Nonpharmacologic Interventions and Seizure Frequency in Patients With Psychogenic Nonepileptic Seizures: An Integrative Review.

BACKGROUND: Psychogenic nonepileptic seizures (PNES) pose a heavy burden on patients' lives and the health care system. The symptoms of PNES are often debilitating and cause high rates of disability and poor quality of life. Many treatment options are available, but there is no clear consensus on best practices. AIM: To critique and synthesize the current literature on nonpharmacologic interventions and effects on seizure frequency in patients with PNES. METHODS: An integrative review guided by the Whittemore and Knafl approach. RESULTS: The review included 24 studies published from 2010 to 2020. Interventions for PNES included individualized psychotherapies, group therapies, multimodal psychotherapies, self-help therapies, and complementary and alternative medicine therapies. Individual psychotherapies such as cognitive behavioral therapy and psychoeducation were the most used treatment modalities. The most effective treatments for seizure frequency reduction were those that included multiple psychotherapy sessions with a health care provider and covered multiple domains (e.g., understanding of diagnosis, identifying triggers, and developing effective coping strategies). CONCLUSIONS: Seizure frequency can be reduced in patients with PNES with multiple nonpharmacologic interventions. However, seizure frequency is not considered a comprehensive outcome measure and provides little insight into other important life domains. Further research is needed on nonpharmacologic interventions for PNES and effects on other areas of life such as sleep, employment status, global functioning, and self-efficacy.

Relationship of sleep to pulmonary function in mucopolysaccharidosis II.

OBJECTIVE: To study the sleep characteristics, pulmonary function, and their relationships in an enzyme naive population of patients with mucopolysaccharidoses (MPS) II (Hunter syndrome). STUDY DESIGN: The analyzed subjects (30 patients with MPS II with a median age of 9 years) had been enrolled in an MPS II natural history study and a phase I/II enzyme replacement clinical study in which they underwent standard polysomnography including spirometry and plethysmography, if cooperative. Descriptive statistics and nonparametric correlation were performed for demographic, sleep, and pulmonary function variables. RESULTS: Median apnea-hypopnea index was 6.4, with obstructive sleep apnea observed in 27/30 subjects. Sleep architecture was characterized by diminished rapid-eye movement sleep duration (median 13%), and decline in sleep efficiency and slow-wave sleep duration in older individuals. Oxygen desaturation below 90% occurred in 26/30 subjects, and hypoventilation above 50 Torr occurred in 11/23 subjects with accurate end-tidal carbon dioxide recordings. Of 15 subjects with reliable spirometry, median forced expiratory volume in 1 second was below 80% predicted in 12/15 subjects. Forced expiratory volume in 1 second in percent-predicted was inversely related to apnea-hypopnea index and increase from baseline end-tidal carbon dioxide (P=.023, rs=-0.58), (P<.001, rs=-0.82). CONCLUSION: Sleep in MPS II is characterized by obstructive sleep apnea, altered sleep architecture, and impaired gas exchange. Sleep disruption is related to daytime pulmonary function, thus both systems should be evaluated when sleep abnormalities are suspected.

Sleep-disordered breathing in Beckwith-Wiedemann syndrome: three patients.

Beckwith-Wiedemann syndrome is associated with craniofacial abnormalities that may predispose patients to sleep-related breathing disorders. There is limited literature on the polysomnography findings for children with this syndrome. Three patients with Beckwith-Wiedemann syndrome underwent polysomnography in our sleep lab and were found to have a variety of sleep-disordered breathing that ranged from obstructive apnea to isolated REM sleep-related hypoxemia-hypoventilation without obstructive apnea. Suspicion for sleep-disordered breathing should be high in children with Beckwith-Wiedemann syndrome.

Gastrointestinal physiology and digestive disorders in sleep.

PURPOSE OF REVIEW: The dynamic interplay of the digestive system and sleep is an excellent example of brain-body interaction. New advances in measuring techniques provide an opportunity to evaluate physiology that is dependent upon the sleep/wake state or circadian rhythm and potentially differentiate between normal and pathological conditions. RECENT FINDINGS: Sleep-related changes in gastrointestinal physiology create vulnerabilities to digestive issues such as reflux, whereas disorders such as duodenal ulcers raise the importance of circadian variations in digestive system function. Advances in the area of normal sleep physiology have furthered our understanding of the underlying cause of irritable bowel syndrome, and the mechanisms by which sleep disruption may aggravate inflammatory bowel disease. Additionally, important early work has shown that the treatment of digestive disorders such as reflux can improve sleep quality just as the improvement in sleep may aid in the treatment of digestive disorders. SUMMARY: For the clinician, these forward steps in our knowledge mark the start of an era in which understanding the effects of the sleep/wake state and circadian rhythms on gastrointestinal physiology promise to yield novel diagnostic and therapeutic opportunities.

Non-REM Parasomnia: The Promise of Precision Medicine.

Our understanding of non-REM parasomnias is just beginning to unfold the potential biomarkers and underlying pathophysiologic processes that lead to these events. Biomarkers need further investigation and will help us to understand better ways to develop risk models and possible mechanisms. Similarly, as we develop more accurate pathophysiologic-based diagnostic testing for non-REM parasomnias, we will begin the evolution toward a physiologic-based classification scheme that aids the application of precision medicine. This article explores currently known characteristics and exploratory features that may aid in this transition to better understanding our individual patients with non-REM parasomnias and tailoring their treatments.

Sleep staging and respiratory events in refractory epilepsy patients: Is there a first night effect?

PURPOSE: We performed this analysis of possible first night effects (FNEs) on sleep and respiratory parameters in order to evaluate the need for two serial night polysomnograms (PSGs) to diagnose obstructive sleep apnea (OSA) in epilepsy patients. METHODS: As part of a pilot multicenter clinical trial investigating the effects of treating sleep apnea in epilepsy, two nights of PSG recording were performed for 40 patients with refractory epilepsy and OSA symptoms. Sleep architecture was examined in detail, along with respiratory parameters including apnea/hypopnea index (AHI) and minimum oxygen saturation. Analysis included two-tailed t-tests, Wilcox sign rank analysis, and Bland Altman measures of agreement. RESULTS: Total sleep time differed between the two nights (night 1,363.8 min + 59.4 vs. 386.3 min + 68.6, p = 0.05). Rapid eye movement (REM) sleep and percentage of REM sleep were increased during night two (night 1: 12.3% + 5.9 vs. night 2: 15.5% + 6.2, p = 0.007), and the total minutes of slow-wave sleep (SWS) were increased (night 1: 35.6 + 60.7 vs. night 2: 46.4 + 68.1, p = 0.01). No other sleep or respiratory variables differed between the two nights. Given an AHI inclusion criterion of five apneas per hour, the first PSG identified all but one patient with OSA. DISCUSSION: Respiratory parameters showed little variability between the first and second nights. Sleep architecture was mildly different between the first and second PSG night. Performing two consecutive baseline PSGs to diagnose OSA may not be routinely necessary in this population.

Incorporating sleep medicine content into medical school through neuroscience core curricula.

OBJECTIVE: To present (1) justification for earmarking sleep medicine education as an essential component of all medical school curricula and (2) various avenues to incorporate sleep medicine exposure into medical school curricula through (primarily) neuroscience and neurology courses. METHODS: Per consensus of a team of leading neurology and sleep medicine educators, an evidence-based rationale for including sleep medicine across a 4-year medical school curriculum is presented along with suggested content, available/vetted resources, and formats for delivering sleep medicine education at various points and through various formats. RESULTS: Growing evidence has linked sleep disorders (e.g., sleep-disordered breathing, chronic insufficient sleep) as risk factors for several neurologic disorders. Medical educators in neurology/neuroscience are now strongly advocating for sleep medicine education in the context of neurology/neuroscience pre and post graduate medical education. Sleep medicine education is also a critical component of a proactive strategy to address physician wellness and burnout. The suggested curriculum proposes a sleep educational exposure time of 2-4 hours per year in the form of lectures, flipped-classroom sessions, clinical opportunities, and online educational tools that would result in a 200%-400% increase in the amount of sleep medicine exposure that US medical schools currently provide. The guidelines are accompanied by the recommendation for use of technological education, to facilitate more seamless curricular incorporation. CONCLUSION: Even in this era with limited flexibility to add content to an already packed medical school curriculum, incorporating sleep medicine exposure into the current medical school curriculum is both justified and feasible.

Sleep Disorders in Childhood Neurogenetic Disorders.

enetic advances in the past three decades have transformed our understanding and treatment of many human diseases including neurogenetic disorders. Most neurogenetic disorders can be classified as "rare disease," but collectively neurogenetic disorders are not rare and are commonly encountered in general pediatric practice. The authors decided to select eight relatively well-known neurogenetic disorders including Down syndrome, Angelman syndrome, Prader-Willi syndrome, Smith-Magenis syndrome, congenital central hypoventilation syndrome, achondroplasia, mucopolysaccharidoses, and Duchenne muscular dystrophy. Each disorder is presented in the following format: overview, clinical characteristics, developmental aspects, associated sleep disorders, management and research/future directions.

Comorbid Sleep Disturbances in Neurologic Disorders.

PURPOSE OF REVIEW: This article provides a review of disturbances of sleep comorbid with common neurologic disorders. RECENT FINDINGS: A wide variety of neurologic disorders are frequently complicated by comorbid sleep disturbances. In many cases, a bidirectional relationship appears to occur between sleep function and the neurologic disease, such that treatment of comorbid sleep disturbances may improve the symptoms of the neurologic disease. SUMMARY: Neurologic disorders are often associated with abnormalities of sleep. Sleep influences the severity of both epilepsy and headache, and treatment of comorbid sleep disorders may improve seizure and headache frequency. Alzheimer disease is characterized by circadian phase delay and poor nighttime sleep and is strongly associated with obstructive sleep apnea. Parkinson disease is associated with several sleep disorders, including insomnia, restless legs syndrome, rapid eye movement (REM) sleep behavior disorder, daytime hypersomnia, and sleep-disordered breathing. Hypoventilation in amyotrophic lateral sclerosis and other neuromuscular disorders often presents initially with sleep problems, and treatment with noninvasive ventilation improves survival and quality of life.

Sleep Apnea and Hypoventilation in Patients with Down Syndrome: Analysis of 144 Polysomnogram Studies.

Patients with Down syndrome (DS) are at risk for both obstructive sleep apnea (OSA) and central sleep apnea (CSA); however, it is unclear how these components evolve as patients age and whether patients are also at risk for hypoventilation. A retrospective review of 144 diagnostic polysomnograms (PSG) in a tertiary care facility over 10 years was conducted. Descriptive data and exploratory correlation analyses were performed. Sleep disordered breathing was common (seen in 78% of patients) with an average apnea-hypopnea index (AHI) = 10. The relative amount of obstructive apnea was positively correlated with age and body mass index (BMI). The relative amount of central sleep apnea was associated with younger age in the very youngest group (0-3 years). Hypoventilation was common occurring in more than 22% of patients and there was a positive correlation between the maximum CO2 and BMI. Sleep disordered breathing, including hypoventilation, was common in patients with DS. The obstructive component increased significantly with age and BMI, while the central component occurred most in the very young age group. Due to the high risk of hypoventilation, which has not been previously highlighted, it may be helpful to consider therapies to target both apnea and hypoventilation in this population.

Sleep and Epilepsy.

Sleep plays an intricate role in the disease process of epilepsy. Despite the complexity of this relationship, the prognosis is a favorable one for patients presenting with sleep disorders and epilepsy. Clinicians need to be vigilant about asking about and addressing sleep complaints in patients with epilepsy. Ultimately, improving sleep and optimizing seizure control can have significant positive effects on the quality of life of these patients.

Feedback-Controlled Transcranial Alternating Current Stimulation Reveals a Functional Role of Sleep Spindles in Motor Memory Consolidation.

Transient episodes of brain oscillations are a common feature of both the waking and the sleeping brain. Sleep spindles represent a prominent example of a poorly understood transient brain oscillation that is impaired in disorders such as Alzheimer's disease and schizophrenia. However, the causal role of these bouts of thalamo-cortical oscillations remains unknown. Demonstrating a functional role of sleep spindles in cognitive processes has, so far, been hindered by the lack of a tool to target transient brain oscillations in real time. Here, we show, for the first time, selective enhancement of sleep spindles with non-invasive brain stimulation in humans. We developed a system that detects sleep spindles in real time and applies oscillatory stimulation. Our stimulation selectively enhanced spindle activity as determined by increased sigma activity after transcranial alternating current stimulation (tACS) application. This targeted modulation caused significant enhancement of motor memory consolidation that correlated with the stimulation-induced change in fast spindle activity. Strikingly, we found a similar correlation between motor memory and spindle characteristics during the sham night for the same spindle frequencies and electrode locations. Therefore, our results directly demonstrate a functional relationship between oscillatory spindle activity and cognition.

Progression of Polysomnographic Abnormalities in Mucolipidosis II (I-Cell Disease).

ABSTRACT: Mucolipidosis II (Inclusion cell or I-cell disease) is an autosomal recessive lysosomal storage disorder clinically comparable to the mucopolysaccharidoses (MPS), characterized by progressive respiratory and neurologic deterioration. Sleep problems, especially obstructive sleep apnea (OSA) and disrupted sleep architecture, are observed in other lysosomal storage diseases but have not been described in mucolipidosis II. We report the progression of polysomnographic abnormalities in a child with mucolipidosis II, demonstrated by worsening sleep-related hypoventilation, OSA, and sleep state fragmentation despite advancing PAP therapy. Background slowing and reduction in spindle activity on limited EEG may reflect progressive CNS disease affecting thalamic neurons.

Obstructive sleep apnea in epilepsy.

Obstructive sleep apnea can affect an individual with epilepsy profoundly. These relatively common disorders can coexist and potentially exacerbate each other. The identification and appropriate treatment of OSA may have far-reaching consequences in improving a patient's quality of life and recurrence of seizures. Clinicians must be aware of the relationship of these disorders and keenly question epilepsy patients, regardless of their body habitus, regarding potential symptoms of sleep apnea. Although the underlying pathogenic mechanisms are unclear, we can model the information gained from the observations to further the understanding of the relationship between sleep and epilepsy.

Treatment of sleep disorders in epilepsy.

The interrelationship of sleep and epilepsy is described. Seizures and their treatment, including antiepileptic medications, may affect sleep. In turn, sleep disorders may influence seizure control and contribute to daytime sleepiness in epilepsy patients. Parasomnias and other sleep-related disorders may mimic epileptic seizures, although the history and video-EEG polysomnography are often useful in distinguishing these events. The treatment of epilepsy patients with sleep disorders or sleep complaints, such as sleepiness or insomnia, is discussed. Diagnosis and treatment of coexisting sleep disorders may improve not only daytime sleepiness, but also seizure control. Sedating AEDs may benefit epilepsy patients with insomnia, and stimulating AEDs may benefit epilepsy patients with daytime sleepiness.

Non-convulsive status epilepticus induced by tiagabine in a patient with pseudoseizure.

Tiagabine, a novel GABA reuptake inhibitor, has been reported to induce non-convulsive status epilepticus (NCSE) in patients with epilepsy. We report a 27 year old female with history of pseudoseizure documented by video-EEG monitoring who presented confusion while on 56 mg per day of tiagabine. Electroencephalography showed generalized sharp and slow wave discharges, consistent with NCSE. The NCSE was terminated by lorazepam and did not recur after tiagabine was discontinued. This case report suggests that tiagabine may induce NCSE in patients without epilepsy.

Driver risk factors for sleep-related crashes.

A population-based case-control study was carried out to examine driver risk factors for sleep-related motor vehicle crashes. Cases included 312 drivers involved in recent North Carolina crashes and identified on police reports as asleep at the time of the crash and 155 drivers identified as fatigued. Controls were 529 drivers also involved in recent crashes but not identified as asleep or fatigued, and 407 drivers not involved in recent crashes. All drivers were contacted for brief telephone interviews. Results showed that drivers in sleep-related crashes were more likely to work multiple jobs, night shifts, or other unusual work schedules. They averaged fewer hours sleep per night, reported poorer quality sleep, were less likely to feel they got enough sleep, were sleepier during the day, drove more often late at night, and had more prior instances of drowsy driving. Compared to drivers in non-sleep-related crashes, they had been driving for longer times, been awake more hours, slept fewer hours the night before, and were more likely to have used soporific medications. Knowledge of specific risk factors for sleep-related crashes is an important first step in reducing the thousands of deaths and injuries each year in the US attributed to drowsy driving.

Insertion of vagal nerve stimulator using local and regional anesthesia.

BACKGROUND: Vagal nerve stimulation (VNS) is a valuable therapy for patients with intractable epilepsy. Placement of a vagal nerve stimulator typically requires general anesthesia, which frequently interrupts anticonvulsant therapy. Insertion of the stimulator using regional/local anesthesia may offer the advantages of continuity of anticonvulsant therapy and implantation in the outpatient setting. METHODS: We retrospectively compared the first 10 consecutive patients undergoing VNS implantation under general anesthesia with the first 12 consecutive patients undergoing VNS implantation under regional/local anesthesia. Patients for the regional/local anesthesia were selected on the basis of their ability to cooperate and follow commands. Regional anesthesia for implantation of the VNS leads was achieved by performing superficial and deep cervical plexus blocks. A local anesthetic field block of a small area of the posterior chest provided anesthesia for insertion of the generator. RESULTS: All of the patients undergoing regional/local anesthesia completed the procedure without difficulty and on an outpatient basis. None complained of discomfort, sedation, nausea, or vomiting and none had seizures in the perioperative period. These results contrasted with the group that underwent general anesthesia (n = 10), who had an 80% incidence of nausea and vomiting and a 30% incidence of postoperative seizures. CONCLUSION: VNS implantation under regional/local anesthesia is proficiently performed as an outpatient procedure with minimal postoperative side effects.

Approach to insomnia in patients with dementia.

Insomnia occurs in one-fourth to one-third of patients with dementia, and can lead to patient and caretaker distress and early institutionalization. An array of effects from the disease, medication, behaviors, and mood issues may play a role in influencing sleep. This perplexing issue can be handled effectively with appropriate evaluation and understanding of basic sleep-wake physiology. For most patients, appropriate timing of cues, modifying behavior, and optimizing medications can improve the patient's and caregiver's quality of life. In this article, we review signs that may help the clinician recognize insomnia early and approach the issue in a logical manner.

Low frequency filtering of nasal pressure channel causes loss of flow limitation.

STUDY OBJECTIVES: The objective of this clinical vignette is to explore whether changes in low filter settings for respiratory waveforms have a clinically significant effect on patient management of obstructive sleep apnea (OSA). DESIGN: This is a case report. METHODS: We collected data from a continuous positive airway pressure (CPAP) titration polysomnogram (PSG) performed in our university based sleep laboratory. We reviewed the flow signal using low frequency filter settings of 0.0, 0.1, 0.3, and 0.5 Hz. RESULTS: We noted that a change in the low frequency filter for respiratory flow caused a change in the appearance of an otherwise flattened waveform indicating flow limitation to no longer appear flat. CONCLUSION: We noted that indiscriminate use of the low frequency filter for nasal pressure and flow estimate channels may lead to greater difficulty recognizing respiratory flow limitation.