Accepted Manuscript

Psychogenic Non-Epileptic Seizures. Diagnosis, Management, and Bioethics

Kaoru Takasaki, BA, Andrea Diaz Stransky, MD, Geoffrey Miller, MA MB MPhil MD
FRCP FRACP

PII: S0887-8994(15)30402-1
DOI: 10.1016/j.pediatrneurol.2016.04.011
Reference: PNU 8899

To appear in: Pediatric Neurology

Received Date: 22 December 2015

Revised Date: 17 April 2016
Accepted Date: 20 April 2016

Please cite this article as: Takasaki K, Diaz Stransky A, Miller G, Psychogenic Non-Epileptic
Seizures. Diagnosis, Management, and Bioethics, Pediatric Neurology (2016), doi: 10.1016/
j.pediatrneurol.2016.04.011.

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 ACCEPTED MANUSCRIPT

Psychogenic Non-Epileptic Seizures. Diagnosis, Management, and Bioethics.

Kaoru Takasaki BA. Yale University School of Medicine.

Andrea Diaz Stransky MD. Child Study Center, Department of Psychiatry, Yale University

School of Medicine.

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Geoffrey Miller MA MB MPhil MD FRCP FRACP. Department of Pediatrics and Program for

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Biomedical Ethics, Yale University School of Medicine.

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Corresponding Author:

Geoffrey Miller MD 333 Cedar Street, Department of Pediatrics, Yale University School of

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Medicine, Box 208064, New Haven, Connecticut, 06520-8064
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Tel: 203 785 5708. Fax: 203 737 2236

geoffrey.miller@yale.edu
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Psychogenic non-epileptic seizures (PNES) are defined as paroxysmal and involuntary events

characterized by changes in level of consciousness, behavior, motor activity, and autonomic

function. PNES are a consequence of maladaptive processing of psychological or social

stressors1 that do not arise from paroxysmal neuronal dysfunction in the cerebral cortex and do

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not have the electroencephalographic (EEG) signature of epileptic seizures. Despite this

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distinction, episodes of PNES may resemble epileptic seizures, particularly to observers without

extensive experience in their diagnosis and treatment, and be very distressing to patients and

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family members looking for pharmacological anti-epileptic management. What is more, the

diagnoses of epilepsy and PNES are not mutually exclusive, further complicating the diagnostic

picture.
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Although there may be strong pressure on physicians to diagnose epilepsy and to treat as

such, it is critical to differentiate between epileptic seizures and PNES, as well as from other
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movement and neurological disorders. In pediatrics, this distinction may be particularly

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challenging given parental anxiety in addition to the wide range of normal developmental
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behaviors and neurological pathologies. Yet proper diagnosis of PNES cannot be compromised,

as it prevents the unnecessary exposure of patients to anti-epileptic drugs and their adverse
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effects, shortens the time to symptom control, and minimizes waste of medical resources. In this

paper we will review the current body of knowledge regarding the characteristic differences
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between epileptic seizures and PNES, the high incidence of psychiatric comorbidities, and the
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associated bioethical issues that arise in an attempt to assist the proper diagnosis and

management of the condition.

Patient and History Characteristics

A detailed history, about both underlying patient characteristics and the context in which the
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seizure events occur, is an important starting point from which to differentiate PNES episodes

from those of epilepsy. A preponderance in adolescent females1 and in those with comorbid

psychiatric conditions has been noted, with up to 84% of children2 and 48.6% of adolescents3

with PNES also carrying a diagnosis of psychiatric illness. In particular, dramatic, emotional,

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and erratic personalities such as those found in cluster B personality disorders have been

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reported4. The authors of multiple studies have indicated that a history of abuse, depression,

anxiety, school phobia, mood disorders, separation anxiety, attention deficit hyperactivity

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disorder, panic disorder, and post-traumatic stress disorder, as well as cognitive impairment,

learning disabilities, and a history of epilepsy are all risk factors for PNES in children1,2,5-11. In

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older patients, precipitants include rape, significant injury, giving birth, loss of a loved one,
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earthquakes, motor vehicle accidents, and loss of a job12. Such a history of trauma, psychiatric

diagnoses, and cognitive impairment is thought to contribute to a decreased ability to effectively

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process and express the emotions that are elicited by stressful events. PNES has thus been
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conceptualized as a type of conversion disorder, or a non-volitional manifestation of social,

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psychological, or even physical distress1. To this end, Salpekar et al. found that children with

PNES, compared to those with epilepsy, are more likely to complain of headaches, faintness, loss
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of voice, dizziness, weakness, trouble walking, difficulty participating in school, and sleep

disturbances13.
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Patient- or family-reported seizure descriptions thought to be fairly unique to PNES

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include recurrence in the same context, occurrence only in the presence of others, frequent

recurrence, long duration, intact memory of the event, and negative history of event-related

injury8,10,11,14. Frequent seizures that predictably occur in a setting such as school, which tests a

child’s academic achievement or ability to relate to peers, strongly support the diagnosis of
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PNES. The tendency for events to happen only in the presence of others suggests that external

stressors are an important trigger and that PNES may be an attempt to communicate emotional

discomfort. Although poorly-controlled or severe epilepsy may present with daily seizure events

or frequent status epilepticus, such a history in an otherwise physically well patient should raise

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clinical suspicion for PNES8. With the exception of status epilepticus, epileptic pediatric seizures

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are on average shorter than three minutes. In contrast, episodes longer than 10 minutes are

typical in PNES6,8, and patients with PNES are frequently diagnosed initially “in status”15.

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The manner in which patients with PNES relate these events differs from those with

epileptic seizures6,8,16. Patients with PNES tend to perceive their seizures as catastrophic to their

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life, and as a “place or space”17 to which they are brought. This catastrophizing, which itself
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negatively affects emotional function, is consistent with the dysfunctional emotional processing

thought to be the pathogenesis of PNES. These patients also have a tendency to focus on the
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details and circumstances surrounding the episodes rather than on the symptoms experienced
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during the episodes themselves. On the other hand, patients with epilepsy tend to normalize their
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seizures as a part of everyday life, and as external, independent phenomena that act upon them.

Their accounts more often focus on the subjective symptoms experienced intra-ictally16.
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Seizure semiology, either reported or physician-observed, forms the other half of the

initial diagnostic workup. Convulsive and atonic/catatonic episodes appear to be the most
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common PNES types, followed by absence-like events8,18. Whereas myoclonic, tonic, and tonic-
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clonic epileptic seizures involve synchronous movements of the neck, waist, or extremities, the

movements in convulsive PNES are often asynchronous8,14,18, such as a bicycling motion of the

legs. The oft-cited side-to-side head shaking of PNES contrasts with the head nods seen in atonic

epilepsy and the fixation of the head in one direction that can be seen in tonic and tonic-clonic
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epilepsy. Eye closure, with or without opposition to opening, has been found to be both a

sensitive and specific predictor of PNES, with a positive predictive value of 0.943 in one study

of both children and adults19. Additionally, tremor, while not specific for PNES, is a commonly

seen feature in pediatric patients6,18. Interestingly, although pelvic thrusting has often been used

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as a distinguishing feature of PNES in adults, it is rarely seen in the pediatric population18.

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During and after PNES events, patients may vocalize comprehensible, emotive content,

unlike the primitive utterances sometimes heard at the beginning of epileptic seizures6,8. The

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timing of these coherent vocalizations in PNES aligns with the tendency for patients to

remember their episodes and to return to baseline at their conclusion, without a post-ictal state.

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Furthermore, patients with PNES also retain the ability to respond to verbal and distracting
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stimuli during and immediately after the episodes6. It is important to stress that nonetheless,

many believe that patients with PNES do not have volitional control over their ictal behavior20.
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Say et al., additionally classify the features of PNES in adolescents by gender18. Between
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the two most common types of PNES events, girls were much more likely to experience atonic
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falls (34% vs. 5.6%, p = 0.02), while boys were more likely to exhibit convulsive, tonic-clonic-

like movements (16.7% vs. 2.3%, p = 0.036). Girls were also more likely to have episodes that
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last longer than typical epileptic seizures, with 84% of girls, compared to 61% of boys,

experiencing events longer than 2 minutes. Additionally, within the broad category of
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“psychosocial stressors,” girls most commonly reported difficulties with peer interactions,
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though not significantly more so than boys, whereas boys most commonly cited academic

struggles, and significantly more so than girls (83.3% vs. 47.7%, p = 0.009). With respect to

psychiatric comorbidities, major depressive disorder was more common in girls, and attention

deficit hyperactivity disorder significantly more common in boys.

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In summary, key distinctions between PNES and epilepsy lie in both patient and seizure

characteristics. Long duration, eye closure, asynchronous movements, frequent recurrence in the

same context, intra-ictal awareness, and lack of post-ictal state are all used to help establish the

diagnosis of PNES. , Psychiatric comorbidities, history of abuse, cognitive impairment, and

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multiple non-specific somatic complaints are some salient patient features that should increase

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suspicion for the condition.

Neurobiological and Laboratory Measures

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The origin of PNES has often been labeled “psychogenic,” implying the absence of a

physiological mechanism. However, PNES are complex disorders that require a biopsychosocial

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conceptualization. In addition to the patient history and semiology discussed above, the use of
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neuroimaging and serum indices can inform the study of PNES. For instance, baseline parietal

lobe dysfunction was found in a small PET study of glucose metabolism comparing patients with
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PNES to healthy controls21. The study identified hypometabolism in the right inferior parietal
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and central region and in the bilateral anterior cingulate cortex. Hypometabolism in the latter has
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been implicated in emotional dysregulation disorders such as generalized anxiety disorder and

post-traumatic stress disorder22. Arthuis also notes that the parietal lobe may be related to the
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paroxystic alteration in consciousness seen in patients with PNES21.

Laboratory values have been used as well, although researchers have disagreed on the
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utility of these measures6,11, and little has been studied in pediatrics specifically. The
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Therapeutics and Technology Subcommittee of the American Academy of Neurology concluded

that both relative and absolute rises in serum prolactin 10 to 20 minutes following an ictal event

were specific for distinguishing generalized tonic-clonic and complex partial epileptic seizures

from PNES23, and Cragar et al. calculated that 89% of patients without a postictal rise in
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prolactin had PNES24. Alving, however, found wide inter- and intra-patient variability in

prolactin levels when repeated measurements were taken, and concluded that a lack of rise in

prolactin level carries only a 40% negative predictive value for PNES25. Prolactin levels may be

“falsely” suppressed due to medications such as dopamine agonists, or elevated due to pregnancy

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or the use of dopamine antagonists8. Meanwhile, Willert et al. found false-positive prolactin

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elevations in up to 42% of patients with PNES26.

Studies of elevations in creatine kinase have also yielded mixed results. A rise in creatine

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kinase is considered more likely in epileptic, particularly generalized tonic-clonic, seizures26-28,

but a statistically significant difference in these levels has not been demonstrated26. Conversely,

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normal creatine kinase levels do not support a diagnosis of PNES. The potential role for creatine
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kinase levels in the workup for PNES is further complicated by challenges in the interpretation

of the values. As in prolactin, there are numerous causes unrelated to seizures that can raise
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creatine kinase, including but not limited to alcohol, statins, cocaine, heroin, thyroid disorders,
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antipsychotic drugs, and ACE inhibitors28. Moreover, elevations in creatine kinase are typically
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seen 24 hours post-ictus, if not longer. Because a high frequency of events is a characteristic of

PNES, the timing may prevent creatine kinase from being an effective diagnostic tool.
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The white cell count has too been shown to significantly increase after generalized tonic-

clonic and to a lesser extent complex partial epileptic seizures, but not after simple partial
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epileptic seizures or PNES29. However, its low specificity for epilepsy limits its use.
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At this point, the data on these neurobiological and serum markers is preliminary, and in

the case of the neurological abnormalities, it is possible that psychiatric comorbidities alone

could explain the hypometabolic findings. Therefore, for now the diagnosis of PNES continues

to rely on video EEG within the right clinical context.

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Differential Diagnosis

Besides epilepsy, there are a number of other neurological disorders, generally limited to those

that affect older children and adolescents that must be considered alongside PNES. Many of

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these differential diagnoses are classified as physiologic non-epileptic events8 or paroxysmal

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non-epileptic events30, defined as “events associated with systemic alterations that produce an

ictus”8 but are neither epileptic nor psychogenic. These include syncope; tics; the paroxysmal

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dyskinesias, either primary or secondary to a neurological disability; and periodic paralyses.

Syncope, one of the most common neurological disorders in adolescents with a prevalence of up

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to 25%6,30, can mimic epileptic and non-epileptic seizures if associated with convulsions. Patient-
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reported pre-syncopal symptoms play a key role in identifying convulsive syncope: dizziness,

pallor, blacking or greying out, feeling hot or diaphoretic, and a rushing noise in the ears are
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frequently reported phenomena that are typically not seen in epilepsy or PNES6,30.
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Tics, too, are very common, affecting up to 20% of school-age children6. While
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sporadically occurring tics may be easy to distinguish from PNES, a significant number of

patients present with a sudden, “explosive” onset of tics that some may confuse with seizures.
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That tics may become more frequent in stressful or uncomfortable situations also overlaps with

the presentation of PNES. However, unlike in PNES, the paroxysmal movements in tic disorder
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can be suppressed, and patients often report a sense of relief following the tic. The age of onset
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can also be helpful, as tic disorders usually present between the ages of 4 and 8, compared to the

typically adolescent onset of PNES6.

Progressive and static encephalopathies can be associated with stereotyped movements

such as dystonic posturing, as well as retention of primitive reflexes such as tonic and vestibular
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responses. Autism and cognitive impairment are also associated with stereotypies lacking an

epileptic EEG signature. These abnormal movements may resemble seizures and can occur in

stressful situations, but should not be difficult to differentiate from PNES given the overall

clinical context.

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Definitive Diagnosis of PNES

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In the workup of seizure-like events, particularly in the differentiation between PNES and

epileptic seizures, video EEG remains the diagnostic gold standard. A recording of an event,

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accompanied by a lack of EEG changes before, during, and after this event, is considered

sufficient for establishing the diagnosis of PNES. Yet before doing so, it is extremely important

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to confirm that the clinical history and seizure semiology are consistent with that of PNES, as
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pediatric patients without epilepsy can have non-specific abnormalities on EEG6.

A significant number of clinical settings do not have readily available video EEG. As
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such, physicians may therefore rely on less definitive tools combined with a high index of
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suspicion8,11. In an analysis of adult patients, LaFrance et al. classified the strength of diagnoses
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made without video EEG as “possible,” “probable,” and “clinically established,” in contrast to

“documented PNES”8. “Possible” PNES relies on a suggestive history and normal inter-ictal
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EEG, although brief periods of monitoring are rarely sufficient to exclude epilepsy. The negative

predictive value of a normal inter-ictal EEG is unknown6,8. “Probable” PNES adds a physician’s
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impressions of a video-recorded or personally witnessed seizure event to the diagnostic criteria

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used for “possible” PNES. Finally, “clinically established” PNES is diagnosed by a positive

clinical history, physician-witnessed event, and negative intra-ictal EEG.

When EEG is inconclusive or unavailable, physicians may turn to alternative diagnostic

methods. Placebo and suggestive induction of PNES events have been used to rule out epileptic
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seizures, which are not triggered by such techniques. Hyperventilation and photic stimulation are

the two methods used in pediatrics.Injection of normal saline is typically avoided in children due

to the associated discomfort and invasiveness, although Popkirov et al. suggest that this

invasiveness may render saline injection a more effective inducer than hyperventilation or photic

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stimulation31. Although induction has been met with ethical concerns, it has been argued that it is

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acceptable because it enables correct and effective treatment30,31; these arguments, and their

relationship to truth telling, and beneficence, will be discussed below.

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The thoughtful use of available tools is critical for a diagnosis that can carry with it a

level of controversy and patient resistance. In the exploration of both evidence-based and

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theoretical elements of PNES, the unifying goal remains a timely and transparent workup that
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leads to safe, effective care; is patient-centered; and strengthens the therapeutic relationship.

Management
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The accurate diagnosis and management of PNES require close collaboration between
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neurologists and psychiatrists. Neurologists can immediately begin management by providing

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patients and their families with psycho-education32, which compared to mere diagnosis

disclosure has been shown to decrease frequency of episodes33. Actively facilitating the
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transition to psychiatric treatment is also a crucial step in the management of PNES32 and should

happen as soon as possible. The best-validated psychiatric approach to PNES, at least in adults,
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is psychotherapy33, and in particular cognitive behavioral therapy (CBT). It conceptualizes PNES

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on a fear escape model and aims to correct maladaptive thinking and behaviors34,35. Besides

CBT, psychodynamic therapy focusing on trauma as an elemental component of PNES has

previously shown some success36. Similarly, psychodynamic interpersonal therapy has been

described as an alternative approach that can reduce seizure frequency and severity, and improve
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overall function37,38. Unfortunately, methodological assessments of psychotherapy techniques are

in general limited by the challenge of designing an adequate placebo.

Pharmacotherapy with antidepressants is potentially beneficial, given the high

comorbidity of anxiety and depression in patients with PNES. The authors of a pilot study of

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sertraline vs. placebo for adult PNES patients found a significant reduction (45%, p = 0.03) in

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seizure frequency in the group receiving SSRI, compared to a slight increase (8%, p = 0.78) in

the group receiving placebo39. A combination of antidepressants and psychotherapy has shown

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some value in adults as well. In a pilot multicenter RCT, using CBT and SSRIs together there

was a 59.3% reduction in reported seizure frequency (p < 0.008) compared to a 51.4% reduction

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(p = 0.01) after CBT only, and both groups reported improvements in overall functioning40. SSRI
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treatment alone, however, failed to reduce seizure frequency, and standard medical care with

supportive therapy affected neither seizure frequency nor global functioning measures.
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Bioethics
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The diagnosis of PNES, and communication with patients and families, may raise ethical

concerns. Questions that arise are, ought subterfuge to be used to diagnose PNES? If the
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diagnosis is reasonably confirmed, ought investigations, believed to be unnecessary, be

performed in order to assuage the concerns of patients and relatives? If there is a fear that a
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psychiatric diagnosis will be met with anger and confrontation, is it ever ethical to use
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euphemism and delay the involvement of a psychiatrist? Our bioethical approach makes use of a

combination of virtue ethics and the social contract that health professionals have with patients.

The contract is a covenant that in this case requires pediatricians to act in a virtuous manner for

the good of the child. The medical virtues include competence, fidelity, truthfulness, integrity,
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compassion, prudence, and courage41.

A shared decision-making process that advocates for children and respects the role of

parents is the ideal. The aim is to obtain permission for investigation and management from the

parents, and assent from the child in a developmentally appropriate manner. The physician will

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want to make the correct diagnosis efficiently and provide the best treatment, but provocation

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techniques threaten ethical propriety and raise the risk of rejection by the parents or child when

the diagnosis is delivered, and may thus compound harm. The physician may fear that disclosure

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of the diagnosis will cause anger from the parents, increase emotional pain in the patient, and

lead to a loss of the therapeutic relationship. The parents may then seek other opinions and thus

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delay, and make more difficult, appropriate treatment.
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In the past, the use of provocative testing for non-epileptic seizures was common despite

many of the practitioners admitting to ethical conflict. Techniques included intravenous saline
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and the suggestion that this might cause a seizure. Does the ethical harm of subterfuge outweigh
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the good that comes from an expedited diagnosis42? Using intravenous saline to provoke a
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seizure without informed consent could be viewed as bodily assault. Perhaps just verbally

provoking the PNES is more acceptable ethically43, with a statement such as “I have seen
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seizures start when we place these electrodes on a person’s head.” Once the EEG is running, a

suggestion may be made that a seizure is about to start, and if abnormal movements then occur
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with a non-epileptic pattern on EEG, the psychogenic nature of the event is confirmed. Although
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some epileptic seizures may be missed with surface scalp recordings, they are not induced by

suggestion. Eijkholt and Lynch argue that this is reasonably ethically acceptable when balancing

benefits and burdens in a utilitarian manner43. They further argue that “deception is only used for

instant diagnostic purposes”. The good that comes from early diagnosis and involvement of
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expert psychiatric counseling and management should not be underestimated, but diagnosis

achieved by deception is ethically suspect.

If the virtues of honesty and trust are to be practiced, it is better to make the diagnosis of

PNES without any taint of dishonesty or deception. Refraining from deceit avoids a threat to

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professional integrity and virtue, and maintains respect—an important principle in bioethics—for

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patients and parents. Deception also does not meet the need for truthfulness and fidelity.

Truthfulness requires that physicians act with no intention to deceive. Fidelity refers to meeting

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the expectations for a good doctor, which allows for the trust that comes from the belief that the

physician is knowledgeable and acting in the interests of the child and family. Fidelity may be

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threatened if there is discord from a difference in opinion concerning evaluation and
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management.

Once PNES is diagnosed, the next challenge to effective management is communication

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of the diagnosis, which may be met with hostility and disbelief44. Skillful, tactful, and honest
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communication is part of the art of clinical medicine. When PNES occur, this art may be
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undermined by the urge to simply deliver the diagnosis and leave further communication and

management to colleagues in psychiatry. Conversely, neurologists may not want to make the
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diagnosis until they have completed an extensive workup despite a strongly suggestive history,

co-morbid conditions, and video EEG findings. When delivering the diagnosis it is important to
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emphasize that no one, particularly the patient, is to blame, and to make clear that PNES is a
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common medical disorder requiring the skills of psychiatry. Suggesting that the events are not

real fosters opposition and mistrust. Truthfulness is required, but other virtues play an important

role in the disclosure of potentially offensive information. Courage is needed to communicate the

diagnosis, which may be emotionally taxing for all parties involved. Honesty, prudence and
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compassion require the careful choice of words that aim to comfort, empathize, and minimize

harm, but do not deceive. The wrong choice of words can trigger hostility, and reinforce shame

and stigma.

Expert disclosure requires time and commitment. There need to be communication

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strategies that reduce the chances of an angry, disbelieving reaction that would in turn increase

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the chances of an undesirable outcome and lead to doctor shopping, delayed diagnosis, and

potentially harmful treatment45. Although communication should be individualized, we would

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recommend starting with encouraging words such as: “I am pleased to say that our investigations

show that we are not dealing with worsening epilepsy, and we have discovered why the

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antiepileptics are not helping. What we have found is a problem we commonly see, and with the
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correct management we have a good chance of controlling these events.” Terms that have been

suggested to describe PNES include “nonepileptic events,” “functional seizures,” “nonepileptic

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attack disorder,” and “stress-related seizures.” These terms are reported to be less offensive than
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“pseudoseizures” or “psychogenic seizures”46,47.

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When PNES are diagnosed, parents may demand further investigation. Although

demanding an investigation or intervention is not an absolute parental right, it may be better to

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prioritize a therapeutic relationship between parents and physicians that promotes the best

management for the child, rather than to trigger demands for a different physician or transfer to
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another institution. If parents request an MRI of the brain, it could be argued that arranging this
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is an act of beneficence with little immediate harm to the patient. The accumulative harms to

health care costs, however, are another matter. But acquiescence to all parental demands may not

be appropriate, such as the continuation of anticonvulsants when the diagnosis of PNES is

believed to be certain and there is no evidence that epileptic seizures also occur44. Physicians are
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not obliged to provide ineffective treatment that can also cause side effects. Again, skillful

counseling of parents is required, and respect should be given to their concerns while explaining

that continuing the medications may lead to unnecessary harm. This may be difficult if the child

continues to have frightening and disruptive events. Immediate involvement of psychiatric

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colleagues is strongly recommended to assist in counseling, and plans for psychosocial

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management after discharge from hospital should also be considered early. Advice on interaction

with outside parties such as school nurses should occur, and action and individual educational

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plans should be part of the management44.

The diagnosis and management of PNES require skill and experience, and a collaborative

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approach between general pediatricians, neurologists, psychiatrists, nursing staff, and other
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professional colleagues. A number of ethical questions may arise in this process, and should be

addressed with the virtues of competence, courage, compassion, prudence, and honesty, and the
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principles of respect, beneficence, and avoidance of unnecessary harm. How to avoid

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confrontation and promote the interests of the patient can be difficult, but should be considered
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prior to counseling the child and parents, and throughout the therapeutic relationship.
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