Standards of Care post-diagnosis Action Duchenne Conference 2015 Michela Guglieri JWMDRC Newcastle upon Tyne [email protected]

Standards of Care post-diagnosis

Action Duchenne Conference 2015

Michela GuglieriJWMDRC Newcastle upon Tyne

[email protected]

Standards of Care for DMD

Publication date: Lancet Neurology January and February 2010NICE accreditation of guideline generation September 2011

Updating process under way


Key implications:Stage specific care




http://www.treat-nmd.eu/dmd/care/family-guide/

TREAT-NMD website

When to suspect DMD

MU

C

S

LE

S

otor milestone delay

nusual gait

peech delay

K

eading to

arly diagnosis

equencing


Diagnosis

DMD can NOT be diagnosed using CK test only

The diagnosis needs to be confirmed using genetic testing

Why is it important to have a genetic diagnosis?It help making plans for the boy’s care

It allows genetic counselling and carrier testing

It prepares for possible participation in clinical trials (mutation-specific)


Getting the right information on DMD

Diagnosis of DMD

Ask your clinician any question you have

Contact with a support group or advocacy organization can be of particular help (www.treat-nmd.eu/ dmdpatientorganisations)

Websites

http://www.actionduchenne.org

http://www.treat-nmd.eu/

http://www.musculardystrophyuk.org/

http://www.parentprojectmd.org/


http://www.actionduchenne.org/










Diagnosis of DMD



Specialised Neuromuscular centre

Critical role in care co-ordination and timely introduction to relevant specialists

Neuromuscular centre

Genetic counsellor

Physician (paediatric neurologist, geneticist)

Physiotherapist

Cardiologist

Respiratory physician

Endocrinologist

Orthopetic surgeon

DieticianAction Duchenne Conference 2015

Genetic counsellor


Family planning

Carrier testing


6 monthly follow up appointments

Monitoring any abnormality or change which might require interventions


Muscle strength and function

Time testing

Range of joint mobility

Activities of daily living

Bone health

Family well being



To understand how the condition is changing

To identify the best time to commence treatment

To monitor the effect of treatment

To advise on changes in the treatment


The North Star Ambulatory Scale


Activity 2 1 0CommentsScore

1. StandStands upright, still and symmetrically, without compensation (with heels flat and legs in neutral) for minimum count of 3 seconds

Stands still but with some degree of compensation (e.g. on toes or with legs abducted or with bottom stuck out) for minimum count of 3 seconds

Cannot stand still or independently, needs support (even minimal)

2. Walk Walks with heel-toe or flat-footed gait patternPersistent or habitual toe walker, unable to heel-toe consistently

Loss of independent ambulation – may use KAFOs or walk short distances with assistance

3. Stand up from chair

Keeping arms folded. Starting position 90º hips and knees, feet on floor/supported on a box step.

With help from thighs / push on chair / prone turn or alters starting position by widening base.

Unable

4. Stand on one leg - right

Able to stand upright in a relaxed manner (no fixation) for count of 3 seconds

Stands but either momentarily or with trunk side-flexion or needs fixation e.g. by thighs adducted or other trick

Unable

5. Stand on one leg - left

Able to stand upright in a relaxed manner (no fixation) for count of 3 seconds

Stands but either momentarily or with trunk side-flexion or needs fixation e.g. by thighs adducted or other trick

Unable

6. Climb box step - right

Faces step – no support neededGoes up sideways / rotates trunk / circumducts hip or needs support

Unable

7. Climb box step - left

Faces step – no support neededGoes up sideways / rotates trunk / circumducts hip or needs support

Unable

8. Descend box step -right

Faces forward, steps down controlling weight bearing leg. No support needed

Sideways, skips down or needs support or uses method that avoids flexing supporting knee - one on the box step

Unable

9. Descend box step -left

Faces forward, steps down controlling weight bearing leg. No support needed

Sideways, skips down or needs support or uses method that avoids flexing supporting knee - one on the box step

Unable

10. Gets to sitting

Starts in supine – may use one hand / arm to push up Uses two arms / pulls on legs or turns towards floor. Unable

11. Rise from floor

No evidence of Gower’s manoeuvre.Exhibits at least one of the components described on page63 – in particular rolls towards floor, and/or use hand(s) on legs

(a) NEEDS external support of object e.g. chair OR (b) Unable

Timed

12. Lifts headIn supine, head must be lifted in mid-line. Chin moves towards chest

Head is lifted but through side flexion or with no neck flexion (protracts)

Unable

13. Stands on heels

Both feet at the same time, clearly standing on heels only (acceptable to move a few steps to keep balance) for count of 3

Only raises forefeet or only manages to dorsiflex one foot.

Unable

14. JumpBoth feet at the same time, clear the ground simultaneously

One foot after the other (skip) or does not fully clear both feet at the same time.

Unable

15. Hop right leg

Clears forefoot and heel off floor Able to bend knee and raise heel, no floor clearance Unable

16. Hop left leg

Clears forefoot and heel off floor Able to bend knee and raise heel, no floor clearance Unable

17. Run (10m)

Both feet off the ground (no double stance phase during running)

‘Duchenne jog’. Walk Timed

TOTAL= /34


Timed functional tests


Time to get up from the floor

Time to run 10 meters

Time to climb and descend 4 steps

Normal motor development


Age Gross Motor milestones

2 years RunningWalking up and down stairs

3 years Climbing steps with alteranting feetBroad jump

4 years Hoping on one footGoing down steps with alternating feetBalancing on each foot for 3-6 seconds


Corticosteroids

Currently, steroids are the only drug available that can improve muscle strength in DMD

Equipoises

When should Corticosteroids be started in DMD?

Which corticosteroids and which regime?

Henriette Van Ruiten: Steroids: current advances (Friday, 6th Nov, 11.30-12.30)


Corticosteroids

When to start?

The plateau phase

Age 4-5 years

Early starter benefit more

Early treatment (< 4 years) might be associated with better long term outcomes

Balance with side effects

2 4 6 yrs

Ricotti et al, 2014


Corticosteroids

FOR DMD studyFind the Optimum Corticosteroid Regime for DMD

Randomized, double blind, multi-centre international study

Aim to compared the three more commonly prescribed corticosteroid regimes in DMD

Prednisolone 0.75 mg/kg daily

Deflazacort 0.9 mg/kg daily

Prednsilone 0.75 mg/kg 10 days on and 10 days off

Benefits and side effects

The study will inform clinician and families about which regime is associated with the higher benefits and better side effect profile


Corticosteroids

225 boys 4-7 years old, steroid naive

www.for-dmd.org @FOR_DMD

Cambridge

Leeds

London

Birmingham

Liverpool

Newcastle

Manchester

GlasgowDr Iain Horrocks, Glasgow

Prof Volker Straub, Newcastle

Dr Anne-Marie Childs, Leeds

Dr Stefan Spinty, Liverpool

Dr Imelda Hughes, Manchester

Dr Helen Roper, Birmingham

Dr Adnan Manzur, London

Dr Gautam Ambegaonkar

http://www.for-dmd.org/

Corticosteroids

What to start?

Prednisolone 0.75 mg/kg daily Deflazacort 0.9 mg/kg daily Prednisolone 0.75 mg/kg 10 days on/10 days off

Alternate day regime has been shown to be less effective than daily regimes

Doses < 0.3 mg/kg/day are not effective

Inclusion criteria for clinical trials are becoming strict on corticosteroid regimes


Corticosteroids

Blood tests (haematology, biochemistry, including glucose)

IgG varicellla Zoster Cardiac check (ECG and Echocardiogram) Bone density scan (DEXA) Eye check (to exclude cataracts)

Discussion about corticosteroids should be done soon after the diagnosis

Pre-steroid assessments


Corticosteroids

Follow up: 3 and 6 months after starting treatment and every 6 months thereafter

Benefits (muscle strength and function)

Side effects (weight, height, urine dipstick, blood pressure, behavior, bone health) Urine dipstick and blood pressure: every 2-3 weeks for the first 3

months


Physiotherapy

Specialised evaluation every 4-6 months

Contracture prevention

Appropriate exercise


Joint contractures are caused by reduced active movements (muscle weakness) and fibrotic changes in muscle tissue

Prevention of joint contractures is important and should be started soon after the diagnosis

Avoid development of reduced joint movement

Better tolerated

Range of joint mobility


Contracture prevention

At early stages, stretching should be limited to the ankles but should be done regularly

Stretching should be done a minimum of 4–6 days per week

At home and/or school

Assessment in clinic

Focus on specific joints depending on age


Exercise

Regular, exercise is recommended

Especially in young boys

High-resistance strength training and eccentric exercise (e.g. Trapolining) are inappropriate

Swimming-pool exercises and recreation-based exercises in the community.

Myoglobinuria can be a indicator of overexertion


Bone Health

Vitamin D supplementations

Vitamin D3 800-1000 IU/L

Any child < 5 years

All boys on steroids

In case of Vitamin D insuffiency/deficiency

Boys with DMD have a reduced bone density even before staeroid treatment

No specific interventions required at early stages


Referrals after diagnosis

Respiratory physician

Force Vital Capacity, Peak cough flow

Pneumococcal vaccination

Annual Flu jab

Cardiologist

ECG and Echo

At diagnosis, every 2 years until the age of 10, annually thereafter


Neurodevelopmental and psychosocial issues

Possible co-existence of Learning disability Speech and language problems ADD/ ADHD, Autism spectrum disorder, OCD

Need for assessment and management

Individualised educational plan

Active attention to social isolation, adjustment, coping


Being ready for clinical trials

Any therapeutic approach is likely to be most successful in early stages of the condition when the muscles are less damaged and therefore in young children

Receiving standards of care

Being on the patient registry


DMD Registry

Database for all patients with DMD (BMD and female carriers)

Genetic and Medical information

Identification of subjects suitable for clinical trials

Geographically locate subjects with specific characteristic (site selection)

Keep patients and families informed about research, clinical trials and outcomes


32Lancet Neurology 2010

Physiotherapyand assistive technology

Cardiac assessment and treatment

Steroid treatment

Pulmonary support

Diagnosis

Support and co-ordination of care

Bone Health

Psychosocial/educational issues

Emergencies

Taking step by step

DMD is a condition that changes with time

Intereventions needs to be adjusted based on the «stage» of the condition and individual needs

Essentials


[email protected]

Questions?


Documents

Standards of Care post-diagnosis Action Duchenne Conference 2015 Michela Guglieri JWMDRC Newcastle upon Tyne [email protected]