Is idiopathic intracranial hypertension without papilledema a risk factor for migraine progression?

The association of chronic migraine (CM) with an idiopathic intracranial hypertension without papilledema (IIHWOP), although much more prevalent than expected in clinical series of CM sufferers, is not included among the risk factors for migraine progression. We discuss the available evidence supporting the existence of a pathogenetic link between CM and idiopathic intracranial hypertensive disorders and suggest a causative role for IIHWOP in migraine progression

On Generalizations of Network Design Problems with Degree Bounds

Iterative rounding and relaxation have arguably become the method of choice in dealing with unconstrained and constrained network design problems. In this paper we extend the scope of the iterative relaxation method in two directions: (1) by handling more complex degree constraints in the minimum spanning tree problem (namely, laminar crossing spanning tree), and (2) by incorporating `degree bounds' in other combinatorial optimization problems such as matroid intersection and lattice polyhedra. We give new or improved approximation algorithms, hardness results, and integrality gaps for these problems.Comment: v2, 24 pages, 4 figure

Perampanel Confirms to Be Effective and Well-Tolerated as an Add-On Treatment in Patients With Brain Tumor-Related Epilepsy (PERADET Study)

Background: Epilepsy is one of the most common symptoms of brain tumors. It is often drug resistant and generally worsen patients' quality of life (QoL). Brain tumors release glutamate among other mediators, contributing to seizures onset, and this is accompanied by an increased AMPA receptors' expression on neuronal cells' membrane. Perampanel (PER) is a relatively new antiseizure medication (ASM) that acts as a selective non-competitive AMPA receptors' antagonist. Given its mechanism of action, we aimed to evaluate through a prospective, observational study, the efficacy and safety of PER as an add-on treatment in patients with brain tumor-related epilepsy (BTRE). The study was called PERADET. Methods: Thirty-six adult patients (intention to treat population-ITT) affected by BTRE, with uncontrolled focal-onset seizures treated with 1–3 ASMs were recruited from four Italian epilepsy centers. Perampanel was added-on, titrated from 2 mg/day up to a maximum of 12 mg/day. Tumor history and therapy, type, and seizures frequency, previous ASMs were collected at 6 and 12 months. A battery of QoL tests were administered at baseline, 6 and 12 months. The primary endpoint was to assess the efficacy of PER by calculating the percent change in seizure frequency and the responder rate. The secondary endpoints were tolerability, retention rate at 12 months, and improvement in quality of life. Results: At the end of 12 months, 21 patients (per protocol population-PP) were available for evaluation. In this population the responder rate (percentage of patients who experienced a 50% or greater reduction in seizure frequency) was 90.4 with 33.3% of patients being seizure-free. In the ITT group the responder rate at the end of 12 months was 66.6 with 25% of patients being seizure free. PER was well tolerated (30.6% of patients experienced an adverse event, none was severe; three needed a treatment interruptions). Conclusions: Our study indicate that PER may be efficacious against BTRE as suggested by its mechanism of action and our current knowledge on mechanisms of brain tumor epileptogenicity. Trial Registration Number (TRN): (Prot. n° 0008872.25-06-2019); RS 919/17

Multicystic encephalomalacia as an end-stage finding in abusive head trauma

Abusive head trauma (AHT) is one of the most severe forms of physical child abuse. If a child initially survives severe AHT the neurological outcome can be poor. In recent years several children were seen who developed multicystic encephalomalacia (MCE) after documented severe AHT. A search of the Netherlands Forensic Institute database in The Hague was performed. Inclusion criteria were cases of AHT between 1999 and 2010 where the child was under the age of 1 year old at the time of trauma. Trauma mechanism and radiological information were collected. Five children, three boys and two girls (mean age 57 days, range 8–142 days) who developed cystic encephalomalacia after inflicted traumatic brain injury were included. Survival ranged from 27 to 993 days. In all cases judicial autopsy was performed. All cases came before court and in each case child abuse was considered to be proven. In two cases the perpetrator confessed, during police interrogation, to shaking of the child only. Although a known serious outcome, this is one of the few reports on MCE as a result of AHT. In all cases the diagnosis was confirmed at autopsy

International consensus on (ICON) anaphylaxis

ICON: Anaphylaxis provides a unique perspective on the principal evidence-based anaphylaxis guidelines developed and published independently from 2010 through 2014 by four allergy/immunology organizations. These guidelines concur with regard to the clinical features that indicate a likely diagnosis of anaphylaxis -- a life-threatening generalized or systemic allergic or hypersensitivity reaction. They also concur about prompt initial treatment with intramuscular injection of epinephrine (adrenaline) in the mid-outer thigh, positioning the patient supine (semi-reclining if dyspneic or vomiting), calling for help, and when indicated, providing supplemental oxygen, intravenous fluid resuscitation and cardiopulmonary resuscitation, along with concomitant monitoring of vital signs and oxygenation. Additionally, they concur that H1-antihistamines, H2-antihistamines, and glucocorticoids are not initial medications of choice. For self-management of patients at risk of anaphylaxis in community settings, they recommend carrying epinephrine auto-injectors and personalized emergency action plans, as well as follow-up with a physician (ideally an allergy/immunology specialist) to help prevent anaphylaxis recurrences. ICON: Anaphylaxis describes unmet needs in anaphylaxis, noting that although epinephrine in 1 mg/mL ampules is available worldwide, other essentials, including supplemental oxygen, intravenous fluid resuscitation, and epinephrine auto-injectors are not universally available. ICON: Anaphylaxis proposes a comprehensive international research agenda that calls for additional prospective studies of anaphylaxis epidemiology, patient risk factors and co-factors, triggers, clinical criteria for diagnosis, randomized controlled trials of therapeutic interventions, and measures to prevent anaphylaxis recurrences. It also calls for facilitation of global collaborations in anaphylaxis research. In addition to confirming the alignment of major anaphylaxis guidelines, ICON: Anaphylaxis adds value by including summary tables and citing 130 key references. It is published as an information resource about anaphylaxis for worldwide use by healthcare professionals, academics, policy-makers, patients, caregivers, and the public

Hyaluronidase of Bloodsucking Insects and Its Enhancing Effect on Leishmania Infection in Mice

Hyaluronidases are enzymes degrading the extracellular matrix of vertebrates. Bloodsucking insects use them to cleave the skin of the host, enlarge the feeding lesion and acquire the blood meal. In addition, resulting fragments of extracellular matrix modulate local immune response of the host, which may positively affect transmission of vector-borne diseases, including leishmaniasis. Leishmaniases are diseases with a wide spectrum of clinical forms, from a relatively mild cutaneous affection to life-threatening visceral disease. Their causative agents, protozoans of the genus Leishmania, are transmitted by phlebotomine sand flies. Sand fly saliva was described to enhance Leishmania infection, but the information about molecules responsible for this exacerbating effect is still very limited. In the present work we demonstrated hyaluronidase activity in salivary glands of various Diptera and in fleas. In addition, we showed that hyaluronidase exacerbates Leishmania lesions in mice and propose that salivary hyaluronidase may facilitate the spread of other vector-borne microorganisms

Educational paper: Abusive Head Trauma Part I. Clinical aspects

Abusive Head Trauma (AHT) refers to the combination of findings formerly described as shaken baby syndrome. Although these findings can be caused by shaking, it has become clear that in many cases there may have been impact trauma as well. Therefore a less specific term has been adopted by the American Academy of Pediatrics. AHT is a relatively common cause of childhood neurotrauma with an estimated incidence of 14–40 cases per 100,000 children under the age of 1 year. About 15–23% of these children die within hours or days after the incident. Studies among AHT survivors demonstrate that approximately one-third of the children are severely disabled, one-third of them are moderately disabled and one-third have no or only mild symptoms. Other publications suggest that neurological problems can occur after a symptom-free interval and that half of these children have IQs below the 10th percentile. Clinical findings are depending on the definitions used, but AHT should be considered in all children with neurological signs and symptoms especially if no or only mild trauma is described. Subdural haematomas are the most reported finding. The only feature that has been identified discriminating AHT from accidental injury is apnoea. Conclusion: AHT should be approached with a structured approach, as in any other (potentially lethal) disease. The clinician can only establish this diagnosis if he/she has knowledge of the signs and symptoms of AHT, risk factors, the differential diagnosis and which additional investigations to perform, the more so since parents seldom will describe the true state of affairs spontaneously

Common Variants in the Type 2 Diabetes KCNQ1 Gene Are Associated with Impairments in Insulin Secretion During Hyperglycaemic Glucose Clamp

Background: Genome-wide association studies in Japanese populations recently identified common variants in the KCNQ1 gene to be associated with type 2 diabetes. We examined the association of these variants within KCNQ1 with type 2 diabetes in a Dutch population, investigated their effects on insulin secretion and metabolic traits and on the risk of developing complications in type 2 diabetes patients. Methodology: The KCNQ1 variants rs151290, rs2237892, and rs2237895 were genotyped in a total of 4620 type 2 diabetes patients and 5285 healthy controls from the Netherlands. Data on macrovascular complications, nephropathy and retinopathy were available in a subset of diabetic patients. Association between genotype and insulin secretion/action was assessed in the additional sample of 335 individuals who underwent a hyperglycaemic clamp. Principal Findings: We found that all the genotyped KCNQ1 variants were significantly associated with type 2 diabetes in our Dutch population, and the association of rs151290 was the strongest (OR 1.20, 95% CI 1.07-1.35, p = 0.002). The risk C-allele of rs151290 was nominally associated with reduced first-phase glucose-stimulated insulin secretion, while the non-risk T-allele of rs2237892 was significantly correlated with increased second-phase glucose-stimulated insulin secretion (p = 0.025 and 0.0016, respectively). In addition, the risk C-allele of rs2237892 was associated with higher LDL and total cholesterol levels (p = 0.015 and 0.003, respectively). We found no evidence for an association of KCNQ1 with diabetic complications. Conclusions: Common variants in the KCNQ1 gene are associated with type 2 diabetes in a Dutch population, which can be explained at least in part by an effect on insulin secretion. Furthermore, our data suggest that KCNQ1 is also associated with lipid metabolism

PDCD10 gene mutations in multiple cerebral cavernous malformations

Cerebral cavernous malformations (CCMs) are vascular abnormalities that may cause seizures, intracerebral haemorrhages, and focal neurological deficits. Familial form shows an autosomal dominant pattern of inheritance with incomplete penetrance and variable clinical expression. Three genes have been identified causing familial CCM: KRIT1/CCM1, MGC4607/CCM2, and PDCD10/CCM3. Aim of this study is to report additional PDCD10/CCM3 families poorly described so far which account for 10-15% of hereditary cerebral cavernous malformations. Our group investigated 87 consecutive Italian affected individuals (i.e. positive Magnetic Resonance Imaging) with multiple/familial CCM through direct sequencing and Multiplex Ligation-Dependent Probe Amplification (MLPA) analysis. We identified mutations in over 97.7% of cases, and PDCD10/CCM3 accounts for 13.1%. PDCD10/CCM3 molecular screening revealed four already known mutations and four novel ones. The mutated patients show an earlier onset of clinical manifestations as compared to CCM1/CCM2 mutated patients. The study of further families carrying mutations in PDCD10/CCM3 may help define a possible correlation between genotype and phenotype; an accurate clinical follow up of the subjects would help define more precisely whether mutations in PDCD10/CCM3 lead to a characteristic phenotype