How to differentiate and treat seizures versus pseudoseizures (Psychogenic Non-Epileptic Seizures, PNES)?

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Differentiating and Treating Seizures vs Psychogenic Non-Epileptic Seizures (PNES)

Video-EEG monitoring is the gold standard for definitively distinguishing epileptic seizures from PNES, and this distinction is critical because treatment paradigms are fundamentally different: antiepileptic drugs for true seizures versus cognitive behavioral therapy for PNES. 1, 2

Key Clinical Differentiating Features

During the Event

Movement characteristics:

  • Epileptic seizures typically present with symmetrical, synchronous bilateral movements, while PNES often show asynchronous, side-to-side thrashing movements 3
  • Many movements are more suggestive of epilepsy than syncope or PNES, which typically has fewer organized movements 3

Eye position:

  • Eyes are typically open during unconsciousness in generalized epileptic seizures 3
  • Eyes are often closed in PNES 3

Duration of unconsciousness:

  • Epileptic seizures: mean 74-90 seconds 3
  • PNES/syncope: typically <30 seconds 3

Tongue biting:

  • Lateral tongue biting is highly specific for epileptic seizures 3
  • Less common or absent in PNES

Oral automatisms:

  • Chewing, smacking, and blinking suggest epileptic seizures 3

Diagnostic Approach

Gold Standard

Video-EEG monitoring (with or without provocative techniques) is the definitive diagnostic test to differentiate epileptic seizures from PNES, as it captures both clinical semiology and electrical brain activity simultaneously 1, 4

Limitations of Biomarkers

  • Neuron-specific enolase, prolactin, and creatine kinase are not reliable for validating the diagnosis 1
  • Do not rely on these markers alone for differentiation

Important Diagnostic Pitfall

Between 10-30% of patients referred to epilepsy centers have PNES misdiagnosed as epilepsy, and one out of four to five patients admitted to video-EEG units with "refractory epilepsy" actually have non-epileptic events of psychogenic origin 1, 5. This creates the critical problem of "pseudo-refractory epilepsy" where patients receive escalating doses of unnecessary antiepileptic drugs.

Dual Diagnosis Challenge

Comorbidity between epilepsy and PNES occurs and represents a serious diagnostic challenge 5. The prevalence of epilepsy in PNES patients is higher than in the general population, and epilepsy may be a risk factor for developing PNES 1.

Psychiatric Comorbidities in PNES

PNES patients have high rates of psychiatric disorders including:

  • Depression and anxiety 1
  • Post-traumatic stress disorder (PTSD) 1
  • Dissociative disorders 1
  • Somatoform symptoms 1
  • History of childhood trauma and abuse 1, 4

According to DSM-5, PNES are classified as conversion disorders, while ICD-10 classifies them as dissociative disorders 1, 5

Treatment Paradigms

For Epileptic Seizures

  • Antiepileptic drugs (ASDs) are the primary treatment 6
  • Status epilepticus requires benzodiazepines followed by phenytoin or fosphenytoin 6
  • EEG testing should be performed when indicated to guide management 6

For PNES

The treatment for PNES is cognitive behavioral therapy, NOT anticonvulsant medication 2

Critical steps in PNES management:

  1. The diagnosis must be clearly communicated to the patient 1
  2. Discontinue unnecessary antiepileptic drugs to prevent side effects and improve quality of life 5
  3. Refer for psychiatric evaluation and treatment of comorbid conditions 1
  4. Neurologist should continue following post-diagnosis PNES patients in collaboration with psychiatry 1
  5. Early therapeutic counseling should be initiated to identify and address underlying psychological causes 4

Prognosis and Outcomes

Even after correct diagnosis, a high proportion of PNES patients continue to have seizures and serious disability 1. Nearly half of patients who become seizure-free remain unproductive, and many continue to have symptoms of psychopathology including other somatoform, depressive, and anxiety disorders 1. Seizure remission alone cannot be considered a comprehensive measure of outcome 1.

Critical Clinical Caveat

Complex partial seizures of frontal origin can present with similar characteristics to PNES and may be confused with PNES 1. This underscores why video-EEG monitoring is essential rather than relying solely on clinical features, as the consequences of misdiagnosis in either direction significantly impact morbidity and quality of life through either untreated epilepsy or unnecessary medication exposure.

References

Research

Seizures and pseudoseizures: The great divide.

Progress in brain research, 2022

Guideline

Generalized Onset Seizures

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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