Spinocerebellar Ataxia Type 8
(“SCA-8”)
The Cognitive and Psychiatric Profile
Lorna Torrens, Elaine Burns, Jon Stone, Mary Porteous, Adam Zeman,
Helen Wright
Robert Fergusson Unit, Royal Edinburgh Hospital; Western
General Hospital, Edinburgh
Case History - Referral, 1998
• 46 year old man with 5 year history:
• neurological signs
– slurred speech, ataxia, impaired dexterity
• cognitive decline
– forgetfulness, difficulty with divided attention
• personality change
– labile mood, aggressive outbursts, inflexibility
Case History - Examination
• Mild limb ataxia
• Dysarthric, slowed repetitive tongue
movements
• MMSE 30/30
• ‘Buoyant’ mood, poor insight
Cognitive Screening
• Predicted FSIQ 110
but < 20th centile on:
–
–
–
–
–
Stroop
Trails A and B
Verbal/Category fluency
Immediate/delayed recall of story
Rey Osterreith figure
Wisconsin (‘very poor’)
MRI Scan
Family History
• Mother, 75 years old
–
–
–
–
–
impulsive and inflexible from 40s
dysarthric
incongruous affect
category fluency: 6 (animals), 4 (letter)
failed Luria test (5 trials)
Spinocerebellar Ataxia Type 8
(“SCA 8”)
•
•
•
•
Koob et al, Nature Genetics, 1999;21:379-384
Family: 21 affected, 20 unaffected carriers:
SCA-8 is a risk factor for expression of condition
DNA based triplet repeat disorder (as is
Huntington’s Disease)
• One of an enlarging family of SCAs
• Unusual - the repeat expansion is transcribed but
not translated
• Myotonic Dystrophy - same mechanism
Reported Clinical Features of
SCA-8
• Cerebellar Signs (almost all)
• Upper Motor Neuron Signs (approx 50%)
• Cognitive Impairments:
– 26% of 68 patients covered in 11 studies (crude
measures?)
SCA-8:
Demographics, MRI
ED
GR
CB
IC
ICa
YB
GH
RH
SM
JG
CM
(AG)
SEX
ONSET
ASSMT
F.H.
MRI
F
34
44
-
+
F
47
57
-
+
M
40
48
+ mother
+
F
52
59
+ brother
+
F
50
56
-
+
F
39
45
-
N
M
70
76
+ father
N
M
47
57
+ father
+
F
28
42
-
N
F
45
51
+ father
N
M
27
30
-
N
M
13
21
-
+
SCA 8:
Neuropsychiatric symptoms
Cognitive Memory Emotional Personality
ED
GR
CB
IC
ICa
YB
GH
RH
JG
SM
CM
(AG)
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
~+
+
+
+
~+
+
Schmahmann & Sherman 1998
“Cerebellar Cognitive Affective
Syndrome”
• 20 Cases of Diseases confined to the
cerebellum resulting in impaired executive
function, visuo-spatial skills and memory.
Personality change including disinhibition
and blunting of affect
The SCA-8 expansion is
associated with neurological
and upper motor neuron signs.
Are there also cognitive
(specifically executive) and / or
affective links?
The Tests
•
•
•
•
•
Methodology
Pre-Morbid IQ
Current FSIQ
Memory Screening
Executive Tests
Executive Function Tests
• COWAT – Verbal Initiation, Speed
• Stroop – Speed, sustained attention, attentional
switching
• Hayling and Brixton – Verbal initiation,
suppression, speed, rule detection and following
• TEA – Visual Elevator Subtest – attentional
switching, speed
• (MWCST)
• (BADS 6 Elements)
The Results...
FSIQ
Memory
Executive Tests
Pr
ed
ic
te
d
Ve
A
F
r b ctu SIQ
al
a
Im l F
Ve m S IQ
Vi r ba edi
at
su l
al De e
I m la
Vi m yed
s u ed
al ia
D te
el
ay
ed
H
ay Str
lin oo
p
g
TE Brix (%
il
t
A
Ti on( e)
m %
i
i
C ng le)
O
(
W %i
A
T le)
(%
ile
)
Pr
ed
ic
te
d
FS
Ve
A
c
rb
tu IQ
al
a
Im l F
Ve me SIQ
r
Vi ba dia
s u l D te
al
e
Im lay
Vi me ed
su
di
at
al
De e
la
ye
d
H
S
ay tro
lin
op
B g(
%
TE rix
to ile
A
Ti n(% )
m
in ile
g
)
C
(
O
W %il
A
T e)
(%
ile
)
Z score
SCA- 8: Mean Scores
Controls: Mean Scores
100
100
80
80
60
60
40
40
20
20
0
0
Average WAIS III Index Scores
SCA-8 Subjects
100
WAIS-III Index Scores
95
90
85
80
75
VCI
POI
WMI
WAIS-III Index
PSI
FSIQ
Memory
Executive Tests
ic
te
d
A c FS I
Q
Ve
tu
al
rb
FS
al
Im
IQ
m
Ve
e
di
rb
at
al
e
Vi
D
su
el
a
al
ye
Im
d
m
Vi
e
di
su
at
al
e
De
la
ye
d
St
Ha
r
oo
yl
p
in
g
(
%
B
TE rixto ile)
A
n(
Ti
%
m
ile
in
)
g
CO
(%
ile
W
AT
)
(%
ile
)
Pr
ed
ed
ic
te
d
FS
Ac
IQ
tu
Ve
al
rb
FS
al
IQ
Im
m
Ve
ed
rb
ia
al
te
De
Vi
su
la
ye
al
d
Im
m
ed
Vi
su
ia
te
al
De
la
ye
d
St
ro
Ha
op
yl
in
g
(%
Br
ile
ix
)
to
TE
n
A
(%
Ti
ile
m
)
in
g
(%
CO
ile
W
)
AT
(%
il e
)
Pr
Percentile
SCA- 8 (Atrophy): CB
Control 1
(Scores percentiles)
(Scores percentiles)
100
100
80
80
60
60
40
40
20
20
0
0
RESULTS
• Significant difference in performance
executive function tests (p = 0.007)
• Non significant trend towards difference in
performance on Visual Memory
• Main discrepancies stemming from Hayling
(p = 0.005) and Stroop (0.015)
• Least difference in performance on Brixton
PFSIQ: SCA-8 vs Controls
130
10
120
110
100
90
8
80
18
70
N=
SUBJECT
11
11
SCA8
Control
Mean Executive Function Tests: SCA-8 vs Controls
120
110
100
90
80
70
60
N=
SUBJECT
11
11
SCA8
Control
160
140
120
140
2
3
10
100
15
120
14
80
60
100
18
40
19
80
STROOP
COWAT
Stroop:SCA-8 vs Controls
COWAT: SCA-8 vs Controls
60
N=
SUBJECT
11
11
SCA8
Control
20
8
0
N=
SUBJECT
11
11
SCA8
Control
TEA: SCA-8 vs
Controls
120
110
100
90
80
70
Brixton: SCA-8 vs
Controls
TEA
60
Hayling: SCA-8 vs
Controls
50
N=
11
11
SCA8
Control
SUBJECT
140
140
19
120
120
100
100
80
60
80
22
19
18
HAYLING
40
20
0
N=
SUBJECT
11
11
SCA8
Control
60
40
N=
SUBJECT
11
11
SCA8
Control
ASPECTS OF EXECUTIVE
FUNCTION?
• Verbal Initiation/Speed - COWAT (p =
0.10), Brixton (but controls)
• Inhibition of automatic responses Accuracy vs Speed (Hayling, Stroop 71 vs
56 secs for part I)
• Processing “load” ?
Mean Scaled Score on Hayling Parts I, II and Error
Score
7
6
Scaled Score
5
4
Control
SCA 8
3
2
1
0
Part I
Part II
Error Score
Is there an “affective”
component?
BDI-II
16
Mild
14
12
8
Minimal
6
4
HADS - Depression
2
0
10
SCA-8
Controls
8
Score
Score
10
6
Normal
4
2
0
SCA-8
Controls
20
18
16
14
12
Moderate
Mild
10
8
6
4
Minimal
HADS - Anxiety
2
0
SCA-8
8
Controls
6
Score
Score
BAI
Normal
4
2
0
SCA-8
Controls
Anxiety Symptoms Reported
•
•
•
•
•
Wobbliness in legs
Unsteady
Numbness or Trembling
Hands Shaking
Shaky
Conclusions
• SCA-8 linked to cognitive change:
– Executive Problems
– PS (not necessarily linked to motor problems)
• SCA-8 may have an affective component:
– Mild depression (Insufficient to account for cognitive
deficits)
– Anxiety (may reflect cerebellar symptoms as opposed
to affective disorder)
Future Thoughts
• Progression
– re-test in approx 2 years
• Mechanisms
– results from present study do not elucidate the
role of the cerebellum in cognition as SCA-8
may affect other brain regions (work underway)