Can epilepsy be misdiagnosed as psychogenic nonepileptic seizures (PNES)?

Can Epilepsy Be Misdiagnosed as PNES?

Yes, epilepsy can absolutely be misdiagnosed as psychogenic nonepileptic seizures (PNES), though the reverse scenario—PNES being misdiagnosed as epilepsy—is far more common and clinically significant. The bidirectional misdiagnosis represents a critical diagnostic challenge with substantial implications for patient morbidity and quality of life.

The Magnitude of the Problem

The misdiagnosis issue is substantial: 25-30% of patients referred to tertiary epilepsy centers with "refractory epilepsy" actually have PNES, not epilepsy 1, 2. However, the reverse scenario—true epilepsy misdiagnosed as PNES—also occurs and carries serious consequences including untreated seizures, potential status epilepticus, and sudden unexpected death in epilepsy (SUDEP) risk 3.

Key Clinical Scenarios Where Epilepsy Gets Misdiagnosed as PNES

1. Overreliance on Single Clinical Features

No single clinical feature is pathognomonic for either condition 2. Clinicians who rely too heavily on supposedly "typical" PNES features (like pelvic thrusting, eye closure, or prolonged duration) may miss true epilepsy, particularly:

• Frontal lobe seizures (which can mimic PNES with bizarre movements and pelvic thrusting) 4
• Complex partial seizures with unusual semiology
• Myoclonic epilepsy with atypical presentations 5

2. Negative or Misinterpreted EEG

This is a critical pitfall. EEG may be normal in people with epilepsy and can be abnormal in people without epilepsy 6. The guidelines explicitly warn that inappropriate use of EEG can lead to misdiagnosis 7. Specifically:

• Ictal EEG may be negative in some partial seizures 8
• Movement artifacts can obscure true epileptiform activity 8
• Overinterpretation of normal variants as epileptiform (phase reversals, sharp transients not meeting strict criteria) contributes to diagnostic errors 8

3. Comorbid Epilepsy and PNES

At least 10% of PNES patients have concurrent epileptic seizures or prior epilepsy 2. In one study, 37.5% of PNES patients had comorbid epilepsy 9. This overlap creates diagnostic confusion where:

• True epileptic seizures may be dismissed as "just PNES"
• Interictal epileptiform abnormalities (present in 77.7% of patients with both conditions) can be misattributed 9
• Comorbid epilepsy is independently associated with ongoing PNES activity, complicating the clinical picture 10

Specific Diagnostic Pitfalls Leading to Misdiagnosis

Features That Can Mislead Clinicians:

• Duration alone is unreliable: While PNES episodes often last longer, some epileptic seizures (particularly frontal lobe) can be prolonged 4
• Eye closure during events: Strongly suggests PNES or psychogenic pseudosyncope, but shallow syncope may also present with closed eyes 4
• Apparent lack of response to benzodiazepines: The recent ESETT trial found that 10% of enrolled "status epilepticus" patients actually had PNES 11, and status non-epilepticus (prolonged PNES) is frequently misdiagnosed and inappropriately treated with escalating antiseizure medications and intubation 12

The Myoclonic Epilepsy Trap:

A recent case report highlights how myoclonic epilepsy was initially misdiagnosed as PNES when initial video-EEG monitoring failed to capture epileptiform activity 5. Only repeat EEG studies revealed generalized spike-and-wave discharges, establishing the correct diagnosis.

The Gold Standard and Its Limitations

Video-EEG monitoring remains the diagnostic gold standard when typical seizures can be recorded 2. However, this requires:

• Capturing a typical event during monitoring
• Absence of epileptiform activity before, during, and after the ictus
• Expert interpretation avoiding overreading of artifacts
• Recognition that movements can generate rhythmic artifacts mimicking electrographic seizures 8

The video analysis is at least as important as the ictal EEG 8. When video-EEG reveals no epileptiform activity during a typical event, thorough neurological and psychiatric histories are needed to confirm PNES 2.

Critical Recommendations to Avoid Misdiagnosis

For Initial Assessment:

1. Obtain detailed witness accounts of symptoms before, during, and after events 7
2. Perform 12-lead ECG as essential part of initial assessment to exclude cardiac causes 7
3. Do not request EEG in absence of clear pointers to epilepsy—if cause of transient loss of consciousness is unclear, start with cardiovascular assessment 7

Red Flags Suggesting True Epilepsy (Not PNES):

• Movements beginning before the fall or at onset of unconsciousness 4
• Symmetrical, synchronous movements 4
• Movements restricted to one limb or one side 4
• Lateral tongue biting (uni- or bilateral) 4
• Loss of consciousness <30 seconds (syncope far more likely than epilepsy; if measured, epileptic seizures average 74-90 seconds) 4
• Stertorous (snoring) breathing suggests epileptic seizure over PNES 4

When PNES Diagnosis Should Be Questioned:

• Poor response to appropriate psychiatric/psychological interventions
• Persistence of "PNES" despite treatment, especially with features atypical for PNES
• Older age at symptom onset (associated with worse PNES outcomes, but may indicate alternative diagnosis) 10
• Presence of definite epileptiform abnormalities on repeat EEG studies

Clinical Consequences of Misdiagnosis

Misdiagnosing epilepsy as PNES leads to:

• Untreated seizures with risk of injury, status epilepticus, and SUDEP
• Increased mortality (epilepsy patients have up to 11-fold higher mortality than controls) 3
• Delayed appropriate antiseizure medication therapy
• Inappropriate psychiatric treatment

The diagnostic delay averages 4.5-7 years 9, during which patients face significant healthcare burden, unnecessary testing, and inappropriate treatments affecting quality of life 13.

Practical Algorithm for Avoiding Misdiagnosis

1. Suspect epilepsy if: movements are stereotyped, brief (<30 sec LOC), begin before fall, involve lateral tongue biting, or occur with stertorous breathing
2. Refer for specialist epilepsy assessment when these features are present 7
3. Do not rely on single EEG—if clinical suspicion remains high despite negative initial EEG, pursue repeat studies or prolonged video-EEG monitoring 5
4. In patients with known PNES who develop new seizure patterns, maintain high index of suspicion for comorbid epilepsy (occurs in 10-37.5% of cases) 2, 9
5. When "status epilepticus" fails to respond to benzodiazepines and second-line agents, strongly consider status non-epilepticus (prolonged PNES) before escalating to intubation 12

The key message: maintain diagnostic humility and pursue repeat evaluation when clinical course doesn't match the diagnosis, as both false-positive and false-negative diagnoses carry substantial morbidity 2, 5.