Chronic widespread musculoskeletal pain, fatigue, depression and disordered sleep in chronic post-SARS syndrome; a case-controlled study

Harvey Moldofsky, John Patcai, Harvey Moldofsky, John Patcai

Abstract

Background: The long term adverse effects of Severe Acute Respiratory Syndrome (SARS), a viral disease, are poorly understood.

Methods: Sleep physiology, somatic and mood symptoms of 22 Toronto subjects, 21 of whom were healthcare workers, (19 females, 3 males, mean age 46.29 yrs.+/- 11.02) who remained unable to return to their former occupation (mean 19.8 months, range: 13 to 36 months following SARS) were compared to 7 healthy female subjects. Because of their clinical similarities to patients with fibromyalgia syndrome (FMS) these post-SARS subjects were similarly compared to 21 drug free female patients, (mean age 42.4 +/- 11.8 yrs.) who fulfilled criteria for fibromyalgia.

Results: Chronic post-SARS is characterized by persistent fatigue, diffuse myalgia, weakness, depression, and nonrestorative sleep with associated REM-related apneas/hypopneas, an elevated sleep EEG cyclical alternating pattern, and alpha EEG sleep anomaly. Post- SARS patients had symptoms of pre and post-sleep fatigue and post sleep sleepiness that were similar to the symptoms of patients with FMS, and similar to symptoms of patients with chronic fatigue syndrome. Both post-SARS and FMS groups had sleep instability as indicated by the high sleep EEG cyclical alternating pattern rate. The post-SARS group had a lower rating of the alpha EEG sleep anomaly as compared to the FMS patients. The post-SARS group also reported less pre-sleep and post-sleep musculoskeletal pain symptoms.

Conclusions: The clinical and sleep features of chronic post-SARS form a syndrome of chronic fatigue, pain, weakness, depression and sleep disturbance, which overlaps with the clinical and sleep features of FMS and chronic fatigue syndrome.

References

    1. Booth CM, Matukas LM, Tomlinson GA, Rachlis AR, Rose DB, Dwosh HY. et al.Clinical Features and Short-term Outcomes of 144 Patients With SARS in the Greater Toronto Area. JAMA. 2003;289:2801–2809. doi: 10.1001/jama.289.21.JOC30885.
    1. Muller MP, Richardson SE, McGeer A, Dresser L, Raboud J, Mazzulli T. et al.Early diagnosis of SARS: lessons from the Toronto SARS outbreak. Eur J Clin Microbiol Infect Dis. 2006;25:230–237. doi: 10.1007/s10096-006-0127-x.
    1. McDonald LC, Simor AE, Su IJ, Malone S, Ofner M, Chen KT, SARS in healthcare facilities, Toronto and Taiwan. Emerg Infect Dis [serial on the Internet] 2004.
    1. Avendano M, Derkach P, Swan S. Clinical course and management of SARS in health care workers in Toronto: a case series. CMAJ. 2003;168(13):1649–1660.
    1. Ksiazek TG, Erdman D, Goldsmith CS, Zaki SR, Peret T, Emery S. et al.A novel coronavirus associated with severe acute respiratory syndrome. N Engl J Med. 2003;348:1953–66. doi: 10.1056/NEJMoa030781.
    1. Marra MA, Jones SJM, Astell CR, Holt RA, Brooks-Wilson A, Brooks-Wilson A, Butterfield, Yaron SN. et al.The Genome Sequence of the SARS-Associated Coronavirus. Science. 2003;300:1399–1404. doi: 10.1126/science.1085953.
    1. Hamming I, Timens W, Bulthuis ML, Lely AT, Navis GJ, van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. Journal of Pathology. 2004;203(2):631–7. doi: 10.1002/path.1570.
    1. Low DE, McGeer A. SARS--one year later. New Engl J Med. 2003;349(25):2381–2. doi: 10.1056/NEJMp038203.
    1. Wahler HR. The physical symptoms inventory: measuring levels of somatic complaining behavior. J Clin Psychol. 1968;24:207–211. doi: 10.1002/1097-4679(196804)24:2<207::AID-JCLP2270240223>;2-G.
    1. Beck AT, Ward CH, Mendelson M, Monk M, Erbaugh J. An inventory for measuring depression. Arch Gen Psychiatry. 1961;4:561–571.
    1. Beck AT, Rial WY, Rickels K. Short form of depression inventory: cross-validation. Psychological Reports. 1974;34:1184–6.
    1. Blanchard EB, Jones-Alexander J, Buckley TC, Forneris CA. Psychometric properties of the PTSD Checklist (PCL) Behav Res Ther. 1996;34:669–73. doi: 10.1016/0005-7967(96)00033-2.
    1. Unger ER, Nisenbaum R, Moldofsky H, Cesta A, Sammut C, Reyes M. et al.Sleep assessment in a population-based study of chronic fatigue syndrome. BMC Neurol. 2004;4(1):6. doi: 10.1186/1471-2377-4-6.
    1. Rechtshaffen A, Kales A. A manual of standardized terminology, techniques and scoring system for sleep stages of human subjects. UCLA Brain Info Serv/Brain Res Inst, LA. 1968.
    1. MacLean AW, Lue F, Moldofsky H. The reliability of visual scoring of alpha EEG activity during sleep. Sleep. 1995;18:565–9.
    1. van den Hoed J, Kraemer H, Guilleminault C, Zarcone VP Jr, Miles LE, Dement WC. et al.Disorders of excessive daytime somnolence: polygraphic and clinical data for 100 patients. Sleep. 1981;4:23–37.
    1. Moldofsky H, Saskin P, Lue FA. Sleep and symptoms in fibrositis syndrome after a febrile illness. J of Rheumatol. 1988;15(2):1701–1704.
    1. Hoddes E, Zarcone V, Smythe H, Phillips R, Dement WC. Quantification of sleepiness: a new approach. Psychophysiology. 1973;10:431–6. doi: 10.1111/j.1469-8986.1973.tb00801.x.
    1. Wolfe F, Smythe HA, Yunus MB, Bennett RM, Bombardier C, Goldenberg DL, The American College of Rheumatology 1990 criteria for the classification of fibromyalgia: report of the multicenter criteria committee. Arthritis Rheum. p. 1990.
    1. Rizzi M, Sarzi-Puttini P, Atzeni F, Capsoni F, Andreoli A, Pecis M. et al.Cyclical Alternating Pattern: A new marker for sleep alteration in patients with fibromyalgia. J Rheumatol. 2004;34:1193–99.
    1. Moldofsky H, Inhaber NH, Guinta DR, Alvarez-Horine SB. The Effects of Sodium Oxybate on Sleep Physiology and Sleep/Wake-Related Symptoms in Patients with Fibromyalgia Syndrome: A double-blind, randomized, placebo-controlled study. J Rheumatol. 2010;37:2156–66. doi: 10.3899/jrheum.091041. Epub 2010 Aug 3.
    1. Rosa AC, Parrino L, Terzano MG. Automatic detection of cyclic alternating pattern (CAP) sequences in sleep: preliminary results. Clin Neurophysiol. 1999;110:585–92. doi: 10.1016/S1388-2457(98)00030-3.
    1. Rosa A, Alves GR, Brito M, Lopes MC, Tufik S. Visual and automatic cyclic alternating pattern (CAP) scoring: inter-rater reliability study. Arq Neuropsiquiatr. 2006;64:578–81.
    1. Weathers F, Ford J. In: Measurement of Stress, Trauma, and Adaptation. Stamm BH, editor. Lutherville, Md: Sidran Press; 1996. Psychometric properties of the PTSD Checklist (PCL-C, PCL-S, PCL-M, PCL-PR)
    1. Parrino L, Boselli M, Spaggiari MC, Smerieri A, Terzano MG. Cyclic alternating pattern (CAP) in normal sleep: polysomnographic parameters in different age groups. Electroencephalography & Clinical Neurophysiology. 1998;107:439–50.
    1. Herridge MS, Cheung AM, Tansey CM, Matte-Martyn A, Diaz-Granados N, Al-Saidi F. et al.One-Year Outcomes In Survivors Of The Acute Respiratory Distress Syndrome. N Engl J Med. 2003;348:683–93. doi: 10.1056/NEJMoa022450.
    1. May KP, West SG, Baker MR. et al.Sleep apnea in male patients with fibromyalgia syndrome. Am J Med. 1993;94:505–508. doi: 10.1016/0002-9343(93)90085-4.
    1. Sergi M, Rizzi M, Braghiroli A. et al.Periodic breathing during sleep in patients affected by fibromyalgia syndrome. Eur Respir J. 1999;14:203–208. doi: 10.1034/j.1399-3003.1999.14a34.x.
    1. Gold AR, Dipalo F, Gold MS, Broderick J. Inspiratory airflow dynamics during sleep in women with fibromyalgia. Sleep. 2004;27:459–466.
    1. Grote L, Ploch T, Heitmann J, Knaack L, Penzel T, Peter JH. Sleep-related breathing disorder is an independent risk factor for systemic hypertension. Am J Respir Crit Care Med. 1999;160:1875–1882.
    1. Fukuda K, Straus SE, Hickie I, Sharpe MC, Dobbins JG, Komaroff A. et al.The chronic fatigue syndrome: a comprehensive approach to its definition and study. Ann Int Med. 1994;121:953–959.
    1. Wolfe F, Smythe HA, Yunus MB, Bennett RM, Bombardier C, Goldenberg DL. et al.The American College of Rheumatology 1990 criteria for the classification of fibromyalgia: report of the multicenter criteria committee. Arthritis Rheum. 1990;33:160–172. doi: 10.1002/art.1780330203.
    1. Branco J, Atalaia A, Paiva T. Sleep cycles and alpha-delta sleep in fibromyalgia syndrome. Journal of Rheumatololog. 1994;21:1113–1117.
    1. Drewes AM, Nielsen KD, Taagholt SJ, Bjerregård K, Svendsen L, Gade J. Sleep intensity in fibromyalgia: focus on the microstructure of the sleep process. Br J Rheumatol. 1995;34:629–635. doi: 10.1093/rheumatology/34.7.629.
    1. Roizenblatt S, Moldofsky H, Benedito-Silva AA, Tufik S. Alpha sleep characteristics in fibromyalgia. Arthritis & Rheumatism. 2001;44:222–30.
    1. Whelton CL, Salit I, Moldofsky Sleep H. Epstein-Barr virus infection, musculoskeletal pain, and depressive symptoms in chronic fatigue syndrome. Journal of Rheumatology. 1992;19:939–943.
    1. Chen R, Chou K, Huang Y, Wang T, Liu S, Ho L. Effects Of A SARS Prevention Programme In Taiwan On Nursing Staff's Anxiety, Depression And Sleep Quality: A Longitudinal Survey. International Journal of Nursing Studies. 2006;43(2):215–225. doi: 10.1016/j.ijnurstu.2005.03.006.
    1. Moldofsky H, Scarisbrick P. Induction of neurasthenic musculoskeletal pain syndrome by selective sleep stage deprivation. Psychosom Med. 1976;38:35–44.
    1. Glass WG, Subbarao K, Murphy B. Murphy PM. Mechanisms of host defense following severe acute respiratory syndrome-coronavirus (SARS-CoV) pulmonary infection of mice. Journal of Immunology. 2004;173:4030–9.
    1. He L, Ding YQ, Che XY, Zhang QL, Huang ZX, Wang HJ. et al.Expression of the monoclonal antibody against nucleocapsid antigen of SARS-associated coronavirus in autopsy tissues from SARS patients. Di Yi Junyi Daxue Xuebao. 2003;23:1128–30.
    1. Gu J, Gong E, Zhang B, Zheng J, Gao Z, Zhong Y. et al.Multiple organ infection and the pathogenesis of SARS. J Exp Med. 2005;202:415–424. doi: 10.1084/jem.20050828.
    1. Xu J, Zhong S, Liu J, Li L, Li Y, Wu X. et al.Detection of severe acute respiratory syndrome coronavirus in the brain:potential role of chemikine mig in pathogenesis. Clin Infect Dis. 2005;41:1089–1096. doi: 10.1086/444461.
    1. Yong G, Kortweg C, McNutt MA, Gu J. Pathogenetic mechanisms of severe acute respiratory syndrome. Virus Research. 2008;133:4–12. doi: 10.1016/j.virusres.2007.01.022.
    1. Netland J, Meyerholz DK, Moore S, Cassell M, Perlman S. Severe acute respiratory syndrome coronavirus infection causes neuronal death in the absence of encephalitis in mice transgenic for human ACE2. J Virol. 2008;82:7264–75. doi: 10.1128/JVI.00737-08.
    1. Hickie I, Davenport T, Wakefield D, Vollmer-Conna U, Cameron B, Vernon SD. et al.Dubbo Infection Outcomes Study Group. Post-infective and chronic fatigue syndromes precipitated by viral and non-viral pathogens: prospective cohort study. BMJ. 2006;333(7568):575. doi: 10.1136/.
    1. Cope H, David A, Pelosi A, Mann A. Predictors of chronic "postviral" fatigue. The Lancet. 1994;344:8926. doi: 10.1016/S0140-6736(94)92833-9.
    1. Lombardi V, Ruscetti FW, Gupta JD, Pfost MA, Hagen KS, Peterson DL. et al.Detection of an Infectious Retrovirus, XMRV, in Blood Cells of Patients with Chronic Fatigue Syndrome. Science. 2009;326:585–589. doi: 10.1126/science.1179052.
    1. van der Meer JWM, Netea MG, Galama JMD, van Kuppeveld FM. Comment on "Detection of an Infectious Retrovirus, XMRV, in Blood Cells of Patients with Chronic Fatigue Syndrome". Science. 2010. p. 328. 825.
    1. Hue S, Gray ER, Gall A, Katzourakis A, Tan CP, Houldcroft CJ, Disease-associated XMRV sequences are consistent with laboratory contamination. Retrovirology. 2010. in press .
    1. Chua SE, Cheung V, Cheung C, McAlonan GM, Wong JW, Cheung EP. et al.Stress and Psychological Impact On SARS Patients During The Outbreak. Can J Psychiatry. 2004;49:201–206.
    1. Hui DS, Joynt GM, Wong KT, Gomersall CD, Li TS, Antonio G. et al.Impact of Severe Acute Respiratory Syndrome (SARS) On Pulmonary Function, Functional Capacity And Quality Of Life In A Cohort Of Survivors. Thorax. 2005;60:401–409. doi: 10.1136/thx.2004.030205.
    1. Chan JWM, Ng CK. Severe Acute Respiratory Syndrome (SARS): A Brief Review With Exploration of the Outcomes, Prognostic Factors and Sequelae. Current Respiratory Medicine Reviews. 2005;1:85–92. doi: 10.2174/1573398052953659.
    1. Chan PK, Tang JW, Hui DS. SARS: clinical presentation, transmission, pathogenesis and treatment options. Clinical Science. 2006;110:193–204. doi: 10.1042/CS20050188.
    1. Maunder R, Hunter J, Vincent L, Bennett J, Peladeau N, Leszcz M. et al.The immediate psychological and occupational impact of the 2003 SARS outbreak in a teaching hospital. CMAJ. 2003;168:1245–51.
    1. Robertson E, Hershenfield K, Grace SL, Stewart DE. The psychosocial effects of being quarantined following exposure to SARS: a qualitative study of Toronto health care workers. Can J Psychiatry. 2004;49:403–407.
    1. Maunder RG, Lancee WJ, Balderson KE, Bennett JP, Borgundvaag B, Evans S. et al.Long-term Psychological and Occupational Effects of Providing Hospital Healthcare during SARS Outbreak. Emerg Infect Dis. 2006;12:1924–32.
    1. Lau HM, Lee EW, Wong C, Ng G, Jones A, Hui D. The Impact of Severe Acute Respiratory Syndrome on the Physical Profile and Quality of Life. Archives of Physical Medicine and Rehabilitation. 2005;86:1134–1140. doi: 10.1016/j.apmr.2004.09.025.
    1. Chua SE, Cheung V, Cheung C, McAlonan GM, Wong JW, Cheung EP. et al.Psychological effects of the SARS outbreak in Hong Kong on high-risk health care workers. Can J Psychiatry. 2004;49:391–3.
    1. Mak IW, Chu CM, Pan PC, Yiu MG, Chan VL. Long-term psychiatric morbidities among SARS survivors. Gen Hosp Psychiatry. 2009;31:318–26. doi: 10.1016/j.genhosppsych.2009.03.001.

Source: PubMed

3
Subscribe