[What about the ISAT results?].
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Biomedical subjects
Publications and source records attributed to D Dormont.
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The authors report a patient with advanced PD, successfully treated by bilateral stimulation of the subthalamic nucleus, who developed acute transient aggressive behavior during intraoperative electrical test stimulation. The electrode responsible for this abnormal behavior was located within the lateral part of the posteromedial hypothalamic region (triangle of Sano). The authors suggest that affect can be dramatically modulated by the selective manipulation of deep brain structures.
We assess the genetic relationships between 49 HIV-1 group O strains from 24 and 25 patients living in Cameroon and France, respectively. Strains were sequenced in four genomic regions: gag (p24) and three env regions (C2-V3, gp41, and for 22 C2-gp41). In each of the genomic regions analyzed, the genetic diversity among the group O strains was higher than that exhibited by group M. We characterize three major group O phylogenetic clusters (O:A, O:B, and O:C) that comprised the same virus strains in each of the genomic regions analyzed. The majority of strains cluster in O:A, a cluster previously identified by analysis of pol and env sequences. Group O recombinants were also identified. Importantly, the distinction between these three major group O clades was weak compared to the strong clustering apparent in the global group M phylogenetic tree that led to the identification of subtypes. Thus, these clusters of group O viruses should not be considered as equivalent to the group M subtypes. This difference between the pattern of group O and the global group M diversity, both taking into account the pandemic status of the group M subtypes and the comparatively small number of group O-infected individuals (the majority being from Cameroon), indicates that the group O phylogeny primarily represents viral divergence in the Cameroon region, analogous to group M viral diversity present in the Democratic Republic of Congo.
Prion related disorders are associated with the accumulation of a misfolded isoform (PrPsc) of the host-encoded prion protein, PrP. There is strong evidence for the involvement of unidentified co-factors in the PrP to PrPsc conversion process. In this study, we show alpha-synuclein-immunoreactive deposits in the central nervous system of various prion diseases (sporadic, iatrogenic and new variant Creutzfeldt-Jakob diseases, and experimental scrapie of hamsters). alpha-Synuclein accumulated close to PrPsc deposits but we did not observe strict colocalization of prion protein and alpha-synuclein immunoreactivities particularly in PrPsc plaques. alpha-Synuclein is thought to be a key player in some neurodegenerative disorders, is able to interact with amyloid structures and has known chaperone-like activities. Our results, in various prion diseases, suggest a role for alpha-synuclein in regulating PrPsc formation.
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Na+-dependent transporters for glutamate (excitatory amino acid transporters, EAATs) clear extracellular glutamate in the brain and prevent excitotoxic neuronal damage. Glutamine synthetase (GS) provides metabolic support for neurones by producing the neurotrophic amino acid glutamine. EAAT and GS expression has recently been demonstrated in macrophages and microglial cells in vitro, and in two models of acute inflammation in vivo. This observation might modify our current understanding of brain inflammation, which considers activated microglia and brain macrophages as the main neurotoxic cells through their production of a variety of neurotoxins, including glutamate. EAAT and GS expression by these cells would entail neuroprotective and neurotrophic properties, counterbalancing the deleterious consequences of microglial activation. Macaque infection by the simian immunodeficiency virus (SIV) is considered the most relevant model for human acquired immunodeficiency syndrome (AIDS), including chronic inflammation of the brain at the early asymptomatic stage of the infection, followed by an AIDS-like disease where neuronal death occurs. We studied the expression of EAAT-2 and GS in the brains of three SIVmac251-infected and two noninfected cynomolgus macaques. We found that both microglia and brain macrophages expressed EAAT-2 and GS in infected primates, suggesting that these cells might, like astrocytes, clear extracellular glutamate and provide glutamine to neurones. Microglia and macrophages could thus have neuroprotective and neurotrophic properties in addition to their production of neurotoxins. This finding might explain the contrast between early intense microglial activation and the late occurrence of neuronal apoptotic cell death, which is mainly observed at the terminal stage of the disease.
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.
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.
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.
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Bone marrow grafting following accidental irradiation exposure should be viewed in the perspective of a severe myeloablative syndrome linked to high medullary damage for a dose range higher than 6-8 Gy, resulting in very late or no recovery. Prognosis will depend on the presence or absence of radio-combined injuries, the toxicity of the transplant procedure, and the risk of rejection induced by insufficient percritical immunosuppression. It is in this context that new cell therapy modalities, which combine enhanced peripheral hematopoietic cell engraftment and high immunosuppressive conditioning regimen with low extrahematological toxicity, inducing early and stable mixed lymphomyeloid chimerism with minimal morbidity, can be considered. Such an approach is being evaluated in the treatment of patients with hematological malignancies at high risk of transplant-related mortality using conventional bone marrow methods.
Anti-myelin basic protein (MBP) autoreactive T cells play a key role in the pathogenesis of multiple sclerosis. Thus, we applied the Immunoscope strategy to cerebrospinal fluid (CSF) and peripheral blood lymphocytes (PBLs) of an HLA-DR2 patient. Both compartments showed major expansion for the V(beta)13S5 chain, which was associated in peripheral blood with significant proliferation of PBLs in response to MBP and the 84-102 HLA-DR2-restricted peptide. Sequencing revealed a unique nucleotide sequence in the CSF that gives rise to the amino acid sequence V(beta)13S5-RPGQGDQETQ-J(beta)2.5 if translated. This CDR3 sequence had already been reported to be reactive against the 84-102 peptide. This specific sequence was not detected in PBLs on day 0, whereas it was readily detectable on day 6 culture samples. Thus, cell culture may lead to enrichment in a T cell clone identified as autoreactive.
Presentation of MIRIAM 2: We describe the materials used for the creation of and the content of a CD-ROM entitled '77 neuroradiological case reports'. We mention the gathering of clinical and imaging data, exclusively provided by a PACS. Our work demonstrates that a CD-ROM is an appropriate interactive medium for radiological teaching. Its creation can be simplified thanks to a PACS, but it nonetheless remains work intensive.
PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSION: 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.
INTRODUCTION: 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. SUBJECTS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.
The neurological complications of Behçet's Disease are observed in 5 to 35 percent of cases depending of series. They included vascular and central nervous system manifestations. Vascular involvement is dominated by cerebral venous thrombosis marked by benign intracerebral hypertension. Prognosis is favourable with steroids and anticoagulation. Arterial involvement (thrombosis or aneurysm) are seldomly observed but increasingly with angio-MRI. Parenchymal involvement is dominated by meningoencephalitis eventually associated with fever. Myelitis and cranial nerve palsy are seldomly encountered. Cerebrospinal fluid is abnormal with lymphocytosis or pleiocytosis. MRI has a high sensitivity with hypersignals in the brainstem, basal ganglia, internal capsule and thalamus. Prognosis of central nervous system involvement is severe. Initially recovery is frequent, but severe impairment occurs due to relapse. In our experience, therapy including steroids, immunosuppressive drugs and colchicine improve short term and long term prognosis due to significant reduction of relapse in patients with good observance.