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.

Microcephaly

Microcephaly

Head circumference more than 2 standard deviations below the mean for sex and gestational age. Terms that are sometimes used synonymously: microcrania, microcephalus. Not a single entity, many conditions may be associated with microcephaly. It may also result from maternal cocaine abuse. It is important to differentiate microcephaly from a small skull resulting from craniosynostosis in which surgical treatment may provide opportunity for improved cerebral development.

Etiology

Effects of maternal cocaine use on the fetal nervous system include: microcephaly 1).

May be present in Dandy Walker malformationAgenesis of the corpus callosumHydranencephaly.

Overshunting (controversial): Microcephaly accounted for ≈ 6% of skull deformities after shunting (about half of these had sagittal synostosis). Some of these changes were reversible (except when complete synostosis was present) if intracranial hypertension recurred.

Diagnosis

Occipitofrontal circumference:

Deviations below the curves or head growth in the premature infant in the neonatal period of less than 0.5 cm/wk (excluding the first few weeks of life) may indicate microcephaly.

Associations

Holoprosencephaly with:

Cyclopia

Ethmocephaly

Cebocephaly

with median cleft lip

with median philtrum-premaxilla anlage

Shaheen et al., previously suggested that a single founder splicing variant in human CTU2 causes a multiple congenital anomalies syndrome consisting of dysmorphic facies, renal agenesis, ambiguous genitalia, microcephalypolydactyly, and lissencephaly (DREAM-PL).

They described five new patients with DREAM-PL phenotype and whose molecular analysis expands the allelic heterogeneity of the syndrome to five different alleles; four of which predict protein truncation. Functional characterization using patient-derived cells for each of these alleles, as well as the original founder allele; revealed a specific impairment of wobble uridine thiolation in all known thiol-containing tRNAs.

This data establish a recognizable CTU2-linked autosomal recessive syndrome in humans characterized by defective thiolation of the wobble uridine. The potential deleterious consequences for the translational efficiency and fidelity during development as a mechanism for pathogenicity represent an attractive target of future investigations 2).


Majewski osteodysplastic primordial dwarfism Type II (MOPD II) is a rare genetic disorder. Features of it include extremely small stature, severe microcephaly, and normal or near-normal intelligence. Previous studies have found that more than 50% of patients with MOPD II have intracranial vascular anomalies, but few successful surgical revascularization or aneurysm-clipping cases have been reported because of the diminutive arteries and narrow surgical corridors in these patients.

Teo et al., report on a large series of patients with MOPD II who underwent surgery for an intracranial vascular anomaly.

In conjunction with an approved prospective registry of patients with MOPD II, a prospectively collected institutional surgical database of children with MOPD II and intracranial vascular anomalies who underwent surgery was analyzed retrospectively to establish long-term outcomes.

Ten patients with MOPD II underwent surgery between 2005 and 2012; 5 patients had moyamoya disease (MMD), 2 had intracranial aneurysms, and 3 had both MMD and aneurysms. Patients presented with transient ischemic attack (TIA) (n = 2), ischemic stroke (n = 2), intraparenchymal hemorrhage from MMD (n = 1), and aneurysmal subarachnoid hemorrhage (n = 1), and 4 were diagnosed on screening. The mean age of the 8 patients with MMD, all of whom underwent extracranial-intracranial revascularization (14 indirect, 1 direct) was 9 years (range 1-17 years). The mean age of the 5 patients with aneurysms was 15.5 years (range 9-18 years). Two patients experienced postoperative complications (1 transient weakness after clipping, 1 femoral thrombosis that required surgical repair). During a mean follow-up of 5.9 years (range 3-10 years), 3 patients died (1 of subarachnoid hemorrhage, 1 of myocardial infarct, and 1 of respiratory failure), and 1 patient had continued TIAs. All of the surviving patients recovered to their neurological baseline.

Patients with MMD presented at a younger age than those in whom aneurysms were more prevalent. Microneurosurgery with either intracranial bypass or aneurysm clipping is extremely challenging but feasible at expert centers in patients with MOPD II, and good long-term outcomes are possible 3).

References

1)

Volpe JJ. Effect of Cocaine Use on the Fetus. N Engl J Med. 1992; 327:399–407
2)

Shaheen R, Mark P, Prevost CT, AlKindi A, Alhag A, Estwani F, Al-Sheddi T, Alobeid E, Alenazi MM, Ewida N, Ibrahim N, Hashem M, Abdulwahab F, Bryant EM, Spinelli E, Millichap J, Barnett SS, Kearney HM, Accogli A, Scala M, Capra V, Nigro V, Fu D, Alkuraya FS. Biallelic Variants in CTU2 Cause DREAM-PL Syndrome and Impair Thiolation of tRNA Wobble U34. Hum Mutat. 2019 Jul 13. doi: 10.1002/humu.23870. [Epub ahead of print] PubMed PMID: 31301155.
3)

Teo M, Johnson JN, Bell-Stephens TE, Marks MP, Do HM, Dodd RL, Bober MB, Steinberg GK. Surgical outcomes of Majewski osteodysplastic primordial dwarfism Type II with intracranial vascular anomalies. J Neurosurg Pediatr. 2016 Dec;25(6):717-723. PubMed PMID: 27611897.

Nontraumatic de novo arachnoid cyst

Nontraumatic de novo arachnoid cyst

Intracranial de novo arachnoid cysts in adults are very rare, suggesting the involvement of head trauma and inflammatory diseases.

Benign extracerebral fluid collections in infancy may constitute a significant risk factor for development of de novo arachnoid cysts. These findings support a 2-hit hypothesis for the development of arachnoid cysts, in which the combination of an embryological defect in arachnoid development followed by a second event leading to impairment of CSF fluid absorption in early childhood could lead to abnormal CSF dynamics and the consequent expansion of fluid collections in the intraarachnoid spaces 1).

Case reports

Yokoyama et al., reported a symptomatic adult case of nontraumatic de novo arachnoid cyst on the ventral medulla oblongata.

A 56-year-old man came to the hospital complaining of dysphagia and writing difficult since 3 months ago. There was no history of head injury or inflammatory disease. A 25-mm cystic lesion was found on the ventral side of the medulla oblongata on brain MRI, and the lower cranial nerve and medulla oblongata were highly compressed. The lesion did not exist on MRI performed 9 years ago. Capsular resection was performed and the histological diagnosis was a typical arachnoid cyst. After the operation, all neurological symptoms disappeared, and no recurrence has been observed after 6 months.

The pathophysiology of nontraumatic de novo arachnoid cysts has many unknown features, and it appears necessary to accumulate further case reports 2).


A 71-year-old male patient with progressive vertigo who had previous brain magnetic resonance imaging studies without abnormalities. Another MRI was performed 3 years from the last study that showed interval development of a large cystic lesion compressing the right cervicomedullary junction, as well as radiologic evidence of neurosarcoidosis. Intraoperative findings showed a cystic mass with clear, gelatinous fluid. The cyst was drained, and the walls were resected and sent to pathology. Histopathologic testing confirmed the lesion was an arachnoid cyst. The patient’s vertiginous symptoms improved after surgery.

This case represents the first incidence of a pathology-proven, nontraumatic de novo arachnoid cyst 3).

References

1)

Mattei TA, Bond BJ, Sambhara D, Goulart CR, Lin JJ. Benign extracerebral fluid collection in infancy as a risk factor for the development of de novo intracranial arachnoid cysts. J Neurosurg Pediatr. 2013 Dec;12(6):555-64. doi: 10.3171/2013.8.PEDS1399. Epub 2013 Oct 4. PubMed PMID: 24093592.
2)

Yokoyama K, Sugie A, Yamada M, Tanaka H, Ito Y, Yamashita M, Kawanishi M. Formation of de Novo Symptomatic Premedullary Arachnoid Cyst in Adult. World Neurosurg. 2019 Jul 10. pii: S1878-8750(19)31935-7. doi: 10.1016/j.wneu.2019.07.029. [Epub ahead of print] PubMed PMID: 31301440.
3)

Clifton W, Rahmathulla G, Tavanaiepour K, Alcindor D, Jakubek G, Tavanaiepour D. Surgically Treated de Novo Cervicomedullary Arachnoid Cyst in Symptomatic Adult Patient. World Neurosurg. 2018 Aug;116:329-332. doi: 10.1016/j.wneu.2018.05.046. Epub 2018 May 16. PubMed PMID: 29777892.
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