Journal of Neurology

, Volume 266, Issue 6, pp 1412–1420 | Cite as

Prognostic significance of body weight variation after diagnosis in ALS: a single-centre prospective cohort study

  • Toshio ShimizuEmail author
  • Yuki Nakayama
  • Chiharu Matsuda
  • Michiko Haraguchi
  • Kota Bokuda
  • Kazuko Ishikawa-Takata
  • Akihiro Kawata
  • Eiji Isozaki
Original Communication



Body weight reduction after disease onset is an independent predictor of survival in amyotrophic lateral sclerosis (ALS), but significance of weight variation after diagnosis remains to be established.


To investigate weight variation after diagnosis and its prognostic significance in patients with ALS as a prospective cohort study.


Seventy-nine patients with ALS were enrolled in this study. At the time of diagnosis and about 1 year later, we evaluated the following parameters: age, sex, onset age, onset region, body mass index (BMI) and premorbid BMI, forced vital capacity and the revised ALS functional rating scale. Annual BMI decline rates (∆BMI) from onset to diagnosis and from diagnosis to about 1 year later were calculated. Patients were followed to the endpoints (death or tracheostomy), and the relationships between ∆BMIs and survival were investigated.


Patients with post-diagnostic ∆BMI ≥ 2.0 kg/m2/year showed shorter survival length than those with < 2.0 kg/m2/year (log-rank test, p < 0.0001), and multivariate analysis using the Cox model revealed post-diagnostic ∆BMI as an independent prognostic factor. No correlation was identified between pre- and post-diagnostic ∆BMIs. Female patients with post-diagnostic ∆BMI < pre-diagnostic ∆BMI showed longer survival than those with the opposite ∆BMI trend (log-rank test, p = 0.0147). Female patients with post-diagnostic weight increase showed longer survival than those with weight decrease (log-rank test, p = 0.0228).


Body weight changes after diagnosis strongly predicts survival in ALS, and weight gain after diagnosis may improve survival prognosis, particularly in female ALS patients.


Amyotrophic lateral sclerosis Body weight Survival Sex difference Nutritional intervention 



Amyotrophic lateral sclerosis


Revised Amyotrophic Lateral Sclerosis Functional Rating Scale


Body mass index


Body mass index decline rate


Forced vital capacity


Interquartile range


Percutaneous endoscopic gastrostomy


Progressive muscular atrophy




TAR DNA-binding protein-43



This study was supported by JSPS KAKENHI [Grant-in-Aid for Scientific Research (B) Nos. 25293449, 16H05583 and 16H03044] from the Ministry of Education, Culture, Sports, Science and Technology of Japan and by the Joint Program for ALS Research (2015–2018) from the Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.

Compliance with ethical standards

Conflicts of interest

Dr. Shimizu reports speaker honoraria from Tanabe Mitsubishi Pharma. The other authors declare that they have no conflict of interest.

Ethical approval

The study was approved by the ethics committee at Tokyo Metropolitan Neurological Hospital (TS-H29-048). All patients provided informed consent to participate in the study, in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.


  1. 1.
    Dupuis L, Pradat PF, Ludolph AC, Loeffler JP (2011) Energy metabolism in amyotrophic lateral sclerosis. Lancet Neurol 10:75–82. CrossRefGoogle Scholar
  2. 2.
    Holm T, Maier A, Wicks P et al (2013) Severe loss of appetite in amyotrophic lateral sclerosis patients: online self-assessment study. Interact J Med Res 2:e8. CrossRefGoogle Scholar
  3. 3.
    Shimizu T (2013) Sympathetic hyperactivity and sympathovagal imbalance in amyotrophic lateral sclerosis. Eur Neurol Rev 8:46–50. CrossRefGoogle Scholar
  4. 4.
    Bouteloup C, Desport JC, Clavelou P et al (2009) Hypermetabolism in ALS patients: an early and persistent phenomenon. J Neurol 256:1236–1242. CrossRefGoogle Scholar
  5. 5.
    Kasarskis EJ, Mendiondo MS, Matthews DE et al (2014) Estimating daily energy expenditure in individuals with amyotrophic lateral sclerosis. Am J Clin Nutr 99:792–803. CrossRefGoogle Scholar
  6. 6.
    Shimizu T, Ishikawa-Takata K, Sakata A et al (2017) The measurement and estimation of total energy expenditure in Japanese patients with ALS: a doubly labelled water method study. Amyotroph Lateral Scler Frontotemporal Degener 18:37–45. CrossRefGoogle Scholar
  7. 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 89:1016–1023. CrossRefGoogle Scholar
  8. 8.
    Desport JC, Preux PM, Truong TC et al (1999) Nutritional status is a prognostic factor for survival in ALS patients. Neurology 53:1059–1063CrossRefGoogle Scholar
  9. 9.
    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 82:628–634. CrossRefGoogle Scholar
  10. 10.
    Paganoni S, Deng J, Jaffa M et al (2011) Body mass index, not dyslipidemia, is an independent predictor of survival in amyotrophic lateral sclerosis. Muscle Nerve 44:20–24. CrossRefGoogle Scholar
  11. 11.
    Shimizu T, Nagaoka U, Nakayama Y et al (2012) Reduction rate of body mass index predicts prognosis for survival in amyotrophic lateral sclerosis: a multicenter study in Japan. Amyotroph Lateral Scler 13:363–366. CrossRefGoogle Scholar
  12. 12.
    McDonnell E, Schoenfeld D, Paganoni S, Atassi N (2017) Causal inference methods to study gastric tube use in amyotrophic lateral sclerosis. Neurology 89:1483–1489. CrossRefGoogle Scholar
  13. 13.
    Miller RG, Jackson CE, Kasarskis EJ et al (2009) Practice parameter update: the care of the patient with amyotrophic lateral sclerosis: drug, nutritional, and respiratory therapies (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 73:1218–1226. CrossRefGoogle Scholar
  14. 14.
    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 383:2065–2072. CrossRefGoogle Scholar
  15. 15.
    Dupuis L, Oudart H, Rene F et al (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 101:11159–11164. CrossRefGoogle Scholar
  16. 16.
    Dorst J, Dupuis L, Petri S et al (2015) Percutaneous endoscopic gastrostomy in amyotrophic lateral sclerosis: a prospective observational study. J Neurol 262:849–858. CrossRefGoogle Scholar
  17. 17.
    Fasano A, Fini N, Ferraro D et al (2017) Percutaneous endoscopic gastrostomy, body weight loss and survival in amyotrophic lateral sclerosis: a population-based registry study. Amyotroph Lateral Scler Frontotemporal Degener 18:233–242. CrossRefGoogle Scholar
  18. 18.
    Heritier AC, Janssens JP, Adler D et al (2015) Should patients with ALS gain weight during their follow-up? Nutrition 31:1368–1371. CrossRefGoogle Scholar
  19. 19.
    Kellogg J, Bottman L, Arra EJ et al (2018) Nutrition management methods effective in increasing weight, survival time and functional status in ALS patients: a systematic review. Amyotroph Lateral Scler Frontotemporal Degener 19:7–11. CrossRefGoogle Scholar
  20. 20.
    Shimizu T, Bokuda K, Kimura H et al (2018) Sensory cortex hyperexcitability predicts short survival in amyotrophic lateral sclerosis. Neurology 90:e1578–e1587. CrossRefGoogle Scholar
  21. 21.
    Brooks BR, Miller RG, Swash M et al (2000) El Escorial revisited: revised criteria for the diagnosis of amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Motor Neuron Disord 1:293–299CrossRefGoogle Scholar
  22. 22.
    de Carvalho M, Dengler R, Eisen A et al (2008) Electrodiagnostic criteria for diagnosis of ALS. Clin Neurophysiol 119:497–503. CrossRefGoogle Scholar
  23. 23.
    Kim WK, Liu X, Sandner J et al (2009) Study of 962 patients indicates progressive muscular atrophy is a form of ALS. Neurology 73:1686–1692. CrossRefGoogle Scholar
  24. 24.
    Cedarbaum JM, Stambler N, Malta E et al (1999) The ALSFRS-R: a revised ALS functional rating scale that incorporates assessments of respiratory function. BDNF ALS Study Group (Phase III). J Neurol Sci 169:13–21CrossRefGoogle Scholar
  25. 25.
    Logroscino G, Traynor BJ, Hardiman O et al (2008) Descriptive epidemiology of amyotrophic lateral sclerosis: new evidence and unsolved issues. J Neurol Neurosurg Psychiatry 79:6–11. CrossRefGoogle Scholar
  26. 26.
    Manjaly ZR, Scott KM, Abhinav K et al (2010) The sex ratio in amyotrophic lateral sclerosis: a population based study. Amyotroph Lateral Scler 11:439–442. CrossRefGoogle Scholar
  27. 27.
    de Jong S, Huisman M, Sutedja N et al L (2013) Endogenous female reproductive hormones and the risk of amyotrophic lateral sclerosis. J Neurol 260:507–512. CrossRefGoogle Scholar
  28. 28.
    Mauvais-Jarvis F, Clegg DJ, Hevener AL (2013) The role of estrogens in control of energy balance and glucose homeostasis. Endocr Rev 34:309–338. CrossRefGoogle Scholar
  29. 29.
    Vercruysse P, Sinniger J, El Oussini H et al (2016) Alterations in the hypothalamic melanocortin pathway in amyotrophic lateral sclerosis. Brain 139:1106–1122. CrossRefGoogle Scholar
  30. 30.
    Vercruysse P, Vieau D, Blum D et al (2018) Hypothalamic alterations in neurodegenerative diseases and their relation to abnormal energy metabolism. Front Mol Neurosci 11:2. CrossRefGoogle Scholar
  31. 31.
    Watanabe H, Atsuta N, Hirakawa A et al (2016) A rapid functional decline type of amyotrophic lateral sclerosis is linked to low expression of TTN. J Neurol Neurosurg Psychiatry 87:851–858. CrossRefGoogle Scholar
  32. 32.
    Jesus P, Fayemendy P, Nicol M et al (2018) Hypermetabolism is a deleterious prognostic factor in patients with amyotrophic lateral sclerosis. Eur J Neurol 25:97–104. CrossRefGoogle Scholar
  33. 33.
    Gorges M, Vercruysse P, Muller HP et al (2017) Hypothalamic atrophy is related to body mass index and age at onset in amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry 88:1033–1041. CrossRefGoogle Scholar
  34. 34.
    Scherz B, Rabl R, Flunkert S et al (2018) mTh1 driven expression of hTDP-43 results in typical ALS/FTLD neuropathological symptoms. PLoS One 13:e0197674. CrossRefGoogle Scholar
  35. 35.
    Cykowski MD, Takei H, Schulz PE et al (2014) TDP-43 pathology in the basal forebrain and hypothalamus of patients with amyotrophic lateral sclerosis. Acta Neuropathol Commun 2:171. CrossRefGoogle Scholar
  36. 36.
    Ahmed RM, Caga J, Devenney E et al (2016) Cognition and eating behavior in amyotrophic lateral sclerosis: effect on survival. J Neurol 263:1593–1603. CrossRefGoogle Scholar
  37. 37.
    Ahmed RM, Irish M, Piguet O et al (2016) Amyotrophic lateral sclerosis and frontotemporal dementia: distinct and overlapping changes in eating behaviour and metabolism. Lancet Neurol 15:332–342. CrossRefGoogle Scholar
  38. 38.
    Jesus P, Marin B, Fayemendy P et al (2018) Resting energy expenditure equations in amyotrophic lateral sclerosis, creation of an ALS-specific equation. Clin Nutr (early online)Google Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of NeurologyTokyo Metropolitan Neurological HospitalFuchuJapan
  2. 2.ALS Nursing Care ProjectTokyo Metropolitan Institute of Medical ScienceTokyoJapan
  3. 3.Department of Nutritional EducationNational Institute of Biomedical Innovation, Health and NutritionTokyoJapan

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