Neuroanatomy, Spinal Cord

Structure and Function

External Features

The spinal cord is a long cylindrical extension of the central nervous system within the vertebral column's cavity. It is approximately 42.3 cm in length in males and 38.9 cm in females.[1] Even though the spinal cord is almost symmetrical, it is enlarged in a fusiform shape in two regions in the form of cervical and lumbosacral enlargements. In the cervical area, this fusiform enlargement is due to the exit of many nerves forming a plexus (the brachial plexus) supplying the upper limb's muscles. This enlargement spreads from the fourth cervical segment to the second thoracic segment. The maximum transverse diameter is present at the level of the C5 segment.[4] Similarly, the lower thoracolumbar enlargement gives rise to a plexus of nerves supplying the lower limb muscles in the form of the lumbosacral plexus. This second enlargement extends from the second lumbar segment to the third sacral segment of the spinal cord.

The lowermost part of the spinal cord tapers in a cone-like fashion and is thus termed the conus medullaris. From the apex of this conus medullaris, an extension of the pia mater, i.e., the filum terminale, descends and gets attached to the coccyx's posterior surface. In midline anteriorly, the cord shows the presence of a deep longitudinal cleft, which is the anterior median fissure. This fissure is the site of the presence of the anterior spinal artery. Similarly, the posterior surface demonstrates a shallow furrow in the midline, the posterior median sulcus. In combination, the anterior median fissure and the posterior median sulcus will divide the whole of the spinal cord into two symmetrical halves - the right and left half, which one can better appreciate in a transverse section.

Further, we can appreciate the shallow depressions on either side as anterolateral and posterolateral sulci. The anterolateral sulcus will be the site of exit of the ventral (motor) roots of the spinal cord. The posterolateral sulcus will be the site for the entry of dorsal (sensory) roots of the spinal cord. 

Transverse Section of the Spinal Cord

On sectioning a spinal cord, two distinct areas are evident with the naked eyes, an inner grey matter, and an outer white matter. The grey matter indicates the collection of cell bodies of neurons. The white matter is the collection of the fibers running through the spinal cord. 

Grey Matter: When taking a transverse section of the spinal cord, in the middle is the grey matter, which appears roughly in the form of an H (butterfly) shaped mass. The grey matter is divisible on each half of the cord into a larger ventral mass –  ventral grey column (anterior/ventral horn) and an elongated dorsal grey column (posterior/dorsal horn). In some parts of the cord (thoracic and upper lumbar regions), a small lateral projection of a grey mater is present between the ventral and dorsal columns. This structure is a lateral grey column (lateral horn). The cells in the anterior horn are called anterior horn cells. The grey matter on both the left and right halves connect by the grey commissure, which contains the central canal. This canal communicates above into the fourth ventricle. The central canal expands at the lower end in the conus medullaris to form the terminal ventricle. The central canal contains CSF and is lined by ependymal cells.[5] For experimental purposes, the grey matter divides into ten laminae. The laminae I to VI occupy the posterior grey column.[6] The lamina VII is in the intermediate region, lamina VIII remains confined to the medial part of the anterior grey column, and lamina IX occupies the lateral part of the anterior grey column. The area around the central canal is distinguished as lamina X.[7] Each of these laminae has unique connections and functions.

White Matter: Surrounding the grey mater superficially, we find the white matter. On either side, the white matter, which is medial to the posterior grey column, forms the dorsal (posterior) funiculus. The white matter that is medial and ventral to the ventral (anterior) grey column forms the ventral (anterior) funiculus. While the white matter lateral to the anterior and posterior grey column forms the lateral funiculus. Each of these areas contains bundles of nerves in tracts that can be ascending or descending.[8] This region is called white because it looks pale due to the presence of myelinated nerve fibers.

There is variation in the amount of the areas occupied by the white and grey matter in different spinal cord levels. The space occupied by the grey matter increases progressively, and the region for white matter decreases as we go craniocaudally.

Even the arrangement of fibers in each funiculus of the white matter is unique. When observing a transverse section of the spinal cord, we find that the posterior funiculus will have ascending sensory fibers arranged into two regions called fasciculus gracilis and fasciculus cuneatus. The anterior funiculus will contain descending motor fibers of olivospinal, tectospinal, lateral vestibulospinal, medial vestibulospinal, anterior corticospinal, anterior spinothalamic, spino-olivary, spino-tectal, and reticulospinal tracts. The lateral funiculi will contain anterior and posterior spinocerebellar, lateral spinothalamic, spino-reticular, lateral corticospinal, rubrospinal, and lateral reticulospinal tracts. 

Arrangement of the Spinal Nerves and Segments

The spinal cord gives rise to a series of spinal nerves on either side. The spinal nerves are mixed nerves and have two roots, an anterior and posterior root. Sometimes they are also termed as ventral and dorsal root, respectively. The anterior or ventral root is motor in nature and gives efferent fibers to skeletal muscles. Sometimes they also contain preganglionic autonomic fibers to blood vessels and internal organs. The posterior or dorsal root is sensory and contains afferent fibers from peripheral receptors from the skin, bones, joints, muscles, and internal organs. Researchers discovered this in the 19th century, and it is known as Bell-Magendie Law.[9]

Each root is an aggregation of the number of rootlets arising from a part of the spinal cord, and that area is called the spinal segment. The spinal nerves are 31 pairs – 8 pairs of cervical, 12 pairs of thoracic, five pairs of lumbar, five pairs of sacral, and one pair of coccygeal nerves.[10] Thus there are 31 pairs of spinal segments. The dorsal nerve roots enter the spinal cord along the postero-lateral sulcus and ventral roots along the anterolateral sulcus. The dorsal root shows a swelling called dorsal nerve root ganglion (spinal ganglion). This ganglion contains cell bodies of pseudounipolar sensory neurons. 

Due to the vertebral column and spinal cord's developmental differences, spinal segments do not lie opposite their corresponding vertebrae. The length and obliquity of the spinal nerves increase progressively caudally before their exit through the intervertebral foramina. This knowledge is vital in laminectomy to relieve spinal cord compression due to traumas and tumors. At the conus medullaris, these roots of nerves in pairs coming from the lower lumbar, sacral, and coccygeal nerves form a bundle of nerves that resembles the tail of a horse and is thus known as cauda equina.

Covering of Spinal Cord

Three meninges surround the spinal cord. From outside inwards, they are the dura mater (thick fibrous membrane), the arachnoid mater, and the pia mater. The space present between the dura and the vertebral canal wall is called the extradural (epidural) space. The space between the dura and arachnoid mater is said to be subdural space. Subarachnoid space is present between the pia mater and arachnoid mater. This space is filled with cerebrospinal fluid. The pia mater is adherent to the spinal cord and extends along with the cord up to the lower border of the L1 vertebra where the spinal cord end. But dura and arachnoid mater extend up to the second sacral vertebra. Between these two vertebral levels, subarachnoid space has spinal nerve roots forming cauda equina. One should remember that the pia mater does not end at L1 but extends beyond this as the thin midline structure called filum terminale, and finally attached to the posterior surface of the coccyx. 

The spinal cord's most important function is to receive, integrate, associate the input, and produce a reflex response.

Embryology

The ectoderm of a trilaminar staged embryo will thicken at the midline to be called the neural plate. This plate depresses to form a neural groove whose ends later fuse to convert it into a neural tube. This tube enlarges at the cranial end and remains tubular at the caudal part. The cranial part forms the brain. The spinal cord develops from the caudal tubular part of this neural tube.[11][12] Maternal dietary supplement of foliate plays a vital role in the closure of the neural tube in the early stages.[13] The neural tube differentiates itself into the ependymal, mantle, and marginal layers from inside out. The mantle proliferates rapidly to form the gray matter, divided into a ventral basal lamina and dorsal alar lamina by the sulcus limitans. The basal lamina develops into the motor area, giving rise to anterior and lateral horns and all the neurons within. The alar lamina develops as a sensory area that gives rise to the posterior horn and all the neurons within it. The cavity within will narrow down to form the central canal. The neural crest cells help in the formation of the ventral sympathetic ganglion and dorsal root ganglion. 

The axons of the neuron start occupying the marginal zone during the fourth week of gestation. The axons now bundle up to form ascending and descending tracts within the marginal zone, further subdividing this region into anterior, posterior, and lateral white columns. With the development of limb buds, there is a simultaneous development of the cervical and lumbar enlargement at the fifth to sixth weeks of gestation. The tracts start forming during the third month, and the corticospinal tract appears by the fifth month of intra-uterine life. The myelination begins at the fourth month of embryonic life from short intersegmental tracts of the spinal cord and continues up to two to three years after birth till the child starts walking. 

The vertebral bodies and the muscles surrounding the spinal cord develop from the surrounding dermatomes. The incomplete development of vertebras leads to several congenital anomalies that this article describes in clinical significance. The length of the spinal cord and the vertebral column are equal in size up to the third month of fetal life. Later the vertebral column develops rapidly in comparison to the spinal cord. Thus the spinal cord ends at a higher level within the vertebral canal. It has receded to the third lumbar vertebra at birth and reaches the first lumbar vertebra by puberty. Thus the spinal nerves arise from the spinal cord at a much higher level than their exit outside through the intervertebral foramina. 

Many studies indicate a crucial role of some critical signaling factors in developing the spinal cord, like retinoic acid, bone morphogenetic proteins, Wnt, fibroblast growth factors, and Hedgehog proteins.[14][15] It is now known whether vascular endothelial growth factors (VEGFs) play a significant role in developing the vessels supplying the spinal cord.[16]

Blood Supply and Lymphatics

Arterial Supply of the Spinal Cord

The spinal cord receives its blood supply from three longitudinal channels that extend along the length of the spinal cord, i.e., one anterior spinal artery and two posterior spinal arteries. The anterior spinal artery runs along the anterior median fissure, and the smaller two posterior spinal arteries pass through the posterolateral sulcus on either side. The vertebral arteries are the main source from where these spinal arteries branch. But it should be remembered that the blood coming from the vertebral arteries supply only the cord's cervical segments. In the lower down region, the spinal arteries receive blood through radicular arteries that reach the cord and the roots of the spinal nerves. The radicular arteries are actually branches from many arteries like the vertebral, cervical, intercostal, lumbar, and even sacral arteries. The largest radicular feeder from the left posterior intercostal artery to the anterior spinal artery is between T9 and T12, called the artery of Adamkewicz. All the radicular and spinal arteries anastomose with each other to form an anastomotic pial plexus called vasocorona.[17] But the better part of the spinal cord is supplied by the anterior spinal artery and its branches.

Veinous Drainage of the Spinal Cord

The veins draining the spinal cord are arranged in the form of a network of six longitudinal channels, i.e., an anteromedian vein, a posteromedian vein, and a pair of anterolateral and posterolateral veins.[17] As the name indicates, the anteromedian and posteromedian channels will be present in the midline anteriorly and posteriorly, respectively, relative to the spinal cord. The anterolateral and posterolateral channels are paired and lie as per their names on either side of the spinal cord. All these channels are interconnected to form a plexus of veins of venous vasocorona. The venous blood from these veins drains into radicular veins. These radicular veins finally drain into the segmental veins.

Nerves

Spinal Nerves

The nerves are of two types based on their origin - the cranial and spinal nerves. Those nerves which begin in the cerebrum or the brain stem are called cranial nerves. There are twelve pairs of cranial nerves. The nerves coming from the spinal cord are called the spinal nerves. There are 31 pairs of spinal nerves coming from the spinal cord and spread on either side of the vertebral column. They are classified into cervical, thoracic, lumbar, sacral, and coccygeal nerves.  The cervical nerves are in eight pairs; the thoracic are twelve pairs, the lumbar and sacral nerves are in five pairs, and one pair of coccygeal nerves.

Spinal Tracts

When we study the transverse section of a spinal cord, we can appreciate many spinal tracts within the white matter. They are categorized into two types - ascending and descending tracts. The descending tracks are mainly motor, and the ascending tracks are sensory.

Some of the most essential descending (motor) tracts passing through the spinal cord are as follows:

1. Cortico-spinal tract (This is also known as the pyramidal tract, which is the most important of the motor tracts)
2. Tectospinal tract
3. Rubrospinal tract
4. Vestibulospinal tract
5. Reticulospinal tracts
6. Olivospinal tract

Some of the most important ascending (sensory) tracts are as follows:

1. Lateral spinothalamic tract (spinal lemniscus)
2. Anterior spinothalamic tract (medial lemniscus)
3. Trigeminal lemniscus
4. Lateral lemniscus
5. Spinotectal tract
6. Spino-olivary tract
7. Ventral spinocerebellar tract
8. Dorsal spinocerebellar tract
9. Dorsolateral tract (of Lissauer)
10. Spino-cervico-thalamic tract

Here we will explain one descending tract in detail to better understand the whole course. 

The cortico-spinal tract arises mainly from the motor area of the cerebral cortex (area 4) with some contribution from the premotor area (area 6), somatosensory area (area 3, 2, 1), and parietal cortex (area 5). The fibers run through the internal capsule's posterior limb and then occupy the middle part of the midbrain's crus cerebri. The tract then occupies the ventral part of the pons and descends through the pyramids in the medulla. At the lower end of the medulla, almost 70 to 80% of the fibers cross to the opposite side of the spinal cord, called the pyramidal (motor) decussation. These crossed fibers enter the lateral funiculus of the spinal cord and continue as the lateral corticospinal tract. They end at various levels of the spinal cord's grey matter by synapsing with internuncial neurons of dorsal and ventral columns. The remaining 20 to 30% of the corticospinal tract fibers, which have not crossed, will descend within the anterior funiculus as the anterior corticospinal tract. Finally, these anterior corticospinal tract fibers too cross to the opposite side at the appropriate levels. Thus all fibers of the corticospinal tract eventually cross to the opposite side and connect the cerebral cortex of one side with the ventral horn cells of the opposite part of the spinal cord. These fibers are called upper motor neurons. The fibers starting in the ventral horn cells and descending downwards will be called lower motor neurons. This knowledge is vital as the clinical presentation of upper and motor neuron lesions are quite different.[18] Any minor injury of these fibers will lead to widespread paralysis of the muscles supplied.

Spinal Cord Lesions

Lesions of the spinal cord fall into the following categories:

1. Lesions of the afferent system:
   1. Dorsal nerve roots
   2. Spinothalamic tract
   3. Posterior white funiculus
   4. Syringomyelia
2. Lesions of the efferent system:
   1. Upper motor neuron lesions
   2. Lower motor neuron lesions
3. Lesions involving upper and lower motor neurons:
4. Lesions involving posterior and lateral funiculi
5. Thrombosis of the spinal artery
6. Hemisections (Brown-Sequard syndrome)
7. Transections 
8. Hereditary diseases: Friedreich ataxia

Details of some of these lesions will be discussed in the section of Clinical Significance. 

Physiologic Variants

The neurotransmitters essential in the modulation of motor and sensory function are serotonin, noradrenaline, and dopamine. These have been observed to decrease spinal cord injuries depending on their incomplete damage to complete spinal injuries.[19]

Surgical Considerations

Lumbar Puncture: This is a clinical procedure by which the CSF is drawn from the subarachnoid space for diagnostic and therapeutic purposes.[20] Here the needle is introduced from the area between the second and third lumbar vertebra into subarachnoid space, and CSF is drawn (in the case of adults). In the case of children, it will be much more below between the third and fourth lumbar space. Even during the age of imaging, the CSF analysis remains consistent in the diagnosis of many significant neurological disorders like Alzheimer's disease, subarachnoid hemorrhage, and others. It also remains the most practical method to differentiate between bacterial and viral meningitis.[20]

Epidural Injections: Epidural anesthesia is a technique where a needle is passed into the epidural to give an analgesic into this space. This method is commonly used to relieve pain in certain conditions like cesarian sections, major abdominal surgeries, thoracotomy, and other conditions.[21][22]

Subdural Injections: It is an observation the injections intended for the epidural space often go unintentionally into the subdural space and lead to many complications.[23]

Paravertebral Block: This is a technique where the nerves are blocked at their roots or plexuses surrounded by the dura mater within the epidural space. These are similar to epidural blocks and done at the cervical, thoracic, lumbar, and sacral regions.[24]

Clinical Significance

Any spinal cord lesion can generally be localized quite easily by understanding the anatomy. There is usually impairment or sensory or motor functions in the lower extremities. It is always important to identify the motor or sensory level to determine the lesion's exact site. In general, the best imaging modality for any suspected spinal cord lesion is magnetic resonance imaging(MRI).

1. Meningitis: It is the infection of meninges (coverings) of the brain. It can be bacterial or viral. Some of the most common being:
   1. Bacterial meningitis: It can be because of bacterias' infection such as Streptococcus pneumoniae, Neisseria meningitides, Listeria monocytogenes, E. coli, Pseudomonas aeruginosa, Klebsiella, Enterobacter, Staphylococcus aureus, and Staphylococcus albus. Streptococcus pneumoniae and Neisseria meningitides are known to be the most common.[25]
   2. Tubercular meningitis: It is due to infection by Mycobacterium tuberculosis. It presents with typical features like a stiff neck, fever, increased intracranial pressure, and headache. The CSF shows increased proteins and decreased glucose levels.[26] It is common in children with primary tuberculosis, patients with malnourishment, and immunodeficiencies like HIV and cancer. Even though rare compared to bacterial meningitis, this can lead to high morbidity and mortality if not detected early and treated.[27]
2. Traumatic injuries of the spinal cord: It is the commonest, accounting for almost 90% of all spinal cord injuries. It frequently results from road traffic accidents, falls, and sports injuries. They can have devastating effects on the life of a person. Lesions in the lower thoracic region lead to paraplegia, and that in the cervical area leads to quadriplegia.[28]
   1. Compression: It can be due to intervertebral disc herniation or the vertebras' dislocation leading to compression of the spinal cord. Symptoms due to compression can be paresis to paralysis. 
   2. Hemisection: Traumatic injuries can lead to an incomplete section of a part of the spinal cord. A classical presentation of a hemisection is the Brown-Sequard syndrome. There is ipsilateral motor loss below the section in this syndrome, contralateral loss of pain, and temperature sensations, with no loss of ipsilateral light touch sensations. 
   3. Complete section: It is a condition where there is the absence of sacral sparing with no sensation in the segment of S4-5 or the lack of voluntary contraction of the anal sphincter.[29]
3. Vascular injuries of the spinal cord:
   1. Anterior cord syndrome: When the anterior spinal artery is blocked, it results in ischemia of the anterior two-thirds of the spinal cord's area supplied by this artery. This ischemia is the commonest cause of spinal cord infarction, often occurs due to aortic manipulation or dissection. The commonest site is the mid-thoracic level due to the best supplies from the origin from the vertebral artery and the artery of Ademkiewicz near its lower end. It presents itself as an incomplete motor paralysis below the site of the lesion. Also seen is the sensory loss relative to pain and temperature; this is called anterior cord syndrome.[30] It may be more easily recognized if the whole cord is affected, sparing only the dorsal columns.
   2. Posterior cord syndrome: It is a syndrome that develops due to ischemia of the posterior spinal artery, affecting the area of the spinal cord supplied by it. It presents itself with an absence of proprioception and vibration sensation, hypotonia, ataxic gait, positive Romberg sign, and the lack of deep tendon reflexes.[31]
   3. Central cord syndrome: This is a non-vascular injury of the spinal cord, especially seen in a hyperextended neck after a road traffic accident. It is said to be the most common among the incomplete spinal cord injuries. It presents itself with severe sensory and motor function loss in the case of the upper limbs compared with the lower limbs.[32]
4. Development anomalies of the spinal cord:
   1. Spina bifida: It is a developmental anomaly of the vertebrates where the laminae fail to fuse with the spinal process. It is said to be one of the most frequent developmental defects of the neural tube.[33] It is usually seen in the lumbosacral region and is identifiable by a tuft of hairs in this region. No other external visible abnormality is visible.
   2. Meningocele: In this condition, too, laminae fail to cover the spinal cord leading to protruding of arachnoid and pia mater as a cystic swelling in this region covered by skin.
   3. Meningomyelocele: This is an extension of meningocele where the cystic swelling will contain a part of the spinal cord with relevant nerves.
   4. Syringo-myelocele: Further to the above, here we see distension of the central canal.
   5. Rachischisis: It is a condition where the neural tube fails to close or incompletely closed. This anomaly can develop both in the brain and spinal cord. When it affects the brain, it is called anencephalus, and when the spinal cord, then it is myelocele. 
5. Herniation: Herniation of the spinal cord is less frequent and usually misdiagnosed for other conditions.[34]
6. Malignancy: They can present themselves as ependymomas, astrocytomas, and hemangioblastomas. Others include lipomas, lymphomas, germ cell tumors, gangliogliomas, and germinomas.[35] They can also rarely metastases from different parts of the body like breast, bone, etc. 
7. Syringomyelia: It is a condition where there is a fluid-filled cavity within the spinal cord. This condition can be due to a disturbance of CSF flow, an intramedullary tumor, or spinal cord tethering.[36]
8. Subacute combined degeneration: It is a rare condition arising due to the deficiency of vitamin B12. It leads to neurological complications with demyelination of the lateral and dorsal spinal cord.[37] Similar pathological findings can also be found in patients with copper deficiency, zinc excess, or HIV infection with myelopathy.
9. Tabes dorsalis: this is selective pathology affecting only the dorsal columns as a late manifestation of neurosyphilis.
10. Transverse myelitis: this is a condition caused by inflammation of the spinal cord. It presents with variable involvement of all functional modalities at and below the site of inflammation. It can occur by itself as an immune-mediated post-infectious problem. It is also commonly involved by an acute relapse of multiple sclerosis. Other inflammatory diseases may also affect the spinal cord, such as Sjogren disease, Behcet's disease, or neuromyelitis optica spectrum disorder.