Central Nervous System In Infants Research Articles

Dietary docosahexaenoic acid but not arachidonic acid influences central nervous system fatty acid status in baboon neonates

The influence of dietary docosahexaenoic acid (DHA, 22:6n-3) and arachidonic acid (AA, 20:4n-6) on infant central nervous system (CNS) composition has implications for neural development, including vision, cognition, and motor function. We consider here combined results of three published studies of DHA/AA-containing formulas and breastfeeding to evaluate the CNS tissue response of baboon neonates with varied concentration and duration of DHA/AA consumption [G.Y. Diau, A.T. Hsieh, E.A. Sarkadi-Nagy, V. Wijendran, P.W. Nathanielsz, J.T. Brenna, The influence of long chain polyunsaturate supplementation on docosahexaenoic acid and arachidonic acid in baboon neonate central nervous system, BMC Med. 3 (2005) 11; A.T. Hsieh, J.C. Anthony, D.A. Diersen-Schade, et al., The influence of moderate and high dietary long chain polyunsaturated fatty acids (LCPUFA) on baboon neonate tissue fatty acids, Pediatr. Res. 61 (2007) 537–45; E. Sarkadi-Nagy, V. Wijendran, G.Y. Diau, et al., The influence of prematurity and long chain polyunsaturate supplementation in 4-week adjusted age baboon neonate brain and related tissues, Pediatr. Res. 54 (2003) 244–252]. A total of 43 neonates born spontaneously at term, or preterm by Cesarean section, consumed diets with DHA–AA (%w/w) at several levels: none (0,0), moderate (0.3, 0.6), or high (>0.6, 0.67 or 1.2). CNS fatty acids were analyzed at 4 and 12 weeks postpartum for term baboons and 7.5 weeks for preterm neonates. CNS DHA was consistently greater by 5–30% in neonates consuming DHA and nearer 30% for cortex. In contrast, CNS AA was unaffected by dietary AA and decreased in all structures with age. Dietary DHA consistently supports greater CNS DHA and maintenance of cortex DHA concentration with feeding duration, while CNS AA is not related to dietary supply. These data on structure-specific LCPUFA accretion may provide insight into neural mechanisms responsible for suboptimal functional outcomes in infants consuming diets that do not support the highest tissue DHA levels.

Extrarenal rhabdoid tumours outside the central nervous system in infancy

Malignant rhabdoid tumours (RT) are increasingly recognized in young children, probably as a consequence of advances in accurate histological diagnosis rather than a true increase in frequency. Although typically presenting as renal tumours in infancy, extrarenal tumours outside the central nervous system (CNS) in children less than 12 months of age are now well recognized, but previous literature on their imaging features is very limited. To demonstrate the imaging features of extrarenal RTs outside the CNS. A retrospective database review was made from 1989 to 2007 of patients diagnosed with extrarenal RT in infancy, i.e. below 12 months of age. There were nine patients (six boys and three girls). The age at presentation varied from 1 to 11 months (average 6 months). Tumours were located in the thorax/mediastinum (n=3), liver (n=3), neck (n=1), shoulder (n=1) and axilla (n=1). The imaging modalities used included US (n=8), CT (n=7) and MRI (n=6). Bone scan was positive in one patient, while metastases at the time of diagnosis occurred in four patients. On MRI the tumours tended to show nonspecific hypointensity on T1-W images and heterogeneous hyperintensity on T2-W images, with heterogeneous enhancement. This is the largest radiological series of extrarenal RTs outside the CNS in infancy. In our series no imaging features were found specific to the diagnosis. A tendency towards large size and mediastinal/paravertebral location were noted. A hypodense solid component on CT and a heterogeneous hyperintensity on T2-W MR images suggest that this tumour should be considered in the routine differential diagnosis of soft-tissue tumours in infancy, in addition to rhabdomyosarcoma.

Guilia Ottaviani: Crib Death. Sudden Unexplained Death of Infants: The Pathologist’s Viewpoint

For decades, crib death or SIDS, the sudden death of an infant under 1 year of age which remains unexplained after a thorough case investigation, including performance of a complete autopsy, examination of the death scene, and review of the clinical history has been one of the main topics of scientific research and routine work in forensic pathology all over the world. The tragedy that parents face when SIDS occurs is one aspect. The main focus for us as forensic pathologists in such cases is to exclude any other causes of death and especially to rule out homicide. This book is based on the author’s PhD dissertation from the University of Milan. Over the last years, Dr. Ottaviani has published a presentable number of scientific papers concerning mainly the cardiac conduction system and the central nervous system in infants and especially in those who have died of SIDS. Dr. Ottavani is a well-recognized researcher in the field of SIDS in clinical pathology and her monograph presents a systematic summary of the investigations carried out and results achieved by her study group. The book is good to read from both an intellectual as well as a scientific point of view. However, the forensic pathologist, probably in contrast to the clinical pathologist who is not so focused as those dealing with cases that occasionally end in a court rooms as previously concealed homicides, misses those aspects dealing with situations when a suspected SIDS case turns out as infanticide. It has been proposed that as many as approximately 10% of deaths attributed to SIDS are actually infanticide, mainly by smothering (leaving no signs of trauma and unremarkable autopsy findings). The inspection of the death scene by the forensic pathologist who performs the autopsy of the infant may be crucial for the later conclusion whether death by suffocation (may this be accidental or intentional by a third party) has to be considered or not. These are the only aspects that one who is involved in forensic death investigation misses when reading this book. Nevertheless, the Ottavaviani book is a good supplement to all the SIDS books currently available.

Cutaneous Rhabdoid Tumor in a Cat

Rhabdoid tumor is a highly aggressive neoplasm of unknown cellular origin in humans, usually occurring in the kidney and central nervous system of infants or children. In older patients, it occurs rarely in other organs, including the skin and soft tissues. A subcutaneous mass in a 13-year-old male mixed-breed cat was composed of nests or sheets of round to polygonal cells with glassy eosinophilic cytoplasmic inclusions. Immunohistochemically, many neoplastic cells expressed vimentin, localized to the cytoplasmic inclusions, whereas the cytoplasm of some neoplastic cells was diffusely positive for neuron-specific enolase, neurofilament, or S-100 protein. By electron microscopy, the cytoplasmic inclusions were found to be composed of aggregates of intermediate filaments. These findings are quite similar to the histologic, immunohistochemical, and ultrastructural features of human rhabdoid tumors and the few rhabdoid tumors reported in animals.

The Role of Toll-Like Receptor 7 (TLR7) in Neuroinflammatory Responses to Retrovirus Infection in Mice (44.41)

Abstract Retrovirus infection in the central nervous system of infants is often associated with strong innate immune responses including production of cytokines and chemokines, activation of astrocytes and microglia and recruitment of macrophages. Understanding how retrovirus infection leads to the induction of these innate immune responses in the CNS is important in determining mechanisms of pathogenesis. Several studies have demonstrated that single-stranded RNA viruses can stimulate macrophages and dendritic cells through toll-like receptor 7 (TLR7). In the current study, we analyzed whether TLR7 was expressed in the neonatal brain and whether TLR7 contributed to retroviral-induced innate immune response. TLR7 was expressed primarily by ependymal and endothelial cells in the brain as detected by immunohistochemistry. Deficiency in TLR7 did not alter interferon beta responses to neurovirulent murine retrovirus infection, virus replication in the brain or virus-mediated neurological disease. However, retrovirus-induced activation of astrocytes and the production of multiple chemokines were suppressed in TLR7 deficient mice compared to wildtype controls. Thus, TLR7 signaling appears to play a significant role in the activation of the innate immune response to retrovirus infection in the neonatal brain. This study was supported by NIH IP20RR020159-01.

A Case of Erythromycin-ResistantUreaplasma urealyticumMeningitis in a Premature Infant

Ureaplasma urealyticum causes infection or colonization of female genital tracts associated with preterm delivery and infertility and the infection of the bloodstream, respiratory tract, and central nervous system in infants, especially in prematures. We report the first case of U. urealyticum meningitis in a premature infant in Korea. She was born with a birth weight of 1,481 gram at 32+3 weeks' gestation and hospitalized for a respiratory care in the NICU in November 2005. Endotracheal aspirates and urine cultures grew U. urealyticum at <10(4) CFU/mL of the specimens at 2-day-old, and cerebrospinal fluid (CSF) cultures grew U. urealyticum at > or = 10(4) CFU/mL of CSF. The patient had a marked CSF pleocytosis, low glucose and high protein content on the 13th hospital day. CSF cultures for ordinary bacteria, mycobacteria and fungi remained negative. U. urealyticum was resistant to erythromycin, tetracycline, ciprofloxacin and pristinamycin, but susceptible to doxycycline. Although she was treated with erythromycin for 30 days, the organism was still isolated four times from the CSF with fluctuation of C-reactive protein (CRP). After the addition of chloramphenicol, CSF cultures became negative in 3 days. However, CRP rose again with increased BUN at the 99th hospital day, and she died on the 103rd hospital day under the diagnosis of a clinical sepsis of unknown origin. In acute meningitis of prematures already colonized with U. urealyticum, ureaplasmal cultures and susceptibility test are warranted in Korea.

ORIGINS OF TACTILE VULNERABILITY IN HIGH-RISK INFANTS

This study examined the degree to which birthweight, gestational age, fetal drug exposure, hazardous postnatal medical events, and a mother's predisposition toward touch predicted the likelihood of an infant's tactile vulnerability during nursing care. The convenience sample included 99 hospitalized infants in their second week of life and their mothers. The design was correlational. A standardized observational assessment was used to code the infant's physiological and behavioral responses to touch during 4 different episodes of nursing care. Chart review was performed to collect information regarding fetal drug exposure, birthweight, gestational age, and postnatal medical events. Mothers completed a questionnaire regarding their own comfort with using touch and being touched. The Tactile Vulnerability Assessment measured infant reactivity to and tolerance for touch during nursing care. The Postnatal Complications Scale identified hazardous medical conditions and treatments experienced by the infant during the first 2 weeks of life, and the Physical Contact Assessment evaluated a mother's predisposition toward touch. The number of hazardous postnatal medical events experienced by an infant was the primary predictor of tactile vulnerability, accounting for 28% of the variance in the infant's likelihood of developing hyperarousal and distress from touch during care. Illicit fetal drug exposure and maternal predisposition toward touch were also significant predictors. The significant relationship of postnatal medical events to tactile vulnerability suggests that it may be associated with the presence of infant pain or injury to the infant's central nervous system. Symptoms of drug withdrawal and the impact of teratogens on arousal regulation may also be implicated in greater distress from touch by infants. In addition, findings suggest the potential for inherited transmission of a vulnerability to touch. Assessment of infant vulnerability, including discussion with parents about their views of the infant's needs regarding touch, may enhance problem identification and early intervention to reduce infant distress and further medical problems.

Children with HIV: improved mortality and morbidity with combination antiretroviral therapy

Advances in the management of children with vertical HIV-1 infection in the developing and developed worlds are discussed in reference to literature published in 2003/4. Studies in mother-to-child transmission are beyond the scope of this review. Improvements in mortality and morbidity from HIV-1 infection following combination antiretroviral therapy are extremely encouraging. There is an increase in the understanding of the immune response to HIV-1 in infants and children and a possible future role for immunomodulatory therapies. Preliminary data are available on the timing of initiation of antiretroviral therapy, the optimization of drug combinations and the clinical interpretation of genotypic resistance testing and therapeutic drug monitoring. Evidence is emerging that early antiretroviral therapy can protect the central nervous system in infants. In resource-limited settings, mortality and morbidity remain extremely high but low-cost health interventions such as prophylactic co-trimoxazole can reduce mortality prior to the expansion of antiretroviral therapy programmes. Further randomized controlled trials assessing antiretroviral therapy combinations with a sustained virological/immunological response with minimal toxicities are required. The roles of therapeutic drug monitoring and resistance testing require further elucidation. The expansion of antiretroviral therapy programmes is essential for children with HIV living in resource-limited settings.

Cortical Release Signs in Psychiatry

To review the role of cortical release signs (CRS) in neuropsychiatry. A thorough literature review was conducted using Medline and Psychlit databases, and other relevant references available to the authors. A number of neurological abnormalities are reported at elevated rates in neuropsychiatric conditions. CRS are a group of primitive reflexes that are present in the neonate but become inhibited as the infant central nervous system (CNS) develops, only to later re-emerge in the context of CNS disease. The clinical elicitation and interpretation of each CRS is described with reference to its neurobiology. The prevalence of CRS in schizophrenia, affective disorder, obsessive-compulsive disorder, Alzheimer's disease, vascular dementia, frontotemporal dementia and other neuropsychiatric illness allows for their use in the clinical management of these patients, including diagnostic assessment, treatment monitoring and prognosis. A number of issues complicate their interpretation in neuropsychiatric illness, including the apparent high base rate of some CRS in non-clinical populations, their increasing prevalence with age, lack of specificity and uncertainty over what constitutes an 'abnormal' response. In some circumstances, CRS may assist in diagnostic differentiation and illness staging.

Lead Exposure and (n-3) Fatty Acid Deficiency during Rat Neonatal Development Affect Subsequent Spatial Task Performance and Olfactory Discrimination

Docosahexaenoic acid [22:6(n-3), DHA] is important for optimal infant central nervous system development, and lead (Pb) exposure during development can produce neurological deficits. Long-Evans strain rats were fed either an (n-3) deficient [(n-3) Def] diet to produce brain DHA deficiency, or an adequate [(n-3) Adq] diet through 2 generations. At the birth of the 2nd generation, the dams were subdivided into 4 groups and supplied drinking water containing either 5.27 mmol/L (Pb) or sodium (Na) acetate until weaning. Rats were killed at 3 wk (weaning) and 11 wk (maturity) for brain Pb and fatty acid analysis. Spatial task and olfactory-cued behavioral assessments were initiated at 9 wk. Rats in the (n-3) Def group had a 79% lower concentration of brain DHA compared with the (n-3) Adq group with no effect of Pb exposure. At weaning, Pb concentrations were 7.17 +/- 0.47 nmol Pb/g of brain (wet weight) in the (n-3) Adq-Pb group and 6.49 +/- 0.63 nmol Pb/g of brain (wet weight) in the (n-3) Def-Pb group. At maturity, the brains contained 1.30 +/- 0.22 and 1.07 +/- 0.12 nmol Pb/g (wet weight), respectively. In behavioral testing, significant effects of both Pb and DHA deficiency were observed in the Morris water maze probe trial and in 2-odor olfactory discrimination acquisition and olfactory-based reversal learning tasks. Both lactational Pb exposure and (n-3) fatty acid deficiency led to behavioral deficits with additive effects observed only in the acquisition of 2-odor discriminations.

Music and Multimodal Stimulation as Developmental Intervention in Neonatal Intensive Care

ABSTRACT: Among developments in neonatal intensive care music therapy clinical services is the music and multimodal stimulation (MMS) procedure established by Standley (1998). The procedure incorporates principles of auditory, tactile, vestibular, and visual stimulation toward the goal of optimizing premature infant development. Since its conception, the procedure has grown into a comprehensive program of developmental intervention, involving not only infants, but also their parents and caregivers. This article includes an explanation of the needs of premature infants in a Neonatal Intensive Care Unit; MMS procedure development, clinical implementation, and benefits; parent and caregiver involvement; and program modifications. Implications for future research are also discussed. Of all infants born annually in the U.S., 11.6% are premature and 7.6% are of low birth weight (LBW). Premature and LBW infants that survive often do so with compromised neurological development (Martin, Hamilton, Ventura, Menacker, & Park, 2002) and usually require lengthy hospitalization (White-Traut, Nelson, Burns, &Cunningham, 1994). Consequently, early intervention begins in the Neonatal Intensive Care Unit (NICU). The environment of the NICU may interfere with the maturation and organization of the infant's central nervous system and fail to meet the infant's developmental needs (White-Traut et al., 1994). Infant neurological development is cephalocaudal and proximodistal, manifested in initially more fully developed receptors of tactile and vestibular stimulation than those of hearing and vision (Owens, 2001). The nature of the NICU can overstimulate the lesser developed distance receptors through continual presence of bright lights and noxious sounds and neglect the more mature tactile and vestibular pathways (White-Traut et al., 1994). Also potentially disrupting to the infant's growth and development are the necessary caregiving and medical procedures (e.g., diapering, bathing, dressing, feeding, assessments of vital signs, lab tests, intravenous line insertions, eye exams, administrations of medications, etc.). Because of restrictions caused by medical needs and staffing limitations, infants in the NICU have minimal opportunity to experience normal cause and effect relationships (e.g., crying to be picked up, fed, etc.) that are vital to cognitive and behavioral development (Vickers, Ohlsson, Lacy, & Horsley, 2000). Research about fetal learning has suggested that the NICU, in addition to providing for the medial needs of the infant, should also provide the necessary requirements for learning through contingent experiences (White-Traut et al., 1994). Appropriate intervention can be effective in promoting growth and development of premature and LBW infants by combating unnatural and potentially stressful environmental factors, and by offering tactile stimulation that would have been provided in the womb (Vickers, Ohlsson, Lacy, & Horsley, 2000). Vickers, Ohlsson, Lacy, and Horsley (2000) compared multiple studies incorporating developmentally based progressions of tactile stimulation, and discovered that infants receiving massage had mean hospitalizations 4.6 days shorter and mean average daily weight gains 5 g greater than those not receiving massage. Motionless touch, on the other hand, appeared to lead to a mean average daily weight loss of 0.2 g. Across multiple studies examined by Field (1995), the provision of separate or combined auditory, tactile, vestibular, and visual (ATVV) stimulation for premature infants has resulted in the following: * increased weight gain * developmental enhancement * lower levels of anxiety and stress hormones * improved overall infant health and immune functioning * more responsive, awake, and active infants * less exhaustion * better state regulation * improved muscle tone * shorter lengths of hospitalization. …

Central nervous system infection in congenital syphilis.

Identification of infants with Treponema pallidum infection of the central nervous system remains challenging. We used rabbit-infectivity testing of the cerebrospinal fluid to detect T. pallidum infection of the central nervous system in infants born to mothers with syphilis. The results were compared with those of clinical, radiographic, and conventional laboratory evaluations; IgM immunoblotting of serum and cerebrospinal fluid; polymerase-chain-reaction (PCR) assay testing of serum or blood and cerebrospinal fluid; and rabbit-infectivity testing of serum or blood. Spirochetes were detected in the cerebrospinal fluid of 19 of 148 infants by rabbit-infectivity testing. Exposure of the infant to antibiotics before cerebrospinal fluid was obtained for rabbit-infectivity testing was associated with a negative test result (P=0.001). Spirochetes were detected in the cerebrospinal fluid in 17 of 76 infants (22 percent) who had no prior antibiotic exposure. These 17 infants included 41 percent (16 of 39) of those with some abnormality on clinical, laboratory, or radiographic evaluation; 60 percent (15 of 25) of those with abnormal findings on physical examination that were consistent with congenital syphilis; and 41 percent (17 of 41) of those with a positive result on IgM immunoblotting or PCR testing of serum, blood, or cerebrospinal fluid, or a positive result on rabbit-infectivity testing of serum or blood. Only one infant who had normal findings on clinical evaluation had a positive cerebrospinal fluid rabbit-infectivity test. Overall, central nervous system infection was best predicted by IgM immunoblotting of serum or PCR assay of serum or blood. Most infants with T. pallidum infection of the central nervous system can be identified by physical examination, conventional laboratory tests, and radiographic studies. However, the identification of all such infants requires the use of additional tests, including IgM immunoblotting and PCR assay.

Histopathology of brain tissue from patients with infantile spasms

This chapter reviews the patterns of neuropathologic abnormality encountered in cortical resections performed for the treatment of infantile spasms (ISS) in the broader context of the larger "universe" of neuropathology seen in the central nervous system of infants with this syndrome as well as older children with intractable epilepsy. Although destructive lesions (encephalomalacia), Sturge-Weber-Dimitri syndrome, and even neoplasms can cause ISS, its most common neuropathologic substrate is cortical dysplasia (CD), representing the result of aberrant neuronal migration to the neocortex from the germinal matrix. Ways to recognize CD morphologically and assess its severity are reviewed, as are special stains and immunohistochemical methods that may be useful in confirming the diagnosis. The similarity and relationship between (sporadic) CD and tubers of tuberous sclerosis are discussed. Future potentially fruitful research directions aimed at refining the clinicopathologic analysis of the role of CD in ISS and epilepsies of older children are briefly considered.

Randomized clinical trials in infancy: methodologic issues

Randomized clinical trials of early nutritional interventions in infants are necessary to establish safety and efficacy of supplementation of infant formulas with LCPUFAS for term and preterm infants. Such trials pose significant methodologic difficulties when applied to infants because of the rapidly changing development of the infant's central nervous system and its interdependence with multiple environmental factors. Current assessments of infant cognitive development in the first year of life lack stability and predictive relationships to later outcomes. Thus, intervention trials need to extend beyond the first two years of life. Small sample sizes, high attrition rates, and lack of attention to confounding variables known to be related to child outcomes are additional problems in the majority of studies to date, especially for preterm populations. Attention to selection and attrition biases and the roles of mediating and moderating factors in affecting intervention effects are also necessary to determine the benefits vs risks of LCPUFA supplementation of infant formula.

Overview of the treatment of infant central nervous system tumors: medulloblastoma as a model.

Overview of the treatment of infant central nervous system tumors: medulloblastoma as a model.

Neonatal Neurobehavioral and Neuroanatomic Correlates of Prenatal Cocaine Exposure: Problems of Dose and Confounding.

Complex methodologic challenges face researchers studying the effects of prenatal cocaine exposure on infant outcome. These include unavoidable imprecision in ascertaining the gestational timing and dose of cocaine to which the fetus was exposed and difficulties in identifying and quantifying the confounding, mediating, and moderating variables. Review of research on neonatal behavioral and cranial ultrasound findings following in utero cocaine exposure is used to illustrate these issues. We conclude that there are measurable but not dramatic dose-related effects of prenatal cocaine exposure on infant central nervous system structure and function. The effects of dose of prenatal cocaine exposure on later child development remain to be determined. Such research would be facilitated by a scientific consensus delineating relative doses of prenatal cocaine exposure.

Eleventh Annual Meeting of the Society for Pediatric Anesthesia, San Diego, California, October 17, 1997

Eleventh Annual Meeting of the Society for Pediatric Anesthesia, San Diego, California, October 17, 1997

Selected pediatric viral infections

Viral infections of the central nervous system in infants and children are uncommon but potentially serious illnesses. Common causes have included the enteroviruses (particularly polioviruses and coxsackieviruses), herpes viruses (type 1 and type 2 herpes simplex, varicella, and cytomegalovirus), arboviruses, rubella, mumps, measles (including subacute sclerosing panencephalitis), and human immunodeficiency virus. Several of these viruses, such as cytomegalovirus, herpes simplex, and vertically transmitted human immunodeficiency virus, may cause congenital infections. Others are acquired later in childhood. In recent years, immunization programs have significantly reduced the occurrence of some of these diseases. A brief survey of the clinical and pathological manifestations of these illnesses will be discussed along with current incidence data.

The Transition to Reaching: Mapping Intention and Intrinsic Dynamics

The onset of directed reaching demarks the emergence of a qualitatively new skill. In this study we asked how intentional reaching arises from infants' ongoing, intrinsic movement dynamics, and how first reaches become successively adapted to the task. We observed 4 infants weekly in a standard reaching task and identified the week of first arm-extended reach, and the 2 weeks before and after onset. The infants first reached at ages ranging from 12 to 22 weeks, and they used different strategies to get the toy. 2 infants, whose spontaneous movements were large and vigorous, damped down their fast, forceful movements. The 2 quieter infants generated faster and more energetic movements to lift their arms. The infants modulated reaches in task-appropriate ways in the weeks following onset. Reaching emerges when infants can intentionally adjust the force and compliance of the arm, often using muscle coactivation. These results suggest that the infant central nervous system does not contain programs that detail hand trajectory, joint coordination, and muscle activation patterns. Rather, these patterns are the consequences of the natural dynamics of the system and the active exploration of the match between those dynamics and the task.

Imaging of the Central Nervous System in Pediatrics and Adolescence

Magnetic resonance imaging (MRI) has taken its place beside computed tomography (CT) and ultrasonography in effective imaging of the central nervous system in infants and children. The major initial impact of MRI in pediatric neuroradiology has been the displacement or replacement of the more expensive and invasive procedures such as angiography, myelography, cisternography, and ventriculography. Ultrasonography remains the screening procedure for fetal and infant central nervous system abnormalities, whereas CT continues to be an effective brain screening technique after loss of the ultrasonography windows with growth of the child. The better the clinical information transmitted to the radiologist in advance of imaging of the patient, the more likely the clinician will receive valuable information in return.