Evidence of neuroinflammation and immunotherapy responsiveness in individuals with down syndrome regression disorder.

BACKGROUND: Down syndrome regression disorder is a symptom cluster consisting of neuropsychiatric regression without cause. This study evaluated the incidence of neurodiagnostic abnormalities in individuals with Down syndrome regression disorder and determined if abnormalities are indicative of responses to therapeutic intervention. METHODS: A retrospective, multi-center, case-control study was performed. Patients were required to have subacute onset and the presence of four of five symptom groups present (cognitive decline, expressive language, sleep derangement, loss of ability to perform activities of daily living, and/or a new movement disorder) and no other explanation for symptoms. RESULTS: Individuals with Down syndrome regression disorder were comparable to a cohort of individuals with only Down syndrome although had higher rates of autoimmune disease (p = 0.02, 95%CI 1.04-1.75). Neurodiagnostic abnormalities were found on EEG (n = 19, 26%), neuroimaging (n = 16, 22%), and CSF (n = 9, 17%). Pleocytosis was appreciated in five cases, elevated total protein in nine, elevated IgG index in seven, and oligoclonal bands in two. Testing within 2 years of symptom onset was more likely to have neurodiagnostic abnormalities (p = 0.01, 95%CI 1.64-37.06). In individuals with neurodiagnostic abnormalities, immunotherapy was nearly four times more likely to have a therapeutic effect than in those without neurodiagnostic abnormalities (OR 4.11, 95%CI 1.88-9.02). In those with normal neurodiagnostic studies (n = 43), IVIg was effective in 14 of 17 (82%) patients as well although other immunotherapies were uniformly ineffective. CONCLUSIONS: This study reports the novel presence of neurodiagnostic testing abnormalities in individuals with Down syndrome regression disorder, providing credence to this symptom cluster potentially being of neurologic and/or neuroimmunologic etiology.

A Community-Based Participatory Research Approach to Hurricane Katrina: When Disasters, Environmental Health Threats, and Disparities Collide.

In 2005, Hurricane Katrina resulted in long-term flooding of 80% of New Orleans, Louisiana. Mold-infested homes gave rise to concerns about increased childhood asthma. To address these concerns, a diverse community-academic partnership used a community-based participatory research (CBPR) approach to implement the Head-off Environmental Asthma in Louisiana (HEAL) study in 2007.The study examined the relationship between post-Katrina mold and other environmental exposures and asthma morbidity, while testing an asthma counselor (AC) intervention. Both the AC intervention and the CBPR approach were effectively implemented in the postdisaster setting. However, homes had lower levels of mold and other allergens than expected, possibly because of the timing of environmental sampling. Also, HEAL illustrated the vulnerability of the study community, especially to the interconnected threats of health disparities, environmental health stressors, and disasters.We examine the implications of these threats for public health science, policy, and practice, not only through the lens of Hurricane Katrina but also for future disasters faced by communities in the Gulf Coast and nationally.

An Unusual Cause of Frequent, Sudden, Transient, Unexplained Falls and New-Onset Status Epilepticus: Case Report and Mini-Review.

We report a 14-year old adolescent Caucasian female, who presented with frequent, sudden, transient, and unexplained falls leading to multiple serious injuries to her head and extremities requiring several visits to the emergency department. She was evaluated numerous times and imaging studies, echocardiogram, electrocardiogram, and electroencephalogram studies were all normal. She eventually presented to outside emergency department with dystonic posturing and status epilepticus and was transferred to our pediatric intensive care unit for further management. She was diagnosed with an uncommon, underrecognized and underdiagnosed condition. To our knowledge there is no such previous report in a pediatric patient.

A comparison of seasonal trends in asthma exacerbations among children from geographic regions with different climates.

BACKGROUND: The fall peak in childhood asthma exacerbations is thought to be related to an increase in viral infections and allergen exposure when children return to school. Whether the seasonality of asthma attacks among children from different geographic regions follows similar trends is unclear. OBJECTIVE: To compare seasonal trends in asthma exacerbations among school-age children who lived in different geographic locations, with different climates, within the United States. METHODS: Hospital billing data bases were examined to determine the monthly number of school-age children who were hospitalized or treated in the emergency department (ED) for asthma exacerbations. Data from four cities within three states were compared. Climate data were obtained from archives of the National Climate Data Center, U.S. Department of Commerce. RESULTS: An annual peak in asthma exacerbations was observed during the fall months (September through November) among children who lived in Charlottesville, Virginia, as well as throughout the state of Virginia. An increase in exacerbations, which peaked in November, was observed for exacerbations among children who lived in Tucson, Arizona, and Yuma, Arizona. In contrast, exacerbations among children from New Orleans, Louisiana, increased in September but remained elevated throughout the school year. Although there was annual variation in the frequency of exacerbations over time, the seasonal patterns observed remained similar within the locations from year to year. A nadir in the frequency of attacks was observed during the summer months in all the locations. CONCLUSION: Seasonal peaks for asthma exacerbations varied among the children who lived in geographic locations with different climates, and were not restricted to the beginning of the school year.

From Design to Dissemination: Implementing Community-Based Participatory Research in Postdisaster Communities.

OBJECTIVES: To review how disasters introduce unique challenges to conducting population-based research and community-based participatory research (CBPR). METHODS: From 2007-2009, we conducted the Head-off Environmental Asthma in Louisiana (HEAL) Study in the aftermath of Hurricane Katrina in a Gulf Coast community facing an unprecedented triple burden: Katrina's and other disasters' impact on the environment and health, historic health disparities, and persistent environmental health threats. RESULTS: The unique triple burden influenced every research component; still, most existing CBPR principles were applicable, even though full adherence was not always feasible and additional tailored principles govern postdisaster settings. CONCLUSIONS: Even in the most challenging postdisaster conditions, CBPR can be successfully designed, implemented, and disseminated while adhering to scientific rigor.

Implementation of evidence-based asthma interventions in post-Katrina New Orleans: the Head-off Environmental Asthma in Louisiana (HEAL) study.

BACKGROUND: Childhood asthma morbidity and mortality in New Orleans, Louisiana, is among the highest in the nation. In August 2005, Hurricane Katrina created an environmental disaster that led to high levels of mold and other allergens and disrupted health care for children with asthma. OBJECTIVES: We implemented a unique hybrid asthma counselor and environmental intervention based on successful National Institutes of Health asthma interventions from the National Cooperative Inner City Asthma (NCICAS) and Inner-City Asthma (ICAS) Studies with the goal of reducing asthma symptoms in New Orleans children after Hurricane Katrina. METHODS: Children (4-12 years old) with moderate-to-severe asthma (n = 182) received asthma counseling and environmental intervention for approximately 1 year. HEAL was evaluated employing several analytical approaches including a pre-post evaluation of symptom changes over the entire year, an analysis of symptoms according to the timing of asthma counselor contact, and a comparison to previous evidence-based interventions. RESULTS: Asthma symptoms during the previous 2 weeks decreased from 6.5 days at enrollment to 3.6 days at the 12-month symptom assessment (a 45% reduction, p < 0.001), consistent with changes observed after NCICAS and ICAS interventions (35% and 62% reductions in symptom days, respectively). Children whose families had contact with a HEAL asthma counselor by 6 months showed a 4.09-day decrease [95% confidence interval (CI): 3.25 to 4.94-day decrease] in symptom days, compared with a 1.79-day decrease (95% CI: 0.90, 2.67) among those who had not yet seen an asthma counselor (p < 0.001). CONCLUSIONS: The novel combination of evidence-based asthma interventions was associated with improved asthma symptoms among children in post-Katrina New Orleans. Post-intervention changes in symptoms were consistent with previous randomized trials of NCICAS and ICAS interventions.

Indoor environmental exposures for children with asthma enrolled in the HEAL study, post-Katrina New Orleans.

BACKGROUND: Rain and flooding from Hurricane Katrina resulted in widespread growth of mold and bacteria and production of allergens in New Orleans, Louisiana, which may have led to increased exposures and morbidity in children with asthma. OBJECTIVES: The goal of the Head-off Environmental Asthma in Louisiana (HEAL) study was to characterize post-Katrina exposures to mold and allergens in children with asthma. METHODS: The homes of 182 children with asthma in New Orleans and surrounding parishes were evaluated by visual inspection, temperature and moisture measurements, and air and dust sampling. Air was collected using vacuum-pump spore traps and analyzed for > 30 mold taxa using bright field microscopy. Dust was collected from the children's beds and bedroom floors and analyzed for mouse (Mus m 1), dust mite (Der p 1), cockroach (Bla g 1), and mold (Alternaria mix) allergens using ELISA. RESULTS: More than half (62%) of the children were living in homes that had been damaged by rain, flooding, or both. Geometric mean indoor and outdoor airborne mold levels were 501 and 3,958 spores/m3, respectively. Alternaria antigen was detected in dust from 98% of homes, with 58% having concentrations > 10 µg/g. Mus m 1, Der p 1, and Bla g 1 were detected in 60%, 35%, and 20% of homes, respectively, at low mean concentrations. CONCLUSIONS: Except for Alternaria antigen in dust, concentrations of airborne mold (ratio of indoor to outdoor mold) and dust allergens in the homes of HEAL children were lower than measurements found in other studies, possibly because of extensive post-Katrina mold remediation and renovations, or because children moved into cleaner homes upon returning to New Orleans.

The Head-off Environmental Asthma in Louisiana (HEAL) study--methods and study population.

BACKGROUND: In the city of New Orleans, Louisiana, and surrounding parishes (NOLA), children with asthma were perilously impacted by Hurricane Katrina as a result of disrupted health care, high home mold and allergen levels, and high stress. OBJECTIVES: The Head-off Environmental Asthma in Louisiana (HEAL) study was conducted to examine relationships between the post-Katrina environment and childhood asthma in NOLA and assess a novel asthma counselor intervention that provided case management and guidance for reducing home mold and allergen levels. METHODS: Children (4-12 years old) with moderate-to-severe asthma were recruited from NOLA schools. Over 1 year, they received two clinical evaluations, three home environmental evaluations, and the asthma intervention. Quarterly end points included symptom days, medication use, and unscheduled emergency department or clinic visits. A community advisory group was assembled and informed HEAL at all phases. RESULTS: Of the children (n = 182) enrolled in HEAL, 67% were African American, and 25% came from households with annual incomes < $15,000. HEAL children were symptomatic, averaging 6.6 symptom days in the 2 weeks before baseline, and had frequent unscheduled visits to clinics or emergency departments (76% had at least one unscheduled visit in the preceding 3 months). In this report, we describe study design and baseline characteristics of HEAL children. CONCLUSIONS: Despite numerous challenges faced by investigators, study staff, and participants, including destroyed infrastructure, disrupted lives, and lost jobs, HEAL was successful in terms of recruitment and retention, the high quality of data collected that will provide insight into asthma-allergen relationships, and the asthma intervention. This success was attributable to using an adaptive approach and refining processes as needed.

Mold exposure and health effects following hurricanes Katrina and Rita.

The extensive flooding in the aftermath of Hurricanes Katrina and Rita created conditions ideal for indoor mold growth, raising concerns about the possible adverse health effects associated with indoor mold exposure. Studies evaluating the levels of indoor and outdoor molds in the months following the hurricanes found high levels of mold growth. Homes with greater flood damage, especially those with >3 feet of indoor flooding, demonstrated higher levels of mold growth compared with homes with little or no flooding. Water intrusion due to roof damage was also associated with mold growth. However, no increase in the occurrence of adverse health outcomes has been observed in published reports to date. This article considers reasons why studies of mold exposure after the hurricane do not show a greater health impact.

Safety and efficacy of oral DMSA therapy for children with autism spectrum disorders: Part A--medical results.

BACKGROUND: This study investigated the effect of oral dimercapto succinic acid (DMSA) therapy for children with autism spectrum disorders ages 3-8 years. METHODS: Phase 1 involved 65 children who received one round of DMSA (3 days). Participants who had high urinary excretion of toxic metals were selected to continue on to phase 2. In phase 2, 49 participants were randomly assigned in a double-blind design to receive an additional 6 rounds of either DMSA or placebo. RESULTS: DMSA greatly increased the excretion of lead, substantially increased excretion of tin and bismuth, and somewhat increased the excretion of thallium, mercury, antimony, and tungsten. There was some increase in urinary excretion of essential minerals, especially potassium and chromium. The Phase 1 single round of DMSA led to a dramatic normalization of RBC glutathione in almost all cases, and greatly improved abnormal platelet counts, suggesting a significant decrease in inflammation. CONCLUSION: Overall, DMSA therapy seems to be reasonably safe, effective in removing several toxic metals (especially lead), dramatically effective in normalizing RBC glutathione, and effective in normalizing platelet counts. Only 1 round (3 days) was sufficient to improve glutathione and platelets. Additional rounds increased excretion of toxic metals.

Safety and efficacy of oral DMSA therapy for children with autism spectrum disorders: part B - behavioral results.

BACKGROUND: This study investigated the effects of oral dimercapto succinic acid (DMSA) therapy on the behavioural symptoms of children with autism spectrum disorders (ASD) ages 3-8 years. METHODS: Phase 1 involved 65 children with ASD who received one round of DMSA (3 days). Participants who had high urinary excretion of toxic metals were selected to continue on to phase 2. In phase 2, 49 participants were randomly assigned in a double-blind design to receive an additional 6 rounds of either DMSA or placebo. RESULTS: The groups receiving one round and seven rounds of DMSA had significant improvements on all the assessment measures. For the seven round group, the degree of improvement on the assessment measures could be partially explained by a regression analysis based on excretion of toxic metals and changes in glutathione (adjusted R2 of 0.28-0.75, p < 0.02 in all cases). One round of DMSA had nearly the same benefit as seven rounds. The assessment measures correlated reasonably with one another at the beginning of the study (r = 0.60-0.87) and even better at the end of the study (r = 0.63-0.94). CONCLUSION: Overall, both one and seven rounds of DMSA therapy seems to be reasonably safe in children with ASD who have high urinary excretion of toxic metals, and possibly helpful in reducing some of the symptoms of autism in those children.

Prevalence of IgE reactivities in mold-allergic subjects to commercially available fungal enzymes.

Fungi are important aeroallergens. However, fungal allergen sources of consistent quality for clinical testing are not readily available. Because some allergens have been identified as enzymes, we assessed the prevalence of IgE reactivity to commercially available fungal enzymes. The purpose of this study was to determine IgE antibody reactivity by radioallergosorbent assay (RAST) to commercially available fungal enzymes in mold-allergic individuals. Sera from 20 subjects with symptoms of respiratory allergies and skin test reactivity to 2 or more fungal allergens (4 conidial [imperfecti] fungi and/or 8 basidiomycetes) were selected. Controls were six atopic individuals with neither history of fungal allergy nor skin test reactivity to fungi. Seventeen commercial fungal enzymes were used as antigens to evaluate the subjects' IgE antibody reactivity by RAST. Sera from most fungus-allergic individuals showed substantial IgE antibody reactivity to enzymes; control sera showed little or no reactivity. The mean reactivity to all commercial enzymes of all subjects tested was RAST > or = 3% with only one exception. The most reactive fungal enzymes were invertase (bakers' yeast, Saccharomyces cerevisiae), cellulase (Trichoderma viride), and glucosidase (brewers yeast, S. cerevisiae) with mean binding of 14.6, 9.5, and 8.8%, respectively. Using RAST results with a combination of four enzymes from S. cerevisiae (brewers yeast glucosidase, bakers' yeast maltase, invertase, and invertase V), a sensitivity of 100% was shown for detecting mold-allergic patients. The studies suggest that fungal enzymes may be useful source materials for the identification of fungal allergens and may also provide readily available source materials to produce improved diagnostic and therapeutic reagents.

Spironolactone might be a desirable immunologic and hormonal intervention in autism spectrum disorders.

Multiple studies now demonstrate that autism is medically characterized, in part, by immune system dysregulation, including evidence of neuroglial activation and gastrointestinal inflammation. This neuroglial process has further been characterized as neuroinflammation. In addition, a subset of autistic children exhibit higher than average levels of androgens. Spironolactone is an aldosterone antagonist and potassium-sparing diuretic with a desirable safety profile. It possesses potent anti-inflammatory and immune modifying properties that might make it an excellent medical intervention for autism spectrum disorders. Furthermore, spironolactone demonstrates substantial anti-androgen properties that might further enhance its appeal in autism, particularly in a definable subset of hyperandrogenic autistic children. One case report is briefly reviewed demonstrating objective clinical improvements in an autistic child after spironolactone administration. Additional research in controlled trials is now needed to further define the risks and benefits of spironolactone use in children with autism.

Wheezing and asthma in early childhood: an update.

Although asthma is the most common chronic disease in children, recent studies show that labeling this condition "asthma," especially in association with chronic wheezing, remains a matter of dispute. Nonetheless, data confirm that wheezing and asthma place great burdens on the caregivers of affected children. A principal source of information on diagnosis and treatment is the practical guide published by the National Asthma Education Prevention Program. The implications for nurses in the management of young children whose wheezing is chronic or who have been diagnosed as having asthma include a need for knowing the program guide's recommendations, assessing the child's family history, teaching primary caregivers an action plan, providing consistent asthma education, encouraging parents to evaluate the child's environment, and identifying related resources.