Assessment of the reliability of the motor unit size index (MUSIX) in single subject "round-robin" and multi-centre settings.

OBJECTIVE: The motor unit size index (MUSIX) is incorporated into the motor unit number index (MUNIX). Our objective was to assess the intra-/inter-rater reliability of MUSIX in healthy volunteers across single subject "round robin" and multi-centre settings. METHODS: Data were obtained from (i) a round-robin assessment in which 12 raters (6 with prior experience and 6 without) assessed six muscles (abductor pollicis brevis, abductor digiti minimi, biceps brachii, tibialis anterior, extensor digitorum brevis and abductor hallucis) and (ii) a multi-centre study with 6 centres studying the same muscles in 66 healthy volunteers. Intra/inter-rater data were provided by 5 centres, 1 centre provided only intra-rater data. Intra/inter-rater variability was assessed using the coefficient of variation (COV), Bland-Altman plots, bias and 95% limits of agreement. RESULTS: In the round-robin assessment intra-rater COVs for MUSIX ranged from 7.8% to 28.4%. Inter-rater variability was between 7.8% and 16.2%. Prior experience did not impact on MUSIX values. In the multi-centre study MUSIX was more consistent than the MUNIX. Abductor hallucis was the least reliable muscle. CONCLUSIONS: The MUSIX is a reliable neurophysiological biomarker of reinnervation. SIGNIFICANCE: MUSIX could provide insights into the pathophysiology of a range of neuromuscular disorders, providing a quantitative biomarker of reinnervation.

Quantitative sensory testing and structural assessment of sensory nerve fibres in amyotrophic lateral sclerosis.

OBJECTIVE: In this prospective study, involvement of sensory nerve fibres in ALS patients was assessed using functional and structural measures in the form of quantitative sensory testing (QST) and skin and nerve biopsies. METHODS: Thirty-two ALS patients and 32 healthy subjects were evaluated with a QST battery comprising thresholds of mechanical detection, mechanical pain, vibration detection, cold detection, warm detection, heat pain, and pinprick sensation. Skin biopsies were evaluated in 31 ALS patients by intraepidermal nerve fibre density (IENFD) and axonal swelling ratios, and growth-associated protein 43 (GAP-43) antibody staining. Sural nerve biopsies were evaluated using teased fibre analysis in eight patients. RESULTS: Mean values for QST parameters and IENFD in ALS patients were within normal range. However, the patients had increased axonal swelling ratios and GAP-43 antibody staining was negative in all patients. CONCLUSIONS: Although QST and IENFD were affected in only a small subset of ALS patients, the axonal swellings observed in all patients indicate that the affection is more frequent, and suggests that IENFD count may not be sufficient. The negative GAP-43 staining suggested an insufficiency of regeneration in small sensory nerve fibres.

Upper motor neuron involvement in amyotrophic lateral sclerosis evaluated by triple stimulation technique and diffusion tensor MRI.

The objective of this study was to evaluate the diagnostic value of triple stimulation technique (TST) and diffusion tensor imaging (DTI) tractography as markers of upper motor neuron (UMN) degeneration in amyotrophic lateral sclerosis (ALS). Fourteen ALS patients fulfilling the El Escorial criteria and 30 control subjects participated in the study. TST amplitude and area ratio were used as an estimate of the degree of central motor conduction failure. DTI fractional anisotropy was used as a quantitative measure of the structural integrity of the corticospinal tract and the posterior limb of the internal capsule. Mean TST amplitude and area ratio were lower in patients than controls, while there were no differences in mean fractional anisotropy of the corticospinal tract or the posterior limb of the internal capsule. TST was abnormal in 7/13 patients (sensitivity 54%) and DTI was abnormal in 3/12 (sensitivity 25%). Combining TST and DTI disclosed abnormalities in 8/11 patients (sensitivity 73%). TST confirmed UMN degeneration in one of every 2.25 patient in the diagnostic categories lower than 'probable' ALS. Using results from TST as a criterion for UMN degeneration, four patients in diagnostic categories lower than 'probable' ALS and without clinical signs of UMN degeneration in the cervical region increased in diagnostic category. Our findings indicate that TST has a significant diagnostic value as an early objective marker of UMN degeneration in ALS, while the value of DTI analysis seems limited.

MUNIX and incremental stimulation MUNE in ALS patients and control subjects.

OBJECTIVE: This study compares the new Motor Unit Number Estimation (MUNE) technique, MUNIX, with the more common incremental stimulation MUNE (IS-MUNE) with respect to reproducibility in healthy subjects and as potential biomarker of disease progression in patients with ALS. METHODS: Thirteen ALS patients and 48 control subjects were prospectively investigated - both groups were studied with MUNIX and IS-MUNE applied on the abductor digiti minimi (ADM) muscle. Additional retest was performed on 14 control subjects. Follow-up tests were carried out on 6 patients. The analysis included measures of reproducibility (Intraclass Correlation Coefficient (ICC)) and diagnostic performance (Receiver Operating Characteristic (ROC) analysis). RESULTS: Test-retest reproducibility was low to moderate for MUNIX and IS-MUNE (ICC=0.38 and 0.56, respectively). Repeated MUNIX and IS-MUNE measurements on the same subject had a mean percentage difference (MPD) of 20% and 46%, respectively (p=0.039). In the control group, the coefficient of variation was markedly lower for MUNIX than for IS-MUNE (26% and 44%, respectively, p<0.0005). In ALS patients MUNIX had a notably better responsiveness in follow-up than IS-MUNE (percent change per month, 9.4 versus 5.6, p=0.046). ROC analysis suggested similar diagnostic accuracy of both tests. CONCLUSIONS: MUNIX is a useful MUNE indicator when assessing progression of lower motor neuron affection in ALS. Furthermore, MUNIX displayed lower intrasubject variability, but no evident better diagnostic yield compared with IS-MUNE. SIGNIFICANCE: This study has established comparative assessment of MUNIX and IS-MUNE performance in test-retest setting and as diagnostic tests on a distal muscle in ALS patients.

Motor Unit Number Index (MUNIX): a novel neurophysiological marker for neuromuscular disorders; test-retest reliability in healthy volunteers.

OBJECTIVE: To investigate the intra-rater and inter-rater test-retest reliability of the Motor Unit Number Index (MUNIX) in healthy subjects in a multicentre setting. METHODS: Six study centres applied the MUNIX technique in 66 healthy subjects. Five to six muscles (biceps brachii, BB; abductor digiti minimi, ADM; abductor pollicis brevis, APB; tibialis anterior, TA; extensor digitorum brevis, EDB and abductor hallucis, AH) were measured in each volunteer four times by two independent examiners. RESULTS: The method was easy to perform and well tolerated. The intraclass correlation coefficient (ICC) varied between centres and muscles. Intra-rater reliability was greatest for the AH (ICC 0.83) and EDB (ICC 0.81). Inter-rater reliability was greatest for the AH (ICC 0.69) and ADM muscles (ICC 0.69). The most critical muscle was the APB muscle (ICC 0.52, total variability). This was mostly due to variability in the compound muscle action potential (CMAP) measurements. MUNIX values of the APB, ADM and TA fell into the same range as in other motor unit number estimation (MUNE) studies. CONCLUSION: MUNIX measurements in multiple muscles show good inter- and intra-rater reliability in healthy subjects. CMAP amplitude must be controlled to optimize reliability. SIGNIFICANCE: Results suggest that MUNIX could serve as a reliable marker for motor neuron loss in diseases like amyotrophic lateral sclerosis.