**7.2 Motor units in asymptomatic FALS (SOD1) carriers**

For the initial part of the study, the baseline MUNE results were grouped together and the means of the groups were compared. The initial aim of the study was to determine if MND was due to a slow gradual attrition of motor neurones over time. If this were the case, the group of asymptomatic SOD1 mutation carriers, would be expected to have a reduced number of motor units, indicating the presence of pre-clinical motor neurone loss. Motor unit estimates in the group of asymptomatic SOD1 mutation carriers were compared to age and sex matched family controls without the SOD1 mutation, and sporadic (non-SOD1) MND patients. To determine whether groups had different numbers of motor units, an unpaired t-test was used. Statistical significance was accepted at a p-value of <0.05.

The numbers of motor units in the groups of population controls, SOD1 negative family controls and asymptomatic SOD1 mutation carriers were similar. In population controls the mean thenar MUNE was 148 with a range of 115 - 254, in SOD1 negative family controls was 138 with a range of 106 - 198 and in asymptomatic SOD1 mutation carriers, 144 with a range of 109 - 199. There was no detectable difference in the mean number of thenar motor units in the group of asymptomatic SOD1 mutation carriers compared to the group of SOD1 negative family controls (thenar p>0.46), or population controls (thenar p>0.70) (Table 1 and Figure 7).


Table 1. Thenar (APB) motor unit number estimates (MUNE number represents mean MUNE).

Protection of Motor Neurons in Pre-Symptomatic Individuals Carrying

SOD 1 Mutations: Results of Motor Unit Number Estimation (MUNE) Electrophysiology 645

Study Groups

Fig. 8. Baseline EDB MUNE subdivided into study groups (The lower boundary of the box is the 25th percentile, and the upper border is the 75th percentile of MUNE. The horizontal line

To assess the test-retest reproducibility of the technique, 69 of the 88 SOD1 family members and population controls were followed over a 1-year period, with thenar and extensor digitorum brevis (EDB) MUNE tests repeated every 3-6 months, depending on patient availability. The difference between MUNE results from the first and second study, and if possible, first and third studies were divided by the MUNE of the first study, and expressed as a percentage change. The results were analysed using Pearson and Spearman correlation

The test-retest correlation of thenar MUNE in asymptomatic subjects was high with a Pearson correlation coefficient of 0.93. The mean difference between MUNE results on separate occasions on the same individual was +/- 3.6%, with a range of 0-11.7% (Table 3).

**Number of Cases Mean MUNE** 

SOD1 Mut Carriers

inside the box represents the median MUNE. The whispers represent the largest and

smallest observed values, i.e. the range). Data is shown in Table 2.

Thenar 1 88 145.7 Thenar 2 69 140.1 Thenar 3 33 140.0 **Thenar Change Range (0 - 11.7%) 3.6%** 

asymptomatic subjects on separate reviews over a one-year period.

Table 3. Reproducibility of mean thenar (APB) motor unit number estimates in

Population Controls

**7.3 Reproducibility of MUNE technique** 

EDB MUNE

200

150

100

50

0

coefficients.

SOD1 Neg Controls

Sporadic MND

### Study Groups

Fig. 7. Baseline thenar (APB) MUNE subdivided into study groups (The lower boundary of the box is the 25th percentile, and the upper border is the 75th percentile of MUNE. The horizontal line inside the box represents the median MUNE. The whispers represent the largest and smallest observed values, i.e. the range). Data is shown in Table 1.

In population controls the mean EDB MUNE was 138 with a range of 119 - 169, in SOD1 negative family controls was 134 with a range of 107 - 180 and in asymptomatic SOD1 mutation carriers, 136 with a range of 111 - 187.

Once again, there was no detectable difference in the mean number of EBD motor units in the group of asymptomatic SOD1 mutation carriers compared to the group of SOD1 negative family controls (EDB p>0.95), or population controls (EDB p>0.50) (Table 2 and Figure 8).


Table 2. EDB motor unit number estimates (MUNE number represents mean MUNE).

Symptomatic sporadic MND subjects showed a definite loss of motor units with fewer motor units compared to all other groups (p<0001) with a mean thenar MUNE of 45 with a range of 5 - 84 and a mean EDB MUNE of 70 with a range of 8 - 82 (Tables 1 and 2).

There was no cross over between thenar and EDB MUNE results in symptomatic and asymptomatic subjects.
