Sleep and epilepsy: A clinical and pathophysiological overview.

The interaction between sleep and epilepsy is complex. A better understanding of the mechanisms linking sleep and epilepsy appears increasingly important as it may improve diagnosis and therapeutic strategies in patients with epilepsy. In this narrative review, we aim to (i) provide an overview of the physiological and pathophysiological processes linking sleep and epilepsy; (ii) present common sleep disorders in patients with epilepsy; (iii) discuss how sleep and sleep disorders should be considered in new therapeutic approaches to epilepsy such as neurostimulation; and (iv) present the overall nocturnal manifestations and differential diagnosis between epileptic seizures and parasomnia.

Parasomnias during trans-meridian and long-distance travel: Critical literature review and clinical practice recommendations.

Parasomnias are undesirable events that occur during sleep. They can be classified into rapid eye movement parasomnias and non-rapid eye movement parasomnias. Those who experience parasomnias may be anxious about travel for many reasons, including the occurrence of unwanted events during the trip, increased exposure to environmental trigger factors, and the propensity for harm to occur due to unfamiliar surroundings while travelling. There is a paucity of literature examining this area. This review summarizes the relevant literature and the clinical experience of the authors to compile clinical practice recommendations. The clinical features of parasomnias and how they relate to trans-meridian and long-distance travel are described. Triggers for non-rapid eye movement parasomnias, particularly the use of sedative hypnotic drugs, alcohol, drug withdrawal, sleep deprivation, emotional stress and environmental stimulations, are described. Management of parasomnias whilst travelling is reviewed, with a particular focus on trigger minimalization. The role for clonazepam and melatonin is outlined. At the pre-travel health consultation, the physician is strongly advised to screen the traveller for co-morbid sleep conditions, which exacerbate parasomnias. Areas for further research are explored, including the extent to which these sleep disorders impact on the travel experience.

TSC1 as a Novel Gene for Sleep-Related Hypermotor Epilepsy: A Child with a Mild Phenotype of Tuberous Sclerosis.

Sleep-related hypermotor epilepsy (SHE) is a rare syndrome that presents with hyperkinetic asymmetric tonic/dystonic seizures with vegetative signs, vocalization, and emotional facial expression, mainly during light non-rapid eye movement sleep stages. The role of various genes (CHRNA4, CHRNB2, CHRNA2, KCNT1, DEPDC5, NPRL2, NPRL3, and PRIMA1) has previously been reported, though genetic etiology is assessed in less than 10% of cases. We report the case of a 5-year-old female carrying the TSC1 variant c.843del p.(Ser282Glnfs*36) who presented with a mild phenotype of tuberous sclerosis, including carbamazepine-responsive SHE, normal neurocognitive functioning, hypomelanotic macules, no abnormalities outside the central nervous system, and tubers at neuroimaging. The presented case extends the list of SHE-related genes to include TSC1, thus suggesting a central pathogenic role of mammalian target of rapamycin (mTOR) cascade dysfunction in SHE and introducing a possible use of mTOR inhibitors in this epileptic syndrome.

Kambakutaisoto Treatment for Children With Night Crying and Arousal Parasomnias Developed During Prolonged Hospitalization for Hematological and Oncological Diseases.

OBJECTIVE: The lack of an established treatment standard prompted an examination of whether kambakutaisoto, an herbal formula, is effective for non-rapid eye movement (NREM)-related parasomnias and night crying (provisionally defined as an infantile form of arousal parasomnia). METHODS: This study included 137 children aged median 4.1 years (range, 0.02-18.5) who were admitted for hematological and oncological diseases. RESULTS: Of 137, 3 children developed recurrent episodes of NREM-related parasomnias, and 3 developed night crying. The proportion of children with night-crying/parasomnia receiving invasive procedures was significantly higher than those without (100% vs. 47%, P = .013). All 6 children with night crying/parasomnia received kambakutaisoto at a dose of 0.13-0.22 g/kg per os and responded from the start of administration with a significant reduction in the number of episodes. No adverse effects were observed. CONCLUSION: Kambakutaisoto may be a safe and promising therapy for night crying and NREM-related parasomnias in children.

Nightmare experience and personality disorder functioning styles in healthy volunteers and nightmare disorder patients.

Nightmares are prevalent in psychiatric disorders, and personality disorder features might be associated with nightmare experience, especially in nightmare disorder patients. The authors invited 219 healthy volunteers and 118 nightmare disorder patients to undergo tests of the Nightmare Experience Questionnaire (NEQ), the Parker Personality Measure (PERM), and the Plutchik-van Praag Depression Inventory. Compared to healthy volunteers, nightmare disorder patients scored significantly higher on annual nightmare frequency and NEQ Physical Effect, Negative Emotion, Meaning Interpretation, and Horrible Stimulation, and higher on PERM Paranoid, Schizotypal, Borderline, Histrionic, Narcissistic, Avoidant, and Dependent styles. Borderline, Schizotypal, and Passive-Aggressive styles in healthy volunteers and Dependent, Avoidant, Histrionic, and Paranoid in patients were significant predictors of some NEQ scales. Higher annual nightmare frequency, higher scale scores of nightmare experience and personality disorder styles, and more associations between the two were found in nightmare disorder patients, implying the need for personality-adjustment therapy for nightmare disorder.

Parasomnias Occurring in Non-Rapid Eye Movement Sleep.

PURPOSE OF REVIEW: This article discusses the clinical manifestations, diagnosis and differential diagnosis, pathophysiology, and management of parasomnias occurring in non-rapid eye movement (REM) sleep. RECENT FINDINGS: Disorders of arousal are characterized by dissociated sleep, with wake and sleep phenomena intermingling, and local sleep, in which different areas of the brain exist simultaneously in different states of wakefulness or sleep. The frequency of arousals from slow-wave sleep with delta or mixed-frequency activity has a high sensitivity but relatively low specificity for the diagnosis of arousal parasomnias. SUMMARY: Disorders of arousal (sleepwalking, sleep terrors, and confusional arousals) are characterized by incomplete awakenings from slow-wave sleep, limited recall of imagery, and partial or complete amnesia. They occur most frequently in childhood. Management includes correction of precipitating factors, attention to safety, behavioral techniques, and medications. Sleep-related eating disorder is a variant of arousal disorders and may be associated with the use of short-acting hypnotics and restless legs syndrome. Complex nocturnal visual hallucinations can occur with visual loss, dementia with Lewy bodies, use of ß-adrenergic receptor antagonists, and anxiety. Exploding head syndrome occurs at wake-sleep transition or on waking during the night, is usually benign, and requires treatment only if significant sleep disruption occurs.

Mastering nocturnal jigsaws in Parkinson's disease: a dusk-to-dawn review of night-time symptoms.

Finding out about night-time symptoms from Parkinson's disease (PD) patients can be a challenge as many patients and their carers cannot recall many symptoms that occur during the night, resulting in an under-recognition or a large variability of responses from clinical interviews and scales. Moreover, technology-based assessments for most night-time symptoms are still not universally available for use in a patient's home environment. Therefore, most physicians rely on their clinical acumen to capture these night-time symptoms based on pieces of patients' history, bedpartner's reports, clinical features, associated symptoms or conditions. To capture more night-time symptoms, the authors identified common nocturnal symptoms based on how they manifest from dusk to dawn with selected features relevant to PD. While some symptoms occur in healthy individuals, in PD patients, they may impact differently. The authors intend this narrative review to provide a practical guide on how these common night-time symptoms manifest and highlight pertinent issues by focusing on prevalence, clinical symptomatology, and specific relationships to PD. It is also important to recognise that PD-specific sleep disturbances increase with advancing disease with additional contributions from ageing, comorbidities, and medication side effects. However, the relative contribution of each factor to individual symptom may be different in individual patient, necessitating clinical expertise for individual interpretation. While there are debatable issues in certain areas, they underlie the complexity of night-time symptoms. Understanding night-time symptoms in PD is like re-arranging jigsaw pieces of clinical information to create, but never complete, a picture for physicians to instigate appropriate management.

Trauma Associated Sleep Disorder: Clinical Developments 5 Years After Discovery.

PURPOSE OF REVIEW: We review recent and growing evidence that provides support for a novel parasomnia, trauma associated sleep disorder (TASD). Based on these findings, we further develop the clinical and polysomnographic (PSG) characteristics of TASD. We also address factors that precipitate TASD, develop a differential diagnosis, discuss therapy, and propose future directions for research. RECENT FINDINGS: Nightmares, classically a REM phenomenon, are prevalent and underreported, even in individuals with trauma exposure. When specifically queried, trauma-related nightmares (TRN) are frequently associated with disruptive nocturnal behaviors (DNB), consistent with TASD. Capture of DNB in the lab is rare but ambulatory monitoring reveals dynamic autonomic concomitants associated with disturbed dreaming. TRN may be reported in NREM as well as REM sleep, though associated respiratory events may confound this finding. Further, dream content is more distressing in REM. Therapy for this complex disorder likely requires addressing not only the specific TASD components of TRN and DNB but comorbid sleep disorders. TASD is a unique parasomnia developing after trauma. Trauma-exposed individuals should be specifically asked about their sleep and if they have nightmares with or without DNB. Patients who report TRN warrant in-lab PSG as part of their evaluation.

Cognitive Behavioural Therapy for Nightmares for Patients with Persecutory Delusions (Nites): An Assessor-Blind, Pilot Randomized Controlled Trial.

OBJECTIVE: Nightmares are relatively common in patients experiencing psychosis but rarely assessed or treated. Nightmares may maintain persecutory delusions by portraying fears in sensory-rich detail. We tested the potential benefits of imagery-focused cognitive behavioural therapy (CBT) for nightmares on nightmare severity and persecutory delusions. METHOD: This assessor-blind parallel-group pilot trial randomized 24 participants with nightmares and persecutory delusions to receive CBT for nightmares delivered over 4 weeks in addition to treatment as usual (TAU) or TAU alone. Assessments were at 0, 4 (end of treatment), and 8 weeks (follow-up). Feasibility outcomes assessed therapy uptake, techniques used, satisfaction, and attrition. The primary efficacy outcome assessed nightmare severity at week 4. Analyses were intention to treat, estimating treatment effect with 95% confidence intervals (CIs). RESULTS: All participants offered CBT completed therapy (mean [SD], 4.8 [0.6] sessions) with high satisfaction, and 20 (83%) participants completed all assessments. Compared with TAU, CBT led to large improvements in nightmares (adjusted mean difference = -7.0; 95% CI, -12.6 to -1.3; d = -1.1) and insomnia (6.3; 95% CI, 2.6 to 10.0; d = 1.4) at week 4. Gains were maintained at follow-up. Suicidal ideation was not exacerbated by CBT but remained stable to follow-up, compared with TAU, which reduced at follow-up (6.8; 95% CI, 0.3 to 3.3; d = 0.7). CBT led to reductions in paranoia (-20.8; 95% CI, -43.2 to 1.7; d = -0.6), although CIs were wide. Three serious adverse events were deemed unrelated to participation (CBT = 2, TAU = 1). CONCLUSIONS: CBT for nightmares is feasible and may be efficacious for treating nightmares and comorbid insomnia for patients with persecutory delusions. It shows promise on paranoia but potentially not on suicidal ideation.

Effects of Sleep-Related Disorders on the Prognosis of Amyotrophic Lateral Sclerosis.

BACKGROUND/OBJECTIVE: In this study, we demonstrated the effects of obstructive sleep apnea syndrome (OSAS) on the prognosis of amyotrophic lateral sclerosis (ALS). However, the effects of sleep-related disorders other than breathing problems are still waiting to be delineated. METHODS: In this longitudinal retrospective and prospective study, we investigated 73 patients with ALS compared to 20 healthy subjects, to determine sleep-related disorders and their impact on disease prognosis. RESULTS: In patients with ALS, the mean respiratory disturbance index (RDI) was 28.0/h, which was significantly higher than that in the controls (p < 0.001). OSAS was present in 67% of the patients, sleep-related hypoxemia was observed in 13.7% of the patients, and 5.4% had central sleep apnea syndrome. In patients with bulbar-onset disease, higher RDI was almost significantly associated with lower survival (p = 0.056). The mean index of periodic leg movements in sleep was significantly higher in patients with ALS (34.0 ± 19.9/h) than that in the controls (12.5 ± 15.5/h; p < 0.001). Periodic leg movements disorder (PLMD) was diagnosed in 23 patients with ALS (31.5%); fragmentary myoclonus was present in 13.7% of patients, and REM-sleep behavior disorder was diagnosed in 4 patients (5.4%). The presence of PLMD in addition to OSAS was significantly associated with worse prognosis and poorer survival (p = 0.040). CONCLUSIONS: These findings emphasize that sleep-related disorders other than OSAS deserve attention in ALS. ALS is a catastrophic and frustrating disease for both patients and physicians; thus, the diagnosis and treatment of comorbid sleep disorders could improve the survival of patients with ALS.

Associations between exploding head syndrome and measures of sleep quality and experiences, dissociation, and well-being.

Exploding head syndrome is a sensory parasomnia characterized by the perception of loud noises and/or a sense of explosion in the head that occurs when transitioning to or from sleep. Despite receiving little attention from both researchers and clinicians, studies suggest that approximately 10%-15% of individuals have episodes, with significant levels of fear occurring in a subset of cases. Using two independent samples, we examine sleep and well-being variables associated with exploding head syndrome. We focused on insomnia symptoms, life stress, anxiety and depression symptoms, and sleep experiences such as sleep paralysis as potential factors associated with exploding head syndrome. Study 1 consisted of 199 female undergraduate students. We found a lifetime prevalence of 37.19%, with 6.54% experiencing at least one episode a month. All variables were associated with exploding head syndrome in univariate analyses, but only insomnia symptoms and sleep paralysis frequency were significantly associated with exploding head syndrome in multiple logistic regression models. Study 2 was an international sample of 1683 participants (age range 18-82, 53.00% female). Lifetime prevalence was 29.59%, with monthly episodes occurring in 3.89% of participants. The same set of variables was investigated as in Study 1, with dissociative experiences during wakefulness and a larger range of sleep experiences also included. Study 2 replicated the results of Study 1. In addition, dissociative experiences during wakefulness and other sleep experiences such as nightmares were associated with exploding head syndrome in multiple logistic regression models. These studies provide valuable first insights into variables associated with exploding head syndrome.Clinical trial information: Study 1 constitutes a planned exploratory outcome of a pilot feasibility study conducted to provide information useful for designing a clinical trial: Name: STOP-pilot. URL: https://clinicaltrials.gov/ct2/show/NCT03062891?term=NCT03062891&rank=1, Registration: NCT03062891.

Oculomotor apraxia and disrupted sleep with nocturnal ballistic bouts in ADCY5-related disease.

OBJECTIVE: To characterise the distinctive eye movement disorder and the sleep-related dyskinesia in Adenylate cyclase 5 (ADCY5) related disease. METHODS: Formal eye movement examination and video-polysomnography in a cohort of patients with ADCY5 mutations. RESULTS: All three patients had an eye movement disorder characterised by oculomotor apraxia with gaze limitation most prominently in the vertical plane. All patients had disrupted sleep architecture with reduced sleep efficiency due to frequent and prolonged arousals and awakenings in the context of dyskinesia, which could arise from any sleep stage. The nocturnal movements could last up to 30 min and be more severe than those seen during day-time. CONCLUSION: Nocturnal exacerbations of dyskinesia ("ballistic bouts") seem to be a characteristic feature of the disease, affect the quality of life of patients and therefore require awareness and symptomatic treatment approaches. Apraxia of eye movements, with predominant difficulties in the vertical plane, was a common finding in our patients with ADCY5 mutations. These features may prompt the diagnosis and help to distinguish ADCY5-related disease from other childhood-onset hyperkinetic movement disorders.

Effects of l-Carnosine Supplementation on Sleep Disorders and Disease Severity in Autistic Children: A Randomized, Controlled Clinical Trial.

Sleep disorders are frequently reported in autistic patients. Evidences suggest that increased oxidative stress and reduced antioxidants may play a major role in the pathogenesis of these disorders. Carnosine acts as an antioxidant, antitoxic and neuroprotective agent. The aim of this trial study was to examine the effects of carnosine supplementation on the sleep disorders and severity of autism core symptoms in autistic patients. In this double-blind, randomized clinical trial, 43 autistic patients (31 boys and 12 girls; aged 4 to 16 years) were divided into two groups of carnosine and control that received 500 mg of carnosine and 500 mg of placebo per day for 2 months, respectively. Sleep disorders were measured using Children's Sleep Habits Questionnaires. Gilliam Autism Rating Scale 2 was used to assess the effects of carnosine supplementation on the autism severity. Carnosine supplementation did not change anthropometric indices (p > 0.05) and showed no effect on autism severity (p > 0.05), whereas it significantly reduced sleep duration (p = 0.04), parasomnias (p = 0.02) and total sleep disorders score by 7.59% (p = 0.006) when compared with the control group. The results suggest that carnosine supplementation could be effective in improving sleep disturbances, in particular sleep duration and parasomnias subscales.

Getting a good night sleep? The importance of recognizing and treating nocturnal hypokinesia in Parkinson's disease.

When Parkinson's disease (PD) patients are asked about the quality of their sleep, their answers are dominated by difficulties associated with impaired mobility in bed, medically referred to as nocturnal hypokinesia. Nocturnal hypokinesia is symptomatic from the mid-stage of the disease, affecting up to 70% of PD patients, and contributes to poor sleep quality, and increased carer burden. Here we explore four areas of nocturnal hypokinesia that are relevant to clinical practice, namely: manifestations and definition; clinical assessment and objective monitoring; etiologies and contributing factors; and evidence-based therapeutic approaches. In addition, we provide an operational definition of what constitutes nocturnal hypokinesia and outline different methods of assessment, ranging from clinical interviews and rating scales to objective night-time monitoring with inertial sensors. Optimal management of nocturnal hypokinesia in PD begins with recognizing its manifestation by inquiring about cardinal symptoms and contributing factors from, not only patients, but also carers, followed by formal assessment, and the application of individualized evidence-based treatment. Night-time dopaminergic treatment is the primary therapy; however, careful clinical judgment is required to balance the benefits with the potential adverse events related to nocturnal dopaminergic stimulation. Future studies are needed to explore the practicality of home-based objective assessment of nocturnal hypokinesia, new therapeutic options not limited to dopaminergic medications, and non-pharmacologic approaches, including training on compensatory strategies and bedroom adaptations.

The sleeping brain in Parkinson's disease: A focus on REM sleep behaviour disorder and related parasomnias for practicing neurologists.

Sleep disorders are identified as common non-motor symptoms of Parkinson's disease (PD) and recently this recognition has been expanded to include parasomnias, encompassing not only REM sleep behaviour disorder (RBD), but also other non-REM forms. RBD, a prototypical parasomnia in PD, exists even in the prodromal stage of the disease, and is characterized by the presence of dream enactment behaviours occurring alongside a loss of normal skeletal muscle atonia during REM sleep. In contrast, non-REM parasomnias are more frequently observed in the late stage PD. However, the development of these disorders often overlaps and it is not uncommon for PD patients to meet the criteria for more than one type of parasomnias, thus making a clinical distinction challenging for practicing neurologists who are not sleep specialists. Indeed, clinical recognition of the predominant form of parasomnia does not just depend on video-polysomnography, but also on an individual physician's clinical acumen in delineating pertinent clinical history to determine the most likely diagnosis and proceed accordingly. In this review article, we highlight the various forms of parasomnias that have been reported in PD, including, but not limited to, RBD, with a focus on clinical symptomatology and implications for clinical practice. In addition, we review the differences in PD-related parasomnias compared to those seen in general populations. With advances in sleep research and better technology for ambulatory home monitoring, it is likely that many unanswered questions on PD-related parasomnias will soon be resolved resulting in better management of this nocturnal challenge in PD.

Sleep and melatonin secretion abnormalities in children and adolescents with fetal alcohol spectrum disorders.

OBJECTIVES: Caregivers describe significant sleep disturbances in the vast majority of children and adolescents, which is diagnosed as fetal alcohol spectrum disorders (FASD), but objective data on sleep disorders in this population are almost completely lacking. Animal models suggest that intrauterine alcohol exposure may disrupt sleep wake patterns, cause sleep fragmentation, and specifically affect the suprachiasmatic nucleus, thus disrupting melatonin secretion. The objective of this pioneering study was to evaluate sleep and melatonin abnormalities in children with FASD using objective, gold-standard measures. METHODS: Children and adolescents (N = 36, 6-18 years) with FASD participated in clinical assessments by sleep specialists, overnight polysomnography (PSG), and a dim light melatonin onset (DLMO) test in a pediatric sleep laboratory. PSG was analyzed according to standardized scoring guidelines and sleep architecture was compared with normative data. DLMOs were determined and melatonin secretion curves were evaluated qualitatively to classify melatonin profiles. Sleep disorders were evaluated according to international diagnostic criteria. RESULTS: There was a high prevalence (58%) of sleep disorders. The most common sleep problems were parasomnias (27.9%) and insomnia (16.8%). The sleep studies showed lower than normal sleep efficiency and high rates of sleep fragmentation. Most participants (79%) had an abnormal melatonin profile. CONCLUSIONS: This study led to the recognition that both sleep and melatonin secretion abnormalities are present in children with FASD. Therefore, to be effective in managing the sleep problems in children with FASD, one needs to consider both the sleep per se and a possible malfunction of the circadian regulation.

Prevalence of sleep disorders and their relationship with core symptoms of inattention and hyperactivity in children with attention-deficit/hyperactivity disorder.

OBJECTIVES: To determine the prevalence of sleep disorders in children with attention-deficit/hyperactivity disorder (ADHD) and in a control population. To examine the relationship between sleep disorders and symptoms of inattention, hyperactivity/impulsiveness and executive dysfunction. MATERIALS AND METHODS: We studied 126 children with ADHD and 1036 control children aged between 5 and 18 years old. Caregivers completed the Pediatric Sleep Questionnaire and the ADHD Rating Scale (ADHD-RS). Children with ADHD were subsequently assessed for executive function with the Conner's Continuous Performance Test (CPT) or with AULA Nesplora. RESULTS: Children with ADHD slept less at night and were more likely to display sleep-related rhythmic movements. Children in the ADHD group who were under 12 years old and who had total ADHD-RS scores over the 90th percentile had more difficulty falling asleep than other children; there was also a relationship between total ADHD-RS scores over the 90th percentile and certain parasomnias in the control population. There was a correlation between shorter duration of night-time sleep and omission errors in children who were 12 or older and who were under pharmacological treatment for ADHD. Bedtime resistance and difficulty falling sleep were more frequent in children with ADHD whose symptoms were not treated pharmacologically, than in children receiving treatment. INTERPRETATION: Symptoms of inattention and hyperactivity are correlated with impaired sleep duration and quality; specifically, there is an association between ADHD symptoms and problems falling asleep and parasomnias, however, the current study does not address the nature and direction of causality. Children with ADHD and receiving methylphenidate had fewer sleep disorders, suggesting that, at least in some children, stimulant treatment is associated with improvement of some aspects of sleep. Shorter sleep duration in adolescents under pharmacological treatment for ADHD tended to result in more errors of omission, suggesting that it is important to promote good sleep habits in this population.

Residual sleep disturbances following PTSD treatment in active duty military personnel.

OBJECTIVE: Sleep disturbances, including nightmares and insomnia, are frequently reported symptoms of posttraumatic stress disorder (PTSD). Insomnia is one of the most common symptoms to persist after evidence-based PTSD treatment. The purpose of this study was to examine the prevalence of sleep disturbances in a sample of active duty military personnel before and after receiving therapy for PTSD in a clinical trial and to explore the associations of insomnia and nightmares with PTSD diagnosis after treatment. METHOD: Sleep parameters were evaluated with the PTSD Checklist in 108 active duty U.S. Army soldiers who had completed at least one deployment in support of the wars in Iraq and Afghanistan and who participated in a randomized clinical trial comparing Group Cognitive Processing Therapy-Cognitive Only Version with Group Present-Centered Therapy. RESULTS: Insomnia was the most frequently reported symptom before and after treatment, with 92% reporting insomnia at baseline and 74%-80% reporting insomnia at follow-up. Nightmares were reported by 69% at baseline and by 49%-55% at follow-up. Among participants who no longer met criteria for PTSD following treatment, 57% continued to report insomnia, but only 13% continued to report nightmares. At baseline, 54% were taking sleep medications, but sleep medication use did not affect the overall results. CONCLUSIONS: Insomnia was found to be one of the most prevalent and persistent problems among service members receiving PTSD treatment. Nightmares were relatively more positively responsive to treatment. For some service members with PTSD, the addition of specific treatments targeting insomnia and/or nightmares may be indicated. (PsycINFO Database Record