Spinocerebellar Ataxia Type 8 (SCA-8) The Cognitive and Psychiatric Profile Lorna Torrens, Elaine Burns, Jon Stone, Mary Porteous, Adam Zeman, Helen Wright

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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 Slide 2 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 Slide 3 Case History - Examination Mild limb ataxia Dysarthric, slowed repetitive tongue movements MMSE 30/30 Buoyant mood, poor insight Slide 4 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) Slide 5 MRI Scan Slide 6 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) Slide 7 Spinocerebellar Ataxia Type 8 (SCA 8) Koob et al, Nature Genetics, 1999;21:379-384 Family: 21 affected, 20 unaffected carriers: riskSCA-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 Slide 8 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?) Slide 9 SCA-8: Demographics, MRI Slide 10 SCA 8: Neuropsychiatric symptoms Slide 11 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 Slide 12 The SCA-8 expansion is associated with neurological and upper motor neuron signs. The SCA-8 expansion is associated with neurological and upper motor neuron signs. Are there also cognitive (specifically executive) and / or affective links? Are there also cognitive (specifically executive) and / or affective links? Slide 13 The Tests Methodology Pre-Morbid IQ Current FSIQ Memory Screening Executive Tests Slide 14 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) Slide 15 The Results... Slide 16 SCA- 8: Mean Scores Controls: Mean Scores FSIQMemory Executive Tests Slide 17 Average WAIS III Index Scores SCA-8 Subjects Slide 18 SCA- 8 (Atrophy): CB (Scores percentiles) Control 1 (Scores percentiles) FSIQMemory Executive Tests Slide 19 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 Slide 20 PFSIQ: SCA-8 vs Controls Slide 21 Mean Executive Function Tests: SCA-8 vs Controls Slide 22 Stroop:SCA-8 vs Controls COWAT: SCA-8 vs Controls Slide 23 TEA: SCA-8 vs Controls Brixton: SCA-8 vs Controls Hayling: SCA-8 vs Controls Slide 24 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 ? Slide 25 Slide 26 Is there an affective component? Slide 27 BDI-II Minimal Mild HADS - Depression Normal Slide 28 HADS - Anxiety BAI Minimal Mild Moderate Normal Slide 29 Anxiety Symptoms Reported Wobbliness in legs Unsteady Numbness or Trembling Hands Shaking Shaky Slide 30 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) Slide 31 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)