Neuromuscular DiseasesNeuromuscular DiseasesНервно-мышечные болезни2222-87212413-0443Publishing House ABV Press46710.17650/2222-8721-2021-11-4-34-47ORIGINAL REPORTSОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯUnknownTherapeutic apheresis in the complex pathogenetic therapy of anti-NMDA encephalitis associated with ovarian teratoma at a late stage of the diseaseТерапевтический аферез в комплексной патогенетической терапии анти-NMDA-энцефалита, ассоциированного с тератомой яичника на позднем этапе заболеванияhttps://orcid.org/0000-0002-3804-6245BardakovS. N.БардаковС. Н.
Russian Federation

Sergey Nikolaevich Bardakov

6 Akademika Lebedeva St., Saint Petersburg 194044

Сергей Николаевич Бардаков

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epistaxis@mail.ruhttps://orcid.org/0000-0001-5379-2863SkulyabinD. I.СкулябинД. И.
Russian Federation

6 Akademika Lebedeva St., Saint Petersburg 194044

194044 Санкт-Петербург, ул. Академика Лебедева, 6

info@abvpress.ruMoshnikovaA. N.МошниковаА. Н.
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197022, Санкт-Петербург, ул. Льва Толстого, 6–8

info@abvpress.ruhttps://orcid.org/0000-0002-4998-3699LapinS. V.ЛапинС. В.
Russian Federation

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info@abvpress.ruhttps://orcid.org/0000-0001-7004-0903SokolovA. A.СоколовА. А.
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194044 Санкт-Петербург, ул. Академика Лебедева, 6

info@abvpress.ruhttps://orcid.org/0000-0001-6362-6543KondratyevaE. A.КондратьеваЕ. А.
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info@abvpress.ruhttps://orcid.org/0000-0003-4627-4974ManuilovA. S.МануиловА. С.
Russian Federation

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194044 Санкт-Петербург, ул. Академика Лебедева, 6

info@abvpress.ruZakharovM. V.ЗахаровМ. В.
Russian Federation

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Russian Federation

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194044 Санкт-Петербург, ул. Академика Лебедева, 6

info@abvpress.ruTsargushV. A.ЦаргушВ. А.
Russian Federation

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194044 Санкт-Петербург, ул. Академика Лебедева, 6

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Russian Federation

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info@abvpress.ruS.M. Kirov Military Medical Academy, Ministry of Defense of RussiaФГБВОУ ВО «Военно-медицинская академия им. С.М. Кирова» Минобороны РоссииPavlov First Saint Petersburg State Medical UniversityФГБОУ ВО «Первый Санкт-Петербургский государственный медицинский университет им. акад. И.П. Павлова» Минздрава РоссииAlmazov National Medical Research Centre, Ministry of Health of RussiaФГБУ «Национальный медицинский исследовательский центр им. В.А. Алмазова» Минздрава РоссииLLC “INVITRO SPb”ООО «Инвитро-СПб»North-Western State Medical University named after I.I. Mechnikov, Ministry of Health of RussiaФГБОУ ВО «Северо-Западный государственный медицинский университет им. И.И. Мечникова» Минздрава РоссииHuman Stem Cell InstituteИнститут стволовых клеток человека2912202111434472912202129122021Copyright ©; 2021, Bardakov S.N., Skulyabin D.I., Moshnikova A.N., Lapin S.V., Sokolov A.A., Kondratyeva E.A., Bulgakova T.V., Manuilov A.S., Zakharov M.V., Belskikh A.N., Tsargush V.A., Deev R.V.Copyright ©; 2021, Бардаков С.Н., Скулябин Д.И., Мошникова А.Н., Лапин С.В., Соколов А.А., Кондратьева Е.А., Булгакова Т.В., Мануилов А.С., Захаров М.В., Бельских А.Н., Царгуш В.А., Деев Р.В.2021Bardakov S.N., Skulyabin D.I., Moshnikova A.N., Lapin S.V., Sokolov A.A., Kondratyeva E.A., Bulgakova T.V., Manuilov A.S., Zakharov M.V., Belskikh A.N., Tsargush V.A., Deev R.V.Бардаков С.Н., Скулябин Д.И., Мошникова А.Н., Лапин С.В., Соколов А.А., Кондратьева Е.А., Булгакова Т.В., Мануилов А.С., Захаров М.В., Бельских А.Н., Царгуш В.А., Деев Р.В.https://creativecommons.org/licenses/by/4.0https://nmb.abvpress.ru/jour/article/view/467

Anti‑NMDA encephalitis is a rare autoimmune disease of the central nervous system caused by the synthesis of autoantibodies to the NR1/NR2 subunits of the NMDA receptor, characterized by the development of acute mental, cognitive, motor, autonomic disorders, epileptic syndrome and central hypoventilation.The article presents a three‑year observation of patient 34 years old with anti‑NMDA ncephalitis associated with late‑ stage ovarian teratoma, accompanied by an increase titer of antibodies to NMDA receptors in serum to 1:640.Based on a detailed analysis of clinical, neurological, neuropsychological (MMSE, MoСA, FAB, 10 words test A.R. Luria) and laboratory‑instrumental characteristics of the disease (titer anti‑NMDA, level of IgG, IgM, IgA, lymphocyte subpopulations, EEG, MRI of the brain, pelvis) suggested a combination scheme of first and second line therapy. The sequential use of two cycles of medium‑volume membrane plasmapheresis (25–30 % of the circulating plasma volume, No. 5 + 5) was carried out in combination with pulse therapy with methylprednisolone 1.0 (No. 4 + 3) and cyclophasphamide 1.0 (No. 2 + 1) on background of persistent ovarian teratoma. Symptom regression was achieved by the end of the first cycle, and full recovery to the initial level of cognitive functions occurred after the second cycle, while maintaining the anti‑NMDA antibody titer to 1:160. After removal of ovarian teratoma, the level of anti‑NMDA decreased in a month to 1:40, and after 7 months it reached normal values (<1:10) against the background of basic pill therapy with methotrexate 12.5 mg/week.Thus, a rational combination and sequence of first and second line therapy and therapeutic apheresis, taking into account the pathogenetic features of each phase of the disease, can quickly achieve complete stable remission in patient with anti‑NMDA encephalitis.

Анти‑NMDA‑энцефалит является редким аутоиммунным заболеванием центральной нервной системы, обусловленным синтезом аутоантител к NR1/NR2‑субъединицам NMDA‑рецептора и характеризующимся развитием острых психических проявлений, когнитивных, двигательных, вегетативных расстройств, эпилептического синдрома и центральной гиповентиляции.В статье представлено 3‑летнее наблюдение пациентки 34 лет с клиническими проявлениями NMDA‑энцефалита, ассоциированного с тератомой яичника на поздней стадии заболевания, сопровождающегося повышением титра антител к NMDA‑рецепторам в сыворотке крови до 1:640.На основании детального анализа клинико‑неврологических, нейропсихологических (MMSE, МоСА, FAB, тест 10 слов А.Р. Лурия) и лабораторно‑инструментальных характеристик заболевания (титр анти‑NMDA, уровни IgG, IgМ, IgА, субпопуляционный состав лимфоцитов, электроэнцефалография (ЭЭГ), магнитно‑резонансная томография (МРТ) головного мозга, малого таза) применена схема комбинации средств 1‑й и 2‑й линий терапии. Проводилось последовательное применение 2 циклов мембранного среднеобъемного плазмафереза (25–30 % объема циркулирующей плазмы, №5 + 5) в сочетании с пульс‑терапией метилпреднизолоном 1,0 г (№4 + 3) и циклофосфамидом 1,0 г (№2 + 1) на фоне сохраняющейся тератомы яичника. Регресс симптоматики был достигнут к концу 1‑го цикла терапевтического афереза, а полное восстановление до исходного уровня когнитивных функций наступило после 2‑го цикла, при сохранении титра анти‑NMDA‑антител до 1:160. После удаления тератомы яичника уровень анти‑NMDA‑антител снизился за месяц до 1:40, а через 7 мес достиг нормальных значений (<1:10) на фоне базисной терапии метотрексатом в таблетках в дозе 12,5 мг/нед.Таким образом, рациональная комбинация и последовательность средств 1‑й и 2‑й линий терапии и терапевтического афереза с учетом патогенетических особенностей каждой фазы заболевания позволила быстро достичь полной устойчивой ремиссии у пациентки с анти‑NMDA‑энцефалитом на позднем этапе заболевания.

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