Cholesterol dysregulation in peripheral blood mononuclear cells of Alzheimer's disease.

Cholesterol and the immune system are involved in Alzheimer's Disease (AD). To investigate the relations among them, we compared the cholesterol content in peripheral blood mononuclear cells (PBMC) of cognitively healthy controls and patients with mild cognitive impairment (MCI) and AD in two independent samples. Free cholesterol content of PBMC was lower in MCI and AD patients, and was modulated by APOE genotype. A decrease of CD8+ and an increase of CD16+ was also found in AD patients. These results suggest that cholesterol levels in PBMCs may represent an early signature of the disease and support the involvement of immune system in AD.

Diabetes Insípida inducida por el embarazo o gestacional: a propósito de un caso / Pregnancy or Gestational Diabetes Insipidus: a purpose of a case

RESUMEN Antecedentes: La incidencia de la diabetes insípida gestacional es aproximadamente 1/30.000 gestaciones. Objetivo: A propósito de un caso de diabetes insípida gestacional ocurrida en nuestra unidad, se decide comunicar y revisar la literatura referente a opciones de manejo y tratamiento del mismo. Caso clínico: Mujer de 38 años, primigesta de 32 semanas con clínica de poliuria y polidipsia con una ingesta hídrica diaria de hasta 7 litros. Tras realizar las pertinentes exploraciones complementarias y descartar otras patologías más frecuentes, se establece el diagnóstico de diabetes insípida gestacional. Conclusiones: La diabetes insípida gestacional es una entidad muy poco frecuente que puede desencadenar en un estado de deshidratación intensa con hipernatremia y su consecuente afectación neurológica. Es importante el diagnóstico precoz para evitar las complicaciones tanto a nivel materno como fetal, así como realizar un manejo multidisciplinar de esta patología.

ABSTRACT Background: The incidence of diabetes insipidus during pregnancy is approximately 1 in 30,000 pregnancies. Objective: We herein report a case of a patient with gestational diabetes insipidus occurring in our unit. We decided to communicate the case and review the literature regarding management and treatment options. Case report: A 38-year-old woman at 32 week of pregnancy with polyuria, polydipsia, and daily water intake of up to 7 liters. After performing the complementary tests and ruling out other more frequent conditions, the diagnosis of gestational diabetes insipidus was established. Conclusion: Gestational diabetes insipidus is a very rare entity that can cause a state of intense dehydration with hypernatremia and its consequent neurological impairment. Early detection is important in order to avoid complications of both mother and fetus, as well as to carry out a multidisciplinary management of this condition.

Infiltrado parahiliar / Parahilar Injection

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En respuesta a «MENTOR: un programa innovador de reclutamiento de residentes» / In response to «MENTOR: A novel program for recruiting residents»

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Impact of sleep loss before learning on cortical dynamics during memory retrieval.

Evidence shows that sleep loss before learning decreases activation of the hippocampus during encoding and promotes forgetting. But it remains to be determined which neural systems are functionally affected during memory retrieval after one night of recovery sleep. To investigate this issue, we evaluated memory for pairs of famous people's faces with the same or different profession (i.e., semantically congruent or incongruent faces) after one night of undisturbed sleep in subjects who either underwent 4hours of acute sleep restriction (ASR, N=20) or who slept 8hours the pre-training night (controls, N=20). EEG recordings were collected during the recognition memory task in both groups, and the cortical sources generating this activity localized by applying a spatial beamforming filter in the frequency domain. Even though sleep restriction did not affect accuracy of memory performance, controls showed a much larger decrease of alpha power relative to a baseline period when compared to sleep-deprived subjects. These group differences affected a widespread frontotemporoparietal network involved in retrieval of episodic/semantic memories. Regression analyses further revealed that associative memory in the ASR group was negatively correlated with alpha power in the occipital regions, whereas the benefit of congruency in the same group was positively correlated with delta power in the left lateral prefrontal cortex. Retrieval-related decreases of alpha power have been associated with the reactivation of material-specific memory representations, whereas increases of delta power have been related to inhibition of interferences that may affect the performance of the task. We can therefore draw the conclusion that a few hours of sleep loss in the pre-training night, though insufficient to change the memory performance, is sufficient to alter the processes involved in retrieving and manipulating episodic and semantic information.

Reparación endovascular de un seudoaneurisma de aorta abdominal de origen desconocido / Endovascular repair of an abdominal aortic pseudoaneurysm of unknown origin

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Linac stereotactic radiosurgery for the treatment of small arteriovenous malformations: lower doses can be equally effective.

OBJECTIVE: The purpose of this study was to examine the efficacy and toxicity of treating small arteriovenous malformations (AVMs) (≤3 cm in diameter) with a median marginal applied dose of 14 Gy. METHODS: Two hundred and thirteen patients diagnosed with AVMs were treated between January 1991 and December 2005. Seventy-three percent of the patients had hemorrhaged prior to treatment, 13% had had previous surgery and 19.2% had had previous embolization. The median follow-up duration was 48.1 months. RESULTS: The Kaplan-Meier analysis estimated that the 36-month obliteration rate was 65.5% for patients undergoing their first stereotactic radiosurgery (SRS) and 68.3% for those undergoing repeated SRS. The Kaplan-Meier analysis estimated the 60-month AVMs obliteration rate for the entire cohort to be 82.4%. The median time to AVM obliteration was 40 ± 2.8 months. We found a statistically significant relationship between the time of obliteration and the following factors: site of the AVMs (sites other than brainstem), a higher prescribed dose and a positive history of previous hemorrhage. Thirteen patients (7.6%) experienced toxicities. CONCLUSIONS: SRS was an effective and safe treatment for AVMs ≤3 cm in diameter, with acceptable toxicity.

Associative memory deficits in mild cognitive impairment: the role of hippocampal formation.

Neuropathological events featuring early stages of Alzheimer's disease (AD) appear in the entorhinal cortex (EC), subiculum (SB) and cornu ammonis 1 (CA1) of hippocampus, which may account for associative memory deficits in non-demented people with mild cognitive impairment (MCI). To test this hypothesis in vivo, we investigated whether volume changes in these regions are related to failures in associative memory in MCI as compared to cognitively normal (CN) elderly subjects. Volume changes in EC and hippocampal subfields were determined by using deformation-based morphometry techniques applied to probabilistic cytoarchitectonic maps derived from post mortem human brains. CN subjects were distinguished from MCI patients by firstly identifying local volume differences in EC and hippocampus, and then evaluating the way in which these anatomical changes correlated with performance in a non-intentional face-location association task. MCI patients not only performed worse than CN elders in building new associations, but they were further unable to benefit from semantic encoding to improve episodic binding. According to our initial hypothesis, local volume reductions in both EC and hippocampal CA accounted for group differences in associative memory whereas atrophy in CA, but not in EC, accounted for semantic encoding of associations. Two main conclusions can be drawn from the present study: i) access to semantic information during encoding does not reduce the episodic deficit in MCI; and ii) EC and hippocampal CA, two regions early affected by AD neuropathology, are responsible, at least partially, for associative memory deficits observed in MCI patients.

Aortoenteric fistula after endovascular abdominal aortic aneurysm treatment with the original Gore Excluder endoprosthesis and Cook aortouniiliac converter for endotension.

We report a case of aortoenteric fistula (AEF) that occurred four years after endovascular abdominal aortic aneurysm repair (EVAR) with the original Gore Excluder endoprosthesis despite uncomplicated stent graft placement without endoleaks or migration on postoperative imaging studies; the patient was reoperated with a Cook aortouniiliac converter for endotension three months before the diagnosis of AEF. To our knowledge, this is the first reported case in the literature of an AEF after EVAR with the Excluder stent graft. Our case demonstrates that EVAR is not a guarantee against the development of AEF, and we suggest that all the patients with the first generation Excluder device should be closely followed-up; if sac enlargement is detected, early conversion to open repair or reinforcement of the entire old endograft should be considered.

Functional neural networks underlying semantic encoding of associative memories.

Evidence suggests that theta oscillations recruit distributed cortical representations to improve associative encoding under semantically congruent conditions. Here we show that positive effects of semantic context on encoding and retrieval of associations are mediated by changes in the coupling pattern between EEG theta sources. During successful encoding of semantically congruent face-location associations, the right superior parietal lobe showed enhanced theta phase synchronization with other regions within the lateral posterior parietal lobe (PPL) and left medial temporal lobe (MTL). However, functional coordination involving the inferior parietal lobe was higher in the incongruent condition. These results suggest a differential engagement of top-down and bottom-up mechanisms during encoding of semantically congruent and incongruent episodic associations, respectively. Although retrieval processes operated on a similar neural network, the main difference with the study phase was the larger amount of functional links shown by the lateral prefrontal cortex with regions of the MTL and PPL. All together, these results suggest that theta oscillations mediate, at least partially, the positive effect of semantic congruence on associative memory by (i) optimizing top-down attentional mechanisms through enhanced theta phase synchronization between dorsal regions of the PPL and MTL and (ii) by adjusting the control of automatic attention to sensory and contextual information reactivated in the MTL through functional connections with the inferior parietal lobe during both encoding and retrieval processes.

[Stability of an oral liquid morphine formulation for pediatric use]. / Estabilidad de una formulación oral líquida de morfina para pediatría.

OBJECTIVE: The aim of this study the determination of the stability of an oral morphine hydrochloride solutions. METHOD: Determinations of a concentrated morphine solution of 4 mg/ml and the impact of two temperatures, 4 degrees C (refrigerator) and 25 degrees C (room) was analyzed via spectrophotometric measurements. RESULTS: Findings showed the high stability of the solutions at 4 degrees C, since no significant degradation was observed during the 30 days of the study, whereas at room temperature stability losses were hardly seen during the first 7 days, reaching 6.8% +/- 0.5% after 15 days. CONCLUSIONS: The tested morphine solution is stable at 4 degrees C during 30 days, but not at room temperature.

Estabilidad de una formulación oral líquida de morfina para pediatría / Stability of an oral liquid morphine formulation for pediatric use

Objetivo: El objetivo del trabajo el estudio de estabilidad desoluciones orales de morfina clorhidrato.Método: Las determinaciones se han realizado mediantemedidas espectrofotométricas de una solución concentrada demorfina de 4 mg/ml, estudiando la influencia de dos temperaturas,4 °C (frigorífico) y 25 °C (ambiente).Resultados: Los resultados obtenidos, señalan la buena estabilidadde las soluciones conservadas a 4 °C, sin observar degradacionessignificativas durante los 30 días que dura el estudio, mientrasque a temperatura ambiente, apenas se observan pérdidas deestabilidad durante los primeros 7 días, siendo a los 15 días laspérdidas de un 6,8 ± 0,5%.Conclusiones: La fórmula propuesta es estable a 4 °C durante30 días, pero no lo es a temperatura ambiente

Objective: The aim of this study the determination of the stabilityof an oral morphine hydrochloride solutions.Method: Determinations of a concentrated morphine solutionof 4 mg/ml and the impact of two temperatures, 4 °C (refrigerator)and 25 °C (room) was analized via spectrophotometric measurements.Results: Findings showed the high stability of the solutions at4 °C, since no significant degradation was observed during the 30days of the study, whereas at room temperature stability losseswere hardly seen during the first 7 days, reaching 6.8% ± 0.5%after 15 days.Conclusions: The tested morphine solution is stable at 4 °Cduring 30 days, but not at room temperature

Precise timing accounts for posttraining sleep-dependent enhancements of the auditory mismatch negativity.

Memory consolidation is a long-lasting dynamic process by which new acquired information is transformed at different analysis levels, from molecules to cognition, without additional practice. Results from a previous study on event-related potentials (ERPs) suggest that part of the neural events promoting changes in the electrophysiological correlates of enhanced automatization in a sound discrimination task occur during sleep. These data were reanalyzed in the present study at the single-trial level, and results indicated that the first night of sleep succeeding training is absolutely required to improve the timing consistency of cortical neural assemblies involved in automatic sound-change detection, as revealed by a significant reduction in the latency-jitter of the MMN response across trials. This change in the regularity of the brain response to previously trained sounds facilitated involuntary switch of attention towards the same sounds when they were task irrelevant, as reflected by the P3a emergence after posttraining sleep. Both responses were, however, prevented in subjects deprived of sleep the night following training in the sound discrimination task. We hypothesize that the reduction in the MMN latency-jitter, which, in turn, triggered an automatic shift of attention, might result from a change in synaptic efficacy and/or neural excitability, rather than from changes in firing synchronization and/or size of representation.

Sensory and motor attentional modulation during the manual gap effect in humans: a high-density ERP study.

The present study investigated reaction time (RT) and event-related potential (ERP) differences between gap and step conditions using visual stimulation and manual responses. RTs during the gap condition were facilitated with respect to those of the step condition. The ERPs, which were obtained from electrodes placed at 58 scalp sites, showed differences when the gap and step conditions were compared for the following components: an early positive component centred at the vertex, an enhanced P1 component, a frontal negativity, a negative lateralized motor potential, and an increased P3. All these results suggest that the facilitation induced by the gap is mediated by a modulation of the neural circuits involved in sensory, motor, and cognitive functions.

Auditory information processing during human sleep as revealed by event-related brain potentials.

The main goal of this review is to elucidate up to what extent pre-attentive auditory information processing is affected during human sleep. Evidence from event-related brain potential (ERP) studies indicates that auditory information processing is selectively affected, even at early phases, across the different stages of sleep-wakefulness continuum. According to these studies, 3 main conclusions are drawn: (1) the sleeping brain is able to automatically detect stimulus occurrence and trigger an orienting response towards that stimulus if its degree of novelty is large; (2) auditory stimuli are represented in the auditory system and maintained for a period of time in sensory memory, making the automatic-change detection during sleep possible; and (3) there are specific brain mechanisms (sleep-specific ERP components associated with the presence of vertex waves and K-complexes) by which information processing can be improved during non-rapid eye movement sleep. However, the remarkably affected amplitude and latency of the waking-ERPs during the different stages of sleep suggests deficits in the building and maintenance of a neural representation of the stimulus as well as in the process by which neural events lead to an orienting response toward such a stimulus. The deactivation of areas in the dorsolateral pre-frontal cortex during sleep contributing to the generation of these ERP components is hypothesized to be one of the main causes for the attenuated amplitude of these ERPs during human sleep.

Complex sound processing during human REM sleep by recovering information from long-term memory as revealed by the mismatch negativity (MMN).

Perceptual learning is thought to be the result of neural changes that take place over a period of several hours or days, allowing information to be transferred to long-term memory. Evidence suggests that contents of long-term memory may improve attentive and pre-attentive sensory processing. Therefore, it is plausible to hypothesize that learning-induced neural changes that develop during wakefulness could improve automatic information processing during human REM sleep. The MMN, an objective measure of the automatic change detection in auditory cortex, was used to evaluate long-term learning effects on pre-attentive processing during wakefulness and REM sleep. When subjects learned to discriminate two complex auditory patterns in wakefulness, an increase in the MMN was obtained in both wake and REM states. The automatic detection of the infrequent complex auditory pattern may therefore be improved in both brain states by reactivating information from long-term memory. These findings suggest that long-term learning-related neural changes are accessible during REM sleep as well.

The initial orienting response during human REM sleep as revealed by the N1 component of auditory event-related potentials.

The large N1 wave of the auditory event-related potentials (ERPs) typically occurring to the first stimulus after a long silent interval seems to be associated with the involuntary initial-orienting response. Since the mechanisms involved in the generation of this brain response are assumed to be activated automatically, the present study aims at determining whether this electrophysiological response can also be elicited during human REM sleep, the sleep stage considered most sensitive to external stimuli. To achieve this goal, the auditory N1 wave was analyzed in wakefulness and REM sleep for frequency deviant tones delivered in several positions (1, 2, 4 and 6) within homogenous stimulus trains separated by different intervals of silence (3, 6 and 9 s), the intra-train stimulus interval being 600 ms. A significant increment in the amplitude of the N1 component for the first deviant tone, as compared with deviants delivered in remaining positions, was observed in both brain states, independently of the inter-train interval length. This result cannot be explained by a release-from-refractoriness effect, since only one deviant was presented in each train and the inter-deviant interval hardly changed from one train to another. The increase in N1 to the first stimulus of the train, probably due to the contribution of the neuronal elements responsible for the supratemporal and non-specific components, may be explained by changes in the silent interval, rather than by variations in the stimulus frequency. The enhanced N1 could be reflecting a general increase in sensory sensitivity associated with the arousal factor of the orienting response. These findings suggest that the brain maintains the potential ability to trigger the brain events responsible for the OR elicitation, even during REM sleep.

[Clinical value of EEG coherence as electrophysiological index of cortico-cortical connections during sleep]. / Valor clínico de la coherencia EEG como índice electrofisiológico de conectividad córtico-cortical durante el sueño.

OBJECTIVE: The technique of EEG coherence gives a non-invasive objective index of the functional relations between the different regions of the cerebral cortex. The main objectives of this study were firstly to obtain methodological information to facilitate its use in any context, whether clinical or in investigation, and secondly to draw attention to the results obtained with this technique during the different phases of sleep, both in healthy persons and in certain clinical conditions where its use in evaluation and/or diagnosis has been shown. DEVELOPMENT: The results derived from the application of coherence analysis during normal sleep show the existence of a high level of interhemisphere connectivity during all phases of sleep. This result has fomented its use in the evaluation and diagnosis of disorders in which it is suspected that there are anomalies in the relation between the two hemispheres, such as neurological changes (agenesis of the corpus callosum, AIDS), psychiatric disorders (depression) and in the prognosis of states of coma. Also, progressive neurone degeneration and neurochemical deficits characteristic of Alzheimer-type dementia suggest that the coherence EEG during the REM phase may give electrophysiological indices in the establishment of the diagnosis and prognosis of the disorder. CONCLUSION: This study shows that the coherence technique is a useful tool when establishing the pattern of cortico-cortical interactions subjacent to different functional states of the brain, both in healthy persons and in those with the different diseases in which there are alterations in cerebral function.

Spectral features of EEG alpha activity in human REM sleep: two variants with different functional roles?

Evidence suggests that an important contribution of spectral power in the alpha range is characteristic of human REM sleep. This contribution is, in part, due to the appearance of well-defined bursts of alpha activity not associated with arousals during both tonic and phasic REM fragments. The present study aims at determining if the REM-alpha bursts constitute a different alpha variant from the REM background alpha activity. Since previous findings showed a selective suppression of background alpha activity over occipital regions during phasic REM fragments and, on the other hand, the density of alpha bursts seem to be independent of the presence or absence of rapid eye movements, one expects to find the same spectral power contribution of alpha bursts in tonic and phasic REM fragments. The results indicated that REM-alpha bursts showed a similar power contribution and topographic distribution (maximum energy over occipital regions) both in tonic and phasic REM fragments. This suggests that two variants of alpha activity with different functional roles are present during the human REM sleep: i) background alpha activity, modulated over occipital regions by the presence of rapid eye movements, which may be an electrophysiological correlate of the visual dream contents; and ii) REM-alpha bursts, independent of the presence of rapid eye movements, which could be facilitating the connection between the dreaming brain and the external world, working as a micro-arousal in this brain state.