Neurološke manifestacije i osobitosti spavanja u osteogenesis imperfecta

Osteogenesis imperfecta (OI) is a rare genetic disorder leading to skeletal fragility, fractures and deformities. The main pathophysiologic eff ect of OI is reduction in either the quality or the quantity of type I collagen, aff ecting the structures that normally contain type I collagen. COL1A1 and COL1A2 genes account for 80% of cases. Our aim was to review relevant information on the neurodevelopment, sleep issues and neurologic complications in OI. The nervous system is involved in OI because of softening of bone at the base of the skull, resulting in upwards migration of the upper cervical spine and odontoid process. The disease may directly involve neurovascular structures, leading to cavernous fi stulas, dissections, or aneurysms. The brain parenchyma can be aff ected in OI, with manifestations such as cerebral atrophy, hydrocephalus and cerebellar hypoplasia. Basilar impression/invagination are serious craniocervical junction abnormalities that can be life threatening. There is still no knowledge about sleep phenotype in OI. Neurologic manifestations and sleep disorders are valuable prognostic factors and are highly important features within the phenotypic complexity of OI. The measures of prevention in OI stress the need of regular monitoring of these issues from an early age and education of both OI patients and their families.Osteogenesis imperfecta (OI) je rijedak genetički poremećaj koji dovodi do krhkosti kostiju, prijeloma i deformiteta. Glavni patofi ziološki učinak OI je smanjenje u kvaliteti ili kvantiteti kolagena tip I te su stoga zahvaćene strukture koje normalno sadrže kolagen tip I. U 80% slučajeva postoje promjene u genima COL1A1 i COL1A2. Naš cilj je bio pretražiti relevantne podatke o neurorazvoju, spavanju i neurološkim komplikacijama u OI. Živčani sustav je zahvaćen u OI zbog omekšavanja kosti na bazi lubanje, što rezultira migracijom gornjeg dijela cervikalne kralježnice i odontoidnog procesusa. Bolest može izravno zahvatiti neurovaskularne strukture pa nastaju kavernozne fi stule, disekcije ili aneurizme. Moždani parenhim je zahvaćen u OI, s kliničkim entitetima kao što su cerebralna atrofi ja, komunicirajući hidrocefalus i cerebelarna hipoplazija. Bazilarna impresija/invaginacija su ozbiljne abnormalnosti kraniocervikalne veze i mogu biti životno ugrožavajuće. Zasad postoji vrlo malo saznanja o obrascima spavanja u OI. Neurološke komplikacije i poremećaji spavanja su korisni prognostički čimbenici i izrazito važne manifestacije unutar složenog fenotipa u OI. Mjere prevencije u OI ukazuju na potrebu redovitog praćenja ove problematike od rane dobi i edukacije bolesnika s OI i njihovih obitelji

Evaluacija utjecaja fizioterapije na kvalitetu života i samopoimanje zdravlja osoba oboljelih od neurofibromatoze tipa 1

Uvod: Neurofibromatoza tip 1 (NF1) je autosomno dominantna genetska bolest koja je uzrokovana promjenom NF1 gena na 17. kromosomu. Bolest se javlja podjednako u oba spola. Jednako tako, može biti naslijeđena od jednog od roditelja ili se može pojaviti prvi put u obitelji kao novonastala promjena NF1 gena. Cilj: Cilj rada je utvrditi postoji li razlika u kvaliteti života između skupine ispitanika oboljelih od NF-a 1 kod kojih je primijenjena fizioterapija i ispitanika s NF-om 1 kod kojih nije primijenjena fizioterapija. Materijali i metode: Uzorak je obuhvaćao N=44 ispitanika. U istraživanju je korišten upitnik za procjenu zdravstvene kvalitete života SF-36 (engl Short form health survey-36) i vizualno analogna skala boli. Rezultati: U domenama upitnika za procjenu zdravstvene kvalitete života prosjek zadovoljstva ispitanika u obje skupine najveći je u domeni fizičkog funkcioniranja (skupina A: M=56,15, skupina B: M=81,45). Prisutna je statistički značajna razlika u stupnju boli između skupina (p<0,01). Zaključak: Rezultati provedenog istraživanja pokazali su dobru kvalitetu života u obje skupine ispitanika. Viša percepcija boli u NF1 skupini A upućuje na potrebu za daljnjim korištenjem fizioterapije, ali i prepoznavanjem emocionalnih poteškoća i depresivnosti kao mogućeg uzroka boli

Parasomnias: differential diagnostic aproach and importance of polysomnography

Parasomnija je poremećaj spavanja s visokom prevalencijom u općoj populaciji. Bez obzira na to što je parasomnija većinom benigne naravi, najčešće predstavlja vrlo neugodan i nepoželjan fenomen u spavanju u djece i odraslih, snižava kvalitetu života, a može biti krivo protumačena i liječena kao epilepsija. Diferencijalna dijagnostika je posebice izazovna u osoba s napadajima s predominantnim kompleksnim motoričkim ponašanjem koji nastaju tijekom hipermotorne epilepsije s noćnim napadajima, kada može dovesti do nepotrebnih i skupih pretraga te neuspješnog liječenja. Koegzistencija parasomnije i epilepsije u istoj obitelji i/ili u iste osobe upućuje na zajedničke neurofiziološke temelje. U ovom preglednom radu opisane su kliničke i neurofiziološke osobitosti najčešćih parasomnija, genetske osnove te pouzdani elementi u diferencijalnoj dijagnostici parasomnija i noćnih epileptičkih napadaja. Prikazana je dijagnostička vrijednost anamnestičkih podataka, video EEG polisomnografije i dijagnostičkih skala. U djece s epilepsijom i parasomnijama, pogotovo u djece koja imaju noćne napadaje, ne smije se zanemariti postojanje dnevne pospanosti i poteškoća spavanja. Svaku osobu s epilepsijom i s dnevnom pospanošću ili sumnjom i na neepileptogene noćne događaje treba poslati na cjelonoćnu polisomnografiju. Liječenje komorbiditeta koji pogoršavanju spavanje u osoba s epilepsijom i kronofarmakologija epilepsije osiguravaju bolji uspjeh liječenja epilepsije. Pravovremeno prepoznavanje postojanja parasomnije omogućava pravilnu procjenu njezinoga zdravstvenog značenja za osobu i utjecaja na kvalitetu života. Uvođenje medicine spavanja u kurikulume diplomskog i poslijediplomskog obrazovanja omogućava adekvatno obrazovanje zdravstvenih radnika i stjecanje potrebnih vještina za rad u specijaliziranim laboratorijima i odjelima za poremećaje spavanja.Parasomnias are sleep disorders with a high prevalence in the general population. Regardless of the fact that parasomnia is mostly benign in nature, it often represents a very unpleasant and undesirable phenomena during sleep in children and adults, lowering the quality of life, and can be misinterpreted and treated as epilepsy. Differential diagnosis is especially challenging in people with seizures with dominant complex motor behavior that occur during hypermotor epilepsy with nocturnal seizures when it can lead to unnecessary and expensive examinations and unsuccessful treatment. The coexistence of parasomnia and epilepsy in the same family and/or in the same person points to the common neurophysiological foundation. This review paper describes the clinical and neurophysiological features of the most common parasomnias, their genetic basis, and reliable elements in the differential diagnosis of parasomnias and nocturnal epileptic seizures. The diagnostic value of anamnestic data, video EEG polysomnography and diagnostic scales is presented. In children with epilepsy and parasomnias, especially in children who have nocturnal seizures, daytime sleepiness and difficulty sleeping should not be ignored. Any person with epilepsy and with daytime sleepiness or suspicion of non-epileptogenic nocturnal events should be sent for overnight polysomnography. Treatment of comorbidities that worsen sleep in people with epilepsy and chronopharmacology of epilepsy ensure better success in the treatment of epilepsy. Timely recognition of the existence of parasomnia allows a proper assessment of its health significance and its impact on the quality of life. The introduction of sleep medicine into the curricula of the graduate and postgraduate education enables adequate education of health workers and the acquisition of the necessary skills for working in specialized laboratories and units for sleep disorders

Kardiorespiracijske komplikacije u bolesnika s osteogenesis imperfecta

Osteogenesis imperfecta (OI) is a hereditary connective tissue disorder, usually caused by dominant mutations of genes coding for collagen type I alpha chains, COL1A1/A2. Although skeletal manifestations of OI are most readily observable, cardiopulmonary disorders in patients with OI are increasingly recognized as life-threatening but treatable disorders. Unfortunately, the majority of patients with moderate to severe types of OI die from or with cardiopulmonary complications. The lungs and the heart are often unrecognizable and neglected organs in patients with OI. In monitoring of patients with OI, attention is mostly focused on monitoring long bone and spine deformities, and indirectly deformities of the chest wall, which have consequences on the development of lung and the airway diseases. Lung disorder is frequently ignored until breathing problems become severe. An important component in patients with OI is obstructive lung disease, sleep disordered breathing, as well as acute and chronic infection often connected with resultant bronchiectasis. In addition to respiratory complications, some patients with OI have serious cardiovascular problems, including severe mitral valve prolapse, aortic valve insuffi ciency and dilation of the aorta, which require cardiac surgery. The diagnosis and management of the lung and cardiovascular complications in some patients with OI are quite diffi cult. In all patients with OI, it is important to recognize and monitor respiratory and cardiovascular manifestations in order to prevent further progression of any complications.Osteogenesis imperfecta (OI) je nasljedna bolest vezivnog tkiva koja je najčešće uzrokovana dominantnim mutacijama gena koji kodiraju alfa lance kolagena tip I, COL1A1/A2. Iako se su skeletne manifestacije najuočljivije, srčanoplućne bolesti u bolesnika s OI sve se više prepoznaju kao za život opasne bolesti koje se mogu liječiti. Nažalost, većina bolesnika s umjerenim do teškim tipovima OI umire zbog srčanoplućnih komplikacija ili s njima. Pluća i srce često ostaju neprepoznati i zanemareni organi u bolesnika s OI. U praćenju bolesnika s OI pozornost je uglavnom usredotočena na praćenje deformiteta dugih kostiju i kralježnice te neizravno na deformitete stijenke prsnog koša koji utječu na razvoj plućnih bolesti i bolesti dišnih putova. Plućni poremećaj često se zanemaruje sve dok problemi s disanjem ne postanu doista teški. U bolesnika s OI važna sastavnica je opstruktivna bolest pluća, poremećaj disanja u snu te akutna i kronična infekcija koja je često povezana s nastankom bronhiektazija. Uz dišne komplikacije neki bolesnici s OI imaju ozbiljne srčanožilne probleme uključujući težak prolaps mitralnog zaliska, insufi cijenciju aortnog zaliska i dilataciju aorte, što zahtijeva operaciju srca. Dijagnostika i zbrinjavanje plućnih i srčanožilnih komplikacija prilično je teško u nekih bolesnika s OI. Kod svih bolesnika s OI važno je prepoznati i pratiti dišne i srčanožilne manifestacije kako bi se spriječilo daljnje napredovanje komplikacija

ANTENATAL DETECTION OF CHROMOSOMAL ABNORMALITIES COMBINING QF-PCR AND CYTOGENETIC ANALYSIS

Aim: To compare the diagnostic values and limitations of quantitative fluorescent polymerase chain reaction (QF-PCR) and conventional cytogenetic analysis in prenatal diagnosis of chromosomal abnormalities. Methods: A prospective study included simultaneous QF-PCR and cytogenetic analysis of 133 prenatal samples routinely obtained by amniocentesis or chorionic villus sampling (CVS). Additionally, QF-PCR analysis was performed on 14 tissue samples collected after termination of pregnancy (TOP) for which karyotyping could not be performed due to culture failure. Results: Among 133 analyzed prenatal samples, chromosomal abnormalities were diagnosed in 12 cases (9%), including 10 cases of numerical chromosomal aberrations and two cases with unbalanced structural rearrangements. Nine out of 12 chromosomal abnormalities were also detected with QF-PCR. However, all cases of major aneuploidies were successfully disclosed with QF-PCR, resulting in 100% detection rate for chromosomes 21, 18, 13, X and Y. Using a set of markers specific for chromosomes 21, 18 and 13, QF-PCR analysis of tissues collected after TOP revealed chromosomopathy in 21.4% of cases (two cases of trisomy 18 and one triploidy). A comparison of STR markers confirmed monozygosity in two monochorionic/diamniotic twin pregnancies. Conclusion: QF-PCR has been shown as a rapid and reliable method for prenatal diagnosis of the most common chromosomal aneuploidies, and as an adequate alternative to conventional karyotyping in cases where cytogenetic analysis is not possible due to failure of culturing process. However, conventional cytogenetics still presents a gold standard for the detection of structural aberrations and rare aneuploidies

Sources of variability in expiratory flow profiles during sleep in healthy young children

Standard lung function tests are not feasible in young children, but recent studies show that the variability of expiratory tidal breathing flow-volume (TBFV) curves during sleep is a potential indirect marker of lower airway obstruction. However, the neurophysiological sources of the TBFV variability in normal subjects has not been established. We investigated sleep stages and body position changes as potential sources for the TBFV curve variability. Simultaneous impedance pneumography (IP), polysomnography (PSG) and video recordings were done in 20 children aged 1.4-6.9 years without significant respiratory disorders during sleep. The early part of expiratory TBFV curves are less variable between cycles of REM than NREM sleep. However, within individual sleep cycles, TBFV curves during N3 are the least variable. The differences in TBFV curve shapes between sleep stages are the main source of overnight variability in TBFV curves and the changes in body position have a lesser impact.Peer reviewe

Guidelines of the Croatian Child Neurology Society for Pharmacotherapy of Epilepsy in Children and Adolescents

Primjena antiepileptičkih lijekova pri liječenju epilepsije u djece i adolescenata, a osobito donošenje odluke o započinjanju farmakoterapije mogu biti zahtjevni i složeni s obzirom na različite farmakoterapijske mogućnosti. Antiepileptičke lijekove treba propisivati prema generičkom nazivlju pojedinog lijeka, a ne prema farmaceutskom odnosno tvornički zaštićenom imenu. Liječenje epilepsije treba započeti lijekom prvog izbora: izvornim (originalnim) lijekom ili generičkim. U smjernicama za farmakoterapiju epilepsija u djece prikazani su opća načela farmakološkog liječenja epilepsije i mogućnosti donošenja odluka o farmakološkom liječenju epilepsija i epileptičkih sindroma u Republici Hrvatskoj. U radu je dan i kratak osvrt na najčešće upotrebljavane i najvažnije antiepileptičke lijekove, njihove neželjene učinke i interakcije. Navedeni su i noviji antiepileptički lijekovi koji još nisu na osnovnoj ili dopunskoj listi lijekova u RH, no primjenjuju se pri liječenju epilepsija u djece i učinkoviti su. Lijekovi prvog izbora za napadaje sa žarišnim početkom i žarišne epilepsije jesu okskarbazepin (razina dokaza: klasa 1A (AAN) i GRADE 1B) i karbamazepin (razina dokaza: klasa 1A (AAN) i GRADE 1B). Antiepileptički lijek prvog izbora za epileptičke napadaje s generaliziranim početkom i generalizirane epilepsije, ponajprije u dječaka, jest valproat (razina dokaza: klasa 1A (AAN) i GRADE 1A). Zbog mogućega teratogenog i nepovoljnog učinka na postnatalni razvoj djece izložene in utero valproatima i lijekovima generički srodnima valproatu kao prvi lijek izbora za generaliziranu epilepsiju bolesnicama se preporučuju levetiracetam (razina dokaza: klasa 1B (AAN) i GRADE 1C) i etosuksimid (potonji za apsanse) (razina dokaza: klasa 1A (AAN), GRADE 1B), i to od dojenačke do kraja generativne dobi. Svakako je opravdana primjena valproata u djevojčica kao lijeka izbora pri nedjelotvornosti ili nuspojavama antiepileptičkog lijeka prvog izbora za generalizirane epilepsije i kada trudnoća nije vjerojatna zbog težine bolesti.The use of antiepileptic drugs in the treatment of epilepsy in children and adolescents, and first of all decision making on pharmacotherapy, may be demanding and complex given the various pharmacologic possibilities. Antiepileptic drugs should be prescribed according to the generic term of a single drug rather than the pharmaceutical/factory-protected name. Treatment of epilepsy should start with the first choice drug: the original or generic drug. Guidelines for pharmacotherapy of epilepsy in children are presented as the general principles of pharmacological treatment of epilepsy and as decision making about pharmacological treatment of epilepsy and epileptic syndromes in the Republic of Croatia. The paper also briefly reviews the most commonly used and most important antiepileptic drugs, their adverse effects and interactions. New antiepileptic drugs that are not yet on the primary or supplemental list of medicines in Croatia are also listed, but are applied in the treatment of epilepsy in children and are effective. The first choices for seizures with focal onset and focal epilepsy are oxcarbazepine (evidence level: class 1A (AAN) and GRADE 1B) and carbamazepine (evidence level: class 1A (AAN) and GRADE 1B). Antiepileptic drug of the first choice for seizures with generalized onset /generalized epilepsy in male patients is valproate (evidence level: class 1A (AAN) and GRADE 1A). Levetiracetam (evidence level: class 1B (AAN) and GRADE 1C) and etosuximid (the latter for absence seizures) (evidence level: class 1A (AAN) and GRADE 1B) are recommended as the drugs of the first choice in the treatment of generalized seizures/epilepsy in female patients since infancy due to possible teratogenic and other adverse effects on postnatal development after intrauterine exposure to valproic acid and valproic acid related drugs. It is certainly justified to use valproate in girls as a therapy in the case of inefficiency/antiepileptic side effects of the first choice therapy for generalized epilepsy, and when pregnancy is unlikely due to the severity of the disease itself

Prospektivno praćenje trudnica na monoterapiji lamotriginom u Hrvatskoj - predkoncepcijsko savjetovanje i praćenje lijekova

We prospectively surveyed 23 pregnant women with epilepsy on lamotrigine monotherapy and reported outcome of their pregnancies, including one fetal intrauterine death, one spontaneous abortion and two preterm deliveries. There were no congenital malformations in their offspring. Women with pregnancy planning and folic acid intake delivered babies with higher values of birth weight and birth length. There was large inter-patient variation during drug monitoring and in the need of dose adjustment. Individual approach to every woman and monotherapy with minimal effective lamotrigine dose with frequent drug monitoring enhances the possibility for successful pregnancy. The management of women with epilepsy should begin with pre-pregnancy counseling. Planned pregnancy enables periconceptional folic acid supplementation. Despite the small number of cases, these data indicate that lamotrigine treatment during pregnancy might be relatively safe. Larger prospective studies are needed to obtain adequate power for statistical analysis including long-term cohort studies.U ovoj studiji smo prospektivno pratili ishod trudnoće u 23 trudnice s epilepsijom koje su uzimale lamotrigin kao monoterapiju. Trudnoća je kod bolesnica rezultirala intrauterinom smrću djeteta u jednom slučaju. spontanim abortusom u jednom slučaju, te prijevremenim porodom u dva slučaja. Kod novorođenčadi nisu zabilježene kongenitalne malformacije. Žene koje su planirale trudnoću i uzimale folnu kiselinu rodile su djecu s višom tjelesnom masom i visinom. Postojala je velika različitost medu bolesnicama u praćenju doze lijeka te u potrebi za usklađivanjem doze. Veća je mogućnost uspješnog planiranja trudnoće ako se svakoj bolesnici pristupi individualno uz minimalnu djelotvornu dozu lijeka (lamotrigin). Liječenje trudnica treba započeti savjetovanjem prije začeća kada je moguće i pravodobno započeti s uzimanjem folne kiseline. Unatoč malom broju slučajeva podaci iz naše studije pokazuju kako liječenje lamotriginom tijekom trudnoće može biti relativno sigurno. Potrebne su veće prospektivne studije kako bi se postigla zadovoljavajuća statistička snaga dobivenih podataka

Fenotip spavanja u djece s Downovim sindromom – izmijenjena arhitektura spavanja i poremećeno disanje u snu

The aim of the study was to assess sleep architecture and breathing in sleep in children with Down syndrome. The study was conducted by using overnight video-polysomnography (V-PSG) in children with Down syndrome and age-matched children from the general population. Analysis of polysomnographic parameters revealed that compared to the norms of healthy age- and maturitymatched children from the general population, children with Down syndrome had significantly shorter sleep latency (p=0.007), shorter total sleep time (p=0.004), lower sleep efficiency (p=0.010), less NREM1 sleep phase (p=0.0002), less NREM3 sleep phase (p=0.034), less REM sleep (p=0.034) in favour of more NREM2 phase but not significantly (p=0.069), and spent more time awake after sleep onset (p=0.0002). Children with Down syndrome had significantly more obstructive sleep apnoeas and hypopnoeas per hour (higher obstructive sleep apnoeas and hypopnoeas index) (p=0.008), but less central sleep apnoea per hour (lower central apnoeas index) (p=0.041), which led to the nonsignificantly lower total apnoea-hypopnoea index (p=0.762) in children with Down syndrome. The mean and longest apnoea duration did not differ significantly between these two groups. Children with Down syndrome had a significantly lower mean and nadir oxygen saturation (p=0.008 and p=0.001, respectively). In conclusion, the majority of respiratory complications in children with Down syndrome can be prevented by raising awareness of sleep disturbances in children with Down syndrome among their parents and health care providers and by introducing early routine V-PSG in the follow up of these children.Cilj: Istražiti arhitektoniku spavanja i disanja tijekom sna u djece s Downovim sindromom. Metode: Cjelonoćna videopolisomnografija (V-PSG) u skupini djece s Downovim sindromom i u onoj iz opće populacije odgovarajuće dobi i zrelosti. Rezultat: Analiza polisomnografskih parametara pokazala je da djeca s Downovim sindromom, u usporedbi s normativima u zdrave djece u općoj populaciji, odgovarajuće dobi i zrelosti, imaju značajno kraću latenciju spavanja (SL) p=0,007, kraće ukupno vrijeme spavanja (TST) p=0,004, nižu efikasnost spavanja (SE) p=0,010, manje NREM1 faze spavanja p=0,0002, manje NREM3 faze spavanja p=0,034, manje REM spavanja p= 0,034 (na račun više površnog NREM2 spavanja, ali ne statistički značajno, p=0,069) i da provode više vremena budni nakon započimanja spavanja (p=0,0002). Djeca s Downovim sindromom imaju značajno više opstruktivnih apneja i hipopneja po satu spavanja (viši OAHI) p=0,008, ali imaju manje centralnih apneja po satu spavanja (niži CAI) p=0,041, što pridonosi statistički neznačajno nižem ukupnom AHI-u (p=0,762) u djece s Downovim sindromom. Prosječno i najdulje trajanje apneja nije se značajno razlikovalo između dviju skupina. Djeca s Downovim sindromom su imala značajno niže i prosječne i nadir saturacije kisika (p=0,008 i p=0,001). Zaključak: Možemo prevenirati većinu respiratornih komplikacija u djece s Downovim sindromom podizanjem svjesnosti njihovih roditelja o poremećajima spavanja u te djece, ali i zdravstvenih djelatnika, te uključivanjem rutinske cjelonoćne videopolisomnografije u njihovo praćenje