Journal of Neurology

, Volume 252, Issue 3, pp 321–331

Frontotemporal white matter changes in amyotrophic lateral sclerosis

  • Sharon Abrahams
  • Laura H. Goldstein
  • John Suckling
  • Virginia Ng
  • Andy Simmons
  • Xavier Chitnis
  • Louise Atkins
  • Steve C. R. Williams
  • P. N. Leigh
ORIGINAL COMMUNICATION

Abstract

Cognitive dysfunction can occur in some patients with amyotrophic lateral sclerosis (ALS) who are not suffering from dementia. The most striking and consistent cognitive deficit has been found using tests of verbal fluency. ALS patients with verbal fluency deficits have shown functional imaging abnormalities predominantly in frontotemporal regions using positron emission tomography (PET). This study used automated volumetric voxel-based analysis of grey and white matter densities of structural magnetic resonance imaging (MRI) scans to explore the underlying pattern of structural cerebral change in nondemented ALS patients with verbal fluency deficits. Two groups of ALS patients, defined by the presence or absence of cognitive impairment on the basis of the Written Verbal Fluency Test (ALSi, cognitively impaired, n = 11; ALSu, cognitively unimpaired n = 12) were compared with healthy age matched controls (n = 12). A comparison of the ALSi group with controls revealed significantly (p < 0.002) reduced white matter volume in extensive motor and non–motor regions, including regions corresponding to frontotemporal association fibres. These patients demonstrated a corresponding cognitive profile of executive and memory dysfunction. Less extensive white matter reductions were revealed in the comparison of the ALSu and control groups in regions corresponding to frontal association fibres. White matter volumes were also found to correlate with performance on memory tests. There were no significant reductions in grey matter volume in the comparison of either patient group with controls. The structural white matter abnormalities in frontal and temporal regions revealed here may underlie the cognitive and functional imaging abnormalities previously reported in non–demented ALS patients. The results also suggest that extra–motor structural abnormalities may be present in ALS patients with no evidence of cognitive change. The findings support the hypothesis of a continuum of extra–motor cerebral and cognitive change in this disorder.

Key words

motor neuron disease executive function verbal fluency structural magnetic resonance imaging 

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Copyright information

© Steinkopff Verlag 2005

Authors and Affiliations

  • Sharon Abrahams
    • 1
  • Laura H. Goldstein
    • 2
  • John Suckling
    • 3
  • Virginia Ng
    • 4
  • Andy Simmons
    • 4
  • Xavier Chitnis
    • 5
  • Louise Atkins
    • 4
  • Steve C. R. Williams
    • 4
  • P. N. Leigh
    • 4
  1. 1.Dept. of PsychologyUniversity of EdinburghEdinburgh EH8 9JZScotland
  2. 2.Dept. of PsychologyInstitute of PsychiatryLondon SE5 8AFUK
  3. 3.Dept. of Psychiatry,University of Cambridge Addenbrooke’s HospitalCambridge CB2 2QQUK
  4. 4.Dept. of NeurologyInstitute of PsychiatryLondon SE5 8AFUK
  5. 5.Dept. of Biostatistics and ComputingInstitute of PsychiatryLondon SE5 8AFUK

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