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Cerebrospinal fluid (CSF) amino acid (AA) levels and CSF/plasma AA ratios in Alzheimer Disease (AD) in relation to nutritional state are not known. Methods: In 30 fasting patients with AD (46% males, 74.4 ± 8.2 years; 3.4 ± 3.2 years from diagnosis) and nine control (CTRL) matched subjects, CSF and venous blood samples were drawn for AA measurements. Patients were stratified according to nutritional state (Mini Nutritional Assessment, MNA, scores). Results: Total CSF/plasma AA ratios were lower in the AD subpopulations than in NON-AD (p < 0.003 to 0.017. In combined malnourished (16.7%; MNA < 17) and at risk for malnutrition (36.6%, MNA 17–24) groups (CG), compared to CTRL, all essential amino acids (EAAs) and 30% of non-EAAs were lower (p < 0.018 to 0.0001), whereas in normo-nourished ADs (46.7%, MNA > 24) the CSF levels of 10% of EAAs and 25% of NON-EAAs were decreased (p < 0.05 to 0.00021). CG compared to normo-nourished ADs, had lower CSF aspartic acid, glutamic acid and Branched-Chain AA levels (all, p < 0.05 to 0.003). CSF/plasma AA ratios were

BackgroundPersistent systemic inflammation leads to multidistrectual body dysfunctions. Attenuation of inflammation may improve patients’ functional and life prognoses. We hypothesized that essential amino acids (EAAs) given to elderly patients in rehabilitation after acute diseases may be associated with a reduced inflammatory state. Therefore, this retrospective study investigated whether the supplementation of EAAs – modulators of immune competence – was associated with a reduced inflammation rate in elderly patients.MethodsThe medical records of 282 patients admitted to the rehabilitation (rehab) institute after acute index events (surgery or medical diseases) (age: 81.18 ± 8.58 years; females: 67.9%) were analyzed.Results46 patients (16.3% of the entire population) had received EAA supplements (S), whereas the remaining 236 patients had not (N-S). Systemic inflammation (I) (serum C-reactive protein (CRP) > 0.5 mg/dL) was present in 67.4% of the I-S group and 57.2% of the I-N-S group. During rehab, the I-S group (but not the I-N-S group) showed a reduction in CRP levels ( p = 0.03) and an increase in circulating lymphocytes ( p = 0.035), immune cells of the adaptive immune system. C-reactive protein levels remained virtually unchanged in non-inflamed patients who received supplements but increased in non-inflamed patients who did not receive supplements ( p = 0.05). Stratified for developed infections, CRP levels reduced in S patients ( p = 0.008) but did not in N-S patients.ConclusionEAA supplementation was associated with reduced inflammation in both inflamed and infected patients. In addition, EAA supplementation was associated with increased circulating lymphocytes in inflamed patients.

Conflicting results about alterations of plasma amino acid (AA) levels are reported in subjects with Alzheimer&rsquo, s disease (AD). The current study aimed to provide more homogeneous AA profiles and correlations between AAs and cognitive tests. Venous plasma AAs were measured in 54 fasting patients with AD (37 males, 17 females, 74.63 &plusmn, 8.03 yrs, 3.2 &plusmn, 1.9 yrs from symptom onset). Seventeen matched subjects without neurodegenerative symptoms (NNDS) served as a control group (C-NNDS). Patients were tested for short-term verbal memory and attention capacity and stratified for nutritional state (Mini Nutritional Assessment, MNA). Compared to C-NNDS, patients exhibited lower plasma levels of aspartic acid and taurine (p &lt, 0.0001) and higher 3-methylhistidine (p &lt, 0.0001), which were independent of patients&rsquo, MNA. In comparison to normonourished AD, the patients at risk of and with malnutrition showed a tendency towards lower ratios of Essential AAs/Total AAs, Branched-chain AAs/Total AAs, and Branched-chain AAs/Essential AAs. Serine and histidine were positively correlated with verbal memory and attention capacity deficits, respectively. Total AAs negatively correlated with attention capacity deficits. Stratifying patients with AD for MNA may identify a dual pattern of altered AAs, one due to AD per se and the other linked to nutritional state. Significant correlations were observed between several AAs and cognitive tests.

BACKGROUND Systemic inflammation and its impact on rehabilitation for patients with non-traumatic haemorrhagic injury (HBI) sequelae has not yet been adequately documented. OBJECTIVE AND METHODS We therefore considered 31 patients with HBI, to determine the serum levels of inflammatory markers (C-Reactive Protein, CRP and or interleukine-6, IL-6) to establish their impact on functional status (Functional Independence Measure, FIM: 18 indicating the worst performance and 126, a normal score). RESULTS The results showed an inflammation prevalence (CRP >0.5 mg/dl and/or IL 6 >7 pg/ml) of 74.2% at admission to Rehab. FIM reduction was more pronounced in inflamed compared to non-inflamed subjects (p < 0.05) and significantly correlated with blood variables sensitive to inflammation, such as alpha 1 globulin (r = - 0.565) and neutrophil/ lymphocyte ratio (r = - 0.52), CRP (r = - 0.365). At discharge from Rehab, the inflammation rate diminished. Inflamed patients showed similar gains in FIM score as their controls. In the entire population, the FIM gain was significantly associated with a gain in serum albumin, only (r = +0.56). CONCLUSIONS We conclude that systemic inflammation is prevalent in HBI patients and contributes to reduce patient functional status. However, during the Rehab stage, inflammation does not hinder the improvement rate of functional capacity.

BackgroundThis retrospective study had two main aims: (1) to document possible correlations between plasma Amino Acids (AAs) and circulating Albumin (Alb) and Haemoglobin (Hb); and (2) to identify which AAs were predictors of Alb and Hb.MethodsThe study considered 125 stroke subjects (ST) (61.6% males; 65.6 +/- 14.9 years) who met the eligibility criteria (absence of co morbidities associated with altered plasma AAs and presence of plasma AAs determined after overnight fasting). Fifteen matched healthy subjects with measured plasma AAs served as controls.ResultsThe best correlations of Alb were with tryptophan (Trp) and histidine (His) (r = + 0.53; p < 0.0001), and those of Hb were with histidine (r = +0.47) and Essential AAs (r = +0.47) (both pConclusionsThe study shows that the majority of plasma AAs were positively correlated with Alb and Hb. The best predictors of circulating Alb and Hb were the levels of tryptophan and glutamine, respectively.

To investigate whether supplementation with oral essential amino acids (EAAs) may reduce the occurrence of nosocomial infection among patients with brain injury (BI: stroke, trauma, anoxic coma).Patients (n = 125; 77 men, 48 women; mean age 63 ± 15 years) with stroke (68.8%), subarachnoid hemorrhage (17.6%), traumatic BI (7.2%), and anoxic BI (6.4%) 88 ± 15 days after the index event. Patients were randomly assigned to 2 months of oral EAAs (n = 63; 8 g/d) or placebo (n = 62).Over the first month of rehabilitation, there were 60 infections in the whole population of 125 patients (48%); however, the rate was 23.2% lower in the EAA group (23 episodes/63 patients; 36.5%) than in the placebo group (37 episodes/62 patients; 59.7%) (P.01). The types of infection were similarly distributed between the 2 groups. Serum levels of prealbumin20 mg/dL and C-reactive protein (CRP)0.3 mg/dL were the best predictors of future infection (prealbumin: odds ratio [OR] = 4.17, confidence interval [CI] 1.84-9.45, P.001; CRP: OR = 3.8, CI 1.71-8.44, P.001).Supplementary EAAs may reduce the occurrence of nosocomial infections in rehabilitation patients with BI. Prealbumin and CRP are the best predictors of future infections.

This study looks at the impact of inflammation during the rehabilitation stage of strokes and its effect on neuro-functional recovery.This study investigated 94 patients suffering from strokes and admitted to rehabilitation. Anthropometric characteristics, serum proteins and inflammatory markers, plasma amino acids and neurofunction were all assessed.55.3% patients had an inflammatory status (Interleukin-6 = 19.24 ± 23.01 pg ml⁻¹ vs. 4.1 ± 1.6 pg ml⁻¹ for non-inflamed subjects (p 0.001). Inflammation was positively linked to positive proteins (alpha-1 globulin, p 0.02) and negatively linked to negative proteins (albumin, p 0.02; prealbumin, p 0.01; transferrin, p 0.05) of the acute-phase response. Inflammation was associated with low plasma concentrations of total amino acids. For the multiple logistic regression analysis, albumin (p 0.001) and body weight maintenance (p 0.001) were independent predictors of patient functional independence. Inflammation in dysphagic stroke (31.9%) patients was associated with more accentuated disability compared to non-inflamed dysphagics. The serum positive reactant alpha 1 globulin was the most powerful predictor of dysphagia severity (p 0.001). At discharge, dysphagia improvement was associated with improved acute-phase negative proteins.An inflammatory status may persist for most patients with strokes during the rehabiliation stage of the disease, its prevalence being higher in dysphagic compared to non-dysphagic subjects. The improvement in circulating albumin and body weight maintenance are predictors of neuro-function, even in dysphagic subjects.

Alterations in muscle protein turnover of the unaffected side of stroke patients could contribute to physical disability. We investigated whether hypercatabolic activity occurred in unaffected arm muscle and whether supplemented essential amino acids (EAAs) could limit muscle hypercatabolism (MH). Thirty-eight dysphagic subacute stroke subjects (n= 19; EAA group) or isocaloric placebo (maltodextrin;n= 19, Plac group). Before randomization, all patients had their arterial (A) and venous (V) amino acids measured and muscle (A − V) differences calculated in the unaffected arm. Eight matched and healthy subjects served as controls. When compared to healthy controls, the entire stroke population showed significant muscle release (= negative value A − V) of the amino acid phenylalanine (phenyl-) indicating a prevalence of MH. Moreover, randomized EAA and Plac groups had similar rates of MH. After 38 days from the start of the protocol, the EAA group but not the Plac group had MH converted to balanced protein turnover or anabolic activity. We concluded that muscle protein metabolism of the unaffected arm of dysphagic subacute stroke individuals could be characterized by MH which can be corrected by supplemented EAAs.

Objectives : The present study aimed at offering a standardized database for cyclic alternating pattern (CAP) parameters across representative ages of life. Methods : CAP parameters were quantified in 40 healthy sleepers and polygraphically investigated in a partially sound-proof recording chamber under a standard laboratory setting. Four age groups were investigated (teenagers: 10–19 years; young adults: 20–39 years; middle-aged: 40–59 years; elderly: 60 years). Each group included 10 subjects (5 males and 5 females). Nocturnal recordings were accomplished after adaptation to the sleep laboratory that also served to rule out the presence of sleep-related disorders. The study indicated that CAP is a natural phenomenon of NREM sleep, with specific age-related characteristics across the life cycle. Results : CAP rate in NREM sleep, defined as the percentage ratio of total CAP time to total NREM sleep time, showed a U-shape profile with minimum in young adults (31.9%), maximum in the elderly group (55.3%), and intermediate values in teenagers (43.4%) and in middle-aged subjects (37.5%). The longest duration of CAP cycles was found among the older subjects (31 s). The highest amounts of subtypes A1 were identified in teenagers ( n =261), while the highest amounts of A2 and A3 subtypes occurred in the elderly group ( n =183). Across the ages, the level of arousal mostly fluctuated in stages 1 and 3, whereas stage 4 emerged as the most stable NREM stage. Overall, stage 2 better reflected the CAP values referred to as total NREM sleep. Conclusions : The periodic arousal fluctuations reflected by CAP are a natural phenomenon of NREM sleep with specific age-related variations across the life cycle.

There is evidence that sleep bruxism is an arousal-related phenomenon. In non-REM sleep, transient arousals recur at 20- to 40-second intervals and are organized according to a cyclic alternating pattern. Polysomnographic recordings from six subjects (two females and four males) affected by sleep bruxism (patients) and six healthy age-and gender-matched volunteers without complaints about sleep (controls) were analyzed to: (1) compare the sleep structure of bruxers with that of non-complaining subjects; and (2) investigate the relations between bruxism episodes and transient arousals. Patients and controls showed no significant differences in conventional sleep variables, but bruxers showed a significantly higher number of the transient arousals characterized by EEG desynchronization. Bruxism episodes were equally distributed between non-REM and REM sleep, but were more frequent in stages 1 and 2 (p < 0.0001) than in slow-wave sleep. The great majority of bruxism episodes detected in non-REM sleep (88%) were associated with the cyclic alternating pattern and always occurred during a transient arousal. Heart rate during the bruxism episodes (69.3 ± 18.2) was significantly higher (p < 0.0001) than that during the pre-bruxing period (58.1 ± 15.9). Almost 80% of all bruxism episodes were associated with jerks at the anterior tibial muscles. The framework of the cyclic alternating pattern offers a unified interpretation for sleep bruxism and arousal-related phenomena.

Since homogeneous samples of insomniacs are difficult to recruit for pharmacotherapy studies, normal sleepers can be used to assess the protective effect of hypnotic drugs, under standardized nonconducive conditions. In particular, a noisy environment is a typical cause of situational insomnia that can be counteracted by a sedative-hypnotic agent. Six healthy middle-aged subjects (three men and three women), with no complaints about sleep, underwent a completely randomized double-blind series of 10 nocturnal polysomnograms with at least 72-h washout intervals. All subjects received a single dose of placebo, zolpidem 10 mg, zopiclone 7.5 mg, lorazepam 1 mg, and triazolam 0.25 mg both under basal and under perturbed conditions. For each individual, five recordings were carried out under basal conditions (sound pressure level not higher than 30 dB) and five recordings under acoustically perturbed conditions (continuous white noise at 55 dB). Sleep quality was assessed by means of a visual analogue scale (VAS). All recordings were scored according to conventional rules (macro-structure) and cyclic alternating pattern (CAP) methodology (microstructure). Statistical analysis was based on a repeated measures analysis-of-variance design integrated by Bonferroni adjusted probabilities. Under placebo, situational insomnia was confirmed by the significant increase in sleep fragmentation (intrasleep wakefulness) and by the significant enhancement of arousal instability (CAP parameters). In contrast to macrostructural information, CAP parameters were highly sensitive in detecting the perturbing effects of noise (mean CAP rate under placebo, 57%) and the protective action of hypnotic drugs during perturbation (mean CAP rate under active medication, 41%). Microstructural analysis enabled us to discriminate hypnotic drugs from placebo, nonbenzodiazepine compounds from benzodiazepine agents, and zopiclone from zolpidem. The latter, in fact, induced the lowest values of CAP rate both under basal (30%) and under noisy (39%) conditions and determined a significant decrease in electroencephalogram arousals. All CAP parameters were significantly correlated with the visual-analogue-scale scores for sleep quality. The use of CAP methodology in a highly standardized model of situational insomnia can be a valid alternative to conventional sleep scoring for the investigation of drug effects on disturbed sleep.

Periodic limb movements in sleep (PLMS) is a disorder characterized by a cyclic pattern of motor phenomena and EEG changes (mostly arousals), both recurring at approximately 20- to 40-s intervals. The periodicity of the PLMS phenomena recalls the physiological EEG arousal rhythm of non-rapid eye movement (NREM) sleep known as the cyclic alternating pattern (CAP). During CAP, arousals and arousal-equivalent features do not appear as isolated events but periodically intrude (phase A) between intervals of background EEG activity (phase B). Though the A phases can be expressed by a variety of EEG patterns, each with a different arousal impact on polygraphic parameters, overall CAP is a sequence of biphasic cycles reflecting a condition of unstable sleep. Twelve middle-aged PLMS subjects complaining of poor sleep were polygraphically compared with 12 age-matched and gender-matched healthy volunteers (controls). With respect to controls, the PLMS recordings showed an enhancement of the more powerful arousals and presented significantly increased amounts of CAP time (+45 min) and CAP rate (+15%). Of all the jerks detected in NREM sleep, 92% occurred in CAP, with the great majority of limb movements (96%) associated with phase A. Ninety-four percent of the nocturnal jerks coupled with phase A started jointly with the onset of the phase or when the latter had already begun. In particular, most of the myoclonic events (67%) occurred in the first 2.5 s of the A phase. The CAP cycles coupled with periodic movements were significantly longer than those without motor events (+6.4 s). Compared to the American Sleep Disorders Association's rules for scoring EEG arousals, the CAP framework offers a more extensive insight into PLMS. In effect, the present study indicates an entrainment of nocturnal myoclonus by means of CAP and sheds light on the complex interactions between arousal mechanisms and motor phenomena during sleep.

Two separate groups of healthy subjects aged between 20 and 30 years underwent a random sequence of two non-consecutive polysomnographic recordings under standard conditions (night basal sleep) and after continuous sleep deprivation (recovery sleep). In the first group of 6 subjects (3 males and 3 females) recovery sleep occurred in the morning (after 24 h of prior waking); in the second group of 6 subjects (3 males and 3 females) recovery sleep occurred in the night (after 36 h of prior waking). In all cases the recording time was restricted to 500 minutes. Scoring was accomplished on conventional sleep variables and on Cyclic Alternating Pattern (CAP) parameters, while statistical analysis was based on a 2 x 2 ANOVA test. Compared to the night basal conditions, total sleep time and total NREM sleep were significantly longer in night recovery sleep and shorter in morning recovery sleep, respectively. No significant differences were found for sleep latency, intra-sleep awakenings, stage 2, REM sleep, NREM stages and slow-wave sleep. Total CAP time, CAP time in slow-wave sleep and all CAP rates were significantly higher in morning recovery sleep and lower in night recovery sleep. The enhanced amounts of CAP time and CAP rates during morning recovery sleep may be the outcome of two opposite forces, i.e. high sleep pressure versus maximum wake propensity. In contrast, the lower values of CAP during night recovery sleep suggest an in-phase associations between strong sleep pressure and the circadian clock.

Summary: Generalized interictal EEG discharges are influenced by a biphasic (phase A and B) modality of arousal control during non-rapid eye movement (REM) sleep termed cyclic alternating pattern (CAP). Each phase A and the following phase B compose a CAP cycle. The percentage ratio of total CAP time to total non-REM sleep time is the CAP rate, a sleep parameter that measures the instability and fragmentation of sleep. Since CAP exerts a powerful influence on generalized interictal EEG discharges during sleep, the polysomnograms of seven epileptic patients affected by a clinically active form of primary generalized epilepsy were matched with those of seven healthy volunteers of the same age and sex to assess the influence of interictal discharges on sleep organization. No remarkable differences emerged when the traditional polysomnographic parameters were compared between the two groups. However, the epileptic patients showed significantly higher CAP rate values (52.7 vs. 34.6% p < 0.003), indicating a greater arousal instability in the sleep records of these subjects. Within the epileptic group, the CAP cycles that included at least one interictal paroxysm were significantly longer than those without EEG discharges (31.2 vs. 25.4 s; p < 0.007). The selective lengthening of CAP cycles is likely due to an exaggeration of the natural activating power of phase A when coupled with EEG paroxysms and an intensification of the inhibitory properties of the following phase B. The dynamic relationships and differences between spindles in animals, k-complexes, and slow-wave bursts in humans may have a functional linkage with epileptic phenomena during sleep. RESUME Les decharges EEG intercritiques sont influencees par les modalites biphasiques (phase A et phase B) du controle des mecanismes d'eveil pendant le sommeil lent, encore appele pattern cyclique alternant (CAP). Chaque phase A et la phase B suivante composent un cycle de CAP. Le pourcentage du temps total en CAP a l'interieur de l'ensemble du sommeil lent represente le taux de CAP, un parametre de sommeil qui mesure I'instabilite et la fragmentation du sommeil. Comme le CAP a une influence importante sur les decharges EEG generalisees pendant le sommeil, les enregistrements polygraphiques de 7 patients epileptiques, suivis pour une forme cliniquement active d'epilepsie generalisee idiopathique, ont ete compares a ceux de 7 volontaires sains apparies pour I'age et le sexe, afin d'etudier I'influence des decharges intercritiques sur l'organisation du sommeil. II n'y a pas eu de differences notables lors de l'utilisation des parametres polysomnographiques traditionnels. Cependant, les patients epileptiques presentaient des valeurs significativement elevees du taux de CAP (52.7% contre 34.6%, p < 0.003), ce qui indique une plus grande instabilite des mecanismes d'eveil pendant le sommeil chez ces patients. Dans le groupe des patients epileptiques, les cycles de CAP comprenant au moins un paroxysme intercritique etait significativement plus long que ceux sans decharges EEG (31.2 secondes contre 25.4 secondes: p < 0.007). L'augmentation selective de duree des cycles de CAP est probablement liee a une exageration du pouvoir activateur nature1 de la phase A lorsqu'elle est couplee a des paroxysmes EEG, et a une intensification des proprietes inhibitrices de la phase B consecutive. Les relations dynamiques et les differences entre les fuseaux chez I'animal, les cas complexes et les bouffees d'ondes lentes chez l'homme, peuvent etre relies fonctionnellement aux phenomenes epileptiques survenant pendant le sommeil. RESUMEN Durante la fase del sueno no-REM, denominada patron ciclico alternante (CAP) las descargas generalizadas interictales en el EEG se modifican por una modalidad bifasica (fase A y B) del control del despertar. Cada fase A y las siguientes fases B componene un ciclo CAP. El porcentaje de la relacion entre el tiempo total de CAP y el tiempo de sueno no-REM se denomina relacion CAP, un parametro del sueno que mide la inestabilidad y fragmentacion del mismo. Puesto que CAP ejerce una influencia potente sobre las descargas generalizadas en el EEG interictal durante el sueno se han comparado los polisomnogramas de 7 enfermos epilepticos que padecian una forma activa clinicamente de epilepsia primaria generalizada con los polisomnogramas de 7 voluntarios sanos de la misma edad y sex0 para determinar la influencia de las descargas interictales sobre la organizacion del sueno. No han surgido diferencias notables cuando los parametros polisomnograficos tradicionales se compararon entre los dos grupos. Sin embargo, los enfermos epilepticos mostraron valores significativamente mas elevados de la relacion CAP (52.7%, 34.6%: p < 0.003), lo que indica una inestabilidad mas elevada en el despertar en los registros durante el sueno de estos sujetos. En el grupo de epilepticos, los ciclos de CAP, que incluian al menos un paroxismo interictal eran significativamente mas prolongados que los EEGs sin descargas (31.2 sec vs. 25.4 sec: p < 0.007). La prolongacion selectiva de los ciclos CAP se debe, probablemente, a una exageracion del poder de activacion natural que tiene la fase A cuando se acopla a paroxismos en el EEG y a una intensificacion de la propiedades inhibitorias de la fase B subsiguiente. La relaciones dinamicas y las diferencias existentes entre los husos en animales y los brotes de ondas lentas y complejos K pueden unirse funcionalmente con fenomenos epilepticos durante el sueno. ZUSAMMENFASSUNG Generalisierte interiktale EEG-Entladungen sind durch eine biphasische (Phase A und B) Modalitat der Arousal-Kontrolle wahrend des Non-REM-Schlafes beeinflusst, die als zyklisch alternierendes Muster (CAP) bezeichnet werden. Ein CAP-Zyklus besteht aus Phase A und der folgenden Phase B. Der prozentuale Anteil der CAP-ZEIT bezogen auf die gesamte NON-REM-Schlafzeit wird als CAP-Rate bezeichnet, ein Schlafparameter, der die Instabilitat und Fragmentation des Schlafes beschreibt. Da CAP einen starken Einfluβ auf generalisierte, interiktale Entladungen wahrend des Schlafes ausubt, wurden die Polysomnogramme von 7 Epileptikern mit einer klinisch aktiven Form einer primar generalisierten Epilepsie untersucht und mit den von 7 gesunden Freiwilligen des gleichen Alters und Geschlechtes verglichen, um den Einfluβ von interiktalen Entladungen auf die Schlaforganisation zu bestimmen. Bei den traditionellen Polysomnogrammparametern ergaben sich keine wesentlichen Unterschiede zwischen beiden Gruppen. Die Epilepsie-Patienten zeigten jedoch eine signifikant hohere CAP-Rate (52.7% gegenuber 34.6%: p < 0.003), was eine gronere Arousal-Instabilitat bei den Schlafableitungen dieser Personen anzeigt. Innerhalb der Epilepsie-Gruppe waren die CAP-Zyklen, die zumindest einen interiktalen Paroxysmus einschlossen, signifikant langer als in EEG-Ableitungen ohne Entladungen (31.2 Sek. gegenuber 25.4 Sek: p < 0.007). Die selektive Verlangerung der CAP-Zyklen ist wahrscheinlich durch ein uberschieβen der naturlich aktivierten Starke der Phase A bedingt, wenn sie an EEG-Paroxysmen gebunden ist, und eine Intensivierung von inhibitorischen Eigenschaften der folgenden Phase B. Die dynamischen Beziehungen und Unterschiede zwischen Spindeln bei Tieren, K-Komplexen und Slow Wave-Ausbruchen beim Menschen konnen eine funktionelle Beziehung zu epileptischen Phanomenen wahrend des Schlafs haben.

Aquilani R, Boselli M, Boschi F, Viglio S, Iadarola P, Dossena M, Pastoris O, Verri M. Branched-chain amino acids may improve recovery from a vegetative or minimally conscious state in patients with traumatic brain injury: a pilot study. Objective To investigate whether supplementation with branched-chain amino acids (BCAAs) may improve recovery of patients with a posttraumatic vegetative or minimally conscious state. Design Patients were randomly assigned to 15 days of intravenous BCAA supplementation (n=22; 19.6g/d) or an isonitrogenous placebo (n=19). Setting Tertiary care rehabilitation setting. Participants Patients (N=41; 29 men, 12 women; mean age, 49.5±21y) with a posttraumatic vegetative or minimally conscious state, 47±24 days after the index traumatic event. Intervention Supplementation with BCAAs. Main Outcome Measure Disability Rating Scale (DRS) as log 10 DRS. Results Fifteen days after admission to the rehabilitation department, the log 10 DRS score improved significantly only in patients who had received BCAAs (log 10 DRS score, 1.365±0.08 to 1.294±0.05; P 10 DRS score in the placebo recipients remained virtually unchanged (log 10 DRS score, 1.373±0.03 to 1.37±0.03; P not significant). The difference in improvement of log 10 DRS score between the 2 groups was highly significant ( P 10 DRS point score of .477 or higher (3 as geometric mean) that allowed them to exit the vegetative or minimally conscious state. Conclusions Supplemented BCAAs may improve the recovery from a vegetative or minimally conscious state in patients with posttraumatic vegetative or minimally conscious state.

Aquilani R, Iadarola P, Contardi A, Boselli M, Verri M, Pastoris O, Boschi F, Arcidiaco P, Viglio S. Branched-chain amino acids enhance the cognitive recovery of patients with severe traumatic brain injury. Objective To investigate whether supplementation with branched-chain amino acids (BCAAs) in patients with severe traumatic brain injury (TBI) improves recovery of cognition and influences plasma concentrations of tyrosine and tryptophan, which are precursors of, respectively, catecholamine and serotonin neurotransmitters in the brain. Design Forty patients with TBI were randomly assigned to 15 days of intravenous BCAA supplementation (19.6g/d) (n=20) or an isonitrogenous placebo (n=20). Setting Tertiary care rehabilitation setting in Italy. Participants Forty men (mean age, 32±15y) with TBI and 20 healthy subjects (controls) matched for age, sex, and sedentary lifestyle. Intervention Supplementation with BCAAs. Main Outcome Measures Disability Rating Scale (DRS) and plasma concentrations of BCAAs, tyrosine, and tryptophan. Results Fifteen days after admission to the rehabilitation department, the DRS score had improved significantly in both the placebo group ( P P P Conclusions Supplemental BCAAs enhance the retrieval of DRS without causing negative effects on tyrosine and tryptophan concentration.

Objective: To measure the readjustments of sleep macro- and microstructure in patients with obstructive sleep apnea syndrome (OSAS) after acute nasal continuous positive airway pressure (NCPAP) treatment. Background: The conventional polysomnographic analysis (macrostructure of sleep) does not necessarily provide the best measures of sleep disruption associated with OSAS. In contrast, microstructural methods of analyzing sleep (i.e., arousals and cyclic alternating pattern) may improve evaluation of patients with OSAS. Method:— Ten patients with OSAS were monitored polygraphically before and during the first night of NCPAP therapy. The results were compared with those of 10 age- and sex-matched controls without sleep-related breathing disorders. Each nocturnal recording was followed by daytime observation using the multiple sleep latency test and Visual Analogue Scale (VAS). Results: The first night of ventilatory therapy was characterized by a remarkable expansion of stages 3 and 4 and of REM sleep. In addition, NCPAP suppressed the presence of cyclic alternating pattern (CAP) in REM sleep and induced an impressive rebound of arousals and of certain CAP variables—i.e., CAP rate, CAP time, number of CAP cycles—which dropped well below the physiologic values expressed by controls. A normal duration of phases A and B was re-established starting the first treatment night. When we matched sleep variables with the indices of daytime function, a significant correlation emerged only between the variations of CAP rate and VAS scores. In particular, improvement of daytime sleepiness was less evident when the ventilatory-induced drop of CAP rate was more pronounced. Conclusions: The application of CAP variables to the microstructural analysis of sleep may expand our knowledge regarding sleep and respiration.

Objective: There is consolidated evidence that stage changes in sleep are closely related to spontaneous EEG fluctuations centered on the 20–40 periodicity of the cyclic alternating pattern (CAP). The present investigation aimed at assessing the involvement of the different components of CAP in the process of build-up, maintenance and demolition of deep non-REM (NREM) sleep. Methods: CAP parameters were quantified in the first 3 sleep cycles (SC1, SC2, SC3), selected from polysomnographic recordings of 25 healthy sound sleepers belonging to an extensive age range (10–49 years). Only ideal SCs were selected, i.e. the ones uninterrupted by intervening wakefulness and in which all stages were represented and linked in a regular succession of a descending branch, a trough and an ascending branch. Results: Among the first 3 SCs, a total amount of 45 (SC1, 16; SC2, 13; SC3, 16) met the inclusion requirements. SC1 contained the highest amount of slow wave sleep (43.7 min) and the lowest values of CAP rate (31.6%). The number of phase A1 subtypes remained unmodified across the 3 SCs (SC1, 48; SC2, 48; SC3, 48), whereas both subtypes A2 (SC1, 9; SC2, 14; SC3, 14) and A3 (SC1, 2; SC2, 8; SC3, 10) increased significantly (P

To test the effects of a hypnotic drug administered on a regular basis, six adults (four women and two men; mean age 37 years) who complained of transient or short-term insomnia, took zolpidem 10 mg at bedtime for 4 consecutive weeks. The period of active treatment, preceded by a baseline placebo night, ended with a 4-night gradual tapering phase followed by 3 nights of placebo administration. After adaptation to the sleep laboratory, all subjects underwent five polysomnographic recordings; baseline placebo (night 1); 1st, 7th and 28th nights of hypnotic medication (nights 2, 3, and 4 respectively); 3rd placebo night after complete tapering (night 5) and completed a morning visual analogue scale (VAS) for evaluating sleep quality. The sleep recordings were scored according to the conventional procedures (macrostructure) and to the cyclic alternating pattern (CAP) rules (microstructure). Data analysis was based on a repeated-measures analysis of variance integrated by post-hoc comparisons. At the macrostructural level, significant overall modifications (p < 0.035) emerged only from slow-wave sleep (SWS). The amounts of SWS were enhanced along the entire drug period, but a significant difference was found only between the baseline night (10%) and the first night of drug administration (20%). At the microstructural level, CAP rate (the ratio of CAP time to non-rapid eye movement sleep time) showed overall significant variations throughout the entire protocol period (p < 0.0001). Compared with baseline night 1 (59%), the CAP rate was significantly lower on drug nights 2 (32%), 3 (37%), and 4 (38%). The increase in the CAP rate found on night 5 (43%) was still significantly below the baseline value. The VAS scores showed significant overall changes (p < 0.0001), with improved values during the active treatment period.

Obstructive sleep apnea syndrome (OSAS) is characterized by multiple interruptions of airflow between periods of arousals. A key feature of OSAS is the 20- to 40-s cyclic pattern of electrophysiologic parameters. The periodicity of the OSAS-related phenomena is reminiscent of the natural electroencephalographic (EEG) arousal rhythm of non-rapid eye movement (NREM) sleep known as the cyclic alternating pattern (CAP). Morphologically, CAP consists of transient arousals (phase A) that periodically interrupt the tonic theta/delta activities of NREM sleep (phase B). Functionally, CAP translates a condition of sustained arousal instability oscillating between a greater arousal level (phase A) and a lesser arousal level (phase B). CAP is also related to the controls of the motor and autonomic mechanisms. On the basis of the information simultaneously derived from EEG activities, muscle tone, and neurovegetative responses, it is possible to distinguish three subtypes of A phases corresponding to different levels of arousal power: A1 (dominated by EEG synchronization and weak activation of polygraphic variables); A2 (mixture of EEG synchronization/desynchronization and intermediate activation of polygraphic variables); and A3 (dominated by EEG desynchronization and strong activation of polygraphic variables). Unlike standard criteria, CAP parameters offer a more suitable perspective for evaluating sleep pathologies in which brief and frequent arousals appear as a prominent feature. The present study aimed at (a) assessing CAP parameters in OSAS patients and (b) investigating the reciprocal interactions between CAP and the cyclic variations in respiratory rate. Twelve obese middle-aged OSAS subjects complaining of daytime sleepiness were polygraphically compared with age-matched and gender-matched volunteers in good health and with no complaints about sleep and wakefulness (controls). In OSAS patients, conventional parameters showed predictable decrements in total sleep time, slow wave sleep, and REM sleep and increases in stage 1 and nocturnal awakenings. Sleep fragmentation was associated with a significant enhancement of CAP and of the A phases with longer and more desynchronized EEG patterns (especially A3). The increase of A3 subtypes permitted scoring and detecting CAP also in REM sleep. The great majority of respiratory pauses (96% in NREM and 80% in REM sleep) were coupled with CAP. All CAP-related respiratory events rose in close temporal connection with a phase B, while effective breathing was always recovered during phase A (especially A2 and A3 subtypes). These data suggest that (a) phase B of CAP offers a vulnerable background for upper airway collapse and for attenuation of biochemical and neural mechanisms in the control of the ventilatory drive and (b) survival in OSAS patients is effected by the enhancement of the strongest components of the natural arousal rhythm at sleep quality's expense.

The standardized scoring criteria of sleep can serve as a rough tool for monitoring the effects of psychoactive compounds, both in normal sleepers and in insomniac patients. More sensitive information on the impact of perturbing factors and drugs during sleep is supplied by the cyclic alternating pattern (CAP) parameters. In particular, CAP rate, which measures the amount of arousal instability during NREM sleep, has been proved of high reliability in a variety of clinical and pharmacological settings. The present study aimed at evaluating the activity of brotizolam (Br) 0.25 mg and triazolam (Tr) 0.25 mg on both conventional and CAP parameters in a model of situational insomnia of intermediate severity. Six middle-aged healthy subjects (three males and three females, aged 40-55 years) with no complaints about sleep, underwent a polysomnographic investigation according to a double-blind crossover design: placebo without noise (night 1), placebo with noise (night 2), brotizolam or triazolam without noise (nights 3 and 5), brotizolam or triazolam with noise (nights 4 and 6). The unperturbed nights consisted of standard recording conditions in a sound-protected sleep laboratory, whereas situational insomnia was accomplished by means of continuous white noise at 55 dBA delivered throughout the night. Subjects received medication orally at bedtime. An interval of at least 48 h was secured between consecutive recordings in the same individual. Compared to baseline conditions, situational insomnia was characterized by a shorter amount of total sleep (-40 min) and by an extension of intrasleep awakenings (+62 min).(ABSTRACT TRUNCATED AT 250 WORDS)

Six middle aged subjects complaining of chronic insomnia associated with dysthymia were investigated in a 2-month single blind study: a 7-day placebo treatment period, followed by a 6-week phase with increasing doses of trazodone controlled release (CR) formulation (50 mg through days 8-10; 75 mg through days 11-13; 150 mg through days 14-49) and then a final 7-day withdrawal period under placebo. Medication was always administered at bedtime. Five polysomnographic recordings were accomplished by each subject (sleep 1: under baseline placebo; sleep 2-3-4; under active treatment; sleep 5: after drug discontinuation). A "blind" EEG reader analysed the traditional polysomnographic variables (macrostructure of sleep) and the amount and percentage ratio (CAP rate) of cyclic alternating pattern (CAP), the microstructural parameter that measures the instability of arousal during sleep. Visual analogue scales (VAS) for the evaluation of subjective sleep quality and the Hamilton rating scale for depression (HAM-D) were regularly assessed across the study. Statistical analysis was based on an ANOVA test with repeated measures completed by means of Bonferroni adjusted probabilities. No significant differences emerged from the macrostructural parameters referred to sleep initiation and maintenance, while significant overall modifications emerged from stage 2 (P < 0.0005), slow wave sleep (P < 0.0001), total CAP time (P < 0.0001) and CAP rate (P < 0.0001). Compared to the placebo baseline night, a significant increase of slow wave sleep (+40 min) and significant reductions of stage 2 (-67 min), CAP time (-90 min) and CAP rate (-23%) were already found on day 4 of treatment (sleep 2).(ABSTRACT TRUNCATED AT 250 WORDS)