Embryology and bony malformations of the craniovertebral junction
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The embryology of the bony craniovertebral junction (CVJ) is reviewed with the purpose of explaining the genesis and unusual configurations of the numerous congenital malformations in this region. Functionally, the bony CVJ can be divided into a central pillar consisting of the basiocciput and dental pivot and a two-tiered ring revolving round the central pivot, comprising the foramen magnum rim and occipital condyles above and the atlantal ring below. Embryologically, the central pillar and the surrounding rings descend from different primordia, and accordingly, developmental anomalies at the CVJ can also be segregated into those affecting the central pillar and those affecting the surrounding rings, respectively.
A logical classification of this seemingly unwieldy group of malformations is thus possible based on their ontogenetic lineage, morbid anatomy, and clinical relevance. Representative examples of the main constituents of this classification scheme are given, and their surgical treatments are selectively discussed.
KeywordsCraniovertebral junction Congenital malformations Genetic control Occipital–cervical instability Cord compression Occipital–cervical fusion Primary somitogenesis Sclerotomal resegmentation Embryology Malformation Surgery
The bony craniovertebral junction (CVJ) can be conceptually divided into two components with respect to the governance of intersegmental movements and functional space for the nervous system. The first component consists mainly of a central pivot made up of the dens and the C2 vertebral body, but the basiocciput, though anatomically part of the foramen magnum, is embryologically and functionally in vertical linearity with the dens and is thus part of the central pillar. The second component consists of two ringed structures surrounding the central pivot, albeit eccentrically. They are the foramen magnum ring, comprising the lateral portion of the basiocciput (clivus), the exocciput including the occipital condyles, and the opisthion; and the atlantal ring, with its anterior and posterior arches and lateral masses. These two superimposing rings transmit the lower brainstem and upper cervical spinal cord, whilst permitting limited rotatory and flexion–extension motions upon each other and round the dental pivot. Straddling these two rings and anchoring upon them are the stabilizing ligaments between the pivot and the rings: the alar and apical dental ligaments at the up-side of the pivot, the transverse atlantal ligament (TAL) across the main dental shaft, and the arching mantle of the tectorial membrane and cruciate ligament, strapping the clivus to the whole of the dens–axis assembly.
Classification of bony malformations of the CVJ according to embryogenesis
Clinically significant CVJ bony malformations
Malformations of central pillar
Malformations of surrounding rings
Disturbance of axial component of occipital sclerotome, proatlas and C1 resegmented sclerotome
Disturbance of lateral component and hypochordal bows of proatlas and C1 resegmented sclerotome
C1 sclerotome anomalies
▪ Aplasia/hypoplasia of odontoid components
▪ Failed midline integration of basioccipital primordium
▪ Hyperplasia of hypochordal bow of proatlas
▪ Aplasia of hypochordal bow of C1
▪ Disturbance of odontoid synchondroses (IBZ)
– Bifid clivus
– Third occipital condyle
– Aplasia and hypoplasia of anterior C1 arch
– Os odontoideum
▪ Basioccipital dysplasia
– Pre-basioccipital arch
▪ Aplasia/hypoplasia of lateral sclerotome
– Ossiculum terminale persistens
– Basilar impression
▪ Hyperplasia of exoccipital sclerotome
– Posterior C1 arch agenesis
▪ Abnormal resegmentation of proatlas centrum
– Hypertrophic occipital condyle
▪ Combined hypochordal bow and lateral sclerotome dysplasia
– Os avis
– Retroflexed dens
▪ Non-resegmentation of proatlas (anterior homeotic transformation)
– Aplasia of lateral mass and anterior C1 arch
▪ Failed midline integration of basal dental segment
– Basilar invagination
– Atlas assimilation
– Combined anterior and posterior C1 arch defects
– Bifid dens
– Basilar kyphosis
▪ Posterior homeotic transformation
– Bifid anterior and posterior C1 arch
In keeping with the anatomical division of the CVJ, clinically significant developmental anomalies affecting, respectively, the “pivot” and “rings” also happen to follow more or less a thematic division of instability versus neural compression. Anomalies of the central pivot usually lead to instability, although basilar impression and a retroflexed dens can cause neural impingement. Anomalies of the surrounding rings result in deformity and crowding, but hypoplasia and aplasia of component parts can result in a weakened frame and loss of ligamentous anchorage.
This paper deals first with the normal development and genetic control of the bony CVJ, followed by descriptions of congenital malformations of this region with emphasis on their embryogenesis and clinical relevance. Special considerations of the techniques and pitfalls of fusion and decompression of the occiput–C1–C2 complex in young children are provided when applicable.
Embryology of the craniovertebral junction
The presomitic stage
At gastrulation, epiblastic cells from the embryonic plate caudal to the head process invaginate through the primitive streak to form mesoderm on each side of the neural plate, whilst cells from both sides of the dorsal lip of Hensen’s node migrate through the primitive pit to integrate into the midline notochord. The embryonic plate thus elongates by new additions to its rear (caudal) aspect .
Primary segmentation: somitogenesis
Due to the constant caudal elongation of the body axis during gastrulation and the addition of new PSM cells with strong fgf8 expression to the rear, the FGF8 gradient is continuously displaced caudally. Accordingly, the determination wavefront also moves slowly in a caudal direction along the body axis. This ensures that the old and new metameric boundaries, at both ends of a new somite, are separated by a distance corresponding to the caudal displacement of the determination wavefront during one period of oscillation of the segmentation clock  (Fig. 8). The speed of new somite production is thus linked to the Clock period, which is species-specific: 30 min for zebrafish, 90 min for chick, and 120 min for mouse .
Differentiation of the somitic mesenchyme
“Resegmentation” of the sclerotome
The term “resegmentation” was originated by Remak in 1855 (“Neugliederung”)  and remains still a subject of controversies [16, 24]. It refers to the fact that the early metameric boundaries between the somites are once again changed and “reshuffled” during the development of the sclerotome, so that the later boundaries between the vertebral bodies do not match up with the original intersomitic clefts .
Shortly after the specifications of the lateral sclerotome into its arcual, costal, and pedicular components, the initially loosely meshed mesenchyme within the perichordal axial sclerotome also begins to show compartmentalization. A cell-dense zone develops at the same level as the dense caudal half of each lateral sclerotome, partly due to medial expansion of the lateral band of condensed tissues from the lateral sclerotome. The axial sclerotome in between these median dense zones remains loosely cellular. Later, the cranial-most layer of the axial dense zone, in line with von Ebner’s fissure in the lateral sclerotome, becomes even more tightly packed and forms the intervertebral boundary zone (IBZ) (Fig. 13, middle). This intervertebral boundary mesenchyme ultimately forms the ring-like annulus fibrosus of the intervertebral disc, permanently enclosing a looser central core of nucleus pulposus made partly of notochordal remnants. The vertebral body itself is mainly made from chondrogenesis in the loose cell zone of the perichordal sclerotome, now called the prevertebra [11, 12, 24, 65], although contributions from the condensed tissue adjacent to the IBZ have been observed [16, 23]. As a final step, the pedicular anlagen from the lateral sclerotomes fuse with the chondrifying prevertebra of the axial sclerotome, whilst the neural arches surround the neural tube to complete the vertebral ring (Fig. 13, right). The costal component becomes the future transverse process but only in the thoracic region is it pre-destined to form ribs.
Thus, the neural arch of the vertebra is derived from the caudal-lateral part of a single somite . However, labelling and transplantation experiments of half-somites have repeatedly demonstrated that each vertebral body is made up of cells from the axial zones of two adjacent somites [2, 3]. Although the exact boundary of individual somite participation is not known , the juxta-positioning of axial and lateral sclerotomal components suggests that each vertebra probably comes from the caudal half of one somite and the rostral half of the somite below . This will explain the slightly off-step registration between the levels of the somite and the resegmented sclerotome [12, 17, 65] on the embryonic axis such that the middle of the resegmented sclerotome lines up with the original intersomitic cleft (Fig. 13, left and middle). Also, since the dense portion of the lateral sclerotome is in line with the dense zone of the axial sclerotome adjacent to the IBZ, it makes perfect sense that the mature pedicle is joined to the cranial and not the caudal half of the vertebral body . It also follows that the spinal nerve, ganglion, and blood vessel from the corresponding somitic segment, being associated with the loose cranial half of the lateral sclerotome, must cross above its own neural arch, and that the corresponding segment of the spinal cord is always slightly more rostral to its companion vertebral body (Fig. 13, right). Given that there are eight cervical somites but only seven resegmented axial sclerotomes and consequently seven cervical vertebrae, the C1 nerve root emerges above the C1 neural arch and the C8 nerve root comes through below the C7 neural arch and above the T1 neural arch, which in fact is derived from the C8 somite. Finally, resegmentation of the sclerotome explains why the original “pre-resegmented” intersomitic vessel ultimately enters the mid-point of the vertebral body as the segmental nutrient artery.
Special developmental features of the CVJ
The CVJ is the product of the occipital somites and the first three cervical somites. There is controversy regarding the proper number of occipital somites in vertebrates. Wilting et al. and others [14, 78, 99] thought that there were five occipital somites in chick and mouse but conceded that the first somite either disappeared early or was an insignificant clan of cells that lacked sclerotomal lineage. Müller and O’Rahilly  studied staged human embryos and concluded that, in humans, there are only four occipital somites that participate in the formation of the skull base. The transitional zone between the skull and the cervical spine is thus taken to be between the fourth and fifth somites. During the fourth week of gestation, there are consequently 4 occipital, 8 cervical, 12 thoracic, 5 lumbar, 5 sacral, and 8 to 10 coccygeal somites, 42 pairs all told.
Occipital somites (somites 1–4) and the proatlas
Following the general schema, the first three occipital somites give rise to an axial perichordal sclerotome and a lateral sclerotome, but no resegmentation takes place here. The axial sclerotomes never subdivide into dense and loose zones and therefore no intervertebral boundary mesenchyme exists. They all eventually fuse into a unit which later chondrifies to become the rostral basioccipital . The first three lateral occipital sclerotomes, like the vertebral sclerotomes, form dense and loose zones, and the loose zones of the second and third lateral occipital sclerotomes foster expansion of the upper and lower hypoglossal nerve roots and artery, whilst the corresponding dense zones form the bony hypoglossal canal.
The lateral dense region of the proatlas becomes the two exoccipitals, which later form the two occipital condyles and the remainder of the anterolateral rim of the foramen magnum (Fig. 14). The lateral loose region promotes emergence of the C1 nerve root. In humans, an additional arcuate cluster of dense proatlas cells ventral to the notochord, aptly called the hypochordal bow, gives rise to the bony anterior clival tubercle on the ventral surface of the basioccipital [64, 65] (Fig. 14).
First three cervical somites (somites 5–7)
During resegmentation, the caudal half of somite 5 and the cranial half of somite 6 combine to produce the first cervical sclerotome; likewise, the second cervical sclerotome is made up of corresponding parts of somites 6 and 7. In the axial region of these sclerotomes destined to form vertebral centra, dense and loose zones appear in regular succession as in the lower cervical sclerotomes. The loose prevertebral zone of the first cervical sclerotome gives rise to the basal segment of the dens, and that of the second cervical sclerotome becomes the body of the axis (Fig. 14). Unlike in the more caudal sclerotomes, however, where the dense IBZ ultimately becomes the annulus and nucleus pulposus of an intervertebral disc, the dense zones in the first two cervical sclerotomes do not form true intervertebral discs and soon disappear . Their intervertebral boundary mesenchyme gradually turns into the upper and lower dental synchondroses that ultimately cement the apical to the basal dens and the basal dens to the body of C2, respectively (Fig. 14).
Lastly, the apical ligament is almost certainly derived from the axial proatlas, and the alar and transverse atlantal ligaments are from the axial component of the first cervical sclerotome in association with the basal dental segments .
The lateral dense zone of the first cervical sclerotome develops into the posterior arch of the atlas, whilst the lateral dense zone of the second cervical sclerotome forms the arch of the axis. Their respective loose zones promote outgrowths of the second and third cervical nerves and segmental arteries. The hypochordal bow of the first cervical sclerotome ventral to the notochord subsequently forms the anterior arch of the atlas (Fig. 14, middle and right) [63, 64, 65, 82]. No definite hypochordal bows are seen caudal to this level and equivalent cells in the lower segments appear to play no role in the formation of the vertebral column.
Genetic control of CVJ development
Hox genes: the control of rostrocaudal specification
Hox genes are expressed in mesodermal and ectodermal cells along the body axis. Each gene has a characteristic and distinct anterior boundary of expression. A temporal and structural colinearity exists between the position of a gene in a cluster and its expression pattern. Thus, genes from the more anterior 3′ locations in the Hox clusters are expressed earlier and always occupy more anterior (cranial) expression domains than genes closer to the posterior 5′ location in the clusters (Fig. 19). For example, Hox a-3 has a more anterior expression domain than Hox a-9 and similarly between Hox d-4 and Hox d-10.
Pax-1: the resegmentation gene
The Pax family of regulatory genes is implicated in sclerotomal resegmentation. Pax genes in vertebrates all contain the highly conserved DNA sequence called “paired-box”. There are nine Pax genes; all except Pax-1 and -9 are involved in development of the central neuraxis. These two exceptions, especially Pax-1 (PAX-1 in the human homologue) [83, 97], control boundary formation between tissues by keeping two cell populations separate, presumably because the transcription factor encoded by Pax-1 differentially regulates cell surface molecules expressed by these two cell populations, thereby divergently influencing their respective fates. This scenario of cellular partitioning is a necessary condition for resegmentation, and Pax-1 action at the future IBZ thus helps to demarcate the site and extent of sclerotomal segregation. The downstream target gene for Pax-1 is unknown, but may involve cell adhesion molecules such as NCAM or cytotactin, or molecules that promote cell-cell communication such as connexins [40, 41, 66, 83].
Pax-1 expression is detected very early in the pre-differentiated somites. Signals from the notochord and ventral floor plate of the neural tube, mediated by the SHH protein, induce the somite to divide into dermomyotome and the ventromedial sclerotome. This coincides with intense expression of Pax-1 ventrally within the sclerotomal field, suggesting that Pax-1 also plays a mediating role in the dorsoventral specification of somites [47, 99].
After somitic differentiation, Pax-1 expression is noted within both the lateral and axial sclerotomes where its timing and fluctuating levels coincide with crucial events of resegmentation. For example, during condensation of the axial sclerotome into the loose and dense halves, Pax-1 expression is weak within the loosely cellular prevertebrae but intense within the dense IBZ [83, 99]. Later, with chondrification of the prevertebra to form the homogeneous vertebral body, Pax-1 is further actively repressed in this location, but persists in high levels at the IBZ where partition of centra takes place, until formation of the intervertebral disc is well underway . Pax-1 level is also enhanced during condensation of the lateral sclerotome to form the neural arch [23, 25, 98].
Conversely, normal fusion of certain adjacent sclerotomes takes place only when Pax-1 expression is turned off. At the CVJ of chick embryos, Pax-1 repression is timed exactly when the occipital sclerotomes fuse to form the basioccipital. The fusion of the two dens primordia with the axis body also coincides with the down-regulation of the Pax-1 gene . Ectopic Pax-1 expression disrupts normal assemblage of the dens axis and basioccipital . Pax-1 is also highly expressed within the transitional zone between the proatlas and the first cervical sclerotome; it may thus also play a role in the separation of the head from the trunk.
Murine Pax-1 mutants undulated show multiple fusion of vertebral bodies and fusion of the dens with the anterior atlantal arch , reminiscent of the human Klippel–Feil syndrome . It is therefore conceivable that hyper- and hyposegmentation defects in humans may be explained by over- and under-expression of PAX-1 during vertebral development.
Disturbance of the axial component of occipital sclerotomes, proatlas and C1–C2 sclerotomes: anomalies of the central pillar
There are two classes of central pivot anomalies: one concerns the dens–axis complex itself and includes the various forms of odontoid dysgenesis; the other afflicts primarily the basiocciput leading to an abnormal relationship between the odontoid and the skull base, comprising such entities as bifid clivus, platybasia, basilar kyphosis, basilar impression and a retroflexed dens.
The making of any part of the vertebral column requires the successful completion of three developmental phases: First, the mesodermal primordium has to be properly formed and, in some cases, assembled during the membranous phase; second, the mesodermal primordium undergoes chondrification in the cartilaginous phase; and finally, in the osseous phase, ossification takes place within the cartilaginous mold to complete the end product. In the case of the dens–axis, there is a fourth phase which involves bony fusion of the upper and lower dental synchondroses (Fig. 16).
Hyperplasia of primordium
Aplasia/hypoplasia of primordium
Disturbance of resegmentation
Failure of midline integration of primordium
Aplasia/hypoplasia of the axial sclerotome of proatlas and first cervical sclerotome: agenesis and hypogenesis of odontoid components
Complete odontoid agenesis in patients with collagenopathy or mucopolysaccharidosis such as Morquio’s disease may not always be due to primordial failure since a completed cartilaginous mold of the dens has been seen in situ, where ossification was found to be defective because of the abnormal connective tissue production. Non-syndromic cases of odontoid agenesis, however, are usually due to aplasia or hypoplasia of centrum primordia. Treatment of symptomatic cases is usually C1–C2 fusion.
Disturbance of the intervertebral boundary mesenchyme of proatlas and first two cervical sclerotomes: os odontoideum and ossiculum terminale persistens
Abrogation of the IBZ during early resegmentation such as in the transgenic mutant mice undulated causes exuberant fusion between sclerotomal units rather than lack of fusion [83, 99]. Thus, when there is non-fusion of discrete individual dental components as in os odontoideum and ossiculum terminale persistens, one may safely assume that the respective IBZ between the proatlas and the first two cervical sclerotomes were initially demarcated but subsequent development of the upper and lower dental synchondroses was unconsummated.
Ossiculum terminale persistens
Illustrative case 1
Abnormal resegmentation of proatlas centrum—os avis
In this rare anomaly, the apical dental segment is attached to the basioccipital and is not fused to the main dental stem. The pivot is thus shortened but firmly fixed to the axis centrum, where a semi-lucent line representing the lower synchondrosis marks the successful integration of the two lower dens–axis components. This anomaly has been called “dystopic os odontoideum” by von Torklus and Prescher [75, 76, 94] to distinguish it from the “orthotopic os odontoideum” used by these authors to designate the common variety of os odontoideum. Their use of the term os odontoideum differs from ours in that they have included both the unfused basal and apical dental segments.
In human malformations, it is not uncommon to find errant ontogeny reverting to a morphological pattern reminiscent of an organ’s phylogenetic past. As case in point, a separate bone between the dens and the basioccipital resembling the attached ossiculum in the human anomaly is found in some fish and reptiles and many birds [29, 31, 39, 75, 76, 85, 100]; hence, our terminology os avis. In higher vertebrates, this bone, the primordium of the apical dens, normally becomes detached from the basioccipital rim, which shares with it a common origin in the proatlas centrum. Lack of proper resegmentation of the proatlas centrum, in essence negating the necessary cleavage, prevents descent and subsequent joining of the apical segment with the centrum of the first cervical sclerotome to complete the dental pivot. The reason for this failure is unknown, but since proatlas resegmentation normally occurs at the transitional zone between somites 4 and 5, a caudal shift of this transitional zone along the body axis may affect the resegmentation process. In transgenic mouse mutant in which Hox a-7 is expressed earlier and more rostrally in its anterior domain, the last occipital somite (O4) is transformed (posteriorly) to become the atlas, bearing a “proatlas” centrum that remains attached to the basioccipital. C1 then becomes C2 and acquires a complete centrum whilst C2 is deleted of its normal dens . This extra “proatlas” bone in the murine mutant very much resembles the os avis in the human malformation and suggests that a Hox gene mutation causing posterior homeotic transformation of segmental identity may indeed underlie the genesis of the os avis.
Treatment of os avis depends on the other anomalies. Pure instability can be remedied with C1–C2 fusion. An absent posterior C1 arch or an occipitalized atlas would mandate inclusion of the occiput into the fusion. Concomitant neural compression due to basilar impression or invagination of the opisthion may require simultaneous decompression.
Failure of midline integration of basal dental segment: the bifid dens
Our entire experience of three cases suggests that the bifid dens is associated with atlantoaxial instability because the central pivot is hypoplastic when bifid. In our first case, the hypoplastic dens is aggravated by the dislocated ossiculum terminale, negating any possibility for TAL anchorage (Fig. 33b, c). In our second and third case, the hypermobile “hemi-os” pops backwards during flexion and accentuates the cord compression (see “Illustrative case 2”).
Stabilization for case 1 had to include the occiput into the fusion because of an incomplete posterior arch of C1. In the other two cases, occipital–cervical fusion is combined with a transoral resection of both halves of the dens to relieve the anterior compression.
Illustrative case 2
Failure of midline integration of basioccipital primordium: bifid clivus
A widely split basioccipital may affect anchorage of the tectorial membrane, which normally straps the odontoid complex to the back of the clivus. The atlanto-occipital joint may become unstable and the cervical spine may appear to have drifted away from the skull (Fig. 35a (right), b). Treatment depends on the degree of instability and consists of occipito-cervical fusion.
Basilar impression, platybasia, retroflexed dens and basilar invagination
Congenital basilar impression, which concerns us here, is less a result of active upward indentation of the dens against the brainstem, as the word “impression” implies, than a drop of the posterior fossa contents on to the erect dens due to a shallow occipital “box” and flattened skull base. The causative occipital dysplasia is due to deformed growth of all three parts of the occipital primordium: the basioccipital (pars basilaris) and the exoccipital (pars lateralis including the condyles and the foramen magnum rim), which enlarge by endochondral ossification, are primarily hypoplastic; and the supraoccipital, the squama, which expands by membranous ossification and therefore depends on growth of the chondrocranial molds of the other two parts, is obligatorily constricted.
In the posterior form of basilar impression, the exoccipitals, derived from the lateral sclerotomes of the proatlas, rise up towards the foramen magnum, bringing with them the occipital condyles and opisthion. Alternatively, the exoccipital bones may be thin and the condyles flat and hypoplastic. In either case, the dens is secondarily elevated towards the cranial cavity without being lordotic or retroflexed. The opisthion, however, often invaginates into the cranial aperture (basilar invagination).
Illustrative case 3
A 12-year-old girl of normal intelligence presented with occipital headache, neurogenic dysphagia, nasal voice and right arm and hand clumsiness. CT showed a steeply elevated occipital condyle (exoccipital), basilar (opisthion) invagination and C1 assimilation (Fig. 40a). There is no platybasia, and the dens, though migrated cranially into the foramen magnum, was not retroflexed (Fig. 39a, right). MR showed severe brainstem and upper cord compression mainly from the invaginating opisthion (Fig. 40b). At surgery, the posterior lip of the foramen was removed by careful drilling under microscopy (Fig. 40c). The thin occipital bone and the bizarre shapes of C2 and C3 precluded the use of regular occipital screw plates and intraaxial cervical screws. We used instead the inside–outside occipital screw plate system affixed to the C2 and C3 laminae with sublaminar cables (Fig. 40d–h). Onlaid autogenous iliac crest grafts were put in place (Fig. 40i–k).
Illustrative case 4
Posterior decompression for Chiari I malformation with coexisting basilar impression carries a much higher late complication rate than for pure cerebellar ectopia. Even if the anterior vector is not initially symptomatic, the slightest amount of post-operative cranial settling after nullification of the dorsal tension band will deliver the brainstem straight on to the pointing dens to cause rapid onset of new brainstem signs . In addition, platybasia and a decrease in the clivus–axis angle (of Wackenheim) (basilar kyphosis) accentuate the forward bending moment acting on the clivus–dens pivot point and accelerate the forward “folding” of the cranio-cervical axis (see “Illustrative case 5” below). It is our distinct impression that this type of post-operative instability occurs far more commonly in the associative type of Chiari I malformation. We therefore avoid removing the C2 lamina during the decompression, if necessary at the expense of resecting the tips of the tonsils.
If symptomatic post-decompression cranial settling does occur despite precautions, calipers skull traction with the neck in slight extension should be rendered under muscle relaxation and sedation for a few days, aiming at reversing the kyphotic deformity and telescoping effect at the foramen magnum. Occiput–C1–C2 fusion should be done after reduction. If brainstem indentation persists, transoral resection of the dens may be necessary.
Illustrative case 5
Disturbances of the lateral sclerotomes and hypochordal bows of proatlas and C1 sclerotome: anomalies of the surrounding ring structures
These can be divided into anomalies of the proatlas and of the C1 resegmented sclerotome.
Anomalies of proatlas
Hyperplasia of the proatlas hypochordal bow—third occipital condyle
Hyperplasia of exoccipital sclerotome—hypertrophic occipital condyle
Hyperplasia of the lateral sclerotome of the proatlas, precursor to the exoccipital bone, results in hypertrophy of the lateral and posterior rim of the foramen magnum including a massively gnarled occipital condyle. Bilateral condylar hypertrophy causes pincers-like cervicomedullary compression and early symptoms , but unilateral hypertrophy can also lead to severe lateral distortion of the lower brainstem and slow neurological deterioration. An uneven atlanto-occipital joint surface and chondromalacia may also produce chronic neck pain and stiffness. Treatment consists of resection of the occipital condyle, followed by occiput–cervical fusion for the expected O–C1 instability.
Illustrative case 6
Assimilation of atlas—non-resegmentation of the proatlas sclerotome
It has already been mentioned that inactivation of Hox d-3 gene expression in mice results in anterior homeotic transformation at the CVJ such that the C1 vertebra takes on an occipital identity and the head–neck transitional zone moves caudally to the C1–C2 junction (Fig. 21). All mutants have assimilation of C1 to the basiocciput [13, 24]. It is therefore tempting to ascribe human cases of isolated C1 assimilation to similar mutations of the human Hox gene homologues. However, in cases of combined C1 assimilation and Klippel–Feil syndrome in which multiple levels of cervical fusion are seen below C2, the Hox gene theory will require multiple Hox mutations and alterations of multiple Hox codes, which is highly improbable. Since Pax-1 expression is involved in resegmentation of all levels of the embryonic axis, inappropriate repression of Pax-1 at the proatlas–C1 sclerotome interphase and other vertebral levels may be involved in associative cases of atlas assimilation.
Assimilation of the atlas to the occiput means that the first mobile segment between the skull and spine has been transferred to the C1–C2 junction, as are all the motion stresses including that of flexion–extension, normally of restricted range at this level and for which the local joint anatomy is ill suited. This also means the supporting myoligamentous structures are more likely to suffer “over-stretch” failure. Almost 60% of Gholve et al.’s patients with C1 assimilation has C1–C2 instability defined as an atlantal–dens interval (ADI) greater than 4 mm in adults and 5 mm in children . McRae and von Torklus and Gehle had similar findings [55, 56, 57, 93]. More than half of Gholve et al.’s patients with instability also had C2–C3 fusion, which adds to the burden of stresses at C1–C2.
The symptoms of C1–C2 instability range from persistent neck pain and stiffness to frank myelopathy. Typically, the neurological deficits begin in the third or fourth decade of life  and tend to worsen with age . We have also seen concomitant hypertrophy of the posterior arch of C2, which accentuates the neural compromise. Management for symptomatic cases is stabilization between occiput and C2–C3 in concert with treatment for the other associated malformations.
Unfused occipital condyle and clivus—posterior homeotic transformation
Anomalies of the C1 resegmentated sclerotome
Aplasia and hypoplasia of the C1 hypochordal bow—anomalies of anterior atlantal arch
Because the atlas in these cases is usually reduced, deformed and feeble, posterior instrument fusion needs to incorporate the occiput and often has to be extended down to C3 or C4 to distribute the stresses on the upright plates. If the child is very young with a large head and puny nuchal musculature, post-operative halo is recommended.
Aplasia and hypoplasia of the lateral C1 sclerotome—anomalies of posterior atlantal arch
Unlike with aplasia of the hypochordal bow and anterior arch defects, the centrum sclerotome of C1 is not affected in posterior arch defects. The dental pivot and TAL anchorage are thus normal (Fig. 53). The C1–C2 complex in patients with posterior arch defects are usually stable, in spite of the intimidating appearance of the radiographs. None of our patients require fusion.
Combined dysplasia of the hypochordal bow and lateral sclerotome of C1-combined anterior and posterior atlantal arch defects and lateral mass aplasia
Bifid ventral and dorsal atlantal arches
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