Skip to main content
Erschienen in: Der Nervenarzt 2/2016

01.02.2016 | Amyotrophe Lateralsklerose | Übersichten

Amyotrophe Lateralsklerose

Eine Multisystemdegeneration

verfasst von: A. Hübers, A. C. Ludolph, A. Rosenbohm, E. H. Pinkhardt, J. H. Weishaupt, Dr. J. Dorst

Erschienen in: Der Nervenarzt | Ausgabe 2/2016

Einloggen, um Zugang zu erhalten

Zusammenfassung

Hintergrund

In den letzten Jahren haben sich zunehmend Hinweise darauf ergeben, dass es sich bei der amyotrophen Lateralsklerose (ALS) nicht um eine reine Motoneuronerkrankung, sondern um eine Multisystemdegeneration mit einer Vielzahl nichtmotorischer Symptome handelt. Diese moderne Auffassung untermauerten neuropathologische und bildgebende Erkenntnisse.

Fragestellung

Es soll die Frage beantwortet werden, welche Erkenntnisse für das Vorliegen einer Multisystemdegeneration sprechen und was dies für Diagnostik und Therapie der Erkrankung bedeutet.

Material und Methode

Zusammenfassung und Bewertung neuester klinischer, bildgebender und neuropathologischer Studien.

Ergebnisse

Die aktuelle Studienlage belegt, dass Symptome der ALS weit über das motorische Nervensystem hinausgehen und insbesondere kognitive Funktionen, die Okulomotorik, das extrapyramidale System und die Sensibilität betreffen. Als neuropathologisches Korrelat findet sich eine stadienhafte Ausbreitung des Proteins „transactive response DNA binding protein 43 kDa“ (TDP-43) über funktionell verbundene kortikale Strukturen.

Schlussfolgerungen

Nichtmotorische Symptome kommen bei der ALS regelmäßig vor, auch wenn sie klinisch zumeist nicht im Vordergrund stehen. Das Wissen um ihr neuropathologisches Korrelat bietet neue Perspektiven für die Diagnostik, aber auch für die Therapie.
Literatur
1.
Zurück zum Zitat Anderson TJ, Macaskill MR (2013) Eye movements in patients with neurodegenerative disorders. Nature reviews. Neurology 9:74–85PubMed Anderson TJ, Macaskill MR (2013) Eye movements in patients with neurodegenerative disorders. Nature reviews. Neurology 9:74–85PubMed
2.
Zurück zum Zitat Ash S, Olm C, Mcmillan CT et al (2015) Deficits in sentence expression in amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener 16:31–39PubMedCentralCrossRefPubMed Ash S, Olm C, Mcmillan CT et al (2015) Deficits in sentence expression in amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener 16:31–39PubMedCentralCrossRefPubMed
3.
Zurück zum Zitat Boeve BF, Boylan KB, Graff-Radford NR et al (2012) Characterization of frontotemporal dementia and/or amyotrophic lateral sclerosis associated with the GGGGCC repeat expansion in C9ORF72. Brain 135:765–783PubMedCentralCrossRefPubMed Boeve BF, Boylan KB, Graff-Radford NR et al (2012) Characterization of frontotemporal dementia and/or amyotrophic lateral sclerosis associated with the GGGGCC repeat expansion in C9ORF72. Brain 135:765–783PubMedCentralCrossRefPubMed
4.
Zurück zum Zitat Braak H, Brettschneider J, Ludolph AC et al (2013) Amyotrophic lateral sclerosis – a model of corticofugal axonal spread. Nature reviews. Neurology 9:708–714PubMedCentralPubMed Braak H, Brettschneider J, Ludolph AC et al (2013) Amyotrophic lateral sclerosis – a model of corticofugal axonal spread. Nature reviews. Neurology 9:708–714PubMedCentralPubMed
5.
Zurück zum Zitat Braumühl A (1932) Pick’s disease and amyotrophic lateral sclerosis. Allg Zeitschrift Fur Psychiatr Psychol Med 96:364–366 Braumühl A (1932) Pick’s disease and amyotrophic lateral sclerosis. Allg Zeitschrift Fur Psychiatr Psychol Med 96:364–366
6.
7.
Zurück zum Zitat Carlomagno Y, Zhang Y, Davis M et al (2014) Casein kinase II induced polymerization of soluble TDP-43 into filaments is inhibited by heat shock proteins. PloS One 9:e90452PubMedCentralCrossRefPubMed Carlomagno Y, Zhang Y, Davis M et al (2014) Casein kinase II induced polymerization of soluble TDP-43 into filaments is inhibited by heat shock proteins. PloS One 9:e90452PubMedCentralCrossRefPubMed
8.
Zurück zum Zitat Chen AL, Riley DE, King SA et al (2010) The disturbance of gaze in progressive supranuclear palsy: implications for pathogenesis. Front Neurol 1:147PubMedCentralPubMed Chen AL, Riley DE, King SA et al (2010) The disturbance of gaze in progressive supranuclear palsy: implications for pathogenesis. Front Neurol 1:147PubMedCentralPubMed
9.
Zurück zum Zitat Chio A, Ilardi A, Cammarosano S et al (2012) Neurobehavioral dysfunction in ALS has a negative effect on outcome and use of PEG and NIV. Neurology 78:1085–1089CrossRefPubMed Chio A, Ilardi A, Cammarosano S et al (2012) Neurobehavioral dysfunction in ALS has a negative effect on outcome and use of PEG and NIV. Neurology 78:1085–1089CrossRefPubMed
10.
Zurück zum Zitat Choksi DK, Roy B, Chatterjee S et al (2014) TDP-43 Phosphorylation by casein kinase Iepsilon promotes oligomerization and enhances toxicity in vivo. Hum Mol Genet 23:1025–1035CrossRefPubMed Choksi DK, Roy B, Chatterjee S et al (2014) TDP-43 Phosphorylation by casein kinase Iepsilon promotes oligomerization and enhances toxicity in vivo. Hum Mol Genet 23:1025–1035CrossRefPubMed
11.
Zurück zum Zitat Cirulli ET, Lasseigne BN, Petrovski S et al (2015) Exome sequencing in amyotrophic lateral sclerosis identifies risk genes and pathways. Science 347:1436–1441 Cirulli ET, Lasseigne BN, Petrovski S et al (2015) Exome sequencing in amyotrophic lateral sclerosis identifies risk genes and pathways. Science 347:1436–1441
12.
Zurück zum Zitat Czell D, Andersen PM, Neuwirth C et al (2013) Progressive aphasia as the presenting symptom in a patient with amyotrophic lateral sclerosis with a novel mutation in the OPTN gene. Amyotroph Lateral Scler Frontotemporal Degener 14:138–140CrossRefPubMed Czell D, Andersen PM, Neuwirth C et al (2013) Progressive aphasia as the presenting symptom in a patient with amyotrophic lateral sclerosis with a novel mutation in the OPTN gene. Amyotroph Lateral Scler Frontotemporal Degener 14:138–140CrossRefPubMed
13.
Zurück zum Zitat DeJesus-Hernandez M, Mackenzie IR, Boeve BF et al (2011) Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS. Neuron 72:245–256 DeJesus-Hernandez M, Mackenzie IR, Boeve BF et al (2011) Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS. Neuron 72:245–256
14.
Zurück zum Zitat Desport JC, Preux PM, Truong TC et al (1999) Nutritional status is a prognostic factor for survival in ALS patients. Neurology 53:1059–1063CrossRefPubMed Desport JC, Preux PM, Truong TC et al (1999) Nutritional status is a prognostic factor for survival in ALS patients. Neurology 53:1059–1063CrossRefPubMed
15.
Zurück zum Zitat Dornblüth O (1889) An anatomical investigation of a case of amyotrophic lateral sclerosis. Neur Zbl 13 Dornblüth O (1889) An anatomical investigation of a case of amyotrophic lateral sclerosis. Neur Zbl 13
16.
Zurück zum Zitat Dorst J, Cypionka J, Ludolph AC (2013) High-caloric food supplements in the treatment of amyotrophic lateral sclerosis: A prospective interventional study. Amyotroph Lateral Scler Frontotemporal Degener 14:533–536CrossRefPubMed Dorst J, Cypionka J, Ludolph AC (2013) High-caloric food supplements in the treatment of amyotrophic lateral sclerosis: A prospective interventional study. Amyotroph Lateral Scler Frontotemporal Degener 14:533–536CrossRefPubMed
17.
Zurück zum Zitat Dorst J, Dupuis L, Petri S et al (2015) Percutaneous endoscopic gastrostomy in amyotrophic lateral sclerosis: a prospective observational study. J Neurol 262(4):849–858CrossRefPubMed Dorst J, Dupuis L, Petri S et al (2015) Percutaneous endoscopic gastrostomy in amyotrophic lateral sclerosis: a prospective observational study. J Neurol 262(4):849–858CrossRefPubMed
18.
Zurück zum Zitat Dorst J, Kuhnlein P, Hendrich C et al (2011) Patients with elevated triglyceride and cholesterol serum levels have a prolonged survival in amyotrophic lateral sclerosis. J Neurol 258:613–617CrossRefPubMed Dorst J, Kuhnlein P, Hendrich C et al (2011) Patients with elevated triglyceride and cholesterol serum levels have a prolonged survival in amyotrophic lateral sclerosis. J Neurol 258:613–617CrossRefPubMed
19.
Zurück zum Zitat Dupuis L, Corcia P, Fergani A et al (2008) Dyslipidemia is a protective factor in amyotrophic lateral sclerosis. Neurology 70:1004–1009CrossRefPubMed Dupuis L, Corcia P, Fergani A et al (2008) Dyslipidemia is a protective factor in amyotrophic lateral sclerosis. Neurology 70:1004–1009CrossRefPubMed
20.
Zurück zum Zitat Fathinia P, Hermann A, Reuner U et al (2013) Parkinson’s disease-like midbrain hyperechogenicity is frequent in amyotrophic lateral sclerosis. J Neurol 260:454–457CrossRefPubMed Fathinia P, Hermann A, Reuner U et al (2013) Parkinson’s disease-like midbrain hyperechogenicity is frequent in amyotrophic lateral sclerosis. J Neurol 260:454–457CrossRefPubMed
21.
Zurück zum Zitat Feneberg E, Hübers A, Weishaupt JH et al (2014) Genetik und Neurochemische Biomarker bei Amyotropher Lateralsklerose und Frontotemporaler Lobärdegeneration. Akt Neurol 41:239–247CrossRef Feneberg E, Hübers A, Weishaupt JH et al (2014) Genetik und Neurochemische Biomarker bei Amyotropher Lateralsklerose und Frontotemporaler Lobärdegeneration. Akt Neurol 41:239–247CrossRef
22.
Zurück zum Zitat Freischmidt A, Wieland T, Richter B et al (2015) Haploinsufficiency of TBK1 causes familial ALS and fronto-temporal dementia. Nat Neurosci 18:631–636CrossRefPubMed Freischmidt A, Wieland T, Richter B et al (2015) Haploinsufficiency of TBK1 causes familial ALS and fronto-temporal dementia. Nat Neurosci 18:631–636CrossRefPubMed
23.
Zurück zum Zitat Galimberti D, Fenoglio C, Serpente M et al (2013) Autosomal dominant frontotemporal lobar degeneration due to the C9ORF72 hexanucleotide repeat expansion: late-onset psychotic clinical presentation. Biol Psychiatry 74:384–391CrossRefPubMed Galimberti D, Fenoglio C, Serpente M et al (2013) Autosomal dominant frontotemporal lobar degeneration due to the C9ORF72 hexanucleotide repeat expansion: late-onset psychotic clinical presentation. Biol Psychiatry 74:384–391CrossRefPubMed
24.
Zurück zum Zitat Gitcho MA, Baloh RH, Chakraverty S et al (2008) TDP-43 A315T mutation in familial motor neuron disease. Ann Neurol 63:535–538 Gitcho MA, Baloh RH, Chakraverty S et al (2008) TDP-43 A315T mutation in familial motor neuron disease. Ann Neurol 63:535–538
25.
Zurück zum Zitat Goldstein LH, Abrahams S (2013) Changes in cognition and behaviour in amyotrophic lateral sclerosis: nature of impairment and implications for assessment. Lancet Neurol 12:368–380CrossRefPubMed Goldstein LH, Abrahams S (2013) Changes in cognition and behaviour in amyotrophic lateral sclerosis: nature of impairment and implications for assessment. Lancet Neurol 12:368–380CrossRefPubMed
26.
Zurück zum Zitat Ichikawa H (2010) Language disorders in ALS/FTLD. Clin Neurol 50:1014–1016 Ichikawa H (2010) Language disorders in ALS/FTLD. Clin Neurol 50:1014–1016
27.
Zurück zum Zitat Iglesias C, Sangari S, El Mendili MM et al (2015) Electrophysiological and spinal imaging evidences for sensory dysfunction in amyotrophic lateral sclerosis. BMJ Open 5:e007659PubMedCentralCrossRefPubMed Iglesias C, Sangari S, El Mendili MM et al (2015) Electrophysiological and spinal imaging evidences for sensory dysfunction in amyotrophic lateral sclerosis. BMJ Open 5:e007659PubMedCentralCrossRefPubMed
28.
Zurück zum Zitat Iwanaga K, Hayashi S, Oyake M et al (1997) Neuropathology of sporadic amyotrophic lateral sclerosis of long duration. J Neurol Sci 146:139–143CrossRefPubMed Iwanaga K, Hayashi S, Oyake M et al (1997) Neuropathology of sporadic amyotrophic lateral sclerosis of long duration. J Neurol Sci 146:139–143CrossRefPubMed
29.
Zurück zum Zitat Ju JS, Fuentealba RA, Miller SE et al (2009) Valosin-containing protein (VCP) is required for autophagy and is disrupted in VCP disease. J Cell Biol 187:875–888PubMedCentralCrossRefPubMed Ju JS, Fuentealba RA, Miller SE et al (2009) Valosin-containing protein (VCP) is required for autophagy and is disrupted in VCP disease. J Cell Biol 187:875–888PubMedCentralCrossRefPubMed
30.
Zurück zum Zitat Kabashi E, Valdmanis PN, Dion P et al (2008) TARDBP mutations in individuals with sporadic and familial amyotrophic lateral sclerosis. Nat Genet 40:572–574 Kabashi E, Valdmanis PN, Dion P et al (2008) TARDBP mutations in individuals with sporadic and familial amyotrophic lateral sclerosis. Nat Genet 40:572–574
31.
Zurück zum Zitat Kassubek J, Muller HP, Del Tredici K et al (2014) Diffusion tensor imaging analysis of sequential spreading of disease in amyotrophic lateral sclerosis confirms patterns of TDP-43 pathology. Brain 137:1733–1740CrossRefPubMed Kassubek J, Muller HP, Del Tredici K et al (2014) Diffusion tensor imaging analysis of sequential spreading of disease in amyotrophic lateral sclerosis confirms patterns of TDP-43 pathology. Brain 137:1733–1740CrossRefPubMed
32.
Zurück zum Zitat Kim HJ, Raphael AR, Ladow ES et al (2014) Therapeutic modulation of eIF2alpha phosphorylation rescues TDP-43 toxicity in amyotrophic lateral sclerosis disease models. Nat Genet 46:152–160PubMedCentralCrossRefPubMed Kim HJ, Raphael AR, Ladow ES et al (2014) Therapeutic modulation of eIF2alpha phosphorylation rescues TDP-43 toxicity in amyotrophic lateral sclerosis disease models. Nat Genet 46:152–160PubMedCentralCrossRefPubMed
33.
Zurück zum Zitat Kleijnen MF, Shih AH, Zhou P et al (2000) The hPLIC proteins may provide a link between the ubiquitination machinery and the proteasome. Mol Cell 6:409–419CrossRefPubMed Kleijnen MF, Shih AH, Zhou P et al (2000) The hPLIC proteins may provide a link between the ubiquitination machinery and the proteasome. Mol Cell 6:409–419CrossRefPubMed
34.
Zurück zum Zitat Kwiatkowski TJ Jr, Bosco DA, Leclerc AL et al (2009) Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis. Science 323:1205–1208 Kwiatkowski TJ Jr, Bosco DA, Leclerc AL et al (2009) Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis. Science 323:1205–1208
35.
Zurück zum Zitat Leveille A, Kiernan J, Goodwin JA et al (1982) Eye movements in amyotrophic lateral sclerosis. Arch Neurol 39:684–686CrossRefPubMed Leveille A, Kiernan J, Goodwin JA et al (1982) Eye movements in amyotrophic lateral sclerosis. Arch Neurol 39:684–686CrossRefPubMed
36.
37.
Zurück zum Zitat Ludolph A, Drory V, Hardiman O et al (2015) A revision of the El Escorial criteria – 2015. Amyotroph Lateral Scler Frontotemporal Degener. doi:10.3109/21678421.2015.1049183 (Epub ahead of print) Ludolph A, Drory V, Hardiman O et al (2015) A revision of the El Escorial criteria – 2015. Amyotroph Lateral Scler Frontotemporal Degener. doi:10.3109/21678421.2015.1049183 (Epub ahead of print)
38.
Zurück zum Zitat Lule 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. Amyotroph Lateral Scler Frontotemporal Degener 16:16–23CrossRefPubMed Lule 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. Amyotroph Lateral Scler Frontotemporal Degener 16:16–23CrossRefPubMed
39.
Zurück zum Zitat Lule D, Kurt A, Jurgens R et al (2005) Emotional responding in amyotrophic lateral sclerosis. J Neurol 252:1517–1524CrossRefPubMed Lule D, Kurt A, Jurgens R et al (2005) Emotional responding in amyotrophic lateral sclerosis. J Neurol 252:1517–1524CrossRefPubMed
40.
Zurück zum Zitat Maruyama H, Morino H, Ito H et al (2010) Mutations of optineurin in amyotrophic lateral sclerosis. Nature 465:223–226 Maruyama H, Morino H, Ito H et al (2010) Mutations of optineurin in amyotrophic lateral sclerosis. Nature 465:223–226
41.
Zurück zum Zitat Mendell JR, Chase TN, Engel WK (1971) Amyotrophic lateral sclerosis: metabolism of central monoamines and treatment with L-dopa. Trans Am Neurol Assoc 96:284–286PubMed Mendell JR, Chase TN, Engel WK (1971) Amyotrophic lateral sclerosis: metabolism of central monoamines and treatment with L-dopa. Trans Am Neurol Assoc 96:284–286PubMed
42.
Zurück zum Zitat Neumann M, Sampathu DM, Kwong LK et al (2006) Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 314:130–133CrossRefPubMed Neumann M, Sampathu DM, Kwong LK et al (2006) Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 314:130–133CrossRefPubMed
43.
Zurück zum Zitat Piepers S, Van Den Berg JP, Kalmijn S et al (2006) Effect of non-invasive ventilation on survival, quality of life, respiratory function and cognition: a review of the literature. Amyotroph Lateral Scler 7:195–200CrossRefPubMed Piepers S, Van Den Berg JP, Kalmijn S et al (2006) Effect of non-invasive ventilation on survival, quality of life, respiratory function and cognition: a review of the literature. Amyotroph Lateral Scler 7:195–200CrossRefPubMed
44.
Zurück zum Zitat Pradat PF, Bruneteau G, Munerati E et al (2009) Extrapyramidal stiffness in patients with amyotrophic lateral sclerosis. Mov Disord 24:2143–2148CrossRefPubMed Pradat PF, Bruneteau G, Munerati E et al (2009) Extrapyramidal stiffness in patients with amyotrophic lateral sclerosis. Mov Disord 24:2143–2148CrossRefPubMed
45.
Zurück zum Zitat Ravits J (2014) Focality, stochasticity and neuroanatomic propagation in ALS pathogenesis. Exp Neurol 262(Pt B):121–126CrossRefPubMed Ravits J (2014) Focality, stochasticity and neuroanatomic propagation in ALS pathogenesis. Exp Neurol 262(Pt B):121–126CrossRefPubMed
46.
Zurück zum Zitat Renton AE, Majounie E, Waite A et al (2011) A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD. Neuron 72:257–268 Renton AE, Majounie E, Waite A et al (2011) A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD. Neuron 72:257–268
47.
Zurück zum Zitat Rosen DR, Siddique T, Patterson D et al (1993) Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature 362:59–62 Rosen DR, Siddique T, Patterson D et al (1993) Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature 362:59–62
48.
Zurück zum Zitat Schreiber H, Gaigalat T, Wiedemuth-Catrinescu U et al (2005) Cognitive function in bulbar- and spinal-onset amyotrophic lateral sclerosis. A longitudinal study in 52 patients. J Neurol 252:772–781CrossRefPubMed Schreiber H, Gaigalat T, Wiedemuth-Catrinescu U et al (2005) Cognitive function in bulbar- and spinal-onset amyotrophic lateral sclerosis. A longitudinal study in 52 patients. J Neurol 252:772–781CrossRefPubMed
49.
Zurück zum Zitat Scotter EL, Chen HJ, Shaw CE (2015) TDP-43 Proteinopathy and ALS: insights into disease mechanisms and therapeutic targets. Neurotherapeutics 12:352–363PubMedCentralCrossRefPubMed Scotter EL, Chen HJ, Shaw CE (2015) TDP-43 Proteinopathy and ALS: insights into disease mechanisms and therapeutic targets. Neurotherapeutics 12:352–363PubMedCentralCrossRefPubMed
50.
Zurück zum Zitat Shaunak S, Orrell RW, O’sullivan E et al (1995) Oculomotor function in amyotrophic lateral sclerosis: evidence for frontal impairment. Ann Neurol 38:38–44CrossRefPubMed Shaunak S, Orrell RW, O’sullivan E et al (1995) Oculomotor function in amyotrophic lateral sclerosis: evidence for frontal impairment. Ann Neurol 38:38–44CrossRefPubMed
51.
Zurück zum Zitat Sreedharan J, Blair IP, Tripathi VB et al (2008) TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis. Science 319:1668–1672 Sreedharan J, Blair IP, Tripathi VB et al (2008) TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis. Science 319:1668–1672
52.
Zurück zum Zitat Suzuki H, Lee K, Matsuoka M (2011) TDP-43-induced death is associated with altered regulation of BIM and Bcl-xL and attenuated by caspase-mediated TDP-43 cleavage. J Biol Chem 286:13171–13183PubMedCentralCrossRefPubMed Suzuki H, Lee K, Matsuoka M (2011) TDP-43-induced death is associated with altered regulation of BIM and Bcl-xL and attenuated by caspase-mediated TDP-43 cleavage. J Biol Chem 286:13171–13183PubMedCentralCrossRefPubMed
53.
Zurück zum Zitat Truini A, Biasiotta A, Onesti E et al (2015) Small-fibre neuropathy related to bulbar and spinal-onset in patients with ALS. J Neurol 262:1014–1018CrossRefPubMed Truini A, Biasiotta A, Onesti E et al (2015) Small-fibre neuropathy related to bulbar and spinal-onset in patients with ALS. J Neurol 262:1014–1018CrossRefPubMed
54.
Zurück zum Zitat 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:e93932PubMedCentralCrossRefPubMed 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:e93932PubMedCentralCrossRefPubMed
55.
Zurück zum Zitat Vance C, Rogelj B, Hortobagyi T et al (2009) Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6. Science 323:1208–1211 Vance C, Rogelj B, Hortobagyi T et al (2009) Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6. Science 323:1208–1211
56.
Zurück zum Zitat Van Langenhove T, Van Der Zee J, Van Broeckhoven C (2012) The molecular basis of the frontotemporal lobar degeneration-amyotrophic lateral sclerosis spectrum. Ann Med 44:817–828PubMedCentralCrossRefPubMed Van Langenhove T, Van Der Zee J, Van Broeckhoven C (2012) The molecular basis of the frontotemporal lobar degeneration-amyotrophic lateral sclerosis spectrum. Ann Med 44:817–828PubMedCentralCrossRefPubMed
57.
Zurück zum Zitat Wang IF, Guo BS, Liu YC et al (2012) Autophagy activators rescue and alleviate pathogenesis of a mouse model with proteinopathies of the TAR DNA-binding protein 43. Proc Natl Acad Sci U S A 109:15024–15029PubMedCentralCrossRefPubMed Wang IF, Guo BS, Liu YC et al (2012) Autophagy activators rescue and alleviate pathogenesis of a mouse model with proteinopathies of the TAR DNA-binding protein 43. Proc Natl Acad Sci U S A 109:15024–15029PubMedCentralCrossRefPubMed
58.
Zurück zum Zitat Weis J, Katona I, Muller-Newen G et al (2011) Small-fiber neuropathy in patients with ALS. Neurology 76:2024–2029CrossRefPubMed Weis J, Katona I, Muller-Newen G et al (2011) Small-fiber neuropathy in patients with ALS. Neurology 76:2024–2029CrossRefPubMed
59.
Zurück zum Zitat Yang C, Tan W, Whittle C et al (2010) The C-terminal TDP-43 fragments have a high aggregation propensity and harm neurons by a dominant-negative mechanism. PloS One 5:e15878PubMedCentralCrossRefPubMed Yang C, Tan W, Whittle C et al (2010) The C-terminal TDP-43 fragments have a high aggregation propensity and harm neurons by a dominant-negative mechanism. PloS One 5:e15878PubMedCentralCrossRefPubMed
60.
Metadaten
Titel
Amyotrophe Lateralsklerose
Eine Multisystemdegeneration
verfasst von
A. Hübers
A. C. Ludolph
A. Rosenbohm
E. H. Pinkhardt
J. H. Weishaupt
Dr. J. Dorst
Publikationsdatum
01.02.2016
Verlag
Springer Berlin Heidelberg
Erschienen in
Der Nervenarzt / Ausgabe 2/2016
Print ISSN: 0028-2804
Elektronische ISSN: 1433-0407
DOI
https://doi.org/10.1007/s00115-015-0030-8

Weitere Artikel der Ausgabe 2/2016

Der Nervenarzt 2/2016 Zur Ausgabe

Mitteilungen der Schlaganfall-Gesellschaft

Mitteilungen der Schlaganfall-Gesellschaft

Mitteilungen der DGPPN

Mitteilungen der DGPPN 2/2016

Einführung zum Thema

Hirntod und Konsequenzen

Neu in den Fachgebieten Neurologie und Psychiatrie