Physiology, Spinal Cord

Cellular Level

The spinal cord is composed of gray and white matter, appearing in a cross-section as H-shaped gray matter surrounded by white matter. The gray matter consists of the cell bodies of motor and sensory neurons, interneurons, and neuropils (neuroglia cells and mostly unmyelinated axons). In contrast, the white matter is composed of interconnecting fiber tracts, which are primarily myelinated sensory and motor axons. The supports of the gray matter’s “H” make up the right dorsal, right ventral, left dorsal, and left ventral horns.

Of note, the thoracic spinal cord is the only region in which lateral horns are found, which are outpouchings of gray matter containing cell bodies of sympathetic nerves. Running longitudinally through the center of the spinal cord is the central canal, which is continuous with the brain’s ventricles and filled with cerebrospinal fluid (CSF).

The white matter is organized into tracts. Ascending tracts carry information from the sensory receptors to higher levels of the CNS, while descending tracts carry information from the CNS to the periphery. The major tracts and their most defining features are as follows:

Ascending Tracts

• Dorsal column: contains the gracile fasciculus and cuneate fasciculus, which together form the dorsal funiculus. The dorsal column is responsible for pressure and vibration sensation, two-point discrimination, movement sense, and conscious proprioception. The dorsal column decussates at the superior portion of the medulla oblongata and forms the medial lemniscus.[3]  
• Lateral spinothalamic: carries pain and temperature information. The lateral spinothalamic tract decussates at the anterior commissure, two segments above the entry to the spinal cord.[3] 
• Anterior spinothalamic: carries crude touch and pressure information. Its decussation is similar to the lateral spinothalamic tract.[3][4]
• Dorsal and ventral spinocerebellar: transmit unconscious proprioception sensory information to the cerebellum. The ventral spinocerebellar tract does not decussate, while the dorsal spinocerebellar tract decussates twice, making both tracts ipsilateral.[3][5]

 Descending Tracts

• Lateral and anterior corticospinal: involved in conscious control of the skeletal muscle. Most lateral corticospinal tract fibers decussate at the inferior portion of the medulla oblongata. In contrast, the anterior corticospinal tract descends ipsilaterally in the spinal cord and decussates at the segmental level. The lateral corticospinal tract also called the pyramidal tract, innervates the contralateral muscles of the limbs, while the anterior corticospinal tract innervates the proximal muscles of the trunk. 
• Vestibulospinal: carries information from the inner ear to control head positioning and modifies muscle tone to maintain posture and balance. The vestibulospinal tract does not decussate.
• Rubrospinal: involved in the movement of the flexor and extensor muscles. The rubrospinal tract originates from the red nuclei in the midbrain and decussates at the start of its pathway.
• Reticulospinal: originates from the reticular formation housed in the brainstem, and it facilitates, influences, and supplements the corticospinal tract.[6] The reticulospinal tract does not decussate. 

There is a laminar distribution of neurons in the gray matter, characterized by density and topography:

• Lamina I is located at the tip of the dorsal horn and is composed of loosely packed neuropils and neurons of low neuronal density.[7] The most abundant neuron in lamina I is the Waldeyer cell, which is large, fusiform, and has a disk-shaped dendritic domain.[8]
• Lamina II is composed mainly of islet cells with rostrocaudal axes and stalked cells with dorsoventral dendritic trees. Islet cells contain gamma-aminobutyric acid (GABA) and are thought to be inhibitory.
• Lamina III has intermediate size cells, including antenna-like and radial neurons.[7] Many of these cells contain GABA or glycine and are also considered inhibitory.[9]
• Lamina IV contains antenna-like and transverse cells, with dendrites that mainly go to Laminas II and III and whose axons are thought primarily to enter the spinothalamic tract. Lateral from lamina IV is the lateral spinal nucleus, which sends signals to lamina IV from the midbrain and brainstem.[7]
• Lamina V and VI are composed of medium-sized multipolar neurons that can be fusiform or triangular. These neurons communicate with the reticular formation of the brainstem. 
• Lamina VII is composed of homogenous medium-sized multipolar neurons and contains, in individual segments, well-defined nuclei, including the intermediolateral nucleus (T1-L1), which has autonomic functions, and the dorsal nucleus of Clarke (T1-L2), which make up the dorsal spinocerebellar tract.
• Lamina VIII consists of neurons with dorsoventrally polarized dendritic trees.
• Lamina IX has the cell bodies of motor neurons, with dendrites extending dorsally into laminas as far as lamina VI. Lamina IX also contains inhibitory interneurons called Renshaw cells, placed at the medial border of motor nuclei.
• Lamina X is the substantia grisea centralis, the gray matter surrounding the central canal. In the distal portion, lamina X consists of bipolar cells with fan-shaped dendritic trees. In the ventral portion, lamina X consists of bipolar cells with poorly ramified longitudinal dendrites.[10] 

Key Points

• Anterior horn: contains motor nerves
• Posterior horn: contains sensory nerves, particularly those for pain and temperature
• Lateral horn: contains autonomic nerves
• Spinothalamic tract: contains sensory nerves, particularly those for pain, temperature, and light touch
• Medial lemniscus (in the brainstem): contains nerves for vibration and proprioception
• Posterior column (in the spinal cord): contains nerves for vibration and proprioception  
• Corticospinal tract: contains motor nerves

Development

Neurulation begins in the trilaminar embryo when part of the mesoderm differentiates into the notochord. The formation of the notochord signals the overlying ectoderm to form the neural plate, the first structure that will become the nervous system. The neural plate folds in on itself, creating the neural tube, initially open at both ends and ultimately closed. From the neural tube comes the primitive brain and spinal cord.[11] 

The development of the nervous system begins at approximately 17 days of gestational age. In the fifth week of gestation, myotomes start to form, allowing the development of rudimentary reflex circuitries. Myelination of the motor tracts begins in the first few months of life and continues into adolescence.

Interestingly, reciprocal excitation shifts to inhibition between nine and twelve months of age. Before that age, supraspinal descending fibers activate interneurons, resulting in extension or flexion. During this period of development, glycine and GABA are excitatory.[12]

Function

The three primary roles of the spinal cord are to send motor commands from the brain to the body, send sensory information from the body to the brain, and coordinate reflexes. 

The spinal cord is the conduit between the brain and the rest of the body, sending motor commands from the motor cortex to the muscles and sensory information from the afferent fibers to the sensory cortex. In certain instances, the spinal cord can act without signals from the brain, as it can independently coordinate reflexes using reflex arcs. Reflex arcs allow the body to respond to sensory information without waiting for input from the brain. The reflex arc starts with a signal from a sensory receptor, which is carried to the spinal cord via a sensory nerve fiber that synapses on an interneuron and is carried over to the motor neuron, which stimulates an effector muscle or organ.[13] 

The spinal cord also contains central pattern generators, interneurons that form the neural circuits that control rhythmic movements. Although the existence of central pattern generators in humans is controversial, the lumbar spinal cord produces rhythmic muscle activation without volitional motor control or step-specific sensory feedback, suggesting their role in human movement.[14]

Mechanism

Within the human body, there are 33 vertebrae and 31 spinal nerves. 

Vertebrae

• Cervical: 7
• Thoracic: 12
• Lumbar: 5
• Sacrum: 5 (fused)
• Coccyx: 4 (fused)

Spinal Nerves

• Cervical: 8
• Thoracic: 12
• 5 Lumbar: 5
• Sacral: 5
• Coccygeal: 1

Cervical nerves C1-C7 exit above their corresponding vertebrae (e.g., C2 exits above C2 and below C1 vertebrae). C8 exits between C7 and T1. The remainder of the spinal nerves exits below their corresponding vertebrae (e.g., the T1 spinal nerve exits below T1 and above T2.)

Three connective tissue layers, termed meninges, conceal the spinal cord. Directly lining the spinal cord is the pia mater, which also thickens to form the denticulate ligament, anchoring the spinal cord in the middle of the vertebral canal. The next layer of meninges is the arachnoid mater. Between the pia mater and the arachnoid mater is the subarachnoid space, which contains CSF. On top of the arachnoid mater is the last layer of meninges, the dura mater. The epidural space separates the meninges from the vertebral column.[15]

The spinal cord extends caudad from the medulla oblongata of the brain stem at the level of the foramen magnum. In an adult human, the spinal cord gives rise to 31 pairs of spinal nerves, each of which originates from the adjacent spinal cord segment: 

• Cervical nerves (C1-C8): the cervical spinal cord is enlarged because spinal nerves from this area go to the upper extremities, which have more neural input and output.[16] All but the first spinal nerve (C1) pass through the intervertebral foramen of the spinal cord, whereas spinal nerve C1 passes between the occipital bone and vertebrae C1. 
• Thoracic nerves (T1-T12)
• Lumbar nerves (L1-L5): the lumbar spinal cord is enlarged because the lower extremities have more neural input and output.
• Sacral nerves (S1-S5)
• Coccygeal nerve (Co1)

Spinal nerves emerge from the spinal cord as rootlets, which join to form two nerve roots. The anterior nerve roots contain motor fibers extending from the anterior horn to peripheral target organs. The motor neurons are multipolar, with at least two dendrites, a single axon, and one or more collateral branches. They control skeletal muscles and the autonomic nervous system. The posterior nerve roots contain sensory fibers and dorsal root ganglia, transmitting sensory information from the periphery toward the CNS. The sensory neurons located at the dorsal root ganglia are pseudounipolar. The anterior and posterior nerve roots converge into spinal nerves, which split into dorsal and ventral rami.

There are five spinal plexuses, which include sensory and motor nerves from the anterior rami:

• Cervical plexus (C1-C5): the deep branches innervate neck muscles, and the superficial branches innervate the skin on the neck, head, and chest. The cervical plexus also has an autonomic function, including controlling the diaphragm and interactions with the vagus nerve.
• Brachial (C5-T1): controls movement and sensation of the upper extremity.
• Lumbar (L1-L4): controls movement and sensation of the abdominal wall, thigh, and external genitals.
• Sacral (L4, L5, S1-S4): controls movement and sensation of the foot, leg, and thigh.
• Coccygeal (S4, S5, Co): innervates the skin around the tailbone.

In adults, the spinal cord tapers to an end, termed the conus medullaris, at the first or second lumbar vertebra level. Past the conus medullaris, a bundle of spinal roots termed the cauda equina extends until the level of S2.

Myotomes: a muscle or group of muscles supplied by one spinal nerve root.

Clinically, myotomes are helpful in evaluating a patient with a complex nerve injury and determining the pattern of neurological deficit. In testing of myotomes, an injury or lesion may be localized to the correct spinal nerve or trunk level.

• C5: shoulder abduction
• C6: elbow flexion, wrist extension
• C7: elbow extension
• C8: wrist flexion, thumb extension
• T1: finger abduction
• T2-L1: chest wall and abdominal muscles
• L2: hip flexion
• L3: knee extension
• L4: ankle dorsiflexion
• L5: great toe extension
• S1: ankle plantar flexion
• S2: knee flexion

Dermatomes: areas of skin supplied by one spinal nerve root (except cranial nerves V1-V3).

Dermatomes exist for each of the spinal nerves, except for C1. Therefore, testing sensory perception or touch in these areas may be helpful to localize spinal cord lesions to a specific cord level or spinal nerve. Major anatomic landmarks associated with dermatome levels are listed below. Note: Depending on the source, there may be minor variations in dermatome level.

Cervical Dermatomes

• C2: crown of the head, posterior scalp, earlobes, lower jaw
• C3: base of the skull, upper neck
• C4: lower neck, upper shoulders
• C5: clavicle
• C6: thumb
• C7: index finger, middle finger
• C8: little finger, ring finger

Thoracic Dermatomes

• T1: upper chest and back, axilla, upper medial arm
• T2, T3: upper chest and back
• T4: level of nipples
• T6: xiphoid process
• T10: umbilicus

Lumbar Dermatomes

• L1: groin, greater trochanter, lower back
• L2, L3: lower back, hips, anterior and inner thighs
• L3: medial knee
• L4: lower back, anterior thigh, anterior knee, medial calf, medial ankle, medial aspect of the great toe
• L5: lower back, anterior and lateral shin, lateral aspect of the great toe and second-fourth toes, top and bottom of the foot along 2-4 toes 

Sacral Dermatomes

• S1: buttock, posterolateral leg, little toe
• S2: buttock, genitals, posteromedial leg
• S3: buttock, genitals
• S2-S4: perineum
• S5: anus

Related Testing

Electrophysiological Testing

Evoked potentials (EPs) measure electrical signals going to the brain and can determine whether there is motor or somatosensory impairment. The signal is detected by electroencephalography (EEG) or electromyography (EMG). Evoked potentials may be used to assess spinal cord damage in the setting of spinal cord injury and tumors, and measure functional impairment and predict disease progression in multiple sclerosis.[17] Somatosensory evoked potentials (SEPs) and motor evoked potentials (MEPs) are frequently used intra-operatively for monitoring and can be used post-operatively as surrogate endpoints to check muscle strength and sensory status.[18] 

Nerve conduction studies determine whether there has been an injury to a spinal nerve root, peripheral nerve, neuromuscular junction, muscle, cranial nerve, or spinal nerve. They can also be used to pinpoint spinal cord lesions. Nerve conduction studies work by stimulating nerves close to the skin or using a needle placed near a nerve or nerve root. Neurologists often use them with needle electromyograms.[19]

Lumbar Puncture 

A lumbar puncture, or spinal tap, samples the CSF from the subarachnoid space. The needle to obtain the sample should be inserted between lumbar spinal canal levels L3 and L4 to avoid contact with the spinal cord.[20] The CSF is then sent to a laboratory to establish whether any insult can be determined. For instance, a lumbar puncture can confirm or exclude bacterial meningitis, which will produce a cloudy fluid suggestive of a high leukocyte count. It is also essential to know when not to use a lumbar puncture. Contraindications to lumbar puncture include signs of cerebral herniation, focal neurological signs, uncorrected coagulopathies, or cardiorespiratory compromise.[21]

Deep Tendon Testing 

One component of the neurological exam is testing the deep tendon reflexes, which are involuntary motor responses to various stimuli that function via reflex arcs within the spinal cord. They can be used to test the function of the motor and sensory nerves at specific spinal cord levels. Reflex grading is on a scale of 0 (absent reflex) to 5+ (sustained clonus).[22] Some commonly tested reflexes are as follows: 

• Biceps reflex: C5, C6
• Brachioradialis reflex: C6
• Triceps reflex: C7
• Patellar reflex: L2-L4
• Achilles reflex: S1 

Additionally, the Babinski reflex, or the extensor plantar reflex, can be seen in newborns but is an abnormal response after six to twelve months of age. If the Babinski reflex is seen after twelve months of age, it may indicate an abnormality in the corticospinal system.[23]

Romberg Test

• The Romberg test is used in the evaluation of posterior column disease. In this test, a patient stands up with their feet placed together and their eyes open. The test is said to be positive if the patient closes their eyes, eliminating their visual cues, and they sway or fall.[24]

Tuning Fork:

• Vibration sense carried by the dorsal column pathway is tested using a tuning fork. While the patient's eyes are closed, a low-frequency tuning fork is applied to various bony prominences, and the patient is instructed to state when the vibration starts and stops.

Pathophysiology

Spinal Cord Injury

Primary spinal cord injury occurs due to local spine deformation, such as direct compression. Secondary spinal cord injury occurs following primary injury and involves cascades of biochemical and cellular processes, including electrolyte disturbances, free radical damage, edema, ischemia, and inflammation.[25] Secondary spinal cord injury has several phases: acute, subacute, and chronic. During the acute phase (up to 48 hours after the primary injury), hemorrhage and ischemia lead to ion balance disruption, excitotoxicity, and inflammation. During the subacute phase (up to two weeks following primary injury), there is a phagocytic response and a reactive proliferation of astrocytes, which leads to a glial scar in the chronic phase. The thinking is that scarification is the critical component to permanent disability because it prevents axonal regeneration; axons otherwise could regenerate, but their growth is blocked. However, that notion has been challenged, and there are suggestions that astrocyte scar formation could aid in regeneration.[26] The scarification process is complete in the chronic phase (over six months after the primary injury).[27]

Developmental Anomalies

Open neural tube defects occur when there is a failure of the neural tube to close. If the neural tube fails to close at the cranial end, the fetus may develop anencephaly. If the failure is at the caudal end, the fetus may have myelomeningocele or open spina bifida. Craniorachischisis can also occur if the entire neural tube remains open. Closed neural tube defects are skin-covered spinal cord developmental anomalies, such as occult spina bifida. Folic acid supplements may lower the risk of some neural tube defects. However, severe folate deficiency in mouse models has not been shown to lead to neural tube defects unless a genetic predisposition exists. Suggestions are that folate can overcome a genetic predisposition for adverse effects, potentially leading to neural tube defects.[28]

Clinical Significance

A spinal cord injury can be classified as complete or incomplete. A complete injury, based on the International Standard Neurological Classification of Spinal Cord Injury (ISNCSCI) examination, developed by the American Spinal Cord Injury Association (ASIA), implies that there is no sensation at the inferior segments of the spinal cord (S4-S5). No deep anal pressure (DAP) or voluntary anal contraction (VAC) is present. If no perianal sensation is present and DAP and VAC are absent, the present function below the level of injury is a zone of partial preservation.[29]

An injury in the cervical region often results in quadriplegia if both sides of the spinal cord are affected and hemiplegia if only one side is affected. Nerves from C3, C4, and C5 stimulate the phrenic nerve, which controls the diaphragm, so injury to C4 and above may result in a permanent need for a ventilator. An injury to the thoracic region often limits the function of nerves related to the lower torso and lower extremities. Usually, it does not affect the upper torso and upper extremities, except in rare cases such as subacute posttraumatic ascending myelopathy (SPAM).[30] Injury to the spinal cord often causes loss of bowel and bladder control, loss of sexual function, and blood pressure dysregulation, as the spinal cord relays autonomic and somatic information.

Incomplete Spinal Cord Injury and Associated Syndromes

• Central cord syndrome: typically occurs in those who suffer a hyperextension injury (i.e., a car accident), leading to upper extremity weakness and urinary retention.[31]
• Posterior cord syndrome: a lesion of the posterior spinal cord leading to loss of proprioception and vibration, hypotonia, decreased deep tendon reflexes, a positive Romberg sign, and an ataxic gait.[32]
• Anterior cord syndrome: caused by a compromised blood supply to the anterior 2/3 of the spinal cord, affecting the spinothalamic and corticospinal tracts, causing motor paralysis below the level of the injury and loss of pain and temperature at and below the level of the injury.[33] Light touch and proprioception are spared.
• Brown-Séquard syndrome: hemisection of the spinal cord leading to ipsilateral weakness and paralysis and contralateral loss of pain and temperature.[34]
• Conus medullaris syndrome: caused by compression of the spinal cord at T12-L2, which leads to sudden, bilateral back pain, symmetrical and bilateral perianal numbness, fasciculations, urinary retention, and impotence.[35]
• Cauda equina syndrome: caused by injury to the nerve roots of L2-S4. Typically, cauda equina syndrome is gradual and unilateral, with more severe radicular pain and less severe back pain than conus medullaris syndrome. Compression of these nerve roots can lead to numbness of the inner thigh (saddle anesthesia), asymmetric areflexic paraplegia, and atrophy.[36]

Complete Spinal Cord Injury

A complete spinal cord injury leads to the loss of all motor and sensory functions below the level of injury or lesion.