Vaccination proposal for patients on onasemnogene abeparvovec therapy.

The approval of disease-modifying treatment in spinal muscular atrophy made the condition less severe. The course of the disease changed, but some new concerns occurred with the different new therapies. The side effects of onasemnogene aboparvovec therapy can raise differential diagnostic challenges and necessitate immune therapy, leading to immunosuppression affecting response to vaccines. We provide a pretherapy screening proposal from an infectological point of view separately for newborns treated presymptomatically and children diagnosed with symptoms at any age. Furthermore, we summarise the guidelines on the vaccination before, during, and after immune therapy (steroids) in onasemnogene aboparvovec-treated patients.

[The transition of children with rare diseases from pediatric to adult care]. / A ritka betegségben szenvedo gyermekek átvezetése a felnottellátásba.

Diagnostics for rare diseases have advanced as a result of technological advancement. Innovative treatments have also made it possible for children with rare disorders to survive into adulthood. Growing up is crucial for someone who has a chronic childhood illness since the change from pediatric to adult treatment comes with new difficulties that might feel like an extra burden from the condition. Transition in rare diseases poses more challenges than in common diseases, because not all health care providers in adult care may have the expertise needed to provide optimal patient care. In addition, longer illness courses and the requirement for adult care in diseases for which there is no prior experience will result from the increasing number of better therapies. Occasionally, new clinical symptoms may appear that are unknown to clinicians. Despite the importance they should have, the majority of rare diseases do not currently have standardized recommendations and standards for the transition phase. Every transfer to adult care should be unique and stick to a predetermined plan. A transition coordinator should ideally work with the pediatrician, the adult specialist, the patient, and parents to support patients during this transition. The needs analysis of caregivers is an essential part in the transition process, too. The parties need to be educated, a protocol outlining the process needs to be developed, and the necessary infrastructure must be in place to support an optimal transition. Orv Hetil. 2022; 163(51): 2021-2026.

Role of faith in strategies of healthcare professionals in intensive care units in end-of-life decision making / A vallásosság szerepe az intenzív osztályon dolgozó orvosok és ápolók véleményének kialakításában az életvégi döntések meghozatalakor.

Összefoglaló. Bevezetés: A haldoklást minden korban kulturális és vallási szabályok vették körül, melyek a mai napig hatnak a társadalomban. A 21. században számos beteg a kórházban, az intenzív osztályon fejezi be életét, ahol nem ritkán kerülhet sor életvégi döntés meghozatalára. Célkituzés: Vizsgálatunk célja annak feltárása volt, milyen hatással van az orvosok és ápolók vallásossága a kezeléskorlátozással kapcsolatos döntésekre az intenzív osztályon. Módszer: Magyarországi intenzív osztályokon dolgozó orvosok és szakdolgozók körében végeztünk kérdoíves felmérést a vallás életvégi döntésekre gyakorolt hatásáról. 189 orvos és 105 ápoló által anonim módon kitöltött kérdoívet elemeztünk. Eredmények: Az intenzív osztályra történo betegfelvételre nem volt hatással a vallásosság, azonban a szabad ágyak száma a vallásos orvosokat erosebben befolyásolta, mint az ateista és választ nem adó orvosokat (<0,0001). A vallásukat gyakorló orvosok szignifikánsan jobban figyelembe vették a hozzátartozó kérését, mint az ateisták (p = 0,0002). A vallásos ápolók gyakrabban folytatnák a beteg kezelését a hozzátartozó kérése ellenére is, ha még látnának esélyt a gyógyulásra, mint a nem vallásosak. Következtetés: Vizsgálatunk alátámasztotta, hogy a világnézet befolyásolja az orvosokat és ápolókat az élet végérol hozott döntésekben. A kezeléskorlátozásról hozott döntés összetett, elengedhetetlen megismerni hozzá a beteg és családjának haldoklással kapcsolatos vallási szokásait, mivel jó életvégi döntés a világnézeti szempontok figyelembevétele nélkül nem hozható. Orv Hetil. 2021; 162(51): 2047-2054. INTRODUCTION: Death has always been surrounded by habits in all ages, influenced by cultural and religious differences. Many patients finish their lives at intensive care units where end-of-life decisions are the part of everyday practice in the 21th century. OBJECTIVE: The goal of our study was to assess how the religious beliefs of physicians and nurses affect their decision on therapy restriction. METHOD: We have performed questionnaire-based enquiries among physicians and nurses working at intensive care units on how religion affects end-of-life decisions. We have analyzed the anonymous questionnaires filled out by 189 physicians and 105 nurses. RESULTS: Our results have confirmed the hypothesis that religion affects decision making about therapy restriction. Patients' admissions were not affected by religious beliefs, but the number of available patient beds influenced the religious physicians more than the atheists ones or the non-responders (<0.0001). Actively religious physicians complied significantly better with the relatives than atheists (p = 0.0002). Religious nurses would continue patient treatment even against the will of relatives more often than atheists if they see a chance for recovery. CONCLUSION: The study supports that religion influences physicians and nurses in their end-of-life decisions. Decisions on therapy restriction are complex; it is important to find out religious beliefs and perception of death among patients and families because good end-of-life decision cannot be made disregarding religious considerations. Orv Hetil. 2021; 162(51): 2047-2054.

Ethnicity-related DMD Genotype Landscapes in European and Non-European Countries.

OBJECTIVE: Genetic diagnosis and mutation identification are now compulsory for Duchenne (DMD) and Becker muscular dystrophies (BMD), which are due to dystrophin (DMD) gene mutations, either for disease prevention or personalized therapies. To evaluate the ethnic-related genetic assortments of DMD mutations, which may impact on DMD genetic diagnosis pipelines, we studied 328 patients with DMD and BMD from non-European countries. METHODS: We performed a full DMD mutation detection in 328 patients from 10 Eastern European countries (Poland, Hungary, Lithuania, Romania, Serbia, Croatia, Bosnia, Bulgaria, Ukraine, and Russia) and 2 non-European countries (Cyprus and Algeria). We used both conventional methods (multiplex ligation-dependent probe amplification [MLPA] followed by gene-specific sequencing) and whole-exome sequencing (WES) as a pivotal study ran in 28 patients where DMD mutations were already identified by standard techniques. WES output was also interrogated for DMD gene modifiers. RESULTS: We identified DMD gene mutations in 222 male patients. We identified a remarkable allele heterogeneity among different populations with a mutation landscape often country specific. We also showed that WES is effective for picking up all DMD deletions and small mutations and its adoption could allow a detection rate close to 90% of all occurring mutations. Gene modifiers haplotypes were identified with some ethnic-specific configurations. CONCLUSIONS: Our data provide unreported mutation landscapes in different countries, suggesting that ethnicity may orient genetic diagnosis flowchart, which can be adjusted depending on the mutation type frequency, with impact in drug eligibility.

Efficacy of nusinersen in type 1, 2 and 3 spinal muscular atrophy: Real world data from Hungarian patients.

INTRODUCTION: Spinal muscular atrophy (SMA) is an autosomal recessive disorder caused by a homozygous deletion of the survival motor neuron (SMN) 1 gene. Nusinersen is an antisense oligonucleotide enhancing the production of the SMN protein. It has received approval by the European Medicines Agency (EMA) in 2017, based on the clinical trials demonstrating the effectiveness of nusinersen in several types of SMA. In Hungary, the first patient received nusinersen treatment in April 2018. Our aim is to summarize our experience regarding the efficacy, safety and tolerability of nusinersen in our patients. METHODS: Data were collected retrospectively in all types of SMA patients (type 1-3) starting treatment with nusinersen in Hungary between April 2018 and December 2019. Motor functions were evaluated at baseline, at the fourth and all following injections. RESULTS: By 31st December 2019, nusinersen therapy was initiated in 54 patients at either of the two Hungarian treatment centres. Mean age of the patients at the start of the treatment was 6.3 years (±5,4 range 0.4-17.9). 13 patients are type 1 (mean 0.78 ± 0.27, range 0.4-1.5 yrs), 21 patients are type 2 (mean 4.5 ± 3.3, range 1.3-12 yrs), 23 patients are type 3 (mean 10.9 ± 5.2, range 2.9-17.9 yrs). Fourteen patients had severe scoliosis, four of them underwent spine stabilizing surgery. During the study period 340 injections were administered without any new safety concerns emerging. The data of 38 patients, who had completed the first six treatments, were included in the final statistical analysis. Motor function has improved in most of the children. By the 307th day visit, on average, a 14.9 (±5,1) point improvement was measured on the CHOP INTEND scale in type 1 patients (p = 0.016). All patients with type 1 SMA who performed the motor evaluation (7/10) have improved by more than four (7-21) points. Regarding type 2 patients, a 7.2 (range -2- 17) point increase from baseline (p < 0.001) on the Hammersmith Functional Motor Scale Expanded (HFMSE) and 4.3 (range: 2-9) point increase (p = 0.031) on the Revised Upper Limb Module (RULM) were found. The distance of the 6 min walk test also increased by 33.9 m on average (range -16 - 106), in type 3 patients. CONCLUSION: According to our results nusinersen has the same safety and tolerability profile as in the clinical trials. In a heterogenic patient population of SMA type 1 and 2, nusinersen showed similar efficacy as seen in the pivotal studies. A clinically and statistically significant improvement of motor functions was also detectable in type 3 patients with heterogeneous age distribution.

[10 years, 600 monitoring sessions--our experience with the video EEG monitoring of children]. / Tíz ev, 600 vizsgálat--gyermekek video-EEG- monitorizálásával szerzett tapasztalataink.

INTRODUCTION: The only Hungarian video EEG laboratory where children of ages 0-18 can be continuously monitored for several days was opened 1 June 2001 at Department of Neurology of Bethesda Children's Hospital. OBJECTIVES: Summarizing our 10 years of experience with the video EEG monitoring (VEM) of children and defining the place of VEM in the treatment of childhood epilepsy in Hungary. PATIENTS AND METHODS: We have processed data from 597 monitoring sessions on 541 patients between June 1, 2001 and 31 May, 2011 based on our database and the detailed summaries of the procedures. RESULTS: 509 patients were under the age of 18. The average length of the sessions was 3.1 days. We have observed habitual episodes or episodes in question in 477 (80%) sessions. 241 (40%) sessions were requested with an epilepsy surgery indication, and 74 patients had 84 operations. 356 (60%) were requested with a differential diagnosis indication, and 191 (53%) cases of epilepsy were diagnosed. We most commonly diagnosed symptomatic generalized epilepsy (57 cases). In 165 sessions the episode in question was not diagnosed as epilepsy. Among the paroxysmal episodes we have identified events of psychogenic origin, movement disorders, sleep disorders and behavioral disorders. Only 3% of the differential diagnosis procedures brought no additional clinical information. DISCUSSION: The diagnostic efficiency in our VEM laboratory is in accordance with the data found in the literature. Besides epilepsy surgery VEM is recommended if suspected epileptic episodes occur and interictal epileptiform signs are not present or are not in accordance with the symptoms, if there is no explanation for therapy resistance and if paroxysmal episodes of non-epileptic origin are suspected but they cannot be identified based on the anamnesis. VEM is also helpful in diagnosing subtle seizures. The procedure has numerous additional benefits in patient care and in training the parents and hospital staff.

A detailed semiologic analysis of childhood psychogenic nonepileptic seizures.

PURPOSE: Psychogenic nonepileptic seizure (PNES) is an important differential diagnostic problem in patients with or without epilepsy. There are many studies that have analyzed PNES in adults; currently, however, there is no systematic assessment of purely childhood PNES semiology. Our study based on a large pediatric video-electroencephalography (EEG) monitoring (VEM) cohort, provides a detailed analysis of childhood PNES and assesses the usability of the current classification system described in adults. METHODS: Medical and video-EEG records of 568 consecutive children (younger than 18 years) who underwent video-EEG monitoring (VEM) at our hospital were reviewed. Aura, type of movement, anatomic distribution, synchrony, symmetry, eye movement, responsiveness, vocalization, hyperventilation, vegetative and emotional signs, presence of eyewitness, and duration of the event were recorded among children with the diagnosis of PNES. We also compared our data with those of earlier adult studies. KEY FINDINGS: Seventy-five archived PNES of 27 children (21 girls; age 8-18 years) were reanalyzed. Nine children (33%) had the diagnosis of epilepsy currently or in the past. Mean age at the time of PNES onset was 11.6 (standard deviation 3.2) years. Mean duration of PNES was longer (269 s) compared to seizures of the epileptic group (83 s; p = 0.002). Eyewitnesses (mostly parents) were present in 89% of cases. Eighty percent of PNES had an abrupt start, with 68% also ending abruptly. In only 15% of events were the patients eyes closed at the beginning of the attack. Patients were unresponsive in 34%. The most frequent motor sign was tremor (25%) with the upper, rather than lower limbs more frequently involved. Pelvic thrusting was seen in only two attacks. Emotional-mostly negative-signs were observed during 32 PNES (43%). Based on Seneviratne et al.'s classification, 18 events (24%) were classified as rhythmic motor PNES, only half the frequency of that previously described in adults. No hypermotor PNES was found. The frequency of complex motor PNES (13%) and mixed PNES (4%) showed similar frequency in children as in adults. Dialeptic PNES was found more frequently among younger children. All PNES belonged to the same semiologic type in 23 patients (85%). SIGNIFICANCE: Because homogeneity of PNES within a patient was high in the pediatric population, we found it useful to classify PNES into different semiologic categories. Dialeptic PNES seems to be more frequent among younger children. Tremor is the most frequent motor sign and usually accompanied by preserved responsiveness in childhood. Negative emotion is commonly seen in pediatric PNES, but pelvic thrusting is a rare phenomenon. We, therefore, suggest a modification of the present classification system in which PNES with motor activity is divided into minor and major motor PNES, and the latter group is subdivided into synchron rhythmic motor and asynchron motor PNES. We believe that our study, a detailed analysis on the semiology and classification of purely childhood PNES might assist the early and precise diagnosis of nonepileptic paroxysmal events.

[General anesthesia during double balloon enteroscopy--Hungarian experiences]. / Kettosballon-enteroszkópiás vizsgálatoknál végzett altatások során szerzett hazai tapasztalatok. Beteg-autonómia az anesztéziában.

UNLABELLED: Double balloon enteroscopy needs sufficient sedation technique, because the examination is uncomfortable and lengthy. The most prevalent sedation method is conscious sedation world-wide. AIM: To demonstrate that double balloon enteroscopy examination can also be safely performed in general anesthesia with intubation and that this method can be an option in patients with severe multiple morbidities. METHODS: A retrospective evaluation of intubation narcosis in patients undergoing double balloon enteroscopy was performed at the 1st Department of Internal Medicine, Semmelweis University. Patients were grouped based on gender, age and physical state. Anesthesia records included the duration of anesthesia, the quantities of medications used and anesthesia-related complications. RESULTS: Data obtained from 108 general anesthesia cases were analyzed. There were no permanent anesthesia-related complications in the period examined. The most frequent side effects of anesthesia were hypotension (30.55%), desaturation (21.29%), and apnea (17.59%). These complications were significantly more frequent among patients with multiple morbidities; however, their incidence was not proportional with the quantity of the medications used or the duration of anesthesia. CONCLUSION: The findings confirm that the most important advantage of general anesthesia over other methods is that it ensures stable airways, which makes it easy to counter-act frequent complications such as desaturation, apnea and aspiration. The number of complications of anesthesia was higher among patients with multiple morbidities, but these complications could be easily overcome in all patient groups. Therefore, this method is highly recommended for patients with multiple morbidities. Intubation narcosis can be also a viable option of conscious sedation for patients without co-morbidities.

[Practice of treatment restriction in Hungarian intensive care units]. / A kezeléskorlátozás gyakorlata a hazai intenzív osztályokon.

UNLABELLED: End of life decisions affect most of patients in intensive care units, thus, it is important to know both local and international practice in accordance with law and ethical principles for intensive care physicians. AIM: To search for local customs of end of life decisions (withholding or withdrawing the therapy, shortening of the dying process), and to compare the data with the international literature. METHODS: In 2007-2008 the first Hungarian survey was performed with the purpose to learn more about local practice of end of life decisions. Questionnaires were sent out electronically to 743 registered members of Hungarian Society of Anesthesiology and Intensive Care. Respecting anonymity, 103 replies were statistically evaluated (response rate was 13.8%) and compared with data from other European countries. RESULTS: As expected, it turned out from replies that the practice of domestic intensive care physicians is very paternal and this is promoted by legal regulations that share a similar character. Intensive care physicians generally make their decisions alone (3.75/5 point) without respecting the opinion of the patient (2.57/5 point) the relatives (2.14/5 point) or other medical personnel (2.37/5 point). Furthermore, they prefer not to start a therapy rather than withdraw an ongoing treatment. Nevertheless, the frequency of end of life decisions (3-9% of ICU patients) is smaller than other European countries. CONCLUSIONS: There is a need for the expansion of patients' right in our country. For end of life decisions, self determinations must be supported and a dialogue must be established between lawmakers and physicians, in order to improve the legal support of this medical practice.

Double balloon enteroscopy examinations in general anesthesia.

AIM: To demonstrate that the double balloon enteroscopy (DBE) can be safely performed in general anesthesia with intubation. METHODS: We performed a retrospective examination between August 2005 and November 2008 among patients receiving intubation narcosis due to DBE examination. The patients were grouped based on sex, age and physical status. Anesthesia records included duration of anesthesia, quantity of medication used and anesthesia-related complications. We determined the frequency of complications in the different groups and their relation with the quantity of medication used and the duration of anesthesia. RESULTS: We compiled data for 108 cases of general anesthesia with intubation. We did not observe any permanent anesthesia-related complications; the most frequent side effects of anesthesia were hypotension (30.55%), desaturation (21.29%), and apnea (17.59%). These complications were significantly more frequent among patients with multiple additional diseases [hypotension (23.1% vs 76.9%, P = 0.005), de-saturation (12.3% vs 69.2%, P < 0.001) and apnea (7.7% vs 53.8%, P = 0.001)], however, their incidence was not proportional to the quantity of medication used or the duration of anesthesia. CONCLUSION: General anesthesia with intubation is definitely a viable option among DBE methods. It is highly recommended in patients with multiple additional diseases.

Prevalence of antiphospholipid and antinuclear antibodies in children with epilepsy.

BACKGROUND: Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by recurrent venous thrombosis or arterial occlusive events and fetal losses associated with elevated levels of antiphospholipid antibodies (aPLs). MATERIAL/METHODS: The presence of antinuclear, anti-beta2-glycoprotein I, and anticardiolipin antibodies were investigated in 60 consecutive children with epilepsy who were followed up in a single Hungarian center. RESULTS: Almost 50% (28/60) of the patients were ANA positive. Twelve (20%) patients had moderate titer (1:160) of ANA. Anti-C1q antibody was positive in 4 cases, all of them symptom free considering renal manifestation of lupus. Interestingly, only 1 child had aCL antibody, while 6/43 patients were LAC positive. Five were also ANA positive among the LAC positive patients (4 children with moderate titer). Anti-beta2GPI antibody positivity was not detected in this cohort of patients. CONCLUSIONS: The clinical relevance of aPL tests in childhood are difficult to explain. In the present study, obviously lower total prevalence of aPLs (aCL and anti-beta2GPI) was observed in children with epilepsy than in previously reported investigations (20-30%). The higher amount of LAC-positive patients indicates that coagulation studies (LAC) should be included in the neuroimmunological assessment of suspected APS patients with epileptic disorders. The difference between the results of serological and LAC studies could be explained by the possible positivity of other, uninvestigated antibodies. The wide spectrum of detected immunological alterations highlight the importance of the participation of pediatric rheumatologists in the management of patients with idiopathic epilepsy or with secondary induced autoimmune disease due to antiepileptic medications.

[Adrenocorticotropic hormone therapy in acquired childhood epileptic aphasia]. / Szerzett gyermekkori epilepszias beszédzavar kezelése adrenokortikotrop hormonnal.

Although Landau-Kleffner syndrome, a childhood-acquired epileptic aphasia, is frequently studied either the underlying pathophysiology or the optimal therapy remained unknown. In our study we aimed to investigate the efficacy of ACTH therapy in Landau-Kleffner syndrome. We have analysed retrospectively the documentation of five children treated by ACTH, who suffered from Landau-Kleffner syndrome. We studied the longitudinal changes of the four most characteristic symptoms and signs of the syndrome: epileptiform EEG, speech and behaviour disorders, seizures together with the ACTH regimes. Besides, we analysed the relation between the starting date of the therapy and its efficacy. Before giving ACTH, epileptiform EEG and speech disorders were observed in all the five children, seizures in four of them, behaviour disorders in three of them. In two patients the speech disorder had been persisting for years before. Due to the starting ACTH stoss-therapy (20 E/day for one-two weeks) all the four examined signs disappeared or showed quick softening in all the five children in maximum two weeks. We adjusted long-term low dose maintenance therapy to avoid relapses in the long-term follow-up. Epileptiform EEGs have normalised in one case and have decreased in four cases. Speech disorders have disappeared in two and have softened in three children. Behaviour disorders have cured in 3/4 cases, softened in one case. Seizures have disappeared in all cases. One child is totally asymptomatic, four of them lives with softened symptoms. Analysing our data we found that the earlier the therapy starts, the more effective it is. On the basis of our data ACTH is an effective treatment for Landau-Kleffner syndrome. After giving it for only a short period, relapses often occur, to avoid relapses adjustment of long term low dose maintenance therapy is advisable.

[Ethical and legal problems of informed consent]. / A tájékozott beleegyezés jogi és etikai problémái.

INTRODUCTION: The previously accepted paternalistic relationship between patients and doctors has changed in last century. The expectation for patients to be involved in medical decisions is growing, but this involvement cannot be imagined without informed consent, hence it became one of the most important elements of a physician's responsibilities. Although informed consent is broadly regulated legally in Hungary, experiences show that practical realization is insufficient. This is also represented in the large number of lawsuits in connection with the inadequate or wrong use of informed consent. The aim of this study was to survey for the first time in Hungary the state of informed consent by the analysis of written consents to anaesthesia. METHODS: The authors collected and studied written consents to anesthesia from 36 hospitals and clinics in Budapest. They studied among others the presence of the following formal elements: individual consent forms for anesthesia, signatures on forms etc. They also examined whether the consents contained all of the conventional elements of informed consent. RESULTS: 61% of hospitals had individual forms for consent to anesthesia. Every consent form required a signature by the patient and almost every form (except two) by the doctor as well. 39% of forms describe the medical treatment in detail and only 25% mention its advantages and disadvantages. 28% of them specify definite risks, but only 19% mention their probability. 67% of the documents refer to the possible need to extend intervention. Patients have to declare whether they permit urgent blood transfusion in 25 institutions (69%). In only two hospitals are patients informed of their rights to revoke consent or to resign from being informed of medical treatment. CONCLUSION: Although all institutions have written consent forms that adhere to legal regulations, in terms of their format and matter they leave much to be desired. It is especially conspicuous that possible risks are named in less than a fourth of all forms, thus they have to be mentioned verbally and this obviously is a source of later arguments. The authors believe that all invasive medical procedures require templates for consent forms put together by professional panels. These forms could then be adapted to all specific medical procedures of the hospital in question.

Innovations: Alcohol & drug abuse: Methadone maintenance in Europe and Hungary: degrees of sociocultural resistance.

Opiate substitution treatment, commonly referred to as maintenance treatment, was introduced in the United States and Europe in the 1960s. This column discusses approaches to opioid maintenance treatment in Europe and focuses on the introduction of methadone maintenance treatment in Hungary. Although persons have received methadone maintenance in Hungary since 1987, consensus guidelines were not adopted until 1998 and were not confirmed by the Hungarian parliament until 2000. Hungary encountered initial difficulties in introducing methadone maintenance, and it is hoped that Hungary's joining the European Union in 2004 will help to make opiate substitution treatment more widely available.

[Methadone maintenance: adoption of a new harm reduction approach in Hungary]. / Metadonkezelés: egy ártalomcsökkento módszer meghonosodása Magyarországon.

Methadone with its favourable physiological effects in comparison to heroin has been the most well-known and widely used tool of substitution treatment in heroinism. Research on efficiency has produced evidence of the fact that methadone maintenance as a model method of harm reduction is an efficient treatment of heroin dependent patients if used in the appropriate dose and indication. Due to its addictive effects, there has been some resistance against its worldwide spreading, especially in Central Eastern Europe. Methadone maintenance became a legal medical method in Hungary during the last ten years with approved classified protocol and manual owing to the consistent efforts of addiction-professionals, who were convinced of the treatment's efficacy. The process involved numerous conflicts, police provisions and media scandals. Professional legitimacy of methadone maintenance may hopefully be proved by research on efficiency in the near future.