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Deepti Anbarasan, MD Deepti Anbarasan, MD

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Deepti Anbarasan MD NYU School of Medicine NYC Neuropsychiatry Private Practice 101919 The Diagnosis of Psychogenic Nonepileptic Seizures from the Neurological amp Psychiatric Perspectives Psychogenic ID: 769909

diagnosis pnes seizures treatments pnes diagnosis treatments seizures symptoms patients psychotherapy medical cbt 2015 eeg epileptic seizure treatment epilepsy

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Deepti Anbarasan, MDNYU School of MedicineNYC Neuropsychiatry, Private Practice10/19/19 The Diagnosis of Psychogenic Nonepileptic Seizures from the Neurological & Psychiatric Perspectives

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.

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

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

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

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

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

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.

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

Etiology of PNES

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). M Arthuis et al. J Neurol Neurosurg Psychiatry 2015;86:1106-1112 ©2015 by BMJ Publishing Group Ltd

Hypometabolism in the bilateral anterior cingulate cortex in patients with psychogenic non-epileptic seizures, in comparison to healthy participants (p-voxel <0.001). M Arthuis et al. J Neurol Neurosurg Psychiatry 2015;86:1106-1112 ©2015 by BMJ Publishing Group Ltd

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;86:1106-1112 ©2015 by BMJ Publishing Group Ltd

Epidemiology of PNES Associated with unemployment, anxiety/depression, and medically unexplained symptoms Coincidence of PNES with ES of 10 to 25%. Accounts for 20 - 50% of discharge diagnoses from inpatient epilepsy monitoring units

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.

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

Diagnosis ILAE Diagnostic certainty Semiology suggestive of PNES PossiblePatient or witness reportProbableVideo recording or witness by clinicianClinically 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 PNES Diagnosis: History, clinical assessment, VEEG

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

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

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 A ttentional and executive functioning deficits Verbal memory, reduced verbal fluency  No group differences on tests for volitional manipulation of symptoms for secondary gain

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

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

Treatments Historical treatments Jean-Martin Charcot (1825-1893) Response to hypnotic suggestion Emotional response to traumatic past Sigmund Freud (1856-1939) Unconscious psychological distress, often sexual factors, led to conversion symptoms Hypnosis and psychoanalysis as treatment modalities to help process distress, facilitate expression/abreaction

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

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

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

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

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

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

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.

Treatments Other interventions Hypnosis Biofeedback Eye movement desensitization and reprocessing (EMDR)

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.