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WORKSHOP: MOTOR EVOKED POTENTIAL TEST: TECHNIQUE AND
CLINICAL APPLICATIONS
How does a MMEP-test work?
Transcranial magnetic stimulation (TMS) and recording of magnetic motor evoked potentials
(MMEP) in ponies was already reported by Mayhew andWashbourne [1] but the technique
was standardized and reviewed by Nollet et al. [2] and Nollet et al. [3]:
In short, the principle of transcranial magnetic stimulation is as follows: A brief current pulse
passes through an insulated coil and induces a brief electromagnetic pulse. When the coil is
placed on the scalp, the electromagnetic pulse is capable of inducing a current within the
brain that leads to excitation of the descending motor tracts. The evoked responses in the
muscles (magnetic motor evoked potentials, MMEP) can be used to assess the functional
integrity of spinal cord motor pathways. On these MMEP, onset latency (= time between
stimulation of the brain and onset of the muscle response) and peak-to-peak amplitude (=
difference between the 2 biggest peaks of opposite polarity) can be measured. In recumbent
or ataxic horses with spinal cord disease, onset latencies are delayed and peak-to-peak
amplitudes are smaller, while the parameters remain normal in cases with orthopaedic issues
[4-6]. In this way, the MMEP test can help differentiating between neurological or orthopaedic
gait abnormalities or to confirm motor deficits in horses suspected of neurological issues.
Why would I use a TMS-MMEP-test?
Spinal ataxia is a common problem in European horses and most frequently caused by
cervical vertebral malformation (CVM). CVM causes static or dynamic compression of the
spinal cord and is commonly seen in warmblood horses and young, rapidly growing
thoroughbreds. However, the diagnosis remains challenging.
The clinical neurological examination is critical in the diagnostic work up, but remains
subjective. Even experienced observers might have a different interpretation of the clinical
symptoms of horses [7]. Furthermore, many studies highlight the controversy, difficulties and
limitations of cervical radiography, myeolography, computed tomography (CT), magnetic
resonance imaging (MRI) and myeloscopy to diagnose spinal cord disease in horses.
Sensitivities (47-50%) and specificities (70-78%) of cervical radiographs and sagittal ratio
calculations are too low for adequate diagnosis of spinal cord compression [8, 9] and
variation between observers is high [10]. Myelography also has a low sensitivity (43-85%)
and additionally requires general anaesthesia and intrathecal contrast injection [9, 11]. Most
CT and MRI scanners can only image the cranial cervical spinal cord because of the limited
diameter of the CT and MRI gantry. This is an important limitation since 37-54% of CVM
lesions occur in the caudal (C5-C7) cervical vertebral column [9, 11]. Furthermore, no flexion
or extension of the neck is possible in CT or MRI scanning [12-14]. Cervical vertebral canal
endoscopy is not routinely performed. There is a high risk of complications associated with
entering the spinal canal or due to neck movement during the procedure. The visual
assessment of subarachnoid space narrowing may not be reliable in cases with mild to
moderate stenosis. So, the very high sensitive diagnostic TMS-MMEP test could provide
interesting information about the functionality of the spinal cord.
Several studies have demonstrated the usefulness of the test in cases with confirmed spinal
cord disease already, but only the functionality of the motor tracts is evaluated. No
information concerning the sensitive function can be gathered. To test the sensitive tracts of
the spinal cord, somatosensory evoked potentials should be measured. With this test, an
electrical stimulus is given at the level of the limb and the provoked response is measured at
the level of the brain. However, the technique is not (yet) common practice in equine
medicine. In experimental circumstances, somatosensory evoked potentials are used to
evaluate the efficacy of analgesic drugs [15, 16] or to evaluate the involvement of the
trigeminal nerve in headshaking horses [17, 18], but the technique to evaluate ataxia as such
is not described.
An alternative to the transcranial magnetic stimulation to evoke MEP could be transcranial
electrical stimulation (TES). TES is thought to be a more robust technique with a reduced
onset latency compared to TMS and less sensitive to the depressive effect of sedatives and
anaesthetics. The technique is developed more recently [19] and normative data are
available [20]. As the electrical stimulation is more painful than the magnetic stimulation, the
horses need to receive a higher dose of sedation and a local subcutaneous ring block
anaesthesia but the results are similar to the magnetic stimulation.
How do I perform a MMEP test?
Equipment necessary:
Sedation: combination of detomidine and butorphanol (both at 10µg/kg)
Magnetic stimulator (output capacity of at least 4 Tesla) + connection cable to EMG
machine
Round 70 mm coil
Standard EMG equipment
Amplifier (with at least 2 channels is preferred for simultaneous measurements)
Electrodes (needle or surface)
o Monopolar, coated, disposable needle electrodes (25-37mm) + leads or
o Adhesive surface electrodes (for example those used for ECG recording in
horses) + leads
Technique:
For practical issues and to minimize discomfort for the horses and examiners, the horses are
sedated with a commonly used combination of detomidine (dose 10µg/kg) and butorphanol
(dose 10µg/kg). Nollet et al. [21] found that there were no significant differences in latency
and amplitude measurements made before and 10 or 30 minutes after sedation with this
combination. Other sedatives or anaesthetics can have a depressive influence on MMEP so
they should be avoided.
Figure 1: Surface electrode placement on the extensor carpi radialis (left) and tibialis
cranialis muscle (right).
For EMG recording, intramuscular needle electrodes or adhesive surface electrodes can be
used. Needle and surface electrodes result in similar latency times, but the surface
electrodes are better tolerated by the horses [22].Two electrodes are placed per limb. Both
are placed at the tibialis cranialis muscle in the pelvic limbs an at the extensor carpi radialis
muscle in the front limbs (figure 1). The ground electrode is attached in the groin or elbow
region respectively. The skin does not need to be clipped. If needle electrodes are used, the
skin is disinfected with alcohol before placement. If surface electrodes are used, the skin has
to be dry for optimal attachment of the electrodes. Depending on the number of channels
available, the connection leads can be put at the electrodes of 1, 2 (left and right side) or 4
limbs. The more limbs tested at the same time, the less magnetic stimulations are required.
Figure 2: Optimal coil positions for MMEP recording at the extensor carpi radialis and
tibialis cranialis muscle (from [3]).
To register the MMEP with the shortest latency time and the biggest amplitude, at least 4
stimulations are necessary. The most influencing factor to gather the best MMEP, is the coil
position. In general, the optimal stimulation site on the equine forehead is median, just
underneath the horizontal line between the base of the ears (figure 2) [3]. Stimulation output
is always set at 100%, being 4 Tesla. If lower intensities are used, latency times are longer
and amplitudes of MMEP are smaller. The direction of the current flow in the coil, the age or
the sex of the horses, or left or right side recordings do not have an influence on the results
in horses. Latency times do alter with height and weight of the horses and are significantly
different in pelvic and thoracic limbs [3, 23]. In human medicine, a lot of attention is paid to
the facilitation principle or the effect of voluntary contraction. It is known that slight voluntary
contraction of the target muscles shortens the onset latency, lowers the threshold and
increases amplitude of MMEP. In horses, it is impossible to standardize this pre-stimulation
muscle tension exactly, but it is tried by ensuring that the horses are standing square
(=weight baring equally divided on 4 feet) the moment of magnetic stimulation.
On the registered MMEP, onset latency and
amplitude values can be determined (figure
3). Onset latency is defined as the shortest
distance between the moment of stimulation
and the first deflection from the baseline
(representing the muscle contraction).
Latency is a valuable parameter with a low
variability. In normal horses, mean ±
standarddeviation of latency, using surface
electrodes, is 21.2 ± 1.4 and 39.2 ± 3.8 ms
for the extensor carpi radialis and tibialis
cranialis muscle, respectively [22]. Using intramuscular needle electrodes, Nollet et al. [23]
found 19.32 ± 2.50 and 30.54 ± 5.28 ms for latency time and 9.54 ± 3.73 and 6.62 ± 3.62 mV
for amplitude, respectively. In horses with mild to severe spinal cord disease, latency time
can be strongly prolonged to 27-100 (or even more) ms in the extensor carpi radialis muscle
and 53-150 ms in the pelvic limbs [5, 6]. Amplitude is measured between the two biggest
peaks of opposite polarity. The parameter is clinically less valuable than latency time and has
a larger variation. Mean ± s.d. of peak-to-peak amplitude in normal horses, using surface
electrodes, is 7.2 ± 4.7 and 3.8 ± 2.4 mV for the extensor carpi radialis and tibialis cranialis
muscle, respectively [22]. Horses with spinal cord disease will often have low amplitudes
(0.2-1.5 mV), in some cases even too low to be measurable [5]. If the thoracic limbs produce
normal MMEP but the pelvic limb MMEP are abnormal, a thoracic or lumbal lesion is
suspected. If MMEP are abnormal at all 4 legs, a cervical spinal cord lesion is suspected and
medical imaging can be used to confirm this.
Figure 3: Example of 4 magnetic motor evoked potentials recorded from the extensor carpi radialis muscle in a horse with indication of onstet latency and peak-to-peak amplitude (from [5])
In conclusion, a MMEP test is easy to perform, sensitive and well tolerated by the horses and
it provides interesting information about the motor function of the spinal cord. Therefore, it
can be considered as a valuable diagnostic tool for neurological examination in horses.
REFERENCES
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