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Rett syndrome
Unmasking complex cardio-respiratory
dysfunction and possible treatment.
Ingegerd Witt Engerström
MD. PhD. Paediatric neurologist
Medical Director, Swedish Rett Center
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RETT SYNDROME
• Rare
(1:10.000 girls)
• Genetic – seldom inherited
(> 99% sporadic)
• Neuro-developmental disorder – not progressive!
• Immature brainstem/brain
• Central control of the autonomic nervous system insufficient/deranged
• Breathing dysrhythmia
• Blood pressure & heart rate uncontrolled
• Blood circulation in tissues deranged
• Agitation and seizures
• Epilepsy
• Gastrointestinal dysfunction
• Incoordination of thoughts and movements
I. Witt Engerström
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Targets
Contro
l
Monitor, Interpretation,
Integration
Drivers
Ski
n Tachycardi
a
C.A
Muscle
s Bradycardia
Ren
al Gut
Skin
Gut
Kidne
y Muscl
e Adrenal
The
Heart Bradycardi
a Tachycardi
a
Clinical exams must
consider these
functional units
(autonomic nuclei)
We are dealing with basic human physiology
We do not expect these controls to be deranged
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Brainstem features
Breathing dysrhythmia, insufficient control of blood gases, unstable blood pressure and heart rate.
Oropharyngeal and gastrointestinal dysfunctions cause swallowing difficulties, aspiration, gastrooesophageal reflux, oesophagitis and constipation.
Agitation, fear, mood swings, difficulty to relax and concentrate, cold and discoloured feet.
Extrapyramidal symptom: dystonia with orthopaedic deformities, muscle wasting, incoordination of thoughts and movements.
I. Witt Engerström
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Organisation of brainstem nuclei in
adults
Sensory Motor
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Subject
NeuroScope
Breathing
movement
We require Cortico-Bulbar Neurophysiology
Transcutaneous
pO2 and pCO2
Beat-to-beat
non-invasive BP
EEG
Video
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I. Witt Engerström
The Frösö Declaration
Addressing the cardiorespiratory challenges posed by Rett Syndrome in Medicine.
Peter O O Julu, Ingegerd Witt Engerström, Stig Hansen, Flora
Apartopoulos, Bengt Engerström, Giorgio Pini, Robert S Delamont, Eric EJ Smeets. The Lancet 200;371:1981-83.
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I. Witt Engerström
Three cardiorespiratory phenotypes
Forceful breathers Feeble breathers Apneustic breathers
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I. Witt Engerström
Three cardiorespiratory phenotypes
Nutritional needs can be doubled the normal value for forceful breathers.
Feeble or apneustic breathers may not restart spontaneous breathing post-operatively due to artificial hyperventilation.
Feeble breathers are sensitive to sedation (Opioids and Diazepam) and these drugs can cause apnoea.
Valsalva's manouver is a common complication in Rett syndrome.
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Am
plit
ud
e
Ramp
inspiration earl
y
lat
e
Expiration
1 s
Measurement of breathing movements :
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0
3500
Am
plit
ud
e 0
3500
Am
plit
ud
e
0
3500
Am
plit
ud
e
10
s
Deep Breathing
Tachypnoea
Hyperventilation
Forceful
Breathing
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0
3500
Am
plit
ud
e
0
3500
Am
plit
ud
e
0
3500
Am
plit
ud
e
5
s
Rapid Shallow
Shallow
Central Apnoea
Feeble
Breathing
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0
3500
Am
plit
ud
e
0
3500
Am
plit
ud
e
0
3500
Am
plit
ud
e
5 s
Regular Breath-holds
Breath-hold
Protracted
inspiration
Apneustic
Breathing
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60
80
100
120
140
160
Sys
tolic
BP
[m
mH
G]
40
60
80
100
120
140
Hea
rt r
ate
[bp
m]
0
20
40
60
80
Res
pir
atio
n [
arb
un
it]
I IIe IIi III IV
0
10
20
30
0 10 20 30 40 50 60 70 80
CV
T [
LV
S]
Figure 2
Valsalva manoevre in girl with Rett syndrome
Time [s]
Some movement artefacts are present
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Treatment of breathing dysfunction
in Rett syndrome • Forceful breathers: Rebreathing of own expired air in
a rebreathing mask with adjusted dead space, when awake.
• Feeble breathers: Assisted breathing with CPAP or Bi-PAP, mainly at night. Sometimes using an oxygen concentrator initially.
• Apneustic breathers: Buspirone to shorten apneustic breaths, if not too much feeble breathing.
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Outcome of treatment of a forceful breather with
Rett syndrome with a rebreathing mask.
• Increased attentiveness and interest at home and in school.
• Face expressive and smiling in stead of mimicless and serious.
• Muscles less tense, more relaxed.
• Increased muscle strength being able to stand up longer.
• Dramatic decrease of seizures.
• Decrease of cyanosis from several times each day to once in 4 months.
• Normal colour of lips and face.
• Normalisation of colour and temperature of feet (earlier cold and bluish).
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Outcome of treatment of a feeble breather with Rett
syndrome with a Bi-PAP/CPAP.
• Her face does not turn grey or blue.
• Her gross motor ability has improved.
• She is calmer and more attentive.
• She resopnds to people around her with a smile.
• She sleeps better at night.
• Dramatic decrease of seizures.
• Normalisation of colour and temperature of feet (earlier cold and bluish).
• Decrease of cyanosis from several times each day to once in 4 months.
• Normal colour of lips and face.
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100 µV
1 sec
11:21:37 – 70 Hz, 0.50 Hz, 50 Hz
A
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12:07:52 – 70 Hz, 0.50 Hz, 50 Hz 100 µV
1 sec
B
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References
• Julu, Witt Engerström, Hansen,
Apartopoulos, Engerström, ESRRA
group: Treating hypoxia in a feeble
breather with Rett syndrome.
Brain&Development 2012.
• Julu, Witt Engerström, Hansen,
Apartopoulos, Engerström, Pini,
Delamont, Smeets: Cardiorespiratory
challenges in Rett syndrome.
The Lancet 2008.
• Julu, Witt Engerström: Assessment of
the maturity related brainstem
functions reveals the heterogenous
phenotypes and facilitates clinical
management of Rett syndrome.
Brain Dev 2005 Nov;27 Suppl 1:S43-
53.
• Julu: In Kerr & Witt Engerström (eds):
Rett Disorder and the developing brain.
Oxford University Press 2001; 131-181.
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Tissue respiration
• Tissue respiration:
Transport from blood
vessles to tissue needs
energy.
• Energy is made by mitichondria in the cells and needs both oxygen and carbon dioxide at right levels.
• Without adequate oxygen or carbon dioxide tissue, respiration becomes anaerobic – produces a slight amount of energy and causes pain. The body gets progressively week, stiff, ”burnt out”.
• May be understood as progression of the disorder.