FACE September 9,2003

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Toward defining the behavioural phenotype in children with FASD

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Presented by Dr. Gail Andrew, medical director, Glenrose FASD Project

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Glenrose FASD Project Clinic

Team: Pediatrician - Dr. Gail Andrew Social Worker - Gail Schuller Psychologist - Dr. Kathy Horne Speech-Language Pathologist - Mary Reynolds Occupational Therapist - Lynne Abele-Webster

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Glenrose Project Background

 Fall 2000 Consultation teams at Glenrose Rehabilitation Hospital, Edmonton and Alberta Children’s Hospital, Calgary  DPN model, Clarren and Astley, Seattle  Funded by Alberta Health and Wellness  Partnerships : Ministries of Children’s Services, Learning and Justice; Community service providers; Caregivers 3

Glenrose Project Mandate

 Clinical: DPN tool for diagnosis Intervention planning  Database: Prevalence Lifespan monitoring Outcomes of intervention  Training: Increase capacity Multidisciplinary teams Mentoring and consultation 4

FACE September 9, 2003

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Questions:

 1. Is there a neurobehavioral pattern specific to prenatal exposure to alcohol?

 2. How does this pattern change across the lifespan of the individual with FASD?

 3.What measures can be used to assess the disability in FASD?

 4. What are the best interventions/supports?

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FACE September 9, 2003

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Concepts:

 Behaviour or learning difficulties are presenting symptoms in FASD  Need to determine deficit in brain function leading to that symptom  Need to connect brain dysfunction to etiology of organic brain damage from prenatal exposure to alcohol (maternal hx) 6

Terminology FASD

 F = Fetal: changes in normal development in utero  A = Alcohol: Teratogen causes cell/process changes and damage  S = Spectrum: damage/difficulties present from mild to severe  D = Disorder: difficulty/inability to function/adapt as expected across lifespan 7

FASD Spectrum of Disability/Dysfunction

Loss of genetic potential

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Behavior

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regulatory disorder ADHD profile mood swings impulsivity poor judgement sensory processing Learning disabilities

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math

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higher order language deficits

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social communication

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deficits memory deficits organizational difficulties Slow learner Mental retardation +/- microcephaly +/- CP +/- seizures Pre-perinatal death Continuum of effect of prenatal exposure to alcohol on brain function through life

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Defining FASD : Variables

 Organic brain damage in utero:  maternal: drugs, nutrition, metabolism  fetal: susceptibility, protective  alcohol: amount, pattern, timing  genetic factors (maternal, paternal, fetal )  Postnatal:  supportive or increased risk rearing  other brain damage 9

Defining FASD: Hallmarks

 Disordered pattern in development and acquiring expected skills  Out of keeping with measured IQ  Increasing difficulty in functioning with age  May not be evident at early age ( skill not expected)  May be masked by supportive environment 10

Defining FASD: Hallmarks

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Pass tests

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Flunk life

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Assessment of Brain Dysfunction

 No single test - need battery by multidisciplinary team  Test from simple to complex in all domains  Need to sample real life functions (executive, adaptive, socialization) by standardized tests and caregiver reports  Consider secondary disabilities, comorbidities, physical health issues 12

Assessment Domains

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Resources:

 DPN model of Clarren and Astley  Glenrose FASD Project  Health Canada National Guidelines  Need for continued research on specificity to FASD phenotype  Need to assess that individual’s pattern to plan interventions 13

Assessment Domains

 Intellectual  Academic achievement  Language and social communication  Attention  Visuospatial  Motor and visuomotor  Sensory processing  Memory  Adaptive and executive functioning 14

Clinical Reports of FASD

 Inattentive, short attention span, not able to regulate responses to environment stimuli, impulsive, act first without thinking  Not learning from experiences or connecting cause and effect  Not able to organize, plan or sequence but live in the now  Slow to learn, need repeated learning, seem to forget especially if overstimulated 15

Clinical Reports of FASD

 Poor and variable memory, not able to generalize to different situation or use stored information  Impaired executive functions such as judgement, reasoning, mental flexibility,adapting, planning  Difficulty with abstract concepts such as math, money, time 16

Clinical Reports of FASD

 Overly talkative, often off topic, interuptive, confabulation, not aware listener is not following, not connecting points or making sense, not communicating  Comprehension of language and nonverbal aspects of communication even more impaired than use of words  Poor social skills, easily victimized, immature 17

Current Research Data

 Memory: short term, encoding, long term, retrieval, working memory, verbal, auditory, nonverbal, visuospatial  Executive function  Attention  Social communication  Relationship to IQ  Correlation to animal research and neuroimaging studies 18

Memory in FASD

 Mattson, Reilly, Roebuck: n = 16, controls  Verbal: slower rate of encoding into short term memory  Continued to learn with repeated trials  Delayed recall accounted for by deficits in initial learning and not in long term memory function or retrieval  Nonverbal: recalled less after delay even when initial learning considered 19

Memory in FASD

 Mattson et al:  Variable rate of learning across trials possibly related to inconsistent attention, not utilizing strategies, more intrusions and preseverations  Carmichael Olson:  Deficits in auditory memory impacted by inattention and language comprehension 20

Memory in FASD

 Uecker and Nadel: (nonverbal memory)  Deficit in immediate but not delayed object recall (implies encoding deficit)  Spatial memory deficit, distorted spatial array  No deficit in facial recognition  Mattson, Reilly etc: n = 22, controls  Subtle differences in interhemispheric transfer in somatosensory domain (corpus callosum) 21  Distorted temporal processing

Executive Function

 Jacobson, Mattson, Coles, Kodituwaku etc:  Deficits in all 4 areas of Delis- Kaplan EF scale not explained by IQ (planning ability, cognitive flexibility, selective inhibition, concept formation and reasoning)  Difficulties in planning, more preservative on incorrect strategies  May be linked to problems using information in working memory 22

Adaptive Function

 Whaley (2001) n = 33, controls  Impaired adaptive function in all areas of Vineland in FASD and children with psychiatric disorders matched for IQ but no significant differences to be a hallmark of FASD  With increasing age FASD showed decline in socialization component 23

Attention

 Review by O’Malley and Nanson (2002)  ADHD pattern common in FASD  Earlier onset, more resistant to stimulant medications, may respond better to Dexedrine (D1 receptor of dopamine in animal model of alcohol damage) compared to ADHD not alcohol exposed  Regulatory difficulties in infancy, hyperactive toddler, later inattentive type 24

Attention

 Kodituawakku et al:  Used Wisconsin Card Sorting Test  More preservative errors suggesting inattention in FASD related to difficulty in shifting responses or attention  More problems in tasks requiring planning and manipulation of information in working memory  No difference on delayed response tasks that 25 required sustained attention

Social Communication

 Disordered language pattern in FASD well recognized but communicative social use of language further impaired than even these abilities  Reflected in social failure and victimization across the lifespan 26

Social Communication

 Coggins (Seattle):  Used narrative test that requires ability to make sense of a picture story through inference and perspective taking  FASD failed cohesion (linking logically) and coherence (information)  Theory: failed to encode necessary inferences 27

Social Communication

 Monnet (2002) : n = 43, controls, adults  Impaired affective prosody ( not getting the emotional or attitudinal inferences of what is said) worse in prenatal alcohol exposed  Pattern in FASD different from that in alcoholics and acquired focal right or left brain injury and more like combination  Right parietal cortex dysfunction, also corpus callosum implicated in FASD pattern 28

Clinical Research in FASD

 Koren et al (2002) n = 52, age 4-18 yr. clinic  Profile of neuropsychological characteristics of 21 deficits and 6 assets done by 2 independent raters with threshold for ARND (FASD) Dx  Identified more problems in academic ability, intelligence, language, memory in ARND  Both groups in referred clinic setting had equal ratings on behaviour and social problems 29

Clinical Research in FASD

 Steinhausen (2003) n = 38, controls  Compared IQ, age matched controls with other diagnoses to FAS/FAE Developmental Behavioural Checklist (Einfield, Tonge)  FAS similar to FAE and both more severe than controls in all areas : disruptive, self absorbed, communication disturbance, anxiety  Persistence over time in psychopathology and cognitive function 30

Glenrose Clinic Experience

 Rationale of DPN model - 4 digit code  Characterizes Fetal Alcohol Spectrum Disorder objectively  Documents alcohol exposure without judging causal role  Considers other pre and post natal factors (multifactorial) 31

Assessment of Brain Function

 History and neurological exam  Psychometric testing  Adaptive functioning / daily life  Caregiver interview  Scales  Direct observation 32

Assessment of Brain Function

 Specific tests of executive function  higher order language  social communication  memory  attention  planning, organizing  sensory issues 33

Glenrose Experience

Question 1  What patterns emerged among the rankings of Growth, Face and Brain Function in children with confirmed prenatal alcohol exposure?

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Glenrose Experience: Participants

 Question 1  N = 75 children  41 male, 34 female  age range 1 year 1 month to 15 years 2 months  All were exposed to alcohol at levels 3 and 4 35

45%

Glenrose Experience: Participants

Gender 55%

Male (41) Female (34) 36

Glenrose Experience: Participants

Age

40.0% 30.0% 32.0% 30.5% 30.5%

Children

20.0% 4.0% 10.0% 0.0% < 4 (2 4) 4 t o 6 (2 3) 7 t o 1 0 (23 ) 11 to 14 (3 ) > 1 4 (2) 3.0% 37

FASD Pilot Project January 2001 to March 2002

15% 12% Ethnicity 17%

Caucasian (13) Aboriginal (42) Metis (11) Other (9)

56%

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Glenrose Experience: Results

None - 16%

Diagnostic Features

Growth - 9% Face - 28% Growth - 9% Face - 28% Brain - 84% None - 16% Brain - 84% 39

Glenrose Experience: Implications

 Brain dysfunction can be present without growth deficiency or typical facial features  If only look at face or growth many children with brain dysfunction would be missed 40

Glenrose Experience

Question 2  What assessed functions most clearly differentiated children ranked as Brain 3 (Static Encephalopathy) from those ranked as Brain 2 (Neurobehavioral Disorder)?

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Glenrose Experience: Participants

 Question 2  subgroup of N being n = 34  17 Brain 2, 17 Brain 3  age range 6 years to 15 years 2 months 42

FASD Pilot Project January 2001 to March 2002

Common Findings in Brain 2 & 3 :  IQ scores variable but considerable scatter  Half of scattered profiles showed statistically significant split but in both directions  Motor skills variable  Discrete measures of basic language usually within average range  < 6 years - 75% variable language delays, expressive better than receptive (early sign) 43

Glenrose Experience: Results

Comparison between Neurobehavioral Disorder (brain 2) and Static Encephalopathy (brain 3) on 8 measures: Lo wer Receptive Language Verbo sity Sequencing Higher Order Language So cial Co mmunicatio n Wo rking M emo ry B ehavio r/A daptive Functio n A ttentio n 0% 20% 40% 60% 80% 100% Brain 2 Brain 3 44

Glenrose Experience: Results

 Sequencing, social communication, and working memory differentiated severity of brain dysfunction  Attention, behavior and adaptive functioning did not differentiate and present in most  Higher order language, verbosity, and receptive language difficulties indicate some differentiation 45

Implications of Glenrose Findings

 Discrete measures of intelligence and basic language skills alone do not predict or indicate degree of dysfunction / disability  Deficits in executive function characterizes FASD and impacts daily living  Not always evident at young age  May be supported by structured environment  Need to reassess over time 46

FACE September 9, 2003

 Questions:  1. Is there a neurobehavioral pattern specific to prenatal exposure to alcohol?

 2. How does this pattern change across the lifespan of the individual with FASD?

 3.What measures can be used to assess the disability in FASD?

 4. What are the best interventions/supports?

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Answer to Questions

 1. Clinical reports and emerging research data support a neurobehavioral phenotype in FASD that is complex (small sample nos.)  2. Increasing difficulty with age and increase in societal expectations  3. Assessment tools in each domain are identifying specific impairments  4. Need to systematically apply to interventions and measure outcomes 48

Future Research

 Need larger sample sizes with control groups from normal population, other brain dysfunction , learning disabilities and behaviour disorders; longitudinal follow up  Testing in clinical situation does not necessarily represent how individual functions in day to day life; need to develop tools to assess this  Apply information to intervention strategies 49