Differential Diagnosis in Neurology

4.8. Infections Affecting the Spinal Cord

• General considerations:
  • Epidural abscess
    • Predisposing factors:
      • Compromised immune system
      • Hematogenous spread from other infections
      • IV drug abuse
      • Prolonged epidural anesthesia
• Clinical features:
  • Severe back or neck pain
  • Intramedullary spread
  • Occasional radicular pain that may precede the myelopathy
  • May present as a Brown–Sequard Syndrome
  • Sudden paralysis from spinal cord infarction
• Laboratory evaluation:
  • Elevated sed rate the most important test; reliable however in only 25–40% of early patient infections.
• MRI evaluation:
  • Increased signal from the disc space on T2 weighted sequences often the first sign of discitis
  • Enhancement of the anterior and posterior longitudinal ligaments; paraspinal muscles and the abscess itself

Gram Negative Infections

• Occur following post-surgical procedures
• At times one month to six weeks delay from the surgical procedure

Staph Aureus

• General considerations:
  • Predisposing causes:
    • IV drug abuse
    • SBE
    • HIV
• Clinical features:
  • Discitis with severe pain on any movement
  • Several segments are involved
  • Sudden paralysis from infarction of the cord
• MRI evaluation:
  • Disc space enhancement
  • Enhancement along anterior and posterior ligaments

Tuberculosis

• General considerations:
  • Lumbar spine > thoracic spine in American patients
  • Cervical > thoracic > lumbar infections in Asian patients
• Clinical features:
  • Associated with thoracic Pott's disease and spinal collapse with spinal cord compression
  • Spinal cord infarction (endarteritis)
  • Cold paravertebral abscess (L1–L4); often minimally painful
• Imaging evaluation:
  • Disc space infection; pus along anterior and posterior ligaments
  • Eburnation of the vertebral end plates

Viral Infections with myelitis

• Myelitis may follow polio or other enterovirus infections of the anterior horn cells
• Varicella virus attacks the dorsal root ganglia and nerve roots as well as the adjacent cord (most often thoracic)
• Parenchymal cord involvement occurs with rabies, HSV, CMV (HIV co infected) HTLV I and II, EBV, simian B virus, and tick borne encephalitis; des encephalitides

Herpes Viruses

• General considerations:
  • Cause acute infections but also have the capacity for latency
  • Reactivated near the site of the original infection
  • Neurological diseases in humans are caused by the following herpes viruses:
    • HHV6
    • Herpes simplex type 1 and 2
    • Varicella virus
    • CMV
    • EBV
    • Simian herpes ("monkey") B-virus

Herpes Simplex Type 1

• General considerations:
  • HSV-1 encephalitis is the most common cause of sporadic encephalitis in the US; approximately 10% of encephalitis cases
  • Acquired by respiratory or salivary contact; the cause of oral herpes
  • 30% of HSV-1 encephalitis occurs by spread into the brain from the nasal epithelium
• Clinical features:
  • Encephalitis
  • Myelitis
  • CSF:
    • Increased pressure
    • Lymphocytic pleocytosis 10–1000 WBC/mm³
    • Glucose is normal or slightly low (30–40 mg/ dL)
    • Protein is elevated (usually 60–80 mg /dL)
  • PCR has sensitivity of 95%
  • Cowdry A intranuclear inclusions

Varicella Zoster

• General considerations:
  • Children may suffer:
    • Self-limited cerebellar ataxia
    • Rare fatal encephalitis
    • Post infections encephalomyelitis
      • One in 2500 patients
    • Reye's Syndrome
    • Congenital varicella
  • Virus is latent in DRG cells
  • Reactivated by:
    • Injury
    • Immunosuppression (disease)
    • Cancer
    • Immunosuppressive drugs
    • HIV
    • Systemic illness
• Clinical features:
  • Most often T5–T12 are the affected dermatomes
  • Thoracic cord myelitis
  • Lumbosacral ganglia involvement causes bladder dysfunction and ileus
  • Zoster sine herpete:
    • Prolonged radicular pain
    • No zoster rash
    • Detectable VZV DNA in CSF
  • Associated neurologic features include:
    • Post herpetic neuralgia:
    • Segmental motor atrophy
    • Large vessel stroke (most often the MCA)
    • Multifocal leukoencephalitis
    • Cerebral vasculopathy

Cytomegaloviruses

• General considerations:
  • Common congenital viral infection; possibly up to 2% of the population
  • Deafness or developmental delay
  • Sexual transmission is route of infection in adults
• Clinical features:
  • In immunocompetent adults:
    • Aseptic meningitis
    • Mononucleosis syndrome
    • Asymptomatic
    • GBS
    • Encephalitis
  • In association with HIV or immunosuppression:
    • Retinitis
    • Lumbosacral radiculitis
    • Encephalitis
    • Lumbosacral myelitis
• Laboratory evaluation:
  • Serology or PCR

Epstein–Barr Virus

• General considerations:
  • Primary infection is usually infectious mononucleosis; nervous system involvement occurs in less than 1% of patients
  • B-cell transforming virus:
    • Associated with CNS and Burkitt's lymphoma
  • Meningoencephalitis has occurred after bone marrow transplantation
• Clinical features:
  • Transverse myelitis
  • GBS syndrome; small fiber neuropathy; autonomic neuropathy; aseptic meningitis and rarely isolated cranial neuropathy
• Laboratory evaluation:
  • CSF, EBV specific antibodies or PCR

Human Herpes Virus Type 6

• General considerations:
  • T-lymphotrophic virus
  • Childhood exanthema subitum
  • Opportunistic infection in HIV and other immunocompromised conditions:
    • May cause T-cell immunodeficiency
• Clinical features:
  • Ascending necrotizing myelitis of the thoracic cord
  • B-Variant most commonly isolated from immunocompromised patients

Cercopithecine Herpes Virus 1 (B Virus)

• General considerations:
  • Carried by old world monkeys
  • Veterinarians and animal handlers at risk; 70% fatality rate
  • Transmitted by animal bit or virus contaminated fomites
  • 70% fatality rate
• Clinical features:
  • Ascending paralysis (longitudinal myelitis)
  • Associated medullary and cortical signs and symptoms occur early

Rabies

• General considerations:
  • Occurs along the Mexican–American border
  • Reservoirs are: dogs, skunks, bats, raccoons, and fox in the USA
  • Usual transmission is by a bite; rarely aerosol transmission (spelunkers)
  • Incubation period is usually 1–2 months
• Clinical features:
  • Prodrome of headache, fever, paresthesia at the inoculation site
  • Acute neurological phase with severe bulbar and autonomic features which progresses to coma
  • Paralytic or myelitic form:
    • Most often from bat bites
    • Paresthesias and weakness of the inoculated extremity
    • Quadriplegia from spinal cord involvement
• CSF:
  • High titers of neutralizing antibodies in the serum and CSF
  • PCR of CSF is positive

Polio Virus and Other Enteroviruses

• General considerations:
  • Enteroviruses are the leading cause of aseptic meningitis that can be identified

Polioviruses

• General considerations:
  • Infections most common in late summer
  • Transmitted by fecal-oral contact; pharyngeal spread during epidemics
  • Most clinically apparent infection causes aseptic meningitis (8%); paralytic form is 1%
• Clinical features:
  • 7–14 day incubation period
  • Prodromal phase of headache and meningeal symptomatology
  • An asymmetric flaccid paralysis occurs; may involve small groups of anterior horn cells (individual finger weakness)
  • Progresses for 3–5 days
  • Dromedary fever, curve maybe seen (two peaks)
  • Transverse myelitis and cerebellitis occur; rare facial weakness
  • Diaphragmatic involvement
  • Severe back pain often occurs 2–3 day
• Laboratory evaluation:
  • CSF:
    • Polymorphonuclearcytosis occurs early with a shift to lymphocytosis after 2 days
    • Slight elevation of protein (100–300 mg/dl)
    • Sugar is normal
  • Virus isolated from CSF, stool, or throat
• Differential diagnosis of viral spinal cord infection:
  • Aseptic meningitis:
    • Viruses
    • Drug induced chemical meningitis
  • Other viral induced paralysis with cellular CSF:
    • CMV
    • Carcinomatosis of the meninges
  • Medullary involvement with cellular CSF
    • Russian spring and summer encephalitis
    • Rabies
  • GBS Syndrome:
    • Antecedent rather than concurrent infection
    • Cranial nerve VII always involved when quadriparesis supervenes
    • CSF cytoalbuminologic dissociation
    • Loss of reflexes except triceps (peculiarly often spared)

Coxsackie A and B

• General considerations:
  • These viruses account for most cases of viral induced disease in the USA
  • West Nile virus must now be considered in this differential as it is spreading across the USA (first cases outside of LaGuardia airport NYC).
• Clinical features:
  • Aseptic meningitis
  • Encephalitis (rare)
  • Cerebellar ataxia (rare)
  • Paralytic spinal cord disease (rare)
  • CSF
    • Poly morphonucleositose 250/mm³
    • Lymphocytic pattern in 2–4 days

Flavivirus (West Nile)

• General considerations:
  • Now spreading across the USA
  • Distributed in Asia, Middle East, parts of Europe, former Soviet Union
  • Rash, lymphadenopathy and pharyngitis are premonitory
  • Crows a reservoir (dead crows a clue to its presence)
• Clinical features:
  • Polio-like spinal cord syndrome with myelitis and flaccid paralysis
  • Aseptic meningitis
  • GBS Syndrome
  • Papillitis
  • Radiculitis

Retrovirus Infection

• General considerations:
  • HIV binds to CD4 receptor
  • Infected macrophages transport the virus into the CNS
  • Vacuolar myelopathy occurs in 25–55% of HIV patients at autopsy
  • CNS a probable reservoir
• Clinical features:
  • Gait dysfunction
  • Spasticity
  • Leg weakness
  • Impaired proprioception and vibration
  • Sphincter dysfunction
  • Evolves over months
  • Associated often with dementia and painful distal symmetrical neuropathy
  • Babinski sign is common
  • Arms are involved late
  • Rare back pain
• Pathology:
  • Vacuolar myelopathy most prominent in the dorsolateral thoracic and cervical cord
  • Vacuolar changes in myelin sheaths with relative sparing of axons

Associated Myelopathies in HIV Patients

• Back and radicular pain more prominent
• More rapid progression than HIV myelopathy
• CMV affects lumbosacral cord in very ill patients
• Varicella and Herpes simplex occur concomitantly:
  • MRI may show T2-weighted images of a swollen cord
• Concomitant HTLV1 and infections occur with HIV
• Epidural abscess is seen with IV drug users
• B12 deficiency may be a contributing factor to myelopathy in HIV
• Rare spinal cord involvement occurs with M. tuberculosis and T gondi
• Epidural metastasis from systemic lymphoma occurs in this setting

HTLV 1 and 2

• General considerations:
  • Primarily seen in the Caribbean basin, Asia, Indian Ocean
  • May coexist with HIV
  • Sexual transmission
• Clinical features:
  • Longstanding slowly progressive course
  • Cervical > thoracic > lumbar cord involvement
  • Severe spasticity
  • Bladder > bowel and sexual dysfunction

Spirochetes

Syphilis

• General considerations:
  • Caused by T. pallidum
  • Spread by sexual contact or vertically from mother to child
  • Untreated 1–5% go on to develop tabes dorsalis; usually is seen 15–20 years after the original infection
• Clinical features:
  • Lightening pains (often thoracic or abdominal); dorsal root ganglia involvement
  • Urinary incontinence
  • Sensory ataxia (positive Romberg's sign)
  • Pupils are abnormal in 90% of patients
  • Argyll Robertson pupils are seen in 50%; other ophthalmological features include:
    • Optic atrophy
    • Ophthalmoplegia and ptosis
    • Uveitis, chorioretinitis and vasculitis
  • Associated disorders:
    • Gastric pharyngeal, laryngeal, genitourinary, intestinal, rectal crisis
  • Stamping gait

Other Causes of Syphilitic Spinal Cord Involvement

• Dorsal root entry zone and dorsal roots are sites of pathology
  • Hitzig spots (dorsal root posterior rami) cause oval areas of anesthesia on the trunk
• Pachymeningitis cervicalis:
  • Compression of the cord by thickened dura
• Anterior and posterior spinal artery occlusion
  • Proliferative endarteritis
• Laboratory evaluation:
  • Oligoclonal bands are present
  • IgM and IgG antibodies are seen in the CSF
  • PCR > 95% positive

Lyme Disease

• General considerations:
  • Borrelia burgdorferi
  • Transmitted by the deer tick Ixodes domini, pacificus, ricinus
• Clinical features:
  • Early disease:
    • Meningitis
    • Cranial neuropathy
    • Bilateral VIIth nerve
  • Late disease:
    • Encephalomyelitis
    • Dementia

Unusual Infections Affecting the Spinal Cord

Actinomycosis

• General considerations:
  • Caused by a gram positive anaerobic or microaerophilic rod
  • Normal in the mouth and genital flora
  • Most infections are cervical, thoracic, pelvic or abdominal
  • "Lumpy jaw" follows dental procedures or oral mucosa trauma
  • Occurs in immunocompetent patients
• Clinical features:
  • Forms draining sinuses with "sulphur granules"
  • Spinal epidural abscess follows vertebral osteomyelitis
    • Primary lung infection

Nocardia Asteroides

• General considerations:
  • Occurs in immunocompromised patients; dental procedures or inhalation
  • Disseminated disease often invades the CNS
  • Spread from pneumonia with cavity pulmonary lesions
• Clinical features:
  • Concomitant cerebral abscess or meningitis
  • Spinal cord involved by vertebral osteomyelitis

Hepatitis B Virus

• General considerations:
  • Associated with fulminant hepatic failure and polyarteritis nodosa
  • Neurological deficits have occurred following hepatitis vaccination
• Clinical features:
  • Transverse cervical or thoracic myelitis
  • Acute cerebral edema
  • Guillain Barré Syndrome
  • Inflammatory neuropathy

Mycoplasma

• General considerations:
  • M. pneumoniae most often causes pulmonary disease
  • Associated with occlusive cerebral vascular disease, arthralgias, rash, cardiac disease
  • Neurologic features are more common in hospitalized patients:
• Clinical features:
  • Transverse myelitis
  • Leukoencephalitis
  • Peripheral neuropathy
  • GBS syndrome
  • Meningoencephalitis
  • Aseptic meningitis
• Laboratory evaluation:
  • Cold agglutinins
  • Complement fixing antibodies

HIV is associated with secondary infective myelopathy

• Toxoplasmosis
• Tuberculosis
• Syphilis
• CMV
• Herpes Simplex 2
• Mycobacterium avium

Chlamydial Diseases

• General considerations:
  • C. psittaci, C. trachomatis; C. pneumonia are human pathogens
  • Birds to humans by aerosol route
• Clinical features of C. psittaci:
  • Fever, cough, myalgia and hepatomegaly
  • Transverse myelitis
  • Meningoencephalitis
  • Cerebellar ataxia
  • Cranial nerve palsy
  • Seizures
• Laboratory evaluation:
  • CSF:
    • >5 lymphocytes
    • Normal protein and sugar
  • Diagnosed by serology

Brucellosis

• General considerations:
  • Caused by B. melitensis primarily
  • Multisystem illness with fever joint pain, sacroiliitis and osteomyelitis
  • Transmitted to humans by unpasteurized milk
• Clinical features:
  • Undulant fever pattern occurs in a 2–4 week cycle
  • Lumbosacral radiculitis (L5–S1) is common
  • Meningitis
  • Epidural abscess with myelitis from vertebral, paravertebral or psoas abscess source
  • Meningovascular disease
  • Encephalitis
  • Subdural empyema
• Laboratory evaluation:
  • CSF:
    • Lymphocytic pleocytosis
    • Low to normal glucose
    • Elevated protein
    • Positive Brucella agglutination tests

Toxoplasmosis

• General considerations:
  • Always in an HIV patient with generalized cerebral disease
  • Retinal involvement
• Clinical features:
  • May selectively involve the conus medullaris of the spinal cord
  • CMV involves the lumbosacral roots

Coccidiomycosis

• General considerations:
  • C. immitis; primarily inhalational route of infection
  • "Valley fever", dry cough with large joint arthralgia; disseminated infection occurs in 1% of patients
  • Osteoarticular and lytic skull and vertebral lesions
  • Occurs in South Western USA
• Clinical features:
  • Lumbosacral spinal cord and root involvement from contiguous vertebral or sacroiliac osteomyelitis
  • Meningitis occurs within six months of the primary infection; primarily a chronic basilar meningitis
• Laboratory evaluation:
  • CSF:
    • Mononuclear or rarely an eosinophilic pleocytosis
    • Low glucose
    • Elevated protein
    • 70% of patients have complement fixing antibody

Spinal Osteomyelitis

• General considerations:
  • Predisposing factors:
    • Elderly debilitated patients
    • Diabetes mellitus
    • Rheumatoid arthritis
    • Catheter placement (epidural for pain management)
    • Surgical procedures
  • Spread:
    • Genitourinary tract
    • Hematogenous spread
      • Batson's plexus (perivertebral venous plexus)
    • Decubitus ulcer:
      • LP through its periphery may cause inadvertent meningitis
    • Phlebitis:
      • Infection spreads to spinal cord by medullary veins
    • Endocarditis:
      • Meningeal seeding often occurs early
  • Infections are initiated by:
    • Neurosurgical and orthopedic procedures most commonly:
      • Discitis; positive T2 weighted image in the disc space and along the anterior and posterior spinal ligaments

Most Common Organisms for Vertebral Osteomyelitis

• Blood cultures are positive in 50% of patients
• Staph aureus (50% of infections)
• Proteus mirabilis
• Candida albicans
• Staphylococci epidermidis
• Citrobacter
• Klebsiella
• Escherichia coli
• Alpha streptococci
• Salmonella
• Tuberculosis
• Brucellosis
• Salmonella (typhoid and paratyphoid)
• Blastomycosis

Spinal Epidural Abscess

• General considerations:
  • Usually they are secondary to systemic infections
  • Alternatively they invade the epidural space from the mediastum, retroperitoneal space
  • Psoas or paraspinal abscess
  • Direct extension from osteomyelitis
  • Penetrating trauma
  • LP
  • Epidural catheters
  • Back surgery.
• Clinical features:
  • Early symptoms are localized back pain or radicular pain
  • The thoracic spine accounts for 50–80% cases > lumbar 20% > cervical 10–25%
  • Early symptoms are overshadowed by para or quadriparesis
  • Peripheral white count and sed rate are usually elevated
• MRI evaluation:
  • Particularly helpful if discitis is the source
• Pathology:
  • Peripheral white count and sed rate are elevated
  • Organisms usually can be cultured

Differential Diagnosis of Acute Epidural Abscess

• Acute epidural hematoma
• Metastasis
• Autoimmune transverse myelitis
• Spinal subdural empyema
• Primary spinal tumor
• Arterial venous malformation
• Embolic disease to the artery of Adamkiewicz
• Spinal hemangioblastoma

Differential Diagnosis of Chronic Epidural Abscess

Chronic Pachymeningitis of the Spinal Cord

• Compression:
  • Idiopathic pachymeningitis
  • Tuberculosis
  • Syphilis (pachymeningitis cervicalis)
  • Meningeal amyloid

Abscess Formation by Location

Cervical

• Retropharyngeal:
  • Dysphagia is a primary symptom (streptococcus)
• Abscess in the neck or supraclavicular fossa:
  • Subclavian vein infections from infected lines
  • Septic involvement of the vertebral artery
    • Inflammation of the vertebral arteries with stroke
    • May also affect blood supply to the brachial plexus

Thoracic Abscess

• Rupture into the pleura
• Dissect along ribs
• Fluctuant subcutaneous mass
• Paravertebral mass
• Ruptures into the epidural space with quadriplegia

Lumbar Abscess

• Flank or psoas abscess
  • Extends into iliac fossa, groin, gluteal fold or thigh
  • Septic medullary spinal veins:
    • Paraparesis

Pott's Disease

• General considerations:
  • Most often thought of as tuberculosis involvement of the spine
  • Less sclerosis in tuberculous spondylosis
  • Tuberculous involvement of the spine is rare in HIV infected patients
  • Most common level is T10 in Americans; in Asians it is cervical and in other ethnic groups it is lumbar (Eskimos)
• Clinical features:
  • Dull aching gnawing pain at the level of involvement
  • Pain is increased by movement
  • Increases during the day; lessens at night
  • Late stages there is a radicular component
  • Low grade fever
  • Anorexia and weight loss
  • Rupture with dissection of pus occurs in 50–85% of patients
  • Paraplegia:
    • Epidural compression
    • Septic thrombophlebitis of spinal cord draining veins
    • Delayed endarteritis
    • Bony sequestrum
    • Granulation tissue
    • Delayed osteoblastic changes

Differential Diagnosis of Pott's Disease

Bacterial Agents

• Staphylococcus aureus:
  • Often seen in IV drug abuser
  • Metastatic to bone marrow which is highly vascular and a major source of growth factors
  • Thoracic > cervical cord

Streptococcus

• Retropharyngeal abscess (from tonsil) also known as Vincent's angina
• Severe dysphagia

Gram Negative Bacteria

• May affect any cord level
• E. coli
• Pseudomonas
• Liver failure a predisposing cause; absence of Kupffer cells

Salmonella

• Most often seen in sickle cell (SS) patients
• Concomitant large joint involvement
• Thoracic > lumbosacral level

Fungal Disease

• Blastomycosis
  • S.E. United States
  • Characteristic skin lesions (raised advancing border)
  • Thoracic cord most often involved (paravertebral mass from lung abscess)

Actinomycosis

• Lung involvement with paravertebral mass
• In the normal flora of the mouth
• Thoracic level of involvement

Cryptococcus

• Lung abscess (found in soil, inhaled)
• Thoracic cord level

Coccidiomycosis

• Lumbosacral involvement (sacroiliac and sacral joint osteomyelitis)
• Contiguous spread to spinal levels

Rarer Differential Diagnoses of Pott's Disease

• Most common tumors are metastatic:
  • 5% of all cancers are metastatic to the spine
• Multiple myeloma with bone destruction
• Ankylosing spondylitis (cervical and thoracic):
  • Myelopathy is precipitated by trauma
• Osteoporosis (thoracic spine with anterior wedge fracture)
• Eosinophilic granuloma (skull, humerus and thoracic spine):
  • Rare vertebral collapse with spinal cord compression
• Osteoid osteoma (usually the pedicle is involved)
• Hemangioma (thoracic vertebral)