| Transcript |
So today we're going to be talking about anisocoria. "-coria" means pupil, "iso" is same and "an-" is not, so "not the same sized pupil." When we're dealing with anisocoria we want to figure out is it the bigger pupil that's the problem or is it the smaller pupil that's the problem. In order to test this hypothesis, we're just going to shine a light into the eye. If the bigger pupil doesn't constrict, then that's the problem pupil. However, if the anisocoria is greater in the dark that means that the little pupil is not dilating. So, testing the light reaction and the size of the pupil in the light and in the dark is how we determine when the anisocoria is from the smaller pupil or the larger pupil. So, let's just take the first scenario which is the light and then we'll do the dark. If the anisocoria is greater in the light that means the bigger pupil is not reacting as well in the light, and that is a problem with the parasympathetic nervous system mediated by the third nerve to its ganglion, the ciliary ganglion, and then the postganglionic fibers which go to the iris. So, when we have a larger pupil that doesn't react to light the problem is somewhere along this pathway. The first thing that we want to make sure of course is that it's not a third nerve palsy. And we can easily do that by looking at the lid and the motility. So, if the lid and motility are normal, it is extremely unlikely that a dilated pupil alone would be a third nerve palsy. And so, one of the things we'd like to do is to make sure that it's not something in the iris or the ciliary ganglion. In order to make sure that it's not the iris, we're just going to look with the slit lamp examination. So, we are going to be looking for iris transillumination defects, sphincter tear, irregularity of the pupil, posterior synechia, or uveitis - something wrong with the muscle. If it's not the muscle, then it's down to the ciliary ganglion, or the connection between the ciliary ganglion and the muscle, called the neuromuscular junction. The most common cause of the neuromuscular junction to be affected is if someone has put drops into their eyes. So, if you have been given a topical dilating agent (a mydriatic) it will dilate your pupil, it won't react to light, there will be nothing wrong with your slit-lamp examination, and it won't react to near as well. And that is pharmacologic mydriasis. We can test this hypothesis by applying pilocarpine, a direct acting parasympathomimetic, at a high dose (1% or 4%). And if we put 1% pilocarpine into a pharmacologically dilated pupil, it won't constrict because it's blocked. The alternative of course is that it's the ciliary ganglion, or the postganglionic nerve. And that we call a tonic pupil. When its idiopathic we call it Adie's tonic pupil. The way to test for Adie's tonic pupil is if the light reaction is poor, the anisocoria is greater in the light, then we test the near reaction. In a ciliary ganglion lesion, the near reaction will be good and that we call light near dissociation of the pupils. The light reaction is good, the poor but the near reaction is good - light near dissociation. And that light near dissociation in association with a tonic reaction at near tells us that it is the Adie's tonic pupil, or some other tonic pupil from surgery or from a tumor in the orbit or whatever is the cause, but most of the time it's idiopathic which we call Adie's. We can test this theory by putting in low dose pilocarpine, but instead of 1 percent, 0.1% pilocarpine. And in a patient whose had denervation from the ciliary ganglion from Adie's tonic pupil, the application of low dose pilocarpine (0.1%) will cause the pupil to constrict vs. the normal eye which shouldn't constrict. So, this will demonstrate denervation super sensitivity and confirm the hypothesis that it's the tonic pupil, and if its idiopathic Adie's tonic pupil. That is pretty much the parasympathetic side of the equation. So your main job - make sure it's not third nerve palsy, look at the slit lamp and the iris, confirm that its not pharmacologically dilated by the history, test the theory with pilocarpine 1%, and if it's the Adie's tonic pupil look for light near dissociation of the pupil, sectoral paresis, and you can test pharmacologically with pilocarpine 0.1%. On the other side of the equation is the anisocoria is greater in the dark. If the anisocoria is greater in the dark then what were dealing with is a sympathetic nervous system problem, or a physiologic anisocoria. And the way to tell the difference is to look for a dilation lag. A dilation lag is a fancy way of saying the smaller pupil doesn't dilate as well as the normal pupil, and there's a lag in time for that dilation to occur. So, the presence of the dilation lag is seen when we turn off the light, the anisocoria is a lot different then it is after 10 seconds because there is a lag dilation. So, the lag allows the dilation to catch up in the sympathetically innervated Horner's syndrome. If you see a dilation lag and the anisocoria is greater in the dark, then we are going to be looking at the lid for a ptosis. But unlike the ptosis in the third nerve palsy which can be quite variable from partial to complete, the ptosis in the Horner's syndrome pupil is usually only 1-2 mm. There's also an upside-down ptosis from the equivalent in the lower lid of the Mueller's muscle. And so, we really have a little bit of ptosis and upside-down ptosis in the Horner's syndrome (1-2 mm). Once we've confirmed that clinically this looks like a Horner's syndrome, then we are going to try to test the integrity of the sympathetic nervous system. Much like we tested the pilocarpine for the parasympathetics, we are going to use direct acting and indirect acting sympathomimetics. The sympathomimetics that we are going to be using are topical cocaine and apraclonidine. So, lets just start with the direct acting sympathomimetics. The direct acting sympathomimetic, apraclonidine, is an alpha agent. It has differential activity for alpha 1 and alpha 2. Under normal conditions, the alpha 2 effect predominates, and if we put apraclonidine in a normal pupil it will either stay the same size or get slightly smaller. If however we have denervation super sensitivity from a Horner's syndrome, the alpha 1 postsynaptic effect will predominate and that smaller pupil will dilate, and this will result in a reversal of the anisocoria or dilation of the Horner's side pupil. So apraclonidine can be used to detect whether we have a Horner's syndrome or not. There are two indirect sympathomimetics that we can also use which are much more difficult to get and maintain because they are controlled substances. And those are cocaine and amphetamines. Cocaine works by inhibiting the reuptake of norepinephrine at the neuromuscular junction. And so, if we put cocaine into a normal pupil it will dilate, but if we put cocaine into a Horner's syndrome pupil it won't dilate as well because there's no norepinephrine in the junction to allow it to dilate. And so the anisocoria will be greater than 1 mm after we give the cocaine compared to the pre-cocaine test. Amphetamines are also indirect acting sympathomimetics, but it works by releasing the norepinephrine at the neuromuscular junction, and therefore it can be used to tell whether we are dealing with a first order, a second order, or a third order neuron Horner's syndrome - and that we call a pre vs. a post ganglionic Horner's. The first and second are preganglionic, and the third order is postganglionic for the Horner's pathway. And as you know, the Horner's pathway begins in the hypothalamus, descends posterior laterally in the brainstem, down to the ciliospinal center of Budge in the spinal cord (that's at C8-T2 level), exits white rami over the apex of the lung, and up the sympathetic chain onto the internal carotid artery, and then travels into the cavernous sinus, a short course on cranial nerve VI, and then V to reach the target organ which is the lid of the pupil. So, it's a very complex oculo-sympathetic pathway composed of a first order neuron from hypothalamus to ciliospinal center of Budge in the spine, a second order neuron over the apex of the lung and onto the carotid, and then synapse at the superior cervical ganglion where it becomes a third order neuron to the cavernous sinus, VI, and then V. So, if we give the indirect acting sympathomimetic hydroxyamphetamine which stimulates norepinephrine at the junction, if the third order neuron is broken, the pupil won't dilate as well. If however it's the preganglionic Horner's syndrome, the first or second order neuron, if we give the hydroxyamphetamine it will dilate. So, once we've confirmed with apraclonidine or cocaine that it is indeed a Horner's syndrome, if we give the amphetamine and it dilates the pupil then we know the problem is preganglionic Horner's. If however it doesn't dilate the pupil as well, that is a postganglionic third order neuron Horner's. Now in reality, we probably don't need to do all of these drops. We're just going to image the entire sympathetic axis from the hypothalamus all the way down the thoracic T2 of the chest with a combination MRI/MRA in the outpatient setting head and neck, and in the emergency room CT/CTA head and neck because what we're looking for is carotid dissection in the acute setting. So that's just a very quick review of anisocoria and how we deal with the parasympathetic and sympathetic side. You can use the drops to confirm what you're looking for, but it's not necessary. Most of the time we can do what we need in clinic. So, the question came up, how does apraclonidine work? If we have a presynaptic junction, in the sympathetic nervous system we have alpha 2 receptors and on the postsynaptic receptor we have alpha 1 receptors. Under normal circumstances, the alpha 1 postsynaptic receptor and the alpha 2 are antagonistic. This is a negative feedback loop that allows us to turn off too much sympathetic activity in the junction. Apraclonidine is preferentially an alpha 2 agent, so when it binds to the presynaptic alpha 2 it actually causes the opposite of what you think it's going to cause. Even though it's a sympathomimetic, which should cause the pupil to dilate, because it is an alpha 2 agent it actually causes the pupil in a normal pupil to get slightly smaller or no change. If however, you have denervation of the sympathetic pathway, then there won't be any release of norepinephrine. There will be upregulation of the alpha 1, and that is a postsynaptic upregulation which we call denervation super sensitivity. This denervation super sensitivity will allow apraclonidine to have an alpha 1 predominating effect now, and when the alpha 1 effect occurs the pupil will dilate. And that means in a Horner's syndrome if you put apraclonidine it might reverse the anisocoria. The small pupil becomes the big pupil, and the big pupil gets slightly smaller. But the end point of the test is dilation of the involved Horner's syndrome miotic pupil. |
