Forensic Sleep Medicine

Patients with sleep disorders can exhibit behavior that includes violent acts. The behavior may occur during various sleep stages, ranges in complexity, and requires an analysis of consciousness. When the behavior harms another person and criminal charges follow, expert testimony will be required to explain the physiology of the disorder and impairments in consciousness that determine criminal culpability, that is, whether there was conscious intent behind the behavior. In this chapter, sleep-related conditions associated with violent behavior are discussed, along with guidelines for presenting scientific testimony in court. These disorders include rapid eye movement (REM) behavior disorder, somnambulism and other non-REM partial awakenings, and hypersomnolence. Feigned symptoms and malingering must be ruled out, and the clinical parameters for them are discussed. While the physiology of sleep disorders has widely been known, admissibility in court is not automatic. Standards for acceptable expert testimony are discussed.

0003 LGI1 and CASPR2 Autoimmunity: Sleep Symptoms, Polysomnography, and Quantitative REM Sleep without Atonia

Introduction Sleep disturbances, including rapid eye movement (REM) behavior disorder (RBD), are known manifestations of voltage-gated-potassium-channel-complex VGKC-IgG seropositivity (VGKC+). Discovery of leucine-rich, glioma inactivated protein 1 (LGI1) and contactin-associated protein 2 (CASPR2) have refined our understanding of VGKC+. VGKC+ without LGI1/CASPR2-IgG (“double-negative”) has lost its clinical significance. Previous detailed sleep analysis of these subtypes has been limited. Methods We performed a retrospective study to characterize clinical and polysomnographic features of LGI1/CASPR2 seropositive (LGI1+/CASPR2+) and VGKC double-negative patients, including quantitative REM sleep without atonia (RSWA). Quantified RSWA was compared to matched controls and normative RSWA percentiles. Results Eleven LGI1+/CASPR2+ (LGI1+, 9) and twelve VGKC double-negative patients were analyzed. Insomnia was seen in 55% of LGI1+/CASPR2+ and 8% of VGKC double-negative patients (p=0.05). The LGI1+/CASPR2+ group had reduced slow wave sleep compared to the VGKC double-negative group. Five LGI1+ patients had clinical dream enactment behavior (DEB). Eight LGI1+ patients met quantitative diagnostic levels of RSWA. Higher RSWA levels were seen in the LGI1+/CASPR2+ group. Ten LGI1+/CASPR2+ patients received immunotherapy; all ten neurologically benefited with sleep benefits in 6/10. Conclusion Sleep disorders such as insomnia and RBD are part of the LGI1/CASPR2 autoimmune phenotype. Objective sleep manifestations can be seen on polysomnogram in the form of reduced N3 and elevated RSWA as compared to controls. Quantitative RSWA analysis identified RBD in more LGI1+ patients than clinical report or qualitative RSWA. In this study, RBD was only seen with LGI1+, not CASPR2+. The intermediate RSWA levels of the VGKC double-negative patients may suggest a spectrum of abnormal motor activity in these related antibodies. Additional studies are needed to further explore the biomarker potential of quantitative RSWA in autoimmune neurological conditions. Support This project was supported by the National Center forResearch Resources, National Institutes of Health, through Grant Number 1 UL1 RR024150- 01.

1027 Differences in Polysomnography-Based Sleep Disorders Between HIV-Infected Persons and Matched Controls

Introduction Sleep disturbance is a prevalent problem among HIV-infected persons. The recognition of comorbid sleep disorders in patients with HIV is currently hampered by limited knowledge of sleep-related symptoms, sleep architecture, and types of sleep disorders. We aimed to compare the differences in sleep-related symptoms and polysomnography-based sleep disorders between HIV-infected persons and controls. Methods The study included 170 men with a Pittsburgh sleep quality index (PSQI) greater than 5, composed of 44 HIV-infected men and 126 male controls who were frequency-matched by sex, age (-/+ 3.0 years) and BMI (-/+ 3.0 kg/m2). For all participants an overnight sleep study using a Somte V1 monitor was conducted. Differences in sleep-related symptoms and sleep disorders between HIV-infected patients and controls were examined using t-tests or Chi-square tests. Results HIV-infected persons with sleep disturbances more often had psychological disturbances (72.7% vs. 40.5%, p<0.001) and suspected rapid eye movement (REM) behavior disorder (RBD) (25.0% vs. 4.8%, p<0.01) than that of controls. The sleep-disordered breathing (SDB) in HIV-infected persons was less common than that in controls (56.8% vs. 87.3%, p<0.001). The mean percentage of REM sleep among HIV-infected patients was higher than that among the controls (20.6% vs. 16.6%, p<0.001). Enuresis was more common in HIV-infected persons than controls (40.9% vs. 22.2%, p=0.02). Conclusion Psychological disturbances and SDB can be the possible explanations of sleep disturbances in HIV-infected persons, in which suspected RBD is notable. Further studies are warranted to examine underlying factors of suspected RBD among HIV-infected persons with sleep disturbances. Support This work was supported by the Ministry of Science and Technology, Executive Yuan of Taiwan [MOST 105-3011-E-006-002], and National Cheng Kung University Hospital [NCKUH-10702022]

0418 Effect of Acute Administration of DORA-12 on Sleep Impairment in the Aged PS19 Mouse Model of Tauopathy

Introduction Aged PS19 mice (MAPT P301S), a mouse model of tauopathy and neurodegeneration, display reduced NREM and REM sleep starting around 8-9 months before death around 12 months. Here, we tested the acute effect of a dual orexin receptor antagonist (DORA-12) on sleep in 11 mice (5 male, 6 female) at 10.3±1.8 months. Methods Two consecutive 24-hour recordings (12/12hr L:D cycle) were scored semi-automatically for non-REM sleep, REM sleep, and wake in mice implanted with EEG/EMG. Mice were treated with either vehicle (day 1) or 100mg/kg of DORA-12 (day 2) by oral gavage at both ZT0 and ZT9. Results After the first dose at ZT0, both latency to the first NREM sleep episode (paired t-test p=0.002) and to the first REM sleep episode (paired t-test p=0.005) was significantly shorter with DORA-12 (NREM: 20.8±17.8 min.; REM: 23.5±21.2 min.) compared to vehicle (NREM: 49.2±22.3 min.; REM: 127.0±93.3 min.). There was no difference in NREM or REM sleep latency observed after the second dose at ZT9. DORA-12 treatment increased NREM duration across the 24hr period (DORA-12: 664±52 min.; Veh: 601±54 min., paired t-test p=0.007) and also after the 2nd dose (DORA-12: 311±65 min.; Veh: 263±84 min., paired t-test p=0.009). DORA-12 treatment also increased REM duration across 24hrs (DORA-12: 61±30 min.; Veh: 48±29 min., paired t-test p=0.014) but not after the 2nd dose alone (DORA-12: 22±14 min.; Veh: 20±15 min., paired t-test p=0.388). Notably in both vehicle and DORA-12 conditions, we observed apparent dream enactment behavior including mastication, paw grasp, and fore limb extension during REM in 3 of 11 PS19 mice (all male), not typically observed in younger PS19 or age-matched non-transgenic mice, suggestive of a possible REM behavior disorder (RBD) phenotype. Wake-like behaviors occurred during theta-dominant EEG but with an EMG amplitude >4SD the preceding NREM sleep baseline for at least > 1sec. Conclusion In aged PS19 mice, DORA-12 was found to decrease the latency to NREM and REM after the first dose while also increasing NREM and REM duration across the entire 24hr recording period. We also capture a heretofore undescribed RBD-like phenotype in aged PS19 tauopathy mice. Support Merck MISP

0815 Violent Parasomnias In Patients With REM Without Atonia. Parasomnia Overlap Disorder Vs Pure Rem Behavior Disorder

Introduction REM-Behavior-Disorder (RBD) patients are known for parasomnias causing self-injury. On literature review, harm to others using a weapon is not well established. Some opinions state REM-parasomnias do not consist of elaborate actions, such firing a gun. This has significant ramifications in forensic medicine when RBD is a consideration. We reviewed our RBD patients to identify instances in which a gun was used during a parasomnic event to characterize clinical features associated with such behaviors. Methods We reviewed over 57 RBD cases from Texas, between 2014-2017 seeking parasomnias in which a gun was used. Results We found two patients in whom a gun was used during a parasomnia, representing < 3.5% of cases. Case-1: 59 y/o F with a 5 year hx of parasomnias of screaming, thrashing, roaming and one instance in which she pointed an unloaded gun at her husband saying she was going to kill him. She had no recollection of the event. NPSG demonstrated REM without atonia, mild OSA (1a AHI of 11/hr) and frequent PLMS. Case-2 presented to a sleep center in 1989 at 33 y/o with 3 year Hx of EDS, found to have mild OSA unresponsive to PAP Tx, then diagnosed with narcolepsy. He later developed cataplexy and progressed to developing parasomnias 15 years later. He demonstrated REM without atonia on a CPAP re-titration NPSG study done in part for his parasomnias, 20 years after original assessment. PLMS were also demonstrated. His parasomnias consisted of yelling, screaming, roaming and one time he woke up finding bullet holes in his closet door with no recollection of firing his gun, which he kept near his bed. Conclusion RBD is associated with a wide range of parasomnic events, almost never captured in the laboratory. These patients had clear RBD findings. It is possible they had Parasomnia Overlap Disorder in which Non-REM parasomnias occur in patients with RBD. PLMS and or OSA may contribute by fragmenting sleep. Nonetheless, it is clear that RBD patients can have elaborate parasomnias involving the use of weapons. More attention of this is noteworthy since reports are lacking in the literature. Support N/A