The matrix metalloproteinase inhibitor RS-130830 attenuates brain injury in experimental pneumococcal meningitis.

BACKGROUND Pneumococcal meningitis (PM) is characterized by high mortality and morbidity including long-term neurofunctional deficits. Neuropathological correlates of these sequelae are apoptosis in the hippocampal dentate gyrus and necrosis in the cortex. Matrix metalloproteinases (MMPs) play a critical role in the pathophysiology of PM. RS-130830 (Ro-1130830, CTS-1027) is a potent partially selective inhibitor of MMPs of a second generation and has been evaluated in clinical trials as an anti-arthritis drug. It inhibits MMPs involved in acute inflammation but has low activity against MMP-1 (interstitial collagenase), MMP-7 (matrilysin) and tumour necrosis factor α converting enzyme (TACE). METHODS A well-established infant rat model of PM was used where live Streptococcus pneumoniae were injected intracisternally and antibiotic treatment with ceftriaxone was initiated 18 h post infection (hpi). Treatment with RS-130830 (75 mg/kg bis in die (bid) i.p., n = 40) was started at 3 hpi while control littermates received the vehicle (succinylated gelatine, n = 42). RESULTS Cortical necrosis was significantly attenuated in animals treated with RS-130830, while the extent of hippocampal apoptosis was not influenced. At 18 hpi, concentrations of interleukin (IL)-1β and IL-10 were significantly lower in the cerebrospinal fluid of treated animals compared to controls. RS-130830 significantly reduced weight loss and leukocyte counts in the cerebrospinal fluid of survivors of PM. CONCLUSION This study identifies MMP inhibition, specifically with RS-130830, as an efficient strategy to attenuate disease severity and cortical brain injury in PM.

Ultra-low dose - new approaches in menopausal hormone therapy.

Despite increasing life expectancy, the age of onset of natural menopause has not significantly changed in recent decades. Thus, women spend about one-third of their lives in an estrogen-deficient state if untreated. There is a need for appropriate treatment of acute symptoms and prevention of the sequelae of chronic estrogen deficiency. International guidelines call for the use of the lowest effective hormone dosage for vasomotor symptom relief, the major indication for menopausal hormone therapy (MHT). In 2011, an oral continuous combined ultra-low-dose MHT was approved in Switzerland. This publication was elaborated by eight national menopause specialists and intends to review the advantages and disadvantages of ultra-low-dose MHT after the first years of its general use in Switzerland. It concludes that, for many women, ultra-low-dose MHT may be sufficient to decrease vasomotor symptoms, but not necessarily to guarantee fracture prevention.

Clinical impact of gastrointestinal bleeding in patients undergoing percutaneous coronary interventions.

BACKGROUND The risk factors and clinical sequelae of gastrointestinal bleeding (GIB) in the current era of drug-eluting stents, prolonged dual antiplatelet therapy, and potent P2Y12 inhibitors are not well established. We determined the frequency, predictors, and clinical impact of GIB after percutaneous coronary interventions (PCIs) in a contemporary cohort of consecutive patients treated with unrestricted use of drug-eluting stents. METHODS AND RESULTS Between 2009 and 2012, all consecutive patients undergoing PCI were prospectively included in the Bern PCI Registry. Bleeding Academic Research Consortium (BARC) GIB and cardiovascular outcomes were recorded within 1 year of follow-up. Among 6212 patients, 84.1% received new-generation drug-eluting stents and 19.5% received prasugrel. At 1 year, GIB had occurred in 65 patients (1.04%); 70.8% of all events and 84.4% of BARC ≥3B events were recorded >30 days after PCI. The majority of events (64.4%) were related to upper GIB with a more delayed time course compared with lower GIB. Increasing age, previous GIB, history of malignancy, smoking, and triple antithrombotic therapy (ie, oral anticoagulation plus dual antiplatelet therapy) were independent predictors of GIB in multivariable analysis. GIB was associated with increased all-cause mortality (adjusted hazard ratio, 3.40; 95% confidence interval, 1.67-6.92; P=0.001) and the composite of death, myocardial infarction, or stroke (adjusted hazard ratio, 3.75; 95% confidence interval, 1.99-7.07; P<0.001) and was an independent predictor of all-cause mortality during 1 year. CONCLUSIONS Among unselected patients undergoing PCI, GIB has a profound effect on prognosis. Triple antithrombotic therapy emerged as the single drug-related predictor of GIB in addition to patient-related risk factors within 1 year of PCI. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT02241291.

Childhood Trauma and Complex Posttraumatic Stress Disorder Symptoms in Older Adults: A Study of Direct Effects and Social-Interpersonal Factors as Potential Mediators

Childhood traumatic events may lead to long-lasting psychological effects and contribute to the development of complex posttraumatic sequelae. These might be captured by the diagnostic concept of complex posttraumatic stress disorder (CPTSD) as an alternative to classic posttraumatic stress disorder (PTSD). CPTSD comprises a further set of symptoms in addition to those of PTSD, namely, changes in affect, self, and interpersonal relationships. Previous empirical research on CPTSD has focused on middle-aged adults but not on older adults. Moreover, predictor models of CPTSD are still rare. The current study investigated the association between traumatic events in childhood and complex posttraumatic stress symptoms in older adults. The mediation of this association by 2 social-interpersonal factors (social acknowledgment as a survivor and dysfunctional disclosure) was investigated. These 2 factors focus on the perception of acknowledgment by others and either the inability to disclose traumatic experiences or the ability to do so only with negative emotional reactions. A total of 116 older individuals (age range = 59–98 years) who had experienced childhood traumatic events completed standardized self-report questionnaires indexing childhood trauma, complex trauma sequelae, social acknowledgment, and dysfunctional disclosure of trauma. The results showed that traumatic events during childhood were associated with later posttraumatic stress symptoms but with classic rather than complex symptoms. Social acknowledgment and dysfunctional disclosure partially mediated this relationship. These findings suggest that childhood traumatic stress impacts individuals across the life span and may be associated with particular adverse psychopathological consequences.

Cortical reorganisation of cerebral networks after childhood stroke: impact on outcome.

BACKGROUND Recovery after arterial ischaemic stroke is known to largely depend on the plastic properties of the brain. The present study examines changes in the network topography of the developing brain after stroke. Effects of brain damage are best assessed by examining entire networks rather than single sites of structural lesions. Relating these changes to post-stroke neuropsychological variables and motor abilities will improve understanding of functional plasticity after stroke. Inclusion of healthy controls will provide additional insight into children's normal brain development. Resting state functional magnetic resonance imaging is a valid approach to topographically investigate the reorganisation of functional networks after a brain lesion. Transcranial magnetic stimulation provides complementary output information. This study will investigate functional reorganisation after paediatric arterial ischaemic stroke by means of resting state functional magnetic resonance imaging and transcranial magnetic stimulation in a cross-sectional plus longitudinal study design. The general aim of this study is to better understand neuroplasticity of the developing brain after stroke in order to develop more efficacious therapy and to improve the post-stroke functional outcome. METHODS The cross-sectional part of the study will investigate the functional cerebral networks of 35 children with chronic arterial ischaemic stroke (time of the lesion >2 years). In the longitudinal part, 15 children with acute arterial ischaemic stroke (shortly after the acute phase of the stroke) will be included and investigations will be performed 3 times within the subsequent 9 months. We will also recruit 50 healthy controls, matched for age and sex. The neuroimaging and neurophysiological data will be correlated with neuropsychological and neurological variables. DISCUSSION This study is the first to combine resting state functional magnetic resonance imaging and transcranial magnetic stimulation in a paediatric population diagnosed with arterial ischaemic stroke. Thus, this study has the potential to uniquely contribute to the understanding of neuronal plasticity in the brains of healthy children and those with acute or chronic brain injury. It is expected that the results will lead to the development of optimal interventions after arterial ischaemic stroke.

Effects of two different memory training approaches in very preterm-born children

Background: Little research has been conducted to assess the effect of using memory training with school-aged children who were born very preterm. This study aimed to determine whether two types of memory training approaches resulted in an improvement of trained functions and/or a generalization of the training effect to non-trained cognitive domains. Methods: Sixty-eight children born very preterm (7¬-12 years) were randomly allocated to a group undertaking memory strategy training (n=23), working memory training (n=22), or a waiting control group (n=23). Neuropsychological assessment was performed before and immediately after the training or waiting period, and at a six-month follow-up. Results: In both training groups, significant improvement of different memory domains occurred immediately after training (near transfer). Improvement of non-trained arithmetic performance was observed after strategy training (far transfer). At a six-month follow-up assessment, children in both training groups demonstrated better working memory, and their parents rated their memory functions to be better than controls. Performance level before the training was negatively associated with the training gain. Conclusions: These results highlight the importance of cognitive interventions, in particular the teaching of memory strategies, in very preterm-born children at early school age to strengthen cognitive performance and prevent problems at school.

Efficacy and effectiveness of an rVSV-vectored vaccine expressing Ebola surface glycoprotein: interim results from the Guinea ring vaccination cluster-randomised trial.

BACKGROUND A recombinant, replication-competent vesicular stomatitis virus-based vaccine expressing a surface glycoprotein of Zaire Ebolavirus (rVSV-ZEBOV) is a promising Ebola vaccine candidate. We report the results of an interim analysis of a trial of rVSV-ZEBOV in Guinea, west Africa. METHODS For this open-label, cluster-randomised ring vaccination trial, suspected cases of Ebola virus disease in Basse-Guinée (Guinea, west Africa) were independently ascertained by Ebola response teams as part of a national surveillance system. After laboratory confirmation of a new case, clusters of all contacts and contacts of contacts were defined and randomly allocated 1:1 to immediate vaccination or delayed (21 days later) vaccination with rVSV-ZEBOV (one dose of 2 × 10(7) plaque-forming units, administered intramuscularly in the deltoid muscle). Adults (age ≥18 years) who were not pregnant or breastfeeding were eligible for vaccination. Block randomisation was used, with randomly varying blocks, stratified by location (urban vs rural) and size of rings (≤20 vs >20 individuals). The study is open label and masking of participants and field teams to the time of vaccination is not possible, but Ebola response teams and laboratory workers were unaware of allocation to immediate or delayed vaccination. Taking into account the incubation period of the virus of about 10 days, the prespecified primary outcome was laboratory-confirmed Ebola virus disease with onset of symptoms at least 10 days after randomisation. The primary analysis was per protocol and compared the incidence of Ebola virus disease in eligible and vaccinated individuals in immediate vaccination clusters with the incidence in eligible individuals in delayed vaccination clusters. This trial is registered with the Pan African Clinical Trials Registry, number PACTR201503001057193. FINDINGS Between April 1, 2015, and July 20, 2015, 90 clusters, with a total population of 7651 people were included in the planned interim analysis. 48 of these clusters (4123 people) were randomly assigned to immediate vaccination with rVSV-ZEBOV, and 42 clusters (3528 people) were randomly assigned to delayed vaccination with rVSV-ZEBOV. In the immediate vaccination group, there were no cases of Ebola virus disease with symptom onset at least 10 days after randomisation, whereas in the delayed vaccination group there were 16 cases of Ebola virus disease from seven clusters, showing a vaccine efficacy of 100% (95% CI 74·7-100·0; p=0·0036). No new cases of Ebola virus disease were diagnosed in vaccinees from the immediate or delayed groups from 6 days post-vaccination. At the cluster level, with the inclusion of all eligible adults, vaccine effectiveness was 75·1% (95% CI -7·1 to 94·2; p=0·1791), and 76·3% (95% CI -15·5 to 95·1; p=0·3351) with the inclusion of everyone (eligible or not eligible for vaccination). 43 serious adverse events were reported; one serious adverse event was judged to be causally related to vaccination (a febrile episode in a vaccinated participant, which resolved without sequelae). Assessment of serious adverse events is ongoing. INTERPRETATION The results of this interim analysis indicate that rVSV-ZEBOV might be highly efficacious and safe in preventing Ebola virus disease, and is most likely effective at the population level when delivered during an Ebola virus disease outbreak via a ring vaccination strategy. FUNDING WHO, with support from the Wellcome Trust (UK); Médecins Sans Frontières; the Norwegian Ministry of Foreign Affairs through the Research Council of Norway; and the Canadian Government through the Public Health Agency of Canada, Canadian Institutes of Health Research, International Development Research Centre, and Department of Foreign Affairs, Trade and Development.

An improved simple rat model for global cerebral ischaemia by induced cardiac arrest

OBJECTIVES Cerebral hypoxic-ischaemic injury following cardiac arrest is a devastating disease affecting thousands of patients each year. There is a complex interaction between post-resuscitation injury after whole-body ischaemia-reperfusion and cerebral damage which cannot be explored in in vitro systems only; there is a need for animal models. In this study, we describe and evaluate the feasibility and efficiency of our simple rodent cardiac arrest model. METHODS Ten wistar rats were subjected to 9 and 10 minutes of cardiac arrest. Cardiac arrest was introduced with a mixture of the short-acting beta-blocking drug esmolol and potassium chloride. RESULTS All animals could be resuscitated within 1 minute, and survived until day 5.General health score and neurobehavioural testing indicated substantial impairment after cardiac arrest, without differences between groups. Histological examination of the hippocampus CA1 segment, the most vulnerable segment of the cerebrum, demonstrated extensive damage in the cresyl violet staining, as well as in the Fluoro-Jade B staining and in the Iba-1 staining, indicating recruitment of microglia after the hypoxic-ischaemic event. Again, there were no differences between the 9- and 10-minute cardiac arrest groups. DISCUSSION We were able to establish a simple and reproducible 9- and 10-minute rodent cardiac arrest models with a well-defined no-flow-time. Extensive damage can be found in the hippocampus CA1 segment. The lack of difference between 9- and 10-minute cardiac arrest time in the neuropsychological, the open field test and the histological evaluations is mainly due to the small sample size.

Genetic polymorphisms associated with the inflammatory response in bacterial meningitis.

BACKGROUND Bacterial meningitis (BM) is an infectious disease that results in high mortality and morbidity. Despite efficacious antibiotic therapy, neurological sequelae are often observed in patients after disease. Currently, the main challenge in BM treatment is to develop adjuvant therapies that reduce the occurrence of sequelae. In recent papers published by our group, we described the associations between the single nucleotide polymorphisms (SNPs) AADAT +401C > T, APEX1 Asn148Glu, OGG1 Ser326Cys and PARP1 Val762Ala and BM. In this study, we analyzed the associations between the SNPs TNF -308G > A, TNF -857C > T, IL-8 -251A > T and BM and investigated gene-gene interactions, including the SNPs that we published previously. METHODS The study was conducted with 54 BM patients and 110 healthy volunteers (as the control group). The genotypes were investigated via primer-introduced restriction analysis-polymerase chain reaction (PIRA-PCR) or polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) analysis. Allelic and genotypic frequencies were also associated with cytokine and chemokine levels, as measured with the x-MAP method, and cell counts. We analyzed gene-gene interactions among SNPs using the generalized multifactor dimensionality reduction (GMDR) method. RESULTS We did not find significant association between the SNPs TNF -857C > T and IL-8 -251A > T and the disease. However, a higher frequency of the variant allele TNF -308A was observed in the control group, associated with changes in cytokine levels compared to individuals with wild type genotypes, suggesting a possible protective role. In addition, combined inter-gene interaction analysis indicated a significant association between certain genotypes and BM, mainly involving the alleles APEX1 148Glu, IL8 -251 T and AADAT +401 T. These genotypic combinations were shown to affect cyto/chemokine levels and cell counts in CSF samples from BM patients. CONCLUSIONS In conclusion, this study revealed a significant association between genetic variability and altered inflammatory responses, involving important pathways that are activated during BM. This knowledge may be useful for a better understanding of BM pathogenesis and the development of new therapeutic approaches.

Application, tolerance and safety of fondaparinux therapy in a German hospital: a prospective single-centre experience.

INTRODUCTION The pentasaccharide fondaparinux is widely approved for prophylaxis and treatment of thromboembolic diseases and therapy of acute coronary syndrome. It is also used off-label in patients with acute, suspected or antecedent heparin-induced thrombocytopenia (HIT). The aim of this prospective observational cohort study was to document fondaparinux' prescription practice, tolerance and therapy safety in a representative mixed German single-centre patient cohort. PATIENTS AND METHODS Between 09/2008 - 04/2009, 231 consecutive patients treated with fondaparinux were enrolled. Medical data were obtained from patient's records. The patients were clinically screened for thrombosis (Wells score), sequelae of HIT (4T's score), and bleeding complications (ISTH-criteria) and subjected to further assessment (i.e. sonography, HIT-diagnostics), if necessary. The mortality rate was assessed 30 days after therapy start. RESULTS Overall, 153/231 patients had a prophylactic, 74/231 patients a therapeutic, and 4/231 patients a successive prophylactic/therapeutic indication. In 11/231 patients fondaparinux was used due to suspected/antecedent HIT, in 5/231 patients due to a previous cutaneous delayed-type hypersensitivity to heparins. Other indications were rare. Three new/progressive thromboses were detected. No cases of HIT, major bleedings, or fatalities occurred. CONCLUSIONS Fondaparinux was well tolerated and was safe in prophylaxis and therapy; prescriptions mostly followed the current approval guidelines and were rarely related to HIT-associated indications (<5% of prescriptions), which is in contrast to previous study results in the U.S. (>94% of prescriptions were HIT-associated). A trend towards an individualised fondaparinux use based on the compound's inherent properties and the patients' risk profiles, i.e., antecedent HIT, bone fractures, heparin allergy, was observed.

Toward stratified treatments for bipolar disorders

In bipolar disorders, there are unclear diagnostic boundaries with unipolar depression and schizophrenia, inconsistency of treatment guidelines, relatively long trial-and-error phases of treatment optimization, and increasing use of complex combination therapies lacking empirical evidence. These suggest that the current definition of bipolar disorders based on clinical symptoms reflects a clinically and etiologically heterogeneous entity. Stratification of treatments for bipolar disorders based on biomarkers and improved clinical markers are greatly needed to increase the efficacy of currently available treatments and improve the chances of developing novel therapeutic approaches. This review provides a theoretical framework to identify biomarkers and summarizes the most promising markers for stratification regarding beneficial and adverse treatment effects. State and stage specifiers, neuropsychological tests, neuroimaging, and genetic and epigenetic biomarkers will be discussed with respect to their ability to predict the response to specific pharmacological and psychosocial psychotherapies for bipolar disorders. To date, the most reliable markers are derived from psychopathology and history-taking, while no biomarker has been found that reliably predicts individual treatment responses. This review underlines both the importance of clinical diagnostic skills and the need for biological research to identify markers that will allow the targeting of treatment specifically to sub-populations of bipolar patients who are more likely to benefit from a specific treatment and less likely to develop adverse reactions.

Demenzverdacht, aber normale neuropsychologische Screening-Untersuchung - wie weiter?

Die Demenz betrifft viele, belastet Angehörige und führt zu hohen Kosten, weshalb die Schweiz eine Sensibilisierungskampagne lancierte, um u.a. die Früherkennung der Demenz zu fördern. Dank der Früherkennung erleben Patienten und Angehörige Vorteile, wie weniger Notfallzuweisungen oder spätere Heimeintritte. Die Früherkennung ist aber schwierig, wenn Patienten zwar Gedächtnisprobleme beklagen, die Screening-Tests aber normal ausfallen. Möglicherweise helfen Geruchstests und weitere klinische Zeichen bei der Entscheidung, welche Patienten weiter abgeklärt werden. Die Zeit für funktionelle Bildgebungen und Biomarker ist noch nicht reif. Zentral bleibt bei kognitiven Beschwerden und normalem Screening das Gespräch mit Patient und Angehörigen, um nächste Schritte gemeinsam zu beschliessen. Der Hausarzt nimmt dabei eine zentrale, koordinierende und beratende Funktion ein, um Menschen mit Gedächtnisstörungen kompetent und effizient zu betreuen.

Acute S100B in serum is associated with cognitive symptoms and memory performance 4 months after paediatric mild traumatic brain injury

OBJECTIVE This study explored whether acute serum marker S100B is related with post-concussive symptoms (PCS) and neuropsychological performance 4 months after paediatric mild traumatic brain injury (mTBI). RESEARCH DESIGN AND METHODS This prospective short-term longitudinal study investigated children (aged 6-16 years) with mTBI (n = 36, 16 males) and children with orthopaedic injuries (OI, n = 27, 18 males) as a control group. S100B in serum was measured during the acute phase and was correlated with parent-rated PCS and neuropsychological performance 4 months after the injury. MAIN OUTCOMES AND RESULTS The results revealed no between-group difference regarding acute S100B serum concentration. In children after mTBI, group-specific significant Spearman correlations were found between S100B and post-acute cognitive PCS (r = 0.54, p = 0.001) as well as S100B and verbal memory performance (r = -0.47, p = 0.006). In children after OI, there were insignificant positive relations between S100B and post-acute somatic PCS. In addition, insignificant positive correlations were found between neuropsychological outcome and S100B in children after OI. CONCLUSIONS S100B was not specific for mild brain injuries and may also be elevated after OI. The group-specific association between S100B and ongoing cognitive PCS in children after mTBI should motivate to examine further the role of S100B as a diagnostic biomarker in paediatric mTBI.

Relative femoral neck lengthening improves pain and hip function in proximal femoral deformities with a high-riding trochanter

BACKGROUND Complex proximal femoral deformities, including an elevated greater trochanter, short femoral neck, and aspherical head-neck junction, often result in pain and impaired hip function resulting from intra-/extraarticular impingement. Relative femoral neck lengthening may address these deformities, but mid-term results of this approach have not been widely reported. QUESTIONS/PURPOSES Do patients who have undergone relative femoral neck lengthening show (1) less hip pain and greater function; (2) improved radiographic parameters; (3) significant complications requiring subsequent surgery; and (4) progression of osteoarthrosis (OA) or conversion to total hip arthroplasty (THA) at mid-term followup? METHODS We retrospectively reviewed 40 patients (41 hips) with isolated relative femoral neck lengthening between 1998 and 2006 with sequelae of Legg-Calvé-Perthes disease (38 hips [93%]), slipped capital femoral epiphysis (two hips [5%]), and postseptic arthritis (one hip [2%]). During this time, the general indications for this procedure included a high-riding greater trochanter with a short femoral neck with abductor weakness and symptomatic intra-/extraarticular impingement. Mean patient followup was 8 years (range, 5-13 years), and complete followup was available in 38 patients (39 hips [95%]). We evaluated pain and function with the impingement test, limp, abductor force, Merle d'Aubigné-Postel score, and range of motion. Radiographic parameters included trochanteric height, alpha angle, and progression of OA. Subsequent surgeries, complications, and conversion to THA were summarized. RESULTS The proportion of positive anterior impingement tests decreased from 93% (38 of 41 hips) preoperatively to 49% (17 of 35 hips) at latest followup (p = 0.002); the proportion of limp decreased from 76% (31 of 41 hips) to 9% (three of 35 hips; p < 0.001); the proportion of normal abductor strength increased from 17% (seven of 41 hips) to 91% (32 of 35 hips; p < 0.001); mean Merle d'Aubigné-Postel score increased from 14 ± 1.7 (range, 9-17) to 17 ± 1.5 (range, 13-18; p < 0.001); mean internal rotation increased to 25° ± 15° (range, 0°-60°; p = 0.045), external rotation to 32° ± 14° (range, 5°-70°; p = 0.013), and abduction to 37° ± 13° (range, 10°-50°; p = 0.004). Eighty percent of hips (33 of 41 hips) showed normal trochanteric height; alpha angle improved to 42° ± 10° (range, 27°-90°). Two hips (5%) had subsequent surgeries as a result of lack of containment; four of 41 hips (10%) had complications resulting in reoperation. Fourteen of 35 hips (40%) showed progression of OA; four of 40 hips (10%) converted to THA. CONCLUSIONS Relative femoral neck lengthening in hips with combined intra- and extraarticular impingement results in reduced pain, improved function, and improved radiographic parameters of the proximal femur. Although lack of long-term complications is gratifying, progression of OA was not prevented and remains an area for future research.

Acute and Chronic Altitude-Induced Cognitive Dysfunction in Children and Adolescents.

OBJECTIVE To assess whether exposure to high altitude induces cognitive dysfunction in young healthy European children and adolescents during acute, short-term exposure to an altitude of 3450 m and in an age-matched European population permanently living at this altitude. STUDY DESIGN We tested executive function (inhibition, shifting, and working memory), memory (verbal, short-term visuospatial, and verbal episodic memory), and speed processing ability in: (1) 48 healthy nonacclimatized European children and adolescents, 24 hours after arrival at high altitude and 3 months after return to low altitude; (2) 21 matched European subjects permanently living at high altitude; and (3) a matched control group tested twice at low altitude. RESULTS Short-term hypoxia significantly impaired all but 2 (visuospatial memory and processing speed) of the neuropsychological abilities that were tested. These impairments were even more severe in the children permanently living at high altitude. Three months after return to low altitude, the neuropsychological performances significantly improved and were comparable with those observed in the control group tested only at low altitude. CONCLUSIONS Acute short-term exposure to an altitude at which major tourist destinations are located induces marked executive and memory deficits in healthy children. These deficits are equally marked or more severe in children permanently living at high altitude and are expected to impair their learning abilities.