Neurodevelopment and Developmental Delay Flashcards
Developmental delay
def
a disturbance in the acquisition of cognitive, motor, language or social skills which has a significant and continuing impact on the developmental progress of a child
Developmental delay
Etiologies list
- CNS malformations
- exposure to endogenous or exogenous maternal toxins
- maternal/fetal infection
- perinatal trauma or birth asphyxia
- prematurity or maternal/fetal malnutrition
- neurocutaneous syndromes
- genetic disorders
- inborn errors of metabolism
- exposure to endogenous or exogenous infant toxins after birth, i.e., hepatic or
renal failure, lead acquired postnatal CNS infection - CNS trauma-Child abuse- can take the form of nonaccidental injury leading to subdural, epidural bleeds, subarachnoid hemorrhages, contusions, concussions, lacerations, intraparenchymal bleeds, shearing injuries.
- neuromuscular disorders with CNS involvement
- idiopathic
Peculiarities of immature brain include…
- presence of developing structures which are not found in adult brain: e.g., germinal matrix.
- injury early in development may interfere with subsequent development and lead to malformation.
- reactions to injury may differ because of immaturity of glial and inflammatory cells.
- cell susceptibility to certain injurious stimuli may differ from adult patterns.
- plasticity of developing nervous system may be able to compensate for damage.
- immaturity of brain function may hinder recognition of significant damage until much later in life.
Antenatal brain development
Stages/gestational age/examples of disorders
6 Stages
Stage
Gestational age
Examples of disorders
Dorsal induction
3-4 weeks
Dysraphic states
Ventral induction
5-6 wks
Holoprosencephalies
Neuronal proliferation
2-4 mo
Micro/macoencephaly
Neuronal migration
3-5 mo
Aberrant gyration (lissencephaly)
Synaptic organization
6mo-yrs postnatal
Mental retardation
Myelination
7mo-yrs postnatal
leukodystrophy
Malformations
def
Malformations are primary structural defects that result from errors of morphogenesis and often interfere with subsequent function .
General principle: malformations and developmental abnormalities are datable to specific times during development.
Which brain structures develop at the same time and should prompt physician to investigate for multiple defects
It should be kept in mind that the cerebral cortex, corpus callosum, cerebellum and deep nuclei develop about the same time. Hence one anomaly should prompt the physician to look hard for others.
Dorsal induction and primary neurulation
(3-4wks GA)
normal embryologic event
formation of neural tube from ectoderm
Dorsal induction and primary neurulation
(3-4wks GA)
neural tube closure defects
list/chars
a. neural tube closure defects: probably reflect failure of closure of neural tube resulting in faulty modeling of skeleton around malformed neural tube
b. anencephaly: failure of anterior neuropore closure with subsequent degeneration of brain
c. myelomeningocele: herniation of meninges and spinal cord through vertebral defect
Dorsal induction and primary neurulation
(3-4wks GA)
defects of axial mesodermal development
Probably result from defective developmental of mesodermal elements without persistent open neural tube
encephalocele: 75% occur in occipital region meningocele: herniation of cerebral or spinal meninges through bony defect failure; spinal forms occur in 1-5/1000 live births, often associated with Arnold-Chiari malformation
Dorsal induction and primary neurulation
(3-4wks GA)
pathogenesis
Genetic factors: various genes, syndromes, populations
environmental influences: teratogens (e.g., thalidomide, carbamazepine), vitamin deficiency (folate), maternal hyperthermia, diabetes mellitus
Ventral induction and formation of brain and face primordial (5-6wks GA)
Normal events
formation of primary brain divisions including cerebral hemispheres, olfactory and optic nerves
Ventral induction and formation of brain and face primordial (5-6wks GA)
defects
a. development is induced by prechordal plate interacting with rostral neural tube
b. disorders: holoprosencephaly/ arrhinencephaly series: spectrum of severity representing failure of development of paired olfactory, telencephalic, and optic vesicles resulting in incomplete formation of forebrain
c. brain defects are usually accompanied maldevelopment of skull and by mid-face defects such as cyclopia (severe form), cleft lip or palate, and other midface defects.
d. implicated pathogenetic factors include trisomies 13 and 18, other genetic and familial forms, maternal diabetes, maternal infections (toxoplasmosis, rubella, syphilis), ETOH
Neuronal proliferation and migration (maximum during months 2-5 GA)
Normal events
Events include neuronal proliferation at ventricular surface and in local masses in subventricular zones (germinal matrix) followed by migration to final destination along radial glial cells (radial route) or along surfaces (tangential route)
formation of cerebral cortex: 3-5 mo GA
formation of cerebellum: 5mo GA to 1 yr
postnatal formation of gyri and sulci reflects growth and maturation of cortex and occurs in an orderly pattern, beginning at about 20wk GA; by term, the gyral pattern approximates the adult pattern.
Neuronal proliferation and migration (maximum during months 2-5 GA)
Disorders of growth
microcephaly (low brain weight) with microcephaly (small head): can be secondary to tissue destruction (e.g., intrauterine infection) or primary (genetic, teratogens such as irradiation or alcohol, unknown)
macrocephaly: rare, associated with various syndromes, failure of programmed cell death (includes familial megalencephaly, hemimegalencephaly, some patients with NF1, etc.)
Neuronal proliferation and migration (maximum during months 2-5 GA)
Disorders of migration
Severe/diffuse forms
agyria (“lissencephaly”)/pachygyria: 3-4 months GA, sporadic and familial cases;
characterized by migrational arrest of neurons in white matter, failure of cortical lamination, and failure of gyration, resulting in a smooth- surfaced (“lissencephalic”) brain. Genes implicated include ARX, DCX, LIS1, and RELN
Neuronal proliferation and migration (maximum during months 2-5 GA)
Disorders of migration
Diffuse or local forms
- heterotopias: masses of neurons left behind in white matter. Gene mutations in FLN A
- cortical dysplasias: areas of disturbed
migration and neuronal-glial differentiation
Neuronal proliferation and migration (maximum during months 2-5 GA)
Clinical manifestation severity/causes
c. clinical manifestations vary with severity of defect but include mental retardation and epilepsy.
d. causes include various genetic syndromes; destructive events occurring during migration may result in focal abnormalities, e.g., polymicrogyria along edges of large defects in the cerebral wall (porencephaly)
Developmental reflexes
Onset/disappearance
rooting
O: birth
D: 3 months
Developmental reflexes
Onset/disappearance
Moro
O: birth
D: 5-6 months
Developmental reflexes
Onset/disappearance
Palmar grasp
O: birth
D: 6 months
Developmental reflexes
Onset/disappearance
Plantar grasp
O: birth
D: 9-10 months
Developmental reflexes
Onset/disappearance
Gallant (truncal incurvation)
O: birth
D: 1-2 months
Developmental reflexes
Onset/disappearance
Tonic neck
O: birth
D: 6 months
Developmental reflexes
Onset/disappearance
landau
O: 3-5 months
D: 2 years
