Spinocerebellar Ataxia Type 8 SCA8

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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
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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

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Case History - Examination

• Mild limb ataxia
• Dysarthric, slowed repetitive tongue movements
• MMSE 30/30
• Buoyant mood, poor insight

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Cognitive Screening

• Predicted FSIQ 110
• but lt 20th centile on
• Stroop
• Trails A and B
• Verbal/Category fluency
• Immediate/delayed recall of story
• Rey Osterreith figure
• Wisconsin (very poor)

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MRI Scan
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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)

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Spinocerebellar Ataxia Type 8 (SCA 8)

• Koob et al, Nature Genetics, 199921379-384
• Family 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 SCAs
• Unusual - the repeat expansion is transcribed but
  not translated
• Myotonic Dystrophy - same mechanism

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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?)

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SCA-8Demographics, MRI
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SCA 8Neuropsychiatric symptoms
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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

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• The SCA-8 expansion is associated with
  neurological and upper motor neuron signs.
• Are there also cognitive (specifically
  executive) and / or affective links?

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The Tests

• Methodology
• Pre-Morbid IQ
• Current FSIQ
• Memory Screening
• Executive Tests

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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)

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The Results...
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SCA- 8 Mean Scores
Controls Mean Scores
FSIQ Memory Executive Tests
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Average WAIS III Index Scores SCA-8 Subjects
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Control 1 (Scores percentiles)
SCA- 8 (Atrophy) CB (Scores percentiles)
FSIQ Memory Executive Tests
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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

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PFSIQ SCA-8 vs Controls
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Mean Executive Function Tests SCA-8 vs Controls
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StroopSCA-8 vs Controls
COWAT SCA-8 vs Controls
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TEA SCA-8 vs Controls
Hayling SCA-8 vs Controls
Brixton SCA-8 vs Controls
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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 ?

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(No Transcript)
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• Is there an affective component?

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BDI-II
Mild
Minimal
HADS - Depression
Normal
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BAI
Moderate
Mild
Minimal
HADS - Anxiety
Normal
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Anxiety Symptoms Reported

• Wobbliness in legs
• Unsteady
• Numbness or Trembling
• Hands Shaking
• Shaky

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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)

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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)