Introduction
Motor Unit Number Estimation (MUNE) is a sensitive measure of the number of functioning motor units
innervating a specific muscle. With appropriate evaluator training, it should be amenable to use in a
multi center clinical trial setting. However, this has proved a challenge to date in the pediatric
setting, in part due to lack of experience with techniques, and lack of time to refine them in the
busy clinical setting. Pediatric neurophysiologists in the U.S. (unlike their European counterparts
and even many of their adult colleagues) do not tend to focus exclusively on neurophysiology.
However, we have routinely performed MUNE evaluation on virtually every infant and child diagnosed
and followed at our center with spinal muscular atropy (SMA) in the EMG laboratory at Primary Children’s
Medical Center in Salt Lake City since 2001. There are a variety of possible MUNE techniques available,
but for tolerability in children, we chose to develop and validate a multipoint technique using only
surface recording electrodes. We chose the ulnar nerve and hypothenar muscle group due to ability to
perform studies in this muscle group across the age and severity spectrum; it is particularly suitable
for neonates, where close proximity to other nerves makes targeted stimulation more challenging for
other nerve/muscle groups. When first using MUNE techniques, collection of test-retest data should be
obtained with each session when possible until the operator is fully comfortable with techniques and
reliability has been established. This entails complete removal and replacement of recording electrodes,
followed by repeat collection of maximum compound motor action potential (CMAP) and single motor unit
action potential (SMUAP or SMUP) responses. Collection of MUNE data typically follows completion of the
collection of a minimum of 5 maximum CMAP responses in our laboratory (see separate CMAP collection
protocol used in our Project Cure Multicenter Investigator’s Network at www.smaoutcomes.org).
This protocol for collection of maximum CMAP as a separate outcome measure significantly reduces
the variability of the maximum amplitude and area measurements observed when collecting only a single
individual max CMAP response. In our hands, when MUNE value is less than 50, collection of at least
10 -15 voluntarily recruited SMUP responses closely approximates MUNE values obtained from recruitment
of SMUPs via low level electrical stimulation, as long as care is taken to collect units across the
size spectrum.
The skin over the ulnar aspect of the palm, the back of the hand, the volar aspect of the wrist
and about the elbow are cleaned with alcohol to remove any sweat, lotion or oil. This is very
important in SMA patients as they tend to sweat excessively. Electrode placement is similar to that
for standard ulnar motor studies. The G1 primary recording electrode is placed over the motor point
of the abductor digiti minimi muscle in the hand, at the midpoint of the line drawn between the ulnar
aspect of the fifth metacarpophalangeal joint (MP-5) and the ulnar aspect of the pisiform bone (P) in
the hand. The G2 reference electrode is placed at the base of the fifth proximal phalanx where is
intersects with the MP-5 joint. An adhesive ground electrode is placed on the back of the hand.
Panel 1: Modified figure from “Anatomic Guide for the Electromyographer” Charles C. Thomas, Publisher, 1980, p4.
Panel 2: Modified figure from “Clinical Electromyography Nerve Conduction Studies” Shin J. Oh, Williams and Wilkins, 1993, p195
The child can lie in the position most comfortable for them, usually on their back or side.
Distraction of attention from the procedure is extremely helpful, even with use of conscious
sedation techniques, to enable the most efficient collection of reliable data. Use of a VHS
video or portable DVD player are extremely helpful in this context, and parents are encouraged
to bring their child’s favorite tapes or DVDs along. Because this or any electrophysiologic
procedure may be anxiety provoking and uncomfortable in some young children, and because
obtaining an adequate number of SMUPs requires a minimum of movement during the procedure,
we generally use a short-acting medication for conscious sedation and reduced anxiety during
the procedure in infants and young children who meet the criteria required for safe sedation.
Details of the sedation protocol are described below.
Filter settings are 10 Hz – 10K Hz. A maximum ulnar compound motor action potential
(CMAP) should be obtained by stimulation at the wrist starting using a stimulus duration
of 50 microsec and an intensity sufficient to elicit a maximum CMAP (the intensity should
be further increased by 15% above that which elicits the maximal response). An ideal maximum
CMAP response should not have an initial positive deflection, although this may be difficult
in very weak SMA type 1 infants due to the extremely low amplitude of the responses;
repositioning of electrodes may be required to ensure the best response. To ensure that
the motor point has been selected, the G1 electrode be moved 2-3 mm distal to the initial
placement, then 2-3 mm proximal to the initial placement for a minimum total of 3 measures,
or more if necessary, to identify a point of maximum CMAP amplitude and negative peak area.
After the initial electrical stimuli are sufficient to obtain a maximum ulnar compound motor action
potential, the electrical stimuli for the remainder of the MUNE procedure to elicit the single motor
unit action potentials (SMUPs) are significantly reduced compared to those used for routine nerve
conduction studies, typically in the range of 5 to 15 mA (duration 50 ms), but sometimes higher in
a chubby infant (with duration of 100 ms).
The motor unit counting procedure itself takes approximately 30 minutes under ideal
circumstances; with use of conscious sedation and necessary pre and post test monitoring,
total testing and monitoring duration is about 60 minutes. If blood draw is added to the end
of the procedure, as is our routine, plan to add up to an additional 15 to 30 minutes.
If test-retest data is obtained, additional time is then required.
For the ulnar nerve, ideal locations to elicit SMUPs is in the volar area from the wrist crease to
several cm proximal to the wrist crease, and just proximal or distal to the ulnar groove at the elbow.
There are a number of issues regarding the actual collection of SMUPs which can only be gained through
observation and experience with the multiple point stimulation (MPS) technique. (1) It is extremely
helpful following the application of electrodes to ask the child or induce them to move their hand in
order to get an idea of the range of voluntarily elicited SMUPs. (2) During the collection procedure,
it is important not to bias yourself to collection of just the smaller or larger SMUPs, but to ensure
that you make every effort to collect SMUPs throughout the range elicited. In patients with type 2 and 3 SMA,
there is often a bimodal population, where 1 or 2 SMUPS can be quite large, and contribute heavily to the CMAP.
Failing to identify and capture such units will greatly effect the MUNE and reduce reliability. At the same time,
one does not want to include a seemingly large SMUP when in fact is represents a combination of several motor units.
(3) There are software features in the MPS program on the Comperio system that can help facilitate the recognition
of true single SMUPs (but this system is no longer routinely available). However, no special software is needed,
and these techniques can be used with any EMG machine. A SMUP must be elicited reliably for a minimum of ten times
without fractionation when one is first becoming familiar with the technique, but once one gains experience,
repeated observation of the same unit morphology at least several times is sufficient to identify it as a unique unit.
Once a reliable SMUP is captured, the stimulating electrode can be moved to a new position along the ulnar
nerve about the wrist or elbow, or the electrode angle can be changed. Collection of SMUPS is continued until
10–20 SMUPs are collected, or for a minimum of 30 minutes, or until no additional SMUPS can be identified.
It is not always possible to identify 10 SMUPs in type 1 and weak type 2 children. Reliability of MUNE values
tends to diminish with increased MUNE values over 50, and collection of additional SMUPs beyond the 10 minimum
specified enhances reliability in this population.
Example of SMUP data:
Sedation is not necessary or desirable in the large majority of patients with SMA type 1,
who tend to move their extremities much less than SMA type 2 and 3 patients. The medication we
use most commonly is the short-acting benzodiazepine medication midazolam, which we administer orally
(or rarely intranasally) in a dose of 0.5 (0.3) mg/kg. Typically, a maximum dose above 5 mg is not necessary,
as only anxiolysis and not sedation, if preferred. We use the intravenous formulation, mixed with flavored syrup,
and it is generally well-tolerated. A repeat dose may be administered in 10 to 20 minutes if sedation is not
satisfactory. The total combined dose should not exceed 10 mg in most cases for ideal conditions. In addition
to minimizing anxiety, this dosing will often impair memory of any discomfort they might experience during this
procedure.
In any child to receive sedation, the child must have taken no food or drink for several hours prior to
the procedure based on national sedation guidelines. They must meet an ASA criteria of at least III.
We have modified and expanded standard ASA criteria to better apply to SMA patients (details below).
A pulse oximetry probe is placed on the child's finger or toe to monitor heart rate and oxygen status throughout
the procedure and for 10 to 15 minutes following the procedure or until they are back to baseline and able to
resume normal feeding status. Sedation is contraindicated in any patient with a baseline oxygen saturation
below 93%. A blood pressure cuff will be placed on an arm or leg to obtain blood pressure readings prior to
the start of the study and intermittently throughout the study. A nurse experienced in sedation monitors the
child during the procedure and afterwards. Suction equipment and oxygen are available at the bedside if needed,
and a pediatric crash cart must be available. These studies should be performed in a location where an
anesthesiologist or team with pediatric resuscitation experience will be available immediately should any
unexpected problems occur.
Following the MUNE procedure, the child will also have blood drawn if that is planned for either clinical
or research protocols. No more than 3 tablespoons of blood will be drawn in each child, and in infants no more
than 1-2 tablespoons or less that 5% of blood volume obtained in children of any age: i.e., 2 ml/kg of weight
(2.2 lbs = 1kg).
The criteria below were developed for purposes of ensuring the safe conscious sedation of SMA study
patients with intranasal midazolam, as requested by the institutional review board at the University of
Utah School of Medicine and Primary Children’s Medical Center. It is used as a guide in determining patient
status prior to the use of sedation. Any patient who has had a respiratory infection with a history
consistent with lower airway congestion or cough in the preceding month prior to evaluation is precluded
from participation until they have been healthy for a minimum period of three weeks. In any child determined
to have an ASA status of IV, sedation is absolutely contraindicated, as is any child with a baseline oxygen
saturation below 93%. The investigator will proceed with caution in patients with ASA status of III using the
criteria below in conjunction with good clinical judgement.
ASA I Minimal hypotonia or muscle weakness; entirely normal breathing pattern; no history of
pneumonia or respiratory compromise with upper respiratory infection; normal feeding pattern; no history
of frank aspiration or coughing or choking with feeds.
ASA II Modest hypotonia; muscle weakness but full antigravity movement at shoulders;
normal breathing pattern; no coughing or choking with feeds. No history of respiratory compromise
with upper respiratory infections.
ASA III Moderate hypotonia; moderate muscle weakness with compromised antigravity movement
at shoulders and hips; no significant discrepancy between chest and abdominal size; NJ or G-tube placement
for nutritional supplementation but gag present with ability to protect airway; no history of choking on secretions;
attempted cough results in visible chest movement. History of respiratory compromise with upper respiratory infections.
ASA IV Severe hypotonia; complete absence of antigravity movement at hips and shoulders;
obvious significant discrepancy between chest and abdominal girth; oxygen saturation shows positional dependence;
significant dependence on abdominal breathing for respiratory support; any history of choking or gagging secretions;
attempted cough results in abdominal movement only.
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