This chapter talks about a 73-year-old right-handed woman who presented at initial consultation with 6 to 8 months history of progressive weakness in her arms bilaterally. Nerve conduction and EMG studies were obtained and showed evidence of denervation changes consistent of amyotrophic lateral sclerosis. Cervical spine MRI showed no abnormal signal in the cord. Brain MRI showed extensive frontotemporal atrophy, bilateral hippocampal atrophy, and periventricular deep white matter T2 hyperintense changes. The diagnostic impression was fronto-temporal dementia with amyotrophic lateral sclerosis (FTD-ALS). Amyotrophic lateral sclerosis (ALS) is a complex neurodegenerative disease involving both upper motor neuron and lower motor neuron characterized by progressive muscle weakness, muscle wasting, and spasticity. ALS has been traditionally considered to be a disorder affecting only motor systems; however, recent developments show that ALS is a multi-system disorder in which motor system deficits are the most prominent manifestations, but non-motor manifestations can also be observed.