Congenital and Developmental Disorder of the Nervous System

"exists at birth"

-does not necessarily imply genetic

-delay in achieving developmental milestones

-failure to achieve cognitive or motor milestones

• Four Spheres
• 1. Language
• 2. Socialization
• 3. Gross Motor
• 4. Fine Motor

Global = all four spheres

• Causes:
• 1. Genetic
• 2. Metabolic
• 3. Cerebral dysgenesis
• 4. Perinatal injury
• 5. Infection of CNS (meningitis)
• 6. Chronic illness

• -delayed cognitive milestones will not be achieved
• -significant limitations in at least two areas of adaptive vehaviour
• -IQ < 70

*** no consensus on when to switch diagnosis from developmental delay to mental retardation

-loss of milestones that had previously been achieved

-high on the ddx: neurodegenerative processes

-disorders that affect the ability to learn specific subject areas (reading, math, spelling, listening, oral expression)

-dyslexia: most common and well-known learning disability

• Epidemiology:
• -disproportionally ID'd in US (may be a social construct)
• -more likely in children with brain injury
• -more likely in children with low socioeconomic status

• "Discrepancy Model"
• -not commensurate with overall intellectual ability

• Dyslexia Pathology:
• -anomalies of cerebral cortex
• -relative symmetry of planum temporale (vs normal asymmetry)

• Treatment:
• -adjust environment with tutors and tools

• -delays in language and socialization
• -often a symptom of an underlying neurological disorder

• Clinical Picture:
• -reduced eye contact
• -obsessions with non-toys
• -obsessions around ordering of objects
• -echolalia (meaningless repetition of speech)
• -stereotypies (repetitive useless movements)

Some show an autistic regression

**R/O Landau Kleffner Syndrome (epileptic aphasia)

• Pathophysiology:
• -unknown
• -some correlation with head size (may be due to disorder of synaptic pruning)

• Epidemiology:
• -1/150
• -boys > girls
• -higher risk in siblings
• -10-20% have genetic etiology

• Pathology:
• -changes in cerebellar vermis
• -abnormal limbic system development

• Evaluation:
• -TIME SENSITIVE
• -screen at 18 months
• -R/O common metabolic and genetic disorders

• Treatment:
• -behavioural Modifications
• -second gen antipsychotics

• -variant of autism spectrum
• -delay in socialization but not language
• -average to above average intelligence ("idiot savant")

• Epidemiology:
• -1/700 births
• -slightly more common in males
• -Primary Risk factor: advanced maternal age

• Presentation:
• -global developmental delay
• -IQ usually ranges 20-85
• -bilateral epicanthal folds
• -midface hypoplasia
• -flat nasal bridge
• -open mouth/protruding tongue
• -CNS: hypotonia, seizures, Alzheimers by 50
• -Congenital heart defects
• -leukemias

• Pathology:
• -lighter weight brains
• -simpler gyri
• -frontal lobes smaller

• Pathophysiology:
• -mostly caused by non-disjunction of chromosome 21 in maternal meiosis
• **mosaicism/Robertsonian translocation: have the facial features but normal intelligence

• Evaluation:
• -karyotype
• -Echo, thyroid studies, CBC, cervical ardiography

• Treatment:
• -therapy

*most common cause of inherited mental retardation

• Epidemiology:
• -less symptomatic in females than males
• -1/2500 males

• Presentation:
• -delays in language and fine motor skills after 1 year
• -ADHD features
• -autism spectrum disorder
• -long thin face, prominent forehead and jaw, large protruding ears, macroorchidism, joint laxity

• Complications:
• -scoliosis
• -dilatation of aortic root
• -mitral valve prolapse

• Pathophysiology:
• -X-linked dominant
• -females may show lyonization
• -abnormal trinucleotide repeat expansion of FMR1 gene
• -RNA-binding protein
• -anticipation

• Presentation:
• -cafe-au-lait macules (hyperpigmented)
• -neurofibromas/plexiform neurofibroma
• -axillary or inguinal freckling
• -optic pathway glioma
• -Lisch nodules (hamartoma in iris)

• Complications:
• -increased incidence of tumors

• Epidemiology:
• -1/4000
• -50% are new mutations
• -autosomal dominant
• -neurofibromin (TSG)

• Treatment:
• -tx tumors according to histopath
• -vigilance for tumors

• Presentation:
• -extremely variable
• -seizures (80-90%)
• -mental retardation (50%)
• -multiple types of skin lesions -hypomelanotic macules
• -subependymal nodules
• -facial angiofibromas
• -lymphangiogmatosis
• -dental enamel pitting
• -renal problems

• Epidemiology:
• -1/6000 births

• Pathophysiology:
• -autosomal dominant
• -mutations in TSC1 (hamartin) and TSC2 (tuberin) tumor suppressor genes

• Treatment:
• -screening: renal U/S, MRI
• -increased risk for cancers

-failure of anterior or posterior neuropores to close (d25 and d27 of gestation)

-75% could be prevented by folic acid supplementation

-elevated levels of AFP

-may be caused by teratogens such as divalproex and carbamazepine

• -failure of anterior neuropore to close
• -both cerebral hemispheres and calvarium are absent

• Epidemiology:
• -0.1-0.7/1000 births
• -many are stillborn, die shortly after birth

• "Spina Bifida"
• -failure to close of posterior neuropore
• -can occur anywhere along the neural tube
• -sac containing maldeveloped cord and meninges

• Mortality approaches 50%
• Often have associated Arnold Chiari malformation

• Epidemiology:
• -4.6/10000 births

• Treatment:
• -shunted hydrocephalus: can have normal intelligence

• -extension of cerebellar vermis that extends into cervical canal
• -extension of fourth ventricle into cervical canal
• -hydrocephalus

In myelomeningocoele thought that the defect fuses to overlying soft tissue and pulls the CNS caudally

-persistence of an embryonic pattern of blood vessels that can occur anywhere in the CNS

• Presentation:
• -most commonly rupture with intracerebral or subarachnoid hemorrhage
• -less often: seizures, HAs, progressive focal deficits

• Epidemiology:
• -1/10000

• Treatment:
• -endovascular embolization
• -surgical resection

• -great cerebral vein malformation
• -one of the more frequent symptomatic vascular malformations in infancy and childhood

-great cerebral vein does NOT develop

• Presentation:
• -audible cranial bruit
• -Neonates: high output CHF
• -Infants: hydrocephalus, compensated CHF
• -Children: CHF, hydrocephalus, hemorhage

• -distended loosely organized channels of thin collagenized walls
• -often in cerebellum, pons, subcortical regions

-often familial

-bleed as often as AC malformations but the hemorrhages are smaller and asymptomatic

• -8-10 Hz
• -faster, action tremor
• -postural
• -absent or minimal when at rest
• -usually arm
• -suppressed by alcohol

• Epidemiology:
• -may be genetic (dominant)
• -415/100000 over 40 years old
• -most often starts late in 2nd decade

• Treatment:
• -beta blockers
• -barbs
• -benzos
• -surgical deep brain stimulation

• -quick, involuntary stereotyped movement of phonation
• -commonly: grunting, blinking, neck jerk
• -Coprolalia (profanity) is rare
• -urge to have type
• -can suppress voluntarily for awhile
• -relief with tic

• Transient Tic Disorder:
• -simple tic for <1yr

• Chronic Tic Disorder:
• -may persist into adulthood

• Tourette's Syndrome:
• -multiple motor and one or more vocal tics
• -present for more than 1 year

• Treatment:
• -non-pharm unless distressing to child
• -a2 agonists
• -antipsychotics

• -persistent, non-progressive encephalopathy with motor dysfunction
• -usually refers to perinatal conditions
• -implies there was an injury or event
• -mental retardation in 25-50%
• -Epilepsy
• -Behavioural problems
• -Speech and language disorders

• Epidemiology:
• -1.2-2.5 children/1000

• Characteristic Patterns:
• 1. Choreoathetotic Cerebral palsy
• 2. Spastic hemiplegia
• 3. Spastic quadriplegia
• 4. Spastic diplegia

• Treatment:
• -multidisciplinary
• -drug treatment for spasticity
• -PT
• -occupational therapy
• -Orthopedic intervention (tendon lengthening)

• -caused by severe hyperbilirubinemia
• -damages basal ganglia (kernicterus)
• -less common now due to phototherapy

• -stroke in contralateral hemisphere
• -Stroke in newborn as common as stroke in elderly!!!

• -global weakness
• -hypertonia
• -hyperreflexia
• -commonly accompanied by mental retardation
• -due to severe anoxic ischemic brain injury (global injury)

• -prominent UMN dysfunction of lower extremities
• -often seen in preemies
• -due to hemorrhages in the germinal matrix

• -most common preventable chemical cause of mental retardation
• -1.9/1000 children
• -no safe level of alcohol

• Presentation:
• -growth deficiency
• -microcephaly
• -mental retardation
• -craniofacial abnormalities (thin upper lip, flat filtrum)
• -congenital heart defects
• -behavioural problems (may be only manifestation)