Nervenheilkunde 2011; 30(10): 755-763
DOI: 10.1055/s-0038-1628422
Deutsche Gesellschaft für Muskelkranke
Schattauer GmbH

Amyotrophe Lateralsklerose

Article in several languages: deutsch | English
S. Körner
1   Neurologische Klinik mit klinischer Neurophysiologie, Medizinische Hochschule Hannover
,
S. Petri
1   Neurologische Klinik mit klinischer Neurophysiologie, Medizinische Hochschule Hannover
,
R. Dengler
1   Neurologische Klinik mit klinischer Neurophysiologie, Medizinische Hochschule Hannover
,
K. Kollewe
1   Neurologische Klinik mit klinischer Neurophysiologie, Medizinische Hochschule Hannover
› Author Affiliations
Further Information

Publication History

Eingegangen am: 04 May 2011

angenommen am: 10 May 2011

Publication Date:
22 January 2018 (online)

Zusammenfassung

Die amyotrophe Lateralsklerose (ALS) ist die häufigste Motoneuronerkrankung im Erwachsenenalter und durch einen selektiven Motoneuronverlust im mittleren Lebensalter charakterisiert. Die Pathogenese der ALS ist nicht vollständig geklärt. Vermutet wird eine multifaktorielle Ätiologie, wobei z. B. genetische Faktoren, oxidativer Stress, ein veränderter RNA-Metabolismus und ein Defizit an Wachstumsfaktoren als mögliche Einflussfaktoren diskutiert werden. Das klinische Bild ist durch ein Nebeneinander von peripheren und zentralen Paresen gekennzeichnet. Betroffen sind die durch die kaudalen Hirnnerven innervierten Muskeln sowie die Extremitätenmuskulatur. Nach einem fokalen Beginn kommt es meist rasch zu einer Generalisierung der Paresen. Die Diagnosestellung erfolgt nach den revidierten El-Escorial-Kriterien, die Sicherheit der Diagnose richtet sich dabei nach dem Ausmaß der Ausbreitung der Symptome.An apparativer Diagnostik kann in erster Linie die Elektromyografie zur Diagnosesicherung beitragen. Nach dem Versagen zahlreicher Medikamentenstudien ist zum aktuellen Zeitpunkt weiterhin nur der Glutamatantagonist Riluzol zur kausalen medikamentösen Therapie der ALS zugelassen. Daher nimmt die symptomatische Therapie zur Linderung, z. B. der Spastik, des Speichelflusses, der Muskelkrämpfe und anderer Symptome, einen hohen Stellenwert ein.

 
  • Literatur

  • 1 Cleveland DW, Rothstein JD. From Charcot to Lou Gehrig: deciphering selective motor neuron death in ALS. Nat Rev Neurosci 2001; 02 (11) 806-19.
  • 2 Rothstein JD. Current hypotheses for the underlying biology of amyotrophic lateral sclerosis. Ann Neurol 2009; 65 (Suppl. 19) S3-S9.
  • 3 Wijesekera LC, Leigh PN. Amyotrophic lateral sclerosis. Orphanet J Rare Dis 2009; 04: 3.
  • 4 Shaw PJ. Molecular and cellular pathways of neurodegeneration in motor neurone disease. J Neurol Neurosurg Psychiatry 2005; 76 (08) 1046-57.
  • 5 Rosen DR. et al. Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature 1993; 362 (6415): 59-62.
  • 6 Pasinelli P, Brown RH. Molecular biology of amyotrophic lateral sclerosis: insights from genetics. Nat Rev Neurosci 2006; 07 (09) 710-23.
  • 7 Neumann M. et al. Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 2006; 314 (5796): 130-3.
  • 8 Mackenzie IR, Rademakers R, Neumann M. TDP-43 and FUS in amyotrophic lateral sclerosis and frontotemporal dementia. Lancet Neurol 2010; 09 (10) 995-1007.
  • 9 Lagier-Tourenne C, Polymenidou M, Cleveland DW. TDP-43 and FUS/TLS: emerging roles in RNA processing and neurodegeneration. Hum Mol Genet 2010; 19 (R1): R46-R64.
  • 10 Shaw PJ, Ince PG, Falkous G, Mantle D. Oxidative damage to protein in sporadic motor neuron disease spinal cord. Ann Neurol 1995; 38 (04) 691-5.
  • 11 Tohgi H. et al. Remarkable increase in cerebrospinal fluid 3-nitrotyrosine in patients with sporadic amyotrophic lateral sclerosis. Ann Neurol 1999; 46 (01) 129-31.
  • 12 Boillee S, Vande VC, Cleveland DW. ALS: a disease of motor neurons and their nonneuronal neighbors. Neuron 2006; 52 (01) 39-59.
  • 13 Williamson TL, Cleveland DW. Slowing of axonal transport is a very early event in the toxicity of ALSlinked SOD1 mutants to motor neurons. Nat Neurosci 1999; 02 (01) 50-6.
  • 14 Schmidt ER, Pasterkamp RJ, van den Berg LH. Axon guidance proteins: novel therapeutic targets for ALS?. Prog Neurobiol 2009; 88 (04) 286-301.
  • 15 Oosthuyse B. et al. Deletion of the hypoxia-response element in the vascular endothelial growth factor promoter causes motor neuron degeneration. Nat Genet 2001; 28 (02) 131-8.
  • 16 Shaw PJ. et al. CSF and plasma amino acid levels in motor neuron disease: elevation of CSF glutamate in a subset of patients. Neurodegeneration 1995; 04 (02) 209-16.
  • 17 Rothstein JD. et al. Abnormal excitatory amino acid metabolism in amyotrophic lateral sclerosis. Ann Neurol 1990; 28 (01) 18-25.
  • 18 Rothstein JD. et al. Selective loss of glial glutamate transporter GLT-1 in amyotrophic lateral sclerosis. Ann Neurol 1995; 38 (01) 73-84.
  • 19 Clement AM. et al. Wild-type nonneuronal cells extend survival of SOD1 mutant motor neurons in ALS mice. Science 2003; 302 (5642): 113-7.
  • 20 Hall ED, Oostveen JA, Gurney ME. Relationship of microglial and astrocytic activation to disease onset and progression in a transgenic model of familial ALS. Glia 1998; 23 (03) 249-56.
  • 21 Troost D, Van den Oord JJ, Vianney JMde Jong. Immunohistochemical characterization of the inflammatory infiltrate in amyotrophic lateral sclerosis. Neuropathol Appl Neurobiol 1990; 16 (05) 401-10.
  • 22 Sekizawa T. et al. Cerebrospinal fluid interleukin 6 in amyotrophic lateral sclerosis: immunological parameter and comparison with inflammatory and non-inflammatory central nervous system diseases. J Neurol Sci 1998; 154 (02) 194-9.
  • 23 Robertson J. et al. Apoptotic death of neurons exhibiting peripherin aggregates is mediated by the proinflammatory cytokine tumor necrosis factoralpha. J Cell Biol 2001; 155 (02) 217-26.
  • 24 Almer G. et al. Increased expression of the pro-inflammatory enzyme cyclooxygenase-2 in amyotrophic lateral sclerosis. Ann Neurol 2001; 49 (02) 176-85.
  • 25 Irwin D, Lippa CF, Swearer JM. Cognition and amyotrophic lateral sclerosis (ALS). Am J Alzheimers Dis Other Demen 2007; 22 (04) 300-12.
  • 26 Lakerveld J, Kotchoubey B, Kubler A. Cognitive function in patients with late stage amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry 2008; 79 (01) 25-9.
  • 27 Murphy JM. et al. Continuum of frontal lobe impairment in amyotrophic lateral sclerosis. Arch Neurol 2007; 64 (04) 530-4.
  • 28 Munte TF. et al. Abnormalities of visual search behaviour in ALS patients detected with event-related brain potentials. Amyotroph Lateral Scler Other Motor Neuron Disord 1999; 01 (01) 21-7.
  • 29 Paulus KS. et al. Visual and auditory event-related potentials in sporadic amyotrophic lateral sclerosis. Clin Neurophysiol 2002; 113 (06) 853-61.
  • 30 Vieregge P. et al. Selective attention is impaired in amyotrophic lateral sclerosis--a study of event-related EEG potentials. Brain Res Cogn Brain Res 1999; 08 (01) 27-35.
  • 31 Petri S. et al. GABA(A)-receptor mRNA expression in the prefrontal and temporal cortex of ALS patients. J Neurol Sci 2006; 250 (1–2): 124-32.
  • 32 Mohammadi B. et al. Changes of resting state brain networks in amyotrophic lateral sclerosis. Exp Neurol 2009; 217 (01) 147-53.
  • 33 Czaplinski A. et al. Flail arm syndrome: a clinical variant of amyotrophic lateral sclerosis. Eur J Neurol 2004; 11 (08) 567-8.
  • 34 Soraru G. et al. Natural history of upper motor neuron-dominant ALS. Amyotroph Lateral Scler 2010; 11 (05) 424-9.
  • 35 Kollewe K. et al. ALSFRS-R score and its ratio: a useful predictor for ALS-progression. J Neurol Sci 2008; 275 (1–2): 69-73.
  • 36 McCullagh S. et al. Pathological laughing and crying in amyotrophic lateral sclerosis: an association with prefrontal cognitive dysfunction. J Neurol Sci 1999; 169 (1–2): 43-8.
  • 37 Younger DS. et al. Primary lateral sclerosis. A clinical diagnosis reemerges. Arch Neurol 1988; 45 (12) 1304-7.
  • 38 Brugman F. et al. Primary lateral sclerosis as a phenotypic manifestation of familial ALS. Neurology 2005; 64 (10) 1778-9.
  • 39 Brooks BR. et al. El Escorial revisited: revised criteria for the diagnosis of amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Motor Neuron Disord 2000; 01 (05) 293-9.
  • 40 Brooks BR. El Escorial World Federation of Neurology criteria for the diagnosis of amyotrophic lateral sclerosis. J Neurol Sci 1994; 124 Suppl: 96-107.
  • 41 Dengler R. et al. Amyotrophic lateral sclerosis: macro-EMG and twitch forces of single motor units. Muscle Nerve 1990; 13 (06) 545-50.
  • 42 Dengler R. et al. Collateral nerve sprouting and twitch forces of single motor units in conditions with partial denervation in man. Neurosci Lett 1989; 97 (1–2): 118-22.
  • 43 Schmalbach S, Dengler R, Petri S. Diagnostik der amyotrophen Lateralsklerose. Journal für Neurologie, Neurochirurgie und Psychiatrie 2010; 11: 1-5.
  • 44 Douglass CP. et al. An evaluation of neurophysiological criteria used in the diagnosis of motor neuron disease. J Neurol Neurosurg Psychiatry 2010; 81 (06) 646-9.
  • 45 de Carvalho M. et al. Electrodiagnostic criteria for diagnosis of ALS. Clin Neurophysiol 2008; 119 (03) 497-503.
  • 46 Carvalho MD, Swash M. Awaji diagnostic algorithm increases sensitivity of El Escorial criteria for ALS diagnosis. Amyotroph Lateral Scler 2009; 10 (01) 53-7.
  • 47 Dengler R. Neue Überlegungen zur klinisch-neurophysiologischen Diagnostik der ALS. Die “Awaji-Kriterien”. Klinische Neurophysiologie 2008; 39: 164-8.
  • 48 Lacomblez L. et al. Long-term safety of riluzole in amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Motor Neuron Disord 2002; 03 (01) 23-9.
  • 49 Lacomblez L. et al. Dose-ranging study of riluzole in amyotrophic lateral sclerosis. Amyotrophic Lateral Sclerosis/Riluzole Study Group II. Lancet 1996; 347 (9013): 1425-31.
  • 50 Lacomblez L. et al. A confirmatory dose-ranging study of riluzole in ALS. ALS/Riluzole Study Group-II. Neurology 1996; 47 (6 Suppl 4): S242-S250.
  • 51 Bensimon G, Lacomblez L, Meininger V. A controlled trial of riluzole in amyotrophic lateral sclerosis. ALS/Riluzole Study Group. N Engl J Med 1994; 330 (09) 585-91.
  • 52 Traynor BJ. et al. An outcome study of riluzole in amyotrophic lateral sclerosis--a population-based study in Ireland, 1996–2000. J Neurol 2003; 250 (04) 473-9.
  • 53 Turner MR. et al. Prognostic modelling of therapeutic interventions in amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Motor Neuron Disord 2002; 03 (01) 15-21.
  • 54 Andersen PM. et al. Good practice in the management of amyotrophic lateral sclerosis: clinical guidelines. An evidence-based review with good practice points. EALSC Working Group. Amyotroph Lateral Scler 2007; 08 (04) 195-213.
  • 55 Bedlack RS. et al. Open-label pilot trial of levetiracetam for cramps and spasticity in patients with motor neuron disease. Amyotroph Lateral Scler 2009; 10 (04) 210-5.
  • 56 Drory VE. et al. The value of muscle exercise in patients with amyotrophic lateral sclerosis. J Neurol Sci 2001; 191 (1–2): 133-7.
  • 57 Marquardt G, Seifert V. Use of intrathecal baclofen for treatment of spasticity in amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry 2002; 72 (02) 275-6.
  • 58 McClelland S. et al. Intrathecal baclofen for spasticity-related pain in amyotrophic lateral sclerosis: efficacy and factors associated with pain relief. Muscle Nerve 2008; 37 (03) 396-8.
  • 59 Elman LB. et al. Venous thrombosis in an ALS population over four years. Amyotroph Lateral Scler Other Motor Neuron Disord 2005; 06 (04) 246-9.
  • 60 Qureshi MM. et al. Increased incidence of deep venous thrombosis in ALS. Neurology 2007; 68 (01) 76-7.
  • 61 Gallagher JP. Pathologic laughter and crying in ALS: a search for their origin. Acta Neurol Scand 1989; 80 (02) 114-7.
  • 62 Vignola A. et al. Anxiety undermines quality of life in ALS patients and caregivers. Eur J Neurol 2008; 15 (11) 1231-6.
  • 63 Wicks P. et al. Prevalence of depression in a 12-month consecutive sample of patients with ALS. Eur J Neurol 2007; 14 (09) 993-1001.
  • 64 Lou JS. Fatigue in amyotrophic lateral sclerosis. Phys Med Rehabil Clin N Am 2008; 19 (03) 533-43.
  • 65 Gil J. et al. Causes of death amongst French patients with amyotrophic lateral sclerosis: a prospective study. Eur J Neurol 2008; 15 (11) 1245-51.
  • 66 Lechtzin N. et al. Early use of non-invasive ventilation prolongs survival in subjects with ALS. Amyotroph Lateral Scler 2007; 08 (03) 185-8.
  • 67 Lo CD. et al. Noninvasive positive-pressure ventilation in ALS: predictors of tolerance and survival. Neurology 2006; 67 (05) 761-5.
  • 68 Bourke SC. et al. Effects of non-invasive ventilation on survival and quality of life in patients with amyotrophic lateral sclerosis: a randomised controlled trial. Lancet Neurol 2006; 05 (02) 140-7.
  • 69 Pinto AC. et al. Respiratory assistance with a non-invasive ventilator (Bipap) in MND/ALS patients: survival rates in a controlled trial. J Neurol Sci 1995; 129 Suppl: 19-26.
  • 70 Bourke SC, Gibson GJ. Non-invasive ventilation in ALS: current practice and future role. Amyotroph Lateral Scler Other Motor Neuron Disord 2004; 05 (02) 67-71.
  • 71 Mendoza M. et al. A comparison of maximal inspiratory pressure and forced vital capacity as potential criteria for initiating non-invasive ventilation in amyotrophic lateral sclerosis. Amyotroph Lateral Scler 2007; 08 (02) 106-11.
  • 72 Gelinas DF, O’Connor P, Miller RG. Quality of life for ventilator-dependent ALS patients and their caregivers. J Neurol Sci 1998; 160 Suppl 1: S134-S136.
  • 73 Mustfa N. et al. The effect of noninvasive ventilation on ALS patients and their caregivers. Neurology 2006; 66 (08) 1211-7.
  • 74 Kaub-Wittemer D. et al. Quality of life and psychosocial issues in ventilated patients with amyotrophic lateral sclerosis and their caregivers. J Pain Symptom Manage 2003; 26 (04) 890-6.
  • 75 Borasio GD. et al. Standards of palliative care for patients with amyotrophic lateral sclerosis: results of a European survey. Amyotroph Lateral Scler Other Motor Neuron Disord 2001; 02 (03) 159-64.
  • 76 Miller RG. et al. Practice parameter update: The care of the patient with amyotrophic lateral sclerosis: drug, nutritional, and respiratory therapies (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2009; 73 (15) 1218-26.
  • 77 Cazzolli PA, Oppenheimer EA. Home mechanical ventilation for amyotrophic lateral sclerosis: nasal compared to tracheostomy-intermittent positive pressure ventilation. J Neurol Sci 1996; 139 Suppl: 123-8.
  • 78 Newall AR, Orser R, Hunt M. The control of oral secretions in bulbar ALS/MND. J Neurol Sci 1996; 139 Suppl: 43-4.
  • 79 Hardiman O. Symptomatic treatment of respiratory and nutritional failure in amyotrophic lateral sclerosis. J Neurol 2000; 247 (04) 245-51.
  • 80 Dupuis L. et al. Dyslipidemia is a protective factor in amyotrophic lateral sclerosis. Neurology 2008; 70 (13) 1004-9.
  • 81 Heffernan C. et al. Nutritional management in MND/ALS patients: an evidence based review. Amyotroph Lateral Scler Other Motor Neuron Disord 2004; 05 (02) 72-83.
  • 82 Desport JC. et al. Nutritional assessment and survival in ALS patients. Amyotroph Lateral Scler Other Motor Neuron Disord 2000; 01 (02) 91-6.
  • 83 Miller RG. 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.
  • 84 Lyall RA. et al. Respiratory muscle strength and ventilatory failure in amyotrophic lateral sclerosis. Brain 2001; 124 (Pt 10): 2000-13.
  • 85 Thornton FJ. et al. Amyotrophic lateral sclerosis: enteral nutrition provision--endoscopic or radiologic gastrostomy?. Radiology 2002; 224 (03) 713-7.
  • 86 Chio A. et al. Percutaneous radiological gastrostomy: a safe and effective method of nutritional tube placement in advanced ALS. J Neurol Neurosurg Psychiatry 2004; 75 (04) 645-7.
  • 87 Grossman M. et al. Impaired action knowledge in amyotrophic lateral sclerosis. Neurology 2008; 71 (18) 1396-401.
  • 88 Abrahams S, Leigh PN, Goldstein LH. Cognitive change in ALS: a prospective study. Neurology 2005; 64 (07) 1222-6.
  • 89 Bak TH, Hodges JR. Motor neurone disease, dementia and aphasia: coincidence, co-occurrence or continuum?. J Neurol 2001; 248 (04) 260-70.
  • 90 Cobble M. Language impairment in motor neurone disease. J Neurol Sci 1998; 160 Suppl 1: S47-S52.
  • 91 Appel SH. et al. Hematopoietic stem cell transplantation in patients with sporadic amyotrophic lateral sclerosis. Neurology 2008; 71 (17) 1326-34.
  • 92 Janson CG. et al. Human intrathecal transplantation of peripheral blood stem cells in amyotrophic lateral sclerosis. J Hematother Stem Cell Res 2001; 10 (06) 913-5.
  • 93 Mazzini L. et al. Stem cell treatment in Amyotrophic Lateral Sclerosis. J Neurol Sci 2008; 265 (1–2): 78-83.
  • 94 Mazzini L. et al. Mesenchymal stem cell transplantation in amyotrophic lateral sclerosis: A Phase I clinical trial. Exp Neurol 2010; 223 (01) 229-37.
  • 95 Deda H. et al. Treatment of amyotrophic lateral sclerosis patients by autologous bone marrow-derived hematopoietic stem cell transplantation: a 1-year follow-up. Cytotherapy 2009; 11 (01) 18-25.
  • 96 Martinez HR. et al. Stem-cell transplantation into the frontal motor cortex in amyotrophic lateral sclerosis patients. Cytotherapy 2009; 11 (01) 26-34.
  • 97 Kollewe K. et al. Klinische Leitlinien zur Behandlung der Amyotrophen Lateralsklerose. Nervenheilkunde 2008; 27: 302-16.
  • 98 Ludolph A, Dengler R. Geschichte, Epidemiologie und diagnostische Kriterien. In: Dengler R. et al. (Eds.) Amyptrophe Lateralsklerose. Stuttgart: Thieme; 2000