FASD Barnsley Oct 11 Dr Raja Mukherjee Consultant Psychiatrist / Honorary Senior Lecturer Lead...

FASD Barnsley Oct 11

Dr Raja MukherjeeConsultant Psychiatrist / Honorary Senior LecturerLead Clinician FASD Behavioural ClinicSurrey and Borders Partnership NHS trust/ St George's university of London

[email protected]

[email protected]

mailto:[email protected]

mailto:[email protected]

Diagnostic Terms1.Fetal Alcohol Syndrome : Confirmed alcohol exposure :•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

Incorrect Proteins

OrgansMalformed

How a Teratogen has effect

Genes

Amino - Acids

Abnormal Proteins

Teratogen e.g. Alcohol

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 AfricaWestern

cape 2002

59.2 78.6

Italy 2006 6.2 28.0 35.2

Croatia 2010 6.4 34.3 40.8

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

Rates• 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

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 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

Relationships

Full FAS

ARND

No identifiableProblem

How it presents

Mukherjee et al JRSM 2006Gray and Mukherjee JMHLD 2007

Reasons for referral

• Growth problems• Behavioural issues• Learning issues• Physical problems

What do people knowMukherjee, Wray, Hollins, Curfs

Themes

• Lack of knowledge• Need for consistent guidance/ Cynicism• Need for education• Lack of support services

Professional AttitudesDo 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

Small headSmall head

Small noseSmall nose

Small midfaceSmall midface

Long philtrum; Long philtrum; Thin upper lipThin upper lip

normalnormalalcohol-exposedalcohol-exposed

MouseMouse fetusesfetuses

Comparison: Child with Comparison: Child with FAS and mouse fetus with FAS and mouse fetus with

fetal alcohol exposurefetal alcohol exposure

Child with FASChild with FAS

Short palpebral fissuresShort palpebral fissures

*

Critical periods and facial features

Modified from Sulik et al.

Normal Alc–Day 7Alc–Day 8

Fetus

Neonate

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 ToolsCDC 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



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!


• Known marker for pixel length

• Allows Calculation of perameters


• Known marker for pixel length• Allows Calculation of perameters• More objective way of

discrimination


Lip Philtrum Guide from 4 Digit Score Schedule : Astley and Clarren University of Seattle


• 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 ?

Bottom Up: Aetiology

Top Down: Phemomenology

Cluster of SymptomsInattention

Hyperactivity

Poor social understanding

Impulsivity

obsessionality

Tics

Poor Planning

Cognitive flexibility problems

Working Memory deficits

Receptive language deficits

Expressive language deficits

Poor imagination

Cluster of Symptoms: ADHD


obsessionality

TicsPoor Planning





Poor imagination

Inattention

Hyperactivity

Impulsivity

Cluster of Symptoms: ASD

Inattention

Hyperactivity


Impulsivity

obsessionality

Tics

Poor Planning





Poor imagination

Cluster of Symptoms: ASD / ADHD

Inattention Hyperactivity


Impulsivityobsessionality

Tics

Poor Planning





Poor imagination

Cluster of Symptoms: FASD

InattentionHyperactivity Poor social understanding

Impulsivity

obsessionality

Tics

Poor Planning





Poor imagination

Characteristic vs. Discriminating symptoms3 Disorders with overlapping symptoms

C

C

DD

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




Poor imagination

FASD Fragile X NoonansDowns

Common Ground

Inattention

Hyperactivity


Impulsivity

obsessionality

Tics

Poor Planning


Poor imagination

Pre FrontalCortex

Damage

FASD

Fragile X

Noonans

Downs

Relationships

Full FAS

ARND

No identifiableProblem

ADHDASD

Mental health problems

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!

Symptoms e .g. Autism Depression

Aetiology e.g. FASD

Level of Functioning

16

11

4

0

2

4

6

8

10

12

14

16

ICD10 F84.0 Childhood Autism Gilberg Aspergers Criteria 2001 No ASD

F84.0 = 76.2%

No ASD = 19.0

Type of Social Impairment

:From DISCO scoring

0

1

2

3

4

5

6

7

Active but odd

Passive

Aloof

Other

FASPartial FASARNDNo FASCombined

Bishop et al: FASD group more likelyto initiate social contact

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

11

9

1

0

2

4

6

8

10

12

DSM IV 314.01ADHD Combined

DSM IV 314.00ADHD Inattentive

Type

Did not meet criteria

No Clear statistical link with the Small numbers between Diagnosis

•Age•IQ•Sex

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

Frontal Temporal Parietal Occipital0

30000

60000

90000

120000

150000

Vol

ume

Lobe

Controls

FASp = .0003

p = .018

p = .030

p = .0002

* Slides Courtesy of Professor E Riley University of San Diego

Cerebrum

CerebellumCorpus Callosum

Cerebellum

75

80

85

90

95

100

NDFASD

FAS

<p 0.001

Mattson et al., 1994

Change in cerebellum size

* 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

Norman and Shallice 86

Activating Impulse

Orange

Action

Peel Orange

Executive control

Schema

Peel orangeschema

Supervisory Attention System = EC

Hungry



Activating Impulse

Orange

Action

Peel Orange

Executive control

Schema

Peel orangeschema

Not Hungry



Activating Impulse

Orange

Action

Peel Orange

Executive control

Schema

Peel orangeschema

Not Hungry

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

CentralExecutive

Visual spatialActive memory

Semantic activememory

Phonological Active memory

Stored visual spatial information

Stored semantic information

Stored phonological information

Long term memory store

Model of relationship between Working memory, Consolidation system and long term memory

Consolidation system

Working MemoryLong Term

Memory Store

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

Striatum(caudate & putamen)

Globus Pallidus(part of lenticular nucleus)

Thalamus

Caudate *Accumbens *

70

75

80

85

90

95

100

NDFASD

FAS***

*

Concordant with animal data


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


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

Anterior CingulateInitiating and

focusing attention

Motivating

Reward

behaviour

Medial

Inhibiting Unwanted behaviour

Lateral

Orbito Frontal Cortex

DorsolateralPre frontal

Cortex

SelectingAnd

MonitoringDirectoryschemas

Motor Response

Stepping on Brake initiated,Stepping on accelerator inhibited

Posterior

Association Areas

Knowledge and action Schemas

Time 1Green light

Time 2ChildCrossing

How the brain organises information

AAAA

DDDD

BBBB

EEEE

CCCC


AAAA

DDDD

BBBB

EEEE

CCCC

Executive Control monitors locates and plans activities


AAAADDDD

BBBB

EEEECCCC



AAAA BBBB

CCCC


How to cross a road

Pedestrian crossing

Cars can kill

Source Monitoring

Individual learns where something is and stores information how items linked

AAAA BBBB

When asked to recall information the source of the learning is muddled

AAAA BBBB

How the brain organises information : External

Support

BBBB


How to cross a roadAAAA

Pedestrian crossing

CCCCCars can kill

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

020406080

FASD

RM

FASD

Bishop

FASD

Langdre

n

Fragil

e X

Downs Syn

drome

Cornelia

de lange

Behavioural phenotype

Behaviouralphenotype

Type of Social Impairment

:From DISCO scoring

0

1

2

3

4

5

6

7

Active but odd

Passive

Aloof

Other

FASPartial FASARNDNo FASCombined

Bishop et al: FASD group more likelyto initiate social contact

Possible correlation with IQ level p=0.005

Vineland adaptive behaviour schedule: adaptive age scores (n=19) (2 not returned)

DomainDomain MinimumMinimum MaximumMaximum AverageAverage

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 Famy 1997 (n=23) Barr 2006 (n=136?)

Total 92Alcohol / Drug Dependence

60 53.5

Major Depression 44 47.9Psychotic Disorder 40 1.4Bipolar 1 20 2.8Anxiety disorder 20 33.8Eating Disorder 16 4.2PD 48

Where can I go for help?

Referral pathways

• Clinical Genetics (diagnosis only)• FASD Specialist (very few around)• Paediatrician• Child psychiatry• Child Psychology• Adult Psychiatry• LD Psychiatry

Often need toSpecify suspecteddiagnosis

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, PRBBAv. Dr. Aiguader 88, 08003 Barcelona, SPAINwww.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

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FASD Barnsley Oct 11 Dr Raja Mukherjee Consultant Psychiatrist / Honorary Senior Lecturer Lead...

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