Development

Mental retardation

• Mental retardation depends on low intelligence quotient (IQ <70, <2SD from mean) and difficulties in adaptive functioning
• Mild mental retardation IQ 50-70
• Moderate/severe mental retardation IQ <50
• ~ 2% population has MR
• 1.4 M : 1 F

Measures of intellectual, neurodevelopmental, and behavioural progress

• Developmental tests:
• Bayley scales of infant development
• 2^nd edition
• Mental development index (MDI)
• Psychomotor development index (PDI)
• 3^rd edition
• Cognitive, language, and motor scales
• Standardized for 1-42 months
• Mean = 100, SD = 15
• Bayley Infant Neurodevelopmental screen (BINS)
• Standardized for 3-24 months
• Denver developmental screening test
• Standardized for birth to 6 years
• Inventory tests personal-social, language, fine motor-adaptive, and gross motor
• Intelligence/cognitive tests:
• Wechsler intelligence scale for children (WISC-IV)
• 6-17 years
• Wechsler preschool and primary scale of intelligence (WPPSI-III)
• 2.5-7.3 years
• Standford-Binet Intelligence Scales (SB5)
• 2-85 years
• Differential Ability Scales (DAS)
• Leiter International Performance Scale (Leiter-R)
• Comprehensive Test of Nonverbal Intelligence (CTONI)
• Neuropsychological tests:
• NEPSY (NEuro and PSYchology)
• Delis-Kaplan Executive Function System (D-KEFS)
• Indirect functional ratings by parent/caregiver
• Vineland Adaptive Behaviour Scales (Vineland-II)
• Infant Development Inventory
• Child Development Inventory
• Domain-specific developmental measures:
• Motor profile:
• Alberta Infant Motor Scale (AIMS)
• Peabody Developmental Motor Scale (PDMS)
• Language skills:
• Peabody Picture Vocabulary Test (PPVT-R)
• Behaviour and ADLs:
• Vineland Adaptive Behaviour Scales (Vineland-II)
• Pediatric Evaluation of Disability Inventory (PEDI)
• Pediatric Functional Independent Measure (WeeFIM)

Goodenough Draw-a-Person Test

• Administered to age 3-15 years
• Told to draw a man, a woman, and themselves
• Score = 3 + a/4 where a = each feature recorded in the picture

Genetic causes of mental retardation

• X-linked disorders:
• Fragile X syndrome
• FMR1 gene, CGG repeat expansion
• >200 copies – Fragile X syndrome
• 55-200 copies – Fragile X-associated tremor/ataxia syndrome (FXTAS)
• FMR protein involved in protein translation in dendrites
• Long, narrow face, large protruding ears, macroorchidism, joint laxity
• 20% have epilepsy
• Many other X-linked disorders, including ARX, MECP2
• Chromosomal disorders:
• Trisomy 21
• Prader-Willi syndrome
• Williams’ syndrome
• Other single-gene mutations:
• Rubinstein-Taybi
• Coffin-Lowry
• Oligophrenin (ORHN1)
• FMR2
• Metabolic disorders:
• PKU
• Galactosemia
• Smith-Lemli-Opitz

Acquired causes of mental retardation

• Prenatal:
• Fetal alcohol syndrome, other maternal substance abuse
• Nutritional (materal PKU, iodine deficiency)
• Infection (rubella, toxoplasmosis, CMV, HIV)
• Stroke
• Perinatal:
• Birth asphyxia
• Infection (HSV encephalitis, GBS meningitis)
• Stroke
• SGA, prematurity
• Hypoglycemia, hyperbilirubinemia
• Postnatal/environmental:
• Toxins (lead)
• Infection (H. flu b meningitis, arbovirus encephalitis)
• Stroke
• Trauma and NAI
• Poor nutrition, poverty

High-yield tests if no hints to diagnosis

• Karyotype with high-resolution banding
• Fragile X mental retardation (FMR1) testing
• MRI brain

Cognitive syndromes

Symptom	Features	Localization
Aphasia Sensory (Wernicke) Motor (Broca’s) Conduction aphasia	Phonetic errors, phonemic errors, paraphasias Decreased production and fluency Poor repetition, normal fluency	Dominant posterosuperior temporal gyrus Dominant inferior frontal gyrus Dominant arcuate fasciculus
Alexia with agraphia		Dominant supramarginal and angular gyri
Dysprosody	Impaired discrimination, production, repetition of intonation/melody/phrasing	Nondominant perisylvian cortex
Agnosia Visual Tactile Auditory Spatial	Achromatopsia, visual object agnosia, prosopagnosia Astereognosis Word deafness, amusia Extinction, neglect	Bilateral occipitaotemporal visual association cortex Contralateral parietal cortex Bilateral temporoparietal cortex Nondominant parietal cortex
Apraxia Ideational Ideomotor Limb-kinetic	Inability to perform learned motor skills Inability to copy gestures or use tools Loss of finger dexterity	Dominant inferior parietal cortex Contralateral and dominant premotor and supplementary motor cortex Contralateral motor cortex
Gerstmann’s syndrome	Dysgraphia, dyscalculia, right-left disorientation, finger agnosia	Dominant angular gyrus of parietal lobe

Attention-Deficit-Hyperactivity Disorder

Either “inattention” or “hyperactivity-impulsivity”.

Symptoms present before age of 7 years.

Impairment from symptoms in 2+ settings (school, work, home)

Clear evidence of clinically significant impairment in social, academic, or occupational function.

Inattention – 6+ symptoms persistent >6 months that is maladaptive and inconsistent with developmental level

• Often fails to give close attention to details or makes careless mistakes in schoolwork, work or other
• Often has difficulty sustaining attention in tasks or play
• Often does not seem to listen when spoken to directly
• Often does not follow through on instructions and fails to finish schoolwork, chores, work duties
• Often has difficulty organizing tasks or activities
• Often avoids, dislikes, or is reluctant to engage in tasks that require sustained mental effort
• Often loses things necessary for tasks or activities
• Often easily distracted by extraneous stimuli
• Often forgetful in daily activities

Hyperactivity-impulsivity – 6+ symptoms for >6 months that is maladaptive and inconsistent with dev level

• Often fidgets with hands or feet or squirms in seat
• Often leaves seat in classroom or other situation where sitting is expected
• Often runs about or climbs excessively where inappropriate (or feelings of restlessness or adults)
• Often has difficulty playing or engaging in leisure activities quietly
• Often “on the go” or acts as if “driven by a motor”
• Often talks excessively
• Often blurts out answers before questions have been completed
• Often has difficulty awaiting turn
• Often interrupts or intrudes on others (butts into conversations or games)

Drug	mg/kg/day	Dosing	Side effects & comments
STIMULANTS
Dextromamphetamine - Dexedrine	0.3-1.0	bid-tid	Insomnia, anorexia, depression, psychosis, high HR/BP, FTT, withdrawal effects, rebound phenomena
L&D amphetamine - Adderall	0.5-1.5	qd-bid
Methylphenidate - Ritalin	1.0-2.0	bid-tid
Mg pemoline - Cylert	1.0-2.5	qd-bid	Rare, serious hepatotoxicity (check LFTs)
LONG-ACTING STIMULANTS
Methylphenidate - Concerta - Ritalin LA	1.0-2.0	qd-bid
L&D amphetamine - Adderall XR	0.5-1.5	qd-bid
SNRIs
Atomoxetine - Strattera	0.5-1.4	qd-bid	Mild anorexia, GI symptoms, mild high BP/HR. Jaundice, high LFTs, suicidal thinking May be helpful with comorbid enuresis, tics, mood disorders

TCAs (imipramine, amitryptyline). SSRIs (fluoxetine, citalopram), Buproprion, Venlafaxine for ADHD and comorbid tics, OCD, mood disorders.

Alpha-agonist (clonidine) for tics, ADHD, aggression, agitation, withdrawal.

Beta-blockers (propranolol) for aggression, agitation, akathisia.

Nonpharmacological therapies include:

• Mimization of distractions (front row, uncluttered desk, minimal distractions)
• Structure, organization techniques (checklists, homework assignment pads)
• Biofeedback, complimentary/alternative therapies

Tic disorders

Transient tic disorder – duration of tics <1 year

Chronic tic disorder – duration of tics >1 year of one type (motor, vocal)

Tourette syndrome – diagnostic criteria

• Multiple motor and at least one vocal tic
• Waxing and waning course
• Onset before age 21 years
• No precipitating illness or medication

Features of Tourette syndrome

• 3M : 1F
• Mean onset 6-7 years
• Soft neurological signs of coordination and fine motor difficulties, synkinesis, restlessness
• Often associated with other neuropsychiatric disorders, e.g., OCD, ADHD, depression/anxiety, episodic rage/self-injurious behaviour, academic difficulties, executive dysfunction.

PANDAS – Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infection

• Prepubertal onset
• Tic disorder or obsessive-compulsive disorder
• Acute fulminant onset
• Associated with group A beta-hemolytic streptococcal infusion
• Associated with neurological abnormalities

Nonpharmacological therapies:

• Behavioural treatments (habit reversal training, support groups, relaxation therapy)
• Acupuncture

Pharmacological therapies:

• Tier 1 medications (milder tics)

• Clonidine
• Guanfacine
• Baclofen
• Clonazepam
• Others: gabapentin, topiramate, levetiracetam

• Tier 2 medications (more severe tics)

• Typical and atypical neuroleptics
• Pimozide, fluphenazine, risperidone, olanzapine, haloperidol, etc
• Pergolide, donepezil
• Botulinum toxin, nicotine patch, delta-9-tetrahydrocannabinol (special cases)

• Experimental:

• Transcranial magnetic stimulation
• Deep brain stimulation

Goal is to minimize tics’ to limit psychosocial effects, not completely rid of tics.

Autistic spectrum disorders

Pervasive developmental disorders

• Autistic disorder
• Asperger’s disorder
• Childhood disintegrative disorder
• Rett’s disorder
• PDD-NOS

Autistic disorder (DSM-IV criteria)

• 6+ items
• Impaired social interaction (2+ of these)
• Impaired nonverbal behaviors (eye gaze, facial expression, body posture, gestures
• Failure to develop appropriate peer relationships
• Lack of spontaneous seeking to share enjoyment, interests, achievements with others
• Lack of social or emotional reciprocity
• Impaired communication (1+ of these)
• Delayed language (including gestures)
• Impaired ability to initiate or sustain conversation
• Stereotyped/repetitive language or idiosyncratic language
• Lack of varied, spontaneous make-believe or appropriate social imitative play
• Restrictive repetitive and stereotypic patterns of behaviour, interests, activities:
• Preoccupation with stereotyped or restricted patterns of interest
• Inflexible adherence to nonfunctional routines/rituals
• Stereotyped/repetitive motor mannerisms (hand flapping, twisting movements)
• Preoccupation with parts of objects
• Delayed/abnormal function in 1+ of these areas before age 3 years:
• Social interaction
• Language in social communication
• Symbolic/imaginative play
• Not Rett’s or childhood disintegrative disorder

Asperger’s disorder

• Normal IQ (no language delay), normal self-help skills, curiosity about environment
• Impairments in social interaction and restrictive/repetitive patterns of behaviour/actiivites
• Difficulty forming friendships due to naïve, inappropriate, one-sided social interactions, lack of empathy
• Desire success in interpersonal relationships and are puzzled by the failure
• Discrepant verbal & nonverbal IQ scores (as opposed to in autism)

Childhood disintegrative disorder

• Rare
• Normal early development
• Neurodevelopmental regression after 24 months, leading to autistic symptoms
• Onset from 3-10 years (usually 3-4 years)
• Profound cognitive regression to mental retardation
• 4M : 1F

Rett’s syndrome

• X-linked dominant, male lethal – MECP2 – methyl-CpG-binding protein 2 – regulates gene expression
• Neurodegenerative disorder, usually females, onset after period of normal development
• Reduced life expectancy (70% survive to 35 years)
• Must have had:
• Normal prenatal/perinatal development
• Normal psychomotor development until 5 months age
• Normal birth head circumference
• Onset of these after period of normal development:
• Decelerated head growth from 5-48 months
• Loss of purposeful hand skills, development of stereotyped hand movements
• Loss of social engagement early on (interaction often develops later)
• Poorly coordinated gait/trunk movements
• Severely impaired expressive/receptive language, severe psychomotor retardation
• Symptoms later become relatively static
• Inconsolable crying, screaming, agitation, food refusal
• Breathing irregularities
• Periodic apnea during wakefulness
• Intermittent hyperventilation
• Seizures, EEG abnormalities
• Scoliosis, growth retardation, small feet
• Atypical Rett syndrome
• XY – severe epileptic encephalopathy
• XXY – classic Rett phenotype
• XY – mental retardation
• XX – classic autistic disorder

Screening tests for ASD:

• Checklist for Autism in Toddlers
• Screening Tool for Autism in Two-year-Olds
• Pervasive Developmental Disorders Screening Test (PDDST-II)
• Social Communication Questionnaire

Diagnostic tests for ASD:

• Childhood Autism Rating Scale (good clinical tool)
• Autism Diagnostic Interview-Revised (ADI) – gold standard
• Autism Diagnostic Observation Schedule-General (ADOS) – gold standard

Investigations in ASD:

• Auditory testing or ABRs
• Lead level if pica
• Metabolic testing only if other clinical or physical signs
• Neuroimaging not needed in autism and macrocephaly

Coexisting medication disorders:

• Feeding and GI problems
• Sleep disturbances
• Epilepsy
• Mitochondrial disorders
• PKU
• Fragile X
• Tuberous sclerosis complex
• Neurofibromatosis
• Prader-Willi syndrome
• Angelman syndrome
• Smith-Lemli-Opitz syndrome

Psychiatry and nonorganic disorders

Somatiform disorders

• Symptoms linked to psychological factors, but not under voluntary control or consciously produced
• Conversion disorder – psychological factors primary role
• Somatization disorder – recurrent, multiple complaints over many years, unrelated to physical disorder

Factitious disorder – intentionally produced due to psychological need, often with personality disorder

Malingering – voluntary produced physical symptoms in persuit of a goal, e.g, financial, legal