Skip to main content

Advertisement

SpringerLink
Log in

Phenotypic differences of amyotrophic lateral sclerosis (ALS) in China and Germany

  • Original Communication
  • Published:
Journal of Neurology Aims and scope Submit manuscript

Abstract

Objective

The aim of this study is to explore phenotypical differences of amyotrophic lateral sclerosis (ALS) between two cohorts from Germany and China.

Methods

Registry-based studies of ALS were conducted in South-West Germany from 2010 to 2014 and an ALS clinic in Beijing from 2013 to 2016, respectively. Demographic and clinical features of 663 German and 276 Chinese ALS patients were collected and compared.

Results

Mean age-at-onset was higher in German than in Chinese ALS patients [66.6 years (95% CI 65.7, 67.5) vs. 53.2 years (95% CI 52.0, 54.5)]. Age distribution of ALS patients peaked around 70–74 years in Germany and 50–54 years in China. Bulbar onset was more prevalent among German than among Chinese patients (35.9 vs. 22.8%). Diagnostic delay was higher in the Chinese than in the German study sample (12 vs. 5 months). Cognitive deficits were more pronounced in the Chinese cohort. Both cohorts differed in smoking habits, prevalence of diabetes and in body mass index (BMI).

Conclusions

The apparent discrepancies between German and Chinese ALS patients (age at onset, gender distribution, bulbar forms, cognitive dysfunction, risk factors) reveal a quite different clinical phenotype in China, maybe due to socioeconomic status, environmental factors or genetic background. The observed differences in phenotype need to be pursued by further epidemiological studies on environmental and genetic risk factors.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Chiò A, Logroscino G, Traynor BJ et al (2013) Global epidemiology of amyotrophic lateral sclerosis: a systematic review of the published literature. Neuroepidemiology 41:118–130

    Article  PubMed  PubMed Central  Google Scholar 

  2. Traxinger K, Kelly C, Johnson BA, Lyles RH, Glass JD (2013) Prognosis and epidemiology of amyotrophic lateral sclerosis: analysis of a clinic population, 1997–2011. Neurol Clin Pract 3:313–320

    Article  PubMed  PubMed Central  Google Scholar 

  3. Atsuta N, Watanabe H, Ito M et al (2009) Research Committee on the Neurodegenerative Diseases of Japan. Age at onset influences on wide-ranged clinical features of sporadic amyotrophic lateral sclerosis. J Neurol Sci 276:163–169

    Article  PubMed  Google Scholar 

  4. Al-Chalabi A, Hardiman O (2013) The epidemiology of ALS: a conspiracy of genes, environment and time. Nat Rev Neurol 9:617–628

    Article  CAS  PubMed  Google Scholar 

  5. Rosenbohm A, Peter RS, Erhardt S, Lulé D, Rothenbacher D, Ludolph AC (2017) Nagel G and the ALS Registry Study Group. Epidemiology of amyotrophic lateral sclerosis in Southern Germany. J Neurol 264:749–757

    Article  PubMed  Google Scholar 

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

    Article  Google Scholar 

  7. Majounie E, Renton AE, Mok K et al (2012) Frequency of the C9orf72 hexanucleotide repeat expansion in patients with amyotrophic lateral sclerosis and frontotemporal dementia: a cross-sectional study. Lancet Neurol 11:323–330

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Zou ZY, Zhou ZR, Che CH, Liu CY, He RL, Huang HP (2017) Genetic epidemiology of amyotrophic lateral sclerosis: a systematic review and meta-analysis. J Neurol Neurosurg Psychiatry. https://doi.org/10.1136/jnnp-2016-315018

    PubMed  Google Scholar 

  9. Körner S, Kollewe K, Fahlbusch M et al (2011) Onset and spreading patterns of upper and lower motor neuron symptoms in amyotrophic lateral sclerosis. Muscle Nerve 43:636–642

    Article  PubMed  Google Scholar 

  10. Wolf J, Woehrle JC, Palm F et al (2014) Incidence of amyotrophic lateral sclerosis in Rhineland-Palatinate, Germany. Amyotroph Lateral Scler Frontotemp Degener 15:269–274

    Article  Google Scholar 

  11. Wei Q, Chen X, Zheng Z, Guo X, Huang R, Cao B, Zeng Y, Shang H (2015) The predictors of survival in Chinese amyotrophic lateral sclerosis patients. Amyotroph Lateral Scler Frontotemp Degener 16:237–244

    Article  CAS  Google Scholar 

  12. Cui F, Liu M, Chen Y, Huang X et al (2014) Epidemiological characteristics of motor neuron disease in Chinese patients. Acta Neurol Scand 130:111–117

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  14. Fang DF, Zhang SS, Guo XY et al (2009) Clinical and genetic features of patients with sporadic amyotrophic lateral sclerosis in south-west China. Amyotroph Lateral Scler 10:350–354

    Article  CAS  PubMed  Google Scholar 

  15. Chen D, Shen L, Wang L et al (2007) Association of polymorphisms in vascular endothelial growth factor gene with the age of onset of amyotrophic lateral sclerosis. Amyotr Lateral Scler 8:144–149

    Article  CAS  Google Scholar 

  16. Qiao L, Li X, Liu M, Cui L (2014) Nature history of amyotrophic lateral sclerosis. Zhonghua Yi Xue Za Zhi 94:674–677

    PubMed  Google Scholar 

  17. Goh KJ, Tian S, Shahrizaila N, Ng CW, Tan CT (2011) Survival and prognostic factors of motor neuron disease in a multi-ethnic Asian population. Amyotroph Lateral Scler 12:124–129

    Article  PubMed  Google Scholar 

  18. Nalini A, Thennarasu K, Gourie-Devi M, Shenoy S, Kulshreshtha D (2008) Clinical characteristics and survival pattern of 1,153 patients with amyotrophic lateral sclerosis: experience over 30 years from India. J Neurol Sci 272:60–70

    Article  CAS  PubMed  Google Scholar 

  19. Kihira T, Yoshida S, Okamoto K et al (2008) Survival rate of patients with amyotrophic lateral sclerosis in Wakayama Prefecture, Japan, 1966–2005. J Neurol Sci 268:95–101

    Article  PubMed  Google Scholar 

  20. Nagel G, Uenal H, Rosenbohm A, Ludolph AC, Rothenbacher D and the ALS Registry Study Group (2013) Implementation of a population-based epidemiological rare disease registry: study protocol of the amyotrophic lateral sclerosis (ALS)—registry Swabia. BMC Neurology 13:22

    Article  PubMed  PubMed Central  Google Scholar 

  21. Brooks BR, Miller RG, Swash M, Munsat TL, World Federation of Neurology Research Group on Motor Neuron Diseases (2000) El Escorial revisited: revised criteria for the diagnosis of amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Motor Neuron Disord 1:293–299

    Article  CAS  PubMed  Google Scholar 

  22. Nasreddine ZS, Phillips NA, Bédirian V et al (2005) The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc 53(4):695–699

    Article  PubMed  Google Scholar 

  23. Dubois B, Litvan I (2000) The FAB: a frontal assessment battery at bedside. Neurology 55(11):1621–1626

    Article  CAS  PubMed  Google Scholar 

  24. Logroscino G, Traynor BJ, Hardiman O et al (2010) Incidence of amyotrophic lateral sclerosis in Europe. J Neurol Neurosurg Psychiatry 81(4):385–390

    Article  PubMed  Google Scholar 

  25. Chiò A, Terreni A, Cucatto A et al (2001) Piemonte and Valle d’Aosta Register for Amyotrophic Lateral Sclerosis (PARALS). Incidence of ALS in Italy: evidence for a uniform frequency in Western countries. Neurology 56(2):239–244

    Google Scholar 

  26. Statistisches Bundesamt/Statistics Germany https://www.destatis.de/DE/ZahlenFakten/GesellschaftStaat/Bevoelkerung/Sterbefaelle/Tabellen/LebenserwartungDeutschland.html Accessed 08 2014

  27. WHO Global Health Observatory Data Repository. http://apps.who.int/gho/data/theme=country&vid=6400 Accessed 8 2014

  28. Shahrizaila N, Sobue G, Kuwabara S, Kim SH, Birks C, Fan DS, Bae JS, Hu CJ, Gourie-Devi M, Noto Y, Shibuya K, Goh KJ, Kaji R, Tsai CP, Cui L, Talman P, Henderson RD, Vucic S, Kiernan MC (2016) Amyotrophic lateral sclerosis and motor neuron syndromes in Asia. J Neurol Neurosurg Psychiatry 87(8):821–830

    Article  CAS  PubMed  Google Scholar 

  29. Zou ZY, Liu MS, Li XG, Cui LY (2016) The distinctive genetic architecture of ALS in mainland China. J Neurol Neurosurg Psychiatry 87(8):906–907

    Article  PubMed  Google Scholar 

  30. Kahana E, Zilber N (1984) Changes in the incidence of amyotrophic lateral sclerosis in Israel. Arch Neurol 41:157–160

    Article  CAS  PubMed  Google Scholar 

  31. Shimohata T, Yanagawa K, Tanaka K, Nishizawa M (2006) Longitudinal analysis of age at onset and initial symptoms in patients with amyotrophic lateral sclerosis. Rinsho Shinkeigtu 46:377–380

    Google Scholar 

  32. Sorensen EJ, Stalker AP, Kurland LT, Windebank AJ (2002) Amyotrophic lateral sclerosis in Olmsted County, Minnesota, 1925–1998. Neurology 59:280–282

    Article  Google Scholar 

  33. Furuta N, Makioka K, Fujita Y, Okamoto K (2013) Changes in the clinical features of amyotrophic lateral sclerosis in rural Japan. Intern Med 52:1691–1696

    Article  PubMed  Google Scholar 

  34. Chiò A, Logroscino G, Hardiman O, Swingler R, Mitchell D, Beghi E et al (2009) Prognostic factors in ALS: a critical review. Amyotroph Lateral Scler 10(5–6):310–323

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank David Ewert for excellent support (figures).

This work was supported by the Deutsche Forschungsgemeinschaft (main number 577 631, project LU 336/15-1) and by the Sino-German Center (no. GZ 867). Furthermore the study was supported by the Bundesministerium für Bildung und Forschung (BMBF MND-Net) and the EU Joint Programme for Neurodegenerative Disease Research (JPND; NEEDSinALS).

The following cooperation partners provided data for the ALS registry Swabia. The ALS registry Study Group: Andres F., Kreiskliniken Reutlingen, Department of Neurology; Arnold G., Klinikum Sindelfingen-Böblingen, Department of Neurology; Asshauer I., Klinikum Friedrichshafen, Department of Psychiatry and Psychotherapy; Baezner H., Bürgerhospital Stuttgart, Department of Neurology; Baier H., ZFP Südwürttemberg Weissenau, Department of Epileptology; Beattie J., Ostalb-Klinikum Aalen, Department of Neurology; Becker T., University of Ulm, Klinikum Günzburg, Department of Psychiatry and Psychotherapy II; Behne F., ZFP Südwürttemberg Weissenau, Department of Epileptology; Bengel D., Oberschwabenklinik Ravensburg, Department of Neurology; Boertlein A., Bürgerhospital Stuttgart, Department of Neurology; Bracknies, V., Klinik Dietenbronn, Department of Neurology; Broer R., Klinikum am Weissenhof, Weinsberg, Department of Psychiatry and Psychotherapy; Alber, B., Klinikum Günzburg, Department of Neurology; Connemann B., University of Ulm, Department of Psychiatry and Psychotherapy III; Dempewolf S., Klinikum Ludwigsburg, Department of Neurology; Dettmers C., Schmieder Kliniken Konstanz, Department of Neurology; Dieterich M., LMU München, Department of Neurology; Etzersdorfer E., Furtbachkrankenhaus Stuttgart, Department of Psychiatry and Psychotherapy; Freund, W., private practice, Biberach; Gersner T., ZfP Zwiefalten, Department of Psychiatry and Psychotherapy; Gold H.-J., Klinikum am Gesundbrunnen Heilbronn, Department of Neurology; Hacke, W., University of Heidelberg, Department of Neurology; Hamann G., Klinikum Günzburg, Department of Neurology; Hecht M., Bezirkskrankenhaus Kaufbeuren, Department of Neurology; Heimbach B., University of Freiburg, Department of Neurology; Hemmer B., TU Muenchen, Department of Neurology; Hendrich C., Klinikum Friedrichshafen, Department of Neurology; Herting B., Diakonie-Klinikum Schwäbisch Hall, Department of Neurology; Huber R., Klinikum Friedrichshafen, Department of Neurology; Huber-Hartmann K., Kliniken Landkreis Heidenheim, Department of Neurology; Hülser P.-J., Fachklinik Wangen, Department of Neurology; Jüttler E., Ostalb-Klinikum Aalen, Department of Neurology; Kammerer-Ciernioch J., Klinikum am Weissenhof, Weinsberg, Department of Psychiatry and Psychotherapy; Kaspar A., Oberschwabenklinik Ravensburg, Department of Neurology; Kern R., Klinikum Kempten, Department of Neurology; Kimmig H., Kliniken Schwenningen, Department of Neurology; Klebe, S., University of Würzburg, Department of Neurology; Kloetzsch C., Schmieder Kliniken Allensbach, Department of Neurology; Klopstock, T., LMU München, Department of Neurology; Kohler, A., Klinikum am Gesundbrunnen Heilbronn, Department of Neurology; Kuethmann A., Bezirkskrankenhaus Memmingen, Department of Psychiatry and Psychotherapy; Lewis D., Marienhospital Stuttgart, Department of Neurology; Lichy C., Klinikum Memmingen, Department of Neurology; Lindner A., Marienhospital Stuttgart, Department of Neurology; Mäurer M., Caritas Krankenhaus Bad Mergentheim, Department of; Maier-Janson W., private practice, Ravensburg; Metrikat J., Bundeswehrkrankenhaus Ulm, Department of Neurology; Meudt O., Klinikum Memmingen, Department of Neurology; Meyer A., Weissenau, Department of Neurology; Müller vom Hagen J., University of Tuebingen, Department of Neurology; Naegele A., Christophsbad Göppingen, Department of Neurology; Naumann M., Klinikum Augsburg, Department of Neurology ; Neher K.-D., Vinzenz von Paul Hospital, Rottweil, Department of Neurology; Neuhaus O., Kliniken Landkreis Sigmaringen, Department of Neurology; Neusch C., private practice, Singen; Niehaus L., Klinikum Winnenden, Department of Neurology; Opherk C., Klinikum am Gesundbrunnen Heilbronn, Department of Neurology; Raape J., ZFP Südwürttemberg Weissenau, Department od Neurology; Ratzka P., Klinikum Augsburg, Department of Neurology; Rettenmayr C., Klinikum Esslingen, Department of Neurology; Riepe MW., Klinikum Günzburg, Department of Gerontopsychiatry; Rothmeier J., ZFP Südwürttemberg Weissenau, Department of Neurology; Sabolek M., Klinik Biberach, Department of Neurology; Schabet M., Klinikum Ludwigsburg, Department of Neurology; Schell C., Kreiskliniken Reutlingen, Department of Neurology; Schlipf T., Klinikum Winnenden, Department of Psychiatry and Psychotherapy; Schmauss M., Bezirkskrankenhaus Augsburg, Department of Psychiatry and Psychotherapy; Schoels L., University of Tübingen, Department of Neurology; Schuetz K., Kliniken Schwenningen, Department of Neurology; Schweigert B., Caritas Krankenhaus Bad Mergentheim, Department of Neurology; Sommer N., Christophsbad Göppingen, Department of Neurology; Sperber W., Kliniken Esslingen, Department of Neurology; Steber C., Bezirkskrankenhaus Augsburg, Department of Psychiatry and Psychotherapy; Steber R., Bezirkskrankenhaus Memmingen, Department of Psychiatry and Psychotherapy; Stroick M., Klinikum Memmingen, Department of Neurology; Synofzik, M., University of Tübingen, Deartment of Neurology; Trottenberg T., Klinikum Winnenden, Department of Neurology; Tumani H., Klinikum Dietenbronn, Department of Neurology; Wahl C., Klinikum Kempten, Department of Neurology; Weber F., Bundeswehrkrankenhaus Ulm, Department of Neurology; Weiler M., University of Heidelberg, Department of Neurology; Weiller C., University of Freiburg, Department of Neurology; Wessig C., University of Würzburg, Department of Neurology; Winkler A., TU München, Department of Neurology.

Author information

Author notes

    Authors and Affiliations

    1. Department of Neurology, Ulm University Clinic, Oberer Eselsberg 45, Ulm, 89081, Germany

      Angela Rosenbohm, Jan Kassubek, Dorothée Lulé & Albert C. Ludolph

    2. Institute of Epidemiology and Medical Biometry, Ulm University, Helmholtzstr. 22, Ulm, 89081, Germany

      Gabriele Nagel, Raphael S. Peter & Dietrich Rothenbacher

    3. Department of Neurology, Peking Union Medical College Hospital, Beijing, China

      Mingsheng Liu, Bo Cui, Xiaoguang Li & Liying Cui

    4. Neuroscience Center, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China

      Liying Cui

    Author notes

    1. The members of ALS Registry Swabia Study Group are moved to acknowledgement.

      • Angela Rosenbohm and Mingsheng Liu contributed equally.

        Authors
        1. Angela Rosenbohm
          View author publications

          You can also search for this author in PubMed Google Scholar

        2. Mingsheng Liu
          View author publications

          You can also search for this author in PubMed Google Scholar

        3. Gabriele Nagel
          View author publications

          You can also search for this author in PubMed Google Scholar

        4. Raphael S. Peter
          View author publications

          You can also search for this author in PubMed Google Scholar

        5. Bo Cui
          View author publications

          You can also search for this author in PubMed Google Scholar

        6. Xiaoguang Li
          View author publications

          You can also search for this author in PubMed Google Scholar

        7. Jan Kassubek
          View author publications

          You can also search for this author in PubMed Google Scholar

        8. Dietrich Rothenbacher
          View author publications

          You can also search for this author in PubMed Google Scholar

        9. Dorothée Lulé
          View author publications

          You can also search for this author in PubMed Google Scholar

        10. Liying Cui
          View author publications

          You can also search for this author in PubMed Google Scholar

        11. Albert C. Ludolph
          View author publications

          You can also search for this author in PubMed Google Scholar

        Consortia

        For the ALS Registry Swabia Study Group

        • F. Andres
        • , G. Arnold
        • , I. Asshauer
        • , H. Baezner
        • , H. Baier
        • , J. Beattie
        • , T. Becker
        • , F. Behne
        • , D. Bengel
        • , A. Boertlein
        • , V. Bracknies
        • , R. Broer
        • , B. Alber
        • , B. Connemann
        • , S. Dempewolf
        • , C. Dettmers
        • , M. Dieterich
        • , E. Etzersdorfer
        • , W. Freund
        • , T. Gersner
        • , H.-J. Gold
        • , W. Hacke
        • , G. Hamann
        • , M. Hecht
        • , B. Heimbach
        • , B. Hemmer
        • , C. Hendrich
        • , B. Herting
        • , R. Huber
        • , K. Huber-Hartmann
        • , P.-J. Hülser
        • , E. Jüttler
        • , J. Kammerer-Ciernioch
        • , A. Kaspar
        • , R. Kern
        • , H. Kimmig
        • , S. Klebe
        • , C. Kloetzsch
        • , T. Klopstock
        • , A. Kohler
        • , A. Kuethmann
        • , D. Lewis
        • , C. Lichy
        • , A. Lindner
        • , M. Mäurer
        • , W. Maier-Janson
        • , J. Metrikat
        • , O. Meudt
        • , A. Meyer
        • , J. Müller vom Hagen
        • , A. Naegele
        • , M. Naumann
        • , K.-D. Neher
        • , O. Neuhaus
        • , C. Neusch
        • , L. Niehaus
        • , C. Opherk
        • , J. Raape
        • , P. Ratzka
        • , C. Rettenmayr
        • , M. W. Riepe
        • , J. Rothmeier
        • , M. Sabolek
        • , M. Schabet
        • , C. Schell
        • , T. Schlipf
        • , M. Schmauss
        • , L. Schoels
        • , K. Schuetz
        • , B. Schweigert
        • , N. Sommer
        • , W. Sperber
        • , C. Steber
        • , R. Steber
        • , M. Stroick
        • , M. Synofzik
        • , T. Trottenberg
        • , H. Tumani
        • , C. Wahl
        • , F. Weber
        • , M. Weiler
        • , C. Weiller
        • , C. Wessig
        •  & A. Winkler

        Corresponding authors

        Correspondence to Liying Cui or Albert C. Ludolph.

        Ethics declarations

        Conflict of interest

        The authors declare that they have no conflict of interest.

        Ethical standards

        All persons gave their informed consent prior to their inclusion in registries. The registries were approved by the Ethics Committee of Ulm University (reference 11/10) and the Research Ethics Committee of the Peking Union Medical College Hospital (PUMCH), respectively. Patients were included after informed written consent had been obtained, as set forth by the Declaration of Helsinki (WMA, 1964–2014).

        Additional information

        The members of ALS Registry Swabia Study Group are moved to acknowledgement.

        Rights and permissions

        Reprints and permissions

        About this article

        Check for updates. Verify currency and authenticity via CrossMark

        Cite this article

        Rosenbohm, A., Liu, M., Nagel, G. et al. Phenotypic differences of amyotrophic lateral sclerosis (ALS) in China and Germany. J Neurol 265, 774–782 (2018). https://doi.org/10.1007/s00415-018-8735-9

        Download citation

        • Received:

        • Revised:

        • Accepted:

        • Published:

        • Issue Date:

        • DOI: https://doi.org/10.1007/s00415-018-8735-9

        Keywords

        Search

        Navigation