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Figure 28-3 The myelogenetic chronology (Reproduced by permission from Yakovlev and Lecours)
aging (MRI) Despite these careful anatomic observations, their correlation with developmental clinical and electroencephalographic (EEG) data has not been precise Childhood, Puberty, and Adolescence Growth of the brain continues, at a much slower rate than before, until 12 to 15 years, when the average adult weight of 1230 to 1275 g in females and 1350 to 1410 g in males is attained Myelination also continues slowly during this period Yakovlev and Lecours, who re-examined Flechsig s classic ndings on the ontogeny of myelination (the term Flechsig s myelinogenic cycle is still used), traced the progressive myelination of the middle cerebellar peduncle, acoustic radiation, and bundle of Vicq d Azyr (mammillothalamic tract) beyond the third postnatal year; the nonspeci c thalamic radiations continued to myelinate beyond the seventh year and bers of the reticular formation, great cerebral commissures, and intracortical association neurons to at least the 10th year and beyond (Fig 28-3) These investigators noted that there was an increasing complexity of ber systems through late childhood and adolescence and perhaps even into middle adult life Similarly, in the extensive studies of Conel and Rabinowicz, depicting the cortical architecture at each year from mid fetal life to the 20th year, the dendritic arborizations and cortical interneuronal connections were observed to increase progressively in complexity; the packing density of neurons, ie, the number of neurons in any given volume of tissue increases through the age of approximately 15 months and then decreases (Fig 28-2) Interesting questions are (1) whether neurons begin to function
only when their axons have acquired a myelin sheath; (2) whether myelination is under the control of the cell body, the axon, or both; and (3) whether the classic myelin stains yield suf cient information as to the time of onset and degree of the myelination process At best these correlations can be only approximate It seems likely that systems of neurons begin to function before the rst appearance of myelin, as shown in conventional myelin stains These correlations need to be restudied, using more delicate measures of function and ner staining techniques, as well as the techniques of quantitative biochemistry and phase and electron microscopy
Physiologic and Psychologic Development
Neural Development in the Fetus The human fetus is capable of a complex series of re ex activities, some of which appear as early as 5 weeks of postconceptional age Cutaneous and proprioceptive stimuli evoke slow, generalized, patterned movements of the head, trunk, and extremities More discrete movements appear to differentiate from these generalized activities Re exes subserving blinking, sucking, grasping, and visceral functions, as well as tendon and plantar re exes, are all elicitable in late fetal life They seem to develop along with the myelination of peripheral nerves, spinal roots, spinal cord, and brainstem By the 24th week of gestation, the neural apparatus is functioning suf ciently well to give the fetus some chance of survival should birth occur at this time However, most infants fail to survive birth at this age, usually ow-
NORMAL DEVELOPMENT OF THE NERVOUS SYSTEM
ing to an inadequacy of pulmonary function Thereafter, the basic neural equipment matures so rapidly that, by the 30th week, postnatal viability is relatively common It seems that nature prepares the fetus for the contingency of premature birth by hastening the establishment of vital functions necessary for extrauterine existence It is in the last trimester of pregnancy that a complete timetable of fetal movements, posture, and re exes would be of the greatest value, for mainly during this period does the need for a full clinical evaluation arise That there are recognizable differences between infants born in the sixth, seventh, eighth, and ninth months of fetal life has been documented by Saint-Anne Dargassies, who applied the neurologic tests earlier devised by Andre-Thomas and herself Her observations are in reference to prevailing postures; control and attitude of head, neck, and limbs; muscle tonus; and grasp and sucking re exes These ndings are of interest and may well be a means of determining exact age, but many more observations are needed with follow-up data on later development before they can be fully accepted as having predictive value Part of the dif culty here is the extreme variability of the premature infant s neurologic functions, which may change literally from hour to hour Even at term there is variability in neurologic functions from one day to the next This variability re ects the traumatic effects of parturition and the effects of drugs and anesthesia given to the mother as well as the inaccurate dating of conception and rapid developmental changes in the brain Development during the Neonatal Period, Infancy, and Early Childhood At term, effective sucking, rooting, and grasping reactions are present The infant is able to swallow and cry, and the startle reaction (Moro re ex, page 505) can be evoked by loud sound and sudden extension of the neck Support and steppage movements can be demonstrated by placing the infant on its feet, and incurvation of the trunk by stroking one side of the back Also present at birth is the placing reaction, wherein the foot or hand, brought passively into contact with the edge of a table, is lifted automatically and placed on the at surface These neonatal automatisms depend essentially on the functioning of the spinal cord, brainstem, and possibly diencephalon and pallidum The Apgar score, a universally used but somewhat imprecise index of the wellbeing of the newly born infant, is in reality a numerical rating of the adequacy of brainstem-spinal mechanisms (breathing, pulse, color of skin, tone, and responsivity) (Table 28-3) Studies of local cerebral glucose metabolism by positron emission tomography (PET) have provided interesting information about the functional maturation of the brain There are remarkable differences between the newborn and the mature individual Neonatal values, adjusted for brain weight, are only one-third those of the adult; except for the primary sensorimotor cortex, they are con ned to brainstem, cerebellum, and thalamus During infancy, there occurs a progressive evolution in the pattern of glucose metabolism in the parietal, temporal, striate, dorsolateral occipital, and frontal cortices, in this order Only by the end of the rst year do the glucose metabolic patterns qualitatively resemble those of the normal young adult (Chugani) Behavior during infancy and early childhood is also the subject of a substantial literature, contributed more by psychologists than neurologists In particular they have explored sensorimotor performance in the rst year and language and social development in early childhood In the rst 6 years of life, the infant and young child traverse far more ground developmentally than they ever will
Table 28-3 Apgar scoring system Heart rate 0 No heart rate 1 Fewer than 100 beats per minutes The baby is not very responsive 2 More than 100 beats per minute The baby is obviously vigorous Respiration 0 Not breathing 1 Weak cry; may sound like wimpering or grunting 2 Good strong cry Muscle tone 0 Limp 1 Some exing (bending) of arms and legs 2 Active motion Re ex response 0 No response to airways being suctioned 1 Grimace during suctioning 2 Grimace and cough or sneeze during suctioning Color 0 The baby s whole body is completely blue or pale 1 Good color in body with blue hands or feet 2 Completely pink or good color
again in a similar period From the newborn state, when the infant demonstrates a few primitive feeding and postural re exes, there are acquired, within a few months, smiling and head and hand-eye control; by 6 months, the ability to sit; by 10 months, the strength to stand; by 12 months, the muscle coordination required to walk; by 2 years, the ability to run; and by 6 years, mastery of the rudiments of a game of baseball or a musical skill On the perceptual side, the neonate progresses, in less than 3 months, from a state in which ocular control is tentative and tonic deviation of the eyes occurs only in response to labyrinthine stimulation to one in which he or she is able to xate and follow an object (This last corresponds to the development of the macula) Much later the child is able to make ne discriminations of color, form, and size Gesell has provided a graphic summation of the variety and developmental sweep of a child s behavior He writes:
At birth the child re exly grasps the examiner s nger, with eyes crudely wandering or vacantly trans xed and by the sixth year the child adaptively scans the perimeter of a square or triangle, reproducing each form with directed crayon The birth cry, scant in modulation and social meaning, marks the low level of language, which in two years passes from babbling to word formation that soon is integrated into sentence structure, and in six years to elaborated syntactic speech with questions and even primitive ideas of causality In personality makeup the school beginner is already so highly organized, both socially and biologically, that he foreshadows the sort of individual he will be in later years
The studies of Gesell and Amatruda and of others represent attempts to establish age-linked standards of behavioral development, but the dif culties of using such rating scales are considerable The components of behavior that have been chosen as a frame of reference are not likely to be of uniform physiologic value or of comparable complexity, and they have seldom been standardized on large populations drawn from different cultures Also, the ex-
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