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Both anti-NMO and anti-MOG antibodies were found to be positive in serum. She was treated with intravenous methyl prednisolone with complete symptomatic resolution.
Double-seropositive APS-onset NMOSD has not been previously reported in literature. An early diagnosis and treatment result in the resolution of APS-related symptoms and prevent further progression of the disease.
Double-seropositive APS-onset NMOSD has not been previously reported in literature. An early diagnosis and treatment result in the resolution of APS-related symptoms and prevent further progression of the disease.
To perform a systematic review and determine the prevalence of rhinorrhea in Parkinson disease (PD).
Of 451 patients with PD and 233 controls, the pooled prevalence of rhinorrhea in patients with PD was 45.0% (95% confidence interval 33.94-56.40), which was significantly greater than that in controls (
< 0.001). The prevalence of self-reported olfactory dysfunction was greater in patients with PD; however, a pooled analysis of studies using objective scores showed no difference. The mean age of patients with PD was greater than that of controls (
= 0.002). The mean age of patients with PD with rhinorrhea was also greater than that of patients with PD without rhinorrhea (
< 0.001), but disease characteristics did not differ.
There is a high prevalence of rhinorrhea in patients with PD; therefore, providers should query for rhinorrhea during visits and understand the treatment options available. Future studies should explore the pathophysiology of rhinorrhea in PD and the relationship between rhinorrhea and disease severity and duration, as well as determine whether treatment-specific outcomes differ in patients with PD.
There is a high prevalence of rhinorrhea in patients with PD; therefore, providers should query for rhinorrhea during visits and understand the treatment options available. Future studies should explore the pathophysiology of rhinorrhea in PD and the relationship between rhinorrhea and disease severity and duration, as well as determine whether treatment-specific outcomes differ in patients with PD.
Disease activity in multiple sclerosis (MS) is highly variable, and there are limited prospective studies on predictors of disease outcomes. The goal of this study is to identify and assess patient characteristics in MS that predict disease activity and worsening.
The study population consisted of a prospective cohort of 1,008 participants with relapsing-remitting onset MS enrolled in the CombiRx trial. Cox regression analysis was used to determine hazard ratio (HR) associations between baseline (BL) demographics, clinical history, MRI metrics, and treatment with outcomes of time to first new disease activity over up to 7 years of follow-up including relapse, MRI activity, and disease worsening.
One thousand eight participants were randomized, with 959 eligible for assessment of disease activity and worsening on follow-up. PHA-767491 solubility dmso In multivariable models, the risk of relapse was higher in participants younger than 38 years at BL than in those older (HR range 1.36-1.43), with the presence of gadolinium (Gd)+ lesing in the multivariable analysis.
Prospective data from a large clinical trial cohort show that younger MS patients with high BL relapses and MRI lesion burden have the highest risk of subsequent disease activity.
Clinical trial registration number NCT00211887. CombiRx was registered at ClinicalTrials.gov (NCT00211887) on September 21, 2005. Study enrollment began in January 2005.
Clinical trial registration number NCT00211887. CombiRx was registered at ClinicalTrials.gov (NCT00211887) on September 21, 2005. Study enrollment began in January 2005.
Epilepsy is an important comorbidity that affects outcomes for people with multiple sclerosis (MS). However, it is unclear whether seizure severity among individuals with coexistence of MS and epilepsy (MS + E) is higher than in those with other focal epilepsies. Our goal was to compare the overall severity of epilepsy in individuals with MS + E vs those with focal epilepsy without MS (E - MS), as defined by seizure-related health care utilization, frequency and duration of status epilepticus, and frequency of antiseizure medication (ASM) regimen changes.
In this hypothesis-generating study, we analyzed a US commercial nationwide deidentified claims data set with >86 million individuals between January 1, 2008, and August 31, 2019. Using validated algorithms, we identified adults with E - MS and those with MS + E. We compared the number and length of seizure-related hospital admissions, the number of claims and unique days with claims for status epilepticus, and the rates of ASM regimen changes between among individuals with MS + E treated with sodium channel blockers/modulators vs other ASM classes shows no significant differences.
This study provides Class III evidence that individuals with MS + E can have more severe epilepsy than those with E - MS.
This study provides Class III evidence that individuals with MS + E can have more severe epilepsy than those with E - MS.
There have been numerous reports of neurologic manifestations identified in hospitalized patients infected with SARS-CoV-2, the virus that causes COVID-19. Here, we identify the spectrum of associated neurologic symptoms and diagnoses, define the time course of their development, and examine readmission rates and mortality risk posthospitalization in a multiethnic urban cohort.
We identify the occurrence of new neurologic diagnoses among patients with laboratory-confirmed SARS-CoV-2 infection in New York City. A retrospective cohort study was performed on 532 cases (hospitalized patients with new neurologic diagnoses within 6 weeks of positive SARS-CoV-2 laboratory results between March 1, 2020, and August 31, 2020). We compare demographic and clinical features of the 532 cases with 532 controls (hospitalized COVID-19 patients without neurologic diagnoses) in a case-control study with one-to-one matching and examine hospital-related data and outcomes of death and readmission up to 6 months after acute hosnt morbidity and mortality postdischarge. Further research is needed to define the effect of neurologic diagnoses during acute hospitalization on longitudinal post-COVID-19-related symptoms including neurocognitive impairment.
The introduction of spinal muscular dystrophy (SMA)-modifying therapies, such as antisense oligonucleotide therapy, has changed the natural history of SMA. Most reports on treatment outcomes have focused on motor scores and respiratory function. The objective of this study is to document the development and progression of scoliosis in patients with SMA1 treated with nusinersen.
A descriptive single-center study was conducted in patients with SMA1 who were treated with nusinersen before 6 months of age. Data were collected on patients who met criteria, including age at the first nusinersen dose, number of nusinersen doses, degree of scoliosis, respiratory parameters, feeding route, and motor scores at baseline and follow-up. The Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) was subanalyzed using axial (AxS) and appendicular motor (ApS) scores to evaluate a possible correlation between scoliosis and axial muscle strength.
From our cohort, 31 percent (11/35) of pamay predict worsening on the total motor scores.Free energy calculations are rapidly becoming indispensable in structure-enabled drug discovery programs. As new methods, force fields, and implementations are developed, assessing their expected accuracy on real-world systems (benchmarking) becomes critical to provide users with an assessment of the accuracy expected when these methods are applied within their domain of applicability, and developers with a way to assess the expected impact of new methodologies. These assessments require construction of a benchmark-a set of well-prepared, high quality systems with corresponding experimental measurements designed to ensure the resulting calculations provide a realistic assessment of expected performance when these methods are deployed within their domains of applicability. To date, the community has not yet adopted a common standardized benchmark, and existing benchmark reports suffer from a myriad of issues, including poor data quality, limited statistical power, and statistically deficient analyses, all of wions, these guidelines should prove useful for assessment of the rapidly growing field of machine learning methods for affinity prediction as well.
Disseminated pediatric low-grade gliomas and glioneuronal tumors (dpLGG/GNTs) are associated with a poorer prognosis than nondisseminated pLGG/GNTs. To date there is no comprehensive report characterizing the genome profile of dpLGG/GNTs and their relative survival. This systematic review aims to identify the pattern of genetic alterations and long-term outcomes described for dpLGG/GNT.
A systematic review of the literature was performed to identify relevant articles. A quality and risk of bias assessment of articles was done using the GRADE framework and ROBINS-I tool, respectively.
Fifty studies published from 1994 to 2020 were included in this review with 366 cases reported. There was sporadic reporting of genetic alterations. The most common molecular alterations observed among subjects were 1p deletion (75%) and
fusion (55%). BRAF p.V600E mutation was found in 7% of subjects. A higher proportion of subjects demonstrated primary dissemination compared to secondary dissemination (65% vs 25%). Firsthogenesis of dpLGG/GNT.
Diagnosis and prognostication of intra-axial brain tumors hinges on invasive brain sampling, which carries risk of morbidity. Minimally-invasive sampling of proximal fluids, also known as liquid biopsy, can mitigate this risk. Our objective was to identify diagnostic and prognostic cerebrospinal fluid (CSF) proteomic signatures in glioblastoma (GBM), brain metastases (BM), and primary central nervous system lymphoma (CNSL).
CSF samples were retrospectively retrieved from the Penn State Neuroscience Biorepository and profiled using shotgun proteomics. Proteomic signatures were identified using machine learning classifiers and survival analyses.
Using 30 µL CSF volumes, we recovered 755 unique proteins across 73 samples. Proteomic-based classifiers identified malignancy with area under the receiver operating characteristic (AUROC) of 0.94 and distinguished between tumor entities with AUROC ≥0.95. More clinically relevant triplex classifiers, comprised of just three proteins, distinguished between tumor entities with AUROC of 0.75-0.89. Novel biomarkers were identified, including GAP43, TFF3 and CACNA2D2, and characterized using single cell RNA sequencing. Survival analyses validated previously implicated prognostic signatures, including blood-brain barrier disruption.
Reliable classification of intra-axial malignancies using low CSF volumes is feasible, allowing for longitudinal tumor surveillance.
Reliable classification of intra-axial malignancies using low CSF volumes is feasible, allowing for longitudinal tumor surveillance.
Standard-of-care treatment for newly diagnosed glioblastoma (ndGBM), consisting of surgery followed by radiotherapy (RT) and temozolomide (TMZ), has improved outcomes compared with RT alone; however, prognosis remains poor. Trotabresib, a novel bromodomain and extraterminal inhibitor, has demonstrated antitumor activity in patients with high-grade gliomas.
In this phase Ib, dose-escalation study (NCT04324840), we investigated trotabresib 15, 30, and 45 mg combined with TMZ in the adjuvant setting and trotabresib 15 and 30 mg combined with TMZ+RT in the concomitant setting in patients with ndGBM. Primary endpoints were to determine safety, tolerability, maximum tolerated dose, and/or recommended phase II dose (RP2D) of trotabresib. Secondary endpoints were assessment of preliminary efficacy and pharmacokinetics. Pharmacodynamics were investigated as an exploratory endpoint.
The adjuvant and concomitant cohorts enrolled 18 and 14 patients, respectively. Trotabresib in combination with TMZ or TMZ+RT was well tolerated; most treatment-related adverse events were mild or moderate.
