What was once a mysterious clinical phenomenon that restored function and completely reversed disease in patients with dementia paralytica over 100 years ago may be now be potentially reinterpreted as an early manifestation of a biologically grounded, HSP-mediated mechanism targeting misfolded TDP-43, rekindling the long-dormant legacy of fever-based treatment not as a historical curiosity but as a renewed frontier in modern molecular medicine. Here, TARDBP is linked to hereditary spastic paraplegia.