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Publisher Summary This chapter studies 64 patients with motor neuron disease (amyotrophic lateral sclerosis (ALS), familial ALS (fALS), progressive muscular atrophy (PMA), and primary lateral sclerosis (PLS)) using multiple point stimulation motor unit number estimation (MUNE), transcranial magnetic stimulation (TMS), proton magnetic resonance spectroscopic imaging (1H MRSI), diffusion tensor imaging (MRDTI), and clinical measures at baseline every 3 months thereafter for 15 months. It discusses the substantial differences in MUNE noted among the motor neuron disease subgroups and mean values for each motor neuron disease subgroup that were significantly lower vs. controls vs. the normal control average. MUNE showed the greatest significant change over time of any measure, clinical or otherwise, tested in this study. The chapter reviews that MUNE clearly delineates lower motor neuron dysfunction, strongly correlates with important clinical functions, such as strength and respiration, and is a highly sensitive marker of disease progression over time. These features make MUNE an important tool for both the study of the pathophysiology of the motor neuron diseases as well as an important measure for incorporation into future clinical trials.

Publisher Summary It has been accepted that both molecular genetics and the overlapping clinical features of syndromes generated too many inconsistencies for precise classification. The mitochondrial diseases have generated debate for three decades, ever since they were first recognized. Even today, there is no consensus about the meaning of the popular phrases to describe them: mitochondrial myopathy, mitochondrial encephalomyopathy, mitochondrial cytopathy, or mitochondrial disease. The uncertainty is a measure of the different criteria used to select the syndromes, which were first clinical and biochemical; then morphological definitions, moving from ultrastructure to histochemistry, were used, followed by human genetics and, finally, molecular genetics. This chapter focuses on disorders of the mitochondrial genome and not metabolic conditions caused by abnormalities of nuclear DNA that affect mitochondrial biochemical function.