Diagnostic Value of Brain Calcifications in Adult-Onset Leukoencephalopathy with Axonal Spheroids and Pigmented Glia.

Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia is a rare neurodegenerative disease resulting from mutations in the colony stimulating factor 1 receptor gene. Accurate diagnosis can be difficult because the associated clinical and MR imaging findings are nonspecific. We present 9 cases with intracranial calcifications distributed in 2 brain regions: the frontal white matter adjacent to the anterior horns of the lateral ventricles and the parietal subcortical white matter. Thin-section (1-mm) CT scans are particularly helpful in detection due to the small size of the calcifications. These calcifications had a symmetric "stepping stone appearance" in the frontal pericallosal regions, which was clearly visible on reconstructed sagittal CT images. Intrafamilial variability was seen in 2 of the families, and calcifications were seen at birth in a single individual. These characteristic calcification patterns may assist in making a correct diagnosis and may contribute to understanding of the pathogenesis of leukoencephalopathy.

Clinicopathologic correlations in 172 cases of rapid eye movement sleep behavior disorder with or without a coexisting neurologic disorder.

OBJECTIVE: To determine the pathologic substrates in patients with rapid eye movement (REM) sleep behavior disorder (RBD) with or without a coexisting neurologic disorder. METHODS: The clinical and neuropathologic findings were analyzed on all autopsied cases from one of the collaborating sites in North America and Europe, were evaluated from January 1990 to March 2012, and were diagnosed with polysomnogram (PSG)-proven or probable RBD with or without a coexisting neurologic disorder. The clinical and neuropathologic diagnoses were based on published criteria. RESULTS: 172 cases were identified, of whom 143 (83%) were men. The mean±SD age of onset in years for the core features were as follows - RBD, 62±14 (range, 20-93), cognitive impairment (n=147); 69±10 (range, 22-90), parkinsonism (n=151); 68±9 (range, 20-92), and autonomic dysfunction (n=42); 62±12 (range, 23-81). Death age was 75±9 years (range, 24-96). Eighty-two (48%) had RBD confirmed by PSG, 64 (37%) had a classic history of recurrent dream enactment behavior, and 26 (15%) screened positive for RBD by questionnaire. RBD preceded the onset of cognitive impairment, parkinsonism, or autonomic dysfunction in 87 (51%) patients by 10±12 (range, 1-61) years. The primary clinical diagnoses among those with a coexisting neurologic disorder were dementia with Lewy bodies (n=97), Parkinson's disease with or without mild cognitive impairment or dementia (n=32), multiple system atrophy (MSA) (n=19), Alzheimer's disease (AD)(n=9) and other various disorders including secondary narcolepsy (n=2) and neurodegeneration with brain iron accumulation-type 1 (NBAI-1) (n=1). The neuropathologic diagnoses were Lewy body disease (LBD)(n=77, including 1 case with a duplication in the gene encoding α-synuclein), combined LBD and AD (n=59), MSA (n=19), AD (n=6), progressive supranulear palsy (PSP) (n=2), other mixed neurodegenerative pathologies (n=6), NBIA-1/LBD/tauopathy (n=1), and hypothalamic structural lesions (n=2). Among the neurodegenerative disorders associated with RBD (n=170), 160 (94%) were synucleinopathies. The RBD-synucleinopathy association was particularly high when RBD preceded the onset of other neurodegenerative syndrome features. CONCLUSIONS: In this large series of PSG-confirmed and probable RBD cases that underwent autopsy, the strong association of RBD with the synucleinopathies was further substantiated and a wider spectrum of disorders which can underlie RBD now are more apparent.

Longitudinal modeling of frontal cognition in APOE ε4 homozygotes, heterozygotes, and noncarriers.

BACKGROUND: Fibrillar amyloid deposition preferentially affects the frontal lobes, temporal pole/neocortex, and posterior cingulate by age 65 years in APOE ε4 carriers prior to the diagnosis of mild cognitive impairment (MCI) and Alzheimer disease (AD), but is it impairing frontally mediated neuropsychological performance? METHODS: A total of 71 ε4 homozygotes (HMZ), 194 ε4 heterozygotes (HTZ), and 356 ε4 noncarriers (NC) who did not differ significantly in mean age (56.6 years), years of education (15.6), gender (70% women), or follow-up duration (6.3 years) had neuropsychological testing every 2 years including the Auditory Verbal Learning Test (AVLT) and frontal/executive tasks sensitive to psychomotor speed, working memory, problem solving, and activity. A subset also received the Iowa Gambling Task (IGT). Findings were then tested in a clinical sample of 27 patients with incident MCI and AD. RESULTS: APOE ε4 carriers had greater acceleration of decline (quadratic effect) than NC on the AVLT (p = 0.04) but not on any frontal test. APOE ε4 HMZ had greater velocity of decline (linear effects) than NC on all mental arithmetic tests: paced auditory serial attention task (PASAT) 3 second (p = 0.01) and 2 second (p = 0.004) versions; and Wechsler Adult Intelligence Scale-Revised arithmetic (p = 0.048). IGT performance did not differ between 12 ε4 HMZ, 27 ε4 HTZ, and 44 NC. Among 27 patients with incident MCI and AD, the PASAT showed progressive decline preceding diagnosis in 50%. CONCLUSIONS: No frontal cognitive effects were as robust as memory decline. APOE ε4 HMZ declined more quickly than NC on mental arithmetic tests related to frontal lobe-mediated working memory ability.

Cerebrovascular risk factors and preclinical memory decline in healthy APOE ε4 homozygotes.

OBJECTIVE: To characterize the effects of cerebrovascular (CV) risk factors on preclinical memory decline in cognitively normal individuals at 3 levels of genetic risk for Alzheimer disease (AD) based on APOE genotype. METHODS: We performed longitudinal neuropsychological testing on an APOE ε4 enriched cohort, ages 21-97. The long-term memory (LTM) score of the Auditory Verbal Learning Test (AVLT) was the primary outcome measure. Any of 4 CV risk factors (CVany), including hypercholesterolemia (CHOL), prior cigarette use (CIG), diabetes mellitus (DM), and hypertension (HTN), was treated as a dichotomized variable. We estimated the longitudinal effect of age using statistical models that simultaneously modeled the cross-sectional and longitudinal effects of age on AVLT LTM by APOE genotype, CVany, and the interaction between the two. RESULTS: A total of 74 APOE ε4 homozygotes (HMZ), 239 ε4 heterozygotes (HTZ), and 494 ε4 noncarriers were included. APOE ε4 carrier status showed a significant quadratic effect with age-related LTM decline in all models as previously reported. CVany was associated with further longitudinal AVLT LTM decline in APOE ε4 carriers (p=0.02), but had no effect in noncarriers. When ε4 HTZ and HMZ were considered separately, there was a striking effect in HMZ (p<0.001) but not in HTZ. In exploratory analyses, significant deleterious effects were found for CIG (p=0.001), DM (p=0.03), and HTN (p=0.05) in APOE ε4 carriers only that remained significant only for CIG after correction for multiple comparisons. CONCLUSION: CV risk factors influence age-related memory decline in APOE ε4 HMZ.

Family history of dementia is a risk factor for Lewy body disease.

Genetic factors are important in Alzheimer disease (AD) and Parkinson disease but have not been well characterized in Lewy body dementia (LBD). The authors obtained family history in patients from an autopsy series of AD and LBD and in living healthy controls. A family history of dementia was more common in both LBD and AD compared with controls, suggesting that genetic factors are as important in LBD as they are in AD.

Cardiac troponin levels following monitored epileptic seizures.

Cardiac arrhythmia associated with myocardial injury is a proposed mechanism for sudden unexplained death in epilepsy. The authors measured serial cardiac troponin levels in 11 patients after monitored seizures. Using highly sensitive assays and criteria, no troponin elevations were seen, indicating that myocardial injury does not occur during uncomplicated seizures. An elevation in postictal troponin elevations should suggest the presence of cardiac injury secondary to neurocardiogenic mechanisms or primary cardiac factors, prompting further evaluation.

Anthropometric assessment of nutritional status in adolescent populations in humanitarian emergencies.

OBJECTIVE: To outline the difficulties and suggest potential solutions in anthropometric assessment of adolescents during humanitarian emergencies. DESIGN: Literature review. SETTING: Multiple settings in which the nutritional status of adolescents has been assessed using anthropometric measurements. SUBJECTS: Adolescents in multiple populations. INTERVENTIONS: None. RESULTS: The use of anthropometry may be more difficult in adolescents than in other age groups because anthropometric indices in normally nourished adolescents change with age and sexual development. Moreover, survey and reference populations may differ in the age at which certain pubertal landmarks are attained, requiring adjustment for differences between survey and reference populations. Adolescent populations may also differ by ethnicity in various body proportions that affect anthropometric indices. Adjustment may be required when the body proportions of adolescents in the reference population differ from those in the population assessed. CONCLUSIONS: Although no definitive recommendation can be made regarding which anthropometric indices are the most appropriate for adolescents, some revisions may improve current practices. Weight-for-height could be used for prepubertal adolescents and body mass index could be used for postpubertal adolescents. Because cut-off points are age-specific, age should be collected as accurately as possible for all adolescents measured during screening or survey activities. The WHO-recommended reference population of US adolescents is inappropriate in most populations of adolescents. Adolescents should never undergo nutritional assessment in isolation; other population subgroups should be included, and other health, nutrition and food data should be collected at the same time. SPONSORSHIP: The United Nations Administrative Committee on Coordination/Sub-Committee on Nutrition.

Safety of neonatal hepatitis B vaccine administration.

OBJECTIVE: To determine whether hepatitis B vaccination of newborns increases the incidence of fever and/or suspected sepsis. METHODS: A prospective clinical study was undertaken at the Kaiser Permanente San Francisco Medical Center involving normal full term newborns born between November 1, 1991, and April 30, 1994. During this time 3302 infants were vaccinated within 21 days of birth with hepatitis B vaccine, and 2353 were not. Clinical and demographic data were collected from Kaiser Permanente's existing clinical information systems, and laboratory data for blood and cerebrospinal fluid (CSF) cultures were obtained from the comprehensive automated regional laboratory reporting system. RESULTS: There were no significant differences between vaccinated and unvaccinated newborns in the proportion of infants who received care for fever (0.8% vaccinated and 1.1% unvaccinated, P = 0.28), allergic reactions, seizures or other neurologic events in the first 21 days of life. Vaccinated newborns were significantly less likely to undergo microbiologic evaluation for possible sepsis. Among vaccinated newborns 4.0% had blood cultures and 1.6% had CSF cultures. Among infants who were not vaccinated 8.3% had blood cultures and 1.6% had CSF cultures (P <0.001 for both tests). CONCLUSION: This study found no evidence that newborn hepatitis B vaccination is associated with an increase in the number of febrile episodes, sepsis evaluations or allergic or neurologic events. In addition our data did not support any increase in medical procedures attributed to receipt of hepatitis B vaccine.

Deacetylravidomycin M, a new inhibitor of IL-4 signal transduction, produced by Streptomyces sp. WK-6326. I. Taxonomy, fermentation, isolation and biological activities.

Streptomyces sp. WK-6326, a soil isolate, was found to produce an inhibitor of interleukin (IL)-4 signal transduction. Two structurally related compounds, a novel one designated deacetylravidomycin M and the known deacetylravidomycin, were isolated from the culture broth by solvent extraction, silica gel column chromatography and HPLC. Deacetylravidomycin M inhibited IL-4-induced CD23 expression in U937 cells without any cytotoxic effect, whereas deacetylravidomycin showed no inhibitory activity.

The accuracy of mortality reporting in displaced persons camps during the post-emergency phase.

For humanitarian organisations, accurate data are essential to identify emerging health problems and determine programme needs. We visited 45 post-emergency phase displaced persons camps and collected three months' mortality data which we compared with organisations' routine mortality reports. Organisations reported 612 deaths and we identified 741 deaths, for a mortality-reporting ratio, defined as the number of organisation-reported deaths divided by the number of investigator-identified deaths, of 83 per cent. For the majority of camps which under-reported deaths, mortality reporting ratios were significantly higher for women than men, and for camps with central mortality registers rather than those without. In the few camps which over-reported deaths, these occurred primarily among children younger than five years of age, probably due to the inclusion of abortions and stillbirths. Despite the overall under-reporting of deaths by humanitarian organisations, the existing health information systems appear to estimate mortality rates adequately in these post-emergency camps. However, organisations should improve the precision and completeness with which they report the characteristics of deaths in order to provide valuable data to target their programmes at the most vulnerable people.

Randomized intervention study comparing several regimens for the treatment of moderate anemia among refugee children in Kigoma Region, Tanzania.

Anemia-specific mortality was markedly elevated among refugee children < 5 years of age in Tanzania. In a randomized, double-blind study, 215 anemic children were initially treated for malaria and helminth infection and then received 12 weeks of thrice-weekly oral iron and folic acid. Group I received placebo and chloroquine treatment for symptomatic malaria infection (i.e., no presumptive anti-malarial treatment given). Group II received placebo and monthly presumptive treatment with sulfamethoxazole-pyrimethamine (SP). Group III also received monthly SP and thrice-weekly vitamins A and C (VAC). Mean hemoglobin concentration increased from 6.6 to 10.2 g/dL, with no significant differences among groups. Group II had lower mean serum transferrin receptor levels (TfR) than group I [P = 0.023]. A greater proportion of participants in group III had normal iron stores (TfR < 8.5 microg/ mL) than in group II [P = 0.012]. Initial helminth and malaria treatment, followed by thrice-weekly iron and folic acid supplements resulted in increased hemoglobin levels. Monthly SP and thrice-weekly VAC contributed to improve iron stores. Monthly SP may have a role in situations where asymptomatic disease is prevalent or where access to care is limited. Because administration of VAC also hastened recovery of iron stores over administration of monthly SP alone, health care personnel could add VAC to the treatment for moderate anemia if maximum recovery of iron stores is desired.

Injections given in healthcare settings as a major source of acute hepatitis B in Moldova.

BACKGROUND: Reported rates of acute hepatitis B are high in many former Soviet Union republics and modes of transmission are not well defined. METHODS: Two case-control studies were undertaken in Moldova to identify risk factors for acute hepatitis B in people aged 2-15 years (children) and > or =15 years (adults). Serologically confirmed acute hepatitis B cases occurring between 1 January 1994 and 30 August 30 1995, were matched on age, sex, and district of residence to three potential controls who were tested for hepatitis B markers to exclude the immune. Stratified odds ratios (SOR) were calculated using bivariate and multivariate methods. RESULTS: In multivariate analysis, compared with the 175 controls, the 70 adult cases (mean age 25 years, 66% male) were more likely to report receiving injections in the 6 months before illness during a dental visit (SOR = 21; 95% CI: 3.7-120), a hospital visit (SOR = 35; 95% CI: 7.2-170), or a visit to the polyclinic (SOR = 13; 95% CI: 2.4-74). Among children, receiving injections during a hospital visit (SOR = 5.2; 95% CI: 1.2-23) was the only exposure reported significantly more often by the 19 cases (mean age 8 years, 68% male) compared with the 81 controls. CONCLUSION: These results, along with reported unsafe injection practices in Moldova, suggest that injections are a major source of hepatitis B virus transmission and highlight the importance of proper infection-control procedures in preventing transmission of blood-borne infections.

PIP: Two case-control studies were conducted between January 1994 and August 1995 to determine the relative importance of injections and other exposures as a source of acute hepatitis B in Moldova among adults (aged 15 years) and children (aged 2-15 years). Results showed that injections in various health care settings were associated with acute hepatitis B and showed a higher proportion among adults compared with children. Contact with an HBsAg-positive person was also associated with illnesses; however, there was no statistically significant association between acute hepatitis B and other exposures. The risk of HBV transmission following percutaneous exposure is high (at least 30%). Calculation of the population attributable to risk suggests that injections associated with acute hepatitis B cases occurred in adults (52%) and children (21%). Adverse effects of injections may not be apparent in causing chronic infections. Transmission of blood-borne pathogens through unsafe injection practices is a problem increasingly identified worldwide.

Prevalence of hepatitis B, D and C virus infections among children and pregnant women in Moldova: additional evidence supporting the need for routine hepatitis B vaccination of infants.

Rates of acute hepatitis B are high in Moldova, but the prevalence of chronic infection is unknown. In 1994, we surveyed children and pregnant women, collected demographic information, and drew blood for laboratory testing. Among the 439 children (mean age, 5 years), the prevalence of antibody to hepatitis B core antigen (anti-HBc) and hepatitis B surface antigen (HBsAg) were 17.1 and 6.8%, respectively. Among the 1098 pregnant women (mean age, 26 years), 52.4% were anti-HBc-positive and 9.7% were HBsAg-positive. Of the HBsAg-positive pregnant women, 35.6% were hepatitis B e antigen (HBeAg) positive and 18.3% had antibodies to hepatitis D virus. The prevalence of antibody to hepatitis C virus was 1.4% in children and 2.3% in pregnant women. The high HBeAg prevalence among HBsAg-positive pregnant women and the high anti-HBc prevalence among children indicate that both perinatal and early childhood transmission contribute to the high hepatitis B virus endemicity in Moldova.

Factors associated with anemia in refugee children.

A nutrition survey was performed in 1990 among children 6 through 35 mo of age living in Palestinian refugee camps in Syria, Jordan, the West Bank, Gaza Strip and Lebanon. Overall, 67% [95% confidence interval (CI): 66, 68] were anemic (hemoglobin <110 g/L), ranging from 54% in the West Bank to 75% in Syria. The following factors were significantly associated with anemia in one or more of three age groups (6-11.9, 12-23.9 and 24-35.9 mo) by logistic regression: living in Syria, Lebanon, or Gaza [with prevalence odds ratios (POR) in the range of 1.4-2.6 depending on the age group and area, relative to children living in Jordan]; never having been breast-fed (POR = 1.7); male sex (POR = 1.2); maternal illiteracy (POR = 1.4 relative to those with >/=6 y of education); having a recent (within 2 wk) or current episode of fever or diarrhea; and stunting. Recent or current illness and stunting interacted in two age groups with the general trend of stunted children with recent or current illness having high POR. Early childhood anemia is associated with factors reflecting poor socioeconomic status and recent diarrheal and febrile illnesses in Palestinian refugee camps.

Incentives and motivators in school-based hepatitis B vaccination programs.

During a school-based vaccination program, incentives and education were offered to help motivate students to participate. Each student at all schools in the program received scholastic credit for returning a signed form, material rewards for receiving each vaccine dose, and free attendance at a social event after completing the vaccine series. In two of four schools, classes received a reward if every student in the classroom returned a signed form within five days: in these schools, 91% and 98% of students returned signed forms within five days, compared to 82% and 85%, respectively, in the two schools without this peer incentive. Approximately half the students receiving the peer incentive reported that it played a motivating role, whereas 60% cited wanting to be protected. Few students named individual rewards as motivators. Although peer incentives appeared effective in encouraging some students to return parent consent or refusal forms, the desire to be protected may have been a stronger motivator.

Immunizations from ground zero: lessons learned in urban middle schools.

The Centers for Disease Control and Prevention funded a three-year demonstration project in San Francisco to assess the feasibility of a large-scale school-based vaccination effort. The project overcame a number of barriers, including lack of pre-existing health services, diversity of home languages, and an every-50-minute-bell schedule. The project targeted seventh graders and all special education students for hepatitis B vaccine (HBVac). Of 4,928 students targeted, 3,509 (71%) consented to vaccination and received the first dose. Of these 3,509 students, 3,256 (93%) completed the three-dose series at school. Key lessons learned include emphasizing a collaborative process in the planning stage, offering an educational component for students, providing an incentive to get timely parental consent, planning distribution and collection of parent materials, and planning vaccination clinics to minimize interrupting the school day. The project clearly demonstrated that, with sufficient attention to political and logistical dimensions, school-based vaccination programs are possible in large urban schools.

Attitudes and educational practices of obstetric providers regarding infant hepatitis B vaccination.

OBJECTIVE: To survey the current knowledge, attitudes, and practices of obstetric providers regarding the education of pregnant women about infant hepatitis B vaccination. METHODS: A questionnaire was mailed to 264 physicians providing obstetric services in San Francisco. Of these, 113 were confirmed to be providing prenatal care. RESULTS: Seventy-six obstetric providers returned completed questionnaires. Among eligible respondents, 79% believed that hepatitis B vaccine should be administered to all infants at birth, and 92% believed that it is feasible to educate all expectant mothers about infant hepatitis B vaccination. However, only 53% of respondents provided such education to all their pregnant patients. Only 23% provided education about other routine childhood immunizations. CONCLUSIONS: Obstetric providers in San Francisco are willing to educate pregnant patients about hepatitis B vaccination but are not always doing so. Providing education in a consistent manner may improve infant hepatitis B vaccination rates and may increase coverage with other childhood vaccines.

Parents' attitudes toward school-based hepatitis B vaccination of their children.

OBJECTIVE: As part of a larger hepatitis B vaccination program in San Francisco, hepatitis B vaccine is offered to seventh-grade students in selected middle schools. We investigated attitudes and beliefs about hepatitis B, hepatitis B vaccine, and school-based vaccination among parents of eligible students. METHODS: A survey was conducted of random samples of parents who consented, refused, or did not respond to a request for vaccination consent. RESULTS: A larger proportion of persons who signed a vaccination consent or refusal form were biological parents and were Asian or white than parents who did not return a signed form. The most common reason for refusing vaccination, given by 84% of refusing parents, was that their children had already been vaccinated against hepatitis B. These parents recognized the severity and duration of hepatitis B virus infection as much as parents consenting to vaccination. About one third of parents who refused vaccination did not agree that schools were good places to vaccinate children. Overall, 116 parents (40%) consulted someone before deciding to consent or refuse; 95 (33%) spoke with a health professional. Most parents not returning signed consent or refusal forms reported that they never received forms from their children or that they returned signed forms to their children, who never delivered them to school. CONCLUSIONS: Most parents accepted school-based vaccination, and obtaining parental consent for school-based vaccination was possible. Nonetheless, new approaches may be needed for those students and parents who do not comply with the consent process.

Progress toward integrating hepatitis B vaccine into routine infant immunization schedules in the United States, 1991 through 1994. Connecticut Hepatitis B Project Group.

OBJECTIVE: We assessed progress toward universal infant immunization against hepatitis B, which was first recommended in November 1991. METHODS: Multiple data sources were used to describe vaccination policies and trends in infant hepatitis B vaccine coverage. RESULTS: As of June 1993, 51% of the 63 local, state, and territorial immunization programs recommended hepatitis B vaccination of all newborns shortly after birth. The number of first dosages of hepatitis B vaccine administered to infants in public sector clinics increased rapidly from late 1992 to 1993, and at the end of 1993 was approximately two thirds the number of first dosages of other infant antigens. In a nationwide survey of hospital nurseries 47% offered hepatitis B vaccine to all newborns. Of 3982 sampled newborns in these hospitals, 36.2% had been vaccinated before discharge. In San Francisco and Connecticut, where public health officials encouraged hospitals to offer hepatitis B vaccination, first-dose coverage at discharge was 82.3% in 1994 and 69.1% in 1993, respectively. Coverage was higher in healthier infants and lower in infants of older or better-educated mothers. Results from the National Health Interview Survey demonstrate that three-dose completion at 12 months of age increased form less than 1% of children born in 1989 to 40% of children born in the fourth quarter of 1992. Vaccination at birth increased from less than 1% of infants born in 1989 to 32% of infants born in the second half of 1993. CONCLUSIONS: Infant hepatitis B vaccination has expanded rapidly since national recommendations were made; however, universal coverage has not been achieved.