What is the pathophysiology of Psychogenic Non-Epileptic Seizures (PNES)?

Pathophysiology of Psychogenic Non-Epileptic Seizures (PNES)

PNES episodes involve motor, sensory, mental, or autonomic manifestations that mimic epileptic seizures but fundamentally lack epileptogenic brain activity—meaning there is no abnormal electrical discharge in the brain that characterizes true epilepsy. 1

Core Neurophysiological Mechanism

PNES represents a functional failure in cognitive-emotional executive control circuitry that leads to the release of prewired motor programs in the context of a destabilized neural system. 2 This is not epilepsy masquerading as something else; it is a distinct neuropsychiatric phenomenon where the brain produces seizure-like activity through psychological rather than electrical mechanisms. 3

The Two-Factor Model

The pathophysiology likely involves orbitofrontal cortex dysfunction combined with psychological stressors, rather than either factor alone. 4 This explains why:

• Frontal lobe dysfunction creates the substrate for abnormal motor output and behavioral manifestations that can closely mimic frontal lobe epilepsy 4
• Psychological stress and trauma serve as triggers that activate these pathways in vulnerable individuals 5, 6

Underlying Psychological Mechanisms

The condition operates through several interconnected pathways:

Dissociative Processes

Trait dissociation and exposure to traumatic events are common but not inevitable correlates of PNES. 5 The dissociative model suggests that PNES occurs when there is a functional failure in cognitive-emotional executive control, leading to release of innate motor programs. 2 Between 38-53% of pediatric PNES cases demonstrate dissociative mechanisms, with many triggered specifically by hyperventilation-induced dissociative states. 2

Autonomic Dysregulation

There is a critical mismatch between subjective reports of anxiety and physical arousal during PNES episodes. 5 This disconnect suggests that the autonomic nervous system and conscious emotional processing are functionally decoupled during events. 5

Several specific physiological triggers have been identified:

• Hyperventilation triggering dissociative PNES (53% of cases) 2
• Innate defense responses presenting as PNES (10% of cases) 2
• Vocal cord adduction, valsalva maneuver activation, or reflex vagal activation (collectively ~6% of cases) 2

Conversion and Somatization

Physical symptom reporting is consistently elevated in patients with PNES, supporting the somatoform/conversion disorder framework. 5 The ICD-10 classifies PNES as dissociative disorders, while DSM-IV places them under somatoform disorders, reflecting ongoing debate about the primary mechanism. 7

Structural and Functional Brain Considerations

While PNES is fundamentally a functional disorder, some patients demonstrate associated brain pathology that may contribute to pathogenesis:

• Right hemisphere abnormalities have been associated with PNES 7
• Nonspecific interictal EEG abnormalities and MRI changes can be present 7
• Head injury may contribute to PNES development in some cases 7, 6
• Comorbid epilepsy occurs in 20-30% of patients, with epilepsy potentially serving as a risk factor for developing PNES 7, 6

Critical Distinction from Epilepsy

PNES does not cause the physiological sequelae of true seizures, such as severe hypoxia, aspiration, cardiac arrhythmias, or the prolonged cerebral dysfunction that can lead to status epilepticus and death. 1 Episodes typically last less than 30 seconds compared to 74-90 seconds for epileptic seizures, and patients do not experience the dangerous metabolic derangements of true seizures. 1, 3

Clinical Heterogeneity

Inconsistent findings in PNES research are attributable to the substantial heterogeneity of patients with this condition. 5 This heterogeneity explains why no single pathophysiological model fully captures all presentations, and why at least six distinct subgroups have been identified based on triggering mechanisms and underlying neurophysiological patterns. 2

Common Risk Factors and Comorbidities

• Childhood trauma and abuse history 7, 6
• Post-traumatic stress disorder 7, 6
• Depression and anxiety disorders 7, 6
• Other dissociative and functional disorders 6
• Personality disorders 6

The pathophysiology is best understood as a destabilized neural system with impaired top-down cognitive-emotional control, allowing psychological stressors to trigger involuntary motor programs that manifest as seizure-like episodes without the underlying epileptogenic electrical activity that defines true epilepsy. 2