Paediatric Cushing’s disease — a literature review of epidemiology, pathogenesis, clinical symptoms, and diagnostics

Cushing’s disease (CD) is characterised by excess production of adrenocorticotropic hormone (ACTH) by a pituitary corticotroph adenoma, which results in hypercortisolaemia. CD is extremely rare in the paediatric population, and few paediatric endocrinology centres have experience in diagnosing and treating this disease. The clinical presentation of hypercortisolaemia is variable, so proper and rapid diagnosis of CD is often challenging. The molecular pathogenesis of CD was largely unknown until recently. The latest research has revealed somatic mutations in the USP8 gene as the most common pathogenic molecular variants of this disease. Herein, we describe the current state of knowledge of paediatric CD epidemiology, molecular pathogenesis, clinical symptoms, and diagnostics

Rola badań obrazowych układu nerwowego w diagnostyce stwardnienia rozsianego u dzieci

Stwardnienie rozsiane (SR) u dzieci od kilku lat budzi coraz większe zainteresowanie. Początki choroby przed 16. rokiem życia stwierdza się nawet u ponad 10% chorych na SR. Choroba u dzieci przebiega jednak inaczej niż u osób dorosłych, inny jest również obraz badań obrazowych za pomocą rezonansu magnetycznego. Z tych względów SR w pediatrycznej grupie wiekowej wymaga także uwzględnienia odmiennych schorzeń w diagnostyce różnicowej. W ostatnich latach zaproponowano odrębne kryteria rozpoznania SR u dzieci. Ze względu na dużą częstość rzutów, a także duże ryzyko wczesnego rozwoju niepełnosprawności SR u dzieci bardzo ważne jest wczesne prawidłowe rozpoznanie i wdrożenie odpowiedniego leczenia. W niniejszej pracy przedstawiono przegląd aktualnych danych dotyczących epidemiologii, patogenezy oraz diagnostyki obrazowej SR u dzieci

Diagnostyka obrazowa nowotworów ośrodkowego układu nerwowego

W niniejszej pracy przedstawiono obraz guzów mózgu i kanału kręgowego w badaniach metodami tomografii komputerowej (TK) i rezonansu magnetycznego (MR, magnetic resonance). Obie techniki są obecnie metodami referencyjnymi w diagnostyce neuroonkologicznej. Metoda MR jest szczególnie ważna w rozpoznawaniu i różnicowaniu guzów ośrodkowego układu nerwowego (OUN), ponieważ stanowi bazę dla nowoczesnej chirurgii stereotaktycznej, a dzięki badaniom funkcjonalnym pozwala na wykonywanie precyzyjnych i oszczędzających zabiegów chirurgicznych. W artykule omówiono cechy różnicujące stopień złośliwości guzów mózgu i rdzenia, symptomatologię neuroradiologiczną zmian nowotworowych OUN i aktualne algorytmy diagnostyczne

Case Report: Adenosine kinase deficiency diagnosed 10 years after liver transplantation: Novel phenotypic insights

Adenosine kinase (ADK) deficiency is a rare inborn error of methionine and adenosine metabolism. So far, a total of 27 patients with ADK deficiency have been reported. Here, we describe the first Polish patient diagnosed with ADK deficiency, aiming to highlight the clinical presentation of disease, emphasize diagnostic difficulties, and report the long-term follow-up. Six-month-old patient presented with cholestatic liver disease, macrocytic anemia, developmental delay, generalized hypotonia, delayed brain myelination, and elevated levels of serum methionine. A decrease of mitochondrial respiratory chain complex II and III activity were found in the postnuclear supernatants obtained from skeletal muscle biopsy. The patient underwent living-donor liver transplantation (LTx) at 14 months of age. Ten-year follow-up after LTx revealed a preserved good liver function, persistent regenerative macrocytic anemia, progressive neurological disease but disappearance of brain MR changes, short stature, and cortisol deficiency. Whole exome sequencing revealed the patient to be affected with two novel ADK variants, which pathogenicity was confirmed biochemically by demonstration of elevated concentration of S-adenosylhomocysteine

Olbrzymi naczyniak jamisty móżdżku u 4-miesięcznego niemowlęcia. Opis przypadku i przegląd piśmiennictwa

Cavernous malformations (CMs) are rare vascular lesions that affect 0.4–0.9% of the population. The diagnosis of CMs is simple in most typical cases although some lesions may present unusual imaging features: localization, signal intensity, or size. Extremely rare giant CMs can mimic neoplastic lesion because of their size. We report a case of giant cerebellar CM that is more than 6 cm in size, diagnosed in 4-month-old boy. We discuss magnetic resonance findings and histopathological features of this lesion.Naczyniaki jamiste to rzadkie zmiany naczyniowe, występujące u 0,4–0,9% populacji. Ich rozpoznanie w większości typowych przypadków jest łatwe, ale niektóre zmiany mogą stwarzać trudności diagnostyczne związane z nietypową lokalizacją, ich intensywnością sygnału lub wielkością. Niezwykle rzadkie gigantyczne naczyniaki jamiste mogą imitować zmiany nowotworowe. Autorzy przedstawiają 4-miesięczne niemowlę, u którego rozpoznano olbrzymi naczyniak jamisty zlokalizowany w móżdżku o wymiarze większym niż 6 cm. Omawiają cechy naczyniaka w badaniu za pomocą rezonansu magnetycznego oraz wynik badania histopatologicznego

Widma spektroskopii wodorowej guzów korowych w przebiegu stwardnienia guzowatego u dzieci

Background: Tuberous sclerosis complex (TSC) is an autosomal dominant multisystem disorder with two gene loci located on chromosomes 9q34 (TSC1) and 16p13 (TSC2). Brain abnormalities in TSC include cortical tubers, subependymal nodules, giant cell astrocytomas, and white matter lesions. Cortical tubers present disordered focal neocortical formation. However, their biology remains to be elucidated. Recently, proton magnetic resonance spectroscopy has been clinically applied to the differential diagnosis of brain changes as a noninvasive neuroimaging tool. The purpose of this study was to investigate cortical tubers by single-voxel proton spectroscopy. Material/Methods: Twenty-four children with TSC were examined using a 1.5T scanner with a standard head coil. The group of patients consisted of 12 girls and 12 boys aged 3 weeks to 28 years (median: 8.66 years). Ten healthy children (examined for other reasons, with normal MR images) were the control group. Integrated MR/MRS examinations were performed. Proton MR spectroscopy images were obtained using single-voxel point resolved spectroscopy, the PRESS technique with TE=35 ms and TR=1500 ms. Results: Proton MR spectroscopy of cortical tubers revealed increased mI/Cr ratio (1.023 versus 0.553 in healthy children) and slightly decreased NAA/Cr (0.952 vs. 1.268) and NAA/Cho ratios (0.948 vs. 1.208) in all the spectra of TSC patients. The Cho/Cr ratio was almost the same as in the control group (1.079 vs. 1.058). Lactate peaks were present in ten cortical tubers. Conclusions: Proton spectroscopy can be useful in the examination of cortical tubers in TSC as a noninvasive method to investigate neurochemistry of the brain

Spinal cord lesions in children and adolescents with multiple sclerosis – Magnetic resonance imaging

Purpose The purpose of our study was to determine the prevalence of spinal cord lesions revealed by magnetic resonance (MR) imaging in children and adolescents with clinically definite multiple sclerosis (MS). Material and methods We retrospectively evaluated the spinal cord magnetic resonance examinations in a group of MS patients consisting of 58 children (37 girls and 21 boys) aged from 7 to 17.8 years (mean 13.7 years). All children met the criteria of clinically definite MS and had typical MS lesions revealed in the brain imaging. Results Spinal cord lesions, regardless of localization, were identified in 36 (62%) patients. In 22 of 58 patients (38%) no lesions were observed. The plaques were found in the cervical spinal cord and the thoracic spinal cord in 30 out of 36 (86.1%) and in 31 out of 36 (88.6%) patients, respectively. Contrast enhancement was noticed in 10 out of 36 patients (27.7%) and was not correlated with the number of lesions present. We noticed a tendency to higher EDSS score in patients with lesions in more than 1 spinal cord region. Our study showed that spinal cord lesions are more frequently present in patients with complex neurological disability. Conclusion The prevalence of spinal cord lesions in children and adolescents with MS is high. Therefore, spinal cord MRI should be included in diagnostic program of MS

Analysis of MRI spectrum of brain abnormalities in tuberous sclerosis complex : data from one institution

Background: Tuberous sclerosis complex (TSC) is an autosomal dominant multisystem disorder with gene loci located on chromosomes 9q34 (TSC1) and 16p13 (TSC2). Brain is the most frequently affected organ. We retrospectively reviewed magnetic resonance features of the brain in 92 patients with tuberous sclerosis, examined in our Institute from 1997 to 2006. Material/Methods: We analyzed MR imaging of the spectrum of supra- and infratentorial brain lesions encountered in TSC. MR examinations were performed with a 1.5 T scanner. The basic imaging protocol included axial SE T1WI, FSE PD, T2WI, FSE FLAIR images, sagittal T1,T2WI and coronal FLAIR images. Axial T1-WI contrast-enhanced images were obtained in each patient. Results: Cortical tubers were found in 89 of the 92 patients (96.74%) and they have been located in frontal and parietal cerebral lobes predominantly. Cerebellar tubers were found in 12/92 (13.04%), cerebral white matter lesions in 34/92 patients (36.96%), subependymal nodules in 80/92 patients (86.96%) and subependymal giant cell astrocytomas in 11/92 of our patients (11.96%). Partial agenesis of corpus callosum, cortical dysplasia, cerebellar atrophy, intracranial arterial aneurysm, enlargement of ventricles and venous malformation were rare associated findings. Administration of gadolinium was useful in detecting and delineation subependymal giant cell astrocytomas - SGCAs. Conclusions: Our study presents a wide range of MR signs and variance of the cerebral manifestations with TSC patients

Plasma Homocysteine and Fibrinogen Levels in Type 2 Diabetics with and without Nocturnal Blood Pressure Fall and Heart Rate Decrease

Wstęp Wpływ podwyższonych stężeń homocysteiny i fibrynogenu na ryzyko wystąpienia chorób układu krążenia jest większy u chorych na cukrzycę typu 2 niż u osób z prawidłową tolerancją glukozy. Chorzy bez spadku ciśnienia tętniczego i zwolnienia akcji serca w godzinach nocnych (tzw. non-dippers) są bardziej narażeni na rozwój powikłań sercowo-naczyniowych. Celem niniejszej pracy była ocena, w jakim stopniu zaburzenia profilu dobowego ciśnienia tętniczego i akcji serca wpływają na stężenie fibrynogenu i homocysteiny w surowicy krwi chorych na cukrzycę typu 2. Materiał i metody Badaniami objęto 87 chorych na cukrzycę typu 2. Oceniano wpływ występowania nefropatii i retinopatii na przebieg profilu dobowego ciśnienia tętniczego i tętna. Na podstawie różnicy dzienno-nocnej podzielono chorych na podgrupę ze spadkiem ciśnienia tętniczego (dippers) i bez jego spadku (non-dippers) w okresie snu. Wyniki Występowanie mikroalbuminurii nie miało wpływu na przebieg profilu dobowego ciśnienia tętniczego i akcji serca. U chorych z retinopatią cukrzycową stwierdzono znamiennie mniejszy spadek ciśnienia tętdaniach niczego w godzinach nocnych. Brak spadku ciśnienia tętniczego w godzinach nocnych wiązał się z wyższym stężeniem homocysteiny. U chorych bez zwolnienia akcji serca w godzinach nocnych zaobserwowano znamiennie wyższe stężenie fibrynogenu. Wnioski Występowanie retinopatii cukrzycowej jest związane ze znamiennie mniejszym spadkiem ciśnienia tętniczego w godzinach nocnych u chorych na cukrzycę typu 2. Brak spadku ciśnienia tętniczego w godzinach nocnych wiąże się z wyższym stężeniem homocysteiny u tych chorych. Zaburzenia profilu dobowego akcji serca u chorych z cukrzycą typu 2 są związane z wyższym stężeniem fibrynogenu.Background The link between high levels of serum homocysteine and fibrinogen and cardiovascular morbidity appears to be much stronger in diabetics than in subjects with normal glucose tolerance. It has been suggested that patients with non-dipping pattern (non-dippers) are at greater risk of target organ damage. The aim of the present study was to evaluate the relationship between blunted diurnal blood pressure and heart rate profile and serum levels of homocysteine and fibrinogen in patients with type 2 diabetes mellitus. Material and methods We studied 87 patients with type 2 diabetes mellitus. We evaluated the impact of retinopathy and nephropathy on diurnal blood pressure and heart rate profile. The patients were grouped according to the presence or lack of nocturnal blood pressure and heart rate decrease. Results Microalbuminuria had no significant effect on diurnal blood pressure profile. Compared to patients without retinopathy, those with this complication had significantly smaller nocturnal blood pressure fall. Non-dipping blood pressure pattern status was linked to higher levels of serum homocysteine. Patients without nocturnal heart rate decrease had significantly greater fibrinogen levels. Conclusions Presence of retinopathy is associated with significantly blunted nocturnal blood pressure fall in type 2 diabetes. Blunted diurnal blood pressure variation in type 2 diabetics is related to higher serum levels of homocysteine. In type 2 diabetics, non-dipping pattern of heart rate profile is linked to higher serum levels of fibrinogen

Spectrum of JAG1 gene mutations in Polish patients with Alagille syndrome

Alagille syndrome (ALGS) is an autosomal dominant disorder characterized by developmental abnormalities in several organs including the liver, heart, eyes, vertebrae, kidneys, and face. The majority (90-94 %) of ALGS cases are caused by mutations in the JAG1 (JAGGED1) gene, and in a small percent of patients (∼1 %) mutations in the NOTCH2 gene have been described. Both genes are involved in the Notch signaling pathway. To date, over 440 different JAG1 gene mutations and ten NOTCH2 mutations have been identified in ALGS patients. The present study was conducted on a group of 35 Polish ALGS patients and revealed JAG1 gene mutations in 26 of them. Twenty-three different mutations were detected including 13 novel point mutations and six large deletions affecting the JAG1 gene. Review of all mutations identified to date in individuals from Poland allowed us to propose an effective diagnostic strategy based on the mutations identified in the reported patients of Polish descent. However, the distribution of mutations seen in this cohort was not substantively different than the mutation distribution in other reported populations