• Information
  1. Introduction
  2. ICD-10 Classification of Autistic Disorders
  3. Symptoms of Classical Autism
  4. Etiology
  5. Characteristics of Other Autistic Spectrum Disorders (Table in Ref [1,3])
  6. Diagnosis
  7. Intervention

A. Introduction

1. Group of developmental brain disorders
2. Boys : Girls 4:1
3. Prevalance 1 to 4 per 1000 (no race predisposition)
4. True autism usually first noted in toddlers 18-36 months of age
5. Absence or delay in speech development
6. About 75% are mentally retarded
7. Very small number have advanced mathmatical, musical, or other abilities

B. ICD-10 Classification of Autistic Disorders

1. Childhood Autism
2. Atypical Autism
3. Rett's Syndrome
4. Other Childhood Disintegrative Disorder
5. Overactive Disorder associated with mental retardation and sterotyped movements
6. Asperger's Disorder
7. Other pervasive developmental disorders
8. Pervasive developmental disorder, unspecified

C. Symptoms of Classical Autism

1. Presence of at least 6 out of 12 potential deficits
   1. All three behavioral domains must be involved
   2. 2 or more deficits in sociability, empathy,and insight into other persons' feelings and agendas
   3. Deficit in cummicative language and imagination
   4. Deficit in behavioral and cognitive flexibility
2. Behavioral Deficits
   1. Lack of interest in others; deficient sociability
   2. Lack of ability to "play"
   3. Decreased need for sleep; frequent awakenings
   4. Self-injurious behavior
3. Communication Deficits
   1. Lack of drive to communicate
   2. Actual lack of word recognition and/or word forming ability
4. Attention and Focus
   1. May have long attention span during individual activities
   2. Unable to focus on joint activities
5. Mental Retardation
   1. Present in ~75% of persons with autism
   2. Creativity usually limited
6. Extraordinary Abilities
   1. Small minority of autistic persons
   2. Musical, mathematical, or visual-spacial abilities may be profound
7. Sensorimotor Abnormalities - present in many autistic persons
8. Epilepsy
   1. By age 25, about 35% of autistic persons have had a seizure
   2. Any type of epileptic syndrome may occur

D. Etiology [5]

1. Generally not understood
2. Prenatal Contributing Factors
   1. Intrauterine rubella
   2. Tuberous sclerosis
   3. Chromosomal abnormalities
   4. Rheubella infection
   5. Cytomegalovirus infection (very uncommon)
   6. Genetic component
3. Genetic Associations
   1. Associated with other genetic diseases in >10% of cases of autism
   2. True autism linked to polymorphisms on chromosomes 7q and 15q
   3. Deletion of 593kb DNA on chromosome 16p11.2 found in >1% of cases []
4. No clear toxicological or other evnironmental basis for disease has emerged
5. Abnormal Brain Growth [6]
   1. Reduced head size (head circumference) at birth autistic versus normal (P<0.001)
   2. Sudden and excessive increase in head size at 1-2 months and 6-14 months
   3. 59% of autistic and 6% of normal infants showed accelerated head growth 6-14 months
6. Neuroanatomic Abnormalities [3]
   1. Fewer neurons and reduced dendritic arborization in amygdala, hippocampus, septum, anterior cingulate, cerebellum
   2. Overall brain size in autism increased 2-10%
   3. Failure to activate fusiform gyrus in response to human faces
7. Autoimmune aspects have been detected
   1. Present in about 50% of patients with autism
   2. Positive serum antinuclear antibody is often present
8. High peripheral serotonin concentrations in ~30% of cases
9. Relationship to Vaccinations
   1. No link with measles-mumps-rubella (MMR) vaccine [7,8,11]
   2. No link with thimerosal-containing vaccine in over 2 million person-years [9]

E. Characteristics of Other Autistic Spectrum Disorders (Table in Ref [1,3])

1. Asperger's Disorder
   1. Usually noted after age 3 years, Male > Female
   2. Poor social skills, lack of insight
   3. Behavioral inflexibility with narrow range of interests
   4. IQ at least 70 (some children are gifted)
   5. Normal speech development
   6. Clumsiness common
   7. Seizures uncommon
   8. Outcomes generally better than childhood autism
2. Disintegrative Disorder
   1. Early development including speech entirely normal, usually noted >2 years
   2. Severe regression between ages 2 and 10 years
   3. Regression affects language, sociability, cognition, daily living skills
   4. Very poor communication and social skills
   5. Seizure disorder common
   6. Outcome very poor
3. Rett's Syndrome
   1. Usually noted ages 5-30 months
   2. Nearly always in girls
   3. Severe global regression in infant girls; very poor communication
   4. Severe mental retardation occurs, but IQ occasionally normal
   5. Lack of language and purposeful had use
   6. Other neurologic deficits
   7. Frequent seizure disorder
   8. Outcome usually very poor
4. Pervasive Development Disorder, Not Otherwise Specified
   1. Variable age at recognition
   2. Less severely affected children
   3. Do not meet criteria for autistic or Asperger's disorder
   4. Variable social skills; fair to good communication
   5. Uncommon seizure disorder
   6. Severe mental retardation
   7. No link to MMR vaccination [11]
   8. Outcome fair to good

F. Diagnosis [5]

1. Various criteria have been devised for classification (see above)
2. Diagnostic and Statistical Methods - 4 (DSM-IV) is recommended for clarifying diagnosis
3. Detailed developmental history is required, followed by comparison with ICD-10 or DSM-IV
4. Differential Diagnosis
   1. Generalized learning disabilities
   2. Specific disorders affecting language, reading, number work, motor coordination, others
   3. Attention deficit and hyperactivity disorder
   4. Tourette's Syndrome
   5. Obsessive Compulsive Disorder

G. Intervention [5]

1. Early identification of disease and behavioral ± medical intervention is critical
   1. Behavior therapy is the cornerstone of current treatment with medications adjunctive
   2. No therapy directed at underlying cause has been found
2. Medicines are strongly recommended to improve behavior and psychiatric components
3. Autism with Serious Behavioral Problems
   1. Includes severe tantrums, aggression, self-injurious behavior
   2. Risperidone (Risperdal®) 0.5-3.5mg/d po effective and well tolerated [10]
   3. Risperidone improved symptoms substantially in 65% of children age 5-17 [10]
   4. Mood stabilizers (Lithium, Valproate) may help with aggressiveness and mood lability
   5. Noradrenergic blockers (ß-blockers, clonidine) for aggressiveness
4. Self-injury may respond to opioid antagonists (for example, Naltrexone)
5. Attention Deficit and Hyperactivity
   1. Stimulants generally recommended
   2. Methylphenidate (Ritalin®) is usually used
6. Depression, Obsessions, Perseveration
   1. May respond to serotonin reuptake inhibitors (SSRI)
   2. Consider fluvoxamine
   3. Trazadone may be added for sleep disorders
7. Buspirone (Buspar®) is the recommended anxiolytic
8. Epilepsy is treated with standard agents
9. Social supports and/or institutionalization are nearly always required
10. In some patients, good progress with behavioral and medical therapy is seen [5]

References

1. Rapin I. 2002. NEJM. 347(5):302
2. Prater CD and Zylstra RG. 2002. Am Fam Phys. 66(9):1667
3. Volkmar FR and Pauls D. 2003. Lancet. 362(9390):1133
4. Yeargin-Allsopp M, Rice C, Karapurkar T, et al. 2003. JAMA. 289(1):49
5. Rapin I. 2001. JAMA. 285(13):1745
6. Courchesne E, Carper R, Akshoomoff N. 2003. JAMA. 290(3):337
7. Madsen KM, Hviid A, Vestergaard M, et al. 2002. NEJM. 347(19):1477
8. Dales L, Hammer SJ, Smith NJ. 2001. JAMA. 285(9):1183
9. Hviid A, Stellfeld M, Wohlfahrt J, Melbye M. 2003. JAMA. 290(13):1763
10. Research Units on Pediatric Psychopharmacology Autism Network. 2002. NEJM. 347(5):314
11. Smeeth L, Cook C, Fombonne E, et al. 2004. Lancet. 364(9438):963
12. Weiss LA, Shen Y, Korn JM, et al. 2008. NEJM. 358(7):667