MR spectroscopy in amyotrophic lateral sclerosis/motor neuron disease

Proton magnetic resonance spectroscopy (1H-MRS) and proton magnetic resonance spectroscopic imaging (1H-MRSI) have been used to identify neuronal dysfunction and/or loss in vivo in patients with various neurological diseases, including amyotrophic lateral sclerosis/motor neuron disease (ALS/MND). Both long and short echo time (TE) proton spectroscopy reveal the brain metabolites choline (Cho), creatine/phosphocreatine (Cr), and N-acetyl (NA) groups. Because NA groups are localized to mature neurons and Cr is homogeneously distributed throughout the brain, the NA/Cr ratio is considered an index of neuronal integrity. Long TE proton spectroscopic studies have revealed significantly decreased NA/Cr values in the sensorimotor cortex and brainstem of patients with ALS, consistent with neuronal dysfunction and/or loss. The amount of NA/Cr decrease appears to be directly proportional to the degree of clinical upper motor neuron deficit. Short TE 1H-MRS and 1H-MRSI also reveal other metabolites such as glutamate (Glu) and glutamine (Gln), which have been implicated in the ALS/MND disease process. Preliminary results of short TE 1H-MRSI of the medulla in patients with ALS/MND have revealed significantly decreased NA/Cr values and abnormally elevated Glu+Gln/Cr ratios, compared to control individuals. The latter values were higher in patients with more rapid disease. Although it is unclear whether the elevation of Glu+Gln/Cr precedes or follows the neuronal (and axonal) degeneration in the medulla of these patients, its occurrence provides in vivo evidence of abnormal glutamate metabolism in the CNS parenchyma of patients with ALS/MND.