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ObjectiveTo assess putative risk factors and outcome of multiple and early recurrent cervical artery dissection (CeAD).MethodsWe combined data from 2 multicenter cohorts and compared patients with multiple CeAD at initial diagnosis, early recurrent CeAD within 3 to 6 months, and single nonrecurrent CeAD. Putative risk factors, clinical characteristics, functional outcome, and risk of recurrent ischemic events were assessed.ResultsOf 1,958 patients with CeAD (mean ± SD age 44.3 ± 10 years, 43.9% women), 1,588 (81.1%) had single nonrecurrent CeAD, 340 (17.4%) had multiple CeAD, and 30 (1.5%) presented with single CeAD at admission and had early recurrent CeAD. Patients with multiple or early recurrent CeAD did not significantly differ with respect to putative risk factors, clinical presentation, and outcome. In multivariable analyses, patients with multiple or early recurrent CeAD more often had recent infection (odds ratio [OR] 1.81, 95% confidence interval [CI] 1.29–2.53), vertebral artery dissection (OR 1.82, 95% CI 1.34–2.46), family history of stroke (OR 1.55, 95% CI 1.06–2.25), cervical pain (OR 1.36, 95% CI 1.01–1.84), and subarachnoid hemorrhage (OR 2.85, 95% CI 1.01–8.04) at initial presentation compared to patients with single nonrecurrent CeAD. Patients with multiple or early recurrent CeAD also had a higher incidence of cerebral ischemia (hazard ratio 2.77, 95% CI 1.49–5.14) at 3 to 6 months but no difference in functional outcome compared to patients with single nonrecurrent CeAD.ConclusionPatients with multiple and early recurrent CeAD share similar risk factors, clinical characteristics, and functional outcome. Compared to patients with single nonrecurrent CeAD, they are more likely to have recurrent cerebral ischemia at 3 to 6 months, possibly reflecting an underlying transient vasculopathy.

Objective:In a cohort of patients diagnosed with cervical artery dissection (CeAD), to determine the proportion of patients aged ≥60 years and compare the frequency of characteristics (presenting symptoms, risk factors, and outcome) in patients aged Methods:We combined data from 3 large cohorts of consecutive patients diagnosed with CeAD (i.e., Cervical Artery Dissection and Ischemic Stroke Patients–Plus consortium). We dichotomized cases into 2 groups, age ≥60 and Results:Among 2,391 patients diagnosed with CeAD, we identified 177 patients (7.4%) aged ≥60 years. In this age group, cervical pain (ORadjusted 0.47 [0.33–0.66]), headache (ORadjusted 0.58 [0.42–0.79]), mechanical trigger events (ORadjusted 0.53 [0.36–0.77]), and migraine (ORadjusted 0.58 [0.39–0.85]) were less frequent than in younger patients. In turn, hypercholesterolemia (ORadjusted 1.52 [1.1–2.10]) and hypertension (ORadjusted 3.08 [2.25–4.22]) were more frequent in older patients. Key differences between age groups were confirmed in secondary analyses. In multivariable, adjusted analyses, favorable outcome (i.e., modified Rankin Scale score 0–2) was less frequent in the older age group (ORadjusted 0.45 [0.25, 0.83]).Conclusion:In our study population of patients diagnosed with CeAD, 1 in 14 was aged ≥60 years. In these patients, pain and mechanical triggers might be missing, rendering the diagnosis more challenging and increasing the risk of missed CeAD diagnosis in older patients.

Background and purpose To investigate the association of anemia on admission with ischaemic stroke (IS), stroke severity and early functional outcome in patients with cervical artery dissection (CeAD) or with IS of other causes (non-CeAD-IS patients). Methods The study sample comprised all patients from the Cervical Artery Dissection and Ischaemic Stroke Patients (CADISP) study without pre-existing disability and with documentation of stroke severity and hemoglobin (Hb) concentration on admission. Anemia was classified as mild (Hb

Background and purpose Patients with ischaemic stroke (IS) caused by a spontaneous cervical artery dissection (CeAD) worry about an increased risk for stroke in their families. The occurrence of stroke in relatives of patients with CeAD and in those with ischaemic stroke attributable to other (non-CeAD) causes were compared. Methods The frequency of stroke in first-degree relatives (family history of stroke, FHS) was studied in IS patients (CeAD patients and age- and sex-matched non-CeAD patients) from the Cervical Artery Dissection and Ischemic Stroke Patients (CADISP) database. FHS ≤ 50 and FHS > 50 were defined as having relatives who suffered stroke at the age of ≤50 or >50 years. FHS ≤ 50 and FHS > 50 were studied in CeAD and non-CeAD IS patients and related to age, sex, number of siblings, hypertension, hypercholesterolemia, smoking and body mass index (BMI). Results In all, 1225 patients were analyzed. FHS ≤ 50 was less frequent in CeAD patients (15/598 = 2.5%) than in non-CeAD IS patients (38/627 = 6.1%) (P = 0.003; odds ratio 0.40, 95% confidence interval 0.22–0.73), also after adjustment for age, sex and number of siblings (P = 0.005; odds ratio 0.42, 95% confidence interval 0.23–0.77). The frequency of FHS > 50 was similar in both study groups. Vascular risk factors did not differ between patients with positive or negative FHS ≤ 50. However, patients with FHS > 50 were more likely to have hypertension and higher BMI. Conclusion Relatives of CeAD patients had fewer strokes at a young age than relatives of non-CeAD IS stroke patients.

Although the zeta-associated protein of 70 kDa (ZAP-70) is overexpressed in patients with chronic lymphocytic leukemia (CLL) displaying unmutated IGVH genes and poor prognosis, a previous microarray study from our group identified overexpression of LPL and ADAM29 genes among unmutated and mutated CLL, respectively. To assess the prognostic value of these genes, we quantified their expression by real-time quantitative polymerase chain reaction (PCR) in a cohort of 127 patients with CLL and correlated this with clinical outcome, IGVH mutational status, and ZAP-70 protein expression. IGVH mutational status, ZAP-70, and the LPL and ADAM29 mRNA ratios (L/A ratio) were predictive of event-free survival for the whole cohort and for patients with stage A disease. in patients in stage B and C, the L/A ratio was an independent prognostic factor, whereas ZAP-70 did not predict survival. Simultaneous usage of the L/A ratio and ZAP-70 expression allowed an almost perfect (99%) assessment of the IGVH status in the 80% of patients with concordant results (L/A(+), ZAP-70(+) or L/A(-), ZAP-70(-)). LPL and ADAM29 gene expression could also be determined by a simple competitive multiplex reverse transcription PCR assay. Overall, quantification of LPL and ADAM29 gene expression is a strong prognostic indicator in CLL, providing better prognostic assessment than ZAP-70 in advanced stages of the disease. Hop La Pitie Salpetriere, Serv Hematol Biol, F-75013 Paris, France Inst Pasteur, Unite Immunohematol & Immunopathol, F-75724 Paris, France Universidade Federal de São Paulo, Disciplina Hematol & Hemoterapia, São Paulo, Brazil Inst Pasteur, Dept Ecosyst & Epidemiol Malad Infect, Paris, France Hop La Pitie Salpetriere, Serv Immunol, Paris, France Inst Pasteur, Ctr Rech Vaccinale & Biomed, Paris, France Universidade Federal de São Paulo, Disciplina Hematol & Hemoterapia, São Paulo, Brazil Web of Science

Clinical findings of pontine infarcts are more frequently described as classical crossed-syndrome. The aim of this study was to analyse clinical presentation of isolated pontine infarcts. From the Besancon Stroke Registry, we retrospectively studied 34 patients with isolated pontine infarcts documented on MRI with a strict centro-bicommissural plane as the reference. MRI were analyzed using an arterial territories mapping of brainstem. Among our 34 pts, none developed a classical crossed-syndrome. A thorough knowledge of vascular anatomy of brainstem is necessary to understand clinical findings. Moreover, this knowledge allow to explain the rare occurrence of pontine crossed-syndrome.

Computed tomography (CT) is widely used for early evaluation of acute strokes. Most importantly, CT excludes acute hemorrhage or other diseases mimicking ischemia. Therefore, CT is the main imaging examination in patients with brain ischemia and when antithrombotic agents are being considered. During the first hours after acute ischemic stroke, the CT does not usually show much in the first 24 hours. However, early abnormal findings on CT scan have been described such as the hyperdense middle cerebral artery sign (HMCAS), and reduced contrast attenuation of the cerebral parenchyma. HMCAS reflects arterial occlusion. Early parenchymal abnormalities, the attenuation of lentiform nucleus (ALN), loss of the insular ribbon (LIR) or hemispheric sulcus effacement (HSE) occur less frequently and they are positive criteria for cerebral in progress. Early parenchymal abnormalities might also predict subsequent infarct extension and hemorrhagic transformation. Therapeutic trials of ischemia in MCA territory involved decision making when the CT may not show obvious ischemic changes. Finally, initial CT findings may also help to predict response to therapy.

Peroxynitrite (ONOO−) is a potent oxidizing and nitrating agent produced by the reaction of nitric oxide with superoxide. It readily nitrates phenolic compounds such as tyrosine residues in proteins, and it has been demonstrated that nitration of tyrosine residues in proteins inhibits their phosphorylation. During immune responses, tyrosine phosphorylation of key substrates by protein tyrosine kinases is the earliest of the intracellular signaling pathways following activation through the TCR complex. This work was aimed to evaluate the effects of ONOO− on lymphocyte tyrosine phosphorylation, proliferation, and survival. Additionally, we studied the generation of nitrating species in vivo and in vitro during immune activation. Our results demonstrate that ONOO−, through nitration of tyrosine residues, is able to inhibit activation-induced protein tyrosine phosphorylation in purified lymphocytes and prime them to undergo apoptotic cell death after PHA- or CD3-mediated activation but not upon phorbol ester-mediated stimulation. We also provide evidence indicating that peroxynitrite is produced during in vitro immune activation, mainly by cells of the monocyte/macrophage lineage. Furthermore, immunohistochemical studies demonstrate the in vivo generation of nitrating species in human lymph nodes undergoing mild to strong immune activation. Our results point to a physiological role for ONOO− as a down-modulator of immune responses and also as key mediator in cellular and tissue injury associated with chronic activation of the immune system.

A comparative analysis of subsets (4B4 and 2H4) within the CD4 lymphocyte subpopulation was made by double marker analysis among 23 healthy heterosexual, 16 healthy HIV seronegative high-risk homosexuals and 82 HIV seropositive subjects. Data show that the significant increase in CD4 lymphocytes observed among seronegative homosexuals corresponds mainly to an increase in CD4-4B4 positive cells while CD4-2H4 subset levels remain comparable to healthy heterosexual controls. A decrease both in CD4-4B4 and CD4-2H4, parallel to a decrease in CD4 subpopulation, was observed in asymptomatic seropositive carriers (SPC) and patients with ARC syndrome (AIDS-related complex) or AIDS (acquired immunodeficiency syndrome). Interestingly, an absolute decrease in CD4 subpopulation in patients with asymptomatic lymph node enlargement (LAS), is chiefly accounted for by a decrease in CD4-4B4 subset. The values of CD4-2H4 subset are significantly higher than those observed for SPC patients and are close to the normal values. These observations are of interest, as no differences between SPC and LAS patients could be detected when CD3, CD4 and CD8 subpopulations were studied.

While outpatient management for chronic neurological diseases is well-established, the impact of inpatient neurological examination in emergency room and university hospital remain largely underestimated. We prospectively studied the role of the neurologist in patient management, in a primary care university hospital. Over a period of 12 months, we prospectively recorded the demographics of patients requiring examination in the emergency room, the initial suspected neurological diagnosis of the emergency room, the final diagnosis of the neurology team, and the patients' outcomes. For each patient, the time between admission, the call and the neurological examination were recorded. Neurological examinations were performed in 2220 patients in whom 75.6 p.100 were performed in the emergency room. These latter patients corresponded to 14 p.100 of all patients admitted in the emergency room. Of examined patients, 52 p.100 were male and mean age was 56.9 +/- 21 years. The time between admission and examination was 32 min. (+/- 36 min), irrespective of the day of the week, and depended on the suspected diagnosis: shorter in stroke and status epilepticus (p0.05), and longer in loss of consciousness and vertigo (p0.01). Forty-four percent of the examinations took place in the evening and night. The reasons for examinations were: stroke (28.3 p.100), epilepsy (17.7 p.100), headaches (8.4 p.100), loss of consciousness (7.9 p.100), cognitive dysfunctions (4.1 p.100), neuropathies (4 p.100) and miscellaneous (8.1 p.100). Neurological examinations modified neurological diagnosis and treatment in more than 86 p.100 of the patients. Following neurological examination, 17.2 p.100 of the patients were able to go home, while the rest were admitted to the stroke unit (27.2 p.100), the general neurological unit (27.3 p.100) or in other departments (28.3 p.100), of which intensive care unit (5.3 p.100) or neurosurgery (5.9 p.100). Emergency neurologic examination improves neurological diagnosis and has a positive impact both on treatment and, more globally, in patient management.

Medical management of cervical arterial dissections is not standardized and has not been the subject of randomized trials. Management is mainly based on the presumed pathophysiology of secondary cerebral infarcts associated with dissections and the individual experience of each treating team. First, a review of the literature regarding medical management of acute and chronic dissections is presented. Then, results from a national study sponsored by the Société Française Neuro-Vasculaire and the Société Française de Neuro-Radiologie evaluating the medical management of this pathology in French neuro-vascular centers will be presented. These data will be useful to generate practical management recommendations and establish guidelines for further studies.

Two long-term cell lines obtained from two cases of large granular lymphocyte lymphocytosis (LGLL) displaying an unusual phenotype are reported here. Patient n. 1 was CD2+ CD3- CD16+ CD8+ CD56- CD57- CD29+ CD45RA+, whereas patient n. 2 was CD2-CD3+ CD8+ CD16+ CD56- CD57+ CD29+ CD45RA+. The cells were large granular lymphocytes by light and electron microscopic criteria and displayed strong antibody-dependent cell mediated cytotoxicity (ADCC) and NK activity. Northern blot analysis revealed aberrant transcripts of TCR beta chains for patient n. 1, and full length TCR alpha and beta transcripts for patient n. 2. In both cases, we were able to establish a long term cell line which functionally revealed strong ADCC and NK activity. Functional implications of these 2 subpopulations are discussed.

Background and purpose Our aim was to investigate whether pulsatile tinnitus (PT) in cervical artery dissection (CeAD) has prognostic significance. Methods All CeAD patients from the CADISP (Cervical Artery Dissection and Ischemic Stroke Patients) study with documentation of PT were analysed. The presence of PT was systematically assessed using a standardized questionnaire. Stroke severity at admission was defined according to the National Institutes of Health Stroke Scale (NIHSS). Excellent outcome after 3 months was defined as a modified Rankin Scale of 0–1. Results Sixty-three of 778 patients (8.1%) reported PT. PT+ patients presented less often with ischaemic stroke (41.3% vs. 63.9%, P < 0.001), more often with dissection in the internal carotid artery (85.7% vs. 64.2%, P = 0.001), less often with vessel occlusion (19.0% vs. 34.1%, P = 0.017) and more often with excellent outcome at 3 months (92.1% vs. 75.4%, P = 0.002). Logistic regression analysis identified PT as an independent predictor of excellent outcome after 3 months [odds ratio (OR) 3.96, 95% confidence interval (CI) 1.22–12.87] adjusted to significant outcome predictors NIHSS on admission (OR 0.82, 95% CI 0.79–0.86), Horner syndrome (OR 1.95, 95% CI 1.16–3.29) and vessel occlusion (OR 0.62, 95% CI 0.40–0.94) and to non-significant predictors age, sex, pain and location of CeAD. Conclusion The presence of PT in CeAD is associated with a benign clinical course and predicts a favourable outcome.