Diagnosis and Treatment of Sleep Apnea in patients' homes: the rationale and methods of the "GoToSleep" randomized-controlled trial.

BACKGROUND: The "Diagnosis and Treatment of Sleep Apnea in Cerebrovascular Disease" (GoToSleep) study is evaluating a strategy to improve the diagnosis and treatment of sleep apnea among veterans with stroke or transient ischemic attack (TIA) who also have hypertension. Specifically, the GoToSleep study was designed to overcome some of the barriers that exist within the Veterans Health Administration (VHA) to the timely diagnosis and treatment of sleep apnea by using ambulatory home-based polysomnography and auto-titrating continuous positive airway pressure (CPAP) to reduce the reliance on laboratory-based sleep studies. METHODS: The GoToSleep study is a prospective, multi-site, randomized, controlled strategy trial among an expected 318 veterans with cerebrovascular disease and hypertension who are assigned to an intervention group or a control group. Patients in the intervention group receive unattended polysomnography at baseline, and those with sleep apnea receive auto-titrating CPAP therapy for up to one year. Patients in the control group receive usual care and unattended polysomnography at the end of the study to identify the rate of undiagnosed sleep apnea. The primary objectives of the GoToSleep study are to determine whether a diagnostic and therapeutic intervention strategy among veterans with cerebrovascular disease and hypertension improves: (1) detection of sleep apnea; (2) appropriate treatment for sleep apnea; and (3) control of hypertension. Twenty-four-hour blood pressure assessments are made at baseline and at the end of the one-year study period for both groups. Antihypertensive medications and their doses are recorded at the time of the 24-hour blood pressure measurements. DISCUSSION: This manuscript provides the rationale for 4 key components of the design of the GoToSleep trial: the inclusion of patients with cerebrovascular disease and hypertension without the use of a measure of daytime sleepiness as an eligibility criterion; the use of portable polysomnography and auto-titrating CPAP in patients' homes rather than using sleep laboratory polysomnography with fixed pressure CPAP; the analytic approach to evaluating change in blood pressure in the context of change in antihypertensive medications; and the use of a usual care control group.

Continuous positive airway pressure: evaluation of a novel therapy for patients with acute ischemic stroke.

BACKGROUND: New approaches are needed to treat patients with stroke. Among acute ischemic stroke patients, our primary objectives were to describe the prevalence of sleep apnea and demonstrate the feasibility of providing auto-titrating continuous positive airway pressure (auto-CPAP). A secondary objective was to examine the effect of auto-CPAP on stroke severity. METHODS: Stroke patients randomized to the intervention group received 2 nights of auto-CPAP, but only those with evidence of sleep apnea received auto-CPAP for the remainder of the 30-day period. Intervention patients received polysomnography 30 days post-stroke. Control patients received polysomnography at baseline and after 30 days. Acceptable auto-CPAP adherence was defined as ≥ 4 h/night for ≥ 75% nights. Change in stroke severity was assessed comparing the NIH Stroke Scale (NIHSS) at baseline versus at 30 days. RESULTS: The 2 groups (intervention N = 31, control N = 24) had similar baseline stroke severity (both median NIHSS, 3.0). Among patients with complete polysomnography data, the majority had sleep apnea: baseline, 13/15 (86.7%) control patients; 30 days, 24/35 (68.6%) control and intervention patients. Intervention patients had greater improvements in NIHSS (-3.0) than control patients (-1.0); P = 0.03. Among patients with sleep apnea, greater improvement was observed with increasing auto-CPAP use: -1.0 for control patients not using auto-CPAP; -2.5 for intervention patients with some auto-CPAP use; and -3.0 for intervention patients with acceptable auto-CPAP adherence. CONCLUSIONS: The majority of acute stroke patients had sleep apnea. Auto-CPAP was well tolerated, appears to improve neurological recovery from stroke, and may represent a new therapeutic approach for selected patients with acute cerebral infarction.

Prevalence, predictors, and outcomes of poststroke falls in acute hospital setting.

Falls are a serious medical complication following stroke. The objectives of this study were to (1) confirm the prevalence of falls among patients with stroke during acute hospitalization, (2) identify factors associated with falls during the acute stay, and (3) examine whether in-hospital falls were associated with loss of function after stroke (new dependence at discharge). We completed a secondary analysis of data from a retrospective cohort study of patients with ischemic stroke who were hospitalized at one of four hospitals. We used logistic regression to identify factors associated with inpatient falls and examine the association between falls and loss of function. Among 1,269 patients with stroke, 65 (5%) fell during the acute hospitalization period. We found two characteristics independently associated with falls: greater stroke severity (National Institutes of Health Stroke Scale [NIHSS] ≥8, adjusted odds ratio [OR] = 3.63, 95% confidence interval [CI]: 1.46-9.00) and history of anxiety (adjusted OR = 4.90, 95% CI: 1.70-13.90). Falls were independently associated with a loss of function (adjusted OR = 9.85, 95% CI: 1.22-79.75) even after adjusting for age, stroke severity, gait abnormalities, and past stroke. Stroke severity (NIHSS >8) may be clinically useful during the acute inpatient setting in identifying those at greatest risk of falling. Given the association between falls and poor patient outcomes, rehabilitation interventions should be implemented to prevent falls poststroke.

Auto-titrating continuous positive airway pressure for patients with acute transient ischemic attack: a randomized feasibility trial.

BACKGROUND AND PURPOSE: Transient ischemic attack (TIA) patients are at risk of recurrent vascular events. The primary objectives were to evaluate among TIA patients the prevalence of sleep apnea and among patients with sleep apnea auto-titrating continuous positive airway pressure (auto-CPAP) adherence. The secondary objective was to describe among TIA patients with sleep apnea the recurrent vascular event rate by auto-CPAP use category. METHODS: All intervention patients received auto-CPAP for 2 nights, but only intervention patients with evidence of sleep apnea received auto-CPAP for the remainder of the 90-day period. Intervention patients received polysomnography at 90 days after TIA. Control patients received polysomnography at baseline and at 90 days. Acceptable auto-CPAP adherence was defined as >or=4 hours per night for >or=75% of nights. Vascular events included recurrent TIA, stroke, hospitalization for congestive heart failure, myocardial infarction, or death. RESULTS: We enrolled 70 acute TIA patients: 45 intervention and 25 control. The majority of patients had sleep apnea: 57% at baseline and 59% at 90 days. Among the 30 intervention patients with airflow obstruction, 12 (40%) had acceptable auto-CPAP adherence, 18 (60%) had some use, and none had no use. Three intervention patients (12%) had recurrent events compared with 1 (2%; P=0.13) control patient. The vascular event rate was highest among sleep apnea patients with no CPAP use: none, 16%; some, 5%; acceptable adherence 0% (P=0.08). CONCLUSIONS: Sleep apnea is common among acute TIA patients. It appears feasible to provide auto-CPAP in the acute TIA period. Larger studies should evaluate whether a strategy of diagnosing and treating sleep apnea can reduce recurrent vascular events after TIA.

Processes of care associated with acute stroke outcomes.

BACKGROUND: Many processes of care have been proposed as metrics to evaluate stroke care. We sought to identify processes of stroke care that are associated with improved patient outcomes after adjustment for both patient characteristics and other process measures. METHODS: This retrospective cohort study included patients 18 years or older with an ischemic stroke or transient ischemic attack (TIA) onset no more than 2 days before admission and a neurologic deficit on admission. Patients were excluded if they resided in a skilled nursing facility, were already admitted to the hospital at stroke onset, or were transferred from another acute-care facility. The combined outcome included in-hospital mortality, discharge to hospice, or discharge to a skilled nursing facility. Seven processes of stroke care were evaluated: fever management, hypoxia management, blood pressure management, neurologic evaluation, swallowing evaluation, deep vein thrombosis (DVT) prophylaxis, and early mobilization. Risk adjustment included age, comorbidity (medical history), concomitant medical illness present at admission, preadmission symptom course, prestroke functional status, code status, stroke severity, nonneurologic status, modified APACHE (Acute Physiology and Chronic Health Evaluation) III score, and admission brain imaging findings. RESULTS: Among 1487 patients, the outcome was observed in 239 (16%). Three processes of care were independently associated with an improvement in the outcome after adjustment: swallowing evaluation (adjusted odds ratio [OR], 0.64; 95% confidence interval [CI], 0.43-0.94); DVT prophylaxis (adjusted OR, 0.60; 95% CI, 0.37-0.96); and treating all episodes of hypoxia with supplemental oxygen (adjusted OR, 0.26; 95% CI, 0.09-0.73). CONCLUSION: Outcomes among patients with ischemic stroke or TIA can be improved by attention to swallowing function, DVT prophylaxis, and treatment of hypoxia.

P300 cognitive evoked potentials before and after liver transplantation.

P300 cognitive evoked potentials have been shown to be effective for the assessment of mild hepatic encephalopathy but no investigations of their use with liver transplantation has been conducted. In this pilot study 12 subjects (7 male, 5 female, average age 43.9-years-old) underwent recording of auditory and visual P300 cognitive evoked potentials prior to liver transplantation and again 3-6 months subsequent to transplantation. Significant increases (p < 0.01) in P300 visual amplitude, as well as significant decreases in visual (p < 0.01) and auditory latencies (p < 0.01) were observed following transplantation. Auditory amplitudes increased but not to a statistically significant degree. P300 cognitive evoked potentials may provide a useful tool for monitoring the cerebral status of liver transplantation patients if combined with established methods such as cognitive testing and EEG. Further research of their usage with these patients is warranted.

Quantitative EEG analysis before and after liver transplantation.

Quantitative EEG has been shown to be effective for the assessment of hepatic encephalopathy. Initial quantitative EEG studies of patients who had undergone liver transplantation demonstrated improvement of frequency and the alpha-theta power ratio in the occipital area. This study involved the assessment of comprehensive quantitative EEG variables over the entire cortex following transplantation. Fourteen subjects underwent EEG recording prior to transplantation. Eight (6 without complications and 2 having problems with rejection) underwent the same recording between 3 and 6 months following transplantation. For all subjects, EEG variables showing significant changes from pre- to post-transplantation included posterior alpha frequency (increase, p < or = .03), central theta absolute power (decrease, p < or = .03), theta relative power over anterior, central, and posterior regions (decrease, p < or = .02, p < or = .01, p < or = .03, respectively), posterior beta absolute power (increase, p < or = .01), and central and posterior beta relative power (increase, p < or = .04, p < or = .04, respectively). When the two subjects with complications were removed from the analyses, these variables and also anterior alpha absolute power (increase, p < or = .02), alpha relative power over anterior, central, and posterior regions (increase, p < or = .05, p < or = .03, p < or = .04, respectively), and anterior and central theta absolute power (decrease, p < or = .05, p < or = .04, respectively) showed significant pre- to post-transplant changes. In conclusion, a combination of quantitative EEG parameters which are most affected by liver transplantation might provide an effective assessment tool for determining and quantitatively monitoring the cerebral status of post-transplant patients.

Risk factors for experiencing psychosis during cocaine use: a preliminary report.

UNLABELLED: Cocaine induced psychosis (CIP) is a common, but not universal side effect of cocaine abuse. Factors underlying the development and severity of CIP remain poorly understood. This study tests the hypothesis that earlier age of initiation of regular use may increase the likelihood of developing CIP, or the severity of CIP symptoms. METHODS: Cocaine use history and severity of CIP (if any) were assessed with the Cocaine Experience Questionnaire in 51 abstinent (3 weeks-1 year) cocaine dependent individuals. Subjects were divided into those with high and low CIP severity, and into those with early age of initiation of regular cocaine use, and later age of initiation. Various cutoffs between early and late age of initiation were used, ranging from 15 to 22 years. RESULTS: From ages 17 through 20, controlling for cumulative duration of use, severity scores were significantly higher for the early initiation group than for the later initiation group (p values ranged from 0.031 to 0.036). Cumulative duration of use, but not age of initiation, significantly predicted initial development of CIP (p=0.044). CONCLUSIONS: The data suggest that early age of initiation of regular cocaine use occurring during vulnerable periods of brain development, may lead to increased severity of CIP.

Somatic implications of generalized and/or focal EEG slowing in psychiatric patients.

The extent of medical follow-up of abnormal screening EEGs secured from psychiatric patients, particularly those reporting slow wave dysrhythmias as the single finding, still varies widely. From an earlier routine EEG screening program for psychiatric inpatients, 103 consecutive cases of abnormal EEGs with generalized, focal, or paroxysmal slowing as the only EEG finding were identified. Despite suggestions for medical follow-up, less than half (44.6%) of the patients received subsequent study. However, 74.2% of patients considered to be without organic pathophysiology at the time of the EEG had positive organic findings on medical follow-up.

Normative data for the unquantified EEG: examination of adequacy for neuropsychiatric research.

Visual inspection of the unquantified electroencephalogram (EEG) remains the sole technique to confidently detect epileptiform discharges. Usefulness of this procedure in psychiatric research is hampered by reported prevalence of abnormalities in normal adults ranging from 4% to 57.5%. In this study, we examined the criteria used in available literature for selecting healthy individuals. Medline, PsychInfo, and textbook chapters were the primary sources for data. Analysis was restricted to studies examining the visual inspection of the EEG in humans. Thirty-eight articles met search criteria. Seven criteria for choosing healthy comparison subjects were used as the bases for this review. The majority of studies met no criteria, one criterion or two criteria. We conclude that the boundaries for normal unquantified EEG are poorly defined.

Auditory and visual P300 evoked potentials do not predict response to valproate treatment of aggression in patients with borderline and antisocial personality disorders.

In this study of patients with borderline personality disorder (BPD) or antisocial personality disorder (ASPD) hospitalized because of aggressive behavior, auditory and visual P300 evoked potentials were obtained prior to treatment with valproate. Eight ASPD patients (8 males, 0 females) and 11 BPD patients (2 males, 9 females) showed improvement, while in 7 patients with ASPD (7 males, 0 females) and 10 patients with BPD (2 males, 8 females), aggression was not improved. Differences in auditory and visual P300 latencies and amplitudes were not significant for either diagnosis, or for both diagnoses combined. These findings suggest that auditory or visual P300 evoked potentials may not be useful for predicting response of aggressive behavior to valproate treatment in patients with BPD or ASPD.

Auditory evoked responses in a comparison between schizophrenia patients with and without premorbid history of drug abuse: report of pilot results.

Evidence for a role for drugs of abuse in the development of chronic psychotic syndromes is scattered throughout 40 years of literature. Electrophysiological studies examining groups believed to have chronic drug-induced psychotic symptoms yielded interesting findings. To our knowledge, no studies directly compared schizophrenia patients whose drug use preceded and those whose drug use followed the onset of psychotic symptoms. Twenty-six schizophrenia patients and 10 healthy control subjects were recruited for the study. Based on the SCID interview, schizophrenia subjects were classified into a Psychosis First (Psy 1st) group (N=11), Drugs First (Drugs 1st; N=8), and No Drug Use (No Drugs; N=7). Schizophrenia subjects were administered the Positive and Negative Symptoms Scale (PANSS). The P300 evoked response and sensory gating were measured for all subjects. Despite the small sample sizes significant differences were found between the groups. Most significantly, the P300 amplitude was smallest in the Drugs 1st as compared to the No Drugs groups, while sensory gating deficit was worst in the Psy 1st group. The data suggest that significant clinical and electrophysiological differences between these groups can be identified. Further research to better define these differences seems warranted.

Morphological and latency abnormalities of the mid-latency auditory evoked responses in schizophrenia: a preliminary report.

INTRODUCTION: Evoked potential (EP) amplitude and latency abnormalities have been extensively examined in schizophrenia. Morphological abnormalities of the mid-latency auditory evoked responses (MLAERs; P50, N100, P200), on the other hand, received very little attention. METHODS: Based on a priori defined set of morphological criteria, the morphology and latency of the MLAERs were blindly compared between stable outpatients with schizophrenia (N=27) and age- and gender-matched healthy control subjects (N=22). The morphology of the MLAERs was considered abnormal if one or more of the components fell outside the expected latency range, if one or more of the components were missing, or if a later occurring component was smaller in amplitude than an earlier occurring one. RESULTS: Of the 27 schizophrenia subjects, 20 had waveforms that were deemed atypical, while only 8 from the control group were classified as atypical (chi(2)=5.52, p<0.02). The latencies of the P50 and N100 components, identified based on morphology, were significantly prolonged in schizophrenia patients. CONCLUSIONS: These preliminary data suggest that morphological abnormalities of the MLAERs in schizophrenia patients are significant and should be taken into consideration when examining the MLAERs of this patient population.

Quantitative EEG findings of a temporal lobe abnormality not detected by magnetic resonance or SPECT imaging in a patient with dementia.

The last three decades have seen significant advances in structural neuroimaging techniques such as computerized tomography and magnetic resonance imaging. These seem to have surpassed EEG as modalities for the identification of focal CNS lesions. Reported here is the case of a patient with a temporal lobe lesion not evident with magnetic resonance imaging or single photon emission computerized tomography but detected by EEG and positron emission tomography. EEG, particularly quantitative EEG, remains a valuable tool for the demonstration of the degree of dysfunctional changes associated with a cerebral lesion.

Acute marihuana (THC) exposure produces a "transient" topographic quantitative EEG profile identical to the "persistent" profile seen in chronic heavy users.

In two published pilot studies and a controlled replication using screened normals, chronic marihuana (THC) use was associated with a unique topographic quantitative EEG profile, consisting of significant elevations of Absolute and Relative Power and Coherence of alpha activity over the bilateral frontal cortex as well as a significant decrease in alpha frequency. This report attempts to establish the causal influence of THC in the above findings by the transient production of this exact quantitative EEG profile in subjects who did not display it at the beginning. Using paced smoking of marihuana with high and low dose THC content and placebo marihuana in a counterbalanced design under double blind conditions, all four of the topographic features of chronic THC exposure were produced as transient effects by THC but not by placebo.

EEG does not predict response to valproate treatment of aggression in patients with borderline and antisocial personality disorders.

Previous investigations of the role of EEG in predicting response of aggressive patients to valproate therapy have yielded mixed results. In this study of borderline and antisocial personality disorder patients hospitalized with aggressive behavior, EEGs were obtained prior to treatment with valproate. Eight of 22 (36.4%) patients subsequently responsive to valproate had nonepileptiform EEG abnormalities, while 5 of 20 (25%) patients not responsive to valproate had nonepileptiform EEG abnormalities. Although more of the valproate responders than nonresponders had EEG abnormalities, the presence of nonepileptiform EEG abnormalities was not a statistically significant (X2 = 0.213, df = 1, p = 0.64) predictor of valproate response in personality disorder patients with aggression.

Quantitative electroencephalography in late-onset schizophrenia.

BACKGROUND AND OBJECTIVES: A variety of electroencephalogram (EEG) abnormalities may occur in schizophrenics who had a typical onset of the disorder in early adulthood. The purpose of this study was to investigate EEG findings in patients with late-onset schizophrenia (onset of illness between ages 40 and 60). METHODS: Ten patients (one male, nine female, average age 52.8 years old) with late-onset schizophrenia underwent magnetic resonance imaging (MRI) of the brain and recording of quantitative EEG. RESULTS: MRI results for seven of the subjects were within normal limits and the other three showed nonspecific changes. Quantitative analysis of EEG variables revealed that for eight of the subjects, absolute power and relative power for the four EEG frequency bands, overall mean frequency, mean frequency for each of the EEG frequency bands, and interhemispheric coherence values did not vary significantly from a normative database of age-matched normal subjects. CONCLUSIONS: Results obtained to some degree replicate the single previous EEG study of late-onset schizophrenia. These findings suggest that the neurophysiological etiology and mechanism of late-onset schizophrenia may differ from that of schizophrenia with a typical age of onset, and that brain abnormalities are not an inevitable accompaniment to late onset of schizophrenia.