Hidden manifestations of multiple sclerosis: a current view on pathogenesis and clinical significance

In patients with multiple sclerosis (MS), hidden symptoms such as cognitive impairment, depression, anxiety, fatigue, and sexual dysfunction significantly affect quality of life and contribute to disability progression. Despite high prevalence, these symptoms often remain underestimated and underdiagnosed in clinical practice. The pathogenesis of hidden manifestations in MS is multifactorial, involving inflammatory, neurodegenerative, vascular, metabolic, and psychosocial mechanisms. Cognitive impairment in patients with MS most commonly includes decreased information processing, memory deficits, and executive dysfunction. Depression and anxiety frequently co-occur; depressive symptoms are associated with hippocampal changes and cortico-limbic network alterations, while anxiety is linked to dysregulation of limbic structures and neuroinflammatory processes. Fatigue is one of the most disabling symptoms in MS, with its pathoge­nesis involving grey matter atrophy, and thalamic lesions. Sexual dysfunction affects more than half of patients and may arise from neurological (primary), somatic (secondary), or psychosocial (tertiary) factors. This review aims to summarize current data on hidden manifestations of MS, their pathogenic mechanisms and clinical significance, as well as to highlight new diagnostic trends. The literature search was performed using Scopus, PubMed, and Web of Science databases with the keywords “multiple sclerosis”, “cognitive impairment”, “depression”, “anxiety”, “fatigue”, and “sexual dysfunction.” Additional references were identified through manual bibliography screening.