 Dr. Pomerance here from MRI Online, we're talking rare diseases today and Charcot-Marie Tooth disease, this enigmatic disorder that you learned about in medical school but thought you'd never see. Well, you will see it. It goes by the abbreviation CMT and there are some other synonyms that you have heard throughout your medical career. Hereditary motor and sensory neuropathy or HMSN, perineal muscular atrophy, distal hereditary motor neuropathy, D-H-M-N, hereditary sensory neuropathy or H-S-N or H-S-A-N, some debate whether that's included in the subset of nomenclature and distal spinal muscular atrophy or D-M-S-A. Now this is one of the few disorders that is named after three doctors who originally described the disease, Jean-Martin Charcot, Pierre-Marie and Howard Henry Tooth. Jean-Martin Charcot is often referred to as the father of neurology and you've heard his name on other disorders. Now in terms of genetics, the genetics center around the duplication of one major gene and that is PMP-22 gene, which you receive one from each parent by the way. In CMT-1 and its common subset, 1A, this is a demyelinating autosomal dominant disorder but it accounts for at least 50% of all the cases of Charcot-Marie Tooth. CMT-2 may involve more the center of the nerve, the axon, it's also autosomal dominant, CMT-4 recessive and these are far less common. This single gene duplication of PMP-22 accounts for at least 50% of the cases, however, there are over 100 gene mutations associated with Charcot-Marie Tooth syndrome that have been described. CMT, while an autosomal dominant disease, it's not just one disease. It has innumerable subtypes and each variant has in common involvement of the myelin sheath of the peripheral nerves. The disease is slowly progressive and variable and can arise without any hereto-famil history in some cases which makes it a bit confusing. CMT is the most common neuropathy in the lower extremities and the perineal and tibial nerves will often be the presenting areas for you and so looking at the lower extremity is going to be very important in these individuals. The symptoms usually present in adolescents. The symptoms are variably motor and sensory. They can be more towards the pure sensory, more towards the pure motor and they involve the hands and feet. The patients may experience foot drop, muscle atrophy, cramping, peristeges, nerve pain, clumsiness, sprain ankles falling and typically when you look at these patients who have progressed to a certain level you'll see something called a stork leg where the upper portion of the leg is nice and plump and then it tapers very abruptly for a long distance. Pescavus or a high arched foot, Pesplanus, a flat foot and then claw hand or hammer toe, a pearl. The longest nerves in the body are affected first so the branches of the sciatic nerve, the perineal nerve and the tibial nerve are commonly affected. There are a couple of other oddities that I wanted to share with you. One is known as NHPP. It's a hereditary neuropathy with a predilection to pressure palsies. Now unlike the other cases of Charcot-Marie-Tooth where there is a PMP22 gene duplication, this one is a gene deletion which makes it all the more interesting. The DMT3, formerly known as Dejurin-Sotus syndrome, some of you have heard this name previously as a subset of giant cell neuropathy with nerve swelling. We no longer use this term, Dejurin-Sotus has fallen out of favor. And then there are hereditary sensory and hereditary motor neuropathies which some people include in Charcot-Marie-Tooth and others divide them into disorders unto themselves. The diagnosis of CMT involves nerve conduction testing, biopsy of the serial nerve, DNA testing, also not shown here, assessing the other members of the family and sometimes imaging. Let's have a look at a real case on MR imaging. This is the 35-year-old man who presents with weakness and clumsiness and also knee pain. He's carrying a small anterior neofusion and what should strike you as you look at the stack of artery, vein, and nerve is the signal of the nerve. Now normally a nerve signal is going to be intermediate and confluent. If you have very high resolution then you may see subunits of the nerves. You might see little dots inside and they should fill that entire space. They should be symmetric. They should each be the same caliber. None of them should demonstrate any crimping or interruption or defects. What we see in this patient, let's look at the tibial nerve right here, is something that's a little bit gray on the outside but rather white on the inside. Let's blow it up. It is a T2-weighted image. Where is that confluent solid gray signal intensity? That's not gray, that's hyper intense in the center and also in the periphery. Only a thin shell of hyper intensity remains. Just to show you that it's not just one slice, it's contiguous. You never, ever see that confluent, beautiful, homogeneous gray signal intensity. This nerve up higher, this tibial nerve up higher when it merges with the perineal nerve will become the sciatic nerve. The sciatic nerve innervates the hamstrings. Let's demagnify or demystify this and look at our semi-membranosis muscle. It looks so much different than it's brethren on either side. That's because it's severely atrophic as a result of this demyelinating peripheral nerve syndrome. Not done yet, we're going to track our perineal nerve which as we go up doesn't quite meet the tibial nerve but it's on its way. Let's blow this up and make it bigger again and look at our perineal nerve. It's so bright within that it's almost cystic appearing. Now let's work our way down, signal, signal, signal, signal and the signal persists for quite a long distance. And remember, this is a disorder that likes to affect the longest nerves in the body. Another tip off to the diagnosis, although subtle, besides that semi-membranosis atrophy which is weird is this. In the lateral compartment you're starting to see a component of myoedema which is the precursor of muscular atrophy and is a form of nerve injury manifest as initial muscle swelling and then the muscle becomes atrophic, small and fat laden. So this is one of our cases of Charcot Marie Tooth. Shall we look at another? This 28-year-old girl presented with leg numbness extending from the knee down so more of a sensory presentation. Let's look at the axial projection. I'll bring out my trusty pen and my MRI online yellow right there and we've got an artery nice and black with flow void in the middle. Then we've got a vein on top of that, it's a little bit larger. And then behind that we have the nerve. So let's take my yellow markers off for a minute and let's look at the nerve. It's got numerous components to it. What is this component? This very bright area. I'm going to put an arrow on it right now so the non-radiologist viewing this video can see it right there. That is cystic degeneration of the myelin of a nerve and also it's axon. Then we've got another finding and that is in the perineal nerve. Look at the bizarre appearance of the perineal nerve. In the prior case, even though I don't have my gray color to show you, the nerve should be a fairly homogeneous structure and occasionally with high resolution you'll see some of its internal subunits. I drew it in yellow but it's really more gray or dark gray. What is this high, fat-like signal intensity that wraps itself around the nerve? This is Schwann cell degeneration, so to speak. And then we look at the coronal projection now and we have an interesting finding that should have been the tip off to the diagnosis in the first place when we hone in on the area that the patient describes as being symptomatic, which was in the outside of the leg. We see that the lateral compartment is a bit atrophic. It has a little too much fat in it. And the fat for the non-radiologist again being the high signal intensity, because this is a fat-weighted T1 weighted image. Whereas the image on the right is a water-weighted image. The fat should be dark, either dark gray or black. Here it's dark gray. And what do we see in the muscle? We see a muscle that is intensely bright all the way up and down in the lateral compartment. And this is an example of myoedema secondary to denervation. So this is a slightly different example from the former case, where you're seeing extensive muscular edema and slightly different manifestations of nerve cell degeneration in one of the variants of Charcot Marie Tooth.