwent subsequent arthroplasty (at 1 and 11 years after the index procedure). DISCUSSION: The enlarged iliofemoral approach allowed anatomic reduction of acetabular fracture. It provided very good long-term results, without excessive morbidity. LEVEL OF EVIDENCE: IV, retrospective non-controlled study.

[Osteo-cutaneous Mycobacterium marinum infection of the elbow and reconstruction with radial collateral artery perforator-based propeller flap]. / Infection ostéo-cutanée du coude à Mycobacterium marinum et reconstruction par un lambeau en hélice basé sur une perforante de l'artère collatérale radiale postérieure.

Mycobacterium marinum is an atypical and non-tuberculosis mycobacterium that mainly leads to cutaneous infections. Infections occur through inoculation of the organism through injury to the skin in the presence of contaminated water or fish. The patient often presents with unspecific symptoms and the evolution, in the absence of adequate treatment, is characterized by an expansion of the cutaneous lesion and a spread to deep structures. Infections of tendon sheaths and joints are described, rarely osteomyelitis. Sure diagnosis is hard to obtain and is established from the medical history and microbiological examination. There are no specific therapeutic guidelines. Double or triple antibiotherapy is often effective and should be continued several months after complete resolution of clinical signs. Surgical debridement is required in cases of invasive or resistant infections. We report the case of a young immunocompetent fishmonger with a rare osteocutaneous M. marinum infection of the elbow. Treatment included large surgical excision of infected skin and bone areas and a triple antibiotics administration. Reconstruction have been ensured by a radial collateral artery perforator-based propeller flap, satisfying appropriates functional and cosmetical concerns of this anatomical region. Surgery and appropriate antibiotics treatment were effective and allowed healing of an invasive cutaneous and bone M. marinum infection.

Reducible valgus flat-foot: assessment of posterior subtalar joint surface displacement by posterior arthroscopy during sinus tarsi expansion screwing.

INTRODUCTION: Subtalar arthroereisis corrects childhood and adult reducible valgus flat-foot in certain indications. Inserting an expansion screw in the sinus tarsi simultaneously corrects the calcaneal valgus of the talocalcaneal divergence and first-ray pronation if these are reducible. The displacement induced in the posterior subtalar joint (decoaptation, translation, rotation) is, however, poorly known. The present study involved arthroscopic assessment of posterior subtalar joint surface displacement during insertion of a talocalcaneal arthroereisis screw, with the hypothesis that displacement varies in three dimensions according to screw size. MATERIAL AND METHOD: Eight specimens were used for the study. All ankles were supple, taken from adult subjects. A 4.5-mm arthroscope was used and measurements were taken with a graduated palpator in the posterior subtalar joint. Three sinus tarsi expansion screws of incremental diameter were assessed. Before and after insertion measurements were made of posterolateral and posteromedial talar exposure on the calcaneus, anteroposterior and lateromedial translation, and talocalcaneal joint-line opening. RESULTS: Medial rotation, varization and anterior translation of the calcaneus were comparable in all cases. Mean lateral opening of the posterior subtalar joint was 0.88 mm with 8-mm screws and 1.25 mm with 16-mm screws. Significant differences between 8 and 16 mm screws were found for lateral subtalar joint opening (P=0.028) and for lateromedial translation (P=0.004). CONCLUSION: Sinus tarsi expansion screwing corrects hindfoot valgus and talocalcaneal divergence by inducing medial translation of the calcaneus under the talus and talar medial rotation and varization, proportional to screw size (medial translation and lateral opening of the subtalar joint). LEVEL OF EVIDENCE: III.

Presence of Ras guanyl nucleotide-releasing protein in striosomes of the mature and developing rat.

Ras signal transduction pathways have been implicated as key regulators in neuroplasticity and synaptic transmission in the brain. These pathways can be modulated by Ras guanyl nucleotide exchange factors, (GEF) which activate Ras proteins by catalysing the exchange of GDP for GTP. Ras guanyl nucleotide-releasing protein (RasGRP), a recently discovered Ras GEF, that links diacylglycerol and probably calcium to Ras signaling pathways, is expressed in brain as well as in T-cells. Here, we have used a highly selective monoclonal antibody against RasGRP to localize this protein within the striatum and related forebrain structures of developing and adult rats. RasGRP immunolabeling was found to be widespread in the mature and developing rat forebrain. Most notably, it presented a prominent patchy distribution throughout the striatum at birth and at all postnatal ages examined. These patches were found to correspond with the striosomal compartment of the striatum, as identified by micro-opioid receptor labeling in the adult. RasGRP-immunoreactivity was also observed in the matrix-like compartment surrounding these patches/striosomes but appeared later in development and was always weaker than in the patches. In both striatal compartments, RasGRP was exclusively expressed by medium-sized spiny neurons and showed no preference for neurons that project either directly or indirectly to the substantia nigra. At the ultrastructural level, immunogold labeling of RasGRP was confined to the cell bodies and dendritic shafts of these output neurons. We conclude that the prominent expression of RasGRP in striosomes may be of significance for diacylglycerol signaling in the striatum, and could be of importance for the processing of limbic-related activity within the basal ganglia.

Astrocytes from cerebral cortex or striatum attract adult host serotoninergic axons into intrastriatal ventral mesencephalic co-grafts.

The identification of axon growth inhibitory molecules offers new hopes for repair of the injured CNS. However, the navigational ability of adult CNS axons and the guidance cues they can recognize are still essentially unknown. Astrocytes may express guidance molecules and are known to have different regional phenotypes. To evaluate their influence on the affinity of adult serotoninergic (5-HT) axons for a projection target, we co-implanted astrocytes from the neonatal striatum, cortex, or ventral mesencephalon together with fetal ventral mesencephalic tissue into the striatum of adult rats. Two months after surgery, quantification after in vitro 5-[1,2-(3)H]serotonin ([(3)H]5-HT) uptake and autoradiography showed that ventral mesencephalic grafts with co-grafted cortical or striatal astrocytes were four times and three times, respectively, more densely innervated by host 5-HT axons than control ventral mesencephalic grafts with or without co-grafted ventral mesencephalic astrocytes. Immunohistochemistry for glial fibrillary acidic protein, vimentin, or chondroitin-sulfate proteoglycans revealed no qualitative or quantitative differences in host astroglial scar or production of inhibitory molecules that could explain these differences in 5-HT innervation. These results demonstrate that astrocytes grown in culture from different brain regions have the potential to influence the growth and maintenance of adult 5-HT axons in a graft of neural tissue from another brain region. It should now be feasible to identify the molecules expressed by cultured cortical or striatal, but not by ventral mesencephalic, astrocytes that have these tropic actions on 5-HT axons of the neostriatum.

Expression of the AMF/neuroleukin receptor in developing and adult brain cerebellum.

The peptide sequence of autocrine motility factor (AMF), a tumor secreted cytokine that induces cell motility, corresponds to that of the previously identified cytokine/enzyme, neuroleukin/glucose-6-phosphate isomerase. Neuroleukin is a neurotrophic factor that promotes neuronal survival and sprouting at the neuromuscular junction. The AMF receptor (AMF-R) has been identified and shown to be highly expressed in malignant tumors with minimal expression in adjacent normal tissue. Neuroleukin mRNA is highly expressed in the cerebellum and we therefore undertook a developmental study of AMF-R expression in rat cerebellum. As determined by immunoblot, AMF-R is expressed at equivalent high levels in brain and cerebellum of postnatal day 5 (P5) and 12 (P12) rats and at significantly reduced levels in the adult. Coimmunofluorescence studies with MAP-2 and gamma-actin revealed that at P12, AMF-R was mainly localized to Purkinje and granule cells. Moreover, the premigratory cells of the external granular layer were also immunoreactive for AMF-R suggesting a role for AMF-R in granule cell migration during cerebellar development in the first two weeks after birth. In the adult, AMF-R distribution was similar to P12, although weaker, and was localized to Purkinje and granule cells. AMF-R labeling of GFAP positive glial processes could not be detected in cerebellar sections although in cerebellar primary cultures, both neurons and glial cells were labeled for AMF-R. In neurons, AMF-R labeling was present in the cell body, neurites and growth cones. These data indicate that regulation of the neurotrophic function of neuroleukin might be regulated spatially and temporally by expression of its receptor, AMF-R, in developing and adult cerebellum.

Serotonin axons of the neostriatum show a higher affinity for striatal than for ventral mesencephalic transplants: a quantitative study in adult and immature recipient rats.

We previously showed that grafts of fetal ventral mesencephalic tissue are practically not innervated by host serotonin (5-HT) axons after implantation into the striatum of rats aged more than 14 days, at variance with transplants of cortical or striatal tissue into the adult striatum, which are well innervated by these axons. Using 5-HT immunohistochemistry and in vitro [3H]5-HT uptake/autoradiography, we have examined and quantified the innervation of ventral mesencephalic versus striatal grafts several months after implantation into the striatum of neonatal (postnatal day 5 or P5), juvenile (P15), and adult rats. Ventral mesencephalic grafts implanted in P5 rats received a moderate 5-HT innervation, while similar grafts implanted in P15 or adult recipients were almost free of any 5-HT fibers (-80%, compared to P5). The density of 5-HT innervation showed a tendency toward higher values in striatal than in ventral mesencephalic grafts (1.6-2 times higher in P5 and adult recipients; 4 times higher in P15 recipients). The difference was more striking, and significant, when only the true striatal portions of the striatal grafts were considered, i.e., DARPP-32-immunopositive areas (4-5 times higher in P5 and adult recipients; 10 times higher in P15 recipients). Accordingly, these DARPP-32-positive areas were also more densely innervated than the DARPP-32-negative zones of the same grafts (3 times higher at any age). The 5-HT innervation density also decreased with increasing age of the recipients in DARPP-32-positive, as well as DARPP-32-negative compartments of the striatal grafts (-75% in adults), but this decrease appeared more gradual (-50% in juveniles) than with mesencephalic grafts. It is concluded that the 5-HT axons innervating the neostriatum have a better affinity for striatal grafts than for ventral mesencephalic grafts or the nonstriatal portions of striatal grafts. In adulthood, the relative affinity of these axons for the different types of grafts is maintained, even though their growth capacity decreases irrespective of the target tissue considered. This experimental model may prove useful for the identification of the receptors and ligands that are responsible for target recognition by 5-HT axons and to test the possibility that the progressive decrease of axonal growth capacity from neonatal age to adulthood be related to a downregulation of such molecules.

Host striatal projections into fetal ventral mesencephalic tissue grafted to the striatum of immature or adult rat.

We have previously reported that few striatal axons from adult host brain innervate intrastriatal grafts of fetal ventral mesencephalic tissue. To see whether the immature rat brain would favor striatal innervation of the graft, unilateral implantation of fetal ventral mesencephalic tissue was carried out at 7 (P7), 14 (P14), or 60 (adults) days of age in neonatally dopamine-(DA)-lesioned and nonlesioned rats. Immunocytochemistry for tyrosine hydroxylase (TH), and/or dopamine- and adenosine 3',5'-monophosphate-regulated phosphoprotein-32 (DARPP-32) was performed 2-6 months later. In the great majority of immature and in all adult recipients, the resulting graft consisted of a distinct intrastriatal mass of tissue surrounded by the host parenchyma. Most TH-immunopositive neurons were found within the confines of such grafts, although some were lying at short distances into the host striatal tissue, particularly in immature recipients. In a few immature recipients, there was, however, extensive intermingling of TH-positive neurons with the adjacent host brain tissue. In all recipients grafted at P7, P14, or as adults, the distinct, intraparenchymal grafts contained moderate numbers of DARPP-32-positive processes, mainly at their periphery. These results indicate that the limited capacity of host striatal neurons to grow axons into transplanted fetal ventral mesencephalic tissue is not markedly different in young versus adult rats. A better integration of the ventral mesencephalic graft into the striatal circuitry of immature--as opposed to adult--recipients should therefore rely more on the higher tendency of DA neurons to become located into the host tissue following transplantation in young rats.