Clinical and literature insights into the frontotemporal dementia and motor neuron disease spectrum

BACKGROUND: Frontotemporal dementia represents a heterogeneous group of neurodegenerative disorders primarily affecting the frontal and temporal lobes. The overlap between FTD and motor neuron disease is increasingly recognized, presenting a complex clinical syndrome characterized by progressive cognitive, behavioral, and motor decline. CASE PRESENTATION: We describe a 69-year-old patient with a 4-year history of excessive ambulation. Over the last year, behavioral changes including disorganized conduct, irritability, spitting, and cold water foot immersion developed. The patient experienced compelling auditory hallucinations driving her to walk continuously for up to 10 h per day. Four months prior to admission, gait impairment with frequent falls, along with hyperorality developed. Neurological examination revealed asymmetric mild weakness, marked muscle atrophy of facial and limb muscles, hyperreflexia, and impaired postural control. Brain MRI showed diffuse cerebral atrophy; electrophysiological studies indicated probable motor neuron disease; and TRODAT SPECT demonstrated impaired presynaptic dopaminergic function bilaterally, consistent with parkinsonism. Final diagnosis was frontotemporal dementia with probable motor neuron disease. LITERATURE REVIEW: A review of the literature highlights the clinical, radiological, and molecular features of FTD-MND overlap, emphasizing the role of TDP-43 pathology, C9orf72 mutations, and the need for multidisciplinary management. Current strategies are symptomatic, though novel therapies such as antisense oligonucleotides and biomarkers like neurofilament light chain (NfL) show promise. CONCLUSIONS: This case highlights the diagnostic complexity of FTD with MND overlap syndrome, emphasizing the need for comprehensive clinical, neuroimaging, and electrophysiological evaluation. Multimodal treatment approaches focusing on behavioral symptoms and functional support are essential for optimizing patient outcomes.