Cervical Spine Differential Diagnosis: A Comprehensive Guide for Clinicians

Introduction

Neck pain is a pervasive complaint encountered across various medical specialties, from orthopedics to emergency medicine and primary care. The array of potential diagnoses for cervical pain is extensive, posing a significant challenge for clinicians aiming for accurate and timely diagnoses. Even experienced physicians may find it daunting to navigate this complex landscape without a systematic approach. While readily identifiable conditions such as cervical disc herniations are often diagnosed through history and physical examination, differentiating rarer etiologies, like spinal infections or tumors, requires a more structured and comprehensive methodology. Delayed diagnosis, particularly in cases of severe pathologies like spinal infections, can significantly impact patient outcomes. Therefore, a robust and exhaustive differential diagnostic approach is crucial to narrow down diagnostic possibilities, minimize unnecessary testing, and expedite accurate diagnoses for patients presenting with neck pain.

This article provides a structured methodology for categorizing the diverse etiologies of neck pain based on simple clinical criteria. Our aim is to offer a practical roadmap that clinicians can use to navigate the extensive list of potential diagnoses and guide the selection of appropriate diagnostic tests and imaging studies. This approach is designed to enhance diagnostic efficiency and accuracy in managing patients with cervical spine complaints. While this review offers a broad overview of potential pathologies, it is intended as a practical guide for differential diagnosis rather than an exhaustive description of each condition.

Existing literature addresses diagnostic workups for back pain, often categorizing pain as acute versus chronic and highlighting “red flags” suggestive of serious pathology. However, the direct application of these approaches to the cervical spine can be limited, and focusing solely on lumbar pain may lead to overlooking critical cervical spine conditions. This review provides a comprehensive and practical systematic approach tailored to the diagnostic challenges of cervical spine pain.

Literature Review

Referred Pain in the Cervical Spine

Referred pain, characterized by pain perceived in a location different from the pain source, is a critical consideration in Cervical Spine Differential Diagnosis. It is paramount to recognize that neck pain can originate from pathologies outside the cervical spine itself.

• Cardiac Conditions: Acute myocardial infarction, particularly involving the inferior wall, can manifest as neck and jaw pain, often accompanied by chest discomfort, shortness of breath, and diaphoresis. Ischemia of the posterior wall of the myocardium can also cause thoracic interscapular pain radiating to the neck.
• Vascular Emergencies: Aortic dissection, especially of the ascending aorta, can present with sudden, severe neck and upper back pain, often described as tearing or ripping. Pulse deficits and signs of shock may or may not be immediately apparent.
• Pulmonary Issues: While less common for direct neck pain referral, conditions like Pancoast tumors (lung cancer at the apex) can invade the brachial plexus and upper ribs, causing shoulder and neck pain. Pleuritic pain from pulmonary embolism or pneumothorax might also be referred to the upper back and neck regions.
• Upper Gastrointestinal Disorders: Esophageal spasm or rupture can sometimes present with upper back and neck pain, although this is less typical than chest pain.
• Cranial and Intracranial Pathology: Brainstem tumors or lesions at the base of the skull can directly cause neck pain, sometimes accompanied by neurological deficits or cranial nerve abnormalities.

It is essential to consider these non-cervical spine origins of pain, especially in patients with atypical presentations or risk factors for systemic diseases.

Trauma and Overuse Injuries of the Cervical Spine

Trauma is a frequent cause of cervical spine pain. A detailed history, when available, is crucial, although in certain situations (altered mental status, nonverbal patients), traumatic injury may not be immediately evident. Conversely, a history of trauma does not automatically confirm a traumatic etiology, and may mask underlying conditions.

• Fractures and Dislocations: Cervical spine fractures and dislocations range from minor spinous process fractures to severe, unstable injuries involving vertebral bodies and ligaments. High-impact trauma, such as motor vehicle accidents or falls, are common causes.
• Strains and Sprains: These are low-energy injuries involving muscle or ligament stretching or tearing due to sudden movements, whiplash, or overuse. Whiplash injury, common in rear-end collisions, is a well-known cause of neck pain and associated symptoms.
• SCIWORA (Spinal Cord Injury Without Radiographic Abnormality): Predominantly seen in children, SCIWORA involves spinal cord injury without fracture or dislocation visible on plain radiographs. MRI is essential for diagnosis.
• Central Cord Syndrome: Hyperextension injuries, particularly in older individuals with pre-existing cervical spondylosis, can cause central cord syndrome, characterized by greater weakness in the upper extremities than lower, sensory disturbances, and bladder dysfunction.
• Pathological Fractures: Osteoporosis, metastatic cancer, and infections can weaken the cervical spine, predisposing to fractures even with minimal trauma.
• Stress Fractures: While less common in the cervical spine than lumbar, stress fractures can occur in athletes involved in repetitive neck movements.
• Brown-Sequard Syndrome: Hemicord lesions, whether traumatic or tumor-related, result in ipsilateral motor weakness and proprioceptive loss, and contralateral pain and temperature sensation loss.

Infections of the Cervical Spine

Infections of the cervical spine, while less common than degenerative conditions, are serious and require prompt diagnosis and treatment.

• Osteomyelitis and Discitis: These infections can be bacterial, fungal, or tuberculous, causing neck pain, fever (variable), and potential neurological deficits. Pain is often constant, may worsen at night, and is unresponsive to typical analgesics.
• Epidural Abscess: A spinal epidural abscess is a neurosurgical emergency. It presents with severe neck pain, fever, and rapidly progressive neurological deficits due to spinal cord compression.
• Paraspinal Abscess: Abscesses in the paraspinal tissues can cause pain and systemic symptoms, sometimes without direct spinal cord compression initially.
• Fungal Infections: More prevalent in immunocompromised individuals, fungal infections of the spine can lead to chronic neck pain and neurological complications.
• Tuberculosis (Pott’s Disease): Spinal tuberculosis typically has a slow, insidious onset, with neck pain, deformity (kyphosis), and progressive neurological deficits.
• Herpes Zoster (Shingles): Reactivation of the varicella-zoster virus can cause radicular neck pain preceding the characteristic vesicular rash. Zoster sine herpete presents with pain but without the rash.
• Acute Flaccid Myelitis: This rare condition can present with neck and back pain along with acute onset of limb weakness or paralysis.

Tumors of the Cervical Spine

Both benign and malignant tumors can affect the cervical spine, causing pain and neurological symptoms.

• Benign Tumors: Osteoid osteoma and osteoblastoma are benign bone tumors that can cause persistent neck pain, often worse at night and relieved by NSAIDs. Schwannomas, arising from nerve sheaths, can cause radicular pain.
• Malignant Tumors: Metastatic disease is the most common malignancy affecting the spine, with lung, breast, prostate, kidney, and thyroid cancers being frequent primary sites. Primary spinal malignancies like myeloma, lymphoma, and chordoma are less common but important to consider.
• Calcifying Pseudoneoplasm of the Spine (CAPNON): This rare, benign lesion can cause mass effect and neurological symptoms.
• Meningioma: Although more common in the thoracic spine, meningiomas can occur in the cervical region and cause cord compression.

Degenerative, Rheumatic, and Autoimmune Conditions of the Cervical Spine

Degenerative changes are the most common cause of chronic neck pain.

• Cervical Spondylosis and Disc Herniation: Degeneration of cervical discs and facet joints, along with disc herniation, are frequent causes of neck pain, radiculopathy (arm pain, numbness, weakness), and myelopathy (spinal cord compression).
• Cervical Spinal Stenosis: Narrowing of the spinal canal can compress the spinal cord, leading to cervical myelopathy, characterized by gait unsteadiness, clumsiness, and upper motor neuron signs.
• Facet Joint Arthropathy: Degeneration of the facet joints can cause localized neck pain, often worsened by extension and rotation.
• Diffuse Idiopathic Skeletal Hyperostosis (DISH): DISH involves ligamentous calcification along the spine and can cause stiffness and pain in the neck and back.
• Crowned Dens Syndrome: Calcium pyrophosphate crystal deposition around the odontoid process causes severe acute neck pain and stiffness.
• Rheumatoid Arthritis (RA): RA frequently affects the cervical spine, particularly the atlantoaxial joint, potentially leading to atlantoaxial subluxation and spinal cord compression.
• Ankylosing Spondylitis (AS): AS and other spondyloarthropathies can cause inflammatory neck pain and stiffness, often worse in the morning and improving with activity.
• Polymyalgia Rheumatica: This inflammatory condition primarily affects older adults, causing neck and shoulder girdle pain and stiffness, often with elevated inflammatory markers.
• Transverse Myelitis: Inflammation of the spinal cord can cause neck pain along with motor and sensory deficits.
• Arachnoiditis: Inflammation of the arachnoid membrane, often due to prior spinal procedures, can cause chronic neck and back pain with radicular symptoms.
• Fibromyalgia and Myofascial Pain Syndrome: These conditions are characterized by chronic widespread pain, including neck pain, with tenderness to palpation in specific areas.

Vascular Disorders Affecting the Cervical Spine

Vascular conditions affecting the spinal cord are rare but can have devastating consequences.

• Spinal Cord Infarction: Obstruction of the vertebral or spinal arteries can lead to spinal cord infarction, presenting with sudden onset of severe neck or back pain and neurological deficits, including paralysis.
• Arteriovenous Malformations (AVMs): Spinal AVMs can cause gradual or sudden onset of neurological symptoms due to vascular steal or hemorrhage.
• Spinal Hemangioma: Aggressive spinal hemangiomas can expand into the spinal canal and compress the spinal cord or nerve roots.
• Epidural or Subdural Hematoma: Spinal hematomas, often related to trauma, anticoagulation, or bleeding disorders, can cause acute neck pain and neurological deficits due to cord compression.
• Vasculitis: Systemic vasculitides, such as Wegener’s granulomatosis, can rarely affect the spinal cord and cause myelopathy.

Congenital and Developmental Cervical Spine Conditions

Congenital anomalies can predispose to neck pain, often later in life due to accelerated degeneration.

• Congenital Malformations: Conditions like Klippel-Feil syndrome (congenital fusion of cervical vertebrae) can cause neck pain and limited range of motion. Chiari malformations can cause neck pain, headaches, and neurological symptoms.
• Syrinx (Syringomyelia): Fluid-filled cavities within the spinal cord can cause a variety of neurological symptoms, including neck pain, weakness, and sensory disturbances.

Psychogenic Neck Pain

Psychological factors can contribute to or exacerbate neck pain. Somatoform disorders and conversion disorders may manifest as neck pain without identifiable physical pathology. Diagnosis is typically made after excluding organic causes.

Metabolic and Endocrine Disorders Affecting the Cervical Spine

Metabolic bone diseases can weaken the cervical spine and contribute to pain.

• Paget’s Disease: Paget’s disease of bone can affect the cervical vertebrae, causing pain and potentially nerve compression.
• Hyperparathyroidism and Renal Osteodystrophy: These conditions can lead to bone demineralization and pathological fractures in the cervical spine.
• Osteomalacia: Softening of the bones due to vitamin D deficiency or other causes can result in generalized skeletal pain, including neck pain.

Iatrogenic Causes of Neck Pain

Medical interventions can sometimes lead to neck pain.

• Failed Neck Surgery Syndrome: Chronic neck pain persisting after cervical spine surgery can be due to various factors, including recurrent disc herniation, spinal stenosis, or post-surgical scarring.
• Medication-Induced Neck Pain: Certain medications, such as statins and bisphosphonates, have been associated with musculoskeletal pain, including neck pain.

Idiopathic Neck Pain

In some cases, the cause of neck pain remains unidentified despite thorough investigation.

• Idiopathic Torticollis: Involuntary muscle contractions in the neck, particularly the sternocleidomastoid muscle, can cause neck pain and abnormal head posture. While often idiopathic, secondary causes should be excluded.
• Sarcoidosis: Sarcoidosis, a systemic granulomatous disease, can rarely affect the cervical spine, causing pain and neurological deficits.

Method for Cervical Spine Differential Diagnosis

A systematic approach is essential for effectively navigating the broad differential diagnosis of cervical spine pain. Based on clinical experience and literature review, we propose a 7-category classification system to guide diagnosis (Table 1). This system utilizes readily available clinical information from history, physical examination, and basic investigations to categorize patients and direct further diagnostic workup.

These categories are designed to be recognizable early in the clinical encounter, facilitating efficient triage and diagnostic planning.

1. Referred Pain from Cranium, Chest, or Upper Abdomen: Consider non-cervical spine sources. Evaluate for associated symptoms and risk factors for cardiac, vascular, pulmonary, or upper abdominal pathology. Initial investigations may include ECG, chest X-ray, or abdominal imaging.

2. Pain with Signs of Infection: Assess for systemic signs of infection (fever, chills, malaise). Laboratory investigations should include complete blood count, inflammatory markers (CRP, ESR), and potentially blood cultures. Imaging (MRI with contrast) is crucial if infection is suspected.

3. Pain with Signs of Nerve Root Compression (Cervical Radiculopathy): Look for radicular pain radiating into the arm, dermatomal sensory changes, myotomal weakness, and reflex abnormalities. MRI of the cervical spine is the imaging modality of choice to visualize nerve root compression. Neurophysiological studies (EMG/NCS) can confirm radiculopathy and assess severity.

4. Pain with Signs of Spinal Cord Compression (Cervical Myelopathy): Identify signs of upper motor neuron dysfunction, such as gait disturbance, hyperreflexia, clonus, and positive Babinski sign. Bowel and bladder dysfunction may also be present. MRI of the cervical spine with and without contrast is mandatory to evaluate for cord compression.

5. Mechanical Neck Pain: Pain related to movement and posture, relieved by rest. Often associated with activities that strain the neck. Plain radiographs may be sufficient for initial assessment. Further imaging (CT or MRI) may be needed if red flags are present or symptoms are persistent.

6. Rheumatic Neck Pain: Pain that is persistent at rest, often worse at night and in the morning, with prolonged morning stiffness. May be associated with other joint involvement. Consider inflammatory markers (ESR, CRP, rheumatoid factor, ANA) and rheumatologic consultation.

7. Pain with Other Characteristics, With or Without Local Tenderness: This category encompasses less typical presentations, including pain associated with metabolic, endocrine, psychogenic, or idiopathic conditions. Diagnosis relies on careful history, physical examination, and targeted investigations based on clinical suspicion.

Table 1. Differential Diagnosis of Cervical Spine Pain Categorized by Clinical Features

1. Referred Pain	2. Pain with Infection	3. Radicular Pain (Nerve Root Compression)	4. Myelopathic Pain (Cord Compression)	5. Mechanical Pain	6. Rheumatic Pain	7. Other Pain
Myocardial Infarction	Osteomyelitis	Cervical Disc Herniation	Cervical Spondylotic Myelopathy	Cervical Strain/Sprain	Rheumatoid Arthritis	Fibromyalgia
Aortic Dissection	Discitis	Foraminal Stenosis	Spinal Stenosis	Whiplash Injury	Ankylosing Spondylitis	Myofascial Pain Syndrome
Angina Pectoris	Epidural Abscess	Tumor (Nerve Sheath)	Tumor (Intradural/Extradural)	Facet Joint Pain	Polymyalgia Rheumatica	Psychogenic Pain
Esophageal Spasm	Meningitis	Osteophyte	Epidural Hematoma/Abscess	Muscle Spasm	Psoriatic Arthritis	Medication-Induced Pain
Pancoast Tumor	Septic Arthritis	Synovial Cyst	Subdural Hematoma	Ligamentous Injury	Reactive Arthritis	Metabolic Bone Disease
	Tuberculosis		Transverse Myelitis	Postural Pain	Gout	Idiopathic Torticollis
	Fungal Infection		AVM	Cervical Instability	Crowned Dens Syndrome	Sarcoidosis
			Syrinx	DISH	SLE
Diagnostic Tools: ECG, Chest X-ray, Upper Abdominal Imaging, Cardiac Enzymes	Diagnostic Tools: CBC, CRP, ESR, Blood Cultures, MRI with Contrast	Diagnostic Tools: MRI Cervical Spine, EMG/NCS	Diagnostic Tools: MRI Cervical Spine with and without Contrast, CT Myelogram (if MRI contraindicated)	Diagnostic Tools: Plain Radiographs, Clinical Examination, CT/MRI if Red Flags	Diagnostic Tools: Inflammatory Markers, Rheumatoid Factor, ANA, Clinical Criteria	Diagnostic Tools: History, Physical Exam, Targeted Investigations based on suspected etiology

AVM, Arteriovenous Malformation; DISH, Diffuse Idiopathic Skeletal Hyperostosis; SLE, Systemic Lupus Erythematosus; ECG, Electrocardiogram; CBC, Complete Blood Count; CRP, C-Reactive Protein; ESR, Erythrocyte Sedimentation Rate; MRI, Magnetic Resonance Imaging; EMG/NCS, Electromyography/Nerve Conduction Studies; CT, Computed Tomography; ANA, Antinuclear Antibodies.

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Discussion

The diagnosis of cervical spine pain presents a significant challenge due to the extensive differential diagnosis. A systematic approach, as proposed in this review, is crucial for efficient and accurate diagnosis, particularly in primary care and emergency settings where clinicians face a high volume of patients with neck pain.

While “red flag” approaches have been advocated for back pain, their limitations in sensitivity and specificity are recognized. Focusing solely on red flags may miss subtle but significant pathologies or lead to unnecessary investigations in patients with benign conditions. Our categorical approach aims to provide a more nuanced and practical framework for clinicians.

Our 7-category system expands upon simpler diagnostic triage models for low back pain, offering a more comprehensive approach applicable to the cervical spine. By considering referred pain, infectious etiologies, radicular and myelopathic syndromes, mechanical pain, rheumatic conditions, and other less common causes, this system encourages a broader differential diagnosis and facilitates targeted investigations. This structured approach is particularly valuable in non-emergency settings, allowing for a more thorough and considered diagnostic process.

The strength of this review lies in its inclusive overview of cervical spine pathologies, ranging from common degenerative conditions to rare systemic disorders. This comprehensive perspective is essential for educating clinicians and promoting a wider consideration of diagnostic possibilities in patients with neck pain. By utilizing this 7-syndrome classification, clinicians can be better equipped to efficiently diagnose the underlying cause of cervical spine pain, minimize unnecessary testing, and optimize patient care.

Author Contribution

EK: Conceptualization, Methodology, Writing.
HS: Methodology, Writing.
NS: Methodology, Writing.
AT: Methodology, Writing.
EB: Methodology, Writing.

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Not applicable.

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Declarations

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Consent for publication obtained.

Conflict of Interest

The authors declare no competing interests.

Footnotes

This article is part of a review series on spinal disorders.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Elisha Krasin and Haggai Schermann contributed equally to this work in the original publication.

References

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Associated Data

Data Availability Statement

Data sharing not applicable to this article as no datasets were generated or analyzed.