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Seminars in Ophthalmology Oct 2023The diagnosis of myasthenia gravis (MG) may be challenging and require multiple specialised testing modalities. Accessing these investigations can involve significant...
BACKGROUND
The diagnosis of myasthenia gravis (MG) may be challenging and require multiple specialised testing modalities. Accessing these investigations can involve significant waiting time and costs. The bedside icepack test (IPT) has been proposed to assist with the diagnosis of MG with ocular features, and may prove an economically viable; however, there have been there is heterogeneity in the literature evaluating the IPT.
OBJECTIVES
A systematic review was performed examining the accuracy, described techniques, and economic implications of the IPT for the diagnosis of MG with ocular features.
METHOD
The databases EMBASE, PubMed, and the Cochrane Library were searched from inception to July 2022. The systematic review adhered to PRISMA guidelines. Eligibility determination was undertaken with a standardised form using appropriate inclusion criteria. The Cochrane risk of bias assessment tool for diagnostic test accuracy was employed to evaluate studies that presented the diagnostic performance of the IPT. The Johanna Briggs Institute Critical Appraisal Checklist for Economic Evaluations was used for the assessment of studies presenting economic evaluations of the IPT.
RESULTS
20 articles met the specified criteria and included a total of 1264 participants. The IPT had a sensitivity ranging from 38.5% to 100%. Specificity was found to be > 95% in six studies. Excluding two outlier results of 25% and 31.3%, the lowest specificity recorded was 62.5%. The most commonly described method of evaluating the IPT involved applying ice to both eyelids and using a >2 mm change as a threshold for a positive test (evaluated with a ruler). There were no adverse effects described with the IPT. There were no studies that formally examined the economic implications of the IPT.
CONCLUSIONS
The IPT is a well-tolerated and readily available diagnostic tool that has an important role in the evaluation of possible MG with ocular features in specific contexts. Despite limited economic evaluation of this test, it is likely the use of the IPT may result in significant financial and time savings.
Topics: Humans; Sensitivity and Specificity; Myasthenia Gravis; Cost-Benefit Analysis
PubMed: 36967601
DOI: 10.1080/08820538.2023.2194984 -
Journal of Neurology Jun 2024The clinical spectrum of melanoma-associated neurological autoimmunity, whether melanoma-associated paraneoplastic neurological syndromes (PNS) or induced by immune... (Comparative Study)
Comparative Study
BACKGROUND
The clinical spectrum of melanoma-associated neurological autoimmunity, whether melanoma-associated paraneoplastic neurological syndromes (PNS) or induced by immune checkpoint inhibitors (ICI), is not well characterized. We aim to describe the clinical spectrum of melanoma-associated neurological autoimmunity.
METHODS
A systematic review of the literature combined with patients from French databases of paraneoplastic neurological syndromes was conducted. All melanoma patients with a possible immune-mediated neurologic syndrome were included and classified according to whether they had previously been exposed to ICI (ICI-neurotoxicity) or not (ICI-naïve) at first neurological symptoms.
RESULTS
Seventy ICI-naïve (literature: n = 61) and 241 ICI-neurotoxicity patients (literature: n = 180) were identified. Neuromuscular manifestations predominated in both groups, but peripheral neuropathies were more frequent in ICI-neurotoxicity patients (39.4% vs 21.4%, p = 0.005) whereas myositis was more frequent in ICI-naïve patients (42.9% vs 18.7%, p < 0.001). ICI-naïve patients had also more frequent central nervous system (CNS) involvement (35.7% vs 23.7%, p = 0.045), classical paraneoplastic syndrome (25.7% vs 5.8%, p < 0.001), and more frequently positive for anti-neuron antibodies (24/32, 75.0% vs 38/90, 42.2%, p = 0.001). Although more ICI-neurotoxicity patients died during the acute phase (22/202, 10.9% vs 1/51, 2.0%, p = 0.047), mostly myositis patients (14/22, 63.6%), mortality during follow-up was higher in ICI-naïve patients (58.5% vs 29.8%, p < 0.001). There was no significant difference in the frequency of life independence (mRS ≤ 2) in the surviving patients in both groups (95.5% vs 91.0%, p = 0.437).
CONCLUSIONS
Melanoma-associated PNS appear remarkably rare. The clinical similarities observed in neurological autoimmunity between ICI-treated and ICI-naïve patients, characterized predominantly by demyelinating polyradiculoneuropathy and myositis, suggest a potential prior immunization against melanoma antigens contributing to ICI-related neurotoxicity.
Topics: Humans; Melanoma; Immune Checkpoint Inhibitors; Paraneoplastic Syndromes, Nervous System; Autoimmunity; Male; Female
PubMed: 38467790
DOI: 10.1007/s00415-024-12252-0 -
European Journal of Neurology Jul 2024This study was undertaken to raise awareness of a role of B cells in immune checkpoint inhibitor (ICI)-associated neurological immune-related adverse events (nirAE).
Beyond T cell toxicity - Intrathecal chemokine CXCL13 indicating B cell involvement in immune-related adverse events following checkpoint inhibition: A two-case series and literature review.
BACKGROUND AND PURPOSE
This study was undertaken to raise awareness of a role of B cells in immune checkpoint inhibitor (ICI)-associated neurological immune-related adverse events (nirAE).
METHODS
A systematic literature review was made, with case observations of a melanoma and a non-small cell lung cancer (NSCLC) patient who developed ICI-associated nirAE with cerebrospinal fluid (CSF) findings indicating B cell involvement.
RESULTS
Two patients receiving ipilimumab/nivolumab for melanoma and chemotherapy/pembrolizumab for NSCLC developed nirAE in the form of myocarditis/myositis/myasthenia gravis overlap syndrome (triple M) and cerebellitis plus longitudinal transverse myelitis (c-LETM), respectively. Intrathecal inflammation with chemokine C-X-C motif ligand (CXCL13) elevation was present in both patients; the triple M case had acetylcholine receptor antibodies, antititin reactivity, altered CD4/CD8 T cell ratio in blood, and depressed programmed death-1 (PD-1) expression on CSF T cells; the c-LETM case showed intrathecal antibody production and plasma cells. Both patients insufficiently responded to first-line treatment. The NSCLC case improved upon administration of B cell-depleting therapy with rituximab, whereas the melanoma patient died before escalation therapy was initiated. Literature research revealed one additional ICI-associated LETM case with intrathecal CXCL13 elevation, three cases with ICI-associated aquaporin-4 antibody neuromyelitis spectrum disorder, and evidence of B cell-mediated toxicity based on antibody-mediated immune pathologies in ICI-associated immune-related adverse events.
CONCLUSIONS
The case observations highlight the plethora of uncertainties in diagnosis and treatment of ICI-associated nirAE, exemplify the heterogeneity of immune mechanisms involved, and suggest a role of B cells, which may be underdiagnosed. Intrathecal CXCL13 may serve as a biomarker of B cell involvement in nirAE, supported by intrathecal immunoglobulin synthesis, presence of plasma cells, and/or recruitment of cognate immune cells.
Topics: Aged; Female; Humans; Antibodies, Monoclonal, Humanized; B-Lymphocytes; Chemokine CXCL13; Immune Checkpoint Inhibitors; Ipilimumab; Lung Neoplasms; Melanoma; Myelitis, Transverse; Nivolumab; T-Lymphocytes
PubMed: 38556899
DOI: 10.1111/ene.16279