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. 2021 Aug 27;12:701170. doi: 10.3389/fneur.2021.701170

Table 1.

Summary of predicted MRS detectable changes in the pathogenesis of ALS.

Ratio Predicted MRS detectable change in ALS
[Glutamate]/[NAA][Glutamine]/[NAA][Glx]/[NAA] Increase
[GABA]/[Glutamate][GABA]/[Glutamine][GABA]/[Glx] Decrease

MRS detects the overall number of molecules within a fixed volume, and therefore loss of glutamatergic and GABAergic neurons may cancel out observed changes in neurotransmitter concentration on a per-neuron basis. Given that NAA is found only in neurons and its MRS signal intensity is correlated with neuronal density, ratios of overall signal intensity of glutamate, glutamine, Glx, and GABA to overall signal intensity of NAA can provide an estimate for the per-neuron concentration of each neurotransmitter. In the pathogenesis of ALS we would expect the concentration of glutamate, glutamine, and Glx per neuron to increase; the concentration of GABA per neuron to decrease; and the overall concentration of NAA to decrease. Ratio predictions for are summarized based on this logic. It is noted that predictions listed hold for all stages of the disease. However, in the late stages, extensive neuronal damage and loss of volume may obscure the ability to detect elevated glutamate in the remaining functional neurons.

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