Skip to main content

Advertisement

SpringerLink
Log in

Epidemiology of amyotrophic lateral sclerosis in Southern Germany

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

Abstract

The objective of this study is to determine the current distribution of clinical phenotypes and to estimate future trends of ALS incidence in Western societies. We report on a clinical-epidemiological registry with a capture–recapture rate of >80% and population-based case–control study in ALS patients in South Western Germany. 1163 incidents of ALS were registered. Clinical and neuropsychological data were prospectively collected from 699 cases. The mean age at onset was 66.6 (SD = 11.6) years in prospective cases (N = 699). The site of onset was more frequently bulbar (34.1%) than lumbosacral (30.7%), cervical (27.0%), or thoracic (3.1%). Cognitive deficits (ranging from 27.5 to 42.1%, depending on the screening instrument) and behavioral changes (29%) were frequently detected. The incidence rate dropped markedly after 79 years of age, and bulbar onset as well as cognitive impairment were more frequent in ALS cases >75 years. The mean survival time of ALS cases from first paresis was 31 months. The age-standardized incidence rate (ASR) of ALS in 2012/2013 was found to be 2.4 (95% CI 2.2–2.7) per 100,000 person-years (resulting in an ASR of 3.1/100,000 with 100% coverage). Based on the predicted age distribution of the German population, the incidence of ALS was estimated to be 4.5/100,000 for men and 3.3/100,000 for women in the year 2050. ALS prevalence will rise to about 9.2–9.8/100,000 person-years in Germany in 2050. An increased proportion of patients with bulbar onset and/or cognitive deficits can be used as basic epidemiologic data on ALS for future health care decisions.

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
Fig. 4

Similar content being viewed by others

References

  1. Oliver D, Borasio GD, Voltz R et al (2014) The development of a concensus paper on palliative care in neurology: the implications for ALS care. Amyotr Lateral Scler Frontotemp Degener 15:117–118

    Google Scholar 

  2. Braak H, Brettschneider J, Ludolph AC, Lee VM, Trojanowski JQ, Del Tredici K (2013) Amyotrophic lateral sclerosis—a model of corticofugal axonal spread. Nat Rev Neurol 9(12):708–714

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Chiò A, Traynor BJ (2015) Motor neuron disease in 2014. Biomarkers for ALS–in search of the promised land. Nat Rev Neurol 11(2):72–74

    Article  PubMed  Google Scholar 

  4. Ludolph A, Drory V, Hardiman O et al (2015) A revision of the El Escorial criteria. Amyotroph Lateral Scler Frontotemporal Degener 16(5–6):291

    Article  PubMed  Google Scholar 

  5. Elamin M, Bede P, Byrne S et al (2013) Cognitive changes predict functional decline in ALS: a population-based longitudinal study. Neurology 80(17):1590–1597

    Article  PubMed  Google Scholar 

  6. Robinson KM, Lacey SC, Grugan P, Glosser G, Grossman M, McCluskey LF (2006) Cognitive functioning in sporadic amyotrophic lateral sclerosis: a six month longitudinal study. J Neurol Neurosurg Psychiatry 77:668–670

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  PubMed  PubMed Central  Google Scholar 

  8. 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 

  9. Uenal H, Rosenbohm A, Kufeldt J et al (2014) Incidence and geographical variation of amyotrophic lateral sclerosis (ALS) in Southern Germany—Completeness of the ALS Registry Swabia. PLoS One 9(4):e93932. doi:10.1371/journal.pone.0093932

    Article  PubMed  PubMed Central  Google Scholar 

  10. Brooks BR (1994) El Escorial World Federation of Neurology criteria for the diagnosis of amyotrophic lateral sclerosis: Subcommittee on Motor Neuron Diseases/Amyotrophic Lateral Sclerosis of the World Federation of Neurology Research Group on Neuromuscular Diseases and the El Escorial Clinical Limits of Amyotrophic LateralSclerosis workshop contributors. J Neurol Sci 124(suppl):96e107

    Google Scholar 

  11. Brooks BR, Miller RG, Swash M, Munsat TL (2000) World Federation of Neurology Research Group on Motor Neuron Diseases. El Escorial revisited: revised criteria for the diagnosis of amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Motor Neuron Disord 1(5):293–299

    Article  CAS  PubMed  Google Scholar 

  12. Nagel G, Unal H, Rosenbohm A, Ludolph AC, Rothenbacher D, 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 Neurol. 17(13):22

    Article  Google Scholar 

  13. 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 

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

    Article  CAS  PubMed  Google Scholar 

  15. Lulé D, Burkhardt C, Abdulla S et al (2015) The Edinburgh Cognitive and Behavioural Amyotrophic Lateral Sclerosis Screen: a cross-sectional comparison of established screening tools in a German-Swiss population. The Edinburgh Cognitive and Behavioural Amyotrophic Lateral Sclerosis Screen: a cross-sectional comparison of established screening tools in a German-Swiss population. Amyotroph Lateral Scler Frontotemporal Degener 16(1–2):16–23

    Article  PubMed  Google Scholar 

  16. Statistisches Bundesamt (2015) (ed.) Bevölkerung Deutschlands bis 2060—13. koordinierte Bevölkerungsvorausberechnung, Wiesbaden. https://www.destatis.de/DE/Publikationen/Thematisch/Bevoelkerung/VorausberechnungBevoelkerung/BevoelkerungDeutschland2060.html

  17. Wolf J, Wöhrle JC, Palm F et al (2014) Incidence of amyotrophic lateral sclerosis in Rhineland-Palatinate, Germany. Amyotroph Lateral Scler Frontotemporal Degener 15(3–4):269–274

    Article  PubMed  Google Scholar 

  18. Wolf J, Safer A, Wöhrle JC et al (2014) Variability and prognostic relevance of different phenotypes in amyotrophic lateral sclerosis—data from a population-based registry. Variability and prognostic relevance of different phenotypes in amyotrophic lateral sclerosis—data from a population-based registry. J Neurol Sci 345(1–2):164–167

    Article  PubMed  Google Scholar 

  19. O’Toole O, Traynor BJ, Brennan P et al (2008) Epidemiology and clinical features of amyotrophic lateral sclerosis in Ireland between 1995 and 2004. J Neurol Neurosurg Psychiatry 79(1):30–32

    Article  PubMed  Google Scholar 

  20. Marin B, Gil J, Preux PM, Funalot B, Couratier P (2009) Incidence of amyotrophic lateral sclerosis in the Limousin region of France, 1997–2007. Amyotroph Lateral Scler 10(4):216–220

    Article  PubMed  Google Scholar 

  21. Huisman MH, de Jong SW, van Doormaal PT et al (2011) Population-based epidemiology of amyotrophic lateral sclerosis using capture-recapture methodology. J Neurol Neurosurg Psychiatry 82(10):1165–1170

    Article  PubMed  Google Scholar 

  22. Chio A, Calvo A, Moglia C, Mazzini L, Mora G (2011) PARALS study group. Phenotypic heterogeneity of amyotrophic lateral sclerosis: a population based study. J Neurol Neurosurg Psychiatry 82(7):740–746

    Article  PubMed  Google Scholar 

  23. Forbes RB, Colville S, Parratt J, Swingler RJ (2007) The incidence of motor neuron disease in Scotland. J Neurol 254(7):866–869

    Article  PubMed  Google Scholar 

  24. Al-Chalabi A, Hardiman O (2013) The epidemiology of ALS: a conspiracy of genes, environment and time. Nat Rev Neurol 9(11):617–628

    Article  CAS  PubMed  Google Scholar 

  25. Kiernan MC, Vucic S, Cheah BC et al (2011) Amyotrophic lateral sclerosis. Lancet 377(9769):942–955

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  27. Fang F, Valdimarsdottir U, Bellocco R et al (2009) Amyotrophic lateral sclerosis in Sweden, 1991–2005. Arch Neurol 66(4):515–519

    Article  PubMed  Google Scholar 

  28. Neilson S, Robinson I, Alperovitch A (1994) Rising amyotrophic lateral sclerosis mortality in France 1968–1990: increased life expectancy and inter-disease competition as an explanation. J Neurol 241(7):448–455

    Article  CAS  PubMed  Google Scholar 

  29. Maasilta P, Jokelainen M, Loytonen M, Sabel CE, Gatrell AC (2001) Mortality from amyotrophic lateral sclerosis in Finland, 1986–1995. Acta Neurol Scand 104(4):232–235

    Article  CAS  PubMed  Google Scholar 

  30. Piemonte and Valle d’Aosta Register for Amyotrophic Lateral Sclerosis (PARALS) (2001) Incidence of ALS in Italy: evidence for a uniform frequency in Western countries. Neurology 56(2):239–244

    Google Scholar 

  31. Pedersen JK, Engholm G, Skytthe A, Christensen K (2016) Academy of Geriatric Cancer Research (AgeCare) Cancer and aging: epidemiology and methodological challenges. Acta Oncol 55(supp1):7–12

    Article  PubMed  PubMed Central  Google Scholar 

  32. 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(1):6–11

    Article  CAS  PubMed  Google Scholar 

  33. Blasco H, Guennoc A-M, Veyrat-Durebex C et al (2012) Amyotrophic lateral sclerosis: a hormonal condition? Amyotroph Lateral Scler 13(6):585–588

    Article  PubMed  Google Scholar 

  34. Paganoni S, Macklin EA, Lee A et al (2014) Diagnostic timelines and delays in diagnosing amyotrophic lateral sclerosis (ALS). Amyotroph Lateral Scler Frontotemporal Degener 15(5–6):453–456

    Article  PubMed  PubMed Central  Google Scholar 

  35. Millul A, Beghi E, Logroscino G, Micheli A, Vitelli E, Zardi A (2005) Survival of patients with amyotrophic lateral sclerosis in a population-based registry. Neuroepidemiology 25(3):114–119

    Article  CAS  PubMed  Google Scholar 

  36. Del Aguila MA, Longstreth WT, McGuire V et al (2003) Prognosis in amyotrophic lateral sclerosis. A population based study. Neurology 60(5):813–819

    PubMed  Google Scholar 

  37. Watermeyer TJ, Brown RG, Sidle KC et al (2015) Impact of disease, cognitive and behavioural factors on caregiver outcome in amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener 16(5–6):316–323

    Article  PubMed  Google Scholar 

  38. Arthur KC, Calvo A, Proce TR et al (2016) Projected increase in amyotrophic lateral sclerosis from 2015 to 2040. Nat Commun 11(7):12408. doi:10.1038/ncomms12408

    Article  Google Scholar 

Download references

Acknowledgements

We thank P. Weydt and L. Dupuis for critical reading of the manuscript. We thank the study nurses I. Kraft-Oberbeck, N. Lämmle, and I. Dobias for their excellent field work, and the medical documentation team T. Brehme, S. Enderle, G. Feike, and B. Och for their excellent technical support. This study was supported by the German Research Council (Deutsche Forschungsgemeinschaft, DFG Grant Number LU 336/15-1).

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.

Burkhard, A., 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 Neurology.

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

Authors and Affiliations

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

    Angela Rosenbohm, Dorothée Lulé & Albert C. Ludolph

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

    Raphael S. Peter, Siegfried Erhardt, Dietrich Rothenbacher & Gabriele Nagel

Authors
  1. Angela Rosenbohm
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Raphael S. Peter
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Siegfried Erhardt
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Dorothée Lulé
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Dietrich Rothenbacher
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Albert C. Ludolph
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Gabriele Nagel
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

The ALS Registry 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
  • , A. Burkhard
  • , 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 author

Correspondence to Albert C. Ludolph.

Ethics declarations

Conflicts 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 the ALS Registry Swabia. The ALS Registry Swabia was approved by the local ethics committee of the University of Ulm (no. 11/10).

Additional information

The members of the ALS registry Study Group are listed in Acknowledgements.

Electronic supplementary material

Below is the link to the electronic supplementary material.

415_2017_8413_MOESM1_ESM.tif

Supplemental Figure. County-specific incidence rates in the year 2009/2010 and 2012/2013 in the Swabian area (TIFF 1531 kb)

Supplementary material 2 (DOCX 15 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Rosenbohm, A., Peter, R.S., Erhardt, S. et al. Epidemiology of amyotrophic lateral sclerosis in Southern Germany. J Neurol 264, 749–757 (2017). https://doi.org/10.1007/s00415-017-8413-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00415-017-8413-3

Keywords

Search

Navigation