Han Lab Publications

Associate Professor of Neurology (Adult Neurology)

Publications

  • Clinical Features of Neurotoxicity Following CD19 CAR T-cell Therapy in Mantle Cell Lymphoma. Blood advances Nie, E. H., Su, Y. J., Baird, J. H., Agarwal, N., Bharadwaj, S., Weng, W. K., Smith, M., Dahiya, S., Han, M. H., Dunn, J. E., Kipp, L. B., Miklos, D. B., Scott, B. J., Frank, M. J. 2024

    Abstract

    CD19 chimeric antigen receptor (CAR) T-cell therapy has proven highly effective for treating relapsed/refractory mantle cell lymphoma (MCL). However, immune effector cell-associated neurotoxicity syndrome (ICANS) remains a significant concern. This study aimed to evaluate the clinical, radiological, and laboratory correlatives associated with ICANS development following CD19 CAR T-cell therapy in patients with MCL. All patients (n = 26) who received standard of care brexucabtagene autoleucel until July 2022 at our institution were evaluated. Laboratory and radiographic correlatives including brain magnetic resonance imaging (MRI) and electroencephalogram (EEG) were evaluated to determine the clinical impact of ICANS. Seventeen (65%) patients experienced ICANS after treatment, with a median onset on day 6. Ten (38%) patients experienced severe (≥ grade 3) ICANS. All ICANS patients had antecedent cytokine release syndrome (CRS), but no correlation was observed between ICANS severity and CRS grade. 92% of EEGs revealed interictal changes; no patients experienced frank seizures due to ICANS. 86% of severe ICANS patients with post-infusion brain MRIs demonstrated acute neuroimaging findings not seen on pretreatment MRI. Severe ICANS was also associated with higher rates of cytopenia, coagulopathy, increased cumulative steroid exposure, and prolonged hospitalization. However, severe ICANS did not affect treatment outcomes of patients with MCL. Severe ICANS is frequently associated with a range of post-infusion brain MRI changes and abnormal EEG findings. Longer hospitalization was observed in severe ICANS patients, especially those with abnormal acute MRI or EEG findings, but there was no discernible impact on overall treatment response and survival.

    View details for DOI 10.1182/bloodadvances.2023011896

    View details for PubMedID 38295285

  • Prevalence, Demographic, and Clinical Factors Associated With Cognitive Dysfunction in Patients With Neuromyelitis Optica Spectrum Disorder. Neurology Vlahovic, L., McDonald, J., Hinman, J., Tomczak, A., Lock, C., Palmer, C. A., Cook, L. J., Yeaman, M. R., Burnett, M. K., Deutsch, G. K., Nelson, L. M., Han, M. H. 2024; 102 (1): e207965

    Abstract

    Neuromyelitis optica spectrum disorder (NMOSD) is a chronic CNS demyelinating autoimmune disorder targeting the astrocyte antigen aquaporin-4 (AQP4), typically presenting with optic neuritis, transverse myelitis, and brain syndromes. Cognitive dysfunction (CD) in NMOSD is under-recognized and poorly understood. The purpose of this study was to evaluate the prevalence and clinical variables associated with CD in NMOSD.This observational retrospective study with longitudinal follow-up describes a clinical cohort seen in the Collaborative International Research in Clinical and Longitudinal Experience Study in NMOSD. Serial Montreal Cognitive Assessments (MoCAs) were performed upon enrollment and at 6-month intervals to evaluate longitudinal cognitive function relative to demographic and disease-related factors. We used 2-tailed t test, analysis of variance, the χ2 test, linear regression for univariable and adjusted analyses and simultaneous linear regression and mixed-effects model for multivariable analyses.Thirty-four percent (75/219) of patients met criteria for CD (MoCA <26); 29% (64/219) showed mild dysfunction (MoCA 20-26/30), and 5% (11/219) showed moderate (MoCA <20/30) dysfunction. Patients with less neurologic disability and lower pain scores had higher MoCA scores (95% CI 0.24-0.65 and 95% CI 0.09-0.42, respectively). Patients with at least high school education scored higher on the MoCA (95% CI 2.2-5). When comparing patients dichotomized for CD, patients never on rituximab scored higher than patients only treated with rituximab (p < 0.029). There was no significant association between annualized relapse rate, age, sex, disease duration, AQP4 serostatus or brain lesions, and CD. CD was more pronounced among Black than White patients (95% CI -2.7 to -0.7). Multivariable analysis of serial MoCA did not indicate change (p = 0.715). Descriptive analysis of serial MoCA showed 30% (45/150) of patients with worsening MoCA performance had impaired language and verbal recall.To our knowledge, this is the largest study of diverse cohort to investigate CD in patients with NMOSD. Our findings demonstrate 34% of patients with NMOSD experience mild-to-moderate CD, while 30% of patients demonstrated decline on serial testing. The substantial prevalence of CD in this pilot report highlights the need for improved and validated screening tools and comprehensive measures to investigate CD in NMOSD.

    View details for DOI 10.1212/WNL.0000000000207965

    View details for PubMedID 38165361

  • A novel mouse model of cerebral adrenoleukodystrophy highlights NLRP3 activity in lesion pathogenesis. bioRxiv : the preprint server for biology Hashemi, E., Narain Srivastava, I., Aguirre, A., Tilahan Yoseph, E., Kaushal, E., Awani, A., Kyu Ryu, J., Akassoglou, K., Talebian, S., Chu, P., Pisani, L., Musolino, P., Steinman, L., Doyle, K., Robinson, W. H., Sharpe, O., Cayrol, R., Orchard, P., Lund, T., Vogel, H., Lenail, M., Han, M. H., Bonkowsky, J. L., Van Haren, K. P. 2023

    Abstract

    We sought to create and characterize a mouse model of the inflammatory, cerebral demyelinating phenotype of X-linked adrenoleukodystrophy (ALD) that would facilitate the study of disease pathogenesis and therapy development. We also sought to cross-validate potential therapeutic targets such as fibrin, oxidative stress, and the NLRP3 inflammasome, in post-mortem human and murine brain tissues.ALD is caused by mutations in the gene ABCD1 encoding a peroxisomal transporter. More than half of males with an ABCD1 mutation develop the cerebral phenotype (cALD). Incomplete penetrance and absence of a genotype-phenotype correlation imply a role for environmental triggers. Mechanistic studies have been limited by the absence of a cALD phenotype in the Abcd1-null mouse.We generated a cALD phenotype in 8-week-old, male Abcd1-null mice by deploying a two-hit method that combines cuprizone (CPZ) and experimental autoimmune encephalomyelitis (EAE) models. We employed in vivo MRI and post-mortem immunohistochemistry to evaluate myelin loss, astrogliosis, blood-brain barrier (BBB) disruption, immune cell infiltration, fibrin deposition, oxidative stress, and Nlrp3 inflammasome activation in mice. We used bead-based immunoassay and immunohistochemistry to evaluate IL-18 in CSF and post-mortem human cALD brain tissue.MRI studies revealed T2 hyperintensities and post-gadolinium enhancement in the medial corpus callosum of cALD mice, similar to human cALD lesions. Both human and mouse cALD lesions shared common histologic features of myelin phagocytosis, myelin loss, abundant microglial activation, T and B-cell infiltration, and astrogliosis. Compared to wild-type controls, Abcd1-null mice had more severe cerebral inflammation, demyelination, fibrin deposition, oxidative stress, and IL-18 activation. IL-18 immunoreactivity co-localized with macrophages/microglia in the perivascular region of both human and mouse brain tissue.This novel mouse model of cALD suggests loss of Abcd1 function predisposes to more severe cerebral inflammation, oxidative stress, fibrin deposition, and Nlrp3 pathway activation, which parallels the findings seen in humans with cALD. We expect this model to enable long-sought investigations into cALD mechanisms and accelerate development of candidate therapies for lesion prevention, cessation, and remyelination.

    View details for DOI 10.1101/2023.11.07.564025

    View details for PubMedID 37986739

    View details for PubMedCentralID PMC10659266

  • Epidemiological and Clinical Outcome Determinants of Post-COVID-19 Myelopathy Sumera, J., Sarkar, T., McDonald, J., Sattarnezhad, N., Nie, E., Kipp, L., Dunn, J., Han, M., Joseph, Y., Tomczak, A., Lock, C. SAGE PUBLICATIONS LTD. 2023: 719
  • Blood Biomarkers Elucidate the Mechanism of Cognitive Dysfunction in Neuromyelitis Optica and Myelin Oligodendrocyte Glycoprotein Antibody Associated Disease Han, M., Vlahovic, L., Wilson, E. SAGE PUBLICATIONS LTD. 2023: 827-828
  • Impacts of Race and Immunotherapy on Maternal and Fetal Outcomes in Pregnant Patients with NMOSD and MOGAD Hla, A., Sarkar, T., McDonald, J., Han, M. SAGE PUBLICATIONS LTD. 2023: 679
  • Longitudinal imaging of microscopic scattering features in the foveal avascular zone of multiple sclerosis using adaptive optics ophthalmoscopy Hargrave, A., Navarro, S., Buickians, D., Kipp, L., Han, M., Kowalski, B., Dubra, A., Moss, H. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2023
  • SARS-CoV-2 Vaccine Immune Response on Anti-Complement Therapy, Eculizumab Sattarnezhad, N., Sumera, J., McDonald, J., Nie, E., Tomczak, A., Joseph, Y., Kalle, S., Sarkar, T., Kipp, L., Lock, C., Dunn, J. E., Han, M. LIPPINCOTT WILLIAMS & WILKINS. 2023
  • Influence of Body Mass Index on B Lymphocyte Repopulation in Multiple Sclerosis Patients Treated with Anti-CD20 Therapy Loeffler, J., Han, M. LIPPINCOTT WILLIAMS & WILKINS. 2023
  • Risk of acute stroke in young patients with new-onset lupus nephritis: a case series Wu, D., Han, M., Lee, S. LIPPINCOTT WILLIAMS & WILKINS. 2023
  • Myelin Oligodendrocyte Glycoprotein Antibody Disease (MOGAD) in conjunction with Allogeneic Bone Marrow Transplantation and Autoimmune Neutropenia: A study of two companion cases and institutional review of the MOGAD clinical phenotype spectrum Nie, E., McDonald, J., Dunn, J., Han, M. LIPPINCOTT WILLIAMS & WILKINS. 2023
  • Clinical and epidemiological correlates of treatment change in patients with NMOSD: insights from the CIRCLES cohort. Journal of neurology Gholizadeh, S., Exuzides, A., Lewis, K. E., Palmer, C., Waltz, M., Rose, J. W., Jolley, A. M., Behne, J. M., Behne, M. K., Blaschke, T. F., Smith, T. J., Sinnott, J., Cook, L. J., Yeaman, M. R., Guthy-Jackson Charitable Foundation CIRCLES Study Group, Aguerre, I., Amezcua, L., Chitnis, T., Lewis, J. C., Engel, C., Han, M. H., Klawiter, E. C., Kocsik, A., Kruse-Hoyer, M., Levine, L., Levy, M., Marcille, M., Mealy, M. A., Moore, S., Mullin, D. S., Nelson, K. E., Onomichi, K. B., Planchon, S. M., Pruitt, A., Repovic, P., Riley, C. S., Rimler, Z., Russo, A. W., Ocampo, C. T., Tomczak, A. J. 2022

    Abstract

    OBJECTIVE: Neuromyelitis optica spectrum disorders (NMOSD) represent rare autoimmune diseases of the central nervous system largely targeting optic nerve(s) and spinal cord. The present analysis used real-world data to identify clinical and epidemiological correlates of treatment change in patients with NMOSD.METHODS: CIRCLES is a longitudinal, observational study of NMOSD conducted at 15 centers across North America. Patients with≥60days of follow-up and receiving on-study maintenance treatment were evaluated. The mean annual relapse rate (ARR) was estimated using negative binomial models; the likelihood of treatment change was estimated using Cox proportional hazards models. Relapses were included as time-varying covariates to estimate the relationship to treatment change.RESULTS: Of 542 patients included, 171 (31.5%) experienced≥1 relapse on the study and 133 patients (24.5%) had≥1 change in the treatment regimen. Two categories of variables significantly correlated with the likelihood of treatment change: (1) relapse: any on-study relapse (hazard ratio [HR]=2.91; p<0.001), relapse phenotypes (HR range=2.15-5.49; p<0.001), and pre-study ARR>0.75 (HR 2.28; p<0.001); 2) disease phenotype: brain syndrome only vs transverse myelitis involvement at onset (HR 2.44; p=0.008), disease duration<1 vs>5years (HR 1.66; p=0.028), or autoimmune comorbidity (HR 1.55; p=0.015). A subset of these factors significantly correlated with shorter time to first rituximab discontinuation.CONCLUSIONS: In CIRCLES, relapse patterns and disease phenotype significantly correlated with changes in the maintenance treatment regimen. Such findings may facilitate the identification of patients with NMOSD who are likely to benefit from treatment change to reduce relapse risk or disease burden and enhance the quality of life.

    View details for DOI 10.1007/s00415-022-11529-6

    View details for PubMedID 36565348

  • A Novel Mouse Model of Cerebral Demyelination in X-Linked Adrenoleukodystrophy Highlights NLRP3 Activation in Lesion Pathogenesis Srivastava, I., Van Haren, K., Hashemi, E., Kaushal, E., Han, M., Lund, T., Bonkowsky, J., Yoseph, E. WILEY. 2022: S174
  • Visualizing Sphingosine-1-Phosphate Receptor 1(S1P1) Signaling During Central Nervous System De- and Remyelination. Cellular and molecular neurobiology Hashemi, E., Yoseph, E., Tsai, H., Moreno, M., Yeh, L., Mehta, S. B., Kono, M., Proia, R., Han, M. H. 2022

    Abstract

    Multiple sclerosis (MS) is an inflammatory-demyelinating disease of the central nervous system (CNS) mediated by aberrant auto-reactive immune responses. The current immune-modulatory therapies are unable to protect and repair immune-mediated neural tissue damage. One of the therapeutic targets in MS is the sphingosine-1-phosphate (S1P) pathway which signals via sphingosine-1-phosphate receptors 1-5 (S1P1-5). S1P receptors are expressed predominantly on immune and CNS cells. Considering the potential neuroprotective properties of S1P signaling, we utilized S1P1-GFP (Green fluorescent protein) reporter mice in the cuprizone-induced demyelination model to investigate in vivo S1P - S1P1 signaling in the CNS. We observed S1P1 signaling in a subset of neural stem cells in the subventricular zone (SVZ) during demyelination. During remyelination, S1P1 signaling is expressed in oligodendrocyte progenitor cells in the SVZ and mature oligodendrocytes in the medial corpus callosum (MCC). In the cuprizone model, we did not observe S1P1 signaling in neurons and astrocytes. We also observed beta-arrestin-dependent S1P1 signaling in lymphocytes during demyelination and CNS inflammation. Our findings reveal beta-arrestin-dependent S1P1 signaling in oligodendrocyte lineage cells implying a role of S1P1 signaling in remyelination.

    View details for DOI 10.1007/s10571-022-01245-0

    View details for PubMedID 35917044

  • Immune cell subset profiling in multiple sclerosis after fingolimod initiation and continued treatment: The FLUENT study. Multiple sclerosis journal - experimental, translational and clinical Mao-Draayer, Y., Cohen, J. A., Bar-Or, A., Han, M. H., Singer, B., Williams, I. M., Meng, X., Elam, C., Weiss, J. L., Cox, G. M., Ziehn, M., Cree, B. A., FLUENT study investigators 2022; 8 (3): 20552173221115023

    Abstract

    Background: Fingolimod is a sphingosine 1-phosphate receptor modulator approved for relapsing MS. Long-term effects on the immunological profile are not fully understood.Objective: Investigate fingolimod's temporal effects on immune cell subsets, and safety outcomes.Methods: In FLUENT, a 12-month, prospective, non-randomized, open-label, phase IV study, adult participants received fingolimod 0.5 mg/day. Changes in immune cell subsets, anti-John Cunningham virus (JCV) antibody index, and serum neurofilament levels were assessed.Results: 165 fingolimod-naive and 217 participants treated for 2-12 years in routine clinical practice were enrolled. Levels of all monitored peripheral lymphocyte subsets were reduced from month 3 in fingolimod-naive participants. Greatest reductions occurred in naive and central memory CD4+and CD8+T cells, and in naive and memory B cells. Most lymphocyte subset levels remained stable in the continuous fingolimod group. Components of the innate immune system remained within reference ranges. No increase in JCV seropositivity was observed. No single cellular subset correlated with anti-JCV antibody index at any time point. Neurofilament levels remained within healthy adult reference limits throughout. No opportunistic infections were reported; no new or unexpected safety signals were observed.Conclusion: FLUENT provides insights into the utility of immunological profiling to evaluate therapy response and potential infection risk.

    View details for DOI 10.1177/20552173221115023

    View details for PubMedID 35936922

  • HLA-DR4-positive Vogt-Koyanagi-Harada (VKH) Syndrome: Review of pathophysiology and clinical correlation (P1-1.Virtual) Loeffler, J., Nie, E., Han, M. LIPPINCOTT WILLIAMS & WILKINS. 2022
  • Immune-mediated diseases and thromboembolic events: a modified Delphi panel. Current medical research and opinion Azimi, N., Caldera, F., Cohen, S., Conners, J., Fernandes, T., Han, M., Strand, V., Tapson, V., Weinberg, A., Weinberg, J., Yarur, A. 2021: 1

    Abstract

    INTRODUCTION: A multidisciplinary panel of physicians was convened to gain understanding of the relationship between thromboembolic events (TEs) and immune-mediated diseases (IMDs).The primary objective of the panel was to assess areas of consensus on the IMD most prone to TE as well as modifiable and unmodifiable factors that might exacerbate or mitigate the risk of TEs.METHODS: Thirteen nationally recognized physicians were selected based on their contributions to guidelines, publications, and patient care. The modified Delphi panel consisted of four rounds of engagement: (1) a semi-structured interview, (2) an expert panel questionnaire, (3) an in-person panel discussion, and (4) a consensus statement survey.RESULTS: Ulcerative colitis and Crohn's disease were identified as two of four IMDs with the highest TE risk. Consensus was reached on several non-modifiable and modifiable characteristics of high-risk. Approaches to reduce TE incidence were identified such as altering treatment, requiring the monitoring of patients for TEs, and modifying patient behaviors. Janus kinase inhibitors and corticosteroids were identified as therapies that required further evaluation given their potential TE risk.DISCUSSION: The panel reached a consensus that several IMDs are at an elevated risk of TEs. Physicians are unable to control most patient level risk factors but can control the therapies being used. Consequently, physicians should consider the specific IMD, be aware of TE risk factors, and take into account risk factors in selecting the therapies to optimally manage their conditions and to reduce the risk of TEs in this population.

    View details for DOI 10.1080/03007995.2021.1932450

    View details for PubMedID 34034599

  • CD317 puts the brakes on dendritic cell trafficking to the CNS. Proceedings of the National Academy of Sciences of the United States of America Barnes, S. E., Han, M. H. 2021; 118 (18)

    View details for DOI 10.1073/pnas.2104740118

    View details for PubMedID 33850053

  • Pericytes regulate vascular immune homeostasis in the CNS. Proceedings of the National Academy of Sciences of the United States of America Torok, O., Schreiner, B., Schaffenrath, J., Tsai, H., Maheshwari, U., Stifter, S. A., Welsh, C., Amorim, A., Sridhar, S., Utz, S. G., Mildenberger, W., Nassiri, S., Delorenzi, M., Aguzzi, A., Han, M. H., Greter, M., Becher, B., Keller, A. 2021; 118 (10)

    Abstract

    Pericytes regulate the development of organ-specific characteristics of the brain vasculature such as the blood-brain barrier (BBB) and astrocytic end-feet. Whether pericytes are involved in the control of leukocyte trafficking in the adult central nervous system (CNS), a process tightly regulated by CNS vasculature, remains elusive. Using adult pericyte-deficient mice (Pdgfb ret/ret ), we show that pericytes limit leukocyte infiltration into the CNS during homeostasis and autoimmune neuroinflammation. The permissiveness of the vasculature toward leukocyte trafficking in Pdgfb ret/ret mice inversely correlates with vessel pericyte coverage. Upon induction of experimental autoimmune encephalomyelitis (EAE), pericyte-deficient mice die of severe atypical EAE, which can be reversed with fingolimod, indicating that the mortality is due to the massive influx of immune cells into the brain. Additionally, administration of anti-VCAM-1 and anti-ICAM-1 antibodies reduces leukocyte infiltration and diminishes the severity of atypical EAE symptoms of Pdgfb ret/ret mice, indicating that the proinflammatory endothelium due to absence of pericytes facilitates exaggerated neuroinflammation. Furthermore, we show that the presence of myelin peptide-specific peripheral T cells in Pdgfb ret/ret ;2D2 tg mice leads to the development of spontaneous neurological symptoms paralleled by the massive influx of leukocytes into the brain. These findings indicate that intrinsic changes within brain vasculature can promote the development of a neuroinflammatory disorder.

    View details for DOI 10.1073/pnas.2016587118

    View details for PubMedID 33653955

  • Novel Foveal Features Associated With Vision Impairment in Multiple Sclerosis. Investigative ophthalmology & visual science Hargrave, A., Sredar, N., Khushzad, F., Yarp, J., Tomczak, A., Han, M., Kipp, L., Dubra, A., Moss, H. E. 2021; 62 (12): 27

    Abstract

    To characterize scattering and hyperreflective features in the foveal avascular zone of people with multiple sclerosis (MS) using adaptive optics scanning laser ophthalmoscopy (AOSLO) and to evaluate their relationship with visual function and MS disease characteristics.Twenty subjects with MS underwent confocal reflectance and non-confocal split-detection AOSLO foveal imaging. Peripapillary retinal nerve fiber layer thickness was measured using optic nerve optical coherence tomography. Blood pressure, intraocular pressure (IOP), and best-corrected high-contrast visual acuity (HCVA) and low-contrast visual acuity (LCVA) were measured. AOSLO images were graded to determine the presence and characteristics of distinct structures.Two distinct structures were seen in the avascular zone of the foveal pit. Hyperreflective puncta, present in 74% of eyes, were associated with IOP and blood pressure. Scattering features, observed in 58% of eyes, were associated with decreased HCVA and LCVA, as well as increased MS duration and disability, but were not associated with retinal nerve fiber layer thickness. Hyperreflective puncta and scattering features were simultaneously present in 53% of eyes.Hyperreflective puncta were associated with parameters affecting ophthalmic perfusion, but they were not associated with MS disease parameters. Scattering features were associated with parameters corresponding to advanced MS, suggesting that they may be related to disease progression. Scattering features were also correlated with reduced visual function independent from ganglion cell injury, suggesting the possibility of a novel ganglion cell-independent mechanism of impaired vision in people with MS.

    View details for DOI 10.1167/iovs.62.12.27

    View details for PubMedID 34581726

  • New Therapeutic Landscape in Neuromyelitis Optica. Current treatment options in neurology Tugizova, M. n., Vlahovic, L. n., Tomczak, A. n., Wetzel, N. S., Han, M. H. 2021; 23 (4): 13

    Abstract

    This review discusses the current treatment trends and emerging therapeutic landscape for patients with neuromyelitis optica spectrum disorder (NMOSD).Conventional immune suppressive therapies, such as B cell depletion, have been used for long-term treatment. However, the availability of recent FDA-approved and investigational drugs has made therapeutic choices for NMOSD more complex.Recent randomized clinical trials have shown that eculizumab, inebilizumab, and satralizumab are efficacious therapies for AQP4 seropositive NMOSD. These therapies may not have the same benefit in patients with seronegative NMOSD, including MOG-associated disease, and further investigation is required in this population. Reliable biomarkers to guide therapy decisions are urgently needed. There is a plethora of promising investigational therapies currently in the pipeline with exciting and novel mechanisms of action.

    View details for DOI 10.1007/s11940-021-00667-3

    View details for PubMedID 33814893

    View details for PubMedCentralID PMC8008025

  • In-depth B cell immunophenotyping to monitor response to anti-CD20 therapy in CNS autoimmunity. Multiple sclerosis and related disorders Su, E., Wetzel, N. S., Oak, J., Kipp, L., Han, M. H. 2020; 46: 102594

    View details for DOI 10.1016/j.msard.2020.102594

    View details for PubMedID 33296989

  • Examining the Link Between Autoimmune Disease and Thromboembolic Events: A Modified Delphi Panel Approach Azimi, N., Caldera, F., Cohen, S., Conners, J., Fernandes, T., Han, M., Strand, V., Tapson, V., Weinberg, A. S., Weinberg, J., Yarur, A. LIPPINCOTT WILLIAMS & WILKINS. 2020: S454
  • White-matter-nulled MPRAGE at 7T reveals thalamic lesions and atrophy of specific thalamic nuclei in multiple sclerosis MULTIPLE SCLEROSIS JOURNAL Planche, V., Su, J. H., Mournet, S., Saranathan, M., Dousset, V., Han, M., Rutt, B. K., Tourdias, T. 2020; 26 (8): 987–92
  • Novel microscopic foveal pit pathology in multiple sclerosis revealed with adaptive optics ophthalmoscopy Hargrave, A., Sredar, N., Razeen, M. M., Khushzad, F., Yarp, J., Leishangthem, L., Tomczak, A., Kipp, L., Han, M., Kowalski, B., Dubra, A., Moss, H. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2020
  • Characterization of Retinal vascular changes in Multiple Sclerosis using Adaptive Optics and OCTA Khushzad, F., Yarp, J., Hargrave, A., Sredar, N., Mahesh, V., Tomczak, A., Kipp, L., Han, M., Dubra, A., Moss, H. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2020
  • Comparison of visual function and retinal structure between phases of multiple sclerosis Yarp, J., Khushzad, F., Leishangthem, L., Mahesh, V., Tomczak, A., Han, M., Kipp, L., Moss, H. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2020
  • Changes in immune cell profile, clinical and safety outcomes in fingolimod-treated patients with relapsing multiple sclerosis in the FLUENT study Mao-Draayer, Y., Cohen, J. A., Bar-Or, A., Han, M. H., Singer, B., Jaitly, N., Kolodny, S., Elam, C., Meng, X., Ziehn, M., Cree, B. C. LIPPINCOTT WILLIAMS & WILKINS. 2020
  • Case series: Hearing loss in neuromyelitis optica spectrum disorders. Multiple sclerosis and related disorders Tugizova, M., Feng, H., Tomczak, A., Steenerson, K., Han, M. 2020; 41: 102032

    Abstract

    BACKGROUND: Aquaporin 4 (AQP4)- and myelin oligodendrocyte glycoprotein (MOG)-associated neuromyelitis optica spectrum disorders (NMOSD) are thought to primarily affect the central nervous system (CNS). However, emerging evidence suggests that there are extra-CNS manifestations of NMOSD, including myopathies, gastrointestinal dysfunction, renal involvement and adverse pregnancy outcomes.1 METHODS: Three patients who reported hearing loss during a NMOSD relapse were identified through a retrospective case review.RESULTS: In this article, we discuss two AQP4-IgG positive NMOSD cases, each presenting with conductive and sensorineural hearing loss, and a case of MOG-IgG-associated NMOSD presenting with sensorineural hearing loss.CONCLUSION: Hearing loss may be present as a relapse in patients with NMOSD. Early recognition and timely treatment are essential to prevent irreversible hearing loss.

    View details for DOI 10.1016/j.msard.2020.102032

    View details for PubMedID 32155460

  • Emergence of rheumatoid arthritis following exposure to natalizumab. Multiple sclerosis and related disorders Su Data, E. n., Novic, J. n., Han, M. H. 2020; 40: 101936

    Abstract

    We report a patient with relapsing-remitting multiple sclerosis, who developed rheumatoid arthritis after exposure to natalizumab. While some multiple sclerosis therapies are known to unmask autoimmune conditions, natalizumab is rarely implicated as a cause of alternative autoimmunity. This case illustrates an unusual clinical scenario which may support recent scientific work suggesting that, when natalizumab blocks T helper 1 cells from entering the central nervous system, T helper 17 cells may continue to migrate into immune-privileged spaces and cause pathologic inflammation. BRIEF BACKGROUND: Multiple sclerosis (MS) patients often suffer from concurrent autoimmune conditions, and may be at increased risk for developing rheumatoid arthritis (RA) (Langer-Gould et al., 2010; Tseng et al., 2016). While alemtuzumab and rituximab are known to unmask underlying autoimmune disorders, natalizumab is not commonly associated with autoimmunity. Here, we report a patient with relapsing-remitting MS who developed acute autoimmune arthropathy following exposure to natalizumab. CASE REPORT: A 45-year-old woman with autoimmune thyroiditis presented after episodes of left arm and right leg numbness. MRI showed multiple supratentorial and spinal cord demyelinating lesions. Lumbar puncture yielded CSF with a lymphocytic pleocytosis (11 leukocytes, 97% lymphocytes), normal protein, normal glucose, elevated immunoglobulin G index (2.24), and multiple unmatched oligoclonal bands. Her initial autoimmune workup revealed elevated anti-thyroid peroxidase antibody and rheumatoid factor (22 IU/mL, reference value < 14 IU/mL). The remainder of the patient's rheumatologic evaluation was normal, including aquaporin-4 antibody, anti-nuclear antibody, complements 3 and 4, and Sjogren's antibodies. She fulfilled 2017 McDonald Criteria for multiple sclerosis, and was started on dimethyl fumarate. Three months later, she developed left foot numbness and urinary incontinence. MRI spine showed a new lesion at C7, and her therapy was escalated to natalizumab. Immediately after her initial natalizumab infusion, she experienced transient neck and shoulder pain with decreased range of motion. She had no history of arthropathy. After her second natalizumab infusion, she developed persistent shoulder and hip pain. Her arthralgias resolved after a course of oral steroids. Two weeks after her second natalizumab infusion, she was seen by a rheumatologist who noted mild synovitis of both elbows and wrists on exam, but no significant inflammation involving her shoulders, fingers, knees, ankles, or feet. This time, she had significantly elevated anticyclic citrullinated peptide IgG (> 300 U/mL, reference value < 3 U/mL) and rheumatoid factor (71 IU/mL). Based on the number of small joints involved, and her positive serology, she met 2010 American College of Rheumatology Criteria for rheumatoid arthritis. Natalizumab was discontinued, and the patient was started on methotrexate, with which her rheumatoid arthritis has been controlled for the past two years.

    View details for DOI 10.1016/j.msard.2020.101936

    View details for PubMedID 31982664