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Melatonin secretion and sleep disorders in patients with spinal cord injuries

Spinal Cord volume 62, pages 143–148 (2024)Cite this article

Subjects

Abstract

Study design

Prospective observational study.

Objectives

To evaluate melatonin secretion, daytime sleepiness and sleep disorders in patients with spinal cord injuries (SCI), and their association with lesion level.

Setting

Specialized neuro rehabilitation hospital in France

Methods

Prospective observational study of patients aged over 18 hospitalized in for spinal cord injury. Sleep quality was measured with the Pittsburgh Sleep Quality Index (PQSI), daytime sleepiness with the Epworth Sleepiness scale (ESS), and melatonin secretion by 24 h urinary dosage of 6-sulphatoxy-melatonin.

Results

213 patients were screened, 21 patients were included: 17 complete (AIS A) and 4 lesions (AIS B), 76% of traumatic origin with 12 tetraplegic and 9 paraplegic, mean 10 (range 0.5–40) years after injury. Mean age was 46.8 ± 14.7 years, mean BMI 23.56 ± 4.1 and men outnumbered women (15 vs 6). Melatonin secretion was analyzed by 24 h secretion and by secretion profile. Comparing retained vs abolished secretion, only 23% (4/17) of patients with a lesion above T8 retained melatonin secretion, compared to 80% (4/5) with a lesion below T8 (p = 0.022). Non significant differences were found in secretion profile in patients who retained secretion: no patient with a lesion above T8 had a normal secretion profile compared to 50% with a lesion below T8 and in the impact of partial vs total lesions above T8 in whom 17% (2/12) of complete ASIA-A lesions and 50% (2/4) of incomplete lesions retained secretion.

Conclusion

Lesions of the spinal cord above T8 are strongly associated with abolition of melatonin secretion.

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Fig. 1: Flow chart.
Fig. 2: Melatonin secretion in AIS A patients with lesions above and below T8.

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Data availability

Anonymised data are available on request from the corresponding author.

References

  1. Bonekat HW, Andersen G, Squires J. Obstructive disordered breathing during sleep in patients with spinal cord injury. Paraplegia. 1990;28:392–8.

    CAS  PubMed  Google Scholar 

  2. Scheer FAJL, Zeitzer JM, Ayas NT, Brown R, Czeisler CA, Shea SA. Reduced sleep efficiency in cervical spinal cord injury; association with abolished night time melatonin secretion. Spinal Cord. 2006;44:78–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Verheggen RJHM, Jones H, Nyakayiru J, Thompson A, Groothuis JT, Atkinson G, et al. Complete absence of evening melatonin increase in tetraplegics. FASEB J. 2012;26:3059–64.

    Article  CAS  PubMed  Google Scholar 

  4. Biering-Sørensen F, Biering-Sørensen M. Sleep disturbances in the spinal cord injured: an epidemiological questionnaire investigation, including a normal population. Spinal Cord. 2001;39:505–13.

    Article  PubMed  Google Scholar 

  5. Panza GS, Sutor T, Gee CM, Graco M, McCully KK, Chiodo A, et al. Is Sleep Disordered Breathing Confounding Rehabilitation Outcomes in Spinal Cord Injury Research? Arch Phys Med Rehabil. 2022;103:1034–45.

    Article  PubMed  Google Scholar 

  6. Spong J, Graco M, Brown DJ, Schembri R, Berlowitz DJ. Subjective sleep disturbances and quality of life in chronic tetraplegia. Spinal Cord. 2015;53:636–40.

    Article  CAS  PubMed  Google Scholar 

  7. Whelan A, Halpine M, Christie SD, McVeigh SA. Systematic review of melatonin levels in individuals with complete cervical spinal cord injury. J Spinal Cord Med. 2020;43:565–78.

    Article  PubMed  Google Scholar 

  8. Zeitzer JM, Ayas NT, Shea SA, Brown R, Czeisler CA. Absence of detectable melatonin and preservation of cortisol and thyrotropin rhythms in tetraplegia. J Clin Endocrinol Metab. 2000;85:2189–96.

    CAS  PubMed  Google Scholar 

  9. Fatima G, Sharma VP, Verma NS. Circadian variations in melatonin and cortisol in patients with cervical spinal cord injury. Spinal Cord. 2016;54:364–7.

    Article  CAS  PubMed  Google Scholar 

  10. Moore RY. Neural control of the pineal gland. Behav Brain Res. 1996;73:125–30.

    Article  CAS  PubMed  Google Scholar 

  11. Claustrat B, Brun J, Chazot G. The basic physiology and pathophysiology of melatonin. Sleep Med Rev. 2005;9:11–24.

    Article  PubMed  Google Scholar 

  12. Lumsden SC, Clarkson AN, Cakmak YO. Neuromodulation of the Pineal Gland via Electrical Stimulation of Its Sympathetic Innervation Pathway. Front Neurosci. 2020;14. https://pubmed.ncbi.nlm.nih.gov/32300290/.

  13. Vollrath L Functional anatomy of the human pineal gland. In: Reiter R, editor. The pineal gland. New York: Raven Press; 1984. p. 285–322.

  14. Vecchierini MF, Kilic-Huck U, Quera-Salva MA, Members of the MEL consensus group of the SFRMS. Melatonin (MEL) and its use in neurological diseases and insomnia: Recommendations of the French Medical and Research Sleep Society (SFRMS). Rev Neurologique. 2021;177:245–59.

    Article  CAS  Google Scholar 

  15. Buysse DJ, Reynolds CF, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res. 1989;28:193–213.

    Article  CAS  PubMed  Google Scholar 

  16. Johns MW. A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep. 1991;14:540–5.

    Article  CAS  PubMed  Google Scholar 

  17. Harthé C, Claustrat B, Brun J, Chazot G. Direct radioimmunoassay of 6-sulfatoxymelatonin in plasma with use of an iodinated tracer. Clin Chem. 1991;37:536–9.

    Article  PubMed  Google Scholar 

  18. Arendt J. Assay of melatonin and its metabolites: results in normal and unusual environments. J Neural Transm Suppl. 1986;21:11–33.

    CAS  PubMed  Google Scholar 

  19. Claustrat B, Chazot G, Brun J, Jordan D, Sassolas G. A chronobiological study of melatonin and cortisol secretion in depressed subjects: plasma melatonin, a biochemical marker in major depression. Biol Psychiatry. 1984;19:1215–28.

    CAS  PubMed  Google Scholar 

  20. Claustrat B, Brun J, Garry P, Roussel B, Sassolas G. A once-repeated study of nocturnal plasma melatonin patterns and sleep recordings in six normal young men. J pineal Res. 1986;3:301–10.

    Article  CAS  PubMed  Google Scholar 

  21. Gezici AR, Karakaş A, Ergün R, Gündüz B. Rhythms of serum melatonin in rats with acute spinal cord injury at the cervical and thoracic regions. Spinal Cord. 2010;48:10–4.

    Article  CAS  PubMed  Google Scholar 

  22. Seifman MA, Gomes K, Nguyen PN, Bailey M, Rosenfeld JV, Cooper DJ, et al. Measurement of serum melatonin in intensive care unit patients: changes in traumatic brain injury, trauma, and medical conditions. Front Neurol. 2014;5. https://pubmed.ncbi.nlm.nih.gov/25477861/.

  23. Kennaway DJ. A critical review of melatonin assays: Past and present. J Pineal Res. 2019;67:e12572.

    Article  PubMed  Google Scholar 

  24. Bubenik GA. Localization, physiological significance and possible clinical implication of gastrointestinal melatonin. Biol Signals Receptors. 2001;10:350–66.

    Article  CAS  Google Scholar 

  25. Vaughan S, Badr M, Kruppe E, Abbas M, Mukkavilli V, Sankari A. Endogenous night time melatonin is preserved in patients with chronic spinal cord injury. Am J Respir Crit Care Med. 2017;195:A4536.

    Google Scholar 

  26. Burns SP, Little JW, Hussey JD, Lyman P, Lakshminarayanan S. Sleep apnea syndrome in chronic spinal cord injury: associated factors and treatment. Arch Phys Med Rehabilit. 2000;81:1334–9.

    Article  CAS  Google Scholar 

  27. Stockhammer E, Tobon A, Michel F, Eser P, Scheuler W, Bauer W, et al. Characteristics of sleep apnea syndrome in tetraplegic patients. Spinal Cord. 2002;40:286–94.

    Article  CAS  PubMed  Google Scholar 

  28. Sankari A, Vaughan S, Bascom A, Martin JL, Badr MS. Sleep-Disordered Breathing and Spinal Cord Injury: A State-of-the-Art Review. Chest. 2019;155:438–45.

    Article  PubMed  Google Scholar 

  29. Charlifue SW, Weitzenkamp DA, Whiteneck GG. Longitudinal outcomes in spinal cord injury: aging, secondary conditions, and well-being. Arch Phys Med Rehabilit. 1999;80:1429–34.

    Article  CAS  Google Scholar 

  30. Kabuto M, Namura I, Saitoh Y. Nocturnal enhancement of plasma melatonin could be suppressed by benzodiazepines in humans. Endocrinologia japonica. 1986;33:405–14.

    Article  CAS  PubMed  Google Scholar 

  31. Härtter S, Wang X, Weigmann H, Friedberg T, Arand M, Oesch F, et al. Differential effects of fluvoxamine and other antidepressants on the biotransformation of melatonin. J Clin Psychopharmacol. 2001;21:167–74.

    Article  PubMed  Google Scholar 

  32. Rosenstein RE, Chuluyan HE, Pereyra EN, Cardinali DP. Release and effect of gamma-aminobutyric acid (GABA) on rat pineal melatonin production in vitro. Cell Mol Neurobiol. 1989;9:207–19.

    Article  CAS  PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. Département de physiologie, explorations fonctionnelles, unité des pathologies du sommeil, AP-HP, Hôpital Raymond Poincaré, GHU Paris Saclay, Garches, France

    Sarah Hartley, Raphaëlla Daville, Julie Di Maria, M. A. Quera-Salva & Antoine Leotard

  2. Service de médecine physique et de réadaptation, Hôpital Raymond Poincaré, GHU Paris Saclay, AP-HP, 104, boulevard Raymond-Poincaré, 92380, Garches, France

    Levy Jonathan & Djamel Bensmail

  3. Sleep Lab Initiative In PMR group (SLIIP), Garches, France

    Levy Jonathan & Antoine Leotard

  4. Centre de Biologie et de Pathologie, Groupement Hospitalier Est, 69677, Bron, France

    Véronique Raverot

  5. Université Paris-Saclay, UVSQ, « End:icap » U1179 Inserm, 78000, Versailles, France

    Julie Di Maria, Djamel Bensmail & Antoine Leotard

  6. CIC 1429 Inserm Hôpital Raymond Poincaré Garches, 92380, Garches, France

    Isabelle Bossard

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  1. Sarah Hartley
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Contributions

SH designed the study, analyzed the data and interpreted the results, drafted and revised the manuscript, approved the final version and are accountable for the work. RD, IB Collected and analyzed the data, interpreted the results, revised the manuscript, approved the final version and are accountable for the work. VR Analyzed melatonin levels, interpreted the results, revised the manuscript, approved the final version and is accountable for the work. MAQS Conceived and designed the study, interpreted the results, revised the manuscript, approved the final version and are accountable for the work. AL, JL, JDM, DB interpreted the results, revised the manuscript approved the final version and are accountable for the work.

Corresponding author

Correspondence to Sarah Hartley.

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Hartley, S., Daville, R., Jonathan, L. et al. Melatonin secretion and sleep disorders in patients with spinal cord injuries. Spinal Cord 62, 143–148 (2024). https://doi.org/10.1038/s41393-024-00959-w

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