Functional/dissociative seizures as a neuroenergetic deficit syndrome: a brain economy failure hypothesis

Functional/dissociative seizures are debilitating and account for up to one-third of presentations to epilepsy monitoring units. Despite this, their pathophysiological mechanism remains poorly understood and available treatments lead to seizure freedom in fewer than half of patients. It is proposed here that functional/dissociative seizures may involve a neuroenergetic deficit syndrome or a brain economy failure where an episodic, insufficient supply of cerebral oxygen is met with an inability of the brain to proactively reorganise the network response. When cerebral oxygen delivery falls below a critical threshold and the brain cannot mount an adaptive reorganisation, neural networks fall sequentially in order of energetic cost, which produces the characteristic symptom profile of functional/dissociative seizures. The subsequent response - convulsions, stiffening, postural collapse - is a physiological rescue mechanism to ensure restoration of cerebral perfusion through skeletal muscle pump activation. This hypothesis accounts for several features of functional/dissociative seizures that are not adequately explained by existing biopsychosocial models. These include the overlap of symptoms with controlled hypoxia; the predominance in females (for the first time linked to documented sex differences in physiological responses to hypoxia); the shift in female-to-male ratio at puberty; the relatively favourable prognosis in paediatric populations; the relapsing-remitting course of the condition; and the heterogeneity of clinical presentations predicted by hub-first, cost-ordered network failure. The paper describes the evidence supporting the hypothesis, its discriminating predictions, and the experimental and clinical approaches for testing it.