Mariarosaria Valente

Sleep organization pattern as a prognostic marker at the subacute stage of post-traumatic coma

OBJECTIVES The aim of this study is to identify the predictive indexes for post-traumatic coma prognosis, which is important to better direct acute and subacute treatments and rehabilitation efforts. The pattern of sleep organization is a potential prognostic marker, but its role has not been established yet in the context of modern critical care. In the present study, we used a new protocol to evaluate the prognostic value of the different levels of sleep-wake organization recorded at the subacute stage of post-traumatic coma. METHODS Twenty-four head-injured comatose patients were monitored with 24h polysomnographic recordings. The predictivity of the different levels of sleep-wake organization on polysomnography was compared with other possible prognostic indexes (i.e. neuroradiological findings, age and Glasgow Coma Scores (GCS)). Main outcome measures were survival and the degree of disability after recovery from coma. RESULTS The presence of organized sleep patterns, but not GCS, was highly predictive of better outcome (odds ratio=10.78, P=0.01), even after correction for potentially confounding variables with multivariate analysis. CONCLUSIONS Our study demonstrates that the sleep-wake organization pattern based on 24h polysomnographic recordings at the subacute stages of post-traumatic coma is a reliable prognostic marker, both for survival and for functional recovery.

Daytime sleepiness is associated with dementia and cognitive decline in older Italian adults: a population-based study.

OBJECTIVE The occurrence of dementia among the elderly has been associated with several, often not modifiable, risk factors. Recent epidemiological studies focused their interest on a possible association between cognitive decline and sleep, a potentially modifiable risk factor. Due to controversial results and limitations of the previous studies, we decided to reexamine the relationship between disturbed sleep and cognitive impairment in the elderly. METHODS Seven hundred fifty subjects aged 65years or older were recruited. The Mini-Mental State Examination (MMSE) and the Global Deterioration Scale (GDS) scores were used to evaluate the severity of cognitive decline. Diagnosis of dementia was made by means of the DSM-IV criteria. The older adults were interviewed in order to assess the presence of several sleep complaints (insomnia, snoring and/or witnessed sleep apneas, restlessness and/or leg jerks, sleepwalking and nightmares). Excessive daytime sleepiness was evaluated by means of a validated questionnaire. The principal caregiver of each older adult took part in the interview, providing the information if the subject was unable to answer because of mental impairment. RESULTS Eighty-six individuals were diagnosed as demented; a large part of them (47.8%), in particular, were recognized as being affected by Alzheimers disease. The prevalence of each sleep complaint in the older adults was as follows: insomnia 84.7%, snoring and/or witnessed sleep apneas 26.2%, restlessness and/or jerks in the legs 25.7%, sleepwalking 0.5%, nightmares 6.4% and daytime somnolence 30.6%. Among sleep disturbances, excessive daytime sleepiness was independently associated with the presence of dementia in the elderly. In addition, the frequency of excessive daytime sleepiness increased progressively across the different categories of cognitive decline, as measured by means of MMSE and GDS scores. CONCLUSIONS Insomnia, the most common sleep complaint in our sample, was not associated with the presence of cognitive decline. As opposed to insomnia, excessive daytime sleepiness was significantly related to dementia. Further studies are needed in order to investigate the direction of this association and to evaluate the possible role of daytime somnolence as an early marker of neurodegenerative disease, particularly Alzheimers disease, in some older adults.

Drugs with anticholinergic properties: cognitive and neuropsychiatric side-effects in elderly patients.

AbstractDrug consumption in older people is usually high and many prescribed medications have unsuspected anticholinergic (ACH) (Table 1) properties. Drug induced ACH side-effects are particularly severe in aging brain and even more in demented patients. This review will focus on the association between ACH drug intake and the risk of developing central nervous system side-effects in elderly people. The threat of developing cognitive impairment, psychosis and delirium will be particularly analyzed.

Drugs with anticholinergic properties as a risk factor for cognitive impairment in elderly people: a population-based study.

Prevention of drug-related problems is a key issue in the aged. Anticholinergic (ACH) drugs are a biologically plausible and potentially modifiable risk factor for cognitive impairment. Therefore, we intended to evaluate the association between ACH drugs and cognitive impairment. Our study comprised 750 subjects aged 65 years or older. Cognitive impairment was evaluated using Mini-Mental State Examination and Global Deterioration Scale. Patients were classified into ACH-drug users and non-ACH-drug users. Those using ACH drugs (20.1%) were more likely to have cognitive impairment than those using non-ACH drugs (odds ratio, 3.18; 95% confidence interval, 1.93-5.23; P < 0.001); this association remained significant even after adjusting for potential confounding variables (odds ratio, 2.30; 95% confidence interval, 1.19-4.45). Our data suggest that ACH drug intake should be regarded a potentially modifiable risk factor for cognitive impairment in the elderly.

Incidence of Transient Ischemic Attack and Early Stroke Risk Validation of the ABCD2 Score in an Italian Population-Based Study

Background and Purpose— The importance of transient ischemic attack (TIA) lies on the short-term risk of stroke, and the ABCD2 score may improve early stroke risk prediction. However, population-based studies are still needed. We aimed to provide data on TIA incidence and to evaluate the ABCD2 predictive ability for early recurrent stroke in a population-based study. Methods— This study is part of a 2-year prospective community-based registry of all cerebrovascular events in the district of Udine (153 312 inhabitants), Friuli Venezia Giulia region, northeast of Italy, between April 1, 2007 and March 31, 2009. Multiple overlapping sources for finding cases were used, combining hot and cold pursuit. Results— We identified 178 TIA, 161 (90.4%) of which were incident. The crude overall annual TIA incidence rate per 1000 residents was 0.52 (95% confidence interval [CI], 0.45–0.61). Incidence rate was 0.45 (95% CI, 0.31–0.65) when standardized to the 2007 Italian population and 0.25 (95% CI, 0.16–0.39) when standardized to the European standard population. Estimates of stroke risk after the index TIA within 2, 7, 30, and 90 days were, respectively, 2.5% (95% CI, 0.7–6.2), 5.6% (95% CI, 2.6–10.3), 6.2% (95% CI, 3.0–11.1), and 11.2% (95% CI, 6.8–17.1). ABCD2 score was strongly associated with stroke occurrence after index TIA: the areas under the receiver operating characteristic curve at 2, 7, 30, and 90 days were, respectively, 0.85 (95% CI, 0.72–0.97), 0.69 (95% CI, 0.56–0.82), 0.69 (95% CI, 0.56–0.85), and 0.76 (95% CI, 0.67–0.86). No patients with an ABCD2 score <4 had a stroke within the 90-day follow-up period. Conclusions— This study adds new data on TIA incidence and prognosis and it further validates the ability of the ABCD2 score to identify patients at early risk for stroke.

Sensory gating deficit assessed by P50/Pb middle latency event related potential in Alzheimer's disease.

Summary: Sensory gating is defined as the brain’s ability to inhibit repetitive and irrelevant incoming sensory stimuli and is supposed to be related to cholinergic transmission. Indeed, Alzheimer’s disease (AD) is characterized by a cholinergic deficit that is believed to be involved in cerebral cortex hyperexcitability and short latency afferent inhibition deficit. Therefore, a sensory gating deficit may be supposed present in AD within the frame of cortex hyperexcitability and loss of cortex modulation of sensory inputs. The authors investigated whether a sensory gating deficit may be present in AD and whether this deficit may be related to the presence of neuropsychiatric symptoms (NPS) and reversed by donepezil treatment. Sensory gating was evaluated using a paired-stimulus auditory P50 event-related potential paradigm. Eighteen drug-naïve probable AD patients (mean age 76.1 years; SD 5.6 years; 13 females and 5 males) and 15 healthy elderly controls (mean age 74.2 years; SD 5.4 years; 10 females and 5 males) were recruited. Sensory gating was evaluated in AD patients before starting therapy and after 1 and 3 months of donepezil treatment. Auditory P50 sensory gating was impaired in AD patients but no correlation was found between gating deficit and NPS. Moreover, AD patients displayed increased P50 amplitude when compared with healthy elderly subjects. Donepezil treatment did not improve P50 sensory gating in AD patients but decreased P50 amplitude. Patients with AD displayed an augmented P50 amplitude, in accordance with previous studies, suggesting increased cortex excitability. Donepezil does not affect P50 sensory gating but reduces P50 amplitude. Donepezil may induce P50 amplitude reduction by means of enhanced dopamine release. Indeed, it has been demonstrated that donepezil induces dopamine release “in vitro.” The findings suggest that AD patients have a sensory gating impairment but the link with both NPS and the cholinergic deficit is doubtful.

A case-control study on restless legs syndrome in nondialyzed patients with chronic renal failure.

Restless legs syndrome (RLS) is a possible consequence of end‐stage renal disease. However, conclusive data on the association between RLS and chronic renal failure (CRF) in nondialyzed patients are still lacking. The aims of this study were: (1) to look for an association between RLS and CRF in nondialyzed patients; (2) to analyze the characteristics of RLS and its consequences on nocturnal rest in nondialyzed patients with CRF; (3) to identify possible predictors of RLS occurrence in nondialyzed patients with CRF. We recruited 138 nondialyzed patients with CRF (mean age: 69.8 ± 11.7 years; male: 61.6%) and 151 controls (mean age: 60.2 ± 18.6 years; male: 42.4%). An expert in sleep medicine investigated the presence of RLS by means of a face‐to‐face interview. Fifteen nondialyzed CRF patients and five controls were diagnosed as RLS affected. A multivariate analysis confirmed that RLS was independently associated with CRF in nondialyzed patients (P = 0.004). CRF patients RLS+ were more commonly women and showed the presence of an iron deficiency compared with the RLS− ones. Independent predictors of RLS in nondialyzed CRF patients were: female sex (OR: 10.7, 95% CI: 2.2–31.3; P = 0.004) and percentage of transferrin saturation (OR: 0.6, 95% CI: 0.4–0.9; P = 0.04). This is the first case‐control study able to recognize an association between RLS and CRF in patients not yet on dialysis. Nephrologists should investigate and treat RLS in their nondialyzed patients with CRF. In particular, physicians should carefully investigate women and patients with iron deficiency in the presence of RLS symptoms.

Restless legs syndrome: diagnosis, epidemiology, classification and consequences.

Restless legs syndrome (RLS) is a sensorimotor disorder characterised by a complaint of an almost irresistible urge to move the legs. RLS is diagnosed clinically by means of the four essential criteria of the International Restless Legs Syndrome Study Group. In doubtful cases, neurophysiological examinations, such as polysomnography and/or a suggested immobilisation test, can be performed to confirm a clinical suspicion of RLS. Several other conditions may present sensorimotor complaints with features similar to RLS; a careful sleep history is required to avoid a misdiagnosis. Three different scales have been validated to assess the severity of RLS. In the general population, RLS prevalence ranges from 0.1% to 11.5%, with a high number of patients affected by a primary form of the sleep disturbance (70%–80%). However, several clinical conditions have been associated with RLS, such as iron deficiency, uraemia, pregnancy and polyneuropathy. Furthermore, recent studies show that RLS may be associated also to type 2 diabetes mellitus and to multiple sclerosis. RLS has a negative impact on sleep, cognitive functions, quality of life and mental status. Higher awareness of RLS among physicians is required; it remains an underdiagnosed clinical condition.

The importance of polysomnography in the evaluation of prolonged disorders of consciousness: sleep recordings more adequately correlate than stimulus-related evoked potentials with patients' clinical status

OBJECTIVES The aim of our study was to evaluate the importance of sleep recordings and stimulus-related evoked potentials (EPs) in patients with prolonged disorders of consciousness (DOCs) by correlating neurophysiologic variables with clinical evaluation obtained using specific standardized scales. METHODS There were 27 vegetative state (VS) and 5 minimally conscious state (MCS) patients who were evaluated from a clinical and neurophysiologic perspective. Clinical evaluation included the Coma Recovery Scale-Revised (CRS-R), Disability Rating Scale (DRS), and Glasgow Coma Scale (GCS). Neurophysiologic evaluation included 24-h polysomnography (PSG), somatosensory EPs (SEPs), brainstem auditory EPs (BAEPs), and visual EPs (VEPs). RESULTS Patients with preservation of each single sleep element (sleep-wake cycle, sleep spindles, K-complexes, and rapid eye movement [REM] sleep) always showed better clinical scores compared to those who did not have preservation. Statistical significance was only achieved for REM sleep. In 7 patients PSG showed the presence of all considered sleep elements, and they had a CRS-R score of 8.29±1.38. In contrast, 25 patients who lacked one or more of the sleep elements had a CRS-R score of 4.84±1.46 (P<.05). Our multivariate analysis clarified that concurrent presence of sleep spindles and REM sleep were associated with a much higher CRS-R score (positive interaction, P<.0001). On the other hand, no significant associations were found between EPs and CRS-R scores. CONCLUSIONS PSG recordings have proved to be a reliable tool in the neurophysiologic assessment of patients with prolonged DOCs, correlating more adequately than EPs with the clinical evaluation and the level of consciousness. The main contribution to higher clinical scores was determined by the concomitant presence of REM sleep and sleep spindles. PSG recordings may be considered inexpensive, noninvasive, and easy-to-perform examinations to provide supplementary information in patients with prolonged DOCs.

Drugs with Anticholinergic Properties as a Risk Factor for Psychosis in Patients Affected by Alzheimer's Disease

Emerging evidence suggests that psychosis in persons with Alzheimers disease (AD) may be linked to the cholinergic deficit associated with the disease. This study sought to evaluate whether anticholinergic (ACH) drugs could be a risk factor for psychosis onset. A total of 230 patients affected with probable AD were recruited. Data on behavioral and psychological symptoms were collected using the Neuropsychiatric Inventory, and diagnosis of psychosis was performed. Patients were divided into those who used ACH drugs and those who used non‐ACH drugs. Those using ACH drugs (18.3%) were more likely to have psychosis than those using non‐ACH drugs (odds ratio (OR)=2.52; 95% confidence interval (CI), 1.27–5.00); this association remained significant even after adjusting for potential confounding variables (OR=2.13; 95% CI, 1.03–4.43). Our data suggest that patients with AD are frequently treated with ACH drugs and that ACH drug intake should be regarded as a potential risk factor for psychosis.