Helen Leonard Anne Marie Williams Jenny Downs

Clinical Severity Score

from Percy et al. (2000)

1: 2: 3: 4: 5: 6: 7: Age at onset of regression Head growth Motor function Crawling and creeping Ambulation Nonverbal communication Language 8: 9: Respiratory dysfunction Epilepsy and seizures 10: Hand use 11: Feeding 12: Onset of stereotypies 13: Somatic growth 14: Autonomic dysfunction 15: Scoliosis

Clinical Features Score

from Kerr et al. (2001) A: Head circumference during first year B: Early developmental progress 0-6 months C: Present head circumference D: Weight E: F: Height 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 S: T: extremities Mood disturbance Sleep disturbance

Clinical Severity Score

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

• Measurement of symptoms that are clinically relevant • Sensitive to interventional change • Use appropriate measurement of signs and symptoms

• 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....

• 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....

• 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

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 > external object function and simple (eg holding cup) > complex (eg playing with toy)

• 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 point scale – “does not reach for objects or people” and “hand clumsiness” – 5

• RTT global severity scales • Kerr – None (54%), reduced or poor (32%), normal(14%) • Pineda – never acquired (11%) – acquired and lost (44%) – lost purposefulness < 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%)

Hand use by mutation

• 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

• • • •

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 can’t 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

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. 2007;

37

(9):1636-46.

Hand function at work

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 – Doesn’t describe pointing, pressing a switch, dexterity...

Level 1

• No evidence of active hand function • N = 25 (18 with mutation)

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 • N=13 (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

Level 3

• Pick up and hold a large object and sometimes a small object • Increased variability, combination of movements and greater potential for function • N=8 (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

Level 4

• Reach, grasp, hold and pick up one of the large objects • Could not grasp, hold and pickup a small object • N=12 (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

Level 5

• Reach, grasp, pick up and hold a small object using a raking grasp • N=10 (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

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

Level 7

• Could achieve level 6 and also demonstrated ability to transfer an object • N=8 (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

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

30 25 20 15 10 5 0 Le ve l 1 Le ve l 2 Le ve l 3 Le ve l 4 Le ve l 5 Le ve l 6 Le ve l 7 Le ve l 8 No mutation identified Mutation positive

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 today’s presentation – Reliability – test retest and intertester R

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