Ictal laughter induced by repetitive transcranial magnetic stimulation in stroke patients: a case series

Background: Repetitive transcranial magnetic stimulation (rTMS) is a well-established neuromodulation technique for post-stroke motor rehabilitation with a favorable safety profile. However, its safety in patients with acute/subacute cerebral infarction remains incompletely characterized, particularly regarding unusual behavioral responses. Gelastic seizures, characterized by stereotyped, inappropriate laughter without a corresponding emotional trigger, are a rare form of focal epilepsy typically associated with hypothalamic hamartomas or other structural brain lesions. Their induction by rTMS has been exceptionally reported. Case presentations: We report two cases of acute ischemic stroke in right-handed middle-aged males who developed stimulus-locked ictal laughter during low-frequency (1 Hz) rTMS applied to the left primary motor cortex (M1) for upper limb rehabilitation. Case 1 was a 48-year-old male with right temporo-parieto-occipital infarction who developed recurrent, uncontrollable ictal laughter during the third rTMS session. The laughter was site-specific and reproducible, elicited only when the coil was positioned over the left M1 and ceasing upon repositioning to the prefrontal area. Post-stimulation video-electroencephalography (VEEG) with bipolar montage analysis revealed sporadic single sharp waves over the right anterior temporal (F8), bilateral dorsolateral prefrontal cortex (F3, 4) during wakefulness. Seven months later, upon re-challenge, the patient promptly reported an urge to laugh, leading to immediate cessation. Case 2 was a 42-year-old male with a right lacunar infarct in the globus pallidus and internal capsule who developed ictal-like laughter during the fifth rTMS session, preceded by a premonitory urge to laugh during the fourth session. Consciousness was fully preserved in both patients, and each reported post-ictal dysphoria. Discontinuation of rTMS resulted in complete symptom resolution, with no recurrence at follow-up. Conclusions: To our knowledge, this is the first report of rTMS-induced ictal laughter in stroke patients. These observations expand the spectrum of rTMS-associated adverse effects, challenge the assumption that low-frequency protocols are uniformly safe in the post-stroke population, and underscore the need for clinical vigilance in patients with structural brain lesions.