Pulmonary edema following generalized tonic clonic seizures is directly associated with seizure duration.

PURPOSE: Postictal pulmonary edema (PPE) is almost invariably present in human and animal cases of sudden unexpected death in epilepsy (SUDEP) coming to autopsy. PPE may be a contributing factor in SUDEP. The incidence of postictal PPE is unknown. We retrospectively investigated PPE following generalized tonic clonic seizures (GTCS) in the epilepsy monitoring unit. METHODS: Chest X-Rays (CXR) following each GTCS were obtained in 24 consecutive patients. Relationship of CXR abnormality to seizure duration, ictal/postictal oxygen desaturation (SpO2), apnea and presence of postictal generalized EEG suppression (PGES) was investigated using logistic regression. RESULTS: Eleven of 24 patients had CXR abnormalities following a GTCS. In these 11 patients, 22 CXR were obtained and abnormalities were present in 15 CXR. Abnormalities included PPE in 7 patients, of which 2 also had focal infiltrates. In 4 patients focal infiltrates were present without PPE. There was no significant difference in mean time to CXR (225 min) following GTCS in the abnormal CXR group versus the normal group of patients (196 min). Mean preceding seizure duration was longer (p=0.002) in GTCS with abnormal CXR (259.7 sec) versus GTCS with normal CXR (101.2 sec). Odds-ratio for CXR abnormality was 20.46 (p=0.006) with seizure duration greater than 100 sec versus less than 100 sec. On multivariable analysis, only the seizure duration was a significant predictor of CXR abnormality (p=0.015). CONCLUSIONS: Radiographic abnormalities are not uncommon following GTCS. The presence of CXR abnormality is significantly associated with the duration of the preceding GTCS. Severe, untreated PPE may be relevant to the pathophysiology of SUDEP.

Postictal generalized EEG suppression is linked to seizure-associated respiratory dysfunction but not postictal apnea.

PURPOSE: The relationship of postictal generalized electroencephalography (EEG) suppression (PGES) with sudden unexpected death in epilepsy (SUDEP) is controversial. It has been suggested that PGES is associated with respiratory inhibition leading to SUDEP, but the relationship between PGES and respiratory depression is unknown. Respiratory rate and amplitude of airflow increase following seizures but there is persistent hypercapnia and hypoxemia. To determine whether seizures with PGES result in respiratory dysfunction, we analyzed respiratory parameters recorded during video-EEG telemetry in patients with localization-related epilepsy. METHODS: Secondarily generalized convulsive seizures (GC) with PGES on scalp EEG or bilateral postictal attenuation (BA) on intracranial recordings were compared to GC without PGES/BA. Oxygen desaturation nadir and duration, end-tidal CO(2) (ETCO(2) ), apnea duration, and duration of the seizure and of the convulsive component were compared in GC with or without PGES/BA. KEY FINDINGS: There was no significant difference between GC with (n = 30) or without PGES/BA (n = 72) for total seizure duration or duration of the convulsion. GC with PGES/BA had a mean oxygen desaturation nadir of 68.8 ± 11.8% (71.5, 43-88) (mean ± standard deviation [median, range]) that was lower (p = 0.002) than seizures without PGES/BA (76.31 ± 10.17% [79, 42-93]). The duration of desaturation was significantly longer and peak ETCO(2) higher in GC with PGES/BA. There was no difference in apnea duration. Apnea did not start during PGES/BA and did not typically extend into the postictal period in GC with or without PGES/BA. SIGNIFICANCE: PGES is not associated with postictal central apnea but is more likely related to the severity of seizure-associated intrinsic pulmonary dysfunction.

Sleepiness, fatigue, and risk of obstructive sleep apnea using the STOP-BANG questionnaire in multiple sclerosis: a pilot study.

PURPOSE: This study aims: (1) to identify patients with multiple sclerosis (MS) who are at high risk for obstructive sleep apnea (OSA) by utilizing the STOP-BANG questionnaire and (2) to evaluate the relationship between OSA risk as determined by the STOP-BANG questionnaire and self-reported sleepiness and fatigue using the Epworth Sleepiness Scale (ESS) and the Fatigue Severity Scale (FSS), respectively. METHODS: A total of 120 consecutive patients presenting to the UC Davis Neurology MS Clinic were invited to participate in an anonymous survey. The exclusion criteria were: age <18 years, indefinite MS diagnosis, or incomplete survey. RESULTS: There were 103 subjects included in our study: 42% of subjects (n = 43) met the criteria for high-risk OSA, 69% of subjects (n = 71) screened high for fatigue (FSS ≥ 4), but only 24 subjects (23%) screened high for excessive daytime sleepiness (ESS > 10). In males, 44% of the variation in ESS scores and 63% in FSS scores were explained by the STOP-BANG components. However, only 17% of the variation in ESS scores and 15% of the variation in FSS scores was explained by the STOP-BANG components in females. CONCLUSIONS: Over 40% of MS patients were identified as high risk for OSA based on the STOP-BANG questionnaire. The STOP-BANG questionnaire offers clinicians an efficient and objective tool for improving detection of OSA risk in MS patients.

Evaluation of the association of menopausal status with delta and beta EEG activity during sleep.

STUDY OBJECTIVES: Women report increasing sleep difficulties during menopause, but polysomnographic measures do not detect sleep disturbances. We examined whether two spectral analysis sleep measures, delta and beta power, were related to menopausal status. DESIGN: The Study of Women's Health Across the Nation (SWAN) Sleep Study compared cross-sectionally spectral sleep measures in women in different stages of menopause. SETTING: Sleep EEG was recorded in the participants' homes with ambulatory recorders. PARTICIPANTS: A multi-ethnic cohort of premenopausal and early perimenopausal (n = 189), late perimenopausal (n = 73), and postmenopausal (n = 59) women. MEASUREMENTS: EEG power in the delta and beta frequency bands was calculated for all night NREM and all night REM sleep. Physical, medical, psychological, and socioeconomic data were collected from questionnaires and diaries. RESULTS: Beta EEG power in NREM and REM sleep in late perimenopausal and postmenopausal women exceeded that in pre- and early perimenopausal women. Neither all night delta power nor the trend in delta power across the night differed by menopausal status. In a multivariate model that controlled for the physical, demographic, behavioral, psychological, and health-related changes that accompany menopause, beta power in both NREM and REM sleep EEG was significantly related to menopausal status. The frequency of hot flashes explained part but not all of the relation of beta power to menopausal status. CONCLUSIONS: Elevated beta EEG power in late perimenopausal and postmenopausal women provides an objective measure of disturbed sleep quality in these women. Elevated beta EEG activity suggests that arousal level during sleep is higher in these women.

Geoepidemiology of COPD and idiopathic pulmonary fibrosis.

Progress in improving patient outcomes and advancing therapeutics in chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) is hampered by phenotypic heterogeneity and variable responsiveness to clinical interventions that are not fully explained by currently held disease paradigms for COPD and IPF. Although these chronic lung diseases differ in their geoepidemiology and immunopathogenesis, emerging evidence suggest that organ-specific autoimmunity may underlie subphenotypes of COPD and IPF. In particular, the links to tobacco smoking, diet, gender, and environment are explored in this review. We also highlight potential mechanisms that could guide future investigations in both laboratory and clinical settings. A paradigm shift is needed in how we think about COPD and IPF, based on geoepidemiology and a broader understanding of disease pathogenesis that may ultimately lead to new therapies and improved patient outcomes.

Algorithms for the assessment and management of insomnia in primary care.

Insomnia is a leading cause of sleep disturbance in primary care practice affecting >30% of people in the United States and can result in psychological and physiological consequences. We aim for a focused discussion of some of the underpinnings of insomnia and practical tips for management (eg, algorithms). A PubMed search was conducted using English language papers between 1997-2007, with the terms "sleep," "insomnia"; "primary care" and "clinics"; "comorbid conditions"; "treatment" and "management." Sleep, psychiatric and medical disorders significantly affect sleep, causing patient suffering, potentially worsening of other disorders and increasing the use of primary care services. We provide an outline for practical assessment and treatment of insomnia in primary care, including the strengths and weaknesses of medications.

Sleep in the ICU: potential mechanisms and clinical implications.

Patients in the ICU are known to have severely disrupted sleep with disturbed circadian pattern, decreased nocturnal sleep time, abnormally increased stages 1 and 2 sleep, and reduced or absent deep sleep. Recent data reveal that a subpopulation of critically ill patients manifests unique EEG sleep patterns. The etiology of sleep disruption in the ICU includes the inherent nature of the environment, medications, ventilator-patient interaction, and the effect of acute illness. How sleep disruption contributes to outcomes in critically ill patients, such as recovery time and weaning from mechanical ventilation, is unknown. This article reviews the literature describing sleep in ICU patients, including recent investigations in patients who require mechanical ventilation, factors that affect sleep in critically ill patients, and the potential mechanisms and clinical implications of disturbed sleep in the ICU setting with directions to consider for future investigations.

Sleep in hospitalized medical patients, part 2: behavioral and pharmacological management of sleep disturbances.

BACKGROUND: As described in Part 1 of this article, multiple factors lead to disrupted sleep in hospitalized medical patients. Recognizing and addressing these factors can help clinicians more effectively manage patients' sleep complaints. METHODS: A PubMed search was conducted by cross-referencing the terms "sleep deprivation," "insomnia," and "sleep"; "hospitalized," "acutely ill," and "critically ill"; and "medication," "drugs," "hypnotics," "benzodiazepines," and "sedatives." The search was limited to English-language articles published between 1997 and 2008. Subsequent PubMed searches were performed to clarify the data described in the initial search. RESULTS: Few articles addressed the topic of the assessment and management of sleep problems in hospitalized medical patients. In Part 2, we propose an evaluation and treatment algorithm that includes recommendations regarding the use of nonpharmacologic and pharmacologic therapies as clinicians consider relevant clinical data. The algorithm is accompanied by 5 tables that include pertinent and practical information to assist clinicians as they manage their inpatients' sleep complaints. CONCLUSIONS: Assessment of a sleep complaint should include a review of factors that could exacerbate patients' sleep. The treatment could then focus on ameliorating these factors, and the judicious use of nonpharmacologic strategies and psychopharmacologic agents.

Sleep in hospitalized medical patients, part 1: factors affecting sleep.

BACKGROUND: Multiple factors lead to sleep disturbances in hospitalized medical patients. Inadequate sleep can lead to both psychological and physiological consequences. METHODS: A PubMed search was conducted using the terms: ("sleep deprivation," "sleep," or "insomnia") and ("hospitalized," "inpatient," "critical illness," or "acute illness") to review the published data on the topic of sleep in hospitalized medical patients. The search was limited to English-language articles published between 1997 and 2008. Subsequent PubMed searches were performed to clarify the data described in the initial search, including the terms "hospital noise," "hospital environment," "obstructive sleep apnea," and "heart failure." RESULTS: Few articles specifically addressed the topic of sleep in hospitalized medical patients. Data were limited to observational studies that included outcomes such as sleep complaints and staff logs of wakefulness and sleep. In Part 1, we review normal sleep architecture, and discuss how major medical disorders, the hospital environment, and medications can disrupt sleep during hospitalization. In Part 2, we will propose an evaluation and treatment algorithm to optimize sleep in hospitalized medical patients. CONCLUSIONS: Hospitalization may severely disrupt sleep, which can worsen pain, cardiorespiratory status, and the psychiatric health of acutely ill patients. Like vital signs, the patient sleep quality reveals much about patients' overall well-being, and should be a routine part of medical evaluation.

Integrating palliative care in severe chronic obstructive lung disease.

Palliative care services for patients with chronic obstructive pulmonary disease (COPD) have been limited in most health care schemes despite the significant impact its symptoms can have on quality of life (QOL). Palliative care must be integrated to address physical and emotional distress and QOL deterioration more effectively. Multi-factorial barriers in current health care systems impede the provision of palliative care, including the lack of familiarity among health care professionals. There are sparse evidence-based studies and guidelines for clinicians to better recognize the need for palliative care in COPD patients compared to the large experience and resources available to cancer patients and hospice care. The multidisciplinary approach of palliative care should help COPD patients navigate through the continuum of chronic disease management. Highest QOL, not necessarily the highest physiologic goals, with relief of physical and emotional suffering, are most important to patients. Hospice care, the last phase of palliative care, can be offered to COPD patients when their goal of care has changed from life-prolonging therapies to comfort treatment. We suggest a scheme for identifying COPD patients for palliative care and for delivering simultaneous disease-directed care to help patients live life to the fullest. Pulmonary rehabilitation offers the best venue for incorporating palliative care. We review the need for, barriers to, and key activities for integrating palliative care into the current health care management of patients living with COPD.

Sleep in critically ill chemically paralyzed patients requiring mechanical ventilation.

OBJECTIVE: To determine sleep characteristics in patients receiving mechanical ventilation who require a neuromuscular blocking agent (NMBA). DESIGN: Observational study. SETTING: Adult medical ICU at a university hospital. PARTICIPANTS: Eighteen patients with respiratory failure requiring mechanical ventilation were classified into three groups based on medication regimen determined a priori: intermittent sedation (IS), continuous sedation (CS), or CS and an NMBA. MEASUREMENTS: Twenty-four-hour polysomnography was performed to determine sleep architecture and fragmentation. Measurement of severity of illness, laboratory indexes, patient-care interventions, and drug dosage were compared between groups, and the effects on sleep staging and fragmentation were analyzed. Sleep stages were scored manually using criteria of Rechtschaffen and Kales, as well as by a modified 50-muV voltage criteria for scoring delta activity. RESULTS: All patients demonstrated abnormal sleep architecture. In each group of patients, the total sleep time (TST) was > 10 h. There was no statistical difference in the delta activity between the two scoring methods; delta activity was increased in all groups: 32.9%, 49.6%, and 43.7% in the IS, CS, and CS/NMBA groups, respectively. Patients receiving NMBAs spent 22% of the sleep period awake. Rapid eye movement sleep could not be detected in the patients receiving NMBAs and was reduced in the other two groups (3.5%). TST, sleep stage, or arousal/awakening index were not statistically correlated with either severity of illness, clinical laboratory indexes, drug dosage, patient-care interventions, or mode of mechanical ventilation. CONCLUSION: TST during a 24-h period is not reduced in patients requiring mechanical ventilation. Delta activity is increased and may reflect age, drug, or a contributing metabolic process. The effect of wakefulness in patients receiving chemical paralysis on recovery and weaning from mechanical ventilation, and overall clinical outcome is unknown.

Interstitial lung disease associated with epidermal growth factor receptor tyrosine kinase inhibitor therapy in non-small-cell lung carcinoma.

Interstitial lung disease is a rare but serious complication of epidermal growth factor receptor tyrosine kinase inhibitor therapy. Although our understanding of this phenomenon remains incomplete, recently there have been significant insights made into the mechanisms of injury, incidence, risk factors, and its clinical manifestations. Japanese patients appear to be at a higher risk (1.6%-3.5%) than patients in the rest of the world (0.3%), and other risk factors, such as coincident interstitial lung disease, concurrent chemotherapy, previous radiation, preexisting pulmonary fibrosis, and male sex, have been identified. In the majority of cases, the histopathology, the acute and often dramatic clinical presentation, and the radiographic findings resemble acute respiratory distress syndrome. Aside from immediate cessation of the offending agent, the treatment is largely supportive, although corticosteroids appear to be of benefit. The mortality remains high at approximately 30%-50%. We present a review of the incidence, risk factors, clinical manifestations, diagnosis, management, and outcome of this disorder.

Severe upper airway obstruction during sleep.

Few disorders may manifest with predominantly sleep-related obstructive breathing. Obstructive sleep apnea (OSA) is a common disorder, varies in severity and is associated with significant cardiovascular and neurocognitive morbidity. It is estimated that between 8 and 18 million people in the United States have at least mild OSA. Although the exact mechanism of OSA is not well-delineated, multiple factors contribute to the development of upper airway obstruction and include anatomic, mechanical, neurologic, and inflammatory changes in the pharynx. OSA may occur concomitantly with asthma. Approximately 74% of asthmatics experience nocturnal symptoms of airflow obstruction secondary to reactive airways disease. Similar cytokine, chemokine, and histologic changes are seen in both disorders. Sleep deprivation, chronic upper airway edema, and inflammation associated with OSA may further exacerbate nocturnal asthma symptoms. Allergic rhinitis may contribute to both OSA and asthma. Continuous positive airway pressure (CPAP) is the gold standard treatment for OSA. Treatment with CPAP therapy has also been shown to improve both daytime and nighttime peak expiratory flow rates in patients with concomitant OSA and asthma. It is important for allergists to be aware of how OSA may complicate diagnosis and treatment of asthma and allergic rhinitis. A thorough sleep history and high clinical suspicion for OSA is indicated, particularly in asthma patients who are refractory to standard medication treatments.