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The Oncologist Sep 2023Hypofractionated stereotactic radiotherapy (hFSRT) is a salvage option for recurrent glioblastoma (GB) which may synergize anti-PDL1 treatment. This phase I study... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Hypofractionated stereotactic radiotherapy (hFSRT) is a salvage option for recurrent glioblastoma (GB) which may synergize anti-PDL1 treatment. This phase I study evaluated the safety and the recommended phase II dose of anti-PDL1 durvalumab combined with hFSRT in patients with recurrent GB.
METHODS
Patients were treated with 24 Gy, 8 Gy per fraction on days 1, 3, and 5 combined with the first 1500 mg Durvalumab dose on day 5, followed by infusions q4weeks until progression or for a maximum of 12 months. A standard 3 + 3 Durvalumab dose de-escalation design was used. Longitudinal lymphocytes count, cytokines analyses on plasma samples, and magnetic resonance imaging (MRI) were collected.
RESULTS
Six patients were included. One dose limiting toxicity, an immune-related grade 3 vestibular neuritis related to Durvalumab, was reported. Median progression-free interval (PFI) and overall survival (OS) were 2.3 and 16.7 months, respectively. Multi-modal deep learning-based analysis including MRI, cytokines, and lymphocytes/neutrophil ratio isolated the patients presenting pseudoprogression, the longest PFI and those with the longest OS, but statistical significance cannot be established considering phase I data only.
CONCLUSION
Combination of hFSRT and Durvalumab in recurrent GB was well tolerated in this phase I study. These encouraging results led to an ongoing randomized phase II. (ClinicalTrials.gov Identifier: NCT02866747).
Topics: Humans; Glioblastoma; Treatment Outcome; Re-Irradiation; Brain Neoplasms; Neoplasm Recurrence, Local; Radiosurgery; Cytokines
PubMed: 37196069
DOI: 10.1093/oncolo/oyad095 -
The Journal of International Medical... Jul 2023The exact etiology of Parsonage-Turner syndrome is unknown, but it is known to be preceded by infection, vaccination, or surgical intervention. In this review, we... (Review)
Review
OBJECTIVES
The exact etiology of Parsonage-Turner syndrome is unknown, but it is known to be preceded by infection, vaccination, or surgical intervention. In this review, we describe associations of Parsonage-Turner syndrome with COVID-19 infection and vaccination.
METHODS
A systematic literature search was conducted using PubMed/MEDLINE, ScienceDirect, and Google Scholar. Microsoft Excel was used for data extraction and statistical analysis. The quality of case reports and case series was assessed using the Joanna Briggs Institute Critical Appraisal Tool.
RESULTS
We selected 44 case reports and 10 case series, including 68 patients (32 post-vaccination and 36 with post-COVID-19 infection Parsonage-Turner syndrome). Middle-aged males were predominantly affected in both groups. The most frequently administered vaccine was Comirnaty (Pfizer) (53%). The mean latency was 11.7 days in the post-vaccination group and 20.3 days in the post-infection group. The most affected nerves in both groups were the axillary, suprascapular, and musculocutaneous nerves; and 78.1% and 38.9% of patients showed partial amelioration of their symptoms in the post-vaccination and post-infection groups, respectively.
CONCLUSION
Post-vaccination Parsonage-Turner syndrome presents earlier than post-infection disease. Pain and sensorimotor deficits of the upper limb are common in both situations. Complete or partial recovery occurs in most cases.
Topics: Male; Middle Aged; Humans; Brachial Plexus Neuritis; COVID-19; Pain; Upper Extremity; Vaccination
PubMed: 37523491
DOI: 10.1177/03000605231187939 -
Journal of Audiology & Otology Jan 2024There have been few investigations on the epidemiology, etiology, and medical management of acute unilateral vestibulopathy (AUV). Short-term pharmaceutical resolutions... (Review)
Review
There have been few investigations on the epidemiology, etiology, and medical management of acute unilateral vestibulopathy (AUV). Short-term pharmaceutical resolutions include vestibular symptomatic suppressants, anti-emetics, and some cause-based therapies. Anticholinergics, phenothiazines, antihistamines, antidopaminergics, benzodiazepines, and calcium channel antagonists are examples of vestibular suppressants. Some of these medications may show their effects through multiple mechanisms. In contrast, N-acetyl-L-leucine, Ginkgo biloba, and betahistine improve central vestibular compensation. Currently, AUV pathophysiology is poorly understood. Diverse hypotheses have previously been identified which have brought about some causal treatments presently used. According to some publications, acute administration of anti-inflammatory medications may have a deleterious impact on both post-lesional functional recovery and endogenous adaptive plasticity processes. Thus, some authors do not recommend the use of corticosteroids in AUV. Antivirals are even more contentious in the context of AUV treatment. Although vascular theories have been presented, no verified investigations employing anti-clotting or vasodilator medications have been conducted. There are no standardized treatment protocols for AUV to date, and the pharmacological treatment of AUV is still questionable. This review addresses the most current developments and controversies in AUV medical treatment.
PubMed: 37953517
DOI: 10.7874/jao.2023.00066 -
Frontiers in Neurology 2023Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is an inflammatory demyelinating disease of the central nervous system (CNS) with the... (Review)
Review
Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is an inflammatory demyelinating disease of the central nervous system (CNS) with the presence of conformation-sensitive antibodies against MOG. The spectrum of MOGAD includes monophasic/relapsing optic neuritis, myelitis, neuromyelitis optica spectrum disorder (NMOSD) phenotype without aquaporin 4 (AQP4) antibodies, acute/multiphasic demyelinating encephalomyelitis (ADEM/MDEM)-like presentation, and brainstem and cerebral cortical encephalitis. There is no apparent female preponderance in MOGAD, and MOGAD can onset in all age groups (age at onset is approximately 30 years on average, and approximately 30% of cases are in the pediatric age group). While prevalence and incidence data have been available for AQP4+ NMOSD globally, such data are only beginning to accumulate for MOGAD. We reviewed the currently available data from population-based MOGAD studies conducted around the world: three studies in Europe, three in Asia, and one joint study in the Americas. The prevalence of MOGAD is approximately 1.3-2.5/100,000, and the annual incidence is approximately 3.4-4.8 per million. Among White people, the prevalence of MOGAD appears to be slightly higher than that of AQP4+ NMOSD. No obvious latitude gradient was observed in the Japanese nationwide survey. The data available so far showed no obvious racial preponderance or strong HLA associations in MOGAD. However, precedent infection was reported in approximately 20-40% of MOGAD cases, and this is worthy of further investigation. Co-existing autoimmune disorders are less common in MOGAD than in AQP4+ NMOSD, but NMDAR antibodies may occasionally be positive in patients with MOGAD. More population-based studies in different populations and regions are useful to further inform the epidemiology of this disease.
PubMed: 37789888
DOI: 10.3389/fneur.2023.1260358 -
International Journal of Molecular... Aug 2023Although there is a substantial amount of data on the clinical characteristics, diagnostic criteria, and pathogenesis of myelin oligodendrocyte glycoprotein (MOG)... (Review)
Review
Pathogenesis, Clinical Features, and Treatment of Patients with Myelin Oligodendrocyte Glycoprotein (MOG) Autoantibody-Associated Disorders Focusing on Optic Neuritis with Consideration of Autoantibody-Binding Sites: A Review.
Although there is a substantial amount of data on the clinical characteristics, diagnostic criteria, and pathogenesis of myelin oligodendrocyte glycoprotein (MOG) autoantibody-associated disease (MOGAD), there is still uncertainty regarding the MOG protein function and the pathogenicity of anti-MOG autoantibodies in this disease. It is important to note that the disease characteristics, immunopathology, and treatment response of MOGAD patients differ from those of anti-aquaporin 4 antibody-positive neuromyelitis optica spectrum disorders (NMOSDs) and multiple sclerosis (MS). The clinical phenotypes of MOGAD are varied and can include acute disseminated encephalomyelitis, transverse myelitis, cerebral cortical encephalitis, brainstem or cerebellar symptoms, and optic neuritis. The frequency of optic neuritis suggests that the optic nerve is the most vulnerable lesion in MOGAD. During the acute stage, the optic nerve shows significant swelling with severe visual symptoms, and an MRI of the optic nerve and brain lesion tends to show an edematous appearance. These features can be alleviated with early extensive immune therapy, which may suggest that the initial attack of anti-MOG autoantibodies could target the structures on the blood-brain barrier or vessel membrane before reaching MOG protein on myelin or oligodendrocytes. To understand the pathogenesis of MOGAD, proper animal models are crucial. However, anti-MOG autoantibodies isolated from patients with MOGAD do not recognize mouse MOG efficiently. Several studies have identified two MOG epitopes that exhibit strong affinity with human anti-MOG autoantibodies, particularly those isolated from patients with the optic neuritis phenotype. Nonetheless, the relations between epitopes on MOG protein remain unclear and need to be identified in the future.
Topics: Animals; Mice; Humans; Myelin-Oligodendrocyte Glycoprotein; Optic Neuritis; Binding Sites; Autoantibodies; Epitopes
PubMed: 37686172
DOI: 10.3390/ijms241713368 -
Animal Cells and Systems 2023Visual impairment is occasionally observed in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Although uveitis and optic...
Visual impairment is occasionally observed in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Although uveitis and optic neuritis have been reported in MS and EAE, the precise mechanisms underlying the pathogenesis of these visual impairments remain poorly understood. This study aims to identify differentially expressed genes (DEGs) in the retinas of mice with EAE to identify genes that may be implicated in EAE-induced visual impairment. Fourteen adult mice were injected with myelin oligodendrocyte glycoprotein to induce the EAE model. Transcriptomes of retinas with EAE were analyzed by RNA-sequencing. Gene expression analysis revealed 347 DEGs in the retinas of mice with EAE: 345 were upregulated, and 2 were downregulated (adjusted -value < 0.05 and absolute log fold change > 1). Gene ontology (GO) analysis showed that the upregulated genes in the retinas of mice with EAE were primarily related to immune responses, responses to external biotic stimuli, defense responses, and leukocyte-mediated immunity in the GO biological process. The expression of six upregulated hub genes (, and t from the STRING analysis and the two significantly downregulated DEGs () were validated by reverse transcription-quantitative polymerase chain reaction. In addition, gene set enrichment analysis showed that the negatively enriched gene sets in EAE-affected retinas were associated with the neuronal system and phototransduction cascade. This study provides novel molecular evidence for visual impairments in EAE and indicates directions for further research to elucidate the mechanisms of these visual impairments in MS.
PubMed: 37808551
DOI: 10.1080/19768354.2023.2264354 -
Frontiers in Immunology 2023Myelin oligodendrocyte glycoprotein antibody-associated autoimmune disease (MOGAD) is a rare monophasic or relapsing inflammatory demyelinating disease of the central...
BACKGROUND
Myelin oligodendrocyte glycoprotein antibody-associated autoimmune disease (MOGAD) is a rare monophasic or relapsing inflammatory demyelinating disease of the central nervous system (CNS) and can mimic multiple sclerosis (MS). The variable availability of live cell-based MOG-antibody assays and difficulties in interpreting low-positive antibody titers can complicate diagnosis. Literature on cerebrospinal fluid (CSF) profiles in MOGAD versus MS, one of the most common differential diagnoses, is scarce. We here analyzed the value of basic CSF parameters to i) distinguish different clinical MOGAD manifestations and ii) differentiate MOGAD from MS.
METHODS
This is retrospective, single-center analysis of clinical and laboratory data of 30 adult MOGAD patients and 189 adult patients with relapsing-remitting multiple sclerosis. Basic CSF parameters included CSF white cell count (WCC) and differentiation, CSF/serum albumin ratio (Q), intrathecal production of immunoglobulins, CSF-restricted oligoclonal bands (OCB) and MRZ reaction, defined as intrathecal production of IgG reactive against at least 2 of the 3 viruses measles (M), rubella (R) and varicella zoster virus (Z).
RESULTS
MOGAD patients with myelitis were more likely to have a pleocytosis, a Q elevation and a higher WCC than those with optic neuritis, and, after review and combined analysis of our and published cases, they also showed a higher frequency of intrathecal IgM synthesis. Compared to MS, MOGAD patients had significantly more frequently neutrophils in CSF and WCC>30/µl, Q>10×10, as well as higher mean Q values, but significantly less frequently CSF plasma cells and CSF-restricted OCB. A positive MRZ reaction was present in 35.4% of MS patients but absent in all MOGAD patients. Despite these associations, the only CSF parameters with relevant positive likelihood ratios (PLR) indicating MOGAD were Q>10×10 (PLR 12.60) and absence of CSF-restricted OCB (PLR 14.32), whereas the only relevant negative likelihood ratio (NLR) was absence of positive MRZ reaction (NLR 0.00).
CONCLUSION
Basic CSF parameters vary considerably in different clinical phenotypes of MOGAD, but Q>10×10 and absence of CSF-restricted OCB are highly useful to differentiate MOGAD from MS. A positive MRZ reaction is confirmed as the strongest CSF rule-out parameter in MOGAD and could be useful to complement the recently proposed diagnostic criteria.
Topics: Adult; Humans; Multiple Sclerosis; Retrospective Studies; Autoimmune Diseases; Antibodies; Immune System Diseases
PubMed: 37744325
DOI: 10.3389/fimmu.2023.1237149 -
Advances in Ophthalmology and Optometry Aug 2023The COVID-19 pandemic has led to the identification of new disease phenotypes associated with infection by the SARS-CoV-2 virus. This includes multiple... (Review)
Review
The COVID-19 pandemic has led to the identification of new disease phenotypes associated with infection by the SARS-CoV-2 virus. This includes multiple neuro-ophthalmological sequelae, which have been associated with COVID-19 infection and administration of COVID-19 vaccines. Some of these associations have a plausible pathophysiological link to the infection or vaccination but true causation has yet to be established. We review the literature for associations reported between COVID-19 infection or vaccination and neuro-ophthalmic sequelae and review the potential pathophysiological processes that may underlie these associations.
PubMed: 37350847
DOI: 10.1016/j.yaoo.2023.03.004 -
Medical Hypothesis, Discovery &... 2023Multiple sclerosis (MS) is a chronic neurodegenerative disease that damages myelinated fibers within the central nervous system. Data obtained using optical coherence...
BACKGROUND
Multiple sclerosis (MS) is a chronic neurodegenerative disease that damages myelinated fibers within the central nervous system. Data obtained using optical coherence tomography (OCT) have recently been identified as a potential biomarker for this disease. We aimed to measure circumpapillary retinal nerve fiber layer thickness (cpRNFLT) using OCT and to compare the results in healthy participants with those of individuals having clinically definitive MS with and without a history of optic neuritis.
METHODS
This cross-sectional study recruited patients with clinically confirmed MS, with and without optic neuritis, and healthy individuals as a control group. We documented demographic characteristics, duration of MS, and time elapsed since the episode of optic neuritis. All participants underwent a thorough ocular examination and measurement of total, superior, and inferior cpRNFLT using swept-source OCT.
RESULTS
In participants with MS, women outnumbered men in the subsets with (90%) and without (64%) optic neuritis. The control group comprised approximately similar numbers of men and women. There was a statistically significant difference in total, superior, and inferior cpRNFLT between study groups (all < 0.001). Pairwise comparisons revealed significantly thinner total, superior, and inferior cpRNFLTs in patients having MS with and without (all < 0.001) optic neuritis when compared with the controls. We found significantly higher total, superior, and inferior cpRNFLTs in women than in men (all < 0.05). However, we found no significant correlation between total, superior, or inferior cpRNFLT and patient age, duration of MS, or time elapsed since the optic neuritis episode (all > 0.05), except for a significant moderate inverse correlation between patient age and total cpRNFLT (r = - 0.41; < 0.05), indicating a loss of total cpRNFLT with age.
CONCLUSIONS
Patients with clinically confirmed MS, with or without optic neuritis, had a significantly decreased cpRNFLT compared to that of healthy individuals. There was a significant inverse correlation between age and total cpRNFLT and a difference in cpRNFLT between the sexes, indicating that age and sex may influence the measurement of cpRNFLT using OCT in patients with MS. As a screening tool, OCT should be used along with other existing diagnostic modalities for patients with definite or suspected MS. Further longitudinal studies including various classifications of MS with or without isolated episodes of optic neuritis, along with diagnostic accuracy studies, could provide more robust conclusions on the suitability of OCT as a biomarker of MS.
PubMed: 38601055
DOI: 10.51329/mehdiophthal1485 -
Journal of Central Nervous System... 2024Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune neuroinflammatory disorder with a prevalence of 1-5/100,000 globally, characterized by attacks of the... (Review)
Review
Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune neuroinflammatory disorder with a prevalence of 1-5/100,000 globally, characterized by attacks of the central nervous system including but not limited to optic neuritis, transverse myelitis and brainstem lesions, including area postrema lesions. These autoimmune attacks can lead to irreversible damage if left untreated, therefore strategies have been developed to prevent relapses. Initial off-label treatments have achieved variable levels of success in relapse prevention, but improved relapse prevention and quality of life remain a goal in the field. A better understanding of the underlying pathophysiology of NMOSD over the last 10 years has led to newer, more specific approaches in treatment, culminating in the first FDA approved treatments in the disease. In this review, we will discuss the seminal trials of PREVENT or Eculizumab in the treatment of aquaporin-4 (AQP4)-IgG positive NMOSD, N-Momentum or Inebilizumab in the study of NMOSD (both AQP4-IgG positive and negative) and SAkura Sky and SAkuraStar which studied satralizumab in AQP4-IgG seropositive and seronegative NMOSD patients. We will also discuss the extension trials of each of these medications and what lead to their approval in AQP4-IgG seropositive NMOSD patients. We will then examine treatments in the pipeline for adult and pediatric NMOSD patients and conclude with discussions on treatment considerations in pregnant patients and how to approach treatment of NMOSD patients during COVID.
PubMed: 38312734
DOI: 10.1177/11795735241231094