Serum Levels of S100b and NSE Proteins in Patients with Non-Transfusion-Dependent Thalassemia as Biomarkers of Brain Ischemia and Cerebral Vasculopathy.

Patients with non-transfusion-dependent thalassemia (NTDT) are at risk of developing brain ischemia. Transcranial Doppler (TCD) has been established as a useful screening tool of cerebrovascular disease in patients with sickle cell disease. Proteins neuron specific enolase (NSE) and S100B are biomarkers that reflect CNS injury. The purpose of this study is to evaluate cerebral vessel vasculopathy and brain damage in NTDT patients using non-invasive methods as TCD and measurement serum levels of NSE and S100B. We included in our study 30 patients with NTDT, aged between 8 and 62 years old (mean: 29.4, median: 32) who presented in our Unit for regular follow-up. We performed in all patients a non-imaging TCD examination and have measured serum S100, NSE and lactate dehydrogenase (LDH) levels. We investigated the possible correlation between TCD results and S100B, NSE and LDH levels as well as between NSE-LDH and S100B-LDH levels by regression analysis. We found a statistically significant relationship for both NSE, S100B with LDH. We also found a statistically significant relationship for S100B and time-averaged mean velocity (TAMV)/peak velocity of left middle cerebral artery (MCA), NSE and pulsatility index (PI)/resistive index (RI) of the left posterior cerebral artery (PCA). TCD results correlated with biomarkers for brain ischemia. This finding enhances the role of TCD as a screening tool for brain ischemia in patients with NTDT.

Microstructural changes in thickened corpus callosum in children: contribution of magnetic resonance diffusion tensor imaging.

BACKGROUND: Thickened corpus callosum is a rare finding and its pathophysiology is not well known. An anomalous supracallosal bundle has been depicted by fiber tracking in some cases but no diffusion tensor imaging metrics of thickened corpus callosum have been reported. OBJECTIVE: To use diffusion tensor imaging (DTI) in cases of thickened corpus callosum to help in understanding its clinical significance. MATERIALS AND METHODS: During a 7-year period five children (ages 6 months to 15 years) with thickened corpus callosum were studied. We determined DTI metrics of fractional anisotropy (FA), mean diffusivity, and axial (λ1) and radial (λ2, λ3) diffusivity and performed 3-D fiber tracking reconstruction of the thickened corpus callosum. We compared our results with data from the literature and 24 age-matched controls. RESULTS: Brain abnormalities were seen in all cases. All children had at least three measurements of corpus callosum thickness above the 97th percentile according to age. In all children 3-D fiber tracking showed an anomalous supracallosal bundle and statistically significant decrease in FA (P = 0.003) and λ1 (P = 0.001) of the corpus callosum compared with controls, but no significant difference in mean diffusivity and radial diffusivity. CONCLUSION: Thickened corpus callosum was associated with abnormal bundles, suggesting underlying axonal guidance abnormality. DTI metrics suggested abnormal fiber compactness and density, which may be associated with alterations in cognition.

Acoustic radiation force impulse imaging-normal values of liver stiffness in healthy children.

BACKGROUND: Acoustic radiation force impulse imaging (ARFI) is a recent ultrasound technique to assess tissue stiffness. OBJECTIVE: Our aim was to describe the feasibility and to define normal ARFI values in liver in children. MATERIALS AND METHODS: ARFI values were measured in 103 children (ages 2 weeks to 17 years) divided into four age groups, at a minimum depth of 3 cm. In 20 children, measurements were done at 3-, 4- and 5-cm depth in the liver to assess the suitability of measurement location. The impact of age groups and of depth groups was examined using multilevel models. The precision of the measurements was determined using intraclass correlation coefficient (ICC). RESULTS: There was no statistical difference between measurements taken at different ages, with a mean propagation velocity of 1.12 m/s (range: 0.73 to 1.45 m/s). There was no significant difference according to the depth of the regions of interest (up to 5 cm). The ICC was 0.77 (95% CI 0.69-0.83). CONCLUSION: ARFI is feasible in children at any age with an acceptable reliability. The depth of measurements in the liver seems to have no influence on test results. We set the standard ARFI elastography values for healthy liver in children.

Changes in Shear Wave Elastography after Lumacaftor/Ivacaftor Treatment in Children with Cystic Fibrosis.

BACKGROUND: Lumacaftor/Ivacaftor (LUM/IVA) is an approved combination therapy for cystic fibrosis (CF) patients homozygous for F508del. OBJECTIVE: This study aimed to detect changes in liver stiffness measurement (LSM) in patients under this treatment. METHODS: The study population consisted of CF patients homozygous for F508del, 6 to 11 years old, who had been treated for six months with LUM/IVA. Shear wave elastography (SWE) was performed in all of them, before and 6 months after the commencement of treatment. RESULTS: Thirty-one patients were included in the study. LSM values after treatment were significantly higher than the values before treatment (medians and interquartile ranges of LSM values before and after treatment: 5.6, 5.3-6.3 kPa and, 6.4, 6.0-7.6 kPa, respectively, p<0.001). CONCLUSION: SWE can detect early changes in LSM in some CF patients treated with LUM/IVA.

Can early MRI distinguish between Kingella kingae and Gram-positive cocci in osteoarticular infections in young children?

BACKGROUND: K. kingae is a common causative organism in acute osteoarticular infections (OAIs) in children under 4 years of age. Differentiation between K. kingae and Gram-positive cocci (GPC) is of great interest therapeutically. OBJECTIVE: Our aim was to identify early distinguishing MRI features of OAIs. MATERIALS AND METHODS: Thirty-one children younger than 4 years of age with OAI underwent MRI at presentation. Of these, 21 were caused by K. kingae and ten by GPC. Bone and soft tissue reaction, epiphyseal cartilage involvement, bone and subperiosteal abscess formation were compared between the two groups. Interobserver agreement was measured. RESULTS: Bone reaction was less frequent (P = 0.0066) and soft tissue reaction less severe (P = 0.0087) in the K. kingae group. Epiphysis cartilage abscesses were present only in the K. kingae group (P = 0.0118). No difference was found for bone abscess (P = 0.1411), subperiosteal abscess (P = 1) or joint effusion (P = 0.4414). Interobserver agreement was good for all criteria. CONCLUSION: MRI is useful in differentiating K. kingae from GPC in OAI. Cartilaginous involvement and modest soft tissue and bone reaction suggest K. kingae.

Sinus pericranii: a scalp mass in a 6-month-old boy.

'Sinus pericranii' is an abnormal communication between the extracranial veins and the dural venous sinuses (usually the superior sagittal and the transverse sinuses). It is a rare childhood abnormality. We report a case of a 6-month-old boy presenting with a scalp swelling in the left parietal region. Ultrasound with color Doppler and MRI showed a dilated epicranial vein that communicated with the superior sagittal sinus. This anomalous venous connection is known as sinus pericranii. We describe the imaging findings, associated abnormalities and management of this rare vascular abnormality.

Adult-onset dominant muscular dystrophy in Greek families caused by Annexin A11.

OBJECTIVE: Mutations in the prion-like domain of RNA binding proteins cause dysfunctional stress responses and associated aggregate pathology in patients with neurogenic and myopathic phenotypes. Recently, mutations in ANXA11 have been reported in patients with amyotrophic lateral sclerosis and multisystem proteinopathy. Here we studied families with an autosomal dominant muscle disease caused by ANXA11:c.118G > T;p.D40Y. METHODS: We performed deep phenotyping and exome sequencing of patients from four large Greek families, including seven affected individuals with progressive muscle disease but no family history of multi-organ involvement or ALS. RESULTS: In our study, all patients presented with an autosomal dominant muscular dystrophy without any Paget disease of bone nor signs of frontotemporal dementia or Parkinson's disease. Histopathological analysis showed rimmed vacuoles with annexin A11 accumulations. Electron microscopy analysis showed myofibrillar abnormalities with disorganization of the sarcomeric structure and Z-disc dissolution, and subsarcolemmal autophagic material with myeloid formations. Molecular genetic analysis revealed ANXA11:c.118G > T;p.D40Y segregating with the phenotype. INTERPRETATION: Although the pathogenic mechanisms associated with p.D40Y mutation in the prion-like domain of Annexin A11 need to be further clarified, our study provides robust and clear genetic evidence to support the expansion of the phenotypic spectrum of ANXA11.

Short MRI Protocol for Excluding Traumatic Lesions of the Scaphoid Bone in Children.

BACKGROUND/AIM: Management of scaphoid trauma includes imaging with repeated X-rays whose interpretation is difficult and often ambivalent. The aim of the study was to propose a fast magnetic resonance imaging (MRI) protocol permitting exclusion of traumatic lesions of the scaphoid bone in children, which would avoid unnecessary immobilization and irradiation in negative cases. PATIENTS AND METHODS: Two pediatric radiologists retrospectively reviewed the X-rays and MRIs of 45 children with clinical suspicion of scaphoid trauma. X-Rays and MRI sequences [short tau inversion recovery (STIR), T1] were scored as: 0 (negative) or 1 (equivocal or positive). X-ray results were compared to those of MRI and interobserver reliability was measured for both methods. RESULTS: MRI was shown to be more reliable than X-ray in excluding pediatric traumatic scaphoid lesions. X-Ray results differed significantly between the two readers (p=0.0001), and the interobserver reliability was low (κ=0.529). For MRI interpretation, there was no significant difference between the two readers' assessments. The interobserver reliability was high (κ=0.9544) and only in one case was there discordance. Absence of scaphoid trauma was confirmed on MRI in 18 out of 45 patients. For these patients, immobilization was reconsidered and no follow-up X-ray was performed. CONCLUSION: Early MRI is useful in the management of pediatric scaphoid trauma. A short MRI protocol consisting of a STIR and a T1 sequence is sufficient for differentiating positive from negative cases and gives a good negative predictive value for exclusion of a traumatic scaphoid lesion.

Congenital Seminal Vesicle Cyst and Ipsilateral Renal Agenesis (Zinner Syndrome): A Rare Association and Its Evolution from Early Childhood to Adolescence.

Zinner syndrome, the association of congenital seminal vesicle cyst and ipsilateral renal agenesis, is more often reported in adults or older adolescents. We present a case of a boy, followed up in our hospital since birth for right renal agenesis who at the age of 4 years presented a right paravesical cyst on ultrasound. The cyst was initially considered as an ureterocele. The diagnosis of Zinner syndrome was made later, at the age of 15 years by ultrasound and magnetic resonance imaging; at that moment the cyst had increased in size and had changed in aspect. This malformation should be considered in the differential diagnosis of a pelvic cyst in male patients with renal agenesis.

Evaluation of Intracranial Cerebral Blood Flow Velocities in Splenectomised and Non-Splenectomised Patients with ß-Thalassemia Intermedia Using Transcranial Doppler Sonography.

BACKGROUND: A high incidence of clinically-silent cerebral ischemic events has been reported in splenectomised patients with ß-thalassemia intermedia (ßTI). These could be due to cerebral large-vessel disease. Based on the example of sickle cell disease, we applied transcranial Doppler sonography (TCD) to evaluate cerebral vessels velocity as a possible indicator of cerebral vasculopathy. PATIENTS AND METHODS: In our study, we included 17 splenectomised and 13 non-splenectomised (control group) patients with ßTI. Non-imaging TCD was performed and the time-averaged mean velocity (TAMV) values of cerebral arteries were measured. RESULTS: There was no statistically significant difference between the two groups concerning age, gender, hemoglobin and hematocrit levels, nor in the TAMV values for all examined vessels (p>0.05). A statistically significant difference was found in platelet count (PLT) (p<0.01) that was higher in splenectomised patients. CONCLUSION: Our results do not support the presence of large-vessel vasculopathy in splenectomised ßTI patients and agree with recent studies reporting that cerebral ischemic events in these patients might be due to microangiopathy or venous thromboembolism.

Chiari I malformation associated with premature unilateral closure of the posterior intraoccipital synchondrosis in a preterm infant.

The authors report a case of a preterm infant at 29 weeks of gestation who gradually developed a Chiari malformation Type I (CM-I) with hydrocephalus due to a premature unilateral fusion of the posterior intraoccipital synchondrosis. Brain ultrasonography results in the 1st week of life were normal. Follow-up ultrasonography showed progressive development of triventricular hydrocephalus. Brain MRI demonstrated the presence of a CM-I and a deformation of the occipital bone. A complementary CT scan was obtained, showing a closure of the right posterior intraoccipital synchondrosis, resulting in a deformation of the posterior cranial fossa. This case shows the close relationship between a malformation of the skull base and the secondary development of a brain malformation. The authors discuss the anatomy of the occipital bone and suggest a probable theory for the premature closure of this synchondrosis and the consequent development of a CM-I. The originality of this case lies in the observation of the natural history of a brain malformation in a preterm infant.