Building Programs to Eradicate Toxoplasmosis Part I: Introduction and Overview.

Purpose Of Review: Review building of programs to eliminate infections.

Recent Findings: Morbidity and mortality from toxoplasmosis led to programs in USA, Panama, and Colombia to facilitate understanding, treatment, prevention, and regional resources, incorporating student work.

Summary: Studies foundational for building recent, regional approaches/programs are reviewed.

Multidisciplinary spina bifida clinic: the Chicago experience.

Open spina bifida (open SB) is the most complex congenital abnormality of the central nervous system compatible with long-term survival. Multidisciplinary care is required to address the effect of this disease on the neurological, musculoskeletal, genitourinary, and gastrointestinal systems, as well as the complex psychosocial impact on the developing child. Individuals with SB benefit from the involvement of neurosurgeons, orthopedic surgeons, urologists, physical medicine and rehabilitation specialists, pediatricians, psychologists, physical/occupational/speech therapists, social workers, nurse coordinators, and other personnel.

Surgical management of myelocystocele: a single-center experience with long-term functional outcomes.

Objective: Myelocystocele (MCC) is an uncommon form of skin-covered spinal dysraphism. The authors aimed to present long-term functional outcomes of patients treated for MCC with and without associated abnormalities of cloacal development (ACD).

Methods: All patients with MCC and at least one tethered cord release (TCR) treated at a single institution between 1982 and 2019 were retrospectively reviewed.

Outcomes of hydrocephalus secondary to congenital toxoplasmosis.

Objective: Hydrocephalus occurs in children with congenital toxoplasmosis and can lead to severe disability. In these cases, the decision to intervene is often influenced by the expectation of neurological recovery. In this study, clinical responses to neurosurgical intervention in children with hydrocephalus secondary to congenital toxoplasmosis are characterized.

Lipomyelomeningocele for the urologist: Should we view it the same as myelomeningocele?

Introduction: The primary urologic objectives for lipomyelomeningocele (LMM) and myelomeningocele (MM) are preserving renal integrity and achieving continence. Due to this common ground, LMM and MM are urologically treated the same. However, unlike MM, LMM may present with no evident functional concerns.

Current Management Strategies of Hydrocephalus in the Child With Open Spina Bifida.

Symptomatic hydrocephalus is a common condition associated with myelomeningocele (open spina bifida). Traditionally, hydrocephalus was treated with insertion of a ventriculo-peritoneal (VP) shunt. This has been the standard of treatment since the introduction of the Holter shunt valve for the VP shunt in the late 1950s.

Patterns of Hydrocephalus Caused by Congenital Toxoplasma gondii Infection Associate With Parasite Genetics.

Four anatomical patterns of hydrocephalus secondary to congenital Toxoplasma gondii infection were identified and characterized for infants enrolled in the National Collaborative Chicago-based Congenital Toxoplasmosis Study. Analysis of parasite serotype revealed that different anatomical patterns associate with Type-II vs Not-Exclusively Type-II strains (NE-II) (P = .035).

Predictors of urinary continence following tethered cord release in children with occult spinal dysraphism.

Objective: Children with occult spinal dysraphism represent a wide spectrum of patients. Previous studies assessing urologic outcomes have in part been deficient due to the inability to appropriately categorize these patients and gather long-term follow-up data. In this study, a uniform set of patients that had occult spinal dysraphism with magnetic resonance imaging findings of a fatty filum terminale (FF) and/or low-lying cord (LLC) was identified.

A critical role of noggin in developing folate-nonresponsive NTD in Fkbp8 -/- embryos.

Purpose: Maternal folate intake has reduced the incidence of human neural tube defects by 60-70 %. However, 30-40 % of cases remain nonresponsive to folate intake. The main purpose of this study was to understand the molecular mechanism of folate nonresponsiveness in a mouse model of neural tube defect.

Amniotic fluid and serum biomarkers from women with neural tube defect-affected pregnancies: a case study for myelomeningocele and anencephaly: clinical article.

Object: The authors sought to identify novel biomarkers for early detection of neural tube defects (NTDs) in human fetuses.

Methods: Amniotic fluid and serum were drawn from women in the second trimester of pregnancy. The study group included 2 women pregnant with normal fetuses and 4 with fetuses displaying myelomeningocele (n = 1), anencephaly (n = 1), holoprosencephaly (n = 1), or encephalocele (n = 1).

Nuclear localization of folate receptor alpha: a new role as a transcription factor.

Folic acid (FA) has traditionally been associated with prevention of neural tube defects; more recent work suggests that it may also be involved in in the prevention of adult onset diseases. As the role of FA in human health and disease expands, it also becomes more critical to understand the mechanisms behind FA action. In this work we examined the hypothesis that folate receptor alpha (FRα) acts as a transcription factor.

Maternal intake of folic acid and neural crest stem cells.

Maternal folic acid (FA) intake has beneficial effects in preventing neural tube defects and may also play a role in the prevention of adult onset diseases such as Alzheimer's disease, dementia, neuropsychiatric disorders, cardiovascular diseases, and cerebral ischemia. This review will focus on the effects of maternal FA intake on neural crest stem cell proliferation and differentiation. Although FA is generally considered beneficial, it has the potential of promoting cell proliferation at the expense of differentiation.

Epigenetic regulation of sensory neurogenesis in the dorsal root ganglion cell line ND7 by folic acid.

The epigenetic mechanism of folic acid (FA) action on dorsal root ganglion (DRG) cell proliferation and sensory neuron differentiation is not well understood. In this study, the ND7 cell line, derived from DRG cells, was used to elucidate this mechanism. In ND7 cells differentiated with dbcAMP and NGF, Hes1 and Pax3 levels decreased, whereas Neurog2 levels showed a modest increase.

Fetal neural tube stem cells from Pax3 mutant mice proliferate, differentiate, and form synaptic connections when stimulated with folic acid.

Although maternal intake of folic acid (FA) prevents neural tube defects in 70% of the population, the exact mechanism of prevention has not been elucidated. We hypothesized that FA affects neural stem cell (NSC) proliferation and differentiation. This hypothesis was examined in a folate-responsive spina bifida mouse model, Splotch (Sp(-/-)), which has a homozygous loss-of-function mutation in the Pax3 gene.

Retethering of transected fatty filum terminales.

Object: Untethering of a tethered spinal cord (TSC) by transecting or removing a fatty filum terminale is a relatively simple procedure that can prevent or ameliorate neurological symptoms, and the postoperative prognosis is usually good. Progressive neurological deterioration caused by recurrent tethering has been rarely reported. The authors present their experience in cases in which a sectioned fatty filum terminale has become retethered.

Role of Pax3 acetylation in the regulation of Hes1 and Neurog2.

Pax3 plays a role in regulating Hes1 and Neurog2 activity and thereby stem cell maintenance and neurogenesis. A mechanism for Pax3 regulation of these two opposing events, during caudal neural tube development, is examined in this study. Pax3 acetylation on C-terminal lysine residues K437 and K475 may be critical for proper regulation of Hes1 and Neurog2.

Folic acid remodels chromatin on Hes1 and Neurog2 promoters during caudal neural tube development.

The mechanism(s) behind folate rescue of neural tube closure are not well understood. In this study we show that maternal intake of folate prior to conception reverses the proliferation potential of neural crest stem cells in homozygous Splotch embryos (Sp(-/-)) via epigenetic mechanisms. It is also shown that the pattern of differentiation seen in these cells is similar to wild-type (WT).

Evidence for associations between the purinergic receptor P2X(7) (P2RX7) and toxoplasmosis.

Congenital Toxoplasma gondii infection can result in intracranial calcification, hydrocephalus and retinochoroiditis. Acquired infection is commonly associated with ocular disease. Pathology is characterized by strong proinflammatory responses.

Neurosurgical management of spina bifida: research issues.

The neurosurgical goal when treating children with spina bifida (predominantly myelomeningocele) is to maintain stable neurological functioning throughout the patient's life time. Unfortunately, few long-term outcome studies are available to help direct the neurosurgical care of a child born with myelomeningocele and often treatment relies more heavily upon the experience of senior practitioners. This article reviews the current literature regarding neurosurgical treatment strategies, with recommendations concerning including prenatal diagnosis, in utero treatment and delivery modes, and postnatal management.

Tethered cord release: a long-term study in 114 patients.

Object: All children born with a myelomeningocele at the authors' institution undergo aggressive treatment to maintain or improve functional outcome. Consequently, when any neurological, orthopedic, and/or urological changes are noted, a search for the cause is initiated. The most common cause of decline in a child born with a myelomeningocele is shunt malfunction.

The changing incidence of myelomeningocele and its impact on pediatric neurosurgery: a review from the Children's Memorial Hospital.

Incidence: Worldwide, the incidence of neural tube defects (NTDs) varies from 0.17 to 6.39 per 1,000 live births.

Transcriptional regulation by Pax3 and TGFbeta2 signaling: a potential gene regulatory network in neural crest development.

Pax3 regulates neural crest cell migration and is critical during neural crest development. TGFbs modify neural crest cell migration and differentiation. TGFbeta2 nullizygous embryos (TGFbeta2(-/-)Pax3(+/+)) display open neural tube and bifid spine, whereas in wild type embryos, the neural tube is closed.