Neonatal Loss of Motor Function in Human Spina Bifida Aperta

Sival, Deborah A; Weerden, T. W. van; Vles, Johan S.H.; Timmer, Albertus; Dunnen, Wilfred F.A. den; Staal-Schreinemachers, A L; Hoving, Eelco W.; Sollie, Krystyna M.; Kranen-Mastenbroek, Vivianne J M; Sauer, Pieter; Brouwer, Oebele F.

doi:10.1542/peds.114.2.427

Cited by 63 publications

(60 citation statements)

References 33 publications

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“…There has been a single report on altered vascular organization in a human MMC, and it was restricted to a newborn infant of 39 weeks. 27 The herein reported vascular density pattern of the MMC placode in utero adds new cytoarchitectural alterations to the previously documented astrocytosis of human MMC 10 and mouse MMC. 23 Because in the MMC mouse both abnormalities start at the same gestational period (embryonic Day 16.5), we postulate that they reflect putative aggression to the placode starting in the same gestational timing.…”

Section: Discussionsupporting

confidence: 55%

“…Authors of some previous studies have described inflammatory signs in the late gestational stages of MMC fetuses. 13,20 George and Cummings 10 have described significant inflammatory infiltrates in specimens obtained during surgical correction of MMC, and Hutchins et al 15 have reported that MMC placodes from stillborn infants have evidence of erosion, but Sival et al 27 have found only inflammatory tissue on the MMC surface in a 39-week-old newborn. These inflammatory findings in cases of MMCs in humans are difficult to interpret given that these inflammations can be caused by surgery or lesions occurring during delivery.…”

Section: Discussionmentioning

confidence: 99%

“…3,[31][32][33][34] In contrast, deficits in the lower limbs and in urodynamic function in patients submitted to MMC correction, through either fetal or classic postnatal surgery, were similar to those of controls. 14,30,27 Attending to these data, the potential benefits of in utero repair of MMC are under scrutiny in a randomized trial designed to compare the clinical outcomes of patients with MMC treated with either fetal or postnatal surgery. 2 Recently, using a mouse model of MMC, we documented astrocytic proliferation during gestation together with neuronal degeneration, after embryonic Day 16.5 (full-term gestation: 19 days), predominantly in the dorsal part of the placode.…”

mentioning

confidence: 99%

“…23 These findings are in accordance with clinical and electromyography findings in newborn humans with MMC who display a loss of leg movements during the first 2 postnatal weeks, suggesting that neuronal damage was initiated before birth. 27 To better characterize the cytological dynamics in the MMC placode that could lead to neuronal degeneration during gestation, we looked for other cytological alterations not clearly evaluated in previous scientific studies. 10,11,15,17,23 In this way we evaluated the changes in vascular structure, frequency of apoptotic cells, and inflammation in the placode of MMC mutant mouse fetuses during the final stages of gestation.…”

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confidence: 99%

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Vascular and apoptotic changes in the placode of myelomeningocele mice during the final stages of in utero development

Reis

Correia‐Pinto

Monteiro

et al. 2008

PED

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Object Myelomeningocele (MMC) is a primary neurulation defect that is associated with devastating neurological disabilities in affected newborns. To better characterize the in utero neurodegenerative process of MMC, the authors investigated the changes in vascular organization, apoptosis, and the presence of inflammatory cells during gestation by using a mutant mouse model of MMC. Methods The curly tail/loop tail (ct/lp) mutant mouse model of MMC was chosen to obtain fetuses at different stages of gestation. Mouse fetuses harboring MMC were harvested by caesarean section at embryonic Days 14.5, 16.5, and 18.5 (complete mouse gestation at 19 days, 6 mice/group); littermate fetuses with the same gestational age but without an MMC were used as controls. Samples of the MMC placode or normal spinal cord were stained for immunocytochemical labeling with caveolin antibody (endothelium marker) and activated caspase-3 antibody (apoptosis marker). Samples were morphometrically analyzed with a computer-assisted image analyzer. Results The MMC mice presented with an increase in vascular density from embryonic Days 16.5–18.5 and an enhanced number of apoptotic cells at embryonic Day 18.5, compared with controls. There were scarce signals of an inflammatory reaction in the MMC placode, as a few infiltrating neutrophils were seen only at embryonic Day 18.5. Conclusions Fetal placodes in MMC mice showed evidence of increased vascular density since embryonic Day 16.5 and increased apoptosis at embryonic Day 18.5. These new data support the view that in utero changes of the MMC placode, occurring during the last stages of gestation, contribute to the neuropathological manifestations in full-term newborns with MMC.

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Section: Discussionsupporting

confidence: 55%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Vascular and apoptotic changes in the placode of myelomeningocele mice during the final stages of in utero development

Reis

Correia‐Pinto

Monteiro

et al. 2008

PED

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“…41 Fetal surgery was recently initiated as an experimental treatment of MMC with the goal of protecting the neural placode by covering the exposed spinal segments of the MMC. 8 , 9 , 44 , 46 , 47 This procedure has achieved excellent results in relation to reversing the associated hindbrain herniation, as well as reducing (from 91 to 59%) the need for insertion of a shunt.…”

Section: Go To Sectionmentioning

confidence: 99%

In utero topographic analysis of astrocytes and neuronal cells in the spinal cord of mutant mice with myelomeningocele

Reis¹,

Correia‐Pinto²,

Monteiro³

et al. 2007

Journal of Neurosurgery: Pediatrics

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Object Myelomeningocele (MMC) is the most severe form of spina bifida causing severe neurological deficits. Injury to the placode has been attributed to in utero aggression. In this study, glial and neuronal cell changes in both number and topography in mice with MMC were investigated during gestation. MethodsThe curly tail/looptail mice model of MMC was used, and fetuses were harvested using caesarean surgery at Days 14.5, 16.5, and 18.5 (full gestation at 19 days). Immunohistochemical analyses of the MMC placodes and the normal spinal cords from the control group were performed using anti-glial fibrillary acidic protein (astrocytes) and mouse anti-neuronal nuclear (neurons) antibodies. Light microscopy was used along with computer-assisted morphometric evaluation.Progressive increases in astrocytes in the spinal cord of all mouse fetuses were found between Days 14.5 and 18.5 of gestation. This increase was significantly higher in the placodes of mice with MMC than in those of normal mice, particularly in the posterior region. Neuronal labeling at Day 14.5 of gestation was similar between mice with MMC and control mice. At Day 16.5 of gestation there was a deterioration of neural tissue in MMC fetuses, mainly in the posterior region, progressing until the end of gestation with a marked loss of neurons in the entire MMC placode. ConclusionsThis study delineated the quantitative changes in astrocytes and neurons associated with MMC development during the late stages of gestation. The detailed topographic analysis of the MMC defines the timing of the intrauterine insult and how the placode lesions progress. This study supports the current concept of placode protection through in utero surgery for fetuses with MMC.KEYWORDS:myelomeningocele; astrocyte; neuronal cell; immunohistochemistry; fetal surgery; pediatric neurosurgery. IntroductionSpina bifida aperta, or MMC, is a primary neurulation defect that is associated with a significant morbidity and mortality rate in the affected children. 6 , 12 , 15 , 34 Myelomeningocele occurs in nearly 1 in every 2000 live births, 29 , 44 even in countries where maternal folic acid supplementation and an early in utero diagnosis of MMC is available. 6 , 34 , 35 Myelomeningocele leads to lifelong and devastating physical disability; MMC newborns present with different degrees of lower extremity paralysis, sexual organ and sphincter dysfunction, tethering of the spinal cord, skeletal abnormalities, brainstem dysfunction, and hydrocephalus, and may develop disorders that require the insertion of ventriculoperitoneal shunts. 3 , 34 , 38 , 43 The mortality rate in children with MMC ranges from 14 to 35% until they reach the age of 5 years. 16 , 34 , 44 , 45 The precise cause of spina bifida is unknown, and is probably of a multifactorial nature. 12 , 33 Data from the experimental induction of MMC in animal models have raised questions about the previously dominant concept of an intrinsic embryonic error causing MMC neurological deficits, 14 , 22 , 27 , 31-33 Go to ...

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Measurement of the Area and Circumference of the Leg

Milani

Barreto

Júnior

et al. 2021

J of Ultrasound Medicine

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Objective-To standardize a new technique to evaluate the fetal leg muscle trophism by measuring the area and circumference, and comparing this technique between normal and fetuses with open lumbosacral spina bifida (SB).Methods-Observational cross-sectional study was carried out on pregnant women with 26 weeks who were divided into two groups: Group I-fetuses with diagnosis of open lumbosacral SB; Group II-normal fetuses (control). In fetuses with SB, subjective evaluation of the lower limbs was performed (muscle echogenicity and leg movements). To estimate the leg muscle trophism, the measurement of the area and circumference of the leg were standardized, and the reproducibility of this method was performed.Results-Thirty-one fetuses with open lumbosacral SB and 51 normal fetuses were evaluated. The measurements of the area and circumference of the leg proved to be highly reproducible (intraclass correlation coefficient-ICC > 0.95). The leg area and circumference measurements were statistically lower in the SB group than in the control group (p < .001). When subjective ultrasound assessment demonstrated hypotrophy of the lower limbs, the measurements of the area and circumference of the leg were statistically lower when compared to normal fetuses (p < .001). Fetuses with open SB with abnormal lower limb movements had lower measurements of the area and circumference of the leg than fetuses with normal movements (p < .001). Conclusion-Anew technique for estimating fetal leg muscle trophism was standardized, which proved to be highly reproducible and was able to show the difference between normal and fetuses with SB.

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Neonatal Loss of Motor Function in Human Spina Bifida Aperta

Cited by 63 publications

References 33 publications

Vascular and apoptotic changes in the placode of myelomeningocele mice during the final stages of in utero development

Vascular and apoptotic changes in the placode of myelomeningocele mice during the final stages of in utero development

In utero topographic analysis of astrocytes and neuronal cells in the spinal cord of mutant mice with myelomeningocele

Measurement of the Area and Circumference of the Leg

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