Michael J. Howell

Proposed Diagnostic Criteria for Night Eating Syndrome

OBJECTIVE To propose criteria for diagnosis of the night eating syndrome (NES). METHOD An international research meeting was held in April 2008, and consensus criteria for NES diagnosis were determined. RESULTS The core criterion is an abnormally increased food intake in the evening and nighttime, manifested by (1) consumption of at least 25% of intake after the evening meal, and/or (2) nocturnal awakenings with ingestions at least twice per week. Awareness of the eating episodes is required, as is distress or impairment in functioning. Three of five modifiers must also be endorsed. These criteria must be met for a minimum duration of 3 months. DISCUSSION These criteria help standardize the definition of NES. Additional aspects of the nosology of NES yet to be fully elaborated include its relationship to other eating and sleep disorders. Assessment and analytic tools are needed to assess these new criteria more accurately.

A review of nighttime eating disorders

Nighttime eating is categorized as either night eating syndrome (NES) or sleep-related eating disorder (SRED). These conditions represent an interruption in the overnight fast that characterizes human sleep. A critical review of the literature on NES and SRED will suggest that they are situated at opposite poles of a disordered eating spectrum. NES could be considered an abnormality in the circadian rhythm of meal timing with a normal circadian timing of sleep onset. Conversely, the feeding behavior in SRED is characterized by recurrent episodes of eating after an arousal from nighttime sleep with or without amnesia. Both conditions are often relentless and chronic. Multiple definitions of night eating have limited our ability to determine the exact prevalence of NES. Studies have suggested that central nervous system (CNS) serotonin modulation may lead to an effective treatment of NES. SRED is frequently associated with other sleep disorders, in particular parasomnias. Early studies have shown that the anti-seizure medication topiramate may be an effective treatment for SRED.

Rapid Eye Movement Sleep Behavior Disorder and Neurodegenerative Disease

IMPORTANCE The dream enactment of rapid eye movement sleep behavior disorder (RBD) is often the first indication of an impending α-synuclein disorder, such as Parkinson disease, multiple-system atrophy, or dementia with Lewy bodies. OBJECTIVE To provide an overview of RBD from the onset of dream enactment through the emergence of a parkinsonian disorder. EVIDENCE REVIEW Peer-reviewed articles, including case reports, case series, retrospective reviews, prospective randomized trials, and basic science investigations, were identified in a PubMed search of articles on RBD from January 1, 1986, through July 31, 2014. FINDINGS Under normal conditions, vivid dream mentation combined with skeletal muscle paralysis characterizes rapid eye movement sleep. In RBD, α-synuclein abnormalities in the brainstem disinhibit rapid eye movement sleep motor activity, leading to dream enactment. The behaviors of RBD are often theatrical, with complexity, aggression, and violence; fighting and fleeing actions can be injurious to patients as well as bed partners. Rapid eye movement sleep behavior disorder is distinguished from other parasomnias by clinical features and the demonstration of rapid eye movement sleep without atonia on polysomnography. Consistent with early neurodegeneration, patients with RBD demonstrate subtle motor, cognitive, and autonomic impairments. Approximately 50% of patients with spontaneous RBD will convert to a parkinsonian disorder within a decade. Ultimately, nearly all (81%-90%) patients with RBD develop a neurodegenerative disorder. Among patients with Parkinson disease, RBD predicts a non-tremor-predominant subtype, gait freezing, and an aggressive clinical course. The most commonly cited RBD treatments include low-dose clonazepam or high-dose melatonin taken orally at bedtime. CONCLUSIONS AND RELEVANCE Treatment of RBD can prevent injury to patients and bed partners. Because RBD is a prodromal syndrome of Parkinson disease (or related disorder), it represents a unique opportunity for developing and testing disease-modifying therapies.

Spinocerebellar ataxia type 26 maps to chromosome 19p13.3 adjacent to SCA6

The dominantly inherited spinocerebellar ataxias (SCA) are a clinically and genetically heterogeneous group of neurodegenerative disorders characterized by progressive gait ataxia, upper limb incoordination, and dysarthria. We studied a six‐generation kindred of Norwegian ancestry with pure cerebellar ataxia inherited in an autosomal dominant pattern. All affected family members had a slowly progressive cerebellar ataxia, with an age of onset range from 26 to 60 years. Brain magnetic resonance imaging study of 11 affected patients showed that atrophy was confined to the cerebellum. After excluding all the known SCAs using linkage analysis or direct mutation screen, we conducted a genomewide genetic linkage scan. With the aid of a novel linkage analysis strategy, we found linkage between the disease locus and marker D19S591 and D19S1034. Subsequent genetic and clinical analysis identified a critical region of 15.55cM interval on chromosome 19p13.3, flanked by markers D19S886 and D19S894, and have established a new genetic locus designated SCA26. The SCA26 locus is adjacent to the genes for Cayman ataxia and SCA6. The region consists of 3.3 million base pairs (Mb) of DNA sequences with approximately 100 known and predicted genes. Identification of the responsible gene for SCA26 ataxia will provide further insight into mechanisms of neurodegeneration. Ann Neurol 2005;57:349–354

A novel therapy for REM sleep behavior disorder (RBD).

STUDY OBJECTIVES RBD may result in sleep related injury (SRI) particularly if a patient exits the bed during dream enactment behavior (DEB). The complex auditory processing and low arousal threshold of REM sleep offers a therapeutic window to halt behavior prior to SRI. We evaluated whether a recorded message prevents SRI in medically refractory RBD. DESIGN Case Series. SETTING Sleep disorders center. PATIENTS Four consecutive RBD patients with continued SRI despite both clonazepam and melatonin therapy. INTERVENTION A pressurized bed alarm customized with a familiar voice to deliver a calming message during vigorous DEB. MEASUREMENTS AND RESULTS The RBDQ-HK evaluated RBD symptoms, and SRI was further quantified with a new clinical tool, the Minnesota Parasomnia Injury Scale. All patients reported a decrease in RBD symptoms and SRI. No injuries occurred post-intervention. Pre-treatment: 5 serious events (SE), 80 minor events (ME), and 193 near events (NE) were noted over 66 patient-months (4.21 events/pt-mo). Post-treatment: 0 SE, 0 ME, and 3 NE were noted after a follow up period of 63 pt-months (0.05 event/pt-mo). There were 176 total bed alarm interventions (2.79 interventions/pt-mo). No adverse effects were reported, and all 4 patients described a minimal burden of treatment. RBD symptoms improved as the average RBDQ-HK score decreased from 68 (range: 53-80) to 54 (range 42-65). CONCLUSION A customized bed alarm may be an effective method to prevent SRI in RBD. This intervention is most suitable for cases of medically refractory RBD and/or for those patients who are unable to tolerate medical therapy.

Parasomnias: An Updated Review

Parasomnias are abnormal behaviors emanating from or associated with sleep. Sleepwalking and related disorders result from an incomplete dissociation of wakefulness from nonrapid eye movement (NREM) sleep. Conditions that provoke repeated cortical arousals, or promote sleep inertia lead to NREM parasomnias by impairing normal arousal mechanisms. Changes in the cyclic alternating pattern, a biomarker of arousal instability in NREM sleep, are noted in sleepwalking disorders. Sleep-related eating disorder (SRED) is characterized by a disruption of the nocturnal fast with episodes of feeding after an arousal from sleep. SRED is often associated with the use of sedative-hypnotic medications; in particular, the widely prescribed benzodiazepine receptor agonists. Recently, compelling evidence suggests that nocturnal eating may in some cases be a nonmotor manifestation of Restless Legs Syndrome (RLS). rapid eye movement (REM) Sleep Behavior Disorder (RBD) is characterized by a loss of REM paralysis leading to potentially injurious dream enactment. The loss of atonia in RBD often predates the development of Parkinson’s disease and other disorders of synuclein pathology. Parasomnia behaviors are related to an activation (in NREM parasomnias) or a disinhibition (in RBD) of central pattern generators (CPGs). Initial management should focus on decreasing the potential for sleep-related injury followed by treating comorbid sleep disorders. Clonazepam and melatonin appear to be effective therapies in RBD, whereas paroxetine has been reported effective in some cases of sleep terrors. At this point, pharmacotherapy for other parasomnias is less certain, and further investigations are necessary.

Restless nocturnal eating: a common feature of Willis-Ekbom Syndrome (RLS).

STUDY OBJECTIVES To determine the frequency of nocturnal eating (NE) and sleep related eating disorder (SRED) in restless legs syndrome (RLS) versus psychophysiological insomnia (INS), and the relationship of these conditions with dopaminergic and sedative-hypnotic medications. DESIGN Prospective case series. SETTING Sleep disorders center. PATIENTS Newly diagnosed RLS or INS. INTERVENTION RLS or INS pharmacotherapy with systematic follow up interview for NE/SRED. MEASUREMENTS AND RESULTS Patients presenting with RLS (n = 88) or INS (n = 42) were queried for the presence of NE and SRED. RLS patients described nocturnal eating (61%) and SRED (36%) more frequently than INS patients (12% and 0%; both p < 0.0001). These findings were not due to arousal frequency, as INS patients were more likely to have prolonged nightly awakenings (93%) than RLS patients (64%; p = 0.003). Among patients on sedative-hypnotics, amnestic SRED and sleepwalking were more common in the setting of RLS (80%) than INS (8%; p < 0.0001). Further, NE and SRED in RLS were not secondary to dopaminergic therapy, as RLS patients demonstrated a substantial drop (68% to 34%; p = 0.0026) in the frequency of NE after dopamine agents were initiated, and there were no cases of dopaminergic agents inducing novel NE or SRED. CONCLUSION NE is common in RLS and not due to frequent nocturnal awakenings or dopaminergic agents. Amnestic SRED occurs predominantly in the setting of RLS mistreatment with sedating agents. In light of previous reports, these findings suggest that nocturnal eating is a non-motor manifestation of RLS with several clinical implications discussed here.

Evaluation of sleep and daytime somnolence in spinocerebellar ataxia type 6 (SCA6)

To determine the frequency of subjective sleep problems in spinocerebellar ataxia type 6 (SCA6), the authors surveyed 25 patients and 25 age-matched controls with the Epworth Sleepiness Scale (ESS) and Pittsburgh Seep Quality Index (PSQI). The ESS was higher in patients with SCA6 (9.12 ± 5.80; CI: 2.28) than in controls (4.96 ± 3.01; CI: 1.18) (p = 0.003, t test). The PSQI was higher in patients with SCA6 (7.96 ± 4.65; CI: 1.86) than in controls (5.08 ± 3.39; CI: 1.36) (p = 0.018, t test).

Spectral EEG analysis and sleepwalking defense: unreliable scientific evidence.

I a recent publication in JCSM,1 Drs. Cartwright and Guilleminault suggest that spectral analysis of the sleep EEG can be used to support a defense of sleepwalking in criminal cases. In particular the authors point to 3 publications that concluded that the sleep of sleepwalkers is defi ned by frequent arousals during SWS (slow wave sleep) as well as—or as a result of—lower % of SWA (slow wave activity).2-4 However, the authors of the study most often referred to have themselves concluded that spectral analysis of the sleep EEG in sleepwalkers is not suitable for forensic use. Gadreau and colleagues2 write: “ Given the likelihood that results of our study could be used in medico-legal settings, it is worth noting that the presence or absence of a decrease of SWA early in the night and of awakenings from SWS in a given individual does not conclusively establish or refute a tendency toward sleepwalking” (pages 4-5). The issue of frequent arousals and changes in SWS% in sleepwalkers as forensic evidence has also been previously reviewed in detail5 and was the subject of a series of letters to the editor of Sleep Medicine Reviews between Drs. Cartwright and Pressman in 2007-8 that readers might fi nd of interest.6-9 As noted by Drs. Cartwright and Guilleminault, establishing a current diagnosis of sleepwalking for a defendant is not the same as establishing that the defendant was sleepwalking during the commission of a crime. Nevertheless, this article suggests that spectral analysis of sleep recorded months or years after the incident offense can be used to support such a sleepwalking defense. There are 3 scientifi c publications currently available that conclude that arousals from SWS sleep and hypersynchronous delta waves are not diagnostic for sleepwalking.10-12 These published scientifi c studies analyzed arousals and SWS using standard visual methods and have reported a lack of statistical sensitivity and especially specifi city as diagnostic markers. Further, there are now more than 7 published studies that report arousals indexes for patients with sleepwalking (see Table 1 in ref. 10). While they are often elevated compared to normal controls there is signifi cant interstudy variability and there is no specifi c cutoff statistically or otherwise to assist in making the diagnosis. Additionally, the Spectral EEG Analysis and Sleepwalking Defense: Unreliable Scientifi c Evidence Mark R. Pressman, Ph.D., F.A.A.S.M.1; Mark Mahowald, M.D., F.A.A.S.M.2; Carlos Schenck, M.D.2; Michel Cramer Bornemann, M.D., F.A.A.S.M.3; Dev Banerjee, M.D.4; Michael Howell, M.D.2; Peter Buchanan, M.D.4; Alon Avidan, M.D., M.P.H., F.A.A.S.M.5 1Lankenau Medical Center and Lankenau Institute for Medical Research, Jefferson Medical School, Villanova School of Law, Villanova, PA; 2University of Minnesota, Minneapolis, MN; 3Sleep Medicine Services, HealthEast Care Systems of Minnesota, Minneapolis, MN; 4NHMRC Centre for Integrated Research and Understanding of Sleep (CIRUS), Woolcock Institute of Medical Research, Sydney, Australia; 5UCLA Sleep Disorders Center, Department of Neurology David Geffen School of Medicine at UCLA, UCLA, Los Angeles, CA

Rapid Eye Movement Sleep Behavior Disorder: Overview and Current Perspective

Rapid eye movement (REM) stage of sleep in normal circumstances is composed of vivid dream mentation associated with physiological skeletal muscle paralysis and thus, quiescence of motor activity. REM sleep behavior disorder (RBD) is a parasomnia characterized by disinhibition of motor control facilitating dream enactment behaviors. These nocturnal motoric behaviors due to lack of REM atonia range from benign limb movements to complex aggressive actions but are often manifested by violent, aggressive flailing, punching and kicking with vocalizations enacting action-filled hostile dreams. Polysomnographic evidence of increased electromyographic tone during REM with or without capturing clinical dream enactment together with careful history helps diagnose RBD. It is considered a prodromal feature of neurodegenerative alpha-synucleinopathies with high rate of eventual phenoconversion. The mainstay of treatment is to first ensure physical safety. When medications are necessary, options include either low-dose clonazepam, high-dose melatonin or both. Yearly surveillance with detailed neurological evaluation is vital for early detection and eventual management of neurodegenerative disorder.