EMBRYONIC DEVELOPMENT & STEM CELL COMPENDIUM
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Appendix 5. Physiologic Development of The Central Nervous System

Review of MEDICAL EMBRYOLOGY Book by BEN PANSKY, Ph.D, M.D.
Appendix 4. Teratogens Known to Cause Human Malformations
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Appendix 6. Prematurity
  1. Prenatal stages
    1. DEVELOPMENT OF CELLULAR FUNCTION: physiologic development of cells usually begins with and parallels their morphologic development, and the 2 processes continually interact with one another
    2. TYPICAL ENZYME SYSTEMS appear in the spinal cord cells before they are seen in the brain. Examples of these are succinic dehydrogenase, ATPase, and cytochrome oxidase
    3. THE APPEARANCE OF NISSL BODIES (cytoplasmic RNA) marks the beginning of increased protein synthesis, resulting in the formation of axon and dendritic processes
    4. SIGNS OF FUNCTIONAL ACTIVITY, such as the onset of electrical activity and reactivity resulting in muscular contractions, as well as suppression of the related reflexes by cephalic structures, are superimposed on the morphologic and chemical changes with cerebral maturation
    5. CEREBRAL MATURATION is slower and more gradual than that of the rest of the CNS and corresponds to the duration of cortical histogenesis. It may be physiologically evaluated by the spontaneous activity of the brain recorded from the skull by the electroencephalogram
      1. Electrical potentials recorded across the amniotic membrane suggest that this activity begins at about day 50 of intrauterine life
      2. Its maturation, which is a function of dendritic development of the neurons, as well as enzymatic development, is usually completed at about 11 years of age
      3. The fetus of 7 months shows anarchic activity with interhemispheric asymmetry, indicating an immature cortex and commissures
      4. At birth, there is slow, more coordinated activity of about 3 to 4 cycles per second with the onset of some symmetry
      5. From 2 to 3 years of age, more rapid activity with alpha waves of about 6 to 7 cycles per second are seen with symmetric activity of greater amplitude being well organized in the occipital regions but less well in the frontal regions
      6. At 13 to 14 years of age, there is still more rapid activity of from 8 to 12 cycles per second, and the alpha waves are well organized on the entire cerebral surface
    6. DURING MATURATION OF THE BRAIN, there are special needs and requirements for oxygen and glycogen
      1. The oxygen consumption in the adult is about 25% of that used by the entire body, whereas in the newborn and young child, it can be as high as 60%. Thus, neonatal anoxia is very serious and may result in intracranial hemorrhage, epilepsy, or even psychomotor retardation
    7. OVERALL DEVELOPMENT: physiologic development parallels histogenesis and begins in the spinal cord. It then follows in the derivatives of the rhombencephalon, the mesencephalon, and the prosencephalon to end with the development of the cerebral cortex. In a sense, it conforms to phylogenetic evolution
      1. Fetal stages of development
        1. Muscular reactions to external stimuli are first seen at about week 8
        2. Spontaneous movements, a sign of medullary maturation, are seen in week 9
        3. Osteotendinous reflexes are seen in month 6
        4. The respiratory centers of the medulla are functional at month 5 and, since maturation of pulmonary alveolar epithelium occurs at about 6 months of gestation, viability is theoretically possible at this age
        5. Archaic reflexes involving subcortical centers are possible
          1. Sucking at month 5 of gestation
          2. Grasping at month 6 of gestation
          3. The inexcitability of the cerebral cortex until this time appears to indicate that these movements are independent of the cortex and may represent very rudimentary instinctive reactions, since they are also seen in anencephalies
        6. Cerebral maturation begins between the months 6 and 7 of gestation, when the basic structures are all completed, although some disease processes may slow down this development, and newborns may then show a psychomotor retardation of one to several months
  1. Postnatal stages
    1. THE POSTNATAL PERIOD is a continuation of the fetal state in terms of nervous system function. Behavior is predominantly reflex and purely subcortical. Movement is instinctual and rudimentary, consisting of flexion and extension or simple reflexes such as crying and coughing
      1. The neocortex becomes excitable about day 10, but in a very weak and diffuse manner, and for a long time, movement is generalized and awkward
      2. Gradually, autonomic movements come under cortical control and are more elaborate, and behavior becomes progressively imitative and expressive
      3. Structural developments in the cortex foretell these activities: neural development coincides with myelinization which proceeds in a cephalocaudal direction
        1. The first fibers to be myelinated are those coming from the motor, visual, and auditory cortex areas
        2. The last fibers to become myelinated at the end of gestation and just before birth are those coming from the association areas
    2. THE MAJOR CLINICAL STAGES OF DEVELOPMENT postnatally are
      1. Regression of the archaic reflexes is seen between the first and third months
      2. Ability to completely right one's head, with stability (head control), from a prone position is seen at about 3 months
      3. Sitting and development of prehension (use of thumb and index finger) usually occurs at about 8 or 9 months
      4. Standing usually occurs at about 9 or 10 months
      5. Walking takes place at about 12 to 15 months
      6. The first words are usually spoken between the 18th month and 2 years
      7. Cerebral maturation usually ends at about 11 years of age
    3. GENERAL BRAIN DEVELOPMENT
      1. The cerebral cortex has a surface of about 700 square cm at birth, 950 square cm at about 5 months, and about 1700 square cm at about 2 years of age, after which time, the surface no longer increases
      2. The brain weighs from 300 to 350 at birth or about one-tenth of its body weight, and its weight increases, as does its volume, mostly during the first 2 years of lif It weighs 800 g at 1 year and 1350 g at maturity
        1. The growth of the brain takes place essentially in the hemispheres, particularly in the frontal lobes
        2. Increase of brain weight continues until about the age of 14 years, but at a slower pace, and is due especially to the multiplication of the neuroglial cells and to the neuronal fiber growth. The central nervous system has most of its neurons at the time of birth
        3. In the adult, the brain represents only about 5% of its body weight as a result of general growth of the total body mass
        4. With growth, a complex pattern of sulci and gyri develops. These permit a considerable increase in the volume of the cerebral cortex without requiring an extensive increase in cranial volume or a reshaping of the cranial vault
      3. Myelinization starts at the fourth fetal month
      4. The cranial nerves are myelinized at birth, and the spinal nerves are completely myelinized by 3 years of age
    4. NORMAL REFLEXES
      1. Moro's reflex (embrace): when the infant is startled by a jarring of the table or crib or by a loud noise, he draws his legs up and brings his arms around, as in an embrace
      2. Tonic neck reflex: in the resting state, the infant's posture is maintained by flexor tonicity of the arms and legs. Lateral rotation of the head to one side abolishes flexor tone on that side, causing extension of the arm and le This reflex is usually not developed fully until one month of age
      3. Grasp reflexes: when the palm is stimulated by one's finger, the infant grasps and holds on; when the sole of the foot is stimulated from the heel forward, the toes turn downward
      4. The deep tendon reflexes are present but tire easily
      5. The abdominal reflexes are inconstant
      6. Babinski's reflex is present, but there is no ankle clonus, and it disappears at about 10 to 16 months
      7. Chvostek's sign is positive in 50% of newborn infants during the first week
      8. The pupils react to light with contraction, but there may be secondary dilation
      9. Swimming and walking reflexes are present during the first weeks
      10. 10. Rooting, sucking, and swallowing reflexes are important to feeding
        1. Rooting reflex: when the infant smells milk, he turns his head to find the source, and when the cheek is touched by a smooth object, the mouth turns toward the object and the lips open as if to grasp a nipple
    5. DEVELOPMENT IS RELATED TO MYELINIZATION and is not a steady process but a pattern of sequences of rapid and slow growth. Motor and sensory controls develop from above and proceed downward so that eye control develops before hand and leg control. Development is related to 3 functioning levels of the CNS: brainstem, archipallium, and neopallium
      1. The newborn functions at brainstem levels
      2. Archipallium, which includes part of the temporal lobe, cingulate gyrus, and basal ganglia, supervenes on the brainstem and can be considered to be responsible for the basic emotions and some primitive motor and sensory control
      3. Neopallium, which includes most of the cerebral hemisphere, has intellectual rather than emotional function and is responsible for skill, discrimination, and fine movements
      4. Clinical application of the above developmental patterns is important
        1. Changes in physical signs in static brain lesions
        2. Upper limb paresis becomes apparent at 5 to 6 months
          1. Lower limb paresis becomes apparent at 10 to 12 months
          2. Abnormalities of coordination, namely, athetoid and involuntary movements, become apparent between 18 and 24 months

            3.
Appendix 4. Teratogens Known to Cause Human Malformations
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Appendix 6. Prematurity
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