Evaluation of a Multiparametric Immunofluorescence Assay for Standardization of Neuromyelitis Optica Serology

Background: Neuromyelitis optica (NMO) is a severely disabling autoimmune disorder of the central nervous system, which predominantly affects the optic nerves and spinal cord. In a majority of cases, NMO is associated with antibodies to aquaporin-4 (AQP4) (termed NMO-IgG). Aims: In this study, we evaluated a new multiparametric indirect immunofluorescence (IIF) assay for NMO serology. Methods: Sera from 20 patients with NMO, 41 patients with multiple sclerosis (MS), 30 healthy subjects, and a commercial anti-AQP4 IgG antibody were tested in a commercial composite immunofluorescence assay ("Neurology Mosaic 17"; Euroimmun, Germany), consisting of five different diagnostic substrates (HEK cells transfected with AQP4, non-transfected HEK cells, primate cerebellum, cerebrum, and optic nerve tissue sections). Results: We identified AQP4 specific and non-specific fluorescence staining patterns and established positivity criteria. Based on these criteria, this kit yielded a high sensitivity (95%) and specificity (100%) for NMO and had a significant positive and negative likelihood ratio (LR+ = ∞, LR- = 0.05). Moreover, a 100% inter- and intra-laboratory reproducibility was found. Conclusions: The biochip mosaic assay tested in this study is a powerful tool for NMO serology, fast to perform, highly sensitive and specific for NMO, reproducible, and suitable for inter-laboratory standardization as required for multi-centre clinical trials

Western blot analysis for the detection of serum antibodies recognizing linear Aquaporin-4 epitopes in patients with Neuromyelitis Optica

The current study presents a western blot assay showing good sensitivity (81%) and specificity (97%) for detecting serum antibodies to Aquaporin-4 (AQP4) in patients with Neuromyelitis Optica (NMO). By using western blot, we were able, for the first time, to distinguish serum immunoreactivity against either of the two AQP4 isoforms, showing that antibodies recognizing the linear AQP4-M1 isoform are specific for NMO. Moreover, the high sensitivity and specificity of the western blot assay in detecting serum anti-AQP4 antibodies in NMO patients suggest that such auto-antibodies may be of linear nature, thus recognizing epitopes that are displayed in denatured protein

Presentation and Validation of the Multiple Sclerosis Depression Rating Scale: A Test Specifically Devised to Investigate Affective Disorders in Multiple Sclerosis Patients

Accurate diagnosis of depression in patients affected by MS is important, as it may be a cause of reduced quality of life and increased suicide risk. We present a new scale, the Multiple Sclerosis Depression Rating Scale (MSDRS), and assess its diagnostic accuracy in comparison to the Beck Depression Inventory (BDI). A total of 94 MS participants were classified as non-depressed (N\u2009=\u200944) or affected by mood disorder associated to MS with depressive manifestations (MSD-MDDM; N\u2009=\u200937) or with a major depression-like episode (MSD-MDL; N\u2009=\u200913). Each participant underwent a psychiatric interview, MSDRS, and BDI; diagnostic accuracy was evaluated using area under the ROC curve (AROC). The diagnostic accuracy of MSDRS and BDI was comparable when diagnosing both MSD-MDDM and MSD-MDL (AROC respectively 0.8998 and 0.8659); the MSDRS showed higher accuracy for the diagnosis of MSD-MDL (AROC respectively 0.9278 and 0.8314; p\u2009=\u2009.038). The MSDRS may be a reliable tool for the diagnosis of depression in MS

Thr124Met myelin protein zero mutation mimicking motor neuron disease

Mutations in myelin protein zero (MPZ) are associated with heterogeneous manifestations. In this study, we report clinical, electrophysiological, pathological, and muscle MRI findings from two relatives with MPZ Thr124Met variants, disclosing different phenotypes. The proband was a 73-year-old female with a 12-year-story of atrophy, weakness, and fasciculations in her proximal and distal lower limbs. EMG examination showed neurogenic signs with active denervation together with reduced sensory action potentials, without sensory symptoms. The initial diagnosis was of a slowly progressive lower motor neuron disease (MND) with subclinical sensory axonal neuropathy. Two years later, the observation of her 60-year-old nephew, who had a distal sensory-motor neuropathy, prompted the analysis of inherited neuropathies-related genes and revealed a MPZ Thr124Met mutation in both cases. Our findings expand the clinical spectrum of MPZ-related neuropathy and highlight that Thr124Met mutation may cause a syndrome mimicking MND. The challenging issue to detect sensory features in the diagnostic MND work up is discussed