Feasibility of Polyclonal Avian Immunoglobulins (IgY) as Prophylaxis against Human Norovirus Infection.

BACKGROUND: Human norovirus (HuNoV) is the leading viral cause of diarrhea, with GII.4 as the predominant genotype of HuNoV outbreaks globally. However, new genogroup variants emerge periodically, complicating the development of anti-HuNoV vaccines; other prophylactic or therapeutic medications specifically for HuNoV disease are lacking. Passive immunization using oral anti-HuNoV antibodies may be a rational alternative. Here, we explore the feasibility of using avian immunoglobulins (IgY) for preventing HuNoV infection in vitro in a human intestinal enteroid (HIE) model. METHODS: Hens were immunized with virus-like particles (VLP) of a GII.4 HuNoV strain (GII.4/CHDC2094/1974/US) by intramuscular injection. The resulting IgY was evaluated for inhibition of binding to histo-blood group antigens (HBGA) and viral neutralization against representative GII.4 and GII.6 clinical isolates, using an HIE model. RESULTS: IgY titers were detected by three weeks following initial immunization, persisting at levels of 1:221 (1:2,097,152) from 9 weeks to 23 weeks. Anti-HuNoV IgY significantly (p < 0.05) blocked VLP adhesion to HBGA up to 1:12,048 dilution (0.005 mg/mL), and significantly (p < 0.05) inhibited replication of HuNoV GII.4[P16] Sydney 2012 in HIEs up to 1:128 dilution (0.08 mg/mL). Neutralization was not detected against genotype GII.6. CONCLUSIONS: We demonstrate the feasibility of IgY for preventing infection of HIE by HuNoV GII.4. Clinical preparations should cover multiple circulating HuNoV genotypes for comprehensive effects. Plans for animal studies are underway.

Effects of Integrated Telehealth-Delivered Cognitive-Behavioral Therapy for Depression and Insomnia in Rural Older Adults.

BACKGROUND: We examined the effects of integrated cognitive-behavioral therapy for depression and insomnia (CBT-D + CBT-I) delivered via videoconferening in rural, middle aged and older adults with depressive and insomnia symptoms. METHOD: Forty patients with depressive and insomnia symptoms were randomized to receive either 10 sessions of CBT-D + CBT-I or usual care (UC). Patients in the integrated CBT condition were engaged in telehealth treatment through Skype at their primary care clinic. Assessments were conducted at baseline, post-treatment, and 3-month follow-up. RESULTS: CBT-D +CBT-I participants had significantly greater improvements in sleep at post-treatment and 3-month follow-up as compared to the UC participants. The time by group interaction for depression was not significant; both the CBT-D + CBT-I and UC conditions had a decrease in depressive symptoms over time. CONCLUSION: While integrated CBT benefits both depression and insomnia symptoms, its effects on depression are more equivocal. Further research should consider expanding the depression treatment component of integrated CBT to enhance effectiveness.

Epilepsy and restless legs syndrome.

OBJECTIVE: Restless legs syndrome (RLS) is a common neurological movement disorder occurring in approximately 10% of the general population. The prevalence of moderately severe RLS is 2.7% overall (3.7% for women and 1.7% for men). Epilepsy is also a common neurological disorder with significant associated morbidity and impact on quality of life. We evaluated the severity and frequency of primary RLS in patients with localization-related temporal lobe epilepsy (TLE) and investigated the role of prodromal RLS symptoms as a warning sign and lateralizing indicator. METHODS: All epilepsy patients seen in the outpatient clinic were screened for movement disorders from 2005 to 2015. Ninety-eight consecutive patients with localization-related TLE (50 right TLE and 48 left TLE) who met inclusion criteria were seen in the outpatient clinic. The control group consisted of 50 individuals with no history or immediate family history of epilepsy. Each patient was evaluated with the International Restless Legs Study Group (IRLSSG) questionnaire, NIH RLS diagnostic criteria, ferritin level, and comprehensive sleep screening including polysomnography. Furthermore, patients with obstructive sleep apnea or a definite cause of secondary restless legs syndrome such as low serum ferritin or serum iron levels were also excluded from the study. RESULTS: There was a significant association between the type of epilepsy and whether or not patients had RLS χ2 (1)=10.17, p<.01, using the χ2 Goodness of Fit Test. Based on the odds ratio, the odds of patients having RLS were 4.60 times higher if they had right temporal epilepsy than if they had left temporal epilepsy, serving as a potential lateralizing indicator. A prodromal sensation of worsening RLS occurred in some patients providing the opportunity to intervene at an earlier stage in this subgroup. SIGNIFICANCE: We identified frequent moderate to severe RLS in patients with epilepsy. The frequency of RLS was much more common than would typically be seen in patients of similar age. The restlessness was typically described as moderately severe. The RLS symptoms were more common and somewhat more severe in the right TLE group than the left TLE group.

Diagnosis and management of childhood epilepsy.

Epilepsy is a relatively common neurologic disorder in children that has important implications for development, parents, and society. Making the correct diagnosis starts with an accurate and complete history that consequently leads to a directed diagnostic workup. This article outlines a diagnostic and management approach to pediatric seizures and epilepsy syndromes. Making the correct diagnosis of epilepsy or nonepileptic imitators allows the practitioner to prescribe appropriate therapy. Initial management for typical epileptic syndromes and seizures and potential adverse effects are discussed. Alternative treatment options for pharmacologically resistant patients such as ketogenic diet, vagal nerve stimulation, and surgery are also discussed. While most children favorably respond to antiepileptic medications, early identification of medication failure is important to ensure optimal neurodevelopment.

Co-occurring insomnia and obstructive sleep apnea.

STUDY OBJECTIVES: Prior research investigating co-occurring insomnia/obstructive sleep apnea (CIO) has mainly focused on comparing comorbid patients, obstructive sleep apnea (OSA), and insomnia (INS) to those with OSA alone. This approach is informative but omits the potentially interesting comparison of comorbid patients to those with INS alone. Our study used an incomplete factorial design, crossing OSA (present or absent) with INS (present or absent) to more clearly focus on the question, is comorbid INS an epiphenomenon of OSA or an independent disorder? METHODS: Our study was an archival analysis from the database of a sleep center comparing consecutively diagnosed patients characterized as OSA or INS. A third group, CIO, was derived from the OSA group. Our study was conducted at an American Academy of Sleep Medicine-accredited sleep disorders center. We studied 299 patients, including 94 OSA, 97 INS, and 108 CIO. Patients ranged from ages 15 to 86years. RESULTS: Groups were compared on polysomnography (PSG), sleep pattern, sleep stages, sleep pathology, self-reported sleep concerns, and self-reported daytime functioning. From a consecutive group of OSA patients, we estimate the prevalence of CIO at 67.4%. Based mainly on multivariate analysis of covariance (MANCOVA) controlling for demographic differences between groups, we found few if any significant differences between CIO and INS alone or between CIO and OSA alone. CONCLUSIONS: The clinical presentation of CIO is indistinguishable from INS alone, both with respect to PSG findings and to self-reported sleep onset and sleep maintenance disturbance. We observed a weak relation between OSA severity and co-occurring INS. These data are consistent with the view that INS with co-occurring OSA is an independent, self-sustaining disorder. We hypothesized that in some unknown proportion of cases, OSA initially instigated the INS, but the INS was then perpetuated and reshaped by sleep concerns and self-defeating compensatory behaviors.

Personality disorder features and insomnia status amongst hypnotic-dependent adults.

OBJECTIVE: To determine the prevalence of personality disorders and their relation to insomnia parameters among persons with chronic insomnia with hypnotic dependence. METHODS: Eighty-four adults with chronic insomnia with hypnotic dependence completed the SCID-II personality questionnaire, two-weeks of sleep diaries, polysomnography, and measures of insomnia severity, impact, fatigue severity, depression, anxiety, and quality of life. Frequencies, between-subjects t-tests and hierarchical regression models were conducted. RESULTS: Cluster C personality disorders were most prevalent (50%). Obsessive-Compulsive personality disorder (OCPD) was most common (n=39). These individuals compared to participants with no personality disorders did not differ in objective and subjective sleep parameters. Yet, they had poorer insomnia-related daytime functioning. OCPD and Avoidant personality disorders features were associated with poorer daytime functioning. OCPD features were related to greater fatigue severity, and overestimation of time awake was trending. Schizotypal and Schizoid features were positively associated with insomnia severity. Dependent personality disorder features were related to underestimating time awake. CONCLUSIONS: Cluster C personality disorders were highly prevalent in patients with chronic insomnia with hypnotic dependence. Features of Cluster C and A personality disorders were variously associated with poorer insomnia-related daytime functioning, fatigue, and estimation of nightly wake-time. Future interventions may need to address these personality features.

Seizure prediction: methods.

Epilepsy, one of the most common neurological diseases, affects over 50 million people worldwide. Epilepsy can have a broad spectrum of debilitating medical and social consequences. Although antiepileptic drugs have helped treat millions of patients, roughly a third of all patients have seizures that are refractory to pharmacological intervention. The evolution of our understanding of this dynamic disease leads to new treatment possibilities. There is great interest in the development of devices that incorporate algorithms capable of detecting early onset of seizures or even predicting them hours before they occur. The lead time provided by these new technologies will allow for new types of interventional treatment. In the near future, seizures may be detected and aborted before physical manifestations begin. In this chapter we discuss the algorithms that make these devices possible and how they have been implemented to date. We also compare and contrast these measures, and review their individual strengths and weaknesses. Finally, we illustrate how these techniques can be combined in a closed-loop seizure prevention system. This article is part of a Supplemental Special Issue entitled The Future of Automated Seizure Detection and Prediction.

Sleep education for paradoxical insomnia.

This case study series investigated a new treatment for paradoxical insomnia patients as there is no standard treatment for this patient group at this time. Four paradoxical insomnia patients had a polysomnography (PSG) sleep study, an unsuccessful brief course of behavioral treatment for insomnia, and then a novel sleep education treatment comprising review of their PSG with video and exploration of the discrepancy between their reported and observed sleep experience. Two patients responded well to sleep education, mainly with improved self-reported sleep onset latency, total sleep time, and Insomnia Severity Index scores; and the other two, who exhibited sleep architecture anomalies, were unresponsive. These findings suggest that sleep education holds promise for some paradoxical insomnia patients. Suggestions for future studies are given.

Low-molecular-weight heparin use in a case of noncardiogenic multifocal perinatal thromboembolic stroke.

A full-term neonate suffered multifocal cerebral infarctions due to multiple large vessel thrombi. Thrombophilia and cardiovascular assessments were negative, but due to the severity of the lesions and the concern for expansion of the thrombi or future embolic events, treatment with low-molecular-weight heparin (LMWH) was initiated. No complications from treatment were experienced. We present this severe case in order to highlight difficult management decisions for newborns with multifocal perinatal thromboembolic stroke and to stress the need for further practice guidelines and research in this area.

Antidepressant medications, neuroleptics, and prominent eye movements during NREM sleep.

Eye movements during stage 2, 3, and 4 sleep have been associated with the use of several selective serotonin reuptake inhibitor (SSRI) medications. This activity has been postulated to be a serotonin effect. The authors identified all cases of nonrapid eye movement (NREM) eye movements observed over a 36-month period in an accredited hospital-based sleep center and then correlated the findings with the patient's medications. The polysomnogram (PSG) studies of 2,959 consecutive adults were evaluated prospectively to identify all patients with atypical eye movements which occurred during NREM sleep. Standard recording, staging and arousal scoring methods were used. The use of antidepressants and neuroleptic medications was recorded for each patient. Eye movements in NREM sleep were detected in 94 PSGs. Of these, 73 patients (78%) were taking a SSRI at the time of the study, and 6 (6%) had taken a SSRI in the past. Thirty-six percent of patients (73 of 201) taking a SSRI had abnormal NREM eye movements on PSG. Other classes of antidepressants, neuroleptics, and benzodiazepines showed a much lower incidence of NREM eye movements. Mirtazapine was rarely related to NREM eye movements. Clonazepam and zolpidem were not associated with atypical eye movements unless used in combination with SSRI medications. Selective serotonin reuptake inhibitors was associated with atypical NREM eye movements, even when the medication had been discontinued months to years before the PSG. Atypical NREM eye movements appear to be related primarily to serotonin and less prominently to dopaminergic medication effects.

Quantitative magnetic resonance angiography of the cerebrovasculature in physiologic and pathologic states.

BACKGROUND: In the past, clinical decisions regarding treatment of neurovascular disorders leading to ischemia have been guided by the percentage of stenosis of the vessel in question. However, such an approach assumes a predictable and stable relationship between the percentage of stenosis and the degree of flow reduction it causes. Historically, this type of relationship has been difficult to document. Thus, a method for noninvasively measuring the absolute flow of specific cerebral arteries is of potential practical value. METHODS: We set to quantify the mean blood flow (Qm, in mL/min) in the cerebral arteries using quantitative magnetic resonance angiography (QMRA), and to compare the findings in normal vessels with those found in vessels considered pathologically narrowed. Specific vascular segments were identified, studied, and the results entered into a database. Statistical analyses of the measurements were carried out using StatPlus for Microsoft Excel. It involved comparing of the Qm found in specific vessels, as well as those found in normal and abnormal vessels, using analysis of variance (ANOVA). The abnormal vessels were selected from specifically identified magnetic resonance angiography (MRA) studies. RESULTS: A total of 57 patients, 26 men and 31 women, with ages ranging from 19 to 86 years (mean = 64.5), underwent MRA with subsequent QMRA of 157 arteries. The latter included 72 internal carotid (ICA), 45 vertebral (VA), 18 common carotid (CCA), 13 middle cerebral (MCA), and nine basilar (BA) arteries. The mean Qm obtained were CCA = 313.9 (+/-115.4), ICA = 231.1 (+/-83.7), VA = 90.5 (+/-45.8), MCA = 92.5 (+/-62.3) and BA = 120.1 (+/-64.5). ANOVA showed significant differences between individual vessels (P < .00001). The values obtained were consistent with those predicted mathematically, as derivatives of their proportional contributions to overall cerebral arterial flow (Qbrain) as a product of the normal cardiac output (CO) [ie, Qbrain = CO*.2]. Further ANOVA of the normal and abnormal vessels showed statistically significant differences between the two groups (186.5 +/- 108.6 vs. 117.9 +/- 76.1, respectively; P= .000514). CONCLUSIONS: The use of QMRA provides the mean for direct measurement of absolute blood flow within the cerebral arteries in physiologic and pathologic states. This technique may be of future importance in characterizing absolute flow compromise in the cerebral arteries under a variety of clinically relevant circumstances.

Focal epileptiform spikes in conjuction with K-complexes.

Dyshormia or epileptiform spikes occurring within K-complexes have been described in patients with generalized epilepsy, with one study reporting that generalized spikes occurred frequently in association with K-complexes. We report the rate of focal epileptiform spikes occurring within K-complexes in localization-related epilepsy. Presurgical or diagnostic long-term video-EEG results of 40 consecutive patients with epilepsy (13 patients with right temporal lobe epilepsy, 20 patients with left temporal lobe epilepsy, and 7 patients with frontal lobe epilepsy) were reviewed. Sleep samples were reviewed and the numbers of K-complexes, spikes, and spikes within K-complexes were recorded. The comparison group consisted of 40 consecutive patients with nonepileptic events who were monitored with long-term video EEG. Focal epileptiform spikes occurring within K-complexes occurred in 2 of 13 (15%) patients with right temporal lobe patients, 6 of 20 (30%) patients with left temporal lobe, and 3 of 7 (42%) patients with extratemporal lobe epilepsy. In most patients, spikes occurring during K-complexes were rare. We identified spikes occurring during K-complexes in patients with localization-related epilepsy. The sharply contoured components of K-complexes or associated sleep spindles may obscure focal spikes within K-complexes. Nevertheless, K-complexes may be associated with focal epileptiform discharges.