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Hypermetabolism associated with worse prognosis of amyotrophic lateral sclerosis

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Abstract

Background and objective

Exploration of hypermetabolism in amyotrophic lateral sclerosis (ALS) with different ethnicities is needed to understand its metabolic implications for clinical management. We aimed to evaluate the features of hypermetabolism and investigate its association with clinical characteristics and prognosis of ALS in a prospective Chinese cohort.

Methods

This prospective study was conducted at Peking University Third Hospital, China from 2017 to 2020. 343 participants were enrolled initially. After strict screening, 147 matched health controls and 93 patients with ALS were eligible and underwent detailed clinical assessments. Disease severity and progression were evaluated using recognized scales. Metabolic assessments included body composition and metabolic index (MI) [hypermetabolism if MI ≥ 120.0%]. Patients were followed up every 6 months for survival analysis.

Results

Compared with controls, hypermetabolism was significantly more prevalent in ALS (p = 0.009). MI was consistently higher in ALS than controls (p = 0.009). Further correlation analysis showed that MI significantly decreased with disease progression, as graded by King’s College staging system (p < 0.001). MI was significantly correlated with fat-free mass and fat mass (p = 0.005 and 0.007). Survival analysis showed that hypermetabolism independently indicated a worse prognosis for ALS (HR = 1.020, CI = 1.004–1.036, p = 0.013).

Conclusion

A significant increase in the prevalence and degree of hypermetabolism was identified in ALS compared with strictly matched controls. Metabolic index, which is significantly associated with disease progression and body composition, is an independent prognostic indicator for a worse survival of ALS.

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Data availability statement

Data are available for collaborative studies with qualified investigators after inquiry.

References

  1. van Es MA, Hardiman O, Chio A et al (2017) Amyotrophic lateral sclerosis. Lancet 390(10107):2084–2098

    Article  PubMed  Google Scholar 

  2. Nolano M, Provitera V, Manganelli F et al (2017) Non-motor involvement in amyotrophic lateral sclerosis: new insight from nerve and vessel analysis in skin biopsy. Neuropathol Appl Neurobiol 43(2):119–132

    Article  CAS  PubMed  Google Scholar 

  3. Chen L, Zhang B, Chen R et al (2015) Natural history and clinical features of sporadic amyotrophic lateral sclerosis in China. J Neurol Neurosurg Psychiatry 86(10):1075–1081

    Article  PubMed  Google Scholar 

  4. Shahrizaila N, Sobue G, Kuwabara S et al (2016) Amyotrophic lateral sclerosis and motor neuron syndromes in Asia. J Neurol Neurosurg Psychiatry 87(8):821–830

    Article  CAS  PubMed  Google Scholar 

  5. Dupuis L, Pradat PF, Ludolph AC, Loeffler JP (2011) Energy metabolism in amyotrophic lateral sclerosis. Lancet Neurol 10(1):75–82

    Article  CAS  PubMed  Google Scholar 

  6. Crugnola V, Lamperti C, Lucchini V et al (2010) Mitochondrial respiratory chain dysfunction in muscle from patients with amyotrophic lateral sclerosis. Arch Neurol 67(7):849–854

    Article  PubMed  Google Scholar 

  7. Steyn FJ, Ioannides ZA, van Eijk RPA et al (2018) Hypermetabolism in ALS is associated with greater functional decline and shorter survival. J Neurol Neurosurg Psychiatry 89(10):1016–1023

    Article  PubMed  Google Scholar 

  8. Vandoorne T, De Bock K, Van Den Bosch L (2018) Energy metabolism in ALS: an underappreciated opportunity? Acta Neuropathol 135(4):489–509

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Desport JC, Preux PM, Magy L et al (2001) Factors correlated with hypermetabolism in patients with amyotrophic lateral sclerosis. Am J Clin Nutr 74(3):328–334

    Article  CAS  PubMed  Google Scholar 

  10. Desport JC, Torny F, Lacoste M, Preux PM, Couratier P (2005) Hypermetabolism in ALS: correlations with clinical and paraclinical parameters. Neurodegener Dis 2(3–4):202–207

    Article  PubMed  Google Scholar 

  11. Bouteloup C, Desport JC, Clavelou P et al (2009) Hypermetabolism in ALS patients: an early and persistent phenomenon. J Neurol 256(8):1236–1242

    Article  CAS  PubMed  Google Scholar 

  12. Wills AM, Hubbard J, Macklin EA et al (2014) Hypercaloric enteral nutrition in patients with amyotrophic lateral sclerosis: a randomised, double-blind, placebo-controlled phase 2 trial. Lancet 383(9934):2065–2072

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Ludolph AC, Dorst J, Dreyhaupt J et al (2020) Effect of high-caloric nutrition on survival in amyotrophic lateral sclerosis. Ann Neurol 87(2):206–216

    Article  PubMed  Google Scholar 

  14. Brand D, Polak M, Glass JD, Fournier CN (2021) Comparison of phenotypic characteristics and prognosis between black and white patients in a tertiary ALS clinic. Neurology 96(6):e840–e844

    Article  PubMed  Google Scholar 

  15. He J, Fu JY, Chen L et al (2020) Multicentre, prospective registry study of amyotrophic lateral sclerosis in mainland China (CHALSR): study protocol. BMJ Open 10(12):e042603

    Article  PubMed  PubMed Central  Google Scholar 

  16. Gordon PH, Cheung YK (2006) Progression rate of ALSFRS-R at time of diagnosis predicts survival time in ALS. Neurology 67(7):1314–1315

    Article  PubMed  Google Scholar 

  17. Lechtzin N, Cudkowicz ME, de Carvalho M et al (2018) Respiratory measures in amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener 19(5–6):321–330

    Article  PubMed  Google Scholar 

  18. Ravits J, Paul P, Jorg C (2007) Focality of upper and lower motor neuron degeneration at the clinical onset of ALS. Neurology 68(19):1571–1575

    Article  PubMed  Google Scholar 

  19. Roche JC, Rojas-Garcia R, Scott KM et al (2012) A proposed staging system for amyotrophic lateral sclerosis. Brain 135(Pt 3):847–852

    Article  PubMed  PubMed Central  Google Scholar 

  20. Benatar M, Zhang L, Wang L et al (2020) Validation of serum neurofilaments as prognostic and potential pharmacodynamic biomarkers for ALS. Neurology 95(1):e59–e69

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Shi K, Liu L, He YJ et al (2016) Body composition and bone mineral status in patients with Turner syndrome. Sci Rep 6:38026

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Miller WM, Spring TJ, Zalesin KC et al (2012) Lower than predicted resting metabolic rate is associated with severely impaired cardiorespiratory fitness in obese individuals. Obesity (Silver Spring) 20(3):505–511

    Article  CAS  Google Scholar 

  23. Weir JB (1949) New methods for calculating metabolic rate with special reference to protein metabolism. J Physiol 109(1–2):1–9

    Article  PubMed  PubMed Central  Google Scholar 

  24. Ellis AC, Rosenfeld J (2011) Which equation best predicts energy expenditure in amyotrophic lateral sclerosis? J Am Diet Assoc 111(11):1680–1687

    Article  PubMed  Google Scholar 

  25. Jésus P, Fayemendy P, Nicol M et al (2018) Hypermetabolism is a deleterious prognostic factor in patients with amyotrophic lateral sclerosis. Eur J Neurol 25(1):97–104

    Article  PubMed  Google Scholar 

  26. Sherman MS, Pillai A, Jackson A, Heiman-Patterson T (2004) Standard equations are not accurate in assessing resting energy expenditure in patients with amyotrophic lateral sclerosis. JPEN J Parenter Enteral Nutr 28(6):442–446

    Article  PubMed  Google Scholar 

  27. Vaisman N, Lusaus M, Nefussy B et al (2009) Do patients with amyotrophic lateral sclerosis (ALS) have increased energy needs? J Neurol Sci 279(1–2):26–29

    Article  PubMed  Google Scholar 

  28. Funalot B, Desport JC, Sturtz F, Camu W, Couratier P (2009) High metabolic level in patients with familial amyotrophic lateral sclerosis. Amyotroph Lateral Scler 10(2):113–117

    Article  CAS  PubMed  Google Scholar 

  29. Georges M, Morélot-Panzini C, Similowski T, Gonzalez-Bermejo J (2014) Noninvasive ventilation reduces energy expenditure in amyotrophic lateral sclerosis. BMC Pulm Med 14:17

    Article  PubMed  PubMed Central  Google Scholar 

  30. Ahmed RM, Ke YD, Vucic S et al (2018) Physiological changes in neurodegeneration - mechanistic insights and clinical utility. Nat Rev Neurol 14(5):259–271

    Article  CAS  PubMed  Google Scholar 

  31. Kasarskis EJ, Berryman S, Vanderleest JG, Schneider AR, McClain CJ (1996) Nutritional status of patients with amyotrophic lateral sclerosis: relation to the proximity of death. Am J Clin Nutr 63(1):130–137

    Article  CAS  PubMed  Google Scholar 

  32. Marin B, Desport JC, Kajeu P et al (2011) Alteration of nutritional status at diagnosis is a prognostic factor for survival of amyotrophic lateral sclerosis patients. J Neurol Neurosurg Psychiatry 82(6):628–634

    Article  CAS  PubMed  Google Scholar 

  33. Dupuis L, Oudart H, René F, de Aguilar JLG, Loeffler JP (2004) Evidence for defective energy homeostasis in amyotrophic lateral sclerosis: benefit of a high-energy diet in a transgenic mouse model. Proc Natl Acad Sci USA 101(30):11159–11164

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. De Vocht J, Blommaert J, Devrome M et al (2020) Use of multimodal imaging and clinical biomarkers in presymptomatic carriers of C9orf72 repeat expansion. JAMA Neurol 77(8):1008–1017

    Article  PubMed  Google Scholar 

  35. Ioannides ZA, Ngo ST, Henderson RD, McCombe PA, Steyn FJ (2016) Altered metabolic homeostasis in amyotrophic lateral sclerosis: mechanisms of energy imbalance and contribution to disease progression. Neurodegener Dis 16(5–6):382–397

    Article  PubMed  Google Scholar 

  36. Al-Sarraj S, King A, Cleveland M et al (2014) Mitochondrial abnormalities and low grade inflammation are present in the skeletal muscle of a minority of patients with amyotrophic lateral sclerosis; an observational myopathology study. Acta Neuropathol Commun 2:165

    Article  PubMed  PubMed Central  Google Scholar 

  37. Jeon GS, Im W, Shim YM et al (2016) Neuroprotective effect of human adipose stem cell-derived extract in amyotrophic lateral sclerosis. Neurochem Res 41(4):913–923

    Article  CAS  PubMed  Google Scholar 

  38. Lu CH, Macdonald-Wallis C, Gray E et al (2015) Neurofilament light chain: A prognostic biomarker in amyotrophic lateral sclerosis. Neurology 84(22):2247–2257

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Tefera TW, Steyn FJ, Ngo ST, Borges K (2021) CNS glucose metabolism in Amyotrophic Lateral Sclerosis: a therapeutic target? Cell Biosci 11(1):14

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Liu MS, Cui LY, Fan DS (2014) Age at onset of amyotrophic lateral sclerosis in China. Acta Neurol Scand 129(3):163–167

    Article  CAS  PubMed  Google Scholar 

  41. Xu L, Chen L, Wang S et al (2020) Incidence and prevalence of amyotrophic lateral sclerosis in urban China: a national population-based study. J Neurol Neurosurg Psychiatry 91(5):520–525

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

This study was funded by the National Natural Science Foundation of China (82001347, 81873484 and 82071426, Dr. D. Fan; 81974197, Dr. J. He), Clinical Core Program of Peking University Third Hospital (BYSY2018032; Dr J. He), and Clinical Cohort Construction Program of Peking University Third Hospital (BYSYDL2019002; Dr D. Fan). The authors are grateful for all the investigators and participants who contributed to the studies.

Author information

Author notes

  1. Ji He and Jiayu Fu authors contributed equally to this work.

Authors and Affiliations

  1. Department of Neurology, Peking University Third Hospital, 49 North Garden Road, Beijing, 100191, Haidian District, China

    Ji He, Jiayu Fu, Lu Chen, Lu Tang, Yixuan Zhang, Xinran Ma, Gaoqi Zhang & Dongsheng Fan

  2. Beijing Municipal Key Laboratory of Biomarker and Translational Research in Neurodegenerative Diseases, Beijing, China

    Ji He, Jiayu Fu, Lu Chen, Lu Tang, Yixuan Zhang, Xinran Ma, Gaoqi Zhang & Dongsheng Fan

  3. Department of Cardiology, Peking University Third Hospital, Beijing, China

    Wei Zhao, Chuan Ren, Ping Liu, Dan Li & Lequn Zhou

  4. Physical Examination Center, Peking University Third Hospital, Beijing, China

    Wei Zhao, Chuan Ren, Ping Liu & Dan Li

  5. Clinical Epidemiology Research Center, Peking University Third Hospital, Beijing, China

    Nan Li

Authors
  1. Ji He
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  2. Jiayu Fu
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  3. Wei Zhao
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Contributions

Concept and design: J. He, J. Fu, W. Zhao, D. Fan. Acquisition, follow-up, or interpretation of data: All authors. Drafting of the manuscript: J. He, J. Fu. Critical revision of the manuscript for important intellectual content: D. Fan, W. Zhao, C. Ren. Statistical analysis: N. Li, J. He, J. Fu. Obtained funding: D. Fan, J. He. Administrative, technical, or material support: P. Liu, L. Chen, D. Li, L. Tang.

Corresponding author

Correspondence to Dongsheng Fan.

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Conflicts of interest

The authors declare that they have no conflict of interest.

Ethical approval

The Research Ethics Committee of Peking University Third Hospital approved our study. This study was performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. All participants gave their informed consent prior to their inclusion in the study.

Consent for publication

All authors have read, validated the accuracy of the data, and approved the final manuscript.

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He, J., Fu, J., Zhao, W. et al. Hypermetabolism associated with worse prognosis of amyotrophic lateral sclerosis. J Neurol 269, 1447–1455 (2022). https://doi.org/10.1007/s00415-021-10716-1

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  • DOI: https://doi.org/10.1007/s00415-021-10716-1

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