Myelomeningocele repair timing

Myelomeningocele repair timing

The optimal time to closure of a newborn with an open neural tube defect (NTD-myelomeningocele) has been the subject of a number of investigations. One aspect of timing that has received attention is its relationship to repair site and central nervous system (CNS) infection that can lead to irreversible deficits and prolonged hospital stays.

Clinical guidelines recommend repair of open spina bifida (SB) prenatally or within the first days of an infant’s life.


A prospective, randomized study (the MOMS trial) has shown that fetal surgery for MMC before 26 weeks’ gestation may preserve neurologic function, reverse the hindbrain herniation of the Chiari II malformation, and obviate the need for postnatal placement of a ventriculoperitoneal shunt. However, this study also demonstrates that fetal surgery is associated with significant risks related to the uterine scar and premature birth. In the future, research will expand our understanding of the pathophysiology of MMC, evaluate the long-term impact of in-utero intervention, and to refine timing and technique of fetal MMC surgery using tissue engineering technology 1).

Controversies

In a cohort from Texas, over one-quarter of patients undergoing postnatal myelomeningocele repair experienced a complication within 30 days. The complication rate was significantly higher in patients who had surgical repair within the first 24 hours of birth than in patients who had surgery after the 1st day of life 2).


Kancherla et al., examined 2006 to 2011 births from the California Perinatal Quality Care Collaborative, linking to hospital discharge and vital records. Selected maternal, infant, and delivery hospital characteristics were evaluated to understand disparities in timely repair. Poisson regression was used to estimate adjusted risk ratios (aRRs) and 95% confidence intervals (CIs).

Overall, 399 of the 450 (89%) infants had a timely repair and approximately 80% of them were delivered in level III/IV hospitals. Infants with hydrocephalus were significantly less likely to have a delayed myelomeningocele repair compared with those without (aRR = 0.22; 95% CI = 0.13, 0.39); infants whose medical care was paid by Medi-Cal or other nonprivate insurance were 2.2 times more likely to have a delayed repair compared with those covered by a private insurance (aRR = 2.23; 95% CI = 1.17, 4.27). Low birth weight was a significant predictor for delayed repair (aRR = 2.06; 95% CI = 1.10, 3.83).

There was a significant disparity in myelomenigocele repair based on medical care payer. Families and hospitals should work together for timely repair in hospitals having specialized multidisciplinary teams. Findings from the study can be used to follow best clinical practices for myelomeningocele repair 3).


Treatment outcomes following documented times to transfer and closure were evaluated at Children’s Hospital of Los Angeles (CHLA) for the years 2004 to 2014. Data of newborns with a myelomeningocele with varying time to repair were also obtained from non-overlapping abstracts of the 2000-2010 Kids’ Inpatient Database (KID) and Nationwide Inpatient Sample (NIS). Poisson multivariable regression analyses were used to assess the effect of time to repair on infection and time to discharge.

At CHLA, 95 neonates who underwent myelomeningocele repair were identified, with a median time from birth to treatment of 1 day. Six (6 %) patients were noted to have postrepair complications. CHLA data was not sufficiently powered to detect a difference in infection following delay in closure. In the NIS, we identified 3775 neonates with repaired myelomeningocele of whom infection was reported in 681 (18 %) patients. There was no significant difference in rates of infection between same-day and 1-day wait times (p = 0.22). Wait times of two (RR = 1.65 [1.23, 2.22], p < 0.01) or more days (RR = 1.88 [1.39, 2.54], p < 0.01), respectively, experienced a 65 % and 88 increase in rates of infection compared to same-day procedures. Prolonged wait time was 32 % less likely at facilities with increased myelomeningocele repair volume (RR = 0.68 [0.56 0.83], p < 0.01). The presence of infection was associated with a 54 % (RR = 1.54 [1.36, 1.74], p < 0.01) increase in the length of stay when compared to neonates without infection.

Myelomeningocele closure, when delayed more than 1 day after birth, is associated with an increased rate of infection and length of stay in the national cohort. High-volume centers are associated with fewer delays to repair. Though constrained by limitations of a national coded database, these results suggest that early myelomeningocele repair decreases the rate of infection 4).


In a retrospective, statewide, population-based study examined infants with open spina bifida (SB) born in Florida 1998-2007. Most infants with SB had surgical repair in the first 2 days of life. Lower level birth hospital nursery care was associated with later repairs 5).

References

1)

Adzick NS. Fetal surgery for spina bifida: past, present, future. Semin Pediatr Surg. 2013 Feb;22(1):10-7. doi: 10.1053/j.sempedsurg.2012.10.003. Review. PubMed PMID: 23395140; PubMed Central PMCID: PMC6225063.
2)

Cherian J, Staggers KA, Pan IW, Lopresti M, Jea A, Lam S. Thirty-day outcomes after postnatal myelomeningocele repair: a National Surgical Quality Improvement Program Pediatric database analysis. J Neurosurg Pediatr. 2016 Oct;18(4):416-422. Epub 2016 Jun 3. PubMed PMID: 27258591.
3)

Kancherla V, Ma C, Grant G, Lee HC, Shaw GM, Hintz SR, Carmichael SL. Factors Associated with Timeliness of Surgical Repair among Infants with Myelomeningocele: California Perinatal Quality Care Collaborative, 2006 to 2011. Am J Perinatol. 2019 Jul 15. doi: 10.1055/s-0039-1693127. [Epub ahead of print] PubMed PMID: 31307103.
4)

Attenello FJ, Tuchman A, Christian EA, Wen T, Chang KE, Nallapa S, Cen SY, Mack WJ, Krieger MD, McComb JG. Infection rate correlated with time to repair of open neural tube defects (myelomeningoceles): an institutional and national study. Childs Nerv Syst. 2016 Sep;32(9):1675-81. doi: 10.1007/s00381-016-3165-4. Epub 2016 Jul 21. PubMed PMID: 27444296.
5)

Radcliff E, Cassell CH, Laditka SB, Thibadeau JK, Correia J, Grosse SD, Kirby RS. Factors associated with the timeliness of postnatal surgical repair of spina bifida. Childs Nerv Syst. 2016 Aug;32(8):1479-87. doi: 10.1007/s00381-016-3105-3. Epub 2016 May 14. PubMed PMID: 27179533; PubMed Central PMCID: PMC5007061.

Myelomeningocele repair

The closure of the skin defect in myelomeningocele (MMC) repair is an essential step that determines the quality of the surgical result. The success of surgical results is related to the decision to use the most suitable techniques, namely flaps or primary closure.

In cases of myelomeningocele, some prefer to place the shunt and close the defect in the same procedure, it reduces the risks inherent to exposure to anesthesia, reduces hospital stay, and related costs. If there is a suspicious of infection, they do not place the shunt on the same procedure 1).

Prenatal therapeutic strategies that interrupt progressive pathological processes offer an appealing approach for treatment of MMC. However, a thorough understanding of pathological progression of MMC is mandatory for appropriate treatment to be rendered 2).

Closure of the defect.

MOMS Trial

see MOMS Trial.

Case series

A prospective study of Zarutskie et al., from the Baylor College of MedicineTexas Children’s HospitalLucile Packard Children’s Hospital Stanfordfrom fetuses diagnosed with open neural tube defect that had in-utero myelomeningocele repair between April 2014 and April 2016. Independent variables were collected from four chronological sets of fetal images: pre-surgery ultrasound, pre-surgery MRI, 6-week post-surgery MRI and pre-delivery ultrasound. The following independent variables were collected from all image sets unless otherwise noted: gestational age, head circumference, mean ventricular width, ventricular volume (VV, MRI only), hindbrain herniation (HBH) score (MRI only), and level of lesion, defined as the upper bony spinal defect (pre-surgery US). Based on these measurements, additional variables were defined and calculated including change in degree of HBH, ventricular width growth (mm/week), and ventricular volume growth (ml/week). The need for hydrocephalus HT (by either ventriculoperitoneal shunt or endoscopic third ventriculostomy and choroid plexus cauterization (ETV-CPC)) was determined by a pediatric neurosurgeon using clinical and radiographic criteria; a secondary analysis was performed using the MOMS trial criteria for hydrocephalus. The predictive value of each parameter was assessed by ROC-curve and logistic regression analyses.

Fifty affected fetuses were included in the study, of which 32 underwent open hysterotomy and 18 fetoscopic repair. Two cases of neonatal death were excluded from the analysis. The mean gestational ages for the pre-surgery ultrasound, pre-surgery MRI, post-surgery MRI and pre-delivery ultrasound were 21.8 ± 2.1 weeks, 22.0 ±1.8 weeks, 30.4 ±1.6 weeks and 31.0 ±4.9 weeks, respectively. A total of 16 subjects required HT. Area under the curve (AUC) of predictive accuracy for HT showed that HBH grading on post-surgery MRI had the strongest predictive value (0.86; p<0.01), outperforming other predictors such as mean ventricular width on pre-surgery US (0.67; p=0.05), post-surgery MRI VV (0.73; p=0.03), MRI VV growth (0.79; p=0.01), change in HBH (0.82; p<0.01), and mean ventricular width on pre-delivery US (0.73; p=0.01). Other variables such as mean ventricular width on pre-surgery and post-surgery MRI, and ventricular growth assessment by MRI or US, had an AUC<0.7. Optimal cut-offs of the variables with the highest AUCs were evaluated to improve prediction. A combination of ventricular volume growth ≥ 2.02 ml/week and/or HBH of 3 on post-surgery MRI were the optimal cut-offs for the best prediction [OR: 42 (95% CI: 4 – 431), accuracy: 84%]. Logistic regression analyses also showed that persistence of severe HBH 6 weeks after surgery by MRI is one of the best predictors for HT [OR 39 (95% CI: 4 – 369), accuracy: 84%]. There was no significant change in the results when the MOMS trial criteria for hydrocephalus were used as the dependent variable 3).


Sanz-Cortés et al., described and compared placental and amniotic histology in women who underwent a fetoscopic myelomeningocele repair to those who underwent an open-hysterotomy myelomeningocele repair. Also, we intended to compare findings from both prenatal repair groups to age-matched control pregnant patients.

Placental and membrane histopathology from 43 prenatally repaired spina bifida cases (17 fetoscopic and 26 open) and 18 healthy controls were retrospectively assessed. Quantitative assessment of histopathology included apoptosis count, maternal and fetal underperfusion scores. Qualitative assessment included the detection of pigmented macrophages and/or signs of placental/amniotic inflammation. Associations between the duration of surgery or the duration of CO2 insufflation and quantitative histological parameters were tested.

Fetoscopic surgery cases did not show significant differences in any of the studied parameters when compared against controls. No differences were detected either when compared to open-repaired cases, except for lower proportion of pigmented laden macrophages in the fetoscopic group (11.8% vs 61.5% p<0.01). No associations between the duration of surgery or the duration of CO2 exposure and any of the quantitative histological parameters were detected.

These preliminary results support the lack of detrimental effects of the use of heated and humidified CO2 gas for uterine insufflation to fetal membranes and placenta 4).

References

1)

Bao N, Lazareff J. How I Do It: Management of spina bifida in a hospital in The People’s Republic of China. Surg Neurol Int. 2015 Jul 23;6(Suppl 11):S337-45. doi: 10.4103/2152-7806.161410. eCollection 2015. PubMed PMID: 26236554; PubMed Central PMCID: PMC4521313.
2)

Smith GM, Krynska B. Myelomeningocele: How we can improve the assessment of the most severe form of spina bifida. Brain Res. 2014 Dec 9. pii: S0006-8993(14)01659-X. doi: 10.1016/j.brainres.2014.11.053. [Epub ahead of print] PubMed PMID: 25498106.
3)

Zarutskie A, Guimaraes C, Yepez M, Torres P, Shetty A, Sangi-Haghpeykar H, Lee W, Espinoza J, Shamshirsaz A, Nassr A, Belfort M, Whitehead W, Sanz Cortes M. Prenatal brain imaging for predicting postnatal hydrocephalus treatment in fetuses that had neural tube defect repair. Ultrasound Obstet Gynecol. 2019 Jan 8. doi: 10.1002/uog.20212. [Epub ahead of print] PubMed PMID: 30620440.
4)

Sanz-Cortés M, Castro E, Sharhan D, Torres P, Yepez M, Espinoza J, Shamshirsaz AA, Nassr AA, Popek E, Whitehead W, Belfort MA. AMNIOTIC MEMBRANE AND PLACENTAL HISTOPATHOLOGICAL FINDINGS AFTER OPEN AND FETOSCOPIC PRENATAL NEURAL TUBE DEFECT REPAIR. Prenat Diagn. 2019 Jan 4. doi: 10.1002/pd.5414. [Epub ahead of print] PubMed PMID: 30609053.

Endovascular Cerebral Aneurysm Repair Market By Medtech Ventures

Endovascular Cerebral Aneurysm Repair MarketEndovascular Cerebral Aneurysm Repair Market

Endovascular Cerebral Aneurysm Repair Market
By Medtech Ventures
Price: $950.00 cart

Product Description

The global market for endovascular cerebral aneurysm repair (ECAR) devices has surpassed the $1 billion mark and currently stands at US$1.1 billion. The market, which has experienced explosive growth over the previous decade, has matured at the current level of technology. In its purest form, the endovascular cerebral aneurysm repair market consists of three broad categories of minimally invasive devices; embolic coils, intracranial stents and access devices. When used alone, or in combination, they allow the intervening physician to use the patient’s arteries as highways to deliver intended therapies, in the form of coils or stents, to the aneurysm location within the patient’s brain. The delivery procedure is performed under real-time visual guidance from high-powered imaging machines in a neurointerventional suite. The endovascular cerebral aneurysm repair market experienced a phenomenal growth phase that saw revenue rise over ten folds in just over a decade, from less than $100 million in 2000 to its current level of $1.1 billion. Current market leaders are seeking cost reductions and profit maximization through consolidation and moving production to lower cost jurisdictions. However, new research in endothelial biology is ushering in a new breed of biotech startups in search for disease modifying molecular targets, which could, theoretically, disrupt the market before the end of this decade. Medtech Ventures’ Endovascular Cerebral Aneurysm Repair Market Report is an exclusive update to the recently changed global landscape of this market. It provides a brief, but thorough, analysis of the market with profiles of leading participant and a solid forecast to 2020.


Product Details

  • Published on: 2014-06-01
  • Original language: English
  • Binding: Paperback
  • 34 pages

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