Childhood encephalitis in Sweden: Etiology, clinical presentation and outcome

Acute encephalitis is a relatively uncommon but potentially harmful CNS inflammation usually caused by infection. The diagnosis is difficult to establish and the etiology often remains unclear. Furthermore, the long-term prognosis of acute encephalitis in children is poorly described. In this study, we characterize childhood encephalitis from a Swedish perspective in regard to etiology, clinical presentation and sequele. We retrospectively studied all children (n=93) who were admitted for acute encephalitis at Karolinska University Hospital in Stockholm during 2000-2004. A confirmed etiological agent was identified in eight cases and a probable one in 37; in 48 cases no etiological agent could be found. Tick-borne encephalitis virus, enterovirus, respiratory syncytial virus, varicella zoster virus and influenza virus predominated and represented 67% of all the confirmed or probable etiologies. Encephalopathy was present in 80% of the children, 81% had fever, 44% had focal neurological findings, and seizures occurred in 40%. EEG abnormalities were seen in 90% and abnormal neuroimaging was present in 30%. The cerebrospinal fluid showed pleocytosis in 55%. There was no mortality, but 60% of the children had persisting symptoms at the time of discharge, 41% of which were moderate to severe. We conclude that the etiology of encephalitis among Swedish children is at large the same as in other European countries with similar vaccination programs. Fever and encephalopathy were seen in a majority of children and the most sensitive tool for making the diagnosis was EEG examination. Furthermore, many children display persisting sequele at discharge for which the strongest predictive factor was focal neurological findings at presentation.     

Cytomegalovirus Infection Incidence and Risk Factors Across Diverse Hematopoietic Cell Transplantation Platforms Using a Standardized Monitoring and Treatment Approach: A Comprehensive Evaluation from a Single Institution

Human cytomegalovirus (CMV) infection and disease remains a significant cause of morbidity and mortality for hematopoietic cell transplantation (HCT) recipients. Disruption of or weak reconstitution of virus-specific cellular immune function, such as with certain HCT approaches, poses significant risk for CMV-related complications. The incidence of and risk factors for CMV infection and the nature of CMV disease were evaluated retrospectively among 356 consecutive HCT recipients transplanted at the National Institutes of Health using all graft sources, including bone marrow, peripheral blood stem cell (PBSC), and umbilical cord blood (UCB), and a range of in vivo and ex vivo approaches for graft-versus-host disease (GVHD) prophylaxis. The cumulative incidence of CMV infection was higher for CMV-seropositive recipients at 33%, regardless of donor CMV serostatus. Patients transplanted with CMV-seropositive donors had a significantly shorter duration of antiviral therapy. Among graft sources UCB was associated with the highest cumulative incidence of CMV infection at 65% and significantly longer treatment duration at a median of 36days, whereas PBSC HCT was associated with the lowest incidence at 26% and the shortest CMV treatment duration at a median of 21days. There were significant differences in the cumulative incidence of CMV infection by T cell manipulation strategy when systemic steroids were included as a risk-modifying event. Over one-third of CMV infections occurred in the setting of systemic steroid administration. CMV disease occurred in 5% of HCT recipients, with 70% of cases in the setting of treatment for GVHD. Although factors related to serostatus, graft source, and GVHD prophylaxis were associated with varied CMV infection incidence, unplanned post-HCT corticosteroid therapy contributed greatly to the incidence of both CMV infection and disease across HCT approaches, highlighting this post-HCT intervention as a key time to potentially tailor the approach to monitoring, preemptive therapy, and even prophylaxis.     

A longitudinal study of maternal serum inhibin-A, inhibin-B, activin-A, activin-AB, pro-alphaC and follistatin during pregnancy

Maternal serum concentrations of inhibin-A, inhibin-B, activin-A, activin-AB, pro-alphaC-related inhibin forms, total follistatin, steroids and gonadotrophins were measured longitudinally in six normal singleton pregnancies. Maternal venous blood was collected randomly during a spontaneous follicular phase prior to donor insemination, at 5, 7, 9, 11, 16, 20, 24, 28, 32 and 36 weeks after the first missed menses and in the early puerperium. Steroid and gonadotrophin profiles conformed to previous reports. While at week 5 of gestation inhibin-A, activin-A and follistatin concentrations were similar to those at the follicular phase, all three increased progressively (P < 0.001) to maximal concentrations in week 36: approximately 48-fold (3740 +/- 1349 ng inhibin-A/ml), approximately 22-fold (6109 +/- 1443 ng activin-A/ml) and approximately 10-fold (3563 +/- 418 ng follistatin/ml) higher. Pro- alphaC concentrations reached a maximum in weeks 5 (approximately 5- fold, P < 0.001) and 36 (1027 +/- 174 pg/ml, P < 0.01). Inhibin-B (71 +/- 23 pg/ml prior to pregnancy) was undetectable (<12 pg/ml) between week 5-16 of gestation but increased slightly in the third trimester (26 +/- 7 pg/ml in week 36). Activin-AB was undetectable throughout pregnancy. Post-partum concentrations of inhibin-A (41 +/- 12 ng/ml), inhibin-B (<12 pg/ml), activin-A (950 +/- 149 pg/ml), pro-alphaC (128 +/- 22 pg/ml) and follistatin (990 +/- 79 ng/ml) were substantially lower than at week 36 of gestation. The activin-A:follistatin ratio increased from 0.5 in week 5 to 1.8 in week 36, suggesting that more free activin-A is available in the maternal circulation during late pregnancy.      

Sphincter electromyography in diagnosis of multiple system atrophy: technical issues

Possible technical reasons for the controversy over the role of sphincter electromyography (EMG) in the diagnosis of multiple system atrophy (MSA) were analyzed. In a review of the literature, a high sensitivity (>60%) was found reported in 11 studies that included late components, and no value of the test was found in 4 studies that excluded them. This was also corroborated in a pilot study of 5 patients with probable MSA. With late components included, the mean motor unit potential (MUP) duration was prolonged in all 4 patients with an adequate single-MUP analysis sample and, with late components excluded, in 2 of 5 patients on multi-MUP analysis. At least in diagnostic EMG of MSA patients, late components should be included in the measurement of MUP duration.     

Evidence that methylphenidate enhances the saliency of a mathematical task by increasing dopamine in the human brain

OBJECTIVE: Methylphenidate is the most commonly prescribed drug for attention deficit hyperactivity disorder (ADHD), yet its therapeutic mechanisms are poorly understood. The objective of this study was to assess if methylphenidate, by increasing dopamine (neurotransmitter involved in motivation) in brain, would enhance the saliency of an academic task, making it more interesting. METHOD: Healthy subjects (N=16) underwent positron emission tomography with [(11)C]raclopride (dopamine D(2) receptor radioligand that competes with endogenous dopamine for binding) to assess the effects of oral methylphenidate (20 mg) on extracellular dopamine in the striatum. The authors compared the effects of methylphenidate during an academic task (solving mathematical problems with monetary reinforcement) and a neutral task (passively viewing cards with no remuneration). In parallel, the effects of methylphenidate on the interest that the academic task elicited were also evaluated. RESULTS: Methylphenidate, when coupled with the mathematical task, significantly increased extracellular dopamine, but this did not occur when coupled with the neutral task. The mathematical task did not increase dopamine when coupled with placebo. Subjective reports about interest and motivation in the mathematical task were greater with methylphenidate than with placebo and were associated with dopamine increases. CONCLUSIONS: The significant association between methylphenidate-induced dopamine increases and the interest and motivation for the task confirms the prediction that methylphenidate enhances the saliency of an event by increasing dopamine. The enhanced interest for the task could increase attention and improve performance and could be one of the mechanisms underlying methylphenidate's therapeutic effects. These findings support educational strategies that make schoolwork more interesting as nonpharmacological interventions to treat ADHD.     

Transcobalamin II deficiency at birth

Transcobalamin II deficiency (# MIM 275350) is a rare, recessively inherited disorder of cobalamin transport that leads to intracellular cobalamin depletion with secondary impairment of methionine synthetase and methyl-malonyl CoA mutase activities. Affected individuals may suffer from long-term neurological sequelae if therapy with intramuscular hydroxocobalamin is not initiated promptly. We report two sisters with complete absence of transcobalamin due to homozygosity for a novel mutation (c.insC110) in the TCN2 gene that leads to a premature stop codon and non-functional protein. The older sister, now 4.5 years old, presented at 6 weeks of age with pancytopenia, protein losing enteropathy and a rapidly declining clinical course. Prompt therapy with 1 mg hydroxocobalamin/day led to full recovery within days. Her now 1.5 year old sister was diagnosed shortly after birth and was started on hydroxocobalamin prior to onset of clinical symptoms. Interestingly, urinary methylmalonic acid excretion was increased significantly during the first days of life suggesting that functional cobalamin deficiency is present also during fetal life, although not giving rise to clinical symptoms until well after birth.     

Clinical precursors of adolescent conduct disorder in children with attention-deficit/hyperactivity disorder

OBJECTIVE: To examine precursors of adolescent conduct disorder (CD) in children with attention-deficit/hyperactivity disorder (ADHD), investigating the significance of childhood oppositional defiant disorder (ODD) and ADHD. METHOD: A total of 151 children with ADHD recruited from child psychiatric and pediatric clinics were assessed through standardized diagnostic interviews at ages 6 to 13 years and in adolescence 5 years later. Using multiple regression analysis, we assessed baseline ODD diagnosis and ODD, CD, and ADHD symptom scores as clinical predictors of adolescent CD diagnosis and symptom scores. RESULTS: Childhood ODD (diagnosis and severity) was significantly associated with adolescent CD (diagnosis and severity), independent of childhood ADHD severity and childhood CD. Children with a diagnosis of ODD were almost three times more likely to develop CD in adolescence (odds ratio = 2.79, 95% CI 1.16-6.70, p = .02). Childhood ADHD severity predicted adolescent CD scores but not diagnosis of CD (although there was a trend toward association). The presence of at least one CD symptom in childhood predicted adolescent CD severity. CONCLUSIONS: ODD is a significant precursor of adolescent CD in children with ADHD independent of ADHD severity. Considering the negative prognosis of ADHD with comorbid CD, it is imperative that clinicians pay specific attention to the presence of childhood ODD behaviors.     

Suicide Timing in 18 States of the United States from 2003–2014

We investigated suicide timing over different time periods by age, sex and race/ethnicity. A total of 122,107 suicide deaths were identified from the population-based U.S. National Violent Death Reporting System in 18?U.S. states from 2003 through 2014. Suicides significantly increased (p 相似文献