Neuropsychiatric Manifestations of Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a debilitating neurological disorder characterized by progressive motor weakness secondary to the loss of motor neurons. Although ALS primarily affects motor neurons, there is a growing recognition that it also affects cognition and behavior, leading to the concept of an ALS-frontotemporal dementia (FTD) continuum. Cognitive impairments that are specific to ALS primarily manifest as executive and language dysfunction. In addition to the cognitive impairment, ALS patients may manifest neuropsychiatric symptoms, including apathy, emotional incontinence, mood disorders, and psychosis. In recent years, advancements in genetic and pathological investigations and imaging techniques have contributed to our understanding of psychiatric manifestations of ALS. The etiology of psychiatric symptoms appears to be influenced by genetic factors, particularly the presence of C9orf72 repeat expansion. The propagation pattern of phosphorylated TDP-43 pathology observed in postmortem brain, along with the distinctive atrophy pattern observed in brain magnetic resonance imaging (MRI) scans of patients with ALS with or without FTD, suggests that the degeneration and disruption of fronto-subcortical networks are responsible for the neuropsychiatric symptoms associated with ALS. In this chapter, we describe the pathophysiological mechanisms, prevalence rates, clinical presentations, assessment methods, and therapeutic approaches pertaining to neuropsychiatric symptoms observed in patients with ALS.