Active bone material containing modified recombinant human bone morphogenetic protein-2 induces bone regeneration in rabbit spina bifida.

This study focuses on spina bifida, which is a high incidence among the current clinical manifestations of human birth defects. Because in the treatment of bone defects, the source of autologous bone is limited and it is easy to cause secondary injury to the patient. At the same time, since the bone tissue in animals needs to perform a variety of biological functions, its complex structure cannot be replaced by a single material. Therefore, in this study, we used Japanese white rabbits to establish an animal model similar to human congenital spina bifida. The established animal model is used to screen the best regenerative repair products for the treatment of congenital spondylolisthesis defects, and to evaluate the safety of regenerative repair products. The results show that bone morphogenetic protein (BMP)-2 combined with collagen material has a better regeneration effect than collagen material alone, and it did not negatively affect the health of animals. This study is not only suitable for the screening of large-scale biomaterials, accelerating the research progress of regenerative repair products, but also conducive to the research on the mechanism of regeneration and repair of various materials.

Effects of general anesthesia with and without thoracic epidural block on length of stay after open spine surgery: a single-blinded randomized controlled trial.

BACKGROUND CONTEXT: Length of hospital stay (LOS) is an important concern in all types of surgery, and the enhanced recovery after surgery (ERAS) protocol has been developed to improve perioperative management and outcomes, which require multidisciplinary management. In terms of pain control, intraoperative regional anesthesia and postoperative opioid-sparing analgesia are recommended. For open spine surgery, we aimed to combine thoracic epidural analgesia to reduce pain and opioid-related side effects, thereby hastening recovery. PURPOSE: This study aimed to compare the length of hospital stay after open complete laminectomy with fusion between general anesthesia and combined general anesthesia involving a single thoracic epidural injection. DESIGN: A randomized single-blinded controlled study. PATIENT SAMPLE: Thirty-eight patients scheduled for elective open laminectomy with fusion between I and III levels were selected. OUTCOME MEASURES: LOS, postoperative pain, patient-controlled morphine consumption at 24 hours, patient satisfaction score, and other opioid-related side effects were recorded. METHODS: Patients were randomly selected to receive standard general anesthesia (GA) or GA combined with a single-shot thoracic epidural at T11-T12 or T12-L1, a block with 10 mL of 0.25% bupivacaine, and 4 mg of morphine. RESULTS: There were no significant differences in the demographic variables between groups. LOS was significantly lower in the combined epidural and/or GA than in the control group (3.78±0.81 [mean±standard deviation] and 4.79±1.51 days, respectively; p=.017). Numeric rating score (at rest) at the post-anesthesia care unit, 24 hours postoperative morphine consumption (mg), operating time, and blood loss were significantly lower in the epidural group. Patients who received combined epidural and/or GA were more likely to report higher patient satisfaction (p=.008). However, the incidence of intraoperative hypotension was significantly higher in the epidural group (72.2% vs. 21.1%, p=.003). The incidences of adverse events and surgical field rating scores did not differ between the 2 patient groups. CONCLUSIONS: Combined lower thoracic epidural and/or GA in patients undergoing elective lumbar spine surgery was associated with decreased LOS.

Magnesium sulfate titration reduces maternal complications following fetoscopic closure of spina bifida.

OBJECTIVE: To evaluate if magnesium sulfate (MgSO4 ) titration following fetoscopic spina bifida closure is associated with fewer maternal complications than the Management of Myelomeningocele Study (MOMS) tocolytic regimen. METHODS: This prospective cohort study included 73 consecutive patients undergoing fetoscopic closure of spina bifida between 2015 and 2020. A policy of using the MgSO4 regimen per the MOMS trial was changed to a flexible one in which MgSO4 was titrated according to the frequency of the uterine contractions following surgery. The frequency of maternal pulmonary edema, low maternal oxygen saturation requiring oxygen supplementation, atelectasis, hypocalcemia, and preterm delivery was compared before and after the policy was changed. RESULTS: A higher proportion of women in the group that used the MOMS MgSO4 regimen had pulmonary edema compared to those in the flexible one (26.1% [6/23] vs. 6% [3/50]; p = 0.024). Multivariate analysis showed that the MOMS tocolytic regimen was independently associated with a higher risk of pulmonary edema (adjusted odds ratio: 8.57; 95% confidence interval: 1.54-47.7; p = 0.014) than a flexible one. There was no difference in the rate of preterm delivery. CONCLUSION: Following fetoscopic closure of spina bifida, the MOMS MgSO4 regimen is associated with an increased risk of pulmonary edema than a more flexible regimen.

Postfolate spina bifida lesion level change.

BACKGROUND: Spina bifida accounts for a large proportion of birth defects in the United States. Studies have evaluated the decrease in prevalence at birth after folate fortification of food grains, but little is known about neurologic functional changes related to fortification. This study assesses the functional level of lesions in the prefortification and postfortification eras. METHODS: Data were collected through retrospective review of medical records from a regional multispecialty clinic in Arizona. This study included individuals born between 1981-1995 (prefortification) and 1999-2013 (postfortification). Patients were included if they had a primary diagnosis of spina bifida with or without hydrocephalus. RESULTS: There was a significant difference in functional lesion level with an 85% reduction in thoracic level lesions in the postfortification era (p < .005). There were no differences in gender or ethnicity across eras; however, Hispanic ethnicity had a higher number of cases overall (51.7%). The most common lesion level in both eras was mid-lumbar, accounting for 35.7 and 34.4% of cases in the prefolate and postfolate eras, respectively. CONCLUSIONS: This study demonstrates a significant difference in the distribution of lesion level of spina bifida patients born in the postfortification era, based on neurologic function. Further research with a larger sample size is needed to determine if this observation holds true nationally.

Executive functions and parenting behaviors in association with medical adherence and autonomy among youth with spina bifida.

OBJECTIVE: This study was designed to examine whether executive functions and parenting behaviors (acceptance, behavioral control, and psychological control) are associated with medical adherence and autonomy among preadolescents and adolescents with spina bifida (SB). METHODS: Questionnaire and observational data were collected from a sample of 8-15 year olds with SB (N = 140) and their mothers, fathers, and teachers. Youth also completed neuropsychological testing. RESULTS: Youth with SB demonstrated impairment on measures of executive functions, based on questionnaire and test data. Executive functions (questionnaire data only) and parenting behaviors were associated with medical adherence, but only executive functions (test data only) were associated with medical autonomy. Analyses also suggest that maternal and paternal behavioral control and paternal psychological control moderate relations between executive functions and adherence. CONCLUSIONS: Interventions that target executive functions and parenting behaviors may facilitate positive health care behavior outcomes among youth with SB.

[Hyperthermia in spina bifida patients treated with oxybutynin]. / Temperaturerhöhung unter Oxybutynin bei Patienten mit Spina bifida.

Paraplegic spina bifida patients often suffer from disturbed sweat secretion in the paretic regions. A diminished sweat production of caudal parts of the body is compensated by an increased secretion of sweat in parts cranial to the lesion to maintain temperature homoeostais. If the sweat secretion is blocked by anticholinergic effects of urotherapeutic drugs (for instance oxybutynin) hyperthermia can result as a side effect as these casuistic examples show.An 8-year-old girl with a lumbar meningomyelocele and a neurogenic bladder reported a dry skin and hyperthermia up to 38,5°C during oral therapy with oxybutynin (0.4 mg per kg body weight) during hot summer days. Similar symptoms were shown by a 7-year-old male patient with a sacral meningomyelocele and neurogenic bladder on oral therapy of 0.35 mg oxybutynin per kg body weight. A 4-year-old female patient with lumbar spina bifida and neurogenic bladder reacted to intravesical administration of 0.4 and 0.3 mg per kg body weight during early summertime with hyperthermia up to 38°C. In this case the medication had been started in wintertime and was primarily well tolerated.Hyperthermia under treatment with anticholinergic drugs has mainly been published for geriatric patients with sometimes fatal outcome. In the pediatric literature there is only one warning regarding the use of oxybutynin in children with spina bifida living in high temperature regions. It is remarkable that hyperthermia can also happen after intravesical administration of oxybutynin in usual dosage.

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. Neurospheres were generated with NSCs from the lower lumbar neural tube of E10.5 wild-type (WT) and Sp(-/-) embryos, in the presence and absence of FA. In the absence of FA, the number of neurospheres generated from Sp(-/-) embryos compared with WT was minimal (P<0.05). Addition of FA to Sp(-/-) cultures increased the expression of a Pax3 downstream target, fgfr4, and rescued NSC proliferative potential, as demonstrated by a significant increase in neurosphere formation (P<0.01). To ascertain if FA affected cell differentiation, FA-stimulated Sp(-/-) neurospheres were allowed to differentiate in the continued presence or absence of FA. Neurospheres from both conditions expressed multi-potent stem cell characteristics and the same differentiation potential as WT. Further, multiple neurospheres from both WT and FA-stimulated Sp(-/-) cell cultures formed extensive synaptic connections. On the whole, FA-mediated rescue of neural tube defects in Sp(-/-) embryos promotes NSC proliferation at an early embryonic stage. FA-stimulated Sp(-/-) neurospheres differentiate and form synaptic connections, comparable to WT.

Metformin therapy to reduce weight gain and visceral adiposity in children and adolescents with neurogenic or myogenic motor deficit.

The aim of this randomized, placebo-controlled study was to explore the effect of metformin in children with a neurogenic or myogenic motor deficit, who are therefore prone to develop overweight, adiposity, and insulin resistance. Study participants (n = 42) had a mean age of 15.5 yr, a short stature (height -2.4 SD), a relatively high BMI (+1.7 SD), and a high body fat fraction (41.9% or +2.8 SD). Abdominal CT confirmed the high fat mass and disclosed a high fraction of visceral fat. As expected, insulin resistance was increased. As compared to placebo, metformin intake for 6 months exerted an insulin sensitizing effect and lowered weight (mean difference of 2 kg within 6 months, p = 0.007) and BMI (p = 0.016). Weight loss appeared to be primarily due to loss of visceral fat ( approximately 20% vs. placebo; p < 0.0001). Results were similar across diagnostic subgroups. In conclusion, metformin treatment for 6 months was associated with a rise in insulin sensitivity and with a reduction of visceral adiposity in children and adolescents with a primary muscle disorder or with a neural tube defect. These findings suggest that insulin resistance underpins, at least partly, the overweight and visceral adiposity of these patients, who are not necessarily obese.

Corticosteroids reduce glial fibrillary acidic protein expression in response to spinal cord injury in a fetal rat model of dysraphism.

BACKGROUND: Exposure of the spinal cord in myelomeningocele (MM) throughout gestation increases spinal injury. Astrocyte activation evidenced by glial fibrillary acidic proteins (GFAP) indicates the extent of injury. Corticosteroids modulate GFAP synthesis, but their effect in MM is unclear. The purpose of this study was to evaluate the GFAP expression in a fetal rat model of dysraphism and the effect of corticosteroid treatment on this marker and on clinical neurological disabilities. METHODS: Dysraphism was surgically created in 2 groups of 48 rat fetuses; group 1: control, and group 2: treated with corticosteroid. Each group was subdivided into fetuses with surgically created MM, controls and shams on day 18.5 of gestation (term = 22 days). Fetuses were harvested on day 21.5, examined for evidence of neurological deficits, and the following clinical parameters were registered: kyphosis, tail deformities, leg deformities, leg paralysis or paresis and pain perception. The fetuses were fixed for GFAP immunostaining. RESULTS: All fetuses with MM in group 1 presented neurological deficits and glial reactions with GFAP expression, as opposed to controls and shams. In group 2, corticosteroid treatment prevented some neurological deficits (18-25%), reducing glial response and GFAP expression. CONCLUSIONS: Experimentally induced dysraphism in the rat fetus is related to glial response and increased GFAP expression in the spinal cord. Corticoid treatment clinically improved nerve injury in some fetuses. It reduced glial reaction and GFAP expression.

Current approaches to the urologic care of children with spina bifida.

Most children born with spina bifida, the most common disabling congenital abnormality, have normal renal function. If left untreated, more than half of these children will have serious renal deterioration by age 5. This deterioration is secondary to hostile neurogenic changes of the bladder. Renal development should follow a normal course when close evaluation and intervention are undertaken during the newborn period and toddler years. As children age, attention is directed to quality-of-life issues, such as the establishment of urinary and bowel continence. Teenagers face the responsibility of understanding their medical condition and should begin to assume responsibility for their own care with eventual transition to the adult health care system. This article describes the foundations of management, beginning at birth, for caring for children with spina bifida.

Assessment of health status in children with spina bifida.

STUDY DESIGN: Prospective multidimensional study by means of: (1) clinical assessment, (2) parental-administered questionnaire for general health (CHQ-PF50), and (3) standardised disability measurements. OBJECTIVES: To assess the health-related quality of life (QoL) and disability in children with spina bifida (SB) and to correlate them with the clinical picture and our previous study on adolescents with SB. SETTING: SB Centre at a University Hospital in Italy. METHODS: A total of 29 consecutive children with SB (mean age 11.4, range 4-14 years)were evaluated through Child Health Questionnaire Parental Form (CHQ-PF50), the FIM instrument, and the Barthel index. RESULTS: Disability was inversely related only (r=0.49; P=0.007) to the physical aspect of the QoL of children. Similarly, the disability was inversely related (r=0.37; P=0.005) to the emotional aspect of QoL of patient's parents. Unexpectedly, for the mental aspects of QoL of patients, major disability was not associated with higher psychological distress and severe role disability due to emotional problems. At clinical examination, findings especially for continence and number of catheterisations were usually related to deterioration of physical aspects of QoL (r=-2.28; P=0.02) in children. CONCLUSION: The multiperspective assessment showed that there is a linear inverse correlation between disability and QoL in children with SB only for physical aspects. Conversely, there is linear inverse correlation between disability and QoL in patient's parents regarding only emotional aspects. Moreover, this study provided useful information for clinical practice underlining that continence problems are those that most affect QoL in children with SB and their parents.

Plasma antidiuretic hormone levels in children with spina bifida.

PURPOSE: Urological management of spina bifida patients is controversial. The goals of therapy of neurogenic bladder are continence, prevention of infections and preservation of urinary tract. Desmopressin has been recently used in a spina bifida population that is dry during the day (daytime continence was achieved with clean intermittent catheterization and anticholinergics) but wet at night. The aim of this study was to assess plasma antidiuretic hormone (ADH) levels in these children. MATERIALS AND METHODS: The study included 24 patients, 11 males and 13 females (mean age 6.4 years) referred to the Spina Bifida Centre of the Catholic University of Rome, and 57 normal age-matched controls. Morning (07.30-08.00 h) plasma ADH levels were measured using a specific radioimmunoassay. RESULTS: Plasma ADH levels (normal range 5-11 microg/l) did not differ between spina bifida population and healthy controls. Serum ADH had a mean of 6.8 microg/l in affected children and a mean of 7.4 microg/l in the controls. CONCLUSION: We conclude that the use of desmopressin in children with spina bifida should be reserved only in patients with decreased secretion of ADH, or may be useful in patients with persistent nocturnal incontinence to reduce night wetting. Therefore, research with a larger population is needed.

Homocysteine metabolism and effects of folic acid supplementation in patients affected with spina bifida.

Folic acid supplementation around conception decreases the risk of having offspring with a neural tube defect. However, the aetiology is often still unknown. This study investigated whether spina bifida patients have lower blood folate and higher fasting and post-methionine-load plasma total homocysteine (tHcy) concentrations than control patients. Moreover, the effects of supplementation with 500 microg folic acid/d on folate and tHcy concentrations were determined. Spina bifida patients (n = 12) and disabled control patients (n = 15) received 4 weeks of placebo treatment followed by 4 weeks of intervention with 500 microg folic acid/d. Blood was collected at the start and after 4 and 8 weeks. A methionine-loading test was performed at the start and the end of the study. At baseline, no significant differences occurred between spina bifida and control patients. Folic acid supplementation significantly increased plasma and red blood cell folate concentrations in both groups. Folic acid decreased fasting tHcy concentrations in control patients by 1.6+/-0.5 micromol/l (p<0.01) and in spina bifida patients by 2.2 +/- 1.3 micromol/l (p = 0.10). This study does not show a derangement in homocysteine metabolism in spina bifida compared to control patients. Moreover, folic acid supplementation seems at least as effective in spina bifida patients as in controls.

Hypothyroidism secondary to topical iodine treatment in infants with spina bifida.

Four infants with spina bifida, who had not undergone surgical closure of a lumbar myelomeningocele, were assessed and investigated for hypothyroidism. From birth, all were treated once daily with an iodine-containing ointment (Betadine) as a local antiseptic applied to the spina defect. All infants showed excess urinary iodine concentration. Two infants, without clinical evidence of hypothyroidism or goitre, showed low serum free thyroxine and high thyroid stimulating hormone concentrations at a mean age of four weeks and were started on thyroxine replacement treatment. Betadine ointment and thyroxine were stopped simultaneously at a mean age of nine months, following which all infants remained euthyroid. Thyroid function tests should be monitored routinely if iodine is applied as a topical antiseptic to infants.