Clinical and electrophysiological examination of pinch strength in patients with amyotrophic lateral sclerosis.

BACKGROUND: The split-hand concept has highlighted the preferential wasting of the thenar side of the hand in amyotrophic lateral sclerosis (ALS). Our objective is to re-explore pinch grip strength to assess whether it has the potential to be a practical biomarker of ALS. METHODS: We measured different pinch grip strengths (thumb, index, and fifth) using a pinch gauge from both hands of 54 ALS patients and correlated this with the Medical Research Council (MRC) score, the upper-limb component of the revised ALS Functional Rating Scale - Revised (ALSFRS-R) score, and compound muscle action potentials (CMAPs) that comprise the split-hand index. RESULTS: Pinch grip strength using any of the three fingers showed a positive correlation with its corresponding CMAP, MRC grading, and upper-limb ALSFRS-R score. The thumb pinch showed the strongest correlation with the split-hand index and MRC grading. CONCLUSIONS: Pinch grip strength test using a simple gauge deserves further study as a potentially practical biomarker of ALS.

Monocytes and neutrophils are associated with clinical features in amyotrophic lateral sclerosis.

Immunity has emerged as a key player in neurodegenerative diseases such as amyotrophic lateral sclerosis, with recent studies documenting aberrant immune changes in patients and animal models. A challenging aspect of amyotrophic lateral sclerosis research is the heterogeneous nature of the disease. In this study, we investigate the associations between peripheral blood myeloid cell populations and clinical features characteristic of amyotrophic lateral sclerosis. Peripheral blood leukocytes from 23 healthy controls and 48 patients with amyotrophic lateral sclerosis were analysed to measure myeloid cell alterations. The proportion of monocytes (classical, intermediates and non-classical subpopulations) and neutrophils, as well as the expression of select surface markers, were quantitated using flow cytometry. Given the heterogeneous nature of amyotrophic lateral sclerosis, multivariable linear analyses were performed to investigate associations between patients' myeloid profile and clinical features, such as the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale, bulbar subscore of the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale, change in Revised Amyotrophic Lateral Sclerosis Functional Rating Scale over disease duration and respiratory function. We demonstrate a shift in monocyte subpopulations in patients with amyotrophic lateral sclerosis, with the ratio of classical to non-classical monocytes increased compared with healthy controls. In line with this, patients with greater disease severity, as determined by a lower Revised Amyotrophic Lateral Sclerosis Functional Rating Scale score, had reduced non-classical monocytes. Interestingly, patients with greater bulbar involvement had a reduction in the proportions of classical, intermediate and non-classical monocyte populations. We also revealed several notable associations between myeloid marker expression and clinical features in amyotrophic lateral sclerosis. CD16 expression on neutrophils was increased in patients with greater disease severity and a faster rate of disease progression, whereas HLA-DR expression on all monocyte populations was elevated in patients with greater respiratory impairment. This study demonstrates that patients with amyotrophic lateral sclerosis with distinct clinical features have differential myeloid cell signatures. Identified cell populations and markers may be candidates for targeted mechanistic studies and immunomodulation therapies in amyotrophic lateral sclerosis.

Hypermetabolism in ALS is associated with greater functional decline and shorter survival.

OBJECTIVE: To determine the prevalence of hypermetabolism, relative to body composition, in amyotrophic lateral sclerosis (ALS) and its relationship with clinical features of disease and survival. METHODS: Fifty-eight patients with clinically definite or probable ALS as defined by El Escorial criteria, and 58 age and sex-matched control participants underwent assessment of energy expenditure. Our primary outcome was the prevalence of hypermetabolism in cases and controls. Longitudinal changes in clinical parameters between hypermetabolic and normometabolic patients with ALS were determined for up to 12 months following metabolic assessment. Survival was monitored over a 30-month period following metabolic assessment. RESULTS: Hypermetabolism was more prevalent in patients with ALS than controls (41% vs 12%, adjusted OR=5.4; p<0.01). Change in body weight, body mass index and fat mass (%) was similar between normometabolic and hypermetabolic patients with ALS. Mean lower motor neuron score (SD) was greater in hypermetabolic patients when compared with normometabolic patients (4 (0.3) vs 3 (0.7); p=0.04). In the 12 months following metabolic assessment, there was a greater change in Revised ALS Functional Rating Scale score in hypermetabolic patients when compared with normometabolic patients (-0.68 points/month vs -0.39 points/month; p=0.01). Hypermetabolism was inversely associated with survival. Overall, hypermetabolism increased the risk of death during follow-up to 220% (HR 3.2, 95% CI 1.1 to 9.4, p=0.03). CONCLUSIONS AND RELEVANCE: Hypermetabolic patients with ALS have a greater level of lower motor neuron involvement, faster rate of functional decline and shorter survival. The metabolic index could be important for informing prognosis in ALS.