Delayed rotation of the cerebellar vermis: a pitfall in early second-trimester fetal magnetic resonance imaging.

We describe two cases in which delayed rotation of the cerebellar vermis simulated a Dandy-Walker malformation (DWM) on early second-trimester magnetic resonance imaging (MRI). Two pregnant women with suspected fetal posterior fossa anomaly on ultrasound examination underwent fetal MRI at 21 (Case 1) and 19 (Case 2) weeks' gestation. In both cases, upward rotation of the cerebellar vermis was noted; on midsagittal imaging, the brainstem-vermis angle was 28° and 43°, respectively, while cerebellar morphometry showed a reduced vermian anteroposterior diameter compared to reference data. The posterior fossa appeared to be mildly enlarged, while all other findings were normal. Follow-up MRI at 28 + 3 weeks' gestation (Case 1) and at 1 postnatal year (Case 2) showed completely normal findings. Both children had normal psychomotor development and neurological examinations at 1 year of age. Incomplete rotation of the cerebellar vermis can be a physiological finding on early second-trimester fetal MRI examination and can simulate DWM or other forms of cerebellar hypoplasia. Embryologically, delayed permeabilization of Blake's pouch could account for the delayed vermian rotation. Follow-up imaging at a later gestational age is crucial to ensure that this condition is not over-reported and to avoid the potential risk of unnecessary pregnancy interruption. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Glucocorticoid receptors in human epicardial adipose tissue: role of coronary status.

BACKGROUND: Epicardial adipose tissue (EAT) is in close contact with coronary vessels and therefore could alter coronary homeostasis. Glucocorticoids are pathophysiological mediators of visceral fat deposition and its associated atherogenic complications. AIM: We investigated in EAT the expression of the glucocorticoid receptor (GR) and its various (A, B, C) promoters. MATERIALS AND METHODS: Paired subcutaneous adipose tissue (SAT) and EAT biopsies were obtained from 15 patients with coronary artery disease (CAD) and 12 patients without CAD (NCAD). GR and 11ß-hydroxysteroid dehydrogenase type 1 protein (11ß-HSD-1, the enzyme which converts inactive cortisone into active cortisol) were studied by immunohistochemistry and GR and its various promoters were studied by mRNA quantitative RT-PCR. RESULTS: GR and 11ß-HSD-1 protein were expressed in adipocytes, stromal areas, isolated stromal cells close to adipocytes, and blood vessels. Total GR mRNA levels did not differ in SAT obtained from NCAD or CAD patients and were decreased in EAT, irrespectively of the coronary status, with parallel changes in promoter B- and C-, but not promoter A-associated transcripts. Total GR mRNA and adipocyte surface in EAT obtained from CAD patients were correlated negatively (p<0.035, r=0.39). CONCLUSIONS: Our findings demonstrate that in EAT, GR gene promoters could play a role in tissue- specific GR expression levels. EAT may be less sensitive to glucocorticoids than SAT, preventing the EAT mass development in CAD patients and suggesting a protective role on coronary homeostasis.

[Long-term therapy for chronic hepatitis B in HIV co-infected patients]. / Traitements à long terme de l'hépatite chronique B chez le patient co-infecté par le VIH.

As human immunodeficiency virus (HIV) and hepatitis B virus (HBV) are acquired through the same routes of contamination, the prevalence of HBV serological markers found in the HIV-infected population is approximately 7%. Liver-related mortality and morbidity is higher in HIV/HBV co-infected patients than in HBV mono-infected patients. Both viruses must be considered before a treatment decision is made. According to the European consensus conference on the treatment of chronic hepatitis B and C in HIV coinfected patients, treatment is based on whether there is an existing indication of anti- HIV therapy or not. In patients with no indication of anti-HIV therapy, drugs with dual anti-viral activity (lamivudine, entecavir, tenofovir disoproxil fumarate) should not be used due to the risk of developing HIV-resistance. Interferon or adefovir in combination with telbivudine are recommended. In patients with an indication of anti-HIV therapy, a backbone of highly active anti-retroviral therapy should include tenofovir in combination with lamivudine or emtricitabine. The same regimen is recommended in patients who develop lamivudine resistance.

A case of late orthostatic headache secondary to lumbar hidden dural fistula 20 months after epidural anesthesia.

The clinical recognition of CSF fistula is a clinical challenge. We report the case of a young woman, who presented with a late orthostatic headache 20 months after epidural anesthesia. She developed a lumbar dural fistula of CSF confirmed in myelography CT scanning and treated successfully with epidural blood patch.

Temporal trends, clinical patterns and outcomes of NAFLD-related HCC in patients undergoing liver resection over a 20-year period.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is an increasing cause of hepatocellular carcinoma (HCC) worldwide. NAFLD-HCC often occurs in noncirrhotic liver raising important surveillance issues. AIM: To determine the temporal trends for prevalence, clinical characteristics and outcomes of NAFLD-HCC in patients undergoing liver resection. METHODS: Consecutive patients with histologically confirmed HCC who underwent liver resection over a 20-year period (1995-2014). NAFLD was diagnosed based on past or present exposure to obesity or diabetes without other causes of chronic liver disease. RESULTS: A total of 323 HCC patients were included, 12% with NAFLD. From 1995-1999 to 2010-2014, the prevalence of NAFLD-HCC increased from 2.6% to 19.5%, respectively, P = .003, and followed the temporal trends in the prevalence of metabolic risk factors (28% vs 52%, P = .017), while hepatitis C-HCC decreased (from 43.6% to 19.5%, P = .003). NAFLD-HCC occurred more frequently in the absence of bridging fibrosis/cirrhosis (63% of cases, P < .001 compared to other aetiologies). Within the NAFLD group, tumour characteristics were similar between F0-F2 and F3-F4 patients, except for a higher proportion of single nodules (95% vs 54%, P < .01). A total of 53% patients had tumour recurrence and 40% died. NAFLD-HCC had similar time to recurrence and survival as HCCs of other aetiologies. Satellite nodules, tumour size, microvascular invasion and male sex but not the aetiology were independently associated with recurrence. CONCLUSION: Non-alcoholic fatty liver disease increased substantially over the past 20 years among resectable HCCs. It is now the leading cause of HCC occuring without/or with only minimal fibrosis. NAFLD patients are older, with larger tumours while survival and recurrence rates are as severe as in other aetiologies.

Phase I study of recombinant human interleukin-2 for pediatric malignancies: feasibility of outpatient therapy. A Pediatric Oncology Group Study.

Published data indicate that when recombinant interleukin-2 (rIL-2) is administered to children as a 15-min i.v. bolus, doses of 18 x 10(6) IU/m2 are poorly tolerated, requiring intensive care unit (ICU) management of IL-2-induced hypotension. We administered rIL-2 as a 1- or 2-h i.v. infusion to 11 children with malignancies refractory to conventional therapy. IL-2 was given every Monday/Wednesday/Friday for 3 weeks. Four children received 12 x 10(6) IU/m2/dose, four received 18 x 10(6) IU/m2/dose, and three received 24 x 10(6) IU/m2/dose (1 Cetus Unit = 6 IU). Fever, chills, flushing, nausea, vomiting, transient weight gain, and oliguria were observed at all three dose levels (not dose-limiting toxicities). Cardiovascular toxicity was significantly reduced compared to the bolus regimen. Mild hypotension was observed at all three dose levels; however, there was no severe dose-limiting hypotension. Because of reduced cardiovascular toxicity, IL-2 was safely administered on an outpatient basis. This regimen induced marginal transient increases in natural killer cell activity and lymphokine-activated killer cell activity. No measurable clinical tumor response was observed in any of the 11 children. The maximum-tolerated dose has not been reached. This regimen allows for a considerable cost reduction (outpatient care instead of ICU care) and safety, making further clinical trials on the use of IL-2 in children more feasible.

Cognitive status of children treated with central nervous system prophylactic chemotherapy for acute lymphocytic leukemia.

Treatment-related cognitive impairments have been reported for survivors of childhood leukemia following prophylactic central nervous system (CNS) treatment with craniospinal radiation. We examined the neurocognitive status of 46 children with acute lymphocytic leukemia (ALL) to assess the impact of a regimen consisting of systemic chemotherapy and prophylactic CNS chemotherapy. By comparing three groups of ALL children (i.e., patients whose diagnosis was recent, patients 1 year postdiagnosis currently receiving CNS prophylactic chemotherapy, and off-therapy patients who had been treated with chemotherapy for 3 years) and their healthy siblings on measures of sequential and simultaneous processing, we were able to examine the effects of CNS prophylactic and systemic chemotherapy at various points during treatment. Results indicate that the children who had received a 3-year course of chemotherapy (off-therapy patients) were more impaired on tasks involving right-hemisphere simultaneous processing than were sibling controls or ALL children whose diagnosis was recent and whose treatment had just begun. Age at diagnosis did not interact with the effects of chemotherapy. These findings support the need for continued evaluation of cognitive functioning in ALL, children receiving CNS prophylactic chemotherapy to identify potential harmful neurocognitive sequelae of treatment.

Non-Hodgkin's lymphoma presenting as a rectal polyp in a child.

Primary lymphoma of the rectum is extremely rare in children. We report here a 10-year-old boy with localized non-Hodgkin's lymphoma, discovered within a rectal polyp. The literature on childhood rectal lymphomas is reviewed. This case illustrates the importance of considering the possibility of malignancy with rectal polyps, even in children.

Ovarian tumors in relapsing acute lymphoblastic leukemia: a review of 23 cases.

Five cases of relapsing acute lymphocytic leukemia (ALL) presenting as an ovarian tumor have been treated at this institution, representing the largest reported series. In a review of the literature we identified 18 additional cases of ovarian leukemic relapse. Together, these 23 patients form the basis for this report. Abdominal pain is the most common presenting symptom of ovarian leukemia. An abdominal mass is usually palpable, and at least four patients had hydronephrosis. Nine patients had documented bilateral ovarian involvement; however, bilateral disease was not a poor prognostic sign. Most ovarian relapses occurred more than 36 months after the original diagnosis of ALL, with these "late'h relapsers responding more favorably to treatment than "early" relapsers. Definitive statements can not be made from a retrospective review of 23 case reports; however, salpingooophorectomy had no obvious advantage over simple biopsy, and there was no obvious advantage to the routine use of radiation therapy. Most failures in treating ovarian leukemia occurred within 2 years. Most failures were systemic rather than local, illustrating the need for aggressive multiagent systemic chemotherapy. Survival after ovarian leukemic relapse is possible, with eight of the 23 patients alive and in complete continuous remission following the ovarian relapse (median follow-up since relapse, 42 months; range, 2 to 135+ months). With the use of more intensive chemotherapy in recent protocols, the frequency of ovarian leukemic relapses appears to be decreasing. At this institution, no child with ALL diagnosed in the 1980s has subsequently developed an ovarian relapse.

[Caudal regression syndrome. Lumbo-sacral agenesis]. / Síndrome de regressão caudal agenesia lombo-sagrada.

Retrospective analysis of six cases of caudal regression syndrome, classified in accordance with vertebral envolvement. The degree of vertebral agenesis, morphology and topography of the conus medularis, neurologic implications (motor, sensitive and autonomous) and associated malformations, of particular importance in some situations of little significant vertebral agenesis are analyzed. Associations with eventual predisponent factors are sought.

[Medullary and intracranial metastases of myxopapillary ependymoma]. / Metástases medulares e encefálicas de ependimomas mixopapilares.

After a brief introduction about the clinical, histological and therapeutic characteristics of myxopapillar spinal ependymoma of cone medullar and filum terminale, three cases with medullar and intracranial seeding of myxopapillar spinal ependymoma are retrospectively reviewed. Surgical resection was total in the child and partial in the adult cases and the histological results were myxopapillar. The diagnosis was made by CT and MRI between 1-2 months before surgical treatment. No extra-neural tumour was found. The mechanisms and factors that influence the seeding of this type of tumour are discussed. The most important literature is reviewed and the cases discussed. The authors stress the importance of surgery on prognosis and the need of an MRI of the whole neural-axis, particularly in children, and subtotal exeresis in adults.

Performance and limitations of steatosis biomarkers in patients with nonalcoholic fatty liver disease.

BACKGROUND: Several steatosis biomarkers are available with limited independent validation. AIM: To determine diagnostic value and limitations of several steatosis biomarkers using liver biopsy as reference standard in a large cohort of patients with suspected NAFLD. METHODS: Three hundred and twenty-four consecutive liver biopsies were included. Histological steatosis was categorised as none (<5%), mild (5-33%), moderate (33-66%) and severe (>66%). Five steatosis biomarkers were measured: fatty liver index (FLI), NAFLD liver fat score (NAFLD-LFS), hepatic steatosis index (HSI), visceral adiposity index (VAI) and triglyceride × glucose (TyG) index. RESULTS: Steatosis grades prevalence was: none 5%, mild 39%, moderate 30% and severe 27%. Except for VAI, the steatosis biomarkers showed a linear trend across the steatosis grades. However, their correlation with the histological amount of steatosis was only weak-moderate. All steatosis biomarkers had an adequate diagnostic accuracy for the presence of steatosis: AUROCs for FLI, LFS, HSI, VAI and TyG were 0.83, 0.80, 0.81, 0.92 and 0.90. However, their ability to quantify steatosis was poor: none of them distinguished between moderate and severe steatosis and the AUROCs for predicting steatosis >33% were 0.65, 0.72, 0.65, 0.59 and 0.59 for FLI, LFS, HSI, VAI and TyG. Both fibrosis and inflammation significantly confounded the association between steatosis biomarkers and steatosis. The steatosis biomarkers were all correlated with HOMA-IR, independent from histological steatosis. CONCLUSIONS: All five steatosis biomarkers can diagnose steatosis and are correlated with insulin resistance. They are confounded by fibrosis and inflammation, and do not accurately quantify steatosis; this may limit their clinical utility. More research is needed to identify truly independent and quantitative markers of steatosis.

A Portuguese case of Fukuyama congenital muscular dystrophy caused by a multi-exonic duplication in the fukutin gene.

Fukuyama congenital muscular dystrophy (FCMD) is one of the most common autosomal recessive diseases among the Japanese population, due to a founder mutation of the fukutin gene (FKTN). Mutations in FKTN are now being described in an increasing number of non-Japanese patients. We report a Portuguese child with FCMD. The diagnosis was supported by clinical, histological, magnetic resonance imaging (MRI) and genetic studies. Genetic analysis of FKTN by Multiplex Ligation Probe Amplification (MLPA) revealed a homozygous duplication from exon 4 to exon 7. This in-frame duplication was confirmed by cDNA analysis. To our knowledge this is the first report of a FCMD case caused by an intragenic gross exonic duplication in the FKTN gene. This report widens the clinical and mutational spectrum in FCMD and corroborates the importance of screening for large deletions and duplications in CMD patients.

Brain MRI findings as an important diagnostic clue in glutaric aciduria type 1.

Glutaric aciduria type 1 is an autosomal recessive disorder caused by deficiency of glutaryl-coenzyme A dehydrogenase, with accumulation of glutaric acid, 3-hydroxyglutaric acid and glutaconic acid. Increased blood glutarylcarnitine levels are the basis for identification of affected infants by newborn screening. Despite the highly variability, this disease usually presents with an acute encephalitis-like encephalopathy in infancy or childhood after a period of normal development. The characteristic neurological sequel is a complex movement disorder due to acute bilateral striatal injury. Frequently, the only abnormality preceding the first episode is a progressive macrocephaly. Although neuroimaging findings are quite variable, the widening of the Sylvian fissures combined with abnormalities of the basal ganglia in a child with macrocephaly should raise the suspicion of this diagnosis. We describe two patients in whom macrocephaly was the only presenting symptom and whose diagnosis was suggested by the brain MRI findings. Our purpose is to illustrate the clinical value of neuroimaging in the diagnosis of glutaric aciduria type 1 even before the onset of neurologic symptoms, which is particularly important if newborn screening is not available.

Progression from isolated steatosis to steatohepatitis and fibrosis in nonalcoholic fatty liver disease.

In patients with nonalcoholic fatty liver disease (NAFLD) isolated steatosis is considered a benign condition with no or minimal rate of progression, in contrast to nonalcoholic steatohepatitis (NASH) which can progress to cirrhosis. We report on a series of six patients with isolated steatosis on an initial liver biopsy, and NASH on a follow-up biopsy performed five years after. All but one of the initial biopsies were longer than 15 mm. At follow-up, inflammation and ballooning were present in all patients and mild fibrosis in three. All patients had one or more features of metabolic syndrome at baseline. Progression to steatohepatitis occurred independent of aminotransferase changes. Five patients experienced an increase in one or several metabolic risk factors during follow-up: body mass index, triglyceride levels, arterial hypertension and/or the HOMA index. One patient did not exhibit progression but was still exposed to metabolic risks factors at the end of follow-up. This report demonstrates that isolated steatosis is not necessarily a benign, non-progressive condition. Current recommendations for the absence of hepatic monitoring in patients with isolated steatosis are not adequate. If metabolic risk factors persist or deteriorate during follow-up and/or non-invasive markers suggest disease progression, a control liver biopsy should be considered.

Superficial siderosis of the central nervous system.

Superficial siderosis of the central nervous system (CNS) is a rare entity characterized by the deposition of hemosiderin in the leptomeninges. In most cases it is caused by chronic and recurrent bleeding into the subarachnoid space as a subclinical form and for long periods of time. The cases described in the literature are associated with tumors, aneurysms, arteriovenous malformations, changes in post-surgical, traumatic cervical and brachial plexus injuries. However, the cause of bleeding is unclear in 40-50% of cases. This report describes the case of a 38-year-old man with a history of trauma with a complete lesion of the left brachial plexus. The patient presented progressively worsening gait imbalance, bilateral deafness, tinnitus and memory loss over two years. Neurological examination disclosed bilateral hearing loss, left upper limb plegia with atrophy of muscle mass, spastic paraparesis with pyramidal signs and gait ataxia. The analytical/genetic study was consistent with hereditary hemochromatosis. In addition to typical findings of siderosis, MR disclosed pseudomeningocele while CT angiography and angiography revealed an aneurysm of the internal carotid artery. Although rare, we should be aware of superficial siderosis especially in imaging studies in patients with deafness or ataxia and in those with lesions of the brachial plexus. The imaging signals are subtle and can easily go unrecognized. The radiological investigation must be extensive to find the primary cause.

Increased plasma level of clotting factors VII and X in hyperlipoproteinemia.

When compared to values obtained in healthy normal-weight normolipidemic controls, the combined activities of clotting factors VII and XI, as well as serum cholinesterase were found to be significantly higher in hyperlipidemic and especially in hypertriglyceridemic subjects. The levels of the vitamin K-dependent clotting factors are positively correlated with the concentration of serum cholesterol, the logarithm of serum triacylglycerol level and serum cholinesterase activity. Based on these data as well as on previous observations concerning an increased plasma level of other liver secretion enzymes in endogenous hypertriglyceridemia, a possible interrelationship between accelerated turnover of lipoproteins, enhanced hepatic protein synthesis and thromboatherosclerosis is suggested.