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International audience; We determined the value of hippocampus (Hp) and basal forebrain (BF) volumes for predicting cognitive decline and treatment response in a double-blind, randomized, placebo-controlled phase 4 trial at 28 academic centers (France) in patients with amnestic mild cognitive impairment (MCI) receiving Donepezil 10 mg daily or placebo over 12 months, and 6 months open label follow-up. Outcome measures were the rates of global and domain specific cognitive decline as non-primary efficacy endpoint. The intention-to-treat (ITT) sample analyzed comprised 215 cases. Baseline Hp volume was a significant predictor of rates of change in global cognitive function in linear mixed effects models. This effect was independent of treatment. BF volume was not associated with rates of global or domain specific cognitive decline. Rates of delayed free recall decline were higher in MCI cases treated with donepezil compared to placebo. Only Hp, but not BF volume was a useful predictor of cognitive decline in suspected prodromal AD patients. Both Hp and BF volumes were poor predictors of treatment response, questioning previous approaches on predicting treatment response without placebo control. clinicalTrials.gov Identifier NCT00403520.

Interaction of HIV with cultured human monocytes triggers not only cytokine production but also the release of natural cytokine inhibitors such as the soluble TNF receptors, levels of which are increased in the circulation of HIV-infected patients. We found that HIV-1 LAI induced the production by human monocytes from HIV-seronegative donors of another type cytokine inhibitor, the IL-1Ra receptor antagonist (IL-1Ra). HIV mainly induced the secreted form (83%) of IL-1Ra through de novo mRNA synthesis. IL-1Ra production was triggered at an early step of the infection process and involved the HIV envelope protein and the CD4 receptor. HIV-triggered IL-1Ra production occurred after a lag time, suggesting an indirect mechanism. Neutralizing Abs to IL-1 beta and IL-10 had no effect, while simultaneous treatment with anti-TNF-alpha, anti-granulocyte-macrophage CSF, and anti-TGF-beta nearly abrogated IL-1Ra release, supporting an indirect induction through the concerted action of the co-produced cytokines. IL-1Ra was induced by HIV in a mean 1,000-fold increase over IL-1 alpha beta, a ratio 20-fold higher than that obtained with LPS. This production masked 80% of IL-1 bioactivity in HIV-induced monocyte supernatants. These results suggest that the net balance between pro-inflammatory cytokines and their natural inhibitors could be critical in the control of the inflammatory process associated with HIV infection.

Recent neuropathologic research suggests thalamic involvement in sporadic Creutzfeldt-Jakob disease (sCJD), which has been disregarded in imaging studies. Diffusion-weighted (DW) MR imaging has the highest sensitivity for the detection of signal intensity (SI) abnormalities in CJD. We hypothesized that pathologic changes in the thalamus in sCJD can be detected by using a subtle analysis of DW MR imaging.Six sCJD patients and nine healthy controls were examined with a 1.5-T system by using DW single-shot spin-echo echo planar (b = 0, 1000 s/mm(2)), T2-weighted turbo spin-echo, and fluid-attenuated inversion recovery sequences. One patient was examined serially (3, 4, and 8 months after onset of symptoms). MR images were reviewed for SI changes in the striatum, hippocampus, mediodorsal thalamic nucleus (MD), and pulvinar thalami. Apparent diffusion coefficients (ADCs) were measured in these areas.All sCJD patients showed increased SI on DW images in the striatum bilaterally. ADCs in these areas were significantly reduced. Four of six sCJD patients showed increased SI on DW images in the pulvinar thalami, whereas ADCs were significantly reduced in all patients (mean ADC +/- SEM: in patients with SI changes, 701 +/- 38; in patients without SI changes, 684 +/- 37; in controls, 853 +/- 15 [P.0001]). No patient showed SI changes in the MD on DW images, whereas ADCs were significantly reduced in all (664 +/- 28 as compared with 800 +/- 24 in controls [P =.0011]). Serial measurements in one sCJD patient showed ADC reduction in the pulvinar thalami preceding the SI changes on DW images.A quantitative analysis of DW images with ADC measurements shows slight MR imaging changes in the thalamus in sCJD when abnormal SI may not be present.

5-HT (serotonin) is known to be involved in neuroinflammation and immunoregulation. The human immunodeficiency virus (HIV) targets cells such as monocytes/macrophages, which colocalize with 5-HT-releasing cell types, mostly platelets. In this study, we investigated the effects of 5-HT on HIV-1-infected macrophages in vitro.Human macrophages cultured in serum-free medium were treated over 7 days with 5-HT at three concentrations (0.01, 1 and 100 microM) with or without agonists and antagonists of 5-HT(1A) and 5-HT(2) receptors. After 7 days of treatment, macrophages were infected with HIV-1/Ba-L and virus replication was monitored over 16 days and expression of proviral HIV DNA was investigated by PCR after 24 h of infection. Cell surface expression of HIV-1/Ba-L receptor (CD4) and coreceptor (CCR5) was investigated by flow cytometry. The CCR5 ligand, macrophage inflammatory protein-1alpha (MIP-1alpha), was quantified by ELISA in cell culture supernatants and MIP-1alpha mRNA expression was assessed by reverse transcriptase-PCR.In vitro, 5-HT downregulated the membranous expression of CCR5 and led to a decrease of HIV-1 infection, probably through its action on 5-HT(1A) receptors. 5-HT (100 microM) was also able to induce overexpression of MIP-1alpha mRNA leading to an increase of MIP-1alpha secretion by human macrophages.The effects of 5-HT on HIV infection could be a consequence of the increase in MIP-1alpha concentrations and/or CCR5 receptor downregulation. These results suggest that 5-HT can inhibit the replication of HIV-1 in primary culture of human macrophages through its action on 5-HT(1A) receptors.

BACKGROUND AND PURPOSE: This study investigated the role of CT as an early predictor of outcome prognosis after glue embolization of spinal dural arteriovenous fistulas (SDAVF). METHODS: Over a 13-year period, 26 patients underwent glue embolization of SDAVF and were retrospectively reviewed. Immediately after embolization, each patient had CT evaluation of cast position. Mean follow-up angiography was 23.4 months (range, 1–87 months; median, 21 months). Both MR images and clinical data (e.g., gait and micturition disabilities according to the Aminoff and Logue disability scale, deep and superficial sensitivity) were analyzed, with a mean follow-up of 37.7 months (range, 12–98 months; median, 28 months). Data were tested by univariate analysis by using Fisher’s exact test and the Kruskall Wallis test, depending on the order of the qualitative variables. RESULTS: Glue was found in the dura mater on CT in 19 (73%) patients. None of these patients had a recanalized fistula on angiography, and the clinical status of all of them improved. Glue was observed in or proximal to the foramen on CT in seven (27%) patients. In five of them, the fistula was recanalized within a mean period of 9 months (range, 3–24 months; median, 6 months) and their clinical status worsened. All five required surgical treatment. On angiography, the absence of fistula recanalization was observed in 21 (81%) patients and correlated with improvements in gait (P = .016), sensitivity (P = .030), and micturition (P = .080). It also correlated with a decrease in the extent of the abnormally high intramedullary T2 signal intensity (P = .002), a decrease in spinal cord diameter (P = .017), and the resolution of prominent perimedullary vessels (P < .001). The presence of glue within the dura mater on CT correlated with the absence of fistula recanalization (P = .045) and with overall improvement in clinical status, including gait and/or sensitivity and/or micturition (P = .042). CONCLUSION: CT evaluation of embolization cast position immediately after embolization may constitute an early and reliable tool for predicting permanent fistula occlusion and the prognosis for outcome.

International audience

National audience; A la suite de l'interdiction des farines animales en alimentation animale, il est nécessaire de mettre au point des procédés simples et économiques pour les valoriser et les décontaminer vis-à-vis de la présence possible de prion pathogène. L'usage des microorganismes est une solution possible. Aussi, des collections de microorganismes capables de croître sur la kératine ou sur des farines animales et sécrétant des protéases capables de dégrader la PrPsc contenue dans les farines animales ont été criblées. Ceci a permis de découvrir trois souches de bactéries thermophiles, isolées de différentes sources chaudes réparties sur la planète, qui sont capables de dégrader la protéine prion infectieuse PrPsc et de croître sur un milieu composé de farines animales. Leur activité protéolytique, de type chymotrypsique pour l'essentiel, est maximale à la température de 60 à 80°C et focalisée sur certaines liaisons peptidiques qui sont nombreuses sur la protéine prion. Leur action découpe ainsi la protéine prion en morceaux plus courts inoffensifs. Les perspectives sont de mettre en oeuvre ces microorganismes thermophiles dont le patrimoine protéolytique permettrait la dégradation des farines animales, actuellement incinérées, et les protéines prions qu’elles renferment.

National audience; A la suite de l'interdiction des farines animales en alimentation animale, il est nécessaire de mettre au point des procédés simples et économiques pour les valoriser et les décontaminer vis-à-vis de la présence possible de prion pathogène. L'usage des microorganismes est une solution possible. Aussi, des collections de microorganismes capables de croître sur la kératine ou sur des farines animales et sécrétant des protéases capables de dégrader la PrPsc contenue dans les farines animales ont été criblées. Ceci a permis de découvrir trois souches de bactéries thermophiles, isolées de différentes sources chaudes réparties sur la planète, qui sont capables de dégrader la protéine prion infectieuse PrPsc et de croître sur un milieu composé de farines animales. Leur activité protéolytique, de type chymotrypsique pour l'essentiel, est maximale à la température de 60 à 80°C et focalisée sur certaines liaisons peptidiques qui sont nombreuses sur la protéine prion. Leur action découpe ainsi la protéine prion en morceaux plus courts inoffensifs. Les perspectives sont de mettre en oeuvre ces microorganismes thermophiles dont le patrimoine protéolytique permettrait la dégradation des farines animales, actuellement incinérées, et les protéines prions qu’elles renferment.

Extra-axial cavernous hemangiomas or angiomas [(hem)angiomas] are relatively rare lesions. They usually arise in relation to the dura mater intracranially or at the spinal level. Most of these lesions have been described in the middle cranial fossa at level of the cavernous sinus. Controversy still exists regarding the exact nature of these extra-axial cavernous angiomas: vascular tumor versus vascular malformation similar to intra-axial cavernomas. It has been suggested that they could represent an adult form of the hemangioma of infancy. Extra-axial cavernous (hem)angiomas often mimic meningiomas and their clinical behavior and imaging appearance are quite different than those of intra-axial cavernous angiomas.Five patients ranging in age from 24 to 63 years with a histologically proven dural cavernous angioma were retrospectively included. The lesions were located at level of the cavernous sinus (4 cases) and falx. CT and MR scans were performed in all cases and angiography in three patients. Four patients underwent surgery and a biopsy was performed in one case. One lesion was embolized before biopsy. Histology was available in all patients.In the operated patients, the lesion was totally resected in 2 cases and partially in the other 2. No postsurgical complication was noted. Histology revealed a vascular malformation composed of large vascular channels lined by flat endothelium and separated by fibroconnective tissue stroma. The pathological diagnosis was cavernous angioma.On the basis of the analysis of the literature and of our cases, intra-cranial extra-cerebral so-called cavernous (hem)angiomas present findings suggesting that they are vascular malformative lesions, analogous to the intra-axial cavernous angioma. A relationship with the hemangiomas of infancy seems unlikely. Correct terms for extra-cerebral cavernous (hem)angiomas are cavernoma, cavernous angioma, or venous vascular malformation of cavernous type . The term hemangioma should be avoided and reserved for the common vascular tumor of infancy.

To describe a reversible neurological condition resembling a crossed midbrain syndrome resulting from high frequency stimulation (HFS) in the midbrain.Postoperative evaluation of quadripolar electrodes implanted in the area of the subthalamic nucleus of 25 patients with Parkinson's disease (PD) successfully treated by HFS.Four of the 25 patients experienced reversible acute diplopia, with dystonic posture and tremor in the contralateral upper limb when the white matter between the red nucleus and the substantia nigra was stimulated. The motor signs resembled those caused by lesions of the red nucleus. The ipsilateral resting eye position was "in and down" (three patients) or "in" (one patient). Enophthalmos was seen. Abduction was impaired and vertical eye movements were limited, but adduction was spared. The movements of the controlateral eye were normal. The ocular signs could be best explained by sustained hyperactivity of the extrinsic oculomotor nerve. Simultaneous tonic contraction of the superior rectus, the inferior rectus, and inferior oblique may cause the enophthalmos and partial limitation of upward and downward eye movements. Antagonist tonic contraction of the ipsilateral medial rectus severely impairs abduction.This crossed midbrain syndrome, possibly resulting from simultaneous activation of oculomotor nerve and lesion-like inhibition of the red nucleus suggests that high frequency stimulation has opposite effects on grey and white matter.

Spinal neurosarcoidosis is rare (0.43 p. 100 of all sarcoidosis) and can be the initial manifestation of the disease. A 43-year-old right handed African man developed a progressive dorsal neck pain, slowly worsened paresthesia weakness in the legs and a gait disturbance. Magnetic resonance imaging (MRI) scan of the cervical and thoracic spinal cord (sagittal T(1)- weighted image) revealed diffuse enlargement of the cord from C2 to T7 with intense intramedullary enhancement from C2 to T3 after administration of contrast material on sagittal T(1)- weighted image. Cranial MRI scan was normal. Radiographs of the chest revealed bilateral symmetric hilar mediastinal lymphadenopathy with no pulmonary infiltrates. Bronchial biopsy demonstrated non caseating granulomas with langerhans giant cells. The serum angiotensin converting enzyme level was elevated. The patient received corticosteroid with good progressive response. His neurologic symptoms improved markedly and twenty months post-treatment MRI showed no abnormality on enhanced T(1)- weighted images. Two years later he had no relapse. Only 6 to 10 p. 100 of patients with neurosarcoidosis have spinal cord involvement, which may account for the first clinical manifestation of the disease. Most patients with neurosarcoidosis have associated extraneurologic abnormalities. The diagnosis is supported usually by extraneurologic biopsies. Spinal cord biopsy needs to be considered on case-by-case basis.

There are two types of diffusion images: so-called "diffusion-weighted" images (DWI) and apparent diffusion coefficient (ADC) images. For certain authors, ADC mapping is crucial for interpreting diffusion images while for others the ADC map adds no further sensitivity or specificity compared with diffusion weighted images. The objective of this work was to determine those situations where ADC mapping modifies image interpretation.T2-weighted and diffusion-weighted (DIF) MRI sequences were acquired in 197 patients with suspected cerebral ischemia (or = 48 hr). For each lesion (239 lesions in the 197 patients), we analyzed MRI interpretation with and without ADC mapping and compared the interpretations with the final diagnosis established on clinical data and complementary explorations.We observed 3 groups. In group A (36% of the lesions), ADC mapping did not change image interpretation. This group was subdivided into 3 subgroups. A1: T2 and DIF weighted images are normal: no lesions and normal ACD map (n = 38 patients); A2: High intensity signal on T2 and low intensity signal on DIF: ischemic sequelae, ADC always increased (n = 32 lesions); A3: T2 normal and high intensity signal on DIF: hyper acute ischemia and ADC always decreased (n = 16 patients) In group B (high intensity signal on T2 and DIF, 54.5% of the lesions), ADC mapping changed the MRI interpretation: there was acute ischemia if the ADC was decreased (n = 113) and "pseudo-ischemic" lesions if the ADC was normal or increased (n = 17 patients). Group C was comprised of 23 lesions with a false negative ADC (9.5%). These lesions were always small recent ischemic lesions (or = 5 mm) with a high intensity signal on DIF and a strictly normal ADC map.ADC mapping was found to be useful in 54.5% of the lesions and should not be considered as solely a research tool but also as a useful tool for routine clinical practice.

L'Agence française de sécurité sanitaire des aliments (AFSSA) a lancé, depuis juillet 1999, comme l'ont souhaité les Ministres à l'occasion de l'installation du Conseil d'administration de l'AFSSA, un travail général d'évaluation scientifique des risques liés à l'alimentation animale. A la suite des deux grandes crises, dont l'origine provient de l'alimentation animale (crise de l'encéphalopathie spongiforme subaiguë (ESB) et crise dioxines), il est apparu important de procéder à un recensement de l'ensemble des questions liées à l'alimentation animale en relation avec la sécurité des aliments et à une analyse des risques dans ce domaine. Le Directeur général de l'Agence française de sécurité sanitaire des aliments a institué un groupe de travail nommé "Alimentation animale et sécurité des aliments" et présidé par le Professeur Dominique Dormont chargé de réaliser cette analyse générale. Ce groupe de travail pourra en outre être saisi pour répondre rapidement à toute demande d'expertise relevant de sa mission, et proposer des projets d'avis ou de recommandations. Le travail de ce groupe doit couvrir l'ensemble des problématiques liées à l'alimentation animale, hors organismes génétiquement modifiés (OGM) et hors alimentation des espèces non destinées à la consommation humaine (animaux de compagnie).

Dural arteriovenous fistulas (dAVFs) can cause cerebral venous hypertension (VHT). The most common mechanism is due to the fact that some dAVFs can drain retrogradelly in cortical (better defined as leptomeningeal) veins (directly or after drainage in a dural sinus) causing venous engorgement and consequently an impairment of the cerebral venous drainage. However, more rarely, dAVFs without a cortical venous drainage can also be responsible for VHT probably due to dAVF shunts causing insufficient antegrade cerebral venous drainage. In addition, dAVFs are often associated with stenosis and/or thrombosis of dural sinus(es) which can worsen the VHT. Raised pressure within the superior sagittal sinus causes impeded cerebrospinal reabsorption in the arachnoid villi allowing increased intracranial pressure. The venous engorgement in the cortical veins can cause a venous congestive encephalopathy analogous to the venous congestive myelopathy of the spinal dural AVFs. Clinically VHT can cause not only symptoms related to increased intracranial pressure but also seizures, neurological deficits, impairment of the cognitive functions and dementia. An important aspect is the risk of hemorrhage in dAVFs with a leptomeningeal venous drainage leading to VHT. Although the term VHT sensu strictu should be used if venous pressure measurements are performed, angiographic criteria for VHT such as delayed circulation time, venous engorgement and abnormal visualization of the cerebral veins are well established. The purpose of our study was to evaluate the angiographic signs of VHT in patients with dAVF and to study the course of the VHT and of the clinical signs of increased intracranial pressure before and after dAVF endovascular treatment. A retrospective chart analysis of 22 patients (13 males, 9 females) ranging in age from 20 to 87 years (mean: 53 ys.) with a dAVF associated with angiographic signs of VHT was performed. Ten dAVFs were located on the transverse/sigmoid sinus(es), 6 on the superior sagittal sinus, 3 on the petro-tentorial incisura, 1 on the inferior petrosal sinus, 1 on the anterior ethmoidal region and 1 on the Galen vein region. All dAVFs had a retrograde leptomeningeal venous drainage. Stenosis or thrombosis of the dural AVF sinus was observed in 17 cases and stenosis or thrombosis of another sinus(es) and/or of the jugular vein in 8 cases. In 11 patients, the angiographic signs of VHT were global affecting the entire cerebral venous drainage and, in the other 11 patients, the VHT was focal. The VHT caused clinical symptoms of increased intracranial pressure in 18 patients. Other clinical findings included: bruit (11 cases), seizures (3 cases), vertigo (3 cases), visual deficits (2 cases) and impairment of cognitive functions (4 cases). Three patients presented hemorrhage (one parenchymal hematoma, one hemorrhagic infarction and one subarachnoid hemorrhage). The 4 patients without clinical symptoms of increased intracranial pressure presented only bruit in 2 cases, bruit and vertigo in 1 case, bruit and hemorrhagic infarction in another one. The dAVFs were treated by endovascular therapy (arterial approach: 3 cases, venous approach: 6 cases and both arterial and venous approach: 13 cases). Endovascular sessions ranged from 1 to 7 (mean: 2.8) for each patient. After the endovascular treatment, in 12 patients with complete occlusion of the dAVF, the disappearance of angiographic signs of VHT and clinical cure were observed. In 8 patients with partial occlusion of the dAVF, the disappearance of angiographic signs of VHT and clinical cure were observed in 4 cases (almost complete dAVF occlusion in 2 cases); in the other 4 cases, only reduction the angiographic signs of VHT and clinical improvement were obtained. In all 16 patients who were clinically cured angiographic signs of VHT disappeared despite the persistence of dAVF shunts as observed in 4 cases. (ABSTRACT TRUNCATED)

PURPOSE: The role of genetic mechanisms and the influence of environmental events in human brain development have been difficult to evaluate. The purpose of this study was to compare the cerebral cortical morphology and midline structures of monozygotic twin pairs using MR imaging. METHODS: Six observers, blinded to twin pairings, evaluated the 3-D renderings of the cortical surface and midline structures from MR images of seven monozygotic twin pairs. A morphometric analysis of the corpus callosum and of the distance between the anterior and posterior commissures was also performed. RESULTS: Despite surprising anatomic differences, the brains of the twin pairs were similar enough to enable the observers to distinguish twin pairs from unrelated subjects. Five of six observers correctly identified the brains of all seven twin pairs; the remaining observer failed to make a correct match in only one of seven pairs. Three of six observers identified the midline sagittal images of the related twins in all seven pairs, and the other three identified the related midline sagittal images in five of seven pairs. The results were statistically significant. CONCLUSION: Although the observed differences in morphologic characteristics between twins necessarily reflect nongenetic influences, the cortical patterns and midline structures of monozygotic twins probably are genetically similar.

To analyse the presurgical evaluation process of mediotemporal lobe epilepsy (MTLE) in relation to electroclinical characteristics of the patients, we reviewed the presurgical data (clinical, EEG, neuropsychological, MRI, FDG-PET and sometimes intracranial EEG) and the post-operative results of 53 consecutive cases treated by antero-medial temporal resection for MTLE (without lesion other than mediotemporal sclerosis). Forty one patients (77 p. 100) had a typical and well-lateralised presentation and were operated without invasive procedure. Twelve patients (23 p. 100) presented less pure data: unusual or absent auras, divergent scalp EEG features (bitemporal, widespread or extratemporal) or absence of MRI-based hippocampal sclerosis or FDG-PET hypometabolism. They were explored by invasive monitoring which confirmed the medial temporal origin of seizures. Outcome (follow-up: 30 months) was excellent in 88 p. 100 of the pure cases (Engel's class I) and less favorable in the more difficult ones (50 p. 100 of class I). In conclusion, the diagnosis and surgical treatment of MTLE can be performed without invasive investigations in the majority of cases owing to the strong contribution of brain imaging and video EEG monitoring. Some patients however present a less pure presentation suggesting more complex epileptogenic networks and associated to relatively less favorable postsurgical results.

PURPOSE: The purpose of our study was to determine the significance of the loss of visualization of digitations in the hippocampal head on high-resolution fast spin-echo MR images in the diagnosis of mesial temporal sclerosis (MTS). METHODS: MR examinations of 193 patients with intractable epilepsy were evaluated retrospectively for atrophy and/or T2 signal changes of the hippocampi. On the basis of these two criteria, MTS was diagnosed in 63 hippocampi. Twenty-four patients had surgery, and MTS was confirmed in all cases. A control group included 60 hippocampi in patients with frontal seizures but no MR-detectable abnormalities. In a second step, visibility of digitations in the hippocampal head was evaluated in the two groups of subjects. RESULTS: In the group of 63 hippocampi in which MTS was diagnosed, digitations were not visible in 51 cases, poorly visible in eight, and sharply visible in four. Twenty-two of 24 hippocampi in which MTS was confirmed histologically had no MR-visible digitations. In the control group, digitations were sharply visible in 55 cases and poorly visible in five. Statistical analysis showed a significant difference in the visualization of digitations between hippocampi with MTS and those in the control group. CONCLUSION: With a sensitivity of 92% and a specificity of 100%, the finding of complete loss of digitations in the hippocampal head may be used as a major diagnostic criterion to establish the MR diagnosis of MTS. This morphologic sign may also be useful in the diagnosis of bilateral MTS or to validate the MR diagnosis of MTS when there is no obvious atrophy or changes in signal intensity.

Recent developments in animal and humans transmissible spongiform encephalopathies have motivated a study on incidence and risk factors of Creutzfeldt-Jakob disease (CJD) in France and 4 other European countries.CJD cases were ascertained through a national network including 250 neurological departments or neuropathological laboratories. CJD cases were classified as definite, probable or possible. Overall incidence rate and age-standardized incidence rates by department were computed. Standardized incidence ratios and their 95% confidence intervals were computed for comparing observed and expected number of CJD cases in each department.Between 1992 and 1995, 216 CJD cases were registered (mean incidence rate: 0.87 per million inhabitants). The distribution of CJD cases was heterogeneous (p0.007). Nevertheless, the distribution of standardized incidence ratios fitted quite well a Poisson distribution. The observed number of CJD cases was significantly higher than expected in 4 departments and lower in 1 department.Incidence of CJD in France is similar to that observed in other European countries. Analysis of distribution of CJD cases by department showed a few significant differences which can be due to random fluctuations.

We report the MR study of a case of high-grade glioma that mimics leptomeningeal carcinomatosis. Superficial gliomas should thus be included in the differential diagnosis of isolated meningeal enhancement.

PURPOSE: To develop a method for direct measurement, using anatomic specimens, of the precision of MR-guided stereotaxic location and to describe its application to a 1.5-T MR unit with a Leksell stereotaxic frame. METHODS: Small pieces of gelfoam (1 X 1 X 1 mm), soaked in gadopentetate dimeglumine, were stereotaxically introduced into formalin-fixed human heads using a Leksell D (three experiments) or G (nine experiments) stereotaxic frame. The head and the frame were then introduced into a 1.5-T MR unit. The target coordinates (as set on the stereotaxic frame by one investigator) were then compared with the MR-determined stereotaxic coordinates (calculated independently by another investigator). The imprecisions Ex, Ey, and Ez in each direction were defined as the differences between the calculated and the chosen coordinates. RESULTS: Regarding the three targets studied with the D frame, mean imprecision Ex was 1.08 +/- 0.50 mm (mean +/- SEM), Ey 0.83 +/- 0.58 mm, and Ez 0.75 +/- 0.25 mm. For the nine targets studied with the G frame, Ex was 0.48 +/- 0.17 mm, Ey 0.69 +/- 0.14 mm, and Ez 0.82 +/- 0.13 mm. Statistical analysis of the results showed no significant difference between Ex or Ey and half the size of a pixel, indicating that, in the axial plane, stereotaxic MR precision is limited only by pixel size. A statistically significant difference was observed in the coronal plane between Ez and half the size of a pixel, but it must be stressed that Ez remained smaller than 1 mm. CONCLUSION: MR-guided stereotaxic location can be used with confidence for most diagnostic, functional, and therapeutic procedures.

The tropism of the human T-cell leukemia virus type 1 (HTLV-1) for the cells of monocyte-macrophage lineage was evaluated by the coculture of blood monocyte-derived macrophages, with irradiated cells of HTLV-1 producing cell lines MT2 or C91/PL. The susceptibility to HTLV-1 was assessed by the detection of viral DNA using the polymerase chain reaction method. HTLV-1 gene expression in the cells was detected using in situ hybridization and by immunofluorescent staining of viral antigen. The presence of type C virus-like particles detected by electron microscopy and the ability to infect normal cord blood lymphocytes demonstrated that the infected macrophages produced infectious virus. These results indicate that human macrophages are susceptible in vitro to productive HTLV-1 infection, and thus might be involved in the pathogenesis of HTLV-1-related diseases.

Objective. —To identify clinical and laboratory parameters at birth that are associated with the rapidly progressive form of human immunodeficiency virus type 1 (HIV-1) disease in children born to infected mothers. Design. —Multicenter, prospective study of infants born to HIV-seropositive mothers. Setting. —A total of 62 obstetric and pediatric centers in France. Participants. —Of 1386 children born to HIV-1—seropositive mothers at least 18 months before the cutoff date, 267 were infected. Infection was defined as serological positivity at 18 months or death from HIV disease before this age. Main Outcome Measure. —Category C events (including opportunistic infections, recurrent severe bacterial infections, cancers, specific encephalopathy, and wasting syndrome) in the new pediatric Centers for Disease Control and Prevention classification during the first year of life, according to clinical, immunological, and virological findings at birth. Results. —The risk of category C manifestations at 12 months was significantly higher when an infected newborn had liver and/or spleen enlargement and/or adenopathies (38.1% vs 15.1%; relative risk [RR], 2.5; 95% confidence interval [CI], 1.4 to 6.0;P Conclusions. —These prognostic markers, particularly virological parameters, are of value in monitoring children infected by HIV and might serve as a basis for early therapeutic intervention. (JAMA. 1996;275:606-610)

Disorders of the nervous system frequently complicate Acquired Immune Deficiency Syndrome (AIDS). They may be related to the development of opportunistic agents (toxoplasmosis, cryptococcossis, cytomegalovirus, JC Virus), or primary CNS lymphoma. There is also a constellation of neurologic disorders which may result from direct Human Immunodeficiency Virus (HIV) replication in the CNS and HIV has been found in brain and CSF of numerous patients suffering from AIDS. The precise cellular localization of HIV is not known, but the macrophage seems to be a strong candidate for HIV replication in CNS.

We report the MR studies of the cervical cord in seven patients presenting juvenile muscular atrophy of distal upper extremity. This illness, also known as monomelic amyotrophy or benign focal amyotrophy, is distinct from the other motor neuron diseases. Seen in young males, it is characterized by muscular atrophy of the hand, and usually of the forearm, most often unilateral. The underlying process, of unknown origin, affects the anterior horn cells in the lower cervical cord. The gradual onset of purely motor disturbances may mimic early amyotrophic lateral sclerosis. This latter diagnosis may be excluded because of clinical stabilization and lack of pyramidal tract involvement. In our series, five MR studies were positive. In three cases we were able to demonstrate focal and unilateral atrophy in the lower cervical cord limited to the anterior horn region. Morphologic MR findings correlated with clinical and electromyographic features. In two other cases the MR-clinical correlation was more complex. No pathologic MR signal was detected on either T1- or T2-weighted images. Although the diagnosis of monomelic muscular atrophy is based on neurologic and neurophysiologic data, MR provides confirmatory evidence as well as useful information contributing to an understanding of this disease.

Three groups of male homosexuals: AIDS (n = 19), HIV seropositive (n = 15), and seronegative partners of seropositive subjects (n = 15), were compared to a heterosexual seronegative control group (n = 13). Twice daily evaluations (8 A.M. and 5 P.M.) of plasma levels of beta-endorphin, ACTH, and cortisol were done by radioimmunoassay. Seropositive subjects and their seronegative partners showed similar levels of neurohormones: 1. An elevation in the ACTH/beta-endorphin ratio in the plasma, (C = 0.69 +/- 0.84, AIDS = 0.44 +/- 0.32, S+ = 0.42 +/- 0.28, and S- = 0.42 +/- 0.5); 2. A loss of normal relationship of the coupling ACTH/total cortisol, (C = 0.00035 +/- 0.00028, AIDS = 0.00042 +/- 0.0034, S+ = 0.00074 +/- 0.00068, and S- = 0.00072 +/- 0.0008. Neuroendocrinological disorders have been observed in HIV-infected subjects and in their seronegative partners. These could be related to their sexual behavior, as well as to the HIV infection. If this last hypothesis is confirmed, the ACTH/beta-endorphin and ACTH/cortisol ratios may be seen as possible early signs of HIV infection.

Gadopentetate dimeglumine-enhanced MR imaging was performed in four patients with chronic dual sinus thrombosis. After injection, intense enhancement of the chronic thrombus was observed in all cases. On three-dimensional time-of-flight MR angiography, performed in one case, the occluded part of the superior sagittal sinus was not distinguishable from a normal sinus because of thrombus enhancement mimicking blood flow. Enhancement of the clot is best explained by organization of the thrombus, which is converted into vascularized connective tissue. It could lead to false-negative results in patients with chronic dural sinus thrombosis studied with contrast-enhanced MR or contrast-enhanced time-of-flight MR angiography techniques.

Symptomatic hemorrhagic transformation is a severe complication of acute ischemic stroke which occurs at a higher frequency after thrombolysis. The present study was designed to analyze whether early DWI can be used for predicting the risk of hemorrhagic transformation with clinical worsening in MCA stroke patients.Of 28 patients with a middle cerebral artery (MCA) infarct and proven MCA or carotid T occlusion on DWI and MR angiography performed within 14 hours after onset (mean 6.5 +/- 3.5 hours, median 5.2 hours), 4 developed hemorrhagic transformation with clinical worsening, while 24 did not. For the 2 groups, we compared admission NIHSS score, site of arterial occlusion, volume of DWI abnormalities, and several apparent diffusion coefficient (ADC) measurements: ADC(infarct) (mean ADC value of the whole infarct), ADC(core) (peak ADC decrease as calculated in a 57 mm(2) circular ROI, manually centered on the ischemic area with the lowest ADC value on the ADC maps), ADC(superficial) and ADC(deep). Discriminant function analysis was used to determine the most accurate predictors of symptomatic hemorrhagic transformation.The best predictor was the ADC(core) (F=5.34, p=2.9%, cut-off value=300 x 10(-6) mm(2)/s). This monovariate model allowed to correctly classify all 4 patients (ADC(core) 300 x 10(-6) mm(2)/s) with subsequent symptomatic hemorrhage, and 17 of the 24 patients without symptomatic hemmorrhage (ADC(core)300 x 10(-6) mm(2)/s) (100% sensitivity, 71% specificity).Although preliminary, these results suggest that a simple measurement of minimum ADC values within an acute MCA stroke could be useful in targeting those patients with a high risk of severe hemorrhagic transformation.

To establish an animal model of AIDS, two different "wild" or "adapted" HIV2 Rod and Eho strains were cultivated on monkey cells from different species (baboons, cynomolgus, Rhesus monkeys). Five different available strains were then injected both by intravenous (i.v.) and intracerebral (i.c.) route into ten Rhesus monkeys. Seven animals seroconverted between days 13 and 230. Reverse transcriptase activity in the lymphocyte culture supernatants was detectable in six of the seven animals that seroconverted, and in one animal that remained seronegative. Lymphopenia and a decrease in the CD4+ cell counts were observed in eight animals. One animal, inoculated with HIV2-Rod "wild type," developed a severe cachexia, with dyspnea, and associated neurological symptoms 150 days after inoculation. This animal was sacrificed on day 220. Pathological examination showed typical lesions of actinomycetes infection in the lungs and in the meninges. Another monkey had significant weight loss associated with lymphadenopathies and pancytopenia. These results suggest that in vivo replication of HIV2 in Rhesus monkeys may induce clinical symptoms of immune deficiency. This method is reproducible and may provide a good model for AIDS.

BACKGROUND AND PURPOSE: Lesions associated with acute stroke are often missed by diffusion-weighted imaging (DWI), suggesting that the sensitivity of this technique for detecting acute ischemic stroke may not be as high as initially thought. Our aim was to estimate the rate of false-negative DWI studies in patients with persistent neurologic deficit due to an ischemic stroke and to identify which stroke lesions are most likely to be missed by DWI. METHODS: We reviewed MR images obtained within 48 hours after stroke onset in 139 patients admitted for symptoms consistent with ischemic stroke in whom the deficit lasted more than 24 hours. Cases of negative initial DWI findings with an ischemic lesion visible on follow-up MR studies and a final diagnosis of arterial ischemic stroke were analyzed in terms of delay between onset of symptoms and initial DWI (MR latency), size and vascular distribution of the lesions, and relationship to findings in patients with positive initial DWI results. RESULTS: We found eight cases (5.8%) of false-negative initial DWI studies, of which four were positive on initial fluid-attenuated inversion recovery (FLAIR) imaging. Follow-up FLAIR/DWI showed a hyperintensity matching clinical presentation in all eight patients. The mean size of the lesion was 0.19 ± 0.16 cm(3). False-negative studies occurred more often in cases of stroke in the posterior (19%) than in the anterior (2%) circulation or when DWI was obtained within 24 hours after symptom onset. Of the six false-negative vertebrobasilar stroke lesions, five were located in the brain stem. In all, 31% of patients with vertebrobasilar ischemic stroke had a false-negative initial DWI study during the first 24 hours. CONCLUSION: A false-negative DWI study is not uncommon during the first 24 hours of ischemic stroke. Vertebrobasilar stroke should therefore not be ruled out on the basis of early negative DWI, especially when symptoms persist and are suggestive of this diagnosis.

Multiple imaging techniques are available to diagnose cervical arterial dissections. It may be possible to image the vessel wall hematoma (US, MRI, 2D or 3D MRA source images, CTA source images), the narrowed arterial lumen (MRA, CTA, catheter angiography), or the hemodynamic impact of the affected vessel. There is no available guideline in the literature regarding the imaging work-up at diagnosis or follow-up. The Société Française Neurovasculaire and the Société Française de Neuroradiologie have sponsored a multi-center study to evaluate current imaging strategies. Results from several centers, while being variable, do share some similarities: the preferred use of non-invasive or minimally invasive techniques to evaluate the vessel wall and the vascular lumen and/or hemodynamic impact, the use of fat suppressed sequences at MRI, the use of Gadolinium enhanced MRA, the limited interest for CT techniques, and the still important use of catheter angiography in selected cases.

Several French teams including clinicians and researchers have created a group within the European network for the study of Creutzfeldt-Jakob disease and other human spongiform encephalopathies. The main objectives are to monitor the incidence of the disease and to search for possible risk factors with a case-control study. The diagnosis is based on neuropathological studies or the identification of an abnormal protein prion in cerebral fragments. The sequence of the gene encoding for the prion protein has was studied from blood or cerebral samples. The early results indicate that the incidence, mortality and clinical presentation remain relatively constant compared with earlier studies. Studying the expression of the 129 codon of the prion protein gene has led to the verification that homozygous methionine/methionine forms predominate in sporadic forms.

Although knowledge has accumulated about GP110-CD4 interaction, viral penetration into human CD4+ lymphocytes remains unclear, in spite of the fact that all studies on HIV infection were performed on cell-transformed lineages, or on human polyclonal CD4+ cells. In order to investigate this viral entrance into susceptible cells, we studied the permissivity of 13 human monoclonal CD4+ lymphocytes by means of reverse transcriptase (RT) assay and immunocapture. We demonstrated a differential susceptibility to HIV of these CD4+ clones. In a second experiment, HIV infection was studied: (1) sequentially by RT assay and P24 immunocapture on several clones; (2) by cocultivation of infected clones with umbilical cord lymphocytes. These experiments suggested existence of permissive and "nonpermissive" CD4+ monoclonal lymphocytes. Slot blot, then PCR, revealed that proviral DNA sequences were detectable in all clones, but were present at lower levels in nonpermissive clones.

BACKGROUND AND PURPOSE: Apart from cases studies, little is known regarding diffusion-weighted imaging of brain lesions associated with human cerebral venous thrombosis (CVT). Our aim was to describe the initial diffusion-weighted imaging patterns observed in brain areas with MR signal changes associated with CVT and to compare them with those of follow-up imaging. METHODS: The cases of nine patients with brain lesions associated with CVT who underwent CT and diffusion-weighted imaging 3 hours to 4 days after sudden neurologic onset were retrospectively reviewed. The apparent diffusion coefficient (ADC) in abnormal brain was compared with that of contralateral normal regions using z score analysis. MR images obtained during 3 to 6 months of follow-up were available for seven patients. RESULTS: All patients had nonhemorrhagic T2-hyperintense brain regions. These were associated with partially hemorrhagic areas on the CT scans of four patients. In nonhemorrhagic edematous areas, ADC was heterogeneous (coexistence of increased, normal, or decreased ADC) in five patients and homogeneous in four. In the latter four patients, ADC values were within normal range in three, whereas a large homogeneous hyperintensity with decreased ADC values (0.3–0.4 10(−)(3)mm(2)/s