Pilot prospective study of post-surgery sleep and EEG predictors of post-operative delirium.

OBJECTIVE: Delirium is a common post-operative complication associated with significant costs, morbidity, and mortality. We sought sleep/EEG predictors of delirium present prior to delirium symptoms to facilitate developing and targeting therapies. METHODS: Continuous EEG data were obtained in 12 patients post-orthopedic surgery from the day of surgery until delirium assessment on post-operative day 2 (POD2). RESULTS: Diminished total sleep time (r=-0.68; p<0.05) and longer latency to sleep onset (r=0.67; p<0.05) on the first night in the hospital were associated with greater POD2 delirium severity. Patients experiencing delirium slept 2.4h less and took 2h longer to fall asleep. Greater waking EEG delta power (r=0.84; p<0.05) on POD1 and less non-REM sleep EEG delta power (r=-0.72; p<0.05) on night 2 also predicted POD2 delirium severity. CONCLUSIONS: Loss of sleep on night1 post-surgery is an early predictor of subsequent delirium. EEG Delta Power alterations in waking and sleep appear to be later indicators of impending delirium. Further work is needed to evaluate reproducibility/generalizability and assess whether sleep loss contributes to causing delirium. SIGNIFICANCE: This first study to prospectively collect continuous EEG data for an extended period prior to delirium onset identified EEG-derived indices that predict subsequent delirium that could aid in developing and targeting therapies.

Double-Blind, Placebo-Controlled, Crossover Study of Armodafinil Treatment of Daytime Sleepiness Associated With Treated Nocturia.

Study Objectives: Nocturia, voids which disturb sleep, is the most common cause of awakenings and is associated with daytime sleepiness. Because the standard treatments for the most common causes of nocturia are relatively ineffective, many treated patients with nocturia are left with residual sleepiness. We carried out this pilot study to evaluate the potential of armodafinil to be an effective means of addressing the sleepiness that persists in many nocturia patients, despite their receiving standard therapy. Methods: This was a double-blind, placebo-controlled, crossover study carried out in 28 patients with nocturia who were receiving standard clinical therapy for their nocturia and who had an Epworth Sleepiness Scale (ESS) score of at least 10. Subjects received 4 weeks of both armodafinil (150-250 mg) and placebo with order randomized. Results: Armodafinil led to statistically significant improvement in sleepiness compared to placebo as indicated by the ESS (the primary outcome; p < .002) as well as the Clinical Global Impression of Improvement in Sleepiness scale (key secondary outcome; p = .01). Armodafinil did not increase nocturic events or significantly increase adverse effects versus placebo. Conclusions: This pilot study, the first double-blind, placebo-controlled trial assessing whether a wake-promoting therapy can improve residual daytime sleepiness in patients with treated nocturia, indicates the promise of armodafinil for addressing this residual sleepiness and provides impetus to carry out a large-scale study to definitively evaluate whether armodafinil is an effective therapy for the many patients with nocturia who experience daytime sleepiness that persists, despite their receiving standard therapy for this condition.

Prolonged Delirium With Catatonia Following Orthotopic Liver Transplant Responsive to Memantine.

A 59-year-old man with nonalcoholic steatohepatitis cirrhosis underwent an orthotopic liver transplant and experienced a complicated postoperative course, including a prolonged delirium. After discharge to rehabilitation, he had 2 subsequent admissions for delirium. On the first readmission, the transplant team started the patient on risperidone and resumed treatment with sertraline. On his second readmission, neurology and psychiatry were consulted. On evaluation, the patient demonstrated signs of catatonia. On the basis of recommendations from psychiatry, the risperidone and sertraline were stopped, and the patient was started on mirtazapine. He failed to demonstrate improvement within the next 48 hours. Extensive work-up demonstrated a multifactorial etiology for his delirium, including calcineurin-related neuropsychiatric toxicity from tacrolimus leading to possible posterior reversible encephalopathy syndrome. However, after the initiation of memantine on hospital day 3-before the cessation of tacrolimus-the patient demonstrated marked improvement in mental status and motor symptoms. His magnetic resonance imaging, in addition to findings that raised concerns about posterior reversible encephalopathy syndrome, had demonstrated bilateral basal ganglia abnormalities on T1 imaging of uncertain origin. It is postulated that these findings served as predisposing factors for the patient's catatonic symptoms. Although it has been described in case reports following liver transplant, catatonia remains an underrecognized neuropsychiatric complication following liver transplant. This case demonstrates the effectiveness of memantine, an N-methyl-D-aspartic acid antagonist that decreases glutamine excitotoxicity, as a potential treatment for catatonia in postliver transplant patients.

A randomized, double-blind, placebo-controlled trial of eszopiclone for the treatment of insomnia in patients with chronic low back pain.

STUDY OBJECTIVES: Insomnia, which is very common in patients with chronic low back pain (LBP), has long been viewed as a pain symptom that did not merit specific treatment. Recent data suggest that adding insomnia therapy to pain-targeted treatment should improve outcome; however, this has not been empirically tested in LBP or in any pain condition treated with a standardized pain medication regimen. We sought to test the hypothesis that adding insomnia therapy to pain-targeted treatment might improve sleep and pain in LBP. DESIGN: Double-blind, placebo-controlled, parallel-group, 1-mo trial. SETTING: Duke University Medical Center Outpatient Sleep Clinic. PATIENTS: Fifty-two adult volunteers with LBP of at least 3 mo duration who met diagnostic criteria for insomnia (mean age: 42.5 y; 63% females). INTERVENTIONS: Subjects were randomized to eszopiclone (ESZ) 3 mg plus naproxen 500 mg BID or matching placebo plus naproxen 500 mg twice a day. MEASUREMENTS AND RESULTS: ESZ SIGNIFICANTLY IMPROVED TOTAL SLEEP TIME (MEAN INCREASE: ESZ, 95 min; placebo, 9 min) (primary outcome) and nearly all sleep measures as well as visual analog scale pain (mean decrease: ESZ, 17 mm; placebo, 2 mm) (primary pain outcome), and depression (mean Hamilton Depression Rating Scale improvement ESZ, 3.8; placebo, 0.4) compared with placebo. Changes in pain ratings were significantly correlated with changes in sleep. CONCLUSIONS: The addition of insomnia-specific therapy to a standardized naproxen pain regimen significantly improves sleep, pain, and depression in patients with chronic low back pain (LBP). The findings indicate the importance of administering both sleep and pain-directed therapies to patients with LBP in clinical practice and provide strong evidence that improving sleep disturbance may improve pain. TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT00365976.

Comparison of diary-derived bladder and sleep measurements across OAB individuals, primary insomniacs, and healthy controls.

INTRODUCTION AND HYPOTHESIS: Can diary-derived bladder and sleep measurements differentiate individuals with overactive bladder syndrome (OAB) from individuals with primary insomnia and healthy controls? METHODS: Bladder- and sleep-diary data were compared in nine OAB, ten insomnia, and five control individuals. One-way analysis of variance (ANOVA) was used for normally and Kruskal-Wallis test for nonnormally distributed variables, followed, when significant effects were found, by pairwise comparisons. RESULTS: OAB individuals woke up as frequently as insomniacs, but their awakenings were respectively shorter in duration (18.6 vs. 38.1 min.) and were predominantly initiated by nocturic events (89.2 vs. 23.9 % respectively). Regardless, their reported quality of sleep was as impaired as for the insomniacs. Furthermore, smaller mean volume voided awakenings were evident not only in those with OAB but also in insomniacs compared to controls. CONCLUSIONS: Bladder- and sleep-diary data provide means to differentiate those with OAB from those with insomnia and healthy controls. Awakenings in OAB individuals were shorter than those with insomnia and much more likely due to the need to void. Thus, a reduction in the number of nocturic voids could be the most appropriate sleep-related outcome for nocturia therapy in individuals with OAB. In addition, limited nocturnal bladder capacity, though expected in OAB, was unexpectedly found in insomnia, possibly reflecting the role of consciousness (wakefulness at night) in modulating bladder sensation.

Laboratory diagnosis of factitious disorder: a systematic review of tools useful in the diagnosis of Munchausen's syndrome.

AIMS: To assist clinicians in the diagnosis of factitious disorder. METHODS: This is a systematic review of the role of laboratory, radiologic, procedural, and pathological modalities to assist in the diagnosis of factitious disorder (Munchausen's syndrome). The review evaluated 3104 article titles and abstracts that were identified from MEDLINE as of January 2010. RESULTS: We found 190 articles that demonstrated techniques that will assist clinicians in recognizing fabricated manifestations of disease. The results are divided into 13 areas of clinical medicine for easy reference. They are further sub-divided by the diseases or conditions that patients have been reported to simulate and the diagnostic techniques suggested by the literature in each case. CONCLUSIONS: Factitious disorder is difficult to diagnose and may present as a wide array of fabricated conditions, but there are a range of laboratory and technical means available to assist clinicians in the 21st Century.

A case of delirium, motor disturbances, and autonomic dysfunction due to baclofen and tizanidine withdrawal: a review of the literature.

We report a case of delirium accompanied by extrapyramidal symptoms and autonomic dysfunction in a 59-year-old man following abrupt cessation of baclofen and tizanidine. An extensive search for the etiology was undertaken, but it was only after a careful history was taken that suspicion for baclofen and tizanidine withdrawal was raised. The delirium and motor disturbances resolved within 24 h of reintroduction of baclofen. Withdrawal from muscle relaxants requires a high index of suspicion but should be considered in patients who manifest signs and symptoms of withdrawal from the medications, particularly visual hallucinations, rigidity and autonomic dysfunction.

Topiramate-induced confusion following a single ingestion of 400 mg.

BACKGROUND: Topiramate is an anticonvulsant medication commonly used for a variety of neurological disorders including migraine prophylaxis. Broadened use of topiramate has brought an increased awareness of toxicity from this medication, particularly central nervous system side effects and metabolic acidosis. OBJECTIVE: We describe a case of topiramate toxicity occurring in a 22-year-old female following the ingestion of two 200 mg tablets, which she was prescribed for the treatment of migraines. RESULTS: During her outpatient cardiology evaluation for suspected postural orthostatic tachycardia syndrome (POTS), the patient experienced flushing and anxiety. Upon transfer to our hospital she was tachycardic, hypertensive, and confused. Her autonomic symptoms were consistent with her prior episodes of autonomic instability, while the confusion was new. Admission laboratory values revealed a metabolic acidosis with a mildly elevated anion gap. A blood topiramate level returned a value of 8.4 mg/L 15 h after the ingestion. Her symptoms cleared within 24 h following admission. CONCLUSION: Clinicians should consider topiramate toxicity in their differential diagnosis for patients with neurological diseases presenting with acute-onset confusion and metabolic acidosis.

Detrusor overactivity persisting at night and preceding nocturia in patients with overactive bladder syndrome: a nocturnal cystometrogram and polysomnogram study.

PURPOSE: Nocturia, a common symptom of overactive bladder syndrome, is associated with substantial adverse consequences and yet its pathophysiology has hardly been studied and the capacity to treat it remains limited. We established methods to study the physiology of overactive bladder associated nocturia and better understand this phenomenon. MATERIALS AND METHODS: We recorded simultaneous, time aligned, nocturnal cystometrogram and polysomnogram data during a single night at a sleep laboratory in 9 patients with overactive bladder and detrusor overactivity on daytime cystometrogram, in 10 patients with insomnia and in 5 healthy controls. RESULTS: We safely recorded simultaneous polysomnography/nocturnal cystometrography data accurately during the sleep period. Nocturnal detrusor overactivity occurred significantly less often in patients with insomnia and controls than in patients with detrusor overactivity plus overactive bladder (p = 0.02) and only in the 10 minutes before nocturia events in the latter (0%, 0% and 67%, respectively, p = 0.002). Patients with detrusor overactivity plus overactive bladder were awake for a shorter period before nocturia events (p <0.001) and had a greater percent of nocturia associated awakenings. Patients with insomnia had more awakenings unrelated to nocturia. Nocturnal polyuria, another cause of nocturia, was not significantly associated with nocturnal detrusor overactivity. CONCLUSIONS: Sleep and bladder pressure physiology may be safely monitored during the sleep period accurately. Nocturnal detrusor overactivity occurs in association with nocturia in most patients with detrusor overactivity plus overactive bladder, does not generally occur during sleep and is not due to sleep disturbance or nocturnal polyuria. This study may provide a foundation for research on overactive bladder related nocturia pathophysiology and treatment.

Modeling slow-wave activity dynamics: does an exponentially dampened periodic function really fit a single night of normal human sleep?

OBJECTIVE: Slow-wave activity (SWA) is believed to be a fundamental measure of sleep homeostasis and is frequently characterized as an exponentially declining periodic dynamical system. The objective of this study is to carry out the first rigorous statistical test of this hypothesized dynamical behavior. METHODS: Delta power (DP) was computed for each epoch and artifacts were visually scored for 18 randomly selected nights from 18 healthy young men. Non-linear least-squares (LS) combined with the simplex algorithm were used to fit a 7-parameter confirmatory model of DP separately for each individual night of data. Individual night testing was employed because the model must apply to individual night data to be of research or clinical utility. RESULTS: Visually, results appeared satisfactory in half of the cases, though the model was never statistically verified. Validation using simulated data suggested that if the exponentially declining sinusoidal model were correct, satisfactory model fit would be expected on 17/18 nights. CONCLUSIONS: An exponentially dampened periodic function does not fit a single night of sleep amongst healthy young men. Historically, averaging across nights was the primary method used to develop such hypothesized model in order to reduce variability in the data. Our validation with simulated data established that this model does not fit individual night data because the data in an individual night do not conform to an exponentially dampened periodic function and not because of variability. SIGNIFICANCE: Further exploratory work is needed to determine how to optimally model single night SWA data.