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[EN] Aging affects sleep and sleep problems are common in older individuals. However, the relationship between objective and subjective tools for analysing sleep and psycho-geriatric variables have not been tested in institutionalised older individuals. This work analyses sleep quality by using actigraphy as an objective tool and validates the Athens and Oviedo sleep questionnaires in octogenarian elderly individuals as subjective scales of sleep perception. All patients wore an actigraph device for one week and then completed the Athens and Oviedo clinical sleep-evaluation questionnaires. Morning cortisol levels in blood plasma and saliva samples were also measured to assess the association between objective and reported sleep patterns. Age, gender, and psycho-geriatric evaluations, including Barthel, Tinetti, and Mini-Mental scale measurements were analysed as variables with the potential to confound the strength of any such associations. There was a significant inverse correlation between the number of awakenings and the time spent awake during night assessed by actigraphy and the total Oviedo questionnaire score, but no significant associations for the other parameters. The blood cortisol concentration appears to be a marker of insomnia related to sleep times of less than four hours and diagnosis of insomnia based on Athens scale and thus, represents a potential marker for sleep interventions.

[EN] Purpose. A literature review is presented that aims to summarize and compare curren methods to evaluate sleep. Methods. Current sleep assessment methods have been classified according to different. criteria; e.g., objective (polysomnography actigraphy) vs.subjective (sleep questionnaires, diaries...), contact vs. contactless devices, and need for medical assistance vs. self-assessment. A comparison of validation studies is carried out for each method, identifying their sensitivity and specificity reported in the literature. Finally, the state of the market has also been reviewed with respect to customers' opinions about current sleep apps. Results. A taxonomy that classifies the sleep, detection methods. IA deseriPtion of each method that includes the tendencies of their underlying technologies lanalyzed in accordance with the literature. A comparison in terms, of precision of existing validation studies and reports. Discussion. In order of accuracy, sleep detection methods may be arranged as follows: Questionnaire < Sleep diary < Contactless devices < Contact devices < Polysotnnography A literature review suggests that current subjective methods present a sensitivity between 73% and 97.7%, while their specificity ranges in the interval 50%-96%. Objective methods such as actigraphy present a sensibility higher than 90%. However, their specificity is low compared to their sensitivity, being one of the limitations of such technology. Moreover, there are other factors, such as the Patients Perception of her or his sleep, that can be provided only by subjective methods. Therefore, sleep detection methods should be combined to produce a synergy between objective and subjective methods. The review of the market indicates the most valued sleep apps, but it also identifies problems and gaps, e.g., many hardware devices have not been validated and (especially software apps) should be studied before their clinical use.

[EN] Sleep assessment is a fundamental part of health evaluation. In fact, many diseases (such as obesity, diabetes, or hypertension, as well as psychiatric, neurological, and cardiovascular diseases) produce sleep disorders that are often used as indicators, diagnosis (symptoms), or even as predictors (eg, for depression) of health. For this reason, many efforts have been devoted to designing methods to control and report on sleep quality. Two of the most used sleep assessment tools are sleep questionnaires and sleep diaries. Both methods have a very low cost are easy to administer do not require a sleep centre (unlike, eg, polysomnography), and can be self-administered. Most important, as it has been shown in recent studies, their accuracy is relatively high. In this survey, we systematically review and compare these tools. We examine the evolution of sleep questionnaires and diaries over time, and compare their structure and usage. We also review the validation studies and comparatives performed in previous studies. This allows us to compare the relative sensitivities and specificities of these methods. Modern sleep diaries come in the form of an app. Therefore, we also present the most advanced and used apps, and discuss their advantages over classical paper diaries.

Treatment of patients with acute liver failure (ALF) is unsatisfactory and mortality remains unacceptably high. Blocking NMDA receptors delays or prevents death of rats with ALF. The underlying mechanisms remain unclear. Clarifying these mechanisms will help to design more efficient treatments to increase patient's survival. The aim of this work was to shed light on the mechanisms by which blocking NMDA receptors delays rat's death in ALF. ALF was induced by galactosamine injection. NMDA receptors were blocked by continuous MK-801 administration. Edema and cerebral blood flow were assessed by magnetic resonance. The time course of ammonia levels in brain, muscle, blood, and urine; of glutamine, lactate, and water content in brain; of glomerular filtration rate and kidney damage; and of hepatic encephalopathy (HE) and intracranial pressure was assessed. ALF reduces kidney glomerular filtration rate (GFR) as reflected by reduced inulin clearance. GFR reduction is due to both reduced renal perfusion and kidney tubular damage as reflected by increased Kim-1 in urine and histological analysis. Blocking NMDA receptors delays kidney damage, allowing transient increased GFR and ammonia elimination which delays hyperammonemia and associated changes in brain. Blocking NMDA receptors does not prevent cerebral edema or blood-brain barrier permeability but reduces or prevents changes in cerebral blood flow and brain lactate. The data show that dual protective effects of MK-801 in kidney and brain delay cerebral alterations, HE, intracranial pressure increase and death. NMDA receptors antagonists may increase survival of patients with ALF by providing additional time for liver transplantation or regeneration. © 2013 Springer Science+Business Media New York.

[Background & Aims]: Low-grade cytotoxic oedema is considered a main contributor to the neurological (motor and cognitive) alterations in patients with hepatic encephalopathy (HE). This assumption is mainly based on studies with cultured astrocytes treated with very large ammonia concentrations or with animal models of acute liver failure with strong HE. However, the possible contribution of cerebral oedema (vasogenic or cytotoxic) to cognitive or motor alterations in chronic mild HE has not been demonstrated. The aim of this work was to assess whether cerebral oedema contributes to cognitive and/or motor alterations in rats with chronic mild HE. [Methods]: Motor activity and coordination and different types of learning and memory were assessed in rats with porta-caval shunts (PCS). Brain oedema was assessed by gravimetry in cerebellum and cortex and apparent diffusion coefficient (ADC) by magnetic resonance in 16 areas. [Results]: Four weeks after surgery, PCS rats show reduced motor activity and coordination, impaired ability to learn a conditional discrimination task in the Y maze and reduced spatial memory in the Morris water maze. PCS rats did not show increased brain water content at 4 or 10 weeks or changes in ADC at 4 weeks. At 10 weeks, increased ADC in some areas is compatible with vasogenic but not cytotoxic oedema. [Conclusion]: Cerebral oedema is not involved in motor and cognitive alterations in rats (and likely in humans) with mild HE. Proper understanding of the mechanisms responsible for the neurological alterations in HE is necessary to design efficient treatments. © 2013 John Wiley & Sons A/S.

[Background]: Glioblastoma, the most frequent and aggressive of all astrocytomas, presents a clear predominance in male humans, but the assessment of sexual differences in its tumourigenesis and growth has received little attention so far. In this study, we aim to identify gender-dependent surrogate markers in an animal model of this cancer by means of magnetic resonance (MR) imaging and biochemical and behavioural studies., [Methods]: A high-grade glioma model developed in male and female rats was used. Multiparametric magnetic resonance images and localized spectra were acquired. The MR parameters linked to tumoural features were quantified. Motor and metabolic activity was also assessed. Postmortem analyses were carried out to measure indicators of malignancy, tumoural metabolism and viability of the blood-brain barrier (BBB)., [Results]: Statistically significant differences dependent on the animal sex were found in the study of pathological indicators like oedema, inflammation, cellularity and microvasculature. Results suggest higher cell proliferative rate, inflammation and vasogenic oedema and or necrosis in glioma-bearing male rats. Haemodynamic parameters measured indicated a major disruption of the BBB, postmortem confirmed, in this sex. Metabolomic and energetic metabolism activity data are in agreement with a major malignancy and aggressiveness of this cancer model on males., [Conclusions]: Gender differences should be taken into account in preclinical studies of glioblastoma models, in the characterization of the tumoural behaviour and consequently in the development and validation of new therapeutic approaches. MR imaging and spectroscopy allow to non-invasively monitor this sexual dimorphism in the diagnosis and prognosis of brain cancer.

[Background and Aims]: Patients with acute liver failure (ALF) often die of intracranial pressure (IP) and cerebral herniation. Main contributors to increased IP are ammonia, glutamine, edema, and blood flow. The sequence of events and underlying mechanisms, as well as the temporal pattern, regional distribution, and contribution of each parameter to the progression of neurologic deterioration and IP, are unclear. We studied rats with ALF to follow the progression of changes in ammonia, glutamine, grade and type (vasogenic or cytotoxic) of edema, blood-brain barrier permeability, cerebral blood flow, and IP. We assessed whether the changes in these parameters were similar between frontal cortex and cerebellum and evaluated the presence, type, and progression of edema in 12 brain areas. [Methods]: ALF was induced by injection of galactosamine. The grade and type of edema was assessed by measuring the apparent diffusion coefficient by magnetic resonance imaging. Cerebral blood flow was measured by magnetic resonance and blood-brain barrier permeability by Evans bluealbumin extravasation. [Results]: Increased IP arises from an early increase of bloodbrain barrier permeability in certain areas (including cerebellum but not frontal cortex) followed by vasogenic edema. Ammonia and glutamine then increase progressively, leading to cytotoxic edema in many areas. Alterations in lactate and cerebral blood flow are later events that further increase IP. [Conclusions]: Different mechanisms in specific regions of the brain contribute, with different temporal patterns, to the progression of cerebral alterations and IP in ALF. © 2011 AGA Institute.

In liver failure, congenital enzymopathies of the urea cycle, and other disorders, ammonia may not be properly detoxified and thus hyperammonemia ensues. Hyperammonemia is considered one of the main factors leading to cerebral edema and related consequences (increased intracranial pressure, brain herniation, and death). Cerebral edema is a critical component of neurological status impairment in patients with hyperammonemia and hepatic encephalopathy (HE). Although cerebral edema is generally classified as cytotoxic (cellular) and vasogenic (extracellular), both components often coexist in the same patient. Both types of edema can occur in acute hyperammonemia and liver failure with cytotoxic edema being a consequence of astrocytes swelling and vasogenic edema, mainly due to blood-brain barrier (BBB) disruption. It is well known that hyperammonemia is a crucial factor in astrocytes swelling and increased BBB permeability; however, the molecular mechanisms by which ammonia causes these alterations are not completely understood. Aquaporins (water channels) are one of the main pathways leading to water influx into the brain and efflux from the brain; consequently, it is conceivable brain aquaporins disturbances are involved in the pathophysiology of cerebral edema in hyperammonemia and HE. This review summarizes brain aquaporins main functions and distribution, and particularly, the aquaporin 4 (AQP-4) alterations induced under hyperammonemia and acute liver failure (ALF).

Diffusion-weighted imaging (DWI) allows the assessment of the water apparent diffusion coefficient (ADC), a measure of tissue water diffusivity which is altered during different pathological conditions such as cerebral oedema. By means of DWI, we repeatedly measured in the same rats apparent diffusion coefficient ADC in different brain areas (motor cortex (MCx), somato-sensory cortex (SCx), caudate-putamen (CPu), hippocampus (Hip), mesencephalic reticular formation (RF), corpus callosum (CC) and cerebellum (Cb)) after 1 week, 4 and 12 weeks of lead acetate exposure via drinking water (50 or 500ppm). After 12 weeks of lead exposure rats received albumin-Evans blue complex administration and were sacrified 1h later. Blood-brain barrier permeability and water tissue content were determined in order to evaluate their relationship with ADC changes. Chronic exposure to lead acetate (500ppm) for 4 weeks increased ADC values in Hip, RF and Cb but no in other brain areas. After 12 weeks of lead acetate exposure at 500ppm ADC is significantly increased also in CPu and CC. Brain areas displaying high ADC values after lead exposure showed also an increased water content and increased BBB permeability to Evans blue-albumin complex. Exposure to 50ppm for 12 weeks increased ADC values and BBB permeability in the RF and Cb. In summary, chronic lead exposure induces cerebral oedema in the adult brain depending on the brain area and the dose of exposure. RF and Cb appeared the most sensitive brain areas whereas cerebral cortex appears resistant to lead-induced cerebral oedema.

Acute ammonia intoxication leads to rapid death, which is prevented by blocking N-methyl-d-aspartate (NMDA) receptors. The subsequent mechanisms leading to death remain unclear. Brain edema seems an important step. The aim of this work was to study the effects of acute ammonia intoxication on different cerebral parameters in vivo using magnetic resonance and to assess which effects are mediated by NMDA receptors activation. To assess edema induction, we injected rats with ammonium acetate and measured apparent diffusion coefficient (ADC) in 16 brain areas. We also analyzed the effects on T1, T2, and T2* maps and whether these effects are prevented by blocking NMDA receptors. The effects of acute ammonia intoxication are different in different brain areas. T1 relaxation time is reduced in eight areas. T2 relaxation time is reduced only in ventral thalamus and globus pallidus. ADC values increased in hippocampus, caudate-putamen, substantia nigra and cerebellar cortex, reflecting vasogenic edema. ADC decreased in hypothalamus, reflecting cytotoxic edema. Myo-inositol increased in cerebellum and substantia nigra, reflecting vasogenic edema. N-acetyl-aspartate decreased in cerebellum, reflecting neuronal damage. Changes in N-acetyl-aspartate, T1 and T2 are prevented by blocking NMDA receptors with MK-801 while changes in ADC or myo-inositol (induction of edema) are not. © 2007 The Authors.