Книги по МРТ КТ на английском языке / The Embryonic Human Brain An Atlas of Developmental Stages. Third Edition. 2006. By Ronan O'Rahilly

THE SPINAL CORD IN THE EMBRYONIC PERIOD

Both the brain and the spinal cord are modifications of a continuous neural tube, so that, although this book is on the brain, it is appropriate to provide a summary of the development of the spinal cord.

The alar and basal laminae of the neural tube (Fig. 21– 7) are separated by the sulcus limitans. The alar laminae, essentially afferent in function, are united by the roof plate, whereas the basal laminae, essentially efferent (the Bell– Magendie “law”), are joined by the floor plate, which is induced by the notochord. At 6 weeks the spinal cord shows ventricular, intermediate, and marginal layers, and all the spinal nerves are present (stage 17).

The following sequence of appearance has been found in the human embryo (Marti et al., 1987): (1) cells of the floor plate, (2) motor neurons, which arise in rostrocaudal and ventrodorsal gradients; (3) cells of the nucleus proprius, and (4) sensory neurons (for pain afferents) in the substantia gelatinosa. Motor neurons, the first neural cells to show expression of neuronal antigens, present synapses very early, namely at stage 15 (Okado, 1981). Synapses between primary afferents and interneurons of the substantia gelatinosa also appear early (stage 17). The first movements observed ultrasonically (Okado, 1981; de Vries, 1992) occur at about 5 12 postfertilizational weeks (probably stage 16).

The trigeminospinal tract enters the cervical region of the cord already at 6 weeks (stage 17), the dorsal funiculus is prominent, and the tractus solitarius soon reaches the thoracic region (stage 19). By the end of the embryonic period (stage 23), the funiculi gracilis et cuneatus, medial lemniscus, corticopinal tracts, and lateral spinothalamic tract are present (Muller¨ and O’Rahilly, 1990a).

At this time the spinal cord still extends as far as the caudal end of the vertebral column (O’Rahilly, Muller,¨ and Meyer, 1980, Fig. 4). Subsequently some dedifferentiation takes place caudally and the spinal cord “ascends” to a lumbar level during the first half of prenatal life, reaching L3 at birth and generally L1 or L2 in the adult. The disproportion in growth between the spinal cord and the vertebral column results in the characteristically increasing obliquity of the roots of the spinal nerves from lower cervical to coccygeal; those of L2 to Co. 1 constitute the cauda equina.

NEUROTERATOLOGY:

(MYELO)MENINGOCELE

Myelomeningocele involves the neural tube and hence appears early, e.g., at stage 10 or 11 in the cervical and thoracic regions. At the lumbosacral level, where it is believed by many to be converted from a myeloschisis, myelomeningocele arises also during the period of primary neurulation (stages 8–12), although it is not a simple failure of neural closure.

Lumbosacral lesions covered by intact skin are believed to appear during secondary neurulation (Lemire et al., 1975), but it should be stressed that lesions in the transitional zone between primary and secondary neurulation are not well understood.

Numerous embryos and fetuses with myelomeningocele have been described (Lemire et al., 1975), including an embryo of stage 14 with caudal myeloschisis. It was believed that the lesion occurred before closure of the neural tube; defects in the basement membrane of the neural ectoderm were noted and the condition was considered to have been a forerunner of lumbosacral myelomeningocele (Lemire et al., 1965).

Meningocele probably arises late in the embryonic period (e.g., stages 18–23) or early in the fetal period. The timing of various anomalies, however, is tentative and the retrospective use of embryological timetables for ascertainment of origin and causes of congenital malformations is hazardous, as frequently stressed by Warkany.

The possible reopening of a closed neural tube may be operative in at least some instances (O’Rahilly and Muller,¨ 1988), especially in cervical or thoracic defects and in meningoceles. Moreover, experimental support is available. For example, the fetuses of rats subjected to cyclophosphamide showed fewer mesenchymal cells, reduced cytoplasmic processes, and poor organization and differentiation. These features, as well as degenerative changes in the neural epithelium, “appeared to underlie the reopening of the closed neural tube” that resulted in exencephaly and cranioschisis (Padmanabhan). Perhaps a mesenchymal defect may be considered, in a certain sense, to be a locus minoris resistentiae that would allow reopening.

It is of interest that neural tube defects at stage 12 are more than 40 times more frequent than the number found at birth, so that most of the affected conceptuses are lost before birth, probably mainly within the embryonic period (Shiota, 1991).

The most noticeable external changes in the fetus are (1) the union of the cerebellar halves and the definition of the vermis, (2) the increasing concealment of the diencephalon and mesencephalon, and (later on) of a part of the cerebellum, by the cerebral hemispheres, (3) further approach of the frontal and temporal poles around the insula, which becomes increasingly buried by opercula,

(4) the appearance of sulci on the hemispheric surface at about the middle of prenatal life, and (5) the decreasing conspicuousness of the flexures, although the longitudinal axis of the cerebral hemispheres is set obliquely in relation to the brain stem throughout life (i.e., the “forebrain angle”

is greater than a right angle). The “C-shaped structures” are listed with Figure 24–5.

Although this book is concerned primarily with the embryonic period, the fetal period is summarized in several chapters in order to provide some degree of continuity between the embryonic and the postnatal brain. The subdivision is based on trimesters because a morphological staging system is not available for the fetal period. Further information concerning the fetal brain is available in such books as those by Barbe´ (1938), Fontes (1944), Lemire et al. (1975), and Gilles et al. (1983), and in the useful atlas by Feess-Higgins and Larroche (1987).

C H A P T E R

CH

24

TRIMESTER 1: EARLY POSTEMBRYONIC PHASE

The period from 8 to 9 weeks, i.e., the week following the embryonic period, is exemplified here by fetuses of 27.5, 33, and 42 mm GL. It has already been

pointed out that morphology and not size is the criterion for staging, and this atlas includes an embryo of 33 mm as well as a fetus of 27.5 mm. It has been mentioned also that a staging system is not (yet) available for the fetal period, and proposals so far have been based on age and fetal length, which do not provide (morphological) stages.

Although fusion of the medial walls of the cerebral hemispheres does not occur during the embryonic period, the events during the fetal period are not as clear. Fusion was denied by Hochstetter (1929), whereas others have supported fusion “between the banks of the median groove” formed in the floor of the longitudinal fissure “by the infolding of the lamina reuniens of His” (Rakic and Yakovlev, 1968). The cavum septi pellucidi is discussed with Figure 26–7.

At the end of the embryonic period proper the spinal cord still reaches to the caudal end of the vertebral column (O’Rahilly, Muller,¨ and Meyer, 1980, Fig. 4). Some dedifferentiation then takes place caudally and the spinal cord “ascends” to a lumbar level during the first half of prenatal life.

Precision

A double m is not used in mamillary because the term is derived from the Latin mamilla, which in turn is a diminutive of mamma, which does have a double m.

Pain Pathways and Prenatal Pain. Receptors, such as those in the skin, appear during the embryonic period, as do also interneurons in the substantia gelatinosa of the spinal cord (stage 17). Moreover, the spinothalamic tract and thalamocortical fibers are identifiable later in the embryonic period (stages 22 and 23 in the authors’ observations). Thalamocortical connections are generally considered to be essential for the perception of pain.

Corticothalamic fibers are probably present early in the fetal period. Thalamocortical fibers form temporary synapses in the cortical subplate during trimester 2 and penetrate the cortical plate in trimester 3, at which time thalamic inputs reach the somatosensory cortex. The functional significance of these immature pathways is not clear, and pain-suppressing systems are not as mature as painconducting ones. Moreover, it is possible that information concerning pain is transferred differently before and after birth. Myelination, however, is not necessary for pain either before or after birth (Fitzgerald, 1993). In addition, there is reason to believe that adverse neonatal experiences may alter the development of the brain, as well as subsequent behavior (Anand and Scalzo, 2000).

It may be concluded that, although nociperception (the actual perception of pain) awaits the appearance of consciousness, nociception (the experience of pain) is present some time before birth. In the absence of disproof, it is merely prudent to assume that pain can be experienced even early in prenatal life (Dr. J. Wisser, Zurich):¨ the fetus should be given the benefit of the doubt.

Figures 24–1 to 24–7 are from a fetus of 33 mm (silverimpregnated). In contrast to stage 23, the external capsule

is now present and the inferior olivary nucleus has five components.