An update on scoliosis in Rett

syndrome

Family Forum 2014: Beyond RespiteDr Jenny Downs, BAppSci(physio), MSc, PhD

The human spine• 33 vertebrae joined with ligaments

and muscles• Top 24 are movable• Protected within is our spinal cord

• Supports upright postures • Bipedalism associated with

development of spinal curves• Support the weight of the head• Absorb shock• Maintain balance

• The spine is vulnerable

Diab, M. “Cobb Angles.” Diagram. Vitale et al. Assessment and Decision Making in Adolescent Idiopathic Scoliosis: Use of theLenke Classification System, 2009.

Australian Rett Syndrome Database (AussieRett)

Scoliosis in Rett syndrome

• Population-based study (n=242 in 2006)

Percentage affected Age

25% 6 y

50% 9 y 9 m

75% 13 y

Ager et al 2006

What influences the development of scoliosis in Rett syndrome?

• Factors that relate to impairments• Mutation - those with the p.R294X or the p.R306C mutation less likely

to develop scoliosis

• Factors that relate to functional abilities• Scoliosis more common if not walking

• Activity provides functional stretch to muscles and builds muscle strength and fitness

Agar et al 2006

Scoliosis guidelines• Project initiated in 2008 due to the poor evidence base

and requests from families for information• Delphi technique

• Literature review• Recruitment of an expert, multidisciplinary and international

panel• Review of successive iterations of clinical management

statements

• Comprehensive set of guidelines• Monitoring• Promotion of an active lifestyle• Indications for spinal surgery• Hospital management

Available at www.interrett.org.au/

Monitoring

• Monitor at 6 to 12 monthly intervals depending on

• Progression of curve• Age of onset• Skeletal maturity• Cobb angle• Ambulation

• Regular observation• Xray if clinical concern

Scoliosis trajectories (n=102)

Conservative management

• The strongest body with the least deformity• We still do not know how best to manage and not clear

that we can reverse a progressive curve, but current options include:

• Bracing• Stretch and activity• A structured postural schedule

• Day and sleep positioning• Over-correction Lotan et al 2005

Bracing• Positive impacts

• Helpful if sitting is difficult • May help to delay the timing of surgery

• Negative impacts• Poorer mobility and can be uncomfortable• Can cause pressure areas, skin irritation, hot

Ager et al 2009

Physical management

Some slides from Bas Jensen and Meir Lotan

Fri Thurs Wed Tue Mon Sun

Physio Hydro Physio Hydro 08:00

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Example of daily curriculum

Lotan 2005

Sleeping positioning – one method

• Place a large piece of Top-to-Toe Mesh over the mattress and tuck it in both sides.

• Put a smaller piece of mesh over the top.

• Put a fibre mattress topper and sheet over the top of the mesh.

• Build support for the person by fixing brackets, pillows, rolls etc between the two layers of mesh http://www.simplestuffworks.co.uk/downloads

Asymmetrical positioning Lotan et al, 2005

Marked progression is not inevitable

• Some develop scoliosis and it remains mild

15 years old 21 years old 23 years old

“We encourage her to sit on the floor with her legs crossed, which she does very wellwith a nice straight back and also keeping her active, walking, bike riding, swimming.”

Progressive scoliosis• Severe scoliosis

• Pain

• Deterioration of sitting and walking

• Restrictive to the lungs

• Spinal fusion considered if the Cobb angle > 50o, in the context

• Osteoporosis

• Gastro-intestinal disorders

• Epilepsy

Spinal fusion• Clinicians consider potential

advantages and risks

• Families consent• Feelings of fear, obligation, guilt

and/or relief “We were making a decision on her

behalf, it wasn’t her decision, she hadn’t really been consulted.”

• Since 1996, 87 (22.1%) Australian girls and women have undergone spinal fusion.

• Following surgery, the literature suggests

• Improved spinal symmetry and sitting

• Stabilised of respiratory and digestive function

• Motor skills at least maintained to pre-operative levels

Medical record review of 54 (62%) girls who underwent spinal fusion at 6 Australian hospitals

Posterior approach 30/52 (58%)

Anterior and posterior 17/52 (33%)

Anterior only 5/52 (10%)

Inclusion of pelvis21/48 (42%)

The hospital stay (n=54)Complications N (%)

Respiratory 22 (40.7%)Over sedation 3 (5.6%)

Wound infection 2 (3.7%)Injury to spinal cord 1 (1.8%) Return to ICU 7 (12.9%)

Number of days Median (range)

In ICU 2 (0 - 23)

In hospital 11.5 (7 – 52)

And what did families think about their hospital care?

• 2011/2012 – family questionnaire included questions on satisfaction with spinal fusion

• General • Specific aspects of the care processes• Open ended questions

• Content analysis for themes

• 63/66 questionnaires returned (response fraction 95.5%)

5-point response scale

Daughter’s characteristics (n=63)

Median (range) years

Diagnosis of scoliosis 8 (1 - 14.5)

Age of surgery 13 (8.3 - 17.9)

Age at questionnaire 21.6 (9.5 - 35.1)

Pre-operative mobility n (%)

Independent walking 4 (6.4%)

Assisted walking 14 (22.2%)

Unable to walk 45 (71.4%)

Levels of satisfaction

Median (range)

General level of satisfaction

5 (2 - 5)

Would recommend to others facing a similar

situation5

(2 – 5)

Feel less anxious about their daughter’s future

health4

(2 – 5)Pre-operative ICU Ward Discharge

What families want at the hospital

• The A team from preoperative preparation until discharge• Confidence, experience and pro-activeness

• Strong clinician family relationships• Regular, clear and consistent information• Decisions take into account the family’s knowledge and point of view

• Pain management• Consistent pain management in ICU and ward settings• Timing of doses and careful assessment for reducing meds

• Surveillance over the longer term• Monitoring of spine• Attention to posture and positioning for seating and sleeping

What about recovery after hospital discharge?

• Very little is known about

• Course of recovery • The emotional journey

experienced by families

Qualitative study

1.Investigate the course of recovery in girls with Rett syndrome

2.Explore family perspectives on spinal fusion

Data collected by Caitlin Marr, Honours student

Interviews – daughter’s characteristics (n=25)

Median (range) years

Age of surgery 12.9 (8.3 - 17.9)

Age at questionnaire 17.3 (10.8 – 26.2)

Pre-operative mobility n (%)

Independent/assisted walking 10 (40%)

Supported standing 11 (44%)

Wheelchair dependent 4 (16%)

The road to recovery … Wellness

•Increased constipation and lethargy in hospital•Appetite, pain and mood improved quickly after discharge

“She seemed happier, she was sitting up straight and looking at the world.”

•Energy levels improved at ~6 months •Improvements in chest-related issues by 12 months

Inpatient rehabilitationGross motor skill Week 1 Week 2

Sitting (n=25) 23 (92%) -Standing (n=21) 8 (38%) 10 (48%)Walking (n=10) 6 (60%) 1 (10%)

How do girls recover gross motor skills after spinal fusion?

Regaining pre-operative sitting –52% by 1 month80% by 3 and 88% by 12 months

Standing and walking

Regaining pre-operative standing 19% by 1 month71% by 6 and 81% by 12 months

Regaining pre-operative walking 20% by 1 month70% by 6 and 80% by 12 months

How did families reduce the emotional burden?

• Preparation • “From the time the surgeon says ‘you’ll need this and that’ start getting an OT and

physio involved to help prepare with the equipment you’ll need”

• Support structures• “For families who haven’t got great informal support, just to make sure they’ve

got good formal supports”

• Confidence in decision, self and staff• “She looked so thrilled, sitting up, big smiles and looking really proud of herself…

we just knew we had made the right decision”

• Finding personal time • “The biggest thing was having more time for myself. Having a break, because it

was 24/7”

Physical activity after spinal fusion

1580 steps

5562 steps

Walks independently before and after fusionAge at fusion: 13 yearsAge data collected: 23 years

Walks min assist before and after fusionAge at fusion: 15 yearsAge data collected: 16 years

Unable to walk before and walking mod assist after fusionAge at fusion: 17 yearsAge data collected: 26 years

320 steps

854 steps

1508 steps

2030 steps

The future …….

• Monitoring scoliosis and promote pro-active lifestyle• Understand the trajectory of scoliosis and the influences of genetic and non-

genetic factors • There is a critical need for us to better understand the best methods of

conservative management

Therapy for Rett syndrome focusing on hand and gross motor

functionFamily Forum 2014: Beyond Respite

Dr Jenny Downs, BAppSci(physio), MSc, PhD

Neurological factors that affect movement

MeCP2 protein first expressed in the

brainstem and thalamus then expressed more

rostrally

Altered muscle tone

1. Low then increasing with age2. May be asymmetrical - spine and hips at risk

Poor balance and ataxia

1. Balance may be harder soon after regression2. May affect sitting, standing and walking

Dyspraxia

1. Thinking about the task at hand2. Recall of past experiences3. Planning the movement4. Convert the planning into action

Hand function• Varies with type of mutation, age, influenced by motivation• Video study of grasping different objects (n=144)

1. Establish rapport with eye gaze and other assisted communication methods

2. Give time give time for performance of the task

3. Give praise for achievements 4. Use appropriate sensory stimulation prior

to functional tasks to increase conscious attention to hands (eg, rubbing lotion on the hand, massage, passive movements)

5. Provide appropriate rewards (eg, music)

1. Supporting the person

1. Identify meaningful and age-appropriate activities 2. Practice hand skills with guided feeding: Support

the initiated movements using the child’s intent and refine the movement

3. Provide choices4. Use cause and effect toys

2. Appropriate tasks

3. The environment supporting the person

1. Ensure sitting posture is well balanced2. Equipment such as wheelchair tray, elbow or hand splints, modified eating and drinking utensils3. Reduce distractions and consider music for mood and behaviour management4. Work with others (eg siblings, teachers, therapist) for consistent support

Gross motor function

• May be affected by altered muscle tone, dyspraxia and co-morbidities of epilepsy and scoliosis

• Video study of 99 girls and women• Age

• Skills generally poorer when older but many still retained the ability to walk

• Genotype • p.R270X and pR168X more severe in comparison to p.R133C, p.R294X and C-

terminal deletions

Sitting

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on chair witha back 10seconds

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Standing

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Transition skills

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Walking skills

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Basic repertoire

Some slides from Bas Jensen and Meir Lotan

Planning and structuring pro-active lifestyles to maintain motor

skills• Treadmill training improved gross motor function and

fitness (n=4) Lotan 2004• Walking and transfer skills improved with practice (n=3)

Larrson 2001• Hydrotherapy associated with improved hand, feeding

and gross motor function (n=1) Bumin 2003 • 4-week structured program of supported feeding led to

improved feeding skills (n=5) Piazza 1993 • Training of switch and adaptive toy use (n=1) Sullivan

1995

Conductive educationGeneral motor skills scores Lotan 2012

Initial 1 6 9 12 16 200

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Intervention periodBaseline

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Conductive educationComplex motor skills scores Lotan

2012

Thus far we have Motor Learning Theory

Intrinsic:1. Feelings of rapport2. Allow time to overcome dyspraxia3. Sensory stimulation prior to the activity3. Give praise and rewards for achievements4. Following performance, adequate rest

Task related:1. Provide choices between activities2. Practice with engaging and age-appropriate activities3. Avoid undue fatigue or stress

Learning of motor skills

Environment related:1. Ensure the setting is safe2. Use equipment and toys to optimize the girl’s motivation 3. Practice the tasks in different ways – eg, walking on hard floor and very soft floor surfaces4. Work with the other therapists and parents so that the goals can be consistently supported5. Create a proactive environment

Need to learnmotor skills

Can we do better?Can we collect the evidence that we need for stronger advocacy of

early intervention programs

Add in the theory of environmental stimulation and

BDNF• Neurotrophins are proteins important for

• Nerve development and connectivity• During development, nerve cells compete for neurotrophins and those that

receive them will grow and develop

MECP2 gene

MeCP2 protein

BDNF gene

Dendritic branching Development of dendritic spines

Environmental enrichment has been tested in mice with a MECP2 mutation

Motor stimulation

Cognitive stimulation

Visual stimulation

Somatosensory stimulation

Baroncelli 2010Copyright 2010 Nature Publishing Group

Soon to start in China ……

• Activities • Consistent with Motor Learning

Theory• A high volume of practice and

physical activity, and biologically, will aim to increase production of BDNF

• Integration of motor activity with choice making, sensory reinforcement, cognitive engagement and social participation

• Up to 4 girls in group “kindy” style sessions, each with a therapist • Sessions –

• 2 hours a day on 5 days in a week• 3 week blocks separated by 1

week off

Acknowledgements• All participating families in Australia and internationally for

contributing information • The Consumer Reference Group for the Australian Rett

Syndrome Study who guide the direction of our research• The families who provided photos and video of their

daughters• NHMRC and NIH funding for our Rett syndrome research