Intoxication au monoxyde de carbone et place de l’oxygénothérapie hyperbare

Hyperbaric oxygen (HBO) is used since more than 50 years for carbon monoxide poisoning. However, HBO protocols and indications are still debated. Neurological (coma and delayed neuropsychological sequelae) and cardiac (ischemic changes with normal coronary arteries) clinical scenarios are explained by complex mechanisms. Carboxyhemoglobin formation, cytochrome oxydase inhibition, oxidative stress, as well as ischemia-reperfusion phenomenon are among these mechanisms. Venous and arterial carboxyhemoglobin levels are not correlated with the patient’s final prognosis and thus not mandatory for indicating the treatment. Conversely, troponin IC measurement is strongly recommended if myocardial involvement is suspected. HBO treatment relies on mechanistic bases: earlier detoxification, anti-oxidant properties, and improvement in cerebral physiology (decrease in intracranial pressure and oedema, and ischemic penumbra preservation). Clinical basis is assessed by the results of the randomized clinical trials (RCTs). Four among the 5 RCTs using > 2 ATA OHB protocols were positive. Two RCTs at 2 ATA level were negative. Therefore, international guidelines recommend OHB with at least 2.5 ATA in patients at risk of delayed neuropsychological sequelae, whatever the objective neurological signs are, in pregnant women, and patients with myocardial involvement. If OHB is not required, normobaric oxygen with high flow rates during at least 8-12 hours is mandatory.     

La sédation comme facteur de risque d’infection acquise en réanimation

Sedative and analgesic drugs are routinely and heterogeneously used in mechanically ventilated patients. Several epidemiologic studies suggested a relationship between sedation and intensive care unit (ICU)-acquired infections. Sedation may promote infection, a common complication in the ICU, associated with a high morbidity, mortality, and cost. Prolongation of exposure to risk factors for infection, microaspiration, gastrointestinal motility disturbances, and microcirculatory effects are the main mechanisms by which sedation may favour infection in the critically ill patients. Experimental evidence based on both human and animal studies suggests that sedatives and analgesics may alter the immunologic response to exogenous stimuli. Clinical studies comparing different sedative agents do not provide evidence to recommend the use of a particular agent to reduce the rate of ICU-acquired infection. However, sedation strategies aiming to reduce the duration of mechanical ventilation including daily interruption of sedatives or nursing-implementing sedation protocols should be promoted.     

Connexin channels provide a target to manipulate brain endothelial calcium dynamics and blood�Cbrain barrier permeability

The cytoplasmic Ca²⁺ concentration ([Ca²⁺]_i) is an important factor determining the functional state of blood–brain barrier (BBB) endothelial cells but little is known on the effect of dynamic [Ca²⁺]_i changes on BBB function. We applied different agonists that trigger [Ca²⁺]_i oscillations and determined the involvement of connexin channels and subsequent effects on endothelial permeability in immortalized and primary brain endothelial cells. The inflammatory peptide bradykinin (BK) triggered [Ca²⁺]_i oscillations and increased endothelial permeability. The latter was prevented by buffering [Ca²⁺]_i with BAPTA, indicating that [Ca²⁺]_i oscillations are crucial in the permeability changes. Bradykinin-triggered [Ca²⁺]_i oscillations were inhibited by interfering with connexin channels, making use of carbenoxolone, Gap27, a peptide blocker of connexin channels, and Cx37/43 knockdown. Gap27 inhibition of the oscillations was rapid (within minutes) and work with connexin hemichannel-permeable dyes indicated hemichannel opening and purinergic signaling in response to stimulation with BK. Moreover, Gap27 inhibited the BK-triggered endothelial permeability increase in in vitro and in vivo experiments. By contrast, [Ca²⁺]_i oscillations provoked by exposure to adenosine 5′ triphosphate (ATP) were not affected by carbenoxolone or Gap27 and ATP did not disturb endothelial permeability. We conclude that interfering with endothelial connexin hemichannels is a novel approach to limiting BBB-permeability alterations.     

Right Hemisphere Recruitment During Language Processing in Frontotemporal Lobar Degeneration and Alzheimer’s Disease

Right hemisphere recruitment of areas homotopical to affected left-sided language areas has classically been described in aphasia following stroke or brain tumors. It may also be a clinically significant mechanism in frontotemporal lobar degeneration (FTLD) and Alzheimer’s disease (AD). In a pooled analysis of previous functional magnetic resonance imaging studies of a modified version of the Pyramids and Palm Trees test, we probed the language network in 19 patients with primary progressive aphasia (nine semantic (SV) and ten agrammatic variant; neuropathologically confirmed FTLD in three cases to date), 15 patients with AD (14 clinically probable and one neuropathologically definite AD to date), and 37 healthy controls. The upper and lower bank of the left posterior superior temporal sulcus (STS) was affected in AD and the left anterior temporal pole (ATP) in primary progressive aphasia (PPA; mainly driven by SV). In the right hemisphere, the posterior STS showed an activity increase in both patient groups compared with controls. In AD, this activity increase correlated positively with naming accuracy. Both in AD and in PPA, the connection strength between right STS and right ATP was decreased compared with controls and this correlated with naming and comprehension scores, respectively. Only in PPA did the right anterior temporal pole show an activity increase, which correlated negatively with comprehension. Right-hemispheric recruitment and disconnections within the right temporal lobe may affect the degree of aphasia in cortical neurodegenerative disease.     

A common neural system is activated in hearing non-signers to process French sign language and spoken French

We used functional magnetic resonance imaging to investigate the areas activated by signed narratives in non-signing subjects naïve to sign language (SL) and compared it to the activation obtained when hearing speech in their mother tongue. A subset of left hemisphere (LH) language areas activated when participants watched an audio-visual narrative in their mother tongue was activated when they observed a signed narrative. The inferior frontal (IFG) and precentral (Prec) gyri, the posterior parts of the planum temporale (pPT) and of the superior temporal sulcus (pSTS), and the occipito-temporal junction (OTJ) were activated by both languages. The activity of these regions was not related to the presence of communicative intent because no such changes were observed when the non-signers watched a muted video of a spoken narrative. Recruitment was also not triggered by the linguistic structure of SL, because the areas, except pPT, were not activated when subjects listened to an unknown spoken language. The comparison of brain reactivity for spoken and sign languages shows that SL has a special status in the brain compared to speech; in contrast to unknown oral language, the neural correlates of SL overlap LH speech comprehension areas in non-signers. These results support the idea that strong relationships exist between areas involved in human action observation and language, suggesting that the observation of hand gestures have shaped the lexico-semantic language areas as proposed by the motor theory of speech. As a whole, the present results support the theory of a gestural origin of language.     

Meningococcal purpura fulminans in children: I. Initial orthopedic management

Background  

Purpura fulminans is a rare and extremely severe infection, mostly due to Neisseria meningitidis frequently causing early orthopedic lesions. Few studies have reported on the initial surgical management of acute purpura fulminans. The aim of this study is to look at the predictive factors in orthopedic outcome in light of the initial surgical management in children surviving initial resuscitation.