Ment Retard Dev Disabil Res Rev
· 2006 · PMID 17061285
·
Publisher ↗
HIV-1 encephalopathy among perinatally infected children in the United States was initially defined by a classic triad of findings that included: (1) developmental delay, (2) secondary or acquired microcephaly, and (3) p...HIV-1 encephalopathy among perinatally infected children in the United States was initially defined by a classic triad of findings that included: (1) developmental delay, (2) secondary or acquired microcephaly, and (3) pyramidal tract neuromotor deficits. The most severe form of this disorder typically occurred among young children who developed rapidly progressive disease in concert with profound immunosuppression, and Pneumocystis jiroveci pneumonitis (PCP). The neuropathogenesis of this disorder appears to involve a cascade of viral products, various cytokines and chemokines, and neurotransmitters which promote ongoing inflammation, excitation, and overstimualtion of the N-methyl-D-aspartate type receptor (NMDAR) system. These subsequently lead to neuronal injury and death secondary to apoptosis or necrosis, astrocytosis, as well as dentritic and synaptic damage. The frequency of the most severe forms of encephalopathy among children has dropped dramatically since the introduction of highly active antiretroviral therapy (HAART). Of concern, however, is the possibility that a more insidious form of this disorder may be occurring presently among older vertically infected children as a result of inadequate penetration of HAART agents into the cerebrospinal fluid (CSF). This paper will review what published data there is as yet that bears on this question.
Ment Retard Dev Disabil Res Rev
· 2006 · PMID 17061284
·
Publisher ↗
Sickle cell disease (SCD) is a blood disorder; however, the central nervous system (CNS) is one of the organs frequently affected by the disease. Brain disease can begin early in life and often leads to neurocognitive dy...Sickle cell disease (SCD) is a blood disorder; however, the central nervous system (CNS) is one of the organs frequently affected by the disease. Brain disease can begin early in life and often leads to neurocognitive dysfunction. Approximately one-fourth to one-third of children with SCD have some form of CNS effects from the disease, which typically manifest as deficits in specific cognitive domains and academic difficulties. We discuss SCD as a neurodevelopmental disorder by reviewing the mechanisms of neurological morbidity in SCD, the timing of these mechanisms, the types of cognitive and behavioral morbidity that is typical, and the interaction of social-environmental context with disease processes. The impact of the disease on families shares many features similar to other neurodevelopmental disorders; however, social-environmental factors related to low socioeconomic status, worry and concerns about social stigma, and recurrent, unpredictable medical complications can be sources of relatively higher stress in SCD. Greater public awareness of the neurocognitive effects of SCD and their impact on child outcomes is a critical step toward improved treatment, adaptation to illness, and quality of life.
Ment Retard Dev Disabil Res Rev
· 2006 · PMID 17061283
·
Publisher ↗
Most children diagnosed today with acute lymphoblastic leukemia (ALL) will be cured. However, treatment entails risk of neurotoxicity, causing deficits in neurocognitive function that can persist in the years after treat...Most children diagnosed today with acute lymphoblastic leukemia (ALL) will be cured. However, treatment entails risk of neurotoxicity, causing deficits in neurocognitive function that can persist in the years after treatment is completed. Many of the components of leukemia therapy can contribute to adverse neurologic sequelae, including craniospinal irradiation, nucleoside analogs, corticosteroids, and antifolates. In this review, we describe the characteristic radiographic findings and neurocognitive deficits seen among survivors of childhood ALL. We summarize what is known about the pathophysiology of delayed treatment-related neurotoxicity, with a focus on the toxicity resulting from pharmacologic disruption of folate physiology within the central nervous system. Finally, we suggest testable strategies to ameliorate the symptoms of treatment-related neurotoxicity or decrease its incidence.
Ment Retard Dev Disabil Res Rev
· 2006 · PMID 16807911
·
Full text
Multiple sclerosis (MS) is an autoimmune demyelinating disorder of the central nervous system (CNS) that is increasingly recognized as a disease that affects children. Similar to adult-onset MS, children present with vis...Multiple sclerosis (MS) is an autoimmune demyelinating disorder of the central nervous system (CNS) that is increasingly recognized as a disease that affects children. Similar to adult-onset MS, children present with visual and sensory complaints, as well as weakness, spasticity, and ataxia. A lumbar puncture can be helpful in diagnosing MS when CSF immunoglobulins and oligoclonal bands are present. White matter demyelinating lesions on MRI are required for the diagnosis; however, children typically have fewer lesions than adults. Many criteria have been proposed to diagnose MS that have been applied to children, mostly above 10 years of age. The recent revisions to the McDonald criteria allow for earlier diagnosis, such as after a clinically isolated event. However, children are more likely than adults to have monosymptomatic illnesses. None of the approved disease-modifying therapies used in adult-onset MS have been approved for pediatrics; however, a few studies have verified their safety and tolerability in children. Although children and adults with MS have similar neurological symptoms, laboratory (cerebrospinal fluid) data, and neuroimaging findings, the clinical course, pathogenesis, and treatment of childhood onset MS require further investigation.
Ment Retard Dev Disabil Res Rev
· 2006 · PMID 16807910
·
Publisher ↗
Perinatal brain injury in survivors of premature birth has a unique and unexplained predilection for periventricular cerebral white matter. Periventricular white-matter injury (PWMI) is now the most common cause of brain...Perinatal brain injury in survivors of premature birth has a unique and unexplained predilection for periventricular cerebral white matter. Periventricular white-matter injury (PWMI) is now the most common cause of brain injury in preterm infants and the leading cause of chronic neurological morbidity. The spectrum of chronic PWMI includes focal cystic necrotic lesions (periventricular leukomalacia; PVL) and diffuses myelination disturbances. Recent neuroimaging studies support that the incidence of PVL is declining, whereas focal or diffuse noncystic injury is emerging as the predominant lesion. Factors that predispose to PVL during prematurity include hypoxia, ischemia, and maternal-fetal infection. In a significant number of infants, PWMI appears to be initiated by perturbations in cerebral blood flow that reflect anatomic and physiological immaturity of the vasculature. Ischemic cerebral white matter is susceptible to pronounced free radical-mediated injury that particularly targets immature stages of the oligodendrocyte lineage. Emerging experimental data supports that pronounced ischemia in the periventricular white matter is necessary, but not sufficient to generate PWMI. The developmental predilection for PWMI to occur during prematurity appears to be related to both the timing of appearance and regional distribution of susceptible oligodendrocyte progenitors. Injury to oligodendrocyte progenitors may contribute to the pathogenesis of PWMI by disrupting the maturation of myelin-forming oligodendrocytes. Chemical mediators that may contribute to white-matter injury include reactive oxygen species glutamate, cytokines, and adenosine. As our understanding of the pathogenesis of PWMI improves, it is anticipated that new strategies for directly preventing brain injury in premature infants will develop.
Ment Retard Dev Disabil Res Rev
· 2006 · PMID 16807909
·
Publisher ↗
In white matter disorders such as leukodystrophies (LD), periventricular leucomalacia (PVL), or multiple sclerosis (MS), the hypomyelination or the remyelination failure by oligodendrocyte progenitor cells involves error...In white matter disorders such as leukodystrophies (LD), periventricular leucomalacia (PVL), or multiple sclerosis (MS), the hypomyelination or the remyelination failure by oligodendrocyte progenitor cells involves errors in the sequence of events that normally occur during development when progenitors proliferate, migrate through the white matter, contact the axon, and differentiate into myelin-forming oligodendrocytes. Multiple mechanisms underlie the eventual progressive deterioration that typifies the natural history of developmental demyelination in LD and PVL and of adult-onset demyelination in MS. Over the past few years, pathophysiological studies have mostly focused on seeking abnormalities that impede oligodendroglial maturation at the level of migration, myelination, and survival. In contrast, there has been a strikingly lower interest for early proliferative and differentiation events that are likely to be equally critical for white matter development and myelin repair. This review highlights the Yin and Yang principles of interactions between intrinsic factors that coordinately regulate progenitor cell division and the onset of differentiation, i.e. the initial steps of oligodendrocyte lineage progression that are obviously crucial in health and diseases.
Ment Retard Dev Disabil Res Rev
· 2006 · PMID 16807907
·
Publisher ↗
Breakdown of oligodendrocyte-neuron interactions in white matter (WM), such as the loss of myelin, results in axonal dysfunction and hence a disruption of information processing between brain regions. The major feature o...Breakdown of oligodendrocyte-neuron interactions in white matter (WM), such as the loss of myelin, results in axonal dysfunction and hence a disruption of information processing between brain regions. The major feature of leukodystrophies is the lack of proper myelin formation during early development or the onset of myelin loss late in life. These early childhood WM diseases are described as hypomyelination or dysmyelination arising from a primary block in normal myelin synthesis because of a genetic mutation expressed in oligodendrocytes, or failure in myelination secondary to neuronal or astroglial dysfunctions (van der Knaap 2001 Dev. Med. Child Neurol. 43:705-712). Here, we describe the pathophysiological parameters of Canavan disease (CD), caused by genetic mutations of the aspartoacylase (ASPA) gene, a metabolic enzyme restricted in the central nervous system (CNS) to oligodendrocytes. CD presents pathophysiological dysfunctions similar to diseases caused by myelin gene mutations, such as Pelizaeus-Merzbacher disease (PMD) and several animal models, such as myelin deficient rat (md), jimpy (jp), shiverer (sh), and quaking (qk viable) mutant mice. These single gene mutations have pleiotropic effects, whereby the alteration of one myelin gene expression disrupts functional expression of other oligodendrocyte genes with an outcome of hypomyelination/dysmyelination. Among all of the known leukodystrophies, CD is the first disorder, which was approved and tested for the adeno-associated virus vector (AAV)-ASPA gene therapy (Leone et al. 2000 Ann. Neurol. 48:27-38; Janson et al. 2001 Trends Neurosci. 24:706-712) without much success following the first two attempts. ASPA gene delivery attempts in animal models have shown a lowering of N-acetyl L-aspartate and a change in motor functions, while sponginess of the WM, a characteristic of CD remained unchanged (Matalon et al. 2003 Mol. Ther. 7 (5, Part 1):580-587; McPhee et al. 2005 Brain Res. Mol. Brain Res. 135:112-121) even with better viral serotype and delivery of the gene during early phase of development (Klugmann et al. 2005 Mol. Ther. 11:745-753). While different approaches are being sought for the success of gene therapy, there are pivotal developmental questions to address regarding the specific regions of the CNS and cell lineages that become the target for the onset and progression of CD symptoms from early to late stages of development.
Pleasure D, Soulika A, Singh SK
… +2 more, Gallo V, Bannerman P
Ment Retard Dev Disabil Res Rev
· 2006 · PMID 16807906
·
Publisher ↗
While the central nervous system (CNS) is generally thought of as an immunopriviledged site, immune-mediated CNS white matter damage can occur in both the perinatal period and in adults, and can result in severe and pers...While the central nervous system (CNS) is generally thought of as an immunopriviledged site, immune-mediated CNS white matter damage can occur in both the perinatal period and in adults, and can result in severe and persistent neurological deficits. Periventricular leukomalacia (PVL) is an inflammatory white matter disease of premature infants that frequently results in cerebral palsy (CP). Clinical and experimental studies show that both hypoxic/ischemic and innate immune mechanisms contribute to the destruction of immature oligodendroglia and of axons in the deep cerebral white matter in PVL. No data are yet available as to whether there is any genetic predisposition to PVL or to its neurological sequelae. Multiple sclerosis (MS) is an inflammatory white matter disease that often begins in young adulthood, causes multifocal destruction of mature oligodendroglia and of axons, and eventually leads to substantial cumulative neurological disability. Certain genetic polymorphisms contribute to susceptibility to MS, and adaptive immune responses to myelin-associated self antigens, or to exogenous antigens that mimic these self antigens, play a central role in the pathophysiology of this disease.
Pronk JC, van Kollenburg B, Scheper GC
… +1 more, van der Knaap MS
Ment Retard Dev Disabil Res Rev
· 2006 · PMID 16807905
·
Publisher ↗
Leukoencephalopathy with vanishing white matter (VWM) is an autosomal recessive brain disorder, most often with a childhood onset. Magnetic resonance imaging and spectroscopy indicate that, with time, increasing amounts...Leukoencephalopathy with vanishing white matter (VWM) is an autosomal recessive brain disorder, most often with a childhood onset. Magnetic resonance imaging and spectroscopy indicate that, with time, increasing amounts of cerebral white matter vanish and are replaced by fluid. Autopsy confirms white matter rarefaction and cystic degeneration. The process of localization and identification of the first two genes related to VWM, EIF2B5 and EIF2B2, was facilitated by two founder effects in the Dutch population. EIF2B5 and EIF2B2 encode the epsilon and beta subunits of translation initiation factor eIF2B. Soon it was shown that mutations in all five eIF2B subunit genes can cause VWM. EIF2B is essential for the initiation of translation of RNA into protein and is involved in regulation of the process, especially under stress conditions, which may explain the sensitivity to stress conditions observed in VWM patients. The pathophysiology of the disease is still poorly understood.
Ment Retard Dev Disabil Res Rev
· 2006 · PMID 16807890
·
Publisher ↗
Inflammation during the perinatal period has become a recognized risk factor for developmental brain injuries over the past decade or more. To fully understand the relationship between inflammation and brain development,...Inflammation during the perinatal period has become a recognized risk factor for developmental brain injuries over the past decade or more. To fully understand the relationship between inflammation and brain development, a comprehensive knowledge about the immune system within the brain is essential. Microglia are resident immune cells within the central nervous system and play a critical role in the development of an inflammatory response within the brain. Microglia are critically involved with both the innate and adaptive immune system, regulating inflammation and cell damage within the brain via activation of Toll-like receptors, production of cytokines, and a myriad of other intracellular and intercellular processes. In this article, microglial physiology is reviewed along with the role of microglia in developmental brain injuries in humans and animal models. Last, microglial functions within the innate and adaptive immune system will be summarized. Understanding the processes of inflammation and microglial activation is critical for formulating effective preventative and therapeutic strategies for developmental brain injuries.
Ment Retard Dev Disabil Res Rev
· 2006 · PMID 16807889
·
Publisher ↗
There is an increasing awareness that the astrocytes in the immature periventricular white matter are vulnerable to ischemia and respond to inflammation. Here we provide a synopsis of the articles that have evaluated the...There is an increasing awareness that the astrocytes in the immature periventricular white matter are vulnerable to ischemia and respond to inflammation. Here we provide a synopsis of the articles that have evaluated the causes and consequences of developmental brain injuries to white matter astrocytes as well as the consequences of several genetic mutations that result in abnormal astrocyte development. Emerging data suggest that the astrocytes are not simply responding to the injury but are likely victims as well as culprits. Given the important roles that astrocytes play in maintaining ionic, neurotransmitter, and metabolic homeostasis in the brain, a more thorough understanding of the mechanisms that lead to their incapacitation, demise, or reactions as well as a better understanding of the stimuli that regulate their neuroprotective and regenerative properties will enable these cells to be manipulated to preserve the integrity of white matter and to potentially provide therapeutics to enhance neonatal regeneration and recovery from brain injury.
Ment Retard Dev Disabil Res Rev
· 2006 · PMID 16435331
·
Publisher ↗
Maltreatment can have a profound adverse effect on the health of individuals with intellectual disabilities (ID). People with ID may also be more likely to experience maltreatment than other groups. Historically, data on...Maltreatment can have a profound adverse effect on the health of individuals with intellectual disabilities (ID). People with ID may also be more likely to experience maltreatment than other groups. Historically, data on prevalence of maltreatment among people with ID have been sparse and methodologically weak but have suggested that the scope of the problem is considerable. Studies published between 1995 and 2005 were reviewed to determine estimated maltreatment prevalence among people with ID based on recent literature. Prevalence estimates for people with ID were compared to estimates for people with no disabilities and people with other types of disabilities. Only five studies provided maltreatment prevalence estimates for people with ID. The limited data suggest that maltreatment is more prevalent for people with ID than for people with no disabilities and may be higher for people with ID than for people with certain other disabilities. Most of the available research is still based on convenience samples. More population-level data are needed to provide reliable estimates of the prevalence of this important health problem.
Ment Retard Dev Disabil Res Rev
· 2006 · PMID 16435330
·
Publisher ↗
In the past, preventive health concerning sexuality of people with intellectual disabilities was addressed through surgical sterilization as part of nationwide eugenic programs in many countries. For more than 30 years n...In the past, preventive health concerning sexuality of people with intellectual disabilities was addressed through surgical sterilization as part of nationwide eugenic programs in many countries. For more than 30 years now, it has come progressively to light in the scientific literature that, besides major ethical and legal problems, these programs also failed to assess many of the individual's needs in sexual health. The fact that an increasing number of people with intellectual disabilities live in the community rather than in institutions has heightened public awareness that these individuals have sexual expectancies, desires, and needs that must be supported through both education and health services. The emergence of AIDS, including descriptions of cases among people with intellectual disabilities, has further demonstrated that surgical sterilization cannot be considered a global option to achieve preventive sexual health. The aim of this paper is to review scientific studies that have assessed the expectancies and support needs of persons with intellectual disabilities in terms of sexual health. These needs vary widely from one individual to another, according to life milieu, level of disability, and potential comorbidity. From this review, it appears that hygiene management, global gynecological care, and prevention of unplanned pregnancy, sexually transmitted diseases, and abuse have been frequently identified as areas in which the presence of intellectual disability dictates specific support needs. Different approaches that have been evaluated to address these issues will also be discussed.
Ment Retard Dev Disabil Res Rev
· 2006 · PMID 16435329
·
Publisher ↗
While much of the industrialized world struggles for clues to the growing rise in obesity in their respective countries, researchers and service providers involved in understanding the health characteristics and health b...While much of the industrialized world struggles for clues to the growing rise in obesity in their respective countries, researchers and service providers involved in understanding the health characteristics and health behaviors of persons with intellectual disability (ID) struggle with their own issues regarding the increased prevalence of obesity in this segment of the population. What is particularly alarming is that adults with ID residing in the United States in smaller, less supervised settings (e.g., group homes and family households) have a significantly higher rate of obesity compared to other countries and those living in larger and more supervised settings (e.g., institutions). These differences support the theory that the environment appears to exert a powerful influence on obesity in this population. Obesity presents a substantial threat to the livelihood of persons with ID and may have an effect on community participation, independent living, and healthy years of life. The lack of research on successful weight reduction strategies for obese persons with ID makes this an important and greatly needed area of research.
Ment Retard Dev Disabil Res Rev
· 2006 · PMID 16435328
·
Publisher ↗
This paper reviews the recent literature on cardiovascular disease (CVD) prevalence, CVD-related mortality, physiological CVD risk factors, and behavioral CVD risk factors in adults with mental retardation (MR). The lite...This paper reviews the recent literature on cardiovascular disease (CVD) prevalence, CVD-related mortality, physiological CVD risk factors, and behavioral CVD risk factors in adults with mental retardation (MR). The literature on the potential influences of modifiable behavioral CVD risk factors and the physiological CVD risk factors are also reviewed. Adults with mild to moderate MR residing in community settings appear to have an elevated disease prevalence, elevated CVD-related mortality, more adverse physiological CVD risk factors, and elevated behavioral risk compared to others with and without MR. Preliminary evidence supports the benefits of participating in the recommended physical activity levels and consuming the recommended diets to reduce the risk for CVD. The lack of large-scale longitudinal or experimental research indicates a gap in the research. The development of research-based, appropriate, primary prevention programs and intervention strategies aimed at lowering the risk for CVD is highly recommended. Programs should focus on educating individuals with MR along with direct care providers and family members on the importance of appropriate dietary concepts, physical activity habits, and regular health screenings by physicians. Programs should be individualized to regional and cultural issues.
Ment Retard Dev Disabil Res Rev
· 2006 · PMID 16435327
·
Publisher ↗
People with ID represent approximately 2% of the population and, as a group, experience poorer health than the general population. This article presents recent conceptualizations that begin to disentangle health from dis...People with ID represent approximately 2% of the population and, as a group, experience poorer health than the general population. This article presents recent conceptualizations that begin to disentangle health from disability, summarizes the literature from 1999 to 2005 in terms of the cascade of disparities, reviews intervention issues and promising practices, and provides recommendations for future action and research. The reconceptualization of health and disability examines health disparity in terms of the determinants of health (genetic, social circumstances, environment, individual behaviors, health care access) and types of health conditions (associated, comorbid, secondary). The literature is summarized in terms of a cascade of disparities experienced by people with ID, including a higher prevalence of adverse conditions, inadequate attention to care needs, inadequate focus on health promotion, and inadequate access to quality health care services. Promising practices are reviewed from the perspective of persons with ID, providers of care and services, and policies that influence systems of care. Recommendations across multiple countries and organizations are synthesized as guidelines to direct future action. They call for promoting principles of early identification, inclusion, and self-determination of people with ID; reducing the occurrence and impact of associated, comorbid, and secondary conditions; empowering caregivers and family members; promoting healthy behaviors in people with ID; and ensuring equitable access to quality health care by people with ID. Their broadscale implementations would begin to reduce the health disparity experienced by people with ID.
Ment Retard Dev Disabil Res Rev
· 2006 · PMID 16435326
·
Publisher ↗
This article reviews research conducted on the cigarette, alcohol, and illicit drug use of adolescents and adults with mental retardation (MR). The majority of the research related to substance use conducted on this popu...This article reviews research conducted on the cigarette, alcohol, and illicit drug use of adolescents and adults with mental retardation (MR). The majority of the research related to substance use conducted on this population has been limited to surveys. Overall, results of these studies suggest that, although substance use is slightly lower among those with MR than among nondisabled comparison groups, it is nonetheless a problem for many individuals. This research is reviewed and a discussion of both the general and specific flaws of these studies follows. Further, the examination of education, prevention, and treatment programs for this population has been overlooked, indicating that individuals with MR are likely not receiving the services most appropriate for them. The article concludes with a discussion of several topics that need to be addressed in future studies, including research on potential best practices in the overlooked areas of substance abuse interventions.