Disk Herniation

Etiology

HNP occurs when part or all of the nucleus pulposus protrudes through the annulus fibrosus. The most common cause of disk herniation is degeneration of the nucleus pulposus, which is associated with the progressive dehydration and instability of the disk that occur with age, eventually leading to symptoms. The second most common cause of disk herniation is trauma. Other causes include connective tissue disorders and congenital disorders such as short pedicles.

Disk herniation is most common in the lumbar spine, followed by the cervical spine, due to biomechanical stress in these more flexible areas. Factors associated with the development of lumbar disk herniation with radiculopathy include middle age (eg, 30–50 years), smoking, higher BMI, the presence of cardiovascular risk factors (in women), and a greater cumulative occupational lumbar load from forward bending postures and manual materials handling.[4] Conversely, the thoracic spine has a lower rate of disk herniation.[5][6] 

Epidemiology

The incidence of HNP is 5 to 20 cases per 1000 adults annually, predominantly affecting individuals aged 30 to 50, and the ratio of men to women is approximately 2:1.[7] Patients with heriated lumbar disks represent 1% to 3% of the population, depending on age and sex. According to the Spine Patient Outcomes Research Trial, the average age of onset is 41, and it is more common in men. The most commonly affected disk levels are L4 to L5 and L5 to S1, accounting for approximately 95% of cases in adults between 25 and 55 years old.[8][9] 

Risk factors include obesity, physical and high-stress occupations, as well as medical comorbidities like diabetes, hyperlipidemia, and a history of smoking [Seminars in Spine Surgery. The epidemiology and pathophysiology of lumbar disc herniation. 2016]. Despite the high prevalence of disk herniation, degenerative disk disease is the underlying cause in less than 5% of patients with back pain.[10] Furthermore, not all lumbar back pain results from disk disease; other etiologies include facet-mediated, myofascial, or visceral conditions; compression fractures; and Schmorl nodes.

Pathophysiology

The pathophysiology of disk herniations involves mechanical, degenerative, and biochemical processes. Degeneration of the intervertebral disks with age predisposes them to injuries. Alterations in capillaries, cell morphology, density within the nucleus pulposus (NP), and the formation of small clefts in the annulus fibrosus (AF) begin early in life. The outer layer of the AF, which prevents herniation, begins to degenerate later in life. Herniation occurs when the NP bulges through the AF, affecting portions of the AF and sometimes the cartilaginous endplate.[Semin in Spine Surg. The epidemiology and pathophysiology of lumbar disc herniation. 2016] The disk herniation may also cause Modic endplate changes, which are alterations in the bone marrow of the vertebral endplates, as seen on MRI. Modic changes are categorized as type 1 (associated with inflammation and edema in the vertebral endplate) or type 2 (characterized by changes indicative of fatty degeneration of the bone marrow). Both types contribute to low back pain.[11] 

Most herniations occur posterolaterally at the weaker points of the AF, which lack structural support from the longitudinal ligaments. Herniations at this location increase the likelihood of nerve root compression. This mechanical compression and an inflammatory response involving chemokines such as tumor necrosis factor-α and interleukin-1 contribute to both pain and degeneration. Elevated levels of fibroblast growth factor and other cytokines attract macrophages that resorb the herniated disk material but also contribute to radicular symptoms by chemically irritating the nerve roots. Large herniations exhibit increased nerve irritation and inflammation-induced changes in the nerve roots (edema and myelin changes) due to higher levels of these cytokines, which promote inflammation and disk resorption.[12][13][14][15]

A healthy disk is typically 7 to 10 mm thick and 4 cm in diameter in the lumbar region, with approximately 20 layers of lamellae.[16] In cases of disk degeneration, this height is lost, and the lamellae degenerate, usually posterolaterally along the posterior longitudinal ligament. The outer third of the lamellae is most richly innervated, so herniation in this area causes more neurogenic symptoms. Another pathological factor is the pH of the disk. A healthy mammalian disk pH is usually 7.2; degenerative disks may have a pH as low as 5.2. Patients with abnormal disk pH may have symptoms due to chemical irritation and present with pain contralateral to the herniation.[17]  

Radicular features are present if a posterolateral herniation compromises the lateral foramen or directly compresses a spinal nerve. A disk herniation in the midline or a stenotic region could compress the cauda equina, resulting in myelopathy. A combination of HNP and ligamentum flavum thickening, a congenitally narrowed pedicle (short pedicle syndrome), or narrowing due to autoimmune diseases can compress the spinal cord above the cauda equina, causing myelopathy. If the narrowing is at the level of the conus medullaris, a classic conus medullaris syndrome with symptoms of saddle anesthesia may be present on physical examination. However, rare cases of pure conus medullaris syndrome without cauda equina involvement presenting with isolated bowel and bladder incontinence have been reported.[17]  

Histopathology

The annulus fibrosus is a laminated fibrous ring composed of collagen and other proteins. The nucleus pulposus is a gelatinous substance rich in water and proteoglycans. Histologic changes to the cartilaginous endplate (CE) contribute to the degeneration and herniation of intervertebral disks. Microscopic changes include abnormal cellular clusters, empty lacunae, extensive neovascularization, and apoptotic, necrotic, and senescent cells. Loss of endplate thickness, avulsions, cracks, fissures, loss of normal matrix staining, fibrosis, and calcification are also observed on histologic examination of CEs in symptomatic individuals. Furthermore, pain scores were higher in patients with vascular mimicry, herniation into the CE, the presence of bone tissue in the CE, and traumatic nodes.[18]

In one study, cartilaginous endplates in herniated disks were evaluated and compared with clinical symptoms and postoperative outcomes. The cellular and tissue composition of herniated disks varied across different age groups and correlated with the severity of symptoms. CE abnormalities were observed with increasing age and were more frequently detected in patients with Modic changes on imaging studies (P < .001). A higher proportion of lumbar disk herniation with a 20% or greater occupancy rate (eg, CEs with a greater content of water and other substances) was found in patients younger than 50 (P = .009). These changes were associated with decreased motor strength preoperatively (P = .007). The postoperative visual analog scale score for low back pain was higher in patients with CE abnormalities than those without in patients older than 50 (P < .001). In multiple regression analysis, CE abnormalities were independently associated with residual low back pain at 1 year postoperatively in older patients (β= .46, P < .001). The study also stated that avulsion-type herniations in patients younger than 50 had a higher CE occupancy rate, which was a potential cause of preoperative motor weakness. Clinical outcomes following diskectomy improved regardless of the presence of CE abnormalities; however, cartilaginous herniation in patients aged 50 or older may affect residual low back pain at 1 year.[19] 

Toxicokinetics

Although there is no specific toxin known to directly target intervertebral disks and cause herniation in isolation, nicotine, most heavy metals, and excessive alcohol intake are associated with advanced spinal disk degeneration.[20]

History and Physical

The history and physical examination should focus on screening for "red flag" signs and symptoms.[21] The patient will likely recall an inciting injury, often due to lifting or twisting. Pain is frequently described as sharp or burning, and usually radiates along the distribution of the compressed nerve root (see Image. Dermatomes). Numbness, tingling, and decreased sensation along the path of the nerve root may also occur; in more severe cases, weakness or instability may be present during ambulation.

Cervical Spine

• History
  • The C6 to C7 level of the cervical spine is the most common site of a herniated disk causing radiculopathy (see Image. Cervical Spine, Magnetic Resonance Image). The history should include the chief concern, onset of symptoms, location, and radiating pattern of pain, and any past treatments. 
• Physical examination
  • On physical examination, particular attention should be given to areas of weakness, sensory abnormalities, and the corresponding myotome and dermatome distribution. Red flags or signs of spinal cord dysfunction should also be evaluated. Facet-loading maneuvers can help differentiate between disk pathology and facet pain.

Typical findings of a solitary nerve lesion due to compression by a herniated disk in the cervical spine:

• C5 nerve: Neck, shoulder, and scapular pain; lateral arm numbness; weakness of shoulder abduction, external rotation, elbow flexion, and forearm supination
  • Abnormal biceps and brachioradialis reflexes
• C6 nerve: Neck, shoulder, scapular, lateral arm, forearm, and hand pain; lateral forearm, first and second digit numbness.
  • Weakness of shoulder abduction, external rotation, elbow flexion, forearm supination, and pronation
  • Abnormal biceps and brachioradialis reflexes
• C7 nerve: Neck, shoulder, and third digit pain, numbness of the second, third, fourth, and volar hand
  • Weakness of the elbow and wrist extensors, forearm pronation, and wrist flexion
  • Abnormal triceps reflex
• C8 nerve: Neck, shoulder, and medial forearm pain, numbness of the medial forearm and medial hand
  • Weakness of digit extension, wrist (ulnar) extension, and distal digit flexion, extension, abduction, and adduction
  • Reflexes: Typically not affected
• T1 nerve: Pain in the neck, medial arm, and forearm, with numbness of the anterior and medial forearm
  • Weakness of the first digit abduction; distal finger flexion, abduction, and adduction
  • Reflexes are not typically affected.

Thoracic Spine

Intervertebral disk degeneration may cause diskogenic pain. Thoracic disk lesions most often occur in the lower thoracic spine. Approximately 75% occur below the level of T8, with T11 to T12 the most common.

• History
  • Most thoracic disk herniations are asymptomatic and discovered incidentally on MRI. Unlike lumbar and cervical disk herniations, thoracic disk herniations often present with atypical symptoms and are frequently diagnosed by exclusion.
• Physical examination
  • Patients may have sensory changes. Severe findings include gait disturbances, paralysis, and cardiovascular abnormalities.

Lumbar Spine

• History
  • A herniated lumbar disk typically presents with sensory and motor abnormalities localized to a specific myotome (see Image. Lumbar Spine Disk Herniation, Magnetic Resonance Image). The history should include the chief concern, the onset of symptoms, the location and radiating pattern of pain, and any past treatments.  
• Physical examination
  • A careful neurologic examination may localize the level of compression. The sensory loss, weakness, pain location, and reflex changes associated with the corresponding levels are described below. Facet-loading maneuvers can help differentiate disk herniation from facet joint–mediated pain.

Typical findings of a solitary nerve lesion due to compression by a herniated disk in the lumbar spine

• L1 nerve: Pain and sensory loss in the inguinal region
  • Hip flexion weakness is rare, and the stretch reflex is typically abnormal
• L2-L4 nerves: Back pain radiating to the anterior thigh and medial lower leg; sensory loss of the anterior thigh and sometimes medial lower leg; hip flexion and adduction weakness; knee extension weakness; and decreased patellar reflex
• L5 nerve: Back pain radiating to the buttock, lateral thigh, lateral leg, dorsum of the foot, and hallux; sensory deficit of the lateral lower leg, dorsum of the foot, webspace of first and second digits of the foot; weakness of hip abduction, knee flexion, ankle dorsiflexion, digit of the foot extension and flexion, foot inversion and eversion; decreased semitendinosus/semimembranosus reflex
• S1 nerve: Back pain radiating to the buttock, lateral or posterior thigh, posterior leg, and lateral or plantar foot
  • Sensory deficit of the posterior leg and the lateral or plantar aspect of the foot
  • Weakness of hip extension, knee flexion, plantar flexion, and ankle plantar flexion of the foot
  • Decreased Achilles reflex; severe cases may have weakness of the medial buttock, perineal, and perianal region
  • Urinary and fecal incontinence, sexual dysfunction (may be present)
• S2-S4 nerves: Sacral or buttock pain radiating to the posterior aspect of the leg or the perineum; sensory deficit of the medial buttock, perineal, and perianal region; absent bulbocavernosus and anal wink reflexes

The straight-leg raise test: With the patient lying supine, the clinician slowly elevates the patient's leg with the knee extended. The test result is positive if it reproduces pain and paresthesia in the extended leg (See Image. Straight Leg Test).[22] 

The contralateral (crossed) straight-leg raise test: The clinician elevates the asymptomatic leg with the patient in the supine position. The test result is positive if the maneuver reproduces pain and paresthesia in the extended leg. The test has a specificity of more than 90%. The distribution of radiating pain is usually a diagnostically valuable indicator. However, this finding does not reliably differentiate between L5 and S1 radiculopathy.[23] Notably, disk herniation can affect any level distal to the lesion, and far lateral herniations irritate the nerve root at that level. For example, a disk herniation at L2 to L3 can result in an isolated L5 radiculopathy.[24]

Evaluation

Over 85% of symptoms of acute herniated disks will resolve within 8 to 12 weeks with conservative management. However, patients who have an abnormal neurologic examination or do not improve with conservative therapy will need further evaluation and treatment.[25][26][27]

Imaging Studies

• Radiography: This imaging technique can identify structural instability with flexion-extension views and diagnose anterolisthesis, characterized by a loss of disk height. Radiographs can also provide insight into fractures and endplate changes, although they do not differentiate between Modic types 1 and 2. However, x-rays cannot provide information on nerve compression or disk herniation. A computed tomography or MRI scan is warranted if radiographs show an acute fracture.
• Computed tomography: This imaging is the preferred study for visualizing bony structures in the spine. CT scans can also show calcified herniated disks. Compared to radiography, CT is less accessible in outpatient settings but more readily available than MRIs. Furthermore, CT myelography is a diagnostic alternative for herniated disks in patients with implanted devices incompatible with MRI.
• Magnetic resonance imaging: MRI is the preferred and most sensitive study for visualizing herniated disks. MRI findings can help surgeons and other clinicians plan procedures and evaluate for malignancy, infection, abscess, and Modic endplate changes.

Treatment / Management

Conservative Treatments

Acute cervical and lumbar radiculopathies due to a herniated disk are primarily managed with nonsurgical treatments. Nonsteroidal anti-inflammatory drugs and physical therapy are first-line therapies. However, physical therapy is not recommended at the initial onset of symptoms. Most cases of disk herniation resolve within a few weeks; thus, it is not recommended to start physical therapy until symptoms persist for at least 3 weeks. Patients who do not improve with conservative treatment or have neurologic deficits require timely surgical referral.[28][29][30][31] 

There is limited evidence to support the use of muscle relaxants, such as cyclobenzaprine, or oral corticosteroids.[32] For cases of severe pain unresponsive to over-the-counter pain medication, opioid analgesics may be considered. However, the adverse effects, risks, and benefits of opioids should be discussed with the patient, and they should only be used for a short duration. Moreover, translaminar epidural injections and selective nerve root blocks are second-line modalities after conservative management, and are indicated for patients who have had symptoms for at least 4 to 6 weeks. There is limited evidence on the efficacy of epidural injections beyond 3 months; however, repeat injections may be considered.[33][34](A1)

Interventional Pain Management

Interventional pain management consists of a spectrum of treatments that overlap with minimally invasive spinal procedures. Trigger point injections are initially performed to treat the soft tissue component of pain and avoid the systemic effects of exogenous corticosteroids. More advanced methods, such as epidural corticosteroid injections, are performed via an interlaminar, transforminal (severe unilateral radiculopathy), or caudal approach with or without a caudal-based catheter. These procedures can be performed concurrently with epidural lysis of adhesions (more common in postlaminectomy cases) or on separate occasions, depending on whether the pain is axial or radicular in origin. The decision is also based on physical examination findings and, in some cases, electromyography. 

More advanced procedures, such as the Intracept procedure, treat the sinuvertebral nerves and denervate the vertebral endplates, particularly in patients with Modic endplate changes. A less standard procedure, intradiscal electrothermal annuloplasty, has essentially fallen out of favor. However, this procedure involved placing a radiofrequency ablation catheter into the NP using a lateral discogram approach, allowing it to wrap around the posterior annulus, and performing a thermal denervation. Some clinicians use the same radiofrequency lesion generator for facet medial branch block and radiofrequency ablation, directing the catheter to the lateral vertebral body and ablating the sinuvertebral nerves. Radiofrequency ablation is typically performed after a successful diagnostic block, whether of the facet joint, sinuvertebral nerve, or more peripheral areas.

Several brands of minimally invasive disk decompression devices, such as the Wolfe endoscopic system. This device features a variety of 1- to 3-mm tools, including a channel for a working tool, light, and water flow. Another device, the DeKompressor, is a handheld, self-contained device powered by a 9-V battery and a simple motor that spins a fixed 1 mm Auger inside a 14-gauge needle in the disk. This device operates on the Archimedes screw principle, removing disk material into a clear reservoir. Using a classic diskogram approach, both devices enter the disk unilaterally, but may also be performed bilaterally.[35]

Medication Management

Medication management encompasses a spectrum of options ranging from anti-inflammatory drugs to narcotic analgesics. Nonsteroidal anti-inflammatory drugs may be helpful initially, but they have several complications (such as renal failure). Muscle relaxants may be beneficial, especially at night, for helping to restore the sleep-wake cycle. Membrane stabilizers (such as anticonvulsants and antidepressants) are often helpful for severe pain radiating down the limb, leg, or other dermatome. Membrane stabilizers can also overlap with other membrane stabilizers and help with sleep. Opioid medications can be helpful for severe pain, but are controversial. There are regional, geographic, administrative, legal, regulatory, and opinion differences as to whether opioids should be used for acute low back pain.    

Osteopathic Manipulation

Osteopathic manipulation has been studied extensively for over a century, and is typically performed by specialized osteopathic clinicians. Osteopathic manipulation can reduce the size of the disk herniation, increase function, and decrease pain.[36] (B3)

Surgical Treatments

Surgical treatment is the last resort when managing a disk herniation. Depending on the clinical presentation, surgical procedures for a herniated disk include laminectomies or discectomies. For cervical spine herniations, anterior cervical decompression and fusion may be required. An artificial disk replacement can also be considered. Surgical procedures for the lumbar spine include a lateral or anterior approach for diskectomy and fusion. The benefits of surgical intervention are moderate and tend to decrease over time.[37] (A1)

Differential Diagnosis

The differential diagnoses for a herniated disk include:

• Cardiac angina
• Cauda equina syndrome
• Compression fracture
• Degenerative spinal stenosis
• Diabetic amyotrophy
• Diskal cyst
• Epidural abscess
• Epidural hematoma
• Infectious diskitis=
• Mechanical back pain
• Metastatic disease
• Neurinoma
• Noncardiac angina
• Osteophytes
• Parsonage-Turner syndrome (brachial neuritis)
• Peripheral nerve entrapment
• Posterior annular tear
• Severe length–dependent peripheral neuropathy
• Synovial cyst
• Thoracic outlet syndrome

Many of these conditions can be excluded with MRI and clinical assessment.

Pertinent Studies and Ongoing Trials

Antagonism or Reduction of Local Inflammatory Mediators

Sustained inflammation is the pathophysiological basis for intervertebral disk degeneration. Effective antagonism or reduction of local inflammatory mediators may help regulate the microenvironment and reshape the extracellular matrix of the disk. One novel therapy is an immunomodulatory hydrogel microsphere system, combining cell membrane–coated mimic technology and surface chemical modification methods by grafting neutrophil membrane–coated polylactic-glycolic acid copolymer nanoparticles loaded with transforming growth factor-β1 onto the surface of methacrylic acid gelatin anhydride microspheres via amide bonds. The nanoparticle-microsphere complex, exhibiting excellent cell-like functions, effectively bound to proinflammatory cytokines and enhanced the release of transforming growth factor-β1. The nanoparticle-microsphere complex significantly inhibited lipopolysaccharide-induced inflammation in nucleus pulposus cells in vitro.[38] 

Protein-Rich Plasma

Platelet-rich plasma in the lumbar spine has a low incidence of adverse events compared to similar spinal injection techniques, with well-documented safety profiles. A systematic review on the use of platelet-rich plasma in lower back pain found the level of supporting evidence to be level II. However, this study did not specifically address disk herniation in isolation.[39]

T-box Transcription Factor T Antagonism

One study investigated the role of T-box transcription factor T (Tbxt) in disk degeneration. Knockdown of Tbxt exacerbates H2O2-induced senescence and apoptosis in nucleus pulposus cells, whereas upregulation of Tbxt significantly protects against intervertebral disk diseases in both in vivo and in vitro settings. Mechanistically, Tbxt enhances the transcription of ATG7 in the NP. This upregulation of ATG7 promotes autophagy, ultimately improving intervertebral disk disease. However, the precise mechanism underlying this senescence and apoptosis remains unclear, and further studies are warranted to clarify this understanding.[40] 

Toxicity and Adverse Effect Management

The toxicity and adverse effects of HNP management vary significantly depending on the procedure or intervention. Possible interventions include physical therapy, osteopathic manipulation, trigger point injections, subarachnoid pain pumps, and surgery, each carrying its own risk profile. Few adverse effects occur with basic lumbar exercises and physical therapy. However, many patients have concomitant medical conditions, such as neuropathy, and are at high risk of falls. The risk can be mitigated by an astute therapist using a gait belt to assist the patient with ambulation.

Furthermore, patients require appropriate education and training on using adaptive equipment, such as standard and fold-down seat walkers, to ensure safety. Other issues can occur during therapy, such as cardiac events or pulmonary embolism, which are unlikely to be related to the treatment itself. Still, they can be precipitated by physical stress. Therefore, most physical therapists are certified in basic life support, and automated external defibrillators are nearly ubiquitous in medical settings.  

Interventional procedures or oral corticosteroids can contribute to secondary hyperglycemia. Patients with type 1 diabetes may require sliding scale insulin coverage in addition to their basal insulin regimen; patients with type 2 diabetes usually do not require added insulin therapy if they remain adequately hydrated (hyperglycemia can cause polyuria and dehydration). In addition, edema of the peripheral extremities can occur using oral or injected corticosteroids. There is also a risk of infection associated with interventional procedures, and although rare, complications such as epidural abscess, meningitis, and soft tissue cellulitis can occur.[41][42] Muscle relaxants and opioids can be sedating and precipitate falls, especially in older adults. All patients receiving an opioid should also be prescribed naloxone and receive education on its proper use. Another designated individual should be aware of the location and indications of naloxone. Furthermore, polypharmacy is common in chronic pain management. Clinical trials have not evaluated the safety or efficacy of more than 2 concurrent medications.

Other potential adverse effects can occur during the ablation of the sinuvertebral nerves or intradiscal thermal radiofrequency ablation of the posterior annulus. Although unlikely, significant vascular or neurologic injury can occur. Additionally, interventional procedures in patients with cardiac pacemakers are generally safe. However, the pacemaker may misinterpret the radiofrequency signal as a nonperfusing, shockable rhythm. To prevent the shock, the defibrillation mode can be disabled during the radiofrequency procedure. If a nonperfusing rhythm occurs, the clinician should stop the radiofrequency ablation and commence resuscitation. Clinicians performing interlaminar injections should be familiar with the management of inadvertent spinal block and capable of placing or referring for epidural blood patches. Interventional procedures such as epidural steroid injections, radiofrequency ablations, and spinal cord stimulator placements should be performed in settings equipped to manage emergencies, including access to lipid rescue protocols for bupivacaine or other high-risk local anesthetics. Bupivacaine is avoided in most spinal and disk procedures because of its toxicity and risk, and lidocaine is used more frequently. Please refer to StatPearls' companion resource, "Lipid Emulsion Therapy," for additional information on this local anesthetic systemic toxicity treatment. 

The likelihood of adverse effects depends on the medication(s) and the patient's comorbid conditions. Nonsteroidal anti-inflammatory drugs are generally safe, but can cause renal failure. Muscle relaxants and opioids can increase the risk of falls and sedation. Opioids can also cause respiratory depression, and naloxone should be available for prevention. Membrane stabilizers and benzodiazepines should not be stopped abruptly to avoid withdrawal, and they carry risks of sedation and potential falls. Several of these medications can be addictive, and patients can develop tolerance over time. Before initiating treatment with opioid medications, patients should undergo careful screening for substance use and mental health disorders. Self-medication is an additional concern, as patients may supplement prescribed treatments with alcohol, other medications, or illicit substances. 

Prognosis

The prognosis of herniated disks is variable, but most cases respond to conservative management. Approximately 30% of patients continue to have back pain after one year.[43] Many herniated disks are asymptomatic and are detected incidentally on advanced imaging studies. Of symptomatic cases, 90% resolve after 6 weeks of conservative management. Surgery may lead to a more rapid recovery of the symptomatic herniated disk, but results are similar to conservative management after 1 year.[44][45]

Complications

Herniated disks can lead to chronic back pain. Furthermore, untreated herniation may result in prolonged nerve damage when severe nerve root compression is present. Most surgical repairs and diskectomies are successful, but some cases require repeat intervention. Economically, symptomatic herniated disks can lead to significant lost productivity and disability. Severe complications of surgery or interventional procedures are paralysis and death, although rare.