Meningitis
Photo 24
Photographs 24 and 25 are typical of the brains of patients who died with fulminant purulent bacterial meningitis. A typical patient may be an army recruit housed in barracks in close contact with individuals who are nasopharygeal carriers of n. meningitidis. The previously unexposed recruit quickly develops fever, severe headache, photophobia, irritability and a stiff neck. What findings do you expect in his spinal fluid. Inflammatory Cells?Blood? Protein-up or down? Glucose-up or down? Gram stain? How about the pressure of his CSF. He may also express severe systemic symptoms. What are they? Why do they occur? The name of this syndrome is the Waterhouse-Friderichsen Symdrome. Going back to these photographs you should note that this is a process confined to the subarachnoid space.
Photo 26
Compare these photos of acute purulent meningitis with photo 26, a chronic predominantly basilar meningitis. Note how difficult it is to see the vessels at the base of the brain because of overlying meningeal inflammation and fibrosis.The distribution in this case is typical of that seen in granulomatous infections such as tuberculosis. Here the patient will have a much more subtle slowly evolving picture which is easily mistaken for non-infectious processes. Multiple cranial nerve findings, hypothalamic dysfunction and gradual elevation of spinal fluid pressure are seen. In predomimnantly basilar infections CSF outflow obstruction is likely. It will lead to slowly developing hydrocephalus. How might that be manifest? Hydrocephalus due to leptomeningeal fibrosis is also a risk in patients treated successfully for acute purulent meningitis. It may occur many months later.
Photo 27
Look at photo 27. This depicts an inflammed vessel within an area of letomeningitis. Veins and arteries included within the inflamed subarachnoid space may become inflamed. Inflamed vessels are prone to thrombosis. In basilar inflammation, when the vessel is an artery, this can lead to relatively large areas of infarction.
Cerebritis & Cerebral Abcess
Photo 28 & Photo 29
Photographs 28 & 29 depict an area of focal cerebritis ( focal infection and inflammation) in 28 and fully formed abcesses in Photo 29. Abcesses develop from areas of cerebritis. What are likely sources of this type of CNS infection. You should have a list which includes local sources as well as systemic ones.
Photo 32 & Photo 32a
In contrast to the macro-abcesses above, 32 depicts a pattern usually seen in severe sepsis when circulating organisms are either bacteria or small yeast fungal forms, namely micrabcesses. These multiple small lesions tend to be in the distal portions of the cerebral circulation.
Viral Infections
Photo 33 & Photo 33a
Photo 34a & Photo 34b
Slide 33 depicts the brain of a person who died within a few days of developing a rapidly evolving picture dominated by headache, temporal lobe seizures, elevated intra-cranial pressure and nuchal rigidity. Do you see the subtle findings in the insula region on the right side. What is you suspicion regarding diagnosis? This patient obviously died. In addition to severe insula temporal lobe meningoencephalitis, the image depicted in 34a was seen. What is it? What types of cells were predominantly seen in the inflammation? What is the most likely diagnosis? Describe a test that would be specific? (answers could include, demonstration of specific protein or nucleic acid sequence). Could you do these tests in life? Do you need a brain biopsy? How about spinal fluid? Are you likely to have started therapy before all the answers are in? The answer is, yes! Herpes simplex meningoencephalitis is a good example of an acute productive, lytic viral infection which excites a cell mediated inflammatory response, rich in lymphocytes, depicted above in photo 34b. Herpes simplex virus can exist in a latent state, within ganglia such as the trigeminal ganglia. Activation usually results in distal spread, along the nerve away from the CNS, with the production of benign surface lesions, such as "cold sores". In this instance, re photos 33 and 34, the virus traveled to the CNS with disastrous results. Other lytic CNS viruses, like the Poliovirus, are blood borne. In addition to herpes simplex, what other virus do you know that travels along peripheral nerves to gain access to the CNS? How about one whose trip to the CNS allows crucial time for vaccination. Click on here to see the characteristic cytoplasmic inclusion body of the entity I am referring to. In contrast to polio and herpes simplex, rabies does not appear to be a very lytic infection. If the individual survives he(she) may have good functional recovery.
The AIDS virus, HIV, apparently enters the CNS early in the infectious process. Brain perivascular macrophages, systemic macrophages which enter and leave the CNS, and microglia, a resident macrophage lineage population within the CNS, appear to be the major infected cell types. Photograph AIDS1, below, an immunohistochemically stained section shows you typical brain perivascular and parenchymal cells of macrophage lineage. The microscopic findings in AIDS encephalitis are not specific. There is palour of white matter, perhaps due to edema and small inflammatory foci throughout white and grey matter, composed mainly of macrophages and few lymphocytes, microglia nodules. Typical HIV infected- multinucleated giant cells can be seen in these foci and associated with perivascular areas. Photograph AIDS2 below depicts a perivascular focus of HIV giant cells. You should keep in mind that giant cell formation is seen in other viral infections, such as measles, as well as in other types of infectious inflammatory reactions, as in tuberculosis and fungal infections. In AIDS, because of severe immunodeficiency, we commonly see several infectious processes within the CNS in addition to HIV. These include fungal and bacterial organisms as well as other viral infections, in particular: cytomegalovirus (CMV) encephalitis, primary brain B-cell lymphoma, an EB virus associated malignancy, and Progressive Multifocal Leukoencephalopathy (PML), a papova virus infection of glia cells which produces demyelination.
Photographs AIDS1 and 2:
Some viruses can elicit a wide spectrum of host responses. The measles virus, for example, can produce 1. acute lytic lesions, not typically of CNS, 2. Post viral immune mediated "allergic' demyelinating lesions of either CNS or PNS, allergic encephalomyelitis or allergic peripheral neuritis, and 3. Subacute Sclerosing Panencepahalitis (SSPE), a Conventional Slow Viral Infection of CNS involving both grey and white matter. To learn more about viruses and demyelinating lesions go to the second "click-on". in the demyelinating disease section which includes Post Measles Encephalomyelitis and PML. The pathogenesis of viral diseases is a fascinating subject that is still very much being written.
