neurojourНеврологический журнал имени Л.О. БадалянаL.O. Badalyan Neurological Journal2686-89972712-794XФГАУ «НМИЦ здоровья детей» Минздрава России10.46563/2686-8997-2023-4-2-74-83coexmfneurojour-97Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESЕстественное течение нейронопатической формы мукополисахаридоза II типа (синдрома Хантера) у детей: наблюдательное когортное исследованиеNatural history of neuronopathic form of Hunter syndrome in children: observational cohort studyhttps://orcid.org/0000-0002-6545-4121ОсиповаЛилия АлександровнаOsipovaLiliya A.

Невролог консультативного отделения консультативно-диагностического центра ФГАУ «НМИЦ здоровья детей», 119991, Москва.

e-mail: liliya-o@yandex.ru

Neurologist of consultative department of Consultative and Diagnostic center, National Medical Research Center of Children’s Health, Moscow, 119991, Russian Federation.

e-mail: liliya-o@yandex.ru

liliya-o@yandex.ruhttps://orcid.org/0000-0002-9562-3774КузенковаЛюдмила М.KuzenkovaLudmila M.noemail@neicon.ruhttps://orcid.org/0000-0001-6415-156XПодклетноваТатьяна В.PodkletnovaTatyana V.noemail@neicon.ruФГАУ «Национальный медицинский исследовательский центр здоровья детей» Минздрава РоссииРоссияNational Medical Research Center of Children’s HealthRussian FederationФГАУ «Национальный медицинский исследовательский центр здоровья детей» Минздрава России; ФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава России (Сеченовский Университет)РоссияNational Medical Research Center of Children’s Health; I.M. Sechenov First Moscow State Medical UniversityRussian Federation202329082023427483Copyright © Осипова Л.А., Кузенкова Л.М., Подклетнова Т.В., 20232023Осипова Л.А., Кузенкова Л.М., Подклетнова Т.В.Osipova L.A., Kuzenkova L.M., Podkletnova T.V.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.neuro-journal.ru/jour/article/view/97Введение

Введение. Мукополисахаридоз II типа (МПС II; синдром Хантера) — прогрессирующее мультисистемное заболевание. Для тяжёлой (нейронопатической) формы МПС II характерно нейродегенеративное течение болезни. Патогенетическая терапия тяжёлой формы заболевания находится в стадии разработки, а посиндромная неврологическая помощь требует усовершенствования. Для рационализации симптоматической помощи пациентам и оценки эффективности новых методов терапии необходимы данные о естественном течении МПС II.

Цель исследования — описать клиническое течение нейродегенеративного процесса у детей с нейронопатической формой МПС II.

Материалы и методы

Материалы и методы. В исследование включены 58 мальчиков с подтверждённым диагнозом МПС II, у 42 пациентов установлена нейронопатическая форма болезни. Изучены анамнез, жалобы, данные неврологических осмотров, описанные в ранее оформленной медицинской документации и полученные на этапе настоящего исследования, описания видео-ЭЭГ-мониторингов, выполненных в ФГАУ «НМИЦ здоровья детей» Минздрава России.

Результаты

Результаты. Описаны спектр и хронология возникновения неврологических симптомов у детей с тяжёлой формой МПС II. Установлено, что навык использования фразовой речи на том или ином этапе развития приобретают 64% пациентов. Пароксизмы насильственного смеха и плача у детей с нейронопатической формой МПС II следует считать проявлением псевдобульбарного аффекта. Показано, что тяжесть нарушений сна у больных нарастает с возрастом. В течение 2 лет после появления эпиактивности на ЭЭГ у пациентов с тяжёлой формой МПС II отсутствие приступов регистрируется значимо чаще, чем дебют эпилепсии (75% по сравнению с 25%; p = 0,046).

Заключение

Заключение. Полученные описания естественного течения тяжёлой формы МПС II могут быть использованы для оптимизации неврологической помощи больным и оценки эффективности новых методов лечения в реальной клинической практике.

Участие авторов

Участие авторов:Осипова Л.А. — концепция; сбор жалоб, анамнеза; неврологический осмотр; обработка и анализ полученных данных; написание текста; редактирован ие текста;Кузенкова Л.М. — концепция; редактирование текста;Подклетнова Т.В. — концепция; сбор жалоб, анамнеза; неврологический осмотр; редактирование текста.Все соавторы — утверждение окончательного варианта статьи, ответственность за целостность всех частей статьи и за информацию об авторах.

Финансирование

Финансирование. Исследование не имело спонсорской поддержки.

Конфликт интересов

Конфликт интересов. Все авторы участвовали в образовательных обучающих мероприятиях при поддержке ООО «Такеда Фармасьютикалс».

Поступила 04

Поступила 04.05.2023Принята к печати 23.05.2023Опубликована 30.06.2023

Introduction

Introduction. Mucopolysaccharidosis type II (MPS II, Hunter syndrome)  (mucopolysaccharidosis type II, MPS II) is a progressive multisystem disorder. Neurodegenerative course characterizes the severe (neuronopathic) form of MPS II. Pathogenetic therapy for the severe form of the disease is under development, and symptomatic neurological treatment is to be improved. Natural history data are required for rationalization of symptomatic care and assessment of emergent treatment effectiveness.

The aim of the study

The aim of the study. To describe the course of neurodegenerative disease in children with neuronopathic form of MPS II.

Materials and methods

Materials and methods. Fifty eight boys with established diagnosis of MPS II were included in the study. The course of  the disease  in 42 patients was classified as neuronopathic. Data on complaints, anamnesis and neurological examination obtained from medical documentation and within the framework of this study, as well as descriptions of video-EEG monitorings, performed in  National Medical Research Center of Children’s Health, were used.

Results

Results. The spectrum and chronology of neurological symptoms in children with severe Hunter syndrome were described. 64% of patients were found to achieve the level of phrasal speech at any time of the development. Laughter or crying paroxysms in children with neuronopathiс MPS II were judged to be a manifestation of pseudobulbar affect. Burden of sleep disorder was demonstrated to increase through the course of the disease. Absence of epileptic seizure was significantly more frequent than epilepsy manifestation during the first two years after epiactivity appears on EEG (75 vs 25%; p = 0.046).

Conclusion

Conclusion. Obtained natural history descriptions of severe MPS II cases are intended to be used in optimization of neurological care for patients and in assessment of emergent treatments’ effectiveness in real clinical practice.

Contribution

Contribution: Osipova L.A. — concept; complaints and anamnesis data collection; neurological examination; data processing and analysis; text writing; text editing;Kuzenkova L.M. — concept; text editing; Podkletnova T.V. — concept; complaints and anamnesis data collection; text editing.All co-authors — are responsible for the integrity of all parts of the manuscript and approval of its final version.

Acknowledgements

Acknowledgements. The study had no sponsorship.

Conflict of interest

Conflict of interest. The authors declare participation in educational activities with the support of Takeda Pharmaceutical Company.

Received

Received: May 4, 2023Accepted:  May 23, 2023Published: June 30, 2023

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The authors declare that there are no conflicts of interest present.