Standards of Care
post-diagnosis
Action Duchenne Conference 2015
Michela Guglieri
JWMDRC Newcastle upon Tyne
Michela.guglieri@Newcastle.ac.uk
Standards of Care for
DMD
Publication date: Lancet Neurology January and February 2010
NICE accreditation of guideline generation September 2011
Updating process under way
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Standards of Care for DMD
Key implications:
Stage specific care
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Standards of Care for
DMD
TREAT-NMD website
http://www.treatnmd.eu/dmd/care/family-guide/
When to suspect DMD
otor milestone delay
nusual gait
peech delay
K
eading to
arly diagnosis
equencing
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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)
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Diagnosis of DMD
 Getting the right information on 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/
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Diagnosis of DMD
http://www.musculardystrophyuk.org/
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Neuromuscular centre
 Specialised Neuromuscular centre
 Critical role in care co-ordination and timely introduction to
relevant specialists
 Genetic counsellor
 Physician (paediatric neurologist, geneticist)
 Physiotherapist
 Cardiologist
 Respiratory physician
 Endocrinologist
 Orthopetic surgeon
 Dietician
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Neuromuscular centre
 Genetic counsellor
 Family planning
 Carrier testing
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Neuromuscular centre
 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
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Muscle strength and function
 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
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Muscle strength and function
Activity
 The North Star
Ambulatory Scale
2
1
0
1. Stand
Stands 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
2. Walk
Walks with heel-toe or flat-footed gait pattern
Loss of independent ambulation – may
Persistent or habitual toe walker, unable to heel-toe consistently use KAFOs or walk short distances with
assistance
Cannot stand still or independently,
needs support (even minimal)
3. Stand up from Keeping arms folded. Starting position 90º hips and knees, feet
chair
on floor/supported on a box step.
With help from thighs / push on chair / prone turn or alters
starting position by widening base.
4. Stand on one Able to stand upright in a relaxed manner (no fixation) for count
leg - right
of 3 seconds
Stands but either momentarily or with trunk side-flexion or needs
Unable
fixation e.g. by thighs adducted or other trick
5. Stand on one Able to stand upright in a relaxed manner (no fixation) for count
leg - left
of 3 seconds
Stands but either momentarily or with trunk side-flexion or needs
Unable
fixation e.g. by thighs adducted or other trick
6. Climb
step - right
box
Faces step – no support needed
Goes up sideways / rotates trunk / circumducts hip or needs
support
Unable
7. Climb
step - left
box
Faces step – no support needed
Goes up sideways / rotates trunk / circumducts hip or needs
support
Unable
8. Descend box Faces forward, steps down controlling weight bearing leg. No
step -right
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 Faces forward, steps down controlling weight bearing leg. No
step -left
support needed
Sideways, skips down or needs support or uses method that
avoids flexing supporting knee - one on the box step
Unable
10.
Gets
sitting
Starts in supine – may use one hand / arm to push up
Uses two arms / pulls on legs or turns towards floor.
Unable
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
In 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
Only raises forefeet or only manages to dorsiflex one foot.
Unable
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
11. Rise
floor
to
from
12. Lifts head
13. Stands
heels
on Both feet at the same time, clearly standing on heels only
(acceptable to move a few steps to keep balance) for count of 3
14. Jump
Both feet at the same time, clear the ground simultaneously
Comments
Score
Unable
Timed
Timed
TOTAL=
/34
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Muscle strength and function
 Timed functional tests
Time to get up from the floor
Time to run
10 meters
Time to climb and descend 4 steps
Muscle strength and function
 Normal motor development
Age
Gross Motor milestones
2 years
Running
Walking up and down stairs
3 years
Climbing steps with alteranting feet
Broad jump
4 years
Hoping on one foot
Going down steps with alternating feet
Balancing on each foot for 3-6 seconds
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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)
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Corticosteroids
When to start?
 The plateau phase
 Age 4-5 years
 Early starter benefit more
2
4
6
yrs
 Early treatment (< 4 years) might be
associated with better long term
outcomes
 Balance with side effects
Ricotti et al, 2014
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Corticosteroids
FOR DMD study
Find 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
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Corticosteroids
 225 boys
 4-7 years old, steroid naive
Dr Iain Horrocks, Glasgow
Glasgow
Newcastle
Prof Volker Straub, Newcastle
Dr Anne-Marie Childs, Leeds
Manchester
Dr Stefan Spinty, Liverpool
Liverpool
Leeds
Dr Imelda Hughes, Manchester
Dr Helen Roper, Birmingham
Dr Adnan Manzur, London
Birmingham
Cambridge
Dr Gautam Ambegaonkar
www.for-dmd.org @FOR_DMD
London
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
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Corticosteroids
 Discussion about corticosteroids should be done soon after the
diagnosis
 Pre-steroid assessments
 Blood tests (haematology, biochemistry, including
glucose)




IgG varicellla Zoster
Cardiac check (ECG and Echocardiogram)
Bone density scan (DEXA)
Eye check (to exclude cataracts)
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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
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Physiotherapy
 Specialised evaluation
every 4-6 months
 Contracture prevention
 Appropriate exercise
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Range of joint mobility
 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
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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
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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 recreationbased exercises in the community.
 Myoglobinuria can be a indicator of
overexertion
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Bone Health
 Boys with DMD have a reduced bone density even
before staeroid treatment
 No specific interventions required at early stages
 Vitamin D supplementations
 Vitamin D3 800-1000 IU/L
 Any child < 5 years
 All boys on steroids
 In case of Vitamin D
insuffiency/deficiency
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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
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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
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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
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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
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Physiotherapy
and assistive
technology
Diagnosis
Steroid treatment
Bone Health
Support and
co-ordination
of care
Emergencies
Pulmonary support
Psychosocial/educatio
nal issues
Cardiac assessment
and treatment
32
Lancet Neurology 2010
Essentials
 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
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Michela.guglieri@ncl.ac.uk
Questions?
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