Uhthoff’s Phenomenon—A Scare or Real Threat to Multiple Sclerosis Patients? A Narrative Review

Background: Uhthoff’s phenomenon (UP) is a transient, fully reversible exacerbation of pre-existing neurological deficits in multiple sclerosis (MS) patients, triggered by minor elevations in core body temperature. In clinical practice, UP is a frequent source of distress, often misidentified as an acute inflammatory disease relapse. Objectives: This narrative review provides a critical analysis of UP, addressing the methodological heterogeneity in its epidemiological estimates, its clinical presentation, and its differential diagnosis from true relapses. Methods: Mechanistically, we synthesize traditional concepts of temperature-dependent conduction block with modern insights into neuroenergetic failure, mitochondrial dysfunction, inflammatory mediators, and autonomic dysregulation. Results: Furthermore, this work delineates current management strategies, establishing a clear distinction between robust evidence-based interventions and expert-informed practical guidance for patient education, physical rehabilitation planning, targeted active/passive cooling, and pharmacological approaches. Conclusion: Characterized as a pseudo-relapse, UP occurs independently of novel focal neuroinflammation. Although it does not inflict permanent structural damage to axons, the transient neuroenergetic crises and accompanying psychological burdens constitute a genuine threat to patient quality of life and functional autonomy, requiring systematic, interdisciplinary care.