BACKGROUND.Although mania is characteristic of bipolar disorder, it can also occur following focal brain damage. Such cases may provide unique insight into brain regions responsible for mania symptoms and identify therapeutic targets. METHODS.Lesion locations associated with mania were identified using a systematic literature search (n = 41) and mapped onto a common brain atlas. The network of brain regions functionally connected to each lesion location was computed using normative human connectome data (resting-state functional MRI, n = 1000) and contrasted with those obtained from lesion locations not associated with mania (n = 79). Reproducibility was assessed using independent cohorts of mania lesions derived from clinical chart review (n = 15) and of control lesions (n = 490). Results were compared with brain stimulation sites previously reported to induce or relieve mania symptoms. RESULTS.Lesion locations associated with mania were heterogeneous and no single brain region was lesioned in all, or even most, cases. However, these lesion locations showed a unique pattern of functional connectivity to the right orbitofrontal cortex, right inferior temporal gyrus, and right frontal pole. This connectivity profile was reproducible across independent lesion cohorts and aligned with the effects of therapeutic brain stimulation on mania symptoms. CONCLUSION.Brain lesions associated with mania are characterized by a specific pattern of brain connectivity that lends insight into localization of mania symptoms and potential therapeutic targets.

Spontaneous transsphenoidal meningoencephalcele is a rare entity, even rarer through the Sternberg’s canal, a congenital defect on the lateral wall of the sphenoid sinus. We report such a case in an obese 52-year-old female with spontaneous cerebrospinal fluid (CSF) rhinorrhoea and recurrent meningitis. Brain CT, MRI and CT cisternography were performed. Surgical correction and short-term follow-up were recorded. CT scan showed a defect on the lateral wall of the right sphenoid sinus filled with a soft tissue mass extending to the nasal cavity. MRI scan revealed brain parenchyma from the right temporal lobe herniated through the sphenoid bone defect. CT cisternography showed 270 mmH2O opening pressure and confirmed the CSF leakage. Surgical correction was performed with resolution of the symptoms. MRI and CT are complementary modalities for evaluating this entity, the first being the method of choice for meningoencephalcele diagnosis although bone defects are best depicted on CT scan. CT cisternography identifies the specific site of leak and confirms benign intracranial hypertension, consistently reported in meningoencephaloceles. Obesity and benign intracranial hypertension have been reported as a combined mechanism allegedly contributing to meningoencephaloceles through congenital skull base defects, by increasing intraabdominal pressure thus decreasing venous return, with augmented intracranial pressure and subsequent reduced absorption of the CSF.

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. Here, we aimed 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. We thus performed a systematic literature search (PROSPERO registration CRD42016053675) on PubMed and Web-Of-Science, using terms that reflect diagnoses and structures of interest, as well as lesional mechanisms. Two researchers reviewed the articles separately according to PRISMA Guidelines, selecting reports of adult-onset hypomania, mania or mixed state following a focal brain lesion, for pooled-analyses of individual patient data. Eligible lesion images were manually traced onto the corresponding MNI space slices, and lesion topography analyzed using standard brain atlases. Using this approach, data from 211 lesional mania patients was extracted from 114 reports. Among 201 cases with focal lesions, more patients had lesions involving exclusively the right (60.7%) than exclusively the left (11.4%) hemisphere. In further analyses of 56 eligible lesion images, while findings should be considered cautiously given the potential for selection bias of published lesion images, right-sided predominance of lesions was confirmed across multiple brain regions, including the temporal lobe, fusiform gyrus and thalamus. These, and several frontal lobe areas, were also identified as preferential lesion sites in comparisons with control lesions. Such 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.

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