Chiarin tyypin 1 epämuodostuma - diagnostinen ja hoidollinen haaste

Vertaisarvioitu. English summary.Chiarin tyypin 1 epämuodostuma (CM1) on yleinen sattumalöydös pään ja kaularangan magneettikuvauksessa. Yleensä sen radiologisena kriteerinä pidetään vähintään 5 mm:n pikkuaivoherniaatiota. CM1:tä aiheuttavat useat tekijät, mutta suurimmalla osalla potilaista pikkuaivoherniaation syytä ei voida tunnistaa. Jos niska-aukko on ahtautunut, saattaa esiintyä oireita. Niistä tavallisin on takaraivolle paikantuva ponnisteluun ja rasitukseen liittyvä lyhytkestoinen päänsärky. CM1 on tavallisin syringomyelian aiheuttaja. Leikkaushoitoa tarjotaan yleensä oireisille potilaille. Parhaiten leikkaus auttaa tyypilliseen CM1:n kriteerit täyttävään päänsärkyyn ja syringomyeliaan. Lasten leikkaustulokset ovat hieman aikuisia paremmat. Oireettoman tai vähäoireisen CM1-potilaan ennuste on hyvä ilman leikkaustakin.Peer reviewe

Outcome after transsphenoidal surgery for pituitary adenoma : The 2000-2010 Helsinki University Hospital Cohort

Pituitary adenomas are the most common tumors of the sella turcica. Our objectives here were to describe the transitional phase from microscopic to endoscopic surgery for nonfunctional pituitary adenomas (NFPAs), and to outline the health-related quality of life (HRQoL) and its determinants after treatment of different pituitary adenomas in a recent cohort from a single pituitary center. We retrospectively collected the relevant data for a total of 320 patients who had undergone primary surgery for a newly diagnosed pituitary adenoma during 2000-2010 at Helsinki University Hospital. The first part of our study included 185 consecutive patients who had transsphenoidal surgery for NFPA. These patients were divided into two groups based on the surgical approach: microscopic and endoscopic. Surgical and endocrinological outcomes were assessed at the 3-month follow-up. The second part of our study used a cross-sectional design and comprised all pituitary adenoma types. Each patient alive was sent a questionnaire (the 15D) assessing the HRQoL a mean of 7.4 years after the primary transsphenoidal surgery. One hundred functional pituitary adenoma (FPA) and 137 NFPA patients responded. We then compared HRQoL (15D scores) between patients and a large sample of an age- and gender-standardized Finnish general population. Independent factors influencing the overall HRQoL (mean 15D score) were estimated using multivariate analysis. A good short-term surgical outcome could be achieved during the initial phase of transition from microscopic to endoscopic transsphenoidal surgery for NFPA patients. Our first endoscopic single-center consecutive case series showed a trend towards improved tumor control but the operative time was longer than with the microscopic technique.The effect of NFPA surgery on pituitary function (hypopituitarism) in both surgical groups was neutral. Current multimodal treatment protocols with optimized hormonal replacement therapies enabled normal or at least near-normal overall HRQoL to be achieved in the majority of patients with all types of pituitary adenomas. Hormonal remission rate of FPAs was 91%. However, patients with Cushing s disease and NFPA had clinically and statistically significant impairments of some single dimensions compared with the general population. Comorbidities were strong determinants of compromised overall HRQoL in patients treated for pituitary adenomas.Aivolisäkeadenooma on tavallisin sellassa eli kallonpohjan turkinsatulassa esiintyvä kasvain. Tämän tutkimuksen tarkoituksena oli kuvailla siirtymävaihetta mikroskooppisesta endoskooppiseen leikkaustekniikkaan toimimattomien aivolisäkeadenoomien hoidossa. Lisäksi selvitimme terveyteen liittyvää elämänlaatua ja siihen vaikuttavia tekijöitä erityyppisten aivolisäkeadenoomien leikkaushoidon jälkeen. Vuosina 2000-2010 Helsingin yliopistollisessa keskussairaalassa leikattiin 320 uutta aivolisäkeadenoomapotilasta, joiden sairauskertomustiedot kerättiin takautuvasti. Ensimmäisen osatyön 185 potilasta, jaettiin kahteen ryhmään leikkaustekniikan (mikroskooppinen ja endoskooppinen) perusteella. Leikkaushoidon vaikutusta arvioitiin seurantakäynnin yhteydessä 3 kuukautta leikkauksen jälkeen. Toisessa ja kolmannessa osatyössä selvitettiin läpileikkaustutkimuksella erityyppisten aivolisäkeadenoomapotilaiden terveyteen liittyvää elämänlaatua keskimäärin 7.4 vuotta transsfenoidaalisen leikkauksen jälkeen. Elämänlaatukyselyyn (15D) vastasi 100 hormonaalisesti toimivan ja 137 toimimattoman aivolisäkeadenooman vuoksi leikattua potilasta, joiden 15D arvoja verrattiin suureen kaltaistettuun suomalaiseen taustaväestöön. Itsenäisiä elämänlaatua selittäviä tekijöitä arvioitiin monimuuttuja-analyysilla. Toimimattomien aivolisäkeadenoomien hyvät leikkaustulokset voitiin säilyttää mikroskooppisesta endoskooppiseen leikkaustekniikkaan tapahtuvan siirtymävaiheen aikana. Endoskooppisesti leikattujen potilaiden ryhmässä oli suuntaus vähäisempään jäännöskasvaimen määrään, mutta leikkausaika oli pidempi verrattuna mikroskooppisesti leikattuun ryhmään. Leikkauksen vaikutus aivolisäkkeen toimintaan (hypopituitarismiin) oli molemmissa toimenpideryhmissä keskimäärin neutraali. Nykymenetelmin leikatuilla ja hoidetuilla aivolisäkeadenoomapotilailla todettiin lähes normaali elämänlaatu (15D indeksi). Toimivista adenoomista 91 % oli hormonaalisessa remissiossa. Cushingin tauti ja toimimattomat aivolisäkeadenoomat kuitenkin heikensivät joitakin yksittäisiä elämänlaadun ulottuvuuksia taustaväestöön verrattuna. Lisäksi oheissairauksien kertyminen oli merkittävä elämänlaatua heikentävä itsenäinen tekijä aivolisäkeadenoomapotilailla

Genetic and Epigenetic Characterization of Growth Hormone-Secreting Pituitary Tumors

Somatic driver mechanisms of pituitary adenoma pathogenesis have remained incompletely characterized; apart from mutations in the stimulatory G alpha protein (G alpha(s) encoded by GNAS) causing activated cAMP synthesis, pathogenic variants are rarely found in growth hormone-secreting pituitary tumors (somatotropinomas). The purpose of the current work was to clarify how genetic and epigenetic alterations contribute to the development of somatotropinomas by conducting an integrated copy number alteration, whole-genome and bisulfite sequencing, and transcriptome analysis of 21 tumors. Somatic mutation burden was low, but somatotropinomas formed two subtypes associated with distinct aneuploidy rates and unique transcription profiles. Tumors with recurrent chromosome aneuploidy (CA) were GNAS mutation negative (Gsp(-)). The chromosome stable (CS) -group contained Gsp(+) somatotropinomas and two totally aneuploidy-free Gsp(-) tumors. Genes related to the mitotic G(1)-S-checkpoint transition were differentially expressed in CA- and CS-tumors, indicating difference in mitotic progression. Also, pituitary tumor transforming gene 1 (PTTG1), a regulator of sister chromatid segregation, showed abundant expression in CA-tumors. Moreover, somatotropinomas displayed distinct Gsp genotypespecific methylation profiles and expression quantitative methylation (eQTM) analysis revealed that inhibitory G alpha (G alpha(i)) signaling is activated in Gsp(+) tumors. These findings suggest that aneuploidy through modulated driver pathways may be a causative mechanism for tumorigenesis in Gsp(-) somatotropinomas, whereas Gsp(+) tumors with constitutively activated cAMP synthesis seem to be characterized by DNA methylation activated G alpha(i) signaling.Peer reviewe

Prognostic Value and Changes of Auditory Brain Stem Response in Children With Bacterial Meningitis in Luanda, Angola

Objective:To assess the role of single and repeated auditory brain stem response (ABR) in predicting mortality and severe neurological injury among children having bacterial meningitis (BM) in Luanda, Angola.Methods:The morphology of ABR traces of 221 children (aged 2?months to 12?years) from admission day was analyzed and compared with age-matched normative data. Absence and delay of traces were compared with mortality and mortality or severe neurological injury in subgroup analyses. Outcome was also evaluated with repeated ABR of 166 children based on presence or absence of responses at 80?dB nHL (normal hearing level) stimulation level.Results:Individually, the absence of typical ABR waveform did not signify poor outcome. At the group level, latencies and interpeak latencies (IPLs) were significantly prolonged among patients with BM in comparison with controls, and the prolongation correlated with higher mortality or severe neurological sequelae.Conclusions:We confirmed the effect of BM on neural conduction time in auditory pathway. However, ABR in similar settings seems not useful for individual prognostication, although at the group level, delayed latencies, IPLs, or both associated with poorer outcome.Peer reviewe

Aivolisäkekasvainten hoito

English summaryPeer reviewe

Posttraumatic epilepsy in intensive care unit–treated pediatric traumatic brain injury patients

Objective Posttraumatic epilepsy (PTE) is a well-described complication of traumatic brain injury (TBI). The majority of the available data regarding PTE stem from the adult population. Our aim was to identify the clinical and radiological risk factors associated with PTE in a pediatric TBI population treated in an intensive care unit (ICU). Methods We used the Finnish Intensive Care Consortium database to identify pediatric ( Results Of the 290 patients included in the study, 59 (20%) developed PTE. Median age was 15 years (interquartile range [IQR] 13-17), and 80% had an admission Glasgow Coma Scale (GCS) score Significance We showed that PTE is a common long-term complication after ICU-treated pediatric TBI. Higher age, moderate injury severity, obliterated suprasellar cisterns, seizures during ICU stay, and surgical treatment are associated with an increased risk of PTE. Further studies are needed to identify strategies to decrease the risk of PTE.Peer reviewe

Molecular alterations in pediatric brainstem gliomas

BackgroundDiffuse intrinsic pontine gliomas (DIPGs) have a dismal prognosis. Previously, diagnosis was based on a typical clinical presentation and magnetic resonance imaging findings. After the start of the era of biopsies, DIPGs bearing H3 K27 mutations have been reclassified into a novel entity, diffuse midline glioma, based on the presence of this molecular alteration. However, it is not well established how clinically diagnosed DIPG overlap with H3 K27-mutated diffuse midline gliomas, and whether rare long-term survivors also belong to this group. MethodsWe studied tumor samples obtained at diagnosis or upon autopsy from 23 children, including two long-term survivors. Based on clinical, radiological, and histological findings, all tumors were previously diagnosed as DIPGs. All samples were analyzed for genetic alterations by next-generation sequencing (NGS) and for protein expression by immunohistochemistry (IHC). ResultsH3 K27 was mutated in NGS or IHC in 20 patients, excluding both long-term survivors. One of these long-term survivors harbored a mutation in IDH1, formerly considered to be an alteration absent in pediatric diffuse brainstem gliomas. Other altered genes in NGS included TP53 (10 patients), MET and PDGFRA (3 patients each), VEGFR and SMARCA4 (2 patients each), and PPAR, PTEN and EGFR in 1 patient, respectively. IHC revealed cMYC expression in 15 of 24 (63%) of all samples, exclusively in the biopsies. ConclusionsEighty-seven percent of the tumors formerly diagnosed as DIPGs could be reclassified as H3 K27-mutated diffuse midline gliomas. Both long-term survivors lacked this alteration. Contrary to former conceptions, IDH1 mutations may occur also in pediatric brainstem gliomas.Peer reviewe

Posttraumatic epilepsy in intensive care unit-treated pediatric traumatic brain injury patients

Objective Posttraumatic epilepsy (PTE) is a well-described complication of traumatic brain injury (TBI). The majority of the available data regarding PTE stem from the adult population. Our aim was to identify the clinical and radiological risk factors associated with PTE in a pediatric TBI population treated in an intensive care unit (ICU).Methods We used the Finnish Intensive Care Consortium database to identify pediatric (Results Of the 290 patients included in the study, 59 (20%) developed PTE. Median age was 15 years (interquartile range [IQR] 13-17), and 80% had an admission Glasgow Coma Scale (GCS) score Significance We showed that PTE is a common long-term complication after ICU-treated pediatric TBI. Higher age, moderate injury severity, obliterated suprasellar cisterns, seizures during ICU stay, and surgical treatment are associated with an increased risk of PTE. Further studies are needed to identify strategies to decrease the risk of PTE.</div

Cerebellar mutism syndrome in children with brain tumours of the posterior fossa

Background: Central nervous system tumours constitute 25% of all childhood cancers; more than half are located in the posterior fossa and surgery is usually part of therapy. One of the most disabling late effects of posterior fossa tumour surgery is the cerebellar mutism syndrome (CMS) which has been reported in up to 39% of the patients but the exact incidence is uncertain since milder cases may be unrecognized. Recovery is usually incomplete. Reported risk factors are tumour type, midline location and brainstem involvement, but the exact aetiology, surgical and other risk factors, the clinical course and strategies for prevention and treatment are yet to be determined. Methods: This observational, prospective, multicentre study will include 500 children with posterior fossa tumours. It opened late 2014 with participation from 20 Nordic and Baltic centres. From 2016, five British centres and four Dutch centres will join with a total annual accrual of 130 patients. Three other major European centres are invited to join from 2016/17. Follow-up will run for 12 months after inclusion of the last patient. All patients are treated according to local practice. Clinical data are collected through standardized online registration at pre-determined time points pre- and postoperatively. Neurological status and speech functions are examined pre- operatively and postoperatively at 1-4 weeks, 2 and 12 months. Pre- and postoperative speech samples are recorded and analysed. Imaging will be reviewed centrally. Pathology is classified according to the 2007 WHO system. Germline DNA will be collected from all patients for associations between CMS characteristics and host genome variants including pathway profiles. Discussion: Through prospective and detailed collection of information on 1) differences in incidence and clinical course of CMS for different patient and tumour characteristics, 2) standardized surgical data and their association with CMS, 3) diversities and results of other therapeutic interventions, and 4) the role of host genome variants, we aim to achieve a better understanding of risk factors for and the clinical course of CMS - with the ultimate goal of defining strategies for prevention and treatment of this severely disabling condition.Peer reviewe