Genome-wide association study confirms extant PD risk loci among the Dutch

In view of the population-specific heterogeneity in reported genetic risk factors for Parkinson's disease (PD), we conducted a genome-wide association study (GWAS) in a large sample of PD cases and controls from the Netherlands. After quality control (QC), a total of 514,799 SNPs genotyped in 772 PD cases and 2024 controls were included in our analyses. Direct replication of SNPs within SNCA and BST1 confirmed these two genes to be associated with PD in the Netherlands (SNCA, rs2736990: P = 1.63 × 10(-5), OR = 1.325 and BST1, rs12502586: P = 1.63 × 10(-3), OR = 1.337). Within SNCA, two independent signals in two different linkage disequilibrium (LD) blocks in the 3' and 5' ends of the gene were detected. Besides, post-hoc analysis confirmed GAK/DGKQ, HLA and MAPT as PD risk loci among the Dutch (GAK/DGKQ, rs2242235: P = 1.22 × 10(-4), OR = 1.51; HLA, rs4248166: P = 4.39 × 10(-5), OR = 1.36; and MAPT, rs3785880: P = 1.9 × 10(-3), OR = 1.19).     

Validation of the Edinburgh Postnatal Depression Scale as a screening tool for postpartum depression in a clinical sample in Hungary

Background

the purpose of the study was to assess the validity of the 10-item Edinburgh Postnatal Depression Scale (EPDS) in screening for postnatal depression (PND) in Hungary.

Methods

between July 2010 and March 2011, a sample of 266 women attending a routine check-up at six weeks post partum completed the newly translated Hungarian version of the EPDS at the Department of Obstetrics and Gynecology, University of Szeged, Hungary, and underwent clinical assessments based on the Structured Clinical Interview for DSM-IV disorders (SCID-I).

Findings

eight (3.0%) of the mothers were diagnosed with major postnatal depression, and 36 (13.5%) with minor depression on the basis of the SCID. Internal consistency of the Hungarian version of the EPDS was satisfactory (Cronbach α coefficients ≥0.727). The best cut-off for major depression was 12/13, with a sensitivity of 100.0%, and a specificity of 97.7%. The area under the ROC curve was found significant for combined (major+minor) depression as well and at a cut-off of 7/8 indicated a sensitivity of 72.7% and a specificity of 86.0%. A factor analysis suggested multidimensionality with two factors (anxiety and depression).

Conclusions

the EPDS showed good validity in the postnatal period in a clinical sample in Hungary.     

Nodule formation and desmoplasia in medulloblastomas-defining the nodular/desmoplastic variant and its biological behavior

Among the variants of medulloblastoma in the current WHO classification of nervous system tumors, the desmoplastic variant, which has been reported to constitute 5%-25% of pediatric medulloblastomas, is defined by its nodular collections of neurocytic cells bounded by desmoplastic internodular zones. We have studied the frequency, morphological features and biological behavior of medulloblastomas in two contemporaneous SIOP/UKCCSG trial cohorts of children with medulloblastomas, CNS9102 (n = 315) and CNS9204 (n = 35), focusing on tumors with nodular and desmoplastic phenotypes. In children aged 3-16 years (CNS9102), the nodular/desmoplastic medulloblastoma represented 5% of all tumors, while in infants aged <3 years (CNS9204) this variant represented 57% of medulloblastomas. Using iFISH to detect molecular cytogenetic abnormalities in medulloblastomas with a nodular architecture, we demonstrated distinct genetic profiles in desmoplastic and non-desmoplastic (classic and anaplastic) tumors; in particular, abnormalities of chromosome 17 occurred in the latter, but not the former. Significantly different outcomes were demonstrated for classic, nodular/desmoplastic and large cell/anaplastic medulloblastomas in both cohorts. In conclusion, the nodular/desmoplastic medulloblastoma appears to have clinical, genetic and biological characteristics that set it apart from other variants of this tumor.     

Characterisation of cannabinoid 1 receptor expression in the perikarya, and peripheral and spinal processes of primary sensory neurons

The cannabinoid 1 (CB1) receptor is expressed by a sub-population of primary sensory neurons. However, data on the neurochemical identity of the CB1 receptor-expressing cells, and CB1 receptor expression by the peripheral and central terminals of these neurons are inconsistent and limited. We characterised CB1 receptor expression in dorsal root ganglia (DRG) and spinal cord at the lumbar 4–5 level, as well as in the urinary bladder and glabrous skin of the hindpaw. About 1/3 of DRG neurons exhibited immunopositivity for the CB1 receptor, the majority of which showed positivity for the nociceptive markers calcitonin gene-related peptide (CGRP) or/and Griffonia (bandeiraea) simplicifolia IB4 isolectin-binding. Virtually all CB1 receptor-immunostained fibres showed immunopositivity for CGRP in the skin, while very few did in the urinary bladder. No CB1 receptor-immunopositive nerve fibres were IB4 positive in either peripheral tissue. Spinal laminae I and II-outer showed the highest density of CB1 receptor-immunopositive punctae, the majority of which showed positivity for CGRP or/and IB4 binding. These data indicate that a major sub-population of nociceptive primary sensory neurons expresses CB1 receptors that are transported to both peripheral and central terminals of these cells. Therefore, the present data suggest that manipulation of endogenous CB1 receptor agonist levels in these areas may significantly reduce nociceptive input into the spinal cord.     

A comparative study of short‐ and long‐TE 1H MRS at 3 T for in vivo detection of 2‐hydroxyglutarate in brain tumors

2‐Hydroxyglutarate (2HG) is produced in gliomas with mutations of isocitrate dehydrogenase (IDH) 1 and 2. The ¹H resonances of the J‐coupled spins of 2HG are extensively overlapped with signals from other metabolites. Here, we report a comparative study at 3 T of the utility of the point‐resolved spectroscopy sequence with a standard short TE (35 ms) and a long TE (97 ms), which had been theoretically designed for the detection of the 2HG 2.25‐ppm resonance. The performance of the methods is evaluated using data from phantoms, seven healthy volunteers and 22 subjects with IDH‐mutated gliomas. The results indicate that TE = 97 ms provides higher detectability of 2HG than TE = 35 ms, and that this improved capability is gained when data are analyzed with basis spectra that include the effects of the volume localizing radiofrequency and gradient pulses. Copyright © 2013 John Wiley & Sons, Ltd.     

Hyperferritinemia is Associated with Serologic Antiphospholipid Syndrome in SLE Patients

Ferritin may play a direct role on the immune system. We sought to determine if elevated levels of ferritin in lupus patients correlate with disease activity and organ involvement in a large cohort. Ferritin levels (gender and age adjusted) were assessed in 274 lupus serum samples utilizing the LIASON Ferritin automated immunoassay method. Significant disease activity was determined if European Consensus Lupus Activity Index (ECLAM)?>?2 or Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)?>?4. Utilizing an EXCEL database, we compared elevated ferritin levels to manifestations grouped by organ involvement, serology, and previous therapy. The patients were predominantly female (89%), median age was 37 years old, and disease duration was 10.6?±?7.7 years. Hyperferritinemia was found in 18.6% of SLE patients. Compared to subjects with normal ferritin levels, a significantly greater proportion of patients with hyperferritinemia had thrombocytopenia (15.4% vs. 33.3%, p?=?0.003) and lupus anticoagulant (11.3% vs. 29.0%, p?=?0.01). Additionally, compared to normoferritinemic subjects, hyperferritinemic subjects had significantly higher total aCL (99.7?±?369 vs. 30.9?±?17.3 GPI, p?=?0.02) and aCL IgM antibody levels (75.3?±?357.4 vs. 9.3?±?10.3 GPI, p?=?0.02), and marginally lower aCL IgG antibody levels (9.2?±?4.9 vs. 9.7?±?3.9 GPI, p?=?0.096). While the ECLAM score significantly correlated with hyperferritinemia (p?=?0.04), the SLEDAI score was marginally associated with hyperferritinemia (p?=?0.1). Serositis was marginally associated with hyperferritinemia, but not with other manifestations. An association with serologic APS was encountered. Hyperferritinemia was associated with thrombocytopenia, lupus anticoagulant, and anti-cardiolipin antibodies suggest that it may be an early marker for secondary antiphospholipid syndrome in SLE patients.     

Current status of epilepsy health care for adult patients from Central and Eastern European Union Countries—A survey of members of the Central Europe Epilepsy Experts Working Group

PurposeThe aim of this survey was to review and compare the current approaches to epilepsy management in Central and Eastern EU (CEEU) countries.MethodThe questionnaire was sent to ten invited experts from Bulgaria, Czech Republic, Estonia, Hungary, Latvia, Lithuania, Poland, Romania, Slovakia, and Slovenia. It focused on the treatment of adults.ResultsThe number of neurologists and epilepsy reference centers is highly variable in CEEU countries. None of the analyzed states has a formal specialization in epileptology. No universal state-approved criteria for reference centers exist in Czech Republic, Estonia, Hungary, Latvia, and Slovenia. Generally, the protocols for epilepsy treatment in CEEU countries, including drug-resistant epilepsy, are in accordance with international guidelines; however, most countries have their own national standards of care and some have local clinical guidelines. Also, the reimbursement systems for antiepileptic drugs in CEEU countries are highly variable. Seven countries have epilepsy surgery centers. The costs of epilepsy surgeries are fully reimbursed, procedures performed abroad may also be covered. The length of time spent on waiting lists for surgery following the completion of preoperative investigations varies from two weeks to three years. The fraction of patients who qualified and were operated on within 12 months ranges from 20% to 100%.ConclusionThe lack of unified procedures pertaining to the evaluation and therapy of epilepsy is reflected by marked differences in access to treatment modalities for patients from CEEU countries.     

Anomalous origin of the right coronary artery from the pulmonary artery

Anomalous origin of the right coronary artery from the pulmonary artery was diagnosed by selective left coronary artery angiography in an asymptomatic five-year-old boy with a continuous murmur. The anomalous coronary artery, along with a cuff of the pulmonary artery, was re-implanted into the aorta. The patient is asymptomatic five years postoperatively.     

Ventriculosubgaleal shunt in the treatment of posthemorrhagic and postinfectious hydrocephalus of premature infants

Purpose

The aim of the study was to compare the characteristics of ventriculosubgaleal shunts during the clinical course of posthemorrhagic and postinfectious hydrocephalus in the neonatal period.

Patients and methods

The study comprised 102 premature babies in whom subgaleal shunt was consecutively inserted between 2006 and 2011. Seventy-two patients had posthemorrhagic hydrocephalus (mean gestational age 27.3?±?2.1 weeks, mean birth weight 1,036.9?±?327.7 g, mean age at insertion 51.4?±?56.2 days) and 30 patients were operated postinfectiously (27.5?±?2.2 weeks, 1,064.7 g?±?310.7 g, 115.9?±?47.8 days).

Results

The mean survival of subgaleal shunts was 87.9 days for the posthemorrhagic group and 75.6 days for the postinfectious group. Only six infants (8.3 %) did not need ventriculoperitoneal shunts later, all posthemorrhagic. There were meaningful differences between two groups with regard to ventriculosubgaleal shunt-related infections (8.3 % in posthemorrhagic versus 20.0 % in postinfectious) and shunt revision rate (6.9 % in posthemorrhagic versus 13.3 % in postinfectious), but these were not statistically significant. The need of ventriculoscopic procedures was notably more frequent in postinfectious group (1.4 versus 23.3 %).

Conclusion

In premature infants with ventriculomegaly, the subgaleal shunt is an effective temporary diversion tool. The complications were less with posthemorrhagic than with postinfectious hydrocephalus. With previous severe infections of prematures, the risk for complications regarding infection and obstruction will be 2.75 and 2.06 (odds ratios) times higher and more frequent need of ventriculoscopic procedures should be considered (odds ratio 21.6).