Date post: | 22-Dec-2015 |
Category: |
Documents |
Upload: | melina-powell |
View: | 212 times |
Download: | 0 times |
Clinical Epilepsy: Syndromes, Causes, and Effects
Russell M. Bauer, Ph.D.
Department of Clinical & Health Psychology
2
Seizures vs Epilepsy
Definition: the clinical manifestation of an abnormal and excessive excitation of a population of cortical neurons
Incidence: approximately 80/100,000 per year
Lifetime prevalence: 9% (1/3 benign febrile convulsions)
Definition: a tendency toward recurrent seizures unprovoked by systemic or neurologic insults
Incidence: approximately 45/100,000 per year Approximately 181,000 people will experience seizures or develop epilepsy each year
Point prevalence: 0.5-1% (2.5 million)14 years or younger
13% 15 to 64 years
63%65 years and older
24%
Cumulative risk of epilepsy through 74 years old: 1.3% - 3.1%
Seizures Epilepsy
3
Partial (focal) Seizures• Simple Partial Seizure
– no loss of awareness
• Complex Partial Seizure– Impaired consciousness/ level of awareness (staring)– Clinical manifestations vary with origin & degree of spread
– Presence and nature of aura
• Temporal lobe: smell, epigastric sensation, deja vu
– Automatisms (manual, oral)
– Other motor activity
Frontal: bicycling and fencing posture
– Duration (typically 30 seconds to 3 minutes)
– Amnesia for event
• Partial Seizure with Secondary Generalization
Localization of Partial Seizure Focus
70%70% 10%10%
20%20%
Temporal Lobe Complex Partial Seizure
Rhythmic 5-7 Hz theta from the mesial temporal lobeRhythmic 5-7 Hz theta from the mesial temporal lobe
6
Primarily Generalized Seizures• Absence
– Typical (3 Hz spike and wave)– Atypical (2.5 to 4.5 Hz spike and wave, polyspike)– Brief staring (<30sec); automatisms rare; not post-ictal confusion
• Myoclonic– Brief, shock-like muscle contractions
- Head- Upper extremities
– Usually bilaterally symmetrical– Consciousness preserved– Precipitated by awakening or falling asleep– May progress into clonic or tonic-clonic seizure– May be associated with a progressive neurolgic deterioration– Juvenile Myoclonic Epilepsy (JME)
• Polyspike wave• Onset late adolescence• Chromosome 6p
– Progressive Myoclonic Epilepsies
• Atonic/ Tonic/ Tonic-Clonic
Absence Seizure3 Hz spike and wave
Seizure vs Epilepsy
Seizures
CardiovascularDrug relatedSyncopeMetabolic (glucose, Na, Ca, Mg)Toxic (drugs, poisons)PoisonInfectiousFebrile convulsionsNonepileptic seizuresAlcohol/drug withdrawalSubstance abusePsychiatric disordersSleep disorders (parasomnias, cataplexy)
Nonepileptic Epilepsy(recurrent seizures)
Idiopathic(primary)
Symptomatic(secondary)
9
Epidemiology of Seizures and Epilepsy
0
10
20
30
4050
60
70
80
90
0 10 20 30 40 50 60 70 80Age
Inci
den
ce p
er 1
00,0
00
Partial
Generalized tonic-clonic
Primary Generalized
Epilepsy: Incidence Rates by Seizure TypeEpilepsy: Incidence Rates by Seizure Type
Data from Rochester, Minn (1935-1979). Adapted with permission from Annegers JF. In: The Treatment of Epilepsy: Principles and Practice. 2nd ed. Baltimore, Md: Williams & Wilkins; 1997:165-172.
Hauser et al, 1992
Ramsay RE, et al. Neurology. 2004;62(5 suppl 2):S24-S29
Hemorrhage2%
Head Trauma7%
Other*19%
Atherosclerosis
15%
Cerebral Infarct
33%
Unknown24%
CHI5%Con
4%
Id85%
D1%
N4%
V1%
Inf0%
.* Includes known etiologies such as arteriovenous malformation and venous angioma.
Seizure Precipitants
Low (less often high) blood glucose
Low sodium
Low calcium
Low magnesium
Stimulant or other proconvulsant toxicity (i.e., cocaine)
Sedative (i.e., valium or alcohol) withdrawal
Severe sleep deprivation
EEG Abnormalities
•Background abnormalities
-Significant asymmetries and/or degree of slowing inappropriate for clinical state
•Transient abnormalities associated with seizures
-Spikes (< 70 m sec)
-Sharp waves (~70 – 200 msec)
-Spike-wave complexes
•May be focal, lateralized or generalized
EEG Abnormalities
Treatment of New Onset Epilepsy
Kwan P, Brodie MJ. N Engl J Med 2000; 342: 314-9.
Sz -fre e w/ 1st AED47%
Sz -fre e w/ 3rd AED/Polythe rapy
4%
Sz -fre e w/ 2nd AED13%
Re fractory/Pharm acore si stan t
36%
S z-free w/ 1st AED
S z-free w/ 2nd AED
S z-free w/ 3rd AED/Polytherapy
Refractory/Pharmacoresistant
Kwan and Brodie. NEJM 2000; 342: 314-319.Mohanraj and Brodie. Epil Behav 2005; 6: 382-387
Kwan and Brodie. NEJM 2000; 342: 314-319.Mohanraj and Brodie. Epil Behav 2005; 6: 382-387
Rational Use of AEDs: All PrescriptionsMarket Dynamics for All Indications and Epilepsy
TOPAMAX14.8%
TRILEPTAL8.0%
LAMICTAL8.1%
GABITRIL1.8%
ZONEGRAN2.1%
KEPPRA4.7%
NEURONTIN60.6%
0
50000000
100000000
150000000
200000000
250000000
300000000
350000000
400000000
450000000
Second Gen. AEDs First Gen. AEDs
27%
44%
9%
5%
15%
Epilepsy
Psychiatric d/ o's
Pain disorders
Headache/ migraineOther
0
10
20
30
40
50 Carbamazepine Depakote DRDepakote ER Depakote sprinklesKeppra LamictalNeurontin PhenytoinTopomax Trileptal
AE
D P
resc
rip
tio
n V
olu
me
(%)
AE
D P
resc
rip
tio
n V
olu
me
(%)
Age Group (years)PharMetrics. April 2002 to June 2003. Source: IMS NPA, Dec. 2003MAT 03/2004
0-17 18-34 35-44 45-54 55-64 0-17 18-34 35-44 45-54 55-64 >>65 65
“All substances are poisons; there is none which is not a poison. The right dose differentiates a poison from a remedy.”
Paracelsus (1493-1541)
Summary of Serious and Non-serious Adverse Events of the Newer AEDs
AED Serious Adverse Events Nonserious Adverse Events
Gabapentin None Weight gain, peripheral edema, behavioral changes
Lamotrigine Rash, including Stevens Johnson and toxic epidermal necrolysis (increased risk for children, also more common with concomitant valproate use and reduced with slow titration); hypersensitivity reactions, including risk of hepatic and renal failure, DIC, and arthritis
Tics and insomnia
Levetiracetam None Irritability/behavior change
Oxcarbazepine Hyponatremia (more common in elderly), rash None
Tiagabine Stupor or spike wave stupor Weakness
Topiramate Nephrolithiasis, open angle glaucoma, hypohidrosis (predominantly children)
Metabolic acidosis, weight loss, language dysfunction
Zonisamide Rash, renal calculi, hypohidrosis (predominantly children)
Irritability, photosensitivity, weight loss
Rational Use of AEDsSo Why Should Prescribing Practices Change?
Patients often required long term (or lifetime) treatment due to driving status
State of Florida *15A-5.004 Neurological Guidelines for Applicants with Seizures (*the following changes to the seizure guidelines became effective in August 1992 and have been used as policy since that date)
1. Applicants and licensed drivers should be seizure free for a period of 2 years before being approved for licensing; but if under regular medical supervision, may apply at the end of 6 months for review by the Medical Advisory Board. “Petit mal” or absence seizures and partial seizures with complex symptomology will also follow these guidelines. The isolated seizure with a normal EEG may be reviewed after 3 months.
2. Applicants and licensed drivers who have been approved after 6 months seizure free may be required to submit follow-up reports at the end of 1 year from the date of approval.
3. Applicants and licensed drivers who have a chronic recurring seizure disorder (or who have been treated for such for 1 year) and medications have been discontinued will not be licensed to drive during the period of drug withdrawal and for a period of 3 months following complete cessation of treatment. If the patient has seizures during this period, licensing may be considered after a 3 month seizure free interval upon return to adequate therapy.
4. If there is a question about the seizure type or the medications the applicant of licensed driver is on, it is the prerogative of the Medical Advisory Board to question the treating physician further in an effort to clarify the nature of the seizures.
5. Blood levels below therapeutic levels are to be considered on an individual basis.
6. Applicants and licensed drivers with only chronic nocturnal seizures will be considered on an individual basis.
7. Applicants and licensed drivers with syncopal episodes who have no clear diagnosis established will be considered on an individual basis
Treatment/Evaluation Sequence for Pharmacoresistent Epilepsy
1st Monotherapy AED Trial
2nd Monotherapy AED Trial
Epilepsy Surgery/VNS Therapy/Neuropace Evaluation
Resective Surgery Stimulator Therapy
3rd Monotherapy/Polytherapy AED Trial
Polytherapy AED Trials
4%
13%47%
36%
Sz-free with 1st AED
Sz-free with 2nd AED
Sz-free with 3rdAED/P olytherapyP harmacoresistant
Kwan P, Brodie MJ. NEJM;342:314-319.
Strongly consider videoEEG Monitoring
Epilepsy
Psychogenic, migraine, syncope, sleep disorders, movement disorder’s, etc.
Non-epileptic
Other Treatments of Epilepsy
• Medical– Experimental AED trials– Ketogenic diet
• Surgical– Resective– Multiple Subpial Transection– Vagal Nerve Stimulator
• Experimental– Thalamic Stimulators– Stereotactic Radiosurgery– Responsive Neurostimulators
Evaluation for Surgery- Neuroimaging
MRI -hippocampal volumetrics
greater than ~0.5cc difference increases chances for seizure remission
-1.5 mm coronal cuts with sequences sensitive to gray-white differentiation and to gliosis
-inversion recovery/high resonance for cortical dysplasia
PET
Ictal/interictal SPECT
MR SpectroscopyDecreased NAA (due to neuronal loss)
Normal to high Cho and Creatine (represents astrocytosis)
Epilepsy Surgery- Neuroimaging
Ganglioglioma Dysembryoplastic Neuroepithelial Tumor
AVM Cavernous AngiomaCortical Dysplasia
Hippocampal atrophy in temporal lobe epilepsy
Evaluation for Surgery- Subdural Grid Electrodes
Left Anterior Temporal Loectomy
Factors Affecting Adaptation in Epilepsy
Seizure-Related
Variables
Treatment-Related
Variables
Non–Seizure-Related
Variables
Factors Affecting Cognitive Function in Epilepsy
Seizure-Related
Variables
Treatment-Related
Variables
Non–Seizure-Related
Variables
What Seizure Related Factors May Affect Cognition in Epilepsy?
EpileptiformActivity
SeizureSyndrome
SeizureBurden
(Duration,Frequency,
Status)
Onset Age Etiology
Seizure-Related Variables That May Affect Cognition and Behavior
EpileptiformActivity
SeizureSyndrome
Ageat
OnsetEtiology
SeizureBurden
(Duration,Frequency,
Status)
Epileptic Syndrome
• Some epilepsy syndromes are known to be associated with more adverse cognitive consequences than others. – Idiopathic Benign syndromes—e.g., BECTS
(Rolandic), absence– Adverse syndromes—e.g., Lennox-Gastaut – Variable syndromes—Localization related
epilepsies
Idiopathic Syndromes
Deficit Outcome
JMEMild executive
deficitsPresumed favorable
Generalized with absence or GTCS
Mild attentional deficits
Unknown
Centrotemporal spikes benign
Mild HeterogeneousMostly favorable (interictal abn)
Occipital epilepsy Mild Heterogeneous Unknown
Elger et al. (2004)
Adverse Syndromes
Deficit Outcome
CSWDSVariable (diffuse or
executive)Variable - duration
dependent
Landau KleffnerAuditory agnosia,
Expressive LanguageVariable – early onset
worse
West Syndrome Retardation, regression Poor, retardation
Lennox-Gastaut Retardation, declinePoor, retardation worse early onset
Elger et al. (2004)
Localization Related Syndromes
Deficit Outcome
FrontalExecutive function,
attention, speedUnknown
Temporal
Material-specific memory (executive 2º
gen), naming, achievement
Very slow deterioration
Parietal Occipital Unknown (variable)Unknown
(heterogeneous)
Elger et al. (2004)
Seizure-Related Variables That May Affect Cognition and Behavior
InterictalEpileptiform
Activity
EpilepticSyndrome
SeizureBurden
(Duration,Frequency,
Localization)
Ageat
OnsetEtiology
Adults with Childhood Seizure Onset
• Less Education• Decreased rates of employment• Lower rates of marriage• Poorer physical health• Increased incidence of psychiatric disorders
Jalava et al., 1997a,b,c, SillanpJalava et al., 1997a,b,c, Sillanpää (ää (1998)1998)
Total and Segmented Volumes(7.8 years vs. 23.3 years)
Hermann et al, Epilepsia 2002;43:1062-71
Total Lobar White Matter
Hermann et al, Epilepsia 2002;43:1062-71
Cause or Effect?
• Does white matter volume abnormality reflect neurodevelopmental abnormality associated with early insult to developing brain?
• Does early lesion affect subsequent normal development of white matter connectivity?
Age of Onset and Neuropsychological Outcome
Early Late Healthy(7.8 yr) (23.3 yr)
ControlsN 37 16 62FSIQ 90* 100 107Naming 47 52 55Verbal Mem 44 51 52NV Mem 46 55 62WCST PE 13 8 8
Hermann et al, Epilepsia 2002;43:1062-71
Childhood TLE Onset
• Generalized cognitive compromise• Reduction in cerebral volume, particularly white
matter (~6-12%)• Cerebral volume reduction not limited to temporal
lobe• Less focal impairment (e.g., memory)• Less surgical risk • Greater likelihood of functional reorganization (e.g.,
bilateral language, pathologic left handedness)
Seizure-Related Variables That May Affect Cognition and Behavior
EpileptiformActivity
SeizureSyndrome
SeizureBurden
(Duration,Frequency,
Localization)
Ageat
OnsetEtiology
Etiology• Individuals with known causes for their
epilepsy (e.g., head injuries, brain infections) typically have more detectable cognitive difficulties than those with no known etiology
Seizure-Related Variables That May Affect Cognition and Behavior
EpileptiformActivity
SeizureSyndrome
SeizureBurden
(Duration,Frequency,
Localization)
Ageat
OnsetEtiology
Seizure Burden
• Individuals with poorly controlled and severe seizures often have more detectable cognitive consequences than individuals with well-controlled and/or minor seizures
Cumulative Seizure Effects?(is epilepsy progressive?)
• Structural Imaging vs Behavior
• Cognitive and behavioral impairments present prior to treatment
• Newly diagnosed L TLE patients have verbal memory impairment
Äikiä, Äikiä, Epilepsy & BehaviorEpilepsy & Behavior (2001) (2001)
Äikiä , Äikiä , Epilepsy ResearchEpilepsy Research 1995;22:157-164 1995;22:157-164
Progressive Hippocampal Sclerosis
• Progressive hippocampal atrophy occurred only in patients with TLE and continuing seizures
• n=12 unilateral TLE• Repeat MRI=2.5-5.2 yr
Fuerst et al, Fuerst et al, Ann Neurol Ann Neurol 2003;53:413-62003;53:413-6
Neuropsychological Effects of Poorly Controlled Seizures
• 20 longitudinal studies in children-adults
• 12/20 reported relationship/decline
• 5/20 mixed results
• 3/20 no relationship
Dodrill, Dodrill, Epilepsy & Behavior Epilepsy & Behavior (2004)(2004)
Neuropsychological Effects of Seizures
• Decreased scores with higher number of seizures
• IQ lower with increased seizure frequency
• Greater performance “improvement” in controls than patients
• Losses seen beyond “memory”
Dodrill, Dodrill, Epilepsy & Behavior Epilepsy & Behavior (2004)(2004)
Cross-sectional TLE Neuropsychological Outcome
Jokeit et al, Jokeit et al, JNNPJNNP 1999;67:44-50 1999;67:44-50
Educational Attainment and Seizure Duration
Jokeit et al, Jokeit et al, JNNPJNNP 1999;67:44-50 1999;67:44-50
Epilepsy and Quality of Life
Seizures, Hypertension, Diabetes, and Seizures, Hypertension, Diabetes, and Heart Disease QoLHeart Disease QoL
Vickrey BG. Vickrey BG. Epilepsia.Epilepsia. 1994 1994;;35:597-60735:597-607
46
49
52
55
58
61
Seizure-freeAurasSeizures
Hypertension/ DiabetesHeart Disease
OverallQualityof Life
EmotionalWell-Being
SocialFunction
Role–Emotional
Energy/Fatigue
Pain Role–Physical
PhysicalFunction
HealthPerception
T-S
CO
RE
N = 166
Comparison of Average MonthlySeizure Rate to HRQOL
N = 194(r = -0.024,P = NS)
Gilliam F, et al. 2000Gilliam F, et al. 2000
QO
LIE
-89
Su
mm
ary
Sco
re
Average Monthly Seizure Rate0 305 15 20 25
100
0
80
60
40
20
10
N = 194(r = -0.71,P<.0001)
Gilliam F, et al. 2000Gilliam F, et al. 2000
Relationship of Adverse Events to QOL Scores
20 30 40 50 60 70
100
80
60
40
20
0
QO
LIE
-89
Su
mm
ary
Sco
re
AEP Summary Score
Psychiatric Comorbidities
Epilepsy General Pop.(range) (range)
Depression 11%–60% 2%–4% Anxiety 19%–45% 2.5%–6.5% Psychosis 2%–8% 0.5%–0.7%
Profile of Mood States Depression Scale Score
50403020100
QO
LIE
-89
Su
mm
ary
Sco
re
100
80
60
40
20
0
r = -0.66r = -0.66p<0.0001p<0.0001
POMSPOMS
QO
LIE
-89
QO
LI E
- 89
Elger et al. (2004)
(non-modifiable) (modifiable)