The authors describe a case of split notochord syndrome with a neuroenteric fistula in a newborn presenting with meningitis. Associated anomalies included agenesis of the corpus callosum, short colon, malrotation, epispadias, and an abnormally high bifurcation of the abdominal aorta and inferior vena cava. The embryological mechanisms and etiologic theories are discussed in short

Lequin, M.H. (Maarten)

Mancini, G.M.S. (Grazia)

Ramshorst, G.H. (Gabrielle) van

Ven, C.P. (Cees) van de

Erasmus University Digital Repository

www.elsevier.com/locate/jpedsurgA case of split notochord syndrome: a child with aneuroenteric fistula presenting with meningitisGabrielle H. van Ramshorsta, Maarten H. Lequinb,Grazia M.S. Mancinic, Cornelis P. van de Vena,*aDepartment of Pediatric Surgery, Erasmus Medical Center/Sophia ChildrenTs Hospital, 3000 CB Rotterdam, the NetherlandsbDepartment of Radiology, Erasmus Medical Center/Sophia ChildrenTs Hospital, 3000 CB Rotterdam, the NetherlandscDepartment of Metabolic Diseases and Clinical Genetics, Erasmus Medical Center, 3000 CB Rotterdam, the Netherlands0022-3468/$ – see front matter D 2006doi:10.1016/j.jpedsurg.2006.09.070* Corresponding author. Tel.: +31 1E-mail address: c.vandeven@erasmuIndex words:Split notochord syndrome;Neuroenteric fistula;MeningitisAbstract The authors describe a case of split notochord syndrome with a neuroenteric fistula in anewborn presenting with meningitis. Associated anomalies included agenesis of the corpus callosum,short colon, malrotation, epispadias, and an abnormally high bifurcation of the abdominal aorta andinferior vena cava. The embryological mechanisms and etiologic theories are discussed in short.D 2006 Elsevier Inc. All rights reserved.Split notochord syndrome (SNS) describes congenitalspinal anomalies, associated with anomalies of the verte-brae, central nervous system, and gastrointestinal tract. Theanomalies arise from a persistent connection betweenendoderm and dorsal ectoderm. Depending on its size,site, and point in time, abnormal splitting of the notochordcan result in a wide variety of malformations and clin-ical symptomatology.1. Case reportA 4-day-old boy was referred to our hospital onsuspicion of meningitis with secondary dehydration andfor evaluation of vertebral anomalies. He was born at37 weeks of gestation through normal vaginal delivery asthe third child of a 26-year-old mother. Birth weight was3010 g. Physical examination revealed normal tonus, minorElsevier Inc. All rights reserved.0 4636240; fax: +31 10 4636802.smc.nl (C.P. van de Ven).facial dysmorphic signs (eg, broad mouth and dysmorphic,normally placed ears with a thin helix), left-sided congenitalhip dysplasia, sacral dimple, and rocker bottom feet. Thepenis showed a mild epispadias, whereas anus, scrotum, andtestes were normal. The mother had smoked duringpregnancy and had not used supplementary folic acid.Besides local treatment of a vaginal yeast infection, no othermedication had been used during pregnancy. The daybefore, the patient had been brought in at the referringhospital with a 2-day history of poor feeding and fever. Hewas jaundiced and showed a tachycardia at a bodytemperature of 398C. Neurologic examination revealed hightonus and a bulging anterior fontanel. The abdomen wasdistended. Abdominal x-ray showed a spinal cleft of thevertebrae of Th 12 and L1 (Fig. 1). The kidneys werenormal on ultrasound. Blood tests showed elevatedC-reactive protein (109 mg/L) and white blood cell count(25,500 cells per cubic millimeter). No lumbar puncture wasattempted because of the vertebral anomalies. Bloodcultures showed growth of Escherichia coli bacteria, afterwhich, antibiotic treatment was switched from amoxicillin/cefotaxim to meropenem.Journal of Pediatric Surgery (2006) 41, E19–E23Fig. 1 Plain x-ray of the spine: showing spinal cleft of thevertebrae of Th 12 and L1.G.H. van Ramshorst et al.E20Magnetic resonance imaging studies (including non-contrast T1- and T2-weighted images) of the brain,abdomen, and spine displayed a wide variety of congenitalmalformations (Figs. 2 and 3). The brain scan revealedcomplete agenesis of the corpus callosum with smallperiventricular calcifications. The abdominal scan showeda left-sided colon. A neuroenteric fistula was suspected atthe splenic flexure. Bifurcations of the abdominal aorta andinferior vena cava were located immediately distal to therenal arteries.Laparotomy by transverse incision, performed on day16 of life, confirmed intestinal malrotation. A colonicstenosis was present. Proximal to the stenosis, a fistula ofapproximately 1 cm in diameter was found, leading into thevertebral cleft (Fig. 4). The fistula was resected and thestenosis was treated by enteroplasty. Postoperative recovery,with reintroduction of enteral feeding, was uneventful.At the age of 5 months, the patient was readmittedwith a mechanical ileus. At laparotomy, a restenosis seemedto be the causal factor. Resection and reanastomosisfollowed. Pathological examination of the resected bowelsection showed presence of ciliary pseudolayered epitheliaand ectopic tissue derivative of the stomach, esophagus,and pancreas.At the age of 10 months, head circumference was foundto grow steadily along the 99th percentile growth line.Magnetic resonance imaging studies of the brain clearlyshowed ventricular distension, but there were no signsof elevated intracranial pressure. Fundoscopy showed aFig. 2 Magnetic resonance imaging—vertebral column axialT1- and T2-weighted images: The magnetic resonance imagingstudy of the spine shows a ventral cleft of vertebral bodies Th 12and L1. A bowel loop projects into this ventral cleft, and may havea connection with the dura. There is a broadened spinal canal.Fig. 3 Magnetic resonance imaging—vertebral column sagittalimage: a bowel loop is visible, projecting into the vertebralcolumn. There is a marked kyphoscoliosis. The sacral dimple,more caudally, is not connected to the spine or the spinal cleft.ig. 4 Peroperative photograph showing a fistula, indicated bye arrow, leading from the colon into the vertebral cleft. Theroximal colon is distended, and is indicated by bx.QTable 1 Associated anomalies, also mentioned by otherauthors of split notochord casesAgenesis of corpuscallosumKanmaz et al [11]Razack and Page [12]Genital deformity Dindar et al [13](peniscrotal transposition)Faris and Crowe [14] (epispadias)Rosselet [15] (absent penis)Kyphoscoliosis Almog et al [16]Aydin et al [17]Kurisu et al [18]Singh and Singh [8]Malrotation Meller et al [20]Alrabeeah et al [9]Kheradpir and Ameri [19]Saunders [21]Short colon Kiristioglu et al [22]Pathak et al [23]Skin dimple Bentley and Smith [6] (case 3)A case of split notochord syndrome E21normal papilla. Ventriculoperitoneal drainage was thereforenot initiated.Presently, at the age of 4 years, the patient’s psychomo-toric development shows impairment of gait with high deep-tendon reflexes and Babinski sign. Speech and mentalFthpdevelopment are age-adequate. He is macrocephalic with anoccipital-frontal circumference (OFC) higher than 2.5 SDand has a marked kyphoscoliosis. Contrast study of theintestine showed no abnormalities except for malrotation ofthe colon.The karyotype is normal (46,XY). The association ofagenesis of corpus callosum with split notochord raised thesuspicion of a microdeletion at chromosome 7q36 involvingboth the Sonic hedgehog (Shh) locus and the HLXB9 locus[1]. Callosal agenesis can be considered as a minimalmanifestation of holopresencephaly. Holoprosencephaly hasbeen described in association with spinal anomalies andtethered cord, with detected deletions at chromosome 1p[2,3]. Fluorescence in situ hybridization studies wereinitiated. No deletion was detected at 7q36, nor at loci1p32 or 1p36. Considering the importance of the Shh genein the embryological development of the notochord andG.H. van Ramshorst et al.E22floor plate [4], the Shh gene was sequenced. No abnormal-ities could be identified. Multiplex ligation-dependent probeamplification of all chromosomal subtelomeric regions didnot reveal any chromosomal aneuploidies [5]. Anotheremerging technique for detection of submicroscopic chro-mosome anomalies could be array comparative genomichybridization. Unfortunately, this technique is not routinelyavailable at our institution.2. DiscussionThe spectrum of SNS includes a wide variety ofcongenital anomalies of the spine, the nervous system,and the gastrointestinal tract. According to Bentley andSmith [6], visceral malformations can be classified intofistulae, sinuses, posterior enteric diverticula, and poste-rior enteric cysts. Complicated anomalies may be easy todetect, even antenatally [7]. Clinical presentation of SNSmay include gastrointestinal obstruction or meningitis[8-10]. More subtle anomalies, such as spina bifidaocculta, may be indicated only by the presence of hyper-trichosis, a nevus, angioma, or a sacral dimple. Associ-ated anomalies are diverse, and those present in our caseas mentioned by others [6,8,9,11-22] are listed in Table 1.Bentley and Smith stated that malformations of the heartand the great vessels have also been associated withabnormal spinal development, but a ready explanation isnot at hand [6].During the third week of gestation, the human embryoconsists of 3 embryological layers: ectoderm, mesoderm,and endoderm. By day 20, the notochordal process hasappeared as a tube in the mesodermal layer. The ventralwall of the notochordal process then begins to fuse withthe endoderm to form the notochordal plate. During a briefperiod, an open neuroenteric canal is formed between theyolk sac cavity and the amniotic cavity. The final remnantsof this canal are located at the tip of the os coccygis. Then,the notochordal process creates the notochord. Somito-meres appear in the paraxial mesoderm, which formsclerotomes. These eventually give rise to the vertebralbodies, vertebral arches, and part of the back of the skull.Remains of yolk sac origin can differentiate into any tissueresembling a part of the gut or its embryological derivates(eg, lung tissue). During the fourth week, the neural plateconverts into the neural tube. Inadequate closure of theneural tube can result in vertebral anomalies. Fixation ofthe gut to, for example, the vertebral column, can inhibitadequate rotation [24].Two main theories explain the etiology of SNS and thepresence of neuroenteric fistula. The first, as suggested byFeller and Sternberg [25], stated that the embryologicalremains of the primitive knot persist and thereby cause thenotochord to be cleft. Bremer [26] supported the secondtheory, which asserts that an accessory or ectopic neuro-enteric canal is formed, passing through all the midlinestructures of the back. Saunders suggested that this canal isformed within a localized duplication or cleft of thenotochord, through which the endoderm (or primitive gut)herniates to adhere to the dorsal ectoderm [21]. Bentley andSmith [6] supported this theory. Beardmore and Wiggles-worth suggested that adhesions between ectoderm andendoderm, possibly with an endomesenchymal tract formedaround these adhesions (as suggested by Pang and Dias[27]), create an accessory neuroenteric canal, bisecting thedeveloping notochord [28].The ultimate form of the abnormality depends on thetime and location of the split and the degree to which thesplit or adhesion persists. Because the spectrum of SNS iswide, treatment options should be individualized. In ourcase, which was the fourth reported case of SNS presentingwith meningitis, treatment primarily consisted of identifica-tion and resection of the neuroenteric fistula.References[1] Horn D, Tfnnies H, Neitzel H, et al. Clinical report: minimal clinicalexpression of the holoprosencephaly spectrum and of Currarinosyndrome due to different cytogenetic rearrangements deleting theSonic Hedgehog Gene and the HLXB9 Gene at 7q363. Am J MedGenet 2004;128A:85 -92.[2] Campbell CG, Wang H, Hunter GW. Interstitial microdeletion ofchromosome 1p in two siblings. Am J Med Genet 2002;111(3):289 -94.[3] Battaglia A. Del 1p36 syndrome: a newly emerging clinical entity.Brain & Development 2005;27:358 -61.[4] Chiang C, Litingtung Y, Lee E, et al. Cyclopia and defective axialpatterning in mice lacking sonic hedgehog gene function. Nature1996;383(6599):407-13.[5] Rooms L, Reyniers E, Van Luijk R, et al. Subtelomeric deletionsdetected in patients with idiopathic mental retardation using multiplexligation-dependent probe amplification (MLPA). Human Mutation2004;23:17 -21.[6] Bentley JF, Smith JR. Developmental posterior enteric remnants andspinal malformations: the split notochord syndrome. Arch Dis Child1960;35:76 -86.[7] Agagni A, Paladini D, Bagolan P, et al. Split notochord syndromevariant: prenatal finding and neonatal management. Prenat Diagn2005;25(1):23 -7.[8] Singh A, Singh R. Split notochord syndrome with dorsal entericfistula. J Pediatr Surg 1982;17(4):412-3.[9] Alrabeeah A, Gillis DA, Giacomantonio M, et al. Neurenteric cysts—a spectrum. J Pediatr Surg 1988;23(8):752 -4.[10] Durham MM, Chahine AA, Ricketts RR. Presacral neuroentericfistula presenting with meningitis and vaginal fistula: a case report. JPediatr Surg 1998;33(10):1558-60.[11] Kanmaz T, Demirbilek S, Ozturk A, et al. The split notochordsyndrome with dorsal enteric fistula. Indian J Pediatr 2002;69(8):729 -30.[12] Razack N, Page LK. Split notochord syndrome: case report.Neurosurgery 1995;37(5):1006 -8.[13] Dindar H, Kanmaz T, Cakmak M, et al. The split notochord syndromewith dorsal enteric fistula, meningomyelocele and imperforate anus.Turk J Pediatr 1999;41(1):147 -50.[14] Faris JC, Crowe JE. The split notochord syndrome. J Pediatr Surg1975;10(4):467-72.[15] Rosselet PJ. A rare cade of rachischisis with multiple malformations.Am J Roentg Radium Ther Nucl Med 1955;73(2):235-40.A case of split notochord syndrome E23[16] Almog B, Leibovitch L, Achiron R. Split notochord syndrome—prenatal ultrasonographic diagnosis. Prenat Diag 2001;21(13):1159-62.[17] Aydin K, Sencer S, Barman A, et al. Case report: spinal cordherniation into a mediastinal neurenteric cyst: CT and MRI finding. BrJ Radiol 2003;76(902):132-4.[18] Kurisu A, Kawachi Y, Maruyama H, et al. Split notochord syndromein an adult presenting with colonic duplication. Report of a case.Dis Colon Recum 1992;35(1):78 -81.[19] Kheradpir MH, Ameri MR. Dorsal herniation of the gut with posterioropening of the terminal colon: a rare manifestation of the splitnotochord syndrome. Z Kinderchir 1983;38(3):186 -7.[20] Meller JL, Loeff DS, Reyes HM. A variant of the split notochordsyndrome. J Pediatr Surg 1989;24(8):733 -5.[21] RLdeCH Saunders. Combined anterior and posterior spina bifida in aliving neonatal human female. Anat Rec 1943;87:255-78.[22] Kiristioglu I, Teitelbaum DH, Dogruyol H. Split notochord syndromewith prolapsed congenital colostomy. J Pediatr Surg 1998;33(3):525-8.[23] Pathak VB, Singh S, Wakhlu AK. Double split of notochord withmassive prolaps of the gut. J Pediatr Surg 1988;23(11):1039 -40.[24] Larsen WJ. Human embryology. 2nd ed. New York, ChurchillLivingstone.[25] Feller A, Sternberg H. Zur Kenntnis der Fehlbildungen derWirbels7ule–I. Die Wirbelkfrperspalte und ihre formale Genese.Virchows Arch path Anat 1929;272:613-40.[26] Bremer JL. Dorsal intestinal fistula: accessory neurenteric canal:diastematomyelia. AMA Arch Path 1952;54:132-8.[27] Pang D, Dias MS. Split cor malformation: part I: a unified theoryof embryogenesis for double spinal cord malformations. Neurosurgery1992;31(3):451 -80.[28] Beardmore HE, Wigglesworth FW. Vertebral anomalies and alimen-tary duplication. Pediatr Clin North Am 1958;5:457-74.

A case of split notochord syndrome: a child with a neuroenteric fistula presenting with meningitis

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A case of split notochord syndrome: a child with a neuroenteric fistula presenting with meningitis

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