NEUROPATHOLOGY MINI-COURSE
FOR RESIDENTS

Presented by William I. Rosenblum, MD
Materials in This Chapter Provided by MG Hadfield, MD

CHAPTER 5 PATHOLOGY OF CNS INFECTIONS

This chapter contains four interrelated sections. The other three sections are:

Section 1 - General Features
Section 3 - Granulomatous Infections
Section 4 - Viral infections, Rickettsial Infections, Prion Diseases

Section 2: Purulent Infections

PRETEST: Answers can be found in the text of this section

1. The principle inflammatory cell for purulent meningitis is the __________.
2. Name a complication of meningitis.
3. True or false: the wall of an abscess is generally thickest on the side facing the ventricle.
4. The collagen in an abscess wall comes from ________________
5. Purulent infections are caused by __________  _________and account for the [majority or minority?] of CNS infections.

THE PURULENT REACTION

The purulent reaction  (image below) is characterized by polymorphonuclear cells mixed with fibrin and bacteria. The great abundance of neutrophils imparts a characteristic creamy, yellow-white appearance to the pus which forms the center of an abscess or fills the subarachnoid space in meningitis.

LEPTOMENINGITIS

A brain with severe meningitis is shown in the image above. Note that the creamy pus completely obscures the underlying cortex in some areas. Pus also tends to collect in the cisterns at the base of the brain. Purulent meningitis is by far the most common CNS infection. Though antibiotics have not materially decreased its incidence, they have markedly increased survival and reduced the complications of this disease.

COMPLICATIONS OF MENINGITIS

The purulent reaction caused by  bacteria may involve the vessels of the subarachnoid space and cause thrombosis resulting in small, cortical infarcts. Thrombosis of the superior sagittal sinus may occur. The underlying brain may also be infected by direct spread from the meningitis and abscesses may form. If the meningitis is allowed to smolder, there will be fibrosis of the subarachnoid space which will impede flow of CSF and cause hydrocephalus. 

This fibrosis may also cause CSF to loculate into arachnoid cysts which may produce pressure effects like a tumor. The cranial nerves may be involved with infection or strangled by reactive connective tissue.

BRAIN ABSCESS

The incidence of brain abscess has been markedly lowered since the antibiotic era. As would be expected, they are found more frequently in individuals who are susceptible to general infection such as diabetics, alcoholics, debilitated and immunosuppressed patients, and the elderly. They are also noted with increased frequency in infants with cyanotic heart disease.

Brain abscesses are most frequently caused by staphylococcus, streptococcus, and pneumococcus and the primary infections are usually located in the sinuses (ear), lungs, or heart valves.

The image above shows a large abscess in the brain. The purulent center is surrounded by a capsule. Often a zone of hyperemia is present adjacent to the wall and there is marked swelling of the adjacent brain tissue.

The evolution of the abscess is as follows: 

• An area of cerebritis begins, in which polymorphonuclear leukocytes are attracted to the invading bacteria.
• Liquefaction of brain tissue rapidly ensues, and at the periphery, a thin rim of granulation tissue composed of new capillaries and fibroblasts is formed. 
• With time, a connective tissue capsule is formed by collagen laid down by infiltrating fibroblasts. Often this is more perfectly formed on the outer aspect of the abscess, presumably due to the contribution of the reservoir of potential  in the adjacent meninges. 
• Due to the poor encapsulation of the medial aspect of an abscess, which abuts upon or is located within the cerebral white matter, the infection tends to form daughter or satellite abscesses medially which may eventually rupture into the ventricular system. 
• Such rupture may lead to rapid death, and in any event, is usually followed by severe ventriculitis and massive meningitis as infected CSF pours into the subarachnoid space. 

Antibiotic therapy greatly decelerates the growth of an abscess, and may allow time for a complete capsule to form after which the abscess may be removed surgically.

The image above reviews the basic structural features of a brain abscess from the histologic point of view. It illustrates (A) the purulent, necrotic center, (B) the thin zone of granulation tissue, and (C) the collagenous connective tissue capsule.