Arthrogryposis in infancy, multidisciplinary approach: case report.

BACKGROUND: Arthrogryposis multiplex congenita is an etiopathogenetically heterogeneous disorder characterised by non-progressive multiple intra-articular contractures, which can be recognised at birth. The frequency is estimated at 1 in 3,000 newborns. Etiopathogenesis of arthrogryposis is multifactorial. CASE PRESENTATION: We report first 26 weeks of life of a boy with severe arthrogryposis. Owing to the integrated rehabilitation approach and orthopaedic treatment a visible improvement in the range of motion as well as the functionality of the child was achieved. This article proposes a cooperation of various specialists: paediatrician, orthopaedist, specialist of medical rehabilitation and physiotherapist. CONCLUSIONS: Rehabilitation of a child with arthrogryposis should be early, comprehensive and multidisciplinary. Corrective treatment of knee and hip joints in infants with arthrogryposis should be preceded by the ultrasound control. There are no reports in the literature on the ultrasound imaging techniques which can be used prior to the planned orthopaedic and rehabilitative treatment in infants with arthrogryposis. The experience of our team indicates that such an approach allows to minimise the diagnostic errors and to maintain an effective treatment without the risk of joint destabilisation.

Radiation effects on development.

It has been widely reported that prenatal exposure to ionizing radiation can interfere with embryonic and fetal development, depending on dose and gestational age in which exposure occurs. According to several studies on animal models, different well-defined stages during prenatal life can be distinguished in relation to teratogenic effects. During the preimplantation stage, elevated doses of radiation can result in abortion, while lower doses may produce genomic damage that is usually repaired. On the other hand, during the organogenesis stage in mice (embryonic day 6.5 [E6.5] to E13.5), irradiation is associated with increased incidence of malformation and intrauterine growth restriction (IUGR). Later exposure is linked to brain damage. Doses used in animal studies are generally higher than those used for diagnostic procedures in humans. Usually, radiation exposure to diagnostic range (<0.05 Gy = 5 rads) is not associated with an increased risk of congenital anomalies. In human studies, elevated doses produce adverse outcomes, depending on stage of development, as in animal studies. Blastogenesis (up to two weeks) is associated with failure to implant or no significant health effects. An increased risk of malformation and growth retardation can be observed for two to seven weeks exposure (organogenesis stage), while exposure at later stages (fetogenesis) is mainly associated with brain damage. In this review we focus on the relevance of estimating the cumulative dose of radiation to the fetus and the gestational age in which exposure occurs, to provide appropriate counseling to pregnant women.

Mathematical simulation of dose-effect relationships for fish eggs exposed chronically to ionizing radiation.

A mathematical model which simulates the observed dose-effect relationships for fish eggs exposed to chronic irradiation is presented. The model assumes that the exposed fish eggs may exist in one of the following states: normally developing, reversibly damaged, and lethally damaged. Reversible damages may be recovered by repairing mechanisms which are spent for the repairing processes. The model was applied to describe the observed differences in effects of chronic exposure for quickly (2 weeks) and slowly (up to 20 weeks) developing fish eggs. Calculations were performed for dose rates of chronic irradiation ranging from 10 to 300 mGy/day. Two types of radiation effects were considered-the effect on eggs survival (percentage of survived eggs at time t), and the depletion of the repairing pool (in percentage of its maximal value). The model predictions have been compared with the experimental data from the EPIC database. This comparison showed that the model adequately describes the radiation effects in fish eggs of different species, within a wide range of chronic radiation exposures.

Estimated fluence-to-absorbed dose conversion coefficients for use in radiological protection of embryo and foetus against external exposure to photons from 50 keV to 10 GeV.

In the literature, no conversion coefficients are available for use in radiological protection of the embryo and foetus against external exposure to photons. This study used the Monte-Carlo code MCNPX to determine mean absorbed doses to the embryo and foetus when the mother is exposed to external photon fields. Monoenergetic photons ranging from 50 keV to 10 GeV were considered. The irradiation geometries included antero-posterior (AP), postero-anterior (PA), lateral (LAT), rotational (ROT), and isotropic (ISO). At each of these standard irradiation geometries, absorbed doses to the foetal brain and body were calculated for the embryo of 8 weeks and the foetus of 3, 6 or 9 months. Photon fluence-to-absorbed-dose conversion coefficients were estimated for the four prenatal ages.

Fluence-to-absorbed dose conversion coefficients for use in radiological protection of embryo and foetus against external exposure to protons from 100 MeV to 100 GeV.

In the literature, no conversion coefficients are available for use in radiological protection of embryo and foetus against external exposure to protons. This study used the Monte Carlo code MCNPX to determine mean absorbed doses to the embryo and foetus when the mother is exposed to proton fields. Monoenergetic protons ranging from 100 MeV to 100 GeV were considered. The irradiation geometries include antero-posterior (AP), postero-anterior (PA), lateral (LAT), rotational (ROT) and isotropic (ISO). At each of these standard irradiation geometries, absorbed doses to the foetal brain and body were calculated for the embryo of 8 weeks and the foetus of 3, 6 or 9 months. Proton fluence-to-absorbed dose conversion coefficients were derived for the four prenatal ages.

Roles of the mammalian subventricular zone in cell replacement after brain injury.

The subventricular zones (SVZs) are essential sources of new cells in the developing brain and remnants of these germinal zones persist into adulthood. As these cells have the capacity to replenish neurons and glia that are turning over, many investigators have assessed the SVZ's role in replacing neural cells eliminated by brain injuries. A review of the literature reveals that the progenitors within the SVZs are vulnerable to chemical, radiation and ischemia-induced damage, whereas the neural stem cells are resilient. With moderate insults, the SVZ can recover, but it cannot recover after more severe injury. Thus, the vulnerability of these cells has important ramifications when considering therapeutic interventions for the treatment of brain tumors and for the prospect of recovery after ischemia. The cells of the perinatal and adult SVZ not only have the capacity to replenish their own numbers, but they also have the capacity to replace neurons and glia after ischemic and traumatic brain injuries. Moreover, the mechanisms underlying these regenerative responses are beginning to be revealed. By reviewing, comparing and contrasting the responses of the SVZs to different injuries, our goal is to provide a foundation from which current and future studies on the potential of the SVZs for cell replacement can be evaluated.

Neutron fluence-to-dose conversion coefficients for embryo and fetus.

A problem of concern in radiation protection is the exposure of pregnant women to ionising radiation, because of the high radiosensitivity of the embryo and fetus. External neutron exposure is of concern when pregnant women travel by aeroplane. Dose assessments for neutrons frequently rely on fluence-to-dose conversion coefficients. While neutron fluence-to-dose conversion coefficients for adults are recommended in International Commission on Radiological Protection publications and International Commission on Radiological Units and Measurements reports, conversion coefficients for embryos and fetuses are not given in the publications. This study undertakes Monte Carlo calculations to determine the mean absorbed doses to the embryo and fetus when the mother is exposed to neutron fields. A new set of mathematical models for the embryo and fetus has been developed at Health Canada and is used together with mathematical phantoms of a pregnant female developed at Oak Ridge National Laboratory. Monoenergetic neutrons from 1 eV to 10 MeV are considered in this study. The irradiation geometries include antero-posterior (AP), postero-anterior (PA), lateral (LAT), rotational (ROT) and isotropic (ISO) geometries. At each of these standard irradiation geometries, absorbed doses to the fetal brain and body are calculated; for the embryo at 8 weeks and the fetus at 3, 6 or 9 months. Neutron fluence-to-absorbed dose conversion coefficients are derived for the four age groups. Neutron fluence-to-equivalent dose conversion coefficients are given for the AP irradiations which yield the highest radiation dose to the fetal body in the neutron energy range considered here. The results indicate that for neutrons <10 MeV more protection should be given to pregnant women in the first trimester due to the higher absorbed dose per unit neutron fluence to the fetus.

Response of avian embryonic brain to spatially segmented x-ray microbeams.

Duck embryo was studied as a model for assessing the effects of microbeam radiation therapy (MRT) on the human infant brain. Because of the high risk of radiation-induced disruption of the developmental process in the immature brain, conventional wide-beam radiotherapy of brain tumors is seldom carried out in infants under the age of three. Other types of treatment for pediatric brain tumors are frequently ineffective. Recent findings from studies in Grenoble on the brain of suckling rats indicate that MRT could be of benefit for the treatment of early childhood tumors. In our studies, duck embryos were irradiated at 3-4 days prior to hatching. Irradiation was carried out using a single exposure of synchrotron-generated X-rays, either in the form of parallel microplanar beams (microbeams), or as non-segmented broad beam. The individual microplanar beams had a width of 27 microm and height of 11 mm, and a center-to-center spacing of 100 microm. Doses to the exposed areas of embryo brain were 40, 80, 160 and 450 Gy (in-slice dose) for the microbeam, and 6, 12 and 18 Gy for the broad beam. The biological end point employed in the study was ataxia. This neurological symptom of radiation damage to the brain developed within 75 days of hatching. Histopathological analysis of brain tissue did not reveal any radiation induced lesions for microbeam doses of 40-160 Gy (in-slice), although some incidences of ataxia were observed in that dose group. However, severe brain lesions did occur in animals in the 450 Gy microbeam dose groups, and mild lesions in the 18 Gy broad beam dose group. These results indicate that embryonic duck brain has an appreciably higher tolerance to the microbeam modality, as compared to the broad beam modality. When the microbeam dose was normalized to the full volume of the irradiated tissue. i.e., the dose averaged over microbeams and the space between the microbeams, brain tolerance was estimated to be about three times higher to microbeam irradiation as compared with broad beam irradiation.

Safety of radiographic imaging during pregnancy.

Maternal illness during pregnancy is not uncommon and sometimes requires radiographic imaging for proper diagnosis and treatment. The patient and her physician may be concerned about potential harm to the fetus from radiation exposure. In reality, however, the risks to the developing fetus are quite small. The accepted cumulative dose of ionizing radiation during pregnancy is 5 rad, and no single diagnostic study exceeds this maximum. For example, the amount of exposure to the fetus from a two-view chest x-ray of the mother is only 0.00007 rad. The most sensitive time period for central nervous system teratogenesis is between 10 and 17 weeks of gestation. Nonurgent radiologic testing should be avoided during this time. Rare consequences of prenatal radiation exposure include a slight increase in the incidence of childhood leukemia and, possibly, a very small change in the frequency of genetic mutations. Such exposure is not an indication for pregnancy termination. Appropriate counseling of patients before radiologic studies are performed is critical.

Health impacts of large releases of radionuclides. Biological effects of prenatal irradiation.

After large releases of radionuclides, exposure of the embryo or fetus can take place by external irradiation or uptake of radionuclides. The embryo and fetus are radiosensitive throughout prenatal development. The quality and extent of radiation effects depend on the developmental stage. During the preimplantation period (one to 10 days postconception, p.c.), a radiation exposure of at least 0.2 Gy can cause the death of the embryo. Malformations are only observed in rare cases when genetic predispositions exist. Macroscopic, anatomical malformations are induced only after irradiation during the major organogenesis (two to eight weeks p.c.). A radiation dose of about 0.2 Gy is a doubling dose for the malformation risk, as extrapolated from experiments with rodents. The human embryo may be more radioresistant. During early fetogenesis (8-15 weeks p.c.) a high radiosensitivity exists for the development of the brain. Radiation doses of 1.0 Gy cause severe mental retardation in about 40% of the exposed fetuses. It must be taken into account that a radiation exposure during the fetal period can also induce cancer. It is generally assumed that the risk exists at about the same level as for children.

Perinatal loss and neurological abnormalities among children of the atomic bomb. Nagasaki and Hiroshima revisited, 1949 to 1989.

Studies of the survivors of the atomic bombing of Hiroshima and Nagasaki who were exposed to ionizing radiation in utero have demonstrated a significant increase in perinatal loss and the vulnerability of the developing fetal brain to injury. These studies have also helped to define the stages in the development of the human brain that are particularly susceptible to radiation-related damage. Exposure at critical junctures in development increases the risk of mental retardation, small head size, subsequent seizures, and poor performance on conventional tests of intelligence and in school. The most critical period, 8 through 15 weeks after fertilization, corresponds to that time in development when neuronal production increases and migration of immature neurons to their cortical sites of function occurs. The epidemiologic data are, however, too sparse to settle unequivocally the nature of the dose-response function and, in particular, whether there is or is not a threshold to damage. If a threshold does exist, it appears to be in the 0.10- to 0.20-Gy fetal-dose range in this vulnerable gestational period.

In utero exposure to A-bomb radiation and mental retardation; a reassessment.

The prevalence of mental retardation in children exposed in utero to the atomic bombs in Hiroshima and Nagasaki has been re-evaluated in reference to gestational age and tissue dose in the fetus. There was no risk at 0-8 weeks post-conception. The highest risk of forebrain damage occurred at 8-15 weeks of gestational age, the time when the most rapid proliferation of neuronal elements and when most, if not all, neuroblast migration to the cerebral cortex from the proliferative zones is occurring. Overall, the risk is five or more times greater in these weeks than in subsequent ones. In the critical period, damage expressed as the frequency of subsequent mental retardation appears to be linearly related to the dose received by the fetus. A linear model is not equally applicable to radiation-related mental retardation after the 15th week, the observed values suggesting that there a threshold may exist. The data are consistent with a probability of occurrence of mental retardation of 0.40% per cGy or 40% per gray.