Radiculopathy and Myelopathy

Radiculopathy and myelopathy represent two distinct patterns of spinal cord and nerve root pathology with critical differences in pathophysiology, presentation, and prognosis. Radiculopathy results from compression or irritation of a single spinal nerve root, causing radiating pain and dermatomal neurological deficits, while myelopathy reflects spinal cord dysfunction affecting multiple levels and producing bilateral signs, weakness below the lesion, and bladder/bowel involvement. Together, these conditions represent common causes of neurological disability, with cervical and lumbar radiculopathy affecting 3-5% of the general population and symptomatic cervical myelopathy affecting approximately 4-5 per 100,000 individuals annually. These entities are critical for board examination preparation as they frequently present in primary care and emergency settings, require systematic diagnostic algorithms to prevent misdiagnosis, and demand prompt recognition of surgical emergencies such as cauda equina syndrome. Understanding the distinction between radiculopathy and myelopathy is essential because treatment approaches, prognosis, and indications for surgical intervention differ fundamentally between the two conditions.

The pathophysiological mechanisms underlying radiculopathy and myelopathy diverge fundamentally based on whether a single nerve root or the spinal cord parenchyma is primarily affected, though these conditions may coexist (myeloradiculopathy).

When spinal nerve roots become compressed—most commonly by intervertebral disc herniation, facet hypertrophy, or stenosis—mechanical pressure initiates a complex inflammatory cascade. The initial mechanical compression reduces blood flow to the nerve root, creating a hypoxic microenvironment that triggers release of damage-associated molecular patterns (DAMPs) from compressed neurons. Herniated disc material itself contains proteoglycans and phospholipids that activate toll-like receptors (TLRs) on resident immune cells, particularly microglia-equivalent cells surrounding nerve roots. This activates NF-κB signaling pathways, leading to production of pro-inflammatory cytokines including TNF-α, IL-6, and IL-8. These cytokines increase vascular permeability, allowing infiltration of macrophages and neutrophils, which further amplify cytokine production in a feed-forward loop. Simultaneously, mechanical compression triggers opening of acid-sensing ion channels (ASICs) and transient receptor potential (TRP) channels on sensory nerve fibers, which are pH-sensitive and respond to the acidic microenvironment created by inflammatory cells and ischemia. This explains why radicular pain often exceeds what pure mechanical compression alone would predict, and why anti-inflammatory treatments (not just decompression) provide symptomatic relief. The compressed nerve root exhibits segmental demyelination at the site of compression, with preserved axons initially, allowing recovery potential if compression is relieved before chronic axonal loss occurs.

Myelopathy results from spinal cord parenchymal injury, with ischemia being the critical final common pathway. When chronic compression (most commonly from cervical spondylosis, stenosis, or ossification of the posterior longitudinal ligament) affects the spinal cord, two ischemic mechanisms operate simultaneously. First, direct mechanical compression reduces blood flow through capillaries within the cord parenchyma, particularly affecting the gray matter which is metabolically more active than white matter. Second, repetitive microtrauma from cord movement against stenotic structures during neck flexion/extension causes tethering injuries that disrupt the microvasculature. Chronic ischemia induces a shift from aerobic to anaerobic metabolism, depleting ATP stores. This ATP depletion impairs function of Na⁺/K⁺-ATPase pumps, leading to failure of the sodium-glutamate antiporter, which normally clears excitatory glutamate from synaptic spaces. Glutamate then accumulates to toxic concentrations, hyperactivating NMDA and AMPA receptors on target neurons. This triggers massive calcium influx into neurons, activating proteases, phospholipases, and mitochondrial dysfunction, ultimately leading to neuronal death. Chronic ischemia also activates astrocytes and microglial cells, which release additional cytokines and reactive oxygen species (ROS), perpetuating the excitotoxic cascade. Diffusion tensor imaging (DTI) studies demonstrate that this process creates areas of reduced axial diffusivity, indicating axonal loss, and increased radial diffusivity, indicating demyelination. Critically, prolonged ischemia leads to irreversible cord atrophy and neuronal loss, explaining why outcomes worsen significantly with duration of symptoms before decompression.

Both radiculopathy and myelopathy involve secondary injury mechanisms that extend damage beyond the initial insult. In radiculopathy, repeated episodes of compression-decompression create a cycle of ischemia-reperfusion injury. During reperfusion, NADPH oxidase activation generates superoxide radicals that damage axonal membranes and mitochondria. In myelopathy, chronic ischemia induces abnormal angiogenesis with immature, leaky vessels that contribute to vasogenic edema (fluid in extracellular space). This edema further increases interstitial pressure, creating a vicious cycle of worsening ischemia. Additionally, hemosiderin deposition from microhemorrhages creates iron-catalyzed free radical generation via Fenton chemistry, causing lipid peroxidation of myelin sheaths. Diffusion-weighted imaging (DWI) hyperintensity in the cord indicates this acute edema and predicts reversibility, while T2-weighted hyperintensity without DWI changes suggests chronic gliosis and permanent injury.

Chronic nerve root compression triggers upregulation of pain neurotransmitter systems, including increased expression of substance P and calcitonin gene-related peptide (CGRP) in dorsal root ganglia neurons. This peripheral sensitization lowers the threshold for firing, explaining why radicular pain may persist even after adequate mechanical decompression if sufficient time has elapsed. In myelopathy, chronic ischemia induces sprouting of intact axons attempting to bypass damaged pathways, but this reorganization is often maladaptive, with crossing fibers creating abnormal connectivity that produces hyperreflexia and spasticity characteristic of cord injury.

Disc herniation accounts for approximately 90% of lumbar radiculopathy and 60% of cervical radiculopathy cases. The intervertebral disc comprises an outer annulus fibrosus (concentric collagen fibers) and inner nucleus pulposus (hydrophilic proteoglycans). With aging, proteoglycan content decreases, reducing turgor and elasticity. Combined with repetitive loading (especially flexion), the nucleus pulposus protrudes through annular tears, potentially contacting and compressing adjacent nerve roots. Mechanical herniations cause radiculopathy through direct compression and secondary inflammatory activation (as described above). Risk factors include age (peak incidence 30-50 years), male predominance (1.5-2:1), smoking (impairs disc nutrition via reduced blood flow), obesity, occupations involving heavy lifting or vibration, and genetic predisposition (twin studies show 60-70% heritability). In the lumbar spine, L4-L5 and L5-S1 disc herniations are most common; in the cervical spine, C6-C7 and C5-C6 are most frequent. Notably, imaging studies demonstrate that disc herniations are extremely common in asymptomatic individuals (25-60% of asymptomatic adults have herniated discs on MRI), emphasizing that imaging findings must correlate with clinical presentation.

Spinal stenosis, defined as narrowing of the spinal canal, nerve root canals, or lateral recesses, causes radiculopathy and myelopathy through both mechanical compression and secondary inflammation. Degenerative stenosis (most common type) results from osteoarthritis of facet joints, osteophyte formation, disc bulging, and hypertrophic ligamentum flavum, typically occurring after age 60. The cervical spine is vulnerable because it normally has the smallest canal diameter (diameter <13 mm considered stenotic); any stenosis can cause myelopathy given the large cross-sectional area occupied by the spinal cord (70% of canal volume in cervical region versus 30% in lumbar region). Congenital stenosis from developmental narrowness of the spinal canal predisposes to symptomatic compression at lower degrees of degenerative change. Lumbar stenosis classically produces neurogenic claudication (leg pain with walking that improves with sitting/forward flexion), distinct from vascular claudication (improves with rest alone). Stenosis is often multi-level; involvement of both central canal and lateral recesses predicts worse outcomes. Canal diameter <10 mm (cervical) or <100 mm² cross-sectional area (lumbar) indicates severe stenosis.

Cervical spondylosis (cervical osteoarthritis) is the most common cause of myelopathy in patients over age 55, resulting from disc degeneration, osteophyte formation, and facet arthropathy. Uncinate process osteophytes are particularly significant in the cervical spine because they can directly compress nerve roots in the lateral gutters. OPLL, common in Asian populations (prevalence 2-4% in Japan versus <1% in Western populations), represents ossification of the posterior longitudinal ligament, a structure normally composed of fibroligamentous tissue. Genetic factors contribute (familial clustering in 7-15% of cases, associated with HLA-B27 in some studies), but the molecular triggers remain incompletely understood; proposed mechanisms include altered osteoblast differentiation favoring ossification and altered bone morphogenetic protein (BMP) signaling. OPLL can be segmental (localized) or continuous (spanning multiple levels); continuous-type OPLL causes more severe myelopathy because it leaves no decompression zone.

Acute trauma causes both radiculopathy and myelopathy through different mechanisms. Nerve root avulsion (traumatic separation from spinal cord) occurs in brachial plexus injuries and produces radiculopathy with loss of sensory action potentials on electromyography (indicating preganglionic injury). Traumatic spinal cord injury (TSCI) results from contusion, laceration, or compression; the pathophysiology progresses from primary mechanical injury (immediate axonal shearing) to secondary injury cascades over hours to days (hemorrhage, edema, inflammation, ischemia). Vertebral fractures, particularly fracture-dislocations or unstable burst fractures, often accompany TSCI. Risk factors include high-velocity motor vehicle accidents, falls from height (especially in elderly), and diving into shallow water.

Discitis (intervertebral disc space infection) from bacteria (especially Staphylococcus aureus, including MRSA) or tuberculosis can erode endplates and cause inflammation-related radiculopathy or myelopathy. Spinal epidural abscess presents with radiculopathy or myelopathy depending on location and can progress to spinal cord infarction if untreated. Meningitis or arachnoiditis (inflammation of arachnoid mater) causes myelopathy through inflammatory swelling of the cord and tethering. Post-infectious arachnoiditis can result from bacterial or tuberculous meningitis and causes chronic myelopathy with adhesions. Demyelinating diseases including multiple sclerosis cause transverse myelitis (TM) presenting as acute myelopathy, while MS can also cause radiculopathy through internodal demyelination.

Copper deficiency causes myelopathy through impaired myelination (copper required for cytochrome c oxidase, involved in myelin formation) and manifests as posterior column syndrome; associated with malabsorption, parenteral nutrition, and excessive zinc supplementation (which inhibits copper absorption). Vitamin B12 deficiency causes subacute combined degeneration (SCD) affecting dorsal root ganglia and both dorsal and lateral columns, producing paresthesias, gait disturbance, and cognitive changes; pernicious anemia (autoimmune intrinsic factor antibodies) is the most common cause in developed countries. Lathyrism (neurolathyrism) from consumption of Lathyrus peas causes chronic myelopathy through β-N-oxalyl-L-α,β-diaminopropionic acid (β-ODAP) toxin. Nitrous oxide abuse causes myelopathy through inactivation of methionine synthase, creating functional B12 deficiency.

Tumors cause radiculopathy and myelopathy through mechanical compression, invasion, or inflammation. Intradural extramedullary tumors (meningiomas, schwannomas/neuromas, and neurofibromas) compress the spinal cord and nerve roots; schwannomas cause progressive radiculopathy through root compression. Intramedullary tumors (ependymomas, hemangioblastomas, syrinx-associated tumors) destroy spinal cord parenchyma directly, causing myelopathy. Extradural metastases from breast, lung, prostate, and lymphoma are most common; can cause epidural spinal cord compression (ESCC), a true emergency. Paraneoplastic myelopathy occurs via immune-mediated mechanisms in lung cancer and other malignancies.

Spinal cord infarction (anterior spinal artery syndrome most common) causes acute myelopathy; etiologies include aortic dissection, aortic surgery, hypotension, arterial thrombosis, or arteriovenous malformations (AVMs). Spinal arteriovenous malformations (dural, intradural, or intramedullary) cause progressive myelopathy through venous hypertension and chronic ischemia. Spinal dural arteriovenous fistula (most common type of spinal AVM) presents with progressive lower extremity weakness and sensory loss.

Tethered spinal cord from filum terminale thickening, lipoma, or syrinx causes progressive myelopathy, particularly with flexion. Chiari malformation (cerebellar herniation through foramen magnum) causes myelopathy through cord compression and syrinx formation. Syringomyelia (cavity formation within spinal cord) from various causes (post-traumatic, Chiari, tethering, tumor-associated, idiopathic) causes progressive myelopathy with distinctive suspended sensory loss pattern (loss of pain/temperature in cape-like distribution).

The hallmark presentation of radiculopathy is radiating pain in a dermatomal distribution corresponding to the affected nerve root. The pain typically originates in the neck or low back and radiates distally into the arm (cervical radiculopathy) or leg (lumbar radiculopathy), often with a sharp, burning, or electric quality. The pain is often triggered or worsened by movements that compress the nerve root (e.g., neck extension and ipsilateral rotation for cervical radiculopathy, forward flexion for some lumbar radiculopathy cases). Patients frequently adopt postural changes to minimize nerve root compression; cervical radiculopathy patients may tilt the head toward the affected side and support the arm, while lumbar radiculopathy patients may list away from the affected side. The pain distribution aids localization: C5 radiculopathy produces lateral arm pain; C6 radiculopathy, lateral forearm and thumb; C7 radiculopathy, dorsal hand and middle finger; C8 radiculopathy, medial arm and small finger; L5 radiculopathy, lateral leg and dorsum of foot; S1 radiculopathy, posterior and lateral leg. Importantly, radiculopathy typically presents with unilateral symptoms, and bilateral or midline presentation should raise suspicion for myelopathy or cauda equina syndrome rather than simple radiculopathy.

Dermatomal sensory loss (in the distribution of the compressed nerve root) is characteristic, though it may be subtle early or inconsistently present. Weakness, when present in radiculopathy, is myotomal (affecting muscles innervated by that root) rather than pattern-based (e.g., hemiparesis). Cervical radiculopathy weakness patterns include: C5 (shoulder abduction weakness—supraspinatus/deltoid innerv

Contraindicated: spinal manipulation in the presence of cord compression, myelopathy, or instability; conservative-only management of cauda equina; routine high-dose methylprednisolone in acute traumatic spinal cord injury, which AANS/CNS guidance does not support as standard care.