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

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.

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.

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.