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Background and purpose: The patterns of long-term risk of SARS-CoV-2 infection, hospitalization for COVID-19, and related death are uncertain in people with Parkinson disease (PD) or parkinsonism (PS). The aim of the study was to quantify these risks compared to a control population cohort, during the period March 2020–May 2021, in Bologna, Northern Italy. Methods: ParkLink Bologna cohort (759 PD, 192 PS) and controls (9226) anonymously matched (ratio=1:10) for sex, age, district, and comorbidity were included. Data were analysed in the whole period and in the two different pandemic waves (March–May 2020 and October 2020–May 2021). Results: Adjusted hazard ratio of SARS-CoV-2 infection was 1.3 (95% confidence interval [CI] = 1.04–1.7) in PD and 1.9 (95% CI=1.3–2.8) in PS compared to the controls. The trend was detected in both the pandemic waves. Adjusted hazard ratio of hospitalization for COVID-19 was 1.1 (95% CI=0.8–1.7) in PD and 1.8 (95% CI=0.97–3.1) in PS. A higher risk of hospital admission was detected in PS only in the first wave. The 30-day mortality risk after hospitalization was higher (p= 0.048) in PS (58%) than in PD (19%) and controls (26%). Conclusions: Compared with controls, after adjustment for key covariates, people with PD and PS showed a higher risk of SARS-CoV-2 infection throughout the first 15 months of the pandemic. COVID-19 hospitalization risk was increased only in people with PS and only during the first wave. This group of patients was burdened by a very high risk of death after infection and hospitalization.

In 2003, the EFNS Task Force was set up for putting forth guidelines for the management of the Restless Legs Syndrome (RLS) and the Periodic Limb Movement Disorder (PLMD). After determining the objectives for management and the search strategy for primary and secondary RLS and for PLMD, a review of the scientific literature up to 2004 was performed for the drug classes and interventions employed in treatment (drugs acting on the adrenoreceptor, antiepileptic drugs, benzodiazepines/hypnotics, dopaminergic agents, opioids, other treatments). Previous guidelines were consulted. All trials were analysed according to class of evidence, and recommendations formed according to the 2004 EFNS criteria for rating. Dopaminergic agents came out as having the best evidence for efficacy in primary RLS. Reported adverse events were usually mild and reversible; augmentation was a feature with dopaminergic agents. No controlled trials were available for RLS in children and for RLS during pregnancy. The following level A recommendations can be offered: for primary RLS, cabergoline, gabapentin, pergolide, ropinirole, levodopa and rotigotine by transdermal delivery (the latter two for short-term use) are effective in relieving the symptoms. Transdermal oestradiol is ineffective for PLMD.

Background: In the light of the new diagnostic criteria for multiple sclerosis (MS) and currently available early treatment, this study aimed to explore whether, and to what extent, disclosure of the diagnosis of MS or clinically isolated syndrome (CIS) affects patients' anxiety, mood and quality of life (QoL). Methods: Eligible participants were all patients referred for the first time to the Neurological Unit who had manifested symptoms suggestive of MS for no more than 6 months. All patients were evaluated for (i) QoL (SEIQoL and MS-QoL54), (ii) Anxiety (STAI) and Depression (CMDI) on study inclusion (T0), 30 days after diagnosis disclosure (T30), and after 1 (T1y) and 2 (T2y) years' follow-up. Results: Two hundred and twenty-nine patients were enrolled; 93 of these were unaware of their diagnosis. Patients who already knew their diagnosis (100 with CIS and 22 with MS) were excluded from the main analyses and used to perform control analyses. At the end of the screening, an MS diagnosis was disclosed to 18 of the 93 patients, whereas a CIS diagnosis was disclosed to 62 patients (12 patients received a diagnosis other than MS or CIS). Thirty days after diagnosis disclosure, irrespective of the diagnosis disclosed, both QoL and Anxiety and Depression were significantly rated as better compared to the start of screening, (p s < 0.03), and this improvement remained stable over the two annual follow-ups. However, as suggested by a significant 'Time' × 'Diagnosis' interaction with regard to both QoL and Anxiety and Depression (p s < 0.02), the effect of the disclosure in the short term differed depending on CIS or MS diagnosis. Specifically, on MSQoL, which is a health-related QoL scale, we found a statically significant improvement, immediately after the diagnosis disclosure, in both the MS and CIS groups (p s < 0.01). Differently, on SEIQoL, which is a non health-related QoL measure, and on the anxiety scale, we observed a statistically significant improvement only in the group which received a MS diagnosis (p s < 0.03). Conclusions: This first prospective study provides objective data showing that early disclosure of MS diagnosis improves both the patient's QoL and psychological well-being. In addition, the results seem to suggest that CIS disclosure does not lead to the same favourable effects. © 2012 Blackwell Publishing Ltd.

Background: We describe the development and clinical validation of a patient self-administered tool assessing the quality of multiple sclerosis diagnosis disclosure. Method: A multiple sclerosis expert panel generated questionnaire items from the Doctor’s Interpersonal Skills Questionnaire, literature review, and interviews with neurology inpatients. The resulting 19-item Comunicazione medico-paziente nella Sclerosi Multipla (COSM) was pilot tested/debriefed on seven patients with multiple sclerosis and administered to 80 patients newly diagnosed with multiple sclerosis. The resulting revised 20-item version (COSM-R) was debriefed on five patients with multiple sclerosis, field tested/debriefed on multiple sclerosis patients, and field tested on 105 patients newly diagnosed with multiple sclerosis participating in a clinical trial on an information aid. The hypothesized monofactorial structure of COSM-R section 2 was tested on the latter two groups. Results: The questionnaire was well accepted. Scaling assumptions were satisfactory in terms of score distributions, item—total correlations and internal consistency. Factor analysis confirmed section 2’s monofactorial structure, which was also test—retest reliable (intraclass correlation coefficient [ICC] 0.73; 95% CI 0.54—0.85). Section 1 had only fair test—retest reliability (ICC 0.45; 95% CI 0.12—0.69), and three items had 8—21% missed responses. Conclusions: COSM-R is a brief, easy-to-interpret MS-specific questionnaire for use as a health care indicator.

Retrospective observations disclosed an overlap between parasomnias and nocturnal frontal lobe epilepsy (NFLE) not only in patients but also in their relatives, suggesting a possible common pathogenetic mechanism. This study aimed to verify whether relatives of patients with NFLE have a higher frequency of parasomnias, namely arousal disorders, and thereby shed light on the still unknown pathophysiologic mechanisms underlying NFLE.We undertook a case-control family study in which we recruited NFLE probands and healthy controls, matched for age, sex, education, and geographic origin. At least four relatives were included for each proband and control. Each subject underwent a standardized interview, with application of the International Classification of Sleep Disorders-Revised (ICSD-R 2001) minimal criteria to diagnose the lifetime prevalence of the main parasomnias.Four hundred fifty-eight individuals were recruited: 33 NFLE probands, 200 relatives of probands, 31 controls, and 194 control relatives. All NFLE probands but one have sporadic NFLE. The lifetime prevalence of the following parasomnias differed in proband relatives versus control relatives: arousal disorders [odds ratio (OR) 4.7, 95% confidence interval (CI) 2.0-11.6; p0.001] and nightmares (OR 2.6, 95% CI 1.6-4.2; p0.001) were more frequent among NFLE proband relatives. In the secondary analysis comparing NFLE probands to controls, arousal disorders (OR 6.3, 95% CI 1.3-31.7; p = 0.023) and bruxism (OR 5.4, 95% CI 1.3-21.7; p = 0.017) were more frequent among NFLE probands.The higher frequency of arousal disorders in NFLE families suggests an intrinsic link between parasomnias and NFLE and an abnormal (possibly cholinergic) arousal system as a common pathophysiologic mechanism.

Study objectives To estimate the reliability of the diagnosis of narcolepsy after clinical interview and polysomnographic evaluation among sleep medicine doctors, before and after training in application of the International Classification of Sleep Disorders (ICSD). Setting Videotaped semi-structured interviews of 10 patients complaining of daytime sleepiness of different etiologies. Questions referred to ICSD criteria for narcolepsy. A further series of 10 cases of narcolepsy without cataplexy were simulated, with at least a random one to three of the ICSD polysomnographic criteria at pathological levels. Participants and design Seventeen doctors were required to classify each videotaped case as "ascertained," "possible," or "excluded" narcolepsy, in two sessions: one before and one after discussion of ICSD criteria. The observers were invited to confirm or exclude the diagnosis of narcolepsy in the 10 simulated cases, according to the given polysomnographic findings, before and after an agreed proposal of the interpretation of ICSD polysomnographic criteria. Interobserver reliability was calculated using Kappa statistics. Interventions N/A. Measurements and results Interobserver reliability of clinical judgement improved from "substantial" at baseline (Kappa 0.61) to "almost perfect" after training (Kappa 0.95). Interobserver reliability of polysomnographic findings was "fair" at baseline (Kappa 0.24), unanimous after the proposed interpretation of ICSD polysomnographic criteria. Conclusions Baseline reliability of diagnostic judgement in suspected narcolepsy was found satisfactory among Italian sleep medicine doctors. Educational training, based on discussion of ICSD criteria, further improved agreement. Diagnosis based on polysomnographic findings, not reliable at baseline, needed a strict interpretation of ICSD criteria to attain standardization.

Background The differential diagnosis between multiple system atrophy parkinsonism type (MSA-P) and Parkinson's disease with orthostatic hypotension (PD+OH) is difficult because the 2 diseases have a similar clinical picture. The aim of this study is to distinguish MSA-P from PD+OH by immunostaining for abnormal phosphorylated α-synuclein at serine 129 (p-syn) in cutaneous nerves. Method We recruited 50 patients with parkinsonism and chronic orthostatic hypotension: 25 patients fulfilled the diagnostic criteria for MSA-P and 25 patients for PD+OH. The patients underwent a skin biopsy from the cervical area, thigh, and leg to analyze somatic and autonomic skin innervation and p-syn in skin nerves. Results Intraneural p-syn positivity was found in 72% of patients with MSA-P, mainly in distal skin sites. More important, p-syn deposits in MSA-P differed from PD+OH because they were mainly found in somatic fibers of subepidermal plexi, whereas scant autonomic fiber involvement was found in only 3 patients. All patients with PD+OH displayed widely distributed p-syn deposits in the autonomic skin fibers of proximal and distal skin sites, whereas somatic fibers were affected only slightly in 4 patients with PD+OH. Skin innervation mirrored p-syn deposits because somatic innervation was mainly reduced in MSA-P. Sympathetic innervation was damaged in PD+OH but fairly preserved in MSA-P. Conclusions The p-syn in cutaneous nerves allows the differentiation of MSA-P from PD+OH; MSA-P mainly shows somatic fiber involvement with relatively preserved autonomic innervation; and by contrast, PD+OH displays prevalent abnormal p-syn deposits and denervation in autonomic postganglionic nerves. © 2020 International Parkinson and Movement Disorder Society.

BACKGROUND Sleep disorders are highly prevalent in the general population and may be linked in a bidirectional fashion to stroke, which is one of the leading causes of morbidity and mortality. AIM Four major scientific societies established a task force of experts in neurology, stroke, respiratory medicine, sleep medicine and methodology to critically evaluate the evidence regarding potential links and the impact of therapy. MATERIALS AND METHODS Thirteen research questions were evaluated in a systematic literature search using a stepwise hierarchical approach: first, systematic reviews and meta-analyses; second, primary studies post-dating the systematic reviews/meta-analyses. A total of 445 studies were evaluated and 88 were included. Statements were generated regarding current evidence and clinical practice. RESULTS Severe obstructive sleep apnoea (OSA) doubles the risk for incident stroke, especially in young to middle-aged patients. Continuous positive airway pressure (CPAP) may reduce stroke risk, especially in treatment-compliant patients. The prevalence of OSA is high in stroke patients and can be assessed by polygraphy. Severe OSA is a risk factor for recurrence of stroke and may be associated with stroke mortality, whilst CPAP may improve stroke outcome. It is not clear if insomnia increases stroke risk, whilst the pharmacotherapy of insomnia may increase it. Periodic limb movements in sleep (PLMS), but not restless limb syndrome (RLS), may be associated with an increased risk of stroke. Preliminary data suggest a high frequency of post-stroke insomnia and RLS and their association with a less favourable stroke outcome, whilst treatment data are scarce. DISCUSSION/CONCLUSION Overall, the evidence base is best for OSA relationship with stroke and supports active diagnosis and therapy. Research gaps remain especially regarding insomnia and RLS/PLMS relationships with stroke.

Objective: Data on COVID-19 outcomes in persons with epilepsy (PWE) are scarce and inconclusive. We aimed to study the risk of hospitalization and death for COVID-19 in a large cohort of PWE from March 1, 2020 to October 31, 2021. Methods: The historical cohort design (EpiLink Bologna) compared adult PWE grouped into people with focal epilepsy (PFE), idiopathic generalized epilepsy (PIGE), and developmental and/or epileptic encephalopathy (PDEE), and a population cohort matched (ratio 1:10) for age, sex, residence, and comorbidity (assessed with the multisource comorbidity score), living in the local health trust of Bologna (approximately 800 000 residents). Clinical data were linked to health administrative data. Results: In both cohorts (EpiLink: n=1575 subjects, 1128 PFE, 267 PIGE, 148 PDEE, 32 other; controls: n=15 326 subjects), 52% were females, and the mean age was 50 years (SD=18). Hospital admissions for COVID-19 in the whole period were 49 (3.1%) in PWE and 225 (1.5%) in controls. The adjusted hazard ratio (aHR) in PWE was 1.9 (95% confidence interval [CI] = 1.4–2.7). The subgroups at higher risk were PFE (aHR=1.9, 95% CI=1.3–2.8) and PDEE (aHR=3.9, 95% CI=1.7–8.7), whereas PIGE had a risk comparable to the controls (aHR=1.1, 95% CI =.3–3.5). Stratified analyses of the two main epidemic waves (March–May 2020, October 2020–May 2021) disclosed a higher risk of COVID-19-related hospitalization during the first epidemic wave (March–May 2020; aHR=3.8, 95% CI=2.2–6.7). Polytherapy with antiseizure medications contributed to a higher risk of hospital admission. Thirty-day risk of death after hospitalization was 14% in both PWE and controls. Significance: During the first 20 months since the outbreak of COVID-19 in Bologna, PWE had a doubled risk of COVID-19 hospital admission compared to a matched control population. Conversely, epilepsy did not represent a risk factor for COVID-19-related death.

Pediatric type 1 narcolepsy (NT1) is often associated with overweight and obesity. Sodium oxybate (SO), approved for the treatment of narcolepsy with cataplexy from the age of 7 years old in the United States, has been associated with weight loss, although longitudinal pediatric studies are lacking. We report a retrospective cohort of 129 consecutive patients with a 4-year follow-up, to analyze the impact of different pharmacological treatments on body mass index (BMI) z-score. At baseline, the prevalence of obesity and overweight was 26.4% (34/129) and 29.5% (38/129), respectively. Patients were divided into three groups: children treated with SO alone (group 1), with SO-combined therapy (group 2), and without SO (group 3). At the end of the first year of follow-up, group 1 and group 2 showed a significant BMI z-score reduction compared to baseline: from 1.2 ± 1.1 to 0.4 ± 1.4 for group 1 (p < 0.001), and from 1.4 ± 1.1 to 1 ± 1.3 for group 2 (p = 0.002), independently from baseline clinical features. In the second year, only group 2 experienced a further and significant BMI z-score decrease (from 1.0 ± 1.2 to 0.6 ± 1.2, p = 0.037). No further significant BMI z-score changes were observed in SO-treated patients in the following years. Instead, children treated without SO developed a significant weight increase between the second and third year of therapy (BMI z-score from 0.3 ± 0.9 to 0.5 ± 0.9). In conclusion, SO treatment in pediatric NT1 is associated with a favorable weight reduction in the first year of treatment.

Introduction We aimed to create standardized protocol for language examination in patients who underwent video-EEG recording and assessed its efficacy in the characterization of ictal language impairment, its ability to differentiate this from impaired awareness, and interobserver reliability in clinical practice. Methods From our database of video-EEG recordings, we selected a representative sample of 63 focal seizures with presumed language impairment. A multidisciplinary team of epileptologists, EEG technicians, and speech therapists analyzed the selected videos to highlight the critical issues of ordinary ictal language evaluation. We subsequently followed a multi-step process to develop the protocol and assess its interobserver reliability. Results A protocol based on seven tests in hierarchical succession was created, summed up in the acronym CA-P-S C-A-R-E (Closed Answers, Pro-speak question, Simple orders, Common object denomination, Audio repetition, Reading, Evoke). Following its preliminary administration for 5 months, we assessed the inter-observer reliability of 16 healthcare professionals in distinguishing between language impairment and impaired awareness among a sample of 10 seizures, finding a substantial agreement (kappa 0.61). Conclusion The proposed protocol, made of simple and easy to memorize tests, is an effective tool that evaluates multiple domains beyond language. Its use could help to recognize ictal aphasia effectively and differentiate it from impaired awareness, minimizing inter-examiner variability.

Study Objectives Narcolepsy type 1 (NT1) is a chronic rare hypersomnia of central origin requiring a combination of behavioral and pharmacological treatments. During the coronavirus disease 2019 (COVID‐19) pandemic, in Italy the population was forced into a lockdown. With this study, we aimed to describe the lockdown impact on NT1 symptom management, according to different patients' working schedule. Methods In the period between 10 April and 15 May 2020, we performed routine follow‐up visits by telephone (as recommended during the COVID‐19 emergency) to 50 patients >18 years old (40% males) under stable long‐term treatment. We divided patients into three groups: unchanged working schedule, forced working/studying at home, and those who lost their job (“lost occupation”). Current sleep–wake habit and symptom severity were compared with prelockdown assessment (six months before) in the three patient groups. Results At assessment, 20, 22, and eight patients belonged to the unchanged, working/studying at home, and lost occupation groups, respectively. While in the lost occupation group, there were no significant differences compared with prepandemic assessment, the patients with unchanged schedules reported more nocturnal awakenings, and NT1 patients working/studying at home showed an extension of nocturnal sleep time, more frequent daytime napping, improvement of daytime sleepiness, and a significant increase in their body mass index. Sleep‐related paralysis/hallucinations, automatic behaviors, cataplexy, and disturbed nocturnal sleep did not differ. Conclusions Narcolepsy type 1 patients working/studying at home intensified behavioral interventions (increased nocturnal sleep time and daytime napping) and ameliorated daytime sleepiness despite presenting with a slight, but significant, increase of weight., The graphical abstract displays that NT1 patients working/studying at home slept more with improved subjective daytime sleepiness, while both NT1 patients working/studying at home and loosing occupation because of the pandemic significantly increased BMI.

Objective Narcolepsy is a lifelong disease, manifesting with excessive daytime sleepiness and cataplexy, arising between childhood and young adulthood. The diagnosis is typically made after a long delay that burdens the disease severity. The aim of the project, promoted by the “Associazione Italiana Narcolettici e Ipersonni” is to develop Red Flags to detect symptoms for early referral, targeting non-sleep medicine specialists, general practitioners, and pediatricians. Materials and methods A multidisciplinary panel, including patients, public institutions, and representatives of national scientific societies of specialties possibly involved in the diagnostic process of suspected narcolepsy, was convened. The project was accomplished in three phases. Phase 1: Sleep experts shaped clinical pictures of narcolepsy in pediatric and adult patients. On the basis of these pictures, Red Flags were drafted. Phase 2: Representatives of the scientific societies and patients filled in a form to identify barriers to the diagnosis of narcolepsy. Phase 3: The panel produced suggestions for the implementation of Red Flags. Results Red Flags were produced representing three clinical pictures of narcolepsy in pediatric patients ((1) usual sleep symptoms, (2) unusual sleep symptoms, (3) endocrinological signs) and two in adult patients ((1) usual sleep symptoms, (2) unusual sleep symptoms). Inadequate knowledge of symptoms at onset by medical doctors turned out to be the main reported barrier to diagnosis. Conclusions This report will hopefully enhance knowledge and awareness of narcolepsy among non-specialists in sleep medicine in order to reduce the diagnostic delay that burdens patients in Italy. Similar initiatives could be promoted across Europe. Electronic supplementary material The online version of this article (10.1007/s10072-018-3666-x) contains supplementary material, which is available to authorized users.

Introduction: The role of drugs in the occurrence of multiple sclerosis (MS) is perceived to be insufficiently investigated. Objective: The aim of this study was to map and assess the evidence on MS occurrence after drug exposure, in order to identify possible signals of causal association. Methods: A search strategy was performed in MEDLINE and Embase as of July 2016; references consistent with the aim of the study were analysed to extract relevant measures of causal association between drugs and MS. The Newcastle-Ottawa Scale and appropriate guidelines from the International Society for Pharmacoepidemiology (ISPE) and the International Society of Pharmacovigilance (ISoP) were used to assess the quality of included studies. Results: After screening 832 articles, 58 were selected (of which 14 were found by checking the reference lists of reviews): 30 case reports and case series, 24 longitudinal studies and four randomized controlled trials. Seven longitudinal studies had good (at least 7 out of 9) quality scores, whereas case reports/case series presented several limitations. Half of included articles focused on immunomodulatory drugs (etanercept, infliximab and adalimumab), especially in case reports/series, suggesting an association with MS occurrence. Contraceptives and antibacterials were investigated in some population-based studies, without definite results. Conclusion: A heterogeneous pharmacological profile of identified classes emerged. Low strength of evidence and conflicting results highlighted the difficulties in addressing the possible contribution of drugs in MS occurrence. Methodological advances are needed, especially to control the confounding role of underlying disease for specific drug classes.

Background Apart from the underlying cardiovascular (CV) risk associated with migraine, both triptans and ergotamines can induce vasoconstriction and potentially increase the risk of serious ischemic events. Because of the low frequency of such events in eligible patients, randomized controlled trials are not exhaustive to assess the drug-related CV risk. Observational studies are, therefore, an essential source of information to clarify this matter of concern. Aim The aim of this study was to systematically review the available published observational studies investigating the risk of serious CV events in triptan or ergotamine users, as compared to unexposed migraineur controls. Methods We systematically searched MEDLINE and EMBASE electronic databases for cohort or case-control studies up to December 1, 2013. Studies retrieved from CDSR, DARE and HTA databases of the Cochrane Library were used for snowballing. Studies investigating the risk of any CV outcome in patients with a migraine diagnosis and exposed to triptans or ergotamines were considered for inclusion. Selection of studies, data extraction, and risk of bias assessment were conducted independently by two reviewers. Pooled odds ratios (ORs) with 95% confidence interval (95% CI) were computed using a random-effects model for studies and outcomes judged eligible for quantitative data synthesis. Results From a total of 3370 citations retrieved, after duplicate removal and screening, only four studies met the inclusion criteria (three nested case-control analyses and one retrospective cohort study). These studies investigated the risk of different CV outcomes associated with either the recency or the intensity of exposure to the studied drugs. As for the intensity of use, the pooled OR of serious ischemic events was 2.28 (95% CI 1.18–4.41; I2 = 0%) for ergotamine use (two studies), whereas for triptans (three studies) it was 0.86 (95% CI 0.52–1.43; I2 = 24.5%). Recent use of ergotamines was not significantly associated with any CV outcome (only one available study). Two studies investigated the risk of stroke related to recent triptan use: the first study reported an OR of 0.90 (0.64–1.26), and the second one suggested an increased risk of 2.51 (1.10–5.71). In this case, because of the high degree of heterogeneity, results were not pooled. Conclusions To date, few comparative observational studies have investigated the CV safety of migraine-specific drugs in clinical practice. Evidence gathered here suggests that intense consumption of ergotamines may be associated with an increased risk of serious ischemic complications. As for triptans, available studies do not suggest strong CV safety issues, although no firm conclusions can be drawn. In particular, evidence on stroke risk is conflicting. However, if an increase of the absolute stroke risk in recently exposed patients does actually exist, it must be small. Overall, residual uncontrolled confounding factors reduce the confidence in the risk estimates collected from the included studies. Further investigations are needed to better define the risk for rare but serious CV events related to triptan and ergotamine use for treatment of migraine.

The beneficial effect of nicotine has been reported in autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) patients, but not tested in sporadic cases. Recently, a nicotine defect in the arousal pathway has been hypothesized even in sporadic NFLE patients and their relatives. This case–control family study was designed to test whether NFLE subjects were more likely to use tobacco than controls, as an indirect marker of cholinergic arousal system dysregulation. At least four relatives were included for each NFLE proband and control. Each subject was questioned about tobacco habits; 434 individuals were recruited. Moreover, we compared NFLE patients with age- and sex-matched controls to determine whether they are more likely to use tobacco. We found a slightly higher trend of tobacco use in NFLE probands compared to that in control subjects; we did not find any significant difference in the distribution of tobacco use among NFLE group compared to that in the control group.

Background Cataplexy is the main motor symptom of narcolepsy/cataplexy and is considered a form of rapid eye movement (REM) sleep motor dyscontrol appearing during wakefulness and elicited by emotions. This study examined the relationship between the frequency of cataplectic attacks in patients with narcolepsy/cataplexy and (a) the clinical and behavioural characteristics of cataplectic attacks, including the emotional tone of trigger events, and (b) the polysomnographic characteristics of daytime sleepiness, nocturnal sleep structure and indices of motor disorders during sleep. Methods A consecutive series of 44 first-diagnosed drug-naive patients with narcolepsy/cataplexy, fulfilling the International Classification of Sleep Disorders, 2nd edition (ICSD-2) clinical and polysomnographic diagnostic criteria, were interviewed to estimate the frequency and clinical characteristics of cataplectic attacks and the occurrence of REM sleep behaviour disorder (RBD). All patients also underwent a video-polysomnographic recording to assess their sleep parameters and indices of altered motor control during sleep. Results Patients were divided into two groups on the basis of the frequency of cataplectic attacks, namely high-frequency ( n =30) or low-frequency ( n =14) depending on whether they estimated they had more or less than one attack per month. High-frequency patients (with a larger proportion of men) reported attacks more often affecting mainly the head, jaw and shoulder muscles and experienced more events among those listed as possible triggers of attacks. Sixty-one percent of patients reported RBD and 43% had an RBD episode at video-polysomnography regardless of the frequency of cataplectic attacks or gender. Lastly, the frequency of periodic leg movements (PLM) per hour was higher in men than women and increased with age. Conclusions Patients with more than one cataplectic attack per month had more frequent involvement of head, jaw and shoulder muscles and were mainly men. The proportions of patients with clinically assessed RBD and an RBD episode documented by video-polysomnography, as well as conspicuous values of PLM per hour, are fairly consistent with those reported in recent small-group studies. Therefore, it seems legitimate to argue that RBD and PLM are nocturnal manifestations intrinsic to narcolepsy/cataplexy and that the gender-related differences in the frequency of attacks and the value of PLM per hour may be indicative of a larger difference in the clinical and polysomnographic characteristics of narcolepsy/cataplexy than hitherto suspected.

Background This is an updated version of the original Cochrane review published in Issue 1, 2008. Narcolepsy is a disorder of the central nervous system, the main symptoms of which are excessive daytime sleepiness (EDS) and cataplexy (an abrupt and reversible decrease in or loss of muscle tone, affecting the limbs or trunk or both, elicited by emotional stimuli). Narcolepsy has an adverse impact on people's quality of life. Together with stimulant drugs (used to control EDS), antidepressants are usually recommended to counteract cataplexy. In addition, some antidepressants are also reported to improve EDS. Objectives To evaluate the effects of antidepressant drugs on EDS, cataplexy, quality of life, and their side effects in people with narcolepsy. Search methods We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library February issue, 2010), MEDLINE (1950 to March 2010), EMBASE (1980 to April 2010), PsycINFO (1872 to March 2010), and CINAHL (1981 to March 2010). Bibliographies of identified articles were reviewed to find additional references. Unpublished randomised trials were searched for by consulting governmental and non-governmental clinical trial registers, disease-specific websites, investigators and experts in the field, pharmaceutical companies/manufacturers. Selection criteria Parallel or cross-over randomised or quasi-randomised controlled trials testing the treatment of narcolepsy with any type of antidepressant drug versus no treatment, placebo, or another antidepressant drug. Data collection and analysis Two review authors independently assessed trial quality and extracted data. Main results Three cross-over and two parallel trials were included with a total of 246 participants. The methodological quality of all studies was unclear. As the trials tested different comparisons, or had a different design or dealt with different outcome measures, meta-analysis was not performed. In one cross-over trial (10 participants) femoxetine had no significant effect in eliminating or reducing EDS but significantly reduced cataplexy. Mild and transient side effects were reported in the femoxetine treatment period by two participants. In a second cross-over trial (56 participants) viloxazine significantly reduced EDS and cataplexy. In a third cross-over trial the authors inappropriately treated the trial design as a parallel study and no conclusions can be reached in favour of either drug. Two more trials with parallel design tested ritanserin versus placebo without finding differences of effectiveness in reducing EDS or cataplexy. Authors' conclusions Since the last version of this review no new studies were found. There was no good quality evidence that antidepressants are effective for narcolepsy or improve quality of life. Despite the clinical consensus recommending antidepressants for cataplexy there is scarce evidence that antidepressants have a positive effect on this symptom. There is a clear need for well-designed randomised controlled trials to assess the effect of antidepressants on narcolepsy.

We performed a 2-year population-based study on status epilepticus (SE) in adults in the rural area of Lugo di Romagna, northern Italy, to verify whether an area of low-level urbanization has a lower risk of occurrence of SE (as recently suggested), different clinical features and short-term prognosis than areas of high-level urbanization. We found crude and age- and sex-adjusted annual incidence rates of SE of 16.5/100 000 and 11.6/100 000, respectively. In patients under 60 years crude incidence was 2.9/100 000 and in the elderly (>/=60 years) 38.6/100 000. Acute symptomatic SE accounted for 30% and a cerebrovascular pathology was the most frequently associated etiologic condition (60%). A history of seizures was reported in 41% of patients. The first therapeutic intervention was mainly benzodiazepines (lorazepam 46%; diazepam 33%). The 30-day case fatality was 7%. We observed that the adult population of an area with a low level of urbanization has the same risk for SE, clinical features and short-term prognosis as European urban areas. The only contrasting result is the 30-day case fatality of 7% against the 39% found in the other Italian study (Bologna), despite the similarity of the SE features in these two areas of the same region. We infer that the short-term prognosis of SE could also be considerably influenced by differences in health service organization (and hence management) possibly due to different levels of urbanization.

To estimate the interobserver reliability (IR) of the minimal diagnostic criteria for the parasomnias provided in the International Classification of Sleep Disorders Revised (ICSD-R).Fifty consecutive subjects underwent a structured interview by three doctors based on the ICSD-R minimal criteria for the diagnosis of 13 parasomnias at any time in life. IR was calculated by Kappa statistics and interpreted according to conventional categories.In the group of Arousal Disorders, IR was "substantial" (kappa 0.74) for confusional arousals, "slight" (kappa 0.36) for sleepwalking, "fair" (kappa -0.02) for sleep terrors. In the group of Wake-Sleep Transition Disorders, IR was "substantial" to "almost perfect", but "moderate" for sleep starts (kappa 0.41). In the group of Parasomnias usually associated with REM Sleep, IR was "substantial" (kappa 0.69) for sleep paralysis, "moderate" (kappa 0.46) for RBD, "fair" (kappa 0.25) for nightmares. In the group of Other Parasomnias, IR was "substantial" to "almost perfect" (kappa between 0.73 and 0.93).When the clinical diagnosis of parasomnias is based on the ICSD-R: 1) the majority of Arousal Disorders and REM sleep parasomnias showed only a "fair" to "moderate" IR; 2) all of the other parasomnias showed a "substantial" to "almost perfect" IR. Nosological entities with unsatisfactory IR share complex motor phenomenology associated with a mental state difficult for the patient to define. The source of disagreement probably lies in the difficulty in interpreting patients' reports. For these parasomnias IR must be verified and possibly improved with training.

The aim of this study was to evaluate the prevalence of mood and eating disorders in patients with menstrual migraine. Quality of life and disability were also assessed. The study confirmed the presence of significant disability and poor quality of life due to migraine even in a selected subgroup of patients affected with menstrual migraine. In contrast with the previous literature we did not find any difference in the prevalence of mood and eating disorders.

Background and Objectives: This study investigated whether the altered organization of post-training sleep in patients with narcolepsy-cataplexy (NC) is associated with a lower off-line improvement in the consolidation of motor skills compared with normal subjects. Study Design: Fourteen drug-naive NC patients, fulfilling the international clinical and polysomnographic diagnostic criteria, and 14 individually-matched controls underwent training at a sequential finger tapping task (FTT) and were re-tested on the next morning (after a night with polysomnographic recording) and after another six nights (spent at home). Setting: Training and retrieval sessions were performed in a controlled laboratory setting. Results: FTT performance was worse in NC patients than controls at training and at both retrieval sessions and showed a fairly different time course (slower than in controls) of consolidation. Several sleep indices (lower values of stage-2 NREM sleep and SWS) were compatible with a lower effectiveness of sleep for consolidation of motor skills in NC patients, although no statistically significant relationship was found between such indices and improvement rate. Conclusion: The consolidation process of motor skills results less effective in NC patients since training and slower than in normal subjects over the week following training. The wider variations in performance scores and sleep parameters of post.-training night in NC patients relative to controls suggest that a) the lower initial consolidation may be due to a less effective encoding consequent to altered prior sleep, and b) the consolidation process over the 24 h following training is negatively influenced not only by the altered characteristics of post-training sleep, but also by the daytime sleepiness following training.

Nocturnal frontal lobe epilepsy (NFLE) is characterized by seizures with complex, often bizarre, violent behaviour arising only or mainly during sleep. These unusual seizures and their occurrence during sleep are often accompanied by normal EEG tracings and neuroradiological findings, making it difficult to distinguish NFLE seizures from other non-epileptic nocturnal paroxysmal events, namely parasomnias. NFLE was described for the first time in 1981, but, as its epileptic origin was controversial, the condition was called nocturnal paroxysmal dystonia. Even though many aspects of parasomnias and NFLE have been clarified in the last two decades, the problem of differential diagnosis remains a challenge for clinicians. This paper discusses some controversial points still under debate. The difficulties in distinguishing nocturnal epileptic seizures from parasomnias reflect just one aspect of the intriguing issue of the pathophysiological relationships between all types of paroxysmal motor behaviours during sleep.

Objectives To measure the accuracy of anamnestic features collected during clinical history for the diagnosis of nocturnal frontal lobe epilepsy (NFLE). Methods A case-control diagnostic study. Participants included a case group of people with ascertained target disease (NFLE group) and a control group of people with sleep disorders potentially confounding for NFLS (NOT-NFLE group), defined by means of a consensus procedure among experts (panel diagnosis as reference standard). Two major clinical patterns defining the semeiology of the epileptic event (i.e. dystonic, DP, and/or hyperkinetic pattern, HP), and 13 additional minor features were identified, formulated as questions, and telephonically administered to NFLE and NOT-NFLE groups by a trained doctor blinded to the final diagnosis. The diagnostic accuracy of each characteristic was tested against the reference standard. Results Out of 262 selected subjects, 101 were recruited; 42 were NFLE and 59 NOT-NFLE. A positive history of DP or HP had a sensitivity of 59.5% and a specificity of 91.5%, irrespective of the other minor anamnestic features. The anamnestic model improved, with a sensitivity of 59.5% and specificity of 96.6%, if at least one of the following four minor anamnestic features was added: (a) duration less than two minutes, (b) unstructured vocalization during the episode, (c) experience of an aura preceding the motor attack, and (d) a history of tonic-clonic seizures during sleep. Conclusions The present study disclosed two major anamnestic patterns and four minor features that we called SINFLE, with unsatisfactory sensitivity but high specificity. These patterns could be the basis for developing future NFLE diagnostic criteria and to quantify the diagnostic accuracy of elements usually collected in the clinical history.

Objectives.— The aim of our study was to investigate the prevalence of sleep disorders in chronic headache patients and to evaluate the role of psychiatric comorbidity in the association between chronic headache and sleep complaints. Background.— The prevalence of sleep disorders in chronic headache has been seldom investigated, although from the earliest description chronic headache has been associated with sleep disturbances. On the contrary, mood disorders are commonly associated with both sleep disturbances and chronic headache – each of which are, in turn, core features of mood disorders. Therefore, it may be important to discriminate between sleep problems that can be attributed to a comorbid psychiatric disorder, and those specifically associated with headache. Only a few studies investigating the association of chronic headache with sleep difficulties have also taken into account to consider the possible role of anxiety and depression. Patients and Methods.— A total of 105 consecutive patients with daily or nearly daily headache and 102 patients with episodic headache, matched by age, sex, and type of headache at onset, underwent a structured direct interview about their sleep habits and psychiatric diseases. Results.— In total, 80 out of 105 patients with chronic headache received a diagnosis of medication overuse headache, 21 patients were classified as chronic migraine and 4 as chronic tension-type headache without drug overuse. Patients.— Patients with chronic headache showed a high prevalence of insomnia, daytime sleepiness, and snoring with respect to controls (67.7% vs 39.2%, 36.2% vs 23.5%, and 48.6% vs 37.2%, respectively). Forty-five patients with chronic headache (42.9%) had psychiatric comorbidity (anxiety and/or depressive disorders), vs 27 episodic headache patients (26.5%). Multivariate analysis disclosed that low educational level, lower mean age at headache onset, and insomnia are independently associated with chronic headache. Conclusions.— Patients with chronic headache had a high prevalence of sleep complaints. Insomnia may thus represent an independent risk factor for headache chronification. Recognition of sleep disorders, alone or in association with depression or anxiety, may be useful in episodic headache patients to prevent chronification.

Objective To evaluate the 5-year variation of health-related quality of life (HRQoL) and mood symptoms in a cohort of patients with narcolepsy. Methods Adults attending the Sleep Centre of the Department of Neurological Sciences, University of Bologna in 1997 and meeting the International Classification of Sleep Disorders-Revised criteria for the diagnosis of narcolepsy were eligible. Included patients self-administered the Medical Outcome Short Form-36 (SF-36) and the Zung depression scale (ZDS) prospectively in 1998 and 2003. Results There was no significant difference between 1998 and 2003 measures of SF-36 and ZDS in the 54 patients included. About 25% of them showed moderate or severe mood symptoms in both observations. ZDS score (inversely) and duration of disease (directly) explained a percentage of variance of role physical, vitality (VT), social functioning (SF) and role emotional. At the second observation VT and SF had a further percentage of variance explained by excessive daytime sleepiness (EDS) and age at onset. Self-reported diabetes frequency doubled after 5 years (from 7% to 17%). Conclusions Patients with narcolepsy show a stable impairment of HRQoL in a 5-year period with respect to Italian normative data. Mood status and EDS negatively influence their HRQoL while disease duration has a positive influence.

Objective To describe the unique case of a middle-aged woman with severe insomnia recurring with a regular infradian period without any other significant clinical condition. To infer the existence of a circadian dysfunction modeled according to the physical phenomenon of the “beats.” Patient/Methods A two-year prospective observation by means of a sleep log was performed during the patient’s normal life. She underwent one month of motor activity recording and also polysomnography, circadian rhythm of body core temperature and psychiatric evaluation during periods with and without insomnia. Results Visual inspection of the 293-day plot of the sleep log disclosed a regular 42-day rhythm of insomnia recurrence confirmed by a Discrete Fourier Transform. During the periods of insomnia, lasting 5–7 days, only moderate mood symptoms (depressive overlapping hypomaniac symptoms) were present. Treatment with sodium valproate was effective in curtailing insomnia. Conclusion The wax and wane infradian modulation of the sleep length suggested the presence of a basic mechanism similar to the physical phenomenon of the “beats,” i.e., a long period modulation of the amplitude of an oscillating system due to the interference of two uncoupled oscillators with a slightly different oscillation frequency. Hypothesizing a dysfunction of the circadian component of sleep, namely two uncoupled circadian cycles, a simple mathematical model estimated the difference of their periods of oscillation |34 ± 2 min| and reproduced the sleep-log data of the drug-free period of observation.

We investigated the prevalence of nocturnal eating (sleep-related eating disorder-SRED or night-eating syndrome-NES) in patients with restless legs syndrome (RLS). One hundred RLS patients living in Emilia-Romagna (Northern Italy) and 100 matched controls randomly selected from the general population received two telephone interviews, and were investigated for socio-demographic characteristics, general health status, and presence of nocturnal eating. Additionally, subjects underwent interviews for psychopathological traits [by means of the Eating Disorder Inventory-2 (EDI-2), the Maudsley Obsessive-Compulsive Inventory (MOCI), the Beck Depression Inventory (BDI)], excessive daytime sleepiness (EDS), and subjective sleep quality. Compared with controls, RLS patients had more frequently pathological MOCI scores (24% versus 10%, P = 0.03), used significantly more drugs for concomitant diseases and had more nocturnal sleep impairment and EDS. SRED was more prevalent in RLS patients than controls (SRED: 33% versus 1%, P < 0.001). Medication use and pathological MOCI scores were more prevalent in RLS patients with SRED than among RLS patients without SRED. Use of dopaminergic or hypnotic drugs for RLS was not correlated with the presence of SRED. We demonstrate an association between RLS and SRED. Prospective studies are needed to establish the mechanisms underlying such association and whether it is causal.

We determined the cerebrospinal fluid (CSF) and serum neuron-specific enolase (NSE) concentrations in 19 patients with acute benign headache. All patients had normal neurological examination, CSF and head computed tomography scan. The final diagnoses were: primary thunderclap headache ( n = 7), primary exertional headache ( n = 3), primary cough headache ( n = 1), migraine without aura ( n = 4), headache unspecified ( n = 2), probable infrequent episodic tension-type headache ( n = 1), headache attributed to hypertensive crisis without hypertensive encephalopathy ( n = 1). A group of 108 healthy subjects served as controls. CSF NSE concentration was 14.16 ng/ml [95% confidence interval (CI) 11.86, 16.47)] in the headache sample (controls 17.19 ng/ml, 95% CI 16.23, 18.15). Serum NSE concentration was 7.50 ng/ml (95% CI 5.20, 9.80) in the headache sample (controls 8.45 ng/ml, 95% CI 7.67, 9.23). CSF/serum ratio was 2.81 (95% CI 2.21, 3.40) in the headache sample (controls 2.23, 95% CI 2.03, 2.42). Acute benign headache is not associated with neuronal damage as estimated by means of CSF and serum NSE concentration.

Summary: Purpose: Nocturnal frontal lobe epilepsy (NFLE) may be associated with sleep fragmentation and reduced sleep efficiency. Daytime sleepiness and disturbed sleep quality have been reported in some patients. We investigated the occurrence of daytime sleepiness-related symptoms and subjective sleep quality in patients with NFLE in comparison with matched controls. Methods: Patients with NFLE at a single epilepsy center and matched controls randomly selected from the general population self-administered questionnaires on daytime sleepiness-related symptoms and subjective sleep quality [Epworth sleepiness scale (ESS), Bologna questionnaire on sleepiness-related symptoms (BQS), Berlin questionnaire]. Results: Thirty-three patients with NFLE and 27 controls were enrolled. “Tiredness after awakening” and “spontaneous mid-sleep awakenings” were more frequent in NFLE patients than in controls (36.4% versus 11.1%, p = 0.04, and 50.0% versus 22.2%, p = 0.03). The frequency of excessive daytime sleepiness (EDS) did not differ between groups. Posthoc analysis showed that patients with a complaint of “midsleep awakenings” had higher ESS and BQS scores than those without (7.3 versus 4.3, p = 0.004, and 5.0 versus 2.2, p = 0.001, respectively) and more frequent “tiredness after awakening” (56.3% versus 18.8%, p = 0.03). Conclusions: Patients with NFLE have no pathological level of EDS with respect to controls. However, daytime sleepiness-related symptoms could be more frequent in a subgroup of patients with subjective disturbed sleep quality, irrespective of the perceived frequency of seizures.

Patients with narcolepsy-cataplexy (NC) present excessive daytime sleepiness (EDS), cataplexy and an altered architecture of nocturnal sleep, with frequent episodes of REM-sleep at sleep onset (SOREM-sleep). This altered organization of nocturnal sleep may be accompanied by some differences in the functioning of the cognitive processes involved in the access, organization and consolidation of information during sleep. This study attempts to ascertain whether the activation of semantic memory during REM-sleep, as measured using a technique of semantic priming (namely, the facilitation of the activation of strongly-related rather than weakly-related and, overall, unrelated pairs of prime-target words) is different in NC patients compared to normal subjects. A lexical decision task (LDT) was carried out twice in wakefulness (at 10a.m. and after a 24h interval) and twice in the period of sleep inertia following awakening from SOREM and 4th-cycle REM-sleep on 12 NC patients and from 1st- and 4th-cycle REM-sleep on 12 matched controls. Reaction time (RT) to target words, taken as a measure of the semantic priming effect, proved to be longer (a) in NC patients than in control subjects; (b) in the period of REM-sleep inertia than in wakefulness; (c) in the first rather than the second session; and (d) for unrelated compared to weakly-related and, overall, strongly-related prime-target pairs. RT in post-REM-sleep sessions was less impaired, compared to waking sessions, and less dependent on the associative strength of prime-target pairs in NC patients than in normal subjects. Finally, RT of NC patients, although longer than that of normal subjects in waking sessions, significantly improved in the second session, as a consequence of either the amount of exercise or the consolidation advantage provided by REM-sleep for the procedural components of the task. The whole picture suggests a greater effectiveness of the activation of semantic memory during (SO)REM-sleep in NC patients rather than in normal subjects, and overall for the organization of new and unexpected relationships (such as those between unrelated pairs) between items of information.

Sleep-related eating disorder (SRED) is characterized by recurrent arousals from sleep associated with compulsive ingestion of food. No controlled therapeutic trials are available for SRED. We assessed the safety, tolerability and efficacy of pramipexole, a dopamine D3-receptor agonist, in the treatment of SRED. Eleven consecutive patients with SRED in the absence of concurrent daytime eating disorders underwent actigraphic recording and subjective sleep diary evaluation for a week before and every week for 2 weeks of treatment with pramipexole 0.18-0.36 mg or placebo, administered in a double-blind crossover randomized sequence. The primary outcomes of the trial were actigraphic measures of night sleep parameters (sleep efficiency, motor activity mean and median, number and duration of wake episodes), secondary outcomes were the number of good sleep nights/weekly, number and duration of nocturnal awakenings/night, and visual analogue preference score. Pramipexole was well tolerated without any patient withdrawing from the study. Pramipexole reduced night-time activity median (P = 0.02) and increased the number of nights of good sleep/week (P = 0.02). All other measurements remained unaffected. Pramipexole at low doses was well tolerated, improving some measures of sleep quality and reducing median night activity in SRED. Further studies with higher dosages and for longer time-periods are warranted.