Mild encephalitis/encephalopathy with a reversible splenial lesion associated with systemic Mycoplasma pneumoniae infection in North America: a case report.

BACKGROUND: Mild encephalitis/encephalopathy with reversible splenial lesion is a clinical-radiological entity found to occur in the setting of an acute systemic inflammatory state with isolated lesions of the splenium of the corpus callosum and mild encephalopathy. Mild encephalitis/encephalopathy with reversible splenial lesion is commonly found to occur in children in the setting of viral infections. It has rarely been associated with Mycoplasma pneumoniae in the United States, unlike in Eastern and Southern Asia where this is much more prominent. CASE PRESENTATIONS: A 5-year-old African-American boy with autism spectrum disorder presented to our emergency department with acute onset intractable vomiting, diarrhea, and abnormal tensing movements for 2 days, following a 6-day period of fatigue, fever, and spastic abdominal pain. Emergent work-up in our department ruled out acute gastrointestinal pathologies. Given the high fevers and encephalopathy, there was concern for meningitis or encephalitis. His cerebrospinal fluid profile was concerning for viral meningitis, however extensive infectious workup was negative. Magnetic resonance imaging of his brain demonstrated a T2 fluid-attenuated inversion recovery sequence hyperintensity in the splenium of the corpus callosum, read as postictal changes by radiology. Continuous video electroencephalography demonstrated mild diffuse encephalopathy without electrographic correlate of his tensing episodes. He was determined to have mild encephalitis/encephalopathy with a reversible splenial lesion in the setting of a postinfectious etiology. He was treated with a single pulse-dose of intravenous methylprednisolone, following which he gradually returned to his baseline the next day. Repeat magnetic resonance imaging and cerebrospinal fluid evaluation demonstrated resolution of previous findings. He was ultimately diagnosed with an acute M. pneumoniae infection, which was determined to be the etiology of his mild encephalitis/encephalopathy with a reversible splenial lesion. CONCLUSIONS: The presentation of mild encephalitis/encephalopathy with a reversible splenial lesion is often nonspecific, with behavioral symptoms ranging from irritability to disturbances in consciousness. Its prevalence is higher in the pediatric population, and is thought to be more of an infection-associated encephalopathy syndrome in this group. The infections are typically viral, more so than bacterial. M. pneumoniae, a small, atypical bacterium lacking a peptidoglycan cell wall, is a common respiratory tract pathogen found in children. Despite infection being so rampant in the pediatric community, very few cases of M. pneumoniae-associated mild encephalitis/encephalopathy with a reversible splenial lesion in the United States have been reported. In Eastern and Southern Asian countries, however, M. pneumoniae-associated mild encephalitis/encephalopathy with a reversible splenial lesion is much more commonly reported. This difference may potentially lie in the prevalence of macrolide-resistant M. pneumoniae, which is significantly higher in Asian countries given more liberal antibiotic use in M. pneumoniae infections. Infections with macrolide-resistant M. pneumoniae are reportedly greater in severity and duration. This amplified state may suggest a correlation between intensity of inflammatory response and the development of mild encephalitis/encephalopathy with a reversible splenial lesion. Given the rarity of M. pneumoniae-associated mild encephalitis/encephalopathy with a reversible splenial lesion in the United States, much remains unknown regarding predilection and optimum treatment strategy. As rates of macrolide-resistant M. pneumoniae begin to rise in the United States, maintaining a high level of suspicion remains key in better understanding this unique phenomenon.

Atypical idiopathic intracranial hypertension presenting as cyclic vomiting syndrome: a case report.

BACKGROUND: Idiopathic intracranial hypertension is a disorder of increased intracranial pressure in the absence of cerebrospinal outflow obstruction, mass lesion, or other underlying cause. It is a rare phenomenon in prepubertal children and is most typically found in women of childbearing age. The classic presentation consists of headaches, nausea, vomiting, and visual changes; however, children present more atypically. We report a case of idiopathic intracranial hypertension in an otherwise healthy, 4-year-old child with atypical symptoms resembling those of cyclic vomiting syndrome. CASE PRESENTATION: A 4-year-old Caucasian, otherwise healthy, male child presented to our emergency department with episodic intermittent early-morning vomiting occurring once every 1-3 weeks without interepisodic symptoms, starting 10 months prior. With outpatient metabolic, autoimmune, endocrine, allergy, and gastroenterology work-up all unremarkable, he was initially diagnosed with cyclic vomiting syndrome. Discovery of mild optic nerve sheath distension on magnetic resonance imaging of the brain 10 months after symptom onset led to inpatient admission and a lumbar puncture notable for an opening pressure of 47 mmHg, with normal cell count and protein levels. He had no changes in visual acuity or optic disc edema on dilated fundoscopic examination. The patient was started on acetazolamide, with resolution of episodic emesis at his last follow-up visit 12 weeks after discharge. CONCLUSIONS: Idiopathic intracranial hypertension presents atypically in prepubescent children, with about one-fourth presenting asymptomatically, and only 13-52% presenting with "classic" symptoms. With a prevalence of only 0.6-0.7 per 100,000, much remains unknown regarding the underlying pathophysiology in this demographic. Cyclic vomiting syndrome, however, has a much higher prevalence in this age group, with a prevalence of 0.4-1.9 per 100. It is thought to be an idiopathic, periodic disorder of childhood, often linked to neurological conditions such as abdominal migraines, epilepsy, mitochondrial disorders, and structural lesions such as chiari malformation and posterior fossa tumors. While cyclic vomiting syndrome is thought to have a benign course, untreated idiopathic intracranial hypertension can have long-term detrimental effects, such as visual loss or even blindness. We present a case of idiopathic intracranial hypertension presenting with symptoms resembling cyclic vomiting syndrome in a 4-year-old child, diagnosed 10 months after initial onset of symptoms. We aim to demonstrate the need for a high level of clinical suspicion and the need for further investigation into underlying pathophysiology in this vulnerable population.

Communication of prostate cancer cells with bone cells via extracellular vesicle RNA; a potential mechanism of metastasis.

The role of extracellular vesicles (EVs) as vehicles for cell-to-cell communication between a tumour and its environment is a relatively new concept. The hypothesis that EVs may be critical in co-opting tissues by tumours to generate distant metastatic niches is particularly pertinent to prostate cancer (PCa), where metastatic-tropism to bone predominates over other tissue types. The potential role of EVs as a means of communication between PCa cells and cells of the bone stroma such as osteoblasts, is yet to be fully explored. In this study, we demonstrate that PCa cell EVs both enhance osteoblast viability and produce a significantly more supportive growth environment for PCa cells when grown in co-culture with EV-treated osteoblasts (p < 0.005). Characterisation of the RNA cargo of EVs produced by the bone-metastatic PCa cell line PC3, highlights the EV-RNA cargo is significantly enriched in genes relating to cell surface signalling, cell-cell interaction, and protein translation (p < 0.01). Using novel techniques to track RNA, we demonstrate the delivery of a set of PCa-RNAs to osteoblast via PCa-EVs and show the effect on osteoblast endogenous transcript abundance. Taken together, by using proof-of-concept studies we demonstrate for the first time the contribution of the RNA element of the PCa EV cargo, providing evidence to support PCa EV communication via RNA molecules as a potential novel route to mediate bone metastasis. We propose targeting PCa EVs could offer a potentially important preventative therapy for men at risk of metastatic PCa.

Beyond Stroke Prevention in Atrial Fibrillation: Exploring Further Unmet Needs with Rivaroxaban.

With improved life expectancy and the aging population, the global burden of atrial fibrillation (AF) continues to increase, and with AF comes an estimated fivefold increased risk of ischaemic stroke. Prophylactic anticoagulant therapy is more effective in reducing the risk of ischaemic stroke in AF patients than acetylsalicylic acid or dual-antiplatelet therapy combining ASA with clopidogrel. Non-vitamin K antagonist oral anticoagulants are the standard of care for stroke prevention in patients with non-valvular AF. The optimal anticoagulant strategy to prevent thromboembolism in AF patients who are undergoing percutaneous coronary intervention and stenting, those who have undergone successful transcatheter aortic valve replacement and those with embolic stroke of undetermined source are areas of ongoing research. This article provides an update on three randomized controlled trials of rivaroxaban, a direct, oral factor Xa inhibitor, that are complete or are ongoing, in these unmet areas of stroke prevention: oPen-label, randomized, controlled, multicentre study explorIng twO treatmeNt stratEgiEs of Rivaroxaban and a dose-adjusted oral vitamin K antagonist treatment strategy in patients with Atrial Fibrillation who undergo Percutaneous Coronary Intervention (PIONEER AF-PCI) trial; the New Approach riVaroxaban Inhibition of factor Xa in a Global trial vs Aspirin to prevenT Embolism in Embolic Stroke of Undetermined Source (NAVIGATE ESUS) trial and the Global study comparing a rivAroxaban-based antithrombotic strategy to an antipLatelet-based strategy after transcatheter aortIc vaLve rEplacement to Optimize clinical outcomes (GALILEO) trial. The data from these studies are anticipated to help address continuing challenges for a range of patients at risk of stroke.

The clinical characteristics of women with recurrent implantation failure.

Recurrent implantation failure (RIF) refers to failure to conceive after three or more in vitro fertilisation (IVF) or embryo transfer cycles. Implantation failure may be due to embryo or uterine factors. There are many controversies surrounding the investigation and management of this condition. The aim of our study was to describe the clinical characteristics and the outcome of investigations of a group of women with recurrent implantation failure. A total of 111 couples with RIF were managed in a dedicated clinic and investigated according to a clinic protocol. The frequency of abnormal investigations were as follows: high (≥ 10 IU/l) FSH, 14/107(13%); high free androgen index 6/78(8%); abnormal hysteroscopic findings 7/45(16%); hydrosalpinges 8/33(24%); persistently elevated ACA or tested positive for lupus anticoagulant 19/108 (18%); abnormal karyotype analysis 3/101(3%); hyperprolactinaemia 1/79(1%); abnormal thyroid function 4/100(4%) and tested positive for thyroid peroxidase antibody 10/104(10%). Specific treatments according to the results of investigation produced a live birth rate of 29%. It was concluded that the findings should help practitioners to construct suitable investigation protocols for the initial management of this condition.

Epigenetic control of fetal gene expression.

Each differentiated cell type has its own epigenetic signature, which reflects its genotype, developmental history, and environmental influences, and is ultimately reflected in the phenotype of the cell and organism. Some cells undergo major epigenetic 'reprogramming' during fetal development. The proper, or improper, handling of these highly sensitive periods may have significant short-term and long-term effects on the newborn and his/her progeny. This review highlights the impact of environmental and nutritional factors on the epigenome and the potential effect of epigenetic dysregulation on maternal and fetal pregnancy outcomes, as well as possible long-term implications.

Effects of growth hormone on in vitro maturation of germinal vesicle of human oocytes retrieved from small antral follicles.

PURPOSE: Evaluation of the effect of GH, administered in vivo, on in vitro maturation of human GV oocytes obtained from small follicles. METHODS: The study included 88 ICSI women stimulated with long agonist protocol. They were randomly allocated to two groups (Group 1, 44 women with 86 GV oocytes), were cotreated with GH (Group 2, no GH: 44 women with 67 GV oocytes). GV oocytes from small follicles were matured in vitro, injected, and their development observed. RESULTS: Resumption of meiosis was significantly higher in Group 1 compared to Group 2 (60 and 37.3% respectively). Significantly more M2 oocytes were obtained in Group 1 than in Group 2 (45.5 and 23.9% respectively). Fertilization rates were also significantly higher (51.9 and 18.8% respectively). No embryos were obtained in Group 2, whereas 21.1% of fertilized oocytes in Group 1 cleaved into class A embryos. CONCLUSION: In vivo administration of GH enhanced in vitro maturation and fertilization of human GV oocytes retrieved from small antral follicles.