Journal of Neurology

, Volume 261, Issue 2, pp 283–290 | Cite as

Can lesions to the motor cortex induce amyotrophic lateral sclerosis?

  • Angela Rosenbohm
  • Jan Kassubek
  • Patrick Weydt
  • Nicolai Marroquin
  • Alexander E. Volk
  • Christian Kubisch
  • Hans-Jürgen Huppertz
  • Markus Weber
  • Peter M. Andersen
  • Jochen H. Weishaupt
  • Albert C. Ludolph
  • The ALS Schwaben Register Group
Original Communication

Abstract

A recent staging effort for amyotrophic lateral sclerosis (ALS) has demonstrated that the TDP-43 neuropathology may initiate focally in the motor cortex in the majority of patients. We searched our data bank for patients with lesions of the motor cortex which preceded disease onset. We performed a search of our patient- and MRI-data bank and screened 1,835 patients with amyotrophic lateral sclerosis for frontal lobe/motor cortex lesions. We found 18 patients with definite ALS who had documented and defined lesions of the motor cortex, which preceded the initial ALS symptoms by 8–42 years. In the vast majority (15/18) of the patients, the onset of ALS was closely related to the focal lesion since it started in a body region reflecting the damaged cortical area. The findings suggest that initial lesions to the motor cortex may be a contributing initiating factor in some patients with ALS or determine the site of onset in individuals pre-disposed to ALS.

Keywords

Frontal lobe lesions Motor cortex lesions Amyotrophic lateral sclerosis Motor neuron disease 

References

  1. 1.
    Charcot J-M (1874) Sclerose laterale amyotrophique. Oevres completes. Bureaux du progres medical 2:249–266Google Scholar
  2. 2.
    Aran F (1850) Recherches sur une maladie non ancore décrite du système musculaire (atrophie musculaire progressive). Archs Gen Méd 14:5–35Google Scholar
  3. 3.
    Ravits JM, La Spada AR (2009) ALS motor phenotype heterogeneity, focality, and spread: deconstructing motor neuron degeneration. Neurology 73:805–811PubMedCentralCrossRefPubMedGoogle Scholar
  4. 4.
    Braak H, Del Tredici K (2011) Alzheimer’s pathogenesis: is there neuron-to-neuron propagation? Acta Neuropathol 121(5):589–595CrossRefPubMedGoogle Scholar
  5. 5.
    Braak H, Del Tredici K (2011) The pathological process underlying Alzheimer’s disease in individuals under thirty. Acta Neuropathol 121:171–181CrossRefPubMedGoogle Scholar
  6. 6.
    Braak H, Del Tredici K, Rub U, de Vos RA, Jansen Steur EN, Braak E (2003) Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol Aging 24:197–211CrossRefPubMedGoogle Scholar
  7. 7.
    Dormann D, Haass C (2011) TDP-43 and FUS: a nuclear affair. Trends Neurosci. doi:10.1016/j.tins.2011.05.002 PubMedGoogle Scholar
  8. 8.
    Dormann D, Rodde R, Edbauer D et al (2010) ALS-associated fused in sarcoma (FUS) mutations disrupt Transportin-mediated nuclear import. EMBO J 29:2841–2857PubMedCentralCrossRefPubMedGoogle Scholar
  9. 9.
    Andersen PM, Forsgren L, Binzer M, Nilsson P, Ala-Hurula V, Keränen ML, Bergmark L, Saarinen A, Haltia T, Tarvainen I, Kinnunen E, Udd B, Marklund SL (1996) Autosomal recessive adult-onset amyotrophic lateral sclerosis associated with homozygosity for Asp90Ala CuZn-superoxide dismutase mutation. A clinical and genealogical study of 36 patients. Brain 119:1153–1172CrossRefPubMedGoogle Scholar
  10. 10.
    Andersen PM, Nilsson P, Keränen ML, Forsgren L, Hägglund J, Karlsborg M et al (1997) Phenotypic heterogeneity in motor neuron disease patients with CuZn-superoxide dismutase mutations in Scandinavia. Brain Res 120:1723–1737Google Scholar
  11. 11.
    Logroscino G, Traynor BJ, Hardiman O et al (2010) Incidence of amyotrophic lateral sclerosis in Europe. J Neurol Neurosurg Psychiatry 81:385–390PubMedCentralCrossRefPubMedGoogle Scholar
  12. 12.
    Chen H, Richard M, Sandler DP, Umbach DM, Kamel F (2007) Head injury and amyotrophic lateral sclerosis. Am J Epidemiol 166:810–816PubMedCentralCrossRefPubMedGoogle Scholar
  13. 13.
    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 252:772–781CrossRefPubMedGoogle Scholar
  14. 14.
    Brettschneider J, Del Tredici KD, Toledo JB, Robinson JL, Irwin DJ, Grossman M, Suh E, Van Deerlin VM, Wood EM, Baek Y, Kwong L, Lee EB, Elman L, McCluskey L, Fang L, Feldengut S, Ludolph AC, Lee VM, Braak H, Trojanowski JQ (2013) Stages of pTDP-43 pathology in amyotrophic lateral sclerosis. Ann Neurol 74(1):20–38. doi:10.1002/ana.23937 PubMedCentralCrossRefPubMedGoogle Scholar
  15. 15.
    Huppertz HJ, Wellmer J, Staack AM, Altenmuller DM, Urbach H, Kroll J (2008) Voxel-based 3D MRI analysis helps to detect subtle forms of subcortical band heterotopia. Epilepsia 49:772–785CrossRefPubMedGoogle Scholar
  16. 16.
    Huppertz HJ (2013) Morphometric MRI analysis. In: Urbach H (ed) MRI in epilepsy. Springer, Berlin, pp 85–88Google Scholar
  17. 17.
    Wagner J, Weber B, Urbach H, Elger CE, Huppertz HJ (2011) Morphometric MRI analysis improves detection of focal cortical dysplasia type II. Brain 134:2844–2854CrossRefPubMedGoogle Scholar
  18. 18.
    Schmidt S, Kwee LC, Allen KD, Oddone EZ (2010) Association of ALS with head injury, cigarette smoking and APOE genotypes. J Neurol Sci 291:22–29PubMedCentralCrossRefPubMedGoogle Scholar
  19. 19.
    Turner MR, Abisgold J, Yeates DG, Talbot K, Goldacre MJ (2010) Head and other physical trauma requiring hospitalisation is not a significant risk factor in the development of ALS. J Neurol Sci 288:45–48CrossRefPubMedGoogle Scholar
  20. 20.
    Johnson VE, Stewart JE, Begbie FD, Trojanowski JQ, Smith DH, Stewart W (2013) Inflammation and white matter degeneration persist for years after a single traumatic brain injury. Brain 136:28–42PubMedCentralCrossRefPubMedGoogle Scholar
  21. 21.
    Blennow K, Hardy J, Zetterberg H (2012) The neuropathology and neurobiology of traumatic brain injury. Neuron 76:886–899CrossRefPubMedGoogle Scholar
  22. 22.
    Moisse K, Mepham J, Volkening K, Welch I, Hill T, Strong MJ (2009) Cytosolic TDP-43 expression following axotomy is associated with caspase 3 activation in NFL-/- mice: support for a role for TDP-43 in the physiological response to neuronal injury. Brain Res 1296:176–186CrossRefPubMedGoogle Scholar
  23. 23.
    Wu CH, Fallini C, Ticozzi N et al (2012) Mutations in the profilin 1 gene cause familial amyotrophic lateral sclerosis. Nature 488(7412):499–503PubMedCentralCrossRefPubMedGoogle Scholar
  24. 24.
    Ingre C, Landers JE, Rizik N, Volk AE, Akimoto C, Birve A, Hübers A, Keagle PJ, Piotrowska K, Press R, Andersen PM, Ludolph AC, Weishaupt JH (2013) A novel phosphorylation site mutation in profilin 1 revealed in a large screen of US, Nordic, and German amyotrophic lateral sclerosis/frontotemporal dementia cohorts. Neurobiol Aging 34:1708.e1–1708.e7CrossRefGoogle Scholar
  25. 25.
    McKee AC, Gavett BE, Stern RA et al (2010) TDP-43 proteinopathy and motor neuron disease in chronic traumatic encephalopathy. J Neuropathol Exp Neurol 69(9):918–929PubMedCentralCrossRefPubMedGoogle Scholar
  26. 26.
    Kiernan MC, Petri S (2012) Hyperexcitability and amyotrophic lateral sclerosis. Neurology 78:1544–1545CrossRefPubMedGoogle Scholar
  27. 27.
    Bohme I, Luddens H (2001) The inhibitory neural circuitry as target of antiepileptic drugs. Curr Med Chem 8:1257–1274CrossRefPubMedGoogle Scholar
  28. 28.
    Harvey RJ, Carta E, Pearce BR et al (2008) A critical role for glycine transporters in hyperexcitability disorders. Front Mol Neurosci 1:1PubMedCentralCrossRefPubMedGoogle Scholar
  29. 29.
    Carunchio I, Mollinari C, Pieri M, Merlo D, Zona C (2008) GAB(A) receptors present higher affinity and modified subunit composition in spinal motor neurons from a genetic model of amyotrophic lateral sclerosis. Eur J Neurosci 28:1275–1285CrossRefPubMedGoogle Scholar
  30. 30.
    Lorenzo LE, Barbe A, Portalier P, Fritschy JM, Bras H (2006) Differential expression of GABAA and glycine receptors in ALS-resistant vs. ALS-vulnerable motoneurons: possible implications for selective vulnerability of motoneurons. Eur J Neurosci 23:3161–3170CrossRefPubMedGoogle Scholar
  31. 31.
    Sasabe J, Aiso S (2010) Aberrant control of motoneuronal excitability in amyotrophic lateral sclerosis: excitatory glutamate/d-serine versus inhibitory glycine/gamma-aminobutanoic acid (GABA). Chem Biodivers 7:1479–1490CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Angela Rosenbohm
    • 1
  • Jan Kassubek
    • 1
  • Patrick Weydt
    • 1
  • Nicolai Marroquin
    • 2
  • Alexander E. Volk
    • 2
  • Christian Kubisch
    • 2
  • Hans-Jürgen Huppertz
    • 5
  • Markus Weber
    • 3
  • Peter M. Andersen
    • 1
    • 4
  • Jochen H. Weishaupt
    • 1
  • Albert C. Ludolph
    • 1
  • The ALS Schwaben Register Group
  1. 1.Department of NeurologyUniversity of UlmUlmGermany
  2. 2.Institute of Human GeneticsUniversity of UlmUlmGermany
  3. 3.Muskelzentrum/ALS ClinicKantonsspital St. GallenSt. GallenSwitzerland
  4. 4.Department of Clinical NeuroscienceUmeå UniversityUmeåSweden
  5. 5.Swiss Epilepsy CentreZürichSwitzerland

Personalised recommendations