| Transcript |
We're going to be talking about pharmacologic testing for the Horner syndrome today. So the pharmacologic topical testing for the oculosympathetic pathway in this case, confirming whether or not we have a Horner syndrome, is really important in establishing whether or not we need to have a workup for this. So, as you know, the most common presentation is that we have an anisocoria, and that means an-not, is o-same, coria-pupil, so we don't have the same size pupil and because it's a sympathetic nervous system deficit in the Horner syndrome, the anisocoria is going to be greater in the dark because the smaller pupil is not dilating properly. And there's going to be a ptosis (usually it's only about a one millimeter or two-millimeter ptosis) and an upside-down ptosis, and that's because the Muller's muscle is in charge of the sympathetic innervation to the lid, and it only controls a very little bit of ptosis. So we've got ptosis, miosis, anisocoria greater in the dark, and we'd like to determine whether this smaller pupil is actually a Horner syndrome. So, to do that, we're going to test the integrity of the sympathetic nervous system, and that means giving a sympathomimetic. So, when we give a sympathomimetic, we are activating the sympathetics, and that can be either done indirectly or directly. So, we'll start with the indirect-acting sympathomimetics that we have available to us. One is topical cocaine for 10% and the other is amphetamine (hydroxyamphetamine) and both hydroxyamphetamine and cocaine are indirect-acting sympathomimetics because they don't directly bind to the receptor itself. What they do is at the neuromuscular junction, there's release of norepinephrine, and that release can be stimulated by hydroxyamphetamine, or we can block the reuptake of norepinephrine, and that is cocaine. So, cocaine blocks the reuptake of norepinephrine, and hydroxyamphetamine increases the stimulation of norepinephrine. And what that means clinically is if we have a Horner's syndrome, we have a block in the sympathetic nervous system pathway, and so if we give cocaine to an eye that's blocked, then blocking the reuptake won't make any difference, and so the anisocoria will be greater, because the normal pupil will dilate and the little pupil either won't dilate or will dilate less. And with hydroxyamphetamine, if the block is in the third-order neuron, this neuron is broken, then giving it the indirect sympathomimetic will not release the norepinephrine because it's broken and that's a third order neuron. However, because the sympathetic pathway has a first-,a second-,and a third-order neuron from the hypothalamus descending posterior-lateral in the brain stem to the ciliospinal center of Budge in the spinal cord, at the C8-T2 level, and then exits white rami as the second-order neuron onto the sympathetic chain, internal carotid, intracavernous carotid is going to carry it after the synapse at that superior cervical ganglion. So, we have a primary-, a secondary-,and a third-order neuron in the sympathetic pathway, so if the lesion is in the primary-,the first-or second-order neuron, the preganglionic pathway(the ganglion here is the superiorcervical ganglion), then if we give hydroxyamphetamine to a pupil that is small because it has a first-or second-order neuron Horner's, it will dilate, because there's nothing wrong with this third-order neuron. So, this is for confirming the Horner's (that's cocaine)and this is for localizing to the pre-or post-ganglionic nerve (that's hydroxyamphetamine). And finally, we have a praclonidine. Apraclonidine is a direct-acting sympathomimetic. Normally, it has alpha-2preferential activity, but under conditions of denervation, like a Horner's syndrome, we have up-regulation of the post-synaptic alpha-1 receptors and what that will do is, normally the alpha-1 and the alpha-2 are antagonistic (the alpha-2 is a negative feedback on the alpha 1 pathway), and so normally if you stimulate thealpha-2, it makes your pupil constrict. However, if you have alpha-1, up-regulation of the postsynaptic receptors from a Horner syndrome, the pupil will dilate. Even though that is a direct-acting sympathomimetic on alpha-2 normally, under denervation conditions the alpha-1 effect will predominate, and what that will do is it will reverse the anisocoria, the bigger pupil will get either slightly smaller or not change, and the smaller pupil will dilate. So, the dilation of the smaller pupil after apraclonidine is the endpoint that we're looking at. It's easier to see if it reverses, but if it just dilates this pupil, that's good enough. It'll also make the lid go up, both the upper lid ptosis and the lower lid retract-ptosis will retract and cause a separate end point that you can use, which is the apraclonidine will make the lid go up. So, in summary, if you see a Horner's syndrome, miosis, anisocoria greater in the dark, ptosis, upside-down ptosis, we're going to think about pharmacologic topical testing with either a direct or an indirect sympathomimetic. The direct-acting sympathomimetic is apraclonidine, which has alpha-2 normal, but under up-regulation from denervation, super sensitivity alpha-1predominates,andinstead of the pupil constricting, which is alpha-2, it'll dilate (alpha-1), and cocaine and hydroxyamphetamine, which are indirect acting sympathomimetics-cocaine for confirming the diagnosis and hydroxyamphetamine for confirming whether it's a pre-ganglionic or a post-ganglionic Horner syndrome. |
