Nervenheilkunde 2003; 22(03): 136-141
DOI: 10.1055/s-0038-1624381
Original- und Übersichtsarbeiten/Original and Review Articles
Schattauer GmbH

Therapie der Amyotrophen Lateralsklerose – aktueller Stand

Current treatment of amyotrophic lateral sclerosis
M. J. Hecht
1   Neurologische Klinik mit Poliklinik, Friedrich-Alexander-Universität Erlangen-Nürnberg (Direktor: Prof. Dr. B. Neundörfer)
› Author Affiliations
Further Information

Publication History

Publication Date:
15 January 2018 (online)

Zusammenfassung

Die Amyotrophe Lateralsklerose (ALS) ist eine progressive neurodegenerative Erkrankung, gekennzeichnet durch den Verlust der oberen und unteren motorischen Neurone. Als ursächliche Therapie ist aktuell lediglich die lebensverlängernde Wirkung von Riluzol bewiesen. Die zusätzliche Gabe von Vitamin E und C könnte oxidative Schädigungen reduzieren, ein positiver Effekt wurde jedoch bisher nicht bewiesen. Die Hoffnungen, die in die Einnahme von Kreatin gesetzt wurden, konnten bisher nicht bestätigt werden. Vielfältige Therapiestudien werden zurzeit durchgeführt, die eine Erweiterung der ursächlichen therapeutischen Möglichkeiten erwarten lassen. In der Betreuung ist die symptomatische Behandlung der ALS entscheidend. Grundlage der symptomatischen Therapie ist die Physiotherapie, oft kombiniert mit Logopädie und Ergotherapie. Diese Basistherapie wird durch die medikamentöse symptomatische Therapie und die Bereitstellung von Hilfsmitteln ergänzt. Zwei entscheidende therapeutische Optionen, die Anlage einer PEG-Sonde und die Möglichkeiten maschineller Atemunterstützung, benötigen rechtzeitige Aufklärung und Beratung. Zur Gewährleistung der Patientenautonomie sind Patientenverfügungen hilfreich.

Summary

Amyotrophic lateral sclerosis is a progressive neurodegenerative disease characterized by the loss of upper and lower motor neurons. Riluzole is still the only proven therapy to prolong survival. The additional use of vitamin E and C might reduce oxidative damage, but a positive effect of vitamin E or C has not been proven yet. The positive effect of creatine seen in transgenic mice has not been confirmed in humans until now. Numerous trials with several compounds are undergoing. One can expect that soon further treatment options are available to slow the progression of the disease. Symptomatic treatment is essential in the care of ALS patients. Basic therapies are physiotherapy, speech and occupational therapy. These basic treatments are amended by symptomatic pharmacological treatment and mechanical aids. Two essential therapeutic options, insertion of PEG and mechanically assisted ventilation, need to be discussed in advance. To guarantee patient autonomy written directives are helpful.

 
  • Literatur

  • 1 American Academy of Neurology. Practice advisory on the treatment of amyotrophic lateral sclerosis with riluzole: report of the quality standards subcommitee of the American Academy of Neurology. Neurology 1997; 49: 657-9.
  • 2 Almer G, Guégan C, Teismann P, Naini A, Rosoklija G, Hays AP. et al. Increased expression of the pro-inflammatory enzyme cyclooxygenase-2 in amyotrophic lateral sclerosis. Ann Neurol 2001; 49: 176-85.
  • 3 Barnes P, Smith M, Conolly M, Mullins P. Combined analysis of long-term survival data from two randomized controlled studies comparing riluzole to placebo. Amyot Lat Scler 2002; 03 (Suppl. 02) 86-7.
  • 4 Beal MF. Coenzyme Q10 administration and its potential for treatment of neurodegenerative diseases. Biofactors 1999; 09 2-4 261-6.
  • 5 Beck M, Karch C, Wiese S, Sendtner M. Motoneuron cell death and neurotrophic factors: basic modells for development of new therapeutic strategies in ALS. Amyot Lat Scler 2001; 02 (Suppl. 01) S55-S68.
  • 6 Bensimon G, Lacomblez L, Meininger V, group atARs. A controlled trial of riluzole in amyotrophic lateral sclerosis. N Engl J Med 1994; 330: 585-91.
  • 7 Blin O, Azulay JP, Desnuelle C, Bille-Turc F, Braguer D, Besse D. et al. A controlled oneyear trial of dextromethorphan in amyotrophic lateral sclerosis. Clin Neuropharmacol 1996; 19 (02) 189-92.
  • 8 Castells LI, Gamez J, Cervera C, Guardia J. Icteric toxic hepatitis associated with riluzole (letter). Lancet 1998; 351: 648.
  • 9 Charcot JM. Lecons sur les maladies du système nerveux. Paris: Delahye 1873
  • 10 Cooper HM, Seaman C. A role for netrin receptors in axon guidance and neuronal migration. Amyot Lat Scler 2002; 03 (Suppl. 02) 33.
  • 11 Coulson EJ. Mechanisms regulating the survival of newly generated motor neurons. Amyot Lat Scler 2002; 03 (Suppl. 02) 33.
  • 12 Cudkowicz M. Clinical trial of topiramate in subjects with amyotrophic lateral sclerosis. Amyot Lat Scler y2002 03 (Suppl. 02) 22.
  • 13 Desnuelle C, Dib M, Garrel C, Favier A. group attA-Ts Multicentre, double-blind, randomized study of alpha-tocopherol versus plazebo in amyotrophic lateral sclerosis. Amyot Lat Scler 2000; 01 (Suppl. 03) 23-4.
  • 141 Doble A. The pharmacology and mechanism of action of riluzole. Neurology 1996; 47 (Suppl. 01) S233-241.
  • 14b Drachmann DB, Frank K, Dykes-Hoberg M. et al. Cyclooxygenase 2 inhibition protects motor neurons and prolongs survival in a transgenic mouse model of ALS. Ann Neurol 2002; 52: 771-8.
  • 15 Eisen A, Stewart H, Schulzer M, Cameron D. Anti-glutamate therapy in amyotrophic lateral sclerosis: A trial using lamotrigine. Can J Neurol Sci 1993; 20: 297-301.
  • 16 Gredal O, Werdelin L, Bak S, Christensen PB, Boysen G, Kristensen MO. et al. A clinical trial of dextromethorphan in amyotrophic lateral sclerosis. Acta Neurol Scand 1997; 96 (01) 8-13.
  • 17 Groeneveld GJ, Veldink JH, Tweel Ivd, Beijer CK, Visser Md, Wokke JHJ. et al. A randomized placebo-controlled trial of creatine in amyotrophic lateral sclerosis. Amyot Lat Scler 2002; 03 (Suppl. 02) 23.
  • 18 Gurney ME, Cutting FB, Zhai P, Doble A, Taylor CP, Andrus PK. et al. Benefit of vitamin E, riluzole, and gabapentin in a transgenic model of familial amyotrophic lateral sclerosis [see comments]. Ann Neurol 1996; 39 (02) 47-57.
  • 19 Hardiman O. Symptomatic treatment of respiratory and nutritional failure in amyotrophic lateral sclerosis. J Neurol 2000; 247: 245-51.
  • 20 Hecht MJ, Graesel E, Tigges S, Hillemacher T, Winterholler M, Hilz MJ. et al. Burden of care in amyotrophic lateral sclerosis. Palliat Med in press.
  • 21 Hecht MJ, Hillemacher T, Graesel E, Tigges S, Winterholler M, Heuss D. et al. Subjective experience and coping with ALS. Amyot Lat Scler in press.
  • 22 Klivenyi P, Ferrante RJ, Matthews RT, Bogdanov MB, Klein AM, Andreassen OA. et al. Neuroprotective effects of creatine in a transgenic animal model of amyotrophic lateral sclerosis. Nat Med 1999; 05 (03) 347-50.
  • 23 Kostic V, Jackson-Lewis V, Bilbao Fd, DuboisDauphin M, Przedborski S. Bcl-2: prolonging life in a transgenic mouse model of familial amyotrophic lateral sclerosis. Science 1997; 277: 559-62.
  • 24 Kriz J, Nguyen MD, Julien JP. Minocycline slows disease progression in a mouse model of amyotrophic lateral sclerosis. Neurobiol Dis 2002; 10 (03) 268-78.
  • 25 Lacomblez L, Bensimon G, Leigh PN, Guillet P, Meininger V, ftalsrsg II. Does-ranging study of riluzole in amyotrophic lateral sclerosis. The Lancet 1996; 347: 1425-31.
  • 26 Li M, Ona VO, Guegan C, Chen M, JacksonLewis V, Andrews LJ. et al. Functional role of caspase-1 and caspase-3 in an ALS transgenic model. Science 2000; 288: 335-9.
  • 27 Ludolph AC, Borasio GD, Hecht MJ, Meyer T, Winkler G. Leitlinien der Deutschen Gesellschaft für Neurologie: Amyotrophe Lateralsklerose. unter www.dgn.org/leitl.shtml.
  • 28 Miller RG. Drug Development and Clinical Trials: Gabapentin (Neurontin®). www.alsa. org/research/drugdev12.cfm.
  • 29 Miller RG, Mitchell JD, Moore DH. Riluzole for amyotrophic lateral sclerosis (ALS)/ motor neuron disease (MND) (Cochrane review). In: The Cochrane Library, 4. issue. Oxford: Update software; 2000.
  • 30 Miller RG, Rosenberg JA, Gelinas DF, Mitsumoto H, Newman D, Sufit R. et al. Practice parameter: the care of the patient with amyotrophic lateral sclerosis (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology: ALS Practice Parameters Task Force. Neurology 1999; 52 (07) 1311-23.
  • 31 Mitsumoto H, Chad DA, Pioro EP. Excitotoxicity and oxidative damage in ALS pathogenesis. In: Mitsumoto H, Chad DA, Pioro EP. (eds). Amyotrophic lateral sclerosis. Philadelphia: F.A. Davis Company; 1998: 197-225.
  • 32 Neundörfer B. Praxis der amyotrophen Lateralsklerose. 1. Auflage. Bremen: Uni-Med 2002
  • 33 North WA, Khan AM, Yamase HT, Sporn JR. Reversible granulocytopenia in association with riluzole therapy. Ann Pharmacother 2000; 34 (03) 322-4.
  • 34 Pioro EP. Antioxidant therapy in ALS. Amyot Lat Scler 2000; 01 (Suppl. 04) 5-15.
  • 35 Remy AJ, Camu W, Ramos J, Blanc P, Larrey D. Acute hepatitis after riluzole administration. J Hepatol 1999; 30 (03) 527-30.
  • 36 Rietze R. Stimulation of endogenous stem cells to replace lost motor neurons. Amyot Lat Scler 2002; 03 (Suppl. 02) 34.
  • 37 Riviere M, Meininger V, Zeisser P, Munsat T. An analysis of extended survival in patients with amyotrophic lateral sclerosis treated with riluzole. Arch Neurol 1998; 55 (04) 526-8.
  • 38 Rosen DR, Siddique T, Patterson D, Figlewicz DA, Sapp P, Hentati A. et al. Mutations in Cu/Zn superoxid dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature 1993; 362: 59-62.
  • 39 Sathasivam S, Ince PG, Shaw PJ. Apoptosis in amyotrophic lateral sclerosis. Neuropathol Appl Neurobiol 2001; 27: 257-74.
  • 40 Sendtner M. Neurotrophic factors. In: Brown RH, Meininger V, Swash M. (eds). Amyotrophic lateral sclerosis. London: Martin Dunitz; 2000: 289-308.
  • 41 Simpson EP, Mosier D, Appel SH. Mechanisms of disease pathogenesis in amyotrophic lateral sclerosis. A central role for calcium. In: Pourmand R, Harati Y. (eds). Neuromuscular disorders. 1 ed.. Philadelphia: Lippincott Williams & Wilkins; 2001: 1-19.
  • 42 Strong MJ, Pattee GL. Creatine and coenzyme Q10 in the treatment of ALS. Amyot Lat Scler 2000; 01 (Suppl. 04) 17-20.
  • 43 Van Den Bosch L, Tilkin P, Lemmens G, Robberecht W. Minocycline delays disease onset and mortality in a transgenic model of ALS. Neuroreport 2002; 13 (08) 1067-70.
  • 44 Winterholler M, Claus D, Bockelbrink A, Borasio GD, Pongratz D, Schrank B. et al. Empfehlungen der bayerischen Muskelzentren in der DGM zur Heimbeatmung bei neuromuskulären Erkrankungen Erwachsener. Nervenarzt 1997; 68: 351-7.