Microdiàlisis cerebral aplicada a l'estudi del metabolisme energètic i a la resposta neuroinflamatòria dels pacients amb traumatisme cranioencefàlic

La tècnica de la microdiàlisis cerebral (MDC) és un instrument que proporciona informació rellevant en la monitorització del metabolisme cerebral en els pacients neurocrítics. El lactat i l’índex lactat-piruvat (ILP) són dos marcadors utilitzats per a la detecció de la hipòxia cerebral en pacients que han patit un traumatisme cranioencefàlic (TCE). Aquests dos marcadors poden estar anormalment elevats en circumstàncies que no cursen amb hipòxia tissular. Per una altra banda la recent aparició dels catèters de MDC amb porus de major mida denominats d’”alta resolució”, permet ampliar el rang de molècules que es poden detectar en el dialitzat. Objectius: 1) descriure les característiques del metabolisme energètic cerebral que s’observa en la fase aguda dels pacients que han patit un TCE en base als dos indicadors del metabolisme anaeròbic: lactat i ILP, i 2) determinar la recuperació relativa (RR) de les molècules implicades en la resposta neuroinflamatòria: de IL-1β, IL- 6, IL-8 i IL-10. Material i mètodes: Es van seleccionar 46 pacients d’una cohort de pacients amb TCE moderat o greu ingressats a la Unitat de Cures Intensives de l’Hospital Universitari de la Vall d’Hebron i monitoritzats amb MDC. Es van analitzar els nivells de lactat i ILP i es va correlacionar amb els nivells de PtiO2. Es van realitzar experiments in vitro per estudiar la recuperació de les membranes de 100 KDa per tal de poder interpretar posteriorment els nivells reals de les molècules estudiades en l’espai extracel•lular del teixit cerebral. Resultats: La concordança entre el lactat i l’índex LP per a determinar episodis de disfunció metabòlica va ser dèbil (índex de kappa = 0,36, IC 95%: 0,34-0,39). Més del 80% dels casos en què el lactat i l’índex LP es trobaven incrementats, els valors de la PtiO2 es van trobar dins els rangs de normalitat (PtiO2&15mmHg). La recuperació de les citoquines a través de la membrana de microdiàlisis va ser menor de l’esperat tenint en compte la mida dels porus de la membrana. Conclusions: el lactat i l’índex LP elevats va ser una troballa freqüent després d’un TCE i no es va relacionar, en la majoria de casos, amb episodis d’hipòxia tissular. Per un altra part la mida del porus de la membrana no és l’únic paràmetre indicador de la RR de macromolècules.

Role of surgery in the management of brain arteriovenous malformations: prospective cohort study.

BACKGROUND AND PURPOSE: Management of brain arteriovenous malformation (bAVM) is controversial. We have analyzed the largest surgical bAVM cohort for outcome. METHODS: Both operated and nonoperated cases were included for analysis. A total of 779 patients with bAVMs were consecutively enrolled between 1989 and 2014. Initial management recommendations were recorded before commencement of treatment. Surgical outcome was prospectively recorded and outcomes assigned at the last follow-up visit using modified Rankin Scale. First, a sensitivity analyses was performed to select a subset of the entire cohort for which the results of surgery could be generalized. Second, from this subset, variables were analyzed for risk of deficit or near miss (intraoperative hemorrhage requiring blood transfusion of ≥2.5 L, hemorrhage in resection bed requiring reoperation, and hemorrhage associated with either digital subtraction angiography or embolization). RESULTS: A total of 7.7% of patients with Spetzler-Ponce classes A and B bAVM had an adverse outcome from surgery leading to a modified Rankin Scale >1. Sensitivity analyses that demonstrated outcome results were not subject to selection bias for Spetzler-Ponce classes A and B bAVMs. Risk factors for adverse outcomes from surgery for these bAVMs include size, presence of deep venous drainage, and eloquent location. Preoperative embolization did not affect the risk of perioperative hemorrhage. CONCLUSIONS: Most of the ruptured and unruptured low and middle-grade bAVMs (Spetzler-Ponce A and B) can be surgically treated with a low risk of permanent morbidity and a high likelihood of preventing future hemorrhage. Our results do not apply to Spetzler-Ponce C bAVMs.

The prognostic value of health-related quality-of-life data in predicting survival in glioblastoma cancer patients: results from an international randomised phase III EORTC Brain Tumour and Radiation Oncology Groups, and NCIC Clinical Trials Group study.

This is one of the few studies that have explored the value of baseline symptoms and health-related quality of life (HRQOL) in predicting survival in brain cancer patients. Baseline HRQOL scores (from the EORTC QLQ-C30 and the Brain Cancer Module (BN 20)) were examined in 490 newly diagnosed glioblastoma cancer patients for the relationship with overall survival by using Cox proportional hazards regression models. Refined techniques as the bootstrap re-sampling procedure and the computation of C-indexes and R(2)-coefficients were used to try and validate the model. Classical analysis controlled for major clinical prognostic factors selected cognitive functioning (P=0.0001), global health status (P=0.0055) and social functioning (P<0.0001) as statistically significant prognostic factors of survival. However, several issues question the validity of these findings. C-indexes and R(2)-coefficients, which are measures of the predictive ability of the models, did not exhibit major improvements when adding selected or all HRQOL scores to clinical factors. While classical techniques lead to positive results, more refined analyses suggest that baseline HRQOL scores add relatively little to clinical factors to predict survival. These results may have implications for future use of HRQOL as a prognostic factor in cancer patients.

Lésions cérébrales du prématuré et techniques d'imagerie à visée pronostique du développement neurocognitif [Cerebral brain injury in preterm infants and the role of neuroimaging in predicting neurodevelopmental outcomes].

Due to advances in neonatal intensive care over the last decades, the pattern of brain injury seen in very preterm infants has evolved in more subtle lesions that are still essential to diagnose in regard to neurodevelopmental outcome. While cranial ultrasound is still used at the bedside, magnetic resonance imaging (MRI) is becoming increasingly used in this population for the assessment of brain maturation and white and grey matter lesions. Therefore, MRI provides a better prognostic value for the neurodevelopmental outcome of these preterms. Furthermore, the development of new MRI techniques, such as diffusion tensor imaging, resting state functional connectivity and magnetic resonance spectroscopy, may further increase the prognostic value, helping to counsel parents and allocate early intervention services.

Multispectral brain morphometry in Tourette syndrome persisting into adulthood.

Tourette syndrome is a childhood-onset neuropsychiatric disorder with a high prevalence of attention deficit hyperactivity and obsessive-compulsive disorder co-morbidities. Structural changes have been found in frontal cortex and striatum in children and adolescents. A limited number of morphometric studies in Tourette syndrome persisting into adulthood suggest ongoing structural alterations affecting frontostriatal circuits. Using cortical thickness estimation and voxel-based analysis of T1- and diffusion-weighted structural magnetic resonance images, we examined 40 adults with Tourette syndrome in comparison with 40 age- and gender-matched healthy controls. Patients with Tourette syndrome showed relative grey matter volume reduction in orbitofrontal, anterior cingulate and ventrolateral prefrontal cortices bilaterally. Cortical thinning extended into the limbic mesial temporal lobe. The grey matter changes were modulated additionally by the presence of co-morbidities and symptom severity. Prefrontal cortical thickness reduction correlated negatively with tic severity, while volume increase in primary somatosensory cortex depended on the intensity of premonitory sensations. Orbitofrontal cortex volume changes were further associated with abnormal water diffusivity within grey matter. White matter analysis revealed changes in fibre coherence in patients with Tourette syndrome within anterior parts of the corpus callosum. The severity of motor tics and premonitory urges had an impact on the integrity of tracts corresponding to cortico-cortical and cortico-subcortical connections. Our results provide empirical support for a patho-aetiological model of Tourette syndrome based on developmental abnormalities, with perturbation of compensatory systems marking persistence of symptoms into adulthood. We interpret the symptom severity related grey matter volume increase in distinct functional brain areas as evidence of ongoing structural plasticity. The convergence of evidence from volume and water diffusivity imaging strengthens the validity of our findings and attests to the value of a novel multimodal combination of volume and cortical thickness estimations that provides unique and complementary information by exploiting their differential sensitivity to structural change.

Effectiveness of holistic neuropsychological rehabilitation for Spanish population with acquired brain injury measured using Rasch analysis.

INTRODUCTION The Rasch model is increasingly used in the field of rehabilitation because it improves the accuracy of measurements of patient status and their changes after therapy. OBJECTIVE To determine the long-term effectiveness of a holistic neuropsychological rehabilitation program for Spanish outpatients with acquired brain injury (ABI) using Rasch analysis. METHODS Eighteen patients (ten with long evolution - patients who started the program > 6 months after ABI- and eight with short evolution) and their relatives attended the program for 6 months. Patients' and relatives' answers to the European Brain Injury Questionnaire and the Frontal Systems Behavior Scale at 3 time points (pre-intervention. post-intervention and 12 month follow-up) were transformed into linear measures called logits. RESULTS The linear measures revealed significant improvements with large effects at the follow-up assessment on cognitive and executive functioning, social and emotional self-regulation, apathy and mood. At follow-up, the short evolution group achieved greater improvements in mood and cognitive functioning than the long evolution patients. CONCLUSIONS The program showed long-term effectiveness for most of the variables, and it was more effective for mood and cognitive functioning when patients were treated early. Relatives played a key role in the effectiveness of the rehabilitation program.

Comparison of three commercially available radio frequency coils for human brain imaging at 3 Tesla.

OBJECTIVE: To evaluate a transverse electromagnetic (TEM), a circularly polarized (CP) (birdcage), and a 12-channel phased array head coil at the clinical field strength of B0 = 3T in terms of signal-to-noise ratio (SNR), signal homogeneity, and maps of the effective flip angle alpha. MATERIALS AND METHODS: SNR measurements were performed on low flip angle gradient echo images. In addition, flip angle maps were generated for alpha(nominal) = 30 degrees using the double angle method. These evaluation steps were performed on phantom and human brain data acquired with each coil. Moreover, the signal intensity variation was computed for phantom data using five different regions of interest. RESULTS: In terms of SNR, the TEM coil performs slightly better than the CP coil, but is second to the smaller 12-channel coil for human data. As expected, both the TEM and the CP coils show superior image intensity homogeneity than the 12-channel coil, and achieve larger mean effective flip angles than the combination of body and 12-channel coil with reduced radio frequency power deposition. CONCLUSION: At 3T the benefits of TEM coil design over conventional lumped element(s) coil design start to emerge, though the phased array coil retains an advantage with respect to SNR performance.

Gender and weight shape brain dynamics during food viewing.

Hemodynamic imaging results have associated both gender and body weight to variation in brain responses to food-related information. However, the spatio-temporal brain dynamics of gender-related and weight-wise modulations in food discrimination still remain to be elucidated. We analyzed visual evoked potentials (VEPs) while normal-weighted men (n = 12) and women (n = 12) categorized photographs of energy-dense foods and non-food kitchen utensils. VEP analyses showed that food categorization is influenced by gender as early as 170 ms after image onset. Moreover, the female VEP pattern to food categorization co-varied with participants' body weight. Estimations of the neural generator activity over the time interval of VEP modulations (i.e. by means of a distributed linear inverse solution [LAURA]) revealed alterations in prefrontal and temporo-parietal source activity as a function of image category and participants' gender. However, only neural source activity for female responses during food viewing was negatively correlated with body-mass index (BMI) over the respective time interval. Women showed decreased neural source activity particularly in ventral prefrontal brain regions when viewing food, but not non-food objects, while no such associations were apparent in male responses to food and non-food viewing. Our study thus indicates that gender influences are already apparent during initial stages of food-related object categorization, with small variations in body weight modulating electrophysiological responses especially in women and in brain areas implicated in food reward valuation and intake control. These findings extend recent reports on prefrontal reward and control circuit responsiveness to food cues and the potential role of this reactivity pattern in the susceptibility to weight gain.

Blood-brain barrier disruption associated with topiramate-induced angle-closure glaucoma of acute onset.

BACKGROUND: Topiramate (Topamax(R)) is an anti-epileptic drug of the sulfamate group used secondarily for bipolar disease. HISTORY AND SIGNS: One week after initiation of topiramate treatment for a bipolar disorder, a 57-year-old man presented with blurred vision. Clinical examination revealed a bilateral conjunctivitis, areflexic mydriasis, severe anterior chamber shallowing, with a myopic shift and vitritis. THERAPY AND OUTCOME: A spinal tap revealed an increased protein content of 1581 mg/L on cerebrospinal fluid (CSF) analysis, being compatible with a rupture of the blood-brain barrier (BBB). UBM exposed bilateral ciliochoroidal effusions with secondary angle-closure. Topiramate was promptly discontinued, whereas visual acuity, intraocular pressure (IOP), and anterior and posterior segments anatomy normalized within 1 week. One month later, bilateral iris atrophy was present. CONCLUSION: The presence of BBB disruption with increased protein content in CSF with simultaneous blood ocular barrier breakdown may suggest a common inflammatory mechanism.

Clinicopathologic correlates in the oldest-old: Commentary on "No disease in the brain of a 115-year-old woman".

den Dunnen et al. [den Dunnen, W.F.A., Brouwer, W.H., Bijlard, E., Kamphuis, J., van Linschoten, K., Eggens-Meijer, E., Holstege, G., 2008. No disease in the brain of a 115-year-old woman. Neurobiol. Aging] had the opportunity to follow up the cognitive functioning of one of the world's oldest woman during the last 3 years of her life. They performed two neuropsychological evaluations at age 112 and 115 that revealed a striking preservation of immediate recall abilities and orientation. In contrast, working memory, retrieval from semantic memory and mental arithmetic performances declined after age 112. Overall, only a one-point decrease of MMSE score occurred (from 27 to 26) reflecting the remarkable preservation of cognitive abilities. The neuropathological assessment showed few neurofibrillary tangles (NFT) in the hippocampal formation compatible with Braak staging II, absence of amyloid deposits and other types of neurodegenerative lesions as well as preservation of neuron numbers in locus coeruleus. This finding was related to a striking paucity of Alzheimer disease (AD)-related lesions in the hippocampal formation. The present report parallels the early descriptions of rare "supernormal" centenarians supporting the dissociation between brain aging and AD processes. In conjunction with recent stereological analyses in cases aged from 90 to 102 years, it also points to the marked resistance of the hippocampal formation to the degenerative process in this age group and possible dissociation between the occurrence of slight cognitive deficits and development of AD-related pathologic changes in neocortical areas. This work is discussed in the context of current efforts to identify the biological and genetic parameters of human longevity.

Structural and functional brain changes in middle-aged type 2 diabetic patients: a cross-sectional study.

BACKGROUND Type 2 diabetes mellitus (T2DM) is an emerging risk factor for cognitive impairment. Whether this impairment is a direct effect of this metabolic disorder on brain function, a consequence of vascular disease, or both, remains unknown. Structural and functional neuroimaging studies in patients with T2DM could help to elucidate this question. OBJECTIVE We designed a cross-sectional study comparing 25 T2DM patients with 25 age- and gender-matched healthy control participants. Clinical information, APOE genotype, lipid and glucose analysis, structural cerebral magnetic resonance imaging including voxel-based morphometry, and F-18 fluorodeoxyglucose positron emission tomography were obtained in all subjects. METHODS Gray matter densities and metabolic differences between groups were analyzed using statistical parametric mapping. In addition to comparing the neuroimaging profiles of both groups, we correlated neuroimaging findings with HbA1c levels, duration of T2DM, and insulin resistance measurement (HOMA-IR) in the diabetic patients group. Results: Patients with T2DM presented reduced gray matter densities and reduced cerebral glucose metabolism in several fronto-temporal brain regions after controlling for various vascular risk factors. Furthermore, within the T2DM group, longer disease duration, and higher HbA1c levels and HOMA-IR were associated with lower gray matter density and reduced cerebral glucose metabolism in fronto-temporal regions. CONCLUSION In agreement with previous reports, our findings indicate that T2DM leads to structural and metabolic abnormalities in fronto-temporal areas. Furthermore, they suggest that these abnormalities are not entirely explained by the role of T2DM as a cardiovascular risk factor.

A neuron-glia signalling network in the active brain.

Glial cells are active partners of neurons in processing information and synaptic integration. They receive coded signals from synapses and elaborate modulatory responses. The active properties of glia, including long-range signalling and regulated transmitter release, are beginning to be elucidated. Recent insights suggest that the active brain should no longer be regarded as a circuitry of neuronal contacts, but as an integrated network of interactive neurons and glia.

JULIDE: a software tool for 3D reconstruction and statistical analysis of autoradiographic mouse brain sections.

In this article we introduce JULIDE, a software toolkit developed to perform the 3D reconstruction, intensity normalization, volume standardization by 3D image registration and voxel-wise statistical analysis of autoradiographs of mouse brain sections. This software tool has been developed in the open-source ITK software framework and is freely available under a GPL license. The article presents the complete image processing chain from raw data acquisition to 3D statistical group analysis. Results of the group comparison in the context of a study on spatial learning are shown as an illustration of the data that can be obtained with this tool.

Controversies about the enhanced vulnerability of the adolescent brain to develop addiction.

Adolescence, defined as a transition phase toward autonomy and independence, is a natural time of learning and adjustment, particularly in the setting of long-term goals and personal aspirations. It also is a period of heightened sensation seeking, including risk taking and reckless behaviors, which is a major cause of morbidity and mortality among teenagers. Recent observations suggest that a relative immaturity in frontal cortical neural systems may underlie the adolescent propensity for uninhibited risk taking and hazardous behaviors. However, converging preclinical and clinical studies do not support a simple model of frontal cortical immaturity, and there is substantial evidence that adolescents engage in dangerous activities, including drug abuse, despite knowing and understanding the risks involved. Therefore, a current consensus considers that much brain development during adolescence occurs in brain regions and systems that are critically involved in the perception and evaluation of risk and reward, leading to important changes in social and affective processing. Hence, rather than naive, immature and vulnerable, the adolescent brain, particularly the prefrontal cortex, should be considered as prewired for expecting novel experiences. In this perspective, thrill seeking may not represent a danger but rather a window of opportunities permitting the development of cognitive control through multiple experiences. However, if the maturation of brain systems implicated in self-regulation is contextually dependent, it is important to understand which experiences matter most. In particular, it is essential to unveil the underpinning mechanisms by which recurrent adverse episodes of stress or unrestricted access to drugs can shape the adolescent brain and potentially trigger life-long maladaptive responses.