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Charles Prober: This is Charles Prober. Morgan Theis: I'm Morgan Theis. Charles Prober: We're back to talk about part 2 of 2 of extrapulmonary disease. The reason we created two videos on this, again, is because tuberculosis is such an important world-wide pathogen. In part 2, we're going to focus on TB infection involving the bones, involving the gastrointestinal tract, the central nervous system, and infection of the heart or around the heart, so-called pericarditis. The bones that are most prominently affected, actually the most common, is the vertebral column. Morgan Theis: That's odd. Charles Prober: It is odd because when compared with other kinds of bone infection, for example, acute hematogenous osteomyelitis, which is usually caused by a staph aureus, the spinal column is actually quite uncommon. It occurs, but it's quite uncommon. Bone infections tend to occur in weightbearing areas because they take so much trauma just in daily life; but with staph, those weightbearing joints are usually the hips and the lower extremeties; not so much the vertebral column. But for TB, the vertebral column is commonly affected and I'm not exactly sure why. Morgan Theis: I have a question about that because back pain is a really common complaint. I think it's like 40% of primary care doctors' chief complaints from patients. How would you distinguish TB in the spinal column, in the vertebral column which is very scary, from your muscle strain or something like that? Charles Prober: That's a very important point. The physical examination can be helpful because with an infection of the vertebral columns, as you push along the back, along the spinal column, you may encounter an area of exquisite tenderness and pain. That would be more suggestive of a bone infection and the bone infection could include tuberculosis. That's all I'm going to say about TB involving the bones. It can involve other bones, but remembering the vertebral column is particularly important. There's a name that is associated with vertebral TB that I'll mention called Pott's disease. Pott's disease is simply tuberculosis of the spinal column. Radiographically what you see is two adjacent vertebrae that tend to be eroded with the infection. Pott's disease. The next form of tuberculosis that I'll mention, extrapulmonary tuberculosis, involves the central nervous system. It's much less common than these other forms that we've already spoken about; estimated to maybe be about 5% of infections. But the problem is, because it involves the central nervous system, it can be very serious, leading to substantial long-term consequences, morbidity, and also potentially leading to death. Though less frequent, it is very important. The thing about tuberculosis involving the central nervous system compared to other regular bacteria, like pneumococcal meningitis or meningococcus, is that tuberculosis tends to be subacute in presentation. The symptoms and signs don't come on over a couple of days, they come on over a couple of weeks or even longer. They sneak up on the patient in terms of causing disease. At the very beginning, the symptoms may be really quite nonspecific, meaning they don't point to any particular kind of infection of even site. The patient may have a couple of weeks of a headache or a little bit of confusion, some slight mental changes. associated with nonspecific things like fever, and feeling rundown and not wanting to eat. sort of those general symptoms that we've also talked about in the context of TB in the chest. But, if it's not recognized as a problem sneaking up on the patient and it continues to progress, the patient may have a progressive decreased level of consciousness and some patients present with very advanced disease, coming in in coma. As you might anticipate, it's better to recognize this earlier rather than later. There are good data, when you treat TB involving the central nervous system, if the infection is treated very early on with the nonspecific symptoms, the patients often do quite well; whereas, if it's not treated until the patient comes in in coma, the patients often do very poorly. Morgan Theis: We were talking about the CNS site. You were talking about meningitis. Is that the main thing that you see or do you see anything else in the central nervous system? Charles Prober: Meningitis is the main thing you see. You've drawn at the base of the brain in green the inflammation, and that's a well placed drawing because you are correct that TB often involves the so-called basilar area of the brain. The reason that that is important is it's an association that will make you think more of TB, but also what often happens is this inflammatory response at the base of the brain entraps the cranial nerves that come off the base of the brain and patients often present with craniopathies, abnormalities in their cranial nerves. So that should be a tip-off to consider tuberculosis more likely. The other important element of it involving the base of the brain is that the infection interferes with the flow of spinal fluid, so it blocks the flow of spinal fluid and these patients may develop increased spinal fluid in the ventricles or hydrocephalus. That's another tip-off that the infection might be involving tuberculosis. When you are evaluating a patient with suspected TB meningitis, or any meningitis for that matter, a spinal tap is usually part of the workup, after you've assured yourself that it's safe. With tuberculosis, the typical results of the spinal tap is there are white cells present. The white cells are often lymphocytes in their nature and they number often in the range of several hundred to maybe a couple of thousand. Also, the protein concentration in the spinal fluid tends to be quite increased and progressively so; so it can go 100, 200 or several hundred. The glucose tends to be a little bit depressed but not as severely so as acute bacterial meningitis caused by pneumococcus. The glucose, instead of being zero like it can be with pneumococcus, may be in the 20 to 30 range. You may see, when a stain is done for tuberculosis, some of those little red characters under the specially stained CSF, but that only occurs about 1/3 of the time that you can actually see them, even with the special stains, microscopically, so you culture them like for other forms of TB and the culture is positive about 80% of the time. There's also a PCR test available for tuberculosis that especially the developing world is used to augment our ability to diagnose it. That's tuberculous meningitis. We're not talking much about treatment here, but one thing that I will throw in is the role of steroids in tuberculous meningitis. More often than not, clinicians do use steroids for this form of TB infection, although it's not without some controversy about whether they should be used. A couple of final things about extrapulmonary sites and then we'll wrap up. The gastrointestinal tract, the gut, can be involved with tuberculosis as well, but it's really quite uncommon, maybe 3% or so, and quite nonspecific like most other forms of tuberculosis. The infection for reasons that aren't clear to me often involves the terminal ileum and the cecum, so down there around the appendiceal area with often a lot of lymph node involvement. One can have obstruction. If the infection is not recognized and treated, it can erode through the gastrointestinal tract, so perforation, and you can get peritonitis and air in the peritoneal cavity. The whole myriad of symptoms that occurs in other parts of the body can also involve the gastrointestinal tract. Morgan Theis: How do you actually get it into the gastrointestinal tract? Can you ever eat stuff that has TB in it, or are you getting it throughout your own body? Charles Prober: Actually both. You can actually ingest, or eat, certain kinds of TB bugs, microbacteria bovus, which is what it sounds like, microbacteria and it comes from cows, can contaminate cow milk. If you ingest unpasteurized cow milk, then that can occur and that's one way you can get TB involving the gastrointestinal tract. The other is that if you have pulmonary disease with tuberculosis and you cough up the TB bacilli, you can then swallow them and that can cause the gut to be infected as well. Another form of tuberculosis, again in the uncommon variety, but continue to emphasize the great imitator characteristics of this infection, tuberculosis can cause infection around the heart, so TB pericarditis. This can be either from direct extension of lymph nodes around the heart that often are involved when you have pulmonary disease, or it also can spread directly through the blood. It seems to be a more common type of infection in the elderly, whose immune system is not as robust as the youth, or in patients who have compromised immunity for other reasons, for example patients infected with human immunodeficiency virus. Involvement of the heart is not good. Mortality is very high, estimated to be almost 50%. The infection, because it has a vigorous inflammatory response associated with it, can cause so-called constrictive percarditis, so the pericardium actually squeezes the heart so the heart can't contract effectively and one dies of heart failure as a result of that. Those are the key elements with regards to extrapulmonary tuberculosis. There are other organs that can be involved that are very, very uncommon, the adrenals and so forth, but the main sites of involvement, lymph nodes very high on the list, and then less likely the other ones that we've spoken about. Morgan Theis: Another great reason to treat this as soon as you can so you don't get all of these extensive complications. Charles Prober: Exactly.