Chapter 28. Normal Development and Deviations in Development of the Nervous System

In this chapter and the next one on aging, we consider the effects of growth, maturation, and aging on the nervous system. These are discussed in some detail because certain aspects of neurologic diseases are meaningful only when viewed against the background of these natural age-linked changes. Developmental diseases of the nervous system, e.g., malformations, genetic defects, and other forms of damage that are acquired in the intrauterine period of life, are considered in Chap. 38.

The establishment of a biologic timescale of human development requires observation of a large number of normal individuals of known ages and testing them for measurable items of behavior. Because of individual variations in the tempo of development, it is equally important to study the growth and development of any one individual over a prolonged period. If these observations are to be correlated with stages of neuroanatomic development, the clinical and morphologic data must be expressed in units that are comparable. Early in life, very precise age periods are difficult to ascertain because of the difficulty in fixing the time of conception. The average human gestational period is 40 weeks (280 days), but birth may occur with survival as early as about 24 or as late as 49 weeks (a time span of almost 5 months), and the extent of nervous system development varies accordingly.

After birth, any given item of behavior or structural differentiation must always have two reference points: (1) to a particular item of behavior that has already been achieved, and (2) to units of chronologic time or duration of life of the organism. The chronologic or biologic scale assumes special significance in early prenatal life. During that period development proceeds at such a rapid pace that small units of time weigh heavily and the organism appears to change literally day by day. In infancy, the tempo of development slows somewhat but is still very rapid in comparison with later childhood.

The neurologist will find it advantageous to organize knowledge of normal development and disease around the timetables for human growth and development listed in Tables 28-1 and 28-2. In addition, the last decade has brought startling advances in the understanding of the genetic and molecular control of neural development. That topic is considered in Chap. 38.

Neuroanatomic Bases of Normal Development

A large body of knowledge has accumulated concerning the functional and structural status of the nervous system during each successive period of life. This information is reviewed briefly in the following paragraphs and is summarized in Table 28-2. It must be kept in mind that development of the nervous system does not proceed stepwise, from one period to the next, but is continuous from conception to maturity. The sequences of development are much the same in all infants, although the rate may vary slightly. Any given behavioral function, in order to be expressed, must await the development of its neural substrate. Furthermore, at any given moment in development, several measurable functions appear in parallel, and it is often a dissociation between them that acquires clinical significance.

Embryonal and Fetal Periods

What we know of the nervous system in the germinal and embryonal periods has been derived from the study of a relatively small number of fetuses that have come into the hands of anatomists. Neuroblastic differentiation, migration, and neuronal multiplication are already well under way in the first 3 weeks of embryonic life. The control of each of these phases (and, later, of connectivity of neurons) is determined by the genome of the organism. Primitive cells destined to become neurons originate in, or close to, the neuroepithelium of the neural tube. These cells proliferate at an astonishingly rapid rate (250,000 per minute, according to Cowan) for a circumscribed period (several days to weeks). They become transformed into bipolar neuroblasts, which migrate in a series of waves toward the marginal layer of what is to become the cortex of the cerebral hemispheres. The first glial cells also appear very early and provide the scaffolding along which the neuroblasts move. Each step in the differentiation and migration of the neuroblasts proceeds in an orderly fashion, and one stage progresses to the next with remarkable precision. The process of neuronal migration is largely completed by the end of the fifth fetal month but continues at a much slower rate up to 40 weeks of gestation, according to the classic studies of Conel and of Rabinowicz. Because the migration of most neurons involves postmitotic cells, the cerebral cortex by this time has presumably acquired its full complement of nerve cells, numbered in the many billions. This concept has been revised in recent years with the discovery that active stem cells in the adult brain generate neurons in the hippocampal formation and in the subventricular matrix zones, giving rise most evidently to olfactory neurons in the adult brain but possibly also to other nerve cells (see Kempermann and also Alvarez-Buylla and Garcia-Verdugo).

Despite the almost universal acceptance of the presence of neuron genesis in the human brain, the methodology that demonstrates it is complex and has been questioned by authoritative individuals such as Rakic, whose perspective should be consulted for a complete portrait of the subject. Actually, we have little idea of the number of nerve cells in the cerebral and cerebellar cortices at different ages. Many more are formed than survive, as programmed cell death (apoptosis) constitutes an important component of development.

Within a few months of mid-fetal life, the cerebrum, which begins as a small bihemispheric organ with hardly a trace of surface indentation, evolves into a deeply sulcated structure. Every step in the folding of the surface to form fissures and sulci follows a temporal pattern of such precision as to permit a reasonably accurate estimation of fetal age by this criterion alone. The major sylvian, rolandic, and calcarine fissures take on the adult configuration during the fifth month of fetal life, the secondary sulci in the sixth and seventh months, and the tertiary sulci, which vary slightly in location from one individual to another, in the eighth and ninth months (see Fig. 28-1 and Table 28-2).

Concomitantly, subtle changes in neuronal organization are occurring in the cerebral cortex and central ganglionic masses. Involved here are the processes of synaptogenesis and axonal pathfinding. Neurons become more widely separated as differentiation proceeds, owing to an increase in the size and complexity of dendrites and axons and enlargement of synaptic surfaces (Fig. 28-2).

The cytoarchitectural patterns that demarcate one part of the cerebral cortex from another (as described in Chap. 22) are already in evidence by the thirtieth week of fetal life and become definitive at 40 weeks and in succeeding months. As the maturational process of cortical neurons proceeds, the patterns of neuronal organization in different regions of the brain (motor, premotor, sensory, and striate cortices, Broca and Wernicke areas) continue to change.

Myelination provides another parallel index of development and maturation of the nervous system and is apparently related to the functional activity of the fiber systems. The timing and precision of these connecting pathways are no less precise and time locked than is neuronal development (see Flechsig's myelinogenic cycle as shown in Fig. 28-3). The acquisition of myelin sheaths by the spinal nerves and roots by the tenth week of fetal life is associated with the beginning of reflex motor activities. Segmental and intersegmental fiber systems in the spinal cord myelinate soon afterward, followed by ascending and descending fibers to and from the brainstem (reticulospinal, vestibulospinal). The acoustic and labyrinthine systems stand out with singular clarity in myelin-stained preparations by the twenty-eighth to thirtieth weeks, and the spinocerebellar and dentatorubral systems by the thirty-seventh week.

Neonatal Period and Infancy

After birth, the brain continues to grow dramatically. From an average weight of 375 to 400 g at birth (40 weeks), it reaches about 1,000 g by the end of the first postnatal year. Glial cells (oligodendrocytes and astrocytes) derived from the matrix zones continue to divide and multiply during the first 6 months of postnatal life. The visual system begins to myelinate about the fortieth gestational week; its myelination cycle proceeds rapidly, being nearly complete a few months after birth. The corticospinal tracts are not fully myelinated until halfway through the second postnatal year. Most of the principal tracts are myelinated by the end of this period. In the cerebrum, the first myelin is seen at 40 weeks in the posterior frontal and parietal lobes, and the occipital lobes (geniculocalcarine tracts) myelinate soon thereafter. Myelination of the anterior frontal and temporal lobes occurs later, during the first year of postnatal life. By the end of the second year, myelination of the cerebrum is largely complete (see Fig. 28-3). These steps in myelination can be followed by MRI. Despite these careful anatomic observations, their correlation with developmental clinical and electroencephalographic 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 1,230 to 1,275 g in females and 1,350 to 1,410 g in males is attained. Myelination also continues slowly during this period. Yakovlev and Lecours, who reexamined Flechsig's classic findings 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 nonspecific thalamic radiations continued to myelinate beyond the seventh year and fibers of the reticular formation, great cerebral commissures, and intracortical association neurons to at least the tenth year and beyond (see Fig. 28-3). These investigators noted that there was an increasing complexity of fiber 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 twentieth year, the dendritic arborizations and cortical interneuronal connections were observed to increase progressively in complexity; the "packing density" of neurons, i.e., the number of neurons in any given volume of tissue increases through the age of approximately 15 months and then decreases (see Fig. 28-2).

Interesting questions are whether neurons begin to function only when their axons have acquired a myelin sheath; whether myelination is under the control of the cell body, the axon, or both; and whether the usual myelin stains yield sufficient 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 first appearance of myelin, at least insofar as shown in conventional myelin stains. These correlations will undoubtedly be restudied using more delicate measures of function and finer 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 reflex 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. Reflexes subserving blinking, sucking, grasping, and visceral functions, as well as tendon and plantar reflexes, 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 twenty-fourth week of gestation, the neural apparatus is functioning sufficiently 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 owing to an inadequacy of pulmonary function. Thereafter, the basic neural equipment matures so rapidly that, by the thirtieth 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 reflexes 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 André-Thomas and herself. Her observations document prevailing postures; control and attitude of head, neck, and limbs; muscle tonus; and grasp and sucking reflexes. These findings 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. Part of the difficulty here is the variability of the premature infant's neurologic functions, which may change literally from hour to hour. Even at term there may be variability in neurologic functions from one day to the next. This variability reflects in part the effects of parturition and the effects of drugs 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 (e.g., Moro reflex, as described further on) 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 flat 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 well-being 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 confined to brainstem, cerebellum, and thalamus. During infancy, there is 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 first 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 first year and language and social development in early childhood. In the first 6 years of life, the infant and young child traverse far more ground developmentally than they ever will again in a similar period. From the newborn state, when the infant demonstrates a few primitive feeding and postural reflexes, 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 is able to fixate on and follow an object. (This last corresponds to the development of the macula.) Later, the child is able to make fine 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 reflexly grasps the examiner's finger, with eyes crudely wandering or vacantly transfixed . . 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 difficulties of using such rating scales are considerable. The components of behavior that have been chosen as a frame of reference for neurological development 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 examinations at specified ages are cross-sectional assessments, which give a limited idea of the dynamics of behavioral development. As already stated, temporal patterns of behavior reveal an extraordinary degree of variation in their emergence, increment, and decrement, as well as marked variation from one individual to another.

Indeed, the predictive value of developmental assessment has been the subject of a lively dispute. Gesell took the position that careful observation of a large number of infants, with accurate recording of the age at which various skills are acquired, permits the establishment of norms or averages. From such a framework one can determine the level of developmental attainment, expressed as the development quotient (DQ = developmental age/chronologic age), and thus ascertain whether any given child has superior, average, or inferior performance. Furthermore, after examining 10,000 infants over a period of 40 years, Gesell concluded that "attained growth is an indicator of past growth processes and a foreteller of growth yet to be achieved." In other words, the DQ predicts potential attainment.

The other position—taken by Anderson and others—is that developmental attainments are of no real value in predicting the level of intelligence but are measures of completely different functions. Illingworth and most clinicians, including the authors, have taken an intermediate position, that the developmental scale in early life is a useful source of information, but it must be combined with a full clinical assessment. When this is done, the clinician has a reasonably certain means of detecting delays in cognitive development and other forms of neurologic impairment.

The trajectory of rapid growth and maturation continues in late childhood and adolescence, although at a slower pace than before. Motor skills attain their maximal precision in the performances of athletes, artists, and musicians, whose peak development is at maturity (age 18 to 21 years). Intelligence and the capacity for reflective thought and the manipulation of mathematical symbols become possible for most individuals only in adolescence and later. Emotional control, precarious in the school age and all through adolescence, stabilizes in adulthood. We tend to think of all these phenomena as being achieved through the stresses of human relations, which are conditioned and habituated by the powerful influences of social approval. In this extensive and pervasive interaction between the individual and the environment, which is the preoccupation of the child psychiatrist, it is well to remember that the processes of extrinsic and intrinsic organization can be separated only for the purpose of analytic discussion. There is always interdependence between them.

Motor Development

As indicated earlier and in Table 28-4, the wide variety and seemingly random movements displayed by the healthy neonate are from birth, and certainly within days, firmly organized into reflexive-instinctual patterns called automatisms. The most testable of the automatisms are blinking in response to light, tonic deviation of the eyes in response to labyrinthine stimulation (turning of the head), prehensile and sucking movements of the lips in response to labial contact, swallowing, avoidance movements of the head and neck, startle reaction (Moro response, see further on) in response to loud noise or dropping of the head into an extended position, grasp reflexes, and support, stepping, and placing movements. This repertoire of movements, as mentioned earlier, depends on reflexes organized mainly at the spinal and brainstem levels. Only the placing reactions, ocular fixation, and following movements (the latter are established by the third month) are thought to depend on emerging cortical connections, but even this is debatable. In the neonatal period, when little of the cerebrum has begun to function, extensive cerebral lesions may cause little derangement of motor function and may pass unnoticed unless special methods of examination—sensory evoked potentials, electroencephalography (EEG), CT, and MRI—are used. Of clinically testable neurologic phenomena in the neonatal period, disturbances of ocular movement, seizures, tremulousness of the arms, impaired arousal reactions and muscular tone, all of which relate essentially to upper brainstem and diencephalic mechanisms, provide the most reliable clues to the presence of neurologic disease. Prechtl and associates have affirmed the importance of disturbances of these neurologic functions at this early age as predictors of delayed development.

During early infancy, the motor system undergoes a variety of differentiations as visual, auditory, and tactile motor mechanisms develop. Bodily postures are modified to accommodate these complex sensorimotor acquisitions. In the normal infant, these emerging motor differentiations follow a time schedule prescribed by the maturation of neural connections. Normalcy is expressed by the age at which each of these appears, as shown in Table 28-4. It is also evident from this table that reflex and instinctual motor activities are the most dependable means of evaluating early development. Moreover, in the normally developing infant, some of these activities disappear as others appear. For example, the grasp reflex, extension of the limbs without a flexor phase, Moro response, tonic neck reflexes, and crossed adduction in response to eliciting the knee jerk gradually become less prominent and are usually not elicitable by the sixth month. The absence of these reflexes in the first few months of life and conversely, their persistence beyond this time indicate a defect in cerebral development, as described in more detail further on, under "Delays in Motor Development." By contrast, neck-righting reflexes, support reactions, the Landau reaction (extending neck and legs when held prone), the parachute maneuver, and the pincer grasp, which are absent in the first 6 months, begin to appear by the seventh to eighth months and are present in all normal infants by the twelfth month.

Because many functions that are classified as "mental" at a later period of life have a different anatomic basis than motor functions, it is not surprising that early motor achievements do not correlate closely with childhood intelligence. The converse does not apply, however; delay in the acquisition of motor milestones often correlates with developmental delay. In other words, most cognitively delayed children sit, stand, walk, and run at a later age than normal children, and deviations from this rule occur mainly in special diseases such as autism.

In the period of early childhood, the reflexive-instinctual activities are no longer of help in evaluating cerebral development, and one must turn to the examination of language functions and learned sensory and motor skills, which are outlined in Tables 28-5 and 28-6.

Quite apart from the early stage of motor development, in later childhood and adolescence one observes a remarkable variation in levels of muscular activity, strength, and coordination. Motor acquisitions of later childhood such as hopping on one foot, kicking a ball, jumping over a line, walking gracefully, dancing, and certain skills in sports are linked to age but there is wide variability in the finesse with which they are performed. Ozeretzkii has combined these in a scale that putatively discloses arrests in motor development in the developmentally delayed. Also in later childhood, precocity in learning complex motor skills as well as skill in games and the development of an all-around interest in athletic activity becomes evident. By adolescence, high individual physical achievement is well recognized. At the other end of the spectrum are instances of motor underachievement, ineptitude, and intrinsic awkwardness; a member of this group will easily stand out and be designated as "an awkward child." Such awkwardness is to be clearly distinguished from the motor impairment associated with a number of cerebral diseases.

Sensory Development

Under normal circumstances, sensory development keeps pace with motor development, and at every age sensorimotor interactions are apparent. However, under conditions of disease, this generalization may not hold; i.e., motor development may remain relatively normal in the face of a sensory defect, or vice versa. The sense organs are fully formed at birth. The neonate is crudely aware of visual, auditory, tactile, and olfactory stimuli, which elicit only low-level reflex responses. Moreover, any stimulus-related response is only to the immediate situation; there is no evidence that previous experience with the stimulus has influenced the response; i.e., that the newborn can learn and remember. The capacity to attend to a stimulus, to fixate on it for any period of time, also comes later. Indeed, the length of fixation time is a quantifiable index of perceptual development in infancy.

Information is available about the time at which the infant makes the first interpretable responses to each of the different modes of stimulation. The most nearly perfect senses in the newborn are those of touch and pain. A series of pinpricks cause distress, whereas an abrasion of the skin seems not to do so. The sense of touch clearly plays a role in feeding behavior. Newborn infants react vigorously to irritating odors such as ammonia and acetic acid, but discrimination between olfactory stimuli is not evident until much later. Sugar solutions initiate and maintain sucking from birth on, whereas quinine (bitter) solutions seldom do, and the latter stimulus elicits avoidance behavior. Hearing in the newborn is manifest within the first few postnatal days. Sharp, quick sounds elicit responsive blinking and sometimes startle. In some infants, the human voice appears to cause similar reactions by the second week. Strong light and objects held before the face evoke reactions in the neonate; later, visual searching is an integrating factor in most projected motor activities.

Sensation in the newborn infant must be judged largely by its motor reactions, so that sensory and motor developments seem to run in parallel but this may be partly artifactual. There are nonetheless discernible maturational stages that constitute sensory milestones, so to speak. This is most apparent in the visual system, which is more easily studied than the other senses. Sustained ocular fixation on an object is observable at term and even in some preterm infants; at these ages it is essentially a reflexive phototropic reaction. It has been observed that the neonate will consistently gaze at some stimuli more often than others, suggesting, according to Fantz, that there must already be some elements of perception and differentiation at this early stage. Voluntary fixation (i.e., following a moving object) is a later development. Horizontal following occurs at about 50 days; vertical following, at 55 days; and following an object that is moving in a circle, at 75 days. Preference for a colored stimulus over a gray one was recorded by Staples by the end of the third month. By 6 months the infant discriminates between colors, and saturated colors can be matched at 30 months. Perception of form, at least as judged by the length of time spent in looking at different visual presentations, is evident at 2 or 3 months of age (Fantz). At this time infants are attracted more to certain patterns than to colors. At 3 months, most infants have discovered their hands and spend considerable time watching their movements. The ages at which infants begin to observe color, size, shape, and numbers can be determined by means of the Terman-Merrill and Stutzman intelligence tests (see Gibson and Olum). Perception of size becomes increasingly accurate in the preschool years. An 18-month-old child discriminates among pictures of familiar animals and recognizes them equally well if they are upside down.

Visual discrimination is reflected in manual reactions, just as auditory discrimination is reflected in vocal responses. Much of early visual development (first year) involves peering at objects, judging their position, reaching for them, and seizing and manipulating them. The inseparability of sensory and motor functions is never more obvious. Sensory deprivation impedes not only the natural sequences of perceptual awareness of the child's surroundings but also the development of all motor activities. Auditory discrimination—reflected in vocalizations such as babbling and, later, in word formation—is discussed further on in connection with language development.

The Development of Intelligence (See also Chap. 21)

The subject of intellectual endowment and the development and testing of intelligence were touched upon in Chap. 21. There it was pointed out that although intelligence is modifiable by training, practice, and schooling, it is much more a matter of native endowment and not simply a question of environment and providing the stimulus to learn, although these are clearly factors. It is evident early in life that some individuals have a superior intelligence; they also clearly maintain this differentiation all through life, and the opposite pertains in others.

Much of the uncertainty about the relative influence of heredity and environment relates to our imprecise views of what constitutes intelligence. The authors tend to agree with those who view intelligence as a general mental capability, embracing a number of primary abilities: the capacity to comprehend complex ideas, learn from experience, think abstractly, reason, plan, draw analogies, and solve problems. Thus intelligence includes a multiplicity of abilities, which probably accounts for a lack of consensus about its mechanism. Everyday experience teaches us that it is not always abstract tasks that suffer most when intelligence is impaired. Indeed, even abstraction is not likely to be a unitary function. Theoreticians, like Carl Spearman, believed that intelligence comprises a general (g), or core, factor and a series of special (s) factors. In contrast, Thurstone conceived of intelligence as a mosaic of factors such as drive and curiosity, verbal and arithmetic ability, memory, capacity for abstract thinking, practical skills in manipulating objects, geographic or spatial sense, and athletic and musical ability—each of which appears to be largely genetically determined. These and other theories concerning intellectual development in the child, such as those of Eysenck and of Gardner, and particularly those of Piaget, were considered briefly in Chap. 21, which may be read as an extension of this section.

The beginnings of the development of intelligence are difficult to discern. It is readily assessed at 8 to 9 months of life, when the infant begins to crawl and explore. Now, learning proceeds rapidly as adults attach names to objects and help the baby manipulate them. Gradually the child acquires verbal facility (learning what words mean), memory, color and spatial perception, a concept of number, and the practical use of tools, each at a particular time according to a schedule set largely by the maturational state of the brain. Nevertheless, in these early achievements individuals differ considerably, reflecting to some extent the influence of their parents and others around them. Also, the young child exhibits elementary modes of thinking but is highly suggestible and often incapable of separating imagination from reality.

Neurologists who need a quick and practical method of ascertaining whether an infant or preschool child is measuring up to normal standards for a particular age will find Table 28-4 useful. The main items are drawn from Gesell and Amatruda and from the Denver Developmental Test. In addition, a variety of intelligence tests have been designed to measure the child's special abilities and increasing success in learning in accordance with age (these are listed in Table 28-5). Starting at age 6 to 7 years, there is a steady improvement in intelligence scores that parallels chronologic age up to about age 13 years; thereafter the rate of advance diminishes. By age 16 to 17 years, performance reaches a plateau, but this is probably an artifact of the commonly used tests, which are designed to predict success in school. Only late in life do test scores begin to diminish, in a manner that is described in the next chapter on aging. Individuals with high or low IQs at 6 years of age tend to maintain their rank at 10, 15, and 20 years unless the early scores were impaired by anxiety, poor motivation, or a gross lack of opportunity to acquire the skills that are necessary to take such tests (language skill in particular). Even then, performance tasks, which largely eliminate verbal and mathematical skills, will disclose many individual differences.

The reliability of intelligence tests and their validity as predictive measures of scholastic, occupational, and economic success have been heatedly debated for many years. This aspect of the subject is discussed in the section on Intelligence in Chap. 21 and need not be repeated here. The most persuasive argument for these tests as an index of some type of native ability is that individuals drawn from a fairly homogeneous environment tend to maintain the same rating on the intelligence scale throughout their lives. While native endowment may set some limits on learning and achievement; opportunity, personality traits, and other factors clearly determine how nearly the individual's full potential is realized.

The Development of Language

Closely tied to the development of intelligence is the acquisition of language. Indeed, facility with language is one of the best indices of intelligence (Lenneberg). The acquisition of speech and language by the infant and child has been observed methodically by a number of eminent investigators, and their findings provide a background for the understanding of a number of derangements in the development of these functions (Ingram; Rutter and Martin).

Early verbalizations consist of babbling, cooing, and lalling stages, during which the infant, a few weeks old, emits a variety of cooing and then, at about 6 months, babbling sounds in the form of vowel–consonant (labial and nasoguttural) combinations. Later, babbling becomes interspersed with pauses, inflections, and intonations drawn from what the infant hears. At first this appears to be a purely self-initiated activity, being the same in normal and deaf infants. However, study of the latter shows that auditory modifications begin within a period of 2 to 3 months; without an auditory sense, babblers do not produce the variety of random sounds of the normal infant, nor do they begin to imitate the sounds made by the mother. Thus motor speech is stimulated and reinforced mainly by auditory sensations, which become linked to the kinesthetic ones arising from the speech musculature. It is not clear whether the capacity to hear and understand the spoken word precedes or follows the first motor speech. Perhaps it varies from one infant to another, but the dependence of motor speech development on hearing is undeniable. Comprehension seems to postdate the first verbal utterance of words in most infants.

Soon babbling merges with echo speech, in which short sounds are repeated parrot-like; gradually longer syllable groups are repeated correctly as the praxic function of the speech apparatus develops. As a general rule, the first recognizable words appear by the end of 12 months. Initially these are attached directly to persons and objects and then are used increasingly to designate objects. The word then becomes the symbol, and this substitution greatly facilitates speaking and later thinking about people and objects. Nouns are learned first, then verbs and other parts of speech. Exposure to and correction by parents and siblings gradually shapes vocal behavior, including the development of a distinctive and enduring accent, to conform to that of the social group in which the child is raised.

During the second year of life, the child begins to use word combinations. They form the propositions, which, according to Hughlings Jackson, are the essence of language (a notion in part echoed by modern linguists as noted in Chap. 23). On average, at 18 months the child can combine an average of 1.5 words; at 2 years, 2 words; at 2.5 years, 3 words; and at 3 years, 4 words. Pronunciation of words undergoes a similar progression; 90 percent of children can articulate all vowel sounds by the age of 3 years. At a slightly later age the consonants p, b, m, h, w, d, n, t, and k are enunciated; ng by the age of 4 years; y, j, zh, and wh by 5 to 6 years; and f, l, v, sh, ch, s, v, and th by 7 years. Girls tend to acquire articulatory facility earlier than boys. The vocabulary increases, so that at 18 months the child knows 6 to 20 words; by 24 months, 50 to 200 words; by 3 years, 200 to 400 words. By 4 years, the child is normally capable of telling stories, but with little distinction between fact and imagination. By 6 years, the average child knows several thousand words. Also by that age, children can indicate spatial and temporal relationships and start to inquire about causality. The understanding of spoken language always exceeds the child's speaking vocabulary; that is to say, most children understand more than they can say.

The next stage of language development is reading. Here there must be an association of graphic symbols with the auditory, visual, and kinesthetic images of words already acquired. Usually the written word is learned by associating it with the spoken word rather than with the seen object. The integrity of the superior gyrus of the temporal lobe (Wernicke area) and contiguous parietooccipital areas of the dominant hemisphere are essential to the establishment of these crossmodal associations. Writing is learned soon after reading, the audiovisual symbols of words being linked to cursive movements of the hand. The tradition of beginning grade school at 5 or 6 years is based not on an arbitrary decision but on the empirically determined age at which the nervous system of the average child is ready to learn and execute the tasks of reading, writing, and, soon thereafter, calculating.

Once language is fully acquired, it is integrated into all aspects of complex action and behavior. Movements of volitional type are activated by a spoken command or the individual's inner phrasing of an intended action. Every plan for the solution of a problem must be cast into language, and the final result is analyzed in verbal terms. Thinking and language are, therefore, inseparable.

Anthropologists see in all this a grander scheme wherein the individual recapitulates the language development of the human race. They point out that in primitive peoples, language consisted of gestures and the utterance of simple sounds expressing emotion and that, over periods of time, movements and sounds became the conventional signs and verbal symbols of objects. Later these sounds came to designate the abstract qualities of objects. Historically, signs and spoken language were the first means of human communication; graphic records appeared much later. Native Americans, for instance, never reached the level of syllabic written language. Writing commenced as pictorial representation and only much later in human evolution were alphabets devised. The reading and writing of words are comparatively late achievements. For further details concerning communicative and cognitive abilities and methods of assessment, the reader may consult the monograph by Minifie and Lloyd.

Sexual Development

The terms sexual and sexuality have several meanings in medical and nonmedical writings. The most obvious one relates to the functions of the male and female sexual organs through which procreation occurs and the survival of the species is assured as well as to behaviors that serve to attract the opposite sex and ultimately lead to mating. The terms refer also to a person's concern or preoccupation with sex or his erotic desires or activities. A more ambiguous meaning has been proposed by some psychologists, for whom the term is equated with all growth and development, the experience of pleasure, and survival.

Much of now discredited Freudian psychoanalytic theory centers on the sexual development of the child and, on the basis of questionable observations, espouses the view that repression of the sexual impulse and the psychic conflicts resulting therefrom are the main sources of neurosis and possibly psychosis.

The following are the main chronologic steps in sexual development, taken from the observations of Gesell and colleagues and itemized in de Ajuriaguerra's monograph. The timetable of menarche and other aspects of sexual development show considerable variation. If sexuality is not allowed natural expression, it often becomes a source of worry and preoccupation. Some 10 percent of the population fails to develop heterosexual orientation. Perverse derangements of psychosexual function are another matter entirely and are not addressed here.

Homosexuality

This denotes a preferential erotic attraction to members of the same sex. Most psychiatrists exclude from the definition of homosexuality those patterns of behavior that are not motivated by specific preferential desire, such as the incidental homosexuality of adolescents and the situational homosexuality of prisoners.

Figures on incidence are difficult to secure. According to the early reports of Kinsey and colleagues, approximately 4 percent of American males are exclusively homosexual and 8 percent have been "more or less exclusively homosexual for at least 3 years, sometime between the ages of 16 and 65." For females, the incidence is lower, perhaps half that for males. It was estimated, on the basis of the examination of large numbers of military personnel during World War II, that 1 to 2 percent of servicemen were exclusively or predominantly homosexual. More recent estimates, both in men and women, range from 1 to 5 percent (see LeVay and Hamer). These widely variable figures share a problem with all estimates derived from surveys and questionnaires: they cannot count people who do not wish to be counted.

The origins of homosexuality are obscure. The authors favor the hypothesis that differences or variations in genetic patterning of the nervous system (possibly of the hypothalamus) set the sexual predilection during early life. Several morphologic studies of the hypothalamus are significant in this regard. Swaab and Hofman have reported that the preoptic zone is three times larger in heterosexual males than it is in females, but it is about the same size in homosexual males as it is in females. As mentioned in Chap. 27, LeVay found that an aggregate of neurons in the suprachiasmatic nucleus of the hypothalamus is two to three times larger in heterosexual men than it is in women, and also two to three times larger in heterosexual than in homosexual men. If confirmed, these findings, which have been disputed by Byne and others, would support the view that homosexuality has a biologic basis. Genetic studies point in the same direction. Pooled data from 5 studies in men show that approximately 57 percent of identical twins (and 13 percent of brothers) of homosexual men are also homosexual. The figures for lesbians are much the same. In most studies, the inheritance pattern of male homosexuality comes from the maternal side, implicating a gene on the X chromosome (LeVay and Hamer) but to suggest there is a simple genetic connection is oversimplified.

Psychoanalytic explanations of homosexuality have never been substantiated. Attempts to demonstrate an endocrine basis for homosexuality have also failed. The most widely held current view is that homosexuality is not a mental or a personality disorder, though it may at times lead to secondary reactive disturbances. The studies of Kinsey and colleagues indicate that a homosexual orientation cannot be traced to a single social or psychologic root. Instead, as indicated above, homosexuality seems to arise from a deep-seated predisposition, biologic in origin and as ingrained as heterosexuality. The status of bisexuality is undetermined.

The Development of Personality and Social Adaptation (See also Chap. 51)

Personality, the most inclusive of all psychologic terms, encompasses the entirety of psychologic traits that distinguish one individual from every other. The notion that one's physical characteristics are determined by inheritance is a fundamental tenet of biology. One has but to observe the resemblances between parent and child to confirm this view. Just as no two persons are physically identical, not even monozygotic twins, so, too, do they differ in any other refined quality one chooses to measure, particularly those that determine behavior and modes of thinking. Strictly speaking, the normal person is an abstraction, just as is a typical example of any disease.

It is in nonphysical attributes that individuals display the greatest differences. Here reference is made to their variable place on a scale of energy, capacity for effective work, sensitivity, temperament, emotional responsivity, aggressivity or passivity, risk taking, ethical sense, flexibility, and tolerance to change and stress. The composite of these qualities constitutes the human personality or character. The current model of personality structure identifies 5 dimensions, which account for the covariation of most personality traits: (1) neuroticism versus emotional stability; (2) extraversion versus introversion; (3) openness to experience versus aversion to change; (4) agreeableness versus irascibility; and (5) conscientiousness versus unscrupulousness, and all five of these are heritable, as discussed in Chap. 51.

In the formation of personality, especially the part concerned with feeling and emotional sensitivity, basic temperament surely plays a large part. By nature, some children from the beginning seem to be happy, cheerful, and unconcerned about immediate frustrations; others are the opposite. By the third month of life, Birch and Belmont recognized individual differences in activity–passivity, regularity–irregularity, intensity of action, approach–withdrawal, adaptivity–unadaptivity, high–low threshold of response to stimulation, positive–negative mood, high–low selectivity, and high–low distractibility. Ratings at this early age were found to correlate with the results of examinations made at age 5 years. Kagan and Moss recognized the trait of timidity as early as 6 months of age and noted that it persists lifelong.

The more common aspects of personality, i.e., anxiety or serenity, timidity or boldness, the power of instinctual drives and need of satisfaction, sympathy for others, sensitivity to criticism, and degree of disorganization resulting from adverse circumstances, are presumed to be genetically determined. Identical twins raised apart are remarkably alike in these and many other personality traits (and have the same IQs, within a few points; Moser et al). Scarr and associates have also demonstrated the strong genetic influence on personality development. The related subject of the development of a moral sense that can be said to be part of an individual's personality has been subject to several competing theories. The interested reader is referred to Damon's summary of the topic.

Chapter 51 discusses disorders of personality and the genetic predisposition to certain personality traits further.

Social behavior, like other neurologic and psychologic functions in general, depends to a great extent on the development and maturation of the brain. Involved also are genetic and environmental factors, for one cannot adapt to society except in the presence of other people; i.e., social interaction is necessary for the emergence of many basic biologic traits. The roots of social behavior are traceable to certain instinctive patterns that are progressively elaborated by conditioned emotional reactions. In the long series of human interactions—first with parents, then with siblings and other children, and finally with a widening circle of individuals in the classroom and community, the capacity to cooperate, to subjugate one's own egocentric needs to those of the group, and to lead or be led appear as secondary modes of response (i.e., secondary to some of the basic impulses of anger, fear, self-protection, love, and pleasure). The sources of these social reactions are even more obscure than those of temperament, character, and intelligence.

In children, difficulty in social adaptation tends first to be manifest by an inability to take their places in a classroom. However, the greatest demands and frustrations in social development are likely to occur in late childhood and adolescence. The development of adult gonadal function and the further evolution of psychosexual impulses create a bewildering array of new challenges in social adaptation. These types of social adjustments continue as long as life continues. As social roles change, as intellectual and physical capacities first advance and later recede, new challenges demand new adaptations.

Delays in Motor Development

A delay in motor development is often accompanied by a delay in cognitive development, in which case both are parts of a developmental lag or immaturity of the entire cerebrum. The most severe forms of delayed motor development, those associated with spasticity and athetosis, are usually manifestations of prenatal and perinatal diseases of the brain subsumed under the term cerebral palsy; these are discussed in Chap. 38.

In assessing developmental abnormalities of the motor system in the neonate and young infant, the following maneuvers, which elicit certain postures and reflexive movements, are particularly useful:

1. The Moro response is the infant's reaction to startle and can be evoked by suddenly withdrawing support of the head and allowing the neck to extend. A loud noise, slapping the bed, or jerking one leg will have the same effect, causing an elevation and abduction of the arms followed by a clasping movement to the midline. This response is present in newborns and infants, it wanes after 2 months and is no longer elicitable after about 5 months of age, and its absence before that time or persistence afterwards indicates a disorder of the motor system. An absent or inadequate Moro response on one side is found in infants with hemiplegia, brachial plexus palsy, or a fractured clavicle. Persistence of the Moro response beyond 4 or 5 months of age is noted only in infants with severe neurologic defects.

2. The tonic neck reflex consisting of extension of the arm and leg on the side to which the head is passively turned and flexion of the opposite limbs, if obligatory and sustained, is a sign at any age of pyramidal or extrapyramidal motor abnormality. Barlow reports that he has obtained this reflex in 25 percent of developmentally delayed infants at 9 to 10 months of age. Fragments of the reflex, such as a brief extension of one arm, may be elicited in 60 percent of normal infants at 1 to 2 months of age and may be adopted spontaneously by the infant up to 6 months of age. As with the Moro response, persistence beyond this age represents a malfunction of the nervous system.

3. The placing reaction in which the foot or hand, brought into contact with the edge of a table, is lifted automatically and placed on the flat surface, is present in all normal newborns. Its absence or asymmetry in infants younger than 6 months of age indicates a motor abnormality.

4. In the Landau maneuver, the infant, if suspended horizontally in the prone position, will extend the neck and trunk and will break the trunk extension when the neck is passively flexed. This reaction is present by age 6 months; its delayed appearance in a hypotonic child is indicative of a faulty motor apparatus.

5. If an infant is held prone in the horizontal position and is then dropped toward the bed, an extension of the arms is evoked, as if to break the fall. This is known as the parachute response and is elicitable in most 9-month-old infants. If it is asymmetrical, it indicates a unilateral motor abnormality.

The detection of gross delays or abnormalities of motor development in the neonatal or early infantile period of life is aided little by tests of tendon and plantar reflexes. Arm reflexes are always rather difficult to obtain in infants, and a normal neonate may have a few beats of ankle clonus. The plantar response tends to be wavering and uncertain in pattern. However, a consistent extension of the great toe and fanning of the toes on stroking the side of the foot is abnormal at any age.

The early detection of cerebral palsy is hampered by the fact that the corticospinal tract is not fully myelinated until 18 months of age, allowing only quasivoluntary movements up to this time. For this reason, a congenital hemiparesis may not be evident until many months after birth. Even then it is manifest only by subtle signs, such as holding the hand in a fisted posture or clumsiness in reaching for objects and in transferring them from one hand to the other. Later, the leg is seen to be less active as the infant crawls, steps, and places the foot. Early hand dominance should always raise the suspicion of a motor defect on the opposite side. In the upper limb, the characteristic catch and yielding resistance of spasticity is most evident in passive abduction of the arm, extension of the elbow, dorsiflexion of the wrist, and supination of the forearm; in the leg, the change in tone is best detected by passive flexion of the knee. However, the time of appearance and degree of spasticity are variable from child to child. The stretch reflexes are hyperactive, and the plantar reflex may be extensor on the affected side. With bilateral hemiplegia, the same abnormalities are detectable, but there is a greater likelihood of pseudobulbar manifestations, with delayed, poorly enunciated speech.

Later, intelligence is likely to be impaired (in 40 percent of hemiplegias and 70 percent of bilateral hemiplegias). In diparesis or diplegia, hypotonia gives way to spasticity and the same delay in motor development except that it predominates in the legs. Aside from the hereditary spastic paraplegias, which may become evident in the second and third years, the common causes of weak spastic legs are prematurity and matrix hemorrhages. These various forms of cerebral palsy are described in Chap. 38.

Developmental motor delay and other abnormalities are present in a large proportion of infants with hypotonia. When the "floppy" infant is lifted and its limbs are passively manipulated, there is little muscle reactivity. In the supine position, the weakness and laxity result in a "frog-leg" posture, along with an increased mobility at the ankles and hips. Hypotonia, if generalized and accompanied by an absence of tendon reflexes, is most often a result of Werdnig-Hoffmann disease (an early life loss of anterior horn cells, a type of spinal muscular atrophy), although the range of possible diagnoses is large and includes diseases of muscle, nerve, and the central nervous system (see Chaps. 38 and 48). The other causes of this type of neonatal and infantile hypotonia include muscular dystrophies and congenital myopathies, maternal myasthenia gravis, polyneuropathies, Down syndrome, Prader-Willi syndrome, and spinal cord injuries, each of which is described in its appropriate chapter. Hypotonia that arises in utero may be accompanied by congenital fixed contractures of the joints, termed arthrogryposis, as discussed in Chap. 48.

Infants who will later manifest a central motor defect can sometimes be recognized by the briskness of their tendon reflexes and by the postures they assume when lifted. In the normal infant, the legs are flexed, slightly rotated externally, and associated with vigorous kicking movements. The hypotonic infant with a defect of the motor projection pathways may extend the legs or rotate them internally, with dorsiflexion of the feet and toes. Exceptionally, the legs are firmly flexed, but in either instance relatively few movements are made.

When hypotonia is a forerunner of an extrapyramidal motor disorder (so-called double athetosis, another type of cerebral palsy), the first hint of abnormality may be opisthotonic posturing of the head and neck. However, involuntary choreic movements usually do not appear in the upper limbs before 5 to 6 months of age and often are so slight as to be overlooked. They worsen as the infant matures and by 12 months assume a more athetotic character, often combined with tremor. Tone in the affected limbs is by then increased but may be interrupted during passive manipulation.

Hypotonia may also be a prelude to a cerebellar motor defect. The ataxia becomes apparent when the infant makes the first reaching movements. Tremulous, irregular movements of the trunk and head are seen when the infant attempts to sit without support. Still later, as the infant attempts to stand, there is unsteadiness of the entire body.

In distinction to the gross deficits in motor development described earlier, there is a distinct group of young children who exhibit only mild abnormalities of muscle tone, clumsiness or unusual postures or rhythmic movements of the hands, tremor, and ataxia ("fine motor deficit"), or "developmental coordination disorders." Such awkwardness in the somewhat older child is referred to as a "soft sign" and has been reviewed by Gubbay and colleagues in what they have called "the clumsy child." Like speech delay and dyslexia, fine motor deficits of this sort are more frequent in males. Tirosh found that intranatal problems were more prevalent among children with fine motor deficits (compared to those with gross motor deficits), as were minor physical anomalies and seizures.

Systemic diseases in infancy pose special problems in evaluation of the motor system. The achievement of motor milestones is delayed by illnesses such as congenital heart disease (especially cyanotic forms), cystic fibrosis, renal and hepatic diseases, infections, and surgical procedures. Under such conditions one does well to deal with the immediate illnesses and defer pronouncements about the status of cerebral function. The brain proves to be simultaneously affected in 25 percent of patients with serious forms of congenital heart disease and an even higher proportion of patients with rubella and coxsackie B viral infections. In a disease such as cystic fibrosis, where the brain is not affected, it is advisable to depend more on the analysis of language development than on assessment of motor function, because muscular activity may be generally enfeebled.

Delays in Sensory Development

Failure to see and to hear are the most important sensory defects affecting the infant and child. When both senses are affected, a severe cerebral defect is usually responsible; only at a later age, when the child is more testable, does it become apparent that the trouble is not with the peripheral sensory apparatus but with the central integrating mechanisms of the brain.

Failure of development of visual function is usually revealed by strabismus and by disorders of ocular movements, as described in Chap. 13. Any defect of the refractive apparatus or the acuity of the central visual pathways results in wandering, jerky movements of the eyes. The optic discs may be atrophic in such cases, but it should be pointed out that the discs in infants tend naturally to be paler than those of an older child. In congenital hypoplasia of the optic nerves, the nerve heads are extremely small. Defects in the retina and choroid are detectable by funduscopy. Faulty vision becomes increasingly apparent in older infants when the normal sequences of hand inspection and visuomanual coordination fail to emerge. Retention of pupillary light reflexes in a sightless child signifies a defect in the geniculocalcarine tracts or occipital lobes—conditions that may be confirmed by MRI and testing of visual evoked responses.

With respect to hearing, again there is the difficulty in evaluating this function in an infant. Normally, after a few weeks of life, alert parents notice that the child makes a brisk startle to loud noises and a response to other sounds. A tinkling bell brought from behind the infant usually results in hearkening or head turning and visual searching, but a lack of these responses warns only of the most severe hearing defects. The detection of slight degrees of deafness, enough to interfere with auditory learning, requires special testing. To make the problem even more difficult, both a peripheral and a central disorder may be present in some conditions, such as the now infrequent disorder of kernicterus. Brainstem auditory evoked responses are particularly helpful in confirming peripheral (cochlear and eighth nerve) abnormalities in the infant and young child. After the first few months, impaired hearing becomes more obvious and interferes with language development, as described further on. It is of interest that the identification and remediation of early (infants) hearing defects by screening leads to higher scores on language tests later in childhood but not improved speech, according to a study by Kennedy and colleagues.

A considerable portion of neuropediatric practice is committed to the diagnosis and management of children with learning disabilities. These problems usually come to light in the school-age child (hence the term school dysfunction), whose aptitude for classroom learning is poorer than the child's general intelligence. The medical referral may be from a parent, teacher, or psychologist. The clinician's objective is to determine by history and examination whether there is (1) a general congenital developmental abnormality impairing intelligence; (2) a specific deficit in reading, writing, arithmetic, or attention, any one of which may interfere with the child's ability to learn; (3) a primary sensory defect, particularly in audition; or (4) neither of these—for example, a behavior disorder or home situation that interferes with schooling.

Once diagnosis is achieved, the goal of management, undertaken in collaboration with psychologists and educators, is to fashion a program of remedial exercises that will maximize the child's skills to a point commensurate with his talent and aptitude, and restore his self-confidence.

Disorders in the Development of Speech and Language

In the pediatric age period and extending into adult life, one encounters an interesting assortment of developmental disorders of speech and language. Many patients with such disorders come from families in which similar speech defects, ambidexterity, and left-handedness are also frequent. Males predominate; in some series, male-to-female ratios as high as 10:1 have been reported.

Developmental disorders of speech and language are far more frequent than acquired disorders, e.g., aphasia. The former include developmental speech delay, congenital deafness with speech delay, developmental word deafness, dyslexia (special reading disability), cluttered speech, infantilisms of speech, and stuttering or stammering, and mechanical disorders such as cleft-palate speech. Often in these disorders, the various stages of language development described earlier are not attained at the usual age and may not be achieved even by adulthood. Disorders of this type, especially those restricted to the language areas of the cerebrum, are far more frequently a result of slowness in the normal processes of maturation than to an acquired disease. With the possible exception of developmental dyslexia (see further on), cerebral lesions have not been described in these cases, although it must be emphasized that only a small number of brains of such individuals have been thoroughly studied by proper methods.

In discussing the developmental disorders of speech and language, we have adopted a conventional classification. Not usually included in such a classification are the many mundane peculiarities of speech and language that are usually accepted without comment: lack of fluency, inability to speak uninterruptedly in complete sentences, and lack of proper intonation, inflection, and melody of speech (dysprosody).

Developmental Speech Delay

Fully two-thirds of children say their first words between 9 and 12 months of age and their first word combinations before their second birthday; when this does not happen, it becomes a matter of parental concern. Children who fail to reach these milestones at the stated times fall into two general categories. In one group there is no clear evidence of cognitive delay or impairment of neurologic or auditory function. In a second group, the speech delay has an overt pathologic basis.

The first group, comprising otherwise normal children who talk late, is the more puzzling. It is virtually impossible to predict whether such a child's speech will eventually be normal in all respects and just when this will occur. Prelanguage speech continues into the period when words and phrases should normally be used in propositional speech. The combinations of sounds are close to the standard of normal vowel–consonant combinations of the 1- to 2-year-old, and they may be strung together as if forming sentences. Yet, as time passes, the child may utter only a few understandable words, even by the third or fourth year. Three of 4 such patients will be boys and often one discovers a family history of delayed speech. When the child finally begins to talk, he may skip the early stages of spoken language and progress rapidly to speak in full sentences and to develop fluent speech and language in weeks or months. During the period of speech delay, the understanding of words and general intelligence develop normally, and communication by gestures may be remarkably facile. In such children, motor speech delay does not presage mental backwardness. (It is said that Albert Einstein did not speak until the age of 4 and lacked fluency at age 9.)

Nevertheless, the eventual acquisition of fluent speech is no guarantee of normalcy (Rutter and Martin). Many such children do have later educational difficulties, mainly because of dyslexia and dysgraphia, a combination that is sometimes inherited as an autosomal dominant trait, again more frequently in boys (see further on). In a smaller subgroup, articulation remains infantile and the content of speech is impoverished semantically and syntactically. Yet others, as they begin to speak, express themselves fluently, but with distortions, omissions, and cluttering of words, but such patients usually acquire normal speech patterns with development.

A second broad group of children with speech delay or slow speech development (no words by 18 months, no phrases by 30 months) comprises those in whom an overt pathologic basis is evident. In clinics where children of the latter type are studied systematically, 35 to 50 percent of cases occur in those with global developmental delay or "cerebral palsy." Hearing deficit explains many of the other cases, as discussed later, and a few represent what appears to be a specific lack of maturation of the motor speech areas or an acquired lesion in these parts. Only in this small, latter group is it appropriate to refer to the language disorder as aphasia, i.e., a derangement or loss of language caused by a cerebral lesion. Aphasia, when it occurs as the result of an acquired lesion (vascular, traumatic) is essentially of the motor variety and typically lasts but a few months in the child. It may be accompanied by a right-sided hemiplegia. An interesting type of acquired aphasia, possibly encephalitic, has been described by Landau and Kleffner in association with seizures and bitemporal focal discharges in the EEG (see "Seizures Presenting in Early Childhood" in Chap. 16).

Congenital Deafness

Speech delay caused by congenital deafness, whether peripheral (loss of pure-tone acuity) or central (pure-tone threshold normal by audiogram), is a most important condition but may at first be difficult to discern. One suspects that faulty hearing is causal when there is a history of familial deaf mutism, congenital rubella, erythroblastosis fetalis, meningitis, chronic bilateral ear infections, or the administration of ototoxic drugs to the pregnant mother or newborn infant—the well-known antecedents of deafness. It is estimated that approximately 3 million American children have hearing defects; 0.1 percent of the school population are deaf and 1.5 percent are hard of hearing. The parents' attention may be drawn to a defect in hearing when the infant fails to heed loud noises, to turn the eyes to sound sources outside the immediate visual fields, and to react to music; but in other instances, it is the delay in speaking that calls attention to it.

As already mentioned, the deaf child makes the transition from crying to cooing and babbling at the usual age of 3 to 5 months. After the sixth month, however, the child becomes much quieter, and the usual repertoire of babbling sounds becomes stereotyped and unchanging, though still uttered with pleasant voice. A more conspicuous failure comes somewhat later, when babbling fails to give way to word formation. Should deafness develop within the first few years of life, the child gradually loses such speech as had been acquired but can be retaught by the lipreading method. Speech, however, is harsh, poorly modulated, and unpleasant, and accompanied by many peculiar squeals and snorting or grunting noises. Social and other acquisitions appear at the expected times in the congenitally deaf child, unlike in the developmentally delayed child. The deaf child seems eager to communicate and makes known all his needs by gesture or pantomime, often very cleverly. The deaf child may attract attention by vivid facial expressions, motions of the lips, nodding, or head shaking. The Leiter performance scale, which makes no use of sounds, will show that intelligence is normal. Deafness can be demonstrated at an early age by careful observation of the child's responses to sounds and by free-field audiometry, but the full range of hearing cannot be accurately tested before the age of 3 or 4 years. Recording of brainstem auditory evoked potentials and testing of the labyrinths, which are frequently unresponsive in deaf mutes, may be helpful. Early diagnosis is important so as to fit the child with a hearing aid and to begin appropriate language training.

In contrast to the child in whom deafness is the only abnormality, the developmentally delayed child generally talks little but may display a rich personality. Autistic children may also be mute; if they speak, echolalia is prominent and the personal "I" is avoided. Blind children of normal intelligence tend to speak slowly and fail to acquire imitative gestures.

Congenital Word Deafness

This disorder, also called developmental receptive dysphasia, verbal auditory agnosia, or central deafness, is rare and may be difficult to distinguish from peripheral deafness. Usually the parents have noted that the word-deaf child responds to loud noises and music, but obviously this does not assure perfect hearing, particularly for high tones. The word-deaf child does not understand what is said, and delay and distortion of speech are evident.

Presumably, the receptive auditory elements of the dominant temporal cortex fail to discriminate the complex acoustic patterns of words and to associate them with visual images of people and objects. Despite intact pure-tone hearing, the child does not seem to hear word patterns properly and fails to reproduce them in natural speech. In other ways the child may be bright, but more often this auditory imperception of words is associated with hyperactivity, inattentiveness, bizarre behavior, or other perceptual defects incident to focal brain damage, particularly of the temporal lobes. Word-deaf children may chatter incessantly and often adopt a language of their own design, which the parents come to understand. This peculiar type of speech is known as idioglossia. It is also observed in children with marked articulatory defects.

Speech rehabilitation of the bright word-deaf child follows along the same lines as that of the congenitally deaf one. Such a child learns to lip-read quickly and is very facile at acting out his or her own ideas.

Congenital Inarticulation

In this developmental defect the child seems unable to coordinate the vocal, articulatory, and respiratory musculature for the purpose of speaking. Again, boys are affected more often than girls, and there is often a family history of the disorder, although the data are not quite sufficient to establish the pattern of inheritance. The incidence is 1 in every 200 children. The motor, sensory, emotional, and social attainments correspond to the norms for age, although in a few cases, a minority in the authors' opinion, there has been some indication of cranial nerve abnormality in the first months of life (ptosis, facial asymmetry, strange neonatal cry, and altered phonation).

In children with congenital inarticulation, the prelanguage sounds are probably abnormal, but this aspect of the speech disorder has not been well studied. Babbling tends to be deficient, and, in the second year, in attempting to say something, the child makes noises that do not sound at all like language; in this way the child is unlike the late talker already described. Again, the understanding of language is entirely normal; the comprehension vocabulary is average for age, and the child can appreciate syntax, as indicated by correct responses to questions by nodding or shaking the head and by the execution of complex spoken commands. Usually such patients are shy but otherwise quick in responding, cheerful, and without other behavioral disorders. Some are bright, but a combination of congenital inarticulation and mild mental slowness is also not uncommon. If many of the spontaneous utterances are intelligible, speech correction should be attempted (by a trained therapist). However, if the child makes no sounds that resemble words, the therapeutic effort should be directed toward a modified school program, and speech rehabilitation usually waits until some words are acquired.

Studies of the cerebra of such patients are not available, and it is doubtful if they would show any abnormality by the usual techniques of neuropathologic examination. Occasionally, suspicion of a lesion is raised by focal changes in the EEG or a slight widening of the temporal horn of the left ventricle. All manner of delayed speech is often attributed to being "tongue-tied," i.e., a short lingual frenulum, but this idea now seems outdated. Also, psychologists have attributed incomplete development of speech to overprotectiveness or excessive pressure by the parents but these are certainly the result rather than the cause of the delay.

A fuller review of this subject can be found in the text The Child with Delayed Speech, edited by Rutter and Martin.

Stuttering and Stammering

These difficulties occur in an estimated 1 to 2 percent of the school population. Often the conditions disappear in late childhood and adolescence; by adulthood, only about 1 in 300 individuals suffer from a persistent stammer or stutter. Mild degrees are to some extent cultivated and permit a pause in speech for collecting one's thoughts, and stammering appears to be an affectation in certain social circles, as in the past among educated Englishmen (and some Americans).

Stammering and stuttering are difficult to classify. In some respects they belong to and are customarily included in the developmental language disorders, but they differ in being largely centered in articulation. There is no valid reason to distinguish between these two forms of the inarticulation, as they are intermingled, and the terms stammer and stutter are now used synonymously. Essentially they represent a disorder of rhythm—an involuntary, repetitive prolongation of speech because of an insuppressible spasm of the articulatory muscles. The spasm may be tonic and result in a complete blocking of speech (at one time referred to specifically as stammering) or clonic speech, i.e., a rapid series of spasms interrupting the emission of consonants, usually the first letter or syllable of a word (stuttering). Certain sounds, particularly p and b, offer greater difficulty than others; paperboy comes out p-p-paper b-b-boy. The problem is usually not apparent when single words are being spoken and dysfluency tends to be worse at the beginning of a sentence or an idea. The severity of the stutter is increased by excitement and stress, as when speaking before others, and is reduced when the stutterer is relaxed and alone or when singing in a chorus. When severe, the spasms may overflow into other groups of muscles, mainly of the face and neck and even of the arms. The muscles involved in stuttering show no fault in actions other than speaking, and all gnostic and semantic aspects of receptive language are intact.

Males are affected four times as often as females. The time of onset of stuttering is mainly at two periods in life: between 2 and 4 years of age, when speech and language are evolving, and between 6 and 8 years of age, when these functions extend to reciting and reading aloud in the classroom. However, there may be a later onset. Many afflicted children have an associated difficulty in reading and writing. If stuttering is mild, it tends to develop or to be present only during periods of emotional stress, and in 4 of 5 children it disappears entirely or almost so during adolescence or the early adult years (Andrews and Harris). If severe, it persists throughout life regardless of treatment but tends to improve as the patient grows older.

Theories of causation are legion, attesting to a lack of actual explanation. Slowness in developing hand and eye preference, ambidexterity, or an enforced change from left- to right-hand use have been popular explanations, of which Orton and Travis were leading advocates. According to their theory, stuttering results from a lack of the necessary degree of unilateral control in the synchronization of bilaterally innervated speech mechanisms. Fox and colleagues support a theory of failure of left hemisphere dominance. By performing PET studies while a subject was reading, they found that the auditory and motor areas of the right hemisphere are activated instead of those of the left hemisphere. However, these explanations probably apply to only a minority of stutterers (Hécaen and de Ajuriaguerra). It is of interest that stutterers activate the motor cortex prematurely when reading words aloud and, as noted by Sandak and Fiez, affected individuals seem to initiate motor programs before the articulatory code is prepared. Recently, several groups have reported subtle structural anomalies in the gray matter of the perisylvian region, but no common theme has emerged, and others are skeptical of these findings (see editorial by Packman and Onslow). It has been commented in the literature on this subject that speech production is a highly distributed system and that compensatory mechanisms used by stutterers may confound interpretation of functional imaging studies.

The disappearance of mild stuttering with maturation has been attributed incorrectly to all manner of treatment (hypnosis, progressive relaxation, speaking in rhythms, etc.) and used to bolster particular theories of causation. Because stuttering may reappear at times of emotional strain, a psychogenesis has been proposed, but—as pointed out by Orton and by Baker and colleagues—if there are any psychologic abnormalities in the stutterer, they are secondary rather than primary. We have observed that many stutterers, probably as a result of this impediment to free social interaction, do become increasingly fearful of talking and may become very self-conscious. By the time adolescence and adulthood are reached, emotional factors are so prominent that many physicians still mistake stuttering for a psychogenic disorder. Usually there is little or no evidence of any personality deviation before the onset of stuttering, and psychotherapy has not had a significant effect on the underlying defect. (The eminent Dr. Stanley Cobb undertook Jungian psychoanalysis for the condition according to R.D. Adams, with no benefit whatsoever.) A strong family history in many cases and male dominance point to a genetic origin, but the inheritance does not follow a readily discernible pattern.

Stuttering is not associated with any detectable weakness or ataxia of the speech musculature. The muscles of speech go into spasm only when called upon to perform the specific act of speaking. The spasms are not invoked by other actions (which may not be as complex or voluntary as speaking), differing in this way from an apraxia and the intention spasm of athetosis. Also, palilalia is a different condition in which a word or phrase, usually the last one in a sentence, is repeated many times with decreasing volume. We are inclined toward a tentative view that stuttering represents a special category of extrapyramidal dystonic movement disorder, much like writer's cramp.

Rarely, in adults as well as in children, stuttering may be acquired as a result of a lesion in the motor speech areas. A distinction has been drawn between developmental and acquired stuttering. The latter is said to interfere with the enunciation of any syllable of a word (not just the first), to favor involvement of grammatical and substantive words, and to be unaccompanied by anxiety and facial grimacing. Such distinctions are probably illusory. The reported lesion sites in acquired stuttering are so variable (right frontal, corpus striatum, left temporal, left parietal) as to be difficult to reconcile with proposed theories of developmental stuttering (see Fleet and Heilman).

Another form of acquired stuttering is more manifestly an expression of an extrapyramidal disorder. Here there occurs a prolonged repetition of syllables (vowel and consonant), which the patient cannot easily interrupt. The abnormality involves throat-clearing and other vocalizations, similar to what is seen in tic disorders.

Treatment

The therapy of stuttering is difficult to evaluate and, on the whole, the therapy of speech-fluency disorders has been a frustrating effort. As remarked earlier, all these disturbances are modifiable by environmental circumstances. Thus a certain proportion of stutterers will become more fluent under certain conditions, such as reading aloud; others will stutter more severely at this time. Again, a majority of stutterers will be adversely affected by talking on the telephone; a minority are helped by this device. Some stutterers are more fluent under conditions of mild alcohol intoxication. Nearly every stutterer is fluent while singing. Schemes such as the encouragement of associated muscular movements ("penciling," etc.) and the adoption of a "theatrical" approach to speaking have been advocated. Common to all such efforts has been the difficulty of achieving carryover into the natural speaking environment. Progressive relaxation, hypnosis, delayed auditory feedback, loud noise that masks speech sounds, and many other ancillary measures may help, but only temporarily. Canevini and colleagues have made the interesting observation that stuttering improved in an epileptic treated with levetiracetam, and Rosenberger has commented on other drug therapies.

Cluttering, or Cluttered Speech

This is another special developmental disorder. It is characterized by uncontrollable speed of speech, which results in truncated, dysrhythmic, and often incoherent utterances. Omissions of consonants, elisions, improper phrasing, and inadequate intonation occur. It is as though the child were too hurried to take the trouble to pronounce each word carefully and to compose sentences. Cluttering is frequently associated with other motor speech impediments. Speech therapy (elocutionary) and maturation may be attended by a restoration of more normal rhythms.

Other Articulatory Defects

Milder speech defects are common in preschool children, having an incidence of up to 15 percent. There are several varieties. One is lisping, in which the s sound is replaced by th, e.g., thimple for simple. Another common condition, lallation, or dyslalia, is characterized by multiple substitutions or omissions of consonants. Milder degrees consist of difficulty in pronouncing one or two consonants that give the impression of "baby talk" and are referred to as "infantilisms." For example, the letter r may be incorrectly pronounced, so that it sounds like w or y; running a race becomes wunning a wace or yunning a yace. In severe forms, speech may be almost unintelligible. The child seems to be unaware that his or her speech differs from that of others and is distressed at not being understood. More important is the fact that in more than 90 percent of cases, the articulatory abnormalities disappear by the age of 8 years, either spontaneously or in response to speech therapy. The latter is usually started if these conditions persist into the fifth year. Presumably the natural cycle of motor speech acquisition has only been delayed, not arrested. Such abnormalities, however, are more frequent among developmentally delayed children than in normal children; with cognitive defects in general, many consonants are persistently mispronounced.

Another disorder is a congenital form of spastic bulbar speech, described by Worster-Drought, in which words are spoken slowly, with stiff labial and lingual movements, hyperactive jaw and facial reflexes, and, sometimes, mild dysphagia and dysphonia. The limbs may be unaffected, in contrast to cerebral palsy.

The mechanical speech disorder resulting from cleft palate is easily recognized. Many of these patients also have a harelip; the two abnormalities together interfere with sucking and later in life with the enunciation of labial and guttural consonants. The voice has an unpleasant nasality; often, if the defect is severe, there is an audible escape of air through the nose.

The aforementioned developmental abnormalities of speech pattern are only sometimes associated with disturbances of higher-order language processing. Rapin and Allen have described a number of such disturbances. In one, which they call the "semantic pragmatic syndrome," a failure to comprehend complex phrases and sentences is combined with fluent speech and well-formed sentences lacking in content. The syndrome resembles Wernicke or transcortical sensory aphasia (Chap. 23). In another, "semantic retrieval-organization syndrome," a severe anomia blocks word finding in spontaneous speech. A mixed expressive–receptive disorder may also be seen as a developmental abnormality; it contains many of the elements of acquired Broca's aphasia (Chap. 23). Recently, a category of "specific language impairment" has been created to encompass all failures to acquire language competence despite normal intelligence.

The role of certain genes, particularly FOXP2, in the development of language is mentioned in Chap. 23. Here it is pointed out that there is an isolated developmental verbal dyspraxia that is caused by a point mutation in this gene but that other disorders, such as dyslexia, have not yielded clearly to genetic analysis as discussed below. However, Vernes and colleagues have found that FOXP2 downregulates a gene (CNTNAP2) that encodes neurexin in the developing cortex. Polymorphisms of the gene are found in children with a number of specific but seemingly unrelated language deficits. They propose that this is a mechanistic link between different developmental language syndromes.

Developmental Dyslexia (Congenital Word Blindness)

This condition, first described by Hinshelwood in 1896, becomes manifest in an older child who is found to lack the aptitude for one or more of the specific skills necessary to derive meaning from the printed word. Also defined as a significant discrepancy between "measured intelligence" and "reading achievement" (Hynd et al), it has been found in 3 to 6 percent of all schoolchildren. There have been several excellent writings on the subject over the past century, to which the interested reader is referred for a detailed account (Orton; Critchley and Critchley; Rutter and Martin; Shaywitz; Rosenberger).

The main problem is an inability to read, spell, and to write words despite the ability to see and recognize letters. There is no loss of the ability to recognize the meaning of objects, pictures, and diagrams. According to Shaywitz, these children lack an awareness that words can be broken down into individual units of sound and that each segment of sound is represented by a letter or letters. This has been summarized as a problem in "phonologic processing," referring to the smallest unit of spoken language, the phoneme, and as a parallel inability of dyslexic individuals to appreciate a correspondence between phonemes and their written representation (graphemes). A defect in the decoding of acoustic signals is one postulated mechanism. In addition to the essential visuoperceptual defect, some individuals also manifest a failure of sequencing ability and altered cognitive processing of language. De Renzi and Luchelli have found a deficit of verbal and visual memory in some affected children as noted below.

Much of what has been learned about dyslexia applies to native speakers of English more than to those who speak Romance languages. English is more complex phonologically than most other languages; e.g., it uses 1,120 graphemes to represent 40 phonemes, in contrast to Italian, which uses 33 graphemes to represent 22 phonemes (see Paulesu et al). Children with native orthographic languages, such as Chinese and Japanese, apparently have a far lower incidence of dyslexia.

Often, before the child enters school, reading failure can be anticipated by a delay in attending to spoken words, difficulty with rhyming games, and speech characterized by frequent mispronunciations, hesitations, and dysfluency; or there may be a delay in learning to speak or in attaining clear articulation. In the early school years there are difficulties in copying, color naming, and formation of number concepts as well as the persistent reversal of letters. The child's writing reflects faulty perception of form and a kind of constructional and directional apraxia. Often, there is an associated vagueness about the serial order of letters in the alphabet and months in the year, as well as difficulty with numbers (acalculia) and an inability to spell and to read music. The complex of dyslexia, dyscalculia, finger agnosia, and right-left confusion is found in a small number of these children and is interpreted as a developmental form of the Gerstmann syndrome described in Chap. 22.

Lesser degrees of dyslexia are found in a large segment of the school population and are more common than the severe ones. Approximately 10 percent of schoolchildren in some surveys have some degree of this disability. The disorder is stable and persistent; however, as a result of effective methods of training, only a few children are unable to read at all after many years in school.

This form of language disorder, unattended by other neurologic signs, is strongly familial, in various series being almost in conformity with an autosomal dominant or sex-linked recessive pattern. Loci on chromosomes 6 and 15 have been implicated but not confirmed. There is also a higher incidence of left-handedness among these persons and members of their families. Shaywitz et al have suggested that the reported predominance of reading disabilities in boys (male-to-female ratios of 2:1 to 5:1) represents a bias in subject selection—many more boys than girls being identified because of associated hyperactivity and other behavioral problems; but to us this does not seem the entire explanation. Our casual clinical experience suggests that there is a genuine and substantial male preponderance. Nonetheless, an estimated 12 to 24 percent of dyslexic children will also have an attention-deficit hyperactivity disorder (ADHD) (see further on).

In the study of dyslexic and dysgraphic children, a number of other apparently congenital developmental abnormalities were documented, such as inadequate perception of space and form (poor performance on form boards and in tasks requiring construction); inadequate perception of size, distance, and temporal sequences and rhythms; and inability to imitate sequences of movements gracefully, as well as slight degrees of clumsiness and reduced proficiency in all motor tasks and games (the clumsy child syndrome as described by Gubbay et al and also by Denckla et al as mentioned earlier in the chapter under "Delays in Motor Development"). These disorders may also occur in brain-injured children; hence there may be considerable difficulty in separating simple delay or arrest in development from a pathologic process in the brain. However, in the majority of dyslexic children these additional features are absent or so subtle as to require special testing for their detection.

A few careful morphometric studies have provided insight into the basis of this disorder. Galaburda and associates have studied the brains of 4 males (ages 14 to 32 years) with developmental dyslexia. In each case there were anomalies of the cerebral cortex consisting of minor neuronal ectopias and architectonic dysplasias, located mainly in the perisylvian regions of the left hemisphere. More in conformity with imaging studies noted below, all of the brains were characterized by relative symmetry of the planum temporale, in distinction to the usual pattern of cerebral asymmetry that favors the planum temporale of the left side. Similar changes have been described in 3 women with developmental dyslexia (Humphreys et al). CT and MRI scanning of large numbers of dyslexic patients (as well as some patients with autism and developmental speech delay) have demonstrated an increased prevalence of relative symmetry (reversed or "atypical" asymmetry) of the temporal planes of the two hemispheres (Rosenberger; Hynd et al). It is important to note, however, that not all patients with developmental dyslexia show this anomalous anatomic asymmetry (Rumsey et al). In other studies, a number of variable alterations of cortical organization were found by Casanova and colleagues, most notably, in one case, an enlargement of the minicolumns in the temporal cortex. (A similar developmental change has been found in the brains of individuals with Down syndrome and with autism.)

Leonard and colleagues, using MRI, demonstrated several other gyral anomalies in dyslexic subjects: in the planum temporale and neighboring parietal operculum of both hemispheres, some gyri were missing and others were duplicated. In some dyslexic individuals, the visual evoked to rapid low-contrast stimuli are diminished. This abnormality has been related to a deficit of large neurons in the lateral geniculate bodies (see Livingstone et al).

Specific spelling difficulty probably represents another developmental language disorder, distinct from dyslexia.

Additional physiologic data from functional imaging studies support the presence of an abnormal temporoparietal cortex in dyslexics. These regions, particularly the posterior portion of the superior temporal, angular, and supramarginal gyri, are selectively activated during reading in normal individuals but not in dyslexics, who activate very restricted regions of the cerebral hemisphere, mainly the Broca area. In addition, they recruit other areas not normally activated during reading, such as the inferior frontal regions. It is noteworthy that Simos and coworkers were able to show that these aberrant patterns (using functional MRI) normalized after several weeks of intensive training. If nothing else, these findings validate the localization of the functional problem in the dominant temporoparietal area, and support the notion that developmental dyslexia is susceptible to improvement by proper training.

Treatment

The steady practice (many hours per week) of a cooperative and motivated child by a skillful teacher over an extended period slowly overcomes the handicap and enables an otherwise intelligent child to read at grade level and to follow a regular program of education. The Orton phonologic method has been one of the most widely used over the years (for details, see Rosenberger). Secondary school and college students with reading deficits successfully resort to tape recorders, tutorial aids, and laptop computers that allow for review of material after classes.

Developmental Dysgraphia

Developmental writing disorders differ from dyslexia in having both linguistic and motor (orthographic) aspects. As indicated earlier, dysgraphias are present in many dyslexic children and may be combined with difficulty in calculation (so-called developmental Gerstmann syndrome). Two forms of dysgraphia have been distinguished. In one there is good spontaneous handwriting and formation of letters and spacing but miswriting of dictated words (linguistic dysgraphia). In the other, there are reversals of letters and letter order and poor alignment (mechanical dysgraphia). It is this latter type that seems to us to be the genuine, or at least the purer, dysgraphia.

Developmental Dyscalculia

This disorder, like dyslexia, usually becomes evident in the first few years of grade school, when the child is challenged by tasks of adding and subtracting and, later, multiplying and dividing. In some instances there is an evident disorder in the spatial arrangements of numbers that has been termed "anarithmetia" as noted in Chap. 22 (supposedly a right hemispheral fault). In others, there is a lexical–graphical abnormality (naming and reading the names of numbers) akin to aphasia.

Probably most of what has been said about the treatment of developmental dyslexia applies to acalculia and agraphia. The usual type of conventional classroom work does little to increase the child's proficiency in writing and arithmetic, but special tutoring and drills aid the student to some extent. All of these impairments may be associated with hyperactivity and attentional defects, as described below (Denckla et al).

Precocious Reading and Calculating

In direct contrast to the conditions discussed above, precocious reading and calculating abilities have also been identified. A 2- or 3-year old child may read with the skill of an average adult. Extraordinary facility with numbers (mathematical prodigies) and memorization ability (eidetic imagery) are comparable traits. One of these special abilities may be observed in a child with a mild form of autism (Asperger syndrome, see Chap. 38). Such children exhibit great skill in performing particular mathematical tricks but are unable to solve simple arithmetical problems or to understand the meaning of numbers ("idiot savant"). In the child with Williams syndrome, language and sometimes musical skills are not so much precocious as relatively normal in comparison to the overall mental deficiency, indicating that not all forms of cognitive delay impair language skills.

Congenital Amusia

One would expect that developmental deficiencies similar to those found for language would exist for music. This uncommon condition, commonly known as tone deafness, has only recently been studied. According to the careful studies of Ayotte and colleagues, there are deficits not only in appreciating pitch variation but also in music memorization, singing, and rhythmicity. These authors propose that the defect in pitch perception is at the root of the other abnormalities. What is also interesting is that amusia occurs without any difficulty in the processing of speech and language, specifically, prosody and prosodic interpretation are preserved. (See Chap. 22 for a discussion of the acquired defects of musical appreciation.)

Attention-Deficit Hyperactivity Disorder

A large portion of ambulatory pediatric neurology practice consists of children who are referred because of failure in school related to overactivity, impulsivity, and inattentiveness. The question often asked is whether they have an identifiable brain disease. According to Barlow, when a large number of such cases is analyzed, fully 85 percent prove to have no major signs of neurologic disease. Perhaps 5 percent are mentally subnormal and another 5 to 10 percent show some evidence of a minimal brain disorder. Many are clumsy. In the larger group without neurologic signs, the IQ is normal, although there are also cases of borderline intelligence. Boys are more often found to be hyperactive and inattentive than girls, just as they often have more trouble in learning to read and write. Dyslexia is frequently associated, as noted earlier. Girls with ADHD tend to have more trouble with numbers and arithmetic.

Human infants exhibit astonishing differences in amount of activity almost from the first days of life. Some babies are constantly on the move, wiry, and hard to hold; others are placid and slack as a sack of meal. Irwin, who studied motility in the neonate, found a difference of 290 times between the most and least active in terms of amount of movement per 24 h.

Once walking and running begin, children normally enter a period of extreme activity, more so than at any other period of life. The degree of activity, which varies widely from one child to another, seems not to be correlated with the age of achieving motor milestones or with motor skill at a later time.

Again, two groups of overactive children can be discerned early in life. In one, infants are constitutionally overactive from birth, sleeping less and feeding poorly; by the age of 2 years, the syndrome is obvious. In the other group, an inability to sit quietly only becomes apparent at the preschool age (4 to 6 years). Seldom do such children remain in one position for more than a few seconds, even when watching television. They are seen as fidgety, constantly in motion, and a bit wild in public places such as restaurants. Attention to any task cannot be sustained, hence the term attention-deficit hyperactivity disorder. As a rule, there is also an abnormal impulsivity and often an intolerance of all measures of restraint.

Currently, three clinical subsyndromes have been delineated: (1) combined hyperactivity, impulsivity, and inattention, which describes approximately 80 percent of affected children; (2) a predominantly inattentive syndrome; and (3) a small group that display only hyperactivity. It is also valuable to point out that a syndrome with most of the features of ADHD can be embedded in several forms of overarching cognitive and developmental delay, including in children with autistic traits. This takes on special significance in the exploration of a genetic basis for attention-deficit disorder, as noted below.

Once the child is in school, the attention deficit becomes a more troubling, practical problem. Now these children must sit still, watch and listen to the teacher when she speaks to another child, and not react to distracting stimuli. They cannot stay at their desks, take turns in reciting, be quiet, or control their impulsivity. The teacher finds it difficult to discipline them and the school often insists that the parents seek medical consultation for the child. A few are so hyperactive that they cannot attend regular classes. Their behavior verges on the "organic drivenness" that has been known to occur in children whose brains have been injured by encephalitis. In certain families, the disorder is probably inherited (Biederman et al). In about half the hyperactivity subsides gradually by puberty or soon thereafter, but in the remainder the symptoms persist in modified form into adulthood (Weiss et al).

It has also become clear that there are a large group of children who have difficulty sustaining concentration but do not manifest hyperactivity or behaviors that betray the attention deficit. It is presumed that they share a similar core problem with hyperkinetic children, and it has been observed that they may be helped in studying and school performance by the same stimulant drugs that are used for the treatment of more overt ADHD. A precise relationship between motor hyperactivity and the inability to concentrate and stay focused on a series of tasks has not been established. It would seem that these are but two aspects of the same fundamental disorder of drive and attention, but it is clear that there are individuals who have difficulty concentrating but who are not manifestly hyperactive. This becomes a particular issue in adults with ostensible ADHD who feel they have always had trouble focusing as discussed further on.

For a number of years there was a tendency to consider children with the hyperkinetic syndrome as having a form of minimal brain disease. "Soft neurologic signs" such as right–left confusion, mirror movements, minimal "choreic" instability of the hands, awkwardness, finger agnosia, tremor, and borderline hyperreflexia were said to be more frequent among them. The issue of mild developmental disorders of coordination constitutes its own subject independent of ADHD. The notion of this type of clumsiness has been known for over a century and was called debilite motrice by Dupre. The connection to ADHD, however, is evident in Annell's description (taken from the review by Kirby and Sugden) ". . awkward in movements, poor at games, hopeless in dancing and gymnastics, a bad writer and defective in communication. He is inattentive, cannot sit still, leaves his shoelaces untied, does buttons wrongly, bumps into furniture, breaks glassware, slips off his chair, kicks his legs against the desk, and perhaps reads badly." Dyslexia is found in approximately 20 percent and a similar clumsiness is known to occur in many developmental disorders and forms of cognitive delay. These signs, however, are seen so often in normal children that their attribution to disease is invalid. Consequently, Schain and others substituted the term minimal brain dysfunction, which is no more accurate and simply restates the problem and, furthermore, may not be accurate in many cases.

Lacking altogether are clinicoanatomic and clinicopathologic correlative data, but some morphologic and physiologic data are available. In an MRI study of the brains of 10 children with ADHD, Hynd and colleagues found the width of the right frontal lobe to be smaller than normal; also fairly consistently, there was a reduction in the volume of the dorsolateral, cingulate, and striatal regions. Unlike dyslexics, in whom the planum temporale tends to be equal in the two hemispheres, the left planum was larger in the attention-deficit cases, just as it is in normals. Also, functional imaging studies have suggested that changes in the striatum underlie the inability of these children to block impulsive reactions and the improvement that is seen with methylphenidate. One would expect the prefrontal cortex to be implicated in such a disinhibitory syndrome but what data exist have been complex and difficult to interpret.

Another approach to understanding the process has been to study a strain of mice that have been genetically altered to eliminate a dopamine transporter gene. These animals display behavioral symptoms that are said to replicate those of ADHD in children and also to respond to stimulants, observations that implicate an abnormality of dopamine and serotonin. This idea is provocative because several genetic linkage studies have suggested an association between ADHD and a polymorphism of the gene that codes for the same dopamine transporter gene. Furthermore, copy number variations in genes that relate to development, a rich field for study in autism, give rise to global forms of cognitive delay that display prominent features of ADHD. Most of these are duplications or deletions that congregate on chromosomes 15 and 16.

Apart from the reports of parents and teachers and observation of the child, one is aided in the diagnosis of ADHD (and other learning disabilities) by psychometry. An observant psychologist, in performing intelligence tests, notes distractibility and difficulty in sustaining any activity. Erratic performance that is not the result of a defect in comprehension is also characteristic. The Vanderbilt Assessment Scale is a checklist that is completed with parents or teachers.

Treatment of ADHD

The treatment of the hyperactive child can proceed reasonably only after medical and psychologic evaluations have clarified the context in which the hyperactivity occurs. If the child is hyperactive and inattentive mainly in school and less so in an unstructured environment, it may be that mild developmental delay or a specific cognitive deficiency or dyslexia, which prevents scholastic success, is a source of frustration and boredom. The child then turns to other activities that may happen to disturb the classroom. Or the hyperactive child may have failed to acquire self-control because of a disorganized home life, and the overactivity may be but one manifestation of anxiety or intolerance of constraint. Clearly problems such as these require a modification of the educational program.

For overactive children of normal intelligence who have failed to control their impulses, who at all times have boundless energy, require little sleep, exhibit a wriggling restlessness (the "choreiform syndrome" of Prechtl and Stemmer), and manifest incessant exploratory activity that repeatedly gets them into mischief, even to their own dismay, medical therapy is justified. Paradoxically, stimulants have a quieting effect on these children, whereas sedatives may do the opposite.

Methylphenidate is the drug most widely used and its use has been validated in several studies. Children weighing less than 30 kg are given 5 mg each morning on school days for 2 weeks, after which the dose can be raised to 5 mg morning and noon. Children weighing more than 30 kg can be given a single 20-mg sustained-release tablet each morning. If methylphenidate proves ineffective after several weeks or cannot be tolerated, dextroamphetamine 2.5 to 5 mg three times daily or a mixed amphetamine-dextroamphetamine are suitable substitutes. Atomoxetine, a norepinephrine inhibitor, is also effective and is not classified as a stimulant but has caused a few cases of liver failure. If these agents control the activity and improve school performance (they can be continued for a number of years), there is then no need to alter the child's school program. It is not clear if there should be a long-term concern about hypertension, but the blood pressure is not generally measured at frequent intervals. If stimulants are ineffective, tricyclic antidepressants, particularly desipramine, may be tried. Multiple medications should be generally avoided. Classroom behavioral conditioning techniques and psychotherapy may be needed for brief periods but are not as effective as medication. Remedial education is reserved for recalcitrant cases. Biederman and Faraone have summarized approaches to treatment.

Adult Attention-Deficit Disorder

Certainly this disease is a lifelong problem for a proportion of children, although it is just as clear that many "outgrow" the hyperactivity and attention deficit. Hill and Schoener estimate that there is a 50 percent decline in prevalence with each 5 years that pass. Other authorities state that the problem persists in 80 percent. In addition to the child with ADHD who grows to adulthood with persistent problems, there recently has emerged an emphasis on a group of adults who present for the first time with features of difficulty focusing or concentrating that they or their physicians attribute to ADHD. The hyperactivity component is generally absent and may not have occurred in childhood, making the validity of the diagnosis uncertain in adults who were not identified as having ADHD in childhood. A study by Kessler and colleagues suggests that 4.4 percent of adults in the United States have the disorder. European investigators use more restrictive criteria for diagnosis and find far lower frequencies in both children and adults, with consequentially far fewer prescriptions being written for stimulant drugs.

An approach to screening in adults has been given by McCann and Roy-Byrne. Most often these adults come to realize they have had a lifelong problem that is similar to the motor restlessness and wandering attention that led to the diagnosis of ADHD in their own children. The efficacy and safety of stimulant drugs in the adult group are not known with certainty, but this class of medications has been tried with some benefit according to many patients. Some data have emerged that the cardiovascular risks are greater in adults than in children; reports of anxiety and palpations, as well as elevations in blood pressure, are common among adults taking the medications.

Many such individuals are of above-average intelligence and have attained high degrees of professional success, perhaps as a result of strategies developed implicitly over the years, such as note taking, organizers, mental reminders to focus, etc. These same adjustments can be quite useful to others who are struggling with the disorder so that medication is not the only alternative to surmount the cognitive problem. In relation to persistent traits of ADHD from childhood, several psychiatrists have pointed out that there may be an increase in drug and alcohol dependence among adolescents with the disorder (Zametkin and Ernst) and a slight overrepresentation of tic disorders such as Gilles de la Tourette syndrome. Our general clinical experience suggests that these additional problems do not arise in the great majority of such children. Recent studies have been reassuring in this regard, but the concern regarding tics has remained.

Enuresis

Voluntary sphincteric control develops according to a predetermined time scale. Usually normal children stop soiling themselves before they can remain dry, and day control precedes night control. Some children are toilet trained by their second birthday, but many do not acquire full sphincteric control until the fourth year. Constant dribbling usually indicates spina bifida, another form of dysraphism, or a tethered cord, but in the boy, one must look also for obstruction of the bladder neck, and in the girl, for an ectopic ureter entering the vagina.

When a child 5 years of age or older wets the bed nearly every night and is dry by day, the child is said to have nocturnal enuresis. This condition afflicts approximately 10 percent of children between 4 and 14 years of age, boys more than girls, and continues in many cases to be a problem even into adolescence and adulthood. Although developmentally delayed children are notably late in acquiring sphincter control (some never do), the majority of enuretic individuals are normal in other respects.

The cause of this condition is disputed. Often there is a family history of the same complaint. Some psychiatrists have insisted that overzealous parents "pressure" the child until he develops a "complex" about his bedwetting; this is highly doubtful. The underlying condition is believed by most neurologists to be a delay in the maturation of higher control of spinal reflex centers during sleep. These and other abnormalities of bladder function in the enuretic child, as well as treatment, are also discussed Chap. 19 in relation to sleep.

Sociopathy

Extremes of egocentricity, lack of understanding of the feelings, needs, and actions of others, and an inability to judge one's own strengths and weaknesses stand as the central issues in a certain type of personality disorder. Such difficulties usually become manifest by adolescence. The complete detachment of the child with psychosis, the amorality of the constitutional sociopath, the major disturbances in thinking of the schizophrenic, and the mood swings of the bipolar also express themselves in many, if not most, instances by adolescence and sometimes by late childhood. Here one confronts a key problem in psychiatry—the extent to which sociopathy has its roots in genetically determined personality traits or in derangements in the affective and social life of the individual consequent to a harmful environment. The answers to these questions cannot be given with finality but most clinicians believe that genetic factors are more important than environmental ones. The discovery that unusually tall males with severe acne vulgaris and aggressive sociopathic behavior may have a karyotype of XYY chromosomes is an extreme but instructive example of a genetic relationship. The patients with Turner syndrome in whom competent social adaptation is linked closely to an X chromosome of paternal origin is another example. Furthermore, there is no critical evidence to show that deliberate alteration of the familial and social environmental measures now so popular have ever prevented sociopathy.

It is during the period of late childhood and adolescence, when the personality is evolving and least stable, that transient symptoms resembling the psychopathologic states of adult life are most frequent and difficult to interpret. Some of these disorders represent the early signs of schizophrenia or bipolar disease. Others are forerunners of sociopathy. But many of these traits have a way of disappearing as adult years are reached so that one can only surmise that they represented either a maturational delay in the attainment of mature social behavior or were expressions of adolescent turmoil, or what has been called "adolescent adjustment reaction."

Many issues that have been touched upon in the preceding discussion are considered more fully in the section on psychiatric disorders (particularly Chap. 51).

(See also Chap. 38)

A symptom complex of incomplete development of global cognitive capacities and certain associated behavioral changes combines many of the developmental abnormalities already discussed. What has been called mental retardation and now, intellectual and developmental delay, stands as the single largest neuropsychiatric disorder in every industrialized society. In deference changed attitudes towards the formerly used term "mental retardation," we employ alternatives in this text. The overall frequency of the problem cannot be stated precisely but rough estimates are that in children between 9 and 14 years of age, approximately 2 percent or slightly more will be unable to profit from conventional education or to adapt socially and, when grown, to live independently.

Using any one of a number of indices of social and cognitive delay, two somewhat overlapping groups are recognized: (1) the mildly impaired (IQ 45 to 70), and (2) the severely impaired, corresponding to an IQ below 45.

The second group, called the pathologically delayed, makes up approximately 10 percent of the mental retardation population. The more mildly affected first group, includes a group of the familial developmentally delayed, is much larger.

Within the severely delayed there are gradations. Because of the objectionable implications of the previously used terms idiot, imbecile, and moron, the developmentally delayed can be grouped instead into four categories: (1) those with profound deficiency, incapable of self-care (IQ below 25); (2) those with severe deficiency, incapable of living an independent existence and essentially untrainable (IQ 25 to 39); (3) those with moderate deficiency, trainable to some extent (IQ 40 to 54); and (4) those with mild deficiency, who are impaired but trainable and to some extent educable. The above terms, while in common use, satisfy neither neurologists nor psychologists because of their generality, embracing as they do any lifelong global deficit in mental capacities. The terms convey no information of the particular type of intellectual impairment, their causes and mechanisms, or their anatomic and pathologic bases. Moreover, they express only one aspect of impaired mental function—the cognitive—and ignore the inadequate development of personality, social adaptation, and behavior. A more comprehensive view is provided by assessing the individual's adaptive abilities along the lines of conceptual, social, and practical skills that allow planning for maximizing independence and productivity.

When the brains of severely affected people are examined by conventional methods, gross lesions are found in approximately 90 percent of cases. Just as noteworthy is the fact that among the remaining 10 percent of the severely delayed, the brains are grossly and microscopically normal. Despite the recent discovery of many mutations that may give rise to a delay in cognitive development only a modest proportion of cases of those with milder deficiency can presently be traced to one of the congenital abnormalities of development that are described in Chap. 38 and the vast majority of the less-severely delayed also lack a recognizable tissue pathology and have not exhibited any of the conventional signs of cerebral disease.

In our view, a more acceptable view of the mildly affected group is that they represent the proportion of the population that is on the low end of the Gaussian curve of intelligence, i.e., they constitute the group that falls between 2 to 3 standard deviations (SD) below the mean (Fig. 28-4) and are the opposite in this respect to genius. Lewis was one of the first to call attention to this large group of mildly delayed individuals and he referred to them by the ambiguous term subcultural. The term familial retardation was in the past applied to this group, because in some of the families, members of the same and previous generations have reduced cognitive ability.

An important advance in the understanding of developmental delay has now emerged from careful genetic studies that have identified specific loci that at which deletions or duplications result in intellectual disability. Some of these express particular syndromes such as cognitive delay with autism or epilepsy; however, the same genetic changes can be found among individuals who have only autism or schizophrenia. While a unifying explanation for these disparate disorders has yet to be defined, they probably have subcellular and synaptic changes in common as summarized by Mefford, Batshaw, Hoffman in their review that is recommended to the reader.

Both the milder and more-severe forms of developmental delay that are associated with physical abnormalities and diseases of the brain, as well as nondysmorphic and genetic forms of delayed development are discussed in Chap. 38.