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Verbal fluency in multiple sclerosis and neuromyelitis optica spectrum disorders: a systematic review and
Panagiotis Grigoriadis1, Christos Bakirtzis2, Spyridon Defteraios3
1School of Medicine, Faculty of Philosophy, Aristotle University of Thessaloniki, Thessaloniki, Greece.
Background:
Cognitive impairment is common in people with multiple sclerosis and neuromyelitis optica spectrum disorders. Verbal fluency in particular has been receiving increasing attention over the last couple of years.
Objective:
This meta-analysis summarizes the existing evidence from previous studies on verbal fluency in people with multiple sclerosis and neuromyelitis optica spectrum disorders.
Methods:
The MOOSE guidelines for meta-analyses of observational studies were followed. A systematic literature search was conducted in MEDLINE, Scopus, and the Cochrane Library from January 1990 to March 2025. Sixty-nine (69) studies were included in the synthesis.
Results:
People with multiple sclerosis performed significantly worse than healthy controls in both phonemic (n = 50, SMD -0.82, 95% CI -0.94 to -0.71, I2 68%, p < 0.00001) and semantic fluency (n = 46, SMD -0.81, 95% CI -0.95 to -0.68, I2 80%, p < 0.00001). Similar results were observed in people with neuromyelitis optica spectrum disorders for phonemic (n = 5; SMD -0.49, 95% CI -0.73 to -0.26, I2 27%, p < 0.0001) and semantic fluency (n = 7, SMD -0.57, 95% CI -0.85 to -0.29, I2 48%, p < 0.0001). No significant differences in performance were found between the two clinical entities for either phonemic (n = 5, SMD -0.01, 95% CI -0.21 to -0.19, I2 0%, p = 0.92) or semantic fluency (n = 5, SMD -0.01, 95% CI -0.39 to -0.41, I2 58%, p = 0.97). Analysis within the group of people with multiple sclerosis indicated poorer performance in those with the progressive forms than in those with relapsing-remitting multiple sclerosis in both phonemic (n = 10, SMD -0.43, 95% CI -0.13 to -0.73, I2 81%, p = 0.005) and semantic fluency (n = 10, SMD -0.55, 95% CI -0.32 to -0.79, I2 64%, p < 0.00001).
Conclusions:
Verbal fluency may be a clinically relevant marker of cognitive dysfunction in multiple sclerosis and neuromyelitis optica spectrum disorders. Routine testing may help identify patients who could benefit from targeted cognitive rehabilitation interventions.
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