Our software package uses a peak detection algorithm. The work on filter settings was performed using that algorithm and therefore what follows in the description here may not apply to programs using an algorithm which is triggered by the slope of the potential as this may be affected by the low-frequency filter settings. There is good deal of debate as to what the potentials produced by stimulation of the nerve or muscle represent [24–26]. It is for this reason that we have tried to distance ourselves from strict single fibre methodology because the requirements for single-fibre potentials to be accurately identified are necessarily extremely stringent and very rarely met by the technique of SPACE. The number of potentials that can safely be considered to be from a single fibre are very few indeed in most examinations. Using the alternative term apparent single fibre action potentials (ASFAP) [24] to cover this in many ways does not go far enough. Our technique is to use the peak detection algorithm to identify the potentials by the algorithm set by the software. If the study is normal and the peaks do not show much variation clearly the peak detection algorithm will have little difficulty in identifying jitter. However, sometimes several potentials may be seen with varying confidence as to their origin. Such a situation is shown in Fig. 10.2 where five potentials are seen none of which would fulfil criteria for a single fibre potential but the measurement, albeit inaccurate, does give you some indication of the degree of abnormality when compared with normative data obtained from similar technique. Once the abnormality becomes pronounced the abnormality on peak detection increases exponentially and any linear relationship between degree of abnormality of the neuromuscular junction and abnormality on jitter measurement can be discounted (Fig. 10.3).

When analysing the data as we increase the intensity from zero until the threshold for individual potentials is reached there is a need to remove those first potentials particularly as they may show some minor jitter until supramaximal stimulation is achieved. Once this is done it is normally acceptable to use the measurements provided by the peak detection algorithm. The only time this is contested is if the program is clearly picking up alternating peaks from a potential with two peaks. This is shown in Fig. 10.4. It is possible to go through and identify those waveforms which only focus on one peak, or more easily, discount that potential from your examination.

Early on in our departmental experience with the technique we formed the impression that the neuromuscular junction was extraordinarily mature with samples of seemingly unaltered potentials appearing in children as young as 6 weeks of age which were indistinguishable to the blinded observer from a child in their teenage years. For this reason we used for a while the normative data obtained in stimulated single fibre EMG or volition SFEMG with the correction factor applied (×0.8) [27] in normal adults [24, 28–34] . With E-norm methodology, which extracts the normative data from laboratory attendances we have been able to confirm the jitter measurements in older children are indeed very similar to adults [35]. From a cohort of 600 cases, we derived an upper limit of normal of 26 μs for the mean jitter for children 2 years of age and older. More detailed analysis of the group under 2 years of age suggested that while some may have extraordinarily mature neuromuscular junctions this state is by no means the rule and we therefore found that under 1 year an upper limit of the mean jitter was 45 μs decreasing in the next year to 33 μs with the adult level being reached at 2 years of age [36]. Our results are calculated as the mean consecutive difference index or MCD-I which is calculated as the value obtained divided by the upper limit of normal.

There are few if any centres that have much experience of the use of this technique in children, which is inexplicable, and whilst there have been a few papers [37, 38] reporting results in limited numbers of subjects our experience is unique. For a period of time certainly from around 1997–2007 our attempts to perform the technique were often greeted by failure and the numbers done per year were very few (Fig. 10.5). Sometimes a maximum of only ten would come through our department in a year. However, after that time possibly related to changes in technique such as using shorter stimulating electrodes, which did not need to be held in position and also the more frequent application of local anaesthetic we saw an exponential increase in the number of cases, which are now at around 120 per year. A recent audit of our experience from 7 July 2007 to 8 February 2016 identified a total of 878 investigations, 501 boys and 377 girls [39]. The mean age was just over 5 years (66 months) but was skewed towards the younger age group with the median 46.5 months. Our hospital is a tertiary referral centre and because of this 114 cases were lost to follow-up. Many of these were from overseas often attending for one visit only. In this group 23 had an abnormal MCD-I ranging between 101 and 294% with 10% of them having MCD-I significantly elevated, defined as greater than 125%. A further group of 104 patients had not completed their investigations and were excluded from the analysis. Thirty six of these had a raised MCD-I, 25 of which were greater than 125%. The remaining cohort was 660 children in whom a diagnosis had been made or neuromuscular abnormality had been ruled out by a neuromuscular specialist.

The diagnosis of myasthenia was considered definite if an associated genetic abnormality was identified or antibodies against the acetylcholine receptor or the MuSK protein had been identified. A further category of probable myasthenia was included in which the diagnosis of myasthenia was felt to be highly likely based on examination by a neuromuscular specialist with additional support from response to pyridostigmine. Ninty four patients had a diagnosis of myasthenia and these are shown in Table 10.1 along with other causes of NMJ abnormality such as botulism, when persistence of neuromuscular blocking agents (NMBA), bringing the total to 106.

In 554 alternative diagnoses were made (Table 10.2). The diagnoses were made with combination of clinical assessment, genetic, histopathological and other ancillary investigations. The diagnosis of a neurogenic abnormality was felt to be secure on neurophysiological grounds only. A proportion of these other cases had abnormalities of jitter and the range of that abnormality as an MCD-I is also shown.