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Quantitative proton magnetic resonance spectroscopy detects abnormalities in dorsolateral prefrontal cortex and motor cortex of patients with frontotemporal lobar degeneration

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Abstract

Frontotemporal lobar degeneration (FTLD) is a neurodegenerative disease of the frontal and temporal neocortex. The single most common pathology underlying FTLD is neuronal degeneration with ubiquitin-positive but tau-negative inclusions consisting of Tar DNA binding proteins (TDP-43). Inclusions containing TDP-43 in neurons are also the most common pathology underlying motor neuron disease (MND). The present study tested the hypothesis that abnormal metabolite patterns within the dorsolateral prefrontal cortex (DLPFC) as well as the motor cortex (MC) may be observed in FTLD patients without motor disorders, using proton magnetic resonance spectroscopy (1H MRS). Twenty-six FTLD patients with cognitive damage and ten controls underwent multivoxel 1H MRS. Absolute concentrations of N-acetyl aspartate (NAA), creatine (Cr), choline (Cho) and myo-inositol (mI) were measured from the DLPFC, the MC and the parietal cortex (PC, an internal control). Statistical analyses were performed for group differences between FTLD patients and controls. Comparisons were also made across brain regions (PC and DLPFC; PC and MC) within FTLD patients. Significant reductions in NAA and Cr along with increased Cho and mI were observed in the DLPFC of FTLD patients compared to controls. Significantly lower NAA and higher Cho were also observed in the MCs of patients as compared to controls. Within the FTLD patients, both the MC and the DLPFC exhibited significantly decreased NAA and elevated Cho compared to the PC. However, only the DLPFC had significantly lower Cr and higher mI. Abnormal metabolite pattern from the MC supports the hypothesis that FTLD and MND may be closely linked.

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Acknowledgments

The support of MRI coordinator Alea Khan and technologists Doris Cain, Tonya Kurtz and Patricia O’ Donnell is gratefully acknowledged. This work was funded by NIH grants AG17586, NS44266 and AG15116.

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Authors and Affiliations

  1. Department of Radiology, University of Pennsylvania, B6 Blockley Hall, 423 Guardian Drive, Philadelphia, PA, 19104, USA

    Sanjeev Chawla, Sumei Wang, John H. Woo, Elias R. Melhem & Harish Poptani

  2. Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA

    Peachie Moore, Lauren Elman, Leo F. McCluskey & Murray Grossman

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  1. Sanjeev Chawla
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  2. Sumei Wang
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Correspondence to Harish Poptani.

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Chawla, S., Wang, S., Moore, P. et al. Quantitative proton magnetic resonance spectroscopy detects abnormalities in dorsolateral prefrontal cortex and motor cortex of patients with frontotemporal lobar degeneration. J Neurol 257, 114–121 (2010). https://doi.org/10.1007/s00415-009-5283-3

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