Diagnostic Approach in an Infant with Spinal Dysraphism

REVIEW ARTICLE eng slo element en article-lang

10.6016/ZdravVestn.2914 doi 6.1.2019 date-received Diagnostic approach in an infant with spinal 30.3.2019 date-accepted dysraphism Human reproduction Reprodukcija človeka discipline Review article Pregledni znanstveni članek article-type Slovenian Diagnostični pristop pri dojenčku s spinalnim disrafizmom Diagnostic approach in an infant with spinal Diagnostični pristop pri dojenčku s spinalnim article-title Medical dysraphism disrafizmom Journal Nataša Šuštar,1 Darja Paro Panjan,2 Damjana Ključevšek,3 David Neubauer,1 Peter Diagnostic approach in an infant with spinal Diagnostični pristop pri dojenčku s spinalnim alt-title Spazzapan,4 Aneta Soltirovska Šalamon2 dysraphism disrafizmom occult dysraphisms, skin dimples, imaging okultni disrafizmi, kožne jamice, slikovne metode, kwd-group techniques, diagnostic algorithm diagnostični algoritem The authors declare that there are no conflicts Avtorji so izjavili, da ne obstajajo nobeni conflict of interest present. konkurenčni interesi. Abstract year volume first month last month first page last page 1 Department of Spinal dysraphisms are congenital malformations of the spinal cord and spine that occur due to Child, Adolescent and 2019 88 11 12 539 553 impaired closure of the neural tube in early embryogenesis. According to the skin coverage, they Developmental Neurology, are divided into open and closed types. While open dysraphisms can be identified by prenatal Division of Paediatrics, investigations, the diagnosis of a closed (occult) dysraphic state is more difficult to establish. name surname aff email University Medical Centre There are specific skin signs over the spine in more than half of these patients, which can help Ljubljana, Ljubljana, Aneta Soltirovska Šalamon 1 [email protected] Slovenia with early diagnosis. Ultrasonography of the spine and spinal cord is the method of choice in the 2 Neonatal Unit, Division diagnostics of occult spinal dysraphism in the first months of life, until the spine is closed. The name surname aff of Paediatrics, University most sensitive diagnostic tool is magnetic resonance imaging, which also represents the gold Nataša Šuštar 1 Medical Centre Ljubljana, standard of preoperative diagnostics. Early diagnosis is important in asymptomatic conditions, Ljubljana, Slovenia as this allows timely surgical treatment of children, who are at greater risk of sudden onset of Darja Paro Panjan 2 3 Unit of Radiology, Division complications or neurological sequelae. In the article, we summarised clinical and radiological of Paediatrics, University Damjana Ključevšek 3 characteristics of dysraphic conditions and formed a diagnostic algorithm to unify an approach Medical Centre Ljubljana, in a child with spinal dysraphism in the first months of life. David Neubauer 1 Ljubljana, Slovenia 4 Department of Peter Spazzapan 4 Neurosurgery, Division of Izvleček Surgery, University Medical Spinalni disrafizmi so prirojene nepravilnosti hrbtenjače in spinalnega kanala, ki nastanejo zara- Centre Ljubljana, Ljubljana, di motenj zapiranja nevralne cevi v zgodnjem embrionalnem razvoju. Glede na kožno kritje jih eng slo aff-id Slovenia delimo na odprte in zaprte. Odprte disrafizme prepoznamo že s prenatalno diagnostiko, težja pa je prepoznava zaprtih (okultnih) stanj. Pri slednjih so nam pri diagnostiki v pomoč določeni Department of Child, Adolescent Klinični oddelek za otroško, 1 Correspondence/ kožni znaki nad hrbtenico, ki so prisotni pri več kot polovici bolnikov. Ultrazvočna preiskava spi- and Developmental Neurology, mladostniško in razvojno Korespondenca: nalnega kanala je v prvih mesecih starosti, dokler hrbtenica ne zakosteni, metoda izbire v diag- Division of Paediatrics, nevrologijo, Pediatrična klinika, Aneta Soltirovska Šalamon, nostiki okultnih spinalnih disrafizmov. Sicer je najobčutljivejše diagnostično orodje magnetno University Medical Centre Univerzitetni klinični center e: [email protected] Ljubljana, Ljubljana, Slovenia Ljubljana, Ljubljana, Slovenija resonančno slikanje, ki predstavlja tudi zlati standard predoperativne diagnostike. Zgodnja pre- Key words: poznava je pomembna tudi v primerih asimptomatskih stanj, ker s tem omogočimo pravočasno Neonatal Unit, Division of Klinični oddelek za 2 occult dysraphisms; kirurško zdravljenje otrok, pri katerih obstaja večje tveganje za nastanek nenadnih zapletov ali Paediatrics, University Medical neonatologijo, Pediatrična skin dimples; imaging nepovratnih nevroloških posledic. V članku smo povzeli klinične in radiološke značilnosti posa- Centre Ljubljana, Ljubljana, klinika, Univerzitetni klinični techniques; diagnostic meznih disrafičnih stanj, ter oblikovali diagnostični algoritem, z namenom poenotenja zgodnje Slovenia center Ljubljana, Ljubljana, algorithm Slovenija obravnave otrok s spinalnim disrafizmom. Ključne besede: Unit of Radiology, Division of Služba za radiologijo, Pediatrična 3 Cite as/Citirajte kot: Šuštar N, Paro Panjan D, Ključevšek D, Neubauer D, Spazzapan P, Soltirovska Šalamon okultni disrafizmi; Paediatrics, University Medical klinika, Univerzitetni klinični A. Diagnostic approach in an infant with spinal dysraphism. Zdrav Vestn. 2019;88(11–12):539–53. Centre Ljubljana, Ljubljana, center Ljubljana, Ljubljana, kožne jamice; slikovne Slovenia Slovenija metode; diagnostični algoritembesede DOI: https://doi.org/10.6016/ZdravVestn.2914 Department of Neurosurgery, Klinični oddelek za 4 Division of Surgery, University nevrokirurgijo, Kirurška klinika, Received: 6. 1. 2019 Medical Centre Ljubljana, Univerzitetni klinični center Accepted: 30. 3. 2019 Copyright (c) 2019 Slovenian Medical Journal. This work is licensed under a Ljubljana, Slovenia Ljubljana, Ljubljana, Slovenija Creative Commons Attribution-NonCommercial 4.0 International License.

Diagnostic approach in an infant with spinal dysraphism 539 HUMAN REPRODUCTION

1 Introduction

Spinal dysraphisms (SD) are a hetero- severity of the neurological impairment, geneous group of congenital abnormal- and the time that elapses from the the clin- ities of the spinal cord and spine. They ical picture until the surgery (6,14,15). are among the most common malformations and occur in 1-2/1000 live births (1). 2 Embryonic development They occur due to improper closure and of the spinal cord and formation of the neural tube in early embryogenesis, due to the activity of certain classification of SD environmental factors or genetic changes (1,2). Among the best known risk factors The development of the spinal cord for SD are genetic predisposition, mater- takes place from the 2nd to the 6th week of nal diabetes, taking certain antiepileptic gestation (GS) in three successive phases: drugs (valproate, carbamazepine), obesity, gastrulation, primary neurulation, and febrile condition in the first weeks of preg- secondary neurulation (2,10). nancy and folic acid deficiency in the diet Between the 2nd and 3rd week of GS, of pregnant women (3-6). The incidence during the process of gastrulation, from has decreased in the last two decades due the bilayered embryonic disc, which con- to folic acid prophylaxis, pre-natal diag- sists of epiblast and hypoblast, a three-lay- nostics, and genetic counseling in familes er disc is formed, from which the ecto- with a high risk of SD (5,6). derm, mesoderm and endoderm develop. According to the skin coverage, SD are From the middle part of the mesoderm, a divided into open and closed SD. Open notochord is formed, which in connection SDs are identified by prenatal investi- with the ectodermal layer forms the neu- gations, and closed ones mostly at birth. roectoderm and the neural plate (2,10,16). The latter, also called occult spinal dysra- Primary neurulation, which occurs be- phisms (OSDs), can be clinically silent for tween the 3rd and 4th week of GS, is the a long time. It is estimated that 43–95% of process of the neural plate transforming these patients have certain skin signs over into the neural tube. On day 17, the lateral the spine that make it easier to suspect parts of the neural plate thicken. Cells at SD (7-13). 75% of closed SDs develop the the junction of neuroectoderm and cuta- tethered spinal cord syndrome, which can neous ectoderm differentiate into neural be expressed at any age and is character- crest cells. ized by a progressive course (14,15). The contractile filaments of the neu- In the first three months of life, until roepithelial cells of the neural plate border the bodies, arches, and the vertebral pro- transform the neural plate into a neural cesses are ossified, ultrasonography (US) groove along the neural axis by folding of the spine is the method of choice for the lateral parts. Between days 21 and 23, recognizing SD (1). In all cases, the final the neural groove merges in the midline to diagnosis is made by magnetic resonance form a neural tube. This is followed by dis- imaging (MRI), which is the most sensi- junction - the separation of the neural tube tive and specific imaging method in diag- from the ectoderm, which runs along the nosing SD (2). It is important to identify surface. The cranial part (anterior neuro- asymptomatic conditions at an early stage pore) closes on the 25th day, and the cau- and thus enable timely surgical treatment dal end (posterior neuropore - S2 level) of children, who are at greater risk of sud- between the 27th and 28th day. den onset of complications or neurological A closed neural tube is the basis for the sequelae. The success of surgery in most development of the entire central nervous cases depends on the type of change, the system. Mesodermal structures penetrate

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Table 1: Embryological classification of spinal dysraphism, according downwards. Between the caudal end of to Acharya et al, 2017 (17). the neural tube and the notochord, a caudal cell mass is formed, from day 16 to 19, Embryological classification of spinal dysraphism between undifferentiated pluripotent cells. A ANOMALIES OF GASTRULATION This is followed by retrograde differentiation, when the caudal end of the neural 1 Disorders of Notochord Formation tube and the notochord are connected a Caudal Regression Syndrome through complex processes of apopto- b Segmental Spinal Dysgenesis sis and further differentiation. The conus medullaris and the filum terminale of the 2 Disorders of Notochord Integration spinal cord are formed from the caudal a Neuroenteric cysts cell mass (2,10,16). b Dorsal enteric fistula Between days 43 and 48 of the GS, the spinal cord begins to seemingly ascend c Split cord malformation (diastematomyelia) due to the growth of the spinal channel, B ANOMALIES OF PRIMARY NEURULATION because the bone structures grow faster 1 Premature Dysjunction than the nervous system. Conus medullaris in children of up to 2 months of age is a Lipomyelomeningocele at a height between L2 and L3, and after 2 b Lipomyelocele months it reaches a physiological level between L1 and L2 (1,10,15). c Intradural lipoma Development disorders of the spine and 2 Nondysjunction spinal cord in different embryonic stages a Dorsal dermal sinus lead to the formation of heterogeneous forms of SD. Their formation is character- b Myelomeningocele ized by two processes: incomplete fusion c Myelocele of central structures and disturbed tis- C COMBINED ANOMALIES OF GASTRULATION sue differentiation outside and inside the AND PRIMARY NEURULATION spinal channel (10,16). Table 1 shows the embryological classification of SD based 1 Hemimyelocele on recent findings on the pathogenesis of 2 Hemimyelomeningocele dysraphic conditions during spinal cord D ANOMALIES OF SECONDARY NEURULATION development (17). Based on the embryo- AND RETROGRESSIVE DIFFERENTIATION logical classification, the classification of SD has become more understandable and, 1 Abnormally long spinal cord above all, more uniform than in clinical 2 Persisting terminal ventricle and radiological classifications (10,16,17). 3 Tight filum terminale Embryological placement of SD is help- ful in assessing the extent of the malfor- 4 Intrasacral-anterior sacral meningocele mation, planning surgical treatment, and 5 Terminal myelocystocele understanding the severity of the clinical picture. dorsally into the area between the ecto- In previous classifications, there were derm and the neural tube and are the basis inconsistencies in the classification of for the development of meninges, verte- certain dysraphisms according to clinical brae, and paraspinal muscles (10,15,16). and radiological features. However, the This is followed by secondary neuru- clinical division into open and closed SD lation, which lasts until the 6th week of is still relevant, as it is most useful in the GS, during which the caudal part of the diagnostic approach when SD is suspected neural tube develops from the S2 level (10). Thus, in order to create a diagnostic

Diagnostic approach in an infant with spinal dysraphism 541 HUMAN REPRODUCTION

algorithm for treating a baby with SD, we coverage is required within 48-72 hours followed, in this article, the clinical classi- after birth. Despite successful surgical fication. correction, neurological deficits in motor skills remain, such as flaccid muscle pare- 3 Open SD sis with impaired or absent tendon reflex- es, sensory disturbances that can lead to In open SD, the tissues are exposed to the development of trophic ulcers, bowel the external environment. More than 98% and bladder incontinence, and lower in- of open SDs is represented by myelome- telligence. Orthopedic deformities, such ningocele (MMK), in which the neuro- as scoliosis, kyphosis, or foot deformities, genic placode – the spinal cord, including may be present at birth and eventually the meningeal envelopes, passes outward progress (15,20). through the posterior bone and skin de- Shortly after the closure of MMK, more fect. In Europe, the mean incidence of than half of patients develop hydrocepha- MMK is 0.41–1.9/1000 births (1,2,18). It lus. To resolve this, ventriculoperitoneal is most often found in the lumbosacral re- shunt or endoscopic ventriculostomy is gion (44%), and less frequently in the tho- required (2). According to imaging find- racolumbar (32%) and lumbar (22%) part ings, 99% of children with MMK have AC (1,2). II. Most are asymptomatic, but 10–30% The clinical picture of MMK depends experience swallowing disorders, central on the location and extent of the defect. apnea, vocal cord paresis, spasticity, and In the newborn, we find different degrees other signs requiring craniocervical de- of lax paresis of the lower limbs, sphincter compression due to compression of the dysfunction, hip dislocation or foot de- brainstem (1,2). formities. The diagnosis of MMK is made Tethered spinal cord syndrome occurs prenatally by determining the alpha feto- in 20–30% after surgical repair of MMK, protein in maternal serum or by amino- so these children need a new procedure centesis and by ultrasound examination (1). Hydromyelia and syringomyelia are of the fetus (2,19). Ultrasound signs of present in 40–80%, diastematomielia or prenatal diagnosis include: formation of longitudinally split spinal cord in 20–40%, affected C or U-shaped vertebrae, open but they are mostly clinically silent. The overlying skin, neurogenic placode in the quality of life after MKK surgery depends area of the defect, narrowing of the skull on congenital deficits and long-term (life- in the forehead (»lemon sign«), ventricu- long) rehabilitation (1,15). lomegaly and small posterior cranial cavi- Open SD also includes hemimyelome- ty with constriction of the cerebellum (19). ningocele, which is a very rare condition in After birth, however, ultrasonography of which MMK covers one part of the split the spinal channel is not performed due spinal cord or diastematomielia (2,18). to possible infection of the tissues exposed to the surroundings. An ultrasonography 4 Closed SD of the head, however, is performed, which shows signs of Arnold-Chiari malforma- 4.1 Skin marks tion type II (AC II), such as hypoplasia of the corpus callosum, shallow posterior Most occult conditions are considered cranial cavity, downward displacement of to be asymptomatic for a long time, so the the pons and upper spinal cord, and pas- diagnosis is usually made in later periods sage of cerebellar tonsils through the fora- or at the appearance of clinical signs (2). men magnum (1,18,20). MRI of the spinal Recognition of OSD in the first months channel and head is performed as part of of life is possible in those children who the preparation for surgery, and surgical have a clinical picture that leads to sus-

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and occur on their own, in large numbers or in conjunction with other skin changes. (2,7,14,20,24). Skin marks over the spine that also suggest SD are discolored skin, local hairiness or tuft of hair, capillary hemangiomas, atretic meningocele, skin protrusion or rudimentary tail, asymmetry of gluteal folds, and duplicated gluteal cleft (12,15). It is also good to be familliar with skin changes over the spine that do not indicate OSD: Mongolian spots, »café au lait«, hypo/hypermelanotic macules or papules, and small infantile hemangiomas. The presence of two or more skin signs means a higher risk of OSD. It is estimated that in three quarters the skin dimples Figure 1: Ultrasound of the spinal channel: A normal position of the are simple and that the possibility of OSD conus medullaris at the lower edge of L1. in these is as rare as in the general pop- picion of SD: subcutaneous mass in the ulation without skin changes (1,7,13,25). spine, paresis of the lower limbs, asym- When a simple dimple is found in a new- metry of movement, bowel and bladder born, ultrasonography of the spinal chan- incontinence, anogenital and genitouri- nel is not necessary, but a child with skin nary malformations, spinal deformities signs that indicate OSD is referred for ul- (scoliosis, sacral agenesis) and asymmetry trasound in his first three months of life in the size and circumference of the lower before the spine is ossified (20,26,27). Due limbs. We also think of OSD in newborns, to good transparency in the first months if certain skin changes are noted over the as well as logistical advantages over MRI, spine. According to various studies, these ultrasonography proved to be an diagnos- occur in a total of 2-8% of healthy chil- tic method of choice in the early identifi- dren (7,9,11,12,21,22). However, we need cation of OSD. Changes in the ultrasound to be familiar with certain characteristics imaging of the spinal channel, indicating that distinguish insignificant skin chang- SD are intraspinal mass, conus medullaris es from those that make us suspect OSD, below the level of L2 – L3 before 2 months so that not all children with skin changes of age or below L1 – L2 after 2 months, over the spine should be treated unneces- reduced or absent cone motility, spinal sarily (12). lipoma, filum more than 2 mm thick and A clinically insignificant or simple skin dermal sinus (Figure 1). MRI, however, is dimple is located medially over the sacrum, important in early diagnosis in high-risk less than 2.5 cm from the anus, is less than newborns with clinical signs, anogenital 5 mm in diameter, and occurs on its own malformations, or signs of syndromes in (7,23). Simple are also the skin dimples, which SD is possible (10,15,18). With ear- called “fossae lumbales” or “dimples of ly detection of OSD, in practice, the deci- Venus”, which lie symmetrically, parame- sion on surgical treatment at a time when dially over the sacrum and are present in the child has no clinical signs is individ- the underlying shorter ligaments of the ual and depends on the type and extent sacroiliac joints (12). Atypical skin dim- of changes present in MRI, the surgeon's ples, which indicate OSD, are located me- decision and the opinion of the child's dially or paramedially over the spine, at a parents or guardians, except in the case distance of more than 2.5 cm above the ofo dermal sinus, in which removal is re- anus, have a diameter of more than 5 mm quired in any case due to the high risk of

Diagnostic approach in an infant with spinal dysraphism 543 HUMAN REPRODUCTION

4.3 Clinically significant closed SD

According to the clinical classification, they are divided into SD with a subcutaneous mass (spinal lipomas passing through the dura, meningocele and myelocystocele) and SD without a subcutaneous mass (dermal sinus, intradural lipom, lipoma of the filum and complex dysraphisms). In most cases, the clinical picture develops due to the tethered spinal cord syndrome or pressure to the spinal cord (10,16).

4.4 Tethered spinal cord

Figure 2: Ultrasound of the spinal channel: A tethered cord in a four- The spinal cord is tethered in all open day-old boy with a 3 × 1 cm vascular skin mark above the coccyx, a skin SDs, and in closed ones due to spinal li- dimple and a skin tag at the end of the coccyx. pomas, dermal sinus, dystematomyelia, and other complex dysraphisms. During infection (9,15). embryonic development, the tethered spinal cord prevents the »ascension« of the 4.2 Physiological Variants spinal cord to the physiological level (18). Ultrasonography of the newborn shows Physiological variants are clinically in- the dorsal position of the conus with a lev- significant.The terminal ventricle is a small el below L2–3, a larger ventricular space cyst surrounded by the ependyma located filled with cerebrospinal fluid and the ab- at the junction of the conus medullaris sence of motility of the conus and nerve into the filum terminale. The longitudi- roots (1) (Figure 2). nal diameter measures up to 10 mm and The level of the conus modullaris is de- the transverse diameter to 2–4 mm and is termined clinically by counting the verte- mostly present only in the first weeks af- brae by various methods (15,18,20). ter birth (1,18). Physiological variants also Tethered spinal cord syndrome is a clin- include a transiently dilated central spinal ical syndrome that is most commonly channel that normally narrows after the expressed in children in the age of rapid first week (1,18,20), a cyst within the filum growth, when the traction forces on the without other changes, and a pseudosinus tethered spinal cord are greatest, or in pro- or pilonidal sinus - a fibrous cord that runs nounced flexion movements of the spine. from the simple skin dimple to coccyx Stretching of the conus, nerve roots, (18,20). and surrounding vessels leads to insuf- Clinically insignificant OSD includes ficient blood flow, leading to ischemia of spina bifida occulta, in which the poste- the conus, myelomalacia, and syringo- rior arches of the vertebrae are absent or hydromyelia (1,20,26). Low back and leg incompletely fused. It is estimated to be pain, gait disorders, sensory and sphincter present in 4% of the general population functions occur, and prolonged condition and does not cause problems on its own leads to progressive problems, spastici- (16). It is most commonly found in the ty, scoliosis, and orthopedic deformities lumbosacral region and may be charac- (1,15,18). MRI shows the low position and terized by a skin dimple or local hairiness dorsal position of the conus and identifies (28). dysraphisms that tether the spinal cord

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which pushes the placode posteriorly, it is located outside, and in lipomyelocele, inside or at the edge of the anatomical border of the spinal channel (2,10). In a newborn with LMMK above the spine, we see a bulge due to the subcutaneous mass, which is mostly located above the lumbar region, and various skin signs may be present on the skin with a possible clinical picture of lower limb paresis, sensory disturbances, orthopedic deformities or neurogenic bladder (Figure 3) (1,15). Lipomas without subcutaneous mass include intradural lipoma and filar lipoma (16). Intradural lipoma is located on the dor- Figure 3: Ultrasound of the spinal channel: There is a poorly bounded sal side of the spinal cord, in most cases in subcutaneous mass around the sacrum, which extends into the spinal the lumbar sacral region. Tethered spinal channel (the arrow head) and partially pushes the cauda equina cord syndrome may develop, or neurolog- forward, in a five-day-old girl with a hemangioma above the sacrum. ical signs may appear due to pressure on MR confirmed a tethered cord associated with a spinal cord lipoma. the spinal cord relative to the affected level (2,18). (11). Surgical relaxation of the tethered Lipoma of the filum terminale means spinal cord is required as soon as possible, a fatty thickening of the filum terminale as the defects are irreversible after a cer- (1). It is estimated that 1.5–5% of healthy tain time (2,15,29). adults have fatty tissue present within the filum terminale. A thickened filum is 4.5 Spinal lipomas a physiological variant if it is not thick- er than 2 mm at the height L5–S1 and if These include intradural lipomas and this is the only finding without signs of a lipomas that pass through the dura. Lipo- tethered spinal cord below the level L1–L2 mas passing through the dura represent (1,2,15,16). approximately 87% of all closed SD with Pang was the first to classify spinal li- a subcutaneous mass (16). These include pomas according to embryonic origin and lipomyelomeningocele (LMMK) and lipo- to divide them into three groups - dorsal myelocele, which are caused by prema- and transitional lipomas, which are the ture disjunction in the process of primary result of primary neurulation disorders, neurulation. Due to the premature separa- and terminal lipomas, which are malfor- tion of the neural tube from the overlying mations of the secondary neurulation (in ectoderm, the mesenchyme, which is the the embryological classification LMMK basis for subcutaneous fat, passes through belongs to the transitional lipomas) (30). the as yet unconnected neural tube. There- He later added the concept of chaotic lipo- fore, in such a segment, the meningeal ma with the characteristics of transitional envelope and bone structure cannot co- and terminal lipoma. Dorsal lipoma does alesce, while the skin cover is preserved. not cover the conus modullaris, whereas LMMK and lipomyelocele differ in where transitional and chaotic lipoma do cover the link between neurogenic placode and it. Chaotic lipoma also covers the roots of lipoma lies. the paraspinal nerves and has the worst In LMMK, due to the dilated subarach- prognosis in terms of clinical progression. noid space in front of the spinal cord, In such cases radical resection is not in

Diagnostic approach in an infant with spinal dysraphism 545 HUMAN REPRODUCTION

place. Caudal lipomas do not involve the unrecognized dermal sinus is an infection conus because they are located lower, in that leads to meningitis, meningoenceph- the region of the filum (31). alitis, or abscess formation, so surgical removal is always necessary (1,2,12,15). 4.6 Meningocele Ultrasound clearly shows the sinus tract (1,18), while MRI is performed to identify In meningocele, only the menin- associated changes before surgery (15,20). ges bulge through the unfused vertebra arches, while the skin above it may be nor- 4.9 Complex SD mal or less developed. It occurs ten times less frequently than MMK (15). It is most Complex SDs include malformations commonly located posteriorly in the lum- that are the result of gastrulation disor- bar region, but rarely lies anteriorly as in ders. Due to defects in the formation of Currarin's syndrome (anal atresia, sacral the notochord, in addition to the develop- agenesis, presacral meningocele) (2,18). ment of the spinal cord, the development Lateral meningocele may be associated of the adjacent organs is also affected. with neurofibromatosis type 1, Marfan or They are recognized prenatally or Ehlers-Danlos syndrome (1,18). Menin- immediately after birth due to certain gocele does not cause neurological defi- anomalies in the back, buttocks, limbs or cits, but with the coexistence of another urogenital area, as well as neurological, or- dysraphic change tethered spinal cord thopedic disorders or bowel and bladder syndrome may develop (15,18). incontinence. These include neurenteric cyst, dorsal enteric fistula, diastematomy- 4.7 Mielocistocele elia, caudal regression syndrome, and segmental spinal dysgenesis (1,2,18). Myelocystocele is a hernia of the dilat- Neurenteric cyst is an extremely ra- ed central part of the spinal channel (sy- re form of OSD. It is a remnant of the ringocele) in the area of the spina bifida neurenteric canal that transiently con- occult. In terminal myelocystocele, the di- nects the amniotic cavity and yolk sac in lated spinal channel passes through a bone the embryo. The cyst secretes mucin and defect within the dural sac (meningocele) is located inside the dural space or within (2,15). Abnormalities of the genitourinary the posterior mediastinum. In the connec- and anorectal systems may be associated tion between the intestine and the skin, it (1,18,20). is called dorsal enteric fistula (2,18). Diastematomyelia or longitudinally 4.8 Dermal sinus split spinal cord accounts for 3.8–5% of all spinal cord anomalies (32). It occurs The dermal sinus is an epithelium-lined during early embryonic development, fistula that represents the connection be- mostly in the thoracolumbar region, and tween the spinal channel and the skin. It is caudally united. It is divided into types occurs in approximately 1/2,500 children I and II: in the first, the spinal cord is sur- (15). There is a dimple on the skin, with- rounded by one dural sac, separated by out or with surrounding hyperperpigmen- a connective septum, and in the second, tation, angiomatosis or hypertrichosis, each hemispinal cord is surrounded by and in 50% of the cases there are dermoid a dural sac, with a bony or cartilaginous changes within the spinal channel. It is septum between them (1,2,15,18,32). Ul- more often found in a midline location trasound most easily shows diastemato- than paramedially, most often in a lumbo- myelia in the axial plane. Due to the tissue sacral region, and less often in a occipital between the hemispinal cords, the spinal region (1,2). A common complication of cord is tethered. Thus, the »ascension« of

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the conus is disabled. Scoliosis, rib anom- vasive, widely available, and inexpensive alies or foot deformities are clinically diag- diagnostic method that can be performed nosed, and in 50% a tuft of hair is present at the crib without sedation or general an- over the spine (1,2,10,15,18,20). esthesia. The movement of the patient, the Caudal regression syndrome occurs in pulsation of the cerebrospinal fluid and 1/7,500 children, in 15% in children of the blood flow do not disturb the image mothers with diabetes (1,15). In clinical- quality, and it also enables a dynamic dis- ly severe forms of caudal agenesis, ultra- play and assessment of the physiological sound can show a high position of the co- movement of the spinal cord. Due to its nus with a blunt ending above L1, and in good resolution, MRI is the gold standard less severe forms a low position of the co- in diagnosing SD before surgery, and in nus with a tethered spinal cord in the area the first months of life it is necessary in of thickened filum or lipoma (1,2,18,20). high-risk children (2,9,20,24,26). In re- Depending on the degree of deformation, cent years, much research has been done the coccyx, sacrum or lumbar spine may to address the question of which cases of be absent. The pelvis is narrower, the glu- suspected SD diagnostic imaging is neces- teal muscles are hypoplastic, the gluteal sary in and to what extent the sensitivity cleft is short and flat. Paresis of the lower of ultrasonography differs from MRI in limbs, sensitization disorders, genitouri- occult conditions. nary anomalies (renal agenesis, hydrone- In a recent retrospective and multi- phrosis, duplication of Mullerian ducts), center study, Kucera and co-authors ex- anal perforation, or anomalies in the de- amined the incidence of tethered spinal velopment of the lower limbs may be pres- cord in children with a simple skin dimple. ent (1,2,15). After examining 3,884 ultrasound results Segmental spinal dysgenesis is an ex- of the spinal channel of healthy newborns tremely rare condition with abnormali- over a period of 12 years, 76 (2.1%) chil- ties in the development of the lumbar or dren with OSD were found, 5 (0.13%) had thoracic spinal channel, congenital para- a tethered spinal cord diagnosed by MRI. plegia, and associated deformities in limb All 5 were treated surgically, and it turned development (2,15). out that 4 children had tethered spinal It is estimated that 10–52% of chil- cords. Research has shown that the risk of dren with anorectal abnormalities have OSD in healthy newborns with a simple SD (15). These types of SD can be part of dimple is very low. Due to the retrospec- the syndrome, as in the VACTERL associ- tive nature of the study, it was not possible ation (vertebral defects, anal atresia, car- to verify that the skin dimples were simple diac defects, tracheo-esophageal fistula, in all children and if the position of the renal anomalies and limb abnormalities), conus was determined correctly with clin- OEIS syndrome (omphalocele, exstrophy, ical vertebral count in all of them (27). In a imperforate anus, spinal defects) and the comparative analysis of ten similar studies, already mentioned Currarin syndrome which included a total of 3,027 children (10,15,20). with a dimple above the sacrum, 5 (0.17%) children underwent surgery for tethered 5 Diagnostic imaging spinal cord (7-9,13,22,23,25,33-35). One study compared the incidence of OSD in Ultrasonography of the spinal channel healthy children with a simple skin dim- is a sensitive method for detecting SD in ple with children without skin signs. In the children in the first three months of life, group of 75 children with a simple dimple, while it is later no longer possible due to ultrasonography showed suspected OSD ossification of spinal growths. It has ma- in one child, while MRI showed normal ny advantages over MRI, as it is a non-in- results. In a control group of 105 children

Diagnostic approach in an infant with spinal dysraphism 547 HUMAN REPRODUCTION Figure 4: Algorithm for early treatment of a child with spinal dysraphism.

without skin dimples, meningocele with a signs, all with abnormal ultrasound scans, spinal cord was detected in one with ultra- and those who have multiple skin signs OPEN SD Suspected SD sound. Research has shown that children over the spine (26). with a simple dimple do not have a high- Interesting are the results of a retro- er risk of OSD compared to those with no spective study by O’Neill and co-authors US of spinal channel – NO + clinical signs + skin signs US of head – YES +/- skin signs - clinical signs skin signs (8). who examined the incidence of SD in 522 MRI of spinal channel + head In one prospective study comparing children according to different skin or children with simple and atypical dimples, clinical signs. Indications for MRI were: Skin dimples no intraspinal changes were found using skin dimple above the sacrum, asymmetry Neurosurgeon ultrasonography in 160 newborns with of gluteal folds, hemangioma, only other simple dimples, and among 20 children skin signs (lipoma, rudimentary tail, lo- with atypical dimples, 8 (40%) had OSD cal hairiness, dysplastic nevus), several Atypical Simple (7). skin signs over the spine and congenital A higher prevalence of OSD has also anomalies (VACTERL, neurogenic blad- been confirmed by research in children der, imperforate anus, caudal agenesis, Subcutaneous mass, asymmetry of move- Local hairiness, tu of with multiple skin signs over the spine. motor skill developmental delay, arthro- Above sacrum or ment, bowel and hair, hemangiomas, Above sacrum or higher, < 2.5 cm above Fosse In one such retrospective study, among gryposis). OSD was diagnosed in as many bladder incontinence, angiomatosis, skin higher, > 2.5 cm above anus medially, lumbales asymmetry in size and protrusions, anus medially/laterally, 36 children with only a dimple above the as 122 (23.4%) children. 4/5 of these had < 0.5 cm in diameter, (»dimples circumference of lower rudimentary tail, > 0.5 cm in diameter, one dimple, of venus«) sacrum, 3 (8%) had OSD, and among 18 a lipoma of the filum or a low position of limbs, spinal deformi- asymmetry of gluteal one/numerous, no other signs children with two or more skin signs, as the conus, and 1/5 had a complex type of ties, anorectal anoma- folds, duplicated +/- other skin signs many as 11 (61%) had OSD (13). OSD (spinal lipoma, diastematomyelia, lies, VACTERL, OEIS gluteal cle Based on the results of these studies, dermal sinus). OSD was most commonly saying that a simple dimple is not a useful diagnosed in the group with only other marker for the diagnosis of SD in healthy skin signs (55%), where also most children US of spinal channel* + US of head children, most authors have suggested that had a complex type of OSD (10/17). The US not necessary the children do not need ultrasonography second group with the most OSD were of the spinal channel (1,8,11,23,27,36). patients with congenital anomalies (36%), Normal US of spinal chan- followed by the group with multiple skin Clinical follow-up Clinical follow-up These results have also been confirmed nel* + US of head by some prospective studies. Ausili and signs (27%). Surprising is the high propor- not necessary (X-ray on suspision colleagues studied the role of ultrasound tion of OSD in children with only a skin of sacral agenesis) DD? and MRI in 439 children who had no dimple above the sacrum (20%), but the ev. MRI Normal clinical signs and had various skin signs study did not define whether these were over the spine. All underwent spinal chan- simple or atypical dimples. In the group nel ultrasound in the first month, and 39 with asymmetry of gluteal folds, 12% of + US signs: children with abnormal ultrasound scans children had OSD, and the proportions of Intraspinal mass, conus < L2-L3 (up to 2 m) or underwent MRI. OSD was confirmed by OSD in other groups were lower (24). The < L1-L2 (aer 2 m) MRI in 22 children. In the group of 400 study showed a higher prevalence of OSD ↓cone motility, spinal lipoma, thickened filum > 2 mm, newborns with normal ultrasound scans, diagnosed by MRI (23.4%) compared to dermal sinus, however, only 1 child developed neurolog- ultrasound (0–3.4%) in similar studies signs of Arnold Chiari II ical signs during follow-up, in which MRI (7,9,14,23-25,27). The differences in these showed dermal sinus and tethered spinal comparisons are not only due to the high- cord. Thus, a total of 23 (5%) children with er resolution of MRI compared to ultra- MRI of spinal channel various skin signs over the spine had OSD. sound, but also due to referrals according SD + MRI of head Normal Research has shown that ultrasonography to different skin signs. The study by O’Neill Cl. follow-up of the spinal channel in newborns with et al. has also shown clearly that the sensi- Neurosurgeon not necessary skin signs is an effective screening meth- tivity and specificity of ultrasound imaging DD, dierential diagnostic; Cl., clinical follow-up, MRI, magnetic resonance imaging; OEIS, omphalocele, exstrophy, imperforate anus, spinal dysraphisms; OSD, occult spinal dysraphism; od for the selection of children, on the ba- are lower compared to MRI, especially in X-ray; SD, spinal disraphism; US, ultrasound scan; VACTERL, vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies and limb abnormalities; sis of which we decide to diagnose using children with minor filum changes (24). It *US of spinal channel can be performed up to and including 3 months of age; m, months of life. MRI. They pointed out that MRI is needed should be noted at this point that it has not by children who have pronounced clinical been investigated how many findings with Figure 4: Algorithm for early treatment of a child with spinal dysraphism.

548 Zdrav Vestn | November – December 2019 | Volume 88 | https://doi.org/10.6016/ZdravVestn.2914 Figure 4: Algorithm for early treatment of a child with spinal dysraphism.REVIEW ARTICLE

signs, all with abnormal ultrasound scans, and those who have multiple skin signs OPEN SD Suspected SD over the spine (26). Interesting are the results of a retrospective study by O’Neill and co-authors US of spinal channel – NO + clinical signs + skin signs US of head – YES +/- skin signs - clinical signs who examined the incidence of SD in 522 MRI of spinal channel + head children according to different skin or clinical signs. Indications for MRI were: Skin dimples skin dimple above the sacrum, asymmetry Neurosurgeon of gluteal folds, hemangioma, only other skin signs (lipoma, rudimentary tail, local hairiness, dysplastic nevus), several Atypical Simple skin signs over the spine and congenital anomalies (VACTERL, neurogenic bladder, imperforate anus, caudal agenesis, Subcutaneous mass, asymmetry of move- Local hairiness, tu of motor skill developmental delay, arthro- Above sacrum or ment, bowel and hair, hemangiomas, Above sacrum or higher, < 2.5 cm above Fosse gryposis). OSD was diagnosed in as many bladder incontinence, angiomatosis, skin higher, > 2.5 cm above anus medially, lumbales asymmetry in size and protrusions, anus medially/laterally, as 122 (23.4%) children. 4/5 of these had < 0.5 cm in diameter, (»dimples circumference of lower rudimentary tail, > 0.5 cm in diameter, one dimple, of venus«) a lipoma of the filum or a low position of limbs, spinal deformi- asymmetry of gluteal one/numerous, no other signs the conus, and 1/5 had a complex type of ties, anorectal anoma- folds, duplicated +/- other skin signs OSD (spinal lipoma, diastematomyelia, lies, VACTERL, OEIS gluteal cle dermal sinus). OSD was most commonly diagnosed in the group with only other skin signs (55%), where also most children US of spinal channel* + US of head had a complex type of OSD (10/17). The US not necessary second group with the most OSD were patients with congenital anomalies (36%), Normal US of spinal chan- Clinical follow-up Clinical follow-up followed by the group with multiple skin nel* + US of head signs (27%). Surprising is the high propor- not necessary (X-ray on suspision tion of OSD in children with only a skin of sacral agenesis) DD? dimple above the sacrum (20%), but the ev. MRI Normal study did not define whether these were simple or atypical dimples. In the group with asymmetry of gluteal folds, 12% of + US signs: children had OSD, and the proportions of Intraspinal mass, conus < L2-L3 (up to 2 m) or OSD in other groups were lower (24). The < L1-L2 (aer 2 m) study showed a higher prevalence of OSD ↓cone motility, spinal lipoma, thickened filum > 2 mm, diagnosed by MRI (23.4%) compared to dermal sinus, ultrasound (0–3.4%) in similar studies signs of Arnold Chiari II (7,9,14,23-25,27). The differences in these comparisons are not only due to the higher resolution of MRI compared to ultra- MRI of spinal channel sound, but also due to referrals according SD + MRI of head Normal to different skin signs. The study by O’Neill Cl. follow-up et al. has also shown clearly that the sensi- Neurosurgeon not necessary tivity and specificity of ultrasound imaging DD, dierential diagnostic; Cl., clinical follow-up, MRI, magnetic resonance imaging; OEIS, omphalocele, exstrophy, imperforate anus, spinal dysraphisms; OSD, occult spinal dysraphism; are lower compared to MRI, especially in X-ray; SD, spinal disraphism; US, ultrasound scan; VACTERL, vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies and limb abnormalities; children with minor filum changes (24). It *US of spinal channel can be performed up to and including 3 months of age; m, months of life. should be noted at this point that it has not been investigated how many findings with Figure 4: Algorithm for early treatment of a child with spinal dysraphism.

Diagnostic approach in an infant with spinal dysraphism 549 HUMAN REPRODUCTION

a small lipoma of the filum are clinically and head is performed. Where ultrasound significant. In one such study, among 436 reveals changes that indicate SD, an MRI subjects who had filar lipoma on MRI, 22 is needed as soon as possible. If the ultra- (5%) had tethered spinal cord syndrome. sound scan result is normal, we continue Among the 249 subjects with filar lipoma with the treatment within the framework who were clinically followed for three and of differential diagnostic possibilities and a half years, only one developed tethered decide on the need for MRI of the central spinal cord syndrome (37). nervous system on the basis of the clinical In studies comparing the sensitivity of picture. ultrasound to MRI in the diagnosis of SD, Children without clinical signs who have one study in 40 patients with neurogenic atypical dimples or other skin signs over bladder showed that the sensitivity of ul- the spine, where OSD is suspected, are re- trasonography for spina bifida was 66.6%, ferred for ultrasound of the spinal chan- for agenesis of the sacrum and vertebral nel and head in the first three months of arch damage 100%, for tethered spinal life. Where ultrasound of the spinal chan- cord 85.7%, for lipoma of the filum ter- nel shows no signs of SD, further imag- minale 100%, and in cases of diagnosis of ing is not required. Given the rare cases intraspinal masses and diastematomyelia described, where, despite a normal ultra- 33.3%. The specificity of the ultrasound sound result, spinal cord syndrome later method ranged between 85.7–100% in developed, clinical monitoring is recom- all dysraphisms (38). In a similar recent- mended for this group. ly published retrospective study analyzing Children without clinical signs, with diagnostic imaging results in 94 newborns ultrasound scan signs characteristic of SD, with anorectal abnormalities, the sensitiv- need an MRI of the spinal channel and ity of the ultrasound for diagnosing teth- head, which, however, can be performed ered spinal cord was 80% and specificity in later months in the time of prepara- 89% (39). Such studies have shown good tion for surgery. This avoids duplication sensitivity and high specificity of the ultra- of examinations and exposing children to sound method in most patients. general anesthesia in their first months. Where the diagnosis is confirmed by MRI, 6 Early treatment algorithm the decision regarding prophylactic sur- for a child with SD gery is individual. However, where the MRI result is negative, no further clinical Based on the cited literature, we devel- monitoring is required. oped an algorithm for treating children In a healthy child with a simple dimple, with suspected SD in the first months of ultrasound is not required. Planned clin- life in order to identify and unify the ap- ical monitoring is not necessary, but we proach to diagnosis early. The algorithm of pay attention to this type of child's charac- early treatment of a child with SD is sche- teristic during medical treatments. matically presented in Figure 4. In a newborn with an open SD, ultra- 7 Conclusion sound of the spinal channel is not required after birth due to possible infection of the Many studies with large populations of surrounding tissues. Ultrasound scan of children with skin changes over the spine the head identifies associated changes in have shown that ultrasound is a sensitive the brain. We consult a neurosurgeon re- method in the early diagnosis of SD. MRI garding MRI before surgery. is in place at early diagnosis in high-risk In children with suspected SD and neu- children, and in cases where ultrasound rological, urological or orthopedic problems, reveals changes, causing suspicion of SD. ultrasound imaging of the spinal channel The proposed algorithm offers a system-

550 Zdrav Vestn | November – December 2019 | Volume 88 | https://doi.org/10.6016/ZdravVestn.2914 REVIEW ARTICLE

atic approach to treating all children with • MRI – magnetic resonance imaging suspected SD. With an emphasis on early • GS – gestation ultrasound diagnosis, it enables efficient • MMK – myelomeningocele and rational screening of children with • AC II – Arnold Chiari Malformation suspected OSD and early identification of type II those who need action. • LMMK – lipomielomeningocele • VACTERL – vertebral defects, anal 8 Abbreviations atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb • SD – spinal dysraphism abnormalities • OSD – occult spinal dysraphism • OEIS – omphalocele, exstrophy, imper- • US – ultrasound scan forate anus, spinal defects

References

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552 Zdrav Vestn | November – December 2019 | Volume 88 | https://doi.org/10.6016/ZdravVestn.2914 REVIEW ARTICLE

38. Alamdaran SA, Mohammadpanah N, Zabihian S, Esmaeeli M, Ghane F, Feyzi A. Diagnostic value of ultrasonography in spinal abnormalities among children with neurogenic bladder. Electron Physician. 2017;9(6):4571-6. DOI: 10.19082/4571 PMID: 28848632 39. van den Hondel D, Sloots C, de Jong TH, Lequin M, Wijnen R. Screening and Treatment of Tethered Spinal Cord in Anorectal Malformation Patients. Eur J Pediatr Surg. 2016;26(1):22-8. PMID: 26394371

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