Title: FASD Barnsley Oct 11
1FASD 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 - Raja.mukherjee_at_sabp.nhs.uk
- rmukherj_at_sgul.ac.uk
2Diagnostic Terms
- 1.Fetal Alcohol Syndrome Confirmed alcohol
exposure - Alcohol Exposure
- Facial pattern of Short palpebral fissures lt /
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
Summary of diagnostic categies and methods.
(Stratton 1996 Hoyme 2005).
3Alcohol as a Teratogen
4How genetics works
Genes
5Abnormal genetics
Genes Faulty
6How a Teratogen has effect
Genes
Teratogen e.g. Alcohol
7Epigenetics
- 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
8Example 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
9Incidence and risk
10Examples of recent prevalence studies using the
same methodology
Prevalence Rates /1000 population Prevalence Rates /1000 population Prevalence Rates /1000 population
FAS PFAS FASD
S Africa Western cape 2002 59.2 78.6
Italy 2006 6.2 28.0 35.2
Croatia 2010 6.4 34.3 40.8
11Rates
- Figure as high as 3.5 has been quoted in
research (may 2006) - We dont know what is the UK figure
- Percentage drinking during pregnancy
- 61 DOH
- 57 IFS
12Rates
- International prevalence
- 1/1000 FAS
- 9.1 / 1000 FASD (OLeary 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 dont know what is the UK figure
- Percentage drinking during pregnancy
- 61 DOH
- 57 IFS
13Risk 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 3.1 0
Low occasional 14.2 Few not as many as figures quoted
Above recommend levels 2.6 Possible more but probably not at levels quoted
Binge 1.9 Unknown but regular binge drinking high risk and probably higher than figures quoted
Moderate heavy 2.5 Probably higher than figures quoted
Heavy 0.6 Higher than figures quoted
Totals 24.9
FASD Risk 1/ 100 or FAS 1./1000
14Relationships
15How it presents
- Mukherjee et al JRSM 2006
- Gray and Mukherjee JMHLD 2007
16Reasons for referral
- Growth problems
- Behavioural issues
- Learning issues
- Physical problems
17What do people knowMukherjee, Wray, Hollins,
Curfs
18Themes
- Lack of knowledge
- Need for consistent guidance/ Cynicism
- Need for education
- Lack of support services
19Professional Attitudes
- Do you feel you have been generally provided with
enough information to acquire knowledge for
yourself? (N 427)
N Valid
Yes 176 41.2
No/ Dont know 251 58.8
20Professional Attitudes
- Do you feel you have been generally provided with
enough information to advise pregnant mothers
safely? (N 417)
N Valid
Yes 115 27.6
No/ Dont know 302 72.4
21Diagnosis
22Facial features
23 Comparison Child with FAS and mouse fetus with
fetal alcohol exposure
Mouse fetuses
Small head
Short palpebral fissures
Small nose
Small midface Long philtrum Thin upper lip
normal
alcohol-exposed
24Critical periods and facial features
Modified from Sulik et al.
Slides Courtesy of Professor E Riley University
of San Diego
25(No Transcript)
26Methods 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.
27Comparison 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 lt10 , CNS deficits 1 out of l brain parameters including OFC lt10 , CNS deficits Or abnormal structure 3 soft hard neurological signs 1 out of several brain parameters including OFC lt3 , CNS deficits
Alcohol Confirmed or unknown Confirmed to be excessive or unknown Confirmed or unknown Confirmed or unknown
28Screening tool Designed and used by Raja
Mukherjee
29Tools 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
304 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)
314- Digit Score and Photographic Software
- She hates me for This!!!
- Forgave me after getting some flowers!
324- Digit Score and Photographic Software
- Known marker for pixel length
- Allows Calculation of perameters
334- Digit Score and Photographic Software
- Known marker for pixel length
- Allows Calculation of perameters
- More objective way of discrimination
344- Digit Score and Photographic Software
Lip Philtrum Guide from 4 Digit Score Schedule
Astley and Clarren University of Seattle
354- 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 Wifes Score 1212 P
- No Physical or CNS abnormalities
36FAS Child 12
37ARND Child 15
38FAS or not? Case 1
39FAS or not? Case 2
? Who was exposed to more alcohol case 1 or 2
40Cause or Effect?
41Top down or bottom up ?
Top Down Phemomenology
Symptoms / Function
Bottom Up Aetiology
42Cluster of Symptoms
Inattention
Poor social understanding
Poor Planning
Receptive language deficits
obsessionality
Hyperactivity
Expressive language deficits
Cognitive flexibility problems
Tics
Poor imagination
Impulsivity
Working Memory deficits
43Cluster of Symptoms ADHD
Poor Planning
Tics
Cognitive flexibility problems
Receptive language deficits
Expressive language deficits
Poor social understanding
obsessionality
Poor imagination
Working Memory deficits
44Cluster of Symptoms ASD
Poor Planning
Inattention
Cognitive flexibility problems
Hyperactivity
Impulsivity
obsessionality
Tics
Receptive language deficits
Expressive language deficits
Poor social understanding
Working Memory deficits
Poor imagination
45Cluster of Symptoms ASD / ADHD
Poor Planning
Cognitive flexibility problems
Inattention
Hyperactivity
Impulsivity
obsessionality
Tics
Receptive language deficits
Expressive language deficits
Poor social understanding
Working Memory deficits
Poor imagination
46Cluster of Symptoms FASD
Working Memory deficits
Poor Planning
obsessionality
Receptive language deficits
Inattention
Poor social understanding
Hyperactivity
Cognitive flexibility problems
Poor imagination
Impulsivity
Expressive language deficits
Tics
47Characteristic vs. Discriminating symptoms3
Disorders with overlapping symptoms
C
D
C
D
D
C Characteristic D Discriminating
48(No Transcript)
49What 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
50Aetiology Vs Phenomenology
51Common Ground
Downs
Pre Frontal Cortex Damage
Noonans
Fragile X
FASD
52Relationships
ADHD
ASD
Mental health problems
No identifiable Problem
Full FAS
ARND
53DC- 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
54Multi axial way of thinking!
Level of Functioning
Aetiology e.g. FASD
Symptoms e .g. Autism Depression
55F84.0 76.2 No ASD 19.0
56 Type of Social ImpairmentFrom DISCO scoring
Bishop et al FASD group more likely to initiate
social contact Possible correlation with IQ
level p0.005
57Management approaches based on pulling all what
has been learnt together
- What does it all mean to me?
58Impulsivity / Distractibility
59- No Clear statistical link with the
- Small numbers between
- Diagnosis
- Age
- IQ
- Sex
60Ranking 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
61Single 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)
62Lobe Analysis
Slides Courtesy of Professor E Riley University
of San Diego
63Change in cerebellum size
Cerebrum
Cerebellum
Corpus Callosum
Slides Courtesy of Professor E Riley University
of San Diego
64Summary 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
65Executive control of Schemas
Executive control
Hungry
Schema
Peel orange schema
Supervisory Attention System EC
Norman and Shallice 86
66Executive control of Schemas
Executive control
Not Hungry
Schema
Peel orange schema
Norman and Shallice 86
67Executive control of Schemas
Executive control
Not Hungry
Schema
Peel orange schema
Norman and Shallice 86
68Decision making
69Ranking 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
70Active 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
71Model of relationship between Working memory,
Consolidation system and long term memory
Long Term Memory Store
Working Memory
Consolidation system
72Hippocampal Circuit
- Entorhinal Cortex -gt
- Dentate Gyrus -gt
- CA3 -gt
- CA1 -gt
- Subiculum -gt
- Fimbria -gt
- Fornix
73Examples 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
74The frontal lobes, making logical decisions
- Concordant with animal data
Slides Courtesy of Professor E Riley University
of San Diego
75White 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
76Summary 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
77A possible model of Executive function integration
Motor Response Stepping on Brake
initiated, Stepping on accelerator inhibited
Posterior Association Areas
Time 2 Child Crossing
Anterior Cingulate Initiating and focusing
attention
Dorsolateral Pre frontal Cortex Selecting And Mon
itoring Directory schemas
Motivating Reward behaviour Medial
Inhibiting Unwanted behaviour Lateral
Time 1 Green light
Knowledge and action Schemas
Orbito Frontal Cortex
78How the brain organises information
A
B
C
D
E
79How the brain organises information
A
B
C
D
E
Executive Control monitors locates and plans
activities
80How the brain organises information
D
A
B
C
E
Executive Control monitors locates and plans
activities
81How the brain organises information
A
B
How to cross a road
Pedestrian crossing
C
Cars can kill
Executive Control monitors locates and plans
activities
82Source Monitoring
83Individual learns where something is and stores
information how items linked
A
B
84When asked to recall information the source of
the learning is muddled
A
B
85How the brain organises information External
Support
B
How to cross a road
Executive Control monitors locates and plans
activities
86Ways of overcoming memory deficts
- Structure and routine
- Repetition
- Not expecting people to learn quickly and
changing your not their experiences - Concrete tasks avoiding ambiguity
87Mental Health
88Rates of Autism in other conditions
89 Type of Social ImpairmentFrom DISCO scoring
Bishop et al FASD group more likely to initiate
social contact Possible correlation with IQ
level p0.005
90Vineland adaptive behaviour schedule adaptive
age scores (n19) (2 not returned)
Domain Minimum Maximum Average
Age 6.10 16.00 9.93 (95CI)
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)
91Secondary 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
92Frequency as a of Psychiatric Diagnoses seen in
cohorts of people with FASD
Famy 1997 (n23) Barr 2006 (n136?)
Total 92
Alcohol / Drug Dependence 60 53.5
Major Depression 44 47.9
Psychotic Disorder 40 1.4
Bipolar 1 20 2.8
Anxiety disorder 20 33.8
Eating Disorder 16 4.2
PD 48
93Where can I go for help?
94Referral pathways
- Clinical Genetics (diagnosis only)
- FASD Specialist (very few around)
- Paediatrician
- Child psychiatry
- Child Psychology
- Adult Psychiatry
- LD Psychiatry
Often need to Specify suspected diagnosis
95FASD Clinic
SPECIALST FETAL ALCOHOL SPECTRUM DISORDER
CLINIC
Information leaflets and referral process
available
96Second European Conference on FASDFetal 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
97Questions
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