PREvention of VENous Thromboembolism in Hemorrhagic Stroke Patients - PREVENTIHS Study: A Randomized Controlled Trial and a Systematic Review and Meta-Analysis.

BACKGROUND: In this randomized trial, currently utilized standard treatments were compared with enoxaparin for the prevention of venous thromboembolism (VTE) in patients with intracerebral hemorrhage (ICH). METHODS: Enoxaparin (0.4 mg daily for 10 days) was started after 72 h from the onset of ICH. The primary outcome was symptomatic or asymptomatic deep venous thrombosis as assessed by ultrasound at the end of study treatment. The safety of enoxaparin was also assessed. We included the results of this study in a meta-analysis of all relevant studies comparing anticoagulants with standard treatments or placebo. RESULTS: PREVENTIHS was prematurely stopped after the randomization of 73 patients, due to the low recruitment rate. The prevalence of any VTE at 10 days was 15.8% in the enoxaparin group and 20.0% in the control group (RR 0.79 [95% CI 0.29-2.12]); 2.6% of enoxaparin and 8.6% of standard therapy patients had severe bleedings (RR 0.31 [95% CI 0.03-2.82]). When these results were meta-analyzed with the results of the selected studies (4,609 patients; 194 from randomized trials), anticoagulants were associated with a nonsignificant reduction in any VTE (OR 0.81; 95% CI 0.43-1.51), in pulmonary embolism (OR 0.53; 95% CI, 0.17-1.60), and in mortality (OR 0.85; 95% CI 0.64-1.12) without increase in hematoma enlargement (OR 0.97; 95% CI, 0.31-3.04). CONCLUSIONS: In patients with acute ICH, the use of anticoagulants to prevent VTE was safe but the overall level of evidence was low due to the low number of patients included in randomized clinical trials.

Preserved cardiac autonomic dynamics during sleep in subjects with spinal cord injuries.

BACKGROUND: Spinal cord injuries (SCI) are associated with altered cardiovascular autonomic control (CAC). Sleep is characterized by modifications of autonomic control across sleep stages; however, no data are available in SCI subjects on CAC during sleep. We aim to assess cardiac autonomic modulation during sleep in subjects with SCI. PATIENTS AND METHODS: 27 participants with a neurological and radiological diagnosis of cervical (Cerv, n = 12, ie, tetraplegic) and thoracic SCI (Thor, n = 15, ie, paraplegic) and healthy subjects (Controls) were enrolled. Overnight polysomnographic (PSG) recordings were obtained in all participants. Electrocardiography and respiration were extracted from PSG, divided into sleep stages [wakefulness (W), non-REM sleep (NREM) and REM] for assessment of CAC, using symbolic analysis (SA) and corrected conditional entropy (CCE). SA identified indices of sympathetic and parasympathetic modulation and CCE evaluated the degree of complexity of the heart period time series. RESULTS: SA revealed a reduction of sympathetic and predominant parasympathetic control during NREM compared to W and REM in SCI patients, independent of the level of the lesion, similar to the Controls. In all three groups, complexity of autonomic regulation was higher in NREM compared to W and REM. CONCLUSIONS: In subjects with SCI, cardiac autonomic control changed across sleep stages, with a reduction of sympathetic and an increase of parasympathetic modulation during NREM compared to W and REM, and a parallel increase of complexity during NREM, which was similar to the Controls. Cardiac autonomic dynamics during sleep are maintained in SCI, independent of the level of the lesion.

Sleep apnea and periodic leg movements in the first year after spinal cord injury.

BACKGROUND: Sleep disturbances are frequently reported by patients with spinal cord injury (SCI). Studies have shown an increased incidence of sleep-disordered breathing (SDB) and periodic leg movements during sleep (PLMS) in people with stable long-term SCI. METHODS: This was a prospective observational study in order to evaluate the features and possible predisposing factors of SDB and PLMS in a heterogenic population of consecutive SCI patients admitted at the Spinal Unit of the Niguarda Hospital within the first year after injury. Each patient underwent a clinical assessment, full polysomnography, and arterial blood gas analysis before and immediately after sleep. Multiple logistic regressions were applied in order to evaluate factors associated with SDB and PLMS. RESULTS: Thirty-five (15 tetraplegic and 20 paraplegic) patients were enrolled. Nine patients (25.7%) had an obstructive SDB and 10 (28.6%) had PLMS. The frequency of SDB was higher in tetraplegic with respect to paraplegic patients (Wald statistic: 7.71; P = 0.0055), whereas PLMs were significantly more frequent in patients with an incomplete motor lesion than in subjects with a complete motor lesion (Wald statistic: 6.14; P = 0.013). CONCLUSION: This study confirms a high frequency of SDB and PLMS in SCI patients in the first year following injury. Independently from possible sub-acute and chronic clinical variables, the level and the completeness of the spinal cord lesion are the main factors associated respectively with an early development of SDB and PLMS.

Transcranial magnetic stimulation in sleep fragmentation: a model to better understand sleep disorders.

OBJECTIVE: To investigate practice-dependent plasticity and cortical inhibition/excitability in good sleepers after a night of sleep fragmentation (SF), by means of transcranial magnetic stimulation (TMS). METHODS: In basal condition (BC), after a full night of spontaneous sleep, and in fragmented condition (FC), after a fragmented night of sleep, motor evoked potential (MEP) amplitude, motor threshold (MT), silent period (SP), and intracortical inhibition were assessed. In both conditions subjects performed, also, a bimanual motor task: MEPs were recorded before and after exercise, and after rest. We evaluated the presence of post-exercise facilitation and delayed facilitation. Subjects reported their alertness level (Stanford Sleepiness Scale-SSS). RESULTS: MT and SSS were significantly increased in SF. Instead, no significant differences for MEP amplitude or SP or intracortical inhibition were found. In both conditions post-exercise facilitation and delayed facilitation were present. CONCLUSION: SF produces disruption of nocturnal sleep and increases daytime sleepiness. Confirmatory features of this clinical behaviour could be that in FC we observed a significant increase in SSS and in MT. SF was unable to modify cortical inhibition\excitability and\or to influence plasticity-related parameters. These results seem inconsistent with some of TMS alterations observed in sleep deprivation (SD) and restless legs syndrome (RLS). We suggest that SD and SF represent different phenomena that can depend on various networks acting on motor cortex. We speculate that alterations in cortical excitability found in RLS are intrinsically related to the underlying disease itself and are not instead directly associated with the SF present in RLS.

Effects of restless legs syndrome on quality of life and psychological status in patients with type 2 diabetes.

PURPOSE: The purpose of this study was to evaluate the effects of restless legs syndrome (RLS) on quality of life (QoL), anxiety, and depression in people with type 2 diabetes. METHODS: One hundred twenty-four patients with type 2 diabetes were enrolled in this study. RLS was diagnosed by a neurologist masked on psychological evaluation. Data on severity, frequency, and duration of the sleep disorder were collected. The Italian version of the SF-36 was used to assess QoL. Psychological status was investigated by a neuropsychologist masked on RLS diagnosis. Patients with a diagnosis of generalized anxiety disorder (GAD) and major depressive disorder (MDD) were considered affected by anxiety and depression, respectively. A modified version of the Hamilton Anxiety and Depression Rating Scales (HARS and HDRS) was also administered. RESULTS: RLS was an independent predictor for several mental domains of the SF-36 and for the mental component summary. Multivariate analysis showed that RLS was an independent predictor of anxiety and depression. RLS severity correlated with HARS and HDRS scores, whereas frequency per week of RLS had a significant correlation only with HARS score. CONCLUSIONS: Among individuals with diabetes, RLS can impair mental health, increasing the risk for anxiety and depression. Since RLS consequences on nocturnal rest and psychological status may impair glycemic control in this population, diabetologists and diabetes educators should investigate for the presence of RLS in their patients and treat them.

Multicenter case-control study on restless legs syndrome in multiple sclerosis: the REMS study.

STUDY OBJECTIVES: To verify the existence of a symptomatic form of restless legs syndrome (RLS) secondary to multiple sclerosis (MS) and to identify possible associated risk factors. DESIGN: Prospective, multicenter, case-control epidemiologic survey. SETTINGS: Twenty sleep centers certified by the Italian Association of Sleep Medicine. PATIENTS: Eight hundred and sixty-one patients affected by MS and 649 control subjects. INTERVENTIONS: N/A. MEASURES AND RESULTS: Data regarding demographic and clinical factors, presence and severity of RLS, the results of hematologic tests, and visual analysis of cerebrospinal magnetic resonance imaging studies were collected. The prevalence of RLS was 19% in MS and 4.2% in control subjects, with a risk to be affected by RLS of 5.4 (95%confidence interval: 3.56-8.26) times greater for patients with MS than for control subjects. In patients with MS, the following risk factors for RLS were significant: older age; longer MS duration; the primary progressive MS form; higher global, pyramidal, and sensory disability; and the presence of leg jerks before sleep onset. Patients with MS and RLS more often had sleep complaints and a higher intake of hypnotic medications than patients with MS without RLS. RLS associated with MS was more severe than that of control subjects. CONCLUSIONS: RLS is significantly associated with MS, especially in patients with severe pyramidal and sensory disability. These results strengthen the idea that the inflammatory damage correlated with MS may induce a secondary form of RLS. As it does in idiopathic cases, RLS has a significant impact on sleep quality in patients with MS; therefore, it should be always searched for, particularly in the presence of insomnia unresponsive to treatment with common hypnotic drugs.

Association of restless legs syndrome in type 2 diabetes: a case-control study.

STUDY OBJECTIVE: To look for an association between restless legs syndrome (RLS) and type 2 diabetes in a case-control study; to analyze the characteristics of RLS in diabetic patients; and to identify possible risk factors for the development of RLS in diabetic patients. DESIGN: A case-control study. SETTING: Diabetic outpatient clinic of a major university hospital. PARTICIPANTS: One hundred twenty-four consecutive outpatients with diabetes and 87 consecutive controls with a previous diagnosis of other endocrine disease. INTERVENTIONS: RLS was diagnosed using the criteria of the International RLS Study Group, and severity of RLS was assessed using the International RLS Study Group Rating Scale. Characteristics of RLS and several laboratory parameters were investigated in diabetic patients and controls affected by the sleep disorder. A clinical diagnosis of polyneuropathy was assessed to evaluate its role as a risk factor for RLS in diabetic patients. MEASUREMENT AND RESULTS: RLS was diagnosed in 22 diabetic patients (17.7%) and in only 5 controls (5.5%), 3 of whom had pituitary and 2 had adrenal gland disorders, and RLS was independently associated with type 2 diabetes (P < 0.04). Even if a clinical diagnosis of polyneuropathy was made in only 27% of diabetic patients affected by RLS, after multivariate logistic regression, the presence of polyneuropathy was the only variable associated with RLS in diabetics (odds ratio, 7.88; 95% confidence interval, 1.34-46.28; P < 0.02). RLS in diabetics showed a frequency of positive family history lower than that known for primary RLS, showed a late age of onset, and manifested itself after the diagnosis of diabetes was made. CONCLUSIONS: This is the first controlled study confirming a significant association between RLS and type 2 diabetes. In diabetic patients, polyneuropathy represents the main risk factor for RLS. However, polyneuropathy only partially explains the increased prevalence of RLS in type 2 diabetics. Clinical characteristics of RLS in diabetic patients are those of a secondary form.