Publications by authors named "A Sebastian Lopez-Chiriboga"

48 Publications

Autoimmune Encephalitis-Related Seizures and Epilepsy: Diagnostic and Therapeutic Approaches.

Mayo Clin Proc 2021 08;96(8):2029-2039

Department of Neurology, Mayo Clinic, Jacksonville, FL. Electronic address:

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http://dx.doi.org/10.1016/j.mayocp.2021.02.019DOI Listing
August 2021

Comparison of MRI Lesion Evolution in Different Central Nervous System Demyelinating Disorders.

Neurology 2021 Sep 14;97(11):e1097-e1109. Epub 2021 Jul 14.

From the Departments of Neurology (E.S., M.B., S.J.P., J.J.C., B.G.W., C.F.L., N.L.Z., J.M.T., A.K., S.B.S.-M., B.M.K., E.P.F.), Radiology (K.N.K., S.A.M., P.P.M.), Laboratory Medicine and Pathology (S.J.P., J.P.F., A.N., E.P.F.), and Ophthalmology (J.J.C., T.G.), Mayo Clinic, Rochester, MN; Department of Neurosciences, Biomedicine, and Movement Sciences (E.S., S.M.), University of Verona, Italy; and Department of Neurology (A.S.L.-C.), Mayo Clinic, Jacksonville, FL.

Background And Objective: There are few studies comparing lesion evolution across different CNS demyelinating diseases, yet knowledge of this may be important for diagnosis and understanding differences in disease pathogenesis. We sought to compare MRI T2 lesion evolution in myelin oligodendrocyte glycoprotein immunoglobulin G (IgG)-associated disorder (MOGAD), aquaporin 4 IgG-positive neuromyelitis optica spectrum disorder (AQP4-IgG-NMOSD), and multiple sclerosis (MS).

Methods: In this descriptive study, we retrospectively identified Mayo Clinic patients with MOGAD, AQP4-IgG-NMOSD, or MS and (1) brain or myelitis attack; (2) available attack MRI within 6 weeks; and (3) follow-up MRI beyond 6 months without interval relapses in that region. Two neurologists identified the symptomatic or largest T2 lesion for each patient (index lesion). MRIs were then independently reviewed by 2 neuroradiologists blinded to diagnosis to determine resolution of T2 lesions by consensus. The index T2 lesion area was manually outlined acutely and at follow-up to assess variation in size.

Results: We included 156 patients (MOGAD, 38; AQP4-IgG-NMOSD, 51; MS, 67) with 172 attacks (brain, 81; myelitis, 91). The age (median [range]) differed between MOGAD (25 [2-74]), AQP4-IgG-NMOSD (53 [10-78]), and MS (37 [16-61]) ( < 0.01) and female sex predominated in the AQP4-IgG-NMOSD (41/51 [80%]) and MS (51/67 [76%]) groups but not among those with MOGAD (17/38 [45%]). Complete resolution of the index T2 lesion was more frequent in MOGAD (brain, 13/18 [72%]; spine, 22/28 [79%]) than AQP4-IgG-NMOSD (brain, 3/21 [14%]; spine, 0/34 [0%]) and MS (brain, 7/42 [17%]; spine, 0/29 [0%]) ( < 0.001). Resolution of all T2 lesions occurred most often in MOGAD (brain, 7/18 [39%]; spine, 22/28 [79%]) than AQP4-IgG-NMOSD (brain, 2/21 [10%]; spine, 0/34 [0%]) and MS (brain, 2/42 [5%]; spine, 0/29 [0%]) ( < 0.01). There was a larger median (range) reduction in T2 lesion area in mm on follow-up axial brain MRI with MOGAD (213 [55-873]) than AQP4-IgG-NMOSD (104 [0.7-597]) ( = 0.02) and MS (36 [0-506]) ( < 0.001) and the reductions in size on sagittal spine MRI follow-up in MOGAD (262 [0-888]) and AQP4-IgG-NMOSD (309 [0-1885]) were similar ( = 0.4) and greater than in MS (23 [0-152]) ( < 0.001).

Discussion: The MRI T2 lesions in MOGAD resolve completely more often than in AQP4-IgG-NMOSD and MS. This has implications for diagnosis, monitoring disease activity, and clinical trial design, while also providing insight into pathogenesis of CNS demyelinating diseases.
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http://dx.doi.org/10.1212/WNL.0000000000012467DOI Listing
September 2021

Brain-responsive neurostimulation in adult-onset rasmussen's encephalitis.

Epilepsy Behav Rep 2021 29;15:100445. Epub 2021 Mar 29.

Mayo Clinic Florida, Jacksonville, FL, United States.

Epilepsy associated with Rasmussen's encephalitis (RE) is highly resistant to standard therapy and continues to present a therapeutic challenge. While epilepsy surgery remains the most effective management for patients with drug-resistant focal epilepsy and RE, hemispherotomy may debilitating consequences on adult patients. Here we present the outcome of a 32-year-old woman with adult-onset Rasmussen's, who was treated with brain-responsive neurostimulation (RNS) after failure of several immunotherapeutic and anti-seizure medications.
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http://dx.doi.org/10.1016/j.ebr.2021.100445DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8063734PMC
March 2021

Positive Predictive Value of Myelin Oligodendrocyte Glycoprotein Autoantibody Testing.

JAMA Neurol 2021 Jun;78(6):741-746

Department of Neurology, Mayo Clinic College of Medicine and Science, Rochester, Minnesota.

Importance: Myelin oligodendrocyte glycoprotein-IgG1-associated disorder (MOGAD) is a distinct central nervous system-demyelinating disease. Positive results on MOG-IgG1 testing by live cell-based assays can confirm a MOGAD diagnosis, but false-positive results may occur.

Objective: To determine the positive predictive value (PPV) of MOG-IgG1 testing in a tertiary referral center.

Design, Setting, And Participants: This diagnostic study was conducted over 2 years, from January 1, 2018, through December 31, 2019. Patients in the Mayo Clinic who were consecutively tested for MOG-IgG1 by live cell-based flow cytometry during their diagnostic workup were included. Patients without research authorization were excluded.

Main Outcomes And Measures: Medical records of patients who were tested were initially reviewed by 2 investigators blinded to MOG-IgG1 serostatus, and pretest probability was classified as high or low (suggestive of MOGAD or not). Testing of MOG-IgG1 used a live-cell fluorescence-activated cell-sorting assay; an IgG binding index value of 2.5 or more with an end titer of 1:20 or more was considered positive. Cases positive for MOG-IgG1 were independently designated by 2 neurologists as true-positive or false-positive results at last follow-up, based on current international recommendations on diagnosis or identification of alternative diagnoses; consensus was reached for cases in which disagreement existed.

Results: A total of 1617 patients were tested, and 357 were excluded. Among 1260 included patients tested over 2 years, the median (range) age at testing was 46 (0-98) years, and 792 patients were female (62.9%). A total of 92 of 1260 (7.3%) were positive for MOG-IgG1. Twenty-six results (28%) were designated as false positive by the 2 raters, with an overall agreement on 91 of 92 cases (99%) for true and false positivity. Alternative diagnoses included multiple sclerosis (n = 11), infarction (n = 3), B12 deficiency (n = 2), neoplasia (n = 2), genetically confirmed adrenomyeloneuropathy (n = 1), and other conditions (n = 7). The overall PPV (number of true-positive results/total positive results) was 72% (95% CI, 62%-80%) and titer dependent (PPVs: 1:1000, 100%; 1:100, 82%; 1:20-40, 51%). The median titer was higher with true-positive results (1:100 [range, 1:20-1:10000]) than false-positive results (1:40 [range, 1:20-1:100]; P < .001). The PPV was higher for children (94% [95% CI, 72%-99%]) vs adults (67% [95% CI, 56%-77%]) and patients with high pretest probability (85% [95% CI, 76%-92%]) vs low pretest probability (12% [95% CI, 3%-34%]). The specificity of MOG-IgG1 testing was 97.8%.

Conclusions And Relevance: This study confirms MOG-IgG1 as a highly specific biomarker for MOGAD, but when using a cutoff of 1:20, it has a low PPV of 72%. Caution is advised in the interpretation of low titers among patients with atypical phenotypes, because ordering MOG-IgG1 in low pretest probability situations will increase the proportion of false-positive results.
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http://dx.doi.org/10.1001/jamaneurol.2021.0912DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8077043PMC
June 2021

Prospective Quantification of CSF Biomarkers in Antibody-Mediated Encephalitis.

Neurology 2021 05 1;96(20):e2546-e2557. Epub 2021 Apr 1.

From the Department of Neurology (G.S.D., A.S.L.-C., N.R.G.-R.), Mayo Clinic, Jacksonville, FL; Departments of Pathology and Immunology (M.Y.Y., E.M.H., J.H.L.) and Neurology (R.C.B., R.L.H., E.M.H., J.H.L., J.C.M., A.F.) and The Charles F. and Joanne Knight Alzheimer Disease Research Center (R.L.H., J.C.M., A.F.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (P.M.D.K.), University of Magdeburg; Department of Neurology and Experimental Neurology (P.M.D.K., H.P.) Charité, Universitätmedizin Berlin, Germany; Department of Medicine (M.J.F.), Cumming School of Medicine, University of Calgary; Department of Medicine (W.M., D.F.T.-W., J.H.), Division of Neurology, University of Toronto, Canada; and NYU Langone Comprehensive Epilepsy Center (C.S.), NYU Langone Health, New York, NY.

Objective: To determine whether neuronal and neuroaxonal injury, neuroinflammation, and synaptic dysfunction associate with clinical course and outcomes in antibody-mediated encephalitis (AME), we measured biomarkers of these processes in CSF from patients presenting with AME and cognitively normal individuals.

Methods: Biomarkers of neuronal (total tau, VILIP-1) and neuroaxonal damage (neurofilament light chain [NfL]), inflammation (YKL-40), and synaptic function (neurogranin, SNAP-25) were measured in CSF obtained from 45 patients at the time of diagnosis of NMDA receptor (n = 34) or / (n = 11) AME and 39 age- and sex-similar cognitively normal individuals. The association between biomarkers and modified Rankin Scale (mRS) scores were evaluated in a subset (n = 20) of longitudinally followed patients.

Results: Biomarkers of neuroaxonal injury (NfL) and neuroinflammation (YKL-40) were elevated in AME cases at presentation, whereas markers of neuronal injury and synaptic function were stable (total tau) or decreased (VILIP-1, SNAP-25, neurogranin). The log-transformed ratio of YKL-40/SNAP-25 optimally discriminated patients from cognitively normal individuals (area under the receiver operating characteristic curve 0.99; 95% confidence interval 0.97, >0.99). Younger age (ρ = -0.56; = 0.01), lower VILIP-1 (ρ = -0.60; < 0.01) and SNAP-25 (ρ = -0.54; = 0.01), and higher log(YKL-40/SNAP-25) (ρ = 0.48; = 0.04) associated with greater disease severity (higher mRS score) in prospectively followed patients. Higher YKL-40 (ρ = 0.60; = 0.02) and neurogranin (ρ = 0.55; = 0.03) at presentation were associated with higher mRS scores 12 months following hospital discharge.

Conclusions: CSF biomarkers suggest that neuronal integrity is acutely maintained in AME, despite neuroaxonal compromise. Low levels of biomarkers of synaptic function may reflect antibody-mediated internalization of cell surface receptors and may represent an acute correlate of antibody-mediated synaptic dysfunction, with the potential to inform disease severity and outcomes.
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http://dx.doi.org/10.1212/WNL.0000000000011937DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205475PMC
May 2021
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