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Spinocerebellar Ataxia Type 8Spinocerebellar Ataxia Type 8(“SCA-8”)(“SCA-8”)
The Cognitive and Psychiatric Profile 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, 1998Case 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 - ExaminationCase History - Examination
• Mild limb ataxia
• Dysarthric, slowed repetitive tongue movements
• MMSE 30/30
• ‘Buoyant’ mood, poor insight
Cognitive ScreeningCognitive 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 ScanMRI Scan
Family HistoryFamily 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 Spinocerebellar Ataxia Type 8 (“SCA 8”)(“SCA 8”)
• Koob et al, Nature Genetics, 1999;21:379-384• Family: 21 affected, 20 unaffected carriers:• SCA-8 is a riskrisk 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 Reported Clinical Features of SCA-8SCA-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:SCA-8:Demographics, MRIDemographics, MRI
SEX ONSET ASSMT F.H. MRI
ED F 34 44 - +
GR F 47 57 - +
CB M 40 48 + mother +
IC F 52 59 + brother +
ICa F 50 56 - +
YB F 39 45 - N
GH M 70 76 + father N
RH M 47 57 + father +
SM F 28 42 - N
JG F 45 51 + father N
CM M 27 30 - N
(AG) M 13 21 - +
SCA 8:SCA 8:Neuropsychiatric symptomsNeuropsychiatric symptoms
Cognitive Memory Emotional Personality
ED +GR +CB + + +ICICa + + +YB + + + +GHRH ~ + ~ +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 The SCA-8 expansion is associated with neurological associated with neurological
and upper motor neuron signs. and upper motor neuron signs.
Are there also cognitive Are there also cognitive (specifically executive) and / or (specifically executive) and / or
affective links?affective links?
The TestsThe Tests
• Methodology
• Pre-Morbid IQ
• Current FSIQ
• Memory Screening
• Executive Tests
Executive Function TestsExecutive 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...The Results...
SCA- 8: Mean ScoresSCA- 8: Mean Scores Controls: Mean ScoresControls: Mean Scores
FSIQFSIQ
MemoryMemory
Executive TestsExecutive Tests
0
20
40
60
80
100
Z s
core
0
20
40
60
80
100
Predi
cted F
SIQAct
ual F
SIQ
Verba
l Im
med
iate
Verba
l Del
ayed
Visua
l Im
med
iate
Visua
l Dela
yed
Stroop
Haylin
g (%ile
)
Brixto
n(%
ile)
TEA Tim
ing (%
ile)
COW
AT (%ile
)
Average WAIS III Index ScoresAverage WAIS III Index Scores
SCA-8 SubjectsSCA-8 Subjects
75
80
85
90
95
100
VCI POI WMI PSI
WAIS-III Index
WA
IS-I
II In
dex
Sco
res
SCA- 8 (Atrophy): CBSCA- 8 (Atrophy): CB
(Scores percentiles)(Scores percentiles)
ControlControl 11
(Scores percentiles)(Scores percentiles)
FSIQFSIQ
MemoryMemory
Executive TestsExecutive Tests
0
20
40
60
80
100
0
20
40
60
80
100
Perc
entil
e
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
1111N =
SUBJECT
ControlSCA8
PR
ED
FS
IQ130
120
110
100
90
80
70
18
8
10
PFSIQ: SCA-8 vs Controls
1111N =
SUBJECT
ControlSCA8
ME
AN
EX
EC
120
110
100
90
80
70
60
Mean Executive Function Tests: SCA-8 vs Controls
1111N =
SUBJECT
ControlSCA8
ST
RO
OP
140
120
100
80
60
40
20
0
18
8
32
1111N =
SUBJECT
ControlSCA8
CO
WA
T
160
140
120
100
80
60
19
14
15
10
Stroop:SCA-8 vs ControlsCOWAT: SCA-8 vs Controls
1111N =
SUBJECT
ControlSCA8
HA
YL
ING
140
120
100
80
60
40
18
19
1111N =
SUBJECT
ControlSCA8T
EA
120
110
100
90
80
70
60
50
1111N =
SUBJECT
ControlSCA8
BR
IXT
ON
140
120
100
80
60
40
20
0
1922
TEA: SCA-8 vsControls
Brixton: SCA-8 vsControls
Hayling: SCA-8 vsControls
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
0
1
2
3
4
5
6
7
Part I Part II Error Score
Sca
led
Sco
re
Control
SCA 8
Is there an “affective” Is there an “affective” component?component?
0
2
4
6
8
10
12
14
16
SCA-8 Controls
Scor
e
BDI-IIBDI-II
Minimal
Mild
HADS - DepressionHADS - Depression
0
2
4
6
8
10
SCA-8 Controls
Sco
re
Normal
0
2
4
6
8
SCA-8 Controls
Sc
ore
HADS - AnxietyHADS - Anxiety0
2
4
6
8
10
12
14
16
18
20
SCA-8 Controls
Scor
e
BAIBAI
Minimal
Mild
Moderate
Normal
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 ThoughtsFuture 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)