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Background and Purpose: Acetylcholine receptor antibody (AChR-Ab) detection is crucial in myasthenia gravis (MG) diagnosis and, currently, the radioimmunoassay (RIA) is the gold standard. However, RIA may detect AChR-Ab against nonpathogenic intracellular epitopes. In this study, we performed fixed cell-based assay (F-CBA) in RIA-AChR-Ab positive subjects without MG symptoms, to assess whether F-CBA could show a higher specificity compared to RIA in detecting pathogenic Abs., Methods: We reviewed medical records of patients referred to our MG outpatient clinic because of RIA-AChR-Ab detection. MG diagnosis was based on clinical examination, electrophysiology and Ab detection. AChR-Abs were tested by RIA in the whole cohort. Serum samples from RIA-positive asymptomatic subjects were retested by F-CBA., Results: Of 605 subjects who tested RIA-AChR-Ab positive, MG diagnosis was confirmed in 599. Six subjects were RIA-AChR-Ab positive although they had never had MG symptoms; in four of these subjects AChR-Abs were not detected by F-CBA, whereas the remaining two (both non-MG thymoma cases) were positive also by F-CBA., Conclusions: RIA false positivity for AChR-Ab is very rare. Previous literature has demonstrated that F-CBA has higher sensitivity than RIA for MG, especially in ocular cases. Our preliminary results show that, in rare instances, F-CBA may be more specific than RIA for MG diagnosis., (© 2024 The Author(s). European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background and Purpose: Post-stroke movement disorders (PMDs) following ischemic lesions of the basal ganglia (BG) are a known entity, but data regarding their incidence are lacking. Ischemic strokes secondary to proximal middle cerebral artery (MCA) occlusion treated with thrombectomy represent a model of selective damage to the BG. The aim of this study was to assess the prevalence and features of movement disorders after selective BG ischemia in patients with successfully reperfused acute ischemic stroke (AIS)., Methods: We enrolled 64 consecutive subjects with AIS due to proximal MCA occlusion treated with thrombectomy. Patients were clinically evaluated by a movement disorders specialist for PMDs onset at baseline, and after 6 and 12 months., Results: None of the patients showed an identifiable movement disorder in the subacute phase of the stroke. At 6 and 12 months, respectively, 7/25 (28%) and 7/13 (53.8%) evaluated patients developed PMDs. The clinical spectrum of PMDs encompassed parkinsonism, dystonia and chorea, either isolated or combined. In most patients, symptoms were contralateral to the lesion, although a subset of patients presented with bilateral involvement and prominent axial signs., Conclusion: Post-stroke movement disorders are not uncommon in long-term follow-up of successfully reperfused AIS. Follow-up conducted by a multidisciplinary team is strongly advisable in patients with selective lesions of the BG after AIS, even if asymptomatic at discharge., (© 2024 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background and Purpose: Serum levels of neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) are promising neuro-axonal damage and astrocytic activation biomarkers. Susac syndrome (SS) is an increasingly recognized neurological condition and biomarkers that can help assess and monitor disease evolution are highly needed for the adequate management of these patients. sNfL and sGFAP levels were evaluated in patients with SS and their clinical relevance in the relapse and remission phase of the disease was assessed., Methods: As part of a multicentre study that enrolled patients diagnosed with SS from six international centres, sNfL and sGFAP levels were assessed in 22 SS patients (nine during a relapse and 13 in remission) and 59 age- and sex-matched healthy controls using SimoaTM assay Neurology 2-Plex B Kit., Results: Serum NfL levels were higher than those of healthy controls (p < 0.001) in SS patients and in both subgroups of patients in relapse and in remission (p < 0.001 for both), with significantly higher levels in relapse than in remission (p = 0.008). sNfL levels showed a negative correlation with time from the last relapse (r = -0.663; p = 0.001). sGFAP levels were slightly higher in the whole group of patients than in healthy controls (p = 0.046) and were more pronounced in relapse than in remission (p = 0.013)., Conclusion: In SS patients, both sNFL and sGFAP levels increased compared with healthy controls. Both biomarkers had higher levels during clinical relapse and much lower levels in remission. sNFL was shown to be time sensitive to clinical changes and can be useful to monitor neuro-axonal damage in SS., (© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background and Purpose: Longitudinally extensive transverse myelitis (LETM) associated with aquaporin-4 autoantibodies (AQP4-IgG) can cause severe disability. Early diagnosis and prompt treatment are critical to prevent relapses. A novel score is described based on clinical and neuroimaging characteristics that predicts AQP4-IgG positivity in patients with LETM., Methods: Patients were enrolled both retrospectively and prospectively from multiple Italian centers. Clinical and neuroimaging characteristics of AQP4-IgG positive and negative patients were compared through univariate and multivariate analysis., Results: Sixty-six patients were included. Twenty-seven (41%) were AQP4-IgG positive and median age at onset was 45.5 years (range 19-81, interquartile range 24). Female sex (odds ratio [OR] 17.9, 95% confidence interval [CI] 2.6-381.9; p = 0.014), tonic spasms (OR 45.6, 95% CI 3.1-2197; p = 0.017) and lesion hypointensity on T1-weighted images (OR 52.9, 95% CI 6.8-1375; p = 0.002) were independently associated with AQP4-IgG positivity. The AQP4-IgG positivity in myelitis (AIM) score predicted AQP4-IgG positivity with 85% sensitivity and 95% specificity. Positive and negative likelihood ratios were 16.6 and 0.2 respectively. The inter-rater and intra-rater agreement in the score application were both excellent., Conclusions: The AIM score predicts AQP4-IgG positivity with good sensitivity and specificity in patients with a first episode of LETM. The score may assist clinicians in early diagnosis and treatment of AQP4-IgG positive LETM., (© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background and Purpose: This study was undertaken to assess the long-term outcome of patients with paraneoplastic and non paraneoplastic autoimmune cerebellar ataxia (ACA) using the Scale for the Assessment and Rating of Ataxia (SARA)., Methods: Patients with subacute cerebellar ataxia admitted to our institution between September 2012 and April 2020 were prospectively recruited. Serum and/or cerebrospinal fluid was tested for neural autoantibodies by indirect immunofluorescence on mouse brain, cell-based assays, and radioimmunoassay. SARA and modified Rankin Scale (mRS) score were employed to assess patients' outcome., Results: Fifty-five patients were recruited, of whom 23 (42%) met the criteria for cerebellar ataxia of autoimmune etiology. Neural autoantibodies were detected in 22 of 23 patients (Yo-immunoglobulin G [IgG], n = 6; glutamic acid decarboxylase 65-IgG, n = 3; metabotropic glutamate receptor 1-IgG, n = 2; voltage-gated calcium channel P/Q type-IgG, n = 2; Hu-IgG, n = 1; glial fibrillary acidic protein-IgG, n = 1; IgG-binding unclassified antigens, n = 7). Thirteen patients were diagnosed with paraneoplastic cerebellar syndrome (PCS) and 10 with idiopathic ACA. All patients received immunotherapy. Median SARA score was higher in the PCS group at all time points (p = 0.0002), while it decreased significantly within the ACA group (p = 0.049) after immunotherapy. Patients with good outcome (mRS ≤ 2) had less neurological disability (SARA < 15) at disease nadir (p = 0.039) and presented less frequently with paraneoplastic neurological syndrome (p = 0.0028). The univariate linear regression model revealed a good correlation between mRS and SARA score both at disease onset (p < 0.0001) and at last follow-up (p < 0.0001). SARA score < 11 identified patients with good outcome., Conclusions: Patients with idiopathic ACA significantly improved after immunotherapy. SARA score accurately reflects patients' clinical status and may be a suitable outcome measure for patients with ACA., (© 2021 European Academy of Neurology.)

Background and Purpose: The objective of this study was to assess the neurological manifestations in a series of consecutive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive patients, comparing their frequency with a population hospitalized in the same period for flu/respiratory symptoms, finally not related to SARS-CoV-2., Methods: Patients with flu/respiratory symptoms admitted to Fondazione Policlinico Gemelli hospital from 14 March 2020 to 20 April 2020 were retrospectively enrolled. The frequency of neurological manifestations of patients with SARS-CoV-2 infection was compared with a control group., Results: In all, 213 patients were found to be positive for SARS-CoV-2, after reverse transcriptase polymerase chain reaction on nasal or throat swabs, whilst 218 patients were found to be negative and were used as a control group. Regarding central nervous system manifestations, in SARS-CoV-2-positive patients a higher frequency of headache, hyposmia and encephalopathy always related to systemic conditions (fever or hypoxia) was observed. Furthermore, muscular involvement was more frequent in SARS-CoV-2 infection., Conclusions: Patients with COVID-19 commonly have neurological manifestations but only hyposmia and muscle involvement seem more frequent compared with other flu diseases., (© 2020 European Academy of Neurology.)

For biologic fixation, press-fit acetabular cups should have initial stability with minimal micromotion and osteoconductive surfaces in contact with bone. Inadequate exposure potentially influences initial stability by increasing the possibility of soft tissue interposition and contamination at the implant-tissue interface. A sawbone model was used to examine how interposed tissue and contamination influence initial cup stability. Seven groups (n = 4) were tested with varying levels of interposed fatty and fibrous tissue placed around the rim of the cup. 54 millimeter in diameter highly porous hemispherical acetabular cups (Stryker, Mahwah NJ) and 54 mm reamed cavities in sawbone blocks were used. Shells were seated and maximum lever out force was recorded for each sample. Cups with fibrous tissue spaced evenly along the rim had a lever out force that was 150% of the control (107 ± 6 vs. 150 ± 12N, p = 0.005), and fatty tissue contamination had a lever out force that was 140% of the control (143 ± 18 vs. 107 ± 6N, p = 0.04). Cups with fibrous tissue placed eccentrically along the rim had a lever out force that was double the control 107 ± 6 N vs. 200 ± 15 N (p = 0.001). Surprisingly, fatty tissue contamination and fibrous tissue interposition at the rim increased initial stability. The eccentrically interposed tissue forced the opposite pole of the cup into the bone, resulting in a more secure press-fit. However, soft tissue interposition decreases implant/bone apposition, and the effect on long term fixation is unknown. Statement of Clinical Significance: Soft tissue interposition between the bone and cup may provide higher initial stability, but its long-term effects are unknown. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res., (© 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Background and Purpose: The detection of antibodies binding neural antigens in patients with epilepsy has led to the definition of 'autoimmune epilepsy'. Patients with neural antibodies not responding to antiepileptic drugs (AEDs) may benefit from immunotherapy. Aim of this study was to evaluate the frequency of autoantibodies specific to neural antigens in patients with epilepsy and their response to immunotherapy., Methods: Eighty-one patients and 75 age- and sex-matched healthy subjects (HS) were enrolled in the study. Two groups of patients were included: 39 patients with epilepsy and other neurological symptoms and/or autoimmune diseases responsive to AEDs (group 1) and 42 patients with AED-resistant epilepsy (group 2). Patients' serum and cerebrospinal fluid were evaluated for the presence of autoantibodies directed to neural antigens by indirect immunofluorescence on frozen sections of mouse brain, cell-based assays and a radioimmunoassay. Patients with AED-resistant epilepsy and neural autoantibodies were treated with immunotherapy and the main outcome measure was the reduction in seizure frequency., Results: Neural autoantibodies were detected in 22% of patients (18/81), mostly from the AED-resistant epilepsy group (P = 0.003), but not in HS. Indirect immunofluorescence on mouse brain revealed antibodies binding to unclassified antigens in 10 patients. Twelve patients received immunotherapy and nine (75%) achieved >50% reduction in seizure frequency., Conclusions: A significant proportion of patients with AED-resistant epilepsy harbor neural-specific autoantibodies. The detection of these antibodies, especially of those binding to synaptic antigens, may predict a favorable response to immunotherapy, thus overcoming AED resistance., (© 2014 EAN.)

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is considered an auto-immune disorder. We evaluated expression of pSTAT1, T-bet, and pSTAT3 in circulating T-cells, B-cells, and monocytes and spontaneous production of interleukin-17 (IL17), interferon-gamma (IFN gamma), and interleukin-10 (IL10) by peripheral blood mononuclear cells (PBMCs) from 14 active CIDP patients compared with 6 patients with long-lasting remission and 20 controls. Active disease patients showed higher pSTAT1, T-bet, and pSTAT3 in CD4(+) T-cells than controls (p < 0.001, p = 0.0002, p = 0.0097, respectively) and remission patients (p < 0.001, p = 0.0036, p = 0.0008, respectively). pSTAT1, T-bet, and pSTAT3 were also higher in monocytes from active CIDP patients than controls (p = 0.0011, p = 0.0041, p = 0.0413, respectively) and remission patients (p = 0.0073, p = 0.0274, p = 0.0251, respectively). Moreover in CD8(+) T-cells, pSTAT3 expression was higher in active CIDP patients than in remission patients (p = 0.0345) and in controls (p = 0.0023). IL17 and IFN gamma production were significantly higher in active CIDP patients than in controls (p < 0.0395, p = 0.0010, respectively); IFN gamma levels were higher also in remission CIDP patients (p = 0.0073). IL10 levels were higher in active phase patients than in controls (p = 0.0334). Our data suggest that pSTAT1, T-bet, and pSTAT3 can be considered putative markers of disease activity and potential targets for specific therapies.

Subject: It has been demonstrated that L-arginine-nitric oxide (NO) system is present in the myometrium during pregnancy where it can regulate uterine contractility., Material and Method: We have studied by immunohistochemistry the localization of constitutive endothelial nitric oxide synthase (ecNOS) and brain nitric oxide synthase (bNOS) in human fetal membranes in term non laboring women., Results: The amniotic epithelium and the trophoblast of chorion layer stained intensively for bNOS, while for ecNOS the immunoreactivity was weak and restricted to trophoblast cells., Conclusion: These findings are suggestive for NO production by the fetal membranes in term pregnancy.