Autoimmune encephalopathies in children: clasifi cation, diagnosis and treatment

Autoimune encefalopatije (AE) klinički se manifestiraju znakovima limbičkog ili difuznog encefalitisa, a prema etiologiji se mogu podijeliti u paraneoplastične i neparaneoplastične. Simptomi i znakovi autoimunog encefalitisa su vrlo varijabilni i najčešće uklju- čuju glavobolju, epileptičke napadaje i nerijetko epileptički status, poremećaje kretanja (ataksiju, diskinezije, koreju, distoniju i tremor), poremećaje pamćenja, ponašanja, psihoze te različite stupnjeve poremećaja svijesti. Autonomna disfunkcija, poremećaji spavanja i hipoventilacija često su dio kliničke slike. Razvoj autoimunih encefalopatija mogu osim tumorskih potaknuti i virusni antigeni, no najčešće okidači ostaju neidentifi cirani. Prema lokalizaciji antigena na koje je autoimunosni proces usmjeren, autoimune se encefalopatije dijele u one uzrokovane protutijelima na intracelularne antigene (Ma2, Hu), a koje su češće u odraslih, paraneoplastičke su etiologije i slabo reagiraju na imunoterapiju te na one uzrokovane protutijelima na površinske, odnosno sinaptičke antigene (N-metil-diaspartatni receptor (NMDAR), kompleks naponom reguliranih kalijevih kanala VGKC /LGI1) koje dobro reagiraju na imunoterapiju. Protutijela u autoimunim encefalopatijama dokazuju se u serumu i cerebrospinalnom likvoru. U cerebrospinalnom se likvoru nalazi blaga pleocitoza i/ili oligoklonske vrpce, a nerijetko je nalaz u likvoru normalan. EEG pokazuje difuzne encefalopatske spore disritmičke promjene ili tzv. „ekstremne delta četke“ te žarišne epileptogene promjene, odnosno paroksizmalna izbijanja u limbičkom encefalitisu. MR mozga u bolesnika s NMDAR protutijelima u pravilu je normalan ili pokazuje prolazne subkortikalne T2 hiperintenzitete, no posebno je značajan za dijagnozu limbičkog encefalitisa udruženog s kompleksom protutijela VGKC/LGI1. Rano prepoznavanje AE-a, kao i poznavanje njegove potencijalne etiologije od izuzetnog je značenja zbog poduzimanja cjelovitog dijagnostičkog postupka i pravodobne primjene odgovarajuće terapije.Autoimmune encephalopathies are clinically manifested as limbic or diff use encephalitis. According to the etiology, they are classifi ed as paraneoplastic and non-paraneoplastic. Signs and symptoms of autoimmune encephalitis are variable. The symptomatology commonly includes headache and epileptic attacks often progressing to epileptic status, movement disorders (ataxia, dyskinesias, chorea, dystonia and tremor), behavior changes, cognitive impairments, psychoses and various degrees of disorders of consciousness. Faciobrachial dystonic seizures can precede the development of limbic encephalitis. Autonomic dysfunction, sleep disorders and hypoventilation are often present. The development of autoimmune encephalopathies can be induced by either tumor or viral antigens. However, in a signifi cant number of cases, disease triggers remain unidentifi ed. According to the localization of target antigens, autoimmune encephalopathies can be divided into those caused by antibodies against intracellular antigens (Ma2,Hu) and those caused by antibodies against cell surface antigens, i.e. synaptic antigens (N-methyl-D-aspartate receptor (NMDAR), voltage-gated potassium channel complex/LGI1). The former are paraneoplastic in origin, more often in adults and respond poorly to immunotherapy. The latter ones can aff ect children as well, and are usually-responsive to immunotherapy. Antibodies can be detected in both cerebrospinal fl uid and serum. Mild pleocytosis and/or oligoclonal bands can be found in cerebrospinal fl uid but in some patients the cerebrospinal examination fi ndings can be completely normal. The electroencephalography fi nding consists of diff use, slow dysrhythmic encephalopathic changes or so-called extreme delta brushes and focal epileptogenic changes, i.e. paroxysmal bursts in case of limbic encephalitis. Magnetic resonance image fi nding of the brain is usually normal or presents transient sub/cortical hyperintensities in T2-weighted images but is signifi cant for the diagnosis of limbic encephalitis. Early recognition of autoimmune encephalopathy is of utmost importance because of the need of proper diagnostic procedure and timely introduction of appropriate therapy

Report on the work of the Reference center for pediatric cardiology Ministry of Health of the Republic of Croatia

Cilj je ovog izvješća u proteklom trogodišnjem razdoblju (2019–2022) prikazati: 1) aktivnosti Referentnog centra, 2) postignute stručne rezultate i primjenu novih metoda, postupaka i unaprjeđenje struke, i 3) znanstvenu i stručnu suradnju s inozemnim ustanovama visoke razine. Rezultati: Referentni je centar jedino mjesto u Republici Hrvatskoj koje kontinuirano zbrinjava populaciju najugroženijih i najtežih bolesnika pedijatrijske dobi sa srčanom patologijom. Ima kontinuirano, 24 sata dostupnu kardiološku, kardiokiruršku, anesteziološku, neonatalnu i intenzivnu skrb za djecu sa složenim prirođenim i stečenim srčanim bolestima. Također su dostupne metode nadomještanja funkcije organa u zatajivanju (ECMO potpora, LVAD-BiVAD, Berlin-Heart pumpa, hemodijaliza, program transplantacije srca / drugih organa), a sve zahvaljujući timskom radu i suradnji tima nekoliko Zavoda. Izvode se složene kardiokirurške operacije u djece s prirođenim srčanim greškama uz jasan trend povećanja broja i složenosti operacija, te uz i dalje prihvatljivo nisku smrtnost. Danas smo u mogućnosti samostalno liječiti gotovo sve srčane bolesti u djece. Godišnje se izvede oko 200 kateterizacija srca u djece. Više od 40% čine intervencijske procedure, a više od 50% tih intervencija izvodi se u dojenačkom periodu. Tijekom protekle tri godine uvedeno je pet novih perkutanih intervencijskih metoda: liječenje nativne koarktacije i rekoarktacije umetanjem stenta, liječenje stenoze pulmonalnih grana umetanjem stenta, perkutano umetanje valvule na pulmonalnu poziciju, dilatacija postojećeg stenta te zatvaranje aortopulmonalnih kolaterala u djece s univentrikulskim srcem. Navedeni iskoraci učinjeni su kontinuiranim zalaganjem članova tima uz potporu i mentorstvo, odnosno kontinuiranu suradnju s inozemnim stručnjacima iz triju inozemnih ustanova (DeutschesHerzZentrum Muenchen, KinderherzZentrum Linz, Kids Heart Center Budapest). Zaključak: Naš centar stoji uz bok rijetkih centara u Europi koji su u mogućnosti izvesti navedene procedure. Navedene su aktivnosti rezultirale unaprjeđenjem kvalitete skrbi na razini RH i temelj su za daljnji planirani rast i razvoj struke u okvirima naše zemlje.The aim of this report is to show in the past three-year period (2019–2022): 1)activities of the Reference Center, 2)achieved professional results and the application of new methods, procedures, and improvement of the profession, and 3)scientific and professional cooperation with high-level foreign institutions. Results: The reference center is the only place in the Republic of Croatia that continuously cares for the population of the most vulnerable children with cardiac pathology. It has continuous, 24-hour cardiology, cardiac surgery, anesthesiology, neonatal and intensive care for children with complex congenital and acquired heart diseases. Organ function replacement are also available (ECMO support, LVAD-BiVAD, Berlin-Heart pump, hemodialysis, heart/other organ transplant program) thanks to the teamwork and cooperation of different Departments. Complex cardiac surgeries are performed in children with a clear trend of increasing the number and complexity of surgeries, with low mortality. Today, we can independently treat almost all congenital heart defects in children. About 200 cardiac catheterizations are performed in children annually. More than 40% are interventional procedures with more than 50% of these interventions performed in infancy. In the past three years, five new percutaneous intervention methods have been introduced: stent insertion in native coarctation and in recoarctation, stent insertion in stenosis of the pulmonary branches, percutaneous valve insertion in the pulmonary position, dilatation of the existing stent, and closure of aortopulmonary collaterals in children with a univentricular heart. The steps were made by the continuous efforts of team members with support, mentoring, and continuous cooperation with foreign experts from three foreign institutions (DeutschesHerzZentrum Muenchen, KinderherzZentrum Linz, KidsHeart- Center Budapest). Conclusion: Our center stands alongside the rare centers in Europe that can perform the abovementioned procedures. The activities resulted in the improvement of the quality of care and form the basis for further development of the profession within the framework of our country

Report on the work of the Reference center for pediatric cardiology Ministry of Health of the Republic of Croatia

Cilj je ovog izvješća u proteklom trogodišnjem razdoblju (2019–2022) prikazati: 1) aktivnosti Referentnog centra, 2) postignute stručne rezultate i primjenu novih metoda, postupaka i unaprjeđenje struke, i 3) znanstvenu i stručnu suradnju s inozemnim ustanovama visoke razine. Rezultati: Referentni je centar jedino mjesto u Republici Hrvatskoj koje kontinuirano zbrinjava populaciju najugroženijih i najtežih bolesnika pedijatrijske dobi sa srčanom patologijom. Ima kontinuirano, 24 sata dostupnu kardiološku, kardiokiruršku, anesteziološku, neonatalnu i intenzivnu skrb za djecu sa složenim prirođenim i stečenim srčanim bolestima. Također su dostupne metode nadomještanja funkcije organa u zatajivanju (ECMO potpora, LVAD-BiVAD, Berlin-Heart pumpa, hemodijaliza, program transplantacije srca / drugih organa), a sve zahvaljujući timskom radu i suradnji tima nekoliko Zavoda. Izvode se složene kardiokirurške operacije u djece s prirođenim srčanim greškama uz jasan trend povećanja broja i složenosti operacija, te uz i dalje prihvatljivo nisku smrtnost. Danas smo u mogućnosti samostalno liječiti gotovo sve srčane bolesti u djece. Godišnje se izvede oko 200 kateterizacija srca u djece. Više od 40% čine intervencijske procedure, a više od 50% tih intervencija izvodi se u dojenačkom periodu. Tijekom protekle tri godine uvedeno je pet novih perkutanih intervencijskih metoda: liječenje nativne koarktacije i rekoarktacije umetanjem stenta, liječenje stenoze pulmonalnih grana umetanjem stenta, perkutano umetanje valvule na pulmonalnu poziciju, dilatacija postojećeg stenta te zatvaranje aortopulmonalnih kolaterala u djece s univentrikulskim srcem. Navedeni iskoraci učinjeni su kontinuiranim zalaganjem članova tima uz potporu i mentorstvo, odnosno kontinuiranu suradnju s inozemnim stručnjacima iz triju inozemnih ustanova (DeutschesHerzZentrum Muenchen, KinderherzZentrum Linz, Kids Heart Center Budapest). Zaključak: Naš centar stoji uz bok rijetkih centara u Europi koji su u mogućnosti izvesti navedene procedure. Navedene su aktivnosti rezultirale unaprjeđenjem kvalitete skrbi na razini RH i temelj su za daljnji planirani rast i razvoj struke u okvirima naše zemlje.The aim of this report is to show in the past three-year period (2019–2022): 1)activities of the Reference Center, 2)achieved professional results and the application of new methods, procedures, and improvement of the profession, and 3)scientific and professional cooperation with high-level foreign institutions. Results: The reference center is the only place in the Republic of Croatia that continuously cares for the population of the most vulnerable children with cardiac pathology. It has continuous, 24-hour cardiology, cardiac surgery, anesthesiology, neonatal and intensive care for children with complex congenital and acquired heart diseases. Organ function replacement are also available (ECMO support, LVAD-BiVAD, Berlin-Heart pump, hemodialysis, heart/other organ transplant program) thanks to the teamwork and cooperation of different Departments. Complex cardiac surgeries are performed in children with a clear trend of increasing the number and complexity of surgeries, with low mortality. Today, we can independently treat almost all congenital heart defects in children. About 200 cardiac catheterizations are performed in children annually. More than 40% are interventional procedures with more than 50% of these interventions performed in infancy. In the past three years, five new percutaneous intervention methods have been introduced: stent insertion in native coarctation and in recoarctation, stent insertion in stenosis of the pulmonary branches, percutaneous valve insertion in the pulmonary position, dilatation of the existing stent, and closure of aortopulmonary collaterals in children with a univentricular heart. The steps were made by the continuous efforts of team members with support, mentoring, and continuous cooperation with foreign experts from three foreign institutions (DeutschesHerzZentrum Muenchen, KinderherzZentrum Linz, KidsHeart- Center Budapest). Conclusion: Our center stands alongside the rare centers in Europe that can perform the abovementioned procedures. The activities resulted in the improvement of the quality of care and form the basis for further development of the profession within the framework of our country