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Monitoring function in Rett syndrome for Clinical Trials

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Monitoring function in Rett syndrome for Clinical Trials Helen Leonard Anne Marie Williams Jenny Downs Clinical Severity Score from Percy et al. (2000) 1: Age at ... – PowerPoint PPT presentation

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Title: Monitoring function in Rett syndrome for Clinical Trials


1
Monitoring function in Rett syndrome for Clinical
Trials
  • Helen Leonard
  • Anne Marie Williams Jenny Downs

2
Clinical Severity Scorefrom Percy et al. (2000)
  • 8 Respiratory dysfunction
  • 9 Epilepsy and seizures
  • 10 Hand use
  • 11 Feeding
  • 12 Onset of stereotypies
  • 13 Somatic growth
  • 14 Autonomic dysfunction
  • 15 Scoliosis
  • 1 Age at onset of regression
  • 2 Head growth
  • 3 Motor function
  • 4 Crawling and creeping
  • 5 Ambulation
  • 6 Nonverbal communication
  • 7 Language

3
Clinical Features Scorefrom Kerr et al. (2001)
  • A Head circumference during
  • first year
  • B Early developmental progress
  • 0-6 months
  • C Present head circumference
  • D Weight
  • E Height
  • F Muscle tone
  • G Spine posture
  • H Joint contractures (not used)
  • I Gross motor function
  • J Hand stereotypies (wringing
    squeezing,patting, mouthing)
  • K Other involuntary movements
  • L Voluntary hand use
  • M Oro-motor function
  • N Intellectual disability
  • O Speech
  • P Epilepsy
  • Q Disturbed awake breathing rhythm
    (hyperventilation, panting, breath holding)
  • R Peripheral circulation of extremities
  • S Mood disturbance
  • T Sleep disturbance

4
Clinical Severity Scorefrom Pineda et al. (2001)
  • 6 Respiratory function
  • 7 Epilepsy
  • 8 Hand use
  • 9 Air swallowing / bloating
  • 10 Onset of stereotypies
  • 1 Age at loss of social interaction
  • 2 Head growth
  • 3 Sitting alone
  • 4 Ambulation
  • 5 Language

5
What do we need for a clinical trial
  • Measurement of symptoms that are clinically
    relevant
  • Sensitive to interventional change
  • Use appropriate measurement of signs and symptoms

6
Normal development of hand function
  • Infants - visually attend to objects and their
    own hands before they can reach and grasp
  • Neonatal period - Reflex palmer grasp, hand to
    mouth
  • 6 months - raking to pick up an object and
    development of reach
  • 7-9 months - scissors grasp, transfers, bangs 2
    objects together, patting etc
  • 9 months inferior pincer grasp
  • 10-12 months superior pincer grasp, pokes
    object with finger, more precise release
  • 12-15 months building tower with 2 cubes
    etc....

7
Normal development of hand function
  • Infants - visually attend to objects and their
    own hands before they can reach and grasp
  • Neonatal period - Reflex palmer grasp, hand to
    mouth
  • 6 months - raking to pick up an object and
    development of reach
  • 7-9 months - scissors grasp, transfers, bangs 2
    objects together, patting etc
  • 9 months inferior pincer grasp
  • 10-12 months superior pincer grasp, pokes
    object with finger, more precise release
  • 12-15 months building tower with 2 cubes
    etc....

8
What do we see in Rett syndrome?
  • Loss of hand function skills during early
    childhood usually to a very low level
  • Usually good head control and potential for
    looking at objects
  • Development of apraxia disorder of skill not
    related to tone, weakness, co-ordination, tremor
  • But may also have altered muscle tone, tremor,
    stiffness, hand stereotypies develop and there is
    an intellectual deficit

9
Hand function in Rett syndrome
  • Poor hand function is one of the core diagnostic
    criteria single most informative early sign of
    RTT
  • Einspieler 2005 video pre-regression suggests
    variations in early hand skills
  • Cass 2003 80 could grasp and 60 could hold
    an object
  • 25-43 can finger feed
  • Umansky 2003 marked restriction of hand
    function, internal gt external object function and
    simple (eg holding cup) gt complex (eg playing
    with toy)

10
Hand function assessment in Rett syndrome
  • Mount 2002 and Cass 2003 broad 8 point Likert
    scale without defined categories
  • Mount 2002 RSBQ does not use hands for
    purposeful grasping 3 point scale
  • Ellaway 2001 Rett Syndrome Symptom Checklist
    yes/ no responses to a series of tasks uses the
    Hand Apraxia scale and the tasks are supposed to
    be summative
  • Fitzgerald 1990 Rett Syndrome Motor-Behavioural
    Assessment does not reach for objects or
    people and hand clumsiness 5 point scale

11
Hand function assessment in RTT (cont)
  • RTT global severity scales
  • Kerr
  • None (54), reduced or poor (32), normal(14)
  • Pineda
  • never acquired (11)
  • acquired and lost (44)
  • lost purposefulness lt 24 months but conserved
    grasping (16)
  • lost purposefulness 2-6 years with conserved
    manipulation (17)
  • acquired and conserved (11)
  • Percy
  • never acquired (11)
  • holding objects acquired and lost (33)
  • holding objects acquired and partially conserved
    (44)
  • acquired and conserved (11)

12
Hand use by mutation
13
Summary of RTT hand assessments
  • Limited characterisation of variability and
    unlikely to be able to capture improvements
    resulting from an intervention
  • The meaning of the categories are not always
    clear and some items/category labels are
    subjective
  • Limited psychometric information
  • Variability in hand function seen on our videos
    and described as case studies in the literature
    (Umansky 2001) therefore a more sensitive
    assessment based on observations and not
    judgements is required

14
Other specific hand function assessments
  • Erhardt Developmental Prehension Assessment
  • 3 sections primary involuntary hand/arm
    patterns, primary voluntary movements,
    pre-writing skills
  • Primary voluntary movements posture, reach,
    grasp and manipulation
  • Score gives a functional age
  • Peabody Developmental Fine Motor Scale
  • Comprises 112 items, 4 skill categories including
    grasping, hand use, eye-hand co-ordination and
    manual dexterity
  • Quality of Upper Extremity Skills Test
  • 4 domains dissociated movements (64 items),
    grasp (24 items), weight bearing (50 items) and
    protective extension (36 items)
  • Each item comprises several subitems and there
    are a total of 174 items which are coded on a
    dichotomous scale of can or cant do
  • Manual Ability Classification System
  • 5 levels, developed for children with cerebral
    palsy
  • Classifies according to how the child handles
    objects with a background of spasticity and less
    relevant to severe intellectual disability

15
Other hand function assessments
  • Physical disability scales eg WeeFIM, Pedi
    scale, some of the arthritis scales (Functional
    Status Index and Health Assessment Questionnaire
  • Items usually relate to feeding and use of
    utensils, opening car doors, dialling on the
    phone
  • Either doesnt capture detail of the hand
    function or may not be relevant to those with a
    severe intellectual disability

16
Hand Apraxia Scale
  • Burd et al 1990
  • 10 items with a yes no response
  • Methods
  • Population characteristics not clear
  • Carer report for responses needed to do skill
    25 of time when asked
  • Reported as summative and continue testing until
    a negative response for an item
  • Represents a suggestion that holding precedes
    picking up and holding large objects precedes
    small objects

17
More thoughts on the Hand Apraxia Scale
  • Scanning of 2004 questionnaire responses show
    that the yes responses are not summative but are
    scattered throughout the 10 items
  • What is functional hand use?
  • Why does ability to finger feed precede ability
    to pick up large objects?
  • Why does picking up a small object come after
    putting a small object in a container and taking
    it out again?
  • Why is drinking from a cup a hand skill?

18
2004 and 2007 video study
  • Families asked to film their daughter picking up
    and holding a selection of large objects (toy,
    small ball, cup, utensil) and a small object
    (sultana, smartie, often demonstrated with a
    dried apricot, small pieces of sandwich etc)
  • Described reach, accuracy, initiation of
    movement, pre-shaping of the hand, transfer,
    raking or pincer grasp to pick up small objects
  • Viewing other activities that gave us additional
    opportunities for observation
  • Development of a video-based evaluation tool in
    Rett syndrome. Journal of Autism and
    Developmental Disorders Fyfe et al.
    200737(9)1636-46.

19
Hand function at work
20
Hand assessment so far
  • N 116, 103 showed hand function, 13 missing
    hand function footage. Best efforts were coded
  • Development of levels based on observation,
    sultana girls were roughly the mid point, worked
    backwards and forwards looking at frequencies
  • So far 8 levels of function
  • Describe picking up objects and transferring
  • Doesnt describe pointing, pressing a switch,
    dexterity...

21
Level 1
  • No evidence of active hand function
  • N 25 (18 with mutation)

22
Level 2
  • (1) hold a large object but not grasp or pick up
    the object OR (2) pick a large object up
    momentarily but drop immediately
  • Represents a single skill
  • N13 (9 with a mutation)
  • 11 could hold and 2 could pick up
  • 6/13 (46.2) looked at the object
  • 4/13 (30.1) had some form of reach

23
Level 3
  • Pick up and hold a large object and sometimes a
    small object
  • Increased variability, combination of movements
    and greater potential for function
  • N8 (5 with mutation)
  • 4/8 (50) looked at the object
  • 3/8 (37.5) could reach
  • 1/8 (12.5) picked up a small object

24
Level 4
  • Reach, grasp, hold and pick up one of the large
    objects
  • Could not grasp, hold and pickup a small object
  • N12 (6 with a mutation)
  • Two could also pick up and hold a small object
    but need help to grasp the small object
  • 11/12 (91.7) looked at the object
  • 8/12 (66.7) reached accurately
  • 3/12 (25.0) initiated movement satisfactorily
  • no close approximation when pre-shaping the hand

25
Level 5
  • Reach, grasp, pick up and hold a small object
    using a raking grasp
  • N10 (7 with a mutation)
  • All girls looked at the object
  • 8/10 (80.0) reached accurately
  • 8/10 (80.0) initiated movement satisfactorily
  • 2/10 (20.0) could transfer
  • 0/10 (0.0)had close pre-shaping of the hand

26
Level 6
  • Reach, grasp, pick up and hold a small object
    using the thumb a scissors, inferior pincer or
    pincer grasp
  • N 20 (19 with mutation)
  • All girls looked at the object
  • All girls reached accurately
  • 15/20 (75.0) initiated movement satisfactorily
  • 0 could transfer
  • 3/20 (15.0) had close pre-shaping of the hand

27
Level 7
  • Could achieve level 6 and also demonstrated
    ability to transfer an object
  • N8 (6 with mutation)
  • All looked at the object
  • All reached accurately
  • 7/8 (87.5) initiated movement satisfactorily
  • None had close approximation of hand orientation
    and size recognition when preshaping hand

28
Level 8
  • Those who could achieve level 7 and who also
    demonstrated close pre-shaping skills of hand
    orientation and size recognition
  • N 6 (3/6 with mutation)
  • All looked at the object, reached accurately and
    initiated movement satisfactorily

29
Distribution of hand function level
30
What next?
  • Validation of scale
  • Construct Relationship between hand function
    and finger feeding, age, genotype, WeeFIM scores
  • Concurrent - relationship between hand function
    and Pineda scale item (existing scale with the
    biggest spread of abilities)
  • Content and face probably reasonable from
    todays presentation
  • Reliability test retest and intertester R

31
Special thanks go to...
  • National Institutes of Health
  • NHMRC
  • Australian Paediatric Surveillance Unit
  • Anne Marie Williams
  • Jenny Downs, Carol Philippe, Philippa Carter, Ami
    Bebbington,Sue Fyfe and the team
  • Janelle Lillis and family
  • Bill Callaghan and the Rett Syndrome Association
    of Australia
  • The families and clinicians who support the
    research so well

Current funding NIH 1 R01 HD043100-01A1 NHMRC
303189
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