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Current Opinion in Ophthalmology Sep 2019Optic pathway gliomas are low-grade neoplasms that affect the precortical visual pathway of children and adolescents. They can affect the optic nerve, optic chiasm,... (Review)
Review
PURPOSE OF REVIEW
Optic pathway gliomas are low-grade neoplasms that affect the precortical visual pathway of children and adolescents. They can affect the optic nerve, optic chiasm, optic tracts and radiations and can either be sporadic or associated with neurofibromatosis type one. Gliomas isolated to the optic nerve (ONG) represent a subgroup of optic pathway gliomas, and their treatment remains controversial. New developments in ONG treatment have emerged in recent years, and it is necessary for clinicians to have a current understanding of available therapies.
RECENT FINDINGS
The current review of the literature covers the background of and recent developments in ONG treatment, with a focus on standard chemotherapy, new molecularly targeted therapies, radiation therapy and surgical resection and debulking.
SUMMARY
Although standard chemotherapy remains the mainstay of ONG treatment, newer molecularly targeted therapies such as mitogen-activated protein kinase kinase inhibitors and bevacizumab represent a promising new treatment modality, and clinical studies are ongoing.
Topics: Adolescent; Antineoplastic Agents; Child; Female; Humans; Male; Molecular Targeted Therapy; Ophthalmologic Surgical Procedures; Optic Chiasm; Optic Nerve Glioma; Optic Nerve Neoplasms; Optic Tract; Radiotherapy
PubMed: 31246635
DOI: 10.1097/ICU.0000000000000587 -
International Journal of Environmental... Mar 2022Wolfram syndrome 1 (WS1) is a rare neurodegenerative disease transmitted in an autosomal recessive mode. It is characterized by diabetes insipidus (DI), diabetes... (Review)
Review
Wolfram syndrome 1 (WS1) is a rare neurodegenerative disease transmitted in an autosomal recessive mode. It is characterized by diabetes insipidus (DI), diabetes mellitus (DM), optic atrophy (OA), and sensorineural hearing loss (D) (DIDMOAD). The clinical picture may be complicated by other symptoms, such as urinary tract, endocrinological, psychiatric, and neurological abnormalities. WS1 is caused by mutations in the gene located on chromosome 4p16 that encodes a transmembrane protein named wolframin. Many studies have shown that wolframin regulates some mechanisms of ER calcium homeostasis and therefore plays a role in cellular apoptosis. More than 200 mutations are responsible for WS1. However, abnormal phenotypes of WS with or without DM, inherited in an autosomal dominant mode and associated with one or more mutations, have been found. Furthermore, recessive Wolfram-like disease without DM has been described. The prognosis of WS1 is poor, and the death occurs prematurely. Although there are no therapies that can slow or stop WS1, a careful clinical monitoring can help patients during the rapid progression of the disease, thus improving their quality of life. In this review, we describe natural history and etiology of WS1 and suggest criteria for a most pertinent approach to the diagnosis and clinical follow up. We also describe the hallmarks of new therapies for WS1.
Topics: Female; Humans; Male; Membrane Proteins; Mutation; Neurodegenerative Diseases; Optic Atrophy; Quality of Life; Wolfram Syndrome
PubMed: 35328914
DOI: 10.3390/ijerph19063225 -
The New England Journal of Medicine Aug 2019Neuromyelitis optica spectrum disorder (NMOSD) is a relapsing, autoimmune, inflammatory disorder that typically affects the optic nerves and spinal cord. At least two... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Neuromyelitis optica spectrum disorder (NMOSD) is a relapsing, autoimmune, inflammatory disorder that typically affects the optic nerves and spinal cord. At least two thirds of cases are associated with aquaporin-4 antibodies (AQP4-IgG) and complement-mediated damage to the central nervous system. In a previous small, open-label study involving patients with AQP4-IgG-positive disease, eculizumab, a terminal complement inhibitor, was shown to reduce the frequency of relapse.
METHODS
In this randomized, double-blind, time-to-event trial, 143 adults were randomly assigned in a 2:1 ratio to receive either intravenous eculizumab (at a dose of 900 mg weekly for the first four doses starting on day 1, followed by 1200 mg every 2 weeks starting at week 4) or matched placebo. The continued use of stable-dose immunosuppressive therapy was permitted. The primary end point was the first adjudicated relapse. Secondary outcomes included the adjudicated annualized relapse rate, quality-of-life measures, and the score on the Expanded Disability Status Scale (EDSS), which ranges from 0 (no disability) to 10 (death).
RESULTS
The trial was stopped after 23 of the 24 prespecified adjudicated relapses, given the uncertainty in estimating when the final event would occur. The mean (±SD) annualized relapse rate in the 24 months before enrollment was 1.99±0.94; 76% of the patients continued to receive their previous immunosuppressive therapy during the trial. Adjudicated relapses occurred in 3 of 96 patients (3%) in the eculizumab group and 20 of 47 (43%) in the placebo group (hazard ratio, 0.06; 95% confidence interval [CI], 0.02 to 0.20; P<0.001). The adjudicated annualized relapse rate was 0.02 in the eculizumab group and 0.35 in the placebo group (rate ratio, 0.04; 95% CI, 0.01 to 0.15; P<0.001). The mean change in the EDSS score was -0.18 in the eculizumab group and 0.12 in the placebo group (least-squares mean difference, -0.29; 95% CI, -0.59 to 0.01). Upper respiratory tract infections and headaches were more common in the eculizumab group. There was one death from pulmonary empyema in the eculizumab group.
CONCLUSIONS
Among patients with AQP4-IgG-positive NMOSD, those who received eculizumab had a significantly lower risk of relapse than those who received placebo. There was no significant between-group difference in measures of disability progression. (Funded by Alexion Pharmaceuticals; PREVENT ClinicalTrials.gov number, NCT01892345; EudraCT number, 2013-001150-10.).
Topics: Adult; Antibodies, Monoclonal, Humanized; Aquaporin 4; Autoantibodies; Complement C5; Complement Inactivating Agents; Disability Evaluation; Disease Progression; Double-Blind Method; Drug Therapy, Combination; Female; Headache; Humans; Immunoglobulin G; Immunosuppressive Agents; Male; Neuromyelitis Optica; Quality of Life; Respiratory Tract Infections; Secondary Prevention
PubMed: 31050279
DOI: 10.1056/NEJMoa1900866 -
ENeurologicalSci Sep 2021•A patient exhibited IgG4-related hypothalamo-hypophysitis.•Prominent high-signal areas of swelling were observed in the hypothalamus, tuber cinereum, infundibulum,...
•A patient exhibited IgG4-related hypothalamo-hypophysitis.•Prominent high-signal areas of swelling were observed in the hypothalamus, tuber cinereum, infundibulum, and bilateral optic nerve systems.•MRI T1WI with contrast media demonstrated enhanced neurohypophysis and cystic swelling, and compressed anterior pituitary.•MRI findings improved rapidly after 4 days of steroid therapy.
PubMed: 34466672
DOI: 10.1016/j.ensci.2021.100362 -
Cancer Cell Dec 2023Intestinal metaplasia (IM) is a pre-malignant condition of the gastric mucosa associated with increased gastric cancer (GC) risk. Analyzing 1,256 gastric samples (1,152...
Intestinal metaplasia (IM) is a pre-malignant condition of the gastric mucosa associated with increased gastric cancer (GC) risk. Analyzing 1,256 gastric samples (1,152 IMs) across 692 subjects from a prospective 10-year study, we identify 26 IM driver genes in diverse pathways including chromatin regulation (ARID1A) and intestinal homeostasis (SOX9). Single-cell and spatial profiles highlight changes in tissue ecology and IM lineage heterogeneity, including an intestinal stem-cell dominant cellular compartment linked to early malignancy. Expanded transcriptome profiling reveals expression-based molecular subtypes of IM associated with incomplete histology, antral/intestinal cell types, ARID1A mutations, inflammation, and microbial communities normally associated with the healthy oral tract. We demonstrate that combined clinical-genomic models outperform clinical-only models in predicting IMs likely to transform to GC. By highlighting strategies for accurately identifying IM patients at high GC risk and a role for microbial dysbiosis in IM progression, our results raise opportunities for GC precision prevention and interception.
Topics: Humans; Stomach Neoplasms; Prospective Studies; Gastric Mucosa; Genomics; Metaplasia; Precancerous Conditions
PubMed: 37890493
DOI: 10.1016/j.ccell.2023.10.004