NEUROPATHOLOGY- INFECTIONS OF THE CNS

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I. MAJOR CATEGORIES OF CNS INFECTIONS
II. CERTAIN GROUPS OF INDIVIDUALS ARE MORE LIKELY TO SUFFER CNS INFECTIONS THAN OTHERS
III. BACTERIAL INFECTIONS
IV. FUNGAL INFECTIONS (MENINGITIS)
V. TUBERCULOSIS
VI. NEUROSYPHILIS
VII. PARASITE INFECTIONS
VIII. VIRAL INFECTIONS

VOCABULARY
Terms you should be familiar with:

Meningitis
Tuberculoma
Neurosyphilis
Unconventional Transmissible Agents
Neural tube defects
Disseminated microabscess
Meningeal neurosyphilis
Meningovascular neurosyphilis
Tabetic neurosyphilis
Neurosyphilitic optic atrophy
Paretic neurosyphilis
Gummatous neurosyphilis
Cowdry type A inclusion
Negri body
Herpes simplex encephalitis
Rabies
Poliomyelitis
Herpes zoster
Progressive Multifocal Leukoencephalopathy

OBJECTIVES: The objectives of these hours are to become familiar with the types of organisms that affect the CNS, to understand the circumstances under which the CNS becomes infected, and to become familiar with the pathogenesis, pathologic features, and clinical features of some of these infections.

I. MAJOR CATEGORIES OF CNS INFECTIONS

• Bacterial: meningitis and abscess
  
  
• Fungal: meningitis and abscess
  
  
• Tuberculosis: tuberculoma and meningitis
  
  
• Neurosyphilis
  
  
• Parasitic
  
  
• Viral
  
  
  • acute
  • chronic
    
    
• Unconventional transmissible agents

II. CERTAIN GROUPS OF INDIVIDUALS ARE MORE LIKELY TO SUFFER CNS INFECTIONS THAN OTHERS

• The very young and the very old
  
  
• Alcoholics
  
  
• Patients with neural tube defects
  
  
• Patients with CNS trauma, or after neurosurgical intervention
  
  
• Patients who are immunocompromised for any reason
  
  
• Patients with sickle cell anemia
  
  
• Patients with cardiac and pulmonary anomalies

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III. BACTERIAL INFECTIONS

Forms of the disease include meningitis, intracranial thrombophlebitis, brain abscess, epidural abscess, and subdural empyema.

• Purulent meningitis
  
  
  • Origin
    • Hematogenous - bacteremia, infected emboli, septic thrombophlebitis
    • Direct extension - otitis, sinusitis, mastoiditis, brain abscess.
    • Penetrating wounds
    • Developmental anomalies (neural tube defects)
  • Common organisms vary depending on the age of the patient
    • Infancy
      • E. coli
      • Group B Strep
      • Staphylococcus
      • L. monocytogenes
    • Childhood
      • H. influenzae
      • Pneumococcus
      • Meningococcus
    • Adulthood
      • Meningococcus
      • Pneumococcus
  • Pathology
    • Hyperemia of meningeal vessels and outpouring of polymorphonuclear (PMN) leukocytes
    • Location of the subarachnoid exudate- pus tends to accumulate along the course of cortical veins
    • Cerebral edema- slight to moderate
    • Nerve cells appear normal at this stage, though function may be deranged
    • CSF - mostly PMN, high protein, low sugar, high pressure, and positive cultures
    • May heal with complete resolution but can heal with fibrosis and hydrocephalus.
    • Meningococcal meningitis frequently accompanied by meningococcemia, myocarditis, petechial adrenal hemorrhage, and sudden death.
      
      
• Abscess (what follows applies for both bacterial and fungal organisms)
  
  
  • Origin
    • Direct extension- sinusitis, mastoiditis
    • Infected emboli- lung the commonest source (abscess, bronchiectasis, occasionally pneumonia). Common with pulmonary AV fistulae and R to L cardiac defects
    • Direct implantation- penetrating trauma
  • Pathogenesis of brain abscess
    • Experimental data suggest preexisting necrosis is required. This probably results from venous infarction secondary to thrombophlebitis when an abscess originates from direct extension from adjacent focus; infected emboli presumably produce occlusion of a small artery or arteriole.
    • Necrosis leads to frank suppuration.
    • After a week or two, a fibrous wall (derived from the vasculature) that may be several mm thick after 4-5 weeks forms.
    • Outside the fibrous wall, there are perivascular, chronic inflammatory cells and white matter edema. An intense astrocytic gliosis takes place with formation of a glial scar.
    • Some lymphocytic pleocytosis of CSF can occur, but CSF exam is not usually helpful and can lead to rapid death from herniation.
  • Location
    • Mastoiditis most commonly leads to temporal lobe or cerebellar abscess.
    • Frontal sinusitis and ethmoiditis most commonly lead to frontal lobe abscess.
    • Metastatic (hematogenously derived) abscesses may occur anywhere.
  • Disseminated microabscesses are usually due to sepsis or acute bacterial endocarditis. Common organisms are Staph and Candida. Patients always have underlying immunosuppression.

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IV. FUNGAL INFECTIONS (MENINGITIS)

• Cause a chronic meningitis, in some instances, granulomatous. Brain and cord may be involved. Most are frequently encountered in an immunocompromised host. Virtually always a secondary infection of the brain.
  
  
• The most common fungal infection in this part of the world is that due to cryptococcus neoformans. The meningitis is more insidious in onset than that of bacterial, with headaches, nausea, vomiting, diplopia, and lethargy. Patients are frequently afebrile. Organism not seen on direct exam of the CSF (India ink, cryptococcal antigen, and cultures are useful).

V. TUBERCULOSIS

• Pathologic response is a typical granulomatous inflammatory response of tuberculosis
  
  
• Three main CNS lesions:
  
  
  • Solitary tuberculoma- caseous encapsulated mass
  • Multiple tuberculomas of brain and meninges. Seen in miliary tuberculosis. Microscopic or a few mm in size
  • Tuberculous meningitis
    • Previously existing tuberculoma of brain or meninges required with continuous seeding into subarachnoid space; i.e. rich focus.
    • Sequence of pathologic events similar to that in bacterial meningitis except for granulomatous features of the inflammation; caseous necrosis; panarteritis with tendency for arterial thrombosis and atypical midline infarction. On healing there is meningeal fibrosis leading to hydrocephalus and high incidence of cranial nerve palsies.
    • CSF: predominance of lymphocytes with high protein, low sugar, and positive culture.

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VI. NEUROSYPHILIS

The various forms of this entity are making a comeback in the age of AIDS. The initial infection is probably always meningeal. This may lead to:

• Meningeal neurosyphilis- A lymphocytic meningitis. May remain asymptomatic. May lead to arteritis or meningeal fibrosis with obstruction to flow of CSF.
  
  
• Meningovascular neurosyphilis- Represents predominance of secondary lesions (syphilitic endarteritis) with thrombosis and ischemic effects in brain and spinal cord.
  
  
• Tabetic neurosyphilis (tabes dorsalis)- Infection extends around and probably into posterior roots of the spinal cord (reason for this selective involvement is not clear) with root inflammation and degeneration. Posterior column degeneration is secondary to the root involvement.
  
  
• Neurosyphilitic optic atrophy- Probably extension of infection into optic nerve with secondary inflammation and degeneration.
  
  
• Paretic neurosyphilis (general paresis)- Picture is lymphocytic meningeal and perivascular inflammation, cortical nerve cell degeneration, small infarcts, astrocyte proliferation, and microglial activation with production of elongated rod forms. Pathogenesis unknown.
  
  
• Gummatous neurosyphilis- Now very rare

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VII. PARASITE INFECTIONS

Cysticercosis important in some parts of the world. The larva form cyst-like structures in subarachnoid space (producing meningitis), in ventricular system (producing hydrocephalus), and in brain (producing focal lesions).

VIII. VIRAL INFECTIONS

• General Points
  
  
  • Viral infections are prone to localize in specific areas of the nervous system- concept of tropism.
  • Virus must be inoculated into host.
  • Routes of spread to the CNS:
    • Neural
    • Olfactory
    • Hematogenous (which most viruses use)
      
      
• Acute Viral Infections- The pathology of acute viral infections is very uniform regardless of the specific virus involved, and consists of:
  
  
  • Acute degeneration of nerve cell
  • Microglial activation forming microglial nodules at sites of degenerating neurons
  • Perivascular lymphocytic infiltrates
  • Astrocytic proliferation.
  • Intracytoplasmic or intranuclear inclusions may be characteristic (e.g., Cowdry type A inclusion in herpes simplex type I) or specific (e.g., the Negri body of rabies) for the disease.
  • Examples to be discussed in class:
    • Herpes Simplex Type I Encephalitis.
    • Rabies
    • Poliomyelitis.
    • Herpes Zoster (shingles).
      
      
• Chronic Viral Infections- signs and symptoms of infection develop over weeks to months. Prototypical example to be discussed in class: progressive multifocal leukoencephalopathy.

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Go Back to Neuropathology

[ Introduction and Objectives | Basic Reactions of the CNS | Vascular Disease | Trauma to the CNS | Alcohol and the CNS | Infections of the CNS | Tumors of the CNS | Diseases of the Myelin Sheath | Spinal Cord Disease | Muscle Disease | Congenital Anomalies of the CNS | Neuropathology of AIDS | Degenerative Diseases of the CNS | Dementia and Related Issues | Unconventional Transmissible Agent (Prion) Diseases ]

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[ CATS Home | About CATS | CATS Teaching Modules | UVM Department of Pathology | Other Pathology Sites | UVM College of Medicine | UVM ]

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Questions? Comments? Send a message to the CATS guru: jkessler@salus.uvm.edu