Luca Carnicelli

Sleep in frontotemporal dementia is equally or possibly more disrupted, and at an earlier stage, when compared to sleep in Alzheimer's disease.

BACKGROUND Conversely to other neurodegenerative diseases (i.e., Alzheimers disease, AD), sleep in frontotemporal dementia (FTD) has not been studied adequately. Although some evidence exists that sleep-wake disturbances occur in FTD, very little is known regarding sleep macrostructure and/or primary sleep disorders. OBJECTIVE To investigate these issues in this population and compare them to similar issues in AD and in healthy elderly (HE). METHODS Twelve drug-naïve behavioral-variant FTD (bvFTD) patients (7 men/5 women) of mean age 62.5 ± 8.6 years were compared to seventeen drug-naïve AD patients (8 men/9 women) of mean age 69.0 ± 9.9 years and twenty drug-naïve HE (12 men/8 women) of mean age 70.2 ± 12.5 years. All participants were fully assessed clinically, through a sleep questionnaire, an interview, and video-polysomnography recordings. RESULTS The two patient groups were comparably cognitively impaired. However, compared to FTD patients, the AD patients had a statistically significant longer disease duration. Overall, the sleep profile was better preserved in HE. Sleep complaints did not differ considerably between the two patient groups. Sleep parameters and sleep macrostructure were better preserved in AD compared to FTD patients, regardless of primary sleep disorders, which occurred equally in the two groups. CONCLUSIONS With respect to AD, FTD patients had several sleep parameters similarly or even more affected by neurodegeneration, but in a much shorter time span. The findings probably indicate a centrally originating sleep deregulation. Since in FTD patients sleep disturbances may be obvious from an early stage of their disease, and possibly earlier than in AD patients, physicians and caregivers should be alert for the early detection and treatment of these symptoms.

Non-rapid eye movement sleep instability in mild cognitive impairment: a pilot study

OBJECTIVE Polysomnographic (PSG) studies in mild cognitive impairment (MCI) are not conclusive and are limited only to conventional sleep parameters. The aim of our study was to evaluate sleep architecture and cyclic alternating pattern (CAP) parameters in subjects with MCI, and to assess their eventual correlation with cognition. METHODS Eleven subjects with MCI (mean age 68.5 ± 7.0 years), 11 patients with mild probable Alzheimers disease (AD; mean age 72.7 ± 5.9 years), referred to the Outpatient Cognitive Disorders Clinic, and 11 cognitively intact healthy elderly individuals (mean age 69.2 ± 12.6 years) underwent ambulatory PSG for the evaluation of nocturnal sleep architecture and CAP parameters. RESULTS Rapid eye movement sleep, CAP rate, and CAP slow components (A1 index) were decreased in MCI subjects and to a greater extent in AD patients, compared to cognitively intact controls. AD showed also decreased slow wave sleep (SWS) relative to healthy elderly individuals. MCI nappers showed decreased nocturnal SWS and A1 subtypes compared to non-nappers. Several correlations between sleep variables and neuropsychological tests were found. CONCLUSIONS MCI and AD subjects showed a decreased sleep instability correlated with their cognitive decline. Such a decrease may be considered as a potential biomarker of underlying neurodegeneration.

Differences in EEG delta frequency characteristics and patterns in slow-wave sleep between dementia patients and controls: a pilot study.

Purpose To evaluate the modifications of EEG activity during slow-wave sleep in patients with dementia compared with healthy elderly subjects, using spectral analysis and period-amplitude analysis. Methods Five patients with dementia and 5 elderly control subjects underwent night polysomnographic recordings. For each of the first three nonrapid eye movement–rapid eye movement sleep cycles, a well-defined slow-wave sleep portion was chosen. The delta frequency band (0.4–3.6 Hz) in these portions was analyzed with both spectral analysis and period-amplitude analysis. Results Spectral analysis showed an increase in the delta band power in the dementia group, with a decrease across the night observed only in the control group. For the dementia group, period-amplitude analysis showed a decrease in well-defined delta waves of frequency lower than 1.6 Hz and an increase in such waves of frequency higher than 2 Hz, in incidence and amplitude. Conclusions Our study showed (1) a loss of the dynamics of delta band power across the night sleep, in dementia, and (2) a different distribution of delta waves during slow-wave sleep in dementia compared with control subjects. This kind of computer-based analysis can highlight the presence of a pathologic delta activity during slow-wave sleep in dementia and may support the hypothesis of a dynamic interaction between sleep alteration and cognitive decline.

What is the role for EEG after sleep deprivation in the diagnosis of epilepsy? Issues, controversies, and future directions.

In patients with a first seizure, the identification of early sensitive and specific biomarkers for formulating a diagnosis of epilepsy is fundamental. Sleep deprivation (SD) has long been used as a means of enhancing EEG sensitivity in the diagnostic process. However, huge methodological differences among the studies addressing this topic have led to highly variable results and often confusing assumptions. Here, we provide a detailed description of the correlations between SD and epilepsy, along with their putative mechanistic explanations derived from experimental studies in animals and humans. We also outline the clinical studies evaluating the role of SD EEG and discuss them critically in terms of: (a) study design and SD EEG methodology; (b) EEG sensitivity and specificity; (c) the role of drug-induced sleep EEG and EEG during spontaneously occurring sleep; and (d) the relevance of patient features, syndromes, and subsyndromes, as well as their correlations with neuroimaging details. Finally, we propose specific studies that might increase the role of SD EEG in the diagnosis and prognosis of epilepsy.

Psychological well-being of patients with insomnia and its relationship with anxiety and depression

The aims of the present study are to evaluate the impact of insomnia on psychological well-being and to examine the associations of insomnia and psychological well-being with anxiety and depression. Forty-one patients attending our hospital-based Centre for sleep medicine were administered scales for the evaluation of insomnia (ISI), anxiety (STAI-Y), depression (BDI-II) and psychological well-being (PWB). The scores were compared to those of a control group of 68 subjects attending the hospital for routine examinations or as accompanying persons. Significant differences between patients and controls were detected for anxiety and depression, as well as for psychological well-being. Even if subclinical on average, anxiety and depression symptoms were significantly related to poor psychological well-being, whereas insomnia per se was not. These findings suggest that patients with insomnia report a relevant impact on their psychological well-being, and that such an impact seems to be strongly associated with concomitant subthreshold symptoms of anxiety and depression. The implications for diagnosis and treatment are discussed.

Controversial Issues on EEG after Sleep Deprivation for the Diagnosis of Epilepsy

EEG after sleep deprivation (SD-EEG) is widely used in many epilepsy centers as an important tool in the epilepsy diagnosis process. However, after more than 40 years of use, there are a number of issues which still need to be clarified concerning its features and role. In particular, the many scientific papers addressing its role in epilepsy diagnosis often differ remarkably from each other in terms of the type of patients assessed, their description and study design. Furthermore, also the length and the type of EEG performed after SD, as well as the length of SD itself, vary dramatically from one study to another. In this paper we shortly underscore the abovementioned differences among the different reports, as well as some interpretations of the findings obtained in the different studies. This analysis emphasizes, if needed, how SD-EEG still represents a crucial step in epilepsy diagnosis, and how additional, controlled studies might further shape its precise diagnostic/prognostic role.

Correlational analysis of electroencephalographic and end-tidal carbon dioxide signals during breath-hold exercise.

The central mechanism of breathing control is not totally understood. Several studies evaluated the correlation between electroencephalographic (EEG) power spectra and respiratory signals by performing resting state tasks or adopting hypercapnic/hypoxic stimuli. The observation of brain activity during voluntary breath hold tasks, might be an useful approach to highlight the areas involved in mechanism of breath regulation. Nevertheless, studies of brain activity with EEG could present some limitations due to presence of severe artifacts. When artifact rejection methods, as independent component analysis, cannot reliably clean EEG data, it is necessary to exclude noisy segments. In this study, global field power in the delta band and end-tidal CO2 were derived from EEG and CO2 signals respectively in 4 healthy subjects during a breath-hold task. The cross correlation function between the two signals was estimated taking into account the presence of missing samples. The statistical significance of the correlation coefficients at different time lags was assessed using surrogate data. Some simulations are introduced to evaluate the effect of missing data on the correlational analysis and their results are discussed. Results obtained on subjects show a significant correlation between changes in EEG power in the delta band and end-tidal CO2. Moreover, the changes in end-tidal CO2 were found to precede those of global field power. These results might help to better understand the cortical mechanisms involved in the control of breathing.

Daytime sleepiness in de novo untreated patients with epilepsy

The aims of our study were to evaluate excessive daytime sleepiness in a group of de novo untreated people with epilepsy using a comprehensive and standardized approach, including subjective evaluation and neurophysiological and performance tests, and to compare these results with those obtained in a control group. Forty-seven patients with epilepsy (17 affected by primary generalized epilepsy and 30 by partial epilepsy), with a new epilepsy diagnosis and never treated, and 44 controls underwent Multiple Sleep Latency Test (preceded by nocturnal polysomnography), simple/complex visual reaction times, and Epworth Sleepiness Scale evaluation. Newly diagnosed and drug-free patients with epilepsy did not differ from controls in any of the tests performed to evaluate daytime sleepiness. In clinical practice, daytime sleepiness is a well-known and frequent complaint of patients with epilepsy, but different mechanisms and causes, such as associated psychiatric or sleep disorders, nocturnal seizures, sleep fragmentation, and antiepileptic drugs, must be taken into account. Excessive daytime sleepiness should not be considered an unavoidable consequence of epilepsy. Thus, a complete diagnostic work-up in patients with epilepsy and sleepiness should be undertaken whenever possible.

Exacerbation of restless legs syndrome presenting as a psychiatric emergency

Sir, We read with great interest the case descriptions by Mehta et al. [1] and Manconi and Fulda [2] and appreciated the highlight on restless legs syndrome (RLS) as a clinical manifestation in emergency. We report a similar, although less dramatic, case. We evaluated in the emergency department a 60-year-old male referred for severe worsening of RLS lasting continuously for 2 days and leading to severe insomnia and leg restlessness. The patient had a history of bipolar depression and impulse control disorder and was treated with valproate 900 mg/day. RLS symptoms started 2 years before but, since they were mild and sporadic, no treatment was suggested. Owing to severe insomnia and worsening of depressive symptoms, mirtazapine 30 mg at bedtime was added. Immediately after, RLS symptoms dramatically worsened. On the second night, pramipexole 0.25 mg in the evening was started with no benefit. In the third afternoon the patient came to the emergency department with severe agitation and restlessness, being unable to sit down without moving. We immediately decided to stop mirtazapine and, due to the anxiety symptoms and previous psychiatric history, we preferred not to use high dosage dopamine agonists and shifted the treatment to tramadol 25 mg and gabapentin 300 mg. The patient refused to be admitted into our ward. However, the next morning he reported an impressive improvement of the symptoms. In the first month, tramadol was gradually discontinued and gabapentin was increased to 600 mg/day. After more than 4 years of follow-up, RLS and bipolar symptoms appear still controlled with gabapentin 600 mg in the evening, valproate CR 300 mg TID and imipramine 12.5 mg TID. This case report is a further example of how RLS could become a real emergency. A drug-related worsening, or occurrence, of RLS symptoms should always be considered in the differential diagnosis of agitation. In this case, although psychiatric history and symptoms of anxiety were confounding factors, correct identification of RLS symptoms (both during the previous years and currently) together with a recent change in antidepressant therapy led to the correct diagnosis. The successful treatment was based on therapy with alpha-delta ligand, but probably even more so on the discontinuation of mirtazapine. It should be underlined that mirtazapine has the highest risk for RLS among second-generation antidepressants [3], typically within the first week, and provokes periodic limb movements even in healthy subjects [4]. However, a similar case report had been described with citalopram [5]. Thus, we would suggest that a list of contraindicated drugs should be diffused to general practitioners, other specialists and also to patients to help the correct treatment of comorbidities in RLS.

Sleep disorders in menopause: results from an Italian Multicentric Study

Menopause in the female life cycle is a special period due to important hormonal, physical and psychological changes. Sleep disruption represents a common complaint for midlife and menopausal women, related to primary sleep disorders, including insomnia, sleep disordered breathing, restless legs syndrome (RLS), mood and anxiety disorder, other medical illness, hormonal-related vasomotor symptoms, and aging per se. Aims of our study were to evaluate the prevalence of sleep disorders in a sample of pre and post menopausal women, and to investigate the relationship between sleep and other medical disorders, and life habits. Among workers in the six participant centers, we enrolled 334 women, aged between 40 and 60 years, that completed a questionnaire that included screening on menarche, menstrual cycle, fertility, parity, menopause, life habits, personal medical and sleep history and related treatment, and self-administered scales for sleep quality (PSQI), excessive daytime sleepiness [Epworth Sleepiness Scale (ESS)], mood disorder [Beck Depression Inventory (BDI)], Berlin Questionnaire for sleep disordered breathing (SDB), IRLS diagnostic interview and Rating Scale. Menopausal and perimenopausal women showed an increased prevalence of poor sleep, high risk of SDB, and mood disorder; menopausal women also reported increased RLS severity. Mood disorder had a significant impact on night sleep measures and excessive daytime sleepiness, as well as on RLS severity, and had a greater prevalence in hypertensive women. Sleep disturbances are frequent in menopausal women. Their aetiology is unclear, but probably multifactorial, and many factors contribute to the sleep disruption. Our data suggest the importance of correctly investigate and address sleep problems associated with menopause, through sleep history, and a sleep study could be obtained if clinically warranted. Pharmacological and behavioural treatment strategies should then be aimed at improving sleep and life quality in perimenopausal and menopausal women.