Italian Association of Sleep Medicine (AIMS) position statement and guideline on the treatment of menopausal sleep disorders.

Insomnia, vasomotor symptoms (VMS) and depression often co-occur after the menopause, with consequent health problems and reductions in quality of life. The aim of this position statement is to provide evidence-based advice on the management of postmenopausal sleep disorders derived from a systematic review of the literature. The latter yielded results on VMS, insomnia, circadian rhythm disorders, obstructive sleep apnea (OSA) and restless leg syndrome (RLS). Overall, the studies show that menopausal hormone therapy (MHT) improves VMS, insomnia, and mood. Several antidepressants can improve insomnia, either on their own or in association with MHT; these include selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), and mirtazapine. Long-term benefits for postmenopausal insomnia may also be achieved with non-drug strategies such as cognitive behavioral therapy (CBT) and aerobic exercise. Continuous positive airway pressure (CPAP) and mandibular advancement devices (MADs) both reduce blood pressure and cortisol levels in postmenopausal women suffering from OSA. However, the data regarding MHT on postmenopausal restless legs syndrome are conflicting.

An Italian investigation on non-tuberculous mycobacteria in an urban water supply.

BACKGROUND: Atypical or non-tuberculous mycobacteria (NTM) are considered opportunistic pathogenic bacteria. They are natural inhabitants of a broad variety of environmental reservoirs, including natural and treated waters. Due to the lack of Italian studies on these microorganisms in drinking water, an investigation was carried out on their occurrence and on species present in a municipal water distribution system in Rome. The presence of the traditional indicators of faecal contaminations and free living amoebae were also verified. METHODS: Two different methodological approaches based on cultural and molecular techniques have been applied in parallel. RESULTS: Mean concentrations of NTM obtained with the two analytical methodologies were roughly 102 CFU/L. Among the numerous NTM species identified, M. chelonae was the most frequently isolated. No correlation of NTM with indicators of faecal contamination and amoebae was found. CONCLUSIONS: Mycobacteria can be present even if routine tests show water to have an excellent hygienic quality.

Recommendations of the Sleep Study Group of the Italian Dementia Research Association (SINDem) on clinical assessment and management of sleep disorders in individuals with mild cognitive impairment and dementia: a clinical review.

Clinical assessment and management of sleep disturbances in patients with mild cognitive impairment and dementia has important clinical and social implications. Poor sleep results in an increased risk of morbidities and mortality in demented patients and is a source of stress for caregivers. Sleep disturbances show high prevalence in mild cognitive impairment and dementia patients and they are often associated one to another in the same patient. A careful clinical evaluation of sleep disorders should be performed routinely in the clinical setting of individuals with cognitive decline. The Sleep Study Group of the Italian Dementia Research Association (SINDem) reviewed evidence from original research articles, meta-analyses and systematic reviews published up to December 2013. The evidence was classified in quality levels (I, II, III) and strength of recommendations (A, B, C, D, E). Where there was a lack of evidence, but clear consensus, good practice points were provided. These recommendations may not be appropriate for all circumstances and should therefore be adopted only after a patient's individual characteristics have been carefully evaluated.

High-molecular-weight kininogen cleavage correlates with disease states in the bradykinin-mediated angioedema due to hereditary C1-inhibitor deficiency.

BACKGROUND: The inherited deficiency of C1-inhibitor (C1-INH), which can be quantitative (type I) or qualitative (type II), is characterized by recurrent attacks of oedema, and it is known as hereditary angioedema due to C1-INH deficiency (HAE-C1-INH). The frequency of symptoms varies widely among patients and in the same patient during life. OBJECTIVE: To identify laboratory markers of disease severity in HAE-C1-INH patients. METHODS: We studied 162 patients with differently severe HAE-C1-INH during remission, 31 HAE-C1-INH patients during attacks, and 81 normal controls, evaluating complement parameters, spontaneous plasma kallikrein activity, the capacity of plasma to inhibit exogenous kallikrein activity, and cleavage of high-molecular-weight kininogen (HK). Sixty-five HAE-C1-INH patients were screened for mutations in the C1-INH gene. RESULTS: As expected, plasma C1-INH levels and activity and C4 levels were low in the HAE-C1-INH patients. Spontaneous plasma kallikrein activity in patients in remission was higher than in controls (P = 0.001) and increased during acute attacks (P = 0.01), whereas the capacity of inhibiting kallikrein activity was lower in patients in remission than in controls (P = 0.001) and further reduced during attacks (P = 0.001). HAE-C1-INH patients in remission had higher levels of cleaved HK than controls (P = 0.001), and these further increased during acute attacks (P = 0.001). Cleaved HK levels were higher in highly symptomatic HAE-C1-INH patients than in those with less frequent attacks (P = 0.001). Thirty-five different mutations in the C1-INH gene were equally distributed in patients with different attack frequencies. CONCLUSIONS: Measuring plasma levels of cleaved HK may be a sensitive mean of assessing disease severity in HAE-C1-INH patients.

Evaluation of the effects of supplementation with Pycnogenol® on fitness in normal subjects with the Army Physical Fitness Test and in performances of athletes in the 100-minute triathlon.

AIM: The aim of this registry study was to evaluate the effects of Pycnogenol® (French pine bark extract) on improving physical fitness (PF) in normal individuals using the Army Physical Fitness Test (APFT). The study evaluated the efficacy of Pycnogenol, used as a supplement, in improving training, exercise, recovery and oxidative stress. METHODS: The study was divided into 2 parts. In PART 1 (Pycnogenol 100 mg/day), the APFT was used to assess an improvement in PF during an 8-week preparation and training program. In PART 2 (Pycnogenol 150 mg/day), the study evaluated the effects of Pycnogenol supplementation in athletes in training for a triathlon. RESULTS: PART 1. There was a significant improvement in both males and females in the 2-mile running time within both groups, but the group using Pycnogenol (74 subjects) performed statistically better than controls (73 subjects). The number of push-ups was improved, with Pycnogenol subjects performing better. Sit-ups also improved in the Pycnogenol group. Oxidative stress decreased with exercise in all subjects; in Pycnogenol subjects the results were significantly better. PART 2. In the Pycnogenol group 32 males (37.9; SD 4.4 years) were compliant with the training plan at 4 weeks. In controls there were 22 subjects (37.2;3.5) completing the training plans. The swimming, biking and running scores in both groups improved with training. The Pycnogenol group had more benefits in comparison with controls. The total triathlon time was 89 min 44 s in Pycnogenol subjects versus 96 min 5 s in controls. Controls improved their performing time on average 4.6 minutes in comparison with an improvement of 10.8 minutes in Pycnogenol subjects. A significant decrease in cramps and running and post-running pain was seen in the Pycnogenol group; there were no significant differences in controls. There was an important, significant post-triathlon decrease of PFR one hour after the end of the triathlon with an average of -26.7, whereas PFR in controls increased. In Pycnogenol subjects there was a lower increase on oxidative stress with a faster recovery to almost normal levels (<330 for these subjects). These variations in PFR values were interpreted as a faster metabolic recovery in subjects using Pycnogenol. CONCLUSION: This study opens an interesting new application of the natural supplementation with Pycnogenol that, with proper hydration, good training and nutritional attention may improve training and performances both in normal subjects and in semi-professional athletes performing at high levels in difficult, high-stress sports such as the triathlon.

Prevalence of sleep disturbances in mild cognitive impairment and dementing disorders: a multicenter Italian clinical cross-sectional study on 431 patients.

BACKGROUND/AIMS: Sleep disturbances are common in the elderly and in persons with cognitive decline. The aim of this study was to describe frequency and characteristics of insomnia, excessive daytime sleepiness, sleep-disordered breathing, REM behavior disorder and restless legs syndrome in a large cohort of persons with mild cognitive impairment or dementia. METHODS: 431 consecutive patients were enrolled in 10 Italian neurological centers: 204 had Alzheimer's disease, 138 mild cognitive impairment, 43 vascular dementia, 25 frontotemporal dementia and 21 Lewy body dementia or Parkinson's disease dementia. Sleep disorders were investigated with a battery of standardized questions and questionnaires. RESULTS: Over 60% of persons had one or more sleep disturbances almost invariably associated one to another without any evident and specific pattern of co-occurrence. Persons with Alzheimer's disease and those with mild cognitive impairment had the same frequency of any sleep disorder. Sleep-disordered breathing was more frequent in vascular dementia. REM behavior disorder was more represented in Lewy body or Parkinson's disease dementia. CONCLUSION: A careful clinical evaluation of sleep disorders should be performed routinely in the clinical setting of persons with cognitive decline. Instrumental supports should be used only in selected patients.

Inter-critical and critical excessive daily sleepiness in episodic migraine patients.

The objective of this study was to determine the relationship between sleepiness and migraine in the intercritical period and to evaluate the time course of critical drowsiness during the attacks. One hundred patients fulfilling IHCD 2nd (2004) criteria for migraine without aura were compared to 100 healthy subjects. Habitual excessive daily sleepiness, evaluated by means of Epworth Sleepiness Scale, was not more frequent in patients with episodic migraine than in controls (12% migraineurs vs. 8% controls, NS). The analysis of critical sleepiness by means of Stanford Sleepiness Scale (SSS) revealed a beginning of sleepiness increase before the attack onset, starting 12 h before, a peak of SSS values at the migraine attack onset and then a gradual decrease to reach baseline values only 12-24 h later. Moreover, patients responding to symptomatic drugs showed a greater and faster decrease of critical sleepiness in comparison with non-responder migraineurs; this finding allows excluding the role of medications in promoting critical somnolence and together with critical drowsiness time-course supports the hypothesis that vigilance impairment could be related to migraine pathogenesis.

[Obstructive sleep apnea syndrome in bus drivers: clinical and polysomnographic study]. / Sindrome delle apnee ostruttive nel sonno in guidatori di autobus: uno studio clinico e polisonnografico.

A Questionnaire on sleep and vigilance disorders has been developed by the Italian Association of Sleep Medicine to help the occupational health physicians in screening for sleep disorders. Aim of this study was to compare the Questionnaire with standardized questionnaires for sleepiness and sleep apnea and with a polysomnographic evaluation. Four hundred sixty-three (463#) commercial bus drivers (454M, 9F; mean age +/- S.D. 41.6 +/- 8.1 yrs; mean body mass index 26.2 +/- 3.6 kg/m2) underwent clinical evaluation that included the Italian Association of Sleep Medicine Questionnaire on sleep and vigilance disorders and two standardized questionnaires (Berlin Questionnaire and Epworth Sleepiness Scale). According to the Italian Association of Sleep Medicine Questionnaire on sleep and vigilance disorders 40 subjects presented an high risk for sleep disturbance and in 28 subject the questionnaires were concordant. Preliminary results (16 patients) showed an high rate of concordance between questionnaire and PSG. These data strongly suggest that sleep disorders and symptoms, that are frequent in a population of professional bus drivers, should be better evaluated during occupational health visit.

[Guidelines for the fitness to drive assessment in people with obstructive sleep apnoea syndrome (OSAS) and narcolepsy]. / Linee guida per l'accertamento dell'idoneità alla guid in soggetti affetti da Sindrome delle apnee ostruttive del sonno (OSAS) e Narcolessia.

Given the prevalence of sleep disorders and sleep deprivation in modern societies, and the correlation between sleepiness and work and driving accidents, the excessive daytime sleepiness is an important issue. Although many studies showed that patients with untreated Obstructive sleep apnoea syndrome (OSAS) and narcolepsy have an higher risk for driving accidents, neither the European Community regulation nor the Italian law of the driving licence mention restrictions for these disorders. In 2010 the scientific association COMLAS (Association of legal medicine professionals of the Italian National Health Service) published the Guidelines for the examination by the Local Medical Commissions. The author presented the guidelines to assess the fitness to drive of people with OSAS or narcolepsy. The proposed criteria, set up in collaboration with the Commission "Sleepiness, Safety and Transportation" of the Italian Association of Sleep Medicine (AIMS), can be considered among the most advanced internationally.

Statistical correlation between enterovirus genome copy numbers and infectious viral particles in wastewater samples.

AIMS: Classic virological tests are time consuming and labour-intensive; real-time RT-PCR has proven to be a fast method to detect and quantify enterovirus genomes in clinical and environmental samples. This method is unable to discriminate between infective and noninfective enterovirus particles; few clinical studies have compared real-time RT-PCR and viral culture. We wondered if the enterovirus genome quantification could be correlated to the infectivity. METHODS AND RESULTS: We used the statistical approach to verify our hypotheses to correlate data, obtained by the standard method (most probable number of cytopathic units-MPNCU) and molecular test (real-time RT-PCR), on wastewater treatment plant samples. Chi-squared test was used, considering several cut-off values ('50'-'100'-'200' genome copy numbers), to determine statistical significance in comparison of the two methods. Chi-square value was not significant when cut-off of 50 (P = 0.103) and 100 (P = 0.178) was assumed but was significant with cut-off of 200 (P = 0.044). CONCLUSION: This limit, 200 genome copy, could be used as cut-off value to indicate enterovirus survival in environmental monitoring. SIGNIFICANT AND IMPACT OF THE STUDY: To introduce a fast procedure that is able to compensate for disadvantages of cell culture method for viral environmental analyses.

Presence and environmental circulation of enteric viruses in three different wastewater treatment plants.

AIMS: The aim of the work was to evaluate the circulation of the viruses and to determine a correlation between faecal indicators and viruses. METHODS AND RESULTS: Raw wastewater and effluent samples were collected from three wastewater treatment plants, during three sampling periods, and analysed, using cultural and molecular methods, to determine bacteria and virus presence. The results show a removal of bacterial indicators, but a limited reduction of the phages. The viral analysis displays the circulation of cultivable enteroviruses and differences in the seasonal-geographical distribution. Hepatitis A virus was found with only two genotypes: IA-IB. Rotavirus was present in 11.11%, 24.14%, 2.78% of the samples in the 1st, 2nd and 3rd sampling periods; Astrovirus in 33.33%, 6.9%, 25%; Adenovirus in 7.41%, 3.45%, 2.78%; Norovirus in 7.41%, 10.34%, 5.56% respectively. Adenovirus was never identified in plants B and C as Rotavirus in plant C. CONCLUSIONS: The presence of faecal indicators was not predictive of the enteric virus presence, whereas a different circulation of Enteroviruses was found in the wastewater treatment plants. SIGNIFICANCE AND IMPACT OF THE STUDY: The study shows the importance and the usefulness of molecular methods to evaluate the virus circulation and the genetic variability of Enteroviruses.

Activation of blood coagulation in bullous pemphigoid: role of eosinophils, and local and systemic implications.

BACKGROUND: Bullous pemphigoid (BP) is a blistering skin disease caused by autoantibodies to hemidesmosomal proteins, with eosinophils participating in blister formation. Eosinophils are a source of tissue factor (TF), an initiator of blood coagulation. OBJECTIVES: To evaluate the local and systemic activation of coagulation in BP. METHODS: We studied 20 patients with active BP (eight re-evaluated during remission) and 40 controls. The coagulation markers prothrombin fragment F1+2 and d-dimer were measured in the plasma of all subjects and in both plasma and blister fluid of patients with BP. TF was evaluated immunohistochemically in skin specimens from the 20 patients and in 20 normal samples. RESULTS: F1+2 and d-dimer levels were higher in plasma of patients with BP (649 +/- 96 pmol L(-1) and 18.52 +/- 3.44 nmol L(-1), respectively) than in plasma of controls (157 +/- 7 pmol L(-1) and 1.42 +/- 0.06 nmol L(-1); P = 0.0001), and were very high in blister fluid (40 449 +/- 3491 pmol L(-1) and 1532.32 +/- 262.81 nmol L(-1); P = 0.0001). Plasma and blister fluid F1+2 and d-dimer levels paralleled blood and tissue eosinophilia and disease severity. In the eight patients re-evaluated during remission, there was a marked reduction in F1+2 (from 1127 +/- 144 to 287 +/- 52 pmol L(-1); P = 0.005) and d-dimer (from 24.03 +/- 4.08 to 4.69 +/- 1.51 nmol L(-1); P = 0.029). Immunohistochemistry revealed strong TF reactivity in BP skin (P = 0.0001), and colocalization studies confirmed eosinophils as a source of TF. CONCLUSIONS: The coagulation cascade is activated in BP and correlates with the severity of the disease and with eosinophilia, indicating that eosinophils play a role in coagulation activation via TF. The hypercoagulability may contribute to inflammation, tissue damage, blister formation and possibly thrombotic risk in BP.

Severe chronic urticaria is associated with elevated plasma levels of D-dimer.

BACKGROUND: Patients with chronic urticaria (CU) frequently show signs of thrombin generation as a result of the activation of the extrinsic pathway of coagulation and signs of fibrinolysis as shown by slightly increased mean D-dimer plasma levels. Here, we studied patients with severe CU to see whether the activation of coagulation and fibrinolysis parallels the severity of the disease. METHODS: Eight consecutive patients with severe exacerbations of CU and 13 with slight CU were studied. Plasma prothrombin fragment F(1+2) as well as D-dimer were measured by ELISA. Serum histamine-releasing activity was assessed by basophil histamine release assay. Seventy-four normal subjects were used as controls. RESULTS: In patients with severe CU, median levels of both D-dimer (11.20 nmol/l) and F(1+2) (592 pmol/l) largely exceeded those found in patients with slight CU [D-dimer: 2.66 nmol/l (P = 0.001) and F(1+2): 228 pmol/l (P = 0.003)] and in normal subjects [D-dimer: 1.41 nmol/l (P = 0.0001) and F(1+2): 159 pmol/l (P = 0.0001)]. Sera from 25% of patients with severe CU and 31% of those with slight CU, but from none of normal subjects, showed in vitro histamine-releasing activity. D-dimer and F(1+2) levels were significantly correlated each other (r = 0.64, P = 0.002) and with CU severity score (r = 0.80-0.90, P = 0.0001), but no correlation was observed between serum histamine-releasing activity and coagulation parameters or severity score. CONCLUSIONS: Severe exacerbations of CU are associated with a strong activation of coagulation cascade and fibrinolysis. Whether this activation is the cause of CU or acts as an amplification system is still a matter of debate.

High prevalence of restless legs syndrome in multiple sclerosis.

Despite the fact that multiple sclerosis (MS) patients often include leg restlessness as a sensory symptom, MS is not mentioned amongst symptomatic restless legs syndrome (RLS) forms. The aim of this study was to estimate RLS prevalence in a large population of MS patients, comparing clinical and MRI findings between patients with and without RLS. Each of the 156 MS patients (100 females, 56 males, mean age 40.7 +/- 10.4) enrolled in a prospective study underwent a medical history interview, a neurological examination with the assessment of the Expanded Disability Status Scale (EDSS), and a structured questionnaire to verify the presence and features of RLS. Conventional brain-spinal MRIs of 99 subjects were also evaluated and compared between patients with and without RLS. Fifty-one subjects (32.7%) (mean age 43.8 +/- 12.8) met the criteria for RLS. In a few patients (8.5%), the RLS preceded clinical MS onset, whilst in the remaining cases the RLS was followed by or was simultaneous with clinical MS onset. Comparing the RLS group with the group without RLS, no significant differences were found in MS duration, gender, and referred sleep habits. The primary progressive MS course was more represented in the RLS group, which also showed a higher EDSS score. RLS is a very common finding in MS patients and should be considered amongst the symptomatic RLS forms. RLS is also associated with higher disability.

Quantitative EEG analysis in post-traumatic anosmia.

Many objective and quantitative methods have been developed to create a procedure or a device to prove, describe and quantify olfactory deficit and anosmia, especially after a head trauma. Electrophysiological testing throughout olfactoelectroencephalography (olfactoEEG) is based on brain activity desynchronisation, and on the subsequent disappearance of alpha activity on the posterior regions after an olfactory stimulus. Yet traditional evaluation of EEG can be difficult, because of little or hardly detectable alpha activity on the posterior regions ('alpha rare'). The aim of this study was to evaluate the Olfactory Stop Reaction (OSR) by means of frequency band power calculation and subsequent topographical mapping in patients with post-traumatic anosmia, who presented 'alpha rare' EEG. Twenty-five consecutive patients, affected by anosmia caused by head trauma, were submitted to an EEG recording with olfactory stimulation. After signal processing and analysis, an Olfactory Stop Reaction was detected in 17 out of 25 patients; moreover, in these patients we detected a significant decrease in alpha band power in the occipital regions and an increase in theta band power on midline frontal and central regions after olfactory stimulation. In the remaining eight patients, no significant variation in band power was observed. In conclusion, an objective evaluation of the olfactory function with this method of automatic EEG signal analysis allows the limits given by psychophysical methods and traditional EEG to be overcome and attempts to fulfil the requirements for standardization of olfactory function evalution.

Rizatriptan does not change cerebral blood flow velocity during migraine attacks.

Rizatriptan represents a major advance in the treatment of migraine attack: inhibition of peripheral trigeminal nerve and constriction of intracranial extracerebral blood vessels have been proposed as its main antimigraine mechanisms of action. Although many studies may suggest that rizatriptan causes highly selective vasoconstriction within intracranial extracerebral vessels (i.e., meningeal arteries), no literature data are available to date on possible cerebral hemodynamic changes in humans after treatment with rizatriptan. The aim of this study was to evaluate the effect of rizatriptan on cerebral blood flow velocity performing transcranial Doppler during spontaneous attacks of migraine without aura. Fourteen patients suffering from migraine without aura were monitored to evaluate mean flow velocity changes on both middle cerebral arteries during migraine attack 30 min before and 120 min after oral administration of rizatriptan 10mg. Monitoring was repeated for 30 min during the pain-free period. All patients turned out to be drug responders and no significant mean flow velocity changes were observed between the pain-free period and pre-treatment phase; besides no significant difference in mean flow velocity value have been detected between the periods after the drug administration during the attack versus both pre-treatment period and pain-free phase. These findings indicate that the antimigraine action of rizatriptan is not associated with clear intracranial cerebral hemodynamic changes and may support its cerebrovascular safety.