https://orcid.org/0000-0002-2833-8826
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Abstract
Purpose
This study aimed to establish the diagnostic accuracy of a previously validated sleep staging system in patients with probable isolated REM sleep behavior disorder (iRBD), and to compare physicians’ diagnoses of iRBD based on REM sleep without atonia (RSWA) to non-REM hypertonia (NRH), a sleep measure independently associated with Parkinsonian spectrum disorders.
Patients and Methods
Twenty-six patients with a history of dream enactment behavior underwent a diagnostic PSG with simultaneous Sleep Profiler (SP) acquisition at two sites. PSG and SP records were sleep staged, and two sleep neurologists independently diagnosed iRBD based on the presence or absence of polysomnographic identified RSWA. Comparisons for PSG vs SP sleep staging and the qualitative presence or absence of PSG-based RSWA vs automated SP-detected NRH was performed using kappa coefficients (k), positive and negative percent agreements (PPA and NPA), and chi-square tests.
Results
The kappa scores from Sites-1 and −2 for PSG vs SP staging were different for Wake (k=0.82 vs 0.65), N2 (k=0.63 vs 0.72) and REM (k=0.83 vs.0.72). The by-site kappa values for stage N3 increased from 0.72 and 0.37 to 0.88 and 0.74 after PSG records were reedited. The kappa values for between-physician agreement in iRBD diagnoses were fair (k = 0.22). The agreement between each physician’s iRBD diagnoses and NRH were also fair (k=0.29 and 0.22). Abnormal NRH agreed with at least one physician’s iRBD diagnosis in 83% of the records. The PPA resulting from between-physician iRBD agreement was stronger and the NPA weaker than the values obtained from comparison of each physician’s iRBD diagnosis and abnormal NRH.
Conclusion
The potential utility of RSWA and stage N3 as neurodegenerative disorder biomarkers was influenced by between-site variability in visual scoring. The degree to which NRH was associated with iRBD was similar to the between-physician agreement in their diagnosis of iRBD using RSWA.
Abbreviations
AASM, American Academy of Sleep Medicine; EEG, Electroencephalography; DEB, Dream enactment behavior; EMG, Electromyography; IRB, Institution Review Board; iRBD, Isolated REM Sleep Behavior Disorder; k, Kappa value; NPA, Negative percent agreement; NPV, Negative predictive value; NRH, Non-REM hypertonia; PPA, Positive percent agreement; PPV, Positive predictive value; PSD, Parkinsonian Spectrum Disorder; PSG, Polysomnography; REM, Rapid Eye Movement sleep; RSWA, REM Sleep Without Atonia; SP, Sleep ProfilerTM.
Ethics Approval
This study complied with the Declaration of Helsinki with the rights, privacy and welfare of the human subjects enrolled in this study protected by approvals from the University of Arizona IRB and Mayo Clinic IRB. Informed consents were obtained prior to each subject’s PSG. The confidentiality of the patient data was maintained throughout the study.
Acknowledgments
The authors recognize Vladislav Velimirovic for his assistance in implementing the NRH algorithms in the Sleep Profiler software.
The individual presented in was provided a written informed consent which granted a photo release and waiver to Advanced Brain Monitoring for unrestricted use of their identifiable image.
Author Contributions
Mr. Levendowski, Dr. St. Louis, and Dr. Lee-Iannotti conceptualized and designed the study. Data acquisition and scoring was overseen by Ms. Angel and/or conducted by Dr. Lee-Iannotti, Mr. Guevarra, and Dr. Shprecher at Site-1, and by Dr. St. Louis, Mr. Timm and Dr. Boeve at Site-2. Data analysis and interpretation was performed by Mr. Levendowski, Dr. St. Louis, and Dr. Neylan. Mr. Levendowski, Dr. St. Louis, Dr. Boeve, Dr. Neylan, Dr. Walsh, Dr. Lee-Iannotti, and Dr. Mazeika. All authors contributed to the drafting, revising, or adding of intellectual content and/or provided critical review to the manuscript. All authors agreed to the selection of the journal, reviewed, and approved the article before submission, and agreed to take responsibility and accountability for the contents of the article.
Disclosure
As shareholders in Advanced Brain Monitoring, Inc. Mr. Levendowski would financially benefit if the SP intellectual property was acquired by a third party. Mr. Levendowski has the following SP patents issued to Advanced Brain Monitoring: US 8,355,769 and 8,639,313 and EP2408353A4. Mr. Levendowski reports grants from National institute of Aging, during the conduct of the study. Dr. Lee-Iannotti serves as a paid advisor to and speaker for Jazz Pharmaceuticals. Dr Shprecher received research support from the Arizona Alzheimer’s Consortium, Abbvie, Acadia, Aptinyx, Axovant, Biogen, Cognition Therapeutics, Eisai, Eli Lilly, Enterin, Neurocrine, Michael J Fox Foundation, NIH, Nuvelution, Roche and Teva; consultant fees from Amneal, Forensis, Emalax, US World Meds/Supernus and Neurocrine; speaker honoraria from Acorda, Amneal, Intermountain Healthcare, Neurocrine, Sunovion, Teva and US World Meds. Dr. Mazeika serves as the Medical Director of Advanced Brain Monitoring, Inc. Dr. Boeve receives honoraria for SAB activities for the Tau Consortium; research support from Alector, Biogen, Transposon and GE Healthcare; research support from the NIH, the Lewy Body Dementia Association, the American Brain Foundation, the Mayo Clinic Dorothy and Harry T. Mangurian Jr. Lewy Body Dementia Program, the Little Family Foundation, and the Ted Turner and Family Functional Genomics Program; grants from Alector, grants from Biogen, grants from Transposon, grants from EIP Pharma, outside the submitted work. None of the other authors reported financial conflicts.