Asymptomatic is not silent: proposal of HTLV-1–associated multiple inflammatory disease as an early neuroinflammatory state

BACKGROUND: Human T-lymphotropic virus type 1 (HTLV-1) infection is classically categorized as either asymptomatic or associated with HTLV-1-associated myelopathy (HAM). However, accumulating clinical evidence suggests that a substantial proportion of individuals labeled as asymptomatic present early inflammatory and neurological manifestations that do not fulfill established HAM diagnostic criteria. RESEARCH DESIGN AND METHODS: We conducted an observational study within a large, long-standing Brazilian HTLV-1 cohort. Between January 2015 and December 2025, adults previously classified as asymptomatic were systematically evaluated during routine follow-up at a specialized outpatient clinic. Standardized clinical and neurological examinations were newly performed by clinicians not previously involved in their care and assessment. These findings were then integrated with neuropsychological, radiological and laboratory assessments. RESULTS: Among individuals previously considered asymptomatic, 24% fulfilled predefined criteria for an intermediate condition termed HTLV-1-associated multiple inflammatory disease (HAMID). HAMID was associated with older age, female sex, higher proviral load, markers of chronic immune activation, subtle spinal cord abnormalities, and measurable cognitive impairment, particularly affecting episodic memory. CONCLUSIONS: HTLV-1 infection encompasses an early, biologically active inflammatory disease stage distinct from both asymptomatic infection and overt HAM. Recognition of HAMID refines the clinical spectrum of HTLV-1 infection and provides a framework for earlier diagnosis, improved risk stratification, and closer clinical surveillance.