Download PDF
Nervenheilkunde 2020; 39(12): 791-800
DOI: 10.1055/a-1193-8454
Übersichtsarbeit

Pharmakologische und nicht pharmakologische Symptomtherapie bei amyotropher Lateralsklerose

Eine ÜbersichtPharmacological and non-pharmacological symptomatic treatment of amyotrophic lateral sclerosisA review
Kirsten Hüning∗
1   Klinik und Poliklinik für Palliativmedizin, Universitätsklinikum Bonn
,
Patrick Weydt∗
2   ALS-Ambulanz und Huntington Ambulanz, Klinik für Neurodegenerative Erkrankungen und Gerontopsychiatrie, Universitätsklinikum Bonn
,
Michaela Hesse∗
1   Klinik und Poliklinik für Palliativmedizin, Universitätsklinikum Bonn
,
Gülay Ates∗
1   Klinik und Poliklinik für Palliativmedizin, Universitätsklinikum Bonn
,
Henning Cuhls∗
1   Klinik und Poliklinik für Palliativmedizin, Universitätsklinikum Bonn
,
Lukas Radbruch∗
1   Klinik und Poliklinik für Palliativmedizin, Universitätsklinikum Bonn
› Author Affiliations
› Further Information
    Permissions and Reprints

ZUSAMMENFASSUNG

Die amyotrophe Lateralsklerose (ALS) stellt mit ihrer fehlenden kausalen Therapierbarkeit und ihren zahlreichen Symptomen eine große Herausforderung für alle Behandelnden und Begleitenden dar. Neben dem Medikament Riluzol, wodurch eine kurze Lebenszeitverlängerung bewirkt werden kann, befinden sich mehrere Wirkstoffe im Stadium der Erprobung im Rahmen von Studien. Für die symptomatische Behandlung der ALS liegen nur wenige randomisierte, placebokontrollierte Studien vor. Die vorliegende Arbeit gibt eine Übersicht über die pharmakologischen und nicht pharmakologischen Therapiemöglichkeiten bei ALS. Es wurden die Datenbanken CENTRAL, Medline, PsycINFO und Pubmed nach Artikeln in englischer Sprache bis August 2018 durchsucht. Die Entwicklungen nach dem Beobachtungszeitraum werden in einem gesonderten Abschnitt behandelt. Mit der systematischen Suchstrategie wurden 232 Publikationen identifiziert, wovon 34 in die Übersicht eingeflossen sind, ein Artikel aus anderer Quelle wurde hinzugefügt. Hierunter befanden sich 9 kontrollierte Studien, von denen 7 die Wirksamkeit therapeutischer Medikamente bei ALS untersuchen. Ein Großteil der Studien basiert auf geringen Patientenzahlen mit sehr unterschiedlichen Angaben zur Effektivität der jeweiligen Interventionen. Neben der Behandlung mit Riluzol 2x50mg/d stellen die nicht invasive Beatmung (NIV), die Versorgung mit einer perkutanen endoskopischen Gastrostomie (PEG) sowie die Betreuung durch ein multidisziplinäres Team Faktoren dar, die die tracheotomiefreie Überlebenszeit der Patienten verlängern können. Die Durchführung weiterer randomisierter, kontrollierter Studien mit höheren Patientenzahlen auch im Bereich der symptomatischen Therapien wird von fast allen zitierten Autoren angeregt. Da die Behandlung mit Riluzol, die Versorgung mit NIV, einer PEG sowie die Anbindung der Patienten an ein multidisziplinäres Team hinsichtlich Überlebenszeit und Erhalt der Lebensqualität relevant sind, gilt es, den Patienten diese Optionen zum geeigneten Zeitpunkt zur Verfügung zu stellen.

ABSTRACT

Amyotrophic lateral sclerosis (motor neuron disease MND) constitutes a huge challenge to all health care professionals and caregivers due to the lack of a causal therapy and the numerous and variable symptoms. In addition to the established treatment with Riluzole, which may prolong the survival time, several other interventions are under investigation in various trials. For the symptomatic treatment of MND only a few randomised controlled trials have been published. This review provides an overview of the pharmacological and non-pharmacological interventions for treatment of this disease. We systematically searched the databases CENTRAL, Medline, PsycINFO and Pubmed regarding articles in English until August 2018. The developments after the period under review are treated in a separate paragraph. With the described systematic search strategy, we identified 232 publications, 34 of which were included in the review, one further article from another source was added (see appendix). There were only nine controlled trials, seven of them about effectiveness of potential drug therapies for ALS. A majority of the controlled studies are based on low patient numbers with very different data on the effectiveness of the interventions. In addition to the treatment with Riluzole, the non-invasive ventilation (NIV), the percutaneous endoscopic gastrostomy (PEG) and care by a multidisciplinary team prolong survival of patients with MND. More randomised, controlled trials with higher patient numbers are needed. Riluzole, the noninvasive ventilation, the PEG and the care by a multidisciplinary team prolong the survival time, and these options should be offered at the right time to all patients suffering from MND.

Schlüsselwörter

Amyotrophe Lateralsklerose - pharmakologische Therapie - nicht pharmakologische Therapie - Palliativmedizin - multidisziplinäres Team

Key words

Amyotrophic lateral sclerosis - pharmacological therapy - non-pharmacological therapy - palliative care - mutidisciplinary team



Publication History

Article published online:
14 December 2020

© 2020. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • Literatur

  • 1 Chiò A, Logroscino G, Traynor B. et al Global epidemiology of amyotrophic lateral sclerosis: a systematic review of the published literature. Neuroepidemiology 2013; 41: 118-130
    CrossrefPubMedGoogle Scholar
  • 2 Czaplinski A, Yen AA, Simpson EP. et al Slower disease progression and prolonged survival in contemporary patients with amyotrophic lateral sclerosis: is the natural history of amyotrophic lateral sclerosis changing?. Archives of neurology 2006; 63: 1139-1143
    CrossrefPubMedGoogle Scholar
  • 3 Peters O, Brown Jr R. Amyotrophic lateral sclerosis. In Neurobiology of Brain Disorders: Elsevier 2015: 262-280
    PubMedGoogle Scholar
  • 4 Lacomblez L, Bouche P, Bensimon G. et al A double-blind, placebo-controlled trial of high doses of gangliosides in amyotrophic lateral sclerosis. Neurology 1989; 39: 1635-1635
    CrossrefPubMedGoogle Scholar
  • 5 Bensimon G, Lacomblez L, Meininger Vf. et al A controlled trial of riluzole in amyotrophic lateral sclerosis. New England Journal of Medicine 1994; 330: 585-591
    CrossrefPubMedGoogle Scholar
  • 6 Cudkowicz ME, van den Berg LH, Shefner JM. et al Dexpramipexole versus placebo for patients with amyotrophic lateral sclerosis (EMPOWER): a randomised, double-blind, phase 3 trial. The Lancet Neurology 2013; 12: 1059-1067
    CrossrefPubMedGoogle Scholar
  • 7 Rosenfeld J, King RM, Jackson CE. et al Creatine monohydrate in ALS: effects on strength, fatigue, respiratory status and ALSFRS. Amyotrophic Lateral Sclerosis 2008; 9: 266-272
    CrossrefPubMedGoogle Scholar
  • 8 Cudkowicz ME, Titus S, Kearney M. et al Safety and efficacy of ceftriaxone for amyotrophic lateral sclerosis: a multi-stage, randomised, double-blind, placebo-controlled trial. The Lancet Neurology 2014; 13: 1083-1091
    CrossrefPubMedGoogle Scholar
  • 9 Lai E, Felice K, Festoff B. et al Effect of recombinant human insulin-like growth factor-I on progression of ALS: a placebo-controlled study. Neurology 1997; 49: 1621-1630
    CrossrefPubMedGoogle Scholar
  • 10 Macchi Z, Wang Y, Moore D. et al A multi-center screening trial of rasagiline in patients with amyotrophic lateral sclerosis: Possible mitochondrial biomarker target engagement. Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration 2015; 16: 345-352
    CrossrefPubMedGoogle Scholar
  • 11 Ludolph AC, Schuster J, Dorst J. et al Safety and efficacy of rasagiline as an add-on therapy to riluzole in patients with amyotrophic lateral sclerosis: a randomised, double-blind, parallel-group, placebo-controlled, phase 2 trial. The Lancet Neurology 2018; 17: 681-688
    CrossrefPubMedGoogle Scholar
  • 12 Cruz MP. Edaravone (Radicava): a novel neuroprotective agent for the treatment of amyotrophic lateral sclerosis. Pharmacy and Therapeutics 2018; 43: 25
    PubMedGoogle Scholar
  • 13 Writing G. for the Edaravone (MCI-186) ALS 19 study group. Safety and efficacy of edaravone in well-defined patients with amyotrophic lateral sclerosis: a randomised, double-blind, placebo-controlled trial. Lancet Neurol 2017; 16: 505-512
    CrossrefPubMedGoogle Scholar
  • 14 Orrell RW, Lane RJ, Ross M. Antioxidant treatment for amyotrophic lateral sclerosis or motor neuron disease. Cochrane Database of Systematic Reviews 2007
    PubMedGoogle Scholar
  • 15 Forshew AD, Bromberg BM. A survey of clinicians’ practice in the symptomatic treatment of ALS. Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders 2003; 4: 258-263
    CrossrefPubMedGoogle Scholar
  • 16 Nakamura C, Bromberg M, Bhargava S. et al Mining online social network data for biomedical research: a comparison of clinicians’ and patients’ perceptions about amyotrophic lateral sclerosis treatments. Journal of medical Internet research 2012; 14: e90
    CrossrefPubMedGoogle Scholar
  • 17 McGeachan AJ, Hobson EV, Al-Chalabi A. et al A multicentre evaluation of oropharyngeal secretion management practices in amyotrophic lateral sclerosis. Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration 2017; 18: 1-9
    CrossrefPubMedGoogle Scholar
  • 18 Verma A, Steele J. Botulinum toxin improves sialorrhea and quality of living in bulbar amyotrophic lateral sclerosis. Muscle & Nerve 2006; 34: 235-237
    CrossrefPubMedGoogle Scholar
  • 19 Neppelberg E, Haugen D, Thorsen L. et al Radiotherapy reduces sialorrhea in amyotrophic lateral sclerosis. European journal of neurology 2007; 14: 1373-1377
    CrossrefPubMedGoogle Scholar
  • 20 Jackson CE, Gronseth G, Rosenfeld J. et al Randomized double-blind study of botulinum toxin type B for sialorrhea in ALS patients. Muscle & Nerve: Official Journal of the American Association of Electrodiagnostic Medicine 2009; 39: 137-143
    CrossrefPubMedGoogle Scholar
  • 21 Jacobs TL, Brown DL, Baek J. et al Trial of early noninvasive ventilation for ALS: a pilot placebo-controlled study. Neurology 2016; 87: 1878-1883
    CrossrefPubMedGoogle Scholar
  • 22 Gruis KL, Brown DL, Lisabeth LD. et al Longitudinal assessment of noninvasive positive pressure ventilation adjustments in ALS patients. Journal of the neurological sciences 2006; 247: 59-63
    CrossrefPubMedGoogle Scholar
  • 23 Butz M, Wollinsky KH, Wiedemuth-Catrinescu U. et al Longitudinal effects of noninvasive positive-pressure ventilation in patients with amyotrophic lateral sclerosis. American journal of physical medicine & rehabilitation 2003; 82: 597-604
    CrossrefPubMedGoogle Scholar
  • 24 Berlowitz DJ, Howard ME, Fiore JF. et al Identifying who will benefit from non-invasive ventilation in amyotrophic lateral sclerosis/motor neurone disease in a clinical cohort. Journal of Neurology, Neurosurgery & Psychiatry 2016; 87: 280-286
    CrossrefPubMedGoogle Scholar
  • 25 Vianello A, Arcaro G, Palmieri A. et al Survival and quality of life after tracheostomy for acute respiratory failure in patients with amyotrophic lateral sclerosis. Journal of critical care 2011; 26: 329. e327-329. e314
    CrossrefPubMedGoogle Scholar
  • 26 McDermott CJ, Bradburn MJ, Maguire C. et al DiPALS: Diaphragm Pacing in patients with Amyotrophic Lateral Sclerosis – a randomised controlled trial. Health Technol Assess 2016; 20: 45
    CrossrefPubMedGoogle Scholar
  • 27 Neudert C, Oliver D, Wasner M. et al The course of the terminal phase in patients with amyotrophic lateral sclerosis. Journal of neurology 2001; 248: 612-616
    CrossrefPubMedGoogle Scholar
  • 28 Andersen PM, Borasio GD, Dengler R. et al Good practice in the management of amyotrophic lateral sclerosis: Clinical guidelines. An evidence-based review with good practice points. EALSC Working Group. Amyotrophic lateral sclerosis 2007; 8: 195-213
    CrossrefPubMedGoogle Scholar
  • 29 Spataro R, Ficano L, Piccoli F. et al Percutaneous endoscopic gastrostomy in amyotrophic lateral sclerosis: effect on survival. Journal of the neurological sciences 2011; 304: 44-48
    CrossrefPubMedGoogle Scholar
  • 30 Burkhardt C, Neuwirth C, Sommacal A. et al Is survival improved by the use of NIV and PEG in amyotrophic lateral sclerosis (ALS)? A post-mortem study of 80 ALS patients. PLoS One 2017: 12
    PubMedGoogle Scholar
  • 31 Raheja D, Stephens HE, Lehman E. et al Patient-reported problematic symptoms in an ALS treatment trial. Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration 2016; 17: 198-205
    CrossrefPubMedGoogle Scholar
  • 32 Gibbons C, Pagnini F, Friede T. et al Treatment of fatigue in amyotrophic lateral sclerosis/motor neuron disease. Cochrane Database of Systematic Reviews 2018
    PubMedGoogle Scholar
  • 33 Vardeny O, Bromberg MB. The use of herbal supplements and alternative therapies by patients with amyotrophic lateral sclerosis (ALS). Journal of herbal pharmacotherapy 2005; 5: 23-31
    CrossrefPubMedGoogle Scholar
  • 34 Nieves JW, Gennings C, Factor-Litvak P. et al Association between dietary intake and function in amyotrophic lateral sclerosis. JAMA neurology 2016; 73: 1425-1432
    CrossrefPubMedGoogle Scholar
  • 35 Qiu H, Li J-h, Yin S-b. et al Dihuang Yinzi, a classical Chinese herbal prescription, for Amyotrophic Lateral Sclerosis: a 12-year follow-up case report. Medicine 2016; 95: 1-10
    Google Scholar
  • 36 Rooney J, Byrne S, Heverin M. et al A multidisciplinary clinic approach improves survival in ALS: a comparative study of ALS in Ireland and Northern Ireland. J Neurol Neurosurg Psychiatry 2015; 86: 496-501
    CrossrefPubMedGoogle Scholar
  • 37 Riva N, Mora G, Sorarù G. et al Safety and efficacy of nabiximols on spasticity symptoms in patients with motor neuron disease (CANALS): a multicentre, double-blind, randomised, placebo-controlled, phase 2 trial. The Lancet Neurology 2019; 18: 155-164
    CrossrefPubMedGoogle Scholar
  • 38 Miller TM, Pestronk A, David W. et al An antisense oligonucleotide against SOD1 delivered intrathecally for patients with SOD1 familial amyotrophic lateral sclerosis: a phase 1, randomised, first-in-man study. The Lancet Neurology 2013; 12: 435-442
    CrossrefPubMedGoogle Scholar
  • 39 Groß M, Summ O. Rehabilitation bei Amyotropher Lateralsklerose. Nervenheilkunde 2019; 38: 249-256
    Article in Thieme ConnectGoogle Scholar
  • 40 Bedlack RS. Amyotrophic lateral sclerosis: current practice and future treatments. Current opinion in neurology 2010; 23: 524-529
    CrossrefPubMedGoogle Scholar
  • 41 Metelmann M, Holzer M, Hermann A. Therapie der Amyotrophen Lateralsklerose. Nervenheilkunde 2019; 38: 402-408
    Article in Thieme ConnectGoogle Scholar
  • 42 Stone CA, O’Leary N. Systematic review of the effectiveness of botulinum toxin or radiotherapy for sialorrhea in patients with amyotrophic lateral sclerosis. Journal of pain and symptom management 2009; 37: 246-258
    CrossrefPubMedGoogle Scholar
  • 43 Squires N, Humberstone M, Wills A. et al The use of botulinum toxin injections to manage drooling in amyotrophic lateral sclerosis/motor neurone disease: a systematic review. Dysphagia 2014; 29: 500-508
    CrossrefPubMedGoogle Scholar
  • 44 Carter GT, Weiss MD, Lou J-S. et al Modafinil to treat fatigue in amyotrophic lateral sclerosis: an open label pilot study. American Journal of Hospice and Palliative Medicine 2005; 22: 55-59
    CrossrefPubMedGoogle Scholar
  • 45 Rabkin JG, Gordon PH, McElhiney M. et al Modafinil treatment of fatigue in patients with ALS: a placebo-controlled study. Muscle & Nerve 2009; 39: 297-303
    CrossrefPubMedGoogle Scholar
  • 46 Mücke M, Cuhls H, Peuckmann-Post V. et al Pharmacological treatments for fatigue associated with palliative care. Cochrane Database of Systematic Reviews 2015
    PubMedGoogle Scholar
  • 47 Dorst J, Chen L, Rosenbohm A. et al Prognostic factors in ALS: a comparison between Germany and China. Journal of neurology 2019; 266: 1516-1525
    CrossrefPubMedGoogle Scholar
  • 48 AC L. Amyotrophe Lateralsklerose (Motoneuronerkrankungen). Leitlinien für Diagnostik und Therapie in der Neurologie. Stuttgart: Thieme; 2012: 254-263
    Google Scholar
  • 49 Borasio G, Voltz R. Palliative Therapie bei amyotropher Lateralsklerose (ALS). Aktuelle Neurologie 1998; 25: 115-122
    Article in Thieme ConnectGoogle Scholar
  • 50 Borasio G, Pongratz D. Gedanken zur Aufklärung bei amyotropher Lateralsklerose (ALS). Der Nervenarzt 1997; 68: 1004-1007
    CrossrefPubMedGoogle Scholar
  • 51 Funke A, Grehl T, Großkreutz J. et al Hilfsmittelversorgung bei der amyotrophen Lateralsklerose. Der Nervenarzt 2015; 86: 1007-1017
    CrossrefPubMedGoogle Scholar
  • 52 Lulé D, Häcker S, Ludolph A. et al Depression und Lebensqualität bei Patienten mit amyotropher Lateralsklerose. Dtsch Arztebl 2008; 105: 397-403
    Google Scholar
  • 53 Gasper-Paetz A, Ates G, Jaspers B. et al Modellprojekt zur Entwicklung eines Konzepts zur Palliativversorgung von Menschen mit Amyotropher Lateralsklerose (ALS). Zeitschrift für Palliativmedizin 2018; 19: V31
    Article in Thieme ConnectGoogle Scholar
  • 54 Young CA, Ellis C, Johnson J. et al Treatment for sialorrhea (excessive saliva) in people with motoneuron disease/amyotrophic lateral sceloris. Cochrane Database of Systematic Reviews 2011
    PubMedGoogle Scholar