Tetraplegia
Tetraplegia, also known as quadriplegia, is a severe form of paralysis resulting from damage to the cervical spinal cord, affecting all four limbs, the trunk, and often pelvic organs, leading to loss of motor function, sensation, and other bodily controls below the level of injury.[1][2] This condition typically arises from spinal cord injuries (SCI) at vertebral levels C1 through T1, where the injury disrupts nerve signals between the brain and body, with higher-level injuries (closer to the skull) causing more extensive impairment, including potential respiratory failure.[3] The primary causes of tetraplegia are traumatic, such as motor vehicle accidents, falls (especially in those over 65), acts of violence, and sports or recreational injuries, while non-traumatic etiologies include degenerative conditions like arthritis, infections, tumors, or disk herniation.[2][4] Globally, over 15 million people live with SCI as of 2024, with cervical injuries—which cause tetraplegia—accounting for approximately 50–60% of cases and disproportionately impacting males (about 78% of new cases since 2015).[4][5] Risk factors include ages 16–30 or over 65, alcohol or substance use (in about 25% of traumatic cases), and underlying conditions like osteoporosis.[2] Symptoms of tetraplegia vary by injury completeness and level but commonly include total or partial loss of voluntary movement and sensation in the arms, hands, legs, and torso; impaired bowel and bladder control; sexual dysfunction; chronic pain or neuropathic sensations; and, in high cervical injuries, difficulty breathing or speaking due to weakened diaphragm and intercostal muscles.[2][3] Complications can encompass autonomic dysreflexia, pressure ulcers, spasticity, respiratory infections, cardiovascular issues, and secondary psychological effects like depression, with the first year post-injury carrying the highest mortality risk from such conditions.[4][6] Treatment focuses on acute stabilization to prevent further damage, followed by multidisciplinary rehabilitation to maximize independence, including medications for pain and spasticity, surgical interventions like decompression or stabilization, assistive devices (e.g., wheelchairs, ventilators), and therapies for physical, occupational, and psychological support.[7][8] While no cure exists for the underlying nerve damage, ongoing research into regenerative therapies, such as stem cells and neural prosthetics, offers hope for improved outcomes.[8]Definition and Terminology
Definition and Scope
Tetraplegia, also known as quadriplegia, is defined as paralysis affecting all four limbs and the trunk due to damage to the cervical spinal cord (neurological levels C1 through C8), resulting in partial or complete loss of motor and sensory function below the level of injury.[9] This condition impairs voluntary movement and sensation in the arms, hands, legs, trunk, and often pelvic organs, distinguishing it from other forms of paralysis by its comprehensive impact on the upper and lower body.[2] The term "tetraplegia" derives from the Greek roots "tetra," meaning four, and "plegia," meaning stroke or paralysis, emphasizing the involvement of all four extremities.[10] In clinical practice, the severity of tetraplegia varies based on the specific cervical spinal cord level affected, with injuries at higher levels (C1-C4) often leading to profound impairments including respiratory compromise due to diaphragmatic involvement, while lower cervical injuries (C5-C8) may preserve some arm and hand function, such as elbow flexion or finger grasp.[1] These variations relate to the neurological levels of spinal cord injury, where function diminishes progressively from the site of damage.[11] Tetraplegia is differentiated from paraplegia, which involves paralysis limited to the lower limbs and trunk resulting from injuries below T1, typically in the thoracic or lumbar regions, thereby sparing upper body motor control.[1] This distinction underscores tetraplegia's broader scope, encompassing both upper and lower body deficits and necessitating comprehensive management of associated dependencies.[6]Historical and Terminological Notes
The term "quadriplegia" was coined in 1895 as a medical descriptor for paralysis affecting both arms and legs, derived from the Latin "quadri-" meaning four and the Greek "-plegia" meaning stroke or paralysis, marking a shift from earlier phrases like "cervical paraplegia" used in the 19th century to denote similar upper-body impairments from spinal damage.[12] This hybrid etymology reflected the evolving nomenclature in neurology during an era when spinal cord injuries were increasingly documented, though systematic care for such conditions remained limited until the mid-20th century. The term gained widespread adoption in clinical contexts following World War II, particularly through the pioneering efforts of Sir Ludwig Guttmann, who established the UK's first specialized spinal injuries unit at Stoke Mandeville Hospital in 1944 and emphasized comprehensive rehabilitation in the post-World War II era.[13] By the late 20th century, "quadriplegia" faced criticism for its mixed linguistic roots and implication of four identical limbs, which inaccurately described human anatomy where upper and lower extremities differ structurally. In response, the American Spinal Injury Association (ASIA) and the International Spinal Cord Society (ISCoS) promoted "tetraplegia"—a purely Greek term from "tetra-" meaning four and "-plegia"—to enhance terminological precision and align with the anatomical reality that affected limbs function as part of a tetrapod (four-limbed) vertebrate structure. This preference aimed to reduce confusion in international medical literature and avoid the pejorative or imprecise connotations of "quadriplegia," such as equating human arms and legs.[14] Key milestones in this terminological evolution include the 1992 revision of the International Standards for Neurological Classification of Spinal Cord Injury, where ASIA, with ISCoS endorsement, first recommended "tetraplegia" over "quadriplegia" for its anatomical and etymological superiority. This was further standardized in the 1997 publication of the International Standards for Neurological and Functional Classification of Spinal Cord Injury by Maynard et al., which formalized "tetraplegia" in global guidelines for assessing and reporting spinal cord impairments, influencing subsequent editions and modern usage. Today, while "quadriplegia" persists as a synonym especially in North American contexts, "tetraplegia" predominates in peer-reviewed literature to promote clarity and consistency.Anatomy and Pathophysiology
Cervical Spinal Cord Anatomy
The cervical spinal cord consists of eight segments (C1-C8), corresponding to the seven cervical vertebrae (C1-C7) that form the skeletal framework of the neck. These vertebrae, including the unique atlas (C1) and axis (C2), encase the spinal cord within the vertebral canal, providing protection while allowing flexibility for head and neck movement. The cervical region features an enlargement of the spinal cord to support the extensive innervation of the upper limbs. Gray matter in the cervical cord is arranged in an H-shaped cross-section, with ventral horns housing alpha motor neurons for skeletal muscle control, dorsal horns processing sensory input, and an intermediate zone for interneurons facilitating reflexes. Surrounding white matter is divided into anterior, lateral, and posterior funiculi, containing myelinated axons that conduct impulses at high speeds for efficient signal relay.[15][16][17] Each cervical segment produces a pair of spinal nerves (C1-C8) via the convergence of dorsal (sensory) and ventral (motor) roots within the intervertebral foramina. The C1-C7 nerves exit superior to their respective vertebrae, while C8 emerges between C7 and T1, enabling precise branching to target tissues. These nerves define specific myotomes and dermatomes: for instance, the C5 myotome governs deltoid and biceps contraction for shoulder abduction and elbow flexion, while its dermatome covers the lateral upper arm; C6 handles wrist extension and sensation along the thumb side of the forearm; C7 controls triceps extension and middle finger sensation; and C8 manages finger flexion with pinky-side innervation. The anterior rami of C3-C5 form the phrenic nerve, which innervates the diaphragm for essential respiratory function, highlighting the cervical cord's critical role in vital processes.[18][15][17] Major white matter tracts in the cervical cord include the lateral corticospinal tract, which descends from the motor cortex after decussating in the medullary pyramids to mediate voluntary skilled movements of the upper body, synapsing in the ventral horn's laminae VII-IX. The anterolateral spinothalamic tract ascends contralateral to its origin, conveying pain and temperature sensations from the upper extremities after crossing in the anterior white commissure shortly after dorsal root entry. The cervical cord integrates seamlessly with the brainstem at the foramen magnum, where descending pathways from higher centers coordinate with local circuits for neck stabilization and upper limb dexterity via the brachial plexus (C5-T1).[16][15][19][20] In normal physiology, descending signals propagate unidirectionally through white matter tracts to excite ventral horn motor neurons, which relay impulses via peripheral nerves to effectors, while ascending sensory volleys travel through dorsal roots and tracts to thalamic relays for conscious perception, ensuring bidirectional brain-periphery communication.[16][15][19]Injury Mechanisms and Pathophysiology
The primary injury in tetraplegia occurs due to mechanical forces applied to the cervical spinal cord, resulting in immediate tissue disruption through mechanisms such as compression, laceration, or transection of axons and supporting structures.[6] Compression often arises from displaced vertebral elements or hematoma, leading to focal deformation of neural tissue, while laceration involves shearing by bone fragments or foreign objects, and transection severs continuity across the cord.[6] These events directly impair neuronal integrity at the injury site, typically in the C1-C8 segments, initiating irreversible loss of function in motor, sensory, and autonomic pathways below the lesion.[21] Secondary injury cascades commence within minutes of the primary insult and evolve over hours to months, exacerbating damage through interconnected biochemical processes. Ischemia results from vascular compression or thrombosis, reducing blood flow and causing hypoxic cell death in the penumbra surrounding the core lesion.[6] Inflammation is triggered by the release of pro-inflammatory cytokines such as TNF-α and IL-1β from activated microglia and infiltrating neutrophils, peaking in the acute phase (first 24-72 hours) and persisting subacutely with macrophage involvement.[21] Excitotoxicity stems from glutamate overload, activating NMDA receptors and causing excessive calcium influx that damages neurons and oligodendrocytes.[6] Oxidative stress arises from reactive oxygen species generated by disrupted mitochondria and enzymatic pathways, leading to lipid peroxidation and protein oxidation.[21] Apoptosis, mediated by caspase activation, contributes to delayed neuronal and glial loss, extending from days to weeks post-injury.[6] The timeline delineates acute events (minutes to days: ischemia, excitotoxicity, initial edema), subacute progression (days to weeks: peak inflammation, apoptosis), and chronic remodeling (months: ongoing oxidative damage and scar maturation).[21] Pathophysiological outcomes include Wallerian degeneration, where distal axons and myelin sheaths disintegrate due to disconnection from their cell bodies, becoming visible on MRI as hyperintense signals in tracts like the corticospinal and dorsal columns within 10-14 weeks.[22] This process begins histologically within 8 days, leading to tract atrophy and functional deficits correlated with impaired evoked potentials.[22] Syringomyelia develops as a fluid-filled cyst (syrinx) within the cord, driven by subarachnoid scarring that alters cerebrospinal fluid dynamics, allowing influx into perivascular spaces and grey matter coalescence, with symptoms often emerging months to years post-injury (mean 9-15 years to diagnosis).[23] In adults, neuroplasticity is constrained by a hostile microenvironment featuring inhibitory molecules like chondroitin sulfate proteoglycans and Nogo-A, glial scar barriers, and reduced regenerative factor expression, limiting axonal sprouting and circuit remodeling compared to developing nervous systems.[24]Etiology
Traumatic Causes
Traumatic causes account for the majority of tetraplegia cases, with approximately 60% of traumatic spinal cord injuries (tSCI) occurring at the cervical level, leading to tetraplegia.[25] In the United States, the primary etiologies include motor vehicle collisions, which comprise about 38% of tSCI cases since 2015, often involving high-speed impacts that target the cervical spine through mechanisms like whiplash-induced hyperextension or hyperflexion.[25] Falls represent around 32% of cases, frequently resulting from household accidents or elevated drops that cause axial loading on the neck.[25] Sports and recreational activities contribute to roughly 8% of tSCI, with diving accidents being a notable example where head-first entry into shallow water leads to forceful axial compression of the cervical vertebrae.[25] Acts of violence, accounting for about 15% of cases, typically involve penetrating injuries such as gunshot or stab wounds to the neck, disrupting the spinal cord directly.[25] These etiologies often result in injury through biomechanical forces including hyperflexion (forward bending beyond normal limits), hyperextension (rearward bending), axial loading (vertical compression), or rotational shear, which fracture or dislocate cervical vertebrae and compress or transect the cord.[26] Age-specific risks highlight varying patterns: motor vehicle collisions and sports injuries predominate in young adults aged 16-30, driven by higher exposure to high-risk activities, while falls are the leading cause in individuals over 65, often due to reduced balance and osteoporosis increasing vertebral fragility.[2][27] Overall, traumatic tetraplegia disproportionately affects males, comprising 78% of new cases since 2015.[25]Non-Traumatic Causes
Non-traumatic causes of tetraplegia encompass a range of endogenous medical conditions that damage or compress the cervical spinal cord, distinct from external mechanical forces. Non-traumatic causes account for a significant and variable proportion of SCI cases, estimated at 20-50% globally depending on region and income level, with higher rates in high-income countries; traumatic injuries comprise the majority in low- and middle-income countries.[4][28] Unlike traumatic injuries, non-traumatic tetraplegia often presents with subacute or progressive onset, though acute presentations occur in vascular or infectious cases, and degenerative causes predominate in older adults.[29] Neoplastic conditions, including intramedullary and extramedullary tumors, represent 15-30% of non-traumatic spinal cord injuries in various studies. These tumors, such as ependymomas, astrocytomas, or metastatic lesions, typically cause progressive compression of the spinal cord, resulting in gradual motor and sensory deficits over weeks to months. Spinal metastases, often from primary cancers like lymphoma or multiple myeloma, are a common subtype in this category.[30][31] Infectious etiologies, such as epidural abscesses or transverse myelitis, contribute to acute or subacute tetraplegia through inflammation or direct cord invasion. These conditions often arise from bacterial, viral, or parasitic sources and can lead to rapid neurological deterioration if untreated, though they account for a smaller proportion compared to neoplastic or degenerative causes in high-income settings.[2][32] Degenerative disorders, particularly cervical spondylosis, are a leading cause, accounting for 20-50% of non-traumatic cases depending on the region and study, with higher proportions (up to 54%) in high-income countries and especially prevalent among individuals over 60 years old. This condition involves age-related wear on the cervical spine, leading to stenosis, disc herniation, or osteophyte formation that progressively compresses the spinal cord, often manifesting as insidious weakness and spasticity in all four limbs.[33][34] Vascular events, including spinal cord infarcts or arteriovenous malformations (AVMs), cause acute tetraplegia through ischemia or hemorrhage, typically in middle-aged or older adults with risk factors like hypertension or atherosclerosis. These represent a significant but variable proportion of cases, emphasizing the role of disrupted blood supply in cord dysfunction.[35][32] Inflammatory and autoimmune diseases, such as multiple sclerosis (MS) or Guillain-Barré syndrome (GBS), can result in tetraplegia via demyelination or immune-mediated attack on the spinal cord. MS often leads to progressive or relapsing-remitting patterns affecting the cervical region, while GBS presents acutely with ascending paralysis that may involve the upper limbs; these etiologies highlight immune dysregulation as a key mechanism.[2][31]Clinical Features
Motor and Sensory Impairments
Tetraplegia, resulting from damage to the cervical spinal cord, leads to significant motor and sensory deficits that impair function in the arms, trunk, legs, and pelvic organs below the level of injury. These impairments arise from disruption of descending motor pathways, such as the corticospinal tracts, and ascending sensory pathways in the spinal cord. In complete injuries, there is total loss of voluntary motor control and sensation below the lesion, while incomplete injuries may preserve partial function. Motor impairments in tetraplegia initially manifest as flaccid paralysis during the acute phase of spinal shock, characterized by areflexia and hypotonia due to temporary loss of descending inhibitory influences on spinal reflexes. This phase typically resolves within days to weeks, giving way to spasticity, where hypertonia and exaggerated reflexes emerge from unopposed spinal reflex activity. The specific motor deficits vary by the neurological level of injury, determined by the most caudal segment with intact innervation:- C1-C3 injuries: Complete paralysis of all four limbs and trunk, with no diaphragmatic function (phrenic nerve at C3-C5), necessitating permanent mechanical ventilation; patients retain only head and neck movement.
- C4 injuries: Partial shoulder elevation and diaphragmatic breathing possible, but no arm or hand function, leading to total dependence for mobility.
- C5 injuries: Preservation of shoulder abduction and elbow flexion (biceps), allowing limited arm positioning but no wrist or hand control.
- C6 injuries: Addition of wrist extension, enabling tenodesis grasp for basic hand function, such as holding objects.
- C7-C8 injuries: Elbow extension (triceps at C7) and finger flexion/extension (C8), permitting improved grasp and some independence in activities like self-feeding.
Autonomic and Other Symptoms
Autonomic dysfunction is a hallmark of tetraplegia due to disruption of supraspinal control over the autonomic nervous system, leading to sympathetic blunting and parasympathetic dominance below the level of injury.[36] This manifests prominently in cardiovascular instability, such as orthostatic hypotension, where systolic blood pressure drops by at least 20 mmHg upon postural change, affecting up to 74% of individuals with tetraplegia and exacerbating risks during mobility transitions.[37] Temperature dysregulation is also common, with impaired sweating and vasodilation causing hypothermia or heat intolerance, particularly in high cervical lesions where thermoregulatory efferents are compromised.[38] Neurogenic bowel and bladder dysfunction further complicates daily management, resulting in incontinence, constipation, or retention due to loss of voluntary control and detrusor-sphincter dyssynergia.[39] Sexual dysfunction is prevalent, with approximately 75% of men experiencing erectile issues and 95% facing ejaculatory difficulties, while women report reduced lubrication and sensation from disrupted reflex arcs.[40] In high cervical tetraplegia, respiratory autonomic issues arise from phrenic nerve involvement, causing diaphragm weakness, hypoventilation, and reliance on accessory muscles or ventilatory support.[41] Beyond autonomic effects, other symptoms include neuropathic pain, which affects 65-85% of individuals and presents as burning or shooting sensations from central or peripheral sensitization below the injury level.[42] Spasticity emerges post-acutely, characterized by velocity-dependent hypertonia and spasms in about 65% of cases, often requiring pharmacological or physical interventions to mitigate interference with function.[43] Fatigue is a pervasive issue, linked to deconditioning, pain, and sleep disturbances, impacting daily activities and quality of life. The initial spinal shock phase, lasting days to weeks, features flaccid hypotonia, areflexia, and absent bulbocavernosus reflex, marking a transient loss of spinal excitability before reflex recovery.[44] Psychosocial symptoms, such as depression and anxiety, occur in 30-50% of individuals with tetraplegia, influenced by the abrupt life changes and chronic symptom burden, though these require targeted mental health support.[45]Diagnosis and Classification
Diagnostic Approaches
Diagnosis of tetraplegia begins with a thorough clinical examination to assess neurological function and localize the injury level in the cervical spinal cord. In the acute setting, emergency providers perform an initial evaluation of sensory function, motor capabilities, and reflexes, guided by symptoms such as limb weakness or sensory loss, while immobilizing the patient to prevent further damage.[7] A comprehensive neurological assessment follows, typically after 72 hours post-injury once spinal shock has begun to resolve, using the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI), which incorporates the American Spinal Injury Association (ASIA) Impairment Scale. This scale grades injury severity from A (complete, no sensory or motor function below the neurological level) to E (normal), based on bilateral testing of light touch and pinprick sensation across 28 dermatomes (scored 0-2 each) and manual muscle testing in 10 key myotomes (scored 0-5 each), helping to map sensory and motor levels.[46][6][47] Reflex testing complements this by evaluating hyperreflexia or absent responses in the lower limbs, which may indicate upper motor neuron involvement during or after the spinal shock phase.[48] Imaging modalities are essential for visualizing structural damage and confirming the diagnosis. Magnetic resonance imaging (MRI) is the preferred method for soft tissue evaluation, providing detailed views of spinal cord edema, hemorrhage, compression, or contusion in the cervical region, with high sensitivity for non-bony pathologies.[6] Computed tomography (CT) scans excel at detecting bony fractures, dislocations, or instability in the vertebrae, often using thin slices (≤3 mm for cervical spine) to assess injury extent with near-100% sensitivity for fractures.[6] Plain X-rays serve as an initial screening tool to evaluate spinal alignment and gross vertebral damage, though they have lower sensitivity for subtle injuries and are typically supplemented by advanced imaging.[7][49] Electrophysiological tests provide objective data on nerve conduction when clinical exams are inconclusive, such as in sedated or uncooperative patients. Electromyography (EMG) assesses muscle electrical activity to differentiate spinal cord from peripheral nerve involvement, while somatosensory evoked potentials (SSEPs) measure signal transmission from peripheral nerves to the brain, aiding in localization of conduction blocks in the cervical cord.[49][48] Differential diagnosis involves excluding conditions mimicking tetraplegia, such as traumatic brain injury or peripheral neuropathy, through integrated clinical history, imaging, and targeted testing; for instance, brain imaging rules out cerebral lesions, while nerve conduction studies distinguish central from peripheral etiologies.[49][48]Lesion Classification
Lesion classification in tetraplegia standardizes the assessment of cervical spinal cord injuries to determine the neurological level of injury (NLI), completeness, and functional impairments, aiding in prognosis and management planning. The International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI), developed by the American Spinal Injury Association (ASIA) and the International Spinal Cord Society (ISCoS), provides the primary framework through a standardized worksheet that evaluates sensory and motor functions across dermatomes and myotomes. [50] [51] The ISNCSCI worksheet determines the sensory level as the most caudal dermatome with normal sensation (light touch and pinprick scores of 2 bilaterally) and the motor level as the lowest key myotome with at least antigravity strength (grade ≥3/5), provided rostral levels are intact (grade 5/5). [50] The neurological level of injury (NLI) is then defined as the most caudal segment where both sensory and motor functions are normal on both sides. [51] For tetraplegia, classification focuses on cervical levels C1–C8, where injuries disrupt innervation to the upper and lower extremities, trunk, and potentially respiratory muscles. Higher lesions (C1–C4) often lack dedicated key myotomes in the ISNCSCI but are assessed via overall function, such as diaphragm integrity at C3–C5; lower lesions (C5–C8) correspond to specific upper limb functions. [6]| Cervical Level | Key Myotomes | Primary Functions Affected |
|---|---|---|
| C1–C4 | None specified (neck flexors/extensors for C1–C3; diaphragm via phrenic nerve for C4) | Head/neck control; respiration (C4 primarily) |
| C5 | Elbow flexors (biceps brachii); deltoid | Shoulder abduction; elbow flexion |
| C6 | Wrist extensors (extensor carpi radialis) | Wrist extension |
| C7 | Elbow extensors (triceps brachii) | Elbow extension; wrist flexion |
| C8 | Finger flexors (flexor digitorum profundus to middle finger) | Finger flexion |