Hypoplasia of the arcuate nucleus and maternal smoking during pregnancy in sudden unexplained perinatal and infant death

Maternal smoking during pregnancy is the most important risk factor for sudden perinatal and infant death in more industrialized countries. The frequent observation of hypoplasia of the arcuate nucleus in the brainstem of these victims prompted the verification of whether maternal cigarette smoking could be related to defective development of this nucleus during intrauterine life, by affecting the expression of specific genes involved in its developmental process. In serial sections of the brainstem of 54 cases of sudden and unexplained fetal and infant deaths (13 stillbirths, 7 neonatal deaths and 34 sudden infant death syndrome (SIDS) victims), morphological and morphometrical analysis was used to observe the different structural alterations of the arcuate nucleus (bilateral hypoplasia, monolateral hypoplasia, partial hypoplasia, delayed neuronal maturation and decreased neuronal density) detected in 24 cases (44%). Correlating this finding with smoking in pregnancy, a significantly increased incidence of cytoarchitectural alterations of the arcuate nucleus was found in stillborns and SIDS victims with smoker mothers compared to victims with non‐smoker mothers. Moreover, the observation of a wide range of developing morphological defects of the arcuate nucleus related to maternal smoking led to the hypothesis that the constituents of the gas phase in cigarette smoke could directly affect the expression of genes involved in the development of this nucleus, such as the homeobox En‐2 gene.     

Early intervention after perinatal stroke: opportunities and challenges

Perinatal stroke is the most common cause of hemiplegic cerebral palsy. No standardized early intervention exists despite evidence for a critical time window for activity‐dependent plasticity to mould corticospinal tract development in the first few years of life. Intervention during this unique period of plasticity could mitigate the consequences of perinatal stroke to an extent not possible with later intervention, by preserving the normal pattern of development of descending motor pathways. This article outlines the broad range of approaches currently under investigation. Despite significant progress in this area, improved early detection and outcome prediction remain important goals.     

New insights into perinatal depression: pathogenesis and treatment during pregnancy and postpartum

Maternal perinatal mental health has enormous consequences for the well-being of the mother, her baby, and the family. Although it is well documented that perinatal depression is both common and morbid, with a prevalence of 10% to 15% in the general population, there remain many critically important unanswered questions about the pathogenesis of perinatal depression and most effective treatment regimens. Current lines of evidence from both human and animal models implicate hormonal dysregulation, abnormalities in hypothalamic-pituitary-adrenal axis activity, and the contributions of genetics and epigenetics as playing key roles in the development of perinatal reproductive mood disorders. Investigations into both human and animal models of perinatal depression offer much promise for the future identification of the underlying pathophysiology and subsequent early identification and/or prevention and appropriate treatment for women at risk for postpartum depression. Lastly, although it is generally accepted that pregnancy is not protective with regard to new onset or relapse of depression, the way to best treat maternal depression during pregnancy and lactation remains hotly debated. Future research in this area will more clearly elucidate the underlying pathogenesis, the potential long-term impact of perinatal depression on the developing fetus, and how best to counsel pregnant women about the risks of untreated major depressive disorder versus the risks of psychopharmacologic treatment during pregnancy and lactation.     

Life after death: grief therapy after the sudden traumatic death of a family member

TOPIC: Survivors of the sudden traumatic death of a family member are at increased risk for complicated grief and bereavement. PURPOSES: To present the complicating factors inherent to sudden traumatic death in order to promote adaptive grieving in the survivors. SOURCES: A comprehensive review of the existing bereavement literature, clinical anecdotes, and therapeutic experiences. CONCLUSIONS: Grief is a process and not an endpoint. The goal of grief is not to forget about the loss, a commonly stated goal of survivors; rather, the goal is to remember the decedent, understand the changes created by the loss, and determine how to reinvest in life.     

Involvement of somatostatin in breathing control before and after birth, and in perinatal and infant sudden unexplained death

The distribution of the somatostatin was studied by immunohistochemistry on serial sections of the 56 brain stems from subjects aged from 30 gestational weeks to 12 postnatal months, dying of both known and unknown causes. The unexplained deaths included 13 sudden intrauterine deaths, 4 sudden neonatal deaths and 24 sudden infant deaths. We observed intense somatostatin positivity in the cell bodies and fibres of many brainstem nuclei prevalently involved in the respiratory activity (parabrachial/K?lliker-Fuse complex, locus coeruleus, hypoglossus nucleus, dorsal vagus motor nucleus, tractus solitarii nucleus, ambiguus nucleus, and reticular formation) in stillbirths. Only in 8 foetuses with unexplained death the hypoglossus nucleus was somatostatin-negative. In the postnatal deaths, the immunopositivity was prevalently limited to the ventrolateral and ventral subnuclei of the tractus solitarii nucleus. In 13 sudden infant death victims and in one case of death due to pneumonia, somatostatin-positivity was also present in the hypoglossus nucleus. We concluded that: 1) the somatostatin is an important foetal breathing-inhibitor, but it becomes important for the physiological control of respiration immediately after delivery; 2) functional alterations of the hypoglossal nucleus can occur in both sudden perinatal and infant deaths and contribute to the induction of both fatal breathing movements in foetuses and abnormal ventilatory control in infants leading to irreversible apneic phenomena.     

Opioid addiction and pregnancy: perinatal exposure to buprenorphine affects myelination in the developing brain

Buprenorphine is a mu-opioid receptor partial agonist and kappa-opioid receptor antagonist currently on trials for the management of pregnant opioid-dependent addicts. However, little is known about the effects of buprenorphine on brain development. Oligodendrocytes express opioid receptors in a developmentally regulated manner and thus, it is logical to hypothesize that perinatal exposure to buprenorphine could affect myelination. To investigate this possibility, pregnant rats were implanted with minipumps to deliver buprenorphine at 0.3 or 1 mg/kg/day. Analysis of their pups at different postnatal ages indicated that exposure to 0.3 mg/kg/day buprenorphine caused an accelerated and significant increase in the brain expression of all myelin basic protein (MBP) splicing isoforms. In contrast, treatment with the higher dose caused a developmental delay in MBP expression. Examination of corpus callosum at 26-days of age indicated that both buprenorphine doses cause a significant increase in the caliber of the myelinated axons. Surprisingly, these axons have a disproportionately thinner myelin sheath, suggesting alterations at the level of axon-glial interactions. Analysis of myelin associated glycoprotein (MAG) expression and glycosylation indicated that this molecule may play a crucial role in mediating these effects. Co-immunoprecipitation studies also suggested a mechanism involving a MAG-dependent activation of the Src-family tyrosine kinase Fyn. These results support the idea that opioid signaling plays an important role in regulating myelination in vivo and stress the need for further studies investigating potential effects of perinatal buprenorphine exposure on brain development.     

Bereavement after caregiving or unexpected death: effects on elderly spouses

Responses to bereavement have been shown to vary depending on whether death is expected or unexpected, and on the nature of family caregiving experiences, but little previous research has examined these factors simultaneously. To address these issues, we utilized prospective data on bereavement from 193 participants in the Changing Lives of Older Couples (CLOC) study, who were assessed both before their loss and at six and 18 months after the death. Participants who experienced either unexpected loss, or expected loss without caregiving, with low-stress caregiving, or with high-stress caregiving completed measures of psychological, social, and health functioning on each occasion. Results showed that unexpected death was associated with marked increases in depression, while the nature of caregiving did not affect the trajectory of any of the psychological well-being measures. All groups except highly stressed caregivers showed improvements in social activity and support after bereavement, suggesting that highly stressed caregivers may be at an increased risk for social isolation during bereavement. Thus experiencing an unexpected death may put bereaved spouses at risk for depression, while high-stress caregiving may lead to problems with social isolation.     

Women with schizophrenia: pregnancy outcome and infant death among their offspring

Schizophrenia in the mother may imply an increased risk of adverse pregnancy outcome. However, inconclusive findings, unknown pathological mechanisms and possible confounding by social factors and smoking requests further explorations. The aim of this study were to (1) examine non-optimal pregnancy outcome using data from a population-based cohort, controlling for covariates known to influence fetal growth; and (2) perform separate analyses of women diagnosed before childbirth and women hospitalized for schizophrenia during pregnancy. The study sample comprised 2096 births by 1438 mothers diagnosed with schizophrenia (of whom 696 mothers were antenatal diagnosed and 188 admitted during pregnancy) and 1,555,975 births in the general population. We found significantly increased risks for stillbirth, infant death, preterm delivery, low birth weight, and small-for-gestational-age among the offspring of women with schizophrenia. Women with an episode of schizophrenia during pregnancy had the highest risks (e.g., low birth weight; OR 4.3, 95% CI 2.9-6.6 and stillbirth; OR 4.4, 95% CI 1.4-13.8). Controlling for a high incidence of smoking during pregnancy among schizophrenic women (51% vs. 24% in the normal population) and other maternal factors (single motherhood, maternal age, parity, maternal education, mothers' country of birth and pregnancy-induced hypertensive diseases) in a multiple regression model, reduced the risk estimates markedly. However, the risks for adverse pregnancy outcomes were even after adjustments generally doubled for women with an episode of schizophrenia during pregnancy compared to women in the control group (e.g., low birth weight; OR 2.3, 95% CI 1.5-3.5, preterm delivery; OR 2.4, 95% CI 1.5-3.8 and stillbirth; OR 2.5, 95% CI 0.8-7.9). The risks for preterm delivery and low birth weight were significantly elevated throughout the analyses. We conclude that schizophrenia in the mother implies an increased risk for poor perinatal outcome, not fully explained by maternal factors, and a need to consider a common familial (probably genetic) vulnerability for pre- and perinatal stress and schizophrenia.     

Clinician perspectives on decision-making capacity after acquired brain injury

Acquired brain injury frequently alters an individual's ability to make health care decisions based on a clear understanding of the situation and options. This exploratory study investigated the ways health care providers address issues of decisionmaking capacity (DMC) on a daily, functional basis. 33 clinicians providing rehabilitation services to persons with acquired brain injury participated in 1 of 5 semi-structured focus groups. All 33 participants, representing 8 different occupations, agreed that DMC determinations affected their practice every day. Participants underscored a multidimensional rather than a unitary definition of DMC, with an emphasis on fluctuating capacities due to the injury. Important concerns were for the safety of the person with brain injury, the health care provider, and community members. Other themes included rehabilitation team involvement, family context, and professional socialization. Clinical determinations of DMC are context dependent and are affected by the abilities of the individual and the substance and consequences of the decision being made and include the concepts of regaining trust and reclaiming capacity.     

Whole-body cooling after perinatal asphyxia: a pilot study in term neonates

In order to test the practicability and safety of whole-body cooling in term neonates with moderate-to-severe hypoxic-ischaemic encephalopathy (HIE) and to report outcomes, a prospective pilot study was carried out in 25 term infants (median postmenstrual age 38 weeks, range 36 to 41 weeks; 20 males, five females). Whole-body cooling, to a target core temperature of 33 to 34 degrees C, started within 6 hours of birth and was maintained for 72 hours. Of the 25 newborn infants (19 Sarnat II and six Sarnat III, 18 outborn), 18 survived, including 13 (72%) with normal cerebral signal by MRI. Temperature instability occurred during cooling in 15 infants, but neither severe haemodynamic instability nor renal failure was seen. Thrombocytopenia developed in 12 infants, including seven with biological disseminated intravascular coagulation. One patient had hypoxaemia with right-to-left shunting through the ductus arteriosus, and seven had limited meningeal or subdural bleeding. Whole-body cooling is feasible in term neonates, with no life-threatening adverse events. Improvements are needed to obtain stable hypothermia for 72 hours.     

Visualizing cell death in experimental focal cerebral ischemia: promises, problems, and perspectives

One of the hallmarks of stroke pathophysiology is the widespread death of many different types of brain cells. As our understanding of the complex disease that is stroke has grown, it is now generally accepted that various different mechanisms can result in cell damage and eventual death. A plethora of techniques is available to identify various pathological features of cell death in stroke; each has its own drawbacks and pitfalls, and most are unable to distinguish between different types of cell death, which partially explains the widespread misuse of many terms. The purpose of this review is to summarize the standard histopathological and immunohistochemical techniques used to identify various pathological features of stroke. We then discuss how these methods should be properly interpreted on the basis of what they are showing, as well as advantages and disadvantages that require consideration. As there is much interest in the visualization of stroke using noninvasive imaging strategies, we also specifically discuss how these techniques can be interpreted within the context of cell death.     

The patient with dementia, the caregiver and the doctor: cognition, depression and quality of life from three perspectives

BACKGROUND: For comprehensive information about the situation of patients with dementia or mild cognitive impairment (MCI), clinicians have to rely on information from different sources, e.g. caregivers or the patients themselves, which may differ from each other. In addition to the assessment of cognitive impairment, the importance of evaluating not only depressive symptoms but also health related quality of life (HRQOL) in clinical research and practice in dementia has increased. OBJECTIVE: To examine about how the ratings of patients, caregivers and clinicians regarding the patients' cognitive impairment, depression and HRQOL relate to each other by comparing these three perspectives by using self- and proxy-rating measures. METHOD: One hundred outpatients with mild to moderate dementia or MCI and their family caregivers participated in this study. Depression and cognitive impairment were examined with self- and proxy-ratings as well as the Mini-Mental Status Examination (MMSE); HRQOL was assessed with the SF-12 Health Survey and the EUROHIS quality of life index. RESULTS: We found high correspondence between caregivers' assessment of cognitive function and MMSE scores, while patients' self-rating did not correlate with MMSE. HRQOL was underestimated by caregivers compared to self-rating. Concerning depression, the patients' assessment was in good accordance with the clinician's evaluation. CONCLUSION: The study suggests that patients with mild to moderate dementia and MCI are important informants of their HRQOL and depressive symptoms, but they underestimate their cognitive deficits. Assessing different perspectives of the patients' HRQOL is relevant in order to obtain a comprehensive understanding of the patients' well-being.     

The impact of social hierarchies on neural response to feedback evaluations after advice giving

Advisors generally evaluate advisee-relevant feedback after advice giving. The response to these feedback—(1) whether the advice is accepted and (2) whether the advice is optimal—usually involves prestige. Prior literature has found that prestige is the basis by which individuals attain a superior status in the social hierarchy. However, whether advisors are motivated to attain a superior status when engaging in advice giving remains uncharacterized. Using event-related potentials, this study investigates how advisors evaluate feedback after giving advice to superior (vs. inferior) status advisees. A social hierarchy was first established based on two advisees (one was ranked as superior status and another as inferior status) as well as participants' performance in a dot-estimation task in which all participants were ranked as medium status. Participants then engaged in a game in which they were assigned roles as advisors to a superior or inferior status advisee. Afterward, the participants received feedback in two phases. In Phase 1, participants were told whether the advisees accepted the advice provided. In Phase 2, the participants were informed whether the advice they provided was correct. In these two phases, when the advisee was of superior status, participants exhibited stronger feedback-related negativity and P300 difference in response to (1) whether their advice was accepted, and (2) whether their advice was correct. Moreover, the P300 was notably larger when the participants' correct advice led to a gain for a superior-status advisee. In the context of advice giving, advisors are particularly motivated to attain a superior status when the feedback involving social hierarchies, which is reflected in higher sensitivity to feedback associated with superior status advisees at earlier and later stages during feedback evaluations in brains.     

New perspectives on improving upper extremity function after spinal cord injury

Injury to the cervical spinal cord adversely affects arm and hand function to varying degrees depending on the level and severity of injury. These impairments typically result in reduced independence in the performance of activities of daily living and limit participation in recreational activities. There is evidence to suggest individuals with incomplete spinal cord injury may benefit from intensive rehabilitation interventions aimed at improving hand and arm function. Massed practice (repetitive activity-based training) and somatosensory stimulation (prolonged peripheral nerve electrical stimulation at submotor threshold intensity) are 2 interventions that have been shown to improve strength and function in individuals with stroke, presumably by changing cortical excitability. These techniques, however, had not previously been investigated in individuals with spinal cord injury (SCI). In this article the stroke and SCI literature supporting the use of massed practice and somatosensory stimulation as a potential rehabilitative tool to promote recovery of function in individuals with incomplete cervical spinal cord injury (SCI) is reviewed. Recently published research using these novel techniques in which a combination of massed practice and somatosensory stimulation resulted in increased pinch grip strength and upper extremity function in individuals with incomplete cervical SCI when compared to subjects participating in massed practice alone is presented.