Significant Motor Cortex Degeneration in ALS According to MRS Findings

Study utilizing metabolic markers and magnetic resonance imaging finds cerebral degeneration is more pronounced in the motor cortex compared with the prefrontal cortex in patients with ALS.

In amyotrophic lateral sclerosis (ALS), cerebral degeneration is typically more pronounced in the motor cortex compared with the prefrontal cortex, according to research published in Neurology: Clinical Practice.

Researchers used single-voxel, proton, magnetic resonance spectroscopy (MRS) to examine cerebral degeneration and neurochemistry in patients with ALS. Participants included 65 individuals with ALS, and 43 age matched healthy controls recruited form multiple ALS clinics. The clinical and neuroimaging protocol was standardized across all sites and investigators evaluated left and right finger and foot taping rates as indicators of upper motor neuron function. Disability was assessed using the ALS Functional Rating Scale-Revised; cognitive function was also evaluated.

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Researchers found that in the motor cortex, total N-acetyl aspartyl moieties (tNAA)/creatinine, tNAA/choline, and tNAA/myo-inositol ratios were reduced by 9% to 12% to in the ALS group compared with control patients (P <.001, P <.001, and P =.002, respectively). No significant group differences for myo-inositol/creatinine and myo-inositol/choline ratios were found between the ALS and control groups. Further, investigators found tNAA/creatinine and tNAA/choline were reduced by 5% and 6% in the prefrontal cortex in the ALS group; this approached but did not reach statistical significance.

In the ALS group, a lower motor tNAA ratios was associated with a reduced foot tapping rate, while lower motor tNAA/myo-inositol was linked to reduced finger tapping rate. Elevated rate of disease progression was associated with lower motor tNAA/choline. A decrease in prefrontal tNAA/creatinine ration was associated with reduced verbal fluence, semantic fluency, and forward and backward digit span. No correlation between ALS Functional Rating Scale-Revised and symptom duration was noted.

Study limitations include the heterogeneity of the ALS population. Researchers suggest that future studies include disease controls, including progressive muscular atrophy, primary lateral sclerosis, and relevant neuropathies.

The Researchers concluded that, “tNAA ratios in the motor region were lower in ALS, indicative of impaired neuronal integrity in the motor cortex and subadjacent white matter. These findings parallel those of previous single-center MRS studies demonstrating abnormal metabolites in this same region.” They went on to add that “[t]his study demonstrates in vivo that cerebral degeneration in ALS is most profound in the motor cortex and less so in the mesial prefrontal cortex, that tNAA/[myo-inositol] ratio remains a promising biomarker of degeneration and one that requires further evaluation.”


Srivastava O, Hanstock C, Chenji S, et al. Cerebral degeneration in amyotrophic lateral sclerosis. A prospective multicenter magnetic resonance spectroscopy study [published online June 5, 2019]. Neurol Clin Pract. doi: 10.1212/CPJ.000000000000674