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Stem Cell Research & Therapy Jul 2022Myelomeningocele (MMC) is a spinal cord congenital defect that leads to paraplegia, sphincter disorders and potential neurocognitive disabilities. Prenatal surgery of...
BACKGROUND
Myelomeningocele (MMC) is a spinal cord congenital defect that leads to paraplegia, sphincter disorders and potential neurocognitive disabilities. Prenatal surgery of MMC provides a significant benefit compared to surgery at birth. Mesenchymal stromal cell (MSC) therapy as an adjuvant treatment for prenatal surgery showed promising results in animal experiments which could be considered for clinical use in human fetuses. Despite numerous reassuring studies on the safety of MSCs administration in humans, no study focused on MSCs biodistribution after a local MSCs graft on the fetal spinal cord.
AIM
The purpose of our study was to assess the biodistribution of umbilical cord-derived mesenchymal stromal cells (UC-MSCs) at birth in lambs who had a prenatal myelomeningocele repair using a fibrin patch seeded with allogenic UC-MSCs.
METHODS
After isolation, UC-MSCs were tagged using a green fluorescent protein (GFP)-containing lentiviral vector. MMC defects were surgically created at 75 days of gestation and repaired 15 days later using UC-MSCs patch. Lambs were delivered at 142 days and sacrificed. DNA extraction was performed among biopsies of the different organs and q-PCR analysis was used to detect the expression of GFP (GFP DNA coding sequence).
RESULTS
In our 6 surviving lambs grafted with UC-MSCs, GFP lentivirus genomic DNA was not detected in the organs.
CONCLUSION
These reassuring data will support translational application in humans, especially since the first human clinical trial using mesenchymal stromal cells for in-utero treatment of MMC started recently in U.S.A.
Topics: Animals; Female; Fetus; Humans; Meningomyelocele; Mesenchymal Stem Cells; Pregnancy; Sheep; Sheep, Domestic; Tissue Distribution; Umbilical Cord
PubMed: 35841029
DOI: 10.1186/s13287-022-02991-0 -
Journal of Pediatric Urology Aug 2022Patients with spina bifida are at risk for developing bladder and renal deterioration secondary to increased bladder storage pressures.
BACKGROUND
Patients with spina bifida are at risk for developing bladder and renal deterioration secondary to increased bladder storage pressures.
OBJECTIVES
To determine the association of home bladder volume and pressure measurements (home manometry) to: 1) detrusor storage pressures on urodynamics (UDS); and 2) the presence of Society of Fetal Urology (SFU) grades 3-4 hydronephrosis on renal bladder ultrasound in patients with spina bifida.
METHODS
Data were prospectively collected on patients with spina bifida and neurogenic bladder requiring clean intermittent catheterization. Patients used a ruler and typical catheterization equipment to measure bladder pressures and volumes at home. Home measurements were compared to UDS detrusor pressures and SFU hydronephrosis grade. Detrusor pressure <20 cm HO at 50% maximal cystometric capacity (MCC) on UDS was used as a measure of safe storage pressures on UDS; conversely, detrusor pressure >20 cm HO was used a measure to capture both unsafe storage pressures and those with potential for unsafe storage pressures. Receiver-operator characteristic curves and area under curve (AUC) were calculated to depict the association between home manometry variables with detrusor pressures on UDS and SFU grades 3-4 hydronephrosis.
RESULTS
Included were 52 patients with a median age of 10.3 years (interquartile range 6.3-14.4 years). Three home manometry measurements (maximum bladder pressure, bladder pressure at maximum catheterized volume, and mean bladder pressure) > 20 cm HO were sensitive for Pdet >20 cm HO at 50% MCC. Maximal bladder pressure >20 cm HO was the most sensitive among home manometry measures (sensitivity 100%, specificity 70%, AUC 0.92 for Pdet >20 cm HO at 50% MCC on UDS; sensitivity 100%, specificity 62%, AUC 0.89 for SFU grade 3-4 hydronephrosis). None of the patients who had maximum home bladder pressure <20 cm HO had SFU grades 3-4 hydronephrosis; conversely, individuals with maximal home bladder pressure >20 cm had a wide range of hydronephrosis grades.
CONCLUSION
None of the patients with maximal home bladder pressure <20 cm HO had grade 3-4 hydronephrosis. Home measurements of maximal bladder pressure, bladder pressure at maximum catheterized volume and mean bladder pressure of >20 cm HO were all sensitive for Pdet >20 cm HO at 50% MCC on UDS. Home manometry is an inexpensive and simple technique to identify patients at risk for and to monitor individuals at high risk of upper tract dilation, without incurring significant cost or morbidity.
Topics: Child; Humans; Adolescent; Urodynamics; Urinary Bladder; Urinary Bladder, Neurogenic; Spinal Dysraphism; Hydronephrosis
PubMed: 35792042
DOI: 10.1016/j.jpurol.2022.06.011 -
Ultrasound in Obstetrics & Gynecology :... Nov 2022During in-utero spina bifida (SB) repair, closure of large defects is often challenging, requiring tissue graft for watertight skin closure. No prior studies have...
OBJECTIVE
During in-utero spina bifida (SB) repair, closure of large defects is often challenging, requiring tissue graft for watertight skin closure. No prior studies have compared primary skin closure vs patch-based repair. Our objective was to compare neonatal and 1-year outcomes associated with these two types of skin closure for in-utero SB repair.
METHODS
This was a prospective cohort study of 102 patients undergoing open prenatal SB repair from September 2011 to August 2021 at a single institution. All patients met the inclusion criteria of the Management of Myelomeningocele Study (MOMS), and the surgical procedure for in-utero SB repair was similar to that described in the MOMS trial. During the surgery, if primary skin approximation was not feasible due to the large size of the defect, the decision was at the discretion of the pediatric neurosurgeon to utilize a patch for closure. Neonatal outcomes at birth and 1-year outcomes were compared between the primary skin and patch-based closure groups.
RESULTS
Of 102 patients included in the study, 70 (68.6%) underwent primary skin closure and 32 (31.4%) patch-based closure. The patch type included acellular bovine skin matrix (Durepair®; n = 31) and human acellular dermal matrix (Alloderm®; n = 1). Fetuses with myeloschisis were more likely to require patch-based repair than those with myelomeningocele. The median time of fetal repair was 4 min longer for patch-based compared with primary skin closure (37 vs 33 min; P = 0.001). Following patch-based repair, neonates had a longer length of stay in the neonatal intensive care unit (NICU) by 24 days (adjusted risk ratio, 2.40 (95% CI, 1.41-4.29)) compared to those that underwent primary skin closure. There was no difference between the two groups in the other neonatal outcomes, including the need for ventriculoperitoneal shunt placement and cerebrospinal fluid leakage. Outcome at 1 year of age was available for 90 infants. Need for wound revision within their first year after birth was more common in infants who underwent patch-based vs those with primary skin closure (19.4% vs 5.1%; P = 0.05). There was no difference between the two groups in other 1-year outcomes, including the need for ventriculoperitoneal shunt placement by 1 year of age and surgery for tethered cord.
CONCLUSIONS
Patch-based closure during SB repair is often needed in fetuses with myeloschisis and is associated with prolonged fetal surgery time, long NICU stay and need for wound revision within the first year after birth. Further studies are required to identify optimal patches for SB repair or alternative methods to improve outcome. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.
Topics: Pregnancy; Infant; Female; Humans; Animals; Cattle; Child; Meningomyelocele; Prospective Studies; Gestational Age; Ventriculoperitoneal Shunt; Spina Bifida Cystica
PubMed: 35751885
DOI: 10.1002/uog.26018 -
JPMA. the Journal of the Pakistan... May 2022To investigate the mutation in Vangl1 gene in patients of myelomeningocele.
OBJECTIVE
To investigate the mutation in Vangl1 gene in patients of myelomeningocele.
METHODS
The cross-sectional study was conducted from July 2017 to December 2017 in the Dow Diagnostic and Research Laboratory, Karachi, after approval from the ethics review committee of Dow University of Health Sciences, Karachi, and comprised clinically diagnosed infants and 10 healthy individuals from the outpatient department of Jinnah Postgraduate Medical Centre, Karachi. Several anatomical parameters were considered, such as size and site of the cyst. Blood samples were drawn and polymerase chain reaction was conducted for the identification of mutation in Vangl1 gene. Mutation analysis was carried out by aligning the sequence with the reference sequence.
RESULTS
Of the 60 subjects, 50(83.3%) were cases with age range 0-10 years, and 10(16.6%) were age matched controls. Majority of the patients 44 (88%) were aged <1 year. Novel mutation in Vangl1 gene was identified at position 239, showing the substitution of valine with glycineV239G. Lumbar region was the most common site for the presentation of myelomeningocele in most of the patients 46(92%).
CONCLUSIONS
The rare mutation of myelomeningocele was found present in the sample, and the disease was found mostly in the lumbar region.
Topics: Carrier Proteins; Child; Child, Preschool; Cross-Sectional Studies; Humans; Infant; Infant, Newborn; Membrane Proteins; Meningomyelocele; Mutation; Pakistan; Polymerase Chain Reaction
PubMed: 35713047
DOI: 10.47391/JPMA.04-611 -
Acta Paediatrica (Oslo, Norway : 1992) Aug 2022To investigate the occurrence of pressure injuries (PIs) in children with myelomeningocele (MMC) and to investigate the association between PIs and orthoses use by...
AIM
To investigate the occurrence of pressure injuries (PIs) in children with myelomeningocele (MMC) and to investigate the association between PIs and orthoses use by disability-specific variables.
METHODS
Population-based registry study including participants in the Swedish multidisciplinary follow-up programme for MMC. Risks of PIs were investigated by birth cohort, country of birth, sex, type of MMC, muscle function level (MFL), and continence status.
RESULTS
Of 180 participants, 29% had PIs recorded. Of the 132 participants with >1 assessment records, 17.4% reported multiple PI occasions. More assessments increased the likelihood of PIs (Odds Ratio [OR] = 1.33, 95% CI 1.15-1.54) and participants born 2015-2018 had a lower OR of PIs than those born 2007-2010 (OR = 0.08, 95% CI = 0.01-0.74). Those at MFL I had lower OR of PIs than those at MFL V (OR = 0.06, 95% CI 0.01-0.64). Of the 73 participants with orthoses on the lower extremities, 47% reported skin irritations/injuries in the last 4 weeks; 30% reported that it made them stop using orthoses.
CONCLUSION
Pressure injuries are common even in young children with MMC. Many have recurring skin irritations. Inspecting for PIs should be part of a daily routine and tools to increase compliance are needed.
Topics: Child; Child, Preschool; Humans; Follow-Up Studies; Meningomyelocele; Sweden; Pressure Ulcer
PubMed: 35567518
DOI: 10.1111/apa.16406 -
Journal of the American Academy of... May 2022Early-onset scoliosis (EOS) is a well-known orthopaedic manifestation in patients with myelomeningocele. The rib-based growing system (RBGS) has been proposed as an...
INTRODUCTION
Early-onset scoliosis (EOS) is a well-known orthopaedic manifestation in patients with myelomeningocele. The rib-based growing system (RBGS) has been proposed as an alternative for these individuals because of the poor outcomes with traditional surgical techniques. We aimed to describe the effect of RBGS in patients with nonambulatory EOS myelomeningocele.
METHODS
We retrospectively reviewed the Pediatric Spine Study Group Multicenter Database for all patients with nonambulatory EOS myelomeningocele treated with RBGS from 2004 to 2019. Demographics, surgical data, radiographic findings, and postoperative complications were obtained. The quality-of-life parameters were assessed postoperatively using the Early-onset Scoliosis Questionnaire-24.
RESULTS
Thirty patients (18 women; 60%) were patients with nonambulatory EOS myelomeningocele treated with RBGS. The mean age at the initial surgery was 5.3 years. The thoracic (T1-T12) spine height showed a significant increase from initial surgery to the most recent follow-up (P < 0.001). Spine (T1-S1) height was also significantly increased (P < 0.001). The postoperative complication rate was 87%. The Early-onset Scoliosis Questionnaire-24 demonstrates significant improvements in the quality-of-life scores (P = 0.037).
CONCLUSION
This study demonstrated that RBGS could improve the reported quality-of-life scores in patients with nonambulatory EOS myelomeningocele when assessed with an EOS-oriented tool. Moreover, we confirmed the ability of RBGS to hold or even correct spinal deformity.
Topics: Child; Female; Follow-Up Studies; Humans; Meningomyelocele; Pelvis; Postoperative Complications; Retrospective Studies; Ribs; Scoliosis; Treatment Outcome
PubMed: 35551145
DOI: 10.5435/JAAOSGlobal-D-22-00090 -
Urology Aug 2022To compare trends in the treatment of patients with myelomeningocele receiving intravesical Botulinum (IVB) toxin and enterocystoplasty.
OBJECTIVE
To compare trends in the treatment of patients with myelomeningocele receiving intravesical Botulinum (IVB) toxin and enterocystoplasty.
METHODS
We identified patients with myelomeningocele in a commercial insurance database from 2008-2017 and stratified them into adult and pediatric samples. Index procedure was identified as either IVB toxin injection or enterocystoplasty. The annual rate of treatments was measured and a change in treatment rate was identified. Time to enterocysplasty was calculated using survival analysis and factors associated with clinical outcomes up to 10 years after index procedure were determined using multivariate Poisson regression.
RESULTS
We identified 60,983 patients with myelomeningocele. Nearly twice as many pediatric patients had an enterocystoplasty (n = 317) compared to IVB (n = 138). Very few adult patients underwent enterocystoplasty (n = 25) compared to IVB (n = 116). We identified a significant increase in the annual rate of IVB use around mid-2010 among pediatric patients and around mid-2009 among adults. Twelve pediatric patients (8.6%) and 5 adults (4.3%) went on to receive an enterocystoplasty. Patients who received IVB as the index procedure experienced significantly lower rates of hospitalization days (RR 0.64; 95% CI 0.53-0.78), emergency department visits (RR 0.72; 95% CI 0.63-0.82), and an increased rate of urologic procedures (RR 1.44; 95% CI 1.28-1.62).
CONCLUSION
The annual rate of IVB use has increased among patients with myelomeningocele. Nearly 1 in 10 pediatric patients and 1 in 20 adults go on to receive enterocystoplasty. Patients who receive IVB experience lower rates of hospitalization and emergency department visits compared to patients who receive enterocystoplasty.
Topics: Adult; Anastomosis, Surgical; Botulinum Toxins; Botulinum Toxins, Type A; Child; Humans; Intestines; Meningomyelocele; Urinary Bladder, Neurogenic; Urologic Surgical Procedures
PubMed: 35523288
DOI: 10.1016/j.urology.2022.04.020 -
Acta Ortopedica Mexicana 2021The aim of the study was to evaluate the outcomes and complications in patients with myelomeningocele who have undergone spinal fusion for neuromuscular scoliosis.
OBJECTIVE
The aim of the study was to evaluate the outcomes and complications in patients with myelomeningocele who have undergone spinal fusion for neuromuscular scoliosis.
MATERIAL AND METHODS
Retrospective study of 40 consecutive patients with myelomeningocele with neuromuscular scoliosis who underwent spinal arthrodesis, treated at our center between July 1991 and July 2028.
RESULTS
Mean follow up was 10 years. There were 19 male and 21 females. The average age at operation was 13 years. The mean preoperative scoliosis curve was 90o. At last follow up, the mean scoliosis curve was 43o. Mean correction of 52%. The average of pelvic obliquity was 19o. At last follow up de obliquity was 9o. Mean correction of 53%. The mean preoperative coronal balance was 28.4 mm. At the last follow up it was 17 mm. Mean correction of 40%. The mean preoperative kyphosis was 50o. At the last follow up it was 41o. Mean correction of 18%. The mean preoperative sagittal balance was 63.3 mm. At the last follow up it was 38.3 mm. Mean correction of 40%. There were 13 complications (32.5%), with infection being the most frequently observed complication.
CONCLUSIONS
The goals of the spinal surgery in patients with MMC are to obtain a stable, balanced and painless spinal fusion. Although the surgical treatment of these patients remains difficult, it is associated with high complication rate.
Topics: Female; Humans; Male; Meningomyelocele; Neuromuscular Diseases; Retrospective Studies; Scoliosis; Spinal Fusion; Treatment Outcome
PubMed: 35451247
DOI: No ID Found -
International Braz J Urol : Official... 2022High-risk bladder pattern can be defined by Urodynamic Evaluation (UE) as overactive bladder with detrusor leak point pressure higher than 40 cmH2O and/or higher filling...
OBJECTIVES
High-risk bladder pattern can be defined by Urodynamic Evaluation (UE) as overactive bladder with detrusor leak point pressure higher than 40 cmH2O and/or higher filling pressures also above 40 cmH2O. We wanted to evaluate response to treatment in myelomeningocele patients operated in utero in this subgroup.
PATIENTS AND METHODS
From our prospective cohort of in utero MMC we have identified patients in the high-risk group. Treatment consisted of anticholinergics (Oxybutynin 0.2 mg/Kg) 2 or 3 times daily in association with CIC. At every UE, patients were reclassified in high-risk or low-risk patterns. Patients not responding were proposed bladder reconstruction or diversion according to age.
RESULTS
Between 2011 to 2020, we have been following 121 patients and 60 (49.6%) of them were initially categorized as high-risk. The initial UE was performed at a mean age of 7.9 months and detrusor overactivity was found in 83.3% (mean maximum pressure of 76.5cmH20). When evaluating patients with 2 or more UE, we identified 44 patients (follow-up: 36.8months). It was observed in the group of patients who underwent 2 to 5 UE, that response to treatment was validated by the finding of 40% of low-risk bladder patterns in the second UE and between 62% to 64% in the third to the fifth UE. The incidence of surgery was 13.3%.
CONCLUSIONS
Early urological treatment of high-risk bladder pattern was effective in approximately 60%. We reinforce the need to correctly treat every patient with myelomeningocele, in accordance with UE, whether undergoing in utero or postnatal treatment.
Topics: Humans; Infant; Meningomyelocele; Prospective Studies; Urinary Bladder; Urinary Bladder, Neurogenic; Urodynamics
PubMed: 35373958
DOI: 10.1590/S1677-5538.IBJU.2022.0053 -
Ultrasound in Obstetrics & Gynecology :... Jan 2023A contributing factor to unsuccessful prenatal spina bifida aperta (SBA) repair via an open approach may be incomplete neurosurgical repair causing persistent in-utero...
OBJECTIVES
A contributing factor to unsuccessful prenatal spina bifida aperta (SBA) repair via an open approach may be incomplete neurosurgical repair causing persistent in-utero leakage of cerebrospinal fluid (CSF) and exposure of the fetal spinal cord to amniotic fluid. We aimed to investigate the neurostructural and neurofunctional efficacy of watertight prenatal SBA repair in a validated SBA fetal lamb model.
METHODS
A well-powered superiority study was conducted in the validated SBA fetal lamb model (n = 7 per group). The outcomes of lambs which underwent watertight or non-watertight multilayer repair through an open approach were compared to those of unrepaired SBA lambs (historical controls) at delivery (term = 145 days). At ∼75 days, fetal lambs underwent standardized induction of lumbar SBA. At ∼100 days, they were assigned to an either watertight or non-watertight layered repair group based on an intraoperative watertightness test using subcutaneous fluorescein injection. At 1-2 days postnatally, as primary outcome, we assessed reversal of hindbrain herniation using magnetic resonance imaging (MRI). Secondary proxies of neuroprotection were: absence of CSF leakage at the repair site; hindlimb motor function based on joint-movement score, locomotor grade and Motor Evoked Potential (MEP); four-score neuroprotection scale, encompassing live birth, complete hindbrain herniation reversal, absence of CSF leakage and joint-movement score ≥ 9/15; and brain and spinal cord histology and immunohistochemistry. As the watertightness test cannot be used clinically due to its invasiveness, we developed a potential surrogate intraoperative three-score skin-repair-quality scale based on visual assessment of the quality of the skin repair (suture inter-run distance ≤ 3 mm, absence of tear and absence of ischemia), with high quality defined by a score ≥ 2/3 and low quality by a score < 2/3, and assessed its relationship with improved outcome.
RESULTS
Compared with unrepaired lambs, lambs with watertight repair achieved a high level of neuroprotection (neuroprotection score of 4/4 in 5/7 vs 0/7 lambs) as evidenced by: a significant 100% (vs 14%) reversal of hindbrain herniation on MRI; low CSF leakage (14% vs 100%); better hindlimb motor function, with higher joint-movement score, locomotor grade and MEP area under the curve and peak-to-peak amplitude; higher neuronal density in the hippocampus and corpus callosum; and higher reactive astrogliosis at the SBA lesion epicenter. Conversely, lambs with non-watertight SBA repair did not achieve the same level of neuroprotection (score of 4/4 in 1/7 lambs) compared with unrepaired lambs, with: a non-significant 86% (vs 14%) reversal of hindbrain herniation; high CSF leakage (43% vs 100%); no improvement in motor function; low brain neuron count in both the hippocampus and corpus callosum; and small spinal astroglial cell area at the epicenter. Both watertight layered repair and high (≥ 2/3) intraoperative skin-repair-quality score were associated with improved outcome, but the watertightness test and skin-repair-quality scale could not be used interchangeably due to result discrepancies.
CONCLUSIONS
Watertight layered fetal SBA repair is neuroprotective since it improves brain and spinal-cord structure and function in the fetal lamb model. This translational research has important clinical implications. A neurosurgical technique that achieves watertightness should be adopted in all fetal centers to improve neuroprotection. Future clinical studies could assess whether a high skin-repair-quality score (≥ 2/3) correlates with neuroprotection. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.
Topics: Pregnancy; Female; Sheep; Animals; Neuroprotection; Spinal Dysraphism; Fetus; Spina Bifida Cystica; Meningomyelocele; Bone Diseases, Developmental
PubMed: 35353933
DOI: 10.1002/uog.24907