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Spreading depolarisation (SD): a potential underlying mechanism in functional neurological disorder (FND)

Nwafor DC, Thohan C, Harge C, Shuttleworth CW, Carlson AP

BMJ case reports, 2025

Abstract

Functional neurological disorder (FND) presents with neurological symptoms lacking a structural correlate and is thought to result from brain network dysfunction. Despite advances in understanding its pathophysiology, several knowledge gaps exist. Spreading depolarisations (SDs), waves of cortical electrical disturbance best known in migraine aura and implicated in conditions like stroke and traumatic brain injury, have not been investigated in the context of FND. We present a patient with recurrent episodes of limb weakness and speech disturbances initially diagnosed as FND. Years later, following a left superficial temporal artery-middle cerebral artery bypass, she developed similar symptoms. Intraoperative electrocorticography revealed SDs coinciding with symptom onset, and treatment with SD inhibitors led to clinical improvement. While further studies are needed to establish causality, this case highlights SD's as a plausible pathophysiological mechanism in a subset of patients with FND and underscores the need for future research exploring their contribution to FND symptoms.

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