Challenging the Assumptions – An Evidence-Based Review of Psychogenic Non-Epileptic Seizures

Previously known (and often referred to) as “pseudoseizures”, psychogenic nonepileptic seizures (PNES) represent a disturbance of motor, sensory, autonomic and cognitive function that closely resemble epileptic seizures. In contrast with epilepsy, this seizure-like activity does not represent abnormal neuronal conduction, but instead is thought to be psychogenic in origin. PNES remains a poorly understood and often stigmatized condition. Through this review of some of the recent literature, we hope to challenge some commonly held assumptions about this relatively common, but not benign, condition.

Epidemiology

While the incidence and prevalence of psychogenic nonepileptic seizures are difficult to estimate (given that not every patient undergoes the diagnostic gold standard video EEG monitoring), its incidence is estimated at 1.5-5 cases per 100,000 persons per year, while the prevalence is estimated from 2-33 per 100,000 persons.¹ The prevalence is estimated based on a year 2000 population-based study in Iceland, which may limit generalizability worldwide, however newer data is sparse. A 2014 literature review found similar results given newer aggregate data, although this review still included these older studies.² In contrast, the incidence of epilepsy worldwide is estimated at 67.77 per 100,000 persons per year, and the prevalence is estimated at 7.6 per 1000 people.³

Clinical features of PNES closely mimic epilepsy, often leading to difficulty in diagnosis. While advances in epilepsy research continue to improve management, rates of epilepsy misdiagnosis remain up to 20%. A 2017 literature review found that of those who are misdiagnosed with epilepsy, up to 23% are ultimately attributed to PNES.⁴ Frontal lobe epilepsy presents particularly similarly to PNES, with brief episodes of impaired (or preserved⁵) consciousness, vocalizations, irregular tonic-clonic movements and normal EEG waveforms⁶, highlighting the difficulty in arriving at an appropriate diagnosis.

Diagnosis

The International League Against Epilepsy recommends diagnosis via a combination of history, video-EEG monitoring and description of a witnessed event.⁷ Video-EEG monitoring shows normal EEG activity during seizure-like episodes. They recommend that PNES be managed without antiepileptic drug treatment, with cognitive behavioral therapy being the most studied form of management.

Episodes of PNES often occur in front of witnesses. A 2005 study by the University of South Florida found that 75% of seizure-like episodes that occurred in the waiting room or exam room were ultimately diagnosed as PNES.⁸ Further, a 2010 UK study noted that, among 254 patients who underwent EEG video monitoring, all 25 who had a seizure-like episode before or during lead placement were found to have PNES.⁹

“Typical” Features

Contrary to popular belief, clinical signs of PNES are often difficult to distinguish. A 2010 review found that, unlike epileptic seizures, PNES do not often occur during sleep and those that occur during apparent sleep are often found to have waveforms indicative of wakefulness on EEG.¹⁰ This same review found that PNES often mimic tonic-clonic or focal seizures with impaired alertness and are less likely to mimic absence, focal seizures with preserved alertness, or atonic seizures. Features found to be typical of PNES include ictal tearfulness, less incidence and less severity of tongue biting and incontinence, absent post-ictal confusion, ictal vocalization, asynchronous movements, pelvic thrusting and side to side body motions.¹⁰

While these features are thought to be typical, no single feature is sensitive or specific enough to diagnose PNES.¹¹ One study challenged physicians from different specialties to diagnose epilepsy or PNES in a series of patients after watching a short video clip of each. While not generalizable worldwide given the small sample size, lack of accompanying EEG and methodology of giving a diagnostic guess after one viewing of the video, diagnoses by Emergency physicians in this particular pool had a sensitivity and specificity of just 63%.¹²

Comorbidities

Interestingly, 5-10% of PNES patients have concurrent epilepsy. Video EEG monitoring of these patients shows both true seizure activity, alongside seizure-like episodes with normal waveforms. In these patients, the psychogenic seizures were found to mimic their epilepsy.¹³

Patients with PNES maintain higher prevalence of psychiatric comorbidities than those with epilepsy alone, however these conditions are also more common in patients with epilepsy than the general population. One study compared neuropsychological profiles of patients with PNES against those with epilepsy and found that psychiatric disease alone is not specific for PNES. While PNES is often thought to be associated with psychosocial stress, stress is also found to precipitate seizures in epilepsy.¹⁴ A 2023 study found no difference in the prevalence of comorbid psychiatric disorders between patients with PNES and those that also had comorbid confirmed epilepsy.¹⁵

Neurologist involvement remains important during the withdrawal of antiseizure medication, although only a minority of patients will achieve cessation of seizure-like activity.¹⁶ Given the gross similarity to seizures, it is important to take note of the differences between PNES and epilepsy.

Recommendations

• Full seizure work-up should be pursued for a first-time seizure, even in the presence of PNES features as they are not independently diagnostic.
• While psychiatric diseases are prevalent in PNES patients, they are also common in patients with epilepsy and their presence should not be considered diagnostic for PNES.
• Distinguishing organic seizure activity from non-epileptic seizure activity is more difficult than one might imagine, and PNES patients are often misdiagnosed.
• Epilepsy can occur concurrently with PNES and some forms of epilepsy may present with similar features of both. Video-EEG remains the gold standard for PNES diagnosis.
• PNES patients should follow up with neurology for safe discontinuation of AEDs as well as continued education and support for non-AED management, including cognitive behavioral therapy.

References

1. Sigurdardottir KR, Olafsson E. Incidence of psychogenic seizures in adults: a population-based study in Iceland. Epilepsia. 1998;39(7):749-52.

2. Asadi-pooya AA, Sperling MR. Epidemiology of psychogenic nonepileptic seizures. Epilepsy Behav. 2015;46:60-5.

3. Fiest KM, Sauro KM, Wiebe S, et al. Prevalence and incidence of epilepsy: A systematic review and meta-analysis of international studies. Neurology. 2017;88(3):296-303.

4. Oto MM. The misdiagnosis of epilepsy: Appraising risks and managing uncertainty. Seizure. 2017;44:143-146.

5. Jobst BC, Siegel AM, Thadani VM, Roberts DW, Rhodes HC, Williamson PD. Intractable seizures of frontal lobe origin: clinical characteristics, localizing signs, and results of surgery. Epilepsia. 2000;41(9):1139-52.

6. Jobst BC, Williamson PD. Frontal lobe seizures. Psychiatr Clin North Am. 2005;28(3):635-51, 648-9.

7. Lafrance WC, Baker GA, Duncan R, Goldstein LH, Reuber M. Minimum requirements for the diagnosis of psychogenic nonepileptic seizures: a staged approach: a report from the International League Against Epilepsy Nonepileptic Seizures Task Force. Epilepsia. 2013;54(11):2005-18.

8. Benbadis SR. A spell in the epilepsy clinic and a history of “chronic pain” or “fibromyalgia” independently predict a diagnosis of psychogenic seizures. Epilepsy Behav. 2005;6(2):264-5.

9. Woollacott IO, Scott C, Fish DR, Smith SM, Walker MC. When do psychogenic nonepileptic seizures occur on a video/EEG telemetry unit?. Epilepsy Behav. 2010;17(2):228-35.

10. Avbersek A, Sisodiya S. Does the primary literature provide support for clinical signs used to distinguish psychogenic nonepileptic seizures from epileptic seizures?. J Neurol Neurosurg Psychiatry. 2010;81(7):719-25.

11. Reuber M, Elger CE. Psychogenic nonepileptic seizures: review and update. Epilepsy Behav. 2003;4(3):205-16.

12. Seneviratne U, Rajendran D, Brusco M, Phan TG. How good are we at diagnosing seizures based on semiology?. Epilepsia. 2012;53(4):e63-6.

13. Henry TR, Drury I. Ictal behaviors during nonepileptic seizures differ in patients with temporal lobe interictal epileptiform EEG activity and patients without interictal epileptiform EEG abnormalities. Epilepsia. 1998;39(2):175-82.

14. Strutt AM, Hill SW, Scott BM, Uber-zak L, Fogel TG. A comprehensive neuropsychological profile of women with psychogenic nonepileptic seizures. Epilepsy Behav. 2011;20(1):24-8.

15. ALKhaldi NA, Paredes-Aragón E, Kim DD, Yu YJ, ALKhateeb M, Mirsattari SM. Psychogenic non-epileptic seizures with and without epilepsy: Exploring the influence of co-existing psychiatric disorders on clinical characteristics and outcomes. Epilepsy Res. 2024 Jan;199:107279. doi: 10.1016/j.eplepsyres.2023.107279. Epub 2023 Dec 12. PMID: 38101178.

16. Reuber M, Mitchell AJ, Howlett S, Elger CE. Measuring outcome in psychogenic nonepileptic seizures: how relevant is seizure remission?. Epilepsia. 2005;46(11):1788-95.