Transcript Slide 1

FASD
Barnsley Oct 11
Dr Raja Mukherjee
Consultant Psychiatrist / Honorary Senior
Lecturer
Lead Clinician FASD Behavioural Clinic
Surrey and Borders Partnership NHS trust/
St George's university of London
[email protected]
[email protected]
1.Fetal Alcohol Syndrome : Confirmed alcohol exposure :
Diagnostic Terms
•Alcohol Exposure
•Facial pattern of Short palpebral fissures < / = 10 percentile, Thin upper lip vermillion, Smooth
philtrum
•Evidence of pre / postnatal growth retardation
•Evidence of Neurocognitive deficits
2Fetal Alcohol Syndrome: No confirmed alcohol exposure
•As above but no alcohol exposure found
3Partial Fetal Alcohol syndrome: Confirmed Alcohol Exposure
•Not all of the above features are present but neurocognitive and some facial features needed
4Alcohol Related Birth Defect (ARBD)
•Confirmed maternal alcohol consumption as well as some but not all of the facial features are
present however the behavioural features or structural abnormalities are more pronounced.
5Alcohol Related Neurodevelopmental Disorder (ARND)
•Confirmed maternal alcohol consumption with the absence of growth retardation or facial features
and with the neurocognitive features being prominent.
6 Fetal Alcohol Spectrum Disorders
•Umbrella term. Not a diagnostic term
Other Terms to be discussed later
Summary of diagnostic categies and methods. (Stratton 1996 Hoyme 2005).
Alcohol as a Teratogen
How genetics works
Genes
Amino Acids
Proteins
Organs
Abnormal genetics
Genes Faulty
Amino –
Acids
coded
incorrectly
Organs
Malformed
Incorrect
Proteins
How a Teratogen has
effect
Genes
Amino Acids
Teratogen e.g.
Alcohol
Abnormal
Proteins
Epigenetics
•
The study of heritable changes in
gene function not controlled by
changes in the DNA sequence.
Epigenetic phenomena play a
significant role in development
and evolution, and include histone
modifications and DNA
methylation
Example of epigenetic in action in genetically identical mice using the 'agouti
viable yellow', or Avy
•
•
•
Avy gene has little or no
methylation, then it is active in all
cells, and the mouse is yellow
Avy is highly methylated, it
switches off throughout the entire
body. This means the mouse is a
sooty-brown colour
In between these two extremes,
Avy can be methylated to varying
degrees
Incidence and risk
Examples of recent prevalence studies using
the same methodology
Prevalence Rates /1000 population
FAS
PFAS
FASD
S Africa
59.2
Western
cape 2002
Italy 2006
6.2
28.0
35.2
Croatia 2010 6.4
34.3
40.8
78.6
Rates
• Figure as high as 3.5 % has been quoted in
research (may 2006)
• We don’t know what is the UK figure
• Percentage drinking during pregnancy
– 61% DOH
– 57% IFS
• International prevalence
– 1/1000 FAS
– 9.1 / 1000 FASD (O’Leary 2003)
– 1-2 / 100 FASD ( University of Washington 2004)
• This figure is changing
• Figure as high as 3.5 % has been quoted in
research (may 2006)
• We don’t know what is the UK figure
• Percentage drinking during pregnancy
– 61% DOH
– 57% IFS
Rates
Risk by drinking group
Level of Alcohol Consumption
Number of Women in
group
(Millions)
Is this true level What should we expect?
Note of caution this is assumption and not
known
Nil
Low occasional
3.1
14.2
0
Above recommend levels
2.6
Binge
1.9
Moderate – heavy
2.5
Heavy
0.6
Totals
24.9
Few not as many as figures
quoted
Possible more but probably not
at levels quoted
Unknown but regular binge
drinking high risk and probably
higher than figures quoted
Probably higher than figures
quoted
Higher than figures quoted
FASD Risk 1/ 100 or FAS 1./1000
Relationships
ARND
No identifiable
Problem
How it presents
Mukherjee et al JRSM 2006
Gray and Mukherjee JMHLD 2007
Reasons for referral
•
•
•
•
Growth problems
Behavioural issues
Learning issues
Physical problems
What do people know
Mukherjee, Wray, Hollins, Curfs
Themes
•
•
•
•
Lack of knowledge
Need for consistent guidance/ Cynicism
Need for education
Lack of support services
Professional Attitudes
Do you feel you have been generally provided with enough
information to acquire knowledge for yourself? (N = 427)
Yes
No/ Don't know
N
Valid %
Yes
176
41.2%
No/ Don’t know
251
58.8%
Professional Attitudes
Do you feel you have been generally provided with enough
information to advise pregnant mothers safely? (N = 417)
Yes
No/ Don't know
N
Valid %
Yes
115
27.6%
No/ Don’t know
302
72.4%
Diagnosis
Facial features
Comparison: Child with
FAS and mouse fetus with
fetal alcohol exposure
Child with FAS
Mouse fetuses
Small head
Short palpebral fissures
Small nose
Small midface
Long philtrum;
Thin upper lip
*
alcohol-exposed
normal
Critical periods and
facial features
Normal Alc–Day 7Alc–Day 8
Fetus
Neonate
Modified from Sulik et
al.
Slides Courtesy of Professor E Riley University of San Diego
Methods of Diagnosis of facial abnormalities: note all of these require
careful history taking and evidence of growth retardation to make the
diagnosis (Chudley 2005)
• Gestalt: Facial pattern recognition requires experience and clear
history. Issues of accuracy and inconsistency often found
• D Score method: computational method for facial pattern based on
careful measurements of abnormalities: requires a high degree of
training and skill restricting practice to a few.
• 4 Digit scoring method and Facial photographic
recognition software: applies areas of history and facial
recognition to four 4-point likhert scales to establish diagnosis.
Requires minimal training and can be used easily by all in clinical
settings.
Comparison between diagnostic Tools
CDC
IOM revised
Canadian
4 Digit
Face
10th percentile
PFL and rank 4/5 on
lip philtrum
10th percentile PFL
and rank 4/5 on lip
philtrum
3rd percentile PFL
and rank 4/5 on lip
philtrum
3rd percentile PFL
and rank 4/5 on lip
philtrum
Growth
Pre / post natal
growth below 10th
percentile
Pre / post natal
growth below 10th
percentile
Pre / post natal
growth below 10th
percentile
Pre / post natal
growth below 10th
percentile
Neurological
1 out of several brain
parameters including
OFC <10 %, CNS
deficits
1 out of l brain
parameters including
OFC <10 %, CNS
deficits
Or abnormal
structure
3+ soft hard
neurological signs
1 out of several brain
parameters including
OFC <3 %, CNS
deficits
Alcohol
Confirmed or
unknown
Confirmed to be
excessive or
unknown
Confirmed or
unknown
Confirmed or
unknown
Screening tool Designed and used by
Raja Mukherjee
Tools to help identify drinking behaviours
•
First Things First
– Ethical considerations
•
•
History and rapport
Screening tools
–
–
–
–
•
MAST
Audit-C
TACE
TWEAK
Biomarkers
– Meconium FFA
– Hair Sample / Urine
analysis
– Blood Test
4 Digit Diagnostic Code
•
•
Astley and Clarren 96,00,02
4 broad categories
–
–
–
–
Growth
Facial features
Brain
Alcohol exposure
•
•
•
•
Based on defined criteria giving score each areas and then diagnosis
26 Categories
Static encephalopathy
A,B,C,E,F, (G,H) relate to FASD diagnoses
•
Caution (requires modification of Alcohol scoring)
4- Digit Score and Photographic Software
• She hates me
for This!!!
• Forgave me
after getting
some flowers!
4- Digit Score and Photographic Software
•
•
Known marker for pixel
length
Allows Calculation of
perameters
4- Digit Score and Photographic Software
•
•
•
Known marker for pixel length
Allows Calculation of
perameters
More objective way of
discrimination
4- Digit Score and Photographic Software
Lip Philtrum Guide from 4 Digit Score Schedule : Astley and Clarren University of Seattle
4- Digit Score and Photographic Software
•
•
•
•
•
•
•
Known marker for pixel
length
Allows Calculation of
perameters
More objective way of
discrimination
Still some subjectivity
Gives a range of Scores
Combined with other
parameters leads to overall
score
My Wife’s Score : 1212 : P
– No Physical or CNS
abnormalities
FAS Child 12
ARND Child 15
FAS or not? Case 1
FAS or not? Case 2
? Who was exposed to more alcohol case 1 or 2
Cause or Effect?
Top down or bottom up ?
Top Down: Phemomenology
Bottom Up: Aetiology
Cluster of Symptoms
Inattention
Poor Planning
Poor social understanding
Receptive language deficits
obsessionality
Hyperactivity
Cognitive flexibility problems
Poor imagination
Expressive language deficits
Tics
Impulsivity
Working Memory deficits
Cluster of Symptoms: ADHD
Inattention
Hyperactivity
Poor Planning
Tics
Cognitive flexibility problems
Impulsivity
Receptive language deficits
Expressive language deficits
Poor social understanding
Poor imagination
obsessionality
Working Memory deficits
Cluster of Symptoms: ASD
Poor Planning
Inattention
Cognitive flexibility problems
Hyperactivity
Impulsivity
obsessionality
Tics
Receptive language deficits
Expressive language deficits
Poor social understanding
Poor imagination
Working Memory deficits
Cluster of Symptoms: ASD / ADHD
Poor Planning
Cognitive flexibility problems
Inattention
Hyperactivity
Impulsivity
obsessionality
Tics
Receptive language deficits
Expressive language deficits
Poor social understanding
Poor imagination
Working Memory deficits
Cluster of Symptoms: FASD
Working Memory deficits
Poor Planning
obsessionality
Receptive language deficits
Hyperactivity
Inattention
Poor social understanding
Cognitive flexibility problems
Poor imagination
Impulsivity
Expressive language deficits
Tics
Characteristic vs. Discriminating symptoms
3 Disorders with overlapping symptoms
C
D
D
C
C = Characteristic: D= Discriminating
D
What is so important about an S?
• Fetal alcohol spectrum Disorder
– Unitary diagnosis
– Separate from others
• Fetal Alcohol Spectrum disorders : note the S!!
– An umbrella term
– Donates the range of conditions that can be encompassed by
the effects of alcohol in utero
– Becomes a teratogenic aetiological factor causing
phenomenological outcomes
– Not mutually exclusive from current diagnostic criteria
Aetiology Vs Phenomenology
Receptive language deficits
Expressive language deficits
Poor social understanding
Poor imagination
FASD
Fragile X
Noonans
Downs
Common Ground
Downs
obsessionality
Inattention
Hyperactivity
Tics
Cognitive flexibility problems
Impulsivity
Poor imagination
Poor Planning
Noonans
Pre
Frontal
Cortex
Damage
Fragile X
Poor social understanding
FASD
Relationships
ADHD
ASD
Mental health
problems
No identifiable
Problem
Full FAS
ARND
DC- LD
•
•
•
•
•
Developed Faculty of Learning
Disability Psychiatry 2001
Multiaxial
1Severity of LD
2Cause of LD
3Psychiatric Disorders
–
–
–
–
–
A Developmental disorders
B Psychiatric illness
C Personality Disorders
D Problem Behaviours
E Other Disorders
Multi axial way of thinking!
Level of Functioning
Aetiology e.g. FASD
Symptoms e .g. Autism
Depression
16
16
14
12
11
10
F84.0 = 76.2%
8
No ASD = 19.0
6
4
4
2
0
ICD10 F84.0 Childhood Autism Gilberg Aspergers Criteria 2001
No ASD
Type of Social
Impairment
:From DISCO scoring
7
6
5
FAS
Partial FAS
ARND
No FAS
Combined
4
3
2
1
0
er
th
O
of
lo
A
t
bu
e
iv
ss
Pa
e
iv
ct
A
Bishop et al: FASD group more likely
to initiate social contact
d
od
Possible correlation with IQ level p=0.005
Management approaches based on pulling
all what has been learnt together
What does it all mean to me?
Impulsivity / Distractibility
12
11
10
9
8
No Clear statistical link with the
Small numbers between
Diagnosis
•Age
•IQ
•Sex
6
4
2
1
0
DSM IV 314.01
ADHD Combined
DSM IV 314.00 Did not meet criteria
ADHD Inattentive
Type
Ranking of most difficult behaviours with score of 1.5
Mean on DBC
DBC Parameter
Mean Score
Easily Distracted
1.95
Over excited
1.86
Impulsive
1.81
Problems with feelings
1.77
Poor sense of danger
1.76
Easily Led
1.75
Poor attention span
1.71
Temper Tantrums
1.70
Impatient
1.65
Irritable
1.61
Tells Lies
1.52
Does not mix with own peer group
1.50
Attention seeking
1.50
Single item analysis of ADHD diagnostic criteria:
inattentive symptoms
Percentage of Group meeting
Criteria (n) Total in group (21)
Not pay attention
81 (17)
Fail to stick at task
76.2 (16)
Not listen when spoken to
81 (17)
Fail to Finish an instruction
95.2 (20)
Difficulties planning
90.5 (19)
Avoid areas find difficult
90.5 (19)
Loose things needed for task
85.7 (18)
Easily distracted
100 (21)
Forgetful
90.5 (19)
Lobe Analysis
150000
Controls
p = .0003
FAS
Volume
120000
90000
p = .0002
p = .018
60000
p = .030
30000
0
Frontal
Temporal
Parietal
Occipital
Lobe
*
Slides Courtesy of Professor E Riley University of San Diego
Change in cerebellum size
Cerebellum
Cerebrum
100
95
90
85
NDFASD
FAS
80
75
Corpus Callosum
*
p < 0.001
Cerebellum
Mattson et al., 1994
Slides Courtesy of Professor E Riley University of San Diego
Summary of other research in this area
• People with FASD is worse in the visual modality than
the auditory. Coles 2002
• Executive function in deficit in people with FASD
Rasmussen 2005
– Not simply related to IQ
– Not related to dysmorphology
• Relationship between frontal brain size and maternal
alcohol consumption Wass et al 2001, Persutte 2000
• Executive functioning not reflective of IQ Connor 2000
Executive control of
Schemas
Executive control
Hungry
Activating
Impulse
Orange
Schema
Peel orange
schema
Action
Peel Orange
Supervisory Attention System = EC
Norman and Shallice 86
Executive control of
Schemas
Executive control
Not Hungry
Activating
Impulse
Orange
Schema
Peel orange
schema
Action
Peel Orange
Norman and Shallice 86
Executive control of
Schemas
Executive control
Not Hungry
Activating
Impulse
Orange
Schema
Peel orange
schema
Action
Peel Orange
Norman and Shallice 86
Decision making
Ranking of most difficult behaviours with score of 1.5
Mean on DBC
DBC Parameter
Mean Score
Easily Distracted
1.95
Over excited
1.86
Impulsive
1.81
Problems with feelings
1.77
Poor sense of danger
1.76
Easily Led
1.75
Poor attention span
1.71
Temper Tantrums
1.70
Impatient
1.65
Irritable
1.61
Tells Lies
1.52
Does not mix with own peer group
1.50
Attention seeking
1.50
Active Memory
Model
Central
Executive
Long term memory store
Visual spatial
Active memory
Stored visual spatial information
Semantic active
memory
Stored semantic information
Phonological
Active memory
Stored phonological information
Model of relationship between Working memory,
Consolidation system and long term memory
Working Memory
Long Term
Memory Store
Consolidation system
Hippocampal Circuit
Entorhinal Cortex ->
Dentate Gyrus ->
CA3 ->
CA1 ->
Subiculum ->
Fimbria ->
Fornix
Examples of other research in this area
• Immediate memory worse than long term memory
Mattson 2002
• Working memory and effects on attention affected by
alcohol Burden 2005
• GABAa receptors affected by alcohol more likely to be
linked to deficits with memory Gibbs 2005
• Linked to Executive deficits already shown
The frontal lobes, making
logical decisions
Frontal Cortex
Thalamus
Caudate * Accumbens
*
100
Striatum
Globus Pallidus
(caudate & putamen)
(part of lenticular nucleus)
95
90
85
80

*
75
NDFASD
70
FAS
***
Concordant with animal data
Slides Courtesy of Professor E Riley University of San Diego
White versus gray
matter
• What is Myelin?
– Clinically delayed myelination it
has been observed
– Riikonen et al., 1999
– alcohol-induced delayed
myelination are due to the
delayed expression of myelin
basic protein (MBP) and
transferrin
– Ozer et al., 2000
Slides Courtesy of Professor E Riley University of San Diego
Summary of other research in this area
• Prenatal alcohol linked to slower processing speed
Burden 2005b
• Trade off between speed and accuracy Sampson 1997
• Problems passing information between hemispheres
Roebuck 2002
A possible model of Executive function integration
Motor Response
Posterior
Stepping on Brake initiated,
Stepping on accelerator inhibited
Anterior Cingulate
Initiating and
focusing attention
Motivating
Reward
behaviour
Medial
Inhibiting
Unwanted
behaviour
Lateral
Orbito Frontal Cortex
Association
Areas
Time 2
Child
Crossing
Dorsolateral
Pre frontal
Cortex
Selecting
And
Monitoring
Directory
schemas
Time 1
Green light
Knowledge
and
action
Schemas
How the brain
organises information
A
B
C
D
E
How the brain
organises information
A
B
D
C
E
Executive Control monitors locates and plans activities
How the brain organises information
D
A
B
C
E
Executive Control monitors locates and plans activities
How the brain organises
information
A
B
Pedestrian
crossing
How to cross a
road
C
Cars can kill
Executive Control monitors locates and plans activities
Source Monitoring
Individual learns where something is and
stores information how items linked
A
B
When asked to recall information the
source of the learning is muddled
A
B
How the brain organises
information : External
Support
B
A
Pedestrian
crossing
How to cross a
road
C
Cars can kill
Executive Control monitors locates and plans activities
Ways of overcoming
memory deficts
•Structure and routine
•Repetition
•Not expecting people to
learn quickly and changing
your not their experiences
•Concrete tasks avoiding
ambiguity
Mental Health
Rates of Autism in other conditions
Behavioural phenotype
80
60
FA
FA SD R
S
M
FA D B
SD ish
La op
ng
dr
Do
e
w Fra n
n
g
Co s Sy ile X
rn nd
el
r
ia om
de e
lan
ge
40
20
0
Behavioural
phenotype
Type of Social
Impairment
:From DISCO scoring
7
6
5
FAS
Partial FAS
ARND
No FAS
Combined
4
3
2
1
0
er
th
O
of
lo
A
t
bu
e
iv
ss
Pa
e
iv
ct
A
Bishop et al: FASD group more likely
to initiate social contact
d
od
Possible correlation with IQ level p=0.005
Vineland adaptive behaviour schedule: adaptive age scores
(n=19) (2 not returned)
Domain
Minimum
Maximum
Average
Age
6.10
16.00
9.93 (95%CI)
Receptive language
1.1
5.6
3.12 (2.56-3.67)
Expressive
language
2.2
13.0
5.23 (3.99-6.46)
Written Language
4.5
14.0
8.73(7.37 – 10.09)
Personal Daily living
Skills
2.3
8.6
5.62 (4.54-6.69)
Domestic Daily
living skills
1.1
11
5.61(4.33-6.90)
Community skills
3.6
10.6
6.27 (5.30 – 7.24)
Interpersonal skills
0.11
10.0
4.2 (3.05 -5.37)
Play/ leisure
socialisation
1.0
8.0
4.56 (3.56 – 5.56)
Coping
1.6
9.6
3.99 (3.11 -4.86)
Secondary Disabilities
Disability
%
Psychiatric problem
90
Disrupted School
experience
60
Trouble with the law
60
Confinement
50
Inappropriate sexual
behaviour
50
Alcohol /Drug
problems
30
Streissguth et al 1996, 2000
Frequency as a % of Psychiatric
Diagnoses seen in cohorts of people
with FASD
Total
Alcohol / Drug
Dependence
Major Depression
Psychotic Disorder
Bipolar 1
Anxiety disorder
Eating Disorder
PD
Famy 1997 (n=23) Barr 2006 (n=136?)
92
60
53.5
44
40
20
20
16
48
47.9
1.4
2.8
33.8
4.2
Where can I go for help?
Referral pathways
•
•
•
•
•
•
•
Clinical Genetics (diagnosis only)
FASD Specialist (very few around)
Paediatrician
Child psychiatry
Often need to
Child Psychology Specify
suspected
Adult Psychiatry
diagnosis
LD Psychiatry
FASD Clinic
SPECIALST
FETAL ALCOHOL SPECTRUM DISORDER CLINIC
Information leaflets and referral
process available
Second European Conference on
FASD
Fetal Alcohol Spectrum Disorder: Clinical and Biochemical
Diagnosis, Screening and Follow-up
Barcelona 21-24 October 2012
Venue: Barcelona Biomedical Research Park, PRBB
Av. Dr. Aiguader 88, 08003 Barcelona, SPAIN
www.prbb.org
Questions
SAVE THE DATE – 13th & 14th October
2011
Launch of UK Professionals Forum on
FASD
(Foetal Alcohol Spectrum Disorders)
Practical guide for those who want to
know what to do