Publications by authors named "Natalia Gonzalez Caldito"

15 Publications

  • Page 1 of 1

Teaching NeuroImages: Central Pontine Myelinolysis in Diabetic Ketoacidosis.

Neurology 2021 Jun 2. Epub 2021 Jun 2.

Department of Neurology & Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX, USA

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1212/WNL.0000000000012301DOI Listing
June 2021

Persistent severe lymphopenia 5 years after dimethyl fumarate discontinuation.

Mult Scler 2021 Feb 23:1352458520988149. Epub 2021 Feb 23.

Department of Neurology & Neurotherapeutics, University of Texas Southwestern Medical School, Dallas, TX, USA/Neurology Section, VA North Texas Health Care System, Dallas, TX, USA.

One known adverse event associated with dimethyl fumarate (DMF) is grade III lymphopenia which usually resolves within 2-3 months upon DMF discontinuation. Here, we report a case of a 50-year-old woman with MS who developed grade III lymphopenia within 6 months of DMF initiation, and despite treatment cessation within the next 6 months, she has continued to have severe persistent lymphopenia for over 5 years. Our observation suggests prolonged and possibly irreversible lymphopenia as a possible adverse event of DMF, and it emphasizes the need for monitoring lymphocyte numbers, and to cease dosing promptly after onset of grade III lymphopenia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1352458520988149DOI Listing
February 2021

Aging and efficacy of disease-modifying therapies in multiple sclerosis: a meta-analysis of clinical trials.

Ther Adv Neurol Disord 2020 28;13:1756286420969016. Epub 2020 Oct 28.

Neurology Section, VA North Texas Health Care System, Medical Service, 4500 South Lancaster Rd., Dallas, TX 75216, USA.

Background: Disease-modifying therapies (DMTs) for multiple sclerosis (MS) are approved for the treatment of disease activity and are effective in reducing relapses and new magnetic resonance imaging (MRI) lesions. However, disease activity generally subsides with time, and age-dependent changes in DMT efficacy are not well-established. We aimed to investigate whether age impacts the efficacy of DMTs in treating disease activity in patients with relapsing-remitting MS (RRMS).

Methods: DMT efficacy related to age was assessed through a meta-analysis of clinical trials that evaluated the efficacy of DMTs in RRMS patients as measured by reductions in the annualized relapse rate (ARR), new T2 lesions, and gadolinium-enhanced lesions on MRI. Using the mean baseline patient age from each trial, a weighted linear regression was fitted to determine whether age was associated with treatment efficacy on a group level.

Results: Group-level data from a total of 28,082 patients from 26 trials of 14 different DMTs were included in the meta-analysis. There were no statistically significant associations between age and reductions in ARR, new T2 lesions, and gadolinium-enhanced lesions of the treatment group compared with placebo.

Conclusion: DMTs for RRMS show efficacy in treating disease activity independent of age as demonstrated by group-level data from DMT clinical trials. Nevertheless, clinical trials select for patients with baseline disease activity regardless of age, thereby not representing real-world patients with RRMS, where disease activity declines with age.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1756286420969016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7838219PMC
October 2020

Adverse event profile differences between rituximab and ocrelizumab: Findings from the FDA Adverse Event Reporting Database.

Mult Scler 2021 Jun 21;27(7):1066-1076. Epub 2020 Aug 21.

Department of Neurology & Neurotherapeutics, Immunology Graduate Program, University of Texas Southwestern Medical Center, Dallas, TX, USA/Neurology Section, VA North Texas Health Care System, Dallas, TX, USA.

Background: Rituximab and ocrelizumab are anti-CD20 monoclonal antibodies that have shown a marked reduction in multiple sclerosis (MS) inflammatory activity. However, their real-world safety profile has not been adequately compared.

Objective: To investigate the adverse event (AE) profile of rituximab and ocrelizumab reported to the Food and Drug Administration Adverse Event Reporting System (FAERS) database.

Methods: The FAERS database was filtered by indication (MS) and drug (rituximab or ocrelizumab). Disproportionality analyses including but not limited to reporting odds ratio (ROR) were conducted to identify drug-AE associations. A signal was detected if the lower limit of the 95% confidence interval of ROR (ROR) exceeded 1.

Results: There were 623 and 7948 reports for rituximab and ocrelizumab, respectively. The most frequent AEs with rituximab and ocrelizumab were infusion-related reaction (4.82%) and urinary tract infection (10.52%), respectively. The strongest drug-AE association for rituximab and ocrelizumab were ear pruritus (ROR: 47.53) and oral herpes (ROR: 38.99), respectively. Ocrelizumab was associated with an almost two times higher frequency of infections than rituximab (21.93% vs 11.05%, respectively).

Conclusion: This study revealed differences in reporting AEs between rituximab and ocrelizumab. Infections were reported more frequently with ocrelizumab. Although speculative, a potentially different or more extensive B-cell depletion by ocrelizumab might explain these findings. Additional pharmacovigilance studies need to be performed to better characterize differences in the AE profile in B-cell-depleting therapies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1352458520949986DOI Listing
June 2021

Neuroimaging Insights Into Early Stages of HIV-Progressive Multifocal Leukoencephalopathy: A Case Report.

J Cent Nerv Syst Dis 2020 7;12:1179573520939339. Epub 2020 Jul 7.

Department of Neurology & Neurotherapeutics, The University of Texas Southwestern Medical Center, Dallas, TX, USA.

This report aims to enhance the understanding of early longitudinal neuroimaging features of progressive multifocal leukoencephalopathy (PML) in human immunodeficiency virus (HIV). Neuroimaging has become crucial in the diagnosis and early recognition of PML. Recognition of magnetic resonance imaging (MRI) features in the early stages of PML is paramount to avoid misdiagnosis and facilitate the delivery of treatments aimed at reducing disease progression. A 49-year-old white man with HIV presented with 4-month progressive left-sided weakness. Neurological examination revealed mild cognitive impairment, left-sided hemiparesis, and somatosense impairment to all modalities. Brain MRI revealed a punctate pattern with innumerable T2-FLAIR (fluid attenuated inversion recovery) hyperintensities in the cortex, brainstem, cerebellum, subcortical, and periventricular areas. Susceptibility-weighted imaging (SWI) revealed hypointensities involving subcortical U-fibers and cortical architecture. A comprehensive diagnostic evaluation was inconclusive. John Cunningham virus (JCV) PCR in cerebrospinal fluid (CSF) was indeterminate. He was started on antiretroviral therapy. Repeat brain MRI performed 1.5 months later, in the setting of further neurological decline, demonstrated progression of the T2-hyperintensities into a large confluent white matter lesion in the right frontoparietal lobe. Despite an indeterminate JCV PCR, the appearance and characteristic progression of the lesions in successive imaging in the setting of severe immunosuppression, with extensive negative infectious workup, was indicative of PML. This clinical experience illustrates unique neuroimaging features of HIV-PML in early stages and its progression over time. It especially highlights the relevance of the SWI sequence in the diagnosis and features observed with disease evolution. Short-term imaging follow-up may assist with the recognition of MRI features consistent with the biology of the infection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1179573520939339DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7343350PMC
July 2020

Protective effects of 4-aminopyridine in experimental optic neuritis and multiple sclerosis.

Brain 2020 04;143(4):1127-1142

NeuroCure Clinical Research Center and Experimental and Clinical Research Center, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health and Max Delbrueck Center for Molecular Medicine, Berlin, Germany.

Chronic disability in multiple sclerosis is linked to neuroaxonal degeneration. 4-aminopyridine (4-AP) is used and licensed as a symptomatic treatment to ameliorate ambulatory disability in multiple sclerosis. The presumed mode of action is via blockade of axonal voltage gated potassium channels, thereby enhancing conduction in demyelinated axons. In this study, we provide evidence that in addition to those symptomatic effects, 4-AP can prevent neuroaxonal loss in the CNS. Using in vivo optical coherence tomography imaging, visual function testing and histologic assessment, we observed a reduction in retinal neurodegeneration with 4-AP in models of experimental optic neuritis and optic nerve crush. These effects were not related to an anti-inflammatory mode of action or a direct impact on retinal ganglion cells. Rather, histology and in vitro experiments indicated 4-AP stabilization of myelin and oligodendrocyte precursor cells associated with increased nuclear translocation of the nuclear factor of activated T cells. In experimental optic neuritis, 4-AP potentiated the effects of immunomodulatory treatment with fingolimod. As extended release 4-AP is already licensed for symptomatic multiple sclerosis treatment, we performed a retrospective, multicentre optical coherence tomography study to longitudinally compare retinal neurodegeneration between 52 patients on continuous 4-AP therapy and 51 matched controls. In line with the experimental data, during concurrent 4-AP therapy, degeneration of the macular retinal nerve fibre layer was reduced over 2 years. These results indicate disease-modifying effects of 4-AP beyond symptomatic therapy and provide support for the design of a prospective clinical study using visual function and retinal structure as outcome parameters.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/brain/awaa062DOI Listing
April 2020

Progressive Multiple Sclerosis Is Associated with Faster and Specific Retinal Layer Atrophy.

Ann Neurol 2020 06 28;87(6):885-896. Epub 2020 Apr 28.

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

Objective: Therapeutic development in progressive multiple sclerosis (PMS) has been hampered by a lack of reliable biomarkers to monitor neurodegeneration. Optical coherence tomography (OCT)-derived retinal measures have been proposed as promising biomarkers to fulfill this role. However, it is unclear whether retinal atrophy persists in PMS, exceeds normal aging, or can be distinguished from relapsing-remitting multiple sclerosis (RRMS).

Methods: 178 RRMS, 186 PMS, and 66 control participants were followed with serial OCT for a median follow-up of 3.7 years.

Results: The estimated proportion of peripapillary retinal nerve fiber layer (pRNFL) and macular ganglion cell + inner plexiform layer (GCIPL) thinning in multiple sclerosis (MS) attributable to normal aging increased from 42.7% and 16.7% respectively at age 25 years, to 83.7% and 81.1% at age 65 years. However, independent of age, PMS was associated with faster pRNFL (-0.34 ± 0.09%/yr, p < 0.001) and GCIPL (-0.27 ± 0.07%/yr, p < 0.001) thinning, as compared to RRMS. In both MS and controls, higher baseline age was associated with faster inner nuclear layer (INL) and outer nuclear layer (ONL) thinning. INL and ONL thinning were independently faster in PMS, as compared to controls (INL:-0.09 ± 0.04%/yr, p = 0.03; ONL:-0.12 ± 0.06%/yr, p = 0.04), and RRMS (INL:-0.10 ± 0.04%/yr, p = 0.01; ONL:-0.13 ± 0.05%/yr, p = 0.01), whereas they were similar in RRMS and controls. Unlike RRMS, disease-modifying therapies (DMTs) did not impact rates of retinal layer atrophy in PMS.

Interpretation: PMS is associated with faster retinal atrophy independent of age. INL and ONL measures may be novel biomarkers of neurodegeneration in PMS that appear to be unaffected by conventional DMTs. The effects of aging on rates of retinal layer atrophy should be considered in clinical trials incorporating OCT outcomes. ANN NEUROL 2020;87:885-896.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ana.25738DOI Listing
June 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1352458519845116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6858526PMC
June 2020

Retinal measurements predict 10-year disability in multiple sclerosis.

Ann Clin Transl Neurol 2019 02 19;6(2):222-232. Epub 2019 Jan 19.

Department of Neurology Johns Hopkins University Baltimore Maryland.

Objective: Optical coherence tomography (OCT)-derived measures of the retina correlate with disability and cortical gray matter atrophy in multiple sclerosis (MS); however, whether such measures predict long-term disability is unknown. We evaluated whether a single OCT and visual function assessment predict the disability status 10 years later.

Methods: Between 2006 and 2008, 172 people with MS underwent Stratus time domain-OCT imaging [160 with measurement of total macular volume (TMV)] and high and low-contrast letter acuity (LCLA) testing ( = 150; 87%). All participants had Expanded Disability Status Scale (EDSS) assessments at baseline and at 10-year follow-up. We applied generalized linear regression models to assess associations between baseline TMV, peripapillary retinal nerve fiber layer (pRNFL) thickness, and LCLA with 10-year EDSS scores (linear) and with clinically significant EDSS worsening (binary), adjusting for age, sex, optic neuritis history, and baseline disability status.

Results: In multivariable models, lower baseline TMV was associated with higher 10-year EDSS scores (mean increase in EDSS of 0.75 per 1 mm loss in TMV (mean difference = 0.75; 95% CI: 0.11-1.39;  = 0.02). In analyses using tertiles, individuals in the lowest tertile of baseline TMV had an average 0.86 higher EDSS scores at 10 years (mean difference = 0.86; 95% CI: 0.23-1.48) and had over 3.5-fold increased odds of clinically significant EDSS worsening relative to those in the highest tertile of baseline TMV (OR: 3.58; 95% CI: 1.30-9.82; = 0.008). pRNFL and LCLA predicted the 10-year EDSS scores only in univariate models.

Interpretation: Lower baseline TMV measured by OCT significantly predicts higher disability at 10 years, even after accounting for baseline disability status.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/acn3.674DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6389740PMC
February 2019

Effect of disease-modifying therapies on subcortical gray matter atrophy in multiple sclerosis.

Mult Scler 2020 03 11;26(3):312-321. Epub 2019 Feb 11.

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

Background: The effects of disease-modifying therapies (DMTs) on region-specific brain atrophy in multiple sclerosis (MS) are unclear.

Objective: To determine the effects of higher versus lower efficacy DMTs on rates of brain substructure atrophy in MS.

Methods: A non-randomized, observational cohort of people with MS followed with annual brain magnetic resonance imaging (MRI) was evaluated retrospectively. Whole brain, subcortical gray matter (GM), cortical GM, and cerebral white matter (WM) volume fractions were obtained. DMTs were categorized as higher (DMT-H: natalizumab and rituximab) or lower (DMT-L: interferon-beta and glatiramer acetate) efficacy. Follow-up epochs were analyzed if participants had been on a DMT for ⩾6 months prior to baseline and had at least one follow-up MRI while on DMTs in the same category.

Results: A total of 86 DMT epochs (DMT-H:  = 32; DMT-L:  = 54) from 78 participants fulfilled the study inclusion criteria. Mean follow-up was 2.4 years. Annualized rates of thalamic (-0.15% vs -0.81%;  = 0.001) and putaminal (-0.27% vs -0.73%;  = 0.001) atrophy were slower during DMT-H compared to DMT-L epochs. These results remained significant in multivariate analyses including demographics, clinical characteristics, and T2 lesion volume.

Conclusion: DMT-H treatment may be associated with slower rates of subcortical GM atrophy, especially of the thalamus and putamen. Thalamic and putaminal volumes are promising imaging biomarkers in MS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1352458519826364DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6689465PMC
March 2020

Spinal cord and infratentorial lesions in radiologically isolated syndrome are associated with decreased retinal ganglion cell/inner plexiform layer thickness.

Mult Scler 2019 12 3;25(14):1878-1887. Epub 2018 Dec 3.

Division of Neuroimmunology and Neurological Infections, Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Background: The role of retinal imaging with optical coherence tomography (OCT) in assessing individuals with radiologically isolated syndrome (RIS) remains largely unexplored.

Objective: To assess retinal layer thicknesses in RIS and examine their associations with clinical features suggestive of increased risk for conversion to multiple sclerosis (MS).

Methods: A total of 30 RIS subjects and 60 age- and sex-matched healthy controls (HC) underwent retinal imaging with spectral-domain OCT, followed by automated segmentation of retinal layers.

Results: Overall, retinal layer thicknesses did not differ between RIS and HC. However, RIS subjects with spinal cord (SC) lesions had lower ganglion cell + inner plexiform layer (GCIP) thickness compared to HC (-4.41 μm;  = 0.007) and RIS without SC lesions (-3.53 μm;  = 0.041). Similarly, RIS subjects with infratentorial (IT) brain lesions had lower GCIP thickness compared to HC (-4.07 μm;  < 0.001) and RIS without IT lesions (-3.49 μm;  = 0.029). Multivariate analyses revealed that the presence of SC or IT lesions were independently associated with lower GCIP thickness in RIS ( = 0.04 and  = 0.03, respectively). Other patient characteristics, including sex, abnormal cerebrospinal fluid, and presence of gadolinium-enhancing or juxtacortical lesions, were not associated with retinal layer thicknesses.

Conclusion: The presence of SC or IT lesions in RIS may be associated with retinal neuro-axonal loss, supporting the presence of more disseminated disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1352458518815597DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6546560PMC
December 2019

Microvascular blood flow velocities measured with a retinal function imager: inter-eye correlations in healthy controls and an exploration in multiple sclerosis.

Eye Vis (Lond) 2018 2;5:29. Epub 2018 Nov 2.

1Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD USA.

Background: The retinal microcirculation has been studied in various diseases including multiple sclerosis (MS). However, inter-eye correlations and potential differences of the retinal blood flow velocity (BFV) remain largely unstudied but may be important in guiding eye selection as well as the design and interpretation of studies assessing or utilizing retinal BFV. The primary aim of this study was to determine inter-eye correlations in BFVs in healthy controls (HCs). Since prior studies raise the possibility of reduced BFV in MS eyes, a secondary aim was to compare retinal BFVs between MS eyes, grouped based on optic neuritis (ON) history and HC eyes.

Methods: Macular arteriole and venule BFVs were determined using a retinal function imager (RFI) in both eyes of 20 HCs. One eye from a total of 38 MS patients comprising 13 eyes with ON (MSON) and 25 eyes without ON (MSNON) history were similarly imaged with RFI.

Results: OD (right) and OS (left) BFVs were not significantly different in arterioles (OD: 3.95 ± 0.59 mm/s; OS: 4.08 ± 0.60 mm/s,  = 0.10) or venules (OD: 3.11 ± 0.46 mm/s; OS: 3.23 ± 0.52 mm/s,  = 0.06) in HCs. Very strong inter-eye correlations were also found between arteriolar ( = 0.84,  < 0.001) and venular ( = 0.87,  < 0.001) BFVs in HCs. Arteriolar (3.48 ± 0.88 mm/s) and venular (2.75 ± 0.53 mm/s) BFVs in MSNON eyes were significantly lower than in HC eyes ( = 0.009 and  = 0.005, respectively). Similarly, arteriolar (3.59 ± 0.69 mm/s) and venular (2.80 ± 0.45 mm/s) BFVs in MSON eyes were also significantly lower than in HC eyes ( = 0.046 and  = 0.048, respectively). Arteriolar and venular BFVs in MSON and MSNON eyes did not differ from each other ( = 0.42 and  = 0.48, respectively).

Conclusions: Inter-eye arteriolar and venular BFVs do not differ significantly in HCs and are strongly correlated. Our findings support prior observations that arteriolar and venular BFVs may be reduced in MS eyes. Moreover, this seems to be the case in both MS eyes with and without a history of ON, raising the possibility of global blood flow alterations in MS. Future larger studies are needed to assess differences in BFVs between MSON and MSNON eyes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40662-018-0123-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6217760PMC
November 2018

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/brain/awy245DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6202573PMC
November 2018

Emerging Applications of Optical Coherence Tomography Angiography (OCTA) in neurological research.

Eye Vis (Lond) 2018 12;5:11. Epub 2018 May 12.

2Division of Neuroimmunology and Neurological Infections, Johns Hopkins Hospital, 600 N. Wolfe St., Baltimore, MD 21287 USA.

Purpose: To review the clinical and research value of optical coherence tomography angiography (OCTA) in the field of neurology.

Methods: Current literature involving OCTA were reviewed through PubMed using the search terms "optical coherence tomography angiography", with "multiple sclerosis", "Alzheimer's disease", "optic neuropathy", or other closely-related terms.

Results: OCTA has been applied in research to advance our understanding of the pathobiology of neurological disorders. OCTA-derived blood flow and vessel density measures are altered in multiple sclerosis (MS), Alzheimer's disease (AD), and various optic neuropathies (ON) in varying regions of the posterior segment vasculature of the eye. These emerging research findings support the occurrence of retinal vascular alterations across a host of neurological disorders and raise the possibility that vasculopathy can be clinically relevant since it contributes to the pathobiology of several neurological disorders.

Conclusion: OCTA may be beneficial for neurological research. Additional investigations using OCTA in neurological disorders will help to further validate its clinical and research utilities in terms of characterizing the role of vasculopathy in neurological disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40662-018-0104-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5956832PMC
May 2018

Analysis of Agreement of Retinal-Layer Thickness Measures Derived from the Segmentation of Horizontal and Vertical Spectralis OCT Macular Scans.

Curr Eye Res 2018 03 14;43(3):415-423. Epub 2017 Dec 14.

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

Purpose: Optical coherence tomography (OCT) is a reliable method used to quantify discrete layers of the retina. Spectralis OCT is a device used for this purpose. Spectralis OCT macular scan imaging acquisition can be obtained on either the horizontal or vertical plane. The vertical protocol has been proposed as favorable, due to postulated reduction in confound of Henle's fibers on segmentation-derived metrics. Yet, agreement of the segmentation measures of horizontal and vertical macular scans remains unexplored. Our aim was to determine this agreement.

Materials And Methods: Horizontal and vertical macular scans on Spectralis OCT were acquired in 20 healthy controls (HCs) and 20 multiple sclerosis (MS) patients. All scans were segmented using Heidelberg software and a Johns Hopkins University (JHU)-developed method. Agreement was analyzed using Bland-Altman analyses and intra-class correlation coefficients (ICCs).

Results: Using both segmentation techniques, mean differences (agreement at the cohort level) in the thicknesses of all macular layers derived from both acquisition protocols in MS patients and HCs were narrow (<1 µm), while the limits of agreement (LOA) (agreement at the individual level) were wider. Using JHU segmentation mean differences (and LOA) for the macular retinal nerve fiber layer (RNFL) and ganglion cell layer + inner plexiform layer (GCIP) in MS were 0.21 µm (-1.57-1.99 µm) and -0.36 µm (-1.44-1.37 µm), respectively.

Conclusions: OCT segmentation measures of discrete retinal-layer thicknesses derived from both vertical and horizontal protocols on Spectralis OCT agree excellently at the cohort level (narrow mean differences), but only moderately at the individual level (wide LOA). This suggests patients scanned using either protocol should continue to be scanned with the same protocol. However, due to excellent agreement at the cohort level, measures derived from both acquisitions can be pooled for outcome purposes in clinical trials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/02713683.2017.1406526DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6097232PMC
March 2018