Publications by authors named "Norah Cowley"

5 Publications

  • Page 1 of 1

Assessment of MRI and US Screening for Tethered Cord Syndrome in Patients Diagnosed With Esophageal Atresia/Tracheoesophageal Fistula.

J Surg Res 2022 Jun 29;279:193-199. Epub 2022 Jun 29.

Division of Pediatric Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin.

Introduction: Infants with esophageal atresia and/or tracheoesophageal fistula (EA/TEF) undergo screening for tethered cord syndrome (TCS) via ultrasound and magnetic resonance imaging. Existing literature lacks data to guide optimal timing of screening and magnetic resonance imaging (MRI) is often delayed until 3-6 mo of age, when it is frequently forgotten. Detethering surgery has a high rate of success in patients with TCS and is often performed prophylactically due to potential irreversible deficits. This study aims to improve screening procedure for infants with EA/TEF.

Methods: A retrospective chart review was done of all EA/TEF patients treated over 6 y (n = 79). The study examined how often each imaging modality was performed and identified a TCS lesion, as well as age of screening/surgical intervention.

Results: Screening for TCS was done with MRI 58% of the time and US 15% of the time. However, 38% of patients did not undergo any screening. Out of the patients with TCS on MRI (n = 19, 41.3%), 73.7% had neurosurgery. Of patients who underwent US (n = 12), nine patients also had MRI later: two reported TCS lesions and subsequently had neurosurgery. Surgical infection rates and complications were 0/14.

Conclusions: MRI demonstrated a higher rate of detecting TCS lesions than US, and patients with TCS frequently had detethering. Patients with ≥3 VACTERL or vertebral anomalies had a higher incidence of TCS on MRI. Patients with vertebral anomalies reported false negative ultrasounds in two cases, suggesting the potential superiority of MRI screening in this subgroup. A third of children did not undergo any imaging and this will require a process improvement.
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June 2022

Aquaporin-4 IgG seropositivity is associated with worse visual outcomes after optic neuritis than MOG-IgG seropositivity and multiple sclerosis, independent of macular ganglion cell layer thinning.

Mult Scler 2020 10 31;26(11):1360-1371. Epub 2019 Jul 31.

Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Background: Comparative studies of characteristics of optic neuritis (ON) associated with myelin oligodendrocyte glycoprotein-IgG (MOG-ON) and aquaporin-4-IgG (AQP4-ON) seropositivity are limited.

Objective: To compare visual and optical coherence tomography (OCT) measures following AQP4-ON, MOG-ON, and multiple sclerosis associated ON (MS-ON).

Methods: In this cross-sectional study, 48 AQP4-ON, 16 MOG-ON, 40 MS-ON, and 31 healthy control participants underwent monocular letter-acuity assessment and spectral-domain OCT. Eyes with a history of ON >3 months prior to evaluation were analyzed.

Results: AQP4-ON eyes exhibited worse high-contrast letter acuity (HCLA) compared to MOG-ON (-22.3 ± 3.9 letters;  < 0.001) and MS-ON eyes (-21.7 ± 4.0 letters;  < 0.001). Macular ganglion cell + inner plexiform layer (GCIPL) thickness was lower, as compared to MS-ON, in AQP4-ON (-9.1 ± 2.0 µm;  < 0.001) and MOG-ON (-7.6 ± 2.2 µm;  = 0.001) eyes. Lower GCIPL thickness was associated with worse HCLA in AQP4-ON (-16.5 ± 1.5 letters per 10 µm decrease;  < 0.001) and MS-ON eyes (-8.5 ± 2.3 letters per 10 µm decrease;  < 0.001), but not in MOG-ON eyes (-5.2 ± 3.8 letters per 10 µm decrease;  = 0.17), and these relationships differed between the AQP4-ON and other ON groups ( < 0.01 for interaction).

Conclusion: AQP4-IgG seropositivity is associated with worse visual outcomes after ON compared with MOG-ON and MS-ON, even with similar severity of macular GCIPL thinning.
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October 2020

Alterations in the retinal vasculature occur in multiple sclerosis and exhibit novel correlations with disability and visual function measures.

Mult Scler 2020 06 16;26(7):815-828. Epub 2019 May 16.

Division of Neuroimmunology and Neurological Infections, Department of Neurology, The Johns Hopkins Hospital, Baltimore, MD, USA.

Background: The retinal vasculature may be altered in multiple sclerosis (MS), potentially acting as a biomarker of disease processes.

Objective: To compare retinal vascular plexus densities in people with MS (PwMS) and healthy controls (HCs), and examine correlations with visual function and global disability.

Methods: In this cross-sectional study, 111 PwMS (201 eyes) and 50 HCs (97 eyes) underwent optical coherence tomography angiography (OCTA). Macular superficial vascular plexus (SVP) and deep vascular plexus (DVP) densities were quantified, and poor quality images were excluded according to an artifact-rating protocol.

Results: Mean SVP density was 24.1% (SD = 5.5) in MS eyes (26.0% (SD = 4.7) in non-optic neuritis (ON) eyes vs. 21.7% (SD = 5.5) in ON eyes,  < 0.001), as compared to 29.2% (SD = 3.3) in HC eyes ( < 0.001 for all MS eyes and multiple sclerosis optic neuritis (MSON) eyes vs. HC eyes,  = 0.03 for MS non-ON eyes vs. HC eyes). DVP density did not differ between groups. In PwMS, lower SVP density was associated with higher levels of disability (expanded disability status scale (EDSS):  = 0.26,  = 0.004; multiple sclerosis functional composite (MSFC):  = 0.27,  = 0.03) and lower letter acuity scores (100% contrast:  = 0.29; 2.5% contrast:  = 0.40; 1.25% contrast:  = 0.31;  < 0.001 for all).

Conclusions: Retinal SVP density measured by OCTA is reduced across MS eyes, and correlates with visual function, EDSS, and MSFC scores.
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June 2020

Brain and retinal atrophy in African-Americans versus Caucasian-Americans with multiple sclerosis: a longitudinal study.

Brain 2018 11;141(11):3115-3129

Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

On average, African Americans with multiple sclerosis demonstrate higher inflammatory disease activity, faster disability accumulation, greater visual dysfunction, more pronounced brain tissue damage and higher lesion volume loads compared to Caucasian Americans with multiple sclerosis. Neurodegeneration is an important component of multiple sclerosis, which in part accounts for the clinical heterogeneity of the disease. Brain atrophy appears to be widespread, although it is becoming increasingly recognized that regional substructure atrophy may be of greater clinical relevance. Patient race (within the limitations of self-identified ancestry) is regarded as an important contributing factor. However, there is a paucity of studies examining differences in neurodegeneration and brain substructure volumes over time in African Americans relative to Caucasian American patients. Optical coherence tomography is a non-invasive and reliable tool for measuring structural retinal changes. Recent studies support its utility for tracking neurodegeneration and disease progression in vivo in multiple sclerosis. Relative to Caucasian Americans, African American patients have been found to have greater retinal structural injury in the inner retinal layers. Increased thickness of the inner nuclear layer and the presence of microcystoid macular pathology at baseline predict clinical and radiological inflammatory activity, although whether race plays a role in these changes has not been investigated. Similarly, assessment of outer retinal changes according to race in multiple sclerosis remains incompletely characterized. Twenty-two African Americans and 60 matched Caucasian Americans with multiple sclerosis were evaluated with brain MRI, and 116 African Americans and 116 matched Caucasian Americans with multiple sclerosis were monitored with optical coherence tomography over a mean duration of 4.5 years. Mixed-effects linear regression models were used in statistical analyses. Grey matter (-0.9%/year versus -0.5%: P =0.02), white matter (-0.7%/year versus -0.3%: P =0.04) and nuclear thalamic (-1.5%/year versus -0.7%/year: P =0.02) atrophy rates were approximately twice as fast in African Americans. African Americans also exhibited higher proportions of microcystoid macular pathology (12.1% versus 0.9%, P =0.001). Retinal nerve fibre layer (-1.1% versus -0.8%: P =0.02) and ganglion cell+ inner plexiform layer (-0.7%/year versus -0.4%/year: P =0.01) atrophy rates were faster in African versus Caucasian Americans. African Americans on average exhibited more rapid neurodegeneration than Caucasian Americans and had significantly faster brain and retinal tissue loss. These results corroborate the more rapid clinical progression reported to occur, in general, in African Americans with multiple sclerosis and support the need for future studies involving African Americans in order to identify individual differences in treatment responses in multiple sclerosis.
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November 2018

Stiffness analysis of 3D spheroids using microtweezers.

PLoS One 2017 22;12(11):e0188346. Epub 2017 Nov 22.

Department of Biomedical Engineering, University of Connecticut, Storrs, Connecticut, United States of America.

We describe a novel mechanical characterization method that has directly measured the stiffness of cancer spheroids for the first time to our knowledge. Stiffness is known to be a key parameter that characterizes cancerous and normal cells. Atomic force microscopy or optical tweezers have been typically used for characterization of single cells with the measurable forces ranging from sub pN to a few hundred nN, which are not suitable for measurement of larger 3D cellular structures such as spheroids, whose mechanical characteristics have not been fully studied. Here, we developed microtweezers that measure forces from sub hundred nN to mN. The wide force range was achieved by the use of replaceable cantilevers fabricated from SU8, and brass. The chopstick-like motion of the two cantilevers facilitates easy handling of samples and microscopic observation for mechanical characterization. The cantilever bending was optically tracked to find the applied force and sample stiffness. The efficacy of the method was demonstrated through stiffness measurement of agarose pillars with known concentrations. Following the initial system evaluation with agarose, two cancerous (T47D and BT474) and one normal epithelial (MCF 10A) breast cell lines were used to conduct multi-cellular spheroid measurements to find Young's moduli of 230, 420 and 1250 Pa for BT474, T47D, and MCF 10A, respectively. The results showed that BT474 and T47D spheroids are six and three times softer than epithelial MCF10A spheroids, respectively. Our method successfully characterized samples with wide range of Young's modulus including agarose (25-100 kPa), spheroids of cancerous and non-malignant cells (190-200 μm, 230-1250 Pa) and collagenase-treated spheroids (215 μm, 130 Pa).
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December 2017