Download PDF
Nervenheilkunde 2017; 36(01/02): 28-32
DOI: 10.1055/s-0038-1635141
Muskelerkrankungen
Schattauer GmbH

Neues zur Amyotrophen Lateralsklerose

Amyotrophic lateral sclerosis
J. Dorst
1   Abteilung Neurologie; Universität Ulm
,
A. C. Ludolph
1   Abteilung Neurologie; Universität Ulm
› Author Affiliations
Further Information

Publication History

eingegangen am: 10 October 2016

angenommen am: 20 October 2016

Publication Date:
03 February 2018 (online)

Also available at
    Permissions and Reprints

Zusammenfassung

Auch wenn die Therapieoptionen der Amyotrophen Lateralsklerose (ALS) nach wie vor unbefriedigend sind und Riluzol das einzige Medikament ist, das den Krankheitsverlauf beeinflusst, so gibt es doch vielfältige neue Forschungsergebnisse hinsichtlich Genetik, Biomarkern und Pathogenese, welche auf die Entwicklung neuer Therapieansätze hoffen lassen. Zudem gibt es Fortschritte auf dem Gebiet der symptomatischen Therapie. In diesem Artikel sollen die wichtigsten Erkenntnisse der ALS-Forschung der vergangenen Jahre zusammengefasst werden.

Summary

Although therapy options for amyotrophic lateral sclerosis are still insufficient with riluzole being the only drug directly influencing the curse of the disease, there are plenty of new research results including genetics, biomarkers, and pathogenesis, which might enable the development of new therapies in the future. Furthermore, there are advances in symptomatic treatment of ALS. In this article we summarize the most important findings in ALS research over recent years.

Schlüsselwörter

Amyotrophe Lateralsklerose - Therapie - Pathogenese - Genetik - Biomarker

Keywords

Amyotrophic lateral sclerosis - therapy - pathogenesis - genetics - biomarkers
 

  • Literatur

  • 1 Freischmidt A, Wieland T, Richter B, Ruf W, Schaeffer V, Muller K. et al. Haploinsufficiency of Neurofilament light chain: A prognostic biomarker in amyotrophic lateral sclerosis. Neurology 2015; 84 (22) 2247-57.
    CrossrefPubMedGoogle Scholar
  • 2 Brenner D, Muller K, Wieland T, Weydt P, Bohm S, Lule D. et al. NEK1 mutations in familial amyotrophic lateral sclerosis. Brain 2016; 139 (Pt 5): e28.
    CrossrefPubMedGoogle Scholar
  • 3 Andersen PM, Al-Chalabi A. Clinical genetics of amyotrophic lateral sclerosis: what do we really know?. Nature Neurology 2011; 07 (11) 603-15.
    Google Scholar
  • 4 Braak H, Brettschneider J, Ludolph AC, Lee VM, Trojanowski JQ, Del Tredici K. Amyotrophic lateral sclerosis – a model of corticofugal axonal spread. Nature Neurology 2013; 09 (12) 708-14.
    Google Scholar
  • 5 Turner MR, Grosskreutz J, Kassubek J, Abrahams S, Agosta F, Benatar M. et al. Towards a neuroimaging biomarker for amyotrophic lateral sclerosis. Lancet Neurology 2011; 10 (05) 400-3.
    CrossrefPubMedGoogle Scholar
  • 6 Lehnert S, Costa J, de Carvalho M, Kirby J, Kuzma-Kozakiewicz M, Morelli C. et al. Multicentre quality control evaluation of different biomarker candidates for amyotrophic lateral sclerosis. Amyotrophic Lateral Sclerosis & Frontotemporal Degeneration 2014; 15 (5–6): 344-50.
    Google Scholar
  • 7 Steinacker P, Feneberg E, Weishaupt J, Brettschneider J, Tumani H, Andersen PM. et al. Neurofilaments in the diagnosis of motoneuron diseases: a prospective study on 455 patients. Journal of Neurology, Neurosurgery, and Psychiatry 2016; 87 (01) 12-20.
    PubMedGoogle Scholar
  • 8 Lu CH, Macdonald-Wallis C, Gray E, Pearce N, Petzold A, Norgren N. et al. Neurofilament light chain: A prognostic biomarker in amyotrophic lateral sclerosis. Neurology 2015; 84 (22) 2247-57.
    CrossrefPubMedGoogle Scholar
  • 9 Weydt P, Oeckl P, Huss A, Muller K, Volk AE, Kuhle J. et al. Neurofilament levels as biomarkers in asymptomatic and symptomatic familial amyotrophic lateral sclerosis. Annals of Neurology 2016; 79 (01) 152-8.
    CrossrefPubMedGoogle Scholar
  • 10 Kassubek J, Muller HP, Del Tredici K, Brettschneider J, Pinkhardt EH, Lule D. et al. Diffusion tensor imaging analysis of sequential spreading of disease in amyotrophic lateral sclerosis confirms patterns of TDP-43 pathology. Brain 2014; 137 (Pt 6): 1733-40.
    CrossrefPubMedGoogle Scholar
  • 11 Rosenbohm A, Muller HP, Hubers A, Ludolph AC, Kassubek J. Corticoefferent pathways in pure lower motor neuron disease: a diffusion tensor imaging study. Journal of Neurology. 2016 Epub 2016/09/15.
    PubMedGoogle Scholar
  • 12 Ince PG, Evans J, Knopp M, Forster G, Hamdalla HH, Wharton SB. et al. Corticospinal tract degeneration in the progressive muscular atrophy variant of ALS. Neurology 2003; 60 (08) 1252-8.
    CrossrefPubMedGoogle Scholar
  • 13 Ravits JM, La Spada AR. ALS motor phenotype heterogeneity, focality, and spread: deconstructing motor neuron degeneration. Neurology 2009; 73 (10) 805-11.
    CrossrefPubMedGoogle Scholar
  • 14 Gorges M, Muller HP, Lule D, Del Tredici K, Brettschneider J, Keller J. et al. Eye Movement Deficits Are Consistent with a Staging Model of pTDP-43 Pathology in Amyotrophic Lateral Sclerosis. PloS one 2015; 10 (11) e0142546.
    CrossrefPubMedGoogle Scholar
  • 15 Ludolph A, Drory V, Hardiman O, Nakano I, Ravits J, Robberecht W. et al. A revision of the El Escorial criteria – 2015. Amyotrophic Lateral Sclerosis & Frontotemporal Degeneration 2015; 1-2.
    Google Scholar
  • 16 Lacomblez L, Bensimon G, Leigh PN, Guillet P, Meininger V. Dose-ranging study of riluzole in amyotrophic lateral sclerosis. Amyotrophic Lateral Sclerosis/Riluzole Study Group II. Lancet 1996; 347 (9013): 1425-31.
    CrossrefPubMedGoogle Scholar
  • 17 Desport JC, Preux PM, Truong TC, Vallat JM, Sautereau D, Couratier P. Nutritional status is a prognostic factor for survival in ALS patients. Neurology 1999; 53 (05) 1059-63.
    CrossrefPubMedGoogle Scholar
  • 18 Desport JC, Preux PM, Magy L, Boirie Y, Vallat JM, Beaufrere B. et al. Factors correlated with hypermetabolism in patients with amyotrophic lateral sclerosis. The American Journal of Clinical Nutrition 2001; 74 (03) 328-34.
    CrossrefPubMedGoogle Scholar
  • 19 Vercruysse P, Sinniger J, El Oussini H, ScekicZahirovic J, Dieterle S, Dengler R. et al. Alterations in the hypothalamic melanocortin pathway in amyotrophic lateral sclerosis. Brain 2016; 139 (Pt 4): 1106-22.
    CrossrefPubMedGoogle Scholar
  • 20 Dorst J, Dupuis L, Petri S, Kollewe K, Abdulla S, Wolf J. et al. Percutaneous endoscopic gastrostomy in amyotrophic lateral sclerosis: a prospective observational study. Journal of Neurology. 2015 Epub 2015/01/27.
    PubMedGoogle Scholar
  • 21 Wills AM, Hubbard J, Macklin EA, Glass J, Tandan R, Simpson EP. et al. Hypercaloric enteral nutrition in patients with amyotrophic lateral sclerosis: a randomised, double-blind, placebo-controlled phase 2 trial. Lancet. 2014 Epub 2014/03/04.
    PubMedGoogle Scholar
  • 22 Dorst J, Kuhnlein P, Hendrich C, Kassubek J, Sperfeld AD, Ludolph AC. Patients with elevated triglyceride and cholesterol serum levels have a prolonged survival in amyotrophic lateral sclerosis. Journal of Neurology 2011; 258 (04) 613-7.
    CrossrefPubMedGoogle Scholar
  • 23 Dupuis L, Corcia P, Fergani A, Gonzalez JLDe Aguilar, Bonnefont-Rousselot D, Bittar R. et al. Dyslipidemia is a protective factor in amyotrophic lateral sclerosis. Neurology 2008; 70 (13) 1004-9.
    CrossrefPubMedGoogle Scholar
  • 24 Dorst J, Cypionka J, Ludolph AC. High-caloric food supplements in the treatment of amyotrophic lateral sclerosis: A prospective interventional study. Amyotrophic Lateral Sclerosis & Frontotemporal Degeneration 2013; 14 (7–8): 533-6.
    Google Scholar
  • 25 Stavroulakis T, Walsh T, Shaw PJ, McDermott CJ. Gastrostomy use in motor neurone disease (MND): a review, meta-analysis and survey of current practice. Amyotrophic Lateral Sclerosis & Frontotemporal Degeneration 2013; 14 (02) 96-104.
    Google Scholar
  • 26 Bourke SC, Tomlinson M, Williams TL, Bullock RE, Shaw PJ, Gibson GJ. Effects of non-invasive ventilation on survival and quality of life in patients with amyotrophic lateral sclerosis: a randomised controlled trial. Lancet Neurology 2006; 05 (02) 140-7.
    CrossrefPubMedGoogle Scholar
  • 27 Boentert M, Brenscheidt I, Glatz C, Young P. Effects of non-invasive ventilation on objective sleep and nocturnal respiration in patients with amyotrophic lateral sclerosis. Journal of Neurology. 2015 Epub 2015/06/17.
    PubMedGoogle Scholar
  • 28 Butz M, Wollinsky KH, Wiedemuth-Catrinescu U, Sperfeld A, Winter S, Mehrkens HH. et al. Longitudinal effects of noninvasive positive-pressure ventilation in patients with amyotrophic lateral sclerosis. American Journal of Physical Medicine & Rehabilitation 2003; 82 (08) 597-604.
    PubMedGoogle Scholar
  • 29 Peysson S, Vandenberghe N, Philit F, Vial C, Petitjean T, Bouhour F. et al. Factors predicting survival following noninvasive ventilation in amyotrophic lateral sclerosis. European Neurology 2008; 59 (3–4): 164-71.
    CrossrefPubMedGoogle Scholar
  • 30 Chio A, Ilardi A, Cammarosano S, Moglia C, Montuschi A, Calvo A. Neurobehavioral dysfunction in ALS has a negative effect on outcome and use of PEG and NIV. Neurology 2012; 78 (14) 1085-9.
    CrossrefPubMedGoogle Scholar
  • 31 Spataro R, Bono V, Marchese S, La Bella V. Tracheostomy mechanical ventilation in patients with amyotrophic lateral sclerosis: clinical features and survival analysis. Journal of the Neurological Sciences 2012; 323 (1–2): 66-70.
    CrossrefPubMedGoogle Scholar
  • 32 Safety and efficacy of diaphragm pacing in patients with respiratory insufficiency due to amyotrophic lateral sclerosis (DiPALS): a multicentre, open-label, randomised controlled trial. Lancet Neurology 2015; 14 (09) 883-92.
    CrossrefPubMedGoogle Scholar
  • 33 Jackson CE, Gronseth G, Rosenfeld J, Barohn RJ, Dubinsky R, Simpson CB. et al. Randomized double-blind study of botulinum toxin type B for sialorrhea in ALS patients. Muscle & Nerve 2009; 39 (02) 137-43.
    CrossrefPubMedGoogle Scholar
  • 34 Guidubaldi A, Fasano A, Ialongo T, Piano C, Pompili M, Masciana R. et al. Botulinum toxin A versus B in sialorrhea: a prospective, randomized, double-blind, crossover pilot study in patients with amyotrophic lateral sclerosis or Parkinson’s disease. Movement disorders 2011; 26 (02) 313-9.
    CrossrefPubMedGoogle Scholar
  • 35 Bello-Haas VD, Florence JM, Kloos AD, Scheirbecker J, Lopate G, Hayes SM. et al. A randomized controlled trial of resistance exercise in individuals with ALS. Neurology 2007; 68 (23) 2003-7.
    CrossrefPubMedGoogle Scholar
  • 36 Drory VE, Goltsman E, Reznik JG, Mosek A, Korczyn AD. The value of muscle exercise in patients with amyotrophic lateral sclerosis. Journal of the Neurological Sciences 2001; 191 (1–2): 133-7.
    CrossrefPubMedGoogle Scholar
  • 37 Lunetta C, Lizio A, Sansone VA, Cellotto NM, Maestri E, Bettinelli M. et al. Strictly monitored exercise programs reduce motor deterioration in ALS: preliminary results of a randomized controlled trial. Journal of Neurology. 2015 Epub 2015/10/20.
    PubMedGoogle Scholar