Neuropsychology of Epilepsy
John Langfitt, Ph.D.
Associate Professor
Neurology & Psychiatry
Strong Epilepsy Center
University of Rochester
Overview



Definitions & Epidemiology
Seizure Types & Cerebral localization
Neuropsychological Effects of Medial
Temporal Lobe Epilepsy and its Surgical
Treatment
What is Epilepsy?

Seizure
– when neural networks fire together in abnormal synchrony

Epilepsy
– recurrent, unprovoked seizures
– does not include single seizures provoked by metabolic
disturbance or trauma

Normal Neural Activity
– low-voltage
– mixed frequency
– pseudorandom (chaotic?)
 Seizure
– extreme voltage
– rhythmic
– paroxysmal
Propagation of Neuronal Signal
PreSynaptic
Neuron
PostSynaptic
Neuron
Cell Body
Axon
Flow of
Action Potential
Synapse
Synaptic Cleft
At Rest
+ +
PreSynaptic
Neuron
-
+
-
+
+
-
- +
+
+
+
+
- + + +
+
-
+
-
PostSynaptic
Neuron
+
+
Synaptic Cleft
Excitatory Post-Synaptic Potential
- + + +
+
- - +
- +
+
+
+
+
+
+ - + - +
+
+ - +
PreSynaptic
Neuron
PostSynaptic
Neuron
Bipolar EEG
-40
-100
1st
2nd
-40 - (-100) = +60
-100 - (-40) = -60
-40 - (-20) = -20
-40
-20
-20
-20 - (-20) = 0
Interictal Discharges
Seizure (Ictal) Discharge
Frequency of Epilepsy





Stroke
Epilepsy
Parkinson’s
Mult. Sclerosis
Huntington’s
>1/100
6/1000
2/1000
2/10,000
4/1,000,000
Causes of Epilepsy
Rochester, Minnesota 1935-1984
Degenerative (4%)
Tumors (4%)
Infectious (3%)
Trauma (6%)
Congenital (8%)
Vascular (10%)
Idiopathic (65 %)
Hauser, 1997
Peak Incidence in Childhood and
Senescene
Prognosis
Silanpaa et al., 2000
Living/Marital Situation
200
180
160
p <.0001
140
120
100
80
60
40
20
0
Single
Live Alone
Dependent
Patients (n=240)
Divorced
Married
w/ Children
General Population
Shackelton, 2003
Employment
120
100
p <.05
80
N
60
40
20
0
Employed
Householder
Patients (n=243)
'Disabled'
General Population
Shackelton, 2003
Living Situation/Health
by Seizure Control at Follow-up
100
90
80
p =.05
p <.01
p <.01
70
60
%
50
p <.05
40
30
20
10
0
Single/Dependent
Gen. Pop.
Good Health
No Sz, No AED
No Sz, AED
Co-morbid Illness
Sz & AED
Shackelton, 2003
Educational/Occupational Status
by Age at Onset
70
p <.01
60
50
%
p <.05
40
30
20
10
0
Low Educ.
Gen. Pop.
College
Onset > 18
Onset 6-18
'Disabled'
Onset < 6
Shackelton, 2003
Percent Never Married
Age > 35 (n=161)
Onset < 22
Onset >= 22
100
80
3/3
60
40
20
0
Yes
No
Yes
No
Special Education
Male Female
Langfitt & Janzen, 2002
USPop
Percent Currently Unemployed
(n=237)
‘Grand-mal’ No ‘Grand-mal’
100
80
60
40
20
0
Yes
No
Yes
No
Psychiatric History
Low IQ
Langfitt & Janzen, 2002
Avg IQ
Summary

Definitions & Epidemiology
– Seizures are rhythmic, paroxysmal neuronal discharges
– Epilepsy is defined as 2 or more unprovoked seizures
– Epilepsy
•
•
•
•
•
is common in the general population
is a symptom, not a disease
reflects a broad range of underlying neuropathology
can be successfully treated with medicine in most patients
and associated problems can lead to activity restrictions and
significant psychosocial burden
Seizure Types
 Partial
– Simple (no loss of
awareness)
• sensory
• motor
– Complex (loss of
awareness)
• involves spread to
both hemispheres
T4-T6
C6-T4
T4-S2
S2-S1
Seizure Types
 Partial
– Simple (no loss of
awareness)
• sensory
• motor
– Complex (loss of
awareness)
• involves spread to
both hemispheres
 Generalized– Primary
•
•
•
•
absence (‘petit mal’)
atonic (‘drop’)
tonic-clonic (‘grand-mal’)
myoclonic (‘jerks’)
– Secondary
• start as partial, but
discharge spreads
throughout brain
Absence (‘petit mal’) Seizure
Seizure Semiology & Cerebral
Localization



Somato-sensory
– tingling/numbness in
contralateral extremity
Focal motor
– hand>face>arm
progression (‘jacksonian
march’)
Visual
– flashing lights (calcarine)
– formed visual
hallucinations (secondary
assn. cortex)




Auditory
– formed auditory
hallucinations (secondary
assn. cortex)
Frontal
– often nocturnal
– thrashing, vocal outbursts,
genital rubbing
Limbic
– olfactory/gustatory
hallucinations, déjà vu,
post-ictal amnesia
Brainstem/Thalamus
– motor arrest, loss of
consciousness, abrupt
change in muscle tone
Summary
 Seizure Types & Cerebral Localization
– Seizures types
•
•
•
•
vary greatly in behavior across individuals
are highly consistent within an individual
are determined by origin and pattern of spread through CNS
vary greatly in severity & functional significance
Conditions Associated with
Epilepsy





Mental Retardation
Cerebral Palsy
Stroke
Lupus
Traumatic Brain Injury





Encephalitis
Meningitis
Tumor
Migrational anomalies
Mesial temporal
sclerosis
Causes of Cognitive & Behavioral
Dysfunction




Underlying disease
Seizures
Psychosocial Factors
Treatments
– Medical
– Surgical
Medial Temporal Lobe Epilepsy
(MTLE)
 Onset 1st 2 decades
‘Cryptogenic’ etiology
Progressive course
Refractory to medical treatment
Significant psychosocial burden
Highly responsive to surgical removal of
epileptogenic tissue
 Quality of life improves with seizure-freedom
 Pre-exisiting memory deficits worsen in some





Selective hippocampal cell loss
(Bratz, 1898)
Normal
Hippocampus
Sclerotic
Hippocampus
Seizure frequency and HC volume
over time
r=.60
p< .007
34 TLE patients
newly diagnosed
1st scan ‘normal’
Clinically apparent MTS
on 2nd scan
Briellmann et al., 2002
Memory and the
Medial Temporal Lobe
 Scoville & Milner, 1957
– Bilateral medial temporal lesions produce anterograde
amnesia
 Penfield & Milner, 1958
– Unilateral medial temporal resections produce amnesia when
there is damage contralaterally before surgery
 Milner, 1972
– Unilateral lesions are associated with material-specific
learning and memory deficits
Mesial Temporal Sclerosis
Neuropsychological Characteristics
 Dominant TL
– Verbal semantic retrieval
deficits prominent
– Episodic memory deficits
common, verbal > nonverbal
– Retrieval impaired,
recognition typically
preserved
– Co-morbid verbal learning
disability may be present
 Non-Dominant TL
– Verbal semantic retrieval
deficits less prominent
– Episodic memory deficits
common, non-verbal >
verbal
– Retrieval impaired,
recognition typically
preserved
– Co-morbid non-verbal
learning disability may be
present
Medical Management REMISSION RATES
in "Intractable" Series
Proportion Remitted
0.2
0.15
Kwan & Brodie, 2000
Mattson et al., 1985
Vickrey et al., 1995
Semah et al., 1998
0.1
Wiebe et al., 2001
0.05
0
0
1
2
3
4
5
6
Mean Years of Follow-up
7
8
9
10
Anterior
Temporal
Lobectomy
Canadian Randomized Trial
Seizure Control
P< .001
Wiebe et al., 2001
Case Series Outcome
Anterior Temporal Lobectomy
100
80
60
%
40
20
0
57
61
61
65
75
80
84
85
Year of Cohort Inception
Class I
Langfitt & Bronstein, 1999
Class II
Class III
Class IV
86
88
Canadian Randomized Trial
Quality of Life
P< .001
Wiebe et al., 2001
EESTLE
Employment
P=.11
Wiebe et al., 2001
Cognitive Effects of ATL
Score/Group
Gain(%)
IQ
No Change(%)
Loss(%)
Verbal IQ
Controls
5
90
5
LTL
8
81
11
RTL
8
86
6
7
88
5
LTL
11
87
2
RTL
6
86
8
8
85
8
LTL
19
77
4
RTL
8
80
12
Performance IQ
Controls
Full Scale IQ
Controls
Chelune et al. 1993
Cognitive Effects of ATL
Score/Group
Episodic Retrieval
Gain(%)
No Change(%)
Loss(%)
Controls
5
92
2
LTL
0
55
45
RTL
2
84
14
Controls
5
85
10
LTL
7
85
9
RTL
6
84
10
Controls
5
88
7
LTL
0
83
17
RTL
4
84
12
Verbal
Visual
Delayed Recall
Chelune et al. 1993
Cognitive Effects of ATL
Semantic Retrieval
LTL - Left dominant
LTL - Right dominant
RTL-Left dominant
30
Naming Change
20
10
0
-10
-20
-30
-40
15.00
20.00
25.00
30.00
35.00
40.00
Age at Surgery (years)
Langfitt & Rausch, 1995
45.00
50.00
Who is at Risk?
(Functional Reserve/Adequacy Hypotheses)
 Contralateral dysfunction associated with severe
post-operative declines
 Functional integrity of the ipsilateral tissue associated
with milder levels of decline
 MRI and neuropsychological variables reflect
functional adequacy of the to-be-resected temporal
lobe
 Chelune & Najm (2000) found combination of side of
surgery, MRI and baseline memory to predict risk of
milder memory decline post-op
Percent with Reliable Decline on One or
Both Verbal Memory Tests
% Worse
100
80
60
2
40
1
20
0
0
Dom -
Dom +
# Baseline
Tests Intact
Ndom - Ndom +
Side/U-MTS
Stroup et al., 2003
Summary
 Neuropsychological Effects of MTLE and Surgery
– MTLE often arises from dysfunctional re-organization of
hippocampal neurons in response to injury
– Re-organization leads to abnormal
• propagation of excitatory inputs, leading to uncontrolled seizures
• disruption of normal mnemonic function of MTL structures
– Seizures can be controlled by removing abnormal circuitry
– Effects on memory
• are more measurable for verbal vs. non-verbal material
• depend on functional integrity of both the remaining (contralateral)
MTL structures and the removed (ipsilateral) MTL structures
– Effects on function
• seizure control leads to significant improvements in quality of life, even
when memory decline occurs