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.

This chapter talks about a 54-year-old right-handed man who was brought to medical attention by his daughter because of progressive speech difficulty over the last 2 years. The patient was clinically diagnosed with fronto-temporal dementia with non-fluent progressive aphasia as well as behavioral symptoms. Sensory and motor nerve conduction studies were normal. EMG needle electromyography showed mixed denervation pattern in the right FDI and left biceps with 2_ fasciculation potentials, positive sharp waves, and fibrillations. Motor units were polyphasic with increase in sharp waves. External examination of the formalin-fixed brain showed no obvious cerebral atrophy or no focal lesions. The base of the brain was unremarkable apart from mild patchy atherosclerosis. Serial coronal sections through the cerebral hemispheres showed a normal ventricular system and deep gray structures. Sections of the brainstem and cerebellum were also unremarkable apart from mild loss of pigmentation of substantia nigra.

This chapter presents the case of a 63-year-old right-handed woman who was referred for language difficulties. Significant deficits were present in executive and visuospatial functions, as well as language. Language was fluent, characterized by frequent semantic paraphasias, jargonophasia, and occasional word finding difficulties, and decreased understanding. The initial clinical diagnostic impression was that of a progressive but primarily focal cognitive disorder involving predominantly language: primary progressive aphasia (PPA). Autopsy confirmed the presence of a large left frontal hematoma with intraventricular spillage. Diffuse staining for b-amyloid was found in meningeal and cortical arteries, consistent with severe cerebral amyloid angiopathy (CAA). The differential diagnosis for PPA includes variants of fronto-temporal dementia (FTD) and atypical Alzheimer's disease (AD). The clinical profile, with the early onset, strong family history, absence of severe memory complaints on history and amnestic deficits on testing, behavioral changes, and a predominance of executive dysfunction, swayed the diagnosis towards FTD.