Nicolas Weiss

The blood-brain barrier in brain homeostasis and neurological diseases.

Brain endothelial cells are unique among endothelial cells in that they express apical junctional complexes, including tight junctions, which quite resemble epithelial tight junctions both structurally and functionally. They form the blood-brain-barrier (BBB) which strictly controls the exchanges between the blood and the brain compartments by limiting passive diffusion of blood-borne solutes while actively transporting nutrients to the brain. Accumulating experimental and clinical evidence indicate that BBB dysfunctions are associated with a number of serious CNS diseases with important social impacts, such as multiple sclerosis, stroke, brain tumors, epilepsy or Alzheimers disease. This review will focus on the implication of brain endothelial tight junctions in BBB architecture and physiology, will discuss the consequences of BBB dysfunction in these CNS diseases and will present some therapeutic strategies for drug delivery to the brain across the BBB.

Drowning associated pneumonia: A descriptive cohort☆

PURPOSE Pneumonia is the most common infectious complication of drowning. Pneumonia is potentially life threatening and should be treated by effective antibiotic therapy. However the risk factors, microbiological causes, diagnostic approach and appropriate therapy for pneumonia associated with drowning are not well described. The microbiological ecology of the body of water where immersion occurred could be of import. The aim of this study was to report on microorganisms involved in pneumonia associated with drowning and out of hospital cardiac arrest after successful cardiopulmonary resuscitation. Additionally, we retrieved and undertook microbiological analysis on samples of water from our local river. METHODS This retrospective study included all patients having suffered an out of hospital cardiac arrest due to drowning and admitted to our tertiary care academic hospital between 2002 and 2010. Data concerning bacteriological lung samples (tracheal aspirate or bronchoalveolar lavage) at admission were reported and compared to bacteriological samples obtained from our local river (the river Seine). RESULTS A total of thirty-seven patients were included in the study. Lung samples were obtained for twenty-one of these patients. Lung samples were positive in nineteen cases, with a high frequency of multi-drug resistant bacteria. Samples from the Seine River found microorganisms similar to those found in drowning associated pneumonia. CONCLUSIONS Drowning associated pneumonia can be due to multi drug resistant bacteria. When treating drowning associated pneumonia, antibiotics should be effective against bacteria similar to those found in the body of water where immersion occurred.

Causes of coma and their evolution in the medical intensive care unit

Epidemiological data regarding the frequency of the different causes of coma and their evolution over time in the ICU are scarce [1–4]. In the 1970s, Plum and Posner [2] described the causes of 500 successive cases of coma. However, since then no specific study focusing on the causes of coma and their evolution over time has been published although the ICU management of brain injuries has progressed tremendously. Some data are available from prospective and retrospective studies assessing coma outcome [3–8], but the different causes of coma were excluded in these studies. These studies, therefore, do not provide a global description of the causes of coma and their evolution. The aim of this study was to describe the causes of coma and their evolution over an 8-year time period in a medical ICU. From January 2001 to December 2008, we retrospectively identified patients who presented with coma in the first 24 h of ICU admission, defined as a Glasgow Coma Scale below 8 in the absence of sedative drugs, and we retrieved their demographic data (supplementary Table). For statistical purposes, four time periods of 2 years each were defined. A total of 2,189 out of 4,482 patients were evaluated. Baseline characteristics of the patients can be found in the supplementary Table. Detailed causes of coma, initial Glasgow Coma Scale and ICU survival are shown Table 1. The frequency of anoxo-ischemic encephalopathy and shock of any origin increased as the causes of coma over the 8-year time period is shown in Table 2. At the same time, the frequency of the other causes of coma remained stable. Among the 2,189 comatose patients, 1,139 (52%) survived to ICU discharge (Table 1). Survival rates according to each cause of coma are given in the Table 1. To our knowledge, this is the largest existing cohort that focused on the causes of coma and their evolution. The study population was comparable in age, sex ratio, and the Glasgow Coma Scale score to previously reported populations of comatose patients as in the Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments (SUPPORT) cohort. SUPPORT, the largest previously available cohort of 596 non-traumatic comatose patients, studied factors such as high risk of death and severe disability [1–8]. However, the SUPPORT cohort excluded drug intoxication and metabolic causes of coma [4]. Plum and Posner [2] found that the most common causes of coma were drug poisons (30%), cerebral hemorrhage including intracerebral, epidural, and subdural hemorrhages (15%), and brainstem infarction (8%). Cardiac arrest represented only 2% in the Plum and Posner cohort. This discrepancy could be somewhat explained by the fact that the Plum and Posner’s study was performed in a neurological ICU, whereas our study was performed in a general medical ICU. Moreover, our study was subject to regular updates of the guidelines for cardiac arrest resuscitation which has improved immediate survival over the last 30 years. This hypothesis is corroborated by the findings of the other previous reports [4–8]. The reason for the Electronic supplementary material The online version of this article (doi:10.1007/s00415-011-6388-z) contains supplementary material, which is available to authorized users.

Revue généraleBiologie de la barrière hématoencéphalique : Partie IBiology of the blood–brain barrier: Part I

The blood-brain barrier provides the central nervous system with a unique protection against the toxic effects of many xenobiotics. This protection results from the unique anatomic and biological structure of the endothelium of blood vessels in the brain. The main features of the blood-brain barrier are the presence of tight intercellular junctions which strictly limit the diffusion of blood-borne solutes and cells into the brain and the polarized expression of transporters which specifically control the cerebral availability of nutrients, drugs or xenobiotics. Recent findings in molecular and cellular biology improved our knowledge of blood-brain barrier permeability and its regulation. The importance of these findings has been recently highlighted by the description of dysfunctions of the blood-brain barrier which could have an impact on the pathophysiology of several neurological diseases. This review focuses on recent advances in our understanding of blood-brain barrier biology and physiology, presenting the structural organization of the blood-brain barrier and the functional regulation of solute permeability and cellular transendothelial migration.

Drowning After Falling from a Medium-Height Bridge: Multiple Trauma Victims

Abstract Introduction. Drowning following a fall from a bridge can lead to cardiac arrest caused by hypoxia, hypothermia, or severe traumatic injury. Every year patients are brought to our hospital who have nearly drowned in the local river after a jump from a bridge (approximate height 16–22 meters). We report traumatic injuries in patients admitted to our hospital for out-of-hospital cardiac arrest due to drowning. Methods. We retrospectively reviewed the charts of all patients admitted to the intensive care units of our hospital for out-of-hospital cardiac arrest due to drowning after a jump from a bridge in the Seine River between 2002 and 2010. All clinical or radiologic evidence of trauma was recorded. Results. A total of 37 patients where admitted to our hospital for out-of-hospital cardiac arrest due to drowning. Fourteen patients had radiologic examinations. Five of these examinations showed evidence of severe trauma. In one case, clinical examination showed evidence of severe peripheral neurologic trauma. Seven of these patients (19%) were discharged from the hospital alive. Conclusions. Patients found nearly drowned in a river spanned by a medium-height bridge should undergo spinal immobilization and complete radiologic examination as soon as possible.

A urinary cause of coma.

Hyperammonemic coma is rare except in association with hepatic encephalopathy. When liver disease is ruled out, hyperammonemia should suggest the existence of a portosystemic shunt or an inherited urea cycle defect [1]. Urinary ureterocolic diversion (UD) that has been widely used for years to treat bladder exstrophy can be responsible for hyperammonemic coma, metabolic hyperchloremic acidosis, and subsequent colonic neoplasia [2–5]. Here, we present a 68-year-old man admitted to the ICU for a hyperammonemic coma secondary to UD by ureterosigmoidostomy. He had a history of congenital bladder exstrophy and epispadias treated in the first year of life by ureterosigmoidostomy and had a recent history of spontaneous reversible coma. Upon admission, the body temperature was 36.2 C, heart rate was 97 beats/min, and blood pressure was 185/84 mmHg. Hypotonic coma without any focal deficit was noted (Glasgow coma scale = 3). Abdominal inspection showed skin atrophy in the hypogastric area, an atrophic penis, and a large laparotomy scar. He subsequently required respiratory assistance. Blood sample results are shown in Table 1. The cerebral CT scan and lumbar puncture were normal. The ammonia level was elevated (346 lmol/L; normal level \50 lmol/L). The initial treatment is given Table 1. Urea cycle disorders were initially ruled out by serum amino acid chromatography and a portosystemic shunt by Doppler ultrasound and CT scan. Bacteriological culture of mixed urine and feces identified wild-type Escherichia coli and Enterococcus faecalis, two urea-splitting bacteria. Treatment by intravenous cefotaxime and oral vancomycin was started. Normalization of ammonemia rapidly ensued. However, a cerebral CT, performed on day 5, showed major cerebral edema in both temporal lobes (Fig. 1). The neurological status of the patient improved and could be weaned from mechanical ventilation on day 10. The cerebral CT scan performed on day 24 was normal; however, the cerebral MRI scan performed on the same day showed diffuse cortical hypersignals on diffusion-weighted images and diffuse hypersignals in both temporal lobes in the FLAIR-weighted images (Fig. 1). During a 2-month period, the patient experienced three relapses of hyperammonemic coma (Table 1). The decision to perform surgical C. Levi and C. Hussenet contributed equally to this work.

Non-invasive positive pressure ventilation (NIPPV)-induced pneumocephalus and pneumoperitoneum in a patient with a one-way flow control ventriculoperitoneal shunt.

Dear Editor, The use of non-invasive positive pressure ventilation (NIPPV) is increasing in the intensive care unit (ICU). Although it is fairly easy to use, NIPPV is associated with complications, e.g., nasal or sinus pain, gastric insufflation, eye irritation, and pneumothorax [1]. We report a patient having a ventriculoperitoneal shunt (VPS) who developed pneumocephalus associated with pneumoperitoneum secondary to NIPPV. A 37-year-old woman was admitted to our ICU for acute respiratory distress. She had a history of von Hippel–Lindau disease (OMIM #193300) with renal cell carcinoma, pancreatic neuroendocrine tumor, and cerebelar hemangioblastoma complicated by obstructive hydrocephaly that required a VPS (Crx Diamond valve DCS225A, Vygon Neuro) and was treated by palliative chemotherapy with sunitinib. Three weeks before admission, she underwent a tooth extraction (tooth no. 18). At admission, aspiration pneumonia was diagnosed and presumptively treated with piperacillin and tazobactam. Because the patient refused orotracheal intubation, NIPPV was started (pressure support level 20 cmH2O, positive end-expiratory pressure 5 cmH2O, inspired oxygen fraction 100%). After 5 min, major abdominal distention appeared. She presented a confusion state with agitation. NIPPV was immediately discontinued. Computed tomography (CT) revealed a pneumocephalus of 12 ml (Fig. 1a, b; asterisks) associated with a massive tension pneumoperitoneum of 5,358 ml (Fig. 1c, d; asterisks) and air in the neck beside the VPS without any sign of digestive tract perforation. Cerebral magnetic resonance imaging (MRI) performed for scheduled evaluation 13 days earlier ruled out any previous pneumocephalus. Exploratory surgical laparotomy performed immediately after CT ruled out any fistula or any digestive tract perforation. Pneumocephalus usually occurs as a postoperative complication after neurosurgery or trauma [2]. Delayed pneumocephalus after VPS placement is unusual and seems to be associated with a skull base defect. We propose that in our patient air could gain access to retropharyngeal spaces via the dental defect secondary to tooth extraction, a process which may be favored by delayed healing secondary

Daily FOUR score assessment provides accurate prognosis of long-term outcome in out-of-hospital cardiac arrest.

BACKGROUND The accurate prediction of outcome after out-of-hospital cardiac arrest (OHCA) is of major importance. The recently described Full Outline of UnResponsiveness (FOUR) is well adapted to mechanically ventilated patients and does not depend on verbal response. OBJECTIVE To evaluate the ability of FOUR assessed by intensivists to accurately predict outcome in OHCA. METHODS We prospectively identified patients admitted for OHCA with a Glasgow Coma Scale below 8. Neurological assessment was performed daily. Outcome was evaluated at 6 months using Glasgow-Pittsburgh Cerebral Performance Categories (GP-CPC). RESULTS Eighty-five patients were included. At 6 months, 19 patients (22%) had a favorable outcome, GP-CPC 1-2, and 66 (78%) had an unfavorable outcome, GP-CPC 3-5. Compared to both brainstem responses at day 3 and evolution of Glasgow Coma Scale, evolution of FOUR score over the three first days was able to predict unfavorable outcome more precisely. Thus, absence of improvement or worsening from day 1 to day 3 of FOUR had 0.88 (0.79-0.97) specificity, 0.71 (0.66-0.76) sensitivity, 0.94 (0.84-1.00) PPV and 0.54 (0.49-0.59) NPV to predict unfavorable outcome. Similarly, the brainstem response of FOUR score at 0 evaluated at day 3 had 0.94 (0.89-0.99) specificity, 0.60 (0.50-0.70) sensitivity, 0.96 (0.92-1.00) PPV and 0.47 (0.37-0.57) NPV to predict unfavorable outcome. CONCLUSION The absence of improvement or worsening from day 1 to day 3 of FOUR evaluated by intensivists provides an accurate prognosis of poor neurological outcome in OHCA.