An Unusual Location of Deep Venous Thrombosis Associated with Ischemic Stroke and Persistent Foramen Ovale

Up to 40% of ischemic strokes have no known cause (cryptogenic). The prevalence of persistent foramen ovale (PFO) amongst patients with cryptogenic stroke (CS) is twice as high as that of the normal population, therefore suggesting a causal relationship between the two entities. However, PFO by itself is not sufficient to cause stroke, as an embolic source is needed. This source is often unknown, making the causal relationship between CS and PFO hard to demonstrate. The most frequent, although still seldom, identifiable cause of embolism in an otherwise cryptogenic stroke associated with PFO is a deep venous thrombosis (DVT) of the lower extremities. Here, we present a unique case of brachiocephalic venous DVT associated with PFO and ischemic stroke in a young patient. As the search for DVT in patients with PFO and stroke is often limited to the lower extremities, this case may suggest that an unspecified number of DVTs are overlooked. Our report lends support to paradoxical embolism as a mechanism of stroke in patients with PFO and does, at least in selected cases, suggest a more detailed search for DVT beyond the lower extremities

Pengaruh Facilitated Tucking Dan Musik Terhadap Respon Nyeri Bayi Prematur Ketika Pengambilan Darah

Manajemen nyeri yang tidak terkontrol pada bayi akan mempengaruhi pertumbuhan dan perkembangan selanjutnya. Salah satu tindakan manajemen nyeri non-farmakologi yang aman bagi bayi prematur adalah facilitated tucking dan pemberian musik. Penelitian ini untuk mengidentifikasi pengaruh kombinasi fasilitated tucking dan musik dalam mengurangi respon nyeri dan durasi menangis bayi prematur saat pengambilan darah. Rancangan kuasi eksperimen dengan pos-ttest control group design dipilih. Sampel penelitian ini adalah 60 bayi prematur yang dirawat di rumah sakit dan dilakukan pengambilan darah. Uji hipotesis menggunakan independent t-test. Kelompok intervensi diberikan facilitated tucking dan musik ketika pengambilan darah. Pengukuran nyeri menggunakan Premature Infant Pain Profile (PIPP) dan durasi menangis diukur dalam detik. Hasil penelitian menunjukkan bahwa rata-rata skor nyeri bayi adalah 7,03 pada kelompok intervensi dan 12,4 pada kelompok kontrol. Rata-rata durasi menangis bayi pada kelompok intervensi adalah 68,5 detik dan kelompok kontrol adalah 105 detik. Uji t menunjukkan perbedaan yang bermakna skor nyeri p 0,000 (α=0,05) dan durasi menangis 0,009 (α=0,05) bayi premature antara kelompok intervensi dan kelompok kontrol. DIsimpulkan bahwa facilitated tucking dan musik telah mengurangi respon nyeri dan durasi tangisan bayi prematur ketika pengambilan darah

Role of glial 14-3-3 gamma protein in autoimmune demyelination

Background: The family of 14-3-3 proteins plays an important role in the regulation of cell survival and death. Here, we investigate the role of the 14-3-3 gamma (14-3-3 γ) subunit for glial responses in autoimmune demyelination. Methods: Expression of 14-3-3 γ in glial cell culture was investigated by reverse transcription polymerase chain reaction (RT-PCR) and immunocytochemistry. 14-3-3 γ knockout mice were subjected to murine myelin oligodendrocyte-induced experimental autoimmune encephalomyelitis (MOG-EAE), an animal model mimicking inflammatory features and neurodegenerative aspects of multiple sclerosis (MS). Results: Expression studies in cell culture confined expression of 14-3-3 γ to both, oligodendrocytes (OL) and astrocytes. RT-PCR analysis revealed an increased expression of 14-3-3 γ mRNA in the spinal cord during the late chronic phase of MOG-EAE. At that stage, EAE was more severe in 14-3-3 γ knockout mice as compared to age- and gender-matched controls. Histopathological analyses on day 56 post immunization (p.i.) revealed significantly enhanced myelin damage as well as OL injury and secondary, an increase in axonal injury and gliosis in 14-3-3 γ −/− mice. At the same time, deficiency in 14-3-3 γ protein did not influence the immune response. Further histological studies revealed an increased susceptibility towards apoptosis in 14-3-3 γ-deficient OL in the inflamed spinal cord. Conclusion: These data argue for a pivotal role of 14-3-3 γ-mediated signalling pathways for OL protection in neuroinflammation

VAV1 and BAFF, via NFκB pathway, are genetic risk factors for myasthenia gravis

Objective To identify novel genetic loci that predispose to early‐onset myasthenia gravis (EOMG) applying a two‐stage association study, exploration, and replication strategy. Methods Thirty‐four loci and one confirmation loci, human leukocyte antigen (HLA)‐DRA, were selected as candidate genes by team members of groups involved in different research aspects of MG. In the exploration step, these candidate genes were genotyped in 384 EOMG and 384 matched controls and significant difference in allele frequency were found in eight genes. In the replication step, eight candidate genes and one confirmation loci were genotyped in 1177 EOMG patients and 814 controls, from nine European centres. Results Allele frequency differences were found in four novel loci: CD86, AKAP12, VAV1, B‐cell activating factor (BAFF), and tumor necrosis factor‐alpha (TNF‐α), and these differences were consistent in all nine cohorts. Haplotype trend test supported the differences in allele frequencies between cases and controls. In addition, allele frequency difference in female versus male patients at HLA‐DRA and TNF‐α loci were observed. Interpretation The genetic associations to EOMG outside the HLA complex are novel and of interest as VAV1 is a key signal transducer essential for T‐ and B‐cell activation, and BAFF is a cytokine that plays important roles in the proliferation and differentiation of B‐cells. Moreover, we noted striking epistasis between the predisposing VAV1 and BAFF haplotypes; they conferred a greater risk in combination than alone. These, and CD86, share the same signaling pathway, namely nuclear factor‐kappaB (NFκB), thus implicating dysregulation of proinflammatory signaling in predisposition to EOMG

Genome-Wide Association Study of Late-Onset Myasthenia Gravis: Confirmation of TNFRSF11A and Identification of ZBTB10 and Three Distinct HLA Associations

To investigate the genetics of late-onset myasthenia gravis (LOMG), we conducted a genome-wide association study imputation of >6 million single nucleotide polymorphisms (SNPs) in 532 LOMG cases (anti-acetylcholine receptor [AChR] antibody positive; onset age ≥50 years) and 2,128 controls matched for sex and population substructure. The data confirm reported TNFRSF11A associations (rs4574025, P = 3.9 × 10−7, odds ratio [OR] 1.42) and identify a novel candidate gene, ZBTB10, achieving genome-wide significance (rs6998967, P = 8.9 × 10−10, OR 0.53). Several other SNPs showed suggestive significance including rs2476601 (P = 6.5 × 10−6, OR 1.62) encoding the PTPN22 R620W variant noted in early-onset myasthenia gravis (EOMG) and other autoimmune diseases. In contrast, EOMG-associated SNPs in TNIP1 showed no association in LOMG, nor did other loci suggested for EOMG. Many SNPs within the major histocompatibility complex (MHC) region showed strong associations in LOMG, but with smaller effect sizes than in EOMG (highest OR ∼2 versus ∼6 in EOMG). Moreover, the strongest associations were in opposite directions from EOMG, including an OR of 0.54 for DQA1*05:01 in LOMG (P = 5.9 × 10−12) versus 2.82 in EOMG (P = 3.86 × 10−45). Association and conditioning studies for the MHC region showed three distinct and largely independent association peaks for LOMG corresponding to (a) MHC class II (highest attenuation when conditioning on DQA1), (b) HLA-A and (c) MHC class III SNPs. Conditioning studies of human leukocyte antigen (HLA) amino acid residues also suggest potential functional correlates. Together, these findings emphasize the value of subgrouping myasthenia gravis patients for clinical and basic investigations and imply distinct predisposing mechanisms in LOMG

Contrasting disease patterns in seropositive and seronegative neuromyelitis optica: A multicentre study of 175 patients

BACKGROUND: The diagnostic and pathophysiological relevance of antibodies to aquaporin-4 (AQP4-Ab) in patients with neuromyelitis optica spectrum disorders (NMOSD) has been intensively studied. However, little is known so far about the clinical impact of AQP4-Ab seropositivity. OBJECTIVE: To analyse systematically the clinical and paraclinical features associated with NMO spectrum disorders in Caucasians in a stratified fashion according to the patients' AQP4-Ab serostatus. METHODS: Retrospective study of 175 Caucasian patients (AQP4-Ab positive in 78.3%). RESULTS: Seropositive patients were found to be predominantly female (p 1 myelitis attacks in the first year were identified as possible predictors of a worse outcome. CONCLUSION: This study provides an overview of the clinical and paraclinical features of NMOSD in Caucasians and demonstrates a number of distinct disease characteristics in seropositive and seronegative patients