Via Research Recognition Day 2024 VCOM-Carolinas

Clinical Case-Based Reports

A Case Report of Neuromyelitis Optica Spectrum Disorder with Emphasis on Acute and Chronic Treatment Madison D. Dudick, OMS-III, Dr. Paul LaPenna, DO. Edward Via College of Osteopathic Medicine, Spartanburg, SC.

Introduction

Figures

Discussion

Neuromyelitis optica spectrum disorder (NMOSD) is a rare idiopathic inflammatory demyelinating disorder which targets the spinal cord and the optic nerve. It was originally classified as a subcategory of multiple sclerosis. In 2004, Lennon and associates evaluated a serum autoantibody marker, NMO-IgG, via indirect immunofluorescence that distinguished NMOSD as an independent disorder.¹ NMOSD now belongs to a category of demyelinating disorders which includes multiple sclerosis and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). These three disorders have similar clinical presentations including vision loss, weakness in the extremities, and loss of sensation. Each disease is differentiated by imaging, laboratory evidence of antibody target, and clinical course.² NMOSD is diagnosed based on two of three clinical criteria, including autoantibodies against aquaporin 4 channels,³ ⁻ ⁵ transverse myelitis over more than three spinal segments, and optic neuritis.⁶ NMOSD is characterized by aggressive relapses with accruing disability. It is paramount to identify and to initiate acute and chronic treatment to prevent relapses. The acute treatment is three-fold. First, steroids are utilized to decrease inflammation.⁷ Second, plasma exchange removes the active antibodies. Lastly, an immunosuppressant is initiated to decrease future relapses.⁸ ⁻ ¹⁰ In 2019, the FDA approved eculizumab, inebilizumab, and satralizumab for long-term treatment.¹¹ Rituximab, a monoclonal antibody to CD20, is a off-label treatment that demonstrated up to 72 weeks without relapses in randomized controlled trials.¹² ⁻ ¹⁴ Context: A 29 year-old black female patient presented to the emergency department with worsening left-sided weakness of her upper and lower extremities. She reported ongoing paresthesias of her hands that began two weeks prior. The paresthesias started in her left hand and spread to the fingertips of her right hand. Over the week, she experienced pins and needles sensations in her left foot. Ambulation became increasingly difficult, as the patient fell several times due to decreased proprioception. The patient had blurry vision and right-sided weakness one year prior. Physical exam demonstrated 4/5 strength in bilateral lower extremities and 3/5 strength in left upper extremity. The patient was unable to ambulate secondary to weakness. She had severe dysmetria with proprioceptive ataxia on cerebellar testing. The pronator drift test showed bilateral abnormalities with the patient drawing her arms into her chest while pronating both hands. Sensation to light touch was decreased on the left side of the body. Babinski sign was positive on the left with 4+ patellar reflex. MRI of brain and cervical spine with and without contrast were ordered. MRI cervical spine illustrated a large segment of demyelination (Figure 1). MRI of brain demonstrated incidental cavernous angiomas but notably, no demyelinating process (Figure 2). This finding prompted lab orders for ANA with reflex, MOGAD, and NMO antibodies. The NMO antibody was positive. Management: Methylprednisolone 1000 mg was initiated for a five day course, coupled with plasma exchange therapy every other day for five sessions. After the acute management, the patient was started on rituximab as a long-term therapy. She received rituximab as two intravenous doses two weeks apart. After fourteen days from initial admission, the patient was approved for and started inpatient rehabilitation for an additional twenty-five days before discharge. Maintenance rituximab doses were scheduled in an outpatient clinic for every six months. Outcome: The patient’s strength, blurry vision, and paresthesias improved over the acute treatment period. She was able to ambulate with a walker upon discharge. Follow-Up: Since discharge from inpatient rehabilitation, the patient has been admitted for another relapse with worsening of ambulation. She will be evaluated by a local neuro-immunologist who specializes in demyelinating disorders. Case Description

References The patient was managed aggressively to increase recovery and to reduce disability from the current and previous attacks. NMOSD is typically treated first with a course of high dose steroids over a period of five to seven days. If refractory, the patient is started on plasma exchange. The patient was initiated on both plasma exchange and methylprednisolone 1000 mg daily for five days. Strength in her proximal muscles and sensation improved. The initial insult was her right leg weakness and blurred vision that had occurred a year prior to her presentation. This event is posited as her first relapse of NMOSD. A retrospective study at a neuro-ophthalmology clinic concluded that treatment with IV methylprednisolone within twenty-one days of symptom onset improves visual outcomes.⁷ Fortunately, the patient’s second episode of optic neuritis improved during the treatment period. The patient had the two intravenous cycles of rituximab while hospitalized. Rituximab haș been associated with reduced annualized relapse rates in AQP4-IgG- seropositive NMOSD.¹⁴ The three new FDA approved therapies offer three different mechanisms of actions. Satralizumab inhibits interleukin 6, inebilizumab reduces CD19 cells, and eculizumab targets the complement system. Neuro-immunologists are hesitant to initiate these medications secondary to their high cost and lack of data in treatment-naive patients.¹¹ The patient’s outcome could have been impacted through earlier detection, diagnosis, and treatment. The patient had presented to multiple specialties, including family medicine, orthopedists, and ophthalmologists. These medical records were not available but could have detailed further information on initial presentation of NMOSD. Conclusion Immediate treatment of NMOSD is vital to decrease morbidity. Further research in the chronic treatment of NMOSD is warranted, particularly in treatment-naive patients. Patients with NMOSD remain on immunosuppressive therapies for an extended time, increasing the risk of infections. Due to insufficient data, it is unclear when cessation of these treatments is indicated. 1. Lennon, V. A., Wingerchuk, D. M., Kryzer, T. J., Pittock, S. J., Lucchinetti, C. F., Fujihara, K., Nakashima, I., & Weinshenker, B. G. (2004). A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. The Lancet, 364(9451), 2106 – 2112. https://doi.org/10.1016/s0140-6736(04)17551-x 2. Sellner, J., Boggild, M., Clanet, M., Hintzen, R. Q., Illes, Z., Montalban, X., Du Pasquier, R. A., Polman, C. H., Sorensen, P. S., & Hemmer, B. (2010). EFNS guidelines on diagnosis and management of neuromyelitis optica. European Journal of Neurology, 17(8), 1019 – 1032. https://doi.org/10.1111/j.1468-1331.2010.03066.x 3. Mader, S., & Brimberg, L. (2019). Aquaporin-4 Water Channel in the Brain and Its Implication for Health and Disease. Cells, 8(2), 90. https://doi.org/10.3390/cells8020090 4. Wei, D. C., & Morrison, E. H. (2023). Histology, Astrocytes. PubMed; StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK545142/# 5. Marignier, R., Nicolle, A., Watrin, C., Touret, M., Cavagna, S., Varrin-Doyer, M., Cavillon, G., Rogemond, V., Confavreux, C., Honnorat, J., & Giraudon, P. (2010). Oligodendrocytes are damaged by neuromyelitis optica immunoglobulin G via astrocyte injury. Brain, 133(9), 2578 – 2591. https://doi.org/10.1093/brain/awq177 6. T, T., K, F., I, N., T, M., I, M., M, N., S, W., Y, S., C, K., J, F., S, S., & Y, I. (2007). Anti-aquaporin-4 antibody is involved in the pathogenesis of NMO: a study on antibody titre. Brain : A Journal of Neurology, 130(Pt 5). https://doi.org/10.1093/brain/awm062 7. Thongmee, W., Padungkiatsagul, T., Jindahra, P., Khongkhatithum, C., Thampratankul, L., & Vanikieti, K. (2020). Prognostic Factors for Visual Outcomes Following the First Episode of NMOSD-Related Optic Neuritis in Affected Eyes. Clinical Ophthalmology, Volume 14, 4271 – 4278. https://doi.org/10.2147/opth.s285443 8. Bonnan, M., Valentino, R., Debeugny, S., Merle, H., Fergé, J.-L., Mehdaoui, H., & Cabre, P. (2018). Short delay to initiate plasma exchange is the strongest predictor of outcome in severe attacks of NMO spectrum disorders. Journal of Neurology, Neurosurgery, and Psychiatry, 89(4), 346 – 351. https://doi.org/10.1136/jnnp-2017-316286 9. Sellner, J., Boggild, M., Clanet, M., Hintzen, R. Q., Illes, Z., Montalban, X., Du Pasquier, R. A., Polman, C. H., Sorensen, P. S., & Hemmer, B. (2010). EFNS guidelines on diagnosis and management of neuromyelitis optica. European Journal of Neurology, 17(8), 1019 – 1032. https://doi.org/10.1111/j.1468-1331.2010.03066.x 10. Ingo Kleiter, Gahlen, A., Nadja Borisow, Fischer, K., Wernecke, K.-D., Wegner, B., Hellwig, K., Pache, F., Ruprecht, K., Joachim Havla, Krumbholz, M., Kümpfel, T., Orhan Aktas, Hartung, H.-P., Marius Ringelstein, Geis, C., Christoph Kleinschnitz, Achim Berthele, Hemmer, B., & Klemens Angstwurm. (2016). Neuromyelitis optica: Evaluation of 871 attacks and 1,153 treatment courses. Annals of Neurology, 79(2), 206 – 216. https://doi.org/10.1002/ana.24554 11. Thon, J. M., Sharkus, R., Thakkar, R., Hunter, K., Siegler, J. E., & Thon, O. R. (2023). Utilization of FDA approved treatments for neuromyelitis optica spectrum disorder in clinical practice: A survey study of academic neuroimmunologists. Multiple Sclerosis and Related Disorders, 80, 105076. https://doi.org/10.1016/j.msard.2023.105076 12. Jade, J. D., Bansi, S., & Singhal, B. (2017). Rituximab in Neuromyelitis Optica Spectrum Disorders: Our Experience. Annals of Indian Academy of Neurology, 20(3), 229 – 232. https://doi.org/10.4103/aian.AIAN_499_16 13. Barreras, P., Vasileiou, E. S., Filippatou, A. G., Fitzgerald, K. C., Levy, M., Pardo, C. A., Newsome, S. D., Mowry, E. M., Calabresi, P. A., & Sotirchos, E. S. (2022). Long-term Effectiveness and Safety of Rituximab in Neuromyelitis Optica Spectrum Disorder and MOG Antibody Disease. Neurology, 10.1212/WNL.0000000000201260. https://doi.org/10.1212/wnl.0000000000201260 14. Koon-Ho, C., & Chi-Yan, L. (2021). Treatment of neuromyelitis optica spectrum disorders, 22(8638), 8638 – 8638. https://doi.org/10.3390/ijms22168638

Figure 1 . MRI Cervical Spine with and without contrast. A long segment of diffuse T2 hyper intense cord signal abnormality extends from the cervicomedullary junction to the level of C7. Multiple areas of patchy enhancement can be seen throughout the cervical cord. Additionally, there is cord expansion with effacement of the cerebrospinal fluid space.

Figure 2 . MRI of brain with and without contrast. No demyelinating process can be identified. Incidental finding of cavernous angiomas within the left temporal and right parietal lobes.

Thank you to Dr. Paul LaPenna for his guidance and advice on this case report. Thank you also to the patient who decided to participate in this case report to increase awareness for the diagnosis and management of her condition.

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2024 Research Recognition Day