“What do you MEAN it’s not epilepsy?” – a Review of Psychogenic Nonepileptic Seizures

Case Presentation:

32-year-old woman with daily recurrent episodes of seizure-like activity that began 4 months ago after a knee injury which resulted in a series of lower extremity surgeries
Referred for EEG by her neurologist for recurrent seizures. Presented to the ED from the EEG lab after having a seizure during photic stimulation testing
Second seizure occurred upon arrival to the ED, during which she reported that her RUE “felt weak”. Speech was garbled but coherent and in complete sentences during the event.
Seizure activity resolved spontaneously within 2 minutes
Basic labs, including CBC, CMP, UA, POC Glucometry, urine toxicology screen, and CT head without contrast all returned within normal limits, and vital signs remained normal
EEG lab was able to record brain activity during the event, and found normal waveforms with no epileptiform activity
Ultimately diagnosed with psychogenic nonepileptic seizures (PNES) and discharged home with close follow up with neurology

Clinical Question: What features of PNES help distinguish it from epilepsy or other seizure mimics?

Summary of Evidence:

Previously known as “pseudoseizures,” PNES represents 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 is a relatively common condition. 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, however it is thought to be from 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 2000 population-based study in Iceland, which may limit generalizability worldwide and after 18 years, 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 recent 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 consciousness, vocalizations, irregular tonic-clonic movements, and normal EEG waveforms,(5,6) highlighting the difficulty in arriving at an appropriate 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)
A review of current literature of the clinical signs of PNES 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, lower incidence 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 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 were accurate only 63% of the time. (12)
Interestingly, 5-10% of PNES patients have concurrent epilepsy. Video EEG monitoring of these patients shows both true seizure activity and 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 studied 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)
Neurologist involvement remains important during the withdrawal of antiseizure medication, although only a minority of patients will achieve cessation of seizure-like activity. (15) 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 (see figure below).
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.
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.

[XX1]Excellent