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Imitators of Epilepsy December 2, 2011
Ronald P. Lesser, M.D.
Professor of Neurology and Neurosurgery
Department of Neurology
The Johns Hopkins Medical Institutions
Baltimore, MD
American Epilepsy Society | Annual Meeting
Disclosure • I in the past, but no longer, have been on Speaker's Bureaus and
have given lectures supported by, or have been a consultant for the following companies, all of which have had or are developing products that could be used to treat epilepsy: Abbott Laboratories, Bertek Pharmaceuticals, Burroughs Wellcome (now GlaxoSmithKline), Cyberonics, Medtronic, Novartis, Ortho-McNeil, Wallace Laboratories, Warner-Lambert/Parke-Davis, Wyeth. I or my spouse have stock in the following companies, each of which has at least one product that can be used to treat epilepsy: Abbott, Johnson & Johnson, Pfizer. I have been a site investigator for studies funded by Lorex Pharmaceuticals, Wallace Laboratories, Warner-Lambert Company and have received funding from Medtronic; none of these have occurred for the past several years. For several years, until 2004/6, I organized a periodic dinner meeting for the Maryland Epilepsy Group. These meetings included meals purchased by Parke-Davis/Pfizer or UCB. They primarily dealt with surgical or imaging topics, but one dealt with mechanisms underlying the effects of anticonvulsants.
American Epilepsy Society | Annual Meeting
Disclosure • Since 1999, I have been, or am, a sub-investigator for a number of
drug studies for which I receive no compensation. These have been funded by the following: Eisei (rufinamide, perampanel), Johnson & Johnson (JNJ-26489112), National Institutes of Health (progesterone), Novartis (oxcarbazepine, rufinamide, BGG492), Parke-Davis (pregabalin), Schwarz Biosciences (lacosamide), Sepracor (eslicarbazepine), SK Bio-Pharmaceuticals (YKP3089), UCB (brivaracetam, lacosamide, levetiracetam), Neuronex (intranasal diazepam), Upsher-Smith (intranasal midazolam). I have received funding from and I am entitled to sales royalty from Bio-logic Systems, Inc (now owned by Natus Medical Incorporated), which has developed products related to my research involving a computerized method for analyzing physiologic data. I also receive royalties from Persyst Development Corporation for sales of software I developed for reporting results of EEG evaluations. The terms of my arrangement with Bio-logic Systems and with Persyst have been reviewed and approved by the Johns Hopkins University in accordance with its conflict of interest policies.
American Epilepsy Society | Annual Meeting
Learning Objectives
• understand characteristics of the most common imitator of epilepsy
• consider etiologies
• consider other disorders that can be confused with epilepsy
• consider treatment
American Epilepsy Society | Annual Meeting
a physical way of expressing
an emotional conflict or concern
The patient may or may not
be aware of the conflict or concern
It may or not be possible
to determine the conflict or concern
Psychogenic Non-Epileptic
Seizures (PNES)
• Iceland
35/100,000 - epilepsy1
1.4/100,000 - PNES1
• United States
29-53/100,000 - epilepsy2
1-2/100,000 - PNES3
1 Sigurdardottir and Olafsson, 1998
2 Hauser and Hesdorffer 1990
3 estimate
Incidence of PNES
Prevalence of PNES
• point prevalence of epilepsy = 0.6%
• 1/3 of all seizures are intractable
• patients with these often go to epilepsy centers
• PNES: 10-20% of patients at epilepsy centers
• therefore 50,000-100,000 patients in U.S.?
– “sampling error”
– delayed diagnosis
-Howell et al. 1989, Hauser and Hesdorffer 1990, Gumnit, 1993
Prevalence of PNES
- Reuber et al., 2002
Age at onset (yrs)
0 10 20 30 40 50 60 70 70 80 0
10
20
30
40
50
60
diagnostic
delay
(yrs)
• 4-77 years old
• 734 women
250 men
- Lesser, 1996
Reported cases – 21 articles
Prevalence of PNES
Age at onset (yrs)
0 10 20 30 40 50 60 70 70 80 0
10
20
30
40
50
60
diagnostic
delay
(yrs)
Prevalence of PNES Diagnostic delay
- Reuber et al., 2002
• Some patients are*
dependent angry or hostile manipulative isolated resistant to psychiatric diagnosis
• This can impede diagnosis
*Groves, 1978
Diagnostic delay
Age at onset (yrs)
0 10 20 30 40 50 60 70 70 80 0
10
20
30
40
50
60
diagnostic
delay
(yrs)
Prevalence of PNES Diagnostic delay
- Reuber et al., 2002
# patients Mean (SD)
PNES +
Sz
AED + 260 7.8y (9.8)
AED - 53 4.9y (6.6)
PNES only AED + 161 8.4y
(10.2)
AED - 53 4.9y (6.6)
“spikes” + 17 12.5y
(15.6)
“spikes” - 195 7.1y (8.7)
- Reuber et al., 2002
Delayed Diagnosis of PNES
• 20-60%
– Özkara and Dreifuss 1993
• 9-30%
– Lesser et al 1983, Meierkord et al 1991, Krumholz and Niedermeyer 1993 Benbadis et al. 2001
• may vary with clinical situation
• any given person may have two diagnoses
• consider each diagnosis by itself
Co-occurrence with Epilepsy
# patients Mean (SD)
PNES +
Sz
AED + 260 7.8y (9.8)
AED - 53 4.9y (6.6)
PNES only AED + 161 8.4y
(10.2)
AED - 53 4.9y (6.6)
“spikes” + 17 12.5y
(15.6)
“spikes” - 195 7.1y (8.7)
Delayed Diagnosis of PNES
- Reuber et al., 2002
Delayed Diagnosis of PNES wicket spike spike
See Krauss et al. 2005
38 patients treated for somatization disorders 53% decrease in subsequent costs
Smith et al. 1995
Delayed Diagnosis → Delayed Treatment
-King et al 1982
#
pts
0
10
20
30
40
50
60
70
80
90
wrong
right
e
e
e
p p
p
e
p
epilepsy
pnes
You’d better ask the doctors here about my illness, sir.
Ask them whether my fit was real or not.
-Smerdyakov to Ivan in The Brothers Karamazov
Accuracy of clinical diagnosis
admission hospital later
-King et al 1982
#
pts
0
10
20
30
40
50
60
70
80
90
wrong
right
e
e
e
p p
p
e
p
epilepsy
pnes
Accuracy of clinical diagnosis
admission hospital later
• epilepsy
• syncope
– Hyperventilation syndrome
• movement disorders, migraine,
parasomnias, g-e reflux
-Wayne 1961, Pedley 1983, Lesser 1985, Betts 1990,
Metrick et al 1991, Vossler 1995, Kapoor 2000
Pseudo-PNES
Syncope medical student volunteers
- Dieter Schmidt
• visual diagnoses/reports can be unreliable
• EEG often needed to verify visual impressions
• patients with frequent seizures
outpatient EEGs may record seizures
• others, admission to EMU needed
withdraw medication
wait for seizures
Accuracy of clinical diagnosis
• Does Sandy have
epilepsy?
PNES?
both?
• Does Nicole have
epilepsy?
syncope?
PNES?
2/3?
3/3?
What about Sandy and Nicole?
• added (10% system)
electrodes often useful
• withdraw anticonvulsants
• interictal spikes can occur
in persons with no history
of epilepsy
• epileptiform vs.
nonspecific EEG changes
• beware of normal variants
and artifacts
EMU Monitoring
• EEG normal with PNES
• scalp EEG often normal
in persons with simple
partial seizures
EMU Monitoring
• often gradual
onset, can be short
• apparent sleep but
actually awake
(EEG)
• symptoms at onset palpitations, malaise,
choking, numbness,
peripheral sensory
changes, pain, odors,
tastes, hallucinations
• usually short
– longer duration in some
• awake or asleep
-Lesser 1985, Thacker et al 1993,
Fakhoury et al 1993, Lancman et al 1994
• symptoms at onset altered mood, experience,
autonomic changes,
peripheral/GI sensory changes,
odors, tastes, hallucinations
Onset
PNES Epilepsy
• behavior changes
• hyperventilation
syndrome
• may resemble
epilepsy
• emotional etiology
• behavior changes
• epigastric
• special senses
• unilateral sensory or
motor
•may have emotional etiology
Onset
PNES Epilepsy
• may or may not
follow anatomic
pathways
• follows anatomic
pathways
Sensory
PNES Epilepsy
•59 y/o priest
•history of alcoholism and depression
•episodes for 13 months
•bilateral weakness, numbness
affecting extremities, rectum
•notes occasional odor
•no loss of consciousness
•meds: phenytoin 300mg
•normal EEGs
Towards the left rectal
On the side
Hip I should say…
Left hip?
Yes
Now right elbow
Right knee, very very light
The left side is still having
a little grumble to it
All right doctor
Now my right just above the right rectal,
that part of the body
Part of the sensation
Left side is all finished
Everything is finished.
•Second sensory area
•Glioblastoma multiforme
•Died within one year
-Penfield and
Jasper 1954
• rigidity, pelvic thrusting*
• quasi-clonic, flailing,
thrashing, trembling
• side-to-side movements**
of head/body
• asynchronous***
• rigidity alone rare
• thrashing, kicking may
occur (frontal lobe)
• bilateral movements
– but focal motor
seizures (frontal lobe)
• usually synchronous,
may be asynchronous
(frontal lobe)
• eyes open
*4% **15% ***9% Leis et al. 1992
• eyes closed
Motor
PNES Epilepsy
• 40 y/o woman
• episodes for 11 months
• tingling, rt scalp
• speech & movement arrest
loss of consciousness GTC sz
2 / week – 3 / 6 weeks
• chest pressure – “cat on chest” & feels “drained”
• speech/movement arrest
nausea, dizziness tired, headache
6 / 9 months
• pacemaker placed after tilt table test
continued episodes, 1 lasting 2 hours
appears distressed, eyes closed
• crying, yelling, screaming, stuttering
• Sobbing
• complex dramatic, tragic, obscene, mystical
• cry at onset of generalized tonic or tonic-clonic seizures
• grunting during clonic movements
• various vocalizations during complex partial seizures
Vocalization
PNES Epilepsy
• bite tongue (tip/side) / lips
• bruises, lacerations
• may not respond during
avoidance testing or to
painful stimulation
– may allow intubation
– complications of
treatment:
respiratory arrest,
septicemia,
pneumonia, urinary
tract infection, cellulitis,
foot drop -Howell et al 1989
• bite tongue (side)
• bruises/lacerations
• no response to
avoidance testing
during generalized
tonic-clonic seizure
• may respond during
complex partial
seizure or postictally
Injury
PNES Epilepsy
• both are reported • both are reported
Urination / Defecation
PNES Epilepsy
• salivation, hyperventilation, choking, coughing, cyanosis, pallor, flushing, headache, chest pain, laryngeal spasm, pharyngeal spasm
• hyperventilation syndrome
• similar
Autonomic Changes
PNES Epilepsy
• usually longer
more than 2
minutes
• usually shorter
less than 2
minutes
Duration
PNES Epilepsy
Prolactin
• 15-30 minutes after attack
• several fold increase
• most accurate:
generalized tonic-clonic
temporal lobe seizures
• less accurate:
simple partial seizures
frontal lobe seizures
• false positives and negatives can occur
Ictal heart rate - staring spells
29
28
1
PNES
36 Total
6 HR < 130%
of baseline
30 HR ≥ 130%
of baseline
CPS
Opherk and Hirsch, 2002
Sens 30/36 = 83%
Spec 28/29 = 97%
Pos pred value 30/31 = 97%
Neg pred value 28/34 = 82%
Seizure induction
• iv’s, moistened patches, photic
stimulation, tuning fork, suggestion
• allow vs. coerce
• 70% inducible
• be sensitive to emotional needs
and sense of dignity of the patient
-Lesser 1985, Lancman et al 1994, Walczak et al 1994,
Slater et al 1995, Devinsky and Fisher 1996, Parra et al 1998,
Benbadis et al 2000, Benbadis 2002, Gates 2002
• often do not easily fit into
standard classifications
• Some patients found to be
psychologically normal
• some but not all studies
find relative increase
in cognitive difficulties
Diagnosis of PNES
Etiology of PNES ≠
• External interactions
• Internal / internalized conflicts
• Psychoses, Schizophrenia
• Personality disorders
• Other
-Gumnit and Gates 1986, Gates and Erdahl 1993,
Kanner et al. 1999, Mökleby et al 2002
Diagnosis of PNES
Etiology of PNES ≠
• External interactions
– inadequate personality, reinforced behaviors, adjustment reaction, family conflict, sexual or physical abuse, anger, hostility
• Internal / internalized conflicts
– affective disorders, panic attacks, anxiety, ocd, misinterpretation, highlighting, conversion/somatization/dissociative/ depersonalization disorders, post-traumatic stress disorders,
• Psychoses, Schizophrenia
• Personality disorders
– borderline, malingering, factitious disorder, histrionic, narcicistic, antisocial, passive-aggressive, avoidant, passive-dependent, substance abuse
• Other
– head trauma, cognitive difficulties, a.d.d., tic, genetic influences
Initiation of treatment is an important
part of the diagnostic process
• tactfully present the diagnosis
• explore possible reasons for disorder
• recommend therapy
– some do well after this single session
but most need more
Lesser et al 1983, Meierkord et al 1991, Shen et al 1990
• little data on usefulness
of psychiatric drugs
• useful for some etiologies
affective disorders
ocd
schizophrenia
• less useful for others
personality disorders
Initiation of treatment is an important
part of the diagnostic process
• In most cases see the patient at least once more
– symptoms improved? exam findings?
– emotional counseling?
• If appropriate, continue following the patient.
Initiation of treatment is an important
part of the diagnostic process
• often only rudimentary data link
seizures, personality, and treatment
• we need to evaluate effectiveness
of specific strategies
in specific types of patients
Initiation of treatment is an important
part of the diagnostic process
The End
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