Sleep Disorders in Leucine-Rich Glioma-Inactivated Protein 1 and Contactin Protein-Like 2 Antibody-Associated Diseases

Abstract

Objective: Sleep disorders are common in voltage-gated potassium channel complex antibody (VGKC-Ab) diseases. The aim was to investigate the sleep disturbances and polysomnography (PSG) characteristics in patients with VGKC-Ab-associated diseases. Methods: Twenty-seven patients with leucine-rich glioma-inactivated protein 1 antibody (LGI1-Ab) encephalitis, seven patients with contactin protein-like 2 antibody (Caspr2-Ab)-associated diseases, and 14 healthy controls with at least one PSG or actigraphy recording were recruited at Peking Union Medical College Hospital from January 2014 to July 2019. Results: Sleep disorders including insomnia, hypersomnia, rapid eye movement (REM) sleep behavior disorder (RBD), periodic limb movements in sleep (PLMS), agrypnia excitata, and obstructive sleep apnea syndrome were observed. Twenty-one PSG recordings from patients with LGI1-Ab encephalitis demonstrated a decrease in total sleep time (TST) (median 365.5, range 184.5-495.5 min), sleep efficiency (70.0%, 47-92%), N3 sleep (9.7%, 0-32.9%), and REM sleep (9.9%, 0.4-27.9%). Of five patients with Caspr2-Ab-associated diseases, TST was found to be 329.5 (167.0-377.5 min), and sleep efficiency was found to be 61.7% (34.6-71.7%). The percentage for N3 and REM sleep was found to be 15.0% (0-34.6%) and 12.7% (0-22.2%), respectively. Both RBD and PLMS were observed more frequently in patients with LGI1-Ab encephalitis. We identified status dissociatus (SD) in five (23.8%) patients with LGI1-Ab encephalitis and two (40%) patients with Caspr2-Ab diseases. The former is more likely to have simple limb movements rather than complex movements, which mimic the contents of their dreams. Continuous insomnia was more common in patients with Caspr2-Ab diseases than patients with LGI1-Ab encephalitis. Patients reported clinical and PSG improvements following immunotherapy. Conclusion: Sleep disorders in patients with VGKC-Ab-associated diseases include decreased TST and poor sleep efficiency. Our studies provide evidence of SD in patients with LGI1-Ab encephalitis.

Clinical Characteristics and Long-Term Prognosis of Anti-LGI1 Encephalitis: A Single-Center Cohort Study in Beijing, China

“…FBDS has been thought to be an indicative seizure type that frequently preceded the onset of limbic encephalitis (30), and the incidence in our study was 33.3%, consistent with some important studies with an incidence of 34-47% (7,8,17); however, some studies reported a higher incidence of 66.7-100% (3,6,26,28,29). In addition to seizures, cognitive dysfunction, psychiatric disturbances, and sleep disorders were relatively common clinical manifestations, which occurred in 82.2, 66.7, and 54.5% of the patients, respectively, and these results were comparable to previous studies that reported incidences of 64.3-100% (3,6,8,11,17,25,26,28,29), 33.3-73% (3,6,8,17,(27)(28)(29), and 18.2-48% (3,8,11,25,26,28), respectively. In terms of auxiliary examinations, the rates of CSF pleocytosis and protein elevation were both 6.8%, and similar results were obtained in previous studies, with rates of 3.7-19.4% and 12.5-23.1%, respectively (3,11,27,29).…”

“…In contrast, the frequency of OB and the rate of increased intrathecal IgG synthesis rate were both higher (30.0 and 17.5%, respectively), suggesting that they may be more sensitive than routine CSF examinations. The incidence of hyponatremia in the present study was also within the scope of previous studies (66.7 vs. 39-80%, respectively) (8,11,17,25,26,28,29); hyponatremia is often caused by inappropriate secretion of the antidiuretic hormone, which may be related to the expression of LGI1 in the hypothalamus and the kidney (31). Additionally, we found that 90.9% of the patients had typical abnormalities reflected in FDG-PET imaging, and 66.7% of the patients had MRI abnormalities, suggesting that the sensitivity of FDG-PET was much higher than that of structural MRI.…”

“…In our cohort, the sex ratio and age structure of the anti-LGI1 encephalitis patients were both similar to previous studies; that is, it usually affects middle-aged or older people and is more common in males (25)(26)(27)(28)(29). Perhaps because all the patients were enrolled from an epilepsy center, all patients (100%) had seizures, although this proportion was similar to the 75-100% reported in previous studies (3,6,8,11,17,(25)(26)(27)(28)(29). Drugresistant epilepsy is the most important core symptom of these patients.…”

“…Similarly, we did not find significant differences, which was perhaps the result of the small sample size. Furthermore, it should be noted that both the sample size and the evaluation method influence statistical results; for example, a previous study focused on aspects of sleep found that all 27 patients with anti-LGI1 encephalitis had sleep disorders (29), and this incidence was much higher than that in other reports and the present study.…”

Electrophysiological Evaluation in Identifying Unique Sleep Features Among Anti-LGI1 Encephalitis Patients During Active and Recovery Phase

“…Compared to the control group, patients during active stage had severe loss of spindles, SWS and REM sleep, suggesting that the evolution of sequential sleep stages was disturbed and reaching deeper stages became more challenging. 3,12,13 We previously reported that there are abundant nocturnal episodic events during active phase of anti-LGI1 encephalitis, thus it is plausible to attribute the disorganized sleep structure to sleep interruption by these motor events. However, as described in this study, patients without motor events still encounter pronounced disruption of sleep structure during the active phase, suggesting that sleep instability in the anti-LGI1 group was independent of the presence of motor events.…”