Obstructive sleep apneas naturally occur in mice during REM sleep and are more prevalent in a mouse model of Down syndrome

Study Objectives. The use of mouse models in sleep apnea research is limited by the belief that central (CSA) but not obstructive sleep apneas (OSA) occur in rodents. With this study we wanted to develop a protocol to look for the presence of OSAs in wild-type mice and, then, to apply it to a mouse model of Down Syndrome (DS), a human pathology characterized by a high incidence of OSAs. Methods. Nine C57Bl/6J wild-type mice were implanted with electrodes for electroencephalography (EEG), neck electromyography (nEMG), diaphragmatic activity (DIA) and then placed in a whole-body-plethysmographic (WBP) chamber for 8h during the resting (light) phase to simultaneously record sleep and breathing activity. The concomitant analysis of WBP and DIA signals allowed the discrimination between CSA and OSA. The same protocol was then applied to 12 Ts65Dn mice (a validated model of DS) and 14 euploid controls. Results. OSAs represented about half of the apneic events recorded during rapid-eye-movement sleep (REMS) in each experimental group while almost only CSAs were found during non-REMS. Ts65Dn mice had similar rate of apneic events than euploid controls but a significantly higher occurrence of OSAs during REMS. Conclusions. We demonstrated for the first time that mice physiologically exhibit both CSAs and OSAs and that the latter are more prevalent in the Ts65Dn mouse model of DS. These findings indicate that mice can be used as a valid tool to accelerate the comprehension of the pathophysiology of all kind of sleep apnea and for the development of new therapeutical approaches to contrast these respiratory disorders.

Development of functional MRI protocols in the study of neurodegenerative diseases: MRI study in patients with REM sleep behavior disorder, idiopathic Parkinson's disease and multisystem atrophy

In the central nervous system, iron in several proteins is involved in many important processes: oxygen transportation, oxidative phosphorylation, mitochondrial respiration, myelin production, the synthesis and metabolism of neurotransmitters. Abnormal iron homoeostasis can induce cellular damage through hydroxyl radical production, which can cause the oxidation, modification of lipids, proteins, carbohydrates, and DNA, lead to neurotoxicity. Moreover increased levels of iron are harmful and iron accumulations are typical hallmarks of brain ageing and several neurodegenerative disorders particularly PD. Numerous studies on post mortem tissue report on an increased amount of total iron in the substantia nigra in patients with PD also supported by large body of in vivo findings from Magnetic Resonance Imaging (MRI) studies. The importance and approaches for in vivo brain iron assessment using multiparametric MRI is increased over last years. Quantitative MRI may provide useful biomarkers for brain integrity assessment in iron-related neurodegeneration. Particularly, a prominent change in iron- sensitive T2* MRI contrast within the sub areas of the SN overlapping with nigrosome 1 were shown to be a hallmark of Parkinson's Disease with high diagnostic accuracy. Moreover, differential diagnosis between Parkinson's Disease (PD) and atypical parkinsonian syndromes (APS) remains challenging, mainly in the early phases of the disease. Advanced brain MR imaging enables to detect the pathological changes of nigral and extranigral structures at the onset of clinical manifestations and during the course of the disease. The Nigrosome-1 (N1) is a substructure of the healthy Substantia Nigra pars compacta enriched by dopaminergic neurons; their loss in Parkinson’s disease and atypical parkinsonian syndromes is related to the iron accumulation. N1 changes are supportive MR biomarkers for diagnosis of these neurodegenerative disorders, but its detection is hard with conventional sequences, also using high field (3T) scanner. Quantitative susceptibility mapping (QSM), an iron-sensitive technique, enables the direct detection of Neurodegeneration

L'influenza del sonno sull'andamento temporale della consolidazione delle abilità procedurali

Background: It is well known, since the pioneristic observation by Jenkins and Dallenbach (Am J Psychol 1924;35:605-12), that a period of sleep provides a specific advantage for the consolidation of newly acquired informations. Recent research about the possible enhancing effect of sleep on memory consolidation has focused on procedural memory (part of non-declarative memory system, according to Squire’s taxonomy), as it appears the memory sub-system for which the available data are more consistent. The acquisition of a procedural skill follows a typical time course, consisting in a substantial practice-dependent learning followed by a slow, off-line improvement. Sleep seems to play a critical role in promoting the process of slow learning, by consolidating memory traces and making them more stable and resistant to interferences. If sleep is critical for the consolidation of a procedural skill, then an alteration of the organization of sleep should result in a less effective consolidation, and therefore in a reduced memory performance. Such alteration can be experimentally induced, as in a deprivation protocol, or it can be naturally observed in some sleep disorders as, for example, in narcolepsy. In this research, a group of narcoleptic patients, and a group of matched healthy controls, were tested in two different procedural abilities, in order to better define the size and time course of sleep contribution to memory consolidation. Experimental Procedure: A Texture Discrimination Task (Karni & Sagi, Nature 1993;365:250-2) and a Finger Tapping Task (Walker et al., Neuron 2002;35:205-11) were administered to two indipendent samples of drug-naive patients with first-diagnosed narcolepsy with cataplexy (International Classification of Sleep Disorder 2nd ed., 2005), and two samples of matched healthy controls. In the Texture Discrimination task, subjects (n=22) had to learn to recognize a complex visual array on the screen of a personal computer, while in the Finger Tapping task (n=14) they had to press a numeric sequence on a standard keyboard, as quickly and accurately as possible. Three subsequent experimental sessions were scheduled for each partecipant, namely a training session, a first retrieval session the next day, and a second retrieval session one week later. To test for possible circadian effects on learning, half of the subjects performed the training session at 11 a.m. and half at 17 p.m. Performance at training session was taken as a measure of the practice-dependent learning, while performance of subsequent sessions were taken as a measure of the consolidation level achieved respectively after one and seven nights of sleep. Between training and first retrieval session, all participants spent a night in a sleep laboratory and underwent a polygraphic recording. Results and Discussion: In both experimental tasks, while healthy controls improved their performance after one night of undisturbed sleep, narcoleptic patients showed a non statistically significant learning. Despite this, at the second retrieval session either healthy controls and narcoleptics improved their skills. Narcoleptics improved relatively more than controls between first and second retrieval session in the texture discrimination ability, while their performance remained largely lower in the motor (FTT) ability. Sleep parameters showed a grater fragmentation in the sleep of the pathological group, and a different distribution of Stage 1 and 2 NREM sleep in the two groups, being thus consistent with the hypothesis of a lower consolidation power of sleep in narcoleptic patients. Moreover, REM density of the first part of the night of healthy subjects showed a significant correlation with the amount of improvement achieved at the first retrieval session in TDT task, supporting the hypothesis that REM sleep plays an important role in the consolidation of visuo-perceptual skills. Taken together, these results speak in favor of a slower, rather than lower consolidation of procedural skills in narcoleptic patients. Finally, an explanation of the results, based on the possible role of sleep in contrasting the interference provided by task repetition is proposed.

Studio dei ritmi circadiani in pazienti in stato vegetativo

Objective: To study circadian rhythms (sleep-wake, body core temperature and melatonin circadian rhythms) in patients in vegetative state (VS) in basal condition and after nocturnal blue light exposure. Methods: Eight patients in VS underwent two experimental sessions of 48 consecutive hours polysomnography with body core temperature (BCT) measurement separated by a 1-week interval. For a week between the two experimental sessions, patients underwent nocturnal blue light exposure (470 nm; 58 μW/cm2 for 4 hours from 11.30 p.m. to 3.30 a.m.). Brain MRI, Level of Cognitive Functioning Scale (LCF) and Disability Rating Scale (DRS) were assessed just before polysomnography. Results: In all patients LCF and DRS confirmed vegetative state. All patients showed a sleep-wake cycle. All patients showed spindle or spindle-like activities. REM sleep was detected in only 7 patients. Patients displayed a greater fragmentation of nocturnal sleep due to frequent awakenings. Mean nocturnal sleep efficiency was significantly reduced (40±22 vs. 74±17) in VS patients respect to controls. A significantly increasing of phase 1 and a significantly reduction of phase 2 and phase 3 were observed too. A modification of diurnal sleep total time and of diurnal duration of REM sleep were found after 1-week nocturnal blue light exposure. All patients displayed a normal BCT 24-h rhythm in basal condition and after nocturnal blue light exposure. A reduction of mean nocturnal melatonin levels in basal condition were observed in VS patients. Melatonin suppression after blue light exposure was observed in only 2 patients in VS. Conclusions: We found disorganized sleep-wake cycle and a normal BCT rhythm in our patients in VS. A reduction of mean nocturnal melatonin levels in basal condition were observed too.

Influenza dell'Omeostasi Idrico-Elettrolitica sul Ciclo Veglia-Sonno

During the wake sleep (W-S) cycle in mammals, the alternation of the different states, wake, NREM sleep (NREMS) and REM sleep (REMS), is associated not only with electroencephalographic or behavioural changes, but also with modifications in the physiological regulations of the organism. The most evident change is the existence of a suspension of the somatic and autonomic thermoregulatory responses during REMS. Since thermoregulation is prevalently controlled by the Preoptic Area-Anterior Hypothalamus (PO-AH), its suspension during REM sleep has been taken as a sign of an impairment of the hypothalamic integrative activity that could explain the modifications in physiological regulation observed in this sleep stage. The recent finding from our laboratory that the secretion of the antidiuretic hormone arginine-vasopressin (AVP) in response to a central osmotic stimulation is quantitatively the same throughout the different stages of the W-S cycle, has shown that hypothalamic osmoregulation is not suspended during REMS. In order to clarify the extent of the hypothalamic involvement in the regulation of the W-S cycle, we have studied the effects of three days of water deprivation and of two days of recovery during which animals were allowed a free access to water, on the architecture of the W-S cycle. The condition of water deprivation represents a severe challenge involving neuroendocrine and autonomic hypothalamic regulations. In contradiction with thermoregulatory studies, in which it has been clearly demonstrated that a thermal challenge selectively reduces REMS occurrence, the results of this study show that REMS occurrence is mildly reduced only in the third day of water deprivation. The most striking effects produced by water deprivation appear to concern NREMS, which shows a selective and significant reduction in its slow EEG activity (delta-power) but not in its duration. The recovery period is mainly characterized by a disruption of the normal circadian rhythm of REMS occurrence and by a rebound of the delta power in NREMS. Thus, an autonomic challenge different from those related to thermoregulation and an endocrine challenge as the continuous secretion of AVP show to exert different effects on the stages of the wake-sleep cycle. Also, this study demonstrates that the impairment of the hypothalamic integrative activity thought to characterize the occurrence of REMS only involves thermoregulatory structures.

Le funzioni metaboliche ed endocrinologiche nella narcolessia con cataplessia

Poco più di dieci anni fa, nel 1998, è stata scoperta l’ipocretina (ovvero orexina), un neuropeptide ipotalamico fondamentale nella regolazione del ciclo sonno-veglia, dell’appetito e della locomozione (de Lecea 1998; Sakurai, 1998; Willie, 2001). La dimostrazione, pochi mesi dopo, di bassi livelli di ipocretina circolanti nel liquido cefalo-rachidiano di pazienti affetti da narcolessia con cataplessia (Mignot 2002) ha definitivamente rilanciato lo studio di questa rara malattia del Sistema Nervoso Centrale, e le pubblicazioni a riguardo si sono moltiplicate. In realtà le prime descrizioni della narcolessia risalgono alla fine del XIX secolo (Westphal 1877; Gélineau 1880) e da allora la ricerca clinica è stata volta soprattutto a cercare di definire il più accuratamente possibile il fenotipo del paziente narcolettico. Accanto all’alterazione del meccanismo di sonno e di veglia, e dell’alternanza tra le fasi di sonno REM (Rapid Eye Movement) e di sonno non REM, sui quali l’ipocretina agisce come un interruttore che stimola la veglia e inibisce la fase REM, sono apparse evidenti anche alterazioni del peso e del metabolismo glucidico, dello sviluppo sessuale e del metabolismo energetico (Willie 2001). I pazienti narcolettici presentano infatti, in media, un indice di massa corporea aumentato (Dauvilliers 2007), la tendenza a sviluppare diabete mellito di tipo II (Honda 1986), un’aumentata prevalenza di pubertà precoce (Plazzi 2006) e alterazioni del metabolismo energetico, rispetto alla popolazione generale (Dauvilliers 2007). L’idea che, quindi, la narcolessia abbia delle caratteristiche fenotipiche intrinseche altre, rispetto a quelle più eclatanti che riguardano il sonno, si è fatta strada nel corso del tempo; la scoperta della ipocretina, e della fitta rete di proiezioni dei neuroni ipocretinergici, diffuse in tutto l’encefalo fino al ponte e al bulbo, ha offerto poi il substrato neuro-anatomico a questa idea. Tuttavia molta strada separa l’intuizione di un possibile legame dall’individuazione dei reali meccanismi patogenetici che rendano conto dell’ampio spettro di manifestazioni cliniche che si osserva associato alla narcolessia. Lo studio svolto in questi tre anni si colloca in questa scia, e si è proposto di esplorare il fenotipo narcolettico rispetto alle funzioni dell’asse ipotalamo-ipofisi-periferia, attraverso un protocollo pensato in stretta collaborazione fra il Dipartimento di Scienze Neurologiche di Bologna e l’Unità Operativa di Endocrinologia e di Malattie del Metabolismo dell’Ospedale Sant’Orsola-Malpighi di Bologna. L’ipotalamo è infatti una ghiandola complessa e l’approccio multidisciplinare è sembrato essere quello più adatto. I risultati ottenuti, e che qui vengono presentati, hanno confermato le aspettative di poter dare ulteriori contributi alla caratterizzazione della malattia; un altro aspetto non trascurabile, e che però verrà qui omesso, sono le ricadute cliniche in termini di inquadramento e di terapia precoce di quelle alterazioni, non strettamente ipnologiche, e però associate alla narcolessia.

Effetti termoregolatori ed ipnici indotti dalla stimolazione farmacologica del bulbo rostroventro mediale nel ratto

Recentemente è stato proposto che i premotoneuroni simpatici deputati al controllo della vasomozione cutanea siano localizzati nel bulbo rostoventromediale, una area che è delimitata rostralmente dal nucleo del nervo faciale (RVMM(io)) e causalmente dal polo rostrale del nucleo olivare inferiore (RVMM(io)). Per esplorare il ruolo che in neuroni contenuti nel RVMM(io) e nel (RVMM(fn) hanno nel controllare la vasomozione periferica, sono state effettuate in ciascuna delle due aree microiniezioni dell’agonista dei recettori GABAA muscimolo, dell’antagonista dei recettori GABAA bicucullina metiodide e di veicolo. La somministrazione di mucimolo induce una massiva vasodilatazione periferica sia se iniettato in RVMM(io) che in RVMM(fn). La disinibizione dei neuroni del RVMM(fn) produce invece una importate vasocostrizione periferica, antagonizzando la vasodilatazione indotta dall’esposizione ad alte temperature ambientali, mentre la disinibizione dei neuroni del RVMM(io) produce una vasodilatazione massimale, che è in grado di antagonizzare anche la vasocostrizione indotta da esposizione a bassa temperatura ambientale. L’inibizione sia dei neuroni del RVMM(io) che del RVMM(fn) induce inoltre modificazioni elettroencefalografiche e ipniche comparabili con quelle osservate durante il torpore. La somministrazione di muscimolo ha prodotto una rapida vasodilatazione periferica, seguita da una profonda ipotermia a da uno spostamento verso sinistra della banda Theta dell’EEG. Durante il periodo di ipotermia, la comparsa sia di sonno NREM che di sonno REM è risultata essere inibita. Questi dati mostrano che: a) a due popolazioni di premotoneuroni simpatici sono localizzati nella regione che va dal RVMM(io) al RVMM(fn), una termoregolatoria, tonicamente attiva e vasocostrittoria, l’altra non termoregolatoria, tonicamente inibita e vasodilatatoria; b) anche in una specie che non è va spontaneamente incontro a torpore, l’ipotermia centrale produce effetti elettroencefalografici simili a quelli osservati durante il torpore.

Cyclic alternating pattern in sleep and its relationship to creativity

Background/Objectives: Sleep has been shown to enhance creativity, but the reason for this enhancement is not entirely known. There are several different physiological states associated with sleep. In addition to rapid (REM) and non-rapid eye movement (NREM) sleep, NREM sleep can be broken down into Stages (1-4) that are characterized by the degree of EEG slow wave activity. In addition, during NREM sleep there are transient but cyclic alternating patterns (CAP) of EEG activity and these CAPs can also be divided into three subtypes (A1-A3) according to speed of the EEG waves. Differences in CAP ratios have been previously linked to cognitive performances. The purpose of this study was to learn the relationship CAP activity during sleep and creativity. Methods: The participants were 8 healthy young adults (4 women), who underwent 3 consecutive nights of polysomnographic recording and took the Abbreviated Torrance Test for Adults (ATTA) on the 2 and 3rd mornings after the recordings. Results: There were positive correlations between Stage 1 of NREM sleep and some measures of creativity such as fluency (R= .797; p=.029) and flexibility ( R=.43; p=.002), between Stage 4 of Non-REM sleep and originality (R= .779; p=.034) and a global measure of figural creativity (R= .758; p=.040). There was also a negative correlation between REM sleep and originality (R= -.827; p= .042) . During NREM sleep the CAP rate, which in young people is primarily the A1 subtype, also correlated with originality (R= .765; p =.038). Conclusions: NREM sleep is associated with low levels of cortical arousal and low cortical arousal may enhance the ability of people to access to the remote associations that are critical for creative innovations. In addition, A1 CAP activity reflects frontal activity and the frontal lobes are important for divergent thinking, also a critical aspect of creativity.

Studio degli aplogruppi mitocondriali nei pazienti con narcocataplessia

La narcolessia è un disturbo del sonno disabilitante caratterizzato da eccessiva sonnolenza diurna associata a disturbi del sonno REM che si manifestano con cataplessia (improvvisa perdita del tono muscolare scatenata da forti emozioni), paralisi del sonno (all’addormentamento o al risveglio) e allucinazioni ipnagogiche. Al momento attuale sono in corso studi di genome-wide solo sul genoma nucleare, l'unico ulteriore materiale genetico non indagato finora per una eventuale predisposizione genetica multifattoriale alla narcolessia è il genoma mitocondriale, che, a causa della sua variabilità, possiede un potenziale ruolo protettivo/predisponente nell’ambito di diverse malattie neurodegenerative, metaboliche ed infettive. Come obiettivo della tesi si propone la ricerca di eventuali polimorfismi sul DNA mitocondriale in grado di agire come fattori di suscettibilità/protezione nei confronti della narcolessia e di confermare quindi l’importante legame tra metabolismo bioenergetico, beta ossidazione e narcolessia. In particolare, vista la già nota capacità degli aplogruppi mitocondriali di modulare l’espressione di diverse malattie neurodegenerative, sono stati identificati i principali aplogruppi mitocondriali in un campione di pazienti con narcolessia successivamente confrontati con una popolazione di controllo per cercare eventuali differenze di distribuzione statisticamente significative tra le due popolazioni. I risultati presentati in questo studio completano con l’analisi del DNA mitocondriale i precedenti studi “genome wide”. L’assenza di associazione statisticamente significativa tra aplogruppi mitocondriali e narcolessia non esclude ancora il ruolo che la variabilità genetica del DNA mitocondriale può giocare nella patogenesi della narcolessia. La definitiva esclusione può essere conclusa solo espandendo la coorte dei pazienti studiati e considerando possibilmente origini etnico-geografiche diverse.

Longitudinal evolution of cognitive functions in patients with multiple system atrophy: a prospective study

Introduction and Background: Multiple system atrophy (MSA) is a sporadic, adult-onset, progressive neurodegenerative disease characterized clinically by parkinsonism, cerebellar ataxia, and autonomic failure. We investigated cognitive functions longitudinally in a group of probable MSA patients, matching data with sleep parameters. Patients and Methods: 10 patients (7m/3f) underwent a detailed interview, a general and neurological examination, laboratory exams, MRI scans, a cardiovascular reflexes study, a battery of neuropsychological tests, and video-polysomnographic recording (VPSG). Patients were revaluated (T1) a mean of 16±5 (range: 12-28) months after the initial evaluation (T0). At T1, the neuropsychological assessment and VPSG were repeated. Results: The mean patient age was 57.8±6.4 years (range: 47-64) with a mean age at disease onset of 53.2±7.1 years (range: 43-61) and symptoms duration at T0 of 60±48 months (range: 12-144). At T0, 7 patients showed no cognitive deficits while 3 patients showed isolated cognitive deficits. At T1, 1 patient worsened developing multiple cognitive deficits from a normal condition. At T0 and T1, sleep efficiency was reduced, REM latency increased, NREM sleep stages 1-2 slightly increased. Comparisons between T1 and T0 showed a significant worsening in two tests of attention and no significant differences of VPSG parameters. No correlation was found between neuropsychological results and VPSG findings or RBD duration. Discussion and Conclusions: The majority of our patients do not show any cognitive deficits at T0 and T1, while isolated cognitive deficits are present in the remaining patients. Attention is the cognitive function which significantly worsened. Our data confirm the previous findings concerning the prevalence, type and the evolution of cognitive deficits in MSA. Regarding the developing of a condition of dementia, our data did not show a clear-cut diagnosis of dementia. We confirm a mild alteration of sleep structure. RBD duration does not correlate with neuropsychological findings.

Regulation of wake-sleep states and state-dependent cardiovascular function in diet-induced obesity rats

Obesity often predisposes to coronary heart disease, heart failure, and sudden death. Also, several studies suggest a reciprocal enhancing interaction between obesity and sleep curtailment. Aim of the present study was to go deeper in the understanding of sleep and cardiovascular regulation in an animal model of diet-induced obesity (DIO). According to this, Wake-Sleep (W-S) regulation, and W-S dependent regulation of cardiovascular and metabolic/thermoregulatory function was studied in DIO rats, under normal laboratory conditions and during sleep deprivation and the following recovery period, enhancing either wake or sleep, respectively. After 8 weeks of the delivery of a hypercaloric (HC) diet, treated animals were heavier than those fed a normocaloric (NC) diet (NC: 441 ±17g; HC: 557±17g). HC rats slept more than NC ones during the activity period (Dark) of the normal 12h:12h light-dark (LD) cycle (Wake: 67.3±1.2% and 57.2 ±1.6%; NREM sleep (NREMS): 26.8±1.0% and 34.0±1.4%; REM sleep (REMS): 5.7±0. 6% and 8.6±0.7%; for NC and HC, respectively; p<0.05 for all). HC rats were hypertensive throughout the W-S states, as shown by the mean arterial blood pressure values across the 24-h period (Wake: 90.0±5.3 and 97.3±1.3; NREMS: 85.1±5.5 and 92.2±1.2; REMS: 87.2±4.5 and 96.5±1.1, mmHg for NC and HC, respectively; p<0.05 for all). Also, HC rats appeared to be slightly bradycardic compared to NC ones (Wake: 359.8±9.3 and 352.4±7.7; NREMS: 332.5±10.1 and 328.9±5.4; REMS: 338.5±9.3 and 334.4±5.8; bpm for NC and HC, respectively; p<0.05 for Wake). In HC animals, sleep regulation was not apparently altered during the sleep rebound observed in the recovery period following sleep deprivation, although REMS rebound appeared to be quicker in NC animals. In conclusion, these results indicate that in the rat obesity interfere with W-S and cardiovascular regulation and that DIO rats are suitable for further studies aimed at a better understanding of obesity comorbidities.

Effetti sulle funzioni autonomiche e sugli stati di veglia e di sonno della manipolazione centrale farmacologica del sistema ipocretinergico nel ratto

Obiettivo della tesi è stato quello di studiare il ruolo svolto dall’ipotalamo laterale (LH) nella regolazione dei processi di integrazione dell’attività autonomica e termoregolatoria con quella degli stati di veglia e sonno. A questo scopo, l’attività dell’LH è stata inibita per 6 ore (Esperimento A) mediante microiniezioni locali dell’agonista GABAA muscimolo nel ratto libero di muoversi, nel quale sono stati monitorati in continuo l’elelttroencefalogramma, l’elettromiogramma nucale, la pressione arteriosa (PA) e la temperatura ipotalamica (Thy) e cutanea. Gli animali sono stati studiati a temperatura ambientale (Ta) di 24°C e 10°C. I risultati hanno mostrato che l’inibizione acuta dell’LH riduce l’attività di veglia e sopprime la comparsa del sonno REM. Ciò avviene attraverso l’induzione di uno stato di sonno NREM caratterizzato da ipersincronizzazione corticale, con scomparsa degli stati transizionali al sonno REM. Quando l’animale è esposto a bassa Ta, tali alterazioni si associano a un ampio calo della Thy, che viene compensato da meccanismi vicarianti solo dopo un paio d’ore dall’iniezione. Sulla base di tali risultati, si è proceduto ad un ulteriore studio (Esperimento B) volto ad indagare il ruolo del neuropeptide ipocretina (prodotto in modo esclusivo a livello dell’LH) nei processi termoregolatori, mediante microiniezioni del medesimo nel bulbo rostrale ventromediale (RVMM), stazione cruciale della rete nervosa preposta all’attivazione dei processi termogenetici. La somministrazione di ipocretina è stata in grado di attivare la termogenesi e di potenziare la comparsa della veglia, con concomitante lieve incremento della PA e della frequenza cardiaca, quando effettuata alle Ta di 24°C o di 10°C, ma non alla Ta di 32°C. In conclusione, i risultati indicano che l’LH svolge un ruolo cruciale nella promozione degli stati di veglia e di sonno REM e, per tramite dell’ipocretina, interviene in modo coplesso a livello del RVMM nella regolazione dei processi di coordinamento dell'attività di veglia con quella termoregolatoria.

Sleep motor activity in parkinsonian syndromes at onset: a prospective study to determine potential diagnostic and prognostic markers

Aim of this study is to describe the possible diagnostic value of sleep disturbances in the differential diagnosis of neurodegenerative diseases characterized by parkinsonism at onset. 42 consecutive patients with parkinsonian features and disease duration up to 3 years were included in the BO-ProPark study. Each patient was evaluated twice, at baseline (T0) and 16 months later (T1). Patients were diagnosed as Parkinson disease (PD, 27 patients), PD plus (PD with cognitive impairment/dementia or dysautonomia, 4 patients) and parkinsonian syndrome (PS, 11 patients). All patients underwent a full night video-polysomnography scored by a neurologist blinded to the clinical diagnosis. Sleep efficiency and total sleep time were reduced in all patients; wake after sleep onset was higher in patients with atypical parkinsonisms than in PD patients. No significant differences between groups of patients were detected in other sleep parameters. The mean percentage of epochs with enhanced tonic muscle EMG activity during REM sleep was higher in PD plus and PS than in PD. No difference in phasic muscle EMG activity during REM sleep was seen between the two groups. REM behaviour disorder was more frequent in PD plus and PS than in PD patients. Our data suggest that REM sleep motor control is more frequently impaired at disease onset in patients with PS and PD plus compared to PD patients. The presence of RBD or an enhanced tonic muscle EMG activity in a patient with recent onset parkinsonian features should suggest a diagnosis of atypical parkinsonism, rather than PD. More data are needed to establish the diagnostic value of these features in the differential diagnosis of parkinsonisms. The evaluation of sleep disorders may be a useful tool in the differential diagnosis of parkinsonism at onset.