Effect of natalizumab on brain atrophy and disability progression in multiple sclerosis patients over 5 years.

BACKGROUND AND PURPOSE: The long-term benefit of natalizumab on brain atrophy progression in multiple sclerosis (MS) patients is unknown. Our aim was to investigate its effect over 5 years. METHODS: This prospective study included 60 relapsing MS patients who started natalizumab treatment in years 2006-2007. RESULTS: At the 5-year follow-up, 20 patients discontinued natalizumab after an average of 29.5 cycles, 27 continued natalizumab treatment with some periods of honeymoon (average of 38.4 infusions) and 13 never stopped natalizumab (average of 60.6 infusions). In multiple linear regression analysis, adjusted for age, sex and baseline magnetic resonance imaging (MRI) status, the number of natalizumab infusions was associated with decrease of relapse rate (adjusted P = 0.037), but no association was found with the progression of disability, accumulation of lesion burden or brain volume loss. However, only one (8%) patient in the continuous monthly group experienced disability progression compared to 10 (37%) in the non-continuous and seven (35%) in the discontinuation natalizumab groups. At the follow-up, two patients had died [one from a fatal case of progressive multifocal leukoencephalopathy (PML) and one from a car accident] and 15 patients were lost to follow-up. There was another case of non-fatal PML over the follow-up. CONCLUSIONS: In line with previous reports, MS patients with longer and continuous use of natalizumab had fewer relapses and remained stable in their disability status. No difference in lesion burden accumulation or brain atrophy development was found in relation to the duration of natalizumab use. PML occurred in 2.5% of patients in this small sample cohort. Given the increased risk of PML and uncertain benefit of prolonged natalizumab use on clinical and MRI outcomes of disease progression found in this study, a careful risk-benefit therapeutic assessment is mandatory.

Retinal nerve fiber layer thickness and thalamus pathology in multiple sclerosis patients.

BACKGROUND AND PURPOSE: Visual impairments are frequent in multiple sclerosis (MS). Optic neuritis can directly reduce retinal nerve fiber layer (RNFL) thickness. Our objectives were to evaluate associations of the RNFL thickness (RNFLT) of MS patients with magnetic resonance imaging (MRI) measures of regional brain atrophy and tissue injury in the post-chiasmatic deep gray matter (GM) section of the visual pathway. METHODS: Retinal nerve fiber layer thickness was measured using optical coherence tomography (OCT) in 96 relapsing-remitting MS (RR-MS) patients and 46 controls. MRI was obtained within ±3 months of OCT. RNFLT associations with MRI measures from diffusion tensor imaging and regional and tissue specific atrophy were assessed. RESULTS: In RR-MS, lower RNFLT was associated with lower white matter volume and lower whole brain volume. Lower RNFLT was associated with lower total deep gray matter volume and lower thalamus volume. Lower RNFLT was associated with greater mean diffusivity (MD) in normal appearing (NA) brain tissue and NA gray matter. Trends were found for lower RNFLT with greater MD in NA white matter and thalamus. RNFLT in controls was not associated with MD. CONCLUSIONS: Lower RNFLT is associated with microscopic tissue injury in NA regions of the brain and with neurodegeneration of the deep gray matter and thalamus in RR-MS.

A ring system detected around the Centaur (10199) Chariklo.

Hitherto, rings have been found exclusively around the four giant planets in the Solar System. Rings are natural laboratories in which to study dynamical processes analogous to those that take place during the formation of planetary systems and galaxies. Their presence also tells us about the origin and evolution of the body they encircle. Here we report observations of a multichord stellar occultation that revealed the presence of a ring system around (10199) Chariklo, which is a Centaur--that is, one of a class of small objects orbiting primarily between Jupiter and Neptune--with an equivalent radius of 124 ± 9 kilometres (ref. 2). There are two dense rings, with respective widths of about 7 and 3 kilometres, optical depths of 0.4 and 0.06, and orbital radii of 391 and 405 kilometres. The present orientation of the ring is consistent with an edge-on geometry in 2008, which provides a simple explanation for the dimming of the Chariklo system between 1997 and 2008, and for the gradual disappearance of ice and other absorption features in its spectrum over the same period. This implies that the rings are partly composed of water ice. They may be the remnants of a debris disk, possibly confined by embedded, kilometre-sized satellites.

Prevalence of radiologically isolated syndrome and white matter signal abnormalities in healthy relatives of patients with multiple sclerosis.

BACKGROUND AND PURPOSE: The exact prevalence of WM signal abnormalities in healthy relatives of MS patients and their impact on disease development has not been fully elucidated. The purpose of this study was to compare WM signal abnormality characteristics and the prevalence of radiologically isolated syndrome in healthy control subjects selected randomly from the population with the healthy relatives of patients with MS. MATERIALS AND METHODS: Healthy control subjects (n = 150) underwent physical and 3T MR imaging examinations. Healthy control subjects were classified as non-familial healthy control subjects (n = 82) if they had no family history of MS or as healthy relatives of patients with MS (n = 68) if they had ≥1 relative affected with MS. The presence of radiologically isolated syndrome was evaluated according to the Okuda criteria; dissemination in space on MR imaging and fulfillment of radiologically isolated syndrome criteria were also evaluated according to Swanton criteria. RESULTS: There was a significantly higher total volume of WM signal abnormality in the healthy relatives of patients with MS compared with the non-familial healthy control subjects (P = .024 for signal abnormality ≥3 mm in size and P = .025 for all sizes). Periventricular localization and the number of lesions in all groups (P = .034 and P = .043) were significantly higher in the healthy relatives of patients with MS; 8.8% of the healthy relatives of patients with MS and 4.9% of non-familial healthy control subjects showed ≥9 WM signal abnormalities; 2.9% of subjects in the healthy relatives of patients with MS group and 2.4% of non-familial healthy control subjects fulfilled radiologically isolated syndrome according to the Okuda criteria, whereas 10.3% and 3.7% of subjects fulfilled radiologically isolated syndrome according to the Swanton criteria. In the healthy relatives of patients with MS, smoking was associated with the presence of WM signal abnormalities, whereas obesity was related to the presence of ≥9 WM signal abnormalities and to fulfillment of radiologically isolated syndrome according to the Swanton criteria. CONCLUSIONS: The frequency of WM signal abnormalities and radiologically isolated syndrome is higher in the healthy relatives of patients with multiple sclerosis patients compared with non-familial healthy control subjects.

Effect of age on MRI phase behavior in the subcortical deep gray matter of healthy individuals.

BACKGROUND AND PURPOSE: It has been demonstrated that increased levels of iron in the brain occur with aging. In this study we investigated the nature of the association between age and SWI-filtered phase values, indicative of iron content, in the subcortical deep gray matter of healthy individuals. MATERIALS AND METHODS: A total of 210 healthy individuals (men: n = 89, women: n = 121), mean age, 39.8 years (standard deviation = 15.5; range = 6-76 years), were imaged on a 3T scanner. Mean MRI phase, mean phase of low-phase voxels, and normalized volumes were determined for total subcortical deep gray matter, caudate, putamen, globus pallidus, thalamus, pulvinar nucleus, hippocampus, amygdala, nucleus accumbens, red nucleus, and substantia nigra. Linear and nonlinear regression models were used to explore the relationship between phase and volume measures, and aging. RESULTS: Mean phase values of subcortical deep gray matter structures showed a quadratic relationship, with individuals in late middle age (40-59 years) having the lowest mean phase values, followed by a reversal of this trend in the elderly. In contrast, mean phase of low-phase voxel measurements showed strong negative linear relationships with aging. Significantly lower phase values were detected in women compared with men (P < .001), whereas no sex differences were observed for mean phase of low-phase voxels. Normalized volume measurements were also linearly related to aging, and women showed smaller normalized volumes of subcortical deep gray matter structures than men (P < .001). Lower mean phase of low-phase voxels was related to decreased volume measures. CONCLUSIONS: A strong association between phase (quadratic effect; phase decreases are followed by increases), mean phase of low-phase voxels (linear effect), volume (linear effect), and age was observed. Low phase was related to brain atrophy.

Research, consumer involvement, and models of care.

Many issues face the National Institute on Disability and Rehabilitation Research (NIDRR) and its role in the encouragement of Traumatic Brain Injury (TBI) rehabilitation research and the development of the TBI model systems of care. Yet, even though many complex difficulties face individuals who have sustained TBI, their families, care givers, researchers, and others whose lives have been changed by TBI, there is reason for optimism. Significant advances have been made in research, consumer involvement, and model systems of care for individuals who have experienced TBL Although accountability is a recurring watchword for public programs, particularly as a result of Federal legislation enacted in 1993, the TBI model systems of care have many attributes of an effective results-oriented system when examined in the light of the new measures of program success.

Consumers' views of the maternity services: implications for change and quality assurance.

The feasibility and usefulness of consumer surveys for quality assurance and planning maternity services were assessed in a postal survey of 1807 women in four health districts representing a range of social and demographic characteristics. A response rate of 79 per cent was achieved. Scope was identified for some reduction in length of stay: 43 per cent of postnatal women wished for a shorter stay than they have actually experienced. The Domino system and a 1-2 days stay were the preferred options (25 and 24 per cent respectively). Six per cent of postnatal women would have preferred a longer stay than experienced and consisted mainly of women with birth complications including caesarean deliveries, women with lack of help at home and Afro-Caribbeans. Schemes to increase continuity of care and make the delivery suite more home-like would be favoured by a large proportion of women. Sixty-five per cent of women regarded continuity of midwifery care and familiarity with the delivering midwife as important. Seventy-five per cent considered a home-like environment in the delivery suite as important, and gave specific suggestions of how this might be achieved. The results show that consumers' surveys are feasible, with a good response rate and range of views expressed by the study population. They can assist in monitoring quality and provide guidance for planning at local and regional levels.

A health visitor investigation of home accidents in pre-school children.

The incidence and characteristics of home accidents in pre-school children were investigated in the northern part of Lambeth with the help of health visitors. Accidents were identified using the notification system from accident and emergency departments to health visitors. The study shows that there is not an easily identifiable group of high risk children so all must be regarded as potentially at risk. It also highlights how important it is that accidents treated at hospital are notified to health visitors and some ways for improving the system are suggested.

Respiratory illness and home environment of ethnic groups.

Factors contributing to differences in the prevalences of respiratory symptoms and diseases among ethnic groups were studied in primary schoolchildren living in 20 inner city areas of England in 1983. The raised prevalences of respiratory symptoms in these groups were compared with results from a national representative sample of children studied in 1982. Data on age, sex, respiratory illness, and social and environmental variables were obtained by questionnaire for 4815 children living in inner cities. The children were classified as white, Afro-Caribbean, Urdu, Gujarati, Punjabi, other Asian, or "other." Significant differences in the prevalence of respiratory conditions were found among the ethnic groups after allowance was made for the effects of interfering variables. Except for asthma all conditions were most prevalent in Afro-Caribbeans and whites. In these two ethnic groups respiratory illness was significantly associated with belonging to a one parent family and the combined use of gas cookers and paraffin heaters at home. Respiratory illness was found to vary in prevalence among ethnic groups but may be perceived differently by different groups. Further studies, measuring lung function, are necessary.

Investigations into the relations between respiratory illness in children, gas cooking and nitrogen dioxide in the U.K.

In 1977 an association was reported between the prevalence of respiratory illness and use of gas for cooking at home in a national sample of six to 11 year olds living in England and Scotland (p less than .10). Other variables such as social class and number of cigarette smokers at home did not seem to explain the association. As the gas cooker is an unflued appliance emitting a variety of pollutants during gas combustion it was suggested that indoor air pollution might explain the finding. Nitrogen dioxide (NO2) was suspected so a series of studies was conducted to investigate the distribution of levels of NO2 in the home, the relative contribution of sources of NO2 to indoor exposure and the relation between respiratory illness in six to 11 year olds and levels of NO2 in the home. The gas cooker was found to be one of the main sources of NO2 in the home. Winter weekly averages in kitchens with gas cookers had a mean of 112.2 ppb (n = 428, range 5-317 ppb). Levels in electric cooking kitchens were significantly lower (n = 87, mean 18 ppb, range 6-188 ppb). Studies of health indicated a relation between respiratory illness and bedroom levels of NO2 over the range 4-169 ppb (p .10). Results for living room levels of NO2 suggested a similar but non-significant relationship (p greater than .10). No relation was found for kitchen levels of NO2. For schoolchildren any effect on health from indoor NO2 is likely to be weak. However other sections of the population such as infants and the elderly who may spend more time indoors and are particularly susceptible to respiratory illness need to be studied to assess fully the impact that NO2 may be having on health.

Suitability of a new turbine spirometer for epidemiological surveys in children.

The performance of a new turbine spirometer, which has several advantages over equipment previously used to measure lung function, was compared with that of a conventional spirometer (Vitalograph) in a cross-over trial on 368 children six to 11 years old. On average, slightly higher values of forced expiratory volume at 0.75 s and forced vital capacity were recorded on the turbine spirometer. These differences occurred mainly in children aged less than eight years. Assuming the Vitalograph remained accurate, there appeared to be a slight tendency for readings on the turbine spirometer to drift downwards at a rate of 0.04 1 per 100 children measured but this was not statistically significant (p greater than 0.10). In conclusion, the machines differed mainly in the youngest age group. Until a recording of the complete expiration curve can be made using the turbine spirometer, it is not possible to assess whether this effect of age arose because of errors in the breath manoeuvre by younger children undetectable in the turbine spirometer or because the simpler design of the spirometer makes it easier than the Vitalograph for young children to use it correctly.

Childhood respiratory illness and the home environment. I. Relations between nitrogen dioxide, temperature and relative humidity.

The relation between the use of gas for cooking, nitrogen dioxide (NO2), temperature and relative humidity was investigated in an urban area of northern England. In a pilot study conducted in a random sample of 40 homes measurements of temperature and relative humidity were not significantly different between homes with a gas cooker and homes with an electric cooker but weekly average levels of NO2 were higher in bedrooms (p less than 0.005) and living rooms (P less than 0.01) of gas homes. In the main study conducted in gas cooking homes only, access was gained to 183 (54.3%) of 337 randomly selected homes. No correlation was found in children's bedrooms between with weekly average level of NO2 (range 4.7 to 160.8 ppb) and weekly average temperature (ranged 7.7 to 22.0 degree C; r = 0.05, p greater than 0.10) or relative humidity (range 37.0 to 98.1%; r = 0.07, p greater than 0.10). Levels of NO2 in the bedroom were positively correlated with those in the living room (range 9.0 to 292.2 ppb; r = 0.39, p less than 0.01). Factors which tended to be associated with high levels of NO2 in the home included gas fires, paraffin heaters and use of the cooker for heating and drying clothes.

Childhood respiratory illness and the home environment. II. Association between respiratory illness and nitrogen dioxide, temperature and relative humidity.

The relation of respiratory illness to nitrogen dioxide (NO2), temperature and relative humidity in homes with a gas cooker was investigated in five and six year old children living in an urban area of the northern England. NO2 was measured for one week in the child's bedroom and living room of each home, and temperature and relative humidity were measured in the bedroom only. Information on respiratory conditions experienced by the child and characteristics of the home was collected in a self-administered questionnaire completed by the child's mother. Access was gained to 183 homes (54.3% of 337) where only gas was used for cooking. Complete information was obtained for 179 (93.7%) of 191 children who lived in the 183 homes. After allowing for the effects of age, sex, social class, and number of cigarette smokers in the home and temperature or relative humidity, no statistically significant relation was found between the prevalence of having one or more respiratory conditions and weekly average levels of NO2 in the bedroom (range 4.7 to 160.8 ppb) or living room (range 9.0 to 292.2 ppb). However, the prevalence of having one or more respiratory conditions tended to be highest in homes with high levels of NO2 and lowest in homes with low levels, consistent with earlier findings. A significant positive association was found between the prevalence of respiratory conditions and relative humidity (p less than .05). A harmful effect on health from NO2 cannot be totally dismissed but if it exists it is weak and difficult to detect in small samples of children.

The epidemiology of indoor nitrogen dioxide in the U.K.

The results of three studies on the effect of gas cooking on the lung function of children are reported. The studies which have been carried out in England and Scotland with children aged 6-11, 6-7 and 5-6 years, respectively, show that there is only a weak association between indoor levels of NO2 and respiratory illness. Nevertheless, the consistency of the difference in the rate of respiratory diseases in children from homes with electric and gas cookers suggest there is some hazard to the use of unflued gas appliances which may warrant further epidemiological investigation.

Respiratory illness in British schoolchildren and atmospheric smoke and sulphur dioxide 1973-7. II: longitudinal findings.

A study was set up to investigate the effects of annual changes in the levels of atmospheric smoke and SO2 on changes in health from 1973 to 1977 in primary schoolchildren from 28 randomly selected areas of England and Scotland. Changes in health were measured by taking the change in number of respiratory conditions reported from one annual examination to the next. The number of areas with data on pollution in each period was 5,9,17, and 14 respectively and within these areas the response rate varied from 65% to 74%. Altogether 857, 1436, 2702, and 2036 children respectively who were of white ethnic origin, aged 6 to 11, and had complete data on sex, social class, and changes in health were studied in each period. In 1973-4 the levels of pollution were highest and showed the greatest decline. The greatest annual mean change in smoke was a decrease from 71.9 to 50.5 microgram/m3 and in SO2 a decrease from 94.2 to 47.6 microgram/m3. However, no relation was found between improvement in health and decreasing levels of pollution. In subsequent years, when the levels of pollution were lower and showed smaller changes, change in health was also unrelated to changes in pollution. Thus no evidence was found to suggest that the levels measured during the study were harmful to health.