This 29-year-old school teacher patient of mine was in excellent health. One day she came in for an illness visit and reported that she had lost all feeling and strength in her left side for 5 minutes the day before. That sounds like a stroke! Or, being so brief, better classified as a TIA: a transient ischemic attack. Ischemia means loss of blood supply. We classify strokes simply into two categories, if possible. Sudden onset in the day time usually means embolic: a clot that flew into the brain from a heart valve, artery, etc. If you wake up with a stroke, it’s usually thrombotic: a clot occurred during very low blood pressure and cardiovascular responses toward the end of sleep, which is similar to a heart attack, an entity that also occurs most commonly during sleep.
Risk factors for stroke? Smoking, high blood pressure, diabetes, and high cholesterol are the biggies. She had none of these. Age is also a major risk factor, and she was “too young” to have a stroke. Birth control pills? But the risk there is largely confined to older women, especially over 40. Most of us would not prescribe oral contraceptives to a smoker over 40, or maybe even to either.
Well, right or wrong, I examined her and found nothing, and sent her home with careful instruction: any repetition of such an event and you call 911!
Not long after that she had an identical event while teaching at school. The kids got help from another teacher, everyone got excited, 911 was called and transported her to the ER, where she was STILL paralyzed on one side. Neurology was called, and by the time the doc showed up, not long, she had cleared everything and returned to normal. TIA, then, observed, and by definition. 30% of folks in that category overall will have a significant stroke in 30 days. A rule to remember.
The neurologist ordered the standard tests of the day, ultrasound of the neck carotid arteries, especially the affected side of the brain, and the heart. All that was found was mitral valve prolapse. That’s a heart valve between the pumping left ventricle and the left atrium, and outflow from there goes everywhere, including the brain. So, could it be the origin of the stroke? Yes, but why her? The condition is so common at about 6% of the population, that it’s hard to attribute a stroke to that condition. So what about the birth control? See above! Then why her?
I’ve set up a straw man with that. What’s the cause? This, or that?
Here’s a different story: Asbestos. We know it causes lung cancer, especially mesothelioma, which is quite rare in the absence of asbestos. You’ve seen the ads from the attorneys on TV, right? But smoking also, right? OK. Smoking raises the risk of lung cancer perhaps 10 times above a nonsmoker. After all, there’s also radon gas under your Appalachian home, uranium, Xrays, cosmic rays, etc. Not every case is from smoking. Oh, and there’s asbestos, which raises your risk about 3x, for a normal nonsmoker. What about the asbestos worker who also smokes? That risk is about 90X a nonsmoking non-asbestos worker. The risk factors don’t just multiply instead of add, they go even higher. This is an example of synergy. The combination is worse than the individual factors. So, if one works in asbestos, it’s imperative not to smoke! More pertinently, I framed the teacher questions in binary: black and white, either or. But that’s not how life and biology work. There are no unitary causes. Lawyers like unitary causation. The law is written to assign zero or 100% responsibility most of the time, but biology is not law. Nearly everything is multifactorial.
So back to the teacher. Two factors, neither of which was enough to trigger a TIA, but together? Synergistic?
The neurologist told her never to use oral contraceptives and to go on low dose aspirin for prevention of another TIA. Both are good advice. Were she to “break through” and have another TIA or stroke despite these two measures, we also have stronger anti-platelet prescription drugs, but aspirin is very powerful in low doses for this. And more is not better. Two aspirin a day is enough to destroy the anti-platelet effect with its opposite. More is not better is another basic rule of biology. Everything that can do good in one dose can do harm if too much. Even water can poison you fatally, if you drink enough of it. Moderation in all things, said the Roman poet. Still true. But when there’s synergy, even the relatively safe can be threatening.