MRS in Motor Neuron Diseases

Abstract

Upper motor neurons (UMN) in the motor cortex and/or lower motor neurons (LMN) in the brainstem and spinal cord are affected in a heterogeneous group of related or pathologically similar adult-onset diseases, collectively termed as motor neuron diseases (MND). Amyotrophic lateral sclerosis (ALS) is the most predominant (85 %) among MND in which both UMN and LMN progressively degenerate. The etiology of ALS is not known in approximately 90 % of patients; however, inheritance of genetic mutations underlies in about 10 % of them. To date, neither conventional neuroimaging techniques nor laboratory tests of body fluids or biopsy samples yielded definitive biomarkers for ALS. Furthermore, molecular and cellular mechanisms involved in this disease remain poorly understood. Proton MRS is well suited to quantify metabolite alterations in the brain, and it has been used on patients with ALS in an effort to gain insight into the pathophysiology of ALS. A brief description on MND and their subtypes, limitations of clinical neuroimaging methods to diagnose ALS, a number of brain metabolites that can be quantified by in vivo MRS and their relevance to MND, and MRS techniques and their limitations are provided. Use of a whole-brain MRSI approach to fully characterize changes within the brain due to disease is described with a sample dataset obtained in a patient with ALS. Changes in the concentration or ratio of brain metabolites in patients with ALS and their pathophysiological significances are described. Finally, the use of MRS methods for longitudinal and therapeutic evaluation studies and future perspectives are discussed.