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 110but < 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 sc

ore

0

20

40

60

80

100

Predic

ted FSIQ

Actual F

SIQ

Verba

l Immed

iate

Verba

l Dela

yed

Visual Im

mediat

e

Visual D

elayed

Stroop

Haylin

g (%ile

)

Brixto

n(%ile

)

TEA Timing

(%ile

)

COWAT (%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-II

I Ind

ex S

core

s

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

EDF

SIQ

130

120

110

100

90

80

70

18

8

10

PFSIQ: SCA-8 vs Controls

1111N =

SUBJECT

ControlSCA8

MEA

NEX

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

WAT

160

140

120

100

80

60

19

14

15

10

Stroop:SCA-8 vs ControlsCOWAT: SCA-8 vs Controls

1111N =

SUBJECT

ControlSCA8

HAY

LIN

G

140

120

100

80

60

40

18

19

1111N =

SUBJECT

ControlSCA8TE

A

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

Scal

ed S

core

ControlSCA 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

Scor

e

Normal

0

2

4

6

8

SCA-8 Controls

Scor

e

HADS - AnxietyHADS - Anxiety02468

101214161820

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)