A brain PET study in patients with narcolepsy-cataplexy.

OBJECTIVE: To investigate brain changes in both basal and cataplectic conditions in awake patients with narcolepsy-cataplexy. BACKGROUND: Recent insights in pathophysiology have demonstrated that narcolepsy-cataplexy is caused by early loss of hypothalamus hypocretin neurons. However, the neurophysiological mechanisms underlying sleepiness and the dramatic cataplexy reaction to positive emotion remain unclear. METHODS: Twenty-one patients with narcolepsy-cataplexy and 21 age- and sex-matched controls were included. Diagnosis of narcolepsy was fully confirmed by polysomnography, HLA DQB1*0602 and CSF hypocretin levels (n=9). Seven patients were free of all drugs, and 14 were treated with psychostimulant and/or anticataplectic drugs. (18)-F-fluorodeoxy glucose positron emission tomography procedures were performed at baseline in all subjects and during cataplexy attacks (n=2). RESULTS: The authors found significant hypermetabolism in narcolepsy-cataplexy in fully awake condition in the limbic cortex specifically in the anterior and mid cingulate cortex, in the right cuneus and lingual gyrus. In contrast, no hypometabolism was found. Hypermetabolism was detected in the cerebellum and pre-postcentral gyri in treated compared with untreated patients. During cataplectic attacks, cerebral metabolism significantly increased in the bilateral pre-postcentral gyri, primary somatosensory cortex, with a marked decrease in the hypothalamus. CONCLUSION: Hypermetabolism was found in the executive network in narcolepsy at baseline in fully awake condition. Wake state assessment during scanning appears critical to avoid results showing altered functional neurocircuitry secondary to sleepiness and not to the underlying neurological disorder per se. Finally, cataplexy attacks were characterised by a hypometabolism in the hypothalamus associated with wide bilateral brain area hypermetabolisms.

Importance of [18F]fluorodeoxyglucose-positron emission tomography scanning for the monitoring of responses to immunotherapy in follicular lymphoma.

We prospectively investigated the use of [18F]fluorodeoxyglucose (FDG)-positron emission tomography (PET) to kinetically monitor cell activation in six follicular lymphoma patients vaccinated with tumor lysate-pulsed autologous dendritic cells. PET revealed additional initial nodes suggestive of lymphoma, that were of less than 10 mm of diameter on computed tomography, and documented disease progression with sensitivity, even within loci with no significant variations of CT findings. Although tracer fixation was not observed in the inguinal nodes draining the dendritic cell intradermal injection sites in the six patients, a transient marked increase in FDG uptake within malignant nodes was observed early after vaccine administration in a patient who achieved complete remission. In non-responding patients, we observed a continuous increase of FDG uptake associated with an increase in the size and number of pathological nodes/locus, or of involved loci. FDG-PET is a non-invasive imaging procedure that might be of crucial interest to detect cell responses induced by immunotherapies.

The diagnostic accuracy of reverse transcription-PCR quantification of cytokeratin mRNA in the detection of sentinel lymph node invasion in oral and oropharyngeal squamous cell carcinoma: a comparison with immunohistochemistry.

PURPOSE: The main goal of sentinel lymph node (SLN) detection in head and neck squamous cell carcinomas is to limit neck dissections to pN+ cases only. However, intraoperative + diagnosis cannot be routinely done using the current gold standard, serial step sectioning with immunohistochemistry. Real-time quantitative reverse transcription-PCR (RT-PCR) is potentially compatible with intraoperative use, proving highly sensitive in detecting molecular markers. This study postoperatively assessed the accuracy of quantitative RT-PCR in staging patients from their SLN. EXPERIMENTAL DESIGN: A combined analysis on the same SLN by serial step sectioning with immunohistochemistry and quantitative RT-PCR targeting cytokeratins 5, 14, and 17 was done in 18 consecutive patients with oral or oropharyngeal squamous cell carcinoma and 10 control subjects. RESULTS: From 71 lymph nodes examined, mRNA levels (KRT) were linked to metastasis size for the three cytokeratins studied (Pearson correlation coefficient, r = 0.89, 0.73, and 0.77 for KRT 5, 14, and 17 respectively; P < 0.05). Histopathology-positive SLNs (macro- and micrometastases) showed higher mRNA values than negative SLNs for KRT 17 (P < 10(-4)) and KRT 14 (P < 10(-2)). KRT 5 showed nonsignificant results. KRT 17 seemed to be the most accurate marker for the diagnosis of micrometastases of a size >450 mum. Smaller micrometastases and isolated tumor cells did not provide results above the background level. Receiver operating characteristic curve analysis for KRT 17 identified a cutoff value where patient staging reached 100% specificity and sensitivity for macro- and micrometastases. CONCLUSION: Quantitative RT-PCR for SLN staging in cN(0) patients with oral and oropharyngeal squamous cell carcinoma seems to be a promising approach.

Correlation of preoperative thallium SPECT with histological grading and overall survival in adult gliomas.

BACKGROUND: The management and prognosis of a glioma depend on the tumour's histological grade. Thus, preoperative prediction of the grade is routinely needed to indicate whether surgery or biopsies are required. It has been proposed that thallium single photon emission computed tomography (SPECT), in a relative short series, will aid this prediction. AIM: To confirm the correlation between the results of preoperative thallium SPECT and grade of tumour as well as patient survival, and to define the cut-off value of the optimal thallium index for the detection of high grade gliomas in a large series of patients. METHODS: One hundred and eighteen patients treated for glioma were retrospectively included in this study. All patients underwent preoperative 201Tl SPECT upon initial presentation and were referred for neurosurgery. Initial scintigraphic findings were correlated with the histological grade of the tumour and overall patient survival. RESULTS: Thallium uptake was highly correlated with histological grade; the mean thallium indices for low grade and high grade gliomas were 1.8 and 4.9, respectively. On the basis of receiver operating characteristic analysis, the optimal cut-off value of the thallium index for the detection of high grade glioma was determined. By using 2.2 as the value for the threshold thallium index, the sensitivity and specificity were 93% and 72%, respectively. Kaplan-Meier estimates of the overall survival curves, as a function of the thallium index, indicated that it was correlated with the overall survival (P<0.001). CONCLUSION: Thallium SPECT provides useful information about the histological grade of the tumour and overall patient survival. Additionally, in spite of its relatively weak resolution, it appears to be a powerful routine clinical tool for the management of gliomas.

Confirmation of the early prognostic value of bone scanning and pinhole imaging of the hip in Legg-Calvé-Perthes disease.

UNLABELLED: In about half of all patients with Legg-Calvé-Perthes disease (LCP), severe hip disorders that could be prevented by early surgery will develop. A prognostic test for this complication is also needed as part of routine care to help the surgeon manage LCD. The purpose of this study was to confirm the prognostic value of the bone scanning and pinhole imaging of the hip in LCP that Conway's group proposed in 1997 and to define accurate prognostic scintigraphic patterns. METHODS: Fifty-eight patients with LCP were recruited at initial presentation and followed for 1 y. Each patient underwent bone scanning initially and after 5, 8, and 12 mo of disease. The severity of the disease was assessed by radiography (the Catterall classification), MRI, and arthrography. Retrospectively, initial scintigraphic findings were correlated with severity. RESULTS: Among the 60 hips studied (2 patients had bilateral disease), severe hip disorders developed in 36. The positive predictive value of the scintigraphic classification proposed by Conway's group was 97% for the B pathway (absence of lateral column formation) and 85% for the A pathway (presence of lateral column formation). The hyperactivity of the metaphyseal growth plates was a sign of poor prognosis. The sensitivity was only 33%, but the positive predictive value was 92%. This prognostic information was obtained in as few as 5 mo after initial presentation. CONCLUSION: This study confirms the high prognostic value of bone scanning in LCP as reported by Conway's group not only in terms of the accuracy of the classification but also in terms of the short time in which the prognostic information can be obtained. Thus, we propose that bone scanning be used as part of routine care for the management of LCP.

Major increase in brain natriuretic peptide indicates right ventricular systolic dysfunction in patients with heart failure.

This study sought to investigate whether the presence of right ventricular systolic dysfunction with pre-existing left ventricular systolic dysfunction is associated with higher plasma brain natriuretic peptide (BNP) levels, compared with patients with isolated left ventricular dysfunction. Eighty-five patients referred for evaluation of isotopic ventricular function were prospectively included in the study. Left (LVEF) and right (RVEF) ventricular ejection fractions were evaluated by gated blood pool scintigraphy and compared with plasma BNP levels. BNP correlated negatively with LVEF, except in patients with ischaemic heart disease (P=0.09) and in patients with LVEF<40% (P=0.11). In contrast, BNP levels correlated negatively with RVEF for all subgroups. Among patients with RVEF<40%, no significant BNP difference was found between patients with or without additional left ventricular systolic dysfunction (P=0.51). Among patients with LVEF<40%, plasma BNP levels were significantly higher in patients with RVEF<40% than in patients with RVEF>/=40% (P=0.004) whereas age, renal function, clinical findings, ventricular volumes, LVEF or medication were not significantly different. In conclusion, an important increase in BNP levels in patients with left ventricular systolic dysfunction should be considered by cardiologists as an indication of high risk of right ventricular dysfunction and should justify further investigation.

Widespread hypermetabolism in symptomatic and asymptomatic episodes in Kleine-Levin syndrome.

BACKGROUND: No reliable biomarkers are identified in KLS. However, few functional neuroimaging studies suggested hypoactivity in thalamic and hypothalamic regions during symptomatic episodes. Here, we investigated relative changes in regional brain metabolism in Kleine-Levin syndrome (KLS) during symptomatic episodes and asymptomatic periods, as compared to healthy controls. METHODS: Four drug-free male patients with typical KLS and 15 healthy controls were included. 18-F-fluorodeoxy glucose positron emission tomography (PET) was obtained in baseline condition in all participants, and during symptomatic episodes in KLS patients. All participants were asked to remain fully awake during the whole PET procedure. RESULTS: Between state-comparisons in KLS disclosed higher metabolism in paracentral, precentral, and postcentral areas, supplementary motor area, medial frontal gyrus, thalamus and putamen during symptomatic episodes, and decreased metabolism in occipital and temporal gyri. As compared to healthy control subjects, KLS patients in the asymptomatic phase consistently exhibited significant hypermetabolism in a wide cortical network including frontal and temporal cortices, posterior cingulate and precuneus, with no detected hypometabolism. In symptomatic KLS episodes, hypermetabolism was additionally found in orbital frontal and supplementary motor areas, insula and inferior parietal areas, and right caudate nucleus, and hypometabolism in the middle occipital gyrus and inferior parietal areas. CONCLUSION: Our results demonstrated significant hypermetabolism and few hypometabolism in specific but widespread brain regions in drug-free KLS patients at baseline and during symptomatic episodes, highlighting the behavioral state-dependent nature of changes in regional brain activity in KLS.

[Combined role of tumor markers and 18fluoro-deoxyglucose-positron emission tomography (18FDG-PET) in follow-up of cancer patients]. / Apport combiné des marqueurs tumoraux et de la tomographie par émission de positons au 18FDG (TEP-18FDG) dans le suivi des patients atteints de cancer.

One of the major indications of tumor markers is the detection of occult disease. Less than 20 % of tumor markers elevations are associated with clinical or radiological findings. Such elevations have led medical community to doubt about the interest of markers follow-up, such as CA 15.3 in breast cancer. Now, positron emission tomography with (18)fluoro-desoxyglucose (18FDG-PET), using metabolic properties of malignant cells, is able to visualize tumor recurrences at an early stage of development, before any occurrence morphologic changes depicted by radiological examinations. Because of its cost and its limited accessibility, this functional technique should only be prescribed following a large set of informative indications, of which tumor markers belong. Early positive, non invasive and cost effectiveness, tumor markers become a precious guide in the prescription of 18FDG-PET in oncology. This article reviews the results of a set of recent studies in colorectal, breast and ovarian cancer.