Dhamidhu Eratne1,2,3, Samantha M Loi1,2,3, Nirbaanjot Walia3, Sarah Farrand1, Qiao-Xin Li4, Shiji Varghese4, Mark Walterfang1,2,3, Andrew Evans5, Ramon Mocellin6, Kunal Dhiman7, Veer Gupta7,8, Charles B Malpas5,9,10, Steven Collins4,11,12, Colin L Masters4,13, Dennis Velakoulis1,2,3. 1. Neuropsychiatry Unit, Royal Melbourne Hospital, Melbourne, VIC, Australia. 2. Melbourne Neuropsychiatry Centre, University of Melbourne and NorthWestern Mental Health, Melbourne, VIC, Australia. 3. Department of Psychiatry, University of Melbourne, Melbourne, VIC, Australia. 4. National Dementia Diagnostics Laboratory, The Florey Institute of Neuroscience and Mental Health and The University of Melbourne, Melbourne, VIC, Australia. 5. Department of Neurology, Royal Melbourne Hospital, Melbourne, VIC, Australia. 6. Delmont Private Hospital, Melbourne, VIC, Australia. 7. School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia. 8. School of Medicine, Deakin University, Melbourne, VIC, Australia. 9. Clinical Outcomes Research Unit (CORe), Department of Medicine, Royal Melbourne Hospital, The University of Melbourne, Melbourne, VIC, Australia. 10. Melbourne School of Psychological Sciences, The University of Melbourne, Melbourne, VIC, Australia. 11. Department of Medicine, Royal Melbourne Hospital, Melbourne, VIC, Australia. 12. Australian National Creutzfeldt-Jakob Disease Registry, The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Melbourne, VIC, Australia. 13. The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Melbourne, VIC, Australia.
Abstract
OBJECTIVE: Neurofilament light has shown promise as a biomarker for diagnosis, staging and prognosis in a wide range of neurological and neurodegenerative disorders. This study explored the utility of cerebrospinal fluid neurofilament light in distinguishing primary psychiatric disorders from neurodegenerative and neurological disorders, a common diagnostic dilemma for psychiatrists and neurologists. METHODS: This cross-sectional retrospective pilot study assessed cerebrospinal fluid neurofilament light on patients referred to a tertiary neuropsychiatry service from 2009 to 2017 for diagnostic assessment of neuropsychiatric and neurocognitive symptoms, where a neurodegenerative disorder was a differential diagnosis, who received lumbar punctures as part of a comprehensive workup. The most recent gold-standard clinical consensus diagnosis was categorised into psychiatric disorder or neurodegenerative or neurological disorder. Data from healthy controls were available for comparison. Data extraction and diagnostic categorisation was blinded to neurofilament light results. RESULTS: A total of 129 participants were included: 77 neurodegenerative or neurological disorder (mean age 57 years, including Alzheimer's dementia, frontotemporal dementia), 31 psychiatric disorder (mean age 51 years, including schizophrenia, major depressive disorder) and 21 healthy controls (mean age 66 years). Neurofilament light was significantly higher in neurodegenerative or neurological disorder (M = 3560 pg/mL, 95% confidence intervals = [2918, 4601]) compared to psychiatric disorder (M = 949 pg/mL, 95% confidence intervals = [830, 1108]) and controls (M = 1036 pg/mL, 95% confidence intervals = [908, 1165]). Neurofilament light distinguished neurodegenerative or neurological disorder from psychiatric disorder with an area under the curve of 0.94 (95% confidence intervals = [0.89, 0.98]); a cut-off of 1332 pg/mL was associated with 87% sensitivity and 90% specificity. CONCLUSION: Cerebrospinal fluid neurofilament light shows promise as a diagnostic test to assist with the often challenging diagnostic dilemma of distinguishing psychiatric disorders from neurodegenerative and neurological disorders. Further studies are warranted to replicate and expand on these findings, including on plasma neurofilament light.
OBJECTIVE: Neurofilament light has shown promise as a biomarker for diagnosis, staging and prognosis in a wide range of neurological and neurodegenerative disorders. This study explored the utility of cerebrospinal fluid neurofilament light in distinguishing primary psychiatric disorders from neurodegenerative and neurological disorders, a common diagnostic dilemma for psychiatrists and neurologists. METHODS: This cross-sectional retrospective pilot study assessed cerebrospinal fluid neurofilament light on patients referred to a tertiary neuropsychiatry service from 2009 to 2017 for diagnostic assessment of neuropsychiatric and neurocognitive symptoms, where a neurodegenerative disorder was a differential diagnosis, who received lumbar punctures as part of a comprehensive workup. The most recent gold-standard clinical consensus diagnosis was categorised into psychiatric disorder or neurodegenerative or neurological disorder. Data from healthy controls were available for comparison. Data extraction and diagnostic categorisation was blinded to neurofilament light results. RESULTS: A total of 129 participants were included: 77 neurodegenerative or neurological disorder (mean age 57 years, including Alzheimer's dementia, frontotemporal dementia), 31 psychiatric disorder (mean age 51 years, including schizophrenia, major depressive disorder) and 21 healthy controls (mean age 66 years). Neurofilament light was significantly higher in neurodegenerative or neurological disorder (M = 3560 pg/mL, 95% confidence intervals = [2918, 4601]) compared to psychiatric disorder (M = 949 pg/mL, 95% confidence intervals = [830, 1108]) and controls (M = 1036 pg/mL, 95% confidence intervals = [908, 1165]). Neurofilament light distinguished neurodegenerative or neurological disorder from psychiatric disorder with an area under the curve of 0.94 (95% confidence intervals = [0.89, 0.98]); a cut-off of 1332 pg/mL was associated with 87% sensitivity and 90% specificity. CONCLUSION: Cerebrospinal fluid neurofilament light shows promise as a diagnostic test to assist with the often challenging diagnostic dilemma of distinguishing psychiatric disorders from neurodegenerative and neurological disorders. Further studies are warranted to replicate and expand on these findings, including on plasma neurofilament light.
Authors: Simon Ducharme; Annemiek Dols; Robert Laforce; Emma Devenney; Fiona Kumfor; Jan van den Stock; Caroline Dallaire-Théroux; Harro Seelaar; Flora Gossink; Everard Vijverberg; Edward Huey; Mathieu Vandenbulcke; Mario Masellis; Calvin Trieu; Chiadi Onyike; Paulo Caramelli; Leonardo Cruz de Souza; Alexander Santillo; Maria Landqvist Waldö; Ramon Landin-Romero; Olivier Piguet; Wendy Kelso; Dhamidhu Eratne; Dennis Velakoulis; Manabu Ikeda; David Perry; Peter Pressman; Bradley Boeve; Rik Vandenberghe; Mario Mendez; Carole Azuar; Richard Levy; Isabelle Le Ber; Sandra Baez; Alan Lerner; Ratnavalli Ellajosyula; Florence Pasquier; Daniela Galimberti; Elio Scarpini; John van Swieten; Michael Hornberger; Howard Rosen; John Hodges; Janine Diehl-Schmid; Yolande Pijnenburg Journal: Brain Date: 2020-06-01 Impact factor: 13.501