Mesial prefrontal cortex degeneration in amyotrophic lateral sclerosis: a high-field proton MR spectroscopy study

Abstract

Background and purpose: Frontotemporal lobar degeneration is responsible for the cognitive abnormalities seen in patients with ALS. We sought to evaluate the in vivo neurochemical changes associated with this pathology indicative of neuronal loss and gliosis.

Materials and methods: Twenty-four patients with ALS (2 with ALS-FTD) and 15 healthy controls were studied. High-field proton MR spectroscopy of the mesial prefrontal cortex was used to determine concentrations of NAA and mIns, markers of neuronal integrity and gliosis, respectively. Metabolite concentrations were correlated with cognitive tests (verbal fluency, ACE).

Results: NAA/mIns was decreased 17% (P =.002). Abnormalities were present to a lesser degree in the individual metabolites NAA (decreased 9%; P =.08) and mIns (increased 11%; P =.06) than the ratio of the 2 metabolites. These measures did not correlate significantly with verbal fluency or the ACE.

Conclusions: Prefrontal lobe degeneration exists in patients with ALS as indicated by an abnormal mesial prefrontal cortex neurochemical profile. Further study is necessary to determine the potential utility of the NAA/mIns ratio as a biomarker for frontal lobe degeneration in ALS.

Figure.

Sagittal (A) and coronal (B) gradient-weighted MR images demonstrate voxel placement in the mesial prefrontal cortex. Representative spectra (C, gray lines) and LCModel fit (C, dark lines) with peaks identified for mIns and NAA are shown for a control subject (left) and patient with ALS (right); note the increased mIns and decreased NAA in the patient with ALS compared with the control subject.