Revisione critica dei risultati e nuovi algoritmi decisionali sulla chirurgia dell'OSAS

Obstructive sleep apnoea/hypopnoea syndrome (OSAHS) is the periodic reduction or cessation of airflow during sleep. The syndrome is associated whit loud snoring, disrupted sleep and observed apnoeas. Surgery aims to alleviate symptoms of daytime sleepiness, improve quality of life and reduce the signs of sleep apnoea recordered by polysomnography. Surgical intervention for snoring and OSAHS includes several procedures, each designed to increase the patency of the upper airway. Procedures addressing nasal obstruction include septoplasty, turbinectomy, and radiofrequency ablation (RF) of the turbinates. Surgical procedures to reduce soft palate redundancy include uvulopalatopharyngoplasty with or without tonsillectomy, uvulopalatal flap, laser-assisted uvulopalatoplasty, and RF of the soft palate. More significant, however, particularly in cases of severe OSA, is hypopharyngeal or retrolingual obstruction related to an enlarged tongue, or more commonly due to maxillomandibular deficiency. Surgeries in these cases are aimed at reducing the bulk of the tongue base or providing more space for the tongue in the oropharynx so as to limit posterior collapse during sleep. These procedures include tongue-base suspension, genioglossal advancement, hyoid suspension, lingualplasty, and maxillomandibular advancement. We reviewed 269 patients undergoing to osas surgery at the ENT Department of Forlì Hospital in the last decade. Surgery was considered a success if the postoperative apnea/hypopnea index (AHI) was less than 20/h. According to the results, we have developed surgical decisional algorithms with the aims to optimize the success of these procedures by identifying proper candidates for surgery and the most appropriate surgical techniques. Although not without risks and not as predictable as positive airway pressure therapy, surgery remains an important treatment option for patients with obstructive sleep apnea (OSA), particularly for those who have failed or cannot tolerate positive airway pressure therapy. Successful surgery depends on proper patient selection, proper procedure selection, and experience of the surgeon. The intended purpose of medical algorithms is to improve and standardize decisions made in the delivery of medical care, assist in standardizing selection and application of treatment regimens, to reduce potential introduction of errors. Nasal Continuous Positive Airway Pressure (nCPAP) is the recommended therapy for patients with moderate to severe OSAS. Unfortunately this treatment is not accepted by some patient, appears to be poorly tolerated in a not neglible number of subjects, and the compliance may be critical, especially in the long term if correctly evaluated with interview as well with CPAP smart cards analysis. Among the alternative options in Literature, surgery is a long time honoured solution. However until now no clear scientific evidence exists that surgery can be considered a really effective option in OSAHS management. We have design a randomized prospective study comparing MMA and a ventilatory device (Autotitrating Positive Airways Pressure – APAP) in order to understand the real effectiveness of surgery in the management of moderate to severe OSAS. Fifty consecutive previously full informed patients suffering from severe OSAHS were enrolled and randomised into a conservative (APAP) or surgical (MMA) arm. Demographic, biometric, PSG and ESS profiles of the two group were statistically not significantly different. One year after surgery or continuous APAP treatment both groups showed a remarkable improvement of mean AHI and ESS; the degree of improvement was not statistically different. Provided the relatively small sample of studied subjects and the relatively short time of follow up, MMA proved to be in our adult and severe OSAHS patients group a valuable alternative therapeutical tool with a success rate not inferior to APAP.

Sonno e funzioni cognitive: ruolo della microstruttura del sonno NREM

STUDY OBJECTIVE: Cyclic Alternating Pattern (CAP) is a fluctuation of the arousal level during NREM sleep and consists of the alternation between two phases: phase A (divided into three subtypes A1, A2, and A3) and phase B. A1 is thought to be generated by the frontal cortex and is characterized by the presence of K complexes or delta bursts; additionally, CAP A1 seems to have a role in the involvement of sleep slow wave activity in cognitive processing. Our hypothesis was that an overall CAP rate would have a negative influence on cognitive performance due to excessive fluctuation of the arousal level during NREM sleep. However, we also predicted that CAP A1 would be positively correlated with cognitive functions, especially those related to frontal lobe functioning. For this reason, the objective of our study was to correlate objective sleep parameters with cognitive behavioral measures in normal healthy adults. METHODS: 8 subjects (4 males; 4 females; mean age 27.75 years, range 2334) were recruited for this study. Two nocturnal polysomnography (night 2 and 3 = N2 and N3) were carried out after a night of adaptation. A series of neuropsychological tests were performed by the subjects in the morning and afternoon of the second day (D2am; D2pm) and in the morning of the third day (D3am). Raw scores from the neuropsychological tests were used as dependent variables in the statistical analysis of the results. RESULTS: We computed a series of partial correlations between sleep microstructure parameters (CAP, A1, A2 and A3 rate) and a number of indices of cognitive functioning. CAP rate was positively correlated with visuospatial working memory (Corsi block test), Trial Making Test Part A (planning and motor sequencing) and the retention of words from the Hopkins Verbal Learning Test (HVLT). Conversely, CAP was negatively correlated with visuospatial fluency (Ruff Figure Fluency Test). CAP A1 were correlated with many of the tests of neuropsychological functioning, such as verbal fluency (as measured by the COWAT), working memory (as measured by the Digit Span – Backward test), and both delay recall and retention of the words from the HVLT. The same parameters were found to be negatively correlated with CAP A2 subtypes. CAP 3 were negatively correlated with the Trial Making Test Parts A and B. DISCUSSION: To our knowledge this is the first study indicating a role of CAP A1 and A2 on behavioral cognitive performance of healthy adults. The results suggest that high rate of CAP A1 might be related to an improvement whereas high rate of CAP A2 to a decline of cognitive functions. Further studies need to be done to better determine the role of the overall CAP rate and CAP A3 on cognitive behavioral performances.

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.

Aspetti cognitivi dell'epilessia frontale notturna

Si tratta di uno studio osservazionale analitico di coorte prospettico volto a rilevare disfunzioni neuropsicologiche nei pazienti affetti da epilessia frontale notturna, attraverso una batteria di test che esplora i seguenti domini cognitivi: intelligenza generale, memoria, linguaggio, funzioni esecutive, attenzione, vigilanza, tempi di reazione, percezione della qualità della vita ed eventuale presenza di sintomi psichiatrici. Lo studio ha un follow up medio di 20 anni e riporta, per la prima volta in letteratura, l’evoluzione clinica dei soggetti che hanno avuto un esordio dell’epilessia in età evolutiva. Fino ad ora, l’epilessia frontale notturna è stata associata a disfunzioni cognitive nei soli casi di famiglie affette e nelle quali è stato possibile rilevare il difetto genetico. Questo studio ha rilevato la prevalenza di disturbi cognitivi e psichici in un campione di 24 soggetti affetti, mediante la somministrazione di una batteria di test specifica. I risultati sono stati analizzati con il programma statistico SPSS. Tutti i soggetti presentano abilità cognitive inferiori alla media in uno o più test ma il quoziente intellettivo risulta normale nei tre quarti del campione. Il ritardo mentale è più frequente e più grave nei soggetti idiopatici rispetto a quelli con alterazioni morfologiche frontali rilevate alla risonanza magnetica. Sono risultati più frequenti i disturbi della memoria, soprattutto quella a lungo termine e del linguaggio rispetto a quelli di tipo disesecutivo. Tutti i soggetti, che non hanno ottenuto un controllo delle crisi, manifestano una percezione della qualità della vita inferiore alla media. E’ stata valutata l’influenza delle variabili cliniche (età di esordio dell’epilessia, frequenza e semeiologia delle crisi, durata della malattia e terapia antiepilettica), le anomalie elettroencefalografiche e le anomalie rilevate alla risonanza magnetica. Le variabili che sono in rapporto con un maggiore numero di disfunzioni neuropsicologiche sono: l’elevata frequenza di crisi all’esordio, l’associazione con crisi in veglia, la presenza di crisi parziali secondariamente generalizzate e l’assunzione di una politerapia. I disturbi psichici prevalgono nei soggetti con anomalie elettroencefalografiche frontali sinistre. I dati neuropsicologici suggeriscono una disfunzione cognitiva prevalentemente fronto-temporale e, assieme ai dati clinici ed elettroencefalografici, sembrano confermare l’origine mesiale e orbitale frontale delle anomalie epilettiche nell’epilessia frontale notturna.

Wavelet analysis of heart rate variability related to nocturnal frontal lobe epilepsy seizures

Introduction: Nocturnal frontal lobe epilepsy (NFLE) is a distinct syndrome of partial epilepsy whose clinical features comprise a spectrum of paroxysmal motor manifestations of variable duration and complexity, arising from sleep. Cardiovascular changes during NFLE seizures have previously been observed, however the extent of these modifications and their relationship with seizure onset has not been analyzed in detail. Objective: Aim of present study is to evaluate NFLE seizure related changes in heart rate (HR) and in sympathetic/parasympathetic balance through wavelet analysis of HR variability (HRV). Methods: We evaluated the whole night digitally recorded video-polysomnography (VPSG) of 9 patients diagnosed with NFLE with no history of cardiac disorders and normal cardiac examinations. Events with features of NFLE seizures were selected independently by three examiners and included in the study only if a consensus was reached. Heart rate was evaluated by measuring the interval between two consecutive R-waves of QRS complexes (RRi). RRi series were digitally calculated for a period of 20 minutes, including the seizures and resampled at 10 Hz using cubic spline interpolation. A multiresolution analysis was performed (Daubechies-16 form), and the squared level specific amplitude coefficients were summed across appropriate decomposition levels in order to compute total band powers in bands of interest (LF: 0.039062 - 0.156248, HF: 0.156248 - 0.624992). A general linear model was then applied to estimate changes in RRi, LF and HF powers during three different period (Basal) (30 sec, at least 30 sec before seizure onset, during which no movements occurred and autonomic conditions resulted stationary); pre-seizure period (preSP) (10 sec preceding seizure onset) and seizure period (SP) corresponding to the clinical manifestations. For one of the patients (patient 9) three seizures associated with ictal asystole were recorded, hence he was treated separately. Results: Group analysis performed on 8 patients (41 seizures) showed that RRi remained unchanged during the preSP, while a significant tachycardia was observed in the SP. A significant increase in the LF component was instead observed during both the preSP and the SP (p<0.001) while HF component decreased only in the SP (p<0.001). For patient 9 during the preSP and in the first part of SP a significant tachycardia was observed associated with an increased sympathetic activity (increased LF absolute values and LF%). In the second part of the SP a progressive decrease in HR that gradually exceeded basal values occurred before IA. Bradycardia was associated with an increase in parasympathetic activity (increased HF absolute values and HF%) contrasted by a further increase in LF until the occurrence of IA. Conclusions: These data suggest that changes in autonomic balance toward a sympathetic prevalence always preceded clinical seizure onset in NFLE, even when HR changes were not yet evident, confirming that wavelet analysis is a sensitive technique to detect sudden variations of autonomic balance occurring during transient phenomena. Finally we demonstrated that epileptic asystole is associated with a parasympathetic hypertonus counteracted by a marked sympathetic activation.

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.

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.

Attività autonomica cardiaca e funzioni neurocognitive nei pazienti affetti da sindrome delle gambe senza riposo (RLS): effetto dei farmaci dopamino agonisti in acuto e a lungo termine

Several studies showed that sleep loss/fragmentation may have a negative impact on cognitive performance, mood and autonomic activity. Specific neurocognitive domains, such as executive function (i.e.,prefrontal cortex), seems to be particularly vulnerable to sleep loss. Pearson et al.(2006) evaluated 16 RLS patients compared to controls by cognitive tests, including those particularly sensitive to prefrontal cortical (PFC) functioning and sleep loss. RLS patients showed significant deficits on two of the three PFC tests. It has been recently reported that RLS is associated with psychiatric manifestations. A high prevalence of depressive symptoms has been found in patients with RLS(Rothdach AJ et al., 2000). RLS could cause depression through its adverse influences on sleep and energy. On the other hand, symptoms of depression such as sleep deprivation, poor nutrition or lack of exercise may predispose an individual to the development of RLS. Moreover, depressed patients may amplify mild RLS, making occasional RLS symptoms appear to meet threshold criteria. The specific treatment of depression could be also implicated, since antidepressant compounds may worsen RLS and PLMD(Picchietti D et al., 2005; Damsa C et al., 2004). Interestingly, treatments used to relieve RLS symptoms (dopamine agonists) seem to have an antidepressant effects in RLS depressed patients(Saletu M et al., 2002&2003). During normal sleep there is a well-regulated pattern of the autonomic function, modulated by changes in sleep stages. It has been reported that chronic sleep deprivation is associated with cardiovascular events. In patients with sleep fragmentation increased number of arousals and increased cyclic alternating pattern rate is associated with an increase in sympathetic activity. It has been demonstrated that PLMS occurrence is associated with a shift to increased sympathetic activity without significant changes in cardiac parasympathetic activity (Sforza E et al., 2005). An increased association of RLS with hypertension and heart disease has been documented in several studies(Ulfberg J et al., 2001; Ohayon MM et al., 2002).