Late-onset bipolar I disorder after resection of a right frontal falx meningioma: tumour, surgery, or medication?

Introduction

Secondary mania arising from structural brain lesions remains a clinically underrecognised presentation. Frontal and temporal lesions, particularly those involving right-hemisphere orbitofrontal and ventrolateral prefrontal circuits, are disproportionately associated with secondary mania compared with parietal or occipital lesions [1,2]. Meningiomas pose a distinct diagnostic challenge because neuropsychiatric symptoms may precede or follow surgical intervention, and the relative contributions of the lesion itself, the operative course, perioperative medication, and subsequent pharmacotherapy are difficult to disentangle. Late-onset first-episode mania in patients aged ≥50 years carries a substantially higher probability of an identifiable organic contributor, and current consensus guidelines recommend neuroimaging as a routine component of the workup in this population [3].

Aims

We present a case of late-onset bipolar I disorder emerging approximately one year after resection of a right frontal falx meningioma, and discuss the potential mechanistic contributions of lesion localisation, perioperative antiseizure medication, and antidepressant exposure.

Case Presentation

A 56-year-old woman with no personal or family psychiatric history underwent right frontal craniotomy for a WHO grade I meningothelial meningioma. She received levetiracetam for 6–7 months postoperatively and subsequently discontinued it. Approximately one year after surgery, she developed a depressive episode characterised by social withdrawal, anhedonia, reduced self-care, decreased appetite, severe insomnia, and hypersensitivity to environmental sounds. At an outside clinic, escitalopram (serotonin reuptake inhibitor) 10 mg/day and olanzapine (dopamine, serotonin receptor antagonist) 2.5 mg/day were initiated. Within one week, she developed a full manic episode with intermittent insomnia, daytime napping, and occasional avolition. She was treated with valproate titrated to 1000 mg/day (last measured plasma level: 72 µg/mL) and olanzapine 10 mg/day, with gradual remission to near-premorbid functioning. Written informed consent was obtained from the patient’s relative.

Discussion

Three overlapping mechanisms warrant consideration. First, the right frontal falx location is consistent with lesional mania networks: pooled lesion-mapping analyses demonstrate that 60.7% of lesional mania cases involve exclusively right-sided lesions (p < 0.0001), with preferential involvement of the superior frontal gyrus, medial orbitofrontal cortex, and anterior cingulate [2]. Right-hemisphere lesions are proposed to produce disinhibition of left-hemisphere reward-processing circuits through loss of orbitofrontal emotion-modulation [1]. Second, levetiracetam is associated with clinically meaningful mood and behavioural adverse effects, including irritability (weighted mean ~9.9%), depression, and psychosis; whether discontinuation contributed to mood destabilisation in this case cannot be excluded [5]. Third, and most directly, escitalopram monotherapy without concurrent mood stabilisation was initiated in a patient with unrecognised bipolar vulnerability. Population-level and randomised controlled evidence consistently demonstrates that antidepressant monotherapy is associated with treatment-emergent mania, particularly in the first months after initiation [4]. The absence of a personal or family psychiatric history, the post-surgical onset, and the right frontal localisation collectively support a secondary (organic) aetiology, while antidepressant exposure likely acted as a precipitant in a vulnerabilised context.

Conclusions

This case illustrates that late-onset mania after frontal meningioma resection is best understood through a convergent-risk framework, in which lesion localisation, perioperative medication, and antidepressant exposure interact to lower the threshold for a manic episode in a previously vulnerable individual.

References

1. Satzer D, Bond DJ. Bipolar Disord. 2016;18(3):205–220.
2. Barahona-Correa JB et al. Transl Psychiatry. 2020;10(1):139.
3. Sajatovic M et al. Bipolar Disord. 2015;17(7):689–704.
4. Oliva V, De Prisco M et al. eClinicalMedicine. 2025;87:103413.
5. Batista S et al. Diagnostics. 2023;13(22):3415.