Clinical Phenomenology and Neuroimaging Correlates in ALS-FTD

  • Catherine Lomen-HoerthEmail author


The overlap of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) has been well documented in FTD patients with co-morbid motor neuron degeneration and in ALS patients with frontotemporal dysfunction. Up to 15% of FTD patients and 30% of ALS patients experience the overlap syndrome. The syndrome may be difficult to identify since patients often present either to a neuromuscular clinic or a memory disorder’s center, each which may have limited expertise in the other specialty. Survival is greatly impacted for both disorders in the co-morbid condition, making identification of this syndrome critical. The clinical characteristics of the overlap syndrome with new diagnostic criteria will be discussed along with screening strategies, including the UCSF Screening battery and clinical neurophysiology techniques. Treatable mimics of this disorder will also be described and management techniques. Neuroimaging findings will be summarized, which show that the frontotemporal impairment in ALS patients lies on a continuum. Identification of the overlap syndrome also provides a unique opportunity to study very early signs of FTD and conversely, very early signs of ALS, to gain greater insight into both disorders.



Supplementary material

12031_2011_9636_MOESM1_ESM.ppt (497 kb)
ESM 1 (PPT 497 kb)


  1. Boxer AL, Mackenzie IR, Boeve BF, Baker M, Seeley WW, Crook R, Feldman H, Hsiung GY, Rutherford N, Laluz V, Whitwell J, Foti D, McDade E, Molano J, Karydas A, Wojtas A, Goldman J, Mirsky J, Sengdy P, Dearmond S, Miller BL, Rademakers R (2011) Clinical, neuroimaging, and neuropathological features of new chromosome 9q-linked FTD-ALS family. J Neurol Neurosurg Psychiatry 82(2):196–203PubMedCrossRefGoogle Scholar
  2. Brooks BR, Miller RG, Swash M, Munsat TL, World Federation of Neurology Research Group on Motor Neuron Diseases (2000) El Escorial revisited: revised criteria for the diagnosis of amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Motor Neuron Disord 1(5):293–299PubMedCrossRefGoogle Scholar
  3. Chang J, Lomen-Hoerth C, Murphy J, Henry R, Kramer J, Miller B, Gorno-Tempini M (2005) A voxel-based morphometry study of patterns of brain atrophy in ALS and ALS/FTLD. Neurology 58:198–208Google Scholar
  4. DeJesus-Hernandez M, Mackenzie IR, Boeve BF, Boxer AL, Baker M, Rutherford NJ, Nicholson AM, Finch NA, Flynn H, Adamson J et al (2011) Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS. Neuron 72, in press. Published online September 21, 2011. doi: 10.1016/j.neuron.2011.09.011
  5. Gordon PH, Goetz RR, Rabkin JG, Dalton K, McElhiney M, Hays AP et al (2010) A prospective cohort study of neuropsychological test performance in ALS. Amyotroph Lateral Scler 11(3):312–320PubMedCrossRefGoogle Scholar
  6. Hodges JR, Davies R, Xuereb J, Kril J, Halliday G (2003) Survival in frontotemporal dementia. Neurology 61(3):349–354PubMedGoogle Scholar
  7. Hu WT, Seelaar H, Josephs KA, Knopman DS, Boeve BF, Sorenson EJ et al (2009) Survival profiles of patients with frontotemporal dementia and motor neuron disease. Arch Neurol 66(11):1359–1364PubMedCrossRefGoogle Scholar
  8. Lomen-Hoerth C, Anderson T, Miller B (2002) The overlap of amyotrophic lateral sclerosis and frontotemporal dementia. Neurology 59:1077–1079PubMedGoogle Scholar
  9. Lomen-Hoerth C, Murphy J, Langmore S, Kramer JH, Olney RK, Miller B (2003) Are amyotrophic lateral sclerosis patients cognitively normal? Neurology 60:1094–1097PubMedGoogle Scholar
  10. Murphy JM, Henry RG, Langmore S, Kramer JH, Miller BL, Lomen-Hoerth C (2007) Continuum of frontal lobe impairment in amyotrophic lateral sclerosis. Arch Neurol 64(4):530–534PubMedCrossRefGoogle Scholar
  11. Neary D, Snowden JS, Gustafson L et al (1998) Frontemporal lobar degeneration. A consensus on clinical diagnostic criteria. Neurology 51:1546–1554PubMedGoogle Scholar
  12. Neary D, Snowden JS, Mann DMA (2000) Cognitive change in motor neurone disease/amyotrophic lateral sclerosis (MND/ALS). J Neurol Sci 180:15–20PubMedCrossRefGoogle Scholar
  13. Olney R, Murphy J, Forshew D, Garwood E, Miller B, Langmore S, Kohn M, Lomen-Hoerth C (2005) The effects of executive and behavioral dysfunction on the course of ALS. Neurology 65:1774–1777PubMedCrossRefGoogle Scholar
  14. Renton AE, Majounie E, Waite A, Simo´ n-Sa´ nchez J, Rollinson S, Gibbs JR, Schymick JC, Laaksovirta H, van Swieten JC, Myllykangas L et al; ITALSGEN Consortium (2011) A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD. Neuron 72, in press. Published online September 21, 2011. doi: 10.1016/j.neuron.2011.09.010
  15. Ringholz GM, Appel SH, Bradshaw M, Cooke NA, Mosnik DM, Schulz PE (2005) Prevalence and patterns of cognitive impairment in sporadic ALS. Neurology 65(4):586–590PubMedCrossRefGoogle Scholar
  16. Robertson ED, Hesse JH, Rose KD, Slama H, Johnson JK, Yaffe K et al (2005) Frontotemporal dementia progresses to death faster than Alzheimer’s disease. Neurology 65(5):719–725CrossRefGoogle Scholar
  17. Rusina R, Ridzon P, Kulist’ak P, Keller O, Bartos A, Buncova M et al (2010) Relationship between ALS and degree of cognitive impairment, markers of neurodegeneration and predictors for poor outcome. A prospective study. Eur J Neurol 17(1):23–30PubMedCrossRefGoogle Scholar
  18. Strong MJ, Grace GM, Freedman M, Lomen-Hoerth C, Woolley S, Goldstein LH et al (2009) Consensus criteria for the diagnosis of frontotemporal cognitive and behavioural syndromes in amyotrophic lateral sclerosis. Amyotroph Lateral Scler 10(3):131–146PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Department of NeurologyUniversity of California, San FranciscoSan FranciscoUSA

Personalised recommendations