Double-Train MEP On A Comeback Kick

Using transcranial electric motor evoked potentials in the operating room has become routine practice for spinal cord monitoring. Recent improvements in the ability to record tcMEP have resulted in increased use during other procedures, like brain surgery, vascular surgery and peripheral nerve monitoring. One of the techniques utilized in the optimization of transcranial motor evoked potentials is double-train MEP.

Some find double-train MEP to be helpful in cases where tcMEP are difficult to elicit using single, multi-pulsed cortical stimulation. But it isn’t always the best way to elicit a response, and only utilized if other optimization strategies fail to reproduce reliable compound muscle action potentials.

Others think double-train MEP should be the new standard and feel reprogramming all single, multi-pulsed MEP templates to double-train tcMEP templates should have been done years ago.

Here I take on the two point of views, just as I would if I was preparing for the D.ABNM exam, to answer the question: “should we be using double-train MEP on all our cases?”

 

Have I used double-train tcMEP before?

Double-Train tcMEP

I'm Not Sold On Double-Train Motor Evoked Potentials

I’d like to clear up some of the hype about double-train MEP. I understand that they may help in some cases where transcranial motors may not be able to be elicited and recorded with single, multi-pulsed tcMEP, but that is not the norm in my experience. I find that increasing the number of pulses does just as well, and sometimes better than using the same number of pulse in a double-train MEP stimulation setup. If you’re familiar with the image found in Journee’s 2007 paper, he shows that the highest amplitude response collected was between 5 and 9 ms. Guess what… setting a double-train MEP with that short of an intertrain interval is no different than just doubling up your pulses. It’s happening at the same or similar time. As a result, I no longer start with 4-5 pulses as made popular by the (Rodi, 1996) paper, but chose to start with 7-9 train pulses.

I Find Good Reason To Start Each Case With Double-Train tcMEP

If you take the time to familiarize yourself with the more recent intraoperative neuromonitoring literature, you’ll see that double train stimulation is all the rage right now. H-reflex, bulbocavernosus reflex, blink reflex, and even peripheral nerve stimulation for SSEP have all shown improved recording outcomes and optimization of collected data. Double-train for transcranial electric stimulation has also shown to be positively affected by preconditioning the cortical and spinal motor neurons to a more excitable state before running a test stimulus. It makes use of all these oligo and polysynaptic pathways to help prime overlapping areas in the alpha motor neurons to reach threshold easier. Making use of spatial summation, especially in an environment with neuro suppressive anesthetics on board, makes all the sense for the get-go. The using what we know about human neurophysiology in our favor is the difference between good neuromonitoring and great neuromonitoring.

Intraoperative EMG bipolar or referential?

“Can you go over the difference in Double-train MEP vs single train MEP?”

Single vs Double-Train MEP

Double-train tcMEP consist of running an initial number of motor evoked pulses, followed by a brief break. The initial set of pulses usually consists of 1-4 pulses, with an interstimulus interval, or ISI, appropriate to the area of most concern. These are referred to as the conditioning stimuli. The brief break in stimulation referred to as the inter-train interval, or ITI, separates the first train of pulses from the second. The second train of pulses usually consists of 4-7 pulses. Again, the interstimulus interval can vary depending on the CMAPs collected. This second set of stimuli is referred to as the test stimuli.

Why Consider A Double-Train Transcranial Electrical Stimulation?

tcMEP do not summate potentials solely by monosynaptic transmissions, such as seen in D-wave monitoring. When stimulating transcranially and recording activity over a muscle, I-waves also play a critical role in bringing the alpha motor neurons to summation through indirect pathways via interneurons. It does this by depolarizing the alpha motor neurons and increasing their excitability, allowing for subsequent stimuli to have a better chance of again causing an action potential.

This was observed as a necessity for transcranial electrical motor evoked potentials in the operating room, where the inhibitory effects of anesthetics on the alpha motor neurons prohibited summation of those neurons and collection of a compound muscle action potential.

In order to overcome the suppressive effects, it was recommended to run a train of stimulation with multiple pulses. These rapid firing pulses, usually using a rate of 200-1000 pulses per second (for my Axon users) or 1-5 ms for the interstimulus interval (for my Cadwell users) took advantage of temporal and spatial summation and allowed collection of a compound muscle action potential under anesthesia.

And as the neuron directly summates on the alpha motor neuron (D-wave), it also has effects on surrounding neurons within its network at both the cortical and spinal cord level. Not only does that allow for other neurons to possibly fire (I-waves), but it also increases the resting membrane potential of those neuronal pools as well.

So after we run a set of tcMEP for a train of say 7 pulses, we get 7 D-waves and (hopefully) a lot more I-waves to help activate a response. We are also left over with some pretty excitable neurons.

These rapidly firing pulses are right at the cusp or very close to the time elapsed during the relative refractory period after a neuron is brought to the threshold (around 1-2 ms). Some of the neurons brought to threshold might not have been able to  create a subsequent response and will have to wait for next pulse or later I-wave potentials in order to fire again. If not, then it just sits closer to the threshold for a little bit and then retreats back to its level of resting membrane potential.

That led to some researchers asking the following question…

“What if we waited for a certain amount of time after an initial stimulation to allow the resting membrane potentials of a large population of cortical and spinal neurons to become more positive… and then hit them with some more pulses?”

The Conditioning Stimuli

By doing a conditioning stimulation, you’re priming the pump for a certain area. You’re allowing a greater area of neurons to become excited and sit closer to the threshold. In theory, you would have more neurons ready to fire should a new wave of pulses be delivered. So when the second train of pulses delivered, it activates a separate area of neurons that has overlap with the conditioned stimuli. This overlapping area, if timed correctly, is where additional facilitation can occur.

double train tcmep CMAP

How much output is needed to prime the pump?

This is important to consider when selecting a number of pulses in the conditioning response. Should you choose a train of 1, you are most likely relying on direct, monosynaptic excitation as your mode of increasing alpha motor neuron excitability (although indirect pathways may be activated with enough power output). Should you choose to use multiple trains with an appropriate interstimulus interval, then you are taking advantage of direct and indirect means of exciting the cortical and spinal neurons.

But we have some restrictions we need to consider when choosing the number of pulses for the conditioning response.

First – There are some time constraints to consider. If we’re looking to record over a head or proximal muscle, then we need to take into account the number of trains + the rate at which we stimulate. To be honest, if you are staying within the recommended tcMEP parameters, you will not have to worry about this. It may become a problem with a longer ISI.

Second – We need to make sure that we do not exceed the limitations of the equipment for output delivery. On the Cadwell, the machine will allow you to adjust the settings outside of what it will actually output. Be aware that once you hit those limitations, you are no longer changing the output.

Third – We need to find the number of pulses that brings a large group of neurons close to the threshold, but not actually bring it to the threshold. This is a conditioned response and there seems to be an inverse relationship between amplitude size of the conditioned stimuli and test stimuli. If we are seeing a CMAP on our conditioned stimuli, then we may be causing excitation of IPSP. You will find yourself better served to allow for more trains to be used on the test stimuli.

The tcMEP Intertrain Interval

The next major consideration is the intertrain interval. As it turns out, there are certain times where the overall excitation is greater than other times, and it is not a straight declining line.

As described by (Journee, 2007), there are times where the test stimuli will have maximal amplitudes for motor evoked potentials, or where excitation is the greatest, and times where there are minimal amplitudes, or where inhibition is the greatest, when compared to the same test subject without any conditioned stimuli.

double train motor evoked potential

So what might be causing the periods of decreased amplitude during double-train MEPs?

  1. It is proposed that many spinal interneurons are acted on through oligo- and polysynaptic pathways that can lead to the summation of both excitatory postsynaptic potentials or inhibitory postsynaptic potentials.
  2. After the conditioned response, the amount of neurotransmitter available at the spinal cord level might be insufficient.
  3. After the conditioned response, there might be some time period were the neurons demonstrates some refractive properties and will not allow the threshold to be reached again for a period of time.
  4. Cortical inhibitory interneurons acting on pyramidal cells causing a “silence period” of muscle activity.
  5. An intensity too great during the conditioning response may evoke a motor response, which also may evoke Renshaw inhibition at the alpha motor neurons following the response. This may effect short durations used on intertrain intervals than longer durations.

As you can see from their studies, a short intertrain interval and long intertrain interval recorded signals that were greater than the amplitude of a single, multi-pulsed train. But in the middle intertrain interval, the signal was less than the single, multi-pulsed response.

Practical use of double-train motor evoked potentials

At this point in time, I think we have some decent guidelines to follow, but nothing set in stone. Additional cases are needed to help validate any recommendations.

That being said, it looks as if double-train motor evoked potentials may help improve signal acquisition, further optimizing responses and allowing for the collection of data in patients with difficult to obtain signals (diabetes, peripheral nerve injury, myelopathic, etc.). Starting points should be as follows:

  • Use a lower stimuli intensity for the conditioning response. Too high of an intensity of the conditioning response may lead to Renshaw inhibition at the spinal cord level and a decrease in amplitudes. Amplitude will increase in tandem up to around 200V, where the conditioning response amplitude will continue to grow while the test response will start to attenuate. A conditioning response of 175-250 V seems to be the sweet spot.
  • Use only a couple of conditioning pulse and more test stimuli. It doesn’t take a lot of pulses to prime the alpha motor neurons, but you can still take advantage of spatial and temporal summation of a multipulse signal for the test stimuli. 4 pulses + 4 pulses do not seem to work as well as 2 or 3 pulses + 6 or 7 pulses.
  • Use either a short duration intertrain (15-40 ms) or a long intertrain interval (around 200-500 ms). A middle duration intertrain interval (40-100ms) seems to have inhibitory effects and a lower amplitude compared to single, multi-pulsed motor evoked potentials.
  • Be cautious of even greater patient movement. We are looking to ramp up the alpha motor horn cells, which will affect proximal muscles as well as distal. This may cause the patient to “jump” more.
My personal experience…

I’ve tried the double-train motor evoked potential on both the Axon and Cadwell. I personally did not see much advantage to using the double train vs a high number of pulses using a single train technique.

Besides trying to improve my own technique, the initial reason I wanted to test out this technique was to see if there were any non-physiological advantages to using it. Mainly speaking… will my machine give me more flexibility?

I wondered if the increasing amount of time between trains would reduce the amount of charge allow me to go a little higher if needed without any additional risk of burns or seizure activity. Since the system will still regulate you on the number of total pulses and intensity delivered, there was no additional benefit there.

optimized tcMEP

But it was still worth trying it out to see if there are physiologic benefits to delivering the motor evoked potentials in this manner.

From my (admittedly limited) experience there was not.

Here are the parameters that I used:

The Champion: Single train = 9 pulses, ISI = 2 ms, pulse duration = 50 us, intensity = 300V

Vs.

The Challenger: Double train = 2 + 7 pulses, ISI = 2 ms, intertrain interval 15 and 250, pulse duration = 50 us, intensity = 300V

The first thing you might see is that I stimulated with 300V, which is higher than recommended elsewhere. On all of the cases monitored, anesthesia was at 0.6-0.8 MAC of an inhalational agent (Desflurane or Sevoflurane) and a remifentanil drip. I did try to dip down to 200V, but the results were way worse at that point. The majority of the cases I tried them on were cases that I was able to get a reliable response with a single train delivery, allowing me additional time before the case started to test out the double-train MEP. I also tried it on a couple of cases with poor, but monitorable recordings. I didn’t observe any benefit. I’ve since then stopped tinkering around with double-train motor evoked potentials, but will still give it a shot if all my other optimization tricks aren’t working.

What about you? Are your results different than mine? Are you so sold on double-train MEP that you switched all your programs to default to it from the start, or do you use it as an optimization strategy?

Joe Hartman DC, DACNB, DABNM

Joe Hartman DC, DACNB, DABNM

Vice President of Clinical Services - Sentient Medical

Joe has worked in the IONM field as a surgical neurophysiologist, trainer, clinical manager and VP of clinical services. He is the owner and lead author of IntraoperativeNeuromonitoring.com where he tries to share his experiences in neuromonitoring in a way that is memorable and actionable. If you have questions about your own career path, feel free to link up with him or shoot him an email.

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