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Psychogenic Nonepileptic Seizures
Table of Contents
Author Information 1
Introduction 2
DEFINITION 2
DIAGNOSIS 4
EPIDEMIOLOGY 4
COMORBID EPILEPSY 7
ASSOCIATED FACTORS 7
POTENTIAL NEUROBIOLOGICAL ORIGIN 8
TREATMENT 10
OUTCOMES 13
Health Care Costs 14
CASE PRESENTATION 15
CONCLUSION 16
BOARD REVIEW QUESTIONS 17
References 17
Hospital Physician Board Review Manual
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Author Information
Epilepsy Board Review Manual
Contributor:
Ali A. Asadi-Pooya, MD
Associate Professor, Jefferson Comprehensive Epilepsy Center, Department of Neurology, Thomas Jefferson University, Philadelphia,
PA; Neurosciences Research Center, Shiraz Medical School, Shiraz University of Medical Sciences, Shiraz, Iran.
Statement of Editorial Purpose
The Epilepsy Board Review Manual is a study guide for trainees and practicing physicians preparing for board examinations in epilepsy. Each manual reviews a topic essential to the current management of patients with epilepsy.
Note from the Publisher
This publication has been developed without involvement of or review by the Amer­ican Board of Psychiatry and Neurology.
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Senior EDITOR
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executive vice president
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www.turner-white.comEpilepsy Volume 3, Part 3 1
Psychogenic Nonepileptic Seizures
Epilepsy Board Review Manual
Psychogenic Nonepileptic Seizures
Ali A. Asadi-Pooya, MD
Introduction
Psychogenic nonepileptic seizures (PNES) are
relatively common occurrences in epilepsy centers.1,2 The International League Against Epilepsy
(ILAE) has identified PNES as 1 of the 10 key
neuropsychiatric conditions associated with epilepsy.3 PNES can significantly affect an individual’s
quality of life and functioning, their families, the
health care system, and even society. Although
PNES are the most common and the most important differential diagnosis of epilepsy, they are
not well characterized and therefore are often
not well diagnosed and treated. Diagnostic delay,
mistreatment of PNES as epilepsy, and poor communication between physicians and patients are
common in practice.3 Several different terms have
been used to describe PNES in the literature.4
This article reviews the current literature about the
definition, recruitment criteria, occurrence, clinical
characteristics, treatment, and prognosis of PNES.
It concludes with a case presentation that highlights key points in the diagnosis and management
of PNES.
DEFINITION
PNES consist of paroxysmal changes in responsiveness, movements, or behavior that superficially
resemble epileptic seizures, but lack a neurobiological origin similar to epileptic seizures and are
not associated with electrophysiological epileptic
changes.5–7 The terms used to describe this condi2 Hospital Physician Board Review Manual
tion reflect the prevailing etiological assumptions
of their times; hysterical seizures, conversion seizures or disorder, functional seizures, functional
neurological symptom disorder, pseudoseizures,
psychogenic seizures, nonepileptic attacks or episodes, and finally, psychogenic nonepileptic seizures (PNES) are some of the terms used to describe this disorder.4
Interestingly, PNES is a condition made unique by
having largely been defined in terms of what it is not,
rather than what it is. Even the newest criteria in the
Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), for conversion disorder
with attacks or seizures, in which the emphasis is
“incompatibility” with a known neurological disorder,
does little to help define PNES clearly and explicitly.8
Based on DSM-5 criteria, PNES is a conversion
disorder, which falls under the diagnostic category
of somatic symptom disorders (Table 1).8
The differential diagnoses of PNES include epilepsy and movement disorders, among other possibilities (eg, syncope). Epilepsy and PNES have
a variety of differing symptoms and signs. For
example, asynchronous limb movements, out-ofphase clonic activity, wax and wane movements
(intermittent shaking movements with episodes of
inactivity), side-to-side head movements, pelvic
movements (especially forward thrusting), dystonic
posturing (including opisthotonos), eyes closed
during the event and resisted eyelid opening, and
nonstereotypical seizure patterns are more often
seen with PNES; however, none of them is pathognomonic for PNES. On the other hand, auras, urine
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Table 1. Diagnostic Criteria (DSM-5) for Psychogenic Nonepileptic Seizures (PNES)
The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) categorizes PNES as a conversion disorder, which is included in the diagnostic category of somatic symptom disorders. According to the DSM-5 classification, neurological symptoms that are
determined to be incompatible with neurological pathophysiology, after appropriate neurological assessment, can be considered conversion
disorder, factitious disorder, or malingering.
DSM-5 criteria for conversion disorder:
1 or more symptoms of altered voluntary motor or sensory function.
• Clinical findings provide evidence of incompatibility between the symptom and recognized neurological or medical conditions.
• The symptom or deficit is not better explained by another medical or mental disorder.
• The symptom or deficit causes clinically significant distress or impairment in social, occupational, or other important areas of functioning or
warrants medical evaluation.
PNES falls under the symptom subtype of “with attacks or seizures.”
Adapted from Benbadis SR. Psychogenic nonepileptic seizures. Medscape. http://emedicine.medscape.com/article/1184694-overview.
incontinence, nocturnal seizures, and ictal injury are
often associated with epileptic seizures; however,
none of them is pathognomonic for epilepsy. Thus,
sometimes clinical differentiation of PNES from
epilepsy proves to be difficult.9–11 Prolonged videoelectroencephalography (video-EEG) monitoring
with ictal recording is considered the optimal test
for the diagnosis of PNES and a definitive diagnosis
is made when typical seizures lack accompanying
electroencephalography (EEG) abnormalities. However, there are patients with epilepsy (eg, frontal
lobe epilepsy) and abnormal movements during
their epileptic seizures with no visible change in their
scalp EEG.9 Frontal lobe seizures are challenging
to diagnose and can be mistaken for nonepileptic
events. Scalp EEG recording is sometimes helpful
in localization but can be misleading in frontal lobe
epilepsy. Studies in patients with refractory frontal
lobe epilepsy have shown few patients have localized interictal epileptiform discharges. Unlike temporal lobe complex partial seizures, the scalp ictal
recording may not be associated with a clear EEG
correlate in 30% of patients.9
The term psychogenic movement disorders (PMD)
has been applied to disorders that manifest with
physical symptoms, specifically abnormal movements, which cannot be attributed to any known
underlying neurological disorders.12 However, the
distinction between PNES and PMD is not always
easy. One retrospective study of comparison of
PMD and PNES revealed more similarities than differences between these 2 conditions.13 In another
study, despite the different physical manifestations
of the 2 conditions, the authors found no differences between the psychiatric profiles, health-related
quality of life, or self-efficacy for self-management
of disease among patients with PNES and PMD.14
In another study, the authors observed that patients with motor conversion disorder had IQ levels
in the average range and intact general cognitive
functioning, suggesting possible mechanistic differences from patients with PNES.15
Because of the challenges of characterizing
PNES, misdiagnosis is common, and symptoms
may be attributed to more than one condition in a
single patient, or different physicians may offer different diagnoses to the same patient. In a previous
study of 350 adult patients with uncontrolled seizures who were taking antiepileptic drugs (AEDs),
9% were proved to have PNES.10 In another similar
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Table 2. Overview of Proposed Diagnostic Levels of Certainty for Psychogenic Nonepileptic Seizures
Diagnostic Level
History
Witnessed Event
Electroencephalography
Possible
+
By witness or self-report/description
Probable
+
Clinically established
+
By clinician, who reviewed video recording or observed event in person, showing semiology typical of PNES
By clinician experienced in diagnosis of seizure
disorders (on video or in person), showing semiology typical of PNES while not on EEG
No epileptiform activity in routine or sleep-deprived
interictal EEG
No epileptiform activity in routine or sleep-deprived
interictal EEG
Documented
+
By clinician experienced in diagnosis of seizure
disorders, showing semiology typical of PNES
while on video-EEG
No epileptiform activity in routine or ambulatory
ictal EEG during a typical ictus/event in which
the semiology would make ictal epileptiform EEG
activity expectable during equivalent epileptic
seizures
No epileptiform activity immediately before, during,
or after ictus captured on ictal video-EEG with
typical PNES semiology
EEG = electroencephalography; PNES = psychogenic nonepileptic seizures; + = history characteristics consistent with PNES.
Adapted with permission from LaFrance WC, Baker GA, Duncan R, et al. 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;54:2005–18.
study in 198 children, this figure was 1.5%.11 As a
result, patients with PNES are at risk of iatrogenic
harm, as they are more likely to receive unnecessary medications (eg, AEDs), emergency treatments, and even hospital admissions.
diagnosis
The diagnosis of PNES may be based on different combinations of data. The combination of
patient history, witness reports, clinician observations, and ictal and interictal EEG and ictal video is
used for diagnostic determination. Four categories
of diagnostic levels of certainty for PNES have
been suggested based on common scenarios
and the combination of data (Table 2).16 In a systematic review of the sensitivity and specificity of
procedures for the differential diagnosis of epileptic from nonepileptic seizures, multiple methods
including seizure induction procedures, Minnesota
Multiphasic Personality Inventory, prolactin levels,
and ictal and postictal symptoms were reviewed;
4 Hospital Physician Board Review Manual
no procedure emerged with both high sensitivity
and specificity and adequately replicated findings.17
However, this review suggested that video-EEG
monitoring has as yet no reliable equivalent among
the range of procedures and observations which
have been investigated. The range of symptoms
presented in PNES suggests that a multi-method
approach may be required.17
EPIDEMIOLOGY
Occurrence
PNES are relatively common. It has been reported that from 5% to 10% of outpatients in epilepsy
clinics and 20% to 40% of inpatients in epilepsy
monitoring units have PNES.1,2,18 In a populationbased prospective study from Scotland, the authors identified first presentations of PNES from a
population of 367,566 persons over 3 years. PNES
were diagnosed in 68 people, in 54 of whom the
diagnosis was confirmed by video-EEG recording, indicating an incidence of 4.9 per 100,000 per
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40
Mean = 22.9011
Standard deviation = 10.13033
N = 188
Number of patients
30
20
10
0
0
20
40
60
Age of onset (years)
Figure 1. Age at onset in patients with psychogenic nonepileptic seizures. (Adapted with permission from Asadi-Pooya AA, Emami
M. Juvenile and adult-onset psychogenic non-epileptic seizures. Clin Neurol Neurosurg 2013;115:1697–1700.)
year.19 In another study, the incidence of PNES
was estimated to be 1.4 per 100,000 per year in
Iceland.20 In a retrospective study of patients referred to a specialist center, the incidence of PNES
in Hamilton County, Ohio, between 1995 and 1998
was determined. The mean incidence of PNES
was 3.03 per 100,000 per year.21
Prevalence data of PNES is scarce, with just 1
study in the literature focusing on this question.
The authors of the study tried to provide an estimate based on a calculation using the following
data as the basis of their calculation: a prevalence
of epilepsy of 0.5% to 1%; a proportion of intracta-
ble epilepsy of 20% to 30%; a percentage of these
referred to epilepsy centers of 20% to 50%; and a
percentage of patients referred to epilepsy centers
that have PNES of 10% to 20%. They concluded
that the prevalence of PNES is somewhere between 1 per 50,000 and 1 per 3000, or 2 to 33 per
100,000, making it a significant psychoneurological
condition.22
Age at onset
PNES tend to begin in adolescence and young
adulthood (Figure 1), although the seizures can
begin at any age.23–33 There are reports about
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Table 3. Demographic Characteristics of Patients with Psychogenic Nonepileptic Seizures
North America (New Hampshire, USA)
North America (Arizona, USA)
South America (Brazil)
South America (Argentine)
Europe (Scotland)
Europe (UK)
Asia (Iran)
Asia (India)
Africa (South Africa)
Australia
Mean Age at Onset (yr)
Mean Time to Confirmed Diagnosis (yr)
33.4
NS
27.85
NS
30.9
31.55
23.2
21.8
NS
32.7
6.51
NS
7.89
11.18
0.6
7.1
5.5
7.4
NS
5.6
Female/Male (ratio)
59/27 (2.18)
142/42 (3.38)
78/24 (3.25)
27/8 (3.37)
44/10 (4.4)
117/43 (2.72)
141/70 (2.01)
44/38 (1.15)
17/5 (3.4)
156/65 (2.4)
NS = not specified.
Adapted with permission from Asadi-Pooya AA, Sperling MR. Epidemiology of psychogenic nonepileptic seizures. Epilepsy Behav 2015;46:60–5.
PNES in young children (as young as 5 years
of age),23,24 and some studies reported PNES in
the elderly (even above 70 years of age).23,25,32
Age at onset in most patients appears to be in
young adulthood, but there is often a significant
delay to have a confirmed diagnosis, and patients
often receive unnecessary treatments (eg, AEDs)
for years before a correct diagnosis is made
(Table 3).18
In one study, the authors dichotomized the patients into 2 groups: those with age at onset below
18 years (juvenile), and those with age at onset
at 18 to 55 years (adult-onset). Age at onset of
PNES did not correlate with clinical manifestations,
although factors potentially predisposing to PNES
were quite different in patients with juvenile-onset
compared to those with adult-onset PNES. History of being abused, academic failure, epilepsy
or family history of epilepsy were more frequently
observed in juvenile PNES, while medical comorbidities were more frequent among patients with
adult-onset PNES.23 In another study, the authors
compared patients with onset of PNES after age
6 Hospital Physician Board Review Manual
55 years (n = 26) to those with onset of the disease
at earlier ages (n = 241). They observed that patients with late-onset PNES were more likely to be
male and to have severe physical health problems,
while they were less likely to report antecedent
sexual abuse.25
Gender
There is a predominance of female gender
among patients with PNES.33–37 The female:male
ratio in one study from China was reported to be
1,35 but studies from 5 continents generally note
PNES to be far more common in females (Table 3).
Lesser examined the sex distribution in 21 studies and found descriptions of 734 women and 250
men who had PNES (female:male ratio = 2.94).36
However, most studies are not specifically designed to determine the demographic characteristics of patients with PNES.
PNES are not only less common in men, but
also more challenging to recognize in the clinic,
and even when suspected, more difficult to confirm
with video-EEG monitoring.34 However, no specific
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Psychogenic Nonepileptic Seizures
or consistent difference in the underlying psychopathology between men and women with PNES
has been reported. In one study (129 women and
59 men), there were no significant demographic
differences between women and men with PNES.
Likewise, seizure characteristics and semiology
were similar among both genders.37 Another study
also tried to determine if gender-specific differences exist in PNES predictors and PNES semiology. The authors investigated 59 women and
27 men, retrospectively. They found significantly
lower rates of reported physical and sexual abuse,
lower rates of previous psychiatric diagnoses, and
lower rates of chronic pain in male patients. However, they found no difference in PNES semiology
between men and women. They concluded that
distinct risk factor criteria but similar semiologic
criteria should be used for the diagnosis of probable PNES in the outpatient clinic in men and
women.33
Comorbid epilepsy
The proportion of patients with PNES who also
have epilepsy has been reported to vary from
5% to 50%.18,22,26,38–41 Criteria for concomitant diagnosis of epilepsy have not been consistent in
literature reports. Having interictal spikes, as most
studies defined their epilepsy cases, does not necessarily mean that epilepsy is also present. Interictal epileptiform abnormalities have been reported
in nonepileptic conditions42 and even in normal
people.43 The key step in making a correct diagnosis of epilepsy is having a standardized approach,
particularly with regard to taking a detailed clinical history. If the diagnosis of epilepsy (vs PNES)
cannot be established by taking history alone, one
should obtain further testing and diagnostic information (eg, prolonged video-EEG monitoring).
In a study of 176 patients with PNES, 103 patients had PNES, without any evidence for epilepsy
or family history of epilepsy; 19 patients had PNES
and concomitant epilepsy, but they did not have
family history of epilepsy; 54 patients had PNES
and family history of epilepsy, but they did not have
concomitant epilepsy. Demographic and clinical
characteristics and associated factors of patients
with PNES with co-existing epilepsy were similar to
those in patients with PNES without co-existing epilepsy.38 It has been speculated that epilepsy may
contribute to the risk for developing PNES not only
through biologic mechanisms, but also because
the experience or observation of epileptic seizures
may provide an opportunity for model learning.44
Associated factors
PNES occur in a heterogeneous patient population. No single mechanism or contributing factor
has been identified that is necessary and sufficient
to explain PNES in all patients.44 The most commonly reported PNES associated factors include
sexual abuse, physical abuse or neglect, traumatic
brain injury, medical comorbidities, and psychiatric comorbidities.2,45–52 The relationship between
childhood sexual abuse and PNES has received
particular attention in the literature. In a study comparing childhood abuse in patients who had PNES
(71 patients) and those who had epilepsy (140
patients), significantly higher rates of both sexual
(24.0% versus 7.1%) and physical (15.5% versus
2.9%) abuse were found in those who had PNES
(P < 0.001).52 In a recent study comparing patients
with PNES only (324 patients) with those who
had epilepsy only (281 patients), history of abuse
(physical or sexual) was more frequent among
those with PNES (odds ratio 3.35, 95% confidence
interval 1.23 to 9.10; P = 0.018).53 However, there
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are discrepancies and inconsistencies among
studies with regard to the interaction between childhood sexual or physical abuse and PNES depending on the study and the design. In one study from
Iran, the authors observed that history of childhood
abuse (12.8%), physical abuse (11.8%), and sexual
abuse (8.1%) were not as common in patients with
PNES, compared to Western patients.2,52 The wide
variety of methods used for assessment of abuse
(sexual and physical) and lack of control populations in most of the published studies make it difficult to establish a cause and effect relationship
between PNES and abuse.
Another commonly reported PNES-associated
factor is traumatic brain injury (TBI). In a study of
92 patients with PNES, 41 (44.6%) had a history
of TBI. Patients with TBI had more mood disorder
diagnoses, were more likely to receive disability,
and had lower global functioning than non-TBI patients with PNES, after adjusting for age and sex.
Patients with TBI and PNES had significantly increased odds for having major depression, behavioral impulsivity, posttraumatic stress disorder diagnosis, and a trauma/abuse history. The authors
concluded that TBI is a significant risk factor in patients with PNES, being associated with increased
psychiatric diagnostic comorbidity, symptom severity, poorer functioning, and increased disability.47
Clinical experience suggests that PNES commonly start in association with or during a period
of exacerbation of another mental disorder. A lifetime history of other somatoform or dissociative
disorders is found in more than 50% of patients
who have PNES. Anxiety or psychotic and bipolar
disorders are less common but are found more
frequently in patients who have PNES than in the
general population. Many patients with PNES have
features of posttraumatic stress disorder (PTSD).44
I should emphasize that an agreed upon distinc8 Hospital Physician Board Review Manual
tion between PNES associated factors and comorbidities is not apparent in the literature and a
complete discussion of psychiatric comorbidities
(eg, depression, anxiety) is too broad to be covered in this review. Often and in most patients with
PNES, several potential interacting factors may be
identified.44 Reuber in his review concluded that
predisposing factors (eg, abuse, neglect) increase
vulnerability to the development of PNES. Precipitating factors may occur over days to months
before the onset of seizures and seem to cause
PNES to start, but these are far from universal.
Factors that have been described as precipitating
PNES include rape, injury, death of or separation
from family members or friends, job loss, accidents,
giving birth, surgical procedures, natural disasters
(eg, earthquakes), relationship difficulties, and
legal action.44 In older people, medical comorbidity
is a common identifiable precipitant.23,37,44 Finally,
perpetuating factors (eg, isolation, anger, anxiety,
depression, misdiagnosis, mistreatment) make it
harder for patients to regain control of seizures or
aggravate the problem once seizures have started
(Figure 2). Even if one factor seems to play a predominant role in a particular patient, other factors
are likely to have contributed and should not be
ignored.44
Potential neurobiological origin
Organic brain dysfunction is associated with
PNES. The neurobiology of PNES is still poorly
understood. Obviously, PNES lack a neurobiological origin similar to epileptic seizures, but emerging
evidences suggest that there is a neurobiological
basis for these events.54 In one study of functional
connectivity networks from resting-state functional
magnetic resonance imaging signal correlations
and structural connectivity networks from diffusion
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Figure 2. Etiology of psychogenic nonepileptic seizures (PNES): a multifactorial model. (Adapted with permission from Reuber M.
The etiology of psychogenic non-epileptic seizures: Toward a biopsychosocial model. Neurol Clin 2009;27:909–24.)
tensor imaging tractography in 17 PNES patients
and 20 healthy controls,55 it was observed that
patients with PNES exhibited altered functional
and structural networks. This study showed that
the coupling strength of functional-structural connectivity was decreased and exhibited high sensitivity and specificity to differentiate patients with
PNES from healthy controls.55 In another study of
functional connectivity density mapping, the authors found that patients with PNES had abnormal
functional connectivity density regions mainly in
the frontal cortex, sensorimotor cortex, cingulate
gyrus, insula, and occipital cortex. Seed-voxel correlation analyses also showed disrupted functional
connectivity between these regions.56 In a recent
study, 18FDG-PET was performed in 16 patients
with PNES and 16 healthy controls. A voxel-byvoxel intergroup analysis was performed to look for
significant differences in interictal resting state cerebral metabolism. In addition, metabolic connectivity was studied using voxel-wise inter-regional
correlation analysis. In comparison to healthy participants, patients with PNES exhibited significant
PET hypometabolism within right inferior parietal
and central regions and within bilateral anterior
cingulate cortices. The authors concluded that regions with hypometabolism might relate to 2 pathophysiological mechanisms that may be involved in
PNES: emotional dysregulation (anterior cingulate
hypometabolism) and dysfunctional processes underlying the consciousness of the self and the environment (right parietal hypometabolism).57
Models explaining the pathogenic mechanisms
leading to PNES are limited. A hypothetical pathophysiological mechanism was proposed in 2011 by
Baslet.51 This pathophysiological model suggested
an alteration in the influence and connection of
brain areas involved in emotion processing onto
other brain areas responsible for sensorimotor
and cognitive processes (Figure 358). PNES were
conceptualized as brief episodes facilitated by an
unstable cognitive-emotional-attention system.51
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Figure 3. Schematic overview of the circuitry involved in cognitive-emotional-executive control. There is significantly higher functional connectivity strengths between regions involved in emotion (eg, insula) and motor planning (eg, precentral sulcus) in patients
with psychogenic nonepileptic seizures (PNES). It appears that healthy controls can control their motor functions without strong
influence of emotions, whereas in patients with PNES emotions can bypass executive control and cause involuntary movement.
(Adapted with permission from van der Kruijs SJ, Bodde NM, Vaessen MJ, et al. Functional connectivity of dissociation in patients
with psychogenic non-epileptic seizures. J Neurol Neurosurg Psychiatry 2012;83:239–47.)
This model is very well supported by the recent
findings discussed above. PNES could be the
result of neurobiological dysfunctions at specific
brain networks.
Treatment
Many professionals diagnosing patients with
PNES refer them to mental health professionals for
treatment.59 At the same time, continued involvement of the neurologist who established the diagnosis is desirable to allow a safe taper of AEDs,
prevent inappropriate treatment, evaluate the development of any new neurological symptoms, and
treat any comorbid neurological condition.60 Once
10 Hospital Physician Board Review Manual
patients enter mental health treatment, no guidelines exist on the type or duration of treatment
that will help them achieve symptom improvement and functional recovery.61 PNES comprise a
heterogeneous population,44 and ideally different
treatment protocols should exist for different PNES
subgroups. In the absence of such guidelines,
treatment of PNES could be conceptualized in 4
phases (Figure 4).61
The initial phase of treatment is diagnosis delivery. In most cases the diagnosis is likely to be
communicated by a neurologist. No research has
been undertaken to establish whether it is effective
to involve the patients’ family members in the discussion of the diagnosis. However, having family
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Psychogenic Nonepileptic Seizures
Symptom
Diagnosis
Delivery
Engagement
Acute
Treatment
Long-term
Followup
Figure 4. Treatment phases in psychogenic nonepileptic seizures (PNES). (Adapted with permission from Baslet G, Dworetzky B,
Perez DL, Oser M. Treatment of psychogenic nonepileptic seizures: updated review and findings from a mindfulness-based intervention case series. Clin EEG Neurosci 2015;46:54–64.)
members present during the presentation may
facilitate understanding of the condition.62 There
is increasing evidence that the process of communicating the diagnosis is a very important and
potentially effective therapeutic step in the management pathway of patients with PNES 62 (See
Prognosis). Table 3 describes the strategies used
for the communication of the diagnosis of PNES by
some experts in the field.
The second phase of treatment is engagement.
Engagement is a pivotal phase of treatment in
PNES. While some patients may be ready to become active participants in mental health treatment
immediately after the diagnosis is delivered to
them, other patients will take longer to accept such
referrals or to meaningfully engage in the treatment process. Use of clinician skills to enhance
behavioral change in the patients may have the
potential to help them move through their treatment
course. Ideally, by the end of this phase, patients
understand their diagnosis, do not seek further diagnostic evaluations elsewhere, establish contact
with a mental health provider, and start to actively
participate in treatment.61
The third phase of treatment involves an acute
intervention. Formal psychiatric assessment should
be arranged and performed. Predisposing, precipitating, and perpetuating factors should be investigated. Individualized psychotherapeutic and
psychopharmacological treatment plans should
be formulated. This phase has a primary goal of
reduction of event frequency. But, improvement
in secondary measures such as severity of psychiatric comorbidities, quality of life, functional
recovery, and medical resource utilization is also
desired.61 In one pilot randomized clinical trial at
3 academic medical centers with mental health
clinicians trained to administer psychotherapy or
psychopharmacology to outpatients with PNES,
34 patients were randomized in a blocked schedule among 3 sites to 1 of 4 treatment arms and
were followed up for 16 weeks.63 The treatment
arms included medication (flexible-dose sertraline) only, cognitive behavioral therapy informed
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Table 3. Strategies Used for the Communication of the Diagnosis of Psychogenic Nonepileptic Seizures
The Expert
The Communication Strategy
Shen
Good news: these seizures are not caused by epilepsy, explain video-EEG findings.
Bad news: we do not know the precise cause of the seizures, but they are nonepileptic—AEDs do not work.
AEDs may cause serious side effects.
“We may never know what these seizures are but can work together on the problems.”
In most cases seizures are eventually related to upsetting emotions of which patients are unaware.
This may be best addressed by a psychiatrist, a psychologist or a counselor.
You are not crazy, the seizures occur at a subconscious level.
Counseling may not control seizures immediately, but seizures can improve as treatment progresses.
Neurologic follow-up will continue.
A history of sexual abuse is discovered in many cases.
The seizures may stop spontaneously. Although they are subconscious, a conscious effort can sometimes stop them.
More seizures may occur before complete control is achieved.
Cover reasons for concluding they do not have epilepsy.
Relay what they do have.
Emphasize they are not suspected of “putting on” the events.
They are not “mad”; the problem is common, and seizures are disabling.
Events are stress related, but stresses may be difficult to identify.
Triggering “stresses” may not be immediately apparent.
Explain relevance of etiologic factors in their case.
Discuss maintaining factors. Worry about seizures may make them worse/more frequent.
Avoidant behavior may make seizures worse.
May improve after correct diagnosis.
Caution that AED withdrawal should be gradual.
Describe psychological treatment.
Include patients' caregivers when delivering this explanation.
Explain how video-EEG works and how it has helped with the diagnosis.
Seizures are emotional/psychological, due to past/present issues, not a medical condition.
List possible predisposing factors as “specimen causes” not directly linked to the patient.
Seizures are not under conscious control, but patients can learn to control them with help from a therapist.
Patients may have anxiety or low mood, but are otherwise not mentally ill or “mad.”
AED treatment does not work, psychological treatment can work, no other treatment is available.
Describe psychological intervention.
Ask whether patients want psychological intervention.
Explain that the symptoms are genuine.
Real events; can be frightening or disabling.
Label. Give a name for the condition. Give alternative names they may hear.
Reassure that this is a common and recognized condition.
Cause and maintaining factors: not epilepsy, predisposing factors difficult to identify, precipitating factors can be related to
stress/emotions, perpetuating factors.
Provide a model for the events (eg, brain becomes overloaded and shuts down).
Treatment. AEDs are not effective.
Evidence that psychological treatment is effective.
Talk about referral to a treatment specialist.
Expectations. Can resolve, can expect improvement.
Mellers
Duncan
Hall-Patch
AED = antiepileptic drug; EEG = encephalography.
Adapted with permission from LaFrance WC Jr, Reuber M, Goldstein LH. Management of psychogenic nonepileptic seizures. Epilepsia 2013;54
Suppl 1:53–67.
12 Hospital Physician Board Review Manual
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Psychogenic Nonepileptic Seizures
psychotherapy (CBT-ip) only, CBT-ip with medication (sertraline), or treatment as usual. The
CBT-ip arm showed a 51.4% seizure reduction
(P = 0.01) and significant improvement from baseline in secondary measures including depression, anxiety, quality of life, and global functioning
(P < 0.001). The combined arm (CBT-ip with
sertraline) showed a 59.3% seizure reduction
(P = 0.008) and significant improvements in some
secondary measures, including global functioning
(P = 0.007). The sertraline-only arm did not show
a reduction in seizures (P = 0.08). The treatmentas-usual group showed no significant seizure
reduction or improvement in secondary outcome
measures (P = 0.19). Participants in the CBT-ip
condition reported significantly fewer visits to the
emergency department during the trial relative
to baseline.63 Other potential psychotherapeutic
interventions include psychodynamic therapy and
group therapies (eg, family therapy if family system
dysfunction is present).62 The pharmacologic treatment plan of patients should include early tapering
and discontinuation of AEDs, unless a specific
AED has a documented beneficial psychopharmacologic effect in an individual patient (eg, lamotrigine for depression or valproate for bipolar disorder).
In people with comorbid epileptic seizures, reduce
high doses of AEDs or polytherapy if possible.
Finally, use psychopharmacologic agents (eg, sertraline, venlafaxine) to treat comorbid mood, anxiety, or psychotic disorders, and possibly to treat
somatoform symptoms directly.62
The final phase of treatment is composed of
long-term interventions. This is particularly relevant
for the subgroup of PNES patients who remain
symptomatic after the acute intervention phase
and who will need ongoing care to optimize the
use of resources and functional recovery. This may
include long-term psychotherapy, case manage-
ment, and ongoing psychotropic management of
psychiatric comorbidities among other individualized interventions.61,62
OUTCOMES
Prognosis
Definitive diagnosis of PNES can lead to appropriate therapy and even cessation of the events.64
In one study, seizure frequency during inpatient
video-EEG monitoring was examined before and
after the diagnosis of PNES being presented to 22
patients. A control group of 10 patients with epilepsy
was also followed from pre- to post-diagnosis. The
number of nonepileptic seizures (in patients with
PNES) or epileptic seizures (in those with epilepsy)
within the 24-hour period prior to diagnosis was
compared with the number of events that occurred
within the 24-hour period after presentation of the
diagnosis. Their findings indicated that patients
with PNES had a significant decrease in the frequency of events after diagnosis, while those with
epilepsy showed no change in event frequency
after diagnosis. Eighteen of 22 patients with PNES
had no further events during an acute follow-up
period.64 However, in a previous review the authors
concluded that communicating to the patient that
the seizures are not epileptic may stop PNES in
short-term, but does little to improve associated
psychological morbidity, distress, or health-related
quality of life. Without dedicated further treatments, PNES are likely to restart in the majority of
patients.62 Unfortunately, longer-term studies suggest that many patients with PNES will continue
to experience seizures despite neurological and
psychotherapeutic care.65 Clinical and personality
factors should be used to provide an individualized
prognosis in patients with PNES. In one study, 164
adult patients with PNES were investigated a mean
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Psychogenic Nonepileptic Seizures
of 11.9 years after manifestation and 4.1 years
after diagnosis of PNES. The responses showed
that 71.2% of patients continued to have seizures
and 56.4% were dependent on social security.
Outcome was better in patients with greater educational attainments, younger onset and diagnosis,
attacks with less dramatic features, fewer additional somatoform complaints, and lower dissociation
scores.65 In a systematic review published in 2011,
the authors concluded that the prognosis of PNES
in adults is poor. From their reviewed data, fewer
than 4 in 10 newly diagnosed adults could be expected to become seizure-free within 5 years after
diagnosis. In children the figure of patients achieving seizure remission appeared to be around 70%,
which indicates a more favorable result.66
Mortality
Scattered evidence suggests that PNES are associated with increased mortality. In one study, the
authors obtained death certificate information in a
cohort of 260 patients who presented with PNES
between 1999 and 2004 from West of Scotland
Regional Epilepsy Service, Southern General Hospital, Glasgow, UK. The follow-up period averaged
7.92 years, during which 17 patients died. Twelve
out of 17 patients who died were under the age
of 75 years, giving a premature mortality rate of
0.58% per year, compared with a Scottish mortality rate for the 40–75 year age-group of 0.41% per
year. These results suggest that a diagnosis of
PNES may be associated with a modest increase
in mortality.67 Serious physical illness is prevalent
in patients with PNES with an onset of their attacks after the age of 55 years. The development
of physical illness (especially where this has been
frightening to the patient) may be an important triggering factor for PNES, at least in a subset of patients.25 This means that the medical comorbidities
14 Hospital Physician Board Review Manual
are probably responsible for increased mortality
seen in patients with PNES and not the disease
itself (ie, PNES). Besides, in the Scottish study
mentioned above, patients came from a population that was deprived relative to the general Scottish population; the authors concluded that some
excess mortality might be expected secondary
to socioeconomic factors.67 On the other hand,
in one study of 43 patients with PNES, 23% reported suicide attempts.68 This may also contribute
to the increased mortality among patients with
PNES.
Health care costs
PNES place a heavy demand on emergency
and nonemergency health care services.69 It has
been observed that most patients who have PNES
diagnosed with video-EEG monitoring experience
substantial subsequent reductions in health care
utilization and costs.69–71 In one study, it was reported that in patients with a new diagnosis of PNES
documented, pre-diagnosis medical costs exceeded $15,000 per patient and loss of work costs
exceeded $22,000 per patient.72 In another study
in 2013, overall costs dropped from the 12-month
period preceding PNES diagnosis (mean costs:
$4567) to the 12-month period following PNES
diagnosis (mean costs: $2783). This equated to a
cost reduction of nearly $1800 per person.71 In another study in 1998, there was an 84% average reduction in total seizure related medical charges in
the 6 months following PNES diagnosis. Average
diagnostic testing charges declined 76%, average
medication charges decreased 69%, outpatient
clinic visits declined 80%, and emergency room
visits declined 97%.69 In a more recent study, the
authors performed a 1-year prospective audit of
use of a group of PNES-related health care items in
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Psychogenic Nonepileptic Seizures
patients with newly diagnosed PNES, from PNES
onset to diagnosis and from diagnosis to 6 months
post-diagnosis. Before diagnosis, 28 patients were
responsible for 14 general practitioner home visits,
31 ambulance calls, 34 emergency department
visits, 21 hospital admissions, 2 standard EEGs,
28 short video-EEG recordings, and 5 ambulatory
EEG recordings. In the 6 months following diagnosis, there were 2 emergency department visits
(94.1% reduction), no hospital admissions (100%
reduction), 2 ambulance calls (93.5% reduction),
no general practitioner visits (100% reduction),
and no EEGs (100% reduction).70 Overall, the
burden of PNES is significant, particularly if it
remains undiagnosed. Early diagnosis of PNES
may save money and reduce the service utilization burden for patients and the health care
system.69–72
Case presentation
A 32-year-old single woman is referred for assessment of drug-resistant seizures. Her seizures
started at age 16. She was at home with her
parents at the time of her first seizure, which was
early in the morning after she woke up; she has no
recall of the event. The patient’s mother reported
that she slumped over, became stiff, and began to
shake; the event lasted about 2 minutes. A second
similar episode occurred 1 month later. She has
never experienced this seizure type again. She
also mentions that she has experienced hand
and body jerks in the morning since she was 15
years of age. At age 23 she developed new episodes of loss of awareness and responsiveness,
stiffening and curving of her body, and intermittent
pedaling for rather long periods, sometimes up to
about 30 minutes. She was visited by a handful of
neurologists and has tried 4 different antiepileptic
drugs (ie, levetiracetam, lamotrigine, valproate,
and zonisamide) with no difference in her current seizure frequency. Currently, she is taking
lamotrigine 300 mg/day and levetiracetam 2000
mg/day. She has a very high health care utilization
pattern. Within the past year she has consulted
3 different neurologists, has been to the emergency department 3 times, and has had 2 hospital
admissions.
Review of past history reveals that she has
had irritable bowel syndrome since age 15. She
also complains of chronic fatigue since she was
16 years of age. From grades 10 through 12, she
missed about 10% of the school days due to health
complaints. At age 22, she was diagnosed with “severe anxiety” and dropped out of college. Various
psychiatric medications were given, but she had a
number of intolerable side effects. Family history is
significant for a 20-year-old brother with epilepsy.
Her mother suffers from major depression.
On neuropsychological testing, she has a normal IQ and memory, and no formal neurocognitive
impairments. On the Beck Depression Inventory,
she scores in the moderately depressed range.
Her Beck Anxiety Inventory score is in the severely
anxious range.
During her 7-day admission at the inpatient
video-EEG monitoring unit, she has 3 of her typical clinical seizures, none of which are associated
with abnormal EEG activity, and all occur with
normal awake posterior dominant rhythm. Her parents agree that the recorded episodes are typical
events. However, her interictal EEG shows 4-Hz
generalized spike-wave complexes. She leaves
the hospital with a diagnosis of both epilepsy (ie,
juvenile myoclonic epilepsy) and PNES.
The health care team delivers the diagnosis to
the patient and her family and also tries to persuade her to be actively engaged in her treatment
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Psychogenic Nonepileptic Seizures
plan. It is decided to slowly taper her levetiracetam
(it has adverse psychiatric effects73) and keep her
on lamotrigine (it is an AED and also a psychotropic agent with positive effects in depression).
Referrals to a psychiatrist and also to a psychotherapist are also arranged.
Discussion
Epilepsy is not rare among patients with PNES. It
is generally accepted that the prevalence of epilepsy is greater among patients with PNES than in the
general population. These 2 disorders have a variety of differing symptoms and signs; however, none
of them is pathognomonic to PNES. Thus, clinical
differentiation of PNES from epilepsy sometimes
proves to be difficult. Video-EEG monitoring with
ictal recording is considered the gold standard test
for the diagnosis of PNES. Diagnosis is achieved
when a patient is observed having typical seizures
without accompanying EEG abnormalities. Family members or witnesses who are familiar with
the patient’s habitual seizures must agree that the
recorded episodes are typical events.38 However,
it is not always easy to distinguish between these
2 disorders, particularly if a patient is affected by
both conditions. Treatment of PNES is not always
an easy task either. The co-existence of these 2
conditions makes their treatment even more difficult and more challenging. Collaboration with
mental health professionals should ideally start
as soon as possible in the management process
of patients with PNES. Mental health services are
best utilized at 3 stages during the management of
PNES: (1) while the diagnosis is being investigated
to identify vulnerability traits, psychosocial factors,
and psychiatric comorbidities; (2) during the delivery of the diagnosis, which also aims to engage
patients in treatment; and (3) for the delivery of
treatment.61
16 Hospital Physician Board Review Manual
Conclusion
PNES consist of paroxysmal changes in responsiveness, movements, or behavior that superficially resemble epileptic seizures, but lack a
neurobiological origin similar to epileptic seizures
and are not associated with electrophysiological
epileptic changes. They are commonly diagnosed
at epilepsy centers. One should have a high index
of suspicion when a patient presents with atypical
epileptic seizure and a high number of PNES risk
factors. The diagnosis of PNES relies on a multidisciplinary evaluation and is usually based on
different combinations of data. The combination of
patient history, witness reports, clinician observations, and ictal and interictal EEG and ictal video
is used for diagnostic determination. Recording a
seizure, while under video-EEG monitoring, is the
most reliable diagnostic test.
The incidence of PNES was estimated to be 1.4
to 4.9 per 100,000 per year and the prevalence is
calculated to be somewhere between 2 and 33 per
100,000, making it a significant psychoneurological
condition. PNES tend to begin in adolescence and
young adulthood, although the seizures can begin
at any age. There is a predominance of female
gender among patients with PNES. The proportion of patients with PNES who also have epilepsy
has been reported to vary from 5% to 50%. PNES
occur in a heterogeneous patient population. No
single mechanism or contributing factor has been
identified that is necessary and sufficient to explain
PNES in all patients. The most commonly reported
PNES associated factors include sexual abuse,
physical abuse or neglect, traumatic brain injury,
medical comorbidities, and psychiatric comorbidities. Even if one factor seems to play a predominant
role in a particular patient, other factors are likely to
have contributed and should not be ignored.
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Psychogenic Nonepileptic Seizures
The neurobiology of PNES is still poorly understood. Obviously, PNES lack a neurobiological
origin similar to epileptic seizures, but emerging evidence suggest that there is a neurobiological basis
for these events. They could be the result of neurobiological dysfunction at specific brain networks.
The initial phase of treatment is diagnosis delivery, the second phase is engagement, and the
third phase involves an acute intervention. At the
third phase, individualized psychotherapeutic and
psychopharmacological treatment plans should
be formulated. This phase has a primary goal of
reduction of event frequency, but improvement
in secondary measures such as severity of psychiatric comorbidities, quality of life, functional
recovery, and medical resource utilization is also
desired. The final phase of treatment is composed
of long-term interventions. Fewer than 40% of
newly diagnosed adults could be expected to become seizure-free within 5-years after diagnosis.
In children, the figure of patients achieving seizure
remission appears to be around 70%, which indicates a more favorable result. Scattered evidence
suggests that PNES are associated with increased
mortality. Overall, the burden of PNES is significant, particularly if it remains undiagnosed. Early
diagnosis of PNES may save money and reduce
the service utilization burden for patients and the
health care system.
Click to test your
knowledge of this topic with
Epilepsy Board Review Questions.
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