Differential Diagnosis in Neurology

6.3. Cervical Root Disease

Congenital Root Diseases

• C1–C3 roots:
  • Abnormal ossification of the odontoid process or the lateral masses of the atlas
  • Platybasia of the skull
  • Basilar impression with C2–C3 impingement
  • Arnold Chiari malformation with traction on posterior roots of C2 and C3 with severe pain; specific cough or Valsalva headache causes C2 traction headache
• Klippel Feil Defect:
  • Congenital fusion of C4–C5 > C5–C6 (C3–C4 rare)
  • Severe pain at this root level
  • Spinal stenosis at or one level above the fusion
  • Associated with Spangle's deformity:
    • Myometric abnormality of C4–C5
    • Shoulder muscles and scapula poorly developed; shoulder elevated
• Syringomyelia
  • Atrophy at the level of the involved root
  • Associated AC type II malformation

T1 Congenital Anomalies of the Thoracic Outlet

• The major components of the thoracic outlet:
  • Sternocostovertebral space:
    • Most proximal part of the thoracic outlet tunnel
    • Anatomy:
      • Anteriorly (sternum)
      • Posteriorly (spine)
      • Laterally (first rib)
    • Subclavian artery, subclavian vein C4–T1 roots of the plexus traverse the space
    • Nerve roots have exited the spine and have not formed trunks
    • Associated structures:
      • Apex of the lung and pleura
      • Sympathetic trunk
      • Jugular vein
      • Lymphatics of the neck
    • May rarely be congenitally narrowed
    • Usual pathology in the sternocostovertebral space
      • Thyroid mass
      • Thymus enlargement
      • Parathyroid mass
      • Lymph nodes
      • Lung mass
      • Pancoast tumor (squamous or adeno cancer of lung)
  • Scalene triangle:
    • Anatomy
      • Anterior scalene muscle anteriorly
      • Middle scalene muscle posteriorly
      • First rib forms the base
    • Anterior scalene muscle:
      • Origins are the transverse processes of C3–C6
      • Insertion on the scalene tubercle of the first rib varies; tubercle insertion is between the subclavian artery and vein and pleural dome
      • Variants of insertion:
        • Behind the artery
        • Between the artery and brachial plexus
        • Entire base of the scalene triangle (traps the neurovascular bundle)
        • Anterior insertion may merge with insertion of middle scalene muscle (20% of patients)
        • C5 and C6 roots may transverse the anterior scalene muscle rather than descend between the anterior and middle scalene muscles
    • Middle scalene muscles:
      • Origin is the transverse processes of C2–C7
      • Insertion-Chassaignac's retro arterial tubercle of the first rib
      • May insert on the fibrous septum of the pleural dome; lateral fibers insert on the second rib
      • C8–T1 roots (individually or together as the lower trunk) compressed by more anterior or forward compression of the middle scalene muscle (sharp anterior edge); the anterior edge of the muscle may also compress the C8–T1 roots
    • First rib:
      • Floor of the scalene triangle
      • T1 closest to the rib
      • Congenital rib anomalies, bony ridges, hypoplasia and inward curvature may compress the neurovascular bundle
    • Scalene triangle congenital variations:
      • Base of the triangle 0.77 cm in men; 0.67 cm in women
      • C5–C6–C7 emerges from the apex of the triangle; the fibers of the middle and anterior scalene muscles merge at the apex. Patients with C5, C6–C7 root involvement have a greater incidence of roots emerging from the apex:
        • Interdigitation of anterior and middle scalene muscles occurs in 70% of symptomatic patients
        • Adherence of C5–C6 roots to the middle scalene muscles
    • Costoclavicular space (compresses the brachial plexus)
    • Pectoralis minor space (compresses the brachial plexus)

Cervical Ribs that Compress Cervical Roots

• 0.17% to 0.74% (average 0.3%) of general population (female > males 2:1) have cervical ribs
• 10% of patients that have cervical ribs are symptomatic
• Symptomatic patients often have suffered arm trauma
• Aneurysmal dilatation or subclavian artery stenosis is most often caused by a rudimentary rib or cervical rib
• Neurological symptoms from cervical ribs are caused by nerve compression primarily of the lower trunk (C8–T1)

Rib-Band Syndrome of Gilliat

• Type II band
• Compresses the C8, T1 roots (lower trunk)
• Paresthesias 4th, 5th finger, medial forearm to medial humerus
• Atrophy and wasting of intrinsic hand muscle
  • Thyroglossal duct cyst (involvement of C3–C4 roots)
  • Branchial cleft cysts (involvement of C2–C5 roots)
  • Short pedicle and block vertebral body:
    • Entrapment of nerve root under the pedicle and in the exit foramina
    • Achondroplasia (at all cervical levels) there are block vertebrae and cervical stenosis

Trauma of Cervical Nerve Roots

Flexion extension injury of the neck (whiplash)

• C8–T1 most frequently involved; congenital anatomical predisposition
• C5–C6 prior to or after having formed the upper trunk
• In association with C2, C3, C4 dorsal root injury
• Immediate pain that worsens over time
• Sympathetic symptomatology particularly with C8, T1 involvement
• Damaged during transaxillary first rib resection:
  • C8, T1 most frequently involved
  • C5–C6 damaged with scalenectomy and neurolysis procedures
  • Flexion and extension injury may damage the ansa hypoglossi
    • Weakness and spasm of sternocleidomastoid, scalene, trapezius muscles (C2–C4)
    • Hyoid, omohyoid muscles are involved
• Pain:
  • Preauricular nerve (C2, C3) distribution posterior roots of C2 and C3
  • Postauricular nerve (C3, C4) distribution posterior roots of C3 and C4
  • C2 root itself (radiation to basiocciput parietal and brow areas)
  • Greater and lesser occipital nerve areas (C2–C4 posterior roots)
• Surgical trauma:
  • C4–C5; C5–C6 roots most often affected
  • Plating and screw procedures
  • Arachnoiditis or direct injury of the affected roots
• High speed trauma (car accident or fall)
  • Spondylolisthesis of cervical vertebrae
  • Avulsion of nerve roots
  • Jumped facet joint
  • Rotary subluxation of facet joint
    • Pain in the neck with radiation into affected segmental distribution
    • Torticollis (to the affected side)
    • Segmental weakness
  • Injury by epidural catheterization with bupivacaine > 0.25% or trauma by the catheter itself

Complex Regional Pain Syndrome (Type I and II)

• Most often after injury to the arm (T2 sympathetic fibers of T1–T14 recurrent nerve of Kunz) carries sympathetic innervation into the arm)
• Multiple nerve roots involved; characteristic hyperalgesia, allodynia (mechanical and thermal; dynamic and static); autonomic dysregulation, movement disorder, atrophy and dystrophy

Red Ear Syndrome

• Ears beet red
• Slightly edematous
• Nonpainful
• Neurogenic edema (release of substance P (SP) and calcitonin gene related peptide (CGRP) from fibers that innervate blood vessels of the ear; mismatch of arteriolar and capillary circulations and sympathetic innervation. There is vasodilatation of the capillaries in the ear (CGRP) and leakage of plasma through the endothelium by SP)

Lax Ligament Syndrome (that Attach the Odontoid Process to the Axis)

• Four ligaments involved:
  • Cruciate ligament (attaches the odontoid to the axis)
  • Lateral ligaments (odontoid to the lateral mass of C1)
  • Ligament from the tip of the odontoid to the rim of the foramen magnum; alar ligament
• Normal posterior odontoid displacement:
  • Children 3–5 mm
  • Adults 1–2 mm
• C2 root primarily involved with spinal cord compression
• Differential diagnosis:
  • Rheumatoid arthritis
    • Frequently tingling of the arms and hands (C2-T1 involvement)
    • Subluxation and spinal cord compression
    • Pannus and erosion of the cruciate ligament
  • Mongolism
  • Ehlers Danlos syndrome
  • Marfan's syndrome
  • Trauma (flexion/extension injury)

Ligament Hypertrophy with cervical root Impingement

• Acromegaly
• Mucopolysaccharidosis
• Posterior ligament ossification syndrome (primarily Japanese patients)
• Idiopathic pachymeningitis
• Hayakawi Syndrome (ligament laxity with cord compression)

Pachymeningitis with Cervical Root Compression

• Syphilis
  • Dense fibrous pachymeningitis particularly of the cervical cord
• Sarcoid
• Tuberculous infection
• Idiopathic pachymeningitis
• Subarachnoid hemorrhage with consequent arachnoiditis
• Hodgkin's and non-Hodgkin's lymphoma

Tumors of the Cervical Nerve Roots

• Schwannoma:
  • Associated with NFT type I chromosome 17
  • May affect multiple nerve roots concomitantly
  • Root and plexiform involvement > in lumbosacral than brachial distributions
  • Dumbbell tumor; may involve the nerve and then grow through the foramina to compress the spinal cord (intradural extramedullary location)
• Neurofibroma:
  • Cannot be dissected from the nerve (grows throughout the nerve)
• Meningioma:
  • Intradural extramedullary nerve root compression
  • Plexiform (en-plaque growth)
• Lymphoma (infiltration of nerve roots)
• Leukemia:
  • Hemorrhage into nerve root (acute presentation)
  • Infiltration of nerve root (insidious presentation)
• Carcinomatosis of the meninges:
  • Lung, breast, GI tract, prostate
  • Asymmetric presentation
  • Weakness, atrophy, anesthesia, loss of reflexes in segmental distribution
• Chordoma:
  • Most common in clivus and sacral vertebrae
  • Greater than 10% at thoracic or cervical levels
• Osteogenic sarcoma (rare)
• Chondrosarcoma (rare)
• Ewing's sarcoma:
  • Greater than 5% axial vertebral involvement
  • Predilection for cervical vertebrae
• Pancoast tumor:
  • Apex of the lung (adeno or squamous carcinoma)
  • Involvement of roots in the sternocostovertebral space
  • Pain (usually burning) along the medial forearm and into 4th and 5th fingers
  • Horner's syndrome (involvement of the sympathetics at C8–T1)
  • May involve T2 sympathetic outflow to the arm
• Lymphomatous B cell: diffuse radiculopathy
• Post X-ray treatment sarcoma:
  • Follows X-RT for breast cancer (most frequently)
  • Involves roots of the brachial plexus C8, T1 > C5–C6
  • Follows X-RT by 15–20 years
  • Associated with myokymia in the irradiated area
  • Associated skin changes; hyperpigmentation, telangiectasia, proliferative endarteritis
• Neuromyotonia:
  • Rippling fasciculations
  • Hodgkin's disease
  • Anti-TA antibodies
• Mixed salivary gland tumors:
  • Infiltrate C1–C4 roots
• Parotid gland tumors:
  • VIIth nerve most frequently involved
  • Cervical C2–C4 roots involved
• Salivary cylindroma:
  • Cervical C1–C4 roots
  • Cranial nerve involvement concomitantly

Infection Involving Cervical Nerve Roots

• Herpes zoster:
  • C5–C6 > C4–C5 > C8–T1
  • Clinical symptomatology:
    • Grouped vesicular eruption in a dermatomal distribution
    • Sensory loss in dermatomal pattern to all modalities (early)
    • Atrophy, weakness, sensory loss in involved myotome
    • May have dermatomal sensory loss weeks to occasionally months prior to vesicular eruption (herpes sine herpete); often burning pain in the dermatomal distribution
  • Post herpetic neuralgia:
    • Spontaneous lancinating pain
    • Deep continuous ache with lancinating exacerbations in involved dermatome
    • Decreased sensory threshold to pinprick, touch or temperature of the dermatome
    • Allodynia to both static and dynamic mechano and thermal stimuli
    • Hyperalgesia of the involved dermatome
    • Neuroma in continuity along the root of the affected dermatome may be cause of post herpetic neuralgia
• Herpes simplex :
  • Single vesicular eruption
  • Painful; ecthymatous base
  • Dermatomal but often regional (several roots involved) pain

• Brucella:
  • Rare cervical involvement (L5 most common root affected)
• Lyme's disease:
  • C5–C6 root most common roots that are involved
  • May be bilateral
  • Often arthralgia or erythema migrans have been noted prior to symptoms
• Staphylococcus aureus (contiguous spread)
  • Usually seen in IV drug abusers
  • Following surgery with accompanying osteomyelitis
  • Disc space involvement first; nerves compromised in foraminal exit areas or laterally
• Viral infection:
  • Parsonage Turner syndrome:
    • Sudden onset of severe lancinating, burning and deep pain
    • C5–C6 dermatomes affected; may be bilateral
    • Cause of neuralgic amyotrophy
    • May affect individual nerves (phrenic)
  • EBV virus
  • Hepatitis C (associated cryoglobulinemic neuropathy)
  • Polio myelitis acute:
    • Usually groups of anterior horn cells are affected
    • Isolated finger involvement
    • Non-dermatomal distribution
    • Fasciculations and atrophy prominent long after cessation of infection
    • Post-polio syndrome follows in a significant percentage of patients
  • Adenovirus
  • Coxsackie virus

Systemic Disease Affecting Cervical Roots

• Diabetes mellitus:
  • Diabetic amyotrophy much more common in L2–L4 distribution
  • Putative involvement of vasonervorum (infarction of roots and plexus)
• Acute intermittent porphyria:
  • C5–C6 roots most commonly involved
  • Most often motor; severe atrophy of involved dermatome that recovers
  • Sensory loss patchy; most often out of a dermatomal distribution
• Variegate porphyria (rare root involvement) may have associated skin rash
• Post X-RT therapy (myokymia)
• Pachymeningitis syndrome (idiopathic)
• Sicca complex:
  • Autoimmune (putative)
  • May have patchy anhidrosis and sensory loss out of a dermatomal distribution
  • Probable dorsal root ganglion neuropathy
  • May involve definable cervical roots
• Amyloidosis:
  • Familial amyloid
  • FOLMA
    • Meningeal involvement with nerve root compression
• Isolated angiitis of the CNS/PNS:
  • Arteritis of the vaso vasorum of cervical nerve roots
• Inflammatory spondyloarthritis with radiculopathy
  • Rheumatoid arthritis
  • Psoriasis
  • Ankylosing spondylitis
  • Crohn's disease
  • Ulcerative colitis
  • Behçet's disease

Vascular Disease of Cervical Nerve Roots

• Arteriovenous malformation:
  • Nerve root (on the root itself)
  • Dural AVM with accompanying compression of the nerve root
• Dilated vein compressing nerve root:
  • Venous congestion from severe cervical spondylosis or stenosis
  • Concomitant venous congestion of the spinal cord (causes myelomalacia)
• Foix–Alajouanine syndrome:
  • Arteriovenous malformation involving the anterior spinal artery
  • Cervical nerve roots and cord may be compressed
• Weber–Klippel–Trenaunay syndrome:
  • Arteriovenous malformation of an extremity
  • Enlargement of the bone and soft tissue components of the extremity
  • Enlarged epidural veins may compress segmental nerve roots
  • May be genetic
• Superficial siderosis:
  • Hemosiderin deposits on nerve roots:
    • Radiculopathy
    • Cranial nerve I and VIII concomitantly involved
    • Repeat bleeds from aneurysms, cavernous hemangiomas or rarely telangiectasia
    • Demonstrated by gradient ECHO MRI evaluation (hemosiderin)
• Arachnoiditis (following admixture of blood):
  • Clumping together and scar formation of nerve roots
    • Secondary to:
      • Multiple surgeries
      • A mixture of blood and myelogram dye
  • Clinical Features:
    • Severe burning pain in several dermatomal distributions
    • Usually regional rather than clear radicular pattern
    • CT/myelogram demonstrates clumping of nerve roots or a featureless dural sac; MRI demonstrates gadolinium enhancement of the scar
    • Minimal weakness; burning pain predominates
    • Asymmetric loss of reflexes
    • Rare bladder involvement
• Aneurysmal rupture of vertebral or anterior spinal artery
  • Arachnoiditis
  • Superficial siderosis

Differential Diagnosis of Cancer vs. X-RT Involvement of Cervical Nerve Roots

Cancer

• Painful (burning)
• C8, T1 roots primarily involved
• Horner's syndrome
• Pancoast tumor of lung apex (adeno or squamous cell carcinoma)

X-RT Treatment

• Dysesthesia or paresthesia; not painful
• C5–C6 primarily involved
• No Horner's syndrome
• Myokymia of the involved segment
• X-RT of breast or Hodgkin's disease most common systemic illness treated