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.

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.