Neuronal Intranuclear Inclusion Disease: A Rare Etiology for Rapidly Progressive Dementia.

INTRODUCTION: Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disorder pathologically characterized by localized neuronal loss, and presence of eosinophilic intranuclear inclusions in neurons and glial cells. CASE REPORT: A 50-year-old man presented with rapidly progressive dementia, behavioral changes, gait disturbances, and incontinence of 3 months duration. His brain magnetic resonance imaging showed diffuse T2/FLAIR hyperintensity of basal ganglia, thalami, cerebral peduncles, ventral pons, and supratentorial white matter with a frontal predominance. Hyperintensity was noted along the corticosubcortical junction on diffusion-weighted images. NIID was suspected and the patient underwent triple biopsy of the sural nerve with adjacent skin and biceps biopsy. Biopsy revealed ubiquitin-positive intranuclear inclusions surrounding the myofibers, and vascular smooth muscles suggestive of NIID. CONCLUSIONS: NIID is a rare neurodegenerative disorder usually diagnosed postmortem. The rectal and skin biopsy had proved helpful in antemortem diagnosis. We have increased the diagnostic armamentarium by showing the presence of intranuclear inclusions in smooth muscle cells of the muscle. Hence, a high degree of suspicion, magnetic resonance imaging features, with nerve/muscle/skin biopsy can help in diagnosis of NIID.

Cardiovascular Oncologic Emergencies.

Oncologic emergencies can present either as a progression of a known cancer or as the initial presentation of a previously undiagnosed cancer. In most of these situations, a very high degree of suspicion is required to allow prompt assessment, diagnosis, and treatment. In this article, we review the presentation and management of cardiovascular oncologic emergencies from primary and metastatic tumors of the heart and complications such as pericardial tamponade, superior vena cava syndrome, and hyperviscosity syndrome. We have included the cardiovascular complications from radiation therapy, chemotherapeutic agents, and biologic agents used in modern cancer treatment.

Sleep: important considerations for the prevention of cardiovascular disease.

PURPOSE OF REVIEW: Sleep plays many roles in maintenance of cardiovascular health. This review summarizes the literature across several areas of sleep and sleep disorders in relation to cardiometabolic disease risk factors. RECENT FINDINGS: Insufficient sleep duration is prevalent in the population and is associated with weight gain and obesity, inflammation, cardiovascular disease, diabetes, and mortality. Insomnia is also highly present and represents an important risk factor for cardiovascular disease, especially when accompanied by short sleep duration. Sleep apnea is a well-characterized risk factor for cardiometabolic disease and cardiovascular mortality. Other issues are relevant as well. For example, sleep disorders in pediatric populations may convey cardiovascular risks. Also, sleep may play an important role in cardiovascular health disparities. SUMMARY: Sleep and sleep disorders are implicated in cardiometabolic disease risk. This review addresses these and other issues, concluding with recommendations for research and clinical practice.

Sleep Duration and Diabetes Risk: Population Trends and Potential Mechanisms.

Sleep is important for regulating many physiologic functions that relate to metabolism. Because of this, there is substantial evidence to suggest that sleep habits and sleep disorders are related to diabetes risk. In specific, insufficient sleep duration and/or sleep restriction in the laboratory, poor sleep quality, and sleep disorders such as insomnia and sleep apnea have all been associated with diabetes risk. This research spans epidemiologic and laboratory studies. Both physiologic mechanisms such as insulin resistance, decreased leptin, and increased ghrelin and inflammation and behavioral mechanisms such as increased food intake, impaired decision-making, and increased likelihood of other behavioral risk factors such as smoking, sedentary behavior, and alcohol use predispose to both diabetes and obesity, which itself is an important diabetes risk factor. This review describes the evidence linking sleep and diabetes risk at the population and laboratory levels.

A Case of Ollier's Disease with P53 Mutation Positive and IDH1 (R132H) Negative Multicentric Gliomas.

Ollier disease is a rare nonhereditary disorder characterized by multiple enchondromas (enchondromatosis). To report a rare case of Ollier disease with gliomas and its mutation analysis. We hereby report a young lady who presented with seizures. She had a past history of multiple bony swellings in the right foot (operated) and swelling over the anterior chest wall for the past 15 years. MRI brain revealed multiple expansile T2/FLAIR hyperintense lesions in right superior and middle frontal gyri, left basifrontal lobe, and left precuneus in the cortical-subcortical location suggestive of glioma. She underwent biopsy which revealed left basifrontal anaplastic astrocytoma, not otherwise specified, WHO grade III, IDH1 (R132H) negative, P53 mutation positive, and ATRX loss of expression. We hereby report a rare case of Ollier disease with multicentric intracranial glioma-IDH1 (R132H) negative, P53 mutation positive, and ATRX loss of expression.

Socioeconomic Inequities in Adherence to Positive Airway Pressure Therapy in Population-Level Analysis.

(a) Background: In patients with sleep apnea, poor adherence to positive airway pressure (PAP) therapy has been associated with mortality. Regional studies have suggested that lower socioeconomic status is associated with worse PAP adherence but population-level data is lacking. (b) Methods: De-identified data from a nationally representative database of PAP devices was geo-linked to sociodemographic information. (c) Results: In 170,641 patients, those in the lowest quartile of median household income had lower PAP adherence (4.1 + 2.6 hrs/night; 39.6% adherent by Medicare criteria) than those in neighborhoods with highest quartile median household income (4.5 + 2.5 hrs/night; 47% adherent by Medicare criteria; p < 0.0001). In multivariate regression, individuals in neighborhoods with the highest income quartile were more adherent to PAP therapy than those in the lowest income quartile after adjusting for various confounders (adjusted Odds Ratio (adjOR) 1.18; 95% confidence interval (CI) 1.14, 1.21; p < 0.0001). Over the past decade, PAP adherence improved over time (adjOR 1.96; 95%CI 1.94, 2.01), but health inequities in PAP adherence remained even after the Affordable Care Act was passed. (d) Conclusion: In a nationally representative population, disparities in PAP adherence persist despite Medicaid expansion. Interventions aimed at promoting health equity in sleep apnea need to be undertaken.

Hemosuccus Pancreaticus.

Hemosuccus pancreaticus (HP) defined as bleeding into the pancreatic duct was first described in 1931 by Lower and Farell. HP also popularly known as wirsungorrhaghia and pseudohemobilia is a rare cause of gastrointestinal bleed. The unfamiliarity of this condition makes HP a diagnostic challenge. HP should be considered in patients with chronic pancreatitis presenting with acute gastrointestinal bleeding. The diagnosis is usually confirmed with a computerized tomography (CT) scan of the abdomen. A mesenteric angiogram with coil embolization can be performed to arrest the bleeding. The literature on this condition is restricted to case reports, case series and retrospective studies. We describe a case of HP in a patient with gastrointestinal bleeding and take this opportunity to review the literature outlining the diagnosis and management of HP.

Severe hypocalcemia mimicking acute inferior ST-segment elevation myocardial infarction.

We report the case of a 52-year-old gentleman, admitted to the medical intensive care unit with multiple organ system dysfunction due to acute severe pancreatitis. He was found to have severe hypocalcemia, bradycardia and an electrocardiogram (EKG) showing ST-segment elevation in infero-lateral leads. The patient was treated with intravenous calcium gluconate with prompt improvement of heart rate and reversal of EKG changes. Subsequent evaluation for myocardial ischemia was negative. We believe the EKG changes mimicking acute ST-segment elevation myocardial infarction were due to severe hypocalcemia. To our knowledge this is very rare occurrence.

The Tale of the Storyteller and the Painter: The Paradoxes in Nature.

INTRODUCTION: Brain as the seat of behavior is acknowledged from the times of Charaka, however where neurology ends and philosophy begins remains an enigma. It is certainly every neurologist's observation that there is loss of function either region based or domain based in progressive diseases of the nervous system making it the seat of all useful activities. However, there are references to occurrence of new skills seen during various illnesses causing progressive cognitive dysfunction. This serves as a pharmaco-sparing agent in behavior management and therefore serves as a rehabilitatory tool. However, its pathomechanism is not clear. PATIENT AND METHODS: Two patients comprising one male and one female who were being evaluated for progressive cognitive dysfunction and were found to have interesting creative skills and are being described. RESULTS: The first patient is a case of young onset behavioral variant frontotemporal dementia and the second patient is a case of neurosarcoidosis. CONCLUSION: The emergence of these skills could be due to disinhibition of some of the innate skills of the patients during degeneration or establishment of new data linking circuits with creative potential during attempted repair.

Unanticipated Nocturnal Oxygen Requirement during Positive Pressure Therapy for Sleep Apnea and Medical Comorbidities.

STUDY OBJECTIVES: Home-based management of sleep-disordered breathing (SDB) generally excludes patients with significant medical comorbidities, but such an approach lacks scientific evidence. The current study examined whether significant medical comorbidities are associated with persistent hypoxia that requires unanticipated nocturnal O2 supplementation to positive airway pressure (PAP) therapy. Conceivably, in such patients, home-based management of SDB may not detect or therefore adequately treat persistent hypoxia. METHODS: In this retrospective study of 200 patients undergoing laboratory-based polysomnography, we ascertained significant medical comorbidities (chronic obstructive pulmonary disease, congestive heart failure, and morbid obesity) and their association with the need for unanticipated O2 supplementation to PAP therapy. Postural oxygen (SpO2) desaturations between upright and reclining positions were determined during calm wakefulness. RESULTS: Postural change in SpO2 during calm wakefulness was greater in patients who eventually needed nocturnal O2 supplementation to PAP therapy than those needing PAP therapy alone (p < 0.0001). The presence of chronic obstructive pulmonary disease (odds ratio [OR] 6.0; 95% confidence interval [CI]; 2.1, 17.5; p = 0.001), morbid obesity (OR 3.6; 95% CI 1.9, 7.0; p < 0.0001), and age older than 50 y (OR 2.8; 95% CI 1.3, 5.9; p = 0.007) but not heart failure were associated with unanticipated need for nocturnal O2 supplementation. A clinical prediction rule of less than two determinants (age older than 50 y, morbid obesity, chronic obstructive pulmonary disease, and postural SpO2 desaturation greater than 5%) had excellent negative predictive value (0.92; 95% CI 0.85, 0.96) and likelihood ratio of negative test (0.08; 95% CI 0.04, 0.16). CONCLUSIONS: Medical comorbidities can predict persistent hypoxia that requires unanticipated O2 supplementation to PAP therapy. Such findings justify the use of medical comorbidities to exclude home management of SDB. COMMENTARY: A commentary on this article appears in this issue on page 7.

Insomnia, Health-Related Quality of Life and Health Outcomes in Children: A Seven Year Longitudinal Cohort.

Insomnia is common in children, and is associated with decreased school performance and increased psychopathology. Although adult insomnia is linked to worsened health-related quality of life (HRQOL), there is insufficient data evaluating insomnia and HRQOL in children. We examined the HRQOL and health associations of insomnia in a longitudinal cohort of 194 children (96 girls, age at study start 8.7 ± 1.6 years, age at data analysis 15.0 ± 1.8 years) over 7 years. International Classification of Sleep Disorders, second edition (ICSD2) derived insomnia was seen intermittently in 27% of children, and was persistent in 4%. Children reporting ICSD2-derived insomnia had lower HRQOL. Additionally, the presence of insomnia was associated with an increased risk of reporting a new medical condition (intermittent insomnia odds ratio 5.9 [95% CI 1.3-26.7, p = 0.04], persistent insomnia odds ratio 8 [95% CI 2.3-27.7, p = 0.001]). Persistent ICSD2-derived insomnia was associated with an increased risk of reporting a new medication (odds ratio 4.9 (95% CI 1.0-23.6), p = 0.049), and reporting a new psychiatric medication (odds ratio 13.7, 95% CI: 2.6-73.5, p = 0.002). These associations were present even after adjusting for socioeconomic factors and the presence of obstructive sleep apnea. Insomnia in children is associated with worsened HRQOL and health outcomes.

Obesity Hypoventilation Syndrome.

Obesity hypoventilation syndrome is a respiratory consequence of morbid obesity that is characterized by alveolar hypoventilation during sleep and wakefulness. The disorder involves a complex interaction between impaired respiratory mechanics, ventilatory drive and sleep-disordered breathing. Early diagnosis and treatment is important, because delay in treatment is associated with significant mortality and morbidity. Available treatment options include non-invasive positive airway pressure (PAP) therapies and weight loss. There is limited long-term data regarding the effectiveness of such therapies. This review outlines the current concepts of clinical presentation, diagnostic and management strategies to help identify and treat patients with obesity-hypoventilation syndromes.

A meta-analysis of sleep-promoting interventions during critical illness.

BACKGROUND: Sleep quality and quantity are severely reduced in critically ill patients receiving mechanical ventilation with a potential for adverse consequences. Our objective was to synthesize the randomized controlled trials (RCTs) that measured the efficacy of sleep-promoting interventions on sleep quality and quantity in critically ill patients. METHODS: We included RCTs that objectively measured sleep with electroencephalography or its derivatives and excluded observational studies and those that measured sleep by subjective reports. The research was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: Of 6022 studies identified, 13 met eligibility criteria involving 296 critically ill patients. Eight trials looked at different modes of mechanical ventilation as sleep interventions, and the remaining 5 involved pharmacologic, nonpharmacologic, or environmental interventions. Meta-analysis of the studies revealed that sleep-promoting interventions improved sleep quantity (pooled standardized mean difference [SMD], 0.37; 95% confidence interval [CI], 0.05-0.69; P = .02) and sleep quality through reduction in sleep fragmentation (SMD, -0.31; 95% CI, -0.60 to -0.01; P = .04). Subgroup analysis revealed that timed modes of ventilation improved sleep quantity when compared with spontaneous modes of ventilation (SMD, 0.45; 95% CI, 0.10-0.81; P = .01). Nonmechanical ventilation interventions tended to improve sleep quantity (SMD, 0.65; 95% CI, -0.03 to 1.33; P = .06) and to reduce sleep fragmentation (SMD, -0.29; 95% CI, -0.61 to 0.03; P = .07). CONCLUSIONS: The synthesized evidence suggests that both mechanical ventilation- and nonmechanical ventilation-based therapies improve sleep quantity and quality in critically ill patients, but the clinical significance is unclear. In the future, adequately powered multicenter RCTs involving pharmacologic interventions to promote sleep in critically ill patients are warranted.

Advances in Positive Airway Pressure Treatment Modalities for Hypoventilation Syndromes.

RATIONALE: Positive airway pressure therapy for hypoventilation syndromes can significantly improve health-related quality of life (HR-QOL), healthcare costs, and even mortality. The sleep-disordered breathing in such individuals are quite complex and require sophisticated devices with algorithms that are designed to accurately detect and effectively treat respiratory events that includes hypoventilation, upper airway obstruction, lower airway obstruction, central apneas and central hypopneas and reduce the work of breathing while maintaining breathing comfort. OBJECTIVES: The therapeutic physiological rationale for the various advanced PAP modalities and the details about the principles of operation and technology implementation are provided here. CONCLUSIONS: The physiological rationale for advanced PAP modalities is sound considering the complexity of sleep-disordered breathing in patients with hypoventilation syndromes. Although such devices are increasingly used in clinical practice, the supporting clinical evidence - specifically comparative-effectiveness studies in real-life conditions -- needs to be performed. Moreover, there is much opportunity for further refining these devices that include the ability of the device to reliably monitor gas-exchange, sleep-wakefulness state, and for reducing variability in device efficacy due to provider-selected device-settings.