Psychogenic nonepileptic seizures (PNES) is the most prevalent type of functional neurological disorder (FND), affecting 2-33 individuals per 100,000 population.1,2 Onset of PNES typically occurs during teen years or young adulthood, with higher rates observed in women compared to men.3

These events “consist of paroxysmal alterations in motor, sensory, autonomic, or cognitive functions that are not associated with ictal epileptiform activity,” according to an American Neuropsychiatric Association report on evidence-based assessment of PNES.1 Although the mechanistic underpinnings of the disorder have not yet been elucidated, PNES is linked to psychiatric dysfunction and does not stem from abnormal electrical activity in the brain.4

However, patients experience real neuropsychiatric symptoms and are susceptible to a reduced quality of life, substantial disability, and elevated mortality and suicide rates.2,5 In light of these findings and the risks of harm associated with an incorrect epilepsy diagnosis, it is critical for clinicians to make the correct diagnosis when a patient presents with symptoms suggestive of PNES.


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Individuals with PNES are often misdiagnosed with epilepsy and may not receive an accurate diagnosis for many years. Among patients referred to tertiary epilepsy centers with refractory seizures, an estimated 10%-40% of cases are ultimately diagnosed as PNES.6

“Epilepsy is a life changing diagnosis,” said Nitin K. Sethi, MD, MBBS, associate professor of clinical neurology at Weill Cornell College in New York who specializes in epilepsy.Some patients with PNES have been diagnosed with epilepsy and have been on multiple antiseizure medications for years.” Along with needlessly enduring side effects of antiepileptic drugs, these medications may exacerbate the symptoms of PNES. Additionally, PNES patients who are misdiagnosed with epilepsy face the stigma and driving restrictions that affect people with epilepsy.

Understanding the Mechanisms Behind PNES

“Like many complex neuropsychiatric disorders, PNES — and functional neurological disorders in general — occur in the context of several biological, psychological, and social factors which interact with each other,” said Gaston C. Baslet, MD, assistant professor of psychiatry at Harvard Medical School and director of the neuropsychiatry division at Brigham and Women’s Hospital in Boston, and lead author of the American Neuropsychiatric Association report on evidence-based assessment of PNES.1

According to Dr Baslet, the medical community’s understanding of brain structure changes and connectivity in patients with FND/PNES is progressing. However, he cautions, that it does lag significantly compared to other neuropsychiatric disorders, like depression.

“Psychological theories have existed for longer, and currently most hypotheses for PNES favor a role of somatic attention/hypervigilance and prediction bias (a “cognitive model”),” he says.8 “This hypothesis is not necessarily contradictory to older, more traditional hypotheses such as conversion or dissociation.”

PNES vs Epileptic Seizures: Symptoms and Comorbidities

Although PNES symptoms may be difficult to distinguish from those of epilepsy on observation alone, some of the clinical features that have been more frequently noted in PNES vs epileptic seizures include rapid recovery as well as “longer duration, fluctuating course, asynchronous movements, pelvic thrusting, side-to-side head or body movement, persistently closed eyes and mouth, ictal crying, recall of ictal experiences and absence of postictal confusion,” according to an article in Acta Epileptologica.2,3

Conversely, occurrence from sleep and post-ictal Babinski sign represent features suggestive of epileptic seizures.2 Further complicating the clinical picture, up to 30% of patients with epilepsy also experience PNES.3

Certain risk factors and comorbidities are more often found in PNES compared to epilepsy. “In the literature, a lot of patients with PNES have stressors such as recent death in the family, relationship problems, or a history of sexual abuse,” Dr Sethi noted. Between 53% and 100% pf patients with PNES have demonstrated psychiatric comorbidities, with higher rates of anxiety disorders, substance use disorders, post-traumatic stress disorder, and personality disorders seen in PNES vs epilepsy.1

Nonetheless, it is important for clinicians to avoid making assumptions that patients with PNES are feigning their symptoms. “The common mistake doctors make is assuming that patients are malingering,” Dr Sethi stated. Conversion disorder, in which psychological distress manifests as physical symptoms, has been cited as the primary psychiatric mechanism involved in PNES. This implies that patients are not consciously feigning symptoms.7

“Malingering or factitious disorder is thought to be less common as a cause of PNES but might be suspected when there is clear, immediate secondary gain resulting in alterations in behavior,” according to a 2022 article published in StatPearls.7

The Importance of VEEG in PNES Diagnosis

“The only way to prove or disprove PNES is by capturing the events on [video-electroencephalogram] VEEG, the gold standard in diagnosing PNES,” Dr Sethi said. With PNES, the event can be observed on video but is not accompanied by EEG features seen with epileptic seizures.2

“The problem is that smaller hospitals may not have VEEG, and it is also expensive,” he added.

Agreeing with Dr Sethi, VEEG provides the highest level of diagnostic accuracy for PNES, said Dr. Baslet. “When this is not feasible because episodes are infrequent or there is limited access to the test (i.e., due to insurance issues), having an expert neurologist who specializes in epilepsy watch a video of an episode can be extremely helpful,” he advised. “These days, with camera phones, it is easier to get those videos. Description alone without a video or accompanying EEG at the time of the episode is relatively inadequate for diagnosis and can lead to an erroneous diagnosis.”

Dr Sethi may advise patients to capture the video with a cell phone when VEEG is not feasible, although timely referral to an epilepsy center is needed if the diagnosis remains unclear.

Once a diagnosis of PNES is confirmed, clinicians should carefully explain to patients in a nonjudgmental manner that these are not epileptic events. Dr Sethi cautions against saying something like, “These are not seizures, they’re all in your head.” With that approach, patients with be justifiably upset. “There’s a reason these are happening,” and patients and their families need support in understanding the diagnosis and seeking appropriate treatment.

If a patient diagnosed with PNES is taking antiepileptic drugs, discontinuation is encouraged, and the patient should be referred for psychiatric care. While PNES often does not stop immediately after the diagnosis is confirmed, it may begin to occur less frequently, with fewer visits to the emergency room. Some cases may eventually resolve completely.

The Challenges of Treating PNES

Skills-based psychotherapy such as cognitive behavioral therapy or mindfulness-based therapy is considered to be the best evidence-based treatment for PNES, Dr Baslet noted. “Other psychotherapeutic approaches may be used as well based on individual circumstances – for example, psychodynamic psychotherapy or trauma-focused therapy such as prolonged exposure.”9,10 Currently, no evidence exists that suggests pharmacological treatment is effective for PNES. Neurostimulation, Dr Baslet explained, is only used for research purposes at this point.

“The psychotherapy that is used for PNES is ‘easy’ to provide, but therapists need to have the support of a team in terms of the diagnosis and back up for questions, Dr Baslet said. “The problem is too common, and we need to involve community providers and not keep treatment for PNES happening only at tertiary academic centers.”

He acknowledged that “The approach to someone who has both PNES and epilepsy is the same for the treatment of PNES, plus there is continuing treatment for epilepsy. There needs to be a lot of discussion on how to differentiate symptoms, and it is sometimes necessary to involve family members in this these discussions.”

PNES patients with the best outcomes are younger, with a shorter duration of events and less serious psychiatric pathology, Dr Sethi said.

To effectively treat this patient population, there needs to be a better understanding of the underlying neurobiology of PNES and FND, said Dr Baslet. This will help to “facilitate identification of other therapeutic strategies such as neurostimulation and mixed approaches using rehabilitative techniques and stimulation.”

References

  1. Baslet G, Bajestan SN, Aybek S, et al. Evidence-based practice for the clinical assessment of psychogenic nonepileptic seizures: A report from the American Neuropsychiatric Association Committee on Research. J Neuropsychiatry Clin Neurosci. Published online August 11, 2020. doi:10.1176/appi.neuropsych.19120354
  2. Aybek S, Perez DL. Diagnosis and management of functional neurological disorder. BMJ. Published online January 24, 2022. doi:10.1136/bmj.o64
  3. Liampas A, Markoula S, Zis P, et al. Psychogenic non-epileptic seizures (PNES) in the context of concurrent epilepsy – making the right diagnosisActa Epileptologica. Published online September 28, 2021. doi:10.1186/s42494-021-00057-x
  4. National Institutes of Health, National Institute of Neurological Disorders and Stroke. Functional Neurologic Disorder. Accessed online March 21, 2022. 
  5. Zhang L, Beghi E, Tomson T, Beghi M, Erba G, Chang Z. Mortality in patients with psychogenic non-epileptic seizures a population-based cohort study. J Neuro Neurosurg Psychiatry. 2022;93(4):379-385. doi:10.1136/jnnp-2021-328035
  6. Widyadharma IPE, Soejitno A, Samatra DPGP, et al. Clinical differentiation of psychogenic non-epileptic seizure: a practical diagnostic approachEgypt J Neurol Psychiatry Neurosurg. Published online February 5, 2021. doi:10.1186/s41983-021-00272-w
  7. Huff JS, Murr N. Psychogenic nonepileptic seizures. In: StatPearls. Treasure Island, FL: StatPearls Publishing; January 24, 2022.
  8. Reuber M, Brown RJ. Understanding psychogenic nonepileptic seizures-Phenomenology, semiology and the Integrative Cognitive Model. Seizure. Published online November 15, 2016. doi:10.1016/j.seizure.2016.10.029
  9. Tolchin B, Baslet G, Martino S, et al. Motivational interviewing techniques to improve psychotherapy adherence and outcomes for patients with psychogenic nonepileptic seizures. J Neuropsychiatry Clin Neurosci. Published online August 30, 2019. doi:10.1176/appi.neuropsych.19020045
  10. Fredwall M, Terry D, Enciso L, Burch MM, Trott K, Albert DVF. Outcomes of children and adolescents 1 year after being seen in a multidisciplinary psychogenic nonepileptic seizures clinic. Epilepsia. Published online August 2, 2021. doi:10.1111/epi.17031