Hi, I'm Devin Rubin, and for this teachable moment, I will be discussing repetitive nerve stimulation, and particularly how do we assess whether a repetitive nerve stimulation study is reliable or not. Repetitive nerve stimulation is an advanced technique that's used to assess for neuromuscular junction disorders, and by repeatedly stimulating a nerve at supermaximal stimuli at relatively slow rates of somewhere between two and four hertz, we're stressing that neuromuscular junction. We're stressing the safety factor of neuromuscular transmission, and in a normal neuromuscular junction, in a normal person that does not have a neuromuscular junction disease, as we give several stimuli at two to three hertz or two to four hertz, the CMAP amplitude with each stimulus should be normal, should be the same, and there should not be any decrease in the amplitude or the area of the CMAP. In contrast, in a patient who has impaired neuromuscular transmission, such as patients with myasthenia gravis or Lambert-Eaton syndrome, there is a drop in amplitude and area with slow rates of repetitive nerve stimulation, and that can be due to a number of factors. In myasthenia gravis, it's because of a reduction in the amount of release of acetylcholine with each stimulus, but there's still sufficient acetylcholine, it's just that the acetylcholine receptors are not functioning appropriately, either because they're blocked or they're degraded, so the acetylcholine does not produce an appropriate in-plate potential at all of the neuromuscular junctions. In Lambert-Eaton myasthenic syndrome or botulism, it's because there's an impaired release of the amount of acetylcholine, even though the receptors are functioning okay. How do we look at a repetitive nerve stimulation study? You can see here on the screen, this is a spinal accessory repetitive nerve stimulation, stimulating at two hertz. In our laboratory, we stimulate at two hertz stimuli, and we give four shocks. Some laboratories will give more shocks, they'll extend that out and give five or six or seven to look for a leveling off of the amplitude, but in our laboratory, we only give four shocks. You can see here on the left side of the screen, you can see the individual waveforms. This is the first stimulus, this is the second, third, and fourth. When I look at a repetitive nerve stimulation study, I first look at the waveforms, and I look to make sure that the waveforms appear reliable. By that, I mean that the waveform morphology should look relatively similar among each waveform, among each stimulus. There should be a stable baseline rather than a bouncing around or unstable baseline, and the markers should be placed appropriately. Here's the onset marker where the response takes off from the baseline, and here's the peak amplitude marker. In this study, each of the four waveforms look fairly identical, the baseline looks fairly stable, and that's a clue to me that this seems to be a reliable study. I then look at the drop in the response, both amplitude and area, between the first shock and each of the successive shocks. We're looking for the maximum reduction in amplitude and area. Usually the maximum drop will be between the first and the fourth or fifth stimuli, and eventually if you continue to give shocks, that amplitude will stabilize and may even improve a little bit. In all cases of true neuromuscular junction diseases, the largest drop between two shocks is between the first and second stimulus. Here you see a big drop between shock one and two and a lesser drop between subsequent stimulus. The maximum drop between shock one and four in amplitude is 31%, the maximum drop in area is 37%, and the area and amplitude decrease in decrement should be relatively similar. If you see a great difference, that should be a red flag that there's some technical problem. So this is a baseline, one baseline set at rest, that decrement here at baseline was 31%, the area decrement was 37%, a second baseline was given, and again, the decrement was 31% and 34%, and a third baseline about 28% and 24%. You can see this in the bar histograms on this study too. These are the first three baseline stimuli, and this decrement should be consistent. If a patient has a 30% decrement on one set and then a few seconds later, there's only a 10% decrement, that should be another red flag that there's a technical problem that's affecting the responses. And that could be patient poor relaxation or movement of the stimulator or movement of the recording electrode. The patient here was then exercised. This patient was exercised for one minute, followed by another set of stimuli. You'll notice something here in this histogram that the amplitude actually increases. So there's a little bit of perhaps pseudo facilitation or increment in the amplitude based on exercise or due to exercise. Oftentimes what happens in myasthenia gravis is that this degree of decrement actually improves also. So there's something called post-exercise improvement or repair of the decrement. This wasn't really seen in this case, and many patients won't necessarily show the repair of the decrement. And then in some cases, we stimulate at 30 seconds, one minute, two minutes, and three minutes following exercise to see if there's worsening of the degree of decrement. And in this case, there was maybe a little bit of worsening, but overall the decrement remained at about 37 or 38%. So this patient did not show post-exercise exhaustion or post-exercise worsening of the decrement. But these are the things that I look for when I'm assessing a repetitive nerve stimulation study. Again, first, are the waveforms similar in appearance? Second is the baseline stable? Third is the degree of decrement similar both between amplitude and area and in each of the baseline stimuli? That helps to ensure that there's consistency and reliability of the study. And fourth, and perhaps most important, the largest drop between two stimuli will always be between the first and second shock with a gradual continued drop up to the fourth or fifth stimuli, and then there'll be some leveling off. If you see a pattern of decrement where the first stimulus, the largest drop is not between stimulus one and two, but maybe it's between three and four, that's a technical problem. And that should be a red flag that it's not a true neuromuscular junction defect. So that's a brief overview of how I interpret repetitive nerve stimulation studies.

repetitive nerve stimulation

neuromuscular junction disorders

compound muscle action potential

myasthenia gravis

Lambert-Eaton syndrome