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.

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.

Absence of cardiovascular disease risk factors in restless legs syndrome.

OBJECTIVE: Restless legs syndrome (RLS) might represent a condition at risk of cardiovascular (and cerebrovascular) disease; the role of sleep periodic leg movements, sleep deprivation, and presence of common risk factors for heart disease in these patients remains to be determined. The aim of this study was to evaluate the eventual presence of risk factors for cerebrovascular disease in RLS. MATERIALS & METHODS: Eighty-seven consecutive patients affected by idiopathic RLS were included in this study together with 81 controls. Blood count, chemistry, and kidney function tests were obtained. We detected subjects suffering from diabetes mellitus, kidney diseases, heart diseases, disk herniation, neuropathy, blood diseases, liver diseases, artery diseases, dyslipidemia, or hypertension. Polysomnography was recorded in 66 patients, and cerebral neuroimaging was obtained in 59 patients with RLS. RESULTS: None of the differences in blood test parameters was statistically significant; however, hypertension was found to be more frequent in controls and dyslipidemia was more frequent in patients with RLS, but this was explained by its higher frequency in patients also affected by obstructive sleep apnea. A diagnosis of cerebrovascular disease was posed for 14 patients with RLS (16.1%), but no predictive factor for its presence was found at the binomial logistic regression. CONCLUSION: Our findings argue against the presence of an altered lipid metabolism as a risk factor for the development of cerebrovascular disease in patients with RLS, even if they do support the idea that cerebrovascular disease might be frequent in this condition.

Turning off artistic ability: the influence of left DBS in art production.

BACKGROUND: The influence of Parkinson's disease (PD) as well as deep brain stimulation (DBS) on visual-artistic production of people who have been artists is unclear. We systematically assessed the artistic-creative productions of a patient with PD who was referred to us for management of a left subthalamic region (STN) DBS. The patient was an artist before her disease started, permitting us to analyze changes in her artistic-creative production over the course of the illness and during her treatment with DBS. METHODS: We collected her paintings from four time periods: Time 1 (Early Pre-Presymptomatic), Time 2 (Later Presymptomatic), Time 3 (Symptomatic), and Time 4 (DBS Symptomatic). A total of 59 paintings were submitted to a panel of judges, who rated the paintings on 6 different artistic qualities including: aesthetics, closure, evocative impact, novelty, representation, technique. RESULTS: Aesthetics and evocative impact significantly declined from Time 2 to Time 4. Representation and technique indicated a curvilinear relationship, with initial improvement from Time 1 to Time 2 followed by a decline from Time 2 to Time 4. CONCLUSIONS: These results suggest that left STN/SNR-DBS impacted artistic performances in our patient. The reason for these alterations is not known, but it might be that alterations of left hemisphere functions induce a hemispheric bias reducing the influence the right hemisphere which is important for artistic creativity. The left hemisphere itself plays a critical role in artistic creativity and DBS might have altered left hemisphere functions or altered the mesolimbic system which might have also influenced creativity. Future studies will be required to learn how PD and DBS influence creativity.

A single question for the rapid screening of restless legs syndrome in the neurological clinical practice.

The purposes of this study were to validate the use of a single standard question for the rapid screening of restless legs syndrome (RLS) and to analyze the eventual effects of the presence of RLS on self-assessed daytime sleepiness, global clinical severity and cognitive functioning. We evaluated a group of 521 consecutive patients who accessed our neurology clinic for different reasons. Beside the answer to the single question and age, sex, and clinical diagnosis, the following items were collected from all patients and normal controls: the four criteria for RLS, the Epworth Sleepiness Scale (ESS), the Clinical Global Impression of Severity (CGI-S), and the Mini-Mental State evaluation. RLS was found in 112 patients (70 idiopathic). The single question had 100% sensitivity and 96.8% specificity for the diagnosis of RLS. ESS and CGI-S were significantly higher in both RLS patient groups than in normal controls. RLS severity was significantly higher in idiopathic than in associated/symptomatic RLS patients. RLS can be screened with high sensitivity and good reliability in large patient groups by means of the single question; however, the final diagnosis should always be confirmed by the diagnostic features of RLS and accompanied by a careful search for comorbid conditions.

Low total cholesterol predicts mortality in the nondemented oldest old.

Several studies have demonstrated the importance of hypercholesterolemia as a cardiovascular risk factor and a direct correlation between the reduction in cholesterolemia and the reduction in cardiovascular mortality in populations younger than 65 years. This correlation is controversial in the elderly and, particularly, in the oldest old. The aim of our study was to evaluate the total cholesterol in the oldest old and to assess the eventual presence of correlation between total cholesterol levels and mortality in a group of nondemented oldest old. A subsample of 40 subjects was extracted from the 103 subjects aged over 84 years living in Troina, a rural village in Sicily. We excluded all subjects under therapy with lipid-lowering drugs, demented, with malnutrition or affected by acute or chronic diseases which might cause death in the short term. At the end, 23 subjects (15 males and 8 females) were included in the study. After 2 years, mortality data of all subjects included in the study were obtained from official registers. The statistical analysis was performed by means of the X(2) test. In all subjects the mean of total cholesterol was of 182+/-32 mg/dl (mean+/-SD) and the body mass index was above 20; 17 subjects were in the normal range, 3 were moderately over-weighed and 3 were severely over-weighed. Overall, mortality rate after 2 years was 30% (7 subjects, 4 males and 3 females). We evaluated the relationship between mortality and 4 factors: sex, age, body mass index (BMI) and serum total cholesterol. Mortality was significantly correlated (p<0.002) only with a low level of total serum cholesterol

Ischemic stroke and fibrinogen in the elderly.

Senescence is accompanied by an important increase in prevalence and incidence of ischemic stroke. The plasma level of fibrinogen tends to increase with age in the elderly similarly to the prevalence of stroke. The aim of our study was to evaluate the age-related increase in fibrinogen plasma level in the elderly and to assess the presence of eventual differences between normal subjects and patients with previous ischemic stroke associated with precerebral atherosclerosis. Eighty inpatients (41 males and 39 females), consecutively admitted to our Geriatric Unit, were included to this study. The patient group was formed 32 subjects (20 males and 12 females) aged 50-79 years, suffering from cerebrovascular disease with one or several previous ischemic stroke episodes, having occurred at least 1 year earlier. The control group consisted of 48 normal subjects (21 males and 27 females) aged 50-79 years. Both control and patient groups were subdivided into three subgroups, according to their age: Group 1 (50-59 years), Group 2 (60-69 years)and Group 3 (70-79 years). The statistical comparison was carried out by means of the Mann-Whithney nonparametric test. In normal controls, a mild age effect is evident because only Group 3 shows fibrinogen levels significantly higher than those of Group 1. On the contrary, in patients with ischemic stroke, an age effect is already evident between Group 2 and Group 1; of course, also the comparison between patient Group 3 and Group I shows a statistically significant difference. Moreover, the levels of fibrinogen were significantly increased in patient Group 2 and 3 when compared to those of their respective age-matched controls. Our data are in agreement with those already available in the literature and demonstrate that fibrinogen in normal aging changes with age and shows a 19 %increase between age Group 1 and Group 3. Patients with ischemic stroke show an earlier and more evident age-related increase in fibrinogen than normal controls. Even if it is not possible to know, if the increase in fibrinogen is a consequence or not of the ischemic stroke, we can affirm that certainly the increased levels of fibrinogen should be considered as an important risk factor in the elderly for cerebrovascular disease and deserve treatment.

Isolated monolateral neurosensory hearing loss as a rare sign of neuroborreliosis.

Lyme disease, or borreliosis, is a zoonosis transmitted by Borrelia burgdorferi which also involves the central nervous system (CNS), in 15% of affected individuals, with the occurrence of aseptic meningitis, fluctuating meningoencephalitis, or neuropathy of cranial and peripheral nerves. Encephalopathy with white matter lesions revealed by magnetic resonance imaging (MRI) scans in late, persistent stages of Lyme disease has been described. In this report, we describe a patient with few clinical manifestations involving exclusively the eighth cranial nerve, monolaterally and diffuse bilateral alterations of the white matter, particularly in the subcortical periventricular regions at cerebral MRI. This single patient study shows that the search for antibodies against Borrelia burgdoferi should always be performed when we face a leukoencephalopathy of unknown origin. An isolated lesion of the eighth cranial nerve can be the only neurologic sign in patients with leukoencephalopathy complicating Lyme disease.

Relationship between Delta, Sigma, Beta, and Gamma EEG bands at REM sleep onset and REM sleep end.

OBJECTIVE: The aim of the present study was to analyze in detail the relationship of two newly introduced measures, related to the Beta and Gamma EEG bands during REM sleep, with Delta and Sigma activity at REM sleep onset and REM sleep end, in order to understand their eventual role in the sleep modulation mechanism. METHODS: For this purpose, power spectra of 1 EEG channel (C4, referred to A1) were obtained by means of the fast Fourier transform and the power of the bands ranging 0.75-4.50 Hz (Delta), 4.75-7.75 (Theta), 8.00-12.25 (Alpha), 12.50-15.00 (Sigma), 15.25-24.75 (Beta), 25.00-34.75 (Gamma 1), and 35.00-44.75 (Gamma 2) was calculated for the whole period of analysis (7 h), in 10 healthy subjects. Additionally, two other time series were calculated: the ratio between Beta and Gamma2, and between Gamma1 and Gamma2 (Beta and Gamma ratios). For each subject, we extracted 3 epochs of 30 min corresponding to the 15 min preceding and the 15 min following the onset of the first 3 REM episodes. Data were then averaged in order to obtain group mean values and standard deviation. The same process was applied to the 30-min epochs around REM sleep end. RESULTS: The course of the Delta band around REM sleep onset was found to be characterized by a first phase of slow decline lasting from the beginning of our window up to a few seconds before REM onset; this phase was followed by a sudden, short decrease centered around REM onset, lasting for approximately 1.5-2 min. At the end of this phase, the Delta band reached its lowest values and remained stable up to the end of the time window. The Sigma band showed a similar course with stable values before and after REM sleep onset. The Beta and Gamma ratios also showed a 3-phase course; the first phase, in this case, was characterized by stable low values, from the beginning of our window up to approximately 5 min before REM onset. The following second phase was characterized by an increase which reached its maximum shortly after REM sleep onset (approximately 1 min). In the last phase, both Beta and Gamma ratios showed stable high values, up to the end of our time window. At REM sleep end, the Delta band only showed a very small gradual increase, the Sigma band presented a more evident gradual increase; on the contrary, both Beta and Gamma ratios showed a small gradual decrease. CONCLUSIONS: The results of the present study show a different time synchronization of the changes in the Delta band and in Beta and Gamma ratios, at around REM sleep onset, and seem to suggest that the oscillations of these parameters might be modulated by mechanisms more complex than a simple reciprocity. All these considerations point to the fact that REM sleep can be considered as a complex phenomenon and the analysis of high-frequency EEG bands and of our Beta and Gamma ratios represent an additional important element to include in the study of this sleep stage.

Somatosensory evoked potentials in patients affected by unilateral cerebrovascular lesions with onset during the perinatal period or adulthood.

Unilateral cerebrovascular lesions occurring during adulthood have been reported to be accompanied by high-amplitude somatosensory evoked potentials over the nonaffected hemisphere; however, the mechanisms by which somatosensory evoked potential amplitude increases over the nonaffected hemisphere are still unclear. To investigate the eventual presence of similar amplitude abnormalities in children, we recorded somatosensory evoked potentials in three groups of patients: one with unilateral cerebrovascular lesions that occurred during the perinatal period and another two with unilateral cerebrovascular lesions occurring during late adulthood or old age. Group 1 was comprised of 12 children and young adults (age range 2 3/12-31 years, 6 males and 6 females) who suffered from unilateral cerebrovascular lesion with perinatal onset. Four control groups were arranged with age matched to that of the patients. Adult patients were subdivided into two subgroups (group 2: n = 10, all males; group 3: n = 18, 12 males and 6 females) on the basis of the presence or absence of sensory impairment over the hemiplegic side. In group 1, the four youngest subjects, aged less than 6 years, were found to show somatosensory evoked potentials of abnormally high amplitude over the nonaffected hemisphere, with a "giant" main negative wave at around 45 ms (range 38.7-49.2), strictly localized over the central areas contralateral to the lesion; in normal controls, there was no such wave. All patients in group 2 were found to be affected by large infarctions in the territory of the middle cerebral artery, whereas patients in group 3 presented with subcortical lesions of the internal capsule isolated or in association with an involvement of the frontal and/or temporal cortex. Regarding somatosensory evoked potential parameters measured over the nonaffected hemisphere in adult/elderly subjects, a significant difference was observed for N20 and P22 latency, which was longer in both groups of patients than in controls. There is a significant difference in the neurophysiologic consequences of unilateral cerebrovascular lesion, as well as over the nonaffected hemisphere, if it occurs during early infancy or during adulthood. Our findings show a new type of "giant" somatosensory evoked potentials in some children affected by unilateral cerebrovascular lesion with perinatal onset.

Nail pathology in patients with hemiplegia.

BACKGROUND: It is well known that nails can be involved in some diseases of the central nervous system; however, no systematic study has been carried out in order to evaluate the incidence and the possible mechanisms of these nail changes in hemiplegia. OBJECTIVES: To study the presence of nail pathology specifically associated with hemiplegia and to evaluate its incidence and its temporal relationship with the onset of the neurological deficit. METHODS: In an open study, fingernails and toenails were examined by a dermatologist; 108 were patients with hemiplegia due to a stroke, consecutively admitted to our Department of Neurology between 1995 and 1998, and 121 were normal controls. RESULTS: Onychodystrophy of fingernails and onychomycosis of toenails were found in both patients with hemiplegia and normal controls. However, three conditions (longitudinal reddish striation, neapolitan nails and unilateral clubbing) were only observed in some patients, always affecting fingernails of the limb affected by hemiplegia. Neapolitan nails were present in three (3%) patients with hemiplegia which had its onset 3-14 months earlier. Hemiplegia had occurred approximately 40 months earlier, on average, in six patients (6%) with longitudinal reddish striation, and 60-120 months prior to unilateral clubbing in another two patients (2%). CONCLUSIONS: In this study we were able to assess the presence of three different fingernail conditions that were characteristically associated with hemiplegia (longitudinal reddish striation, neapolitan nails and unilateral clubbing), to evaluate their incidence and to study the delay with which these changes occur after a stroke.

Cerebrovascular CO2 reactivity in migraine with aura and without aura. A transcranial Doppler study.

INTRODUCTION: We studied by means of Transcranial Doppler (TCD) recordings the CO2 cerebrovascular reactivity in migraine patients during the headache-free period. MATERIAL & METHODS: In three groups of subjects (15 controls, 15 suffering from migraine with aura and 15 from migraine without aura) the middle cerebral artery (MCA) mean flow velocity (MFV) was recorded under basal condition and hypocapnia induced by hyperventilation. Relative MFV, PI (Pulsatility Index) changes and Reactivity Index (RI) were calculated. RESULTS: Reactivity Index values were: 0.019 +/- 0.007 (mean +/- SD) in control subjects: 0.029 +/- 0.008 in migraine with aura; 0.022 +/- 0.008 in migraine without aura. Statistical analysis showed a significantly (P < 0.05) increased RI in migraine with aura group. CONCLUSION: Cerebrosvascular CO2 reactivity is increased during the interictal period in migraine with aura patients.