1. The Diagnosis of Psychogenic Nonepileptic Seizures from the Neurological & Psychiatric Perspectives
Deepti Anbarasan, MD
NYU School of Medicine
NYC Neuropsychiatry, Private Practice
10/19/19

2. Psychogenic Nonepileptic Seizures (PNES)
Paroxysmal episodes of altered subjective or objective manifestations that resemble epileptic seizures but are not associated with abnormal neuronal epileptiform activity on EEG.
Most common and well-known conversion disorder.

3. Epidemiology of PNES Estimated prevalence is 30/100,000 individuals
3:1 ratio for women:men
Mean age of onset of 31 years (+/- 15 years)
Lifetime physical or sexual abuse: 23% to 77%
Mild traumatic brain injury

4. Epidemiology of PNES Predisposing factors
Temperament (expectation and anxiety traits)
Early childhood experiences
Precipitating and perpetuating factors
Attention
Expectation
Stress/Arousal
Dissociation/Hypnosis
Voluntariness

5. Epidemiology of PNES Specific circumstances Bereavement
Being in or witnessing an accident
School phobia or difficulties in school (including bullying, specific learning difficulties, or unrealistic expectations) in early-onset cases
Health-related trauma in late–onset cases

6. Epidemiology of PNES
Presence of medical comorbidities (Dixit et al, 2013)
Fibromyalgia
Chronic fatigue syndrome
Chronic pain syndrome
Tension Headaches
Irritable bowel syndrome
Asthma, migraines, GERD
Presence of at least one of these as a diagnostic test for PNES
Sensitivity of 65.6%: probability that patients with PNES evaluated will have at least one of these illnesses
Specificity of 73%: illnesses are specific to patients with PNES

7. Etiology of PNES
No single etiological model to explain phenomenon: multifactorial that comprises biological, psychological, and social factors.
Lies at the interface of neurology and psychiatry
Involuntary, stimulus-driven behavioral response due to limited adaptive behaviors and excessive vulnerabilities
No typical phenotype: oscillating and simultaneous existence of hyperarousal responses & hypoarousal responses
Vulnerabilities: dissociation, avoidance behaviors, PTSD or anxiety, personality structure, interpersonal dynamics, society and family factors
Hyperarousal (hypervigilance, somatic preoccupation, emotional reactivity and underregulation)
Hypoarousal (dissociation, avoidance, alexithymia, emotional overregulation)

8. Etiology of PNES Psychiatric hypotheses
Per DSM-5, conversion disorder is characterized by the following:
One or more symptoms of altered voluntary motor or sensory function
Clinical findings that show evidence of incompatibility between the symptoms and recognized neurological or medical conditions
Symptoms or deficit that are not better explained by another medical or mental disorder
Symptoms or deficit that cause clinically significant distress or impairment in social, occupational, or other important areas of functioning or warrants medical evaluation.
Vulnerabilities: dissociation, avoidance behaviors, PTSD or anxiety, personality structure, interpersonal dynamics, society and family factors
Hyperarousal (hypervigilance, somatic preoccupation, emotional reactivity and underregulation)
Hypoarousal (dissociation, avoidance, alexithymia, emotional overregulation)

10. Etiology of PNES Biological hypotheses
Trend towards right hemispheric dysfunction and frontotemporal pathology
Implicated structural/functional regions
Prefrontal-insular-amygdala: emotional regulation and awareness, sensory processing of emotionally valent information
Posterior parietal cortex (PPC): self-referential processing and motor perceptual/intentional awareness; body-mind integraation
Supplementary motor area (SMA) and cerebellum: motor planning and coordination
Posterior insula receives visceral-somatic sensory afferents from the thalamus and mid-insula integrates affectively/motivationally valenced information from the AC, amygdala, and OFC to help with sensory processing. Anterior insula is linked to emotional awareness.
PPC implicated in motor intentional awareness and self-agency, alien hand syndrome, misattributions in neuropsych disorders including delusions of control, and impairments of body-self integration eg. Out of body experiences, nihilistic delusions.

11. Etiology of PNES
Post-traumatic PNES
Automatic ‘cut-off phenomenon’ in response to cued or spontaneous intrusion into consciousness of unspeakable memories
Developmental PNES
Response to struggles related to coping with complex life tasks and milestones during one’s psychosocial development.

12. Hypometabolism in the right inferior parietal and central region in patients with psychogenic non-epileptic seizures, in comparison to healthy participants (p-voxel <0.001).
Hypometabolism in the right inferior parietal and central region in patients with psychogenic non-epileptic seizures, in comparison to healthy participants (p-voxel <0.001). Parietal lobe - dysfunctional processes underlying the consciousness of self and the environment
M Arthuis et al. J Neurol Neurosurg Psychiatry 2015;86:
©2015 by BMJ Publishing Group Ltd

13. Hypometabolism in the bilateral anterior cingulate cortex in patients with psychogenic non-epileptic seizures, in comparison to healthy participants (p-voxel <0.001).
Hypometabolism in the bilateral anterior cingulate cortex in patients with psychogenic non-epileptic seizures, in comparison to healthy participants (p-voxel <0.001). Issues with emotional dysregulation
M Arthuis et al. J Neurol Neurosurg Psychiatry 2015;86:
©2015 by BMJ Publishing Group Ltd

14. Increase in metabolic connectivity in patients with psychogenic non-epileptic seizures, in comparison to healthy participants, between the bilateral anterior cingulate cortex and the left parahippocampal gyrus (p-voxel <0.001).
Increase in metabolic connectivity in patients with psychogenic non-epileptic seizures, in comparison to healthy participants, between the bilateral anterior cingulate cortex and the left parahippocampal gyrus (p-voxel <0.001).
M Arthuis et al. J Neurol Neurosurg Psychiatry 2015;86:
©2015 by BMJ Publishing Group Ltd

15. Epidemiology of PNES Coincidence of PNES with ES of 10 to 25%.
Associated with unemployment, anxiety/depression, and medically unexplained symptoms
Coincidence of PNES with ES of 10 to 25%.
Accounts for % of discharge diagnoses from inpatient epilepsy monitoring units

16. Implications of PNES
Quality of life
Unnecessary use of seizure medications due to misdiagnosis in 2/3 of patients
Untreated comorbidities
Associated with high medical utilization rates
High personal and societal costs ($900 million annually)
Higher premature mortality rate in PNES subjects when compared to general population.

17. Diagnosis Thorough history-taking and physical examination
VEEG monitoring in EMU is gold standard of diagnosis

18. Diagnosis PNES Diagnosis: History, clinical assessment, VEEG
ILAE Diagnostic certainty
Semiology suggestive of PNES
Possible
Patient or witness report
Probable
Video recording or witness by clinician
Clinically established
Video recording or witness by clinician experienced in diagnosis of seizure disorders (no simultaneous EEG data)
Documented
Video-EEG-recording of attack evaluated by clinician experienced in diagnosis of seizure disorders

19. Diagnosis Every semiology needs to be characterized
Prompt diagnosis allows for
Sooner implementation of appropriate psychological and psychiatric treatments
Allow for taper off antiepileptic drugs if appropriate
Reassurance related to accurate diagnosis and starting more appropriate treatment course

20. Diagnosis If VEEG unavailable: Ambulatory EEG
Poor video quality or EEG quality
Cannot engage with patient
Cannot perform medication taper
Prolactin level: doubling of level in first 10 to 20 minutes after convulsive epileptic seizure
False positives if taking dopamine antagonists or with breast augmentation
False negatives if frontal lobe seizure, late status epilepticus, dopamine agonists

21. Diagnosis Neuropsychological testing
Used adjunctively with clinical assessment and video-EEG monitoring
Findings (Willment et al, 2015)
Differences in personality inventories: conversion, somatic, dissociative, anxious, and depressive symptoms
Attentional and executive functioning deficits
Verbal memory, reduced verbal fluency 
No group differences on tests for volitional manipulation of symptoms for secondary gain

22. Clinical features suggestive of PNES
Eye Closure
Thrashing or Pelvic thrusting
Opisthotonus
Side-to-side head shaking
Prolonged duration (>4 minutes)
Stopping and starting
Suggestibility
Faster recovery to baseline after the event
Eliciting a good seizure history is critical: onset, typical semiology, treatments; history of trauma, bullying, psychosocial stressors, medically unexplained symptoms or pain.

23. Differential diagnosis
Epilepsy – frontal lobe epilepsy, absence seizures
Periodic limb movements of sleeps – occur only during sleep with repetitive, stereotyped limb movements, usually legs
Convulsive syncope
Factitious disorder
Malingering
Factitious disorder – symptoms increase when requests for unnecessary interventions are declined or there is increase in sz frequency when time for discharge.

24. André Brouillet in 1887
Entitled Une leçon clinique à la Salpêtrière, periode de contortions ("During the contortions"), it depicts "a woman convulsing and assuming the opisthotonus posture, "the hysteric's classic posture“
Jean-Martin Charcot lecturing at the Salpetriere

25. Treatments Historical treatments Jean-Martin Charcot (1825-1893)
Response to hypnotic suggestion
Emotional response to traumatic past
Sigmund Freud ( )
Unconscious psychological distress, often sexual factors, led to conversion symptoms
Hypnosis and psychoanalysis as treatment modalities to help process distress, facilitate expression/abreaction
First description of functional neurological symptoms was by JMC. “Hystero-epilepsy”: paroxysmal episodes that were similar, but not identical, to epileptic seizures (arc-de-cercle posturing)
Sigmund Freud ( ) Postulated that unconscious psychological distress, often sexual factors, led to hysterical symptoms (Studies of Hysteria)
Hysterical patients suffered from “incompletely abreacted psychical traumas” that were converted into a symptom
Used hypnosis and psychoanalysis as treatment modalities to help process distress, facilitate expression, and bring connection between trauma & symptom to consciousness (theoretically resolves symptom)

26. Treatments First therapeutic intervention in the EMU
Deliver a ‘real’ diagnosis of PNES (not epilepsy)
Multidisciplinary presentation of diagnosis
Facilitate awareness that they do not suffer from epilepsy and that events have psychological underpinnings
Psychotherapy referral to reduce PNES vulnerability
Involvement of neurologist post-diagnosis
Immediate relief and reduction in health care demand

27. Hall-Patch et al: multicenter trial in UK with standardized protocol (leaflets for patient and communication strategy for physician) for new diagnosis presentation with 50 subjects
Conversation covered 14 points addressing domains of patients' illness
After 3 months, 14% of patients were seizure-free and 63% reported a >50% reduction in seizure frequency.
Helps patients if physicians effectively communicate a psychological etiologic model for PNES at time of diagnosis.

28. Treatments Psychotherapy Pharmacotherapy Combination therapy
CBT, Prolonged Exposure Therapy, Mindfulness- Based Psychotherapy
Psychodynamic
Group
Pharmacotherapy
Combination therapy
Other strategies

29. Treatments Cognitive Behavioral Therapy
Validated for many conditions including PNES (Goldstein, LaFrance)
Increase awareness of their dysfunctional thoughts and learn to develop new behavioral responses
May be conceptualized as dissociative responses when confronted with circumstances one tends to avoid
Goldstein et al, Neurology 2010
Emphasizes certain concepts through 12 outpatient sessions: (1) engagement in treatment; (2) reinforcement of independence; (3) distraction, relaxation, and refocusing techniques at the earliest signs of an event; (4) graded exposure to avoided situations; (5) cognitive restructuring; and (6) relapse prevention.
Both active and control groups received “standard medical care” (SMC): up to seven neuropsychiatric appointments that focused on psychoeducation, support measures, & AED withdrawal.
Active group received 12 sessions of CBT by CBT-trained nurse therapist
Baseline event frequency similar in 2 groups (CBT + SMC, n = 33, 12 events a month; SMC, n =31, 8 events a month)
CBT group had significantly lower frequency of events after 12 sessions (2 events/month vs 6.75 events/month for SMC group) with large between-group effect size (0.75).
At 6 month followup, CBT group had 1.5 events per month vs 5 for SMC group with medium between-group effect size (0.42) but no longer statistically significant (p = 0.08)
CBT group tended to be more likely to have experienced 3 months of seizure freedom
Both groups improved in some health service use measures and on the Work and Social Adjustment Scale.
Confounder: greater therapist contact in CBT group may help explain loss of effects over time
CBT open-label, uncontrolled trial (LaFrance et al, Epilepsy Behav, 2009)
17 of 20 subjects completed 12-week outpatient CBT protocol with key points including mood-cognition-environment connections; identification of moods, situations, and thoughts; relaxation techniques; healthy communication; and examination of internal and external triggers.
Mean event frequency decreased significantly from week 1 (17.2 per week) through end of treatment (7.1 per week) with p=
11/17 subjects reported no events in final week of CBT
Mean scores on scales of depression, anxiety, somatic symptoms, QOL, and psychosocial functioning showed improvement from baseline to end of treatment
Interpretation limited as no follow-up after 12 weeks

30. Treatments Cognitive Behavioral Therapy
CODES - COgnitive behavioural therapy vs standardised medical care for adults with Dissociative non-Epileptic Seizures
UK-based multicenter, randomized-controlled trial that evaluates the clinical and cost-effectiveness of 12 sessions of specifically tailored CBT vs standard medical care for patients with PNES
368 subjects randomized across 27 sitesz
Goldstein et al, Neurology 2010
Emphasizes certain concepts through 12 outpatient sessions: (1) engagement in treatment; (2) reinforcement of independence; (3) distraction, relaxation, and refocusing techniques at the earliest signs of an event; (4) graded exposure to avoided situations; (5) cognitive restructuring; and (6) relapse prevention.
Both active and control groups received “standard medical care” (SMC): up to seven neuropsychiatric appointments that focused on psychoeducation, support measures, & AED withdrawal.
Active group received 12 sessions of CBT by CBT-trained nurse therapist
Baseline event frequency similar in 2 groups (CBT + SMC, n = 33, 12 events a month; SMC, n =31, 8 events a month)
CBT group had significantly lower frequency of events after 12 sessions (2 events/month vs 6.75 events/month for SMC group) with large between-group effect size (0.75).
At 6 month followup, CBT group had 1.5 events per month vs 5 for SMC group with medium between-group effect size (0.42) but no longer statistically significant (p = 0.08)
CBT group tended to be more likely to have experienced 3 months of seizure freedom
Both groups improved in some health service use measures and on the Work and Social Adjustment Scale.
Confounder: greater therapist contact in CBT group may help explain loss of effects over time
CBT open-label, uncontrolled trial (LaFrance et al, Epilepsy Behav, 2009)
17 of 20 subjects completed 12-week outpatient CBT protocol with key points including mood-cognition-environment connections; identification of moods, situations, and thoughts; relaxation techniques; healthy communication; and examination of internal and external triggers.
Mean event frequency decreased significantly from week 1 (17.2 per week) through end of treatment (7.1 per week) with p=
11/17 subjects reported no events in final week of CBT
Mean scores on scales of depression, anxiety, somatic symptoms, QOL, and psychosocial functioning showed improvement from baseline to end of treatment
Interpretation limited as no follow-up after 12 weeks

31. Treatments Mindfulness Based Psychotherapy
Mindfulness defined as, “paying attention in a particular way: on purpose, in the present moment and non- judgmentally.”
Lends itself to PNES as it focuses on one’s difficulty in recognizing, accepting and/or managing their emotions
Baslet et al, 2019
12-session course of MBT for PNES led to improvement in event frequency, intensity, and quality of life.
PNES frequency decreased by 0.12 events/ week for every successive session

32. Treatments Psychopharmacological interventions
No specific treatment for PNES
Target serotonergic deficits associated with symptoms like impulsivity, compulsive tendencies, depression, anxiety
LaFrance (Neurology, 2010) – use of sertraline showed 45% decrease in event frequency when compared to control
Pintor et al: use of venlafaxine over 5 months showed 50% decrease in seizures in 15 of 19 patients and 50% improvement in HAM-D scores in 11 of 19 patients
MINI, SCID for dissociative disorders at onset
PRIMARY OUTCOES: BDI, symptom checklist 90 (SCL 90), seizure diary

33. Treatments Combination treatment
NES Treatment Trial at 3 centers (LaFrance et al. JAMA Psychiatry; 2014) over 16 weeks
4 arms: sertraline only, CBT-informed psychotherapy (CBT-ip) only, CBT-ip + sertraline, standard medical care
2 psychotherapy arms exhibited a reduction in seizures (51% in CBT-ip arm, 59% in CBT-ip + sertraline arm) and improvements in depression, anxiety, QOL, global functioning.
Other arms did not show significant reduction in seizures
Findings supported the use of a manualized psychotherapy and training of clinicians in combination treatment.
MINI, SCID for dissociative disorders at onset
PRIMARY OUTCOES: BDI, symptom checklist 90 (SCL 90), seizure diary

34. Treatments Other interventions Hypnosis Biofeedback
Eye movement desensitization and reprocessing (EMDR)
EMDR
effective in PTSD to help process trauma memories while integreating new positive information; hope is to get rid of associated arousal (emotional & cognitive neuroentrainment)
Client will attend to emotionally disturbing material in brief, sequential dosess while focusing on external stimulus eg. Therapist directe lateral eye movements but can also do hand tapping
Smooth pursuit as in REM activates hemispheres, downregulares limbic region and integration of dysfunctional info
Mindfulness: targets subjects’ difficulty in recognizing, accepting and/or managing their emotions

35. Long-term prognosis Knowledge of diagnosis alone is insufficient
Resurgence of PNES and high healthcare utilization without ongoing care though access can be difficult
Positive prognostic factors: adherence with psychotherapy, briefer duration of symptoms, comorbid epilepsy, younger age
40% of newly diagnosed adults became seizure-free within 5 years after diagnosis.
Quality of Life (tends to be even worse than in patients diagnosed with medically refractory epilepsy due to ongoing events, psychological factors, social factors including negative perceptions by medical staff & caretakers/loved ones)
Safety issues (impact on driving and activity)
Practical issues (work/school, relationship)
Potentially limited treatment options and resources
EMDR
effective in PTSD to help process trauma memories while integreating new positive information; hope is to get rid of associated arousal (emotional & cognitive neuroentrainment)
Client will attend to emotionally disturbing material in brief, sequential dosess while focusing on external stimulus eg. Therapist directe lateral eye movements but can also do hand tapping
Smooth pursuit as in REM activates hemispheres, downregulares limbic region and integration of dysfunctional info
Mindfulness: targets subjects’ difficulty in recognizing, accepting and/or managing their emotions