Embryology and Anatomy of the Spine

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Embryology and Anatomy of the Spine

SPINAL CORD DEVELOPMENTEarly Embryologic Events• 3rd week: Bilaminar germ disc evolves into trilaminar germ

disc• Trilaminar germ disc

○ Ectoderm: Part of amniotic cavity○ Mesoderm: Forms midline hollow central tube

(notochordal process)– Extends along long axis of embryonic disc

○ Endoderm: Part of yolk sac cavity• Day 18: Notochord and remainder of intraembryonic

mesoderm induce development of neural plate○ Neural plate grows in length and width until day 21,

when neurulation begins○ Neural plate gives rise to most of central nervous system

• Day 21: Notochord (primitive vertebral column) formed○ Key structure in signaling normal neural development

Neurulation• Primary: Formation of cephalic spine to level of conus• Secondary: Formation of spine caudal to level of conus

Primary Neurulation• Occurs between days 18-28

○ Formation of neural tube– Neural plate folds and elevates, forming trough

(neural groove)– Fusion of resultant neural folds– Before complete fusion, neuroectoderm cells give rise

to neural crest cells– Neural crest cells will later migrate to various parts of

body and contribute to variety of tissues□ Autonomic nervous system, adrenal medulla,

tissues of head and neck○ Neural tube open at both ends temporarily

– Communicates freely with amniotic fluid– Cranial and caudal openings of neural tube are called

neuropores• Simultaneously, somites paramedian to notochord

differentiate to form sclerotome cells○ Precursors to vertebral column

• Day 22-23 (4 weeks): Neural tube closure begins atoccipitocervical level○ Closure extends bidirectionally○ Neural canal: Hollow center of neural tube later

becomes– Ventricular system of brain– Central canal of spinal cord

• Day 24: Complete cranial neuropore closure is achieved○ Cranial end of neural tube will become brain

• Day 26: Caudal neuropore closure○ Caudal end of neural tube will become spinal cord

• Closed neural tube is required for normal development ofneural arch

Dysjunction• Final phase of primary neurulation• Neural tube separates from overlying ectoderm• Premature dysjunction

○ Perineural mesenchyme can access neural groove andependymal lining → differentiates into fat

○ Prevents complete neural tube closure○ May result in lipomatous malformation spectrum

– Intradural lipoma– Lipomyelomeningocele: Subcutaneous fatty mass

contiguous with neural placode/lipoma throughposterior dysraphism□ Lipomyelomeningocele accounts for 20-56% of

occult spinal dysraphism– Tethered cord may result

□ Lipomatous malformation prevents normal ascentof cord as vertebral column elongates

• Nondysjunction○ Failure of dysjunction to occur○ Ectodermal-neuroectodermal tract forms → prevents

mesenchymal migration○ Results in focal or widespread spinal dysraphism and

open neural tube defects– Myelomeningocele: Open neural tube defect with

meningocele and neural elements– Myelocystocele: Enlarged central spinal cord canal

(inner cyst) protrudes through osseous dysraphicdefect into dilated subarachnoid space (outer cyst)

– Dorsal dermal sinus: Midline/paramedian stratifiedsquamous epithelial-lined sinus tract

• At end of primary neurulation, spine is formed fromcephalic end of embryo through level of conus

Secondary Neurulation• Formation of spine caudal to level of conus• Days 28-48: Caudal neural tube forms via process referred

to as secondary neurulation or canalization○ Below or distal to posterior neuropore, undifferentiated

cells form primitive streak or caudal cell mass– Once caudal neuropore closes, neural tissue is laid

down as neural cord○ Rostral neural tube extends into caudal eminence○ Caudal cell mass forms vacuoles that fuse to form distal

neural tube– Day 48: Transient ventriculus terminalis appears in

future conus– These cells eventually form conus medullaris, cauda

equina, and filum terminale• Terminal cord undergoes retrogressive differentiation

○ Occurs over ensuing gestational period and into earlypostnatal period

• Secondary neurulation is less precise and leads to widerange of malformations○ Tethered cord

– Most common lesion in caudal cell mass dysplasiaspectrum

– Low-lying cord with thickened filum terminale○ Caudal regression

– Type 1: Foreshortened terminal vertebral columnwith high conus termination; severe associatedanomalies

– Type 2: Low-lying tethered cord with milderassociated anomalies

– Associated anomalies: Renal hypoplasia, pulmonaryhypoplasia, anorectal malformations

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– Associated spinal anomalies: Open dysraphism,segmentation and fusion anomalies, split cordmalformations

○ Terminal myelocystocele– Hydromyelic cord terminating in skin-covered

myelocystocele– Anorectal and visceral anomalies result in high

morbidity○ Anterior sacral meningocele

– Large meningocele traversing enlarged sacralforamen produces presacral cystic mass

○ Sacrococcygeal teratoma– Primitive streak incompletely regresses and leaves

caudal remnant– Occurs due to residual totipotent cell rests (Hensen

node) → 3 cell layers with varying proportions ofmature and immature elements

• Spinal cord ascent○ At 12-weeks gestational age, spinal cord extends entire

length of developing spinal column○ Vertebral column and dura elongate disproportionately

compared to spinal cord– Conus medullaris ascends relative to vertebrae; filum

terminale elongates○ Nerve roots exit at levels of their respective foramen○ Nerve roots then grow longer to accommodate this

relative ascension of spinal cord– Forms cauda equina (sheath of nerve roots inferior to

conus)• Conus should be at or above L3-L4 after 18-weeks

gestation○ This process extends into postnatal period

– By 2 months of age, conus is located at adult level□ Final position is near L1-L2 interspace

– Conus below L2 after 1st month of life, in term infant,is probably abnormal□ Needs evaluation for tethered cord

VERTEBRAL BODY DEVELOPMENTCartilaginous Stage• Week 4: Notochord induces surrounding paraxial

mesoderm derived from primitive streak○ Forms paired somite blocks: Myotomes and sclerotomes○ Myotomes form paraspinous muscles and skin covering○ Sclerotomes divide into medial and lateral formations

– Form vertebral body, intervertebral disc, meninges,spinal ligaments (medial), and posterior spinalelements (lateral)

– Migrate from somites and surround adjacent neuraltube and notochord

– Ventral portion of sclerotome surrounds notochordand forms rudiment of vertebral body

– Dorsal portion of sclerotome surrounds neural tube,forms precursors to neural arch, and condenses toproduce spinous processes

– Notochord will degenerate and involute where it issurrounded by vertebral body

– Notochordal remnant between vertebra expands toform nucleus pulposus of intervertebral discs

○ Failure of notochord induction leads to incompletedivision of neural plate → neurenteric cyst ordiastematomyelia

• Week 6: Cartilaginous stage of vertebral developmentoccurs when chondrification centers appear○ Chondrification centers appear in each mesenchymal

vertebral body○ 2 centers in each mesenchymal vertebral body fuse at

end of embryonic period– Forms cartilaginous centrum

○ At the same time, centers of vertebral arches fuse witheach other and with centrum of vertebral body

○ Spinous and transverse processes develop fromextensions of chondrification centers of vertebral arch

Ossification Stage• Vertebral ossification begins during embryonic period and

ends by age 25• Vertebral body centrum forms from fusion of ventral and

dorsal primary ossification center• At end of embryonic period, there are 3 primary

ossification centers for each vertebrae, including○ Centrum○ Each 1/2 of vertebral arch

• Week 8: Ossification is visible○ Ossification begins in lower thoracic and upper lumbar

regions○ Ossification progresses both cranial and caudal

• Week 13: 3 ossification centers present in vertebrae C1-L3• At birth, each vertebra consists of 3 bony parts connected

by cartilage

Anomalies of Vertebral Formation and Segmentation• Abnormal vertebrae may replace normal vertebrae or be

supernumerary• Failure of vertebral formation (total or partial)

○ Degree and location of vertebral formation failurepredicts morphology– Unilateral chondral center defect and failure of

ossification → hemivertebrae• Failure of vertebral segmentation

○ Block vertebrae with posterior elements fusion• More severe segmentation and fusion defect → increased

incidence of concurrent malformations○ Neuraxis anomalies: Tethered cord, abnormal alignment

(kyphosis, scoliosis), dysraphism○ Visceral organ anomalies

FAILURE OF NEURAL TUBE CLOSUREClinical Implications• Failure of any part of neural tube to close disrupts

development of nervous system and disrupts induction ofoverlying vertebral arches

• Timing of event is such that other systems are alsoimpacted○ Look for associated visceral and anorectal malformations

• Look for consequences of abnormal innervation○ Abnormal lower extremity positioning

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(Top) On day 18, the notochord (primitive vertebral column) and intraembryonic mesoderm induce development of the neural plate. Theneural plate will grow in length and width until day 21, when primary neurulation begins. The neural plate folds and resultant neuralfolds fuse. (Bottom) Neural tube closure begins at 4 weeks at the occipitocervical region. The hollow center of the neural tube willbecome the central canal of the spinal cord and ventricular system of the brain. During primary neurulation, the neural tube separatesfrom the overlying ectoderm in a process called dysjunction. Early dysjunction results in perineural mesenchyme access to the neuralgroove, which differentiates into fat (intradural lipoma); it may also prevent closure of the neural tube (lipomyelomeningocele). Ifdysjunction fails to occur, a spectrum of open neural defects results.

Neural groove

Primary neurulation

Neural plate

Notochord

Neural crest cells

Neural ectoderm

Fusion of neural folds

Migration of neural crest cells

Cranial neuropore

Cutaneous ectoderm

Notochord

Neural crest

Neural tube separates fromectoderm

Center of neural tube

Neural tube closure atoccipitocervical region

Notochord

Notochord

Cutaneous ectoderm

Cutaneous ectoderm

Neural crest

NEURAL TUBE EMBRYOLOGY

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(Top) Graphic of neural tube closure as viewed from above is shown. At either end, there is an opening, the cranial and caudalneuropore, which are open to the amniotic fluid at this stage. The cranial neuropore closes by day 24 and will become the brain. Thecaudal end closes by day 26. (Bottom) Cross section of an embryo shows the neural tube, which has formed dorsal to the notochord.The neural tube will form the spinal cord and neural crest cells migrate throughout the body and give rise to diverse tissues, includingganglia of the autonomic nervous system, adrenal medulla, and tissues of the head and neck. Somites form from the mesoderm andform multiple tissues. The medial somite is the sclerotome, which will form the vertebral column. Secondary neurulation begins at thecaudal eminence and forms the conus medullaris, cauda equina, and filum terminale of the spinal cord.

Caudal neuropore (unclosedcaudal end)

Neural tube complete

Body ectoderm

Neural fold

Neural grove

Somites

Neural tube closed andcomplete

Cranial neuropore (unclosedcranial end)

Sclerotome

Embryo showing level ofsection

Caudal eminence (site ofsecondary neurulation)

Aorta and inferior vena cava

Neural crest

Notochord

Dorsal mesentery

Gut tube

Coelomic cavity

Neural tube

Somite

NEURAL TUBE EMBRYOLOGY

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(Top) Axial graphic shows the normal ossification centers within the developing vertebrae. The vertebral body and neural arch primaryossification centers (beige) are forming within the cartilaginous (blue) vertebral axis. Coronal graphic illustrates the normal appearanceof the sacral ossification centers and cartilage. The sacrum and coccyx are the last portions of the vertebral column to ossify. (Middle)Coronal ultrasound of the lumber spine at 22 weeks shows the ossification center (centrum) within the vertebral body; the remainder ofthe vertebral body is cartilaginous. (Bottom) Sagittal transabdominal ultrasound at 19.5 weeks (top) shows normal ossification andalignment of the lumbar spine. The coccyx and sacrum are unossified, which is an expected finding. At 22 weeks (bottom), there hasbeen more complete ossification. Ossification should be complete by 25 weeks.

Cartilaginous spinous process

Lamina

Transverse processPedicle

Ossified centrum of vertebral body

S1 ossification center

Neural arch ossification center

Cartilaginous coccyx

Gluteal muscles

Intervertebral disc

Iliac crest

Cartilaginous portion of vertebral body

Ossified portion of vertebral body(centrum)

Kidney

Unossified coccyx

Ossification centers S1-S4

Unossified sacrum and coccyx

Ossification centers S1 and S2

FETAL SPINE

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(Top) 3D ultrasound is ideal for evaluating the spine as all 3 planes can be evaluated with 1 acquisition. A 3D bone algorithm renders askeletal view. (Middle) Sagittal graphic shows the normal appearance of the lumbar spinal column, conus medullaris, cauda equina, andcentral spinal canal. A correlative sagittal ultrasound of a fetal spine shows the normal hypoechoic appearance of the cord with ahyperechoic central canal. The lumbar portion of the spinal cord widens slightly compared to the thoracic portion. The normal cordascends during gestation and should be at or above L3-L4 after 18 weeks and L1-L2 by 2 months of age. (Bottom) Sagittal T2 fetal MR(left) and newborn (right) shows the neural axis. The ossified portion of the vertebral bodies is hypointense with hyperintenseintervertebral discs. The spinal cord is surrounded by high-signal CSF. MR is an excellent tool for evaluating spinal dysraphism or cordabnormalities suspected on ultrasound.

Coronal plane

Sagittal plane

Scapula

Transverse process

Rib

Vertebral Body

Laminae

Axial plane

Pedicles

Central canal

Central canal

Spinous processes

Spinous processes

Spinal cord

Conus medullaris

Nerve roots

Cauda equina

Conus medullaris

L1 vertebral body

L3-L4 intervertebral disc

Cerebrospinal fluid

Spinal cord

Ossified portion of L1 vertebral body

Cartilaginous portion of vertebral body

L4-L5 disc

Paraspinous musculature

FETAL SPINE

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Embryology and Anatomy of the Spine