Infections & Myelopathy

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INFECTIONS & MYELOPATHY

General
CSF features
Geographic distribution

Abscess
AIDS
Central European encephalitis
CSF eosinophilia
Dengue
Enterovirus: D68; 71
HIV
HTLV I & II
Parasites
Poliomyelitis: Acute
Spirochete
Tuberculosis
Varicella zoster
West Nile
Whipple's

Neuromuscular Disorders

Tabes dorsalis

General features ⁴

Geographic Distribution

Viruses
- Human T-cell lymphotropic virus: Japan, sub-Saharan Africa,Middle East, Caribbean islands, and Central and South America
- Poliovirus: Sub-Saharan Africa, Middle East, Indian subcontinent
- Japanese encephalitis: China, South & Southeast Asia
- Tick-borne encephalitis; Europe, Russia, China
Bacteria
- Borrelia burgdorferi (Bannwarth meningoradiculitis): Central Europe, US (New England, Atlantic coast, northern Midwest, Pacific Northwest)
Parasites
- Gnathostoma spinigerum: Southeast Asia (Cambodia, Laos, Myanmar, Indonesia, Philippines, and Malaysia)
- Echinococcus granulosum (Hydatid): Middle East, South America, New Zealand, Mediterranean coast
- Taenia solium: Central and South America, Sub-Saharan Africa, South & Southeast Asia
- Schistosoma mansoni: Central and South America
- S. mansoni & haematobium: Sub-Saharan Africa
Fungi
- Blastomyces dermatitidis: Southern, Midwestern, Eastern United States
- Coccidioides immitis: Southwestern US, Mexico, Central & South America

Myelopathies: CSF features

	Protein	Glucose	Cells
Abscess	High	Low	Neutrophils
Tuberculosis	High	Low	Lymphocytes
Virus	High	Normal	Lymphocytes
Fungus	High	Low	Lymphocytes
Parasite	High	Normal	Eosinophils
Immune	High	Normal	Lymphocytes

Polio

Polio virus
- Enterovirus
  - RNA, single stranded
  - Subgroup of Picornaviridae
  - 3 serotypes
    - All can cause paralytic disease
    - Type 1: Most common cause of epidemic paralytic polio
- Transmission: Fecal-Oral
- Human susceptibility
  - 2° to Polio virus receptor (PVR; CD155; NECL5)
- Spread: Lymphatics to Blood to CNS
- Neurons: Virus replicates & releases RNA into cytoplasm
Epidemiology
- Outbreaks: Most common in late summer
- Affected patients: Usually > 6 month of age; 6 mo to 3 years
- Most cases: Afghanistan, Nigeria, Pakistan, Egypt, Syria
- Paralytic disease
  - 1% to 2% of infections
  - More likely with increased age
  - Male > Female
Course: Events after viral exposure
- Asymptomatic with viremia: 90% to 95%
- Minor illness: 1 to 5 days after exposure
  - Fever
  - Malaise, Myalgia
  - Sore throat, GI upset
- Major illness
  - Timing: 4 to 20 days post-infection; Usually < 1 week
  - Aseptic meningitis
  - Fever
  - Pain
    - Headache
    - Stiff neck & Back pain: Muscle stiffness
- Paralytic disease
  - Frequency
    - 50% of those with major illness
    - 0.1% to 1% of infected patients; Mean 0.2%
  - Timing: After 2 to 5 days of illness; Up to 3 weeks
  - Motor: Weakness +
    - Onset: Fulminent, Acute, or Subacute
    - Focal or Asymmetric
    - Proximal > Distal
    - Legs > Arms > Bulbar (20%)
    - Tendon reflexes
      - Early
        
        May be increased
      - Paralytic phase
        
        Reduced in affected limbs after 12 to 24 hours
    - Muscle atrophy: After 2 to 3 weeks
    - Course
      - Improvement
        
        Onset: After few weaks
        
        Maximal: At 6 to 9 months
      - Residual weakness: 60% to 70%
  - Dysautonomia, Acute
    - Blood pressure instability
    - Cardiac arrhythmia
    - GI: Atony, Constipation
    - Urinary retention
    - Sweating: Increased or Decreased
  - Other clinical
    - Fasciculations: Localized
    - Pain: Intense myalgia, hyperesthesia
  - Mortality
    - Children: 2% to 5%
    - Adults: 15% to 30%
  - Differential diagnosis
    - Viral: Anterior horn cell disease
      - Poliomyelitis
      - Enterovirus: D68; 71
      - Coxsackie A & B
      - Echoviruses
      - West Nile
    - Immune: Acute neuropathies
    - Porphyria
    - Toxins
    - Myelitis
  - Lab
    - CSF
      - Pleocytosis
        
        Acute: Polys
        
        > 72 hours: Lymphocytes
        
        Clear from CSF after 1 week
      - Protein: High; Increase over 1st 3 weeks
    - Diagnostic
      - Serology
        
        Serum: 4-fold titer rise
        
        CSF: IgM poliovirus specific
      - Culture: Stool positive in 90% by 20 days
    - Electrodiagnostic
      - Early
        
        Selective loss of motor axons at 7 to 10 days
        
        CMAP amplitudes small
        
        NCV: Normal velocities
        Sensory: Normal
      - EMG
        
        Acute
        
        Fibrillations & PSW: After 2 to 3 weeks
        
        Reduced recruitment
        
        Chronic
        
        CMAPs: Large amplitude; Long duration
    - Spinal cord pathology: Anterior horn
      - Inflammation
        
        Perivascular
        
        Mononuclear cell
      - Anterior horn cells
        
        Loss
        
        Abnormal morphology
        
        Chromatolysis
    - Muscle: Chronic
      - Fiber type grouping: Large
Also see
- Post-polio syndrome

Wikipedia Polio: Leg atrophy Egypt 1403-1365 BC
From Bramwell: Atlas of Clinical Medicine Polio: Arm atrophy

From Bramwell: Diseases of the Spinal Cord

Polio: Small ventral horn

Polio: Abnormal motor neuron cell bodies

Polio: Spinal cord perivascular inflammation

From Barnes & Miller: Brain 1907;30;101

Other Viruses

Varicella zoster

Transverse myelitis

Acquired Immunodeficiency Syndrome (AIDS)

R. Schmidt

HIV myelopathy

Cytomegalovirus
- Lumbosacral polyradiculopathy
HIV: Chronic myelopathy
- Frequency: 5% to 20% of late stage AIDS
- Onset: Late stages of AIDS
- Clinical
  - Weakness: Legs; Symmetric or asymmetic
  - Pyramidal signs: Leg spasticity
  - Urinary frequency/incontinence: May be presenting feature
  - Sensory loss: Mild
  - Associated CNS features: Dementia
  - Course: Progressive
- Pathology
  - Vacuolar
  - Prominent posterior column involvement

Human T-cell Lymphotrophic Virus, Type I (HTLV I)

Epidemiology
- Common in West Indies (Caribbean basin), Japan, Centrla Africa, Iranian Jews
- US risk groups
  - Intravenous drug abusers
  - Immigrants from high-risk areas
  - Often associated with coinfection with HTLV-II or HIV
  - Endemic in certain parts of the southeastern US (Native Amerindian population)
- Myelopathy in 1% of patients with infection
- Most infected patients are asymptomatic
- Transmission
  - Vertical transmission: Mother to child
    - Through breast-feeding: Especially past 6th month
    - Related to: High maternal provirus levels & High HTLV-I antibody titer
  - Sexual
    - More common male to female
    - Inefficient
  - Parenteral: Via lymphocytes
    - Blood
    - Organ transplantation
Clinical
- Myelopathy: Progressive spastic paraparesis (HAM/TSP)
  - Nosology
    - Tropical spastic paraparesis
    - HTLV-1-associated myelopathy (HAM)
  - Genetic association
    - Interferon, λ-3 (IFNL3 IL28B) Gene Polymorphism SNP rs8099917 Genotype GG: OR 7.16
  - Clinical
    - Onset
      - Age: 3rd to 5th decade
      - 20 to 30 years after initial infection
      - Abnormal gait
      - Slow development: Usual pattern; Over years
      - Rapid development: Reported after blood transfusion or organ transplantation
    - Motor: Leg weakness
    - Pyramidal signs
      - Arms & Legs
      - Hyperreflexia
      - Spasticity
    - Symmetric
    - Autonomic: Urinary & fecal incontinence
    - Sensory: Minor changes
    - Other occasional neural features
      - Optic atrophy
      - Sensorineural hearing loss
      - Cerebellar symptoms
      - Cognitive deficits
  - Pathology
    - Chronic inflammation: Middle to lower thoracic cord
    - Spinal cord atrophy: Involvement of pyramidal tracts & posterior columns
    - Meningeal thickening
- Motor disorder: "ALS-like syndrome"; Often atypical features
  - Epidemiology: Described in few patients
  - Clinical: Variable syndromes
    - Pyramidal features
    - Lower motor neuron
      - Weakness: Often proximal
      - Muscle wasting
      - Fasciculations
    - Urinary incontinence
  - Pathology: Anterior gray horn of spinal cord; Ventral spinal nerve roots
  - EMG: Denervation, acute & chronic, in lower thoracic paraspinal muscles
- Polyneuropathy³
  - Frequency
    - Clinical: 1% to 6% of infected patients; ? More with associated myelopathy
    - Electrophysiological findings: Up to 40% to 50%
  - Clinical
    - Sensory loss: Distal legs
    - Tendon reflexes: Less at ankles than at knees
    - May occur in absence of myelopathy
    - Treatment: Reports of improvement when inflammation found on biopsy
  - NCV: Axon loss
    - Normal velocities
    - Mildly reduced SNAP amplitudes in legs
  - Pathology
    - Reduced density of large and small myelinated axons
    - Regenerating clusters
    - Inflammation: Perivascular; CD4 & CD8 cells
  - CSF: High protein; Pleocytosis
- Myopathy
  - Inclusion Body Myositis
    - Weakness: Proximal
    - Course: Slowly progressive
    - Serum CK: Mildly elevated
    - Muscle pathology: Myopathy; Vacuoles; Endomysial inflammation
  - Inflammatory myopathy
    - Variable association with HTLV-1 infection
    - Occcasional patients: Asymmetric proximal weakness
    - Serum CK: May be high
    - Treatment: Reports of improvement with corticosteroids
    - HAM/TSP patients: Inflammation in muscle may be found
- Other syndromes with HTLV-1 infection
  - Sjögren's syndrome
  - T-cell leukemia: Adult
  - Uveitis
  - Arthropathy & synovitis
  - Pulmonary abnormalities
  - Thyroiditis
Laboratory
- CSF: Mild increase in protein & cells; High IgG
- MRI
  - Spinal cord: Increased T2 signal; Cord atrophy
  - Subcortical: Leukoencephalopathy
- False positive: Lyme; Syphilis; Antiphospholipid antibody
Possible treatments
- Methylprednisolone, IV
- Interferon-alpha ¹

Human T-cell lymphotrophic virus, Type II ²

African-American, often Indian descent
Onset: 34 to 70 years
Clinical
- Most patients asymptomatic
- Spastic paraparesis or quadriparesis
- Spinal sensory loss
- Progressive
  - Non-ambulatory in < 5 years
  - Faster than HTLV I
CSF: ± high protein, ± oligoclonal bands

Spirochetes

Syphilis
- Meningovascular
- Arachnoiditis
- Tabes dorsalis
Lyme
- Spastic paraparasis
- Bladder dysfunction

Tuberculosis

Arachnoiditis & meningitis
- Often progresses to complete block
- Very high CSF protein
Tuberculoma: Paraspinal or Vertebral; Rarely intramedullary

Parasitic infections

Types
- Schistosomiasis (Trematode): Granulomatous intrathecal mass lesions
- Echinococcus granulosis (Cestode): Hydatid cysts
- Taenia solium: Leptomeningeal cysts
- Paragonimus westermani (Trematode): With pulmonary & cerebral disease
Laboratory: Eosinophilic cells in CSF

Abcesses

Locations
- Extradural
- Intramedullary (rare)
Associated with bacteremia

Whipple's disease

Organism: Tropheryma whippelii
Clinical
- Epidemiology
  - Middle age
  - Males > Females
  - More common in farmers or with expoure to dirt
  - Noth America & Europe
- Cervical myelopathy: Spastic quadriparesis
- Other signs of CNS Whipple's: May be absent
  - CNS
    - Dementia
    - Myoclonus
    - Ataxia
  - Eye: Supranuclear ophthalmoplegia; Visual loss; Nystagmus; Ptosis
  - Polyneuropathy: Rare
  - Oculofacial skeletal myorhythmia
  - GI signs: Diarrhea; Abdominal pain
  - Systemic: Arthralgias; Fever; Weight loss
- Progression: Months
Lab
- CSF: Often normal
- MRI: High signal in CNS, Spinal cord (cervical)& Medulla
- Diagnosis
  - PCR of small intestine cells
  - PAS positive GI mucosal cells
External link: Ophthalmic Whipple's

CSF eosinophilia

Helminthic infections
- Nematode: Rarely cause 1^o spinal disease
  - Angiostrongyliasis
  - Gnathostomiasis
  - Strongyloidiasis
  - Toxocariasis
  - Trichinosis
- Cestodes
  - Cysticercosis
  - Echinococcosis
- Trematodes
  - Paragonimiasis
  - Schistosomiasis
Lupus erythematosis
Sarcoidosis
Drug or contrast agent reactions
Hodgkin's lymphoma
Idiopathic hypereosinophilic syndrome

Also see Infections & Neuromuscular Disease
Return to Myelopathies
Return to Neuromuscular Home Page

1. Neurology 1996;46:1016-1021
2. Ann Neurol 1996;40:714-723
3. J Neurological Sci 2003;206:17�21, Semin Neurol 2005;25:315-327
4. Continuum 2012;18:1351-1373

10/13/2022