[Infection associated cerebral vasculitis]. / Vascularites cérébrales associées aux infections.

Infections are a frequent cause of cerebral vasculitis, important to diagnose because a specific treatment may be required. Infection-associated vasculitis can be caused by angiotropic pathogens (varicella zoster virus, syphilis, aspergillus). They can be associated with subarachnoidal meningitis (tuberculosis, pyogenic meningitis, cysticercosis). They can appear contiguously to sinuses or orbital infection (aspergillosis, mucormycosis). Finally, they also may be due to an immune mechanism in the context of chronic infections (hepatitis B virus, hepatitis C virus, human immunodeficiency virus). Cerebral vasculitis are severe conditions and their prognosis is directly linked to early recognition and diagnosis. Infectious causes must therefore be systematically considered ahead of cerebral vasculitis, and the appropriate investigations must be determined according to the patient's clinical context. We propose here an update on the infectious causes of cerebral vasculitis, their diagnosis modalities, and therapeutic options.

Anticoagulation decisions in elderly patients with stroke.

Primary and secondary prevention of stroke is often a challenge in elderly patients due to the increase in both thrombotic and hemorrhagic risks with age. In some cases, there is sufficient data in the elderly population to allow recommendations or anticoagulation decisions to be made, such as for the indication of anticoagulation to prevent stroke related to atrial fibrillation (AF) or the choice of oral anticoagulant therapy in this situation. In other situations, the less robust data leave some questions; this is the case for the delay to initiate an oral anticoagulant therapy after an AF-related ischemic stroke, for the management of antithrombotic treatment after a stroke of undetermined cause or after intracranial bleeding or in a high-risk bleeding situation associated with stroke in the elderly subject. These issues will be discussed in this paper.

[Ultrasound in emergency medicine]. / L'échographie en médecine d'urgence préhospitalière.

Ultrasound has revolutionized the practice of emergency medicine, particularly in prehospital setting. About a patient with dyspnea, we present the role of ultrasound in the diagnosis and emergency treatment. Echocardiography, but also hemodynamic ultrasound (vena cava) and lung exam are valuable tools. Achieving lung ultrasound and diagnostic value of B lines B are detailed.

Hyperglycemia and the fate of apparent diffusion coefficient-defined ischemic penumbra.

BACKGROUND AND PURPOSE: Previous data have shown the feasibility of identifying ischemic penumbra in patients with acute stroke by using a semiautomated analysis of ADC maps. Here, we investigated whether the fate of ADC-defined penumbra was altered by HG. We also examined the interaction between HG and arterial recanalization on infarct growth. MATERIALS AND METHODS: We examined 94 patients by using MR imaging within 6 hours of stroke onset and a follow-up MR imaging within 7 days. The ADC-defined tissue-at-risk was calculated from the early MR imaging. Patients were classified according to high (>7 mmol/L; n = 34/94, HG) or normal (n = 60/94) baseline SGL. The impact of HG status on infarct growth was assessed by using multiple regression models and analysis of the slopes of regression lines for each group. Interaction between HG status and arterial recanalization on infarct growth was investigated by using multiple regression analysis. RESULTS: The slope of the predicted versus observed infarct growth regression line was steeper in HG than non-HG patients (P = .0008), suggesting that infarct growth within ADC-defined tissue-at-risk was increased in HG patients. The effect was 2.8 times more severe in nonrecanalized patients (P = .01) than in patients with recanalization (P = .001). CONCLUSIONS: ADC-defined tissue-at-risk may represent ischemic penumbra because part of this area may be salvaged in normal SGL patients. The toxicity in HG patients seems to be more related to penumbra-infarction transition than reperfusion injury in humans because the effect was larger in nonrecanalized than in recanalized patients.

Detection of paroxysmal atrial fibrillation with transtelephonic EKG in TIA or stroke patients.

BACKGROUND: Paroxysmal atrial fibrillation (PAF) may remain underdiagnosed after stroke, as suggested by long-duration EKG monitoring. Here we report the sensitivity of transtelephonic EKG monitoring (TTM) for detection of PAF in patients following a recent stroke or TIA and a negative 24-hour Holter. METHODS: We analyzed data from 98 consecutive patients with TTM and noncardioembolic TOAST stroke (n = 78) or TIA (n = 20). Most were cryptogenic events (82%). Patients started TTM 0.8 months (interquartile range 0.4-2.5) after the indexed event and randomly recorded about 1 EKG per day for 1 month. Univariate and multivariate analyses were run to identify PAF predictors. RESULTS: Seventeen PAF episodes were detected in 9.2% (9/98) of the patients. The estimated duration of PAF episodes ranged from 4 to 72 hours. Two predictors were identified: premature atrial ectopic beats (more than 100) in 24-hour routine Holter (odds ratio [OR] = 11.0; 95% confidence interval [CI] 1.9-62; p = 0.007) and nonlacunar anterior circulation DWI hypersignals (OR = 9.9; 95% CI 1.1-90.6; p = 0.04). The PAF detection rate varied from 42.6% for patients meeting both criteria to 0% for patients with neither of them. CONCLUSIONS: Transtelephonic EKG monitoring increases detection rate of paroxysmal atrial fibrillation in stroke and TIA patients whose 24-hour Holter result was negative, especially if they had frequent premature atrial ectopic beats, recent anterior circulation infarct on MRI, or both.

Reliability of the ECASS radiological classification of postthrombolysis brain haemorrhage: a comparison of CT and three MRI sequences.

BACKGROUND: Postthrombolysis brain haemorrhagic transformations (HT) are often categorized with the CT-based classification of the European Cooperative Acute Stroke Study (ECASS). However, little is known about the reliability of this classification and its extension to MRI. Our objective was to compare the inter- and intraobserver reliability of this classification on CT and 3 MRI sequences. METHODS: Forty-three patients with postthrombolysis HT on CT or at least 1 of the 3 MRI sequences: fluid-attenuation inversion recovery (FLAIR), diffusion-weighted imaging (DWI), and T2* gradient recalled echo (T2*GRE) were selected. Twelve control patients without any bleeding were added to avoid a bias based on a pure HT-positive cohort. Each series of images were independently classified with the ECASS method by 6 blinded observers. Inter- and intraobserver reproducibility was categorized from poor to excellent depending on kappa values. RESULTS: The inter- and intraobserver overall concordance of the classification was good for T2*GRE, DWI and CT (kappa > 0.6) and moderate for FLAIR (kappa < 0.6). The interobserver concordance for parenchymal haematomas was excellent for T2*GRE (kappa > 0.8) and moderate for CT, FLAIR and DWI. CONCLUSION: The T2*GRE sequence is the most reproducible method to categorize postthrombolysis HT and has an excellent reliability for the severe parenchymal haematoma category, suggesting that this sequence should be used to assess HT in thrombolytic therapy trials.

[Complex visual hallucinations following occipital infarct and perception of optical illusions]. / Hallucinations visuelles complexes après infarctus occipital et perception d'illusions visuelles.

INTRODUCTION: The physiopathology of visual hallucinations in the hemianopic field secondary to occipital infarct is uncertain. CASE REPORT: We report the case of a patient with a history of occipital infarct who presented nonstereotyped complex hallucinations in the quadranopic field resulting from a second controlateral occipital infarct. Based on an experience with motion optical illusions, we suggested that the association of these two occipital lesions, involving the V5 motion area on the one side and the V1 area on the other side, could have produced the complex hallucinations due to a release phenomenon. The patient experienced simultaneously a double visual consciousness, with both hallucinations and real visual perceptions. CONCLUSION: The study of perceptual illusions in patients with visual hallucinations could illustrate the innovative theory of visual consciousness as being not unified but constituted of multiple microconsciousnesses.

Characterization of HRG22, a human homologue of the putative tumor suppressor gene HIC1.

Database searches identified on chromosome 22q11.2, a region subject to translocations, an homologue of the HIC1 (hypermethylated in cancer) candidate tumor suppressor gene located at 17p13.3. This gene was termed HRG22 for HIC1-related gene on chromosome 22. We have characterized a new HRG22 upstream coding exon and defined the complete coding sequence of the human and zebrafish HRG22 genes. Alignment of the HRG22 and HIC1 proteins from various species revealed high sequence homology in their N-terminal BTB/POZ and five C-terminal C(2)H(2) zinc finger domains and highlighted a conserved GLDLSKK/R peptide in their middle region. The full-length HRG22 and HIC1 proteins colocalize onto nuclear dots and share several functional properties since their BTB/POZ domains heterodimerize and are autonomous transcriptional repression domain insensitive to Trichostatin A, a histone deacetylase (HDAC) inhibitor. Thus, HIC1 and HRG22 define a subgroup of BTB/POZ domains unable to recruit repressing complexes containing an HDAC activity.

Identification in the human candidate tumor suppressor gene HIC-1 of a new major alternative TATA-less promoter positively regulated by p53.

HIC-1 (hypermethylated in cancer 1), a BTB/POZ transcriptional repressor, was isolated as a candidate tumor suppressor gene located at 17p13.3, a region hypermethylated or subject to allelic loss in many human cancers and in the Miller-Dieker syndrome. The human HIC-1 gene is composed of two exons, a short 5'-untranslated exon and a large second coding exon. Recently, two murine HIC-1 isoforms generated by alternative splicing have been described. To determine whether such isoforms also exist in human, we have further analyzed the human HIC-1 locus. Here, we describe and extensively characterize a novel alternative noncoding upstream exon, exon 1b, associated with a major GC-rich promoter. We demonstrate using functional assays that the murine exon 1b previously described as coding from computer analyses of genomic sequences is in fact a noncoding exon highly homologous to its human counterpart. In addition, we report that the human untranslated exon is presumably a coding exon, renamed exon 1a, both in mice and humans. Both types of transcripts are detected in various normal human tissues with a predominance for exon 1b containing transcripts and are up-regulated by TP53, confirming that HIC-1 is a TP53 target gene. Thus, HIC-1 function in the cell is controlled by a complex interplay of transcriptional and translational regulation, which could be differently affected in many human cancers.

Recruitment of SMRT/N-CoR-mSin3A-HDAC-repressing complexes is not a general mechanism for BTB/POZ transcriptional repressors: the case of HIC-1 and gammaFBP-B.

Hypermethylated in cancer (HIC-1), a new candidate tumor suppressor gene located in 17p13.3, encodes a protein with five C(2)H(2) zinc fingers and an N-terminal broad complex, tramtrack, and bric à brac/poxviruses and zinc-finger (BTB/POZ) domain found in actin binding proteins or transcriptional regulators involved in chromatin modeling. In the human B cell lymphoma (BCL-6) and promyelocityc leukemia (PLZF) oncoproteins, this domain mediates transcriptional repression through its ability to recruit a silencing mediator of retinoid and thyroid hormone receptor (SMRT)/nuclear receptor corepressor (N-CoR)-mSin3A-histone deacetylase (HDAC) complex, a mechanism shared with numerous transcription factors. HIC-1 appears unique because it contains a 13-aa insertion acquired late in evolution, because it is not found in its avian homologue, gammaF1-binding protein isoform B (gammaFBP-B), a transcriptional repressor of the gammaF-crystallin gene. This insertion, located in a conserved region involved in the dimerization and scaffolding of the BTB/POZ domain, mainly affects slightly the ability of the HIC-1 and gammaFBP-B BTB/POZ domains to homo- and heterodimerize in vivo, as shown by mammalian two-hybrid experiments. Both the HIC-1 and gammaFBP-B BTB/POZ domains behave as autonomous transcriptional repression domains. However, in striking contrast with BCL-6 and PLZF, both HIC-1 and gammaFBP-B similarly fail to interact with members of the HDAC complexes (SMRT/N-CoR, mSin3A or HDAC-1) in vivo and in vitro. In addition, a general and specific inhibitor of HDACs, trichostatin A, did not alleviate the HIC-1- and gammaFBP-B-mediated transcriptional repression, as previously shown for BCL-6. Taken together, our studies show that the recruitment onto target promoters of an HDAC complex is not a general property of transcriptional repressors containing a conserved BTB/POZ domain.

Evolutionary divergence in the broad complex, tramtrack and bric à brac/poxviruses and zinc finger domain from the candidate tumor suppressor gene hypermethylated in cancer.

Hypermethylated in cancer, a new candidate tumor suppressor gene located in 17p13.3, encodes a protein with five Krüppel-like C2H2 zinc finger motifs and a N-terminal protein/protein interaction domain called broad complex, tramtrack and bric à brac/poxviruses and zinc finger domain. Hypermethylated in cancer appears unique in the broad complex, tramtrack and bric à brac/poxviruses and zinc finger family since it contains a 13 amino acid insertion located in a loop between the conserved beta-strand beta5 and helix alpha5 which are involved in dimerization and scaffolding of the broad complex, tramtrack and bric à brac/poxviruses and zinc finger domain. Cloning and sequencing of a murine hypermethylated in cancer gene suggests that this insertion has been acquired late in the evolution since it is present in two mammalian hypermethylated in cancer genes but absent in its zebrafish and avian counterparts. This is a unique example of a high divergence of the same broad complex, tramtrack and bric à brac/poxviruses and zinc finger domain in different species.

The carboxy-terminal end of the candidate tumor suppressor gene HIC-1 is phylogenetically conserved.

HIC-1 (hypermethylated in cancer), a new candidate tumor suppressor gene located in 17p13.3, encodes a protein with five Krüppel-like C2H2 zinc finger motifs and a N-terminal protein-protein interaction domain called BTB/POZ. These two domains appeared as the only conserved regions found between human HIC-1 and its avian homologue, gammaFBP-B, isolated as a transcriptional repressor of the gammaF-Crystallin gene. We have recloned the HIC-1 gene and found four nucleotide differences within the 3' part of its published coding sequence. The corrected HIC-1 C-terminal end exhibits now significant homology (70%) to the chicken gammaFBP-B C-terminal end and appears thus as a third phylogenetically conserved domain that may serve an important, yet unknown function in HIC-1.