Right-sided brain lesions predominate among patients with lesional mania: evidence from a systematic review and pooled lesion analysis

ABSTRACT Background Despite claims that lesional mania is associated with right-hemisphere lesions, supporting evidence is scarce, and association with specific brain areas has not been demonstrated. Aims To test whether focal brain lesions in lesional mania are more often right-than left-sided, and if lesions converge on areas relevant to mood regulation. Methods We performed a systematic literature search (PROSPERO registration CRD42016053675) on PubMed and Web-Of-Science, using terms that reflected diagnoses and structures of interest, and lesional mechanisms. Two researchers reviewed the articles separately according to PRISMA Guidelines, to select reports of adult-onset hypomania, mania or mixed state following a focal brain lesion. When available, eligible lesion images were manually traced onto the corresponding slices of MNI space, and lesion topography analyzed using standard brain atlases. Pooled-analyses of individual patient data were performed. Results Data from 207 lesional mania patients was extracted from 110 reports. Among patients with focal lesions (N=197) more patients had lesions involving the right (84.3%) than the left (34.5%) hemisphere. Among 54 lesion images that were available, right-sided predominance of lesions was confirmed, and found to be was conserved across multiple brain regions, including the temporal lobe, fusiform gyrus and thalamus. These, in addition to several frontal lobe areas, were also identified as preferential lesion sites in comparisons with control lesions. Conclusions Pooled-analyses, based on the most comprehensive dataset of lesional mania available to date, confirm a preferential association with right-hemisphere lesions, while suggesting that several brain areas/circuits, relevant to mood regulation, are most frequently affected.