View of Diagnostic approach in an infant with spinal dysraphism

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1 Department of Child, Adolescent and Developmental Neurology, Division of Paediatrics, University Medical Centre Ljubljana, Ljubljana, Slovenia

2 Neonatal Unit, Division of Paediatrics, University Medical Centre Ljubljana, Ljubljana, Slovenia

3 Unit of Radiology, Division of Paediatrics, University Medical Centre Ljubljana, Ljubljana, Slovenia

4 Department of

Neurosurgery, Division of Surgery, University Medical Centre Ljubljana, Ljubljana, Slovenia

Correspondence/

Korespondenca:

Aneta Soltirovska Šalamon, e: neta.soltirovska@kclj.si Key words:

occult dysraphisms;

skin dimples; imaging techniques; diagnostic algorithm

Ključne besede:

okultni disrafizmi;

kožne jamice; slikovne metode; diagnostični algoritembesede Received: 6. 1. 2019 Accepted: 30. 3. 2019

6.1.2019 date-received

30.3.2019 date-accepted

Human reproduction Reprodukcija človeka discipline

Review article Pregledni znanstveni članek article-type

Diagnostic approach in an infant with spinal

dysraphism Diagnostični pristop pri dojenčku s spinalnim

disrafizmom

article-title Diagnostic approach in an infant with spinal

dysraphism Diagnostični pristop pri dojenčku s spinalnim

disrafizmom

alt-title occult dysraphisms, skin dimples, imaging

techniques, diagnostic algorithm okultni disrafizmi, kožne jamice, slikovne metode, diagnostični algoritem

kwd-group The authors declare that there are no conflicts

of interest present. Avtorji so izjavili, da ne obstajajo nobeni

konkurenčni interesi. conflict

year volume first month last month first page last page

2019 88 11 12 539 553

name surname aff email

Aneta Soltirovska Šalamon 1 neta.soltirovska@kclj.si

name surname aff

Nataša Šuštar 1

Darja Paro Panjan 2

Damjana Ključevšek 3

David Neubauer 1

Peter Spazzapan 4

eng slo aff-id

Department of Child, Adolescent and Developmental Neurology, Division of Paediatrics, University Medical Centre Ljubljana, Ljubljana, Slovenia

Klinični oddelek za otroško, mladostniško in razvojno nevrologijo, Pediatrična klinika, Univerzitetni klinični center Ljubljana, Ljubljana, Slovenija

1

Neonatal Unit, Division of Paediatrics, University Medical Centre Ljubljana, Ljubljana, Slovenia

Klinični oddelek za neonatologijo, Pediatrična klinika, Univerzitetni klinični center Ljubljana, Ljubljana, Slovenija

2

Unit of Radiology, Division of Paediatrics, University Medical Centre Ljubljana, Ljubljana, Slovenia

Služba za radiologijo, Pediatrična klinika, Univerzitetni klinični center Ljubljana, Ljubljana, Slovenija

3

Department of Neurosurgery, Division of Surgery, University Medical Centre Ljubljana, Ljubljana, Slovenia

Klinični oddelek za

nevrokirurgijo, Kirurška klinika, Univerzitetni klinični center Ljubljana, Ljubljana, Slovenija

4

Diagnostic approach in an infant with spinal dysraphism

Diagnostični pristop pri dojenčku s spinalnim disrafizmom

Nataša Šuštar,¹ Darja Paro Panjan,² Damjana Ključevšek,³ David Neubauer,¹ Peter Spazzapan,⁴ Aneta Soltirovska Šalamon²

Abstract

Spinal dysraphisms are congenital malformations of the spinal cord and spine that occur due to impaired closure of the neural tube in early embryogenesis. According to the skin coverage, they are divided into open and closed types. While open dysraphisms can be identified by prenatal investigations, the diagnosis of a closed (occult) dysraphic state is more difficult to establish.

There are specific skin signs over the spine in more than half of these patients, which can help with early diagnosis. Ultrasonography of the spine and spinal cord is the method of choice in the diagnostics of occult spinal dysraphism in the first months of life, until the spine is closed. The most sensitive diagnostic tool is magnetic resonance imaging, which also represents the gold standard of preoperative diagnostics. Early diagnosis is important in asymptomatic conditions, as this allows timely surgical treatment of children, who are at greater risk of sudden onset of complications or neurological sequelae. In the article, we summarised clinical and radiological characteristics of dysraphic conditions and formed a diagnostic algorithm to unify an approach in a child with spinal dysraphism in the first months of life.

Izvleček

Spinalni disrafizmi so prirojene nepravilnosti hrbtenjače in spinalnega kanala, ki nastanejo zara- di motenj zapiranja nevralne cevi v zgodnjem embrionalnem razvoju. Glede na kožno kritje jih 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 kožni znaki nad hrbtenico, ki so prisotni pri več kot polovici bolnikov. Ultrazvočna preiskava spinalnega kanala je v prvih mesecih starosti, dokler hrbtenica ne zakosteni, metoda izbire v diagnostiki okultnih spinalnih disrafizmov. Sicer je najobčutljivejše diagnostično orodje magnetno resonančno slikanje, ki predstavlja tudi zlati standard predoperativne diagnostike. Zgodnja prepoznava je pomembna tudi v primerih asimptomatskih stanj, ker s tem omogočimo pravočasno kirurško zdravljenje otrok, pri katerih obstaja večje tveganje za nastanek nenadnih zapletov ali nepovratnih nevroloških posledic. V članku smo povzeli klinične in radiološke značilnosti posa- meznih disrafičnih stanj, ter oblikovali diagnostični algoritem, z namenom poenotenja zgodnje obravnave otrok s spinalnim disrafizmom.

Cite as/Citirajte kot: Šuštar N, Paro Panjan D, Ključevšek D, Neubauer D, Spazzapan P, Soltirovska Šalamon A. Diagnostic approach in an infant with spinal dysraphism. Zdrav Vestn. 2019;88(11–12):539–53.

DOI: https://doi.org/10.6016/ZdravVestn.2914

Slovenian Medical

Journal

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1 Introduction

Spinal dysraphisms (SD) are a heterogeneous group of congenital abnormalities of the spinal cord and spine. They are among the most common malformations and occur in 1-2/1000 live births (1).

They occur due to improper closure and formation of the neural tube in early embryogenesis, due to the activity of certain environmental factors or genetic changes (1,2). Among the best known risk factors for SD are genetic predisposition, maternal diabetes, taking certain antiepileptic drugs (valproate, carbamazepine), obesity, febrile condition in the first weeks of preg- nancy and folic acid deficiency in the diet of pregnant women (3-6). The incidence has decreased in the last two decades due to folic acid prophylaxis, pre-natal diagnostics, and genetic counseling in familes with a high risk of SD (5,6).

According to the skin coverage, SD are divided into open and closed SD. Open SDs are identified by prenatal investigations, and closed ones mostly at birth.

The latter, also called occult spinal dysraphisms (OSDs), can be clinically silent for a long time. It is estimated that 43–95% of these patients have certain skin signs over the spine that make it easier to suspect SD (7-13). 75% of closed SDs develop the tethered spinal cord syndrome, which can be expressed at any age and is character- ized by a progressive course (14,15).

In the first three months of life, until the bodies, arches, and the vertebral processes are ossified, ultrasonography (US) of the spine is the method of choice for recognizing SD (1). In all cases, the final diagnosis is made by magnetic resonance imaging (MRI), which is the most sensitive and specific imaging method in diagnosing SD (2). It is important to identify asymptomatic conditions at an early stage and thus enable timely surgical treatment of children, who are at greater risk of sudden onset of complications or neurological sequelae. The success of surgery in most cases depends on the type of change, the

severity of the neurological impairment, and the time that elapses from the the clinical picture until the surgery (6,14,15).

2 Embryonic development of the spinal cord and classification of SD

The development of the spinal cord takes place from the 2nd to the 6th week of gestation (GS) in three successive phases:

gastrulation, primary neurulation, and secondary neurulation (2,10).

Between the 2nd and 3rd week of GS, during the process of gastrulation, from the bilayered embryonic disc, which con- sists of epiblast and hypoblast, a three-layer disc is formed, from which the ectoderm, mesoderm and endoderm develop.

From the middle part of the mesoderm, a notochord is formed, which in connection with the ectodermal layer forms the neuroectoderm and the neural plate (2,10,16).

Primary neurulation, which occurs be- tween the 3rd and 4th week of GS, is the process of the neural plate transforming into the neural tube. On day 17, the lateral parts of the neural plate thicken. Cells at the junction of neuroectoderm and cutaneous ectoderm differentiate into neural crest cells.

The contractile filaments of the neu- roepithelial cells of the neural plate border transform the neural plate into a neural groove along the neural axis by folding the lateral parts. Between days 21 and 23, the neural groove merges in the midline to form a neural tube. This is followed by dis- junction - the separation of the neural tube from the ectoderm, which runs along the surface. The cranial part (anterior neuropore) closes on the 25th day, and the caudal end (posterior neuropore - S2 level) between the 27th and 28th day.

A closed neural tube is the basis for the development of the entire central nervous system. Mesodermal structures penetrate

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dorsally into the area between the ectoderm and the neural tube and are the basis for the development of meninges, vertebrae, and paraspinal muscles (10,15,16).

This is followed by secondary neuru- lation, which lasts until the 6th week of GS, during which the caudal part of the neural tube develops from the S2 level

downwards. Between the caudal end of the neural tube and the notochord, a caudal cell mass is formed, from day 16 to 19, between undifferentiated pluripotent cells.

This is followed by retrograde differentiation, when the caudal end of the neural tube and the notochord are connected through complex processes of apopto- sis and further differentiation. The conus medullaris and the filum terminale of the spinal cord are formed from the caudal cell mass (2,10,16).

Between days 43 and 48 of the GS, the spinal cord begins to seemingly ascend due to the growth of the spinal channel, because the bone structures grow faster than the nervous system. Conus medullaris in children of up to 2 months of age is at a height between L2 and L3, and after 2 months it reaches a physiological level between L1 and L2 (1,10,15).

Development disorders of the spine and spinal cord in different embryonic stages lead to the formation of heterogeneous forms of SD. Their formation is character- ized by two processes: incomplete fusion of central structures and disturbed tissue differentiation outside and inside the spinal channel (10,16). Table 1 shows the embryological classification of SD based on recent findings on the pathogenesis of dysraphic conditions during spinal cord development (17). Based on the embryological classification, the classification of SD has become more understandable and, above all, more uniform than in clinical and radiological classifications (10,16,17).

Embryological placement of SD is help- ful in assessing the extent of the malformation, planning surgical treatment, and understanding the severity of the clinical picture.

In previous classifications, there were inconsistencies in the classification of certain dysraphisms according to clinical and radiological features. However, the clinical division into open and closed SD is still relevant, as it is most useful in the diagnostic approach when SD is suspected (10). Thus, in order to create a diagnostic Table 1: Embryological classification of spinal dysraphism, according

to Acharya et al, 2017 (17).

Embryological classification of spinal dysraphism

A ANOMALIES OF GASTRULATION

1 Disorders of Notochord Formation a Caudal Regression Syndrome b Segmental Spinal Dysgenesis 2 Disorders of Notochord Integration

a Neuroenteric cysts

b Dorsal enteric fistula

c Split cord malformation (diastematomyelia)

B ANOMALIES OF PRIMARY NEURULATION

1 Premature Dysjunction

a Lipomyelomeningocele

b Lipomyelocele

c Intradural lipoma

2 Nondysjunction

a Dorsal dermal sinus

b Myelomeningocele

c Myelocele

C COMBINED ANOMALIES OF GASTRULATION

AND PRIMARY NEURULATION

1 Hemimyelocele

2 Hemimyelomeningocele

D ANOMALIES OF SECONDARY NEURULATION

AND RETROGRESSIVE DIFFERENTIATION 1 Abnormally long spinal cord

2 Persisting terminal ventricle 3 Tight filum terminale

4 Intrasacral-anterior sacral meningocele

5 Terminal myelocystocele

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algorithm for treating a baby with SD, we followed, in this article, the clinical classification.

3 Open SD

In open SD, the tissues are exposed to the external environment. More than 98%

of open SDs is represented by myelome- ningocele (MMK), in which the neuro- genic placode – the spinal cord, including the meningeal envelopes, passes outward through the posterior bone and skin defect. In Europe, the mean incidence of MMK is 0.41–1.9/1000 births (1,2,18). It is most often found in the lumbosacral region (44%), and less frequently in the thoracolumbar (32%) and lumbar (22%) part (1,2).

The clinical picture of MMK depends on the location and extent of the defect.

In the newborn, we find different degrees of lax paresis of the lower limbs, sphincter dysfunction, hip dislocation or foot deformities. The diagnosis of MMK is made prenatally by determining the alpha feto- protein in maternal serum or by amino- centesis and by ultrasound examination of the fetus (2,19). Ultrasound signs of prenatal diagnosis include: formation of affected C or U-shaped vertebrae, open overlying skin, neurogenic placode in the area of the defect, narrowing of the skull in the forehead (»lemon sign«), ventricu- lomegaly and small posterior cranial cavity with constriction of the cerebellum (19).

After birth, however, ultrasonography of the spinal channel is not performed due to possible infection of the tissues exposed to the surroundings. An ultrasonography of the head, however, is performed, which shows signs of Arnold-Chiari malformation type II (AC II), such as hypoplasia of the corpus callosum, shallow posterior cranial cavity, downward displacement of the pons and upper spinal cord, and pas- sage of cerebellar tonsils through the fora- men magnum (1,18,20). MRI of the spinal channel and head is performed as part of the preparation for surgery, and surgical

coverage is required within 48-72 hours after birth. Despite successful surgical correction, neurological deficits in motor skills remain, such as flaccid muscle paresis with impaired or absent tendon reflex- es, sensory disturbances that can lead to the development of trophic ulcers, bowel and bladder incontinence, and lower in- telligence. Orthopedic deformities, such as scoliosis, kyphosis, or foot deformities, may be present at birth and eventually progress (15,20).

Shortly after the closure of MMK, more than half of patients develop hydrocepha- lus. To resolve this, ventriculoperitoneal shunt or endoscopic ventriculostomy is required (2). According to imaging findings, 99% of children with MMK have AC II. Most are asymptomatic, but 10–30%

experience swallowing disorders, central apnea, vocal cord paresis, spasticity, and other signs requiring craniocervical de- compression due to compression of the brainstem (1,2).

Tethered spinal cord syndrome occurs in 20–30% after surgical repair of MMK, so these children need a new procedure (1). Hydromyelia and syringomyelia are present in 40–80%, diastematomielia or longitudinally split spinal cord in 20–40%, but they are mostly clinically silent. The quality of life after MKK surgery depends on congenital deficits and long-term (life- long) rehabilitation (1,15).

Open SD also includes hemimyelome- ningocele, which is a very rare condition in which MMK covers one part of the split spinal cord or diastematomielia (2,18).

4 Closed SD

4.1 Skin marks

Most occult conditions are considered to be asymptomatic for a long time, so the diagnosis is usually made in later periods or at the appearance of clinical signs (2).

Recognition of OSD in the first months of life is possible in those children who have a clinical picture that leads to sus-

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picion of SD: subcutaneous mass in the spine, paresis of the lower limbs, asymmetry of movement, bowel and bladder incontinence, anogenital and genitourinary malformations, spinal deformities (scoliosis, sacral agenesis) and asymmetry in the size and circumference of the lower limbs. We also think of OSD in newborns, if certain skin changes are noted over the spine. According to various studies, these occur in a total of 2-8% of healthy children (7,9,11,12,21,22). However, we need to be familiar with certain characteristics that distinguish insignificant skin changes from those that make us suspect OSD, so that not all children with skin changes over the spine should be treated unneces- sarily (12).

A clinically insignificant or simple skin dimple is located medially over the sacrum, less than 2.5 cm from the anus, is less than 5 mm in diameter, and occurs on its own (7,23). Simple are also the skin dimples, called “fossae lumbales” or “dimples of Venus”, which lie symmetrically, paramedially over the sacrum and are present in the underlying shorter ligaments of the sacroiliac joints (12). Atypical skin dim- ples, which indicate OSD, are located me- dially or paramedially over the spine, at a distance of more than 2.5 cm above the anus, have a diameter of more than 5 mm

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 are simple and that the possibility of OSD in these is as rare as in the general population without skin changes (1,7,13,25).

When a simple dimple is found in a newborn, ultrasonography of the spinal channel is not necessary, but a child with skin signs that indicate OSD is referred for ultrasound in his first three months of life before the spine is ossified (20,26,27). Due to good transparency in the first months as well as logistical advantages over MRI, ultrasonography proved to be an diagnostic method of choice in the early identification of OSD. Changes in the ultrasound imaging of the spinal channel, indicating SD are intraspinal mass, conus medullaris below the level of L2 – L3 before 2 months of age or below L1 – L2 after 2 months, reduced or absent cone motility, spinal lipoma, filum more than 2 mm thick and dermal sinus (Figure 1). MRI, however, is important in early diagnosis in high-risk newborns with clinical signs, anogenital malformations, or signs of syndromes in which SD is possible (10,15,18). With early detection of OSD, in practice, the decision on surgical treatment at a time when the child has no clinical signs is individual and depends on the type and extent of changes present in MRI, the surgeon's decision and the opinion of the child's parents or guardians, except in the case ofo dermal sinus, in which removal is required in any case due to the high risk of Figure 1: Ultrasound of the spinal channel: A normal position of the

conus medullaris at the lower edge of L1.

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infection (9,15).

4.2 Physiological Variants

Physiological variants are clinically insignificant. The terminal ventricle is a small cyst surrounded by the ependyma located at the junction of the conus medullaris into the filum terminale. The longitudi- nal diameter measures up to 10 mm and the transverse diameter to 2–4 mm and is mostly present only in the first weeks after birth (1,18). Physiological variants also include a transiently dilated central spinal channel that normally narrows after the first week (1,18,20), a cyst within the filum without other changes, and a pseudosinus or pilonidal sinus - a fibrous cord that runs from the simple skin dimple to coccyx (18,20).

Clinically insignificant OSD includes spina bifida occulta, in which the poste- rior arches of the vertebrae are absent or incompletely fused. It is estimated to be present in 4% of the general population and does not cause problems on its own (16). It is most commonly found in the lumbosacral region and may be charac- terized by a skin dimple or local hairiness (28).

4.3 Clinically significant closed SD

According to the clinical classification, they are divided into SD with a subcutane- ous 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

The spinal cord is tethered in all open SDs, and in closed ones due to spinal lipomas, dermal sinus, dystematomyelia, and other complex dysraphisms. During embryonic development, the tethered spinal cord prevents the »ascension« of the spinal cord to the physiological level (18).

Ultrasonography of the newborn shows the dorsal position of the conus with a level below L2–3, a larger ventricular space filled with cerebrospinal fluid and the ab- sence of motility of the conus and nerve roots (1) (Figure 2).

The level of the conus modullaris is determined clinically by counting the vertebrae by various methods (15,18,20).

Tethered spinal cord syndrome is a clin- ical syndrome that is most commonly expressed in children in the age of rapid growth, when the traction forces on the tethered spinal cord are greatest, or in pronounced flexion movements of the spine.

Stretching of the conus, nerve roots, and surrounding vessels leads to insuf- ficient blood flow, leading to ischemia of the conus, myelomalacia, and syringo- hydromyelia (1,20,26). Low back and leg pain, gait disorders, sensory and sphincter functions occur, and prolonged condition leads to progressive problems, spasticity, scoliosis, and orthopedic deformities (1,15,18). MRI shows the low position and dorsal position of the conus and identifies dysraphisms that tether the spinal cord Figure 2: Ultrasound of the spinal channel: A tethered cord in a four-

day-old boy with a 3 × 1 cm vascular skin mark above the coccyx, a skin dimple and a skin tag at the end of the coccyx.

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(11). Surgical relaxation of the tethered spinal cord is required as soon as possible, as the defects are irreversible after a certain time (2,15,29).

4.5 Spinal lipomas

These include intradural lipomas and lipomas that pass through the dura. Lipo- mas passing through the dura represent approximately 87% of all closed SD with a subcutaneous mass (16). These include lipomyelomeningocele (LMMK) and lipo- myelocele, which are caused by prema- ture disjunction in the process of primary neurulation. Due to the premature separation of the neural tube from the overlying ectoderm, the mesenchyme, which is the basis for subcutaneous fat, passes through the as yet unconnected neural tube. There- fore, in such a segment, the meningeal envelope and bone structure cannot co- alesce, while the skin cover is preserved.

LMMK and lipomyelocele differ in where the link between neurogenic placode and lipoma lies.

In LMMK, due to the dilated subarach- noid space in front of the spinal cord,

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- sal side of the spinal cord, in most cases in the lumbar sacral region. Tethered spinal cord syndrome may develop, or neurological signs may appear due to pressure on the spinal cord relative to the affected level (2,18).

Lipoma of the filum terminale means a fatty thickening of the filum terminale (1). It is estimated that 1.5–5% of healthy adults have fatty tissue present within the filum terminale. A thickened filum is a physiological variant if it is not thick- er than 2 mm at the height L5–S1 and if this is the only finding without signs of a tethered spinal cord below the level L1–L2 (1,2,15,16).

Pang was the first to classify spinal lipomas according to embryonic origin and to divide them into three groups - dorsal and transitional lipomas, which are the result of primary neurulation disorders, and terminal lipomas, which are malfor- mations of the secondary neurulation (in the embryological classification LMMK belongs to the transitional lipomas) (30).

He later added the concept of chaotic lipo- ma with the characteristics of transitional and terminal lipoma. Dorsal lipoma does not cover the conus modullaris, whereas transitional and chaotic lipoma do cover it. Chaotic lipoma also covers the roots of the paraspinal nerves and has the worst prognosis in terms of clinical progression.

In such cases radical resection is not in Figure 3: Ultrasound of the spinal channel: There is a poorly bounded

subcutaneous mass around the sacrum, which extends into the spinal channel (the arrow head) and partially pushes the cauda equina forward, in a five-day-old girl with a hemangioma above the sacrum.

MR confirmed a tethered cord associated with a spinal cord lipoma.

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place. Caudal lipomas do not involve the conus because they are located lower, in the region of the filum (31).

4.6 Meningocele

In meningocele, only the meninges bulge through the unfused vertebra arches, while the skin above it may be normal or less developed. It occurs ten times less frequently than MMK (15). It is most commonly located posteriorly in the lumbar region, but rarely lies anteriorly as in Currarin's syndrome (anal atresia, sacral agenesis, presacral meningocele) (2,18).

Lateral meningocele may be associated with neurofibromatosis type 1, Marfan or Ehlers-Danlos syndrome (1,18). Menin- gocele does not cause neurological deficits, but with the coexistence of another dysraphic change tethered spinal cord syndrome may develop (15,18).

4.7 Mielocistocele

Myelocystocele is a hernia of the dilated central part of the spinal channel (sy- ringocele) in the area of the spina bifida occult. In terminal myelocystocele, the dilated spinal channel passes through a bone defect within the dural sac (meningocele) (2,15). Abnormalities of the genitourinary and anorectal systems may be associated (1,18,20).

4.8 Dermal sinus

The dermal sinus is an epithelium-lined fistula that represents the connection between the spinal channel and the skin. It occurs in approximately 1/2,500 children (15). There is a dimple on the skin, without or with surrounding hyperperpigmen- tation, angiomatosis or hypertrichosis, and in 50% of the cases there are dermoid changes within the spinal channel. It is more often found in a midline location than paramedially, most often in a lumbosacral region, and less often in a occipital region (1,2). A common complication of

unrecognized dermal sinus is an infection that leads to meningitis, meningoenceph- alitis, or abscess formation, so surgical removal is always necessary (1,2,12,15).

Ultrasound clearly shows the sinus tract (1,18), while MRI is performed to identify associated changes before surgery (15,20).

4.9 Complex SD

Complex SDs include malformations that are the result of gastrulation disorders. Due to defects in the formation of the notochord, in addition to the development of the spinal cord, the development of the adjacent organs is also affected.

They are recognized prenatally or immediately after birth due to certain anomalies in the back, buttocks, limbs or urogenital area, as well as neurological, orthopedic disorders or bowel and bladder incontinence. These include neurenteric cyst, dorsal enteric fistula, diastematomyelia, caudal regression syndrome, and segmental spinal dysgenesis (1,2,18).

Neurenteric cyst is an extremely ra- re form of OSD. It is a remnant of the neurenteric canal that transiently con- nects the amniotic cavity and yolk sac in the embryo. The cyst secretes mucin and is located inside the dural space or within the posterior mediastinum. In the connection between the intestine and the skin, it is called dorsal enteric fistula (2,18).

Diastematomyelia or longitudinally split spinal cord accounts for 3.8–5% of all spinal cord anomalies (32). It occurs during early embryonic development, mostly in the thoracolumbar region, and is caudally united. It is divided into types I and II: in the first, the spinal cord is surrounded by one dural sac, separated by a connective septum, and in the second, each hemispinal cord is surrounded by a dural sac, with a bony or cartilaginous septum between them (1,2,15,18,32). Ul- trasound most easily shows diastematomyelia in the axial plane. Due to the tissue between the hemispinal cords, the spinal cord is tethered. Thus, the »ascension« of

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the conus is disabled. Scoliosis, rib anomalies or foot deformities are clinically diagnosed, and in 50% a tuft of hair is present over the spine (1,2,10,15,18,20).

Caudal regression syndrome occurs in 1/7,500 children, in 15% in children of mothers with diabetes (1,15). In clinically severe forms of caudal agenesis, ultrasound can show a high position of the conus with a blunt ending above L1, and in less severe forms a low position of the conus with a tethered spinal cord in the area of thickened filum or lipoma (1,2,18,20).

Depending on the degree of deformation, the coccyx, sacrum or lumbar spine may be absent. The pelvis is narrower, the gluteal muscles are hypoplastic, the gluteal cleft is short and flat. Paresis of the lower limbs, sensitization disorders, genitourinary anomalies (renal agenesis, hydrone- phrosis, duplication of Mullerian ducts), anal perforation, or anomalies in the development of the lower limbs may be present (1,2,15).

Segmental spinal dysgenesis is an ex- tremely rare condition with abnormalities in the development of the lumbar or thoracic spinal channel, congenital para- plegia, and associated deformities in limb development (2,15).

It is estimated that 10–52% of children with anorectal abnormalities have SD (15). These types of SD can be part of the syndrome, as in the VACTERL associ- ation (vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies and limb abnormalities), OEIS syndrome (omphalocele, exstrophy, imperforate anus, spinal defects) and the already mentioned Currarin syndrome (10,15,20).

5 Diagnostic imaging

Ultrasonography of the spinal channel is a sensitive method for detecting SD in children in the first three months of life, while it is later no longer possible due to ossification of spinal growths. It has many advantages over MRI, as it is a non-in-

vasive, widely available, and inexpensive diagnostic method that can be performed at the crib without sedation or general anesthesia. The movement of the patient, the pulsation of the cerebrospinal fluid and the blood flow do not disturb the image quality, and it also enables a dynamic dis- play and assessment of the physiological movement of the spinal cord. Due to its good resolution, MRI is the gold standard in diagnosing SD before surgery, and in the first months of life it is necessary in high-risk children (2,9,20,24,26). In recent years, much research has been done to address the question of which cases of suspected SD diagnostic imaging is necessary in and to what extent the sensitivity of ultrasonography differs from MRI in occult conditions.

In a recent retrospective and multi- center study, Kucera and co-authors examined the incidence of tethered spinal cord in children with a simple skin dimple.

After examining 3,884 ultrasound results of the spinal channel of healthy newborns over a period of 12 years, 76 (2.1%) children with OSD were found, 5 (0.13%) had a tethered spinal cord diagnosed by MRI.

All 5 were treated surgically, and it turned out that 4 children had tethered spinal cords. Research has shown that the risk of OSD in healthy newborns with a simple dimple is very low. Due to the retrospective nature of the study, it was not possible to verify that the skin dimples were simple in all children and if the position of the conus was determined correctly with clinical vertebral count in all of them (27). In a comparative analysis of ten similar studies, which included a total of 3,027 children with a dimple above the sacrum, 5 (0.17%) children underwent surgery for tethered spinal cord (7-9,13,22,23,25,33-35). One study compared the incidence of OSD in healthy children with a simple skin dimple with children without skin signs. In the group of 75 children with a simple dimple, ultrasonography showed suspected OSD in one child, while MRI showed normal results. In a control group of 105 children

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without skin dimples, meningocele with a spinal cord was detected in one with ultrasound. Research has shown that children with a simple dimple do not have a higher risk of OSD compared to those with no skin signs (8).

In one prospective study comparing children with simple and atypical dimples, no intraspinal changes were found using ultrasonography in 160 newborns with simple dimples, and among 20 children with atypical dimples, 8 (40%) had OSD (7).A higher prevalence of OSD has also been confirmed by research in children with multiple skin signs over the spine.

In one such retrospective study, among 36 children with only a dimple above the sacrum, 3 (8%) had OSD, and among 18 children with two or more skin signs, as many as 11 (61%) had OSD (13).

Based on the results of these studies, saying that a simple dimple is not a useful marker for the diagnosis of SD in healthy children, most authors have suggested that the children do not need ultrasonography of the spinal channel (1,8,11,23,27,36).

These results have also been confirmed by some prospective studies. Ausili and colleagues studied the role of ultrasound and MRI in 439 children who had no clinical signs and had various skin signs over the spine. All underwent spinal chan- nel ultrasound in the first month, and 39 children with abnormal ultrasound scans underwent MRI. OSD was confirmed by MRI in 22 children. In the group of 400 newborns with normal ultrasound scans, however, only 1 child developed neurological signs during follow-up, in which MRI showed dermal sinus and tethered spinal cord. Thus, a total of 23 (5%) children with various skin signs over the spine had OSD.

Research has shown that ultrasonography of the spinal channel in newborns with skin signs is an effective screening method for the selection of children, on the basis of which we decide to diagnose using MRI. They pointed out that MRI is needed by children who have pronounced clinical

signs, all with abnormal ultrasound scans, and those who have multiple skin signs over the spine (26).

Interesting are the results of a retrospective study by O’Neill and co-authors who examined the incidence of SD in 522 children according to different skin or clinical signs. Indications for MRI were:

skin dimple above the sacrum, asymmetry of gluteal folds, hemangioma, only other skin signs (lipoma, rudimentary tail, local hairiness, dysplastic nevus), several skin signs over the spine and congenital anomalies (VACTERL, neurogenic bladder, imperforate anus, caudal agenesis, motor skill developmental delay, arthro- gryposis). OSD was diagnosed in as many as 122 (23.4%) children. 4/5 of these had a lipoma of the filum or a low position of the conus, and 1/5 had a complex type of OSD (spinal lipoma, diastematomyelia, dermal sinus). OSD was most commonly diagnosed in the group with only other skin signs (55%), where also most children had a complex type of OSD (10/17). The second group with the most OSD were patients with congenital anomalies (36%), followed by the group with multiple skin signs (27%). Surprising is the high propor- tion of OSD in children with only a skin dimple above the sacrum (20%), but the study did not define whether these were simple or atypical dimples. In the group with asymmetry of gluteal folds, 12% of children had OSD, and the proportions of OSD in other groups were lower (24). The study showed a higher prevalence of OSD diagnosed by MRI (23.4%) compared to ultrasound (0–3.4%) in similar studies (7,9,14,23-25,27). The differences in these comparisons are not only due to the higher resolution of MRI compared to ultrasound, but also due to referrals according to different skin signs. The study by O’Neill et al. has also shown clearly that the sensitivity and specificity of ultrasound imaging are lower compared to MRI, especially in children with minor filum changes (24). It 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.

OPEN SD

US of spinal channel – NO US of head – YES

MRI of spinal channel + head

Neurosurgeon

Suspected SD

+ clinical signs

+/- skin signs + skin signs - clinical signs

Skin dimples

Atypical Simple

Subcutaneous mass, asymmetry of movement, bowel and bladder incontinence, asymmetry in size and circumference of lower limbs, spinal deformities, anorectal anomalies, VACTERL, OEIS

Local hairiness, tuft of hair, hemangiomas, angiomatosis, skin protrusions, rudimentary tail, asymmetry of gluteal folds, duplicated gluteal cleft

Above sacrum or higher, > 2.5 cm above anus medially/laterally,

> 0.5 cm in diameter, one/numerous, +/- other skin signs

Above sacrum or higher, < 2.5 cm above anus medially,

< 0.5 cm in diameter, one dimple, no other signs

Fosse lumbales (»dimples of venus«)

US of spinal channel* + US of head

Normal

ev. MRIDD?

US of spinal chan-

nel* + US of head Clinical follow-up

Normal

US not necessary

Clinical follow-up not necessary (X-ray on suspision

of sacral agenesis)

+ US signs: Intraspinal mass, conus < L2-L3 (up to 2 m) or

< L1-L2 (after 2 m)

↓cone motility, spinal lipoma, thickened filum > 2 mm, dermal sinus, signs of Arnold Chiari II

Normal

Cl. follow-up not necessary MRI of spinal channel

+ MRI of head SD

Neurosurgeon

DD, differential diagnostic; Cl., clinical follow-up, MRI, magnetic resonance imaging; OEIS, omphalocele, exstrophy, imperforate anus, spinal dysraphisms; OSD, occult spinal dysraphism;

X-ray; SD, spinal disraphism; US, ultrasound scan; VACTERL, vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies and limb abnormalities;

*US of spinal channel can be performed up to and including 3 months of age; m, months of life.

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signs, all with abnormal ultrasound scans, and those who have multiple skin signs over the spine (26).

Interesting are the results of a retrospective study by O’Neill and co-authors who examined the incidence of SD in 522 children according to different skin or clinical signs. Indications for MRI were:

skin dimple above the sacrum, asymmetry of gluteal folds, hemangioma, only other skin signs (lipoma, rudimentary tail, local hairiness, dysplastic nevus), several skin signs over the spine and congenital anomalies (VACTERL, neurogenic bladder, imperforate anus, caudal agenesis, motor skill developmental delay, arthro- gryposis). OSD was diagnosed in as many as 122 (23.4%) children. 4/5 of these had a lipoma of the filum or a low position of the conus, and 1/5 had a complex type of OSD (spinal lipoma, diastematomyelia, dermal sinus). OSD was most commonly diagnosed in the group with only other skin signs (55%), where also most children had a complex type of OSD (10/17). The second group with the most OSD were patients with congenital anomalies (36%), followed by the group with multiple skin signs (27%). Surprising is the high propor- tion of OSD in children with only a skin dimple above the sacrum (20%), but the study did not define whether these were simple or atypical dimples. In the group with asymmetry of gluteal folds, 12% of children had OSD, and the proportions of OSD in other groups were lower (24). The study showed a higher prevalence of OSD diagnosed by MRI (23.4%) compared to ultrasound (0–3.4%) in similar studies (7,9,14,23-25,27). The differences in these comparisons are not only due to the higher resolution of MRI compared to ultrasound, but also due to referrals according to different skin signs. The study by O’Neill et al. has also shown clearly that the sensitivity and specificity of ultrasound imaging are lower compared to MRI, especially in children with minor filum changes (24). It 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.

OPEN SD

US of spinal channel – NO US of head – YES

MRI of spinal channel + head

Neurosurgeon

Suspected SD

+ clinical signs

+/- skin signs + skin signs - clinical signs

Skin dimples

Atypical Simple

Subcutaneous mass, asymmetry of movement, bowel and bladder incontinence, asymmetry in size and circumference of lower limbs, spinal deformities, anorectal anomalies, VACTERL, OEIS

Local hairiness, tuft of hair, hemangiomas, angiomatosis, skin protrusions, rudimentary tail, asymmetry of gluteal folds, duplicated gluteal cleft

Above sacrum or higher, > 2.5 cm above anus medially/laterally,

> 0.5 cm in diameter, one/numerous, +/- other skin signs

Above sacrum or higher, < 2.5 cm above anus medially,

< 0.5 cm in diameter, one dimple, no other signs

Fosse lumbales (»dimples of venus«)

US of spinal channel* + US of head

Normal

ev. MRIDD?

US of spinal chan-

nel* + US of head Clinical follow-up

Normal

US not necessary

Clinical follow-up not necessary (X-ray on suspision of sacral agenesis)

+ US signs:

Intraspinal mass, conus < L2-L3 (up to 2 m) or

< L1-L2 (after 2 m)

↓cone motility, spinal lipoma, thickened filum > 2 mm, dermal sinus, signs of Arnold Chiari II

Normal

Cl. follow-up not necessary MRI of spinal channel

+ MRI of head SD

Neurosurgeon

DD, differential diagnostic; Cl., clinical follow-up, MRI, magnetic resonance imaging; OEIS, omphalocele, exstrophy, imperforate anus, spinal dysraphisms; OSD, occult spinal dysraphism;

X-ray; SD, spinal disraphism; US, ultrasound scan; VACTERL, vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies and limb abnormalities;

*US of spinal channel can be performed up to and including 3 months of age; m, months of life.

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a small lipoma of the filum are clinically significant. In one such study, among 436 subjects who had filar lipoma on MRI, 22 (5%) had tethered spinal cord syndrome.

Among the 249 subjects with filar lipoma who were clinically followed for three and a half years, only one developed tethered spinal cord syndrome (37).

In studies comparing the sensitivity of ultrasound to MRI in the diagnosis of SD, one study in 40 patients with neurogenic bladder showed that the sensitivity of ultrasonography for spina bifida was 66.6%, for agenesis of the sacrum and vertebral arch damage 100%, for tethered spinal cord 85.7%, for lipoma of the filum terminale 100%, and in cases of diagnosis of intraspinal masses and diastematomyelia 33.3%. The specificity of the ultrasound method ranged between 85.7–100% in all dysraphisms (38). In a similar recent- ly published retrospective study analyzing diagnostic imaging results in 94 newborns with anorectal abnormalities, the sensitivity of the ultrasound for diagnosing tethered spinal cord was 80% and specificity 89% (39). Such studies have shown good sensitivity and high specificity of the ultrasound method in most patients.

6 Early treatment algorithm for a child with SD

Based on the cited literature, we developed an algorithm for treating children with suspected SD in the first months of life in order to identify and unify the approach to diagnosis early. The algorithm of early treatment of a child with SD is sche- matically presented in Figure 4.

In a newborn with an open SD, ultra- sound of the spinal channel is not required after birth due to possible infection of the surrounding tissues. Ultrasound scan of the head identifies associated changes in the brain. We consult a neurosurgeon regarding MRI before surgery.

In children with suspected SD and neu- rological, urological or orthopedic problems, ultrasound imaging of the spinal channel

and head is performed. Where ultrasound reveals changes that indicate SD, an MRI is needed as soon as possible. If the ultrasound scan result is normal, we continue with the treatment within the framework of differential diagnostic possibilities and decide on the need for MRI of the central nervous system on the basis of the clinical picture.

Children without clinical signs who have atypical dimples or other skin signs over the spine, where OSD is suspected, are re- ferred for ultrasound of the spinal channel and head in the first three months of life. Where ultrasound of the spinal channel shows no signs of SD, further imaging is not required. Given the rare cases described, where, despite a normal ultrasound result, spinal cord syndrome later developed, clinical monitoring is recom- mended for this group.

Children without clinical signs, with ultrasound scan signs characteristic of SD, need an MRI of the spinal channel and head, which, however, can be performed in later months in the time of preparation for surgery. This avoids duplication of examinations and exposing children to general anesthesia in their first months.

Where the diagnosis is confirmed by MRI, the decision regarding prophylactic surgery is individual. However, where the MRI result is negative, no further clinical monitoring is required.

In a healthy child with a simple dimple, ultrasound is not required. Planned clinical monitoring is not necessary, but we pay attention to this type of child's characteristic during medical treatments.

7 Conclusion

Many studies with large populations of children with skin changes over the spine have shown that ultrasound is a sensitive method in the early diagnosis of SD. MRI is in place at early diagnosis in high-risk children, and in cases where ultrasound reveals changes, causing suspicion of SD.

The proposed algorithm offers a system-

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atic approach to treating all children with suspected SD. With an emphasis on early ultrasound diagnosis, it enables efficient and rational screening of children with suspected OSD and early identification of those who need action.

8 Abbreviations

• SD – spinal dysraphism

• OSD – occult spinal dysraphism

• US – ultrasound scan

References

1. Unsinn KM, Geley T, Freund MC, Gassner I. US of the spinal cord in newborns: spectrum of normal findings, variants, congenital anomalies, and acquired diseases. Radiographics. 2000;20(4):923-38. DOI: 10.1148/

radiographics.20.4.g00jl06923 PMID: 10903684

2. Kumar J, Afsal M, Garg A. Imaging spectrum of spinal dysraphism on magnetic resonance: A pictorial review. World J Radiol. 2017;9(4):178-90. DOI: 10.4329/wjr.v9.i4.178 PMID: 28529681

3. Dupépé EB, Patel DM, Rocque BG, Hopson B, Arynchyna AA, Bishop ER, et al. Surveillance survey of family history in children with neural tube defects. J Neurosurg Pediatr. 2017;19(6):690-5. DOI: 10.3171/2016.12.

PEDS1668 PMID: 28362184

4. Kar A, Kar T, Kanungo S, Guru L, Rath J, Dehuri P. Risk factors, organ weight deviation and associated anomalies in neural tube defects: A prospective fetal and perinatal autopsy series. Indian J Pathol Microbiol. 2015;58(3):285-91. DOI: 10.4103/0377-4929.162832 PMID: 26275247

5. Arth A, Kancherla V, Pachón H, Zimmerman S, Johnson Q, Oakley GP. A 2015 global update on folic acid- preventable spina bifida and anencephaly. Birth Defects Res A Clin Mol Teratol. 2016;106(7):520-9. DOI:

10.1002/bdra.23529 PMID: 27418029

6. Copp AJ, Adzick NS, Chitty LS, Fletcher JM, Holmbeck GN, Shaw GM. Spina bifida. Nat Rev Dis Primers.

2015;1(1):15007. DOI: 10.1038/nrdp.2015.7 PMID: 27189655

7. Kriss VM, Desai NS. Occult spinal dysraphism in neonates: assessment of high-risk cutaneous stigmata on sonography. AJR Am J Roentgenol. 1998;171(6):1687-92. DOI: 10.2214/ajr.171.6.9843314 PMID: 9843314 8. Gibson PJ, Britton J, Hall DM, Hill CR. Lumbosacral skin markers and identification of occult spinal

dysraphism in neonates. Acta Paediatr. 1995;84(2):208-9. DOI: 10.1111/j.1651-2227.1995.tb13612.x PMID:

7756811

9. Robinson AJ, Russell S, Rimmer S. The value of ultrasonic examination of the lumbar spine in infants with specific reference to cutaneous markers of occult spinal dysraphism. Clin Radiol. 2005;60(1):72-7. DOI:

10.1016/j.crad.2004.06.004 PMID: 15642296

10. Tortori-Donati P, Rossi A, Biancheri R, Cama A. Magnetic resonance imaging of spinal dysraphism. Top Magn Reson Imaging. 2001;12(6):375-409. DOI: 10.1097/00002142-200112000-00003 PMID: 11744877 11. Schropp C, Sörensen N, Collmann H, Krauss J. Cutaneous lesions in occult spinal dysraphism—correlation

with intraspinal findings. Childs Nerv Syst. 2006;22(2):125-31. DOI: 10.1007/s00381-005-1150-4 PMID:

15875199

12. Kumar A, Kanojia RK, Saili A. Skin dimples. Int J Dermatol. 2014;53(7):789-97. DOI: 10.1111/ijd.12376 PMID:

24738724

13. Guggisberg D, Hadj-Rabia S, Viney C, Bodemer C, Brunelle F, Zerah M, et al. Skin markers of occult spinal dysraphism in children: a review of 54 cases. Arch Dermatol. 2004;140(9):1109-15. DOI: 10.1001/

archderm.140.9.1109 PMID: 15381552

14. Chern JJ, Aksut B, Kirkman JL, Shoja MM, Tubbs RS, Royal SA, et al. The accuracy of abnormal lumbar sonography findings in detecting occult spinal dysraphism: a comparison with magnetic resonance imaging. J Neurosurg Pediatr. 2012;10(2):150-3. DOI: 10.3171/2012.5.PEDS11564 PMID: 22747088

• MRI – magnetic resonance imaging

• GS – gestation

• MMK – myelomeningocele

• AC II – Arnold Chiari Malformation type II

• LMMK – lipomielomeningocele

• VACTERL – vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities

• OEIS – omphalocele, exstrophy, imperforate anus, spinal defects

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15. Dias M, Partington M; Section on neurologic surgery. Congenital Brain and Spinal Cord Malformations and Their Associated Cutaneous Markers. Pediatrics. 2015;136(4):e1105-19. DOI: 10.1542/peds.2015-2854 PMID:

26416933

16. Tortori-Donati P, Rossi A, Cama A. Spinal dysraphism: a review of neuroradiological features with embryological correlations and proposal for a new classification. Neuroradiology. 2000;42(7):471-91. DOI:

10.1007/s002340000325 PMID: 10952179

17. Acharya UV, Pendharkar H, Varma DR, Pruthi N, Varadarajan S. Spinal dysraphism illustrated; Embroyology revisited. Indian J Radiol Imaging. 2017;27(4):417-26. DOI: 10.4103/ijri.IJRI_451_16 PMID: 29379236 18. Nair N, Sreenivas M, Gupta AK, Kandasamy D, Jana M. Neonatal and infantile spinal sonography: A

useful investigation often underutilized. Indian J Radiol Imaging. 2016;26(4):493-501. DOI: 10.4103/0971- 3026.195788 PMID: 28104945

19. Coleman BG, Langer JE, Horii SC. The diagnostic features of spina bifida: the role of ultrasound. Fetal Diagn Ther. 2015;37(3):179-96. DOI: 10.1159/000364806 PMID: 25341807

20. Meyers AB, Chandra T, Epelman M. Sonographic spinal imaging of normal anatomy, pathology and magnetic growing rods in children. Pediatr Radiol. 2017;47(9):1046-57. DOI: 10.1007/s00247-017-3845-6 PMID: 28779192

21. Deeg KH, Lode HM, Gassner I. Spinal sonography in newborns and infants - part II: spinal dysraphism and tethered cord. Ultraschall Med. 2008;29(1):77-88. DOI: 10.1055/s-2007-963212 PMID: 17610176

22. Chern JJ, Kirkman JL, Shannon CN, Tubbs RS, Stone JD, Royal SA, et al. Use of lumbar ultrasonography to detect occult spinal dysraphism. J Neurosurg Pediatr. 2012;9(3):274-9. DOI: 10.3171/2011.12.PEDS11351 PMID: 22380955

23. Ben-Sira L, Ponger P, Miller E, Beni-Adani L, Constantini S. Low-risk lumbar skin stigmata in infants: the role of ultrasound screening. J Pediatr. 2009;155(6):864-9. DOI: 10.1016/j.jpeds.2009.06.003 PMID: 19643444 24. O’Neill BR, Gallegos D, Herron A, Palmer C, Stence NV, Hankinson TC, et al. Use of magnetic resonance

imaging to detect occult spinal dysraphism in infants. J Neurosurg Pediatr. 2017;19(2):217-26. DOI:

10.3171/2016.8.PEDS16128 PMID: 27911245

25. Henriques JG, Pianetti G, Henriques KS, Costa P, Gusmão S. Minor skin lesions as markers of occult spinal dysraphisms—prospective study. Surg Neurol. 2005;63(1):S8-12. DOI: 10.1016/j.surneu.2004.09.017 PMID:

15629346

26. Ausili E, Maresca G, Massimi L, Morgante L, Romagnoli C, Rendeli C. Occult spinal dysraphisms in newborns with skin markers: role of ultrasonography and magnetic resonance imaging. Childs Nerv Syst.

2018;34(2):285-91. DOI: 10.1007/s00381-017-3638-0 PMID: 29075839

27. Kucera JN, Coley I, O’Hara S, Kosnik EJ, Coley BD. The simple sacral dimple: diagnostic yield of ultrasound in neonates. Pediatr Radiol. 2015;45(2):211-6. DOI: 10.1007/s00247-014-3110-1 PMID: 24996813

28. Fidas A, MacDonald HL, Elton RA, Wild SR, Chisholm GD, Scott R. Prevalence and patterns of spina bifida occulta in 2707 normal adults. Clin Radiol. 1987;38(5):537-42. DOI: 10.1016/S0009-9260(87)80150-2 PMID:

3311565

29. Lode HM, Deeg KH, Krauss J. Spinal sonography in infants with cutaneous birth markers in the lumbosacral region—an important sign of occult spinal dysrhaphism and tethered cord. Ultraschall Med.

2008;29(5):281-8. DOI: 10.1055/s-2007-963169 PMID: 17610175

30. Pang D. Disorders of the Pediatric Spine. New York: Raven Press; 1995. pp. 175-201.

31. Pang D, Zovickian J, Wong ST, Hou YJ, Moes GS. Surgical treatment of complex spinal cord lipomas. Childs Nerv Syst. 2013;29(9):1485-513. DOI: 10.1007/s00381-013-2187-4 PMID: 24013320

32. Pang D, Dias MS, Ahab-Barmada M. Split cord malformation: Part I: a unified theory of embryogenesis for double spinal cord malformations. Neurosurgery. 1992;31(3):451-80. DOI: 10.1227/00006123-199209000- 00010 PMID: 1407428

33. Sneineh AK, Gabos PG, Keller MS, Bowen JR. Ultrasonography of the spine in neonates and young infants with a sacral skin dimple. J Pediatr Orthop. 2002;22(6):761-2. DOI: 10.1097/01241398-200211000-00013 PMID: 12409903

34. Weprin BE, Oakes WJ. Coccygeal pits. Pediatrics. 2000;105(5):E69. DOI: 10.1542/peds.105.5.e69 PMID:

10799633

35. Herman TE, Oser RF, Shackelford GD. Intergluteal dorsal dermal sinuses. The role of neonatal spinal sonography. Clin Pediatr (Phila). 1993;32(10):627-8. DOI: 10.1177/000992289303201012 PMID: 8261728 36. Lee AC, Kwong NS, Wong YC. Management of Sacral Dimples Detected on Routine Newborn Examination:

a Case Series and Review. HK J Paediatr. 2007;12:93-5.

37. Cools MJ, Al-Holou WN, Stetler WR, Wilson TJ, Muraszko KM, Ibrahim M, et al. Filum terminale lipomas:

imaging prevalence, natural history, and conus position. J Neurosurg Pediatr. 2014;13(5):559-67. DOI:

10.3171/2014.2.PEDS13528 PMID: 24628511

(15)

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