Hello, everyone. My name is Dr. Monique Alcântara, and I'm here to talk about hereditary and acquired neuropathies that can present with demyelinating features and how we can try to differentiate them using nerve conduction studies. Why is the differential diagnosis of demyelinating neuropathy so important? I'll start by giving you three reasons. First, Charcot-Marie-Tooth disease is the most commonly inherited neuromuscular disorder. And the most common CMT subtype, CMT1A, is a demyelinating neuropathy. So it's very likely that you'll come across those patients at some point in your practice. Second, some neuropathies with demyelinating features can be treated. Therefore, finding a potentially treatable cause is especially relevant for acquired neuropathies. Third, expensive and ineffective treatments can be avoided, especially in hereditary neuropathies. Now I'll try to show a simplified approach for the diagnosis of CMT. Based on the upper limb motor nerve conduction velocity, CMT can be classified into demyelinating types, CMT1 that presents with reduced velocities, usually less than 38 meters per second, axonal type CMT2 with preserved velocities but reduced amplitudes, and intermediate types with velocities ranging from 25 to 45 meters per second. The genetic classification is far more complex, as more than 100 genes have been identified for CMT and related disorders. But fortunately, only four subtypes account for the majority of CMT cases. The most frequent subtype is the autosomal dominant CMT1A, 60% of all cases, followed by the X-linked dominant CMT1X, then by CMT2A and CMT1B. This is one example of the classic demyelinating phenotype, CMT1A, where we can see a right median motor nerve conduction study recorded from the APB muscle with prolonged distal latencies, as you can see here, at 10 milliseconds, reduced amplitudes at 3.9 millivolts, and reduced conduction velocities at 19 meters per second. There is no evidence of conduction block or temporal dispersion. Now I will present a couple of cases where the diagnosis could be challenging, given the subtle phenotypes. Also, the family history can be misleading in cases with late-onset presentations, variable penetrance, or consanguinity. This is an example of a patient with CMT1A and minimal disability, who tested positive for the PMP22 duplication after one proband tested positive. Here we can see again a right median motor nerve conduction study with prolonged distal latencies, similar to the first example, but with preserved amplitudes at 7.4 and reduced conduction velocities. But now the velocities are in the intermediate range, almost in the axonal range, around 38 meters per second. The right side picture is from a fibular motor nerve conduction study of the same patient with prolonged distal latencies, preserved amplitudes at 3.6 millivolts, and reduced conduction velocities around 33 meters per second. In both upper and lower limbs, we can observe a uniform slowing of nerve conduction velocities. Now let's look at another less common phenotype, which usually presents with significant variability between women and men. CMTX1 can present with asymmetric motor deficits, non-uniform reduction in conduction velocities, conduction blocks, and velocities in the intermediate range. Those findings can be misinterpreted as an acquired neuropathy. In this example, we can see a left motor nerve conduction study with borderline to prolonged distal latencies, reduced motor amplitudes at 0.8, reduced conduction velocities at 21 meters per second, and with a partial motor conduction block. Although we have to be very cautious here when interpreting conduction blocking the tibial nerve, especially in the presence of small distal amplitudes. Now I'm going to shift gears and show some patterns that should raise the index of suspicion of a treatable neuropathy. In this example, we can see a classic presentation of CIDP, chronic inflammatory demyelinating polyradiculoneuropathy. We can see a right median motor nerve conduction study with prolonged distal latencies, normal amplitudes at 5.8, and reduced conduction velocities at 29 meters per second, also with temporal dispersion. In another patient, we can see an example of conduction block where the motor amplitude dropped from 5.3 to 1.87 millivolts. As you know, the diagnosis of CIDP requires a combination of clinical and electrodiagnostic features with exclusions to eliminate other disorders that may mimic CIDP. Now I would like to leave my final message with some examples of treatable, uncommon acquired neuropathy that should be thoroughly investigated even when the index of suspicion is low. Here we can see an example of POEMS, which stands for polyneuropathy organomegaly endocrinopathy and protein and skin changes. POEMS can present with some features of demyelination, such as prolonged distal latencies and reduced velocities, but in contrast with CIDP, very uncommonly presents with conduction block. In this case, there is reduced distal amplitudes and a conduction block. In the second example, we have a patient with hereditary TTR amyloidosis with absent distal motor and sensory potential. In a proximal fibular motor nerve conduction study recording from the tibialis anterior muscle, there were borderline demyelinating features, such as prolonged latencies and reduced velocities, but without fulfilling the electrodiagnostic criteria for CIDP. These are some of the references that I used in this presentation. Thank you for listening to this presentation.

neuropathies

demyelinating features

Charcot-Marie-Tooth disease

nerve conduction studies

hereditary vs acquired

ncs

CMT