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Les lésions pseudo-tumorales constituent une entité diagnostique rare mais importante à identifier en neuroradiologie. Ces lésions peuvent survenir au cours des pathologies inflammatoires (maladies systémiques, vascularites, démyélinisantes), infectieuses, et vasculaires. Par ailleurs, chez un patient ayant une tumeur traitée, la pseudo-progression et la radionécrose constituent également un diagnostic différentiel non tumoral important à individualiser de l’évolution tumorale. Le diagnostic de pseudotumeur ou d’évolution pseudo-tumorale peut être difficile à réaliser en imagerie. Toutefois, certaines caractéristiques IRM en séquence conventionnelle et en diffusion, perfusion et spectroscopie permettent d’évoquer le caractère pseudo-tumoral d’une lésion. La présence d’éventuelles lésions intracrâniennes associées peut orienter vers une maladie systémique ou infectieuse. Une lésion en hyposignal T2 oriente vers une granulomatose ou une histiocytose, surtout si une atteinte méningée ou hypothalamo-hypophysaire est associée. Les lésions non tumorales ne sont généralement pas hyperperfusées. Enfin, en l’absence de diagnostic étiologique de certitude, l’évolution spontanée ou sous traitement de ces lésions est un élément diagnostique fondamental.

To compare the sensitivity and specificity of 1.5-T and 3.0-T diffusion-weighted MRI (DWI) to detect hyperacute ischemic stroke lesions.

ObjectiveTo analyze the clinical findings, treatment, outcome, and prevalence of cerebral venous thrombosis CVT in a large cohort of patients with Behçets disease BD from a single center.MethodsWe reported a series of 64 consecutive patients with CVT who fulfilled the international criteria for BD. Multivariate analysis was performed to define factors that affect prognosis.ResultsAmong a cohort of 820 patients with BD, CVT was present in 64 7.8. Compared with BD patients without CVT, those with CVT had lower parenchymal central nervous system involvement 4.7 versus 28.7; P 0.0001 and higher extraneurologic vascular lesions 62.5 versus 38.8; P 0.03. Up to 90 of patients responded to anticoagulation therapy without severe hemorrhagic complications. Neither steroid nor immunosuppressant use provided better outcome. Severe visual loss due to optic atrophy was the main complication of CVT, being found in 15 of patients. In multivariate analysis, papilledema odds ratio OR 7.1, 95 confidence interval 95 CI 1.6–31.9 and concurrent prothrombotic risk factors OR 4.6, 95 CI 1.1–20.2 were independently associated with the occurrence of sequelae. Factors associated with relapse of thrombosis were concurrent prothrombotic risk factors hazard ratio HR 4.9, 95 CI 1.5–15.4 and a peripheral venous thrombosis HR 2.8, 95 CI 0.7–10.5. After a mean ± SD followup of 8.2 ± 6.9 years, 4 deaths unrelated to CVT were noted.ConclusionCVT in patients with BD may result in serious neurologic outcomes. Anticoagulation represents a safe and effective therapy. Extensive investigation of prothrombotic disorders should be considered.

Stimulation of the subthalamic nucleus is an effective treatment for advanced Parkinson disease (PD) and is currently performed after a mean disease duration of 14 years, when severe motor complications have resulted in marked loss of quality of life. We examined whether surgery at an early stage would maintain quality of life as well as improve motor function.

High-frequency stimulation of the subthalamic nucleus (STN) is an effective treatment for advanced Parkinson disease (PD). The clinical and preoperative predictive factors of the best postoperative outcome have been identified. Radiologic predictive factors were investigated.

The HIV-1 central nervous system infection leads to the onset of neurological impairments called AIDS dementia complex (ADC). PAF plays an important role in this pathology, as it is an HIV-1-induced neurotoxin produced by infected or activated macrophages and microglia, in the brain. We previously reported that PAF-antagonists bearing a trisubstituted piperazine presented in vitro anti-HIV-1 activity in human macrophages. To improve the pharmacological activities of our lead compound, 1a, we modified its carbamate function and evaluated both its antiretroviral and anti-PAF activities. One carbamate derivative (10c) demonstrated a similar antiviral activity but a higher anti-PAF potency, whereas 4a, with an ureide function, presents an increased antiviral activity and can be considered as a pure antiretroviral drug, as it does not present PAF-antagonism. Moreover, we measured the ability of 1a to cross the blood−brain barrier, using the in situ mouse brain perfusion method and its plasmatic concentrations after iv and po administration. The transport parameter measured (Kin) proves that 1a is able to cross this biological barrier, but a pharmacokinetic study reveals its weak bioavailability in rats.

Les ence´phalopathies subaigue¨s spongiformes transmissibles (ESST) sont des maladies neurode´ge´ne´ratives lentes toujours mortelles qui sont induites par des agents transmissibles non conventionnels (ATNC) ou prions. Les prions ont une re´sistance inhabituelle aux proce´de´s d'inactivation, et la composition exclusivement prote´ique des fractions infectieuses spe´cifiques indiquent que ces agents pourraient e^tre des entite´s infectieuses purement prote´iques. Le seul composant variant avec le titre infectieux chez le sujet infecte´ est la quantite´ de prote´ine PrP, une prote´ine de l'ho^te qui s'accumule sous une forme pathologique la PrP. Chez l'individu infecte´, la prote´ine PrP devient re´sistante partiellement aux enzymes prote´olytiques et e´chappe au catabolisme cellulaire. L'hypothe`se du prion suppose que la pathoge´nicite´ est lie´e uniquement a` l'acquisition d'une conformation pathologique par la prote´ine PrP. L'apparition, en 1996, de 10 cas d'une nouvelle variante de la maladie de Creutzfeldt-Jakob (vMCJ) chez des sujets de moins de 40 ans a fait proposer l'hypothe`se que l'agent bovin e´tait passe´ dans l'espe`ce humaine. La contamination par l'agent bovin a tout de suite e´te´ e´voque´e. A` ce jour, 142 cas de vMCJ ont e´te´ de´crits (dont 132 en Grande-Bretagne et six en France), et les conse´quences de sante´ publique du passage a` l'homme de cet agent bovin ne sont pas encore totalement estime´es.

We synthesized a series of N-(N-acetyl-l-cysteinyl)-S-acetylcysteamine (10) analogues bearing various acyl groups on thiol cysteine or cysteamine residues, to investigate the structure−activity relationship for pro-GSH and anti-HIV properties in human macrophages. The S-substituents were ranked in the following order of efficacy:  H ≥ acetyl > isobutyryl > pivaloyl > benzoyl. We found that none of these derivatives had pro-GSH or antiviral activities in vitro higher than that of 10, but several displayed similar levels of anti-HIV activity, making them possible candidates for use as adjuvant therapies in conjunction with HAART, for treating neurological aspects of HIV infection.

New formamidine-3TC (3TC = 2‘,3‘-dideoxy-3‘-thiacytidine) analogues have been synthesized through various methods, and their antiviral activities (HIV, HBV) have been evaluated in vitro. Anti-HIV-1 in acutely infected MT-4 cells and peripheral blood monocellular cells (PBMCs) showed that compounds substituted by N,N-diarylformamidine side chains at the 4-N nucleic base position (compounds 3 and 8−11) had at least equivalent anti-HIV activity as 3TC (EC50 = 0.5 and 11.6 μM, respectively). Moreover, the newly synthesized compounds demonstrated higher anti-HBV activity (EC50 ranging from 0.01 to 0.05 μM) compared to the parent nucleoside 3TC (EC50 = 0.2 μM). It should be underlined that these new promising derivatives inhibited HIV in cells of a macrophage lineage, which are known to be cellular reservoir for HIV. These results were particularly of interest, since the antiviral activities appeared not to be mediated through the formamidine bond hydrolysis and consequently the release of free 3TC. These new analogue series were found to be highly stable to hydrolysis even after prolonged incubation in different biological media (t1/2 ranged from 48 to 120 h). This enzymatic stability, coupled to the fact that no delay in the antiviral response was observed compared to the free 3TC antiviral response, suggest that this new N,N-diarylformamidine nucleoside series should not be considered as classical prodrugs.

Diffusion weighted imaging (DWI) may represent a valuable tool in the early diagnosis of spinal cord diseases. The purpose of this paper was to test the feasibility of a single shot fast spin echo (SSFSE) DWI in normal and abnormal spinal cord, and to evaluate its use in routine clinical imaging. We used a SSFSE sensitive to diffusion (b = 600 s/mm2) with multi-slice or single slice technique to study normal (32 cases) or abnormal (39 cases) spinal cords. Apparent diffusion coefficient (ADC) maps were calculated. Single slice sequences were significantly more reliable than multi-slice sequences for measurement of ADC. In normal subjects, mean ADC values were remarkably similar at both cervical and thoracic levels. Increased ADC values were detected in patients with cord trauma, myelitis, dural malformation, glioma, syringomyelia or metastasis, whereas decreased ADC values were detected in a patient with cervical intraspinal metastasis. This is the first report of the feasibility of a single slice SSFSE diffusion sequence for routine spinal cord imaging. The measurement of ADC may be of diagnostic value for the insight it offers on the pathophysiology of parenchymal damage.

OBJECTIVE: to analyse 24 parkinsonian patients successfully treated by bilateral STN stimulation for the presence of behavioural disorders. METHOD: patients were evaluated retrospectively for adjustment disorders (social adjustment scale, SAS), psychiatric disorders (comparison of the results of psychiatric interview and the mini international neuropsychiatric inventory) and personality changes (IOWA scale of personality changes). RESULTS: parkinsonian motor disability was improved by 69.5% and the levodopa equivalent daily dosage was reduced by 60.5%. Social adjustment (SAS) was considered good or excellent in nine patients, moderately (n=14), or severely (n=1) impaired in 15 patients. Psychiatric disorders consisted of amplification or decompensation of previously existing disorders that had sometimes passed unnoticed, such as depressive episodes (n=4), generalised anxiety (n=18), and behavioural disorders with drug dependence (n=2). Appearance of mild to moderate emotional hyperreactivity was reported in 15 patients. Personality traits (IOWA scale) were improved in eight patients, unchanged in seven, and aggravated in eight CONCLUSION: Improvement in parkinsonian motor disability induced by STN stimulation is not necessarily accompanied by improvement in psychic function and quality of life. Attention is drawn to the possible appearance of personality disorders and decompensation of previous psychiatric disorders in parkinsonian patients who are suitable candidates for neurosurgery. We suggest that a careful psychological and psychiatric interview be performed before surgery, and emphasise the need for psychological follow up to ensure the best possible outcome.

Objective: To describe a reversible neurological condition resembling a crossed midbrain syndrome resulting from high frequency stimulation (HFS) in the midbrain. Methods: 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. Results: 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. Conclusion: 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.

High‐frequency stimulation of the subthalamic nucleus (STN) constitutes one of the most effective treatments for advanced forms of Parkinson’s disease. The cost and potential risks of this procedure encourage the determination of clinical characteristics of patients that will have the best postoperative outcome. Forty‐one Parkinson’s disease patients underwent surgery for bilateral STN stimulation. The selection criteria were severe parkinsonian motor disability, clear response of symptoms to levodopa, occurrence of disabling levodopa‐related motor complications and the absence of dementia and significant abnormalities on brain MRI. Clinical evaluation was performed 1 month before and 6 months after surgery. The improvement in the activities of daily living subscale of the Unified Parkinson’s Disease Rating Scale, Part II (UPDRS II) and parkinsonian motor disability (UPDRS III) was greater when the preoperative scores for activities of daily living and parkinsonian motor disability, in particular axial symptoms, such as gait disorders and postural instability assessed at the time of maximal clinical improvement (on drug), were lower. Age and disease duration were not predictive, but parkinsonian motor disability tended to be more improved in patients with younger age and shorter disease duration. The severity of levodopa‐related motor complications was not a predictive factor. The outcome of STN stimulation was excellent in levodopa‐responsive forms of Parkinson’s disease, i.e. in patients with selective brain dopaminergic lesions, and moderate in patients with axial motor symptoms and cognitive impairment known to be less responsive or unresponsive to levodopa treatment, i.e. when brain non‐dopaminergic lesions develop in addition to the degeneration of the nigrostriatal dopaminergic system. The results are consistent with the classical inclusion criteria for STN stimulation, but imply that the decision to operate on the oldest patients and/or patients with gait and postural disorders, who are poorly responsive to levodopa, should be weighed carefully.

High-frequency stimulation of the subthalamic nucleus (STN) constitutes one of the most effective treatments for advanced forms of Parkinson's disease. The cost and potential risks of this procedure encourage the determination of clinical characteristics of patients that will have the best postoperative outcome. Forty-one Parkinson's disease patients underwent surgery for bilateral STN stimulation. The selection criteria were severe parkinsonian motor disability, clear response of symptoms to levodopa, occurrence of disabling levodopa-related motor complications and the absence of dementia and significant abnormalities on brain MRI. Clinical evaluation was performed 1 month before and 6 months after surgery. The improvement in the activities of daily living subscale of the Unified Parkinson's Disease Rating Scale, Part II (UPDRS II) and parkinsonian motor disability (UPDRS III) was greater when the preoperative scores for activities of daily living and parkinsonian motor disability, in particular axial symptoms, such as gait disorders and postural instability assessed at the time of maximal clinical improvement (on drug), were lower. Age and disease duration were not predictive, but parkinsonian motor disability tended to be more improved in patients with younger age and shorter disease duration. The severity of levodopa-related motor complications was not a predictive factor. The outcome of STN stimulation was excellent in levodopa-responsive forms of Parkinson's disease, i.e. in patients with selective brain dopaminergic lesions, and moderate in patients with axial motor symptoms and cognitive impairment known to be less responsive or unresponsive to levodopa treatment, i.e. when brain non-dopaminergic lesions develop in addition to the degeneration of the nigrostriatal dopaminergic system. The results are consistent with the classical inclusion criteria for STN stimulation, but imply that the decision to operate on the oldest patients and/or patients with gait and postural disorders, who are poorly responsive to levodopa, should be weighed carefully.

Les ence´phalopathies subaigue¨s spongiformes transmissibles sont des maladies neurode´ge´ne´ratives dont les agents e´tiologiques, les ATNC, sont encore inconnus. La the´orie du prion postule que ces agents seraient compose´s exclusivement d'une prote´ine de l'ho^te, la PrP, sous une conformation pathologique sans modification de la se´quence primaire en acides amine´s. Les ATNC sont particulie`rement re´sistants aux proce´de´s d'inactivation chimiques et physiques, et peuvent persister dans l'environnement pendant plusieurs anne´es. Par ailleurs, ces agents sont capables de franchir les barrie`res d'espe`ce, comme le montre l'e´mergence de la nouvelle variante de la maladie de Creutzfeldt-Jakob induite par l'exposition de la population humaine a` l'agent de l'ence´phalopathie spongiforme bovine.

It has been shown recently that the generation of an abnormal transmembrane form of the prion protein (CtmPrP) is involved in the neurodegeneration process during inherited and infectious prion diseases but a causative relationship has never been established. We wanted to know if and how the proposed transmembrane domain of PrP could induce neuronal dysfunction. Thus, we investigated the neurotoxic properties of two peptides whose sequences are encompassed within this domain. We show that PrP peptides 118–135 and 105–132 as well as an amidated more soluble peptide 105–132 induce the death of pure cortical neurons originating from normal and PrP knockout mice. This can be correlated with the high propensity of these peptides to insert stably into and to destabilize cell membranes. Through this study, we have identified a novel mechanism of neurotoxicity for PrP, which directly involves membrane perturbation; this mechanism is independent of fibril formation and probably corresponds to the effect of the transmembrane insertion of CtmPrP.

Discriminating Creutzfeldt-Jakob disease (CJD) from dementia with Lewy bodies (DLB) may be clinically difficult to achieve. The authors describe 10 patients with DLB initially referred to the French Network of Human Spongiform Encephalopathies as having suspected CJD. In a series of 465 autopsied cases, DLB ranked second among degenerative alternative diagnoses to CJD. The authors analyzed the factors that contributed to misleading the diagnosis, and suggest that the detection of 14-3-3 protein in CSF may be useful to distinguish CJD from DLB.

ABSTRACTWe assessed the anti-human immunodeficiency virus (anti-HIV) activity in vitro of new platelet-activating factor (PAF) receptor antagonists, as PAF and viral replication are thought to be involved in HIV neuropathogenesis. We found that PMS-601 inhibited proinflammatory cytokine synthesis and HIV replication in macrophages and potentiated the antiretroviral activity of zidovudine. These results suggest that PMS-601 is of potential value as an adjuvant treatment for HIV infection.

Abstract: We evaluated the feasibility and use of diffusion-weighted and fluid-attenuated inversion-recovery pulse sequences performed as an emergency for patients with acute ischaemic stroke. A 5-min MRI session was designed as an emergency diagnostic procedure for patients admitted with suspected acute ischaemic stroke. We reviewed routine clinical implementation of the procedure, and its sensitivity and specificity for acute ischaemic stroke over the first 8 months. We imaged 91 patients (80 min to 48 h following the onset of stroke). Clinical deficit had resolved in less than 3 h in 15 patients, and the remaining 76 were classified as stroke (59) or stroke-like (17) after hospital discharge. Sensitivity of MRI for acute ischaemic stroke was 98 %, specificity 100 %. MRI provided an immediate and accurate picture of the number, site, size and age of ischaemic lesions in stroke and simplified diagnosis in stroke-like episodes. The feasibility and high diagnostic accuracy of emergency MRI in acute stroke strongly support its routine use in a stroke centre.

Excessive levels of PAF and cells of macrophage lineage appear to play an important role in neuronal cell injury, inflammatory syndrome, and HIV replication in CNS resulting in AIDS dementia complex (ADC). The beneficial effects of PAF receptor antagonists are evident and give rise to expected therapeutic strategies for neurotrauma. Piperazine derivatives bearing a “cache-oreilles” (ear-muff) electronic distribution are able to inhibit in vitro PAF effects and, thus, could be used in pathologies where this mediator is involved. Therefore, their potential anti-HIV activity was investigated, and we find that (i) these PAF antagonists are effectively active in HIV-infected monocyte-derived macrophages (MDM) but there is no correlation between both anti-HIV and anti-PAF activities; (ii) the presence of a carbamate function (compounds 1a−d) is favorable to the antiviral activity; (iii) the lipophilicity of the substituent on the piperazinic cycle seems to be less important for the anti-PAF activity than for the antiviral one. Our leading compound, PMS 601 (compound 1a), presents a dual activity with IC50 of 8 and 11 μM for anti-PAF and anti-HIV activity, respectively, without cytotoxic events at 1000 μM in MDM. Although its mode of action is not clearly defined, these data suggest that PMS 601, which displays no effect on acellular reverse transcriptase or protease tests, deserves further investigation in the treatment of HIV-1-associated dementia.

To determine the contribution of methionine/valine (Met/Val) polymorphism at codon 129 of the prion protein (PrP) gene in the neuropathologic pattern and mechanisms of lesion development in sporadic Creutzfeldt–Jakob disease.

The histopathological response of scrapie-infected hamsters treated at the late stage of the infection with an “anti-scrapie” drug, a polyene macrolide antibiotic designated MS-8209, was evaluated in the brain. The results showed that (1) MS-8209 prolonged significantly the incubation time of the experimental disease, (2) MS-8209 delayed the appearance of spongiosis and astrogliosis in the brain, (3) immunodetection of abnormal prion protein and glial fibrillary acidic protein was significantly reduced in the central nervous system. In addition, this report indicates that polyene antibiotics markedly delay the development of the classical brain lesions that result from scrapie infection.

To estimate the statistical distribution of the incubation period of Creutzfeldt-Jakob disease (CJD) in human growth hormone (hGH) recipients in France.

A centrofollicular hyperplasia is present within secondary lymphoid organs during all the asymptomatic phase of the HIV disease. Although this hyperplasia has been well characterized by histological studies, the nature of the phenotypic alterations in B cell populations occurring within HIV⁺ lymphoid organs remains to be established. By immunohistochemistry, we thus investigated whether a particular germinal center (GC) B cell population was increased during HIV-induced hyperplasia and whether any phenotypic change was specific to HIV-1 infection. As compared to normal tonsils (three cases) and HIV^- hyperplastic lymph nodes (eight patients), we observed a loss of GC polarization in all HIV⁺ sections (11 patients), with no more delineation between dark and light zones, as shown by Ki67, CD10, CD77, CD95 and CD86 staining. In contrast to CD86 expression which remained as intensive in HIV⁺ as in HIV^- lymph nodes, CD80 staining was strongly decreased in GC of HIV⁺ lymph nodes but not in their extrafollicular zones. The loss of CD80 expression from CD19⁺ B cells was also observed by cytometric analysis of cell suspensions of three HIV⁺ patients. Although we found no evidence of an increase in a particular GC B cell subset in HIV-1-induced hyperplasia, the strong GC disorganization observed may induce impaired cell-cell interactions and thus participate in the loss of CD80 antigen. In contrast to HIV^- situations where CD80 and CD86 was similarly expressed on B cells, the lower level of CD80 expression in HIV⁺ GC may favor T_h2 T cell responses through CD86-CD28 interactions.

Oxidative stress and glutathione (GSH) deficit may play an important role in HIV infection pathogenesis, and oral administration of GSH-replenishing drugs such as N-acetylcysteine (NAC) and 2-oxothiazolidine-4(R)-carboxylic acid (OTC) may be associated with an increased survival rate of HIV-infected patients. Nevertheless, beneficial effects of these molecules are restricted in vivo by the high concentrations that are necessary to obtain biological effects, rapid extracellular metabolization, and low availability and plasma concentrations. We synthesized OTC derivatives that are more lipophilic than OTC and theoretically able to overcome these limitations and to generate, in addition to cysteine, other substrates of the γ-glutamyl cycle. Their antiviral effects were investigated in human HIV-1/Ba-L-infected monocyte-derived macrophages. In our experimental conditions, OTC exhibited anti-HIV-1 effects and little cytotoxicity at high doses. None of the nine tested derivatives showed higher cytotoxicity than OTC, nor anti-HIV-1/Ba-L activity.

An atypical HIV-1 strain (CAM001) was identified in a pregnant Cameroonian woman in 1995. HMA subtyping of the env region was unsuccessful, and sequence analyses were performed. Unique sequence motifs were found at the V3 tip (GAGRALHA and GAGRAWIHA), and phylogenetic studies showed that the env C2-V5 sequence branched within group M but remained distinct from all known HIV-1 subtypes, while p17 gag branched with the subtype F sequences. Four other HIV group M viruses, undetermined by HMA, of African origin were found to cluster with CAM001 in the C2-V5 sequences. With the BLAST method, we found in databases three strains whose V3 sequences also clustered with CAM 001. These unusual env sequences from eight HIV-1 strains derived from Cameroon formed a separate cluster in HIV-1 group M, which we designated k.

Abstract: We report a retrospective analysis of MRI in 206 patients with intractable seizures and describe the findings in bilateral mesial temporal sclerosis (MTS) on fast spin-echo (FSE) and fast fluid-attenuated inversion-recovery (fFLAIR) sequences. Criteria for MTS were atrophy, signal change and loss of the digitations of the head of the hippocampus. In patients with bilateral MRI signs of MTS, correlation with clinical electro, volumetric MRI data and neuropsychological tests, when available, was performed. Bilateral MTS was observed in seven patients. Bilateral loss of the digitations and signal change on fFLAIR was seen in all seven. In three, bilateral atrophy was obvious. In two patients, mild bilateral atrophy was observed and in two others, the hippocampi were: asymmetrical, with obvious atrophy on only one side. Volumetric data confirmed bilateral symmetrical atrophy in five patients, and volumes were at the lowest of the normal range in the other two. The EEG showed temporal abnormalities in all patients, unilateral in five and bilateral in two. All patients had memory impairment and neuropsychological data confirmed visual and verbal memory deficits; two patients failed the Wada test on both sides. High-resolution T2-weighted FSE and fFLAIR sequences allow diagnosis of bilateral MTS, which has important therapeutic and prognostic implications.

A centrofollicular hyperplasia is present within secondary lymphoid organs during all the asymptomatic phase of the HIV disease. Although this hyperplasia has been well characterized by histological studies, the nature of the phenotypic alterations in B cell populations occurring within HIV+ lymphoid organs remains to be established. By immunohistochemistry, we thus investigated whether a particular germinal center (GC) B cell population was increased during HIV-induced hyperplasia and whether any phenotypic change was specific to HIV-1 infection. As compared to normal tonsils (three cases) and HIV- hyperplastic lymph nodes (eight patients), we observed a loss of GC polarization in all HIV+ sections (11 patients), with no more delineation between dark and light zones, as shown by Ki67, CD10, CD77, CD95 and CD86 staining. In contrast to CD86 expression which remained as intensive in HIV+ as in HIV- lymph nodes, CD80 staining was strongly decreased in GC of HIV+ lymph nodes but not in their extrafollicular zones. The loss of CD80 expression from CD19+ B cells was also observed by cytometric analysis of cell suspensions of three HIV+ patients. Although we found no evidence of an increase in a particular GC B cell subset in HIV-1-induced hyperplasia, the strong GC disorganization observed may induce impaired cell-cell interactions and thus participate in the loss of CD80 antigen. In contrast to HIV- situations where CD80 and CD86 was similarly expressed on B cells, the lower level of CD80 expression in HIV+ GC may favor Th2 T cell responses through CD86-CD28 interactions.

Because of the high level of accuracy needed in neurosurgery, many computer-assisted surgery (CAS) and augmented reality techniques have been developed in this field. A common issue with all of these techniques is registration between preoperative three-dimensional images (computed tomography and magnetic resonance imaging) and the patient in the operating room. We present, in the first part of this paper, a survey of the latest CAS technologies, using fully automatic registration without fiducial landmarks. All of the registration algorithms described are based on minimization of a cost function. We then describe our approach. Our cost function is simply the mean square error (MSE), minimized by the iterative closest point algorithm (ICP). Because the weak point of the ICP algorithm is the closest point computational cost, we precalculate it by a "closest point map," inspired from classical distance map. We finally perturb the found solution to eliminate local minima close to the global minimum. This paper summarizes the various methods presented. We study the shape of the different cost functions and show that there is no need for a complex cost function. MSE has sufficiently good convergence properties to reach a position very close to the global minimum. We also demonstrate the influence of a final perturbation of the found solution to improve registration. Finally, we test the registration on different regions of the patient's head.

Using ourin vitromodel of normal B cell infection, we investigated whether cellular interactions and/or cytokines directing the B cell response also regulate HIV replication. Phorbol esters and CD40 Ab plus IL4, added prior to infection, substantially increased subsequent viral replication. Postinfection, IL2 with or without IL4 and, to a lesser extent, CD40/CD40L interactions enhanced viral replication. In contrast, IL10 down-regulated HIV replication induced by cytokines, without affecting spontaneous or CD40 Ab-induced replication. Both enhancing and inhibitory effects of cytokines on viral replication were independent of their ability to modulate B cell proliferation. Thus, these two phenomena seem to be independently regulated in human B cells.

Inflammation is a frequent result of radiation damage, especially after therapeutic irradiation. Monocytes and macrophages play an important role in inflammatory cytokine secretion. However, knowledge of monocyte macrophage involvement in the pathogenesis of inflammation is still incomplete. In this study, we investigated the inflammatory cytokine regulation after in vitro gamma-irradiation of monocytes macrophages. Semiquantitative RT-PCR after irradiation revealed no significant induction of interleukin 1beta or tumour necrosis factor-alpha mRNA expression. When induction was observed, for only two donors out of seven, only interleukin 6 gene expression was affected by irradiation, with a 5-14-fold increase in level according to the donor, 2h after irradiation compared with sham-irradiated cells. For only one of seven donors tested, monocytes macrophages responded to 10-Gy gamma-rays by releasing inflammatory cytokines.

Two series of new nucleoside derivatives, acyclic nucleosides and tricyclic base nucleosides, were screened for cellular toxicity and against HIV-1. Compounds were tested on MT4, MT2, U937 cell lines and PBMCs in multiwell tissue culture plates. Cells were infected in vitrowith 2 TCID50/105cells or 0.2 TCID50/105cells of HIV-1-LAV-1. Two out of eight tricyclic derivatives showed little cytotoxicity; at 100μM, only two acyclic compounds exhibited cellular toxicity in U937 cells. In vitro, none of these 19 compounds demonstrated any efficient activity against the lentiviral HIV infection and replication. Furthermore, combinations of these acyclonucleosides with ddC or AZT did not inhibit HIV-1-LAV-1 replication additively or synergistically. Because acyclonucleosides did not induce any cytotoxic effect, other compounds of this family should be investigated.

Abstract: To study the long-term evolution of cerebral lesions in neuro-Behçet's disease, MRI was carried out on 12 patients, with follow-up from 1.5 to 6 years (mean 3.5 years). On the first MRI, 66 lesions in all were found; each patient had 1–10 lesions (mean 5.5). There were 30 (46 %) lesions in the brain stem, 18 (27 %) in the basal ganglia region and 18 (27 %) in the periventricular white matter. Of these 22 (33 %) were small, 31 (47 %) medium-size and 13 (20 %) large lesions. On the last MRI, 60 lesions were found; each patient had 1–10 lesions (mean 5). At this time 31 lesions (52 %) were in the brain stem, 13 (22 %) in the basal ganglia region and 16 (26 %) in the periventricular white matter. There were 41 (68 %) small, 13 (22 %) medium-size and 6 (10 %) large lesions. About 40 % of the lesions disappeared, 35 % reduced in size and 25 % remained unchanged. No lesion had enlarged. Of the 60 final lesions 20 (34 %) were not observed on the first study. Small new lesions were found in 5 of 12 patients (42 %), and were asymptomatic. Medium-size or large new lesions were found in 2 patients (17 %) who had stopped steroid treatment and had a neurological relapse. Enlargement of the ventricular system or worsening of initial cerebral atrophy was observed in 9 of 12 patients. Appearance of small lesions and worsening of cerebral atrophy on long-term follow-up suggest the possibility of subclinical progression of cerebral vasculitis and should be considered in the prognosis of neuro-Behçet's disease.

The macrophage-secreted 92-kDa type IV collagenase and metalloproteinases play a critical role in cell microenvironment regulation and cell movement. HIV infection of macrophages might be capable of deregulating the expression of these gelatinases. Hence, human monocyte-derived-macrophages were infected by lymphotropic HIV-1/Lai and monocytropic HIV-1/DAS isolates. Gelatinase activity and gelatinase and inhibitor (TIMP, α2M) biosyntheses were evaluated in supernatants and cellular extracts. Our data suggest that HIV infection facilitates gelatinase secretion and intracellular inhibitor retention. These argue for the increase of free proteinase that could degrade barriers, which would permit cell movement and viral dissemination into tissues.