Frontotemporal white matter changes in amyotrophic lateral sclerosis

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.

Usefulness of diffusion tensor imaging in amyotrophic lateral sclerosis: potential biomarker and association with the cognitive profile

“…It was observed that the greater involvement of white matter (lower FA values in DTI) was significantly associated with the presence of cognitive deficits. These findings support previous studies with voxel-based morphometry, which observed that ALS patients showed greater cognitive dysfunction and atrophy in extra-motor regions 19 . Recently, diverse authors have reported an association between alterations in DT images and disease severity in patients with ALS 6,10 .…”

Widespread Microstructural White Matter Involvement in Amyotrophic Lateral Sclerosis: A Whole-Brain DTI Study

“…The DTI pattern of predominantly frontal WM injury clearly reflects the frontal executive dysfunction that characterizes our patients with ALS and has been also extensively described in other cohorts of patients with ALS. 47,48 However, we cannot directly validate this hypothesis in our population because our patients did not show overt signs of cognitive impairment, and we did not perform an extensive neuropsychological assessment. Nonetheless, the location of the diffusivity changes in the associative tracts of the frontal lobes that we report in the present study is in line with similar FA and RD changes described in patients with the behavioral variant of frontotemporal dementia.…”

Morphometric correlates of dysarthric deficit in amyotrophic lateral sclerosis

“…The literature of reference here is even more heterogeneous, as a number of volumetric studies found no cross-sectional differences in WM between patients and healthy controls (e.g. 33,35), while other studies reported WM decrease (36)(37) or even increase (32,38). As described in a recent review, ALS is a disease characterised by a remarkable level of clinical heterogeneity (39).…”