Wednesday, August 23, 2017

Infections of the Central Nervous System

Hopefully my last "disease infodumping" post for a while! Next week's posts will be on bacterial diagnosis.

Once again, this post started with some brief anatomy. Basically you just need to know what the meninges are, and what the central and peripheral nervous systems are. You also need to know that the blood-brain barrier allows some things to cross (particularly lipid-soluble substances like chloramphenicol), but not others (though this may change during inflammation, as inflammation compromises the blood-brain barrier). I've written more detail than you probably want to know in this earlier post.

Also, just some quick terminology. Meningitis is inflammation of the meninges, encephalitis is inflammation of the brain, and meningoencephalitis is inflammation of both meninges and brain.

Bacterial meningitis

Bacterial meningitis is pretty damn nasty. It starts off suspiciously benign, with a headache, fever and stiff neck, and sometimes some nausea and vomiting. A few patients may develop the distinctive skin rash that does not fade under pressure. Later on, patients experience convulsions and go into a coma. Even survivors of meningitis don't always get away scot-free, as complications include hearing loss, epilepsy, brain damage and learning difficulties. Risk factors for bacterial meningitis include age (infants and young adults), living in a densely-populated community (e.g. university dormitory), compromised immunity, and travelling to an endemic area.

The main causes of bacterial meningitis are S. pneumoniae, H. influenzae and N. meningitidis, though there are many others. Gram-negatives can release endotoxin, and gram-positives can release cell wall fragments, leading to inflammation and shock. Diagnosis can be done via a lumbar puncture and Gram stain. Treatment is generally via broad-spectrum third generation cephalosporins. Close contacts are often treated as well in order to prevent the spread of disease.

N. meningitidis is an aerobic, gram-negative diplococcus that has a polysaccharide capsule. It infects the throat before entering the blood and causing meningitis. When it proliferates in the bloodstream (i.e. sepsis), it can destroy tissue, which may lead to limb amputation. Thankfully, vaccines have been developed against the capsular serotypes, which are A, B, C, W and Y. In Australia, there is currently a free vaccine available against A, C, W and Y for those aged between 15 and 19.

H. influenzae is a gram-negative pleomorphic rod (i.e. it can appear in slightly different shapes). It is part of our commensal flora, but some capsules (particularly type b) can be more pathogenic. There is now a vaccine against H. influenzae type b, which has reduced the mortality rate.

S. pneumoniae is a gram-positive coccus that has a capsule. It commonly lives in the nasopharynx, so a lot of people are healthy carriers. S. pneumoniae is actually the leading cause of bacterial meningitis. There is a vaccine available, but it only covers a fraction of the more than 90 serotypes of S. pneumoniae.

Listeriosis

Listeriosis is caused by Listeria monocytogenes, which is a gram-positive rod. It is excreted in animal faeces and distributed in soil and water, and is spread by contaminated food. Symptoms include fever, headache, altered mental state, neck stiffness and seizures. It is more likely to affect the immunocompromised and elderly. Infection during pregnancy is particularly problematic as Listeria can cross the placenta, which may cause stillbirth. If the foetus makes it to term, they may have brain injury or die at a young age. As such, pregnant women are often advised to avoid high-risk foods, such as soft cheeses.

Leprosy

Leprosy is caused by Mycobacterium leprae, an acid-fast rod related to M. tuberculosis. M. leprae is unique in that it grows in the peripheral nervous system, as well as in skin cells (it prefers outer, cooler areas of the body). It can survive ingestion by macrophages, invade cells of the peripheral nervous system myelin sheath, and cause damage via a cell-mediated immune response.

Tetanus

Tetanus is caused by Clostridium tetani, which is an obligately anaerobic, endospore-forming, gram-positive rod. The bacteria do not spread from the site of infection and there is no inflammation, but they can release neurotoxins upon death. These neurotoxins can spread through the peripheral nerves and blood to reach the CNS, where they block the muscle relaxation pathway. The jaw is affected first, which is why tetanus is also known as "lockjaw," but later on back spasms and so forth can result. Death is usually due to respiratory muscle spasms. Tetanus is vaccine-preventable, so get yo' tetanus shots, kids!

Viral meningitis

In contrast to bacterial meningitis, viral meningitis is more common, but thankfully much less serious (and can sometimes be mistaken for a cold!). It is usually caused by enteroviruses and herpes viruses, and normally resolves without treatment.

Poliomyelitis

Polio is best known for its ability to cause paralysis, but in fact the paralytic form is quite rare, and more likely to occur in people who contract the disease for the first time in adolescence. (That's not to say that it isn't devastating, however.) Most of the time, it causes no symptoms, or only mild symptoms, such as headache, sore throat, fever and nausea. Polio multiplies in the throat and small intestines before invading the tonsils, lymph nodes and intestines. From the lymph nodes, polio can enter the blood, causing viraemia. Often the viraemia is only transient and does not cause disease, but if it is persistent, the virus can enter the CNS and nerve cells, killing off motor neurons, resulting in paralysis. Thankfully, two vaccines (the Salk and Sabin vaccines) have mostly eradicated polio from the world.

Rabies 

Rabies can be acquired from the bite of an infected animal. It has a long incubation period, so if you are bitten, a rabies vaccination will actually help you. The virus replicates in the muscle before travelling along peripheral nerves to the CNS, causing encephalitis. Symptoms include periods of agitation as well as spasms of the mouth or pharynx (which might be set off by just the sight of water). The disease is pretty much 100% fatal in humans. Thankfully, rabies is pretty rare in Australia (I think it's only found in bats). Well, I guess that's compensation for the number of other things that can kill us here!

Arboviral encephalitis

Encephalitis can also be caused by arthropod-borne (insect-borne) viruses, or arboviruses. Symptoms include chills, headache, fever, mental confusion, coma, and death. Examples include Japanese encephalitis and West Nile Virus.

Fungal meningitis

Fungal meningitis is pretty rare, and is more common in the immunocompromised. The main cause of fungal meningitis is Cryptococcus, which is a yeast that reproduces by budding. It has large polysaccharide capsules and is found in soil that has been contaminated by pigeon and chicken droppings.

Protozoal or amoebic meningitis

Protozoal meningitis is also very rare, and is usually always fatal (partly because it is often misdiagnosed as bacterial meningitis until it is too late). One cause of protozoal meningitis is Naegleria fowleri, which causes primary amoebic meningoencephalitis (PAM). It is found in recreational fresh water, and while many people are infected by it at some point, very few people actually become sick. Those that do become sick, though, are pretty much screwed, as there are only a few known survivors.

African trypanosomiasis (sleeping sickness)

African trypanosomiasis is caused by two subspecies of flagellated protozoans, Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense. Both species are spread by tsetse flies. T. b. gambiense causes Gambiense disease, which causes CNS symptoms after a few weeks to months, which eventually lead to death. T. b. rhodesiense causes Rhodesiense disease, which is relatively rare in humans (usually found more in livestock) and more acute, with symptoms occurring in days and death occurring in weeks to months.

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