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New Anti-Seizure Medications

Elia M Pestana Knight, MD Cleveland Clinic Epilepsy Center

Nothing to disclose

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Topics for this lecture  Antiepileptic Drugs

  What are antiepileptic drugs?   Historical development of the drugs   How doctors select the drugs to treat the

seizures?   Common side effect   Drug interactions

 A case for the need of Epilepsy and Psychiatry team interaction

Antiepileptic Drugs

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What are antiepileptic drugs?

 Antiepileptic drugs (AEDs)

 Anticonvulsant medications

 Antiseizure medications

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Antiseizure medications  Drugs that decrease the frequency and/or

severity of seizures in people with epilepsy

 Treat the symptom of seizures, not the underlying epileptic condition

 They don’t change the course of the disease

Antiepileptic drugs   Drugs that prevent the development of recurrent

seizures in people at risk

  Drugs that reduce seizure frequency and severity outlasting the treatment period   Example: after head trauma, stroke, brain tumors, etc.

  Animal studies suggest that Levetiracetam and Ethosuximide are potential antiepileptic drugs BUT there are no studies in humans to support this

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Use of antiseizure medications  Epilepsy  Pain treatment

  Neuralgias, neuropathic pain, etc.  Migraine prophylaxis  Treatment of bipolar disorder, mood disorder

and anxiety

Historical development of the drugs

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History of AEDs in the U.S.   1857 – Bromides

  1882 – Paraldehyde (not longer in use in USA)

  1912 – Phenobarbital (PB)

  1937 – Phenytoin (PHT)

  1944 – Trimethodione

  1953 – Acetazolamide

  1954 - Primidone

  1960 – Ethosuximide

  1963 - Diazepam

  1974 – Carbamazepine (CBZ)

  1972 – Clorazepate and Lorazepam

  1975 – Clonazepam (CZP)

  1978 – Valproate (VPA)

New AEDs in the U.S.   1993 – Felbamate (FBM), gabapentin (GBP)

  1995 – Lamotrigine (LTG)

  1996 – Fosphenytoin

  1997 – Topiramate (TPM), tiagabine (TGB)

  1999 – Levetiracetam (LEV)

  2000 – Oxcarbazepine (OXCBZ), zonisamide (ZNS)

  2005 - Pregabalin (PGB)

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Newer Drugs  2008 – Lacosamide (Vimpat)  2008 – Rufinamide (Banzel)  2009 – Vigabatrin (Sabril)  2011 – Ezogabine (Potiga) and Clobazam

(Onfi)  2012 – Perampanel (Fycompa)  When? – CBD oil – IF …..

No FDA approved AEDs  Bromides (1857)  Sulthiame  Stiripentol (2001)

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Other treatments, diet and devices  Sex hormones: Progesterone  Diets: Ketogenic diet, Low glycemic diet,

modified Atkins diet  Devices: Vagus Nerve Stimulator (VNS) and

Neuropace  Epilepsy Surgery

How doctors select the drugs to treat the seizures?

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Selecting the AEDs   Seizure types or syndrome   Rational polytherapy   Age of the patient (oral suspension, chewable,

sprinkles for children)   Dosing schedule   Comorbidities and other medical conditions   Potential side effects and toxicity   Interaction with other drugs   Cost-effectiveness

Goals of treatment  Reduced number of seizures  Minimal adverse events or side effects  Best quality of life possible

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Common side effects

Adverse Effects Acute dose-related: reversible

Idiosyncratic   Uncommon - rare   Potentially serious or life threatening

Chronic: reversibility and seriousness vary

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Acute - Dose-Related Adverse Effects of AEDs

Neurologic/psychiatric: most common •  Sedation, fatigue -  All AEDs, except unusual with LTG and FBM -  More pronounced with traditional AED

•  Unsteadiness, poor coordination, dizziness -  Mainly traditional AEDs -  May be sign of toxicity with many AEDs

•  Tremor – valproate •  Depression ????

Acute, Dose-Related Adverse Effects of AEDs (cont.)

•  Parenthesis (topiramate, zonisamide)

•  Diplopia, blurred vision, visual distortion (carbamazepine, lamotrigine)

•  Mental/motor slowing or impairment (topiramate at higher doses)

•  Mood or behavioral changes (levetiracetam)

•  Changes in libido or sexual function (carbamazepine, phenytoin, phenobarbital)

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Acute, Dose-Related Adverse Effects of AEDs (cont.)

Gastrointestinal (nausea, heartburn) Mild to moderate laboratory changes

•  Hyponatremia: carbamazepine, oxcarbazepine •  Increases in ALT or AST: valproate •  Leukopenia: •  Thrombocytopenia: valproate

P-Slide 23

Acute, Dose-Related Adverse Effects of AEDs (cont.)

Weight gain/appetite changes   Valproic acid   Gabapentin   Pregabalin

Weight loss   Topiramate   Zonisamide   Felbamate

P-Slide 24

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Idiosyncratic Adverse Effects of AEDs

Toxic Epidermal necrolysis Stevens-Johnson syndrome

  More common in lamotrigine, patients receiving valproate and/or aggressively titrated.

Signs of potential Stevens-Johnson syndrome   Hepatic damage   Early symptoms: abdominal pain, vomiting, jaundice   Laboratory monitoring probably not helpful in early detection   Patient education   Fever and mucus membrane involvement

HLA-B 1502 and AED induced rash  Racial groups: Han Chinese and other South

East Asian groups  Drugs: Carbamazepine, Oxcarbazepine,

Phenytoin, Fosphenytoin

 US FDA recommendations:   Genotypic all Asian descend patients before

therapy   (Ferrell and McLeod. Pharmacogenomics 2008)

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AED Hypersensitivity Syndrome

Characterized by rash, systemic involvement hydrolase Cross-reactivity

  Phenytoin   Carbamazepine   Phenobarbital   Oxcarbazepine

Relative cross reactivity - lamotrigine

Idiosyncratic Adverse Effects of AEDs

Hematologic damage  Marrow aplasia, agranulocytosis, aplastic anemia  Early symptoms: abnormal bleeding, acute onset of fever,

symptoms of anemia  Laboratory monitoring probably not helpful in early

detection  Felbamate aplastic anemia approx. 1:5,000 treated

patients  Patient education

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Other idiosyncratic reactions  Serum sickness  Pancreatitis

Long-Term Adverse Effects of AEDs Endocrine/Metabolic Effects

•  Osteomalacia, osteoporosis •  Carbamazepine •  Phenobarbital •  Phenytoin •  Oxcarbazepine •  Topiramate •  Valproate •  Zonisamide

•  Folate (anemia, teratogenesis) •  Phenobarbital •  Phenytoin •  Carbamazepine •  Valproate •  Lamotrigine •  Topiramate

•  Altered connective tissue metabolism or growth (facial coarsening, hirsutism, gingival hyperplasia or contractures) •  Phenytoin •  Phenobarbital

Neurologic •  Neuropathy •  Cerebellar syndrome - phenytoin

Sexual Dysfunction - 30-60% •  Phenytoin •  Carbamazepine •  Phenobarbital •  Primidone

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Drug interactions

Pharmacokinetic Interactions

Be aware that drug interactions may occur when there is the:

  Addition of a new medication when an inducer/inhibitor is present.

  Addition of inducer/inhibitor to an existing medication regimen.

  Removal of an inducer/inhibitor from chronic medication regimen.

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Hepatic Drug Metabolizing Enzymes and Specific AED Interactions

Phenytoin: CYP2C9/CYP2C19   Inhibitors: valproate, ticlopidine, fluoxetine, topiramate,

fluconazole

Carbamazepine: CYP3A4/CYP2C8/CYP1A2   Inhibitors: ketoconazole, fluconazole, erythromycin,

diltiazem Lamotrigine: UGT 1A4

  Inhibitor: valproate   Important note about oral contraceptives (OCPs):

  OCP efficacy is decreased by inducers,   including: phenytoin, phenobarbital, primidone, carbamazepine;

and higher doses of topiramate and oxcarbazepine   OCPs and pregnancy significantly decrease serum levels of

lamotrigine.

Potent inducers   Carbamazepine, Phenobarbital, Phenytoin

  Effect of induction is seen within the first 3 weeks of treatment

  Caution when prescribing Bupropion, Quetiapine, etc

  Definitively have a significant effect over the metabolism of   Sex hormones   Vitamin D   Thyroid hormones   Lipid metabolism   Folic acid

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Mild inducers  Clobazam, eslicarbazepine, felbamate,

lamotrigine, oxcarbazepine, rufinamide, topiramate, vigabatrin, and vaproic acid

 Can be inducers at higher doses  Sometime have combined inhibitor effects   It can take months before the maximum effect

is seen  Effect on systemic metabolism is present at a

lesser degree

AEDs and Drug Interactions Although many AEDs can cause pharmacokinetic

interactions, several agents appear to be less problematic.

AEDs that do not appear to be either inducers or inhibitors of the CYP system include:

Gabapentin Lamotrigine (low dose) Pregabalin Tiagabine Levetiracetam Zonisamide

P-Slide 36

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AEDs and Foods  Grapefruit juice

A case for the need of Epilepsy and Psychiatry team interaction

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Case 1. Marcella  15 years old

  left handed female

  refractory right parieto-occipital epilepsy status post partial right occipital cortical resection at age 13 years

 seizure-free for a month

 Seizures recurred

Past Antiepileptic Medications

 Carbamazepine, Lamotrigine, Zonisamide

Current Antiepileptic Medications •  Keppra 2,000 mg bid •  Trileptal 1,200 mg bid •  Other Meds: Prozac, Folic acid,

multivitamin, Vitamin D

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Seizure onset

T8P8

P8O2

Fp1F3

F3C3

C3P3

P3O1

Fp2F4

F4C4

C4P4

P4O2

Ictal onset : P8, O2

Pre-op MRI

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Pre-op PET

Pre-op Neuropsychological Evaluation

 Report :   Full scale IQ=77(6th%-borderline)

  Verbal scale=78(7th%-borderline)   Performance scale=81(10th%-borderline)

  Visual immediate memory=109(73rd%-high average)   Visual delayed memory=103(58th%average to high

average)   Verbal immediate memory=69(2nd%-low average to poor)   Verbal delayed memory=72(3rd%-low average to poor)

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Her Medical Comorbidities  Morbid Obesity

  Weight = 145 kg = 319 lbs

 Mild to Moderate Asthma

 Obstructive Sleep Apnea

Her Neuropsychiatric Comorbidities

  Depression   treated with Prozac

10mg   suicidal ideation

  Anxiety   not treated

  Migraine without aura   chronic daily

headaches

 Learning disability   in need of IEP   home schooled

  Epilepsy stigma   bullying at school   poor peer

acceptance

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Anesthesiologist

Sleep Medicine

Pulmonologist

Endocrinologist

Neurosurgeon

Epileptologist

Psychiatrist

Pediatrician

Child and Family

The Knowledge Program  Developed at the Cleveland Clinic

 Screening tool for neuropsychiatry comorbidities

 Katzan I et al. 2011

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Take home points  Antiseizure medications are prescribed taking

into account a number of factors  Keep in mind drug drug interaction when

prescribing antiseizure medications  A multidisciplinary team, that includes a

Psychiatrist, is a very important part of the care for patients with epilepsy

QUESTIONS

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Jana E. Jones, PhD Associate Professor

Department of Neurology University of Wisconsin

School of Medicine & Public Health May 20, 2015

Anxiety Disorders in Epilepsy

Outline 1. Anxiety & Adults with Epilepsy 2. Anxiety & Children with Epilepsy 3. Anxiety & Quality of Life 3. Treatment Options 4. Conclusions

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•  15%  to  25%  Community  prevalence.  

•  16%  to  25%  Hospital  prevalence.  

•  11%  to  32%  prevalence  among  surgery  candidates.

Vazquez & Devinsky, 2003

DSM/ICD  Based  Diagnoses  

Victoroff  (1994)        32%  Manachanda  et  al.  (1996)      11%  Perini    et  al.  (1996)        16%  Altschuler  et  al.  (1999)          5%  Glosser  et  al.  (2000)        22%  Swinkles  et  al.  (2001)        25%  Jones  et  al.  (2007)          35%  Tellez-­‐Zenteno  et  al.  (2007)      22%  Brandt  et  al.  (2010)        20%  Kanner  et  al.  (2010)        15%  

Mean = 20% Median = 21%

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• A large number of participants have more than one diagnosis (n=59). (Jones et al., 2005)

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Anxiety  in  Pediatric  Epilepsy  

Observational Studies

Authors Measure Outcome in epilepsy __________________________________________________________

Ettinger et al. (1998) RCMAS 16% elevated anxiety

Williams et al. (2003) RCMAS 23% elevated anxiety

Baki et al. (2004) STAI 49% mild to mod. Anxiety

Vega et al. (2011) BASC 30% elevated anxiety

__________________________________________________________

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Controlled Studies

Authors Measure Outcome _____________________________________________________

Oguz et al. (2002) STAI High state & trait anxiety

Baker et al. (2005) SADS/LOI High social anxiety & obsessive

symptoms Loney et al. (2008) RCMAS Elevated anxiety _____________________________________________________

DSM  based  studies                                                    Anxiety  Disorders      

Alwash  et  al.  (2000)        48.5%  

OM  et  al.  (2001)        13.0%  

Adewuya  &  Ola  (2005)      31.4%  

Caplan  et  al.  (2005)        36.0%    

Jones  et  al.  (2007)        35.8%  

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New Onset Sample •  Children  with  new-­‐onset  epilepsy  (n  =  180)  and  healthy  first-­‐degree  cousin  controls  (n  =  107).  

•  Study  parVcipants  were  recruited  from  pediatric  neurology  clinics  at  two  large  Midwestern  medical  centers.  

•  Children  with  epilepsy  were  included:        (1)  diagnosis  of  epilepsy  within  the  past  12  months        (2)  chronological  age  between  8–18  years        (3)  no  other  developmental  disabiliVes  (e.g.  auVsm,  

 intellectual  disability)      (4)  no  other  neurological  disorder  and  normal  clinical        

 MRI.  •  Children  and  parents  parVcipated  in  a  structured  psychiatric  interview  (K-­‐SADS)  at  baseline.    

Prevalence  of  Current  Anxiety  Disorders  at  Baseline Epilepsy  (n=180)

Control  (n=107)

Any  Axis  I  Disorder 113  (62.8%) 28  (26.2%) Any  Anxiety  Disorder  70  (38.9%) 19  (17.8%) Specific  Phobia      36  (20.0%) 11  (10.3%) Social  Phobia     16  (8.9%) 1  (1.0%) SeparaTon  Anxiety     13  (7.2%) 0 Generalized  Anxiety  Disorder     15  (8.3%) 5  (4.7%) Anxiety  NOS     15  (8.3%) 6  (5.6%) Number  of  Anxiety  Disorders Single  Anxiety  Disorder 48  (68.6%) 15  (78.9%) Two  or  More  Anxiety  Disorders 22  (31.4%)  4  (21.1%)

1  No  cases  of  Agoraphobia  and  Panic  Disorders

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0  

2  

4  

6  

8  

10  

12  

14  

16  

18  

20  

22  

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Specific  Phobia   Social  Phobia   SeparaVon  Anxiety  Prevalence  (percent)   Median  Age  of  Onset  (years)  

Common anxiety disorders in childhood: Prevalence and age of onset (Kessler et al., 2012)

New  Onset  Epilepsy  with  &  without  Anxiety  

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Jones et al., 2015

Jones et al., 2015

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Jones et al., 2015

Jones et al., 2015

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MRI Findings  •  Anxiety is a common psychiatric

comorbidity in children with recent-onset epilepsy.

•  Potential neuroanatomical substrate consisting of volumetric enlargement of the amygdala. Daley et al. (2008) reported a similar finding.

•  Thinner cortex in orbital and other regions of prefrontal cortex.

MRI findings

•  There are abnormalities in brain structures that are involved in the networks found in individuals with anxiety disorders in the general population.

•  These anatomic findings: – are evident early in the course of epilepsy. – are not related to chronicity of seizures. – are linked to a family history of anxiety and

depressive disorders.

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2 Year Follow-up

•  Children with epilepsy returned for follow-up 2 years after their baseline evaluation.

•  Healthy controls also returned.

•  The KSADS was repeated with child and parent separately.

Jones et al. (2015)

Jones et al., in progress

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In  epilepsy,  suicide  aMempters  had  elevated  anxiety  compared  to  those  with  no  history  of  suicide  aMempts.        

Batzell  &  Dodrill  (1986)  

•  At  Baseline:      –  42%  children  with  epilepsy  and  anxiety  had  suicidal  thoughts.      –  45%  children  with  epilepsy  and  no  anxiety.    

•  At  Follow-­‐up:    –  21%  children  with  epilepsy  and  anxiety  had  suicidal  thoughts.    

–  34%  children  with  epilepsy  and  no  anxiety.    

•  Suicidal  thoughts  are  common  in  children  with  epilepsy  and  anxiety.  

•  Suicidal  thoughts  are  also  quite  common  in  children  with  epilepsy  without  anxiety.    

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Poorer HRQOL is significantly associated with increased symptoms of anxiety.

Proportion of variance in HRQOL accounted for by demographic, clinical epilepsy and anxiety variables.

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Treatment Recommendations

•  No  randomized  controlled  trials  for  the  treatment  of  anxiety  disorders  in  children  or  adults  with  epilepsy,  including  pharmacological  and  nonpharmacological  intervenVons.    

•  Very  lidle  evidence  regarding  specific  pracVce  parameters  for  the  treatment  anxiety  disorders  in  adults  or  children.    

Baseline: KSADS interview Questionnaires

3-month follow up: Booster session Parent Meeting Questionnaires

Level 7: Begin Exposure Tasks

Parent Meeting Questionnaires Level 2:

Physical signs of anxiety

Level 1: CBT & anxiety Parent Meeting

Level 12: Exposure Tasks Parent Meeting Questionnaires

Levels 8-11: Exposure Tasks

Level 3: Relaxation

Parent Meeting

Levels 4-6: Anxious thoughts, coping

thoughts, problem solving, & self-reward

Skill Building Phase

Skill Practice Phase

Camp Cope-A-Lot Intervention Outline (Khanna & Kendall, 2008)

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(Blocher et al., 2013)r

(Jones et al., 2014) al

Piers-Harris-2 at baseline, week 7, 12 and 3 months

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Pharmacological Treatment

•  There are no randomized controlled trials of the use of SSRIs in the treatment of anxiety disorders in adults or children with epilepsy.

•  There is evidence to suggest that seizure frequency is not adversely impacted by the introduction of SSRIs.

•  Anxiety  is  common  in  adults  and  children  with  epilepsy.  

•  There  are  potenTal  neuroanatomical  substrates  idenTfied  in  children  with  epilepsy  similar  to  those  reported  in  the  general  populaTon.    

•  Anxiety  has  a  negaTve  impact  on  overall  QOL.  

•  Anxiety  is  frequently  under  recognized  and  under  treated.    

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•  Only  1/3  of  children  with  epilepsy  and  mental  health  problems  receive  treatment  (OM  et  al.,  2001).  

•  Parents  report  that  emoTonal  and  behavioral  problems  are  very  concerning  to  them  (Wu  et  al.,  2008).  

•  Neurologists  &  pediatricians  who  treat  children  with  epilepsy  feel  there  is  a  resistance  on  the  part  of  mental  health  providers  to  treat  children  with  epilepsy  (Smith  et  al.,  2007).  

Acknowledgements  University  of  Wisconsin      UCLA  Bruce  P.  Hermann,  PhD      Rochelle  Caplan,  MD  Carl  Stafstrom,  MD,  PhD  David  Hsu,  MD,  PhD      Mayo/Nemours  Children’s  Hospital  Fred  Edelman,  MD        Raj  Sheth,  MD  Lucy  Zawadzki,  MD  Chris  Ikonomidou,    MD      Rosalind  Franklin  University  Daren  Jackson,  PhD        Michael  Seidenberg,  PhD    Kevin  Dabbs,  MS            Jacque  Blocher        Funding:  Connie  Sung,  MPh        RO1  NINDS  4435-­‐06-­‐07  Mayu  Fujikawa,  MS        People  Against  Childhood  Epilepsy  Michelle  Szomi        (PACE)  Dace  Almane,  MS        1KL2RR025012-­‐01  Kelly  Darby,  MS  Kate  Young,  MS  

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Gaston  Baslet,  M.D.  Division  of  Neuropsychiatry  Department  of  Psychiatry  

Brigham  and  Women’s  Hospital  Harvard  Medical  School  

  I  have  no  conflicts  of  interest  to  disclose    I  will  be  discussing  off  label  use  of  medications  

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Psychogenic Non Epileptic Seizures are paroxysmal episodes of altered consciousness, movement, sensation or experience resembling epileptic seizures, but not associated with ictal

electrical discharges in the brain or other recognized physiological paroxysms  

 Most  common  condition  misdiagnosed  as  epilepsy.  

  Average  of  7  years  until  correct  diagnosis  is  made.  

  25-­‐33%  of  EMU  admissions  diagnosed  as  PNES.1  

  12%  in  outpatient  Neurology  Clinics.2    Annual  incidence  in  Scotland  is  3-­‐5  per  100,000  but  this  is  an  underestimate.3  

1. Reuber et al, Neurology, 2002; 2. Reuber, Epilepsy and Behavior, 2008; 3. Duncan et al, Epilepsy and Behavior, 2011.  

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Neurologist   Psychiatrist  

Symptom   Presentation   Engagement   Acute  treatment                          Phase  

Long-­‐term  Follow-­‐up  

Baslet et al, Clin EEG Neurosci, 2014

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  A.  One  or  more  symptoms  of  altered  voluntary  motor  or  sensory  function.    B.  Clinical  findings  provide  evidence  of  incompatibility  between  the  

symptom  and  recognized  neurological  or  medical  conditions.    C.  The  symptom  or  deficit  is  not  explained  by  another  medical  or  mental  

disorder.    D.  The  symptom  or  deficit  causes  clinically  significant  distress  or  impairment  

in  social,  occupational,  or  other  important  areas  of  functioning  or  warrants  medical  evaluation  

  Specifier:  with  weakness  or  paralysis,  with  abnormal  movement  (PMD),  with  swallowing  symptoms,  with  speech  symptom,  with  attacks  or  seizures  (PNES),  with  anesthesia  or  sensory  loss,  with  special  sensory  symptom,  with  mixed  symptom.  

  Specifier:  acute  episode  (<  6  months),  persistent  (>  6  months).    Specifier:  with  psychological  stressor,  without  psychological  stressor.  

American Psychiatric Association, 2013 PNES: Psychogenic Non-Epileptic Seizures; PMD: Psychogenic Movement Disorder.

Levels  of  Diagnostic  Certainty  

History   Witnessed  event   EEG  

Possible   +   By  witness  or  self-­‐report/  description  

No  epileptiform  activity  in  routine  or  sleep  deprived  interictal  EEG  

Probable   +   By  clinician  who  reviewed  video  recording  in  person,  showing  semiology  typical  of  PNES  

No  epileptiform  activity  in  routine  or  sleep  deprived  interictal  EEG  

Clinically  established  

+   By  clinician  experienced  in  diagnosis  of  sz  disorders  (on  video  or  in  person)  showing  semiology  typical  of  PNES  

No  epileptiform  activity  in  routine  or  ambulatory  EEG  during  a  typical  ictus/  event  in  which  the  semiology  would  make  ictal  epileptiform  EEG  expectable  during  equivalent  epileptic  sz  

Documented   +   By  clinician  experienced  in  diagnosis  of  sz  disorders,  showing  semiology  typical  of  PNES,  on  video  EEG  

No  epileptiform  activity  immediately  before,  during  or  after  ictus  captured  on  ictal  video  EEG  with  typical  PNES  semiology  

La  France  et  al,  Epilepsia,  2013  

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Signs  that  favor  PNES   Evidence  from  primary  studies  

Sensitivity  (%)  for  PNES   Specificity  (%)  for  ES  

Long  duration  Fluctuating  course  

Asynchronous  movements  

Pelvic  thrusting  

Side-­‐to-­‐side  head  or  body  movements  Closed  eyes  

Ictal  crying  

Memory  recall  

Good  Good    

Good  (FLS  excluded)  

Good  (FLS  excluded)  

Good  (convulsive  events  only)  Good  

Good  

Good  

69  (events)  47-­‐88  (patients)  44-­‐96  (events)  9-­‐56  (patients)  1-­‐31  (events)  7.4-­‐44  (patients)  25-­‐63  (events)  15-­‐36  (patients)  34-­‐88  (events)  52-­‐96  (patients)  13-­‐14  (events)  3.7-­‐37  (patients)  63  (events)  77-­‐88  (patients)  

96  96-­‐100  93-­‐96  93-­‐100  96-­‐100  92-­‐100  96-­‐100  92-­‐100  74-­‐100  97  100  100  96  90  

Signs  that  favor  ES   Evidence  from  primary  studies  

Sensitivity  for  ES   Specificity  for  ES  

Occurrence  from  EEG-­‐confirmed  sleep  Post-­‐ictal  confusion  

Stertorous  breathing  

Good  

Good  

Good  (convulsive  events  only)  

31-­‐59  (events)  -­‐  61-­‐100  (events)  67  (patients)  61-­‐91  (events)  

100  -­‐  88  84  100  

Other  signs   Evidence  from  primary  studies  

Gradual  onset  Non-­‐stereotyped  events  Flailing  or  thrashing  movements  Opisthotonus  Tongue  biting  Urinary  incontinence  

Insufficient  Insufficient  Insufficient  Insufficient  Insufficient  Insufficient  

La  France  et  al,  Epilepsia,  2013  

PNES:  psychogenic  non-­‐epileptic  seizures  ES:  epileptic  seizures  

Psychosocial  Factors  Child/Adult  Trauma  Family  Dysfunction  Interpersonal  communication  Adverse  life  events  

Psychiatric  Conditions  Depression,  Anxiety,  PTSD  Somatoform  Disorders  Dissociative  Disorders  Personality  Disorders  Substance  Abuse  Eating  Disorders  

Neurological  Conditions  Epilepsy  Migraine  

Chronic  pain  Head  Trauma  

Neuropsychological  Deficits/  Vulnerability  Traits  

Avoidance  Impulsivity  

Somatic  preoccupation  Alexithymia  

Emotion  regulation  styles  Limited  effort  Suggestibility  ?  

PNES  

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  As  a  psychiatrist,  you  can  establish  the  diagnosis  of  PNES  after  carefully  reviewing  the  exam  and  tests  that  confirm  incompatibility  between  the  symptom  and  the  preserved  physiological  functioning.    

  Always  confer  with  a  neurologist.  

  Early  screening  for  risk  factors  can  help  you  formulate  an  explanatory  model  for  the  patient.  

  There  is  growing  evidence  of  effective  treatments  for  PNES,  mostly  based  on  psychotherapeutic  interventions.    

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Symptom   Presentation   Engagement   Acute  treatment                          Phase  

Long-­‐term  Follow-­‐up  

Baslet  et  al,  Clin  EEG  Neurosci,  2014  

MDD:  Major  Depressive  Disorder;  Kanner  et  al,  Neurology,  1999  

Class I, n = 13 Class II, n = 12 Class III, n = 20

Psychiatric variable n (%) n (%) n (%)

Recurrent MDD 1 (8) 2 (17) 14 (70)

Personality disorder 1 (8) 3 (25) 16 (80)

Chronic abuse 3 (23) 1 (8) 16 (80)

Denial of psychosocial problems

0 8 (75) 1 (5)

What  happens  after    an  acute  intervention  in  PNES?  

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  Patient  filled  postal  questionnaire  (n=164)    4.1  years  post-­‐PNES  diagnosis    71%  of  patients  continue  to  be  symptomatic.1  

  Complaint  at  doctor’s  visit  over  6  months  (n=167)  

  5-­‐10  years  post-­‐PNES  diagnosis    26%  of  patients  continue  to  complain  of  seizures.  

  Significant  reduction  in  ED  visits  and  AED  prescription,  but  not  in  employment  rates.2  

1.  Reuber  et  al,  Annals  of  Neurology,  2003  2.  Duncan  et  al,  JNNP,  2014        

  There  is  a  variety  of  outcome  patterns  in  PNES  patients.  

  Identifying  subgroups  of  patients  with  different  outcomes  may  help  customize  treatment  protocols  for  subpopulations  and  improve  overall  functional  outcomes.  

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APA 2015

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Falcone et al Psychiatric comorbidities in patients undergoing epilepsy surgery- AES 2009

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EXAMPLE OF SEIZURE DRAWING THAT DEPICTS THE THEME OF HELPLESSNESS OR DEPRESSION

10-year-old boy with complex partial seizures depicts himself inside a coffin, screaming, ‘‘Let me out!’’

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16-year-old boy with left temporal lobe epilepsy and generalized tonic–clonic seizures.

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Make sure that you listen, make sure that you care, make sure you are watching — something’s always there. Adwoa Boakye

Release Emily Good

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QOL

Seizures

Ability to Think And

Remember

Neuro and Physical

Limitations

Inattention and Mood

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