Motor unit number estimation via MScanFit MUNE in spinal muscular atrophy.

INTRODUCTION/AIMS: MScanFit MUNE (MScanFit) is a novel tool to derive motor unit number estimates (MUNEs) from compound muscle action potential (CMAP) scans. Few studies have explored its utility in 5q spinal muscular atrophy (SMA5q) patients, assessing only the abductor pollicis brevis (APB) muscle. We aimed to assess different distal muscles in pediatric and adult SMA5q patients, further evaluating clinical-electrophysiological correlations. METHODS: We analyzed MScanFit parameters reflecting the extent of denervation (MUNE; N50) and parameters of collateral reinnervation in APB, abductor digiti minimi (ADM), and tibialis anterior (TA) muscles. SMA patients were clinically evaluated using standardized motor function clinical scales, including the Hammersmith Functional Motor Scale - Expanded and the Revised Upper Limb Module. RESULTS: A total of 23 SMA5q (9 SMA type 2 and 14 SMA type 3) and 12 age-matched healthy controls (HCs) were enrolled. SMA patients showed lower MUNE and N50 values and higher parameters of collateral sprouting in all muscles compared to HC (p < .001). SMA type 2 patients demonstrated lower MUNE and higher collateral reinnervation values in APB and TA compared to SMA type 3 (p < .05). Walker patients showed higher values of MUNE and N50, and lower parameters of reinnervation in all muscles compared to sitters (p < .05). MScanFit parameters showed strong correlations (Rho-values ranging from .72 to .83) with clinical measurements. MUNE values were abnormal in muscles that were not clinically affected. DISCUSSION: MScanFit parameters showed promise as an outcome measure. Further studies, particularly longitudinal ones, are needed to evaluate MScanFit in measuring response to treatments.

AFG3L2 and ACO2-Linked Dominant Optic Atrophy: Genotype-Phenotype Characterization Compared to OPA1 Patients.

PURPOSE: Heterozygous mutations in the AFG3L2 gene (encoding a mitochondrial protease indirectly reflecting on OPA1 cleavage) and ACO2 gene (encoding the mitochondrial enzyme aconitase) are associated with isolated forms of Dominant Optic Atrophy (DOA). We aimed at describing their neuro-ophthalmological phenotype as compared with classic OPA1-related DOA. DESIGN: Cross-sectional study. METHODS: The following neuro-ophthalmological parameters were collected: logMAR visual acuity (VA), color vision, mean deviation and foveal threshold at visual fields, average and sectorial retinal nerve fiber layer (RNFL), and ganglion cell layer (GCL) thickness on optical coherence tomography. ACO2 and AFG3L2 patients were compared with an age- and sex-matched group of OPA1 patients with a 1:2 ratio. All eyes were analyzed using a clustered Wilcoxon rank sum test with the Rosner-Glynn-Lee method. RESULTS: A total of 44 eyes from 23 ACO2 patients and 26 eyes from 13 AFG3L2 patients were compared with 143 eyes from 72 OPA1 patients. All cases presented with bilateral temporal-predominant optic atrophy with various degree of visual impairment. Comparison between AFG3L2 and OPA1 failed to reveal any significant difference. ACO2 patients compared to both AFG3L2 and OPA1 presented overall higher values of nasal RNFL thickness (P = .029, P = .023), average thickness (P = .012, P = .0007), and sectorial GCL thickness. These results were confirmed also comparing separately affected and subclinical patients. CONCLUSIONS: Clinically, DOA remains a fairly homogeneous entity despite the growing genetic heterogeneity. ACO2 seems to be associated with an overall better preservation of retinal ganglion cells, probably depending on the different pathogenic mechanism involving mtDNA maintenance, as opposed to AFG3L2, which is involved in OPA1 processing and is virtually indistinguishable from classic OPA1-DOA.

Chromatic Pupillometry in Isolated Rapid Eye Movement Sleep Behavior Disorder.

BACKGROUND: Melanopsin retinal ganglion cell (mRGC)-mediated pupillary light reflex (PLR) abnormalities have been documented in several neurodegenerative disorders including Parkinson's disease. Overall, isolated rapid eye movement (REM) sleep behavior disorder (iRBD) represents the strongest prodromal risk factor for impending α-synucleinopathies. OBJECTIVES: To quantitatively compare PLR and mRGC-mediated contribution to PLR in 16 iRBD patients and 16 healthy controls. METHODS: iRBD and controls underwent extensive neuro-ophthalmological evaluation and chromatic pupillometry. In iRBD, PLR metrics were correlated with clinical variables and with additional biomarkers including REM atonia index (RAI), DaTscan, and presence of phosphorylated-α-synuclein (p-α-syn) deposition in skin biopsy. RESULTS: We documented higher baseline pupil diameter and decreased rod-transient PLR amplitude in iRBD patients compared to controls. PLR rod-contribution correlated with RAI. Moreover, only iRBD patients with evidence of p-α-syn deposition at skin biopsy showed reduced PLR amplitude compared to controls. CONCLUSION: The observed PLR abnormalities in iRBD might be considered as potential biomarkers for the risk stratification of phenoconversion of the disease. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.