Autoimuni encefalitis u bolesnika s encefalitisom prouzročenim protutijelima na anti-N-metil-D-aspartat receptore

master's thesis

• Title (english): Autoimmune encephalitis in patients with encephalitis due to anti-N-methyl-D-aspartate receptor antibodies
• Author: Katarina Galiot
• Mentor: Marija Santini (mentor)
• Committee member: Bruno Baršić (predsjednik povjerenstva)
• Committee member: Goran Tešović (član povjerenstva)
• Committee member: Marija Santini (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Infectious Diseases); Zagreb
• Defense date and country: 2017-07-14, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Infectology

Abstract

Novi klinički entitet, anti-NMDA receptor (anti-NMDAR) encefalitis opisan je 2007. godine kao autoimuni paraneoplastični poremećaj povezan s IgG protutijelima usmjerenima na NR1 podjedinicu N-metil-D-aspartat receptora. Riječ je o potencijalno letalnom, ali najčešće reverzibilnom obliku encefalitisa koji dobro odgovara na imunoterapiju. Ova bolest primarno pogađa mlade žene i često je povezana s teratomom jajnika. Epidemiološke studije pokazuju da on predstavlja najčešći oblik autoimunog... More encefalitisa, odmah nakon akutnog diseminiranog encefalomijelitisa (ADEM). U 70% pacijenata bolest počinje prodromalnim stadijem da bi nakon 5-14 dana kliničkom slikom dominirali psihijatrijski simptomi, epileptički napadaji, gubitak pamćenja, snižena razina svijesti te znakovi autonomne nestabilnosti s mogućom potrebom za mehaničkom ventilacijom. Za dijagnozu najznačajniji je pronalazak anti-NMDAR protutijela u cerebrospinalnom likvoru uz limfocitnu pleocitozu. Terapija se sastoji od prve (kortikosteroidi, plazmafereza, intravenski imunoglobulini) i druge linije imunoterapije (ciklofosfamidi, rituksimab) te odstranjenja tumora, ako je potrebno. Kako do sada nisu opisani slučajevi anti-NMDAR encefalitisa u odrasle populacije u Republici Hrvatskoj, cilj ovog rada je po prvi puta prikazati šest pacijentica liječenih na Zavodu za intenzivnu medicinu i neuroinfektologiju u Klinici za infektivne bolesti „Dr. Fran Mihaljević“, kojima je dokazan ovaj oblik autoimunog encefalitisa. Sve pacijentice bile su prethodno hospitalizirane na psihijatrijskom i/ili neurološkom odjelu te je prosječno vrijeme od prvih simptoma bolesti do dijagnoze iznosilo 32 dana. Od psihijatrijskih simptoma isticale su se vidne i/ili slušne halucinacije te agitiranost, dominantan poremećaj spavanja bila je nesanica, a orofacijalna diskinezija bila je najčešći oblik poremećaja pokreta. Kod samo jedne pacijentice pronađen je tumor, teratom desnog jajnika. Sve su pozitivno odgovorile na imunoterapiju te relaps bolesti nije uočen kod niti jedne bolesnice. Uzimajući u obzir da 4-6% pacijenata s izoliranim psihijatrijskim epizodama imaju anti-NMDAR encefalitis, primarna svrha ovog rada je podići svijest među svim kliničarima, osobito psihijatrima, neurolozima i infektolozima, o ovom kliničkom entitetu koji zaslužuje svoje mjesto u diferencijalnoj dijagnozi akutne i kronične psihoze te o važnosti traženja organskog uzroka kod prividno primarne psihijatrijske bolesti. Less

Abstract (english)

In 2007 a new clinical entity was described, anti-NMDA receptor (anti-NMDAR) encephalitis, an autoimmune, paraneoplastic disorder associated with IgG autoantibodies directed against NR1 subunit of the N-methyl-D-aspartate receptor. It is potentially lethal, but most often reversible form of encephalitis which responds to immunotherapy very well. This disease primarily affects young women and is often associated with ovarian teratoma. Epidemiological studies show that it is the most... More common form of autoimmune encephalitis, and it comes immediately after acute disseminated encephalomyelitis (ADEM). In 70% of patients the disease begins with a prodromal stage, and after 5-14 days the clinical picture is dominated by psychiatric symptoms, seizures, memory loss, decreased level of consciousness, and autonomic dysfunction often requiring mechanical ventilation. In order to make a diagnosis, the most important factor is the finding of specific antibodies to NMDA receptors in cerebrospinal fluid, along with lymphocytic pleocytosis. Therapy consists of the first (corticosteroids, therapeutic plasma exchange, intravenous immunoglobulins) and the second line of immunotherapy (cyclophosphamide, rituximab) along with the removal of tumor, if necessary. As no cases of anti-NMDAR encephalitis in the adult population in the Republic of Croatia have been described so far, the purpose of this study was to present six patients treated at the Department of Intensive Medicine and Neuroinfectology at the University Hospital for Infectious Diseases “Dr. Fran Mihaljević”, to whom this form of autoimmune encephalitis was proved. All patients were previously hospitalized at the psychiatric and/or neurological department and the average time which passed from disease onset to the diagnosis amounted to 32 days. The most prominent psychiatric symptoms were visual and/or auditory hallucinations as well as agitation, dominant sleep disorder was insomnia, and orofacial dyskinesia was the most common form of movement disorder. Tumor was found in only one patient, a right ovary teratoma. All patients responded positively to immunotherapy and relapse was not observed. Taking into account that 4-6% of patients with isolated psychiatric episodes have anti-NMDAR encephalitis, the primary purpose of this paper is to raise awareness among all clinicians, especially psychiatrists, neurologists and infectiologists, not only about a new clinical entity which deserves its place in differential diagnosis of acute and chronic psychosis, but also about the importance of seeking the organic cause in the apparently primary psychiatric disease. Less

• Keywords: anti-NMDAR encefalitis; teratom; organska psihoza; autonomna nestabilnost; imunoterapija
• Keywords (english): anti-NMDAR encephalitis; teratoma; organic psychosis; autonomic dysfunction; immunotherapy
• Language: croatian
• URN:NBN: urn:nbn:hr:105:574159
• Study programme: Title: Medicine; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: doktor/doktorica medicine (doktor/doktorica medicine)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2018-03-15 11:12:51