Clinical, radiological, pathological and prognostic features of general paresis: a cohort study

General paresis is a rare type of syphilis characterized by progressive cognitive impairment and psychiatric syndromes. It is often misdiagnosed because of its rarity and similarity to other diseases. We aimed to investigate the clinical, radiological, pathological and prognostic features of general paresis comprehensively and to compare it with other dementias. Between August 2019 and January 2024, patients were recruited from a memory clinic setting at the National Center for Neurological Disorders in China. Participants underwent clinical evaluation, laboratory testing and imaging and were followed after treatment. Comparative analysis was conducted on clinical features and neuropsychiatric assessments, and brain image features were investigated using linear regression models and SuStaIn models. Seventy-eight patients were included, with 90% being male. The median duration from symptom onset to the first diagnostic visit was 15 months. Sixty-three patients were followed for an average of 1.4 years. Cognitive impairment emerged as the most common symptom, and half of the patients co-existed with motor symptoms. Impairment across all cognitive domains accompanied by positive psychiatric symptoms raised suspicion for general paresis and distinguished it from Alzheimer's disease, frontotemporal dementia and anti-LGI1 encephalitis-related dementia. Common imaging abnormalities in general paresis included whole-brain atrophy and cortical hypointensity. Hippocampus-predominant and hippocampus-sparing atrophy subtypes were identified. Autoimmune responses in general paresis were demonstrated through the detection of autoimmune encephalitis antibodies in 11% of patients. Pathological amyloid changes were observed in 26% of patients, and elevated total tau levels were found in 30%. Seventy per cent of patients showed improvement following treatment, with a reduction in the number of symptoms observed across all cases. This study identifies specific clinical syndromes and radiological features of general paresis and refines the understanding of its prognosis. We provide clues to distinguish general paresis from other dementias, facilitating early diagnosis and treatment. The role of novel pathological changes in general paresis needs to be studied further.