Fetal Alcohol Spectrum Disorder/ 정고운


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Fetal Alcohol Spectrum Disorder/ 정고운

  1. 1. Neuropsychological Characteristics ofFetal Alcohol Spectrum DisordersMother Safe Conference2013.04.16.Goun Jeong, M.D.Department of Pediatrics,Cheil General Hospital & Women’s Healthcare Center
  2. 2. Introduction• Fetal alcohol syndrome (FAS)– The most severe form of FASD① Facial anomalies② Growth retardation③ CNS anomalies• Fetal alcohol spectrum disorder (FASD)– Effect of maternal alcohol consumption duringpregnancy– Not a diagnostic term– Umbrella terminology
  3. 3. Discovery of FASD• 1968, Lemoine et al.– Outcome of children of alcoholic mothers• 1973, Jones and Smith– ‘Fetal alcohol syndrome’ was first introduced• 1978, Clare and Smith– ‘Fetal alcohol effects’• 1996, Institute of Medicine (IOM)– replaced FAE with ARBD and ARND– New classification of FASD
  4. 4. Diagnostic Criteria of FASD• 2000, Astley and Clarren– 4-Digit Diagnostic Coding system– To eliminate the ambiguities of IOM system• 2005, Chudley et al.– Canadian Diagnostic Guidelines– IOM system + 4-Digit Diagnostic Code system• 2005, Hoyme et al.– Revised IOM Diagnostic Classification System
  5. 5. Revised IOM Criteria for Diagnosis of FASDI. FAS With Confirmed Maternal Alcohol Exposure (all of A–D)(A) Confirmed maternal alcohol exposure(B) Minor facial anomalies (≥2)(1) Short palpebral fissures (p10%)(2) Thin vermilion border of the upper lip (score 4 or 5)(3) Smooth philtrum (score 4 or 5)(C) Prenatal and/or postnatal growth retardation(1) Height and/or weight p10%(D) Deficient brain growth and/or abnormal morphogenesis (≥1)(1) Structural brain abnormalities(2) Head circumference p10%II. FAS Without Confirmed Maternal Alcohol ExposureIB, IC, and ID as above
  6. 6. III. Partial FAS With Confirmed Maternal Alcohol Exposure (all A-C)(A) Confirmed maternal alcohol exposure(B) Minor facial anomalies (≥2)(1) Short palpebral fissures (p10%)(2) Thin vermilion border of the upper lip (score 4 or 5)(3) Smooth philtrum (score 4 or 5)(C) One of the following other characteristics:(1) Prenatal and/or postnatal growth retardation(a) Height and/or weight p10%(2) Deficient brain growth or abnormal morphogenesis (≥1)(a) Structural brain abnormalities(b) Head circumference p10%(3) Complex pattern of behavioral or cognitive abnormalitiesIV. Partial FAS Without confirmed Maternal Alcohol ExposureIIIB and IIIC, as above
  7. 7. V. ARBD (all of A-C)(A) Confirmed maternal alcohol exposure(B) Minor facial anomalies (≥2)(1) Short palpebral fissures (p10%)(2) Thin vermilion border of the upper lip (score 4 or 5)(3) Smooth philtrum (score 4 or 5)(C) Congenital structural defect (≥1)if the patient displays minor anomalies only, X 2 must be present)cardiac/skeletal/renal/eyes/ears/minor anomaliesVI. ARND (both A and B)(A) Confirmed maternal alcohol exposure(B) At least 1 of the following:(1) Deficient brain growth or abnormal morphogenesis (≥1)(a) Structural brain abnormalities(b) Head circumference p10%(2) Complex pattern of behavioral or cognitive abnormalities
  8. 8. Clinical Manifestations of FASD
  9. 9. Variability of Adverse Fetal Outcomes• the amount of alcohol• genetic variation• maternal nutrition• maternal age• socioeconomic status• the timing of exposure
  10. 10. Facial Anomalies of FASD
  11. 11. Facial Anomalies of FASD
  12. 12. Timing?• Facial signs of FAS are most evident between8 months - 8 years of age• In adolescent or adult, earlier childhood pictures may beuseful to uncover facial features• Not smilingSmile lead to narrowing of the upper lipand thinning of the philtrum
  13. 13. Growth Retardation• Growth pattern characteristic of FASD usually presents inthe prenatal period and persists as a consistentimpairment over time• Usually below 10 percentileGrowth delay may diminishin adolescence and adult
  14. 14. CNS Anomalies• Cerebrumvolume reduction of the cranial vault and brain– 12% compared to control– Parietal, Temporal, Inferior frontal lobe– Lt hemisphere > Rt hemisphere– white matter hypoplasia– visuospatialdeficits,verbalmemory,impulsiveness
  15. 15. • Cerebellum– reduction in the anterior vermis (lobule I-V)– motor coordination and balance impairments• Basal ganglia– caudate nucleus– connection with cortical and subcortical motor areas– control voluntary motor function– executive function, motivation, social behavior,perseverative behavior• Corpus callosum– role in the coordination of various functions– Agenesis, thinning, hypoplasia, partial agenesis
  16. 16. FASD Related Other Abnormalities• Midface hypoplasia, Hypertelosism, High arched palate• Micrognathia,Joint contracture, Scoliosis,Hemivertebrae, Radioulnar synostosis, Brachydactyly,Clinodactyly, CamptodactylySkeletal• Septal defects, Hypoplastic pulmonary arteries, TOF• Pectus excavatum or carinatumCardiac• Pyelonephritis, Hydronephrosis, Dysplastic kidney• Ureteral duplications, uni/bilateral hypoplasiaRenal• Strabismus, Retinal vascular anomaliesOcular• Conductive HL, SNHLAuditory
  17. 17. Differential DiagnosisWilliams syndrome Cornelia de LangesyndromeVelocardiofacialsyndromeDubowitz syndromeFetal anticonvulsant syndrome, especially hydantoin and valproateMaternal PKU fetal effectsNoonan syndromeToluene embryopathy
  18. 18. Neuropsychological DisturbancesCognitive impairment• Overall intellectualperformance• Executive function• Learning and memory• Language• Visual-spatial ability• Motor function• Attention• Activity levelBehavioral problems• Adaptive dysfunction• Academic difficulties• Psychiatric disorders
  19. 19. General Intelligence• The majority of FAS are not intellectually disabled• FAS is considered one of the leading identifiable causesof mental retardation (Abel and Sokol 1987; Pulsifer 1996)• Many affected individuals exhibit impaired intellectualabilities, even in the absence of facial features, growthretardation (Dalen et al. 2009; Mattson et al. 1997)• Significant relation between general cognitive functionand degree of dysmorphic features and growth deficiency(Ervalahti et al. 2007)
  20. 20. • FAS have mean IQ scores significantly lower than thosewith partial FAS and ARND (Chasnoff et al. 2010)• Average IQ estimate of individuals with heavy prenatalalcohol exposure– 70 for FAS (Streissguth et al. 1991)– 80 for nondysmorphic individuals (Mattson et al. 1997)• IQ score is significantly correlated with psychopathology– Children with moderate and severe intellectualdisability experienced greater psychiatric disturbance– IQ score below 50 indicated poor psychiatric outcome(Steinhausen et al. 1994)• Results of lower levels of alcohol exposure have beenconflicting
  21. 21. Executive Function• The ability to maintain an appropriate problem-solvingset for attainment of a future goal• Related to frontal-subcortical circuit• BRIEF– Behavior Rating Inventory of Executive Functioning– Parent/teacher report of executive function in children– Children and adolescents ages 5-18– 86 items questionnaire– 8 subscale and 2 validity indices
  22. 22. Executive function:Problem-Solving and Planning• Increased perseverations on incorrect strategies• Increased rule violations• Fewer passed items overall(Aragon et al. 2008; Green et al. 2009;Kodituwakku et al. 1995; Mattson et al. 1999)
  23. 23. Executive function:Concept Formation and Set-Shifting• Difficulties forming and identifying abstract concepts andshifting to new conceptual categories• More errors and complete fewer categories on theWisconsin Card Sorting Test (WCST) (McGee et al. 2008)• Differences among groups of alcohol-exposed children(FAS, partial FAS, and ARND) were not significant(Chasnoff al. 2010)Wisconsin Card Sorting Testhttp://ertslab.com/web/portfolio/card-sorting-test
  24. 24. • Completed fewer sorts and received fewer points for theirdescription using California Card Sorting Test of theDelis-Kaplan Executive Functioning System (D-KEFS)(McGee et al. 2008)• Less able to generate concepts independently• Less able to recognize categories when cued by theexaminer• Needed more sentences to form a correct response• Made more set loss errors (Mattson and Riely 1991)• Difficulties forming and shifting concepts and thinkinganalytically
  25. 25. Executive function:Fluency• Deficits on both traditional and set-shifting measures ofverbal and nonverbal fluency• Although deficits are noted in both letter and categoryfluency, deficits are greater on letter fluency tasks(Kodituwakku et al 2006;Mattson and Riley 1999;Rasmussen and Bisanz 2009; Vaurio et al. 2008)• Findings within the nonverbal domain have been unclear
  26. 26. Executive function:Inhibitory Control• Stroop testGreen Red Blue Purple Blue PurpleBlue Purple Red Green Purple Green• Children with prenatal heavy alcohol exposure makemore error, particularly on the switching and interferenceconditions (Connor et al. 2000;Mattson et al. 1999)• Poor Go/No-go taskClick on the PLAIN green dot when it appears. IGNORE the patterned dot!http://cognitivefun.net/test/17
  27. 27. Executive function:Working Memory• Deficits in the ability to hold and manipulate informationin working memory (Green et al. 2009; McGee et al. 2008)Verbal working memory• Digit span subtest of the Wechsler Intelligence Scales forChildren (WISC)short-term auditory memory and attention (verbal memory)For Digit Span forward tester would read numbers like "2, 3, 9, 1"and child would respond with the same numbersFor Digit Span backward the tester would read numbers like "24, 3, 7, 12"and child would respond "12, 7, 3, 24"• Recall fewer digits, especially backwards condition(Aragon et al. 2008; Carmichael Olson et al. 1998; O’Hare et al. 2009)
  28. 28. Visuo-Spatial working memory• More errors and poorer use of strategy on acomputerized task of spatial working memory(Green et al. 2009)Cambridge NeuropsychologicalTest Automated Battery (CANTAB)
  29. 29. Learning and Memory• Hippocampus is particularly sensitive to the teratogeniceffects of prenatal alcohol exposure (animal study)• A number of clinical studies have reported learning andmemory deficits in children with heavy alcohol exposure• Impaired both verbal and nonverbal skill
  30. 30. Learning and Memory:Verbal Learning and Memory• Deficits in both learning and recall of verbal information(Mattson et al. 1996; Mattson and Roebuck 2002)• These deficits are present in both children with andwithout the physical features of FAS(Mattson et al. 1998; Mattson and Roebuck 2002)• Children with FASD exhibit superior memory during bothimmediate and delayed recall involving a story ratherthan word list• Recalled more information on the story task but alsoencountered more inaccurate information (Pei et al. 2008)• These abilities might improve with age in less affectedchildren (Richardson et al. 2002; Willford et al. 2004)
  31. 31. Learning and Memory:Nonverbal Learning and Memory• A lower rate of learning across acquisition trials and lessrecall of information after a delay period• Limited research and inconsistent results
  32. 32. Language• Wide range (Abel 1990)– absence of comprehensible speech– mild dysarthria or lisping• Poor receptive language (Russel et al. 1991)• Impairments include– Word comprehension (Conry 1990; Matton et al. 1998)– Naming ability (Mattson et al. 1998)– Articulation (Becker et al. 1990)– Grammatical and semantic abilities (Becker et al. 1990)– Pragmatics (Abkarian 1992)– Expressive and receptive skills (Aragon et al. 2008)
  33. 33. Visual-Spatial Ability• Limited research• Beery-Buktenica Developmental Test of Visual MotorIntegration– copy drawings of geometric forms– Visual perception– Motor coordination– The full (27 items) 7yr- adult– The short (18 items) 3-7yr
  34. 34. Constructional apraxia?Although children with FAS were able to remember the essential featuresof a clock, they disregarded details like spacing between number
  35. 35. • significantly greater difficulty processing local featurescompared to global feature
  36. 36. Motor Function• Heavy alcohol exposure: impairment both fine and grossmotor skill• Young children with FAS show clinically importantdevelopmental delay in fine but not gross motor skills(Kalberg et al. 2006)• Teratogenic effects of alcohol to brain regions associatedwith motor functioning such as the cerebellum and BG
  37. 37. • Other findings of motor impairment– Postural instability– Atypical gait– Delayed motor reaction timing– Impaired fine motor speed and coordination– Increased motor timing variability– Poor hand/eye coordination– Dysfunctional force regulation– Atypical trajectories in goal-directed arm movement– Impaired oculomotor control– Poor sensory processing and sensorimotor performance– Weak grasp
  38. 38. • Peripheral motor nerve damage– Atypical muscle development– Reduced motor neurons– Poor peripheral nerve myelination– Slowed nerve conductivity• Skeletal malformations of the hands and feet• Delayed skeletal maturity
  39. 39. • Does the observed deficits persist into adolescence andadulthood?– Adults with FASD perform worse than controls ontests of fine motor control and balance and that thedose-dependent effects of alcohol on motorcoordination during childhood continued to beapparent in adulthood among individuals previouslydiagnosed with FAS or ARND (Connor et al. 2006)– In a subsequent study with adolescent subjects, groupdifferences were not observed (Simmons et al. 2006)NOYES
  40. 40. Attention and Activity Levels• Hyperactivity and attention deficits are frequentlyobserved in individuals with heavy alcohol exposure– Attention deficit in more than 60% of prenatal alcoholexposed children (LaDue et al. 1992)– higher rate of ADHD (Fryer et al. 2007)– hyperkinetic disorder (Steinhausen et al. 1993)• Attention deficit is not global– differential deficits in visual and auditory attention
  41. 41. Academic Impairments• Difficulties in academic function– Both verbal (reading and spelling) and mathematicseven after controlling for IQ– Mathematics has emerged as a specific weakness– Maybe associated with abnormalities in left and rightparietal regions and the medial frontal gyrus
  42. 42. Secondary Disabilities• Wide range of maladaptive, behavioral and emotionaldisturbances• Psychiatric problem– ADHD– schizophrenia, depression, personality disorders– Increased risk for major depressive disorder inchildhood• Disrupted school experience• Dependent living• Trouble with the law• Inappropriate sexual behavior• Addiction
  43. 43. Conclusion• Individuals exposed to alcohol during pregnancy exhibita wide range of long-lasting impairments inneuropsychological and behavioral domains• Affected children perform relatively well on simple taskbut show greater impairment on more complex tasks• Recent studies have examined the specificity of thesedeficits through development of a neuropsychologicalprofile