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Sanjay Kalra, MD; Christopher C. Hanstock, PhD; W. R. Wayne Martin, MD; Peter S. Allen, PhD; Wendy S. Johnston, MD

Arch Neurol. 2006;63:1144-1148.

Background  Clinical assessment is insensitive to the degree of cerebral involvement in amyotrophic lateral sclerosis (ALS). Regional brain concentrations N-acetylaspartylglutamate (NAA) plus myo-inositol (Ins), as measured by magnetic resonance spectroscopy, are respectively decreased and increased, suggesting that these compounds may provide a biomarker of the degree of cerebral involvement in ALS.

Objective  To test the hypothesis that the NAA/Ins ratio may provide an index of cerebral involvement in patients with ALS.

Design  High-field (3.0-T) magnetic resonance spectroscopy was performed to determine the NAA/creatine plus phosphocreatine (NAA/Cr), NAA/choline (NAA/Cho), Ins/Cr, and NAA/Ins ratios in the motor cortex.

Participants  Seventeen patients with ALS and 15 healthy control subjects were studied.

Results  In patients with ALS, the greatest abnormality was a 22% decrease in NAA/Ins (71% sensitivity and 93% specificity, P = .001); Ins/Cr was increased 18% (88% sensitivity and 53% specificity, P = .04), NAA/Cr was decreased 10% (88% sensitivity and 47% specificity, P = .04), and NAA/Cho was decreased 14% (53% sensitivity and 87% specificity, P = .047). Correlation of the ALS Functional Rating Scale with NAA/Ins approached statistical significance (R = 0.43, P = .07).

Conclusion  The NAA/Ins ratio may provide a meaningful biomarker in ALS given its optimal sensitivity and specificity profile.

Author Affiliations: Division of Neurology, Department of Medicine (Drs Kalra, Martin, and Johnston), and Department of Biomedical Engineering (Drs Hanstock and Allen), University of Alberta, Edmonton.

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