Michel A. Cramer Bornemann

Implanted upper airway stimulation device for obstructive sleep apnea

Previous feasibility studies have shown that electrical stimulation of the hypoglossal nerve can improve obstructive sleep apnea (OSA). The current study examined the safety and preliminary effectiveness of a second generation device, the Upper Airway Stimulation (UAS) system, and identified baseline predictors for therapy success.

Alcohol-induced sleepwalking or confusional arousal as a defense to criminal behavior: a review of scientific evidence, methods and forensic considerations

An increasing number of criminal cases have claimed the defendant to be in a state of sleepwalking or related disorders induced by high quantities of alcohol. Sleepwalkers who commit violent acts, sexual assaults and other criminal acts are thought to be in a state of automatism, lacking conscious awareness and criminal intent. They may be acquitted in criminal trials. On the other hand, criminal acts performed as the result of voluntary alcohol intoxication alone cannot be used as a complete defense. The alcohol‐induced sleepwalking criminal defense is most often based on past clinical or legal reports that ingestion of alcohol directly ‘triggers’ sleepwalking or increased the risk of sleepwalking by increasing the quantity of slow wave sleep (SWS). A review of the sleep medicine literature found no sleep laboratory studies of the effects of alcohol on the sleep of clinically diagnosed sleepwalkers. However, 19 sleep laboratory studies of the effects of alcohol on the sleep of healthy non‐drinkers or social drinkers were identified with none reporting a change in SWS as a percentage of total sleep time. However, in six of 19 studies, a modest but statistically significant increase in SWS was found in the first 2–4 h. Among studies of sleep in alcohol abusers and abstinent abusers, the quantity and percentage of SWS was most often reduced and sometimes absent. Claims that direct alcohol provocation tests can assist in the forensic assessment of these cases found no support of any kind in the medical literature with not a single report of testing in normative or patient groups and no reports of validation testing of any sort. There is no direct experimental evidence that alcohol predisposes or triggers sleepwalking or related disorders. A legal defense of sleepwalking resulting from voluntarily ingested alcohol should be consistent with the current state of art sleep science and meet generally accepted requirements for the diagnosis of sleepwalking and other parasomnias.

Long-term Maintenance Treatment of Restless Legs Syndrome With Gabapentin Enacarbil: A Randomized Controlled Study

OBJECTIVE To assess maintenance of efficacy and tolerability of gabapentin enacarbil in patients with moderate to severe primary restless legs syndrome (RLS). PATIENTS AND METHODS This study (conducted April 18, 2006, to November 14, 2007) comprised a 24-week, single-blind (SB) treatment phase (gabapentin enacarbil, 1200 mg) followed by a 12-week randomized, double-blind (DB) phase. Responders from the SB phase (patients with improvements on the International Restless Legs Scale [IRLS] and investigator-rated Clinical Global Impression-Improvement scale at week 24 and stable while taking a gabapentin enacarbil dose of 1200 mg for at least 1 month before randomization) were randomized to gabapentin enacarbil, 1200 mg, or placebo once daily at 5 pm with food. The primary end point was the proportion of patients experiencing relapse (worse scores on the IRLS and investigator-rated Clinical Global Impression of Change scale on 2 consecutive visits at least 1 week apart or withdrawal because of lack of efficacy) during the DB phase. RESULTS A total of 221 of 327 patients completed the SB phase, 194 (96 in the gabapentin enacarbil group and 98 in the placebo group) were randomized to DB treatment, and 168 (84 in the gabapentin enacarbil group and 84 in the placebo group) completed the DB phase. A significantly smaller proportion of patients treated with gabapentin enacarbil (9/96 [9%]) experienced relapse compared with the placebo-treated patients (22/97 [23%]) (odds ratio, 0.353; 95% confidence interval, 0.2-0.8; P=.02). Somnolence and dizziness were the most common adverse events. One death occurred (unintentional choking during the SB phase) and was judged as being unrelated to the study drug. No clinically relevant changes were observed in laboratory values, in vital signs, or on electrocardiograms. CONCLUSION Gabapentin enacarbil, 1200 mg, maintained improvements in RLS symptoms compared with placebo and showed long-term tolerability in adults with moderate to severe primary RLS for up to 9 months of treatment.

Violence in sleep

Although generally considered as mutually exclusive, violence and sleep can coexist. Violence related to the sleep period is probably more frequent than generally assumed and can be observed in various conditions including parasomnias (such as arousal disorders and rapid eye movement sleep behaviour disorder), epilepsy (in particular nocturnal frontal lobe epilepsy) and psychiatric diseases (including delirium and dissociative states). Important advances in the fields of genetics, neuroimaging and behavioural neurology have expanded the understanding of the mechanisms underlying violence and its particular relation to sleep. The present review outlines the different sleep disorders associated with violence and aims at providing information on diagnosis, therapy and forensic issues. It also discusses current pathophysiological models, establishing a link between sleep-related violence and violence observed in other settings.

Thalidomide inhibits lipoarabinomannan-induced upregulation of human immunodeficiency virus expression.

Mycobacterium tuberculosis accelerates the progression of human immunodeficiency virus type 1 (HIV-1) infection. The results of this study, which show that thalidomide inhibits the upregulation of HIV-1 expression in U1 cells stimulated with mycobacterial lipoarabinomannans, support the rationale behind conducting controlled trials of this immunodeficiency agent with patients dually infected with HIV-1 and M. tuberculosis.

A case of reversible restless legs syndrome (RLS) and sleep-related eating disorder relapse triggered by acute right leg herpes zoster infection: Literature review of spinal cord and peripheral nervous system contributions to RLS

Restless legs syndrome (RLS) is thought to be due to abnormalities of iron metabolism in the central nervous system; however, occasional cases are associated with lesions of the spinal cord, spinal rootlets, and peripheral nervous system. This is a case report of RLS exacerbated by shingles with a review of the literature of extra-cerebral lesions or disorders causing or contributing to RLS.

Violent parasomnias: forensic implications

Abstract Parasomnias are defined as unpleasant or undesirable behavioral or experiential phenomena that occur predominately or exclusively during the sleep period. Most parasomnias represent the simultaneous admixture of wakefulness and sleep. This chapter focuses on the clinical features, pathophysiology, diagnosis, and treatment of the two most common parasomnias: (1) disorders of arousal (confusional arousals, sleepwalking, and sleep terrors), which represent admixtures of wakefulness and nonrapid eye movement sleep; and (2) rapid eye movement (REM)-sleep behavior disorder (RBD), which is a manifestation of admixed wakefulness and REM sleep. Disorders of arousal are very common, perhaps part of the normal human condition, and are not the manifestation of underlying psychiatric disease. RBD is often the harbinger of degenerative neurological conditions, particularly the synucleinopathies (Parkinsons disease, dementia with Lewy bodies, and multiple system atrophy); it is a frequent accompaniment of narcolepsy with cataplexy, and may be induced by numerous medications, particularly the selective serotonin reuptake inhibitors and the serotonin–norepinephrine reuptake inhibitors.  Parasomnia behaviors underscore the fact that consciousness, being ever so evanescent, exists on a broad spectrum and is not an easily delineated dichotomous state. Such a dynamic understanding of consciousness has significant scientific, legal, and social implications raising interesting and difficult questions regarding awareness, responsibility, culpability, and even what it means to be human. Emphasis is placed upon the importance of the emerging field of Sleep Forensics in the evaluation of violent, injurious, or alleged criminal behaviors resulting from these parasomnias.

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

Alcohol, sleepwalking and violence: lack of reliable scientific evidence.

Sir, The recent Letter to the Editor by Drs Ebrahim and Fenwick (2012) challenges one sentence in a 2010 article published in Brain (Siclari et al. , 2010) stating that, because of the lack of reliable evidence, alcohol-induced sleepwalking should not be allowed as a defence to criminal acts. This, in turn, refers to an article published 22 years ago (Mahowald et al. , 1990). Drs Ebrahim and Fenwick express concern that defendants who have allegedly committed criminal acts while severely intoxicated with alcohol are potentially being denied a valid defence. In our opinion, claims of alcohol-induced sleepwalking violence or sleep sex …

When and where do synucleinopathies begin

New treatments hold great promise for neurodegenerative disorders such as the synucleinopathies, including pharmacologic, mechanical (deep brain and cortical stimulation, growth factor infusion), and cell-based and gene therapies.1,2 A number of nonmotor signs and symptoms may be present long before the appearance of typical clinical features (table). This prodromal phase has been referred to as the presymptomatic, subclinical, preclinical, or premotor period, which may range from 4 to 6 years, and is thought to be related to nondopaminergic lower brainstem structures or autonomic plexuses. However, the article by Claassen et al.3 in this issue of Neurology ® extends that interval to half a century for REM sleep behavior disorder (RBD) as a harbinger for synucleinopathies (Parkinson disease [PD], multiple system atrophy, pure autonomic failure, and dementia with Lewy bodies). View this table: Table Early nonmotor harbingers of synucleinopathies Human RBD was at one time an isolated observation—simply the consequence of REM sleep without atonia (RWA). Follow-up of middle-aged and older patients with “idiopathic” RBD revealed, however, a surprise: some patients with RBD, after nearly 2 decades, developed PD, with increasing percentages of patients with RBD manifesting some …