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International Journal of Molecular... Apr 2021Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an ultra-rare disease for which there are currently no validated outcome measures for assessing...
Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an ultra-rare disease for which there are currently no validated outcome measures for assessing therapeutic intervention efficacy. The aim of this study was to identify a plasma and/or serum microRNA (miRNA) biomarker panel for MNGIE. Sixty-five patients and 65 age and sex matched healthy controls were recruited and assigned to one of four study phases: (i) discovery for sample size determination; (ii) candidate screening; (iii) candidate validation; and (iv) verifying the performance of the validated miRNA panel in four patients treated with erythrocyte-encapsulated thymidine phosphorylase (EE-TP), an enzyme replacement under development for MNGIE. Quantitative PCR (qPCR) was used to profile miRNAs in serum and/or plasma samples collected for the discovery, validation and performance phases, and next generation sequencing (NGS) analysis was applied to serum samples assigned to the candidate screening phase. Forty-one differentially expressed candidate miRNAs were identified in the sera of patients ( < 0.05, log fold change > 1). The validation cohort revealed that of those, 27 miRNAs were upregulated in plasma and three miRNAs were upregulated in sera ( < 0.05). Through binary logistic regression analyses, five plasma miRNAs (, miR-193a-5p, , and and three serum miRNAs (, and ) were shown to robustly distinguish MNGIE from healthy controls. Reduced longitudinal miRNA expression of was observed in all four patients treated with EE-TP and coincided with biochemical and clinical improvements. We recommend the inclusion of the plasma exploratory miRNA biomarker panel in future clinical trials of investigational therapies for MNGIE; it may have prognostic value for assessing clinical status.
Topics: Biomarkers; Case-Control Studies; Gene Expression Profiling; Humans; Intestinal Pseudo-Obstruction; MicroRNAs; Muscular Dystrophy, Oculopharyngeal; Ophthalmoplegia
PubMed: 33916195
DOI: 10.3390/ijms22073681 -
British Medical Journal Feb 1976
Topics: Adult; Eye Movements; Humans; In Vitro Techniques; Male; Ophthalmoplegia; Tetanus
PubMed: 1252781
DOI: 10.1136/bmj.1.6007.437 -
British Medical Journal Jan 1979
Topics: Humans; Hypothyroidism; Ophthalmoplegia; Thyroxine
PubMed: 760981
DOI: 10.1136/bmj.1.6156.124-c -
British Medical Journal May 1971
Topics: Eye Movements; Humans; Ophthalmoplegia
PubMed: 5576020
DOI: 10.1136/bmj.2.5759.468 -
Annals of the New York Academy of... Apr 2015The ocular motor system provides several advantages for studying the brain, including well-defined populations of neurons that contribute to specific eye movements.... (Review)
Review
The ocular motor system provides several advantages for studying the brain, including well-defined populations of neurons that contribute to specific eye movements. Generation of rapid eye movements (saccades) depends on excitatory burst neurons (EBN) and omnipause neurons (OPN) within the brainstem, both types of cells are highly active. Experimental lesions of EBN and OPN cause slowing or complete loss of saccades. We report a patient who developed a permanent, selective saccadic palsy following cardiac surgery. When she died several years later, surprisingly, autopsy showed preservation of EBN and OPN. We therefore considered other mechanisms that could explain her saccadic palsy. Recent work has shown that both EBN and OPN are ensheathed by perineuronal nets (PN), which are specialized extracellular matrix structures that may help stabilize synaptic contacts, promote local ion homeostasis, or play a protective role in certain highly active neurons. Here, we review the possibility that damage to PN, rather than to the neurons they support, could lead to neuronal dysfunction-such as saccadic palsy. We also suggest how future studies could test this hypothesis, which may provide insights into the vulnerability of other active neurons in the nervous system that depend on PN.
Topics: Brain Stem; Cardiac Surgical Procedures; Humans; Motor Cortex; Ophthalmoplegia; Pons; Postoperative Complications; Raphe Nuclei; Saccades
PubMed: 25721480
DOI: 10.1111/nyas.12666 -
AJNR. American Journal of Neuroradiology 1987Internuclear ophthalmoplegia is a gaze disorder characterized by impaired adduction on the side of a lesion involving the medial longitudinal fasciculus with dissociated...
Internuclear ophthalmoplegia is a gaze disorder characterized by impaired adduction on the side of a lesion involving the medial longitudinal fasciculus with dissociated nystagmus of the abducting eye. Eleven patients with internuclear ophthalmoplegia (nine with clinical multiple sclerosis, two with clinical infarction) underwent MR imaging with spin-echo techniques on a 1.5-T system. Nine patients also had CT. MR showed focal or nodular areas of high signal intensity on T2-weighted images in the region of the medial longitudinal fasciculus in 10 of 11 patients. In one of four patients with internuclear ophthalmoplegia who had MR after intravenous gadolinium-DTPA, an enhancing ring lesion was seen in the region of the medial longitudinal fasciculus on short TR/TE images, indicating active blood-brain-barrier disruption, which correlated with this patient's recent-onset internuclear ophthalmoplegia. CT failed to show the lesions in all nine patients examined. This report demonstrates the superiority of MR in evaluating gaze disorders attributable to brainstem dysfunction, such as internuclear ophthalmoplegia, and correlates MR findings with the relevant neuroanatomy of the medial longitudinal fasciculus.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Brain Stem; Female; Humans; Magnetic Resonance Spectroscopy; Male; Middle Aged; Multiple Sclerosis; Neural Pathways; Ophthalmoplegia
PubMed: 3105283
DOI: No ID Found -
AJNR. American Journal of Neuroradiology Jul 2020Miller Fisher syndrome, also known as Miller Fisher variant of Guillain-Barré syndrome, is an acute peripheral neuropathy that can develop after exposure to various...
Miller Fisher syndrome, also known as Miller Fisher variant of Guillain-Barré syndrome, is an acute peripheral neuropathy that can develop after exposure to various viral, bacterial, and fungal pathogens. It is characterized by a triad of ophthalmoplegia, ataxia, and areflexia. Miller Fisher syndrome has recently been described in the clinical setting of the novel coronavirus disease 2019 (COVID-19) without accompanying imaging. In this case, we report the first presumptive case of COVID-19-associated Miller Fisher syndrome with MR imaging findings.
Topics: Adult; Betacoronavirus; COVID-19; Coronavirus Infections; Humans; Magnetic Resonance Imaging; Male; Miller Fisher Syndrome; Ophthalmoplegia; Pandemics; Pneumonia, Viral; SARS-CoV-2
PubMed: 32467190
DOI: 10.3174/ajnr.A6609 -
Frontiers in Immunology 2023To investigate the incidence of immune-related adverse events (irAEs) of immune checkpoint inhibitor (ICI) therapy and to report the clinical features, management, and...
PURPOSE
To investigate the incidence of immune-related adverse events (irAEs) of immune checkpoint inhibitor (ICI) therapy and to report the clinical features, management, and outcomes of ophthalmic irAEs.
METHODS
We retrospectively reviewed the medical records of patients who received ICI therapy from January 2016 to September 2022 at Peking Union Medical College Hospital and analyzed the incidence of systemic and ophthalmic adverse effects of this therapy.
RESULTS
Of 962 patients, 248 (25.8%) experienced irAEs. The first-year incidences of total irAEs and ophthalmic irAEs were 23.5% and 1.1%. The most common ICI received by the patients was pembrolizumab (373; 38.8%). Nearly half of the patients (477; 49.6%) had lung cancer. Combination therapy was associated with an increased incidence of irAEs without statistical significance. Patients with lung cancer presented with an increased incidence of total irAEs (p = 0.003) and ophthalmic irAEs (p = 0.032). Eleven patients had ophthalmic manifestations, including ophthalmoplegia (6/11), conjunctivitis (3/11), reactive cutaneous capillary endothelial proliferation (RCCEP) (1/11), and orbital inflammation (1/11). Eight patients had concomitant extra-ophthalmic irAEs. Furthermore, ICIs were discontinued in nine patients, and most ophthalmic manifestations were well controlled with topical and systemic steroids. Ten patients were treated with intravenous or oral steroids. However, cancer progression occurred in five out of eleven patients after the interruption of ICIs.
CONCLUSION
IrAEs are correlated with ICI regimens and underlying neoplasia. In our Chinese cohort, patients have a higher risk of ophthalmoplegia than uveitis. Early recognition and multidisciplinary consultation are crucial for optimal treatment of ophthalmic irAEs.
Topics: Humans; Immune Checkpoint Inhibitors; Antineoplastic Agents, Immunological; Retrospective Studies; Lung Neoplasms; Ophthalmoplegia
PubMed: 37033964
DOI: 10.3389/fimmu.2023.1130238 -
The British Journal of Ophthalmology Jun 1968
Topics: Adolescent; Blepharoptosis; Humans; Jaw Abnormalities; Male; Movement Disorders; Ophthalmoplegia
PubMed: 5665949
DOI: 10.1136/bjo.52.6.484 -
The British Journal of Ophthalmology Nov 1956
Topics: Oculomotor Muscles; Ophthalmoplegia, Chronic Progressive External; Paralysis
PubMed: 13374242
DOI: 10.1136/bjo.40.11.686