Review of Their Dysembryology

Clinical Anatomy 26:928–932 (2013)

REVIEW

Hypoplastic Occipital Condyle and Third Occipital Condyle: Review of their Dysembryology

R. SHANE TUBBS,1 PATRICK RYAN LINGO,1 1 2 MARTIN M. MORTAZAVI, AND AARON A. COHEN-GADOL * 1Pediatric Neurosurgery, Children’s Hospital, Birmingham, Alabama 2Goodman Campbell Brain and Spine, Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, Indiana

Disruption or embryologic derailment of the normal bony architecture of the craniovertebral junction (CVJ) may result in symptoms. As studies of the embryology and pathology of hypoplasia of the occipital condyles and third occipital condyles are lacking in the literature, the present review was per- formed. Standard search engines were accessed and queried for publications regarding hypoplastic occipital condyles and third occipital condyles. The literature supports the notion that occipital condyle hypoplasia and a third occipital condyle are due to malformation or persistence of the proatlas, respectively. The Pax-1 gene is most likely involved in this process. Clinically, condylar hypoplasia may narrow the foramen magnum and lead to lateral medullary compression. Additionally, this maldevelopment can result in transient vertebral artery compression secondary to posterior subluxation of the occiput. Third occipital condyles have been associated with cervical canal stenosis, hypoplasia of the dens, transverse ligament laxity, and atlanto-axial instability causing acute and chronic spinal cord compression. Treatment goals are focused on craniovertebral stability. A better understanding of the embryology and pathology related to CVJ anomalies is useful to the clinician treating patients presenting with these entities. Clin. Anat. 26:928–932, 2013. VC 2013 Wiley Periodicals, Inc.

Key words: anatomy; craniovertebral junction; occiput; pathology; skull base

INTRODUCTION rare developmental abnormalities of the CVJ that can lead to instability and compression of important sur- The craniovertebral junction (CVJ) refers to the rounding neurovascular structures (Fig. 1) (Menezes, bony structures, ligaments, and articulations that 1998; Piper and Traynelis, 1998). Understanding surround the cervicomedullary junction. This funnel- their embryology, anatomy, biomechanics, and path- shaped enclosure, which includes the caudal portions ologic inﬂuence on the CVJ can help neurosurgeons of the occipital bone, atlas, axis, and associated liga- determine the best treatment of these complex ments, protects the medulla oblongata and upper anomalies. Herein we review the literature regarding cervical spinal cord (Menezes et al., 2001). As part hypoplasia of the occipital condyle and the presence of the occipito-atlantal joint, the occipital condyles contribute largely to ﬂexion and extension of the head and neck. The median (third) occipital condyle, *Correspondence to: Aaron A. Cohen-Gadol, MD, MSc, Goodman also known as condylus tertius, is a remnant of the Campbell Brain and Spine, Indiana University Department of Neu- occipital vertebrae anterior to the foramen magnum rological Surgery, 355 W. 16th Street, Suite 5100, Indianapolis, (Rao, 2002). This structure can articulate with the IN 46202, USA. E-mail: [email protected] dens or the atlas and limit CVJ motion (Menezes, Received 20 July 2012; Revised 17 October 2012; Accepted 21 1998; Rao, 2002) and should be distinguished from October 2012 basilar processes (Kale et al., 2009). Hypoplastic Published online 21 January 2013 in Wiley Online Library occipital condyles and a third occipital condyle are (wileyonlinelibrary.com). DOI 10.1002/ca.22205

VC 2013 Wiley Periodicals, Inc. Hypoplastic Occipital Condyle and TOC 929

sents the final cellular separation of the skull and cervical spine. After primary segmentation, Hox genes specify the rostral-caudal identity of cells within the somites. Pax-1 expression influences cellular partitioning between tissues and thus plays a central role in resegmentation (Pang and Thompson, 2011). The hypocentrum of the proatlas forms the anterior tubercle of the clivus, whereas the centrum forms the apex of the dens and the apical ligament. The neural arch divides into ventral-rostral and dorsal-caudal segments. The ventral-rostral segment gives rise to the occipital condyles, the anterior U-shape of the foramen magnum, and the alar and cruciate ligaments. The dorsal-caudal segment forms the posterior arch and lateral masses of the atlas Fig. 1. Inferior view of the skull base of an adult (Menezes and VanGilder, 1989; Menezes, 1998, skull identified with a left hypoplastic occipital condyle 2008; Menezes and Fenoy, 2009). At an early stage and third occipital condyle (TOC). The TOC and hypo- in development, a dense band of connective tissue plastic left condyle and normal right-sided condyle have forms ventral to each vertebral segment called the been highlighted for clarity. hypochordal bow. The hypochordal bow associated with the proatlas normally regresses, but the one of a third occipital condyle. The proposed embryol- associated with the first cervical somite contributes ogy, clinical presentation, and treatment are pre- to the formation of the anterior arch of the atlas sented. (Menezes and VanGilder, 1989; Menezes, 1998, Following a search in human species and in the 2008; Rao, 2002). English language using PubMed, 23 articles were Failure of any of the above developmental proc- found detailing the ‘‘occipital condyle’’ and hypopla- esses can lead to anomalies of the CVJ. Thus, sia or ‘‘hypoplastic.’’ A search for ‘‘third occipital con- descriptions of CVJ developmental malformations are dyle’’ resulted in six articles, and a search for ‘‘con- based on the underlying embryologic disturbance. dylus tertius’’ resulted in five publications. Developmental errors can lead to hyperplasia, apla- sia/hypoplasia, midline fusion failure, and resegmentation anomalies. Hypoplasia of the lateral elements Embryology of the proatlas, including the neural arch, can lead to occipital condylar hypoplasia (Fig. 1) (Menezes, During the fourth week of gestation, paraxial mes- 1998; Menezes et al., 2001; Pang and Thompson, oderm adjacent to the neural tube and notochord 2011). Persistence or hyperplasia of the hypochordal segments form 42 somites. There are 4 occipital, 8 bow of the proatlas may contribute to the formation cervical, 12 thoracic, 5 lumbar, 5 sacral, and 8–10 of an abnormal articulation between the clivus, the coccygeal pairs of somites. Each somite forms an apical dens, and the anterior arch of the atlas known outer dermatome, inner myotome, and medial scle- as the third occipital condyle (Menezes and Van- rotome. The cervical through coccygeal sclerotomes Gilder, 1989; Menezes, 1998, 2008; Rao, 2002). Of eventually fuse in the midline to form the vertebral note, the notochord has a course through the loca- bodies of the spinal column. The first and second tion of the third occipital condyle (David et al., occipital sclerotomes form the clivus, and the third 1998). sclerotome forms the jugular tubercles. Development of the fourth sclerotome, also known as the proatlas (Fig. 2), is key to understanding the anatomy and Anatomy malformations of CVJ. Key to the present review, the occipital condyles are derived from the proatlas The occipital condyles are convex projections (Menezes and VanGilder, 1989; Menezes, 1998, located at the anterior-lateral margins of the fora- 2008; Menezes and Fenoy, 2009). Lastly, it should men magnum (Moore and Dalley, 2006). They artic- be mentioned that the resegmentation of the ulate with the superior facets of the atlas to form the somites is still a matter of some debate, especially atlanto-occipital joints (Menezes and VanGilder, resegmentation of their lateral portions (Aoyama and 1989; Moore and Dalley, 2006). They are condyloid Asamoto, 2000; Huang et al., 2000). synovial joints with weak capsules that provide little Unlike the first three occipital somites, the fourth stabilization. These joints are reinforced by anterior occipital somite undergoes resegmentation, a pro- and posterior atlanto-occipital membranes, which cess in which the original rostral-caudal boundaries extend from the anterior and posterior arches of the of the somites are reorganized to include cells atlas to the basion and opisthion, respectively derived from adjacent somites (Fig. 2). The caudal (Moore and Dalley, 2006). half of the fourth occipital somite fuses with the ros- Blood supply to the atlanto-occipital joints is pri- tral half of the first cervical somite to form the tran- marily through a vascular arcade derived from the sitional proatlas sclerotome. At the resegmentation vertebral arteries. Occipital branches of the external boundary, the severance line forms, and this repre- carotid artery also contribute to this blood supply. 930 Tubbs et al.

Fig. 2. Schematic drawing (after Pang and Thomp- aspect of the proatlas gives rise to the occipital condyle. son, 2011) of the proposed normal embryology of the Note the severance line through the proatlas and the re- craniocervical junction. Note that the hypochordal bow sultant bony derivations (color coded). [Color ﬁgure can of the proatlas forms the third occipital condyle (repre- be viewed in the online issue, which is available at sented here as the basion) and that the more posterior wileyonlinelibrary.com.]

Lymphatic drainage is via the retropharyngeal nodes occipital joints is 13–15 (Menezes and VanGilder, that communicate with the deep upper cervical 1989; Menezes et al., 2001; Moore and Dalley, 2006). chain. A watershed area exists for drainage of the In adults, the angle of the axis of the atlanto-occipital paranasal sinuses and nasopharynx and thus the joints, the Schmidt–Fisher angle (Fig. 3), is normally potential exists for retrograde inflammation of the 1248–1278. In children, the occipital condyles are atlanto-occipital joints from coincident sinusitis with smaller, and the Schmidt–Fisher angle is more obtuse, resultant ligamentous laxity (Grisel’s syndrome) making the atlanto-occiptal joints of youth inherently (Menezes and VanGilder, 1989; Menezes et al., less stable than those of adults (Menezes and Van- 2001). Gilder, 1989; Piper and Traynelis, 1998). Within the occipito–atlanto–axial complex, the Almost no two sets of occipital condyles are alike ovoid occipital condyles fit into the obliquely-oriented, in their dimensions, and much of the variability is elliptically cupped superior facets of the atlas. This accounted for by age and sex. Based on a study of unique geometry primarily allows flexion-extension 202 adult human skulls, the average size of an occi- and some lateral bending, but precludes meaningful pital condyle was 23.4 mm 3 10.6 mm 3 9.2 mm rotation. The average range of motion at the atlanto- (Naderi et al., 2005). However, studies have failed Hypoplastic Occipital Condyle and TOC 931

as part of Morquio disease, Conradi syndrome, and spondyloepiphyseal dysplasia (Piper and Traynelis, 1998; Menezes and Vogel, 2008). Because of its potential articulation with the dens or the anterior arch of the atlas, a third occipital condyle may limit flexion-extension of the atlanto-occipital joints (Rao, 2002). Third occipital condyles have been associated with cervical canal stenosis, hypoplasia of the dens, transverse ligament laxity, and atlanto-axial instability causing acute and Fig. 3. Posterior view of the craniocervical junction chronic cord compression (Kotil and Kalayci, 2005; of an adult skeleton illustrating the Schmidt–Fisher Figueiredo et al., 2008). All developmental angle, which is normally 1248–1278. abnormalities of the CVJ, including occipital condylar hypoplasia and a third occipital condyle, may be asymptomatic and discovered incidentally at autopsy, to show a correlation between condyle length, head during cadaveric dissection, or through radiographic circumference, and foramen magnum anterior–pos- evaluation (Menezes and VanGilder, 1989; Piper terior diameter (Guidotti, 1984; Naderi et al., 2005). and Traynelis, 1998; Menezes et al., 2001; v Luding- Several morphologic variants of the human occipital hausen et al., 2002; Rao, 2002). condyle exist. Up to 50% of condyles are oval- The constellation of symptoms that can present shaped. Other variants include kidney-like, S-like, from CVJ instability secondary to occipital condylar eight-like, triangular, ring-like, two-portioned, and hypoplasia or an anomalous third occipital condyle deformed (Naderi et al., 2005). The occipital con- may result from compression of the lower brainstem, dyles may be duplicated (Tubbs et al., 2005) or cervical spine, cranial nerves, or blood supply. The grooved (Das et al., 2006). No specific condylar most common symptom is suboccipital neck pain abnormalities appear more commonly in males ver- radiating to the cranial vertex. The most common sus females. neurologic sign is myelopathy associated with When present, the third occipital condyle is a mid- monoparesis, hemiparesis, paraparesis, or tetrapare- line projection of the clivus located at the anterior sis (Menezes and VanGilder, 1989; Menezes et al., margin of the foramen magnum (Smoker, 1994; 2001). Sensory abnormalities are usually related to Menezes, 1998; v Ludinghausen et al., 2002; Rao, compression of the dorsal columns (Menezes and 2002). It has a narrow base and broader inferior sur- VanGilder, 1989). Brain stem and cranial nerve dys- face that may possess an articular facet for the apex function can present as nystagmus, opthalmoplegia, of the dens (Rao, 2002). More rarely, it may also dysphagia, respiratory difficulty, and sleep apnea. articulate with the anterior arch of the atlas The most common cranial nerve affected with such (Menezes, 1998; Rao, 2002). Third occipital condyles malformations is the vestibulocochlear nerve, result- have been measured up to 6.5 mm in length and 6 ing in hearing loss. Transient disruption of the verte- mm in transverse diameter (Rao, 2002). bral and anterior spinal arteries from instability at the CVJ can lead to focal neurologic deficit or vascu- Pathology lar symptoms such as confusion, vertigo, visual field loss, or basilar migraine (Menezes and VanGilder, Occipital condylar hypoplasia results in flattening 1989; Menezes et al., 2001). Often only a minor of the condyles and elevation of the atlas and axis trauma or manipulation of the head and neck can relative to the skull base. This can be confirmed precipitate symptoms. For example, Samdani et al. radiographically by measurement of the Schmidt– (2009) described a rare presentation of acute torti- Fisher angle, which will be greater than 1258 in the collis after a minor fall in a 5-year-old boy. The presence of occipital condylar hypoplasia. These underlying etiology was discovered to be an asym- defects can be unilateral or bilateral and are often metric hypoplastic occipital condyle (Samdani et al., associated with the paramedian type of basilar inva- 2009). Figueiredo et al. (2008) presented a case of gination (Menezes and VanGilder, 1989; Piper and acute-on-chronic cervicomedullary compression Traynelis, 1998). This is because they share a com- causing tetraplegia in a 40-year-old man during a mon embryological defect, hypoplasia of the parts of roller coaster ride secondary to a third occipital con- fourth occipital somite forming the lateral aspects of dyle and associated atlanto-axial instability. the foramen magnum (Menezes, 1998; Piper and Traynelis, 1998; Menezes et al., 2001; Pang and Thompson, 2011). When the defect is unilateral or Treatment asymmetric, a compensatory scoliotic change of the cervical spine may occur. The foramen magnum Clinical spinal stability has been defined by White itself is often narrowed in the presence of condylar and Panjabi (1990) as the ability of the spine under hypoplasia and may cause lateral medullary com- physiologic loads to limit displacement so as to pre- pression. Condylar hypoplasia restricts movement of vent injury to the spinal cord and nerve roots, and to the atlanto-occiptal joint and can lead to transient prevent incapacitating pain due to structural vertebral artery compression secondary to posterior changes. If instability at the CVJ secondary to occipi- subluxation of the occiput (Menezes and VanGilder, tal condylar hypoplasia or a third occipital condyle is 1989). Hypoplastic condyles can occur in isolation or detected clinically based on the signs and symptoms 932 Tubbs et al. described above, then intervention is indicated. No Guidotti A. 1984. Morphometrical considerations on occipital con- one procedure can be used for the management of dyles. Anthropol Anz 42:117–119. all patients with CVJ instability. The goals of treat- Hong JT, Takigawa T, Sugisaki K, Espinoza Orias AA, Inoue N, An ment are to reduce or decompress the deformity in HS. 2011. 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