Human anatomy informatics
e35
1.2
YRATNEMMOC
Fig. 2.1.3 The entry for the trophectoderm in the ontology of human developmental anatomy, shown in the OBO-Edit browser. The hierarchies showing
lineage and parts are on the left and the relationships included in the ontology are on the right. (With permission from Day-Richter J, Harris MA,
Haendel M et al 2007 OBO-Edit--an ontology editor for biologists. Bioinformatics 23(16):2198–2200.)
that the cross-species anatomy ontology Uberon (Mungall et al 2012) abnormal (diseased) phenotypes to defined elements of anatomy
has become critical, as it can be used to define phenotype ontology (Schofield and Hancock 2012). Once this has happened, collating and
terms from all species and, thus, allow crossing of the species divide. integrating a wide range of human tissue-associated data computation-
Using this approach, it is possible, for example, to assert that there is a ally will become possible (Yue et al 2005).
relationship between clinodactyly in humans, bent digits in the mouse In the clinic, we are now beginning to see the application of formal
and, more distantly, pectoral fin abnormalities in zebrafish. Recent anatomy ontology frameworks to diagnostics and interventions. For
advances that use model organism data to prioritize candidate genes example, the FMA has been incorporated into RadLex, the unified lan-
for rare diseases would not be possible without the formalization and guage of radiology terms from the Radiological Society of North
integration of anatomical ontologies (Hoehndorf et al 2013). America, which is used by radiologists and instrument developers for
indexing and retrieval of radiology information resources (Mejino et al
2008). More recently, FMA terms have been integrated with cortical
Prospects
parcellation terminologies (Turner et al 2010), presaging the future pen-
etration of ontologies through imaging, radiotherapy and surgery. Clini-
The current state of human anatomy informatics is that the core ontolo- cians are increasingly becoming used to handling and interpreting data
gies are in place but their formal tissue IDs (FMAID and EHDAA2) have from highly sophisticated instrumentation, and it will be necessary to


yet to be used to annotate data in the ways now being employed for include an understanding of the informatic basis of the software used
other model organisms. Over the coming few years, we can expect a in daily practice in medical training: a topic missing now from all but
start to be made in annotating human data on gene expression and the most specialized and advanced courses.
REFERENCES
Bard JB 2005 Anatomics: the intersection of anatomy and bioinformatics. Druzinsky R, Mungall C, Haendel M et al 2013 What is an anatomy ontol-
J Anat 206:1–16. ogy? Anat Rec 296:1797–99.
Bard JL, Kaufman MH, Dubreuil C et al 1998 An internet-accessible database Firth HV, Richards SM, Bevan AP et al 2009 DECIPHER: Database of Chro-
of mouse developmental anatomy based on a systematic nomenclature. mosomal Imbalance and Phenotype in Humans Using Ensembl
Mech Dev 74:111–20. Resources. Am J Hum Genet 84:524–33.


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Hoehndorf R, Schofield PN, Gkoutos GV 2013 An integrative, translational Stromme P 1991 The diagnosis of syndromes by use of a dysmorphology
approach to understanding rare and orphan genetically based diseases. database. Acta Paediatr Scand 80:106–9.
Interface Focus 3:20120055. Theiler K 1989 The House Mouse: Atlas of Embryonic Development. New
Kohler S, Doelken SC, Mungall CJ et al 2014 The Human Phenotype Ontol- York: Springer-Verlag.
ogy project: linking molecular biology and disease through phenotype Turner JA, Mejino JL, Brinkley JF et al 2010 Application of neuroanatomical
data. Nucleic Acids Res 42(Database issue):D966–74. ontologies for neuroimaging data annotation. Frontiers Neuroinform 4.
Mejino JL, Rubin DL, Brinkley JF 2008 FMA-RadLex: an application ontology doi: 10.3389/fninf.2010.00010 (eCollection).
of radiological anatomy derived from the foundational model of Xue L, Yi H, Huang Z et al 2011 Global gene expression during the human
anatomy reference ontology. AMIA Annu Symp Proc 6:465–9. organogenesis: from transcription profiles to function predictions. Int J
Mungall CJ, Torniai C, Gkoutos GV et al 2012 Uberon, an integrative multi- Biol Sci 7:1068–76.
species anatomy ontology. Genome Biol 13:R5. Xue L, Cai J, Ma J et al 2013 Global expression profiling reveals genetic
Rosse C, Mejino JL Jr 2003 A reference ontology for biomedical informat- programs underlying the developmental divergence between mouse and
ics: the Foundational Model of Anatomy. J Biomed Inform 36: human embryogenesis. BMC Genomics 14:568.
478–500. Yue L, Reisdorf WC 2005 Pathway and ontology analysis: emerging
Rosse C, Mejino JLV 2007 The Foundational Model of Anatomy Ontology. approaches connecting transcriptome data and clinical endpoints.


In: Burger A, Davidson D, Baldock R (eds), Anatomy Ontologies for Current Molec Med 5:11–21.
Bioinformatics: Principles and Practice, London: Springer, pp 59–117.
Schofield PN, Hancock JM 2012 Integration of global resources for human
genetic variation and disease. Hum Mutat 33:813–16.


COMMENTARY
An evolutionary consideration of
2.2
pharyngeal development
Anthony Graham, Victoria L Shone
The pharynx is a complex region of the body that is involved in numer-
ous critical functions; in pondering its mature anatomical organiza-
tion, it can be difficult to discern the rules that underpin its
construction. However, there is an underlying logic that is evident if
one considers how this region of the body is formed during embryo-
genesis. The pharyngeal apparatus has its developmental origin in a
series of bulges found on the lateral surface of the head at early stages:
the pharyngeal arches. In humans, there are five pharyngeal arches,
numbered 1, 2, 3, 4 and 6. It has been suggested that a fifth arch exists
transiently during embryogenesis, although there is no substantive evi-
Expanding
dence to support this. second arch Cervical sinus
The development of the pharyngeal arches is complex, because they
comprise a number of disparate embryonic cell types (see Fig. 36.3). A B
Externally, the arches are circumscribed by ectoderm, and internally, by
endoderm; each has a mesenchymal core of neural crest cells that sur-
round a central group of cranial paraxial mesodermal cells. The differ-
ent embryonic populations that constitute the arches must be
coordinated so that each will form the appropriate derivative at the right
time and place, and so that those derivatives have the morphology
associated with their specific pharyngeal arch.
For many years, it was believed that it was the neural crest cells that
directed the development of the arches. However, it was subsequently
shown that rudimentary pharyngeal arches can form in the absence of
neural crest cells (Veitch et al 1999). Moreover, other studies have high-
Cervical cysts
lighted the significance of the segmentation of the endoderm in direct-
Cervical cyst with external
ing pharyngeal arch development. A key event in the development of fistula
the pharyngeal arches is the formation of outpocketings within the
Cervical cysts
endoderm, the pharyngeal pouches, of which there are four; mutants
with internal


that fail to segment the endoderm fail to form pharyngeal arches (Pio- Cervical cysts
fistula
trowski et al 2000). The pharyngeal pouches form at distinct positions with internal
along the rostrocaudal axis and will eventually contact the overlying C D and external
fistulae
ectoderm, which invaginates to meet the pouches (see Figs 36.3, 36.4).
It should be noted that in animals and animal embryos the rostrocaudal Fig. 2.2.1 Normal and abnormal internalization of the lower posterior
axis is referred to as anteroposterior. These portions of the ectoderm are pharyngeal arches. A, A longitudinal section through the pharyngeal
termed the pharyngeal clefts. It is this apposition between the pouches arches at the point where the second pharyngeal arch is expanding to
cover the posterior arches. B, The end results of the expansion of the
and clefts that will define the anterior and posterior (rostral and caudal)
second pharyngeal arch. The caudal edge of the second pharyngeal arch
margins of each pharyngeal arch. Significantly, it is the formation of the
has fused with the subjacent tissue, which results in formation of a sinus
pharyngeal pouches that is the first indication of pharyngeal arch for-
between the inner surface of the second arch and the external surface of
mation. Thus, neural crest cells and cranial paraxial mesoderm migrate
the posterior arches. This sinus is subsequently eradicated. C, Two of the
into pre-existing epithelial segments that have been previously formed
consequences that result from the incomplete loss of the sinus following
by the pharyngeal pouches. The endoderm then signals to other tissues
the fusion of the caudal edge of the second arch; if the sinus is not lost,
of the arches and directs their development. It has been shown that
then this cavity persists as a cervical cyst. If the caudal edge of the
fibroblast growth factor (FGF) signalling emanating from the endoderm second arch also does not fuse properly with the subjacent tissue, then


promotes chondrogenesis within the neural crest, and the pouches also this results in a cyst with an external opening, or fistula. D, The two other
induce the formation of the epibranchial placodes (Graham 2008). consequences that can result from incomplete loss of the sinus following
These are ectodermal thickenings that will give rise to the neurones of fusion of the caudal edge of the second arch. A cyst will form and this
the geniculate, petrosal and nodose ganglia. However, in general, sub- can have an internal opening, or fistula, or it may have both internal and
sequent pharyngeal arch development will involve a complex interplay external openings, or fistulae.
of signals from the different constituent tissues.
At later stages, this segmental origin of our pharynx is obscured as
development progresses, with the majority of the arches partaking in a
complex remodelling that results in their obliteration (Fig. 2.2.1; see It is also important to note that there are significant differences
also Table 36.1, Fig. 36.7). This process involves the posterior expansion between the development of the anterior and posterior pharyngeal
of the second pharyngeal arch, so that it comes to cover all posterior arches. The two most anterior pharyngeal pouches form at the same
arches (see Fig. 2.2.1) (Richardson et al 2012). This results in these time, while the more posterior pouches form sequentially. The develop-
posterior arches becoming enclosed in a cavity, the cervical sinus of His, ment of the posterior pouches is also under the control of distinct
which, in turn, is eliminated by the apposition and fusion of its walls, signalling pathways. It has been shown that retinoid and Wnt signalling
yielding a smooth outline to the external surface of the neck (see Fig. is required for the formation of the more posterior pouches but not the
2.2.1, Fig. 36.10). Significantly, there are instances in which this remod- anterior (Quinlan et al 2002, Choe et al 2013). One key gene for the


elling is abnormal and this can result in the presence of a cervical cyst, formation of the posterior, but not anterior, pharyngeal pouches is Tbx1
arising from the persistence of the sinus; this may or may not be associ- (Xu et al 2005). This gene is required to drive proliferation within the
ated with internal and/or external openings, or fistulae (see Figs 2.2.1, endoderm; in mutants that lack Tbx1 function, the posterior pharyngeal
36.4C). Such malformations represent the second most common con- pouches fail to form and the neural crest fails to become segregated.
genital lesions of the head and neck in children. Patients with DiGeorge syndrome present with defects of posterior e37


An evolutionAry considerAtion of phAryngeAl development
e38
2
noitces
pharyngeal arch derivatives and this is strongly associated with muta- requires the gene gcm2, and both arise from the posterior pharyngeal
tions in Tbx1, suggesting that the aetiological basis of this syndrome pouches where the early developmental programme for gill formation
lies in a failure of the formation of the posterior pouches. persists in the amniote posterior pharynx (Okabe and Graham 2004).
A pervasive influence on how the pharyngeal region is organized is Furthermore, although as adults we do not have an operculum, this
its evolutionary history; it is through this that one can appreciate the structure does exist as an embryonic entity (Richardson et al 2012). The
significance of the differences between development of the anterior posteriorly expanding second arch that covers our posterior arches is
versus the posterior pharyngeal arches. In all gnathostomes, the first homologous to the developing operculum of fish. This is driven by shh
two pharyngeal arches form the jaw and hyoid, while the more pos- signalling in both amniotes and fish, and these structures express the
terior arches are gill-bearing. In many fish, these are covered by a protec- same key genes. The situation in amniotes differs from that in fish,
tive flap, the operculum, which helps to draw water into the pharyngeal however, in that the leading edge of the caudally expanding second arch
cavity and pass it over the gills, aiding respiration. Thus, the vertebrate fuses with the epithelium at the level of the cardiac eminence. Crucially,
pharynx is fundamentally split into an anterior region primarily con- this event mirrors what is seen during amphibian metamorphosis,
cerned with feeding and a posterior region concerned with respiration. where the gills are also internalized; significantly, both the proper
However, it is believed that, when the vertebrates colonized land, the fusion of the posterior edge of the second arch in amniotes and amphib-
pharynx was substantially remodelled; with a shift to lung-based respi- ian metamorphosis require thyroid hormone signalling. Thus, the fact


ration, the gills and the operculum were lost. that the anterior and posterior pharyngeal arches are underpinned by
Yet, more recently, it has been demonstrated that the gills were not different developmental programmes betrays our evolutionary history
lost from amniotes but were transformed into the parathyroid primor- and indicates that the ancestral functional division between the anterior
dia. The development of both the gills and the parathyroid glands and posterior pharynx still exists in amniotes.
REFERENCES
Choe CP, Collazo A, Trinh le A et al 2013 Wnt-dependent epithelial transi- Richardson J, Shono T, Okabe M et al 2012 The presence of an embryonic
tions drive pharyngeal pouch formation. Dev Cell 24:296–309. opercular flap in amniotes. Proc Royal Soc B 279:224–9.
Graham A 2008 Deconstructing the pharyngeal metamere. J Exp Zool Veitch E, Begbie J, Schilling TF et al 1999 Pharyngeal arch patterning in the
310B:336–44. absence of neural crest. Curr Biol 9:1481–4.
Okabe M, Graham A 2004 The origin of the parathyroid gland. Proc Natl Xu H, Cerrato F, Baldini A 2005 Timed mutation and cell-fate mapping
Acad Sci USA 101:17716–19. reveal reiterated roles of Tbx1 during embryogenesis, and a crucial func-
Piotrowski T, Nusslein-Volhard C 2000 The endoderm plays an important tion during segmentation of the pharyngeal system via regulation of
role in patterning the segmented pharyngeal region in zebrafish (Danio endoderm expansion. Development 132:4387–95.
rerio). Dev Biol 225:339–56.
Quinlan R, Gale E, Maden M et al 2002 Deficits in the posterior pharyngeal
endoderm in the absence of retinoids. Dev Dyn 225:54–60.


CHAPTER
16
Overview of the nervous system
The human nervous system is the most complex product of evolution. sensory endings; and special visceral sensory neurones are related to the
The activity of its billions of neurones and glia constitutes the physical special sense of taste.
basis of consciousness, experience, thought and behaviour. Research to The spinal cord and brain communicate with the rest of the body
elucidate the systems and circuits involved in normal neural develop- via the spinal and cranial nerves respectively. These nerves contain affer-
ment and function is one of the most active areas of contemporary ent fibres that bring information into the CNS from sensory receptors,
biology and medicine, and yet our understanding of these processes, and efferent fibres that convey instructions from the CNS to peripheral
which is essential for translational success, remains far from effector organs. The spinal cord and brainstem can control many aspects
complete. of bodily function by reflex action mediated via interconnections of
The nervous system has two major divisions, the central nervous varying complexity between the afferent and efferent components of
system (CNS) and the peripheral nervous system (PNS). The CNS con- the spinal and cranial nerves. Numerous descending connections from
sists of the brain, spinal cord, optic nerve and retina, and contains the the brain may modulate this activity. Afferent input to the spinal cord
majority of neuronal cell bodies. The PNS includes all nervous tissue and brainstem is channelled into various ascending pathways, some of
outside the CNS and consists of the cranial and spinal nerves, the which eventually impinge upon the cerebral cortex, conferring con-
peripheral autonomic nervous system (ANS) and the special senses scious awareness.
(taste, olfaction, vision, hearing and balance). It is composed mainly To provide the energy required by constant neuronal activity, the
of the axons of sensory and motor neurones that pass between the CNS CNS has a high metabolic rate and a rich blood supply (Ch. 19). A
and the body. The ANS is subdivided into sympathetic and parasympa- blood–brain barrier controls the neuronal environment and imposes
thetic components. It consists of neurones that innervate secretory
glands and cardiac and smooth muscle, and is concerned primarily with
control of the internal environment. Neurones in the wall of the gas- A


trointestinal tract form the enteric nervous system (ENS) and are
capable of sustaining local reflex activity that is independent of the
CNS. The ENS contains as many intrinsic neurones in its ganglia as
B
the entire spinal cord and is often considered as a third division of
the nervous system.
The detailed microstructure of the nervous system is described in
Chapter 3 and the development of the nervous system is described in
Chapter 17.
CENTRAL NERVOUS SYSTEM
The brain and spinal cord (see Fig. 45.1A) contain the great majority
of neuronal cell bodies in the nervous system. In many parts of the
CNS, neuronal cell bodies are grouped together and are, more or less, C
segregated from axons. The generic term for such collections of cell
bodies is grey matter. Small aggregations of neuronal cell bodies, which
usually share a common functional role, are termed nuclei. Neuronal
dendrites and synaptic interactions are mostly confined to grey matter.
Axons tend to be grouped together to form white matter, so called
because axons are often ensheathed in myelin, which confers a paler
colouration. Axons that pass between similar origins or destinations
Special somatic sensory (vestibulocochlear)
within the CNS tend to run together in defined pathways, or tracts. General somatic sensory
These often cross the midline (decussate), which means that one half Special visceral sensory (taste)
of the body is, in many respects, controlled by, and sends information General visceral sensory
to, the opposite side of the brain. Visceral motor
Some groups of neurones in the spinal cord and brainstem that Branchial motor
Somatic motor
subserve similar functions are organized into longitudinal columns.
The neurones in these columns may be concentrated into discrete,
discontinuous nuclei in some areas, e.g. the cranial nerve nuclei of the Dorsal sensory column
brainstem, or they may form more or less continuous longitudinal Ventral motor column
bands, as in much of the spinal cord (Fig. 16.1). Efferent neurones
constitute three such columns. The axons of motor neurones in the Intermediate (lateral) visceral motor column
somatic motor column innervate muscles derived from head somites.
Fig .16 .1 The arrangement of sensory and motor cell columns in the


The two other columns are related to specialized features of head mor-
spinal cord and brainstem . In each of parts A, B and C, dorsal is towards
phology: neurones in the branchial motor column innervate muscles
the top of the diagram . A, The organization of the primitive spinal cord
derived from the wall of the embryonic pharynx (branchial muscles)
with a dorsal sensory column, a ventral motor column, and segmentally
and the visceral motor column supplies preganglionic parasympathetic
arranged dorsal and ventral nerve roots . B, The adult thoracic spinal cord
fibres to glands and visceral smooth muscle. Four longitudinal cell with sensory and somatic motor columns and an additional intermediate
columns are related to sensory functions. The general somatic sensory (lateral) visceral motor column . C, The arrangement of multiple
column essentially deals with general sensory information from the longitudinal columns in the brainstem, where the motor column is now
head; special somatic sensory neurones are related to the special senses subdivided into three, and the sensory column into four . For further
and receive vestibular and auditory input; general visceral sensory neu- information about the embryological aspects of the early nervous system,
rones deal with information from widespread and varied visceral consult Chapter 17 . 227


OvERvIEw Of THE NERvOuS SySTEm
228
3
NOITCES
Dorsal horn Afferent neurone, cell body White matter Dorsal horn
Lateral horn White matter
Dorsal root of spinal nerve Central canal Dorsal root ganglion
Spinal nerve
Ventral root of spinal nerve Efferent neurone, cell body
Grey matter Ventral horn
Fig .16 .2 A transverse section through the spinal cord, illustrating the
disposition of grey and white matter and the attachment of dorsal and
ventral spinal nerve roots .
severe restrictions on the types of substance that can pass from the
bloodstream into nervous tissue.
Grey matter Ventral horn
SPINAL CORD Fig .16 .3 A transverse section through the spinal cord at lumbar level .
The section has been stained for nerve fibres, leaving the grey matter
The spinal cord lies within the vertebral column, in the upper two- relatively unstained . (Figure enhanced by B Crossman .)
thirds of the vertebral canal, and is continuous rostrally with the
medulla oblongata of the brainstem. For the most part, the spinal cord
receives afferent input from, and controls the functions of, the trunk the pons. The cerebellum consists of paired hemispheres united by a
and limbs. Afferent and efferent connections between the periphery and median vermis and lies within the posterior cranial fossa, dorsal to the
the spinal cord travel in 31 pairs of segmentally arranged spinal nerves pons, medulla and caudal midbrain, with all of which it has numerous
that attach to the cord as a linear series of dorsal and ventral rootlets. fibre connections.
Adjacent groups of rootlets unite to form dorsal and ventral roots that The prosencephalon is subdivided into the diencephalon and the
combine to form the spinal nerves proper (Fig. 16.2). The dorsal and telencephalon. The diencephalon equates mostly to the thalamus and
ventral roots are functionally distinct. Dorsal roots carry primary affer- hypothalamus, but also includes the smaller epithalamus and subtha-
ent nerve fibres from neuronal cell bodies located in dorsal root ganglia, lamus. The telencephalon is mainly composed of the two cerebral


whereas ventral roots carry efferent fibres from neuronal cell bodies hemispheres or cerebrum. The diencephalon is almost completely
located in the spinal grey matter. embedded in the cerebrum and is, therefore, largely hidden from the
Internally, the spinal cord consists of a central core of grey matter exterior. The human cerebrum constitutes the major part of the brain.
surrounded by white matter. The grey matter is configured in a charac- It occupies the anterior and middle cranial fossae and is directly related
teristic H, or butterfly, shape that has projections known as dorsal to the cranial vault. It consists of two cerebral hemispheres. The surface
(posterior) and ventral (anterior) horns (Fig. 16.3). In general, neu- of each hemisphere is convoluted into a complex pattern of ridges (gyri)
rones situated in the dorsal horn are primarily concerned with sensory and furrows (sulci). Internally, each hemisphere has an outer layer of
functions whilst those in the ventral horn are mostly associated with grey matter, the cerebral cortex, beneath which lies a thick mass of white
motor activities. At thoracic and upper lumbar levels of the spinal cord matter (Fig. 16.7). One of the most important components of the
a small lateral horn is additionally present, marking the location of the cerebral white matter, the internal capsule (see Fig. 16.9), contains
cell bodies of preganglionic sympathetic neurones. The central canal, a nerve fibres that pass to and from the cerebral cortex and lower levels
vestigial component of the ventricular system, lies at the centre of the of the neuraxis. Several large nuclei of grey matter, the basal ganglia or
spinal grey matter and runs the length of the cord. The white matter of basal nuclei, are partly embedded in the subcortical white matter. Nerve
the spinal cord consists of ascending and descending tracts that link fibre connections between corresponding areas on either side of the
spinal cord segments to one another and the spinal cord to the brain. brain cross the midline within commissures, by far the largest being the
corpus callosum.
During prenatal development, the walls of the neural tube thicken
BRAIN greatly but never completely obliterate the central lumen. Although the
latter remains in the spinal cord as the vestigial central canal, it becomes


The brain (encephalon) lies within the cranium. The brain receives greatly expanded in the brain to form a series of interconnected cavities
information from, and controls the activities of, the trunk and limbs, or ventricles (Ch. 18). In two regions, the fore- and hindbrain, parts of
mainly through connections with the spinal cord. It also possesses 12 the roof of the neural tube do not generate nerve cells but become thin,
pairs of cranial nerves through which it communicates mostly with folded sheets of highly vascular secretory tissue, the choroid plexuses.
structures of the head and neck. The brain is divided into major regions These secrete cerebrospinal fluid that fills the ventricles. The cavity of
on the basis of ontogenetic growth and phylogenetic principles (Figs. the rhombencephalon becomes expanded to form the fourth ventricle,
16.4–16.6). Ascending in sequence from the spinal cord, the principal which lies dorsal to the pons and upper half of the medulla. Caudally,
divisions are the rhombencephalon or hindbrain, the mesencephalon the fourth ventricle is continuous with a canal in the caudal medulla
or midbrain, and the prosencephalon or forebrain. and, through this, with the central canal of the spinal cord. The fourth
The rhombencephalon is subdivided into the myelencephalon or ventricle is continuous with the subarachnoid space through three
medulla oblongata, metencephalon or pons, and the cerebellum. The openings in its roof (the foramina of Luschka and of Magendie). At its
medulla oblongata, pons and midbrain are collectively referred to as rostral extent, the fourth ventricle is continuous with a narrow channel,
the brainstem, which lies upon the basal portions of the occipital and the cerebral aqueduct, which passes through the midbrain. The rostral
sphenoid bones (clivus). The medulla oblongata is the most caudal part end of the cerebral aqueduct opens out into the third ventricle, a
of the brainstem and is continuous with the spinal cord below the level narrow, slit-like, midline cavity that is bounded laterally by the dien-


of the foramen magnum. The pons lies rostral to the medulla and is cephalon. At the rostral end of the third ventricle, a small aperture on
distinguished by a mass of transverse nerve fibres that connect it to the each side leads into the large lateral ventricle that is located within each
cerebellum. The midbrain is a short segment of brainstem, rostral to cerebral hemisphere (see Fig. 16.4C).


Central nervous system
229
61
RETPAHC
A Olfactory organs B
Lateral ventricle
Telencephalon
Forebrain
Rostral choroid plexus
(Prosencephalon)
Diencephalon
Eye
Midbrain
(Mesencephalon) Third ventricle C Lateral ventricle Third ventricle
Cerebral aqueduct Choroid plexus of
Pons, cerebellum lateral ventricle
Fourth ventricle
(Metencephalon)
Hindbrain
(Rhombencephalon)
Medulla oblongata
Caudal choroid plexus
(Myelencephalon)
Spinal cord
Cerebral aqueduct
Choroid plexus
Fourth ventricle of fourth ventricle
Fig .16 .4 Nomenclature and arrangement of the major divisions of the brain . A, The major features of the basic brain plan, including their relationships to
the major special sensory organs of the head . B, The corresponding regions in the adult brain, seen in sagittal section . C, The organization of the
ventricular system in the brain .
The general senses include touch, pressure, vibration, pain, thermal
sensation and proprioception (perception of posture and movement).
Stimuli from the external and internal environments activate a diverse
Cerebral hemisphere
range of receptors in the skin, viscera, muscles, tendons and joints (Ch.
3). Afferent impulses from the trunk and limbs are conveyed to the
spinal cord in spinal nerves, while those from the head are carried to
the brain in cranial nerves. The detailed anatomy of the complex path-
ways by which the various general senses impinge on consciousness
levels is better understood by reference to certain common organiza-
tional principles. Whilst undoubtedly oversimplified and subject to
exceptions, this schema is helpful in emphasizing the essential similari-
ties that exist between the ascending sensory systems.
In essence, ascending sensory projections related to the general
senses consist of a sequence of three neurones that extends from periph-
eral receptor to contralateral cerebral cortex (Fig. 16.8). These are often
referred to as primary, secondary and tertiary neurones or first-, second-
and third-order neurones. Primary afferents have peripherally located
sensory endings and cell bodies that lie in dorsal root ganglia or the
Pons


sensory ganglia associated with certain cranial nerves. Their axons enter
the CNS through spinal or cranial nerves and terminate by synapsing
on the cell bodies of ipsilateral second-order neurones; the precise loca-
tion of this termination depends on the modality.
Medulla
oblongata Primary afferent fibres carrying pain, temperature and coarse touch/
pressure information from the trunk and limbs terminate in the dorsal
Cerebellum horn of the spinal grey matter, near their point of entry into the spinal
cord. Homologous fibres from the head terminate in the trigeminal
sensory nucleus of the brainstem. The cell bodies of second-order neu-
rones are located in either the dorsal horn or the trigeminal sensory
nucleus. Their axons decussate and ascend to the ventral posterior
nucleus of the contralateral thalamus as the spinothalamic or the
trigeminothalamic tract, respectively; they synapse on the cell bodies of
Fig .16 .5 The base of the brain, showing the major divisions and cranial
third-order neurones in the thalamus. Axons of third-order neurones
nerves (see also Fig . 19 .2) . (Figure enhanced by B Crossman .)
pass through the internal capsule to reach the cerebral cortex, terminat-
ing in the postcentral gyrus of the parietal lobe, which is also known
as the primary somatosensory cortex.
OVERVIEW OF ASCENDING SENSORY PATHWAYS Primary afferent fibres carrying proprioceptive information and fine
(discriminative) touch from the trunk and limbs ascend ipsilaterally in
Sensory modalities are conventionally described as being either special the spinal cord as the dorsal columns (fasciculus gracilis and fasciculus
senses or general senses. The special senses are olfaction, vision, taste, cuneatus); they end by synapsing on second-order neurones in the
hearing and vestibular function. Afferent information is encoded by dorsal column nuclei (nucleus gracilis and nucleus cuneatus) of the
highly specialized sense organs and transmitted to the brain in cranial medulla. Axons of second-order neurones decussate in the medulla and
nerves I, II, VII, VIII and IX. then ascend as the medial lemniscus to the ventral posterior nucleus of


OvERvIEw Of THE NERvOuS SySTEm
230
3
NOITCES
Fig .16 .6 A sagittal section of the brain . (Figure
Corpus
enhanced by B Crossman .)
callosum
Cerebral
hemisphere
Thalamus
Choroid plexus
of third
ventricle
Cerebral Interventricular
aqueduct foramen
Midbrain Septum
pellucidum
Fourth
ventricle Hypothalamus
Cerebellum
Pons
Medulla
oblongata
Hand
White matter
nuclV ee un
s
t ora fl tp ho as late mri uo sr Leg So matosensory
c
Cerebral cortex ortex
Corpus callosum
Lateral ventricle
Caudate nucleus
Internal capsule Face
Putamen Thalamus
Globus pallidus
Hippocampus
Midbrain
Trigeminal ganglion
Trigeminal Touch
nerve Pain/temperature
Pons Pons
Medial lemniscus Medulla oblongata
Medulla oblongata
Dorsal columns
Touch/proprioception
Spinothalamic tract
Spinal nerve
Pain/temperature
Dorsal root ganglion Spinal cord
Fig .16 .8 The organization of general sensory pathways showing
Fig .16 .7 A section through the cerebral hemisphere and brainstem, first-order, second-order and third-order neurones .
showing the disposition of grey and white matter, the basal ganglia and
the internal capsule . (Dissection by EL Rees; photograph by Kevin
Fitzpatrick, London .)
Terminologia Anatomica specifies cortical axons that innervate
motor or sensory nuclei of cranial nerves according to their connections
the contralateral thalamus, where they synapse on the cell bodies of as follows: fibrae corticonucleares bulbi (medullary corticonuclear
third-order neurones. Axons of third-order neurones pass through the fibres); fibrae corticonuclearis pontinis (pontine corticonuclear fibres);
internal capsule to reach the cerebral cortex, terminating in the primary and fibrae corticonuclearis mesencephali (mesencephalic corticonu-
somatosensory cortex. A similar homologous projection exists for affer- clear fibres).


ents derived from the head. Corticospinal (pyramidal tract) fibres originate from widespread
regions of the cerebral cortex, including the primary motor cortex of
the frontal lobe where the opposite half of the body is represented in
OVERVIEW OF DESCENDING MOTOR PATHWAYS a detailed somatotopic fashion. The fibres descend throughout the
length of the brainstem. The majority then cross to the contralateral
Corticofugal fibres descend through the internal capsule and pass into side in the motor decussation of the pyramids in the medulla. Thereaf-
the brainstem, where many of them terminate, innervating the cranial ter, they continue caudally as the lateral corticospinal tract of the spinal
nerve nuclei and other brainstem nuclei such as the red nucleus, reticu- cord, which terminates in association with interneurones and motor
lar nuclei, olivary nuclei, etc. The term ‘corticobulbar’ has been used for neurones of the spinal grey matter (Fig. 16.9). The principal function
many years to describe cortical projections to brainstem nuclei but it is of the corticonuclear and corticospinal tracts is the control of fine,
a misnomer. The suffix ‘bulbar’ is derived from ‘bulb’, an obsolete name fractionated movements, particularly of those parts of the body where
for the medulla oblongata: clearly, corticofugal fibres that terminate in delicate muscular control is required. These tracts are particularly
the midbrain and/or pons cannot be described as corticobulbar. The important in speech (corticonuclear tract) and movements of the hands
term ‘corticobulbar’ has been replaced by ‘corticonuclear’. (corticospinal tract).


Peripheral nervous system
231
61
RETPAHC
Leg Hand nuclei of the thalamus and subthalamus, and with the brainstem. They
Internal capsule
appear to be involved in the selection of appropriate behavioural
Motor
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abnormalities of muscle tone (Crossman and Neary 2014). The basal
ganglia are sometimes described as being part of the so-called ‘extrapy-
ramidal (motor) system’. This term is used to distinguish between the
effects of basal ganglia disease and those of damage to the ‘pyramidal’
(corticospinal) system. However, the progressive elucidation of the
anatomy of the basal ganglia and of the pathophysiology of motor
Face
disorders has revealed the close functional interrelationship between
the two ‘systems’, and has rendered the terms that distinguish them
largely obsolete (Brodal 1981). The cerebellum (Ch. 22) has rich con-
nections with the brainstem, particularly the reticular and vestibular
nuclei, and with the thalamus. It is concerned with the coordination of
movement; cerebellar disorders cause ataxia, intention tremor and
Corticonuclear fibres hypotonia.
Corticospinal fibres
PERIPHERAL NERVOUS SYSTEM
Motor cranial nerve fibres
The PNS is composed mainly of spinal nerves, cranial nerves, their
Motor decussation of pyramids ganglia and their ramifications that carry afferent and efferent neurones


between the CNS and the rest of the body. It also includes the peripheral
part of the autonomic nervous system, notably the sympathetic trunks
and ganglia, and the enteric nervous system, composed of plexuses of
nerve fibres and cell bodies in the wall of the gastrointestinal tract.
SPINAL NERVES
Motor spinal nerve fibres
Spinal nerves are the means by which the CNS receives information
Fig .16 .9 The corticospinal and corticonuclear tracts . from, and controls the activities of, the trunk and limbs. Spinal nerves
are considered in detail elsewhere on a regional basis (Sections 4–9).
There are 31 pairs of spinal nerves (8 cervical, 12 thoracic, 5 lumbar,
The concept of ‘upper’ and ‘lower’ motor neurones is fundamental 5 sacral, 1 coccygeal) and these contain a mixture of sensory and motor
in clinical neurology because the motor signs and symptoms of damage fibres. They originate from the spinal cord as continuous series of dorsal
to each category are different and are indicative of the anatomical site and ventral nerve rootlets. Adjacent groups of rootlets fuse to form
of the lesion. Lower motor neurones are the alpha motor neurones dorsal and ventral roots, which then merge to form the spinal nerves
located in the brainstem and spinal cord that innervate the extrafusal proper. The dorsal roots of spinal nerves contain afferent nerve fibres
muscle fibres of skeletal muscle. The term upper motor neurones refers from cell bodies located in dorsal root ganglia. These cells give off both
collectively to all the descending pathways that impinge upon the activ- centrally and peripherally directed processes and do not have synapses
ity of lower motor neurones but, in common parlance, the term is often on their cell bodies. The ventral roots of spinal nerves contain efferent
equated with the corticonuclear and corticospinal tracts. The terms fibres from cell bodies located in the spinal grey matter. These include
upper and lower motor neurone lesion are used clinically to distin- motor neurones innervating skeletal muscle and preganglionic auto-
guish, for example, between the effects of a stroke in the internal capsule nomic neurones.
(a typical upper motor neurone lesion) and those of motor neurone Spinal nerves exit from the vertebral canal via their corresponding


disease (a typical lower motor neurone lesion). intervertebral foramina. They then divide to form a large ventral (ante-
Lower motor neurone lesions cause paralysis or paresis of specific rior) ramus and a smaller dorsal (posterior) ramus. In general terms,
muscles because they have lost their direct innervation. There is also the ventral ramus innervates the limbs together with the muscles and
loss or reduction of tendon reflex activity and reduced muscle tone. skin of the anterior part of the trunk. The dorsal ramus innervates the
Spontaneous muscular contractions (fasciculation) occur and affected post-vertebral muscles and the skin of the back. The nerve fibres within
muscles atrophy over time. Upper motor neurone lesions cause paraly- the ventral rami serving the upper and lower limbs are redistributed
sis or paresis of movements as a result of loss of higher control. There within brachial and lumbosacral plexuses, respectively.
is increased tendon reflex activity and increased muscle tone, and no
muscle atrophy occurs. A positive plantar (Babinski) reflex is present.
The combination of paralysis, increased tendon reflex activity and CRANIAL NERVES
hypertonia is referred to as spasticity.
The pathophysiology underlying the symptoms of upper motor Cranial nerves are the means by which the brain receives information
neurone lesions is complex. This is because many descending pathways from, and controls the activities of, the head and neck, and to a lesser
other than the corticonuclear and corticospinal tracts exist and they also extent the thoracic and abdominal viscera. The component fibres, their
influence lower motor neurone activity. These pathways include corti- route of exit from the cranial cavity, their subsequent peripheral course
cofugal projections to the brainstem (e.g. corticoreticular and cortico- and the distribution and functions of the cranial nerves are considered
pontine) that traverse the internal capsule and numerous pathways that in detail elsewhere on a regional basis (Sections 4, 7, 8). Their origins,
originate within the brainstem itself (e.g. reticulospinal, vestibulospi- destinations and connections within the CNS are considered in this
nal). Clearly, these pathways may be compromised to varying extents, section.


depending on the site of a lesion. Their involvement is believed to be There are 12 pairs of cranial nerves that are individually named and
important in the pathophysiological mechanisms that underlie the gen- numbered (Roman numerals) in a rostrocaudal sequence (Table 16.1).
eration of spasticity. Pure corticospinal tract lesions, which are exceed- Unlike spinal nerves, only some cranial nerves are mixed in function,
ingly rare in humans because corticospinal tract fibres lie in close carrying both sensory and motor fibres; others are purely sensory or
relationship to other pathways throughout most of their course, are purely motor. The first cranial nerve (I; olfactory) has an ancient lineage
believed specifically to cause deficits in delicate, fractionated move- and is derived from the forerunner of the cerebral hemisphere. It retains
ments and to induce the positive plantar reflex. this unique position through the connections of the olfactory bulb, and
Two other major systems that contribute to the control of movement is the only sensory cranial nerve that projects directly to the cerebral
are the basal ganglia and the cerebellum. The basal ganglia are a group cortex rather than indirectly via the thalamus. The areas of cerebral
of large subcortical nuclei, the major components being the caudate cortex receiving olfactory input have a primitive cellular organization
nucleus, putamen and globus pallidus (see Fig. 16.7; Ch. 24). These and are an integral part of the limbic system, which is concerned with
structures have important connections with the cerebral cortex, certain the emotional aspects of behaviour. The second cranial nerve (II; optic)


OvERvIEw Of THE NERvOuS SySTEm
232
3
NOITCES
Table 16.1 Summary of cranial nerves
No. Name Components Cells of origin Main central connections Exit from skull Distribution and function
I Olfactory Special somatic afferent Olfactory receptor cells To olfactory bulb, anterior perforated Foramina of Olfaction
in nasal mucosa substance, piriform cortex cribriform plate
II Optic Special somatic afferent Ganglion cells of retina To lateral geniculate nucleus of Optic canal Vision
thalamus, pretectal area of
midbrain
III Oculomotor Somatic efferent Oculomotor nucleus From visual cortical areas, medial Superior orbital Motor to medial rectus, inferior rectus, superior
longitudinal fasciculus fissure rectus, inferior oblique, levator palpebrae superioris
III Oculomotor General visceral efferent Edinger–Westphal From pretectal area of midbrain Superior orbital Parasympathetic to sphincter pupillae and ciliary
nucleus fissure muscles, via ciliary ganglion, mediating pupillary
constriction and accommodation
IV Trochlear Somatic efferent Trochlear nucleus From visual cortical areas, medial Superior orbital Motor to superior oblique
longitudinal fasciculus fissure
Trigeminal division:
V Ophthalmic (V) General somatic afferent Trigeminal (semilunar) To trigeminal sensory nucleus Superior orbital Sensation from forehead, scalp, eyelids, nose and
i
ganglion fissure eye, including conjunctiva
Maxillary (V) General somatic afferent Trigeminal (semilunar) To trigeminal sensory nucleus Foramen rotundum Sensation from mid-face, lower eyelid, nasal cavity ii
ganglion and paranasal sinuses, upper lip, maxillary teeth
and palate
Mandibular (V) General somatic afferent Trigeminal (semilunar) To trigeminal sensory nucleus Foramen ovale Sensation from lower face and scalp, tongue and floor
iii
ganglion of mouth, mandibular teeth and part of external ear
General somatic afferent Mesencephalic part of To trigeminal sensory nucleus, Foramen ovale Proprioception from muscles of mastication,


trigeminal sensory cerebellum temporomandibular joint
nucleus
Mandibular (V) Branchial (special Trigeminal motor nucleus From precentral gyrus Foramen ovale Motor to muscles of mastication (temporalis,
III
visceral) efferent masseter, medial and lateral pterygoids), tensor
tympani
VI Abducens Somatic efferent Abducens nucleus From visual cortical areas, medial Superior orbital Motor to lateral rectus
longitudinal fasciculus fissure
VII Facial General somatic afferent Geniculate ganglion To trigeminal sensory nucleus, Internal acoustic Sensation from part of tympanic membrane, external
cerebellum meatus acoustic meatus and skin behind pinna.
Proprioception from facial muscles
VII Facial Special visceral afferent Geniculate ganglion To nucleus solitarius Internal acoustic Taste from anterior two-thirds of tongue
meatus
VII Facial General visceral efferent Superior salivatory From olfactory areas, nucleus Internal acoustic Parasympathetic to lacrimal gland and mucous
nucleus solitarius meatus membrane of nasal and oral cavities (via
pterygopalatine ganglion) and submandibular and
sublingual salivary glands (via submandibular
ganglion) causing secretion and vasodilation
VII Facial Branchial (special Facial nucleus From precentral gyrus Internal acoustic Motor to ‘muscles of facial expression’, stapedius,
visceral) efferent meatus posterior belly of digastric and stylohyoid
VIII Vestibulocochlear
Vestibular division Special somatic afferent Vestibular ganglion To vestibular nuclei, cerebellum Internal acoustic Sensations of equilibrium and motion
meatus
Cochlear division Special somatic afferent Spiral ganglion To cochlear nuclei Internal acoustic Hearing
meatus
IX Glossopharyngeal General somatic afferent Glossopharyngeal ganglia To trigeminal sensory nucleus Jugular foramen General sensation from posterior one-third of tongue,
oropharynx and middle ear
IX Glossopharyngeal General visceral afferent Glossopharyngeal ganglia To nucleus solitarius Jugular foramen Sensory from carotid body (chemoreceptors) and
carotid sinus (baroreceptors)


IX Glossopharyngeal Special visceral afferent Glossopharyngeal ganglia To nucleus solitarius Jugular foramen Taste from posterior one-third of tongue
IX Glossopharyngeal General visceral efferent Inferior salivatory From olfactory areas, nucleus Jugular foramen Parasympathetic to parotid salivary gland (via otic
nucleus solitarius ganglion), causing secretion and vasodilation
IX Glossopharyngeal Branchial (special Nucleus ambiguus From precentral gyrus Jugular foramen Motor to stylopharyngeus
visceral) efferent
X Vagus General somatic afferent Superior (jugular) To trigeminal sensory nucleus Jugular foramen General sensation from pharynx, larynx, trachea,
ganglion oesophagus, part of auricle and external auditory
meatus
X Vagus General visceral afferent Inferior (nodose) ganglion To nucleus solitarius Jugular foramen Sensory from thoracic and abdominal viscera
Sensory from aortic arch (baroreceptors) and aortic
bodies (chemoreceptors)
X Vagus General visceral efferent Dorsal motor nucleus of From hypothalamus, nucleus Jugular foramen Parasympathetic to glands and smooth muscle in the
vagus solitarius pharynx, larynx, thoracic and abdominal viscera
X Vagus Branchial (special Nucleus ambiguus From precentral gyrus, sensory Jugular foramen Motor to pharyngeal, external laryngeal and
visceral) efferent nuclei of brainstem oesophageal striated muscles
XI *Accessory
Cranial root Branchial (special Nucleus ambiguus From precentral gyrus, sensory Jugular foramen Motor to muscles of soft palate and intrinsic muscles
visceral) efferent nuclei of brainstem of larynx (distributed via vagus)
Spinal root Branchial (special Spinal cord segments From precentral gyrus Jugular foramen Motor to sternocleidomastoid and trapezius
visceral) efferent C1–C5
XII Hypoglossal Somatic efferent Hypoglossal nucleus From precentral gyrus Hypoglossal canal Motor to all intrinsic and extrinsic muscles of the
tongue, except palatoglossus
Key
General somatic afferent


Special somatic afferent
General visceral afferent
Special visceral afferent
Somatic efferent
General visceral efferent
Branchial (special visceral) efferent
*The existence of a ‘cranial root’ of the accessory nerve, with its cell bodies in the nucleus ambiguus and a distribution as given in Table 16.1, is controversial. There is a view that the ‘spinal root’ of the accessory nerve
should be regarded as the accessory nerve proper (sometimes called the ‘spinal accessory nerve’) and that the vagus nerve supplies the muscles of the soft palate and the intrinsic muscles of the larynx. See Chapter 21 for
further details.


Autonomic nervous system
233
61
RETPAHC
consists of the axons of second-order visual neurones and these termi-
AUTONOMIC NERVOUS SYSTEM
nate in the thalamus. The other ten pairs of cranial nerves attach to the
brainstem and most of their component fibres originate from, or ter-
minate in, the cranial nerve nuclei of the brainstem. The autonomic nervous system represents the visceral component of
The sensory fibres in individual spinal and cranial nerves have char- the nervous system. It consists of neurones located within both the CNS
acteristic, but often overlapping, peripheral distributions. As far as the and the PNS that are concerned with the control of the internal environ-
innervation of the body surface is concerned, the area that is supplied ment, through the innervation of secretory glands and cardiac and
by a particular spinal or cranial nerve is referred to as a dermatome smooth muscle. Its functions are, however, closely integrated with those
(Greenberg 2003), whereas the areas of skin supplied by particular of the somatic nervous system.
peripheral nerves are often referred to as the peripheral nerve fields (or Visceral efferent pathways differ from their somatic equivalents in
cutaneous nerve distributions). There is marked overlap between der- that the former are interrupted by peripheral synapses, there being a
matomes of adjacent spinal nerves, particularly for the segments least sequence of at least two neurones between the CNS and the target
affected by development of the limbs, i.e. the second thoracic to the structure (Fig. 16.11). These are referred to as preganglionic and post-
first lumbar (Ladak et al 2013). In some regions, e.g. the upper anterior ganglionic neurones, respectively. The somata of preganglionic neu-
thoracic wall, the cutaneous nerves that supply adjoining areas are not rones are located in the visceral efferent nuclei of the brainstem and in
derived from consecutive spinal nerves and in these instances the the lateral grey columns of the spinal cord. Their axons, which are
overlap between dermatomes is minimal; these boundaries give more usually finely myelinated, exit from the CNS in certain cranial and
reliable and clinically useful borders (Apok et al 2011). Maps of der- spinal nerves, and then pass to peripheral ganglia, where they synapse


matome distribution are useful in clinical neurology as a guide to with postganglionic neurones. The axons of postganglionic neurones
identify the location of pathology in patients with peripheral sensory are usually unmyelinated. Postganglionic neurones are more numerous
deficits, but it is important to remember that they are approximations. than preganglionic ones; one preganglionic neurone may synapse with
Dermatome maps are somewhat inconsistently reported by different 15–20 postganglionic neurones, which permits the wide distribution of
authors, reflecting the fact that the maps are composites that have been many autonomic effects.
compiled to a large extent by clinical observations on patients with The autonomic nervous system is divided into three major parts:
cranial or spinal nerve pathology, and also that considerable normal sympathetic, parasympathetic and enteric. These differ in organization
individual variation exists (Fig. 16.10) (Lee et al 2008). Common to all and structure but are functionally integrated. Most, but not all, struc-
published maps are areas of sensory overlap along borders of contigu- tures innervated by the autonomic nervous system receive both sympa-
ous spinal nerves and axial lines where non-contiguous spinal nerves thetic and parasympathetic fibres, whereas the enteric nervous system
meet, and across which very little or no sensory overlap occurs. Detailed is a network of neurones intrinsic to the wall of the gastrointestinal
dermatome maps are described on a regional basis. The motor axons tract.
of individual spinal and cranial nerves tend to innervate anatomically Two long-held dogmas are that the sympathetic and parasympa-
and functionally related groups of skeletal muscles, which are referred thetic nervous systems are functionally antagonistic (because activation
to as myotomes. of their respective efferents has opposing actions on target structures)
A C2 B
C2
C3
C4
C2
C5
C2
C4 C6
C3 C3
C5 T1 C7 T1 C8 C4 C4
T2 T2 T2
T3 T4 T3 T2 T3 T4 T3
T T4 5 T6 T5 T T4 5 T6 T5 T2
TT 76 T8 T T7
9


C8 C5 TT 76 T8 T7 C5
T8 T10 T1 T8 T10 T9
TT 19 0 T12 L1T11 C7 TT 19 0 T12 T11 T1 C7
T11 L2 T11
L3 L1
T12 L4 T12
L5 C8
L1 L1 L2
C C6 7 C8 L2 S2 S2 C8CC 76 C6 C7 S3 SS 43 C8C6
L2 S5
L3
S1
L3 L3
S2
L4
L4
L5
L5 S2 L4
S1 L5
S1
S1 L5 S1
S1
L5 S1 L4 L5
Fig .16 .10 Typical dermatome maps, illustrating some of the variations reported by different authors . A, Dermatome map based on Keegan JJ, Garrett
FD 1948 The segmental distribution of the cutaneous nerves in the limbs of man . Anat Rec 102:409–439 . Mainly used in literature in the USA .
B, Dermatome map based on Moffat DB 1993 Lecture Notes on Anatomy, 2nd edn . Oxford: Blackwell Scientific . Mainly used in literature in the UK .


OvERvIEw Of THE NERvOuS SySTEm
234
3
NOITCES
Eye Sphincter pupillae Fig .16 .11 Efferent pathways of the autonomic
Ciliary nervous system .
Dilator pupillae
III
Ciliaris
Pterygopalatine
VII Lacrimal gland
Mucous membrane of nasal cavity
Brainstem
Submandibular Submandibular salivary gland
VII
IX
Sublingual salivary gland
X
Otic Oral mucosa
C1
Parotid salivary gland
Superior cervical
ganglion
Heart
T1 Larynx
Trachea
Bronchi
Greater
splanchnic nerves Coeliac Oesophagus
Stomach
Spinal cord Abdominal vessels
Lesser
splanchnic
nerves
Liver and ducts
Superior Pancreas
mesenteric
L1 Suprarenal gland
Inferior
mesenteric Small intestine
S1
Large intestine
Rectum
Pelvic splanchnic
nerves Kidney
Bladder
Ganglion
Sexual organs
Parasympathetic pathways
Sympathetic pathways
Postganglionic fibres to blood vessels, glands and arrector pili
External genitalia
and that sympathetic reactions are mass responses whereas parasympa- from the stimulation of somatic receptors in the skin and other tissues.
thetic reactions are usually more localized. A better concept is that the Peripheral autonomic activity is integrated at higher levels in the brain-
two sets of neurones constitute an integrated system for the coordinated stem and cerebrum, including various nuclei of the brainstem reticular
neural regulation of visceral and homeostatic functions. Moreover, even formation, thalamus and hypothalamus, the limbic lobe and prefrontal
though widespread activation of the sympathetic nervous system may neocortex, together with the ascending and descending pathways that
occur, e.g. in association with fear or rage, it is recognized that the interconnect these regions.
sympathetic nervous system is also capable of discrete activation. In The classical concept of autonomic neurotransmission is that pre-
general, sympathetic activity results in the constriction of cutaneous ganglionic neurones of both sympathetic and parasympathetic systems


arteries (increasing blood supply to the heart, muscles and brain), are cholinergic and that postganglionic parasympathetic neurones are
cardiac acceleration, an increase in blood pressure, contraction of also cholinergic while those of the sympathetic nervous system are
sphincters and depression of peristalsis, all of which mobilize body noradrenergic. The discovery of neurones that do not use either acetyl-
energy stores for dealing with increased activity. Parasympathetic activ- choline or noradrenaline (norepinephrine) as their primary transmitter,
ity results in cardiac slowing and an increase in intestinal glandular and the recognition of a multiplicity of substances in autonomic nerves
and peristaltic activities, which may be considered to conserve body which fulfil the criteria for a neurotransmitter or neuromodulator, have
energy stores. greatly complicated neuropharmacological concepts of the autonomic
Autonomic activity is not initiated or controlled solely by the reflex nervous system (Burnstock 2013). Thus, adenosine 5′-triphosphate
connections of general visceral afferent pathways; nor do impulses in (ATP), numerous peptides and nitric oxide have all been implicated in
these pathways necessarily activate general visceral efferents. For the mechanisms of cell signalling in the autonomic nervous system. The
example, in many situations demanding general sympathetic activity, principal co-transmitters in sympathetic nerves are ATP and neuropep-
the initiator is somatic and typically arises from the special senses tide Y; in parasympathetic nerves vasoactive intestinal polypeptide
or the skin. Rises in blood pressure and pupillary dilation may result (VIP); and in enteric nerves ATP, VIP and substance P.


Autonomic nervous system
235
61
RETPAHC
SYMPATHETIC NERVOUS SYSTEM Preganglionic sympathetic neurones release acetylcholine as their prin-
cipal neurotransmitter.
The sympathetic trunks are two ganglionated nerve cords that extend On reaching the sympathetic trunk, preganglionic fibres behave in
on either side of the vertebral column from the cranial base to the one of several ways (see Fig. 16.13). They may synapse with neurones
coccyx. The ganglia are joined to spinal nerves by short connecting in the nearest ganglion, or traverse the nearest ganglion and ascend or
nerves called white and grey rami communicantes. Preganglionic axons descend in the sympathetic chain to end in another ganglion. A pre-
join the trunk through the white rami communicantes while postgan- ganglionic fibre may terminate in a single ganglion or, through collat-
glionic axons leave the trunk in the grey rami. In the neck, each sym- eral branches, synapse with neurones in several ganglia. Preganglionic
pathetic trunk lies posterior to the carotid sheath and anterior to the fibres may traverse the nearest ganglion, ascend or descend and, without
transverse processes of the cervical vertebrae. In the thorax, the trunks synapsing, emerge in one of the medially directed branches of the
are anterior to the heads of the ribs, in the abdomen they lie anterola- sympathetic trunk to synapse in the ganglia of autonomic plexuses
teral to the bodies of the lumbar vertebrae, and in the pelvis they are (mainly situated in the midline, e.g. around the coeliac and mesenteric
anterior to the sacrum and medial to the anterior sacral foramina. arteries). More than one preganglionic fibre may synapse with a single
Anterior to the coccyx the two trunks meet in a single, median, terminal postganglionic neurone. Uniquely, the suprarenal gland is innervated
ganglion. Cervical sympathetic ganglia are usually reduced to three by directly by preganglionic sympathetic neurones that traverse the sym-
fusion. The internal carotid nerve, a continuation of the sympathetic pathetic trunk and coeliac ganglion without synapse.


trunk, issues from the cranial pole of the superior ganglion and accom- The somata of sympathetic postganglionic neurones are located
panies the internal carotid artery through its canal into the cranial mostly either in the ganglia of the sympathetic trunk or in ganglia in
cavity. There are between 10 and 12 (usually 11) thoracic ganglia, 4 more peripheral plexuses. The axons of postganglionic neurones are,
lumbar ganglia, and 4 or 5 ganglia in the sacral region. therefore, generally longer than those of preganglionic neurones, an
The cell bodies of preganglionic sympathetic neurones are located exception being some of those that innervate pelvic viscera. The axons
in the lateral horn of the spinal grey matter of all thoracic segments and of ganglionic cells are unmyelinated. They are distributed to target
the upper two or three lumbar segments (Fig. 16.12). Their axons are organs in various ways. Those from a ganglion of the sympathetic trunk
myelinated with diameters of 1.5–4 µm. They leave the cord in the may return to the spinal nerve of preganglionic origin through a grey
corresponding ventral nerve roots and pass into the spinal nerves, ramus communicans, which usually joins the nerve just proximal to the
but soon leave in white rami communicantes to join the sympathetic white ramus, and are then distributed through ventral and dorsal spinal
trunk (Fig. 16.13). Neurones like those in the lateral grey column rami to blood vessels, sweat glands, hairs, etc., in their zone of supply.
exist at other levels of the cord above and below the thoracolumbar Segmental areas vary in extent and overlap considerably. The extent of
outflow and small numbers of their fibres leave in other ventral roots. innervation of different effector systems, e.g. vasomotor, sudomotor,
etc., by a particular nerve may not be the same. Alternatively, postgan-
glionic fibres may pass in a medial branch of a ganglion direct to par-
ticular viscera, or innervate adjacent blood vessels, or pass along them
externally to their peripheral distribution. They may ascend or descend
before leaving the sympathetic trunk as described above. Many fibres


are distributed along arteries and ducts as plexuses to distant
effectors.
The principal neurotransmitter released by postganglionic sympa-
Dorsal horn thetic neurones is noradrenaline (norepinephrine). The sympathetic
system has a much wider distribution than the parasympathetic. It
innervates all sweat glands, the arrector pili muscles, the muscular walls
Lateral horn of many blood vessels, the heart, lungs and respiratory tree, the abdomi-
nopelvic viscera, the oesophagus, the muscles of the iris, and the non-
Ventral horn striated muscle of the urogenital tract, eyelids and elsewhere.
Postganglionic sympathetic fibres that return to the spinal nerves are
vasoconstrictor to blood vessels, secretomotor to sweat glands and
motor to the arrector pili muscles within their dermatomes. Those that
accompany the motor nerves to voluntary muscles are probably only
dilatory. Most, if not all, peripheral nerves contain postganglionic sym-
Fig .16 .12 A transverse section through the thoracic spinal cord .
pathetic fibres. Those reaching the viscera are concerned with general
Preganglionic sympathetic neurones are located in the lateral horn . (Figure
vasoconstriction, bronchial and bronchiolar dilation, modification of
enhanced by B Crossman .)
glandular secretion, pupillary dilation, inhibition of gastrointestinal
muscle contraction, etc. A single preganglionic fibre probably synapses
with the postganglionic neurones in only one effector system, which
Preganglionic neurone means that effects such as sudomotor and vasomotor actions can be
in lateral horn
separate.
Sympathetic
chain
Grey ramus PARASYMPATHETIC NERVOUS SYSTEM
communicans
Spinal nerve Preganglionic parasympathetic neuronal cell bodies are located in
certain cranial nerve nuclei of the brainstem (see Fig. 21.1) and in the
intermediate grey matter of the second to fourth sacral segments of the
spinal cord. Efferent fibres, which are myelinated, emerge from the CNS
only in the oculomotor, facial, glossopharyngeal and vagus nerves, and
in the second to fourth sacral spinal nerves. Preganglionic parasympa-


thetic neurones are cholinergic.
Ventral root of The cell bodies of postganglionic parasympathetic neurones are
spinal nerve White ramus mostly sited distant from the CNS, either in discrete ganglia located
communicans
To coeliac and near the structures innervated, or dispersed in the walls of viscera. In
Sympathetic
Preganglionic neurone mesenteric ganglia ganglion the cranial part of the parasympathetic system there are four small
Postganglionic neurone Postganglionic peripheral ganglia – ciliary, pterygopalatine, submandibular and otic
neurone – that are all described on a regional basis in Section 4. These are effer-
ent parasympathetic ganglia, unlike the trigeminal, facial, glossopha-
Fig .16 .13 Outflow from preganglionic sympathetic neurones in the lateral
horn of the spinal cord . Preganglionic axons may synapse on a ryngeal and vagal sensory ganglia, all of which are concerned exclusively
postganglionic neurone in a sympathetic ganglion at the same segmental with afferent impulses and contain the cell bodies of sensory neurones.
level, or may pass into the sympathetic chain to synapse on a The cranial parasympathetic ganglia are also traversed by afferent fibres,
postganglionic neurone in a more rostral or caudal sympathetic ganglion, postganglionic sympathetic fibres and, in the case of the otic ganglion,
or may pass to a ganglion in an autonomic plexus in the abdominal by branchial efferent fibres; however, none of these fibres synapse in
cavity, e .g . the coeliac ganglion . the ganglia. Postganglionic parasympathetic fibres are usually unmyeli-


OvERvIEw Of THE NERvOuS SySTEm
236
3
NOITCES
nated and shorter than their counterparts in the sympathetic system posterior lingual region, the palatine tonsils and pharynx, but they do
because the ganglia in which the parasympathetic fibres synapse are not innervate taste buds. They also innervate the carotid sinus and the
either in or near the viscera they supply. Postganglionic parasympathetic carotid body, which contain receptors sensitive to tension and changes
neurones are cholinergic. in chemical composition of the blood. Impulses from these receptors
are essential to circulatory and respiratory reflexes.
Visceral afferents that enter the spinal cord through spinal nerve
ENTERIC NERVOUS SYSTEM roots terminate in the spinal grey matter. Almost all the central proc-
esses of vagal and glossopharyngeal afferent fibres end in the nucleus
AND INTRINSIC NEURONES
solitarius of the medulla. About 5% of the vagal afferents project
directly to, and terminate in, the upper cervical spinal cord (C1–2),
Many peripheral autonomic ganglia contain neurones derived from the
where they are believed to contribute to referred sensations, as well as
neural crest during embryonic development that are anatomically dis-
to propriospinal mechanisms of nociceptive modulation. Visceral affer-
tinct from classical sympathetic and parasympathetic neurones. Con-
ents establish connections within the CNS that mediate autonomic
nections between these intrinsic neurones allow them to sustain and
reflexes. In addition, afferent impulses probably mediate visceral sensa-
modulate visceral activities by local reflex mechanisms. The enteric
tions such as hunger, nausea, sexual excitement, vesical distension, etc.
nervous system consists of many millions of neurones and enteric Visceral pain fibres may follow these routes. Although viscera are insen-
glial cells grouped into ganglionated plexuses lying in the wall of
sitive to cutting, crushing or burning, excessive tension in smooth
the gastrointestinal tract; ganglia containing neuronal cell bodies
muscle and some pathological conditions produce visceral pain. In
and glia are connected by bundles of axons to form myenteric and


visceral disease, vague pain may be felt near the viscus itself (visceral
submucous plexuses that extend from the oesophagus to the anal
pain) or in a cutaneous area or other tissue whose somatic afferents
sphincter. This intrinsic circuitry mediates numerous reflex functions
enter spinal segments receiving afferents from the viscus, a phenome-
including the contractions of the muscular coats of the gastrointestinal
non known as referred pain. If inflammation spreads from a diseased
tract, secretion of gastric acid, intestinal transport of water and electro-
viscus to the adjacent parietal serosa (e.g. the peritoneum), somatic
lytes, and the regulation of mucosal blood flow (Poole and Furness
afferents will be stimulated, causing local somatic pain, which is com-
2012). Although complex interactions occur between the enteric and
monly spasmodic. Referred pain is often associated with local cutane-
sympathetic and parasympathetic nervous systems, the enteric nervous
ous tenderness. For further reading on visceral pain, see Bielefeldt and
system is capable of sustaining local reflex activity independent of
Gebhart (2013).
the CNS.
Afferent fibres in pelvic splanchnic nerves innervate pelvic viscera
Since intrinsic neurones survive after section of the extrinsic sympa-
and the distal part of the colon. Vesical receptors are widespread; those
thetic and parasympathetic nerves, organs that are transplanted are not
in muscle strata are associated with thickly myelinated fibres and are
truly denervated. Separation from their autonomic input often has no
believed to be stretch receptors, possibly activated by contraction. Pain
obvious impact on the non-striated muscle or glands innervated by
fibres from the bladder and proximal urethra traverse both the pelvic
autonomic fibres; contraction may be unaffected and no structural
splanchnic nerves and the inferior hypogastric plexus, hypogastric
changes ensue. This has been variously attributed to the continued
nerves, superior hypogastric plexus and lumbar splanchnic nerves to
activity of local plexuses or to the intrinsic activity of visceral muscle.
reach their cell bodies in ganglia on the lower thoracic and upper
In some important instances, however, denervation does result in ces-


lumbar dorsal spinal roots; the significance of this dual sensory pathway
sation of activity, e.g. in sweat glands, pilomotor muscle, orbital non-
is uncertain. Lesions of the cauda equina abolish pain from vesical
striated muscle and the suprarenal medulla.
overdistension, but hypogastric section is ineffective. Pain fibres from
the uterus traverse the hypogastric plexus and lumbar splanchnic nerves
to reach somata in the lowest thoracic and upper lumbar spinal ganglia,
VISCERAL AFFERENT PATHWAYS and hypogastric division may relieve dysmenorrhoea. Afferents from
the uterine cervix traverse the pelvic splanchnic nerves to reach their
Visceral afferent pathways in many ways resemble somatic afferent path- somata in the upper sacral spinal ganglia; stretching the cervix uteri
ways. The peripheral processes of visceral afferents run through auto- causes pain but cauterization and biopsy excisions do not.
nomic ganglia or plexuses, and possibly through somatic nerves. Their In general, afferent fibres that accompany pre- and postganglionic
central processes accompany somatic afferent fibres through cranial sympathetic fibres have a segmental arrangement and end in spinal cord
nerves or dorsal spinal roots into the CNS, where they establish con- segments from which preganglionic fibres innervate the region or viscus
nections that mediate autonomic reflexes and visceral sensation. concerned. General visceral afferents entering thoracic and upper
General visceral afferent fibres from the viscera and blood vessels lumbar spinal segments are largely concerned with pain. Nociceptive
accompany their efferent counterparts, and are the peripheral processes impulses from the pharynx, oesophagus, stomach, intestines, kidneys,
of unipolar cell bodies located in some cranial nerve and dorsal root ureter, gallbladder and bile ducts seem to be carried in sympathetic
ganglia. They are contained in the vagus, glossopharyngeal and possibly pathways. Cardiac nociceptive impulses enter the spinal cord in the first
other cranial nerves; the second to fourth sacral spinal nerves, distrib- to fifth thoracic spinal nerves, mainly via the middle and inferior


uted with the pelvic splanchnic nerves; and thoracic and upper lumbar cardiac nerves, but some fibres pass directly to the spinal nerves. It is
spinal nerves, distributed through rami communicantes and alongside said that there are no general visceral afferents in the superior cardiac
the efferent sympathetic innervation of viscera and blood vessels. nerves. Peripherally, the fibres pass through the cardiac plexuses and
The cell bodies of vagal general visceral afferent fibres are in the along the coronary arteries. Myocardial anoxia may evoke symptoms of
superior and inferior vagal ganglia. Their peripheral processes are dis- angina pectoris in which pain is typically presternal, and is also referred
tributed to terminals in the pharyngeal and oesophageal walls where, to much of the left chest, and radiates to the left shoulder, the medial
acting synergistically with glossopharyngeal visceral afferents in the aspect of the left arm, along the left side of the neck to the jaw and
pharynx, they are concerned with swallowing reflexes. Vagal afferents occiput, and down to the epigastrium. Cardiac afferents carried in vagal
are also believed to innervate the thyroid and parathyroid glands. In cardiac branches are concerned with the reflex depression of cardiac
the heart, vagal afferents innervate the walls of the great vessels, the activity. Ureteric pain fibres, also running with sympathetic fibres, are
aortic bodies and pressor receptors, where they are stimulated by raised presumably involved in the agonizing renal colic that follows obstruc-
intravascular pressure. In the lungs they are distributed via the pulmo- tion by calculi. Afferent fibres from the testis and ovary run through the
nary plexuses. They supply bronchial mucosa, where they are probably corresponding plexuses to somata in the tenth and eleventh thoracic
involved in cough reflexes; bronchial muscle, where they encircle myo- dorsal root ganglia.
cytes and end in tendrils, which are sometimes regarded as muscle Some primary afferent neurones, innervating the gut, lungs, heart
spindles and which are believed to be stimulated by change in the and blood vessels, also appear to have an efferent function in that they


length of myocytes; interalveolar connective tissue, where their knob- release transmitters from their peripheral endings during the axon
like endings, together with terminals on myocytes, may evoke Hering– reflex. The primary substances released in this way are substance P,
Breuer reflexes; the adventitia of pulmonary arteries, where they may calcitonin gene-related peptide (CGRP) and ATP. These act on target
be pressor receptors; and the intima of pulmonary veins, where they cells to produce vasodilation, increased venular permeability, changes
may be chemoreceptors. Vagal visceral afferent fibres also end in the in smooth muscle contractility, degranulation of mast cells and a variety
gastric and intestinal walls, digestive glands and the kidneys. Fibres of effects on leukocytes and fibroblasts, a process collectively known as
ending in the gut and its ducts respond to stretch or contraction. Gastric ‘peripheral neurogenic inflammation’. The local release of such sub-
impulses may evoke sensations of hunger and nausea. stances may play a trophic role in the maintenance of tissue integrity
The cell bodies of glossopharyngeal general visceral afferents are in and repair in response to injury (for further reading, see Xanthos and
the glossopharyngeal ganglia. Their peripheral processes innervate the Sandkühler (2014)).


Surface anatomy
237
61
RETPAHC
SURFACE ANATOMY
Superior cervical
sympathetic ganglion
Carotid body The surface positions of cerebral structures, meningeal arteries and
Inferior cervical dural venous sinuses may be approximated via a number of standard-
sympathetic ganglion ized reference lines and planes.
Cerebralsulciandlobes
Cardiac plexus
The central sulcus (Rolandic fissure) and lateral sulcus (Sylvian fissure)
Thoracic sympathetic of the cerebral hemispheres can be landmarked via the cranium using
ganglion multiple methods, the most common being that developed by Taylor
and Haughton (Fig. 16.15) (Taylor and Haughton 1900, Taylor et al
1980). Recent analysis of these methods has shown them to be accurate
Greater splanchnic
nerve to within a few millimetres (Reis et al 2011). Using Taylor–Haughton
Coeliac ganglion craniometric lines, the lateral sulcus sits on the frontozygomatic
(Sylvian) line, which passes from the frontozygomatic suture to a point
Suprarenal medulla 75% the way along the nasion–inion midsagittal line. The lateral sulcus
extends posteroinferiorly from the Sylvian point, which is located
around the region of the pterion. The lateral sulcus has also been shown
to align with the anterior part of the squamosal suture in a zone
2.5–4.0 cm anterior to the external acoustic meatus (Rahmah et al
Para-aortic body 2011). The position of the central sulcus is approximated via a line
passing from the superior Rolandic point, situated approximately 2 cm
posterior to the midpoint of the nasion–inion midsagittal line, to the
Hypogastric plexus inferior Rolandic point, situated at the intersection of the frontozygo-
matic line with the pre-auricular/condylar line. Alternatively, the posi-
tion of the central sulcus can be approximated using a line passing from
the superior Rolandic point to the midpoint of the zygomatic arch, with
Ganglion impar the central sulcus ending at the point of intersection of this line with


the frontozygomatic line (Rhoton 2002). The superior extent of the
Vas deferens parieto-occipital sulcus sits at the point of intersection of the frontozy-
gomatic line and the 75% point on the nasion–inion line. The approxi-
mate positions of the lobes of the brain, and of the precentral and
Chromaffin tissue postcentral gyri, can be determined following localization of the central,
lateral and parieto-occipital sulci (Fig. 16.16).
Chromaffin tissue deep
to overlying structures
Vertebralcolumn,spinalcordandmeninges
Fig .16 .14 The principal aggregations of ‘classic’ chromaffin tissue in the
human neonate . The aggregates in pale blue lie deep to overlying
The surface positions of the termination of the spinal cord and dural
structures .
sac can be mapped relative to the vertebrae and their spinous processes
(see Ch. 43).
PARAGANGLIA
Duralvenoussinuses
Paraganglia are extra-suprarenal aggregations of neuroepithelial cells.
They are all derived from the neural crest and all synthesize and store The superior sagittal sinus passes along the nasion–inion midsagittal
catecholamines (Fig. 16.14). Paraganglia can be divided into two broad line on the inner surface of the cranial vault (Fig. 16.17). In the majority
categories: non-chromaffin, related to the parasympathetic system, par- of subjects it deviates to the right of the sagittal plane/superior sagittal
ticularly in the head and neck, where they tend to be associated with suture by up to 11 mm (Tubbs et al 2001, Samadian et al 2011). The
the glossopharyngeal or vagus nerves (carotid body, promontory of the confluence of the dural venous sinuses (torcular herophili) sits mainly
middle ear, tunica adventitia of the jugular bulb, facial canal, ganglion to the upper right side of the inion (Sheng et al 2012). The position of


nodosum, larynx); and chromaffin, connected with the orthosympa- the lower border of the proximal transverse sinus is best approximated
thetic system (in the sympathetic ganglia of various viscera and a variety via the insertion of semispinalis capitis into the cranium (Tubbs et al
of thoracolumbar para-aortic retroperitoneal sites). Small paraganglia 2000). The course of the transverse sinus has been shown to vary widely
have also been reported incidentally in the urinary bladder, prostate, and no single plane or surface marking can be used to predict its route
gallbladder, splenic capsule and mesosigmoid. Their functions differ accurately (Sheng et al 2012). The asterion, found at the junction of the
with location: some cells act as interneurones, others as sources of lambdoid, occipitomastoid and parietomastoid sutures, sits over the
neuroendocrine secretion. Paraganglionic catecholamine release occurs junction between the transverse and sigmoid sinuses in 81% of subjects,
mainly in response to chemical rather than to neural stimuli. Extra- inferior to it in 15% and superior to it in 4% (Sheng et al 2012).
suprarenal chromaffin tissue is prominent in the fetus, and acts as the
main source of catecholamines while the suprarenal medulla is imma- Middlemeningealartery
ture. Although many paraganglia degenerate soon after birth, others
persist into adulthood, often as microscopic paraganglia. The surface positions of the anterior and posterior branches of the
Paraganglia are well vascularized and their secretory cells are usually middle meningeal artery can be determined relative to cranial land-
close to one or more fenestrated capillaries. Most have a sympathetic marks (see Fig. 26.8A).
innervation and act as endocrine organs, e.g. suprarenal medullary
chromaffin cells. Those associated with the parasympathetic system
probably have activities on local nerve endings, e.g. the carotid body. Bonus e-book images
Paraganglia produce regulatory peptides, particularly enkephalins, and
store them as cytoplasmic granules until stimulated to release them.


Their secretions may exert a local paracrine action on nearby cells, in Fig .16 .15 Cranial reference lines, craniometric points and cerebral
addition to having remote endocrine effects. sulci .
Paragangliomas have been found in practically every site in which
normal paraganglia are known to occur; carotid body paragangliomas Fig .16 .16 Cerebral sulci, gyri and lobes .
are the most common and important group of extra-suprarenal para-
gangliomas (accounting for approximately 60% of head and neck para- Fig .16 .17 Cranial suture joints, fontanelles and dural venous
gangliomas). For further reading, see Rosai (2011) and Lack and sinuses .
Wieneke (2013).


Overview of the nervous system
237.e1
61
RETPAHC
50% 50%
10 6
1
525%
2
1
3
17
75%
25%
Frontal Lobe 2
Precentral Pg oy sr tu cs
entral
gyrus
Pariet 3al Lobe
9
75%
4
6
11 5 4 7 Occipital Lobe
Temporal Lobe
Nasion 16 7 Nasion 8
Cerebellum
8
15 12
9 Inion Inion
13 14
Fig .16 .15 Cranial reference lines, craniometric points and cerebral sulci . Fig .16 .16 Cerebral sulci, gyri and lobes . Key: 1, Rolandic line/central
Key: 1, Rolandic line/central sulcus (green line); 2, pre-auricular/ sulcus (green line); 2, pre-auricular/mandibular condylar line orientated
mandibular condylar line orientated perpendicular to the infra-orbitomeatal perpendicular to the infra-orbitomeatal line; 3, frontozygomatic/Sylvian
line; 3, frontozygomatic/Sylvian line passing from the frontozygomatic line passing from the frontozygomatic suture (8) to a point 75% of the
suture (16) to a point 75% of the way along the nasion–inion midsagittal way along the nasion–inion midsagittal line; 4, lateral sulcus/Sylvian
line; 4, lateral sulcus/Sylvian fissure (red line); 5, nasion–inion midsagittal fissure (red line); 5, nasion–inion midsagittal line; 6 (green dot), superior
line; 6, lateral sulcus/Sylvian fissure alternative location (blue line): aligns Rolandic point 2 cm posterior to the midpoint of the nasion–inion line (at
anteriorly with the anterior part of the squamosal suture in a zone the 53–55% point of the nasion–inion line); 7 (yellow dot), inferior Rolandic


2 .5–4 .0 cm anterior to the external acoustic meatus; 7, line from the point; 8 (pink dot), frontozygomatic suture; 9 (purple dot), superior extent
superior Rolandic point (green dot) to the midpoint of the zygomatic arch of the parieto-occipital sulcus . (Adapted with permission from Drake RL,
(15, blue dot); 8, Reid’s baseline/Frankfurt plane; 9, infra-orbitomeatal line; Vogl AW, Mitchell A, Tibbitts R, Richardson P (eds), Gray’s Atlas of
10 (green dot), superior Rolandic point 2 cm posterior to the midpoint of Anatomy, Elsevier, Churchill Livingstone . Copyright 2008 .)
the nasion–inion line (at the 53–55% point of the nasion–inion line); 11
(yellow dot), inferior Rolandic point; 12 (orange dot), porion; 13 (black
dot), orbitale; 14 (red dot), auricular point; 15 (blue dot), midpoint of
zygomatic arch; 16 (pink dot), frontozygomatic suture; 17 (purple dot),
superior extent of the parieto-occipital sulcus . (Adapted with permission
from Drake RL, Vogl AW, Mitchell A, Tibbitts R, Richardson P (eds),
Gray’s Atlas of Anatomy, Elsevier, Churchill Livingstone . Copyright 2008 .)


OvERvIEw Of THE NERvOuS SySTEm
237.e2
3
NOITCES
1
2
3 2
2
4
5
10
7
6
9
8
Fig .16 .17 Cranial suture joints, fontanelles and dural venous sinuses .
Key: 1, bregma (site of infant anterior fontanelle); 2, superior sagittal
sinus: commonly deviates to the right of the sagittal suture by up to
11 mm (black arrows); 3, sagittal suture: sits on the nasion–inion
midsagittal line; 4, coronal suture; 5, lambda (site of infant posterior
fontanelle); 6, inion: normally sits below and left of the confluence of
sinuses and below the level of the internal occipital protruberance;
7, lambdoid suture; 8, asterion (site of infant posterolateral mastoid
fontanelle): sits over (in 81%), just below (in 15%) or just above (in 4%)
the transverse–sigmoid sinus junction; 9, transverse sinus: the variable
course makes accurate surface localization difficult; 10, pterion (site of
infant anterolateral sphenoidal fontanelle) . (Adapted with permission from
Tunstall R, Shah N; Surface Anatomy (Pocket Tutor series), 2012, JP
Medical Ltd .)


Overview of the nervous system
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RETPAHC
REFERENCES
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Brodal A 1981 Neurological Anatomy in Relation to Clinical Medicine, 3rd e18199.
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emphasis on clinical relevance. Contains a particularly good account of Surgical Pathology, 10th ed. Edinburgh: Elsevier, Mosby. Ch. 16,
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Burnstock G 2013 Cotransmission in the autonomic nervous system. Handb Samadian MI, Nazparvar B, Haddadian K et al 2011 The anatomical relation
Clin Neurol 117:23–35. between the superior sagittal sinus and the sagittal suture with surgical
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Poole DP, Furness JB 2012 Enteric nervous system structure and neurochem- Tubbs RS, Salter G, Elton S et al 2001 Sagittal suture as an external landmark
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294–310. 15:43–53.


CHAPTER
17
Development of the nervous system
The entire nervous system and the special sense organs originate from mesenchyme. There is fusion initially of the surface ectoderm, followed
three sources, each derived from specific cell populations of the early by fusion of the neural ectoderm. The neural ectodermal cells become
epiblast termed neural ectoderm. The first source to be clearly deline- elongated and then wedge-shaped. It has been suggested that the forces
ated is the neural plate, which gives rise to the central nervous system needed to shape the neural tube are intrinsic to the cells of the neurec-
(CNS), the somatic motor nerves and the preganglionic autonomic toderm and, indeed, it has been demonstrated that human embryonic
nerves. The second source is from cells at the perimeter of the neural stem cells can self-organize into three-dimensional neural structures
plate, neural crest cells, which remove themselves by epithelial/ (Sasai et al 2012, Eiraku and Sasai 2012). Epithelial populations are
mesenchymal transition from the plate and migrate away just prior to established in the embryo with the formation of the epiblast. Three
its fusion into a neural tube. These cells give rise to the majority of the main control pathways that maintain apicobasal polarity have been
neurones and glia of the peripheral nervous system (PNS), i.e. the described. When the neural tube is closing, its walls consist of a pseu-
somatic sensory nerves, the somatic and autonomic ganglia, postgan- dostratified layer of columnar neural epithelial cells (see below). The
glionic autonomic nerves, and suprarenal and chromaffin cells. They cells increase in length and develop numerous longitudinally disposed
also give rise to significant mesenchymal populations in the head. The microtubules. The borders of their luminal ends are firmly attached to
third source is from ectodermal placodes, which constitute a focal adjacent cells by junctional complexes; the cytoplasmic aspect of the
thickening of the ectoderm covering the embryonic head. They contrib- complexes is associated with a dense paraluminal web of microfila-
ute cells to the cranial sensory neurones and form the olfactory epithe- ments. The nuclei assume basal positions, which, together with contrac-


lia, the epithelia of the inner ear and, by a non-neuronal contribution, tion of apically arranged actin, imparts a slight wedge conformation on
the lens of the eye. some of the cells, and creates a hinge point.
The position of hinge points within the neural plate confers different
characteristics on the formed neural tube. With a median hinge point,
NEURULATION
the neural folds remain relatively straight and the tube in this position
has a slit-shaped lumen; this can be seen from the initial region of
Primary neurulation begins at stage 9 and is completed during stage 12 fusion rostralwards. If dorsolateral hinge points are added, the resulting
(Fig. 17.1). The process, although continuous spatially and temporally, neural tube is rhombic, and the hinge points describe the position of
has been envisaged as four stages. It begins with local elongation of the the sulcus limitans. If all the neuroepithelial cells exhibit some apical
ectoderm cells in a midline zone of the embryonic disc and their re- narrowing, then the resulting tube has a circular lumen. The rostral
organization into a pseudostratified epithelium, the neural plate. This slit-shaped profile of the neural tube may depend more on support
is followed by reshaping and bending of the neural plate into a neural from adjacent tissues than the caudal end of the tube, where neurula-
groove, which subsequently closes to form a neural tube bidirectionally tion is generated by the neuroepithelium. The transition from primary
from the mid portion to its cranial and caudal ends. A continuous to secondary neurulation (see below) continues the production of a
surface ectoderm forms dorsal to the tube. neural tube with a circular lumen.
Primary neurulation depends on cellular changes within the neural Fusion of the neural tube starts in embryos with 4–6 somites, at the
plate; in the trunk, it may also involve movements of the paraxial level of somites 1 and 2, forming the future rhombencephalon. The
tube closes caudally and rostrally, forming sequentially cervical and
thoracic cord regions, then mesencephalic and prosencephalic brain
regions. Rostrally, two sites of fusion can be seen. The initial fusion,


termed α, or the dorsal lip of the rostral neuropore, proceeds caudo-
rostrally. A second site, termed β, or the terminal lip of the rostral
neuropore, closes from the rostral end of the neural plate and proceeds
rostrocaudally (O’Rahilly and Müller 2002). Closure of these lips of the
rostral neuropore is completed when 19–20 pairs of somites are present.
Caudal neuropore closure starts when approximately 29 somites are
present and the site of closure corresponds to the level of the future
somite 31 (the level of the future second sacral vertebra) (O’Rahilly and
Müller 2004).
Secondary neurulation starts from the closure of the caudal neuro-
pore at stage 12 and ends at about stage 17; it is the process by which
the caudal portion of the neural tube is formed in the absence of a
neural plate. At the time of caudal neuropore closure, the caudal midline
cells are generically termed the caudal eminence (O’Rahilly and Müller
2004). A specific population of mesenchymal cells, the caudoneural
hinge or junction, shares the same molecular markers as the primitive
node. These cells aggregate at the midline and undergo mesenchymal/
epithelial transformation, producing a cellular cylinder that is contigu-
ous with the caudal end of the neural tube. Further elongation of the
caudal neural tube involves cavitation of the neural cylinder. Neural
crest cells delaminate from the dorsal surface of the cylinder in a rostro-
caudal direction and, concurrently, the paraxial mesenchyme undergoes
Fig. 17.1 A scanning electron micrograph of a neurulating rat embryo somitogenesis.
comparable to a stage 10 human embryo (22–24 days). The expanded
brain region can be seen at the top of the image, with somite formation
EARLY BRAIN REGIONS
occurring centrally as neurulation proceeds caudally. Caudally, the ridge
of underlying neural crest cells can be seen medial to the unsegmented
paraxial mesenchyme. (Photograph by P Collins; printed by S Cox, Prior to the closure of the neural tube, the neural folds become consid-


238 Electron Microscopy Unit, Southampton General Hospital.) erably expanded in the head region; the first indication of a brain and


Neurulation
239
71
RETPAHC
Telencephalon
Diencephalon 1
Primary neuromeres
Diencephalon 2
Prosencephalon
1 M D2 D1
Mesencephalon 2
A
A 3
Buccopharyngeal
B membrane
Rhombomeres C B 4
D 5
C 6
7 Endoderm
Spinal region D
8
Notochord
3 brain regions 5 brain regions
Telencephalon
Prosencephalon
Diencephalon
Mesencephalon Mesencephalon
Metencephalon
Rhombencephalon
Myelencephalon
Fig. 17.2 The primary brain regions, neuromeres and their expansion during neurulation.
its major divisions can be seen at stage 10 (Fig. 17.2). Regional expan- Table 17.1 Derivatives of the cerebral regions from caudal to rostral
sions – prosencephalon (forebrain), mesencephalon (midbrain) and
Cerebral region Derivatives
rhombencephalon (hindbrain) – have been called the three primary
cerebral vesicles, although the term ‘vesicle’ in this context has been Rhombencephalon (or hindbrain)
considered inappropriate to describe localized accelerations of growth 1. Myelencephalon Medulla oblongata
in the wall of the brain. As the neural tube closes, the neural wall Caudal part of the fourth ventricle
Inferior cerebellar peduncles
appears to form a series of ridges and depressions perpendicular to
its long axis. These transient repeating segments are termed primary 2. Metencephalon Pons
Cerebellum
neuromeres, and initially six can be identified: the prosencephalon,
Middle part of the fourth ventricle
mesencephalon and four subdivisions of the rhombencephalon, rhom- Middle cerebellar peduncles
bomeres A, B, C and D. The primary neuromeres themselves become
3. Isthmus rhombencephali Superior medullary velum
subdivided during stages 10, 11 and 12, and a total of 16 secondary Superior cerebellar peduncles