Spinocerebellar Ataxia Type 8 (“SCA-8â€‌)

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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. - PowerPoint PPT Presentation

Text of Spinocerebellar Ataxia Type 8 (“SCA-8â€‌)

  • 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, 199846 year old man with 5 year history:neurological signsslurred speech, ataxia, impaired dexteritycognitive declineforgetfulness, difficulty with divided attentionpersonality changelabile mood, aggressive outbursts, inflexibility

  • Case History - ExaminationMild limb ataxiaDysarthric, slowed repetitive tongue movementsMMSE 30/30Buoyant mood, poor insight

  • Cognitive ScreeningPredicted FSIQ 110but < 20th centile on:StroopTrails A and BVerbal/Category fluencyImmediate/delayed recall of storyRey Osterreith figure

    Wisconsin (very poor)

  • MRI Scan

  • Family HistoryMother, 75 years oldimpulsive and inflexible from 40sdysarthricincongruous affectcategory fluency: 6 (animals), 4 (letter)failed Luria test (5 trials)

  • Spinocerebellar Ataxia Type 8 (SCA 8)Koob et al, Nature Genetics, 1999;21:379-384Family: 21 affected, 20 unaffected carriers:SCA-8 is a risk factor for expression of condition DNA based triplet repeat disorder (as is Huntingtons Disease)One of an enlarging family of SCAsUnusual - the repeat expansion is transcribed but not translatedMyotonic Dystrophy - same mechanism

  • Reported Clinical Features of SCA-8Cerebellar 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

    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:Neuropsychiatric symptoms

    Cognitive

    Memory

    Emotional

    Personality

    ED

    +

    GR

    +

    CB

    +

    +

    +

    IC

    ICa

    +

    +

    +

    YB

    +

    +

    +

    +

    GH

    RH

    ~ +

    ~ +

    JG

    +

    +

    +

    SM

    +

    +

    +

    CM

    +

    (AG)

    +

    +

  • Schmahmann & Sherman 1998Cerebellar 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 TestsMethodology Pre-Morbid IQ Current FSIQMemory ScreeningExecutive Tests

  • Executive Function TestsCOWAT Verbal Initiation, SpeedStroop Speed, sustained attention, attentional switchingHayling and Brixton Verbal initiation, suppression, speed, rule detection and followingTEA Visual Elevator Subtest attentional switching, speed (MWCST)(BADS 6 Elements)

  • The Results...

  • SCA- 8: Mean ScoresControls: Mean ScoresFSIQMemoryExecutive Tests

    Grouped Average

    4161

    25.666666666749.75

    55.7565.9166666667

    20.646666666762.4483333333

    SCA-8

    Controls

    Data Table

    Middle points for averages:

    Percentiles:

    Predicted FSIQActual FSIQVerbal ImmediateVerbal DelayedVisual ImmediateVisual DelayedStroopHayling (%ile)Brixton(%ile)TEA Timing (%ile)COWAT (%ile)StroopHayling (%ile)Brixton(%ile)TEA Timing (%ile)COWAT (%ile)

    MrsCowan6627508499MrsCowan2.0-4.025

  • Average WAIS III Index ScoresSCA-8 Subjects

    Grouped Average

    4161

    25.666666666749.75

    55.7565.9166666667

    20.646666666762.4483333333

    SCA-8

    Controls

    Data Table

    Middle points for averages:

    Percentiles:

    Predicted FSIQActual FSIQVerbal ImmediateVerbal DelayedVisual ImmediateVisual DelayedStroopHayling (%ile)Brixton(%ile)TEA Timing (%ile)COWAT (%ile)StroopHayling (%ile)Brixton(%ile)TEA Timing (%ile)COWAT (%ile)

    MrsCowan6627508499MrsCowan2.0-4.025

  • SCA- 8 (Atrophy): CB(Scores percentiles)Control 1(Scores percentiles) FSIQMemoryExecutive Tests

    Data Table

    Middle points for averages:

    Percentiles:

    Predicted FSIQActual FSIQVerbal ImmediateVerbal DelayedVisual ImmediateVisual DelayedStroopHayling (%ile)Brixton(%ile)TEA Timing (%ile)COWAT (%ile)StroopHayling (%ile)Brixton(%ile)TEA Timing (%ile)COWAT (%ile)

    MrsCowan6627508499MrsCowan2.0-4.025

  • RESULTSSignificant difference in performance executive function tests (p = 0.007)Non significant trend towards difference in performance on Visual MemoryMain discrepancies stemming from Hayling (p = 0.005) and Stroop (0.015)Least difference in performance on Brixton

  • PFSIQ: SCA-8 vs Controls

  • Mean Executive Function Tests: SCA-8 vs Controls

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

  • TEA: SCA-8 vsControlsBrixton: SCA-8 vsControlsHayling: 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 ?

  • Chart1

    6.14.5

    64.1

    6.55.2

    Control

    SCA 8

    Scaled Score

    Mean Scaled Score on Hayling Parts I, II and Error Score

    Sheet1

    Part IPart IIError Score

    Control6.166.5

    SCA 84.54.15.2

  • Is there an affective component?

  • BDI-IIMinimalMildHADS - DepressionNormal

    Grouped Average

    4161

    25.666666666749.75

    55.7565.9166666667

    20.646666666762.4483333333

    SCA-8

    Controls

    Data Table

    Middle points for averages:

    Percentiles:

    Predicted FSIQActual FSIQVerbal ImmediateVerbal DelayedVisual ImmediateVisual DelayedStroopHayling (%ile)Brixton(%ile)TEA Timing (%ile)COWAT (%ile)StroopHayling (%ile)Brixton(%ile)TEA Timing (%ile)COWAT (%ile)

    MrsCowan6627508499MrsCowan2.0-4.025

  • HADS - AnxietyBAIMinimalMildModerateNormal

    Grouped Average

    4161

    25.666666666749.75

    55.7565.9166666667

    20.646666666762.4483333333

    SCA-8

    Controls

    Data Table

    Middle points for averages:

    Percentiles:

    Predicted FSIQActual FSIQVerbal ImmediateVerbal DelayedVisual ImmediateVisual DelayedStroopHayling (%ile)Brixton(%ile)TEA Timing (%ile)COWAT (%ile)StroopHayling (%ile)Brixton(%ile)TEA Timing (%ile)COWAT (%ile)

    MrsCowan6627508499MrsCowan2.0-4.025

  • Anxiety Symptoms ReportedWobbliness in legsUnsteadyNumbness or TremblingHands ShakingShaky

  • ConclusionsSCA-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 ThoughtsProgressionre-test in approx 2 yearsMechanismsresults from present study do not elucidate the role of the cerebellum in cognition as SCA-8 may affect other brain regions (work underway)

    Jon Stone 2000SCA-8 is one in a growing family of inherited Cerebellar AtaxiasLiterature Review - 0.7% of normal population have gene expansionUnclear at this stage which additional conditions have to be met for expression of symptoms

    Schmahmann & Sherman, 1998: Cerebellar Cognitive Affective Syndrome. 20 cases of diseases confined to the cerebellum - resulting in impaired executive function, visuo-spatial organisation and memory. Personality change - blunted affect or dis-inhibited behaviour.Schmahmann and Sherman (1998) Cerebellar Cognitive Affective Syndrome.Methodology - Minimal Load on Individuals with Motor Probs- Matched Controls (IQ within +/-1 SD, Sex, Age, Education)Pre-Morbid IQ- WTAR Current Full Scale IQ - WAIS-IIIMemory Screening - Logical MemoryExecutive TestsExecutive Function Tests - Planning, Organising, Sequencing, Shifting of Cognitive Set, Initiation, Inhibition

    COWATStroop - Dysarthria still hope for interference/intrusion. Cognitive inhibition of over-learned response in favour of unusual oneHayling and Brixton - Hayling Response initiation, Response suppression {error score and time. Brixton Rule attainment most commonly reported dysexecutive sign. CLASS of error perseveration, misapplication of strategy, guessing/bizarre. Any findings from data?TEA Visual Elevator - Flexibility, Changing train of thought, timing(MWCST)(BADS 6 Elements)Discussion re difference between Predicted and Acutal FSIQPSI

    40th Percentile = 9761st Percentile = 10421st Percentile = 88Actual FSIQ: CB = 104 Control = 11890 -110 = Average50% of pop IQ 25%ile - 75%ile