Confirming the diagnosis of epilepsy Disclosures at first - - PowerPoint PPT Presentation

2/16/2018 1

Confirming the diagnosis of epilepsy at first presentation

Jacqueline A French MD Professor of Neurology NYU Langone School of Medicine

• I am President of the Epilepsy Study Consortium. All consulting is done on behalf of the

consortium, and fees are paid to the consortium. The NYU Comprehensive Epilepsy Center receives salary support from the consortium;

• I have acted as a consultant for Acadia, Acorda, Adamas, Alexza, Anavex, Axcella

Health, Biogen, BioPharm Solutions, Cavion, Cerecor, Concert Pharmaceuticals, Covance, CuroNZ, Eisai, Empatica, Engage, Georgia Regents University, Glaxo Smith- Kline, GW Pharma, J&J Pharmaceuticals, Marinus, MonosolRx, Monteris, Nestle-Health Science, Neurelis, Novartis, Otsuka, Ovid, Pfizer, Pfizer-Neusentis, Sage Therapeutics, Shire, SK Life Sciences, Sunovion, Takeda, UCB Inc., Upsher Smith, Ultragenyx, Xenon Pharmaceuticals, Xeris, Zogenix and Zynerba

• I have received grants from Acorda, Alexza, Eisai Medical Research, LCGH, Lundbeck,

Pfizer, SK Life Sciences, Sunovion, Takeda, and UCB, Epilepsy Research Foundation, Epilepsy Study Consortium, Epilepsy Therapy Project, and NINDS

• I am on the editorial board of Lancet Neurology, Neurology Today and Epileptic

disorders.

Disclosures

• Two major recent events in first epilepsy

diagnosis

• ILAE new definition of epilepsy
• AAN guideline on treatment of a single

seizure

Newly diagnosed epilepsy

• The new ILAE “practical” definition of epilepsy is:
• At least two unprovoked (or reflex) seizures occurring >24

h apart;

• One unprovoked (or reflex) seizure and a probability of

further seizures similar to the general recurrence risk (at least 60%) after two unprovoked seizures, occurring over the next 10 years;

• Diagnosis of an epilepsy syndrome.

New diagnosis of Epilepsy

Fisher R et al. LAE official report: a practical clinical definition of epilepsy. Epilepsia. 2014 Apr;55(4):475-82

2/16/2018 2

• The new ILAE “practical” definition of epilepsy is:
• At least two unprovoked (or reflex) seizures occurring >24

h apart;

• One unprovoked (or reflex) seizure and a probability of

further seizures similar to the general recurrence risk (at least 60%) after two unprovoked seizures, occurring over the next 10 years;

• Diagnosis of an epilepsy syndrome.

New diagnosis of Epilepsy

Fisher R et al. LAE official report: a practical clinical definition of epilepsy. Epilepsia. 2014 Apr;55(4):475-82

• Conclusion:
• Adults with an unprovoked first seizure should be informed

that sz recurrence risk is greatest early within the first 2 years (21%–45%) (Level A), and clinical variables associated with increased risk may include:

• a prior brain insult (Level A),
• an epileptiform EEG (Level A),
• An abnormal CT/MRI(Level B)
• a nocturnal seizure (Level B).

AAN Guideline

• Immediate antiepileptic drug (AED) therapy, as compared with

delay of treatment pending a second seizure, is likely to reduce recurrence risk within the first 2 years (Level B)

• Clinicians’ recommendations whether to initiate immediate

AED treatment after a first seizure should be based on individualized assessments that weigh the risk of recurrence against the AEs of AED therapy.

AAN Guideline

2/16/2018 3

• Treatment after a single seizure may be

appropriate

AAN and ILAE conclusion

• At the point of a treatment decision, there may be fewer (or even
• ne) event(s), making diagnosis more difficult. Clinician should

try to nail the diagnosis as early as possible

• Was it a seizure?
• If it was a seizure (or seizures), is it epilepsy?
• There is a major cost to patient and healthcare system of delay
• f diagnosis

The fundamentals of diagnosis

• It has been estimated that 5-10% of outpatients in epilepsy clinics

and 20–40% of the patients admitted for video-EEG monitoring have NES (non-epileptic seizures), in both developed and developing countries

Asadi-Pooya AA, Sperling MR. Epidemiology of psychogenic nonepileptic

• seizures. Epilepsy Behav. 2015;46:60-5

How often is a seizure not a seizure?

GI

CARDIO- VASCULAR

ENDO- CRINE PSYCH META- BOLIC NEURO- LOGIC SLEEP D/O

PSYCHOGENIC PHEOCHROMO CYTOMA HYPOGLYCEMIA SYNCOPE ARRHYTHMIA TIA PAROXYSMAL DYSTONIA MIGRAINE PARASOMNIA

www.epilepsydiagnosis.org/epilepsy-imitators.html#overview

BREATH-HOLDING TICS STEREOTYPIES DYSKINESIA

If it is not a seizure, what is it?

2/16/2018 4 What is it? What is it? What is it?

Reuber et al, NEUROLOGY 2002;58:493–495

Delay to NES diagnosis at different ages

2/16/2018 5

• In actuality, most of the time, particularly early in the course of

diagnosis, events are not frequent enough to capture on video-EEG

• In this case, asking the family to capture on phone video is
• ften useful, but even then, the diagnosis may be difficult
• When even a phone video is not available, a diagnosis must

rest on a precise history.

What if there is no video-EEG?

• 12 y.o presents at the ED with headache, abdominal pain, after

event last evening

• Previous evening, pt was riding in car, felt nauseated, shaky. Mom

reports patients speech was slurred and was having trouble getting words out.; his "eyes looked shifty" and his hands were shaking. He then "passed out" for a few minutes and was very sleepy. They got home and he was able to walk out of the car, speech still seemed slurred, was c/o abdominal pain.

• EEG, MRI, exam normal

Was it a seizure?

• While out to dinner, child felt dizzy. She fell backward. She was stiff, was

shaking, eyes rolled back with her pupils being dilated. Foaming at the mouth was present. Child was rolled onto her left side and EMS was

• called. Post-ictal for 15 min, confused, disoriented.
• Then shortly after while at the ER, child proceeded to the following. Per Dr.

XYZ note (ED physician): "She had right sided facial grimacing her head turned to the right. Her eyes deviated to the right and her head went back and then her right arm started. Then (right arm) extending and having generalized tonic-clonic movements and then the left arm did so and was definitely a progression from a partial onset seizure.

Was it a seizure?

• Pt rehearsing for her school performance and singing. She then went

silent and stopped singing. One minute later she was coming around and was able to answer questions appropriately. She states she remembers singing and then remembers coming to when she was sitting on the floor. No loss of tone, bowel or bladder incontinence.

• Four other episodes- She will suddenly stop her activity and stare

straight ahead. She does not have any abnormal movements with this. She is able to follow instructions to sit down. Episodes will last from 30 seconds to max 1 minute and then resolve. Afterwards, she is confused and will take 5-10 minutes to return to baseline.

Was it a seizure?

2/16/2018 6

• EEG: Left hemispheric slowing and epileptiform activity consistent

with focal left hemisphere cerebral dysfunction.

• MRI bilateral occipital gray matter heterotopia more pronounced
• n the left than on the right.

Was it a seizure?

• 8 Epileptologists, 12 neurologists

and 20 internists watched 150 videos of epileptic seizures, psychogenic non-epileptic seizures, and non-epileptic physiologic events

• Epileptologists performed the

best, and accuracy improved as more events were observed

Even observed seizure semiology may not be diagnostic

Epilepsy Behav. 2014 Dec;41:197-202 Epilepsy Behav. 2014 Dec;41:197-202 Epilepsy Behav. 2014 Dec;41:197-202

Jin et al, Epilepsy Behav 2014 41:197-202

Epilepsy Behav. 2014 Dec;41:197-202

• As evidenced in the examples, presence of certain seizure

characteristics (eg forced head turning,vocalizations, salivation,

• ral automatisms, etc), can increase the diagnostic certainty of a

seizure

• However, families/observers may not describe these features

unless they are asked for them.

• Even physician observers may not describe these if they are not

prompted to

Don’t ask-Won’t tell

• DISCOVER (Diagnostic Interview Conducted Outside Video EEG

Recording)-Structured interview that can be used to ensure important characteristics are queried.

• Has been used for all patients enrolled in HEP
• Both subject and observer (if available) are interviewed
• Allows for more precise diagnosis to confirm epilepsy as well

as seizure type

Structured interview form may help

Friedman et al, Neurology February 12, 2013; 80 (7 Supplement)

2/16/2018 7

• What is the very first thing that happens to you during this seizure type?

_________________________________________________________________________ Describe what happens next and then, in order, the rest of the events that occur with this seizure type : If awareness is lost during this seizure, patient may describe what he/she is told by others.

__________________________________________________________________________________

How long does the seizure last ? _______________________________________

☐ 1-30s ☐ 30s-1min ☐ 1-5min ☐ >5min ☐ variable (write time above) ☐ unknown

When this seizure is at its strongest, can you: Still hear when people are speaking to you?

☐ Always ☐ Sometimes ☐ Never ☐ Not Sure/Unknown

Still understand what is going on and/or what people are saying?

☐ Always ☐ Sometimes ☐ Never ☐ Not Sure/Unknown

Remember what happens during this seizure?

☐ Always ☐ Sometimes ☐ Never ☐ Not Sure/Unknown

With this seizure type, do you ever: bite your tongue?

☐ Always ☐ Sometimes ☐ Never ☐ Not Sure/Unknown

lose bowel control?

☐ Always ☐ Sometimes ☐ Never ☐ Not Sure/Unknown

lose bladder control?

☐ Always ☐ Sometimes ☐ Never ☐ Not Sure/Unknown

DISCOVER form

• Do people observe you doing any of the following during this seizure ?

Altered awareness Notes: ______________________________ Decreased ability to respond Notes: ______________________________ Mouth movement (e.g. lip smacking) Notes: ______________________________ Drooling Notes: ______________________________ Glassy stare Notes: ______________________________ Eyes closed throughout Notes: ______________________________ Purposeless/aimless hand movements Notes: ______________________________ One hand/arm stiff or in an abnormal posture (☐ Right ☐ Left ☐ Either ☐ Not Sure) One side of the body stiff (☐ Right ☐ Left ☐ Either ☐ Not Sure) Both sides of the body stiff Notes: ______________________________ Falling to the ground/losing posture Notes: ______________________________ Talking nonsense Notes: ______________________________ Speaking repetitive phrases Notes: ______________________________ Other noises __________________ None of the above Unknown/not sure

• With this seizure, do people tell you that you stiffen and shake all over?

☐ Yes ☐ Sometimes ☐ Never ☐ Not Sure/Unknown

DISCOVER

• Describe what happens and then, in order, the rest of the events that

happen with this seizure: (Write description verbatim, then check off symptoms in Q3 & 4) ______________________________________DDo you observe any

• f the following during this seizure ?
• Mouth movement (e.g. lip smacking) Notes______________________________
• Drooling

Notes:______________________________

• Glassy stare

Notes:______________________________

• Eyes closed throughout

Notes: ______________________________

• Purposeless/aimless hand movements Notes:______________________________
• One hand/arm stiff or in an abnormal posture (☐ Right ☐ Left ☐ Either ☐ Not Sure)
• One side of the body stiff (☐ Right ☐ Left ☐ Either ☐ Not Sure)
• Both sides of the body stiff

Notes: ______________________________

• Falling to the ground/losing posture

Notes: ______________________________

• Talking nonsense

Notes: ______________________________

• Speaking repetitive phrases

Notes: ______________________________

• Other noises __________________

DISCOVER for observer

• In addition, often a history obtained by

physician will focus on GTCC, and will not capture “the whole story”

Don’t ask-Won’t tell

2/16/2018 8

• Mary L. is 27 years old. While at work without

warning, began making a “moaning sound”. She slipped from the chair, and shook for 1-2

• minutes. She bit her tongue, and afterwards

was very confused, coming to when the ambulance was present.

• She went to a neurologist, and had an EEG

which showed left temporal spikes

• Would you treat?

The saga of Mary L.

• Mary was started on Keppra 500 BID.
• Mary felt she was not “being taken seriously”

and went to a second neurologist. The second neurologist said “I would not have done anything different”

• Mary then came to us at NYU. We asked one

critical question

The saga of Mary L.

• The question: Do you ever have any strange spells that seem

to come out of nowhere, that don’t make sense in context?

• “Why no, other than my “panic attacks”. I often get them in new

situations, but sometimes not.”

• “I used to have them while driving-They feel like a pressure in my

head, then rushing down my body. Sometimes I would find when they were over, both feel were off the pedals”

• Did any one see them? “Yes, once I had one talking to my mom,

at the kitchen table”

• Mom says” She was talking, and suddenly she was talking

nonsense, and she was staring off with a glazed look” it lasted 30 seconds or so. When it was over we didn’t want to embarrass her, so we never mentioned it again”

The saga of Mary L.

• Video-EEG performed-There were 5

electrographic seizures in 48 hours.

Conclusion-Mary L

2/16/2018 9

• Observational study of 500 patients with

newly diagnosed epilepsy, recruited from 35 US and international centers

• Each patient must have diagnosis confirmed
• Either abnormal EEG/MRI and confirmed
• n review by one member of study, or

normal EEG/MRI and confirmed on review by 4 members of adjudication team

• Enrolled within 4 months of diagnosis

Human Epilepsy Project

• 56% of patients presented with “subtle seizures” (seizures

without major vocalization or motor activity)

Median time to diagnosis in patients with SS was 337 days (mean 1593.7 days) compared to 110.5 days (mean 264.5 days) in those with DS (p < 0.0001). 6 Motor vehicle accidents

• ccurred prior to diagnosis in

subjects with subtle seizures

Delay to diagnosis of subtle seizures

• Phenomenology
• EEG
• Imaging/Etiology

What can we do to get a better diagnosis from the beginning?

• Patient report
• Enhanced with structured

interview

• Observer report
• Enhanced with structured

interview

• Video (eg phone)
• Video-EEG

Ways to elicit event phenomenology

2/16/2018 10 How about EEG?

• .8-6.6 % of healthy volunteers
• 0-5.6% of healthy children
• 8.1% of non-epilepsy outpatients
• 10% of community inpatients and outpatients
• 60% of non-epilepsy patients with autism

1.So E. J Clin Neurophysiol 2010;27: 229–238

• 2. Chez et al, Epilepsy and Behavior, 2006 8;1:267–271

EEG can be abnormal in patients without epilepsy1,2

• Study of 127 patients who were

diagnosed with PNES. Of these, 41 (32%) had a history of “epileptiform” EEG.

• They obtained 15 of the

records-All showed normal EEG that had been over- interpreted

Benbadis and Tatum, Journal of Clin Neurophysiol (2003 ;20(1):42-4)

And Normal EEG can be read as abnormal

• One piece of diagnostic information cannot

be used in isolation

• Tests are flawed, and there is a rate of false

positives

• The likelihood that a positive test is a true

positive is dependent on the a priori likelihood that the person has the disease

Bayesian Logic

2/16/2018 11

• Aminoff et al-4% of 948 patients without epilepsy had

epileptiform discharges (spikes or sharp waves) on 30 minute EEG

• 52% of 764 patients with epilepsy had epileptiform

discharge

• If I have NO SYMPTOMS and an abnormal EEG,

there is a high likelihood (90%) that the test is a false positive

• If I have episodic events of motor arrest, and an MRI

with a cortical dysplasia, there is a high likelihood (90%) the test is a true positive.

• If the events are somewhere in the middle, there is a

70-80%

Inter-ictal EEG and probability of epilepsy

0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1

Adjusted probability Prior probability

PRIOR PROBABILITY BASED ON CLINICAL HISTORY

ADJUSTED PROBABILITY BASED ON EEG

Goodin and Aminoff, Lancet. 1984 Apr 14;1(8381):837-9

• After review by the diagnostic core, 10% of

patients considered to have definite epilepsy by the referring epileptologists were rejected due to uncertainty about diagnosis

• These patients might be considered to have

“probable” or “possible” epilepsy.

Patients rejected in HEP study

• Minimum diagnostic criteria exist for many neurologic illnesses
• Multiple sclerosis
• Alzheimer’s disease
• Parkinson’s disease
• Non-epileptic seizures
• Yet there are no diagnostic criteria for epilepsy!-Should there be?

Minimum Diagnostic criteria for an epilepsy diagnosis?

2/16/2018 12

ILAE Proposed Diagnostic Levels-Non-Epileptic Seizure

La France WC et al Epilepsia. 2013;54(11):2005-18

• Diagnostic criteria for epilepsy would have to

consider the following elements

• Etiology
• MRI
• EEG
• Presence of certain phenomenologic

characteristics could increase diagnostic certainty

What criteria look like for epilepsy?

• Recurrent episodes of abnormal motor or sensory function,

awareness or behavior, with duration from 1 second to 5 minutes.

• Events should be relatively stereotyped (although multiple types
• f events with some stereotypy of at least the majority is

acceptable).

• Description of the abnormal behavior should be available either

from the patient, if cognitively competent during the episode, or from another reliable observer.

• There should be absence of evidence for a competing

explanation for the events (e.g., syncope, TIA, sleep disorder, confusional migraine, movement disorder, delirium, psychogenic episodes).

Diagnostic criteria-Example

• It is important to try to make a firm diagnosis early in

the course of epilepsy, using phenomenology, coupled with EEG and imaging

• A good history (from patient and observer) is very

important.

• Tests should be interpreted based on epilepsy

probability

• Many patients present with subtle seizures, and

patients with new GTCC should be asked about them

Conclusion