How to monitor the brain in septic patients?

Brain injury is frequently observed after sepsis and may be primarily related to the direct effects of the septic insult on the brain (e.g., brain edema, ischemia, seizures) or to secondary/indirect injuries (e.g., hypotension, hypoxemia, hypocapnia, hyperglycemia). Management of brain injury in septic patients is first focused to exclude structural intracranial complications (e.g., ischemic/hemorrhagic stroke) and possible confounders (e.g., electrolyte alterations or metabolic disorders, such as dysglycemia). Sepsis-associated brain dysfunction is frequently a heterogeneous syndrome. Despite increasing understanding of main pathophysiologic determinants, therapy is essentially limited to protect the brain against further cerebral damage, by way of "simple" therapeutic manipulations of cerebral perfusion and oxygenation and by avoiding over-sedation. Non-invasive monitoring of cerebral perfusion and oxygenation with transcranial Doppler (TCD) and near-infrared spectroscopy (NIRS) is feasible in septic patients. Electroencephalography (EEG) allows detection of sepsis-related seizures and holds promise also as sedation monitoring. Brain CT-scan detects intra-cerebral structural lesions, while magnetic resonance imaging (MRI) provides important insights into primary mechanisms of sepsis-related direct brain injury, (e.g., cytotoxic vs. vasogenic edema) and the development of posterior reversible encephalopathy. Together with EEG and evoked potentials (EP), MRI is also important for coma prognostication. Emerging clinical evidence suggests monitoring of the brain in septic patients can be implemented in the ICU. The objective of this review was to summarize recent clinical data about the role of brain monitoring - including TCD, NIRS, EEG, EP, CT, and MRI - in patients with sepsis and to illustrate its potential utility for the diagnosis, management and prognostication.

Scoring criteria for portable monitor recordings: a comparison of four hypopnoea definitions in a population-based cohort.

RATIONALE: Limited-channel portable monitors (PMs) are increasingly used as an alternative to polysomnography (PSG) for the diagnosis of obstructive sleep apnoea (OSA). However, recommendations for the scoring of PM recordings are still lacking. Pulse-wave amplitude (PWA) drops, considered as surrogates for EEG arousals, may increase the detection sensitivity for respiratory events in PM recordings. OBJECTIVES: To investigate the performance of four different hypopnoea scoring criteria, using 3% or 4% oxygen desaturation levels, including or not PWA drops as surrogates for EEG arousals, and to determine the impact of measured versus reported sleep time on OSA diagnosis. METHODS: Subjects drawn from a population-based cohort underwent a complete home PSG. The PSG recordings were scored using the 2012 American Academy of Sleep Medicine criteria to determine the apnoea-hypopnoea index (AHI). Recordings were then rescored using only parameters available on type 3 PM devices according to different hypopnoea criteria and patients-reported sleep duration to determine the 'portable monitor AHIs' (PM-AHIs). MAIN RESULTS: 312 subjects were included. Overall, PM-AHIs showed a good concordance with the PSG-based AHI although it tended to slightly underestimate it. The PM-AHI using 3% desaturation without PWA drops showed the best diagnostic accuracy for AHI thresholds of ≥5/h and ≥15/h (correctly classifying 94.55% and 93.27% of subjects, respectively, vs 80.13% and 87.50% with PWA drops). There was a significant but modest correlation between PWA drops and EEG arousals (r=0.20, p=0.0004). CONCLUSION: Interpretation of PM recordings using hypopnoea criteria which include 3% desaturation without PWA drops as EEG arousal surrogate showed the best diagnosis accuracy compared with full PSG.

Identification of the regions involved in phonological assembly using a novel paradigm.

Here we adopt a novel strategy to investigate phonological assembly. Participants performed a visual lexical decision task in English in which the letters in words and letterstrings were delivered either sequentially (promoting phonological assembly) or simultaneously (not promoting phonological assembly). A region of interest analysis confirmed that regions previously associated with phonological assembly, in studies contrasting different word types (e.g. words versus pseudowords), were also identified using our novel task that controls for a number of confounding variables. Specifically, the left pars opercularis, the superior part of the ventral precentral gyrus and the supramarginal gyrus were all recruited more during sequential delivery than simultaneous delivery, even when various psycholinguistic characteristics of the stimuli were controlled. This suggests that sequential delivery of orthographic stimuli is a useful tool to explore how readers, with various levels of proficiency, use sublexical phonological processing during visual word recognition.

New-onset refractory status epilepticus: Etiology, clinical features, and outcome.

OBJECTIVES: The aims of this study were to determine the etiology, clinical features, and predictors of outcome of new-onset refractory status epilepticus. METHODS: Retrospective review of patients with refractory status epilepticus without etiology identified within 48 hours of admission between January 1, 2008, and December 31, 2013, in 13 academic medical centers. The primary outcome measure was poor functional outcome at discharge (defined as a score >3 on the modified Rankin Scale). RESULTS: Of 130 cases, 67 (52%) remained cryptogenic. The most common identified etiologies were autoimmune (19%) and paraneoplastic (18%) encephalitis. Full data were available in 125 cases (62 cryptogenic). Poor outcome occurred in 77 of 125 cases (62%), and 28 (22%) died. Predictors of poor outcome included duration of status epilepticus, use of anesthetics, and medical complications. Among the 63 patients with available follow-up data (median 9 months), functional status improved in 36 (57%); 79% had good or fair outcome at last follow-up, but epilepsy developed in 37% with most survivors (92%) remaining on antiseizure medications. Immune therapies were used less frequently in cryptogenic cases, despite a comparable prevalence of inflammatory CSF changes. CONCLUSIONS: Autoimmune encephalitis is the most commonly identified cause of new-onset refractory status epilepticus, but half remain cryptogenic. Outcome at discharge is poor but improves during follow-up. Epilepsy develops in most cases. The role of anesthetics and immune therapies warrants further investigation.

Clinical neurophysiology in disorders of consciousness: brain function monitoring in the ICU and beyond.

Over the past two decades, electrophysiology has undergone unprecedented changes thanks to technical improvements, which simplify measurement and analysis and allow more compact data storage. This book covers in detail the spectrum of electrophysiology applications in patients with disorders of consciousness. Its content spans from clinical aspects of the management of subjects in the intensive care unit, including EEG, evoked potentials and related implications in terms of prognosis and patient management to research applications in subjects with ongoing consciousness impairment. While the first section provides up-to-date information for the interested clinician, the second part highlights the latest developments in this exciting field. The book comprehensively combines clinical and research information related to neurophysiology in disorder-of- consciousness patients, making it an easily accessible reference for neuro-ICU specialists, epileptologists and clinical neurophysiologists as well as researchers utilizing EEG and event-related potentials.

Acrodermatitis enteropática: tratamiento con Zinc

Se presenta un nuevo caso de Acrodermatitis Enteropática en un lactante de 2,5 meses de vida, fruto de embarazo gemelar bivitelino pretérmino (36 S), de aparición gradual desde los 15 días de vida. Había seguido lactancia artificial exclusivamente desde su nacimiento, al igual que su hermano gemelo que no presentó la enfermedad. Entre los exámenes complementarios destacaba una importante hipozincemia, fosfatasas alcalinas descendidas, alteraciones en la inmunidad celular, rasgos de inmadurez cerebral en el EEG y discreta atrofia vellositaria en la muestra biópsica intestinal. El Tratamiento con sulfato de Zinc a la dosis de 10 mg/Kg/día hizo remitir el cuadro clínico y analítico en pocos días. A los 4 meses de edad abandonó el tratamiento, reapareciendo a los 22 días los síntomas digestivos y cutáneos; la zincemia en ese momento era elevada (175 mcg/dl). Esta falta de relación entre la zincemia y la clínica sugiere que en la Acrodermatitis Enteropática el defecto de transporte del Zn afecta no sólo al enterocito sino también a otras células del organismo y que el criterio para mantener el tratamiento y fijar la dosis debe ser clínico y no analítico.

Investigating the functions of subregions within anterior hippocampus.

Previous functional MRI (fMRI) studies have associated anterior hippocampus with imagining and recalling scenes, imagining the future, recalling autobiographical memories and visual scene perception. We have observed that this typically involves the medial rather than the lateral portion of the anterior hippocampus. Here, we investigated which specific structures of the hippocampus underpin this observation. We had participants imagine novel scenes during fMRI scanning, as well as recall previously learned scenes from two different time periods (one week and 30 min prior to scanning), with analogous single object conditions as baselines. Using an extended segmentation protocol focussing on anterior hippocampus, we first investigated which substructures of the hippocampus respond to scenes, and found both imagination and recall of scenes to be associated with activity in presubiculum/parasubiculum, a region associated with spatial representation in rodents. Next, we compared imagining novel scenes to recall from one week or 30 min before scanning. We expected a strong response to imagining novel scenes and 1-week recall, as both involve constructing scene representations from elements stored across cortex. By contrast, we expected a weaker response to 30-min recall, as representations of these scenes had already been constructed but not yet consolidated. Both imagination and 1-week recall of scenes engaged anterior hippocampal structures (anterior subiculum and uncus respectively), indicating possible roles in scene construction. By contrast, 30-min recall of scenes elicited significantly less activation of anterior hippocampus but did engage posterior CA3. Together, these results elucidate the functions of different parts of the anterior hippocampus, a key brain area about which little is definitely known.

Altered Sleep Homeostasis in Rev-erbα Knockout Mice.

STUDY OBJECTIVES: The nuclear receptor REV-ERBα is a potent, constitutive transcriptional repressor critical for the regulation of key circadian and metabolic genes. Recently, REV-ERBα's involvement in learning, neurogenesis, mood, and dopamine turnover was demonstrated suggesting a specific role in central nervous system functioning. We have previously shown that the brain expression of several core clock genes, including Rev-erbα, is modulated by sleep loss. We here test the consequences of a loss of REV-ERBα on the homeostatic regulation of sleep. METHODS: EEG/EMG signals were recorded in Rev-erbα knockout (KO) mice and their wild type (WT) littermates during baseline, sleep deprivation, and recovery. Cortical gene expression measurements after sleep deprivation were contrasted to baseline. RESULTS: Although baseline sleep/wake duration was remarkably similar, KO mice showed an advance of the sleep/wake distribution relative to the light-dark cycle. After sleep onset in baseline and after sleep deprivation, both EEG delta power (1-4 Hz) and sleep consolidation were reduced in KO mice indicating a slower increase of homeostatic sleep need during wakefulness. This slower increase might relate to the smaller increase in theta and gamma power observed in the waking EEG prior to sleep onset under both conditions. Indeed, the increased theta activity during wakefulness predicted delta power in subsequent NREM sleep. Lack of Rev-erbα increased Bmal1, Npas2, Clock, and Fabp7 expression, confirming the direct regulation of these genes by REV-ERBα also in the brain. CONCLUSIONS: Our results add further proof to the notion that clock genes are involved in sleep homeostasis. Because accumulating evidence directly links REV-ERBα to dopamine signaling the altered homeostatic regulation of sleep reported here are discussed in that context.

Weakened functional connectivity in patients with psychogenic non-epileptic seizures (PNES) converges on basal ganglia.

BACKGROUND: Psychogenic non-epileptic seizures (PNES) are involuntary paroxysmal events that are unaccompanied by epileptiform EEG discharges. We hypothesised that PNES are a disorder of distributed brain networks resulting from their functional disconnection.The disconnection may underlie a dissociation mechanism that weakens the influence of unconsciously presented traumatising information but exerts maladaptive effects leading to episodic failures of behavioural control manifested by psychogenic 'seizures'. METHODS: To test this hypothesis, we compared functional connectivity (FC) derived from resting state high-density EEGs of 18 patients with PNES and 18 age-matched and gender-matched controls. To this end, the EEGs were transformed into source space using the local autoregressive average inverse solution. FC was estimated with a multivariate measure of lagged synchronisation in the θ, α and β frequency bands for 66 brain sites clustered into 18 regions. A multiple comparison permutation test was applied to deduce significant between-group differences in inter-regional and intraregional FC. RESULTS: The significant effect of PNES-a decrease in lagged FC between the basal ganglia and limbic, prefrontal, temporal, parietal and occipital regions-was found in the α band. CONCLUSION: We believe that this finding reveals a possible neurobiological substrate of PNES, which explains both attenuation of the effect of potentially disturbing mental representations and the occurrence of PNES episodes. By improving understanding of the aetiology of this condition, our results suggest a potential refinement of diagnostic criteria and management principles.

Circulating progenitor cells during exercise, muscle electro-stimulation and intermittent hypobaric hypoxia in patients with traumatic brain injury. A pilot study

BACKGROUND: Circulating progenitor cells (CPC) treatments may have great potential for the recovery of neurons and brain function. OBJECTIVE: To increase and maintain CPC with a program of exercise, muscle electro-stimulation (ME) and/or intermittent-hypobaric-hypoxia (IHH), and also to study the possible improvement in physical or psychological functioning of participants with Traumatic Brain Injury (TBI). METHODS: Twenty-one participants. Four groups: exercise and ME group (EEG), cycling group (CyG), IHH and ME group (HEG) and control group (CG). Psychological and physical stress tests were carried out. CPC were measured in blood several times during the protocol. RESULTS: Psychological tests did not change. In the physical stress tests the VO2 uptake increased in the EEG and the CyG, and the maximal tolerated workload increased in the HEG. CPC levels increased in the last three weeks in EEG, but not in CyG, CG and HEG. CONCLUSIONS: CPC levels increased in the last three weeks of the EEG program, but not in the other groups and we did not detect performed psychological test changes in any group. The detected aerobic capacity or workload improvement must be beneficial for the patients who have suffered TBI, but exercise type and the mechanisms involved are not clear.

Microstructural Brain Differences Predict Functional Hemodynamic Responses in a Reward Processing Task

Many aspects of human behavior are driven by rewards, yet different people are differentially sensitive to rewards and punishment. In this study, we showthat white matter microstructure inthe uncinate/inferiorfronto-occipitalfasciculus, defined byfractional anisotropy values derived from diffusion tensor magnetic resonance images, correlates with both short-term (indexed by the fMRI blood oxygenation level-dependent response to reward in the nucleus accumbens) and long-term (indexed by the trait measure sensitivity to punishment) reactivityto rewards.Moreover,traitmeasures of reward processingwere also correlatedwith reward-relatedfunctional activation in the nucleus accumbens. The white matter tract revealed by the correlational analysis connects the anterior temporal lobe with the medial and lateral orbitofrontal cortex and also supplies the ventral striatum. The pattern of strong correlations suggests an intimate relationship betweenwhitematter structure and reward-related behaviorthatmay also play a rolein a number of pathological conditions, such as addiction and pathological gambling.

A hybrid feature selection approach for the early diagnosis of Alzheimer's disease

Objective. Recently, significant advances have been made in the early diagnosis of Alzheimer’s disease from EEG. However, choosing suitable measures is a challenging task. Among other measures, frequency Relative Power and loss of complexity have been used with promising results. In the present study we investigate the early diagnosis of AD using synchrony measures and frequency Relative Power on EEG signals, examining the changes found in different frequency ranges. Approach. We first explore the use of a single feature for computing the classification rate, looking for the best frequency range. Then, we present a multiple feature classification system that outperforms all previous results using a feature selection strategy. These two approaches are tested in two different databases, one containing MCI and healthy subjects (patients age: 71.9 ± 10.2, healthy subjects age: 71.7 ± 8.3), and the other containing Mild AD and healthy subjects (patients age: 77.6 ± 10.0; healthy subjects age: 69.4± 11.5). Main Results. Using a single feature to compute classification rates we achieve a performance of 78.33% for the MCI data set and of 97.56 % for Mild AD. Results are clearly improved using the multiple feature classification, where a classification rate of 95% is found for the MCI data set using 11 features, and 100% for the Mild AD data set using 4 features. Significance. The new features selection method described in this work may be a reliable tool that could help to design a realistic system that does not require prior knowledge of a patient's status. With that aim, we explore the standardization of features for MCI and Mild AD data sets with promising results.

Diferencias en la dimensionalidad electroencefalograma entre vigilia y sueño profundo

Differences in dimensionality of electroencephalogram during awake and deeper sleep stages. The nonlinear dynamical systems theory provides some tools for the analysis of electroencephalogram (EEG) at different sleep stages. Its use could allow the automatic monitoring of the states of the sleep and it would also contribute an explanatory level of the differences between stages. The goal of the present paper is to address this type of analysis, focusing on the most different stages. Estimations of dimensionality were compared when six subjects were awake and in a deep sleep stage. Greater dimensionality involves more complexity because the system receives more external influences. If this dimensionality is maximum, we can consider that the time series is a noisy one. A smaller dimensionality involves lower complexity because the system receives fewer inputs. We hypothesized that we would find greater dimensionality when subjects were awake than in a deep sleep stage. Results show a noisy time series during the awake stage, whereas in the sleep stage, dimensionality is smaller, confirming our hypothesis. This result is similar to the findings reached previously by other authors.

Role of Selected Spectral Attributes in the Perception of Synthetic Vowels

This thesis is an experimental study regarding the identification and discrimination of vowels, studied using synthetic stimuli. The acoustic attributes of synthetic stimuli vary, which raises the question of how different spectral attributes are linked to the behaviour of the subjects. The spectral attributes used are formants and spectral moments (centre of gravity, standard deviation, skewness and kurtosis). Two types of experiments are used, related to the identification and discrimination of the stimuli, respectively. The discrimination is studied by using both the attentive procedures that require a response from the subject, and the preattentive procedures that require no response. Together, the studies offer information about the identification and discrimination of synthetic vowels in 15 different languages. Furthermore, this thesis discusses the role of various spectral attributes in the speech perception processes. The thesis is divided into three studies. The first is based only on attentive methods, whereas the other two concentrate on the relationship between identification and discrimination experiments. The neurophysiological methods (EEG recordings) reveal the role of attention in processing, and are used in discrimination experiments, while the results reveal differences in perceptual processes based on the language, attention and experimental procedure.