Severe Monkeypox in Hospitalized Patients - United States, August 10-October 10, 2022.

As of October 21, 2022, a total of 27,884 monkeypox cases (confirmed and probable) have been reported in the United States.§ Gay, bisexual, and other men who have sex with men have constituted a majority of cases, and persons with HIV infection and those from racial and ethnic minority groups have been disproportionately affected (1,2). During previous monkeypox outbreaks, severe manifestations of disease and poor outcomes have been reported among persons with HIV infection, particularly those with AIDS (3-5). This report summarizes findings from CDC clinical consultations provided for 57 patients aged ≥18 years who were hospitalized with severe manifestations of monkeypox¶ during August 10-October 10, 2022, and highlights three clinically representative cases. Overall, 47 (82%) patients had HIV infection, four (9%) of whom were receiving antiretroviral therapy (ART) before monkeypox diagnosis. Most patients were male (95%) and 68% were non-Hispanic Black (Black). Overall, 17 (30%) patients received intensive care unit (ICU)-level care, and 12 (21%) have died. As of this report, monkeypox was a cause of death or contributing factor in five of these deaths; six deaths remain under investigation to determine whether monkeypox was a causal or contributing factor; and in one death, monkeypox was not a cause or contributing factor.** Health care providers and public health professionals should be aware that severe morbidity and mortality associated with monkeypox have been observed during the current outbreak in the United States (6,7), particularly among highly immunocompromised persons. Providers should test all sexually active patients with suspected monkeypox for HIV at the time of monkeypox testing unless a patient is already known to have HIV infection. Providers should consider early commencement and extended duration of monkeypox-directed therapy†† in highly immunocompromised patients with suspected or laboratory-diagnosed monkeypox.§§ Engaging all persons with HIV in sustained care remains a critical public health priority.

Using the Patient Safety Huddle as a Tool for High Reliability.

A Patient Safety Huddle was developed at a community hospital (Providence Little Company of Mary Medical Center, San Pedro, California) through consultation with key stakeholders. The goal was to become a high reliability organization by improving communication across different departments, troubleshooting operational problems, focusing on safety and quality metrics, and reporting unusual occurrences. The Patient Safety Huddle involved executives in development and implementation, respect for employee time, ensuring accountability, and empowering frontline staff to foresee and deal with safety issues. The current template of the Patient Safety Huddle agenda and the Documentation Tools used to address patient safety issues are provided.

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.

Role of iron in neurotoxicity: a cause for concern in the elderly?

PURPOSE OF REVIEW: To explore the role of iron physiology in the brain of healthy adults and review how increased brain iron deposition has been associated with common neurodegenerative diseases that affect the elderly. RECENT FINDINGS: Because iron plays a role in oxygen transportation, myelin synthesis, neurotransmitter production, and electron transfers, it serves as a crucial cofactor in normal central nervous metabolism. However, an increased level of brain iron may promote neurotoxicity due to free radical formation, lipid peroxidation, and ultimately, cellular death. Advanced neuroimaging techniques and pathological studies have demonstrated increased brain iron with aging, and increased iron deposition has also been observed in patients with a constellation of neurological diseases, including Alzheimer's disease, Parkinson's disease, and stroke. SUMMARY: Pathologic and neurologic imaging coupled with experimentation have increased our understanding of the link between iron and neurodegeneration. A potential implication is that disease-modifying therapies aimed at removing excess iron may one day be part of the armamentarium employed by clinicians to decrease the burden of neurodegenerative diseases in the elderly.

Membrane bound IL-15 is increased on CD14 monocytes in early stages of MS.

IL-15 is a pro-inflammatory cytokine whose three-dimensional structure is similar to that of IL-2. IL-2 and IL-15 have similar as well as distinct biological functions. An active form of IL-15 that is membrane bound has also been described. Furthermore, IL-15 is known to play a role in autoimmune diseases. We thus investigated the expression of membrane bound IL-15 on monocytes (CD14+ cells) and studied its effect on T cell activation in MS patients. We found that unstimulated CD14+ cells from relapsing remitting MS patients had increased membrane bound IL-15. Those with high surface levels of IL-15 on monocytes were in the early stages of the disease. In addition, we found that T cells of MS patients had enhanced responsiveness to IL-15 and there was increased expression of IL-15 receptor on CD4+ T cells. Thus, IL-15 may be an important cytokine that drives Th1 responses early in the course of the disease and could serve as a target for immunotherapy and as an early marker in the immunologic staging of MS.

The prevalence and awareness of sleep apnea in patients suffering chronic pain: an assessment using the STOP-Bang sleep apnea questionnaire.

PURPOSE: Some patient subsets are at higher risk of sleep apnea, including patients with chronic pain. However, it is unclear whether patients and their caregivers are aware of the possibly increased risk of sleep apnea in this population. Chronic pain is often treated with opioids which may decrease both the central respiratory drive and the patency of the upper airway, potentially contributing to this sleep disorder. Using a self-reporting questionnaire approach in the chronic pain population, this study surveyed patient and caregiver awareness surrounding the risk of sleep apnea. In addition, we looked at the influence of opioid therapy on the prevalence of sleep apnea. PARTICIPANTS AND METHODS: Consecutive patients presenting to a pain clinic were invited to participate anonymously in a survey that included the STOP-Bang sleep apnea questionnaire, which assesses patients' knowledge, testing, diagnosis, or treatment of sleep apnea and whether their caregivers had discussed with them their increased risk of sleep apnea and opioid use. RESULTS: Among 305 participating patients, 58.2% (n=173) screened positive for sleep apnea. Among the 202 patients on opioid therapy, 59.2% (116/202) were STOP-Bang positive (score ≥3). However, only 37.5% (n=72/173) of these patients had discussed their risk of sleep apnea with a caregiver and only 30.7% (n=59) underwent testing. Against expectation, opioids did not increase the prevalence of sleep apnea in our study population. CONCLUSION: Chronic pain patients had a high risk of sleep apnea, regardless of opioid prescription. Most patients were unaware of their increased risk and denied undergoing the necessary testing. Greater attention to screening, testing, and education for sleep apnea needs to be paid in chronic pain patients, especially given the potentially dangerous ramifications of opioid-induced sleep apnea.

Magnetic resonance imaging of iron deposition in neurological disorders.

Deposition of iron in the brain is proposed to play a role in the pathophysiology of the normal aging process and neurodegenerative diseases. Whereas iron is required for normal neuronal metabolism, excessive levels can contribute to the formation of free radicals, leading to lipid peroxidation and neurotoxicity. Magnetic resonance imaging (MRI) is a powerful tool to detect excessive iron in the brain and longitudinally monitor changes in iron levels. Iron deposition is associated with a reduction in the T2 relaxation time, leading to hypointensity on spin-echo and gradient-echo T2-weighted images. The MRI changes associated with iron deposition have been observed both in normal aging and in various chronic neurological diseases, including multiple sclerosis, Alzheimer disease, and Parkinson disease. Magnetic resonance imaging metrics providing information about iron concentrations include R2, R2', and R2*. The purpose of this review is to discuss the role of iron and its detection by MRI in various neurological disorders. We will review the basic biochemical properties of iron and its influence on MRI signal. We will also summarize the sensitivity and specificity of MRI techniques in detecting iron. The MRI and pathological findings pertaining to brain iron will be reviewed with respect to normal aging and a variety of neurological disorders. Finally, the biochemistry and pathophysiology surrounding iron, oxidative stress, free radicals, and lipid peroxidation in the brain will be discussed, including therapeutic implications. The potential role of iron deposition and its assessment by MRI provides exciting potential applications to the diagnosis, longitudinal monitoring, and therapeutic development for disorders of the brain.

Axonal damage in multiple sclerosis patients with high versus low expanded disability status scale score.

BACKGROUND: The pathophysiological basis for differences in disability in patients with multiple sclerosis is unclear. METHODS: We used magnetic resonance imaging to examine whether differences in disability in cohorts of multiple sclerosis patients with similar T2-weighted lesion volume and disease duration were associated with a more destructive disease process in the more disabled patients. RESULTS: The benign and severely disabled groups had similar brain atrophy metrics and similar decreases of the neuronal marker, N-acetylaspartate, in the normal appearing white matter of the cerebrum on magnetic resonance spectroscopy examination in vivo. The severely disabled cohort had more spinal cord atrophy. CONCLUSION: The dissociation of spinal cord atrophy and cerebral atrophy between these two groups suggests that the difference between the more benign and more disabled groups cannot be explained by a more aggressive pathological process that is affecting the entire neuroaxis in a homogeneous fashion.

The underdiagnosis of sleep disorders in patients with multiple sclerosis.

STUDY OBJECTIVES: To report at a population level the prevalence of restless legs syndrome, insomnia, and the risk of obstructive sleep apnea in multiple sclerosis patients. Sleep patterns and associations with fatigue and daytime sleepiness were identified. METHODS: A cross-sectional study was performed using a written survey that was mailed to 11,400 individuals from the Northern California Chapter of the National Multiple Sclerosis (MS) Society Database who self-identified as having MS. The survey included individual questions relating to demographics as well as several standard validated questionnaires related to primary sleep disorders, sleepiness, fatigue severity, and sleep patterns. RESULTS: Among the 11,400 surveys mailed out, 2,810 (24.6%) were returned. Of these, 2,375 (84.5%) met the inclusion criteria. Among the completed surveys, 898 (37.8%) screened positive for obstructive sleep apnea, 746 (31.6%) for moderate to severe insomnia, and 866 (36.8%) for restless legs syndrome. In contrast, only 4%, 11%, and 12% of the cohort reported being diagnosed by a health care provider with obstructive sleep apnea, insomnia, and restless legs syndrome, respectively. Excessive daytime sleepiness was noted in 30% of respondents based on the Epworth Sleepiness Scale. More than 60% of the respondents reported an abnormal level of fatigue based on the Fatigue Severity Scale. Both abnormal fatigue and sleepiness scores were associated with screening positive for obstructive sleep apnea, insomnia, and restless legs syndrome. CONCLUSION: A significant percentage of MS subjects in our sample screened positive for one or more sleep disorders. The vast majority of these sleep disorders were undiagnosed. Greater attention to sleep problems in this population is warranted, especially in view of fatigue being the most common and disabling symptom of MS.

New and unconventional treatments for obstructive sleep apnea.

Although continuous positive airway pressure, oral appliances and surgical modifications of the airway are considered as part of the routine management of patients with obstructive sleep apnea, many new and unconventional therapies exist. Many of the trials using these new alternatives have been limited by insufficient data, poor trial design, small sample size, unclear inclusion criteria, lack of randomization, and lack of blinding, and on occasion are biased by retrospective design. Bariatric surgery, positional therapy, auto-titrating positive airway pressure, serotonin agents, wake promoting agents, genioglossus stimulation surgery, supplemental oxygen, nasal dilators, nasal expiratory resistor devices and oropharyngeal exercises will be reviewed. As obstructive sleep apnea impacts the individual and society at large, further research is needed to explore new therapeutic treatment options for obstructive sleep apnea. Therapeutic trials for obstructive sleep apnea must be of rigorous design to prove clinical effectiveness while taking into account both patient satisfaction and cost effectiveness.

Obstructive sleep apnea.

Obstructive sleep apnea (OSA) affects millions of Americans and is estimated to be as prevalent as asthma and diabetes. Given the fact that obesity is a major risk factor for OSA, and given the current global rise in obesity, the prevalence of OSA will increase in the future. Individuals with sleep apnea are often unaware of their sleep disorder. It is usually first recognized as a problem by family members who witness the apneic episodes or is suspected by their primary care doctor because of the individual's risk factors and symptoms. The vast majority remain undiagnosed and untreated, despite the fact that this serious disorder can have significant consequences. Individuals with untreated OSA can stop breathing hundreds of times a night during their sleep. These apneic events can lead to fragmented sleep that is of poor quality, as the brain arouses briefly in order for the body to resume breathing. Untreated, sleep apnea can have dire health consequences and can increase the risk of hypertension, diabetes, heart disease, and heart failure. OSA management has also become important in a number of comorbid neurological conditions, including epilepsy, stroke, multiple sclerosis, and headache. Diagnosis typically involves use of screening questionnaires, physical exam, and an overnight polysomnography or a portable home study. Treatment options include changes in lifestyle, positive airway pressure, surgery, and dental appliances.

Sleep disorders in patients with multiple sclerosis.

Patients with multiple sclerosis (MS) often have unrecognized sleep disorders at higher frequency than the general population. Sleep disorders such as sleep disordered breathing, insomnia, REM sleep behavior disorder, narcolepsy and restless legs syndrome have all been reported in the MS population. Notably, the most common symptom of MS is "fatigue," which itself has been correlated with sleep disturbances. Sleep disorders may impact the quality of life of the MS patient population. This paper reviews the association of sleep disorders with MS, and discusses the association of sleep disruption with MS fatigue.

Deep gray matter involvement on brain MRI scans is associated with clinical progression in multiple sclerosis.

BACKGROUND: Conventional brain MRI lesion measures have unreliable associations with clinical progression in multiple sclerosis (MS). Gray matter imaging may improve clinical-MRI correlations. METHODS: We tested if gray matter MRI measures and conventional measures of lesions/atrophy predicted clinical progression in a 4-year longitudinal study of 97 patients with MS. Baseline and follow-up brain MRI were analyzed for basal ganglia and thalamic normalized T2 signal intensity, whole brain T2-hyperintense lesion volume, and whole brain atrophy. Logistic regression tested the ability of baseline or on-study change in MRI to predict disability progression, as reported by area under the receiver operator characteristics curve (AUC). RESULTS: Lower caudate T2-intensity at baseline (P= .04; AUC = .69) and on-study decreasing T2-intensity in the putamen (P= .03; AUC = .70) and thalamus (P= .01; AUC = .71) were the MRI variables associated with clinical progression when regression modeling was adjusted for length of follow-up interval, baseline EDSS, disease duration, age, and sex. CONCLUSIONS: Gray matter T2-hypointensity, suggestive of excessive iron deposition is associated with worsening disability in patients with MS. Gray matter MRI assessment may be able to capture neurodegenerative aspects of the disease, with more clinical relevance than derived from conventional MRI measures. J Neuroimaging 2009;19:3-8.

Neurological disorders in pregnancy from a neuroimaging perspective.

Pregnancy can precipitate new neurological diseases as a result of the alterations in physiology that accompany the pregnant state. The pregnant patient presenting with neurological problems poses both diagnostic and therapeutic challenges, often forcing the clinician to rely on neuroimaging as part of the workup. This review discusses potential risks to the embryo and fetus posed by computed tomography (CT) and magnetic resonance imaging (MRI), the imaging studies most often used to study the central nervous system. Imaging features of a variety of neurological conditions associated with pregnancy are discussed, including pre-eclampsia and eclampsia, Wernicke's encephalopathy, cerebral venous thrombosis, ischemic stroke, postpartum angiopathy, and lymphocytic hypophysitis.

The role of edema and demyelination in chronic T1 black holes: a quantitative magnetization transfer study.

PURPOSE: To use quantitative magnetization transfer imaging (qMTI) in an investigation of T1-weighted hypointensity observed in clinical magnetic resonance imaging (MRI) scans of multiple sclerosis (MS) patients, which has previously been proposed as a more specific indicator of tissue damage than the more commonly detected T2 hyperintensity. MATERIALS AND METHODS: A cross-sectional study of 10 MS patients was performed using qMTI. A total of 60 MTI measurements were collected in each patient at a resolution of 2 x 2 x 7 mm, over a range of saturation pulses. The observed T1 and T2 were also measured. qMT model parameters were estimated using a voxel-by-voxel fit. RESULTS: A total of 65 T2-hyperintense lesions were identified; 53 were also T1 hypointense. In these black holes, the qMTI-derived semisolid pool fraction F correlated negatively with T(1,obs) (r2 = 0.76; P < 0.0001). The water pool absolute size (PDf) showed a weaker correlation with T(1,obs) (positive, r2 = 0.53; P < 0.0001). The magnetization transfer ratio (MTR) showed a similarly strong correlation with F and a weaker correlation with PDf (r2 = 0.18; P < 0.04). CONCLUSION: T1 increases in chronic black holes strongly correlated with the decline in semisolid pool size, and somewhat less to the confounding effect of edema. MTR was less sensitive than T(1,obs) to liquid pool changes associated with edema.