Neural tube defects

Neural tube defects

Pediatr Clin N Am 51 (2004) 389 – 419 Neural tube defects Bruce A. Kaufman, MD, FACS, FAAPa,b,* a Department of Neurosurgery, Medical College of Wis...

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Pediatr Clin N Am 51 (2004) 389 – 419

Neural tube defects Bruce A. Kaufman, MD, FACS, FAAPa,b,* a

Department of Neurosurgery, Medical College of Wisconsin, 9000 West Wisconsin Avenue, Milwaukee, WI 53201, USA b Department of Pediatric Neurosurgery, Children’s Hospital of Wisconsin, 9000 West Wisconsin Avenue, Milwaukee, WI 53201, USA

Defects of the neural tube encompass a wide range of congenital spine and spinal cord defects. These defects involve the imperfect development of the neuropore during embryogenesis and the subsequent maldevelopment of the adjacent bone and mesenchymal structures. Neural tube defects are the most common birth defects seen by neurosurgeons. The primary lesions involve the spinal portion of the central nervous system. The presenting manifestations and the sequelae can affect a seemingly disparate array of structures and function, including the brain, the bony spine, the extremities, and bowel and bladder function. The more severe types have been described as being the most complex developmental defects compatible with life. Thus, the care of these patients requires evaluation and attention to primary lesion and also to the affected systems outside the nervous system, at presentation and during the lifelong follow-up many of these patients require.

Definitions The terminology of neural tube defects can be confusing, and the classifications vary among authors. The term spinal dysraphism includes the overall group of defects derived from the maldevelopment of the ectodermal, mesodermal, and neuroectodermal tissues. The term spina bifida cystica typically refers to the meningoceles and myelomeningoceles, whereas the term spina bifida aperta has been used to categorize the subgroup of defects that are open or exposed. Unfortunately, the nonspecific term spina bifida has become commonly associated with the open spinal dysraphism of myelomeningocele. Occult spinal dysraphism is the appropriate term for the various closed spinal defects, such as diastematomyelia, tight filum terminale, dorsal dermal sinus, and * Pediatric Neurosurgery, Children’s Hospital of Wisconsin, 9000 West Wisconsin Avenue, Milwaukee, WI 53201. E-mail address: [email protected] 0031-3955/04/$ – see front matter D 2004 Elsevier Inc. All rights reserved. doi:10.1016/S0031-3955(03)00207-4

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spinal lipoma. Spina bifida occulta, in the strictest definition, refers only to bone fusion defects of the spine identified on plain-film radiographs. These defects typically involve a failure of posterior arch fusion at one or more levels, usually in the lower lumbar/sacral region.

History The myelomeningocele and associated hydrocephalus were known to Hippocrates, Aristotle, and other ancient physicians [1]. In the early twentieth century, surgical techniques had progressed to allow the closure of open defects without immediate perioperative mortality caused by infection, but the untreated hydrocephalus led to impaired mental and physical function in most of the survivors [2]. With the effective treatment of hydrocephalus by shunting in the 1950s, most myelomeningocele patients received aggressive care. As they survived, however, many continued to suffer from significant physical and mental disabilities, such as deformity of the extremities, severe scoliosis, shunt infections, and significant urinary dysfunction and failure [3]. From this experience an extensive debate ensued over the relative merits and the ethics of selecting for treatment only the patients with the best prognosis [4]. In 1986, McLone reviewed the largest series of unselected and aggressively treated patients and compared them with a group of highly selected patients who had been treated [4– 6]. When comparing factors including urinary and bowel continence, renal function, ambulation, mortality, and intelligence, he found the aggressively treated but unselected patient populations had better function than the selected groups. It has become clear that the aggressive treatment of all but moribund patients can allow many to lead productive lives.

Epidemiology The incidence and epidemiology of the open forms of spinal dysraphism are the most frequently studied. In North America, the incidence of myelomeningocele has previously been reported at approximately 1 per 1000 live births [7,8]. In the United States the overall incidence evaluated using a population-based surveillance method was found to be 4.6 cases per 10,000 births, but during the period 1983 through 1990 there was a gradual decline in the rate from 5.9 to 3.2 cases per 10,000 births [9]. The overall incidence has been declining for the past 15 years [7,10]. Although geographic and ethnic variability in the incidence of myelomeningocele has been reported, the recent population survey has shown no geographic variation and a relative uniformity of incidence developing in all ethnic groups [11]. Factors such as the season of birth, maternal age, or parity have not been correlated with the incidence of myelomeningocele [7,12,13]. Drugs and infections have for the most part not been implicated as putative teratogens. Valproic

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acid is one exception and has been associated with neural tube defects in the children of some women taking the medication [14 – 18]. Nutritional deficiency states have been suspected for many years. Controlled interventional studies have clearly shown a substantial reduction in risk of neural tube defects with the use of folic acid dietary supplements. The most rigorous randomized, controlled study was performed by the British Medical Research Council and yielded a 72% reduction in the risk of a neural tube defect [19]. The United States Public Health Service recommended that all women of childbearing age who are capable of becoming pregnant should consume 0.4 mg of folic acid per day to reduce the risk of a pregnancy affected with a neural tube defect [20]. Genetic factors do seem to have a role in some cases [21]. The risk of one child having spinal dysraphism is estimated at 0.1% to 0.2%, but with one affected sibling the risk of a second affected child increases to 2% to 5%, and the risk of a third affected child increases again to 10% to 15% [8,22]. These occurrences do not fit a Mendelian pattern of transmission. Other genetic mechanisms of transmission, such as an X-linked recessive gene, a dominant gene with variable penetrance, or polygenic transmission, have been suggested to explain this tendency to recur within families [23]. Spina bifida occulta is much more prevalent than the open forms of dysraphism. Between 17% and 30% of the normal population has been found to have a spinal defect [24]. Spina bifida occulta is seen more commonly in males and most frequently at the L5 or S1 level. By itself, this frequent finding of bony dysraphism is of no clinical significance. Finding a significant underlying dysraphic state is much more likely when spina bifida occulta is associated with subtle neurologic symptoms or with cutaneous abnormalities such as hypertrichosis, dimples, sinus tracts, or capillary hemangiomas in the same area.

Normal embryology The lesions of neural tube defects are all variations on the normal development of the spine and spinal cord. Reviewing the normal embryology allows a better understanding of these defects and the anatomic relationships seen on diagnostic studies. Only a brief review of the pertinent embryology is presented here. The embryo is trilaminar by approximately days 16 and 17 (embryonic stage 7). The endoderm ultimately develops into the gut structures, the mesoderm into the musculature and skeleton, and the ectoderm into the skin and nervous system. The process of neurulation, or neural tube formation, begins with the development of the notochord (stages 8 – 12, days 18 – 27). The underlying notochord causes the overlying ectoderm to differentiate into the neural plate. The cells of the neural plate proliferate on each side of a developing longitudinal groove, forming the neural folds. Laterally, the neural plate is in continuity with the ectoderm from which it is derived (Fig. 1A). As the neural folds grow, they meet and fuse in the midline forming the neural tube (stage 10, days 22 and 23) (Fig. 1B). At closure, the superficial ectoderm

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Fig. 1. Normal embryology. (A) Formation of the neural plate. The notochord has induced the formation the neural plate, contiguous with the neural crest and ectoderm. As the neural plate cells proliferate, the edges begin to come together in the midline. The somites and mesoderm forms laterally. (B) Neural tube formation. The neural plate has met in the midline and fused, with the neural crest tissue forming dorsally. The ectoderm has undergone disjunction, disconnecting from the neural tissue and fusing to form the future skin. (From Kaufman BA. Spinal dysraphism. In: Bridwell KH, Dewald RL, editors. The textbook of spinal surgery. 2nd edition. Philadelphia: JB Lippincott; 1994. p. 368 – 9; with permission.)

disconnects from the neural tube (disjunction) and then fuses in the midline, dorsal to the tube. This fusion reconstitutes a continuous ectoderm (the future skin). The mesenchyme migrates from the sides into a position between the neural tube and ectoderm, ultimately forming the meninges, neural arches, and paraspinal muscles. The lower portion of the spinal cord forms by a separate process called canalization, with the caudal cell mass forming from the aggregation of undifferentiated cells, the remnants of the notochord, and the caudal end of the neural tube adjacent to the developing hindgut and mesonephros. Along this distal canal, the cells differentiate toward glia. The most cephalic portion becomes the conus medullaris. The remainder involutes (retrogressive differentiation) to form the filum terminale. At the time the conus medullaris is formed, it is located at approximately the second or third coccygeal level. There is no further involution of the spinal cord, but the spinal column grows at a relatively faster rate than the spinal cord, resulting in the apparent ascension of the conus. The ascension occurs rapidly between 8 and 25 weeks of gestation, with the conus generally opposite L2 at birth, reaching the normal adult level of L1-L2 in the months after birth [25].

Open dysraphism—myelomeningocele Embryology The myelomeningocele, an open spinal cord defect, could result from a primary failure of the neural tube to close or from a secondary reopening of the closed neural tube [26,27]. Experimental evidence supports both these theories, but the best evidence suggests that a primary failure to close results in the neural

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plate remaining flat until birth [28]. The Chiari II malformation is thought to develop later in gestation [29]. With failure of the neural tube closure, the ectoderm remains attached and lateral to the neuroectoderm. The mesenchyme and somites remain in a lateral position, forming the bony, cartilaginous, and muscular elements of the sides of the canal. At the level of the defect, the neural structures are everted, the laterally placed laminae are bifid, and pedicles are rotated outward [30]. If there is extensive displacement and rotation of the pedicles, the paraspinal muscles end up positioned anterior to the midcoronal plane of the spine. In this position, they become functional flexors of the spine rather than extensors, causing or aggravating a kyphosis. Several theories attempt to explain the neurologic deficits associated with an open spinal cord defect. The neurologic injury may be the result of a two-hit process [31,32]. The first hit is the maldevelopment of the neural tube and the associated structural abnormalities. The second hit may be the result of neural tissue exposure to amniotic fluid. Several animal models lend support to the hypothesis that exposure to the amniotic fluid results in damage to normal spinal cord tissue. In the typical animal model, exposing and opening of the dura exposes a previously normal spinal cord to the surrounding amniotic fluid. The animals are then placed back into the womb, and gestation is continued until the animals are delivered by Cesarean section [31,33,34]. Animals whose spinal cord was exposed to amniotic fluid showed some neurologic deficit ranging from weakness to deformity in the lower extremities [31,34]. Histologically, necrosis and erosion of the exposed dorsal spinal cord was noted in all cases, with very little acute inflammation identified [31,34]. These studies support the hypothesis that exposure of normal spinal cord tissue to amniotic fluid can result in destruction similar to that seen in myelomeningocele. In other animal studies where the spinal defect is repaired in utero, there has been an improvement in neurologic function [31,33,34]. The histologic picture was also better, with better preservation of spinal cord cytoarchitecture, although the area of repair was not completely normal [31,33]. Antenatal evaluation and treatment – fetal surgery for myelomeningocele With the routine use of antenatal screening tests, the prenatal diagnosis of myelomeningocele is being made more frequently. Antenatal diagnosis can allow a more thorough education of the expectant parents, with discussion of what they can expect at and after birth held in a less stressful environment. At the Children’s Hospital of Wisconsin, these discussions include an explanation of the malformation, an outline of the immediate postnatal evaluation, a review of the surgery to close the defect, and a discussion of the frequently associated hydrocephalus and its treatment with shunting. Early antenatal diagnosis and the encouraging results of the animal studies have prompted several groups to offer antenatal surgical closure of myelomeningoceles, hoping to improve the neurologic outcome in these patients. The

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clinical success seen in the animal models has not been completely realized in humans, however. There has not been consistent improvement in lower extremity motor or bladder functions [35]. As more patients have been treated with antenatal surgery, the incidence of shunt dependence has seemed lower in the fetal surgery patients [36,37]. Because a large portion of the lifetime morbidity and mortality in myelomeningocele patients is related to the treatment of hydrocephalus and shunting, with mortality reaching 1% per year, any significant decrease in the incidence of shunting has the potential to improve the health of these patients significantly. Unfortunately, it is not yet clear whether the observed decrease in shunting in fetal surgery patients is real or merely a function of selection bias or deferred diagnosis of hydrocephalus and later shunting. There does, however, seem to be a real and significant decrease in the incidence or severity of Chiari II malformations in the patients treated with fetal surgery. The long-term significance of this finding is not yet clear. Fetal surgical repair of myelomeningocele is not without risks. The overall mortality rate of the surgery itself is at least 4% [37]. Following in utero repair, there is a reported increase in the incidence of oligohydramnios (48% versus 4%), preterm uterine contractions (50% versus 9%), an earlier estimated gestational age (33.2 versus 37 weeks), and a smaller birth weight (2171 g versus 3075g) [36]. Thus, the younger and smaller infants born after in utero repair could have the problems of prematurity added to those of the myelomeningocele. Maternal risks must also be considered. Maternal complications that have been reported include uterine rupture, placental abruption, and maternal bowel obstruction caused by adhesions that can occur after hysterotomy [36,38]. In addition, the hysterotomy may commit the mother to a future of cesarean sections. In hopes of defining the risks versus benefits of fetal myelomeningocele repair to patients and families, several institutions in conjunction with the National Institute of Child Health and Human Development have initiated a prospective, randomized clinical trial. The Management of Myelomeningocele Study (MOMS) will compare the outcome of intrauterine repair of fetal myelomeningocele at 19 to 25 weeks of gestation with that obtained by standard postnatal repair. Outcomes to be measured include death, the need for ventricular shunting by 1 year of life, and neurologic function at 30 months of age. The study will enroll 200 women whose fetuses have spina bifida, 100 in each arm of the study. A central screening process will be followed by an extensive baseline evaluation, including a medical record review, ultrasound evaluation, MRI, physical examination, social work evaluation, and psychologic screening. They will receive education about spina bifida and prenatal surgery. Eligible women will receive the baseline evaluation, surgery, and follow-up visits at one of the three MOMS institutions. The women assigned to prenatal surgery will be scheduled for the surgery within 3 days, and they will have to stay near the MOMS center until after delivery. The postnatal surgery group will travel back to the MOMS center to deliver. Children and their parents will return to their assigned MOMS center at 1 year and at 2.5 years of age for follow-up evalua-

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tion assessing motor function, developmental progress, bladder and kidney function, and brain development. Postnatal presentation The initial evaluation of the baby born with a myelomeningocele is oriented toward promptly identifying any associated problems, particularly those that might preclude prompt closure of the spinal defect. The immediate neurosurgical goal is to protect and preserve neurologic function by closing the defect and preventing infection. Routine neonatal care is begun immediately. The defect is protected from trauma and drying by applying a sterile, nonsticking dressing moistened with saline. Neurotoxic substances such as providone-iodine (Betadine) should not be applied to the malformation. Parenteral antibiotics covering gram-positive and -negative bacteria are begun and continued only through surgical closure of the defect. Evaluation of the cardiac, gastrointestinal, and genitourinary systems is undertaken, because embryologically these systems formed concurrently with or adjacent to the malformed neurologic system. Portable ultrasound examinations of the head and urinary system are obtained, evaluating for hydrocephalus and hydronephrosis, respectively. Plain-film radiographs of the entire spine looking for possible occult dysraphism outside the obvious defect are done in the neonatal ICU. The incidence of additional dysraphism can approach 10%. The presence or absence of the baby’s neurologic function must be defined, often among a confusing picture of abnormal reflexes, or even the occasional presence of spinal shock [39]. Asymmetry in the neurologic examination is common with routine myelomeningoceles but can also represent the presence of additional and not immediately obvious malformations such as diastematomyelia. The lowest level of sensory denervation is found by examining the child when quiet or sleeping. A sharp stimulus is applied, starting distally and working proximally, watching for a facial grimace or cry. Motor function is determined by applying painful stimulus to the upper extremities (or an unaffected portion of the body) and watching the lower extremities for voluntary motion. The exposed neural plate, called the neural placode, is often red and raw appearing. (Fig. 2A) This surface represents what should have been the interior of the spinal cord. There is a midline groove, which is continuous with the central canal of the spinal cord. Cerebrospinal fluid (CSF) exiting from the central canal should not be mistaken for a frank rupture of the underlying sac. The plate is surrounded by membranous tissue of varying width, formed by the skin and remnants of the arachnoid. Most myelomeningoceles found at birth are in the lumbosacral region, but, when they occur at higher levels, the spinal cord and canal may have a normal configuration above and below the defect. When a small amount of fluid is present, the neural plate is flush with the skin of the back (myelocele). A large amount of fluid causes the sac to enlarge, and the plate is elevated above the back (myelomeningocele). Through general usage, the term myelomeningocele has been used for both these entities.

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Fig. 2. Myelomeningocele. (A) Myelomeningocele. The exposed neural placode is seen connected to skin by varying degrees of membranous tissue that will be resected. The midline groove is apparent (white arrowheads); the central canal is at the superior aspect of the groove (large white arrow). (B) Myelomeningocele cross-sectional anatomy. The neural placode resembles a spinal cord that has been opened on its posterior aspect. The central groove is the remnant of the central canal. The nerve roots exit from the bottom of the placode but are in correct anatomical relationship. The dura mater lines the spinal canal but is abnormally attached to the skin. The somites and mesoderm forms laterally. (From Kaufman BA. Spinal dysraphism. In: Bridwell KH, Dewald RL, editors. The textbook of spinal surgery. 2nd edition. Philadelphia: JB Lippincott; 1994. p. 370; with permission.)

The ventral surface structures of the neural plate are in the same relative positions as in a normal cord. (Fig. 2B) The ventral roots lie just lateral to the midline, and the dorsal root pairs arise lateral to the ventral roots. Functional roots may cross through the subarachnoid space and exit through the neural foramina in the usual fashion. There are also frequently dysmorphic and

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nonfunctional roots that leave the neural plate and end blindly on the adjacent tissues. The sac is lined by arachnoid, and the dura mater forms the outermost layer of the open spinal canal. Surgery The surgery to close the defect should be performed early to decrease the incidence of infection and ventriculitis and thus the risk of impaired mental and physical function [40]. If the sac is not leaking, closure within 24 to 72 hours should be undertaken [41]. The time can be used to evaluate and prepare the baby and to begin counseling and educating the parents. If the sac is leaking, more prompt closure, usually within 24 hours is indicated. Only 15% of the babies will manifest significant hydrocephalus at the time of closure, but more than 90% will develop it subsequently, and most of these will require CSF diversion [30,42]. A ventriculoperitoneal shunt may be placed at the same time as spinal defect closure in patients with enlarged ventricles [43]. Several techniques for the repair of myelomeningoceles have been reported [44 – 46]. The surgery is done under appropriately monitored general anesthesia, with adequate intravenous access and bladder catheterization if indicated. Perioperative antibiotics may be used, but no evidence exists that postoperative antibiotics prevent meningitis or ventriculitis. In general, the surgical repair involves disconnecting the neural placode from the surrounding skin tissue, then recreating and closing the dural sac. Graft material is not used because of problems with tissue healing or the induction of inflammation and retethering [47]. The typical skin closure involves undermining the skin and subcutaneous tissue to the flanks and suturing the edges together. Rarely, relaxing incisions or rotational flaps are required. Some have advocated myocutaneous flap rotation for good closures [48 – 50], but it has the potential for interfering with the truncal musculature and later mobility as the child grows. Significant thoracolumbar kyphosis is present in approximately 15% of the myelomeningoceles at birth and may be so severe that the vertebral bodies actually lie dorsal to the plane of the back. This kyphosis makes closure more difficult and also risks immediate and delayed skin breakdown at the site of the bony prominence. Kyphectomy by means of vertebrectomy at the time of myelomeningocele closure has been used in these cases [51]. Postoperatively, routine neonatal care is undertaken. The baby is positioned on either side or on the abdomen, avoiding compression of the back and closure. The wound is observed daily for signs of infection, CSF leak, or wound breakdown. The patient without a shunt is observed for the symptoms and signs of progressive hydrocephalus. These signs include apneas, pulse drops, decreased activity, an increase in the head circumference, and tenseness of the fontanelle or spinal repair. Serial ultrasound examinations are also used to follow the size of the cerebral ventricles. If hydrocephalus develops, the patient is checked for signs of infection; if none are identified, a shunt is emplaced.

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The operative mortality associated with myelomeningocele repair has been reduced to nearly zero [6]. With careful dissection and the use of bipolar coagulation, blood loss is minimal. Wound infection remains somewhat problematic (up to 12% in one series), but wound dehiscence or other major sequelae are infrequent [52]. When CSF leakage occurs, it is usually self-limited or resolves with appropriate shunting of the underlying hydrocephalus.

Closed dysraphism General presentation The occult dysraphic states, those with skin completely covering the neural tissue, include spinal lipomas, diastematomyelia, dermal sinuses, myelocystoceles, the tight filum terminale, and the loosely defined tethered cord. Although these conditions arise from different errors of embryology, they all result in tethering of the spinal cord, with symptoms that result more from the tethering than from the specific embryopathy [53,54]. A number of cutaneous findings are markers for some of these underlying hidden dysraphic defects [55,56]. There may be a hairy patch, a nevus, an appendage or skin tag, or a small dimple with a pinhole. Hypertrichosis is commonly associated with diastematomyelia, and a large subcutaneous fat collection is associated with spinal lipomas. Any combination of these findings may be present in a given defect. A dimple or pinhole is usually found in conjunction with a dorsal dermal sinus. Such a pit located above the lumbosacral junction is so frequently associated with an intraspinal component that it should be operatively evaluated regardless of the radiologic findings. Any dimples or pits located off the midline also warrant further investigation and likely exploration. A midline sinus or pit overlying or at the end of the coccyx, however, does not have an intraspinal component and does not need further radiologic or surgical evaluation. The term tethered cord syndrome has become synonymous with a complex of symptoms and findings associated with various spinal dysraphic states [53,54, 57 – 61]. The symptoms can include weakness of the lower extremities, deterioration of gait, changes in urinary continence, and the development of scoliosis. Untreated occult dysraphic states may demonstrate this syndrome at any age, although it is seen most commonly in young children or young adults. Those with a previously treated lesion (typically myelomeningocele or spinal lipoma) may redevelop a tethered cord syndrome in the years after treatment because of retethering. The approach to patients with these symptoms has changed from acceptance of the deterioration as a part of the disease process to aggressive surgical management and untethering of the spinal cord in an attempt to arrest symptom progression. Pain in the lower back radiating into the legs, perineum, or genitals is a frequent complaint [53,57]. Flexion of the back causes increased pain; a more

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lordotic posture or pelvic tilting decreases the pain but can aggravate gait changes. There is often concurrent spasticity. Gait changes are also a frequent presenting complaint and may be accompanied by postural changes [56]. Up to 30% of the patients manifest a change in gait, particularly when sensory or motor deficits extend into the lower lumbar or sacral region. Sensory changes are rarely a presenting complaint. They may be quite vague, asymmetric, and need not be present in a dermatomal distribution [56]. A decrease in perineal sensation may be the earliest change. Urologic symptoms are much less common, and younger children rarely come to attention because of them. As the children become older, failure to toilet train, incontinence, and frequent infections make the diagnosis more obvious. When all patients with occult lesions are carefully examined, however, it is quite common to find abnormal urologic function [62]. In most patients the focus of tethering is in the lower thoracic or lumbosacral regions. Higher lesions, however, may have more extensive neurologic symptoms and deficits [63]. Patients with lesions tethering the cervical cord can have patchy numbness and lack of coordination of all four extremities, with atrophy of portions of the upper extremities. Weakness may be asymmetric, and deep tendon reflexes may range from hypoactive to hyperactive. As with the lower lesions, the cutaneous manifestations that may be present are often ignored until more severe neurologic deficits have developed. Several pathophysiologic mechanisms have been proposed to account for the symptoms seen in tethered cords. Tethering may limit the dissipation of motion over several spinal levels, and there may be more focal traction on the cord, leading to injury of the neural tissue. This mechanism might also explain the association of symptom onset with physical exertion or patient growth [58,64,65]. Vascular injury to the cord secondary to the stretching has also been suggested as a causative factor and may account for the symptoms that are noted to be slowly progressive [58,59]. Certainly, direct distortion of the nerve roots around a lipoma or neural plaque has been observed and may relate to some findings of weakness, incontinence, and pain [58].

Lipomyelomeningocele Lipomyelomeningoceles (or spinal cord lipomas) are occult dysraphic states consisting of a partial dorsal myeloschisis with lipoma fused to the dorsal aspect of the open spinal cord [66]. McLone et al [67] have proposed that premature ectodermal disjunction can account for this entity. If the ectodermal junction with the neural folds separates prematurely, mesenchyme can migrate into contact with the inside of the forming neural tube (Fig. 3) The inside of the neural tube, normally not in contact with the mesenchyme, can only induce the mesenchyme to differentiate into fat. The outside of the neural tube will induce the mesenchyme to form the normal pia arachnoid and dura and normal subarachnoid spaces to form ventral to the neural plate [40,56,68]. The ectoderm fuses dorsally,

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Fig. 3. Lipoma and premature disjunction. One embryologic theory suggests that the ectoderm undergoes premature disjunction from the neural tube, allowing mesenchyme to contact the interior of the neural tube. The mesenchyme is induced to form fat, which is in continuity with the subcutaneous fat. The remainder of the spinal canal and coverings form normally. (From Kaufman BA. Spinal dysraphism. In: Bridwell KH, Dewald RL, editors. The textbook of spinal surgery. 2nd edition. Philadelphia: JB Lippincott; 1994. p. 374; with permission.)

with the skin subsequently covering the underlying defect. Myeloschisis results from the mesenchymal tissue preventing neural tube closure. Presentation and evaluation No series document the natural history of spinal cord lipomas [40,60,65,67, 69 – 72]. Most patients are normal at birth and through the first year of life, although sudden neurologic deterioration has been observed. The incidence of neurologic deficits begins to increase during the second year of life, and by early childhood most patients will probably have some deficit [60,65,67]. The patients are frequently referred at an early age for evaluation of the deformity caused by the subcutaneous fat. The mass is typically located above the intergluteal cleft but may extend into one buttock [66]. Fifty percent have associated cutaneous markings, such as a midline dimple or dermal sinus, a hairy patch, or a hemangiomatous nevus [67]. Many physicians have considered this problem to be primarily cosmetic, and resection of the cutaneous stigmata was often undertaken at an early age without addressing the unrecognized intraspinal component. Families would be unaware of or ignore the subtle and progressive neurologic deficits that concurrently involve the lower extremities and bladder. These patients could present as adults with acutely aggravated deficits [40,73,74]. It is now recognized that these infants and children with cutaneous stigmata of dysraphism require a careful neurologic examination and thorough urologic evaluation, often including urodynamics. Neurodiagnostic imaging provides the information needed for proceeding with appropriate surgery. In neonates, ultrasound examination of the distal spine and lipoma can often delineate the lipoma and spinal dysraphism but is of limited utility in planning surgery. Plain-film radiography shows increased lumbar lordosis, segmentation errors of the vertebral bodies (hemivertebrae, fused vertebrae), and sacral deformities (partial agenesis) in up to 50% of the patients [30,75]. In all patients, MRI allows direct visualization of the neural plate, the orientation of the plate

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within the canal, and its orientation with respect to the lipoma and is the best test for planning surgery. Treatment The only effective treatment is surgery that untethers the spinal cord from its connection to the surrounding tissues. There is no need to attempt total removal of the fat attached to the cord, because to do so would inevitably injure the adjacent neural tissue. Several series have documented the successful and safe untethering of spinal cords from lipomas, with minimal morbidity and mortality [40,65,76].

Dermal sinus tracts Dermal sinus tracts are seen most frequently in regions of the spine representing the last place of neural tube closure. Dermal sinus tracts occur in approximately 1 in 2500 live births [77]. Their embryologic development may be explained by incomplete disjunction (Fig. 4) [56]. If the ectoderm remains attached to the forming neural tube in one spot, then, as the spinal cord becomes more distant from its anatomic spinal column location, a tract lined by epithelia and surrounded by dermal elements is drawn out, seemingly ascending the canal. The intraspinal termination of the tract may then be several levels cephalic to its skin origin. The tracts traverse the subcutaneous tissue and deep fascia directly from their skin origin. Most pass under or through a bifid lamina and then penetrate the dura [30,78]. The tract picks up a dural investment as it enters the spinal canal and can end at the filum terminale or connect directly to the conus medullaris [79,80]. Focal expansion of this ectoderm-derived tract results in dermoid or epidermoid tumor formation. Up to 60% of the dermal sinuses entering the spinal canal include or end in an epidermoid or dermoid tumor [78]. Only approxi-

Fig. 4. Dermal sinus tract and incomplete disjunction. If the ectoderm fails to separate from the neural tube at a spot, then a dermal connection can develop between the skin and the spinal cord. Because the spinal cord and surrounding tissues grow at differing rates, the dermal sinus tract will seem to travel quite distant to the connection to the cord. (From Kaufman BA. Spinal dysraphism. In: Bridwell KH, Dewald RL, editors. The textbook of spinal surgery. 2nd edition. Philadelphia: JB Lippincott; 1994. p. 383; with permission.)

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mately 30% of intraspinal dermoid tumors have an associated sinus tract, however [81,82]. Previously, patients with dermal sinuses were usually diagnosed after treatment for recurrent meningitis or after signs of spinal cord tethering became evident. The meningitis may be bacterial, but aseptic meningitis caused by leakage of the dermal elements into the CSF can occur [83 – 85]. If there is a growing epidermoid or dermoid tumor, symptoms may be caused by mass effect on the adjacent neural tissue [30,83]. This entity is now diagnosed earlier than in the past, because primary care physicians are more aware of it and investigate the otherwise innocuous cutaneous manifestations. Careful examination of the back in these patients almost always reveals some cutaneous manifestation, usually a pinhole (ostium) in the midline [78,83,86]. The ostium often has a few hairs arising from it. There may be more than one hole, or the hole may be off midline. Sometimes a hemangioma may surround the ostium. Dermal sinuses at sacral and coccygeal levels rarely have intraspinal extension or tethering of the cord. There is no role for probing or injecting contrast media or stains into any of these tracts. The radiographic evaluation of these tracts is less revealing than in other forms of spinal dysraphism. There may not be obvious spinal dysraphism on plain-film radiographs. Although ultrasound can be used in neonates to define the level of the conus and the presence of intraspinal masses, the absence of these abnormalities does not exclude the presence of a tethering sinus tract. Both MRI and CT scanning may miss the intraspinal portions of these small tracts. Only occasionally is the extraspinal portion seen contrasted against the fatty subcutaneous tissue through which it passes. MRI does yield valuable information about the position of the conus and the presence of any intraspinal tumors. Because of the limited intraspinal visualization provided by any of the radiographic studies, however, any dermal sinus noted above the sacrococcygeal region should be explored operatively regardless of the neuroradiologic findings. The goals of surgery are to untether the spinal cord from the tract, removing any access for infection, and to remove any associated epidermoid or dermoid tumors.

Altered caudal development The normal embryogenesis of the distal end of the spinal cord and filum terminale involves the formation of the caudal cell mass, canalization of the mass, and then retrogressive differentiation of these structures [87 – 89]. Aberrations in these developmental steps can lead to the formation of a tight filum terminale or a myelocystocele, both forms of occult spinal dysraphism. During embryogenesis, adjacent structures are the precursors for the hindgut and urogenital systems. Anomalies of these structures are frequently associated with these dysraphic states; tight filum terminale has been associated with anal malformations, and myelocystoceles often occur concomitantly with extrophy of the bladder and cloacal extrophy [56,90].

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Tight filum terminale Classically, patients with tight filum terminale present with symptoms of a tethered cord and are found to have a short, thickened filum terminale and a low-lying conus medullaris, without other tethering pathology [91 – 93]. A subgroup of patients has been found with the typical clinical presentation but with the conus at a more normal position; these patients respond to standard surgical sectioning of the filum [94,95]. The embryologic error accounting for the tight filum is not clear [56]. Females are more often affected than males, and the typical age of presentation relates to periods of rapid gain in height, 5 to 15 years [92]. The symptoms and signs are typical of tethered cord patients. Motor weakness, pain, and bladder dysfunction are most frequent. Scoliosis is present in 17% to 25% of patients [92,93]. A cutaneous marker (skin dimple, hemangioma, or hypertrichosis) is present in 50% [56,92]. MRI is an excellent study for defining the tethered cord and thickened filum while ruling out other pathologic conditions. The conus medullaris is found below L2 in 82% to 86% of these patients [92,96]. On axial imaging, the thecal sac may appear triangular in shape because of a filum tightly stretched against the dura dorsally; the filum may be difficult to distinguish in these cases [30]. The filum is usually thickened and contains fat [94]. Fat in the filum is seen in 6% of the normal population but in 91% of those with tethering [97]. In 10% to 15% of patients, no filum is identified and the spinal cord is demonstrated extending to the bottom of the thecal sac [92]. A filar fibrolipoma may be present in as many as 29% of the patients and is easily seen as either a low-density mass on CT or a mass with high signal intensity on T1-weighted MRI. Surgical treatment is straightforward, using a limited laminectomy below the level of the conus. The filum terminale is dissected clear of normal nerve rootlets, coagulated, and divided. As with other forms of tethered spinal cords, symptomatic relief occurs frequently, and reversal of scoliosis has been reported in up to one third of the patients [92,93].

Dysraphism associated with anorectal malformations There is clearly an association between congenital anomalies of cloacal-derived structures and tethering lesions of the caudal spinal cord [98 –100]. More than 50% of patients with anorectal, urogenital, or sacral anomalies are found by MRI to have lesions tethering the spinal cord [98,100]. The anorectal and urogenital structures arise from a common cloaca at approximately 7 weeks’ gestation. The future caudal neural tube develops just dorsal to the cloaca at approximately 4 to 7 weeks’ gestation. Because of the proximity of both location and timing of development, it is not surprising that teratogenic events might affect both regions concurrently or might affect one region with induced changes in the other. Pang [99] gives an extensive review of

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the normal embryology and potential aberrations of this region that could lead to associated caudal anomalies and spinal cord tethering. Patients with severe cloacal anomalies tend to have more frequent and complex spinal cord anomalies. For example, cloacal extrophy is associated with more severe cord anomalies than is imperforate anus, whereas a high imperforate anus tends to have more complex cord anomalies than seen with low imperforate anus. Tethering lesions are not excluded by normal sacral radiographs, low imperforate anus, or the absence of symptoms, however [98]. Most of these patients are clinically stable, although it may be difficult to separate symptoms and signs of neurologic dysfunction from those caused by the structural anomalies. MRI screening for evidence of occult spinal cord tethering is recommended in all patients with urogenital, anorectal, and sacral anomalies. If abnormalities are discovered, prophylactic untethering should be performed. Because these patients are clinically stable, neurosurgical intervention can be delayed in those patients undergoing significant abdominal or pelvic reconstructions.

Split-cord malformations The term split-cord malformation (SCM) has been used to categorize several seemingly disparate malformations including diastematomyelia, neurenteric cyst, dorsal intestinal fistula, intestinal duplication, diverticula, and malrotation [101]. Abnormalities in the formation of the neurenteric canal (either its persistence or the formation of an accessory neurenteric canal), have long been suggested as a cause of diastematomyelia. Pang et al [101] have presented a unified theory of embryogenesis based on the presence of an anomalous neurenteric canal, and they have compiled an extensive collection of experimental and clinical data to support this theory. They seem to have accounted for the many variations in abnormal anatomy associated with the split-cord anomalies. SCMs can be classified into two types, based on the anatomy of the clefted region [101]. SCM type I consists of two hemicords, each within a dural sac and separated by a dural-sheathed, rigid osseo-cartilaginous septum. SCM type II has the two hemicords contained within a single dural tube but separated by a nonrigid, fibrous median septum. The true incidence of SCM type II is not known but has been reported to be between 16% and 60% [102 – 104].

Diastematomyelia The term diastematomyelia was first used in 1837 by Ollivier to describe a spinal cord split sagitally, with two dural sleeves that reformed above and below the split. In current usage, diastematomyelia refers to the sagittal cleaving of the spinal cord or filum terminale over one or many levels. The site of cord cleaving is most frequently in the thoracolumbar region; cervical and upper thoracic diastematomyelia is uncommon [55,102,105]. The cord reunites distally in 90%

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of the cases, but the split in the spinal cord often extends well above and below any dural split [55]. Presentation and evaluation All reviews of this entity have reported a marked predominance of female patients, approaching three to one [55,102,105,106]. Cutaneous manifestations, most commonly a hairy patch or nevus often marking the level of the diastematomyelia, are present in most patients (50% – 90%), [55,102,105]. Up to 25% of patients with diastematomyelia concurrently have myelomeningocele. In these patients the diastematomyelia is often not detected until long after the closure of the myelomeningocele [55,102,106]. A relatively small percentage of patients with diastematomyelia are completely without symptoms, and the SCM is discovered after investigation of the cutaneous findings or during incidental evaluation of the spine [106]. Although up to 40% of the patients may be without symptoms or signs initially nearly all, if followed without surgery, manifest some neurologic change [55,107]. Patients remaining asymptomatic into adulthood may suddenly deteriorate [64,108]. Adult patients share many of the presenting findings with children but present more frequently with dysesthetic pain, often perineal or perianal, and urologic dysfunction [105,109]. Their symptoms are often initiated or exacerbated by physical activity. Children have pain much less frequently, usually without the perineal component or dysesthetic quality, and have an insidious progression of symptoms. Most patients with SCM present with symptoms of the tethered cord syndrome, with as many as 75% having at least one orthopedic deformity [55,56,105]. In some patients, scoliosis may be the only symptom, with the severity of the scoliosis progressing as the patient gets older [30]. Whether the scoliosis has a neurologic basis is unclear, because almost all patients concurrently have multiple vertebral anomalies, most commonly segmentation errors including hemivertebrae, butterfly vertebrae, and fused and bifid laminae [30]. It has been estimated that 5% of the patients with congenital scoliosis have diastematomyelia [110]. A collection of findings involving the legs, back, and trunk with a normal neurologic examination has been termed the orthopedic syndrome. This syndrome is seen in 20% to 60% of diastematomyelia patients [55,106,111]. The patient will have a stiff or painful lower back, scoliosis, and a congenitally shorter or smaller leg and foot on one side. The foot may show varus, valgus, or cavus deformities. In adult patients, chronic foot ulceration or poor wound healing with intact sensation has been described. Neurologic symptoms predominate in the other large group of patients. There is unilateral calf wasting with weakness of the ankle and an absent ankle reflex. These patients may manifest mixed upper and lower motor neuron signs, with hyperreflexia of the ipsilateral knee and other leg. Up to 50% of these patients also have scoliosis [106]. There is obviously some overlap in the clinical presentation of these two groups.

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The pathophysiology of symptoms in diastematomyelia has been thought to involve primarily traction on the spinal cord caused by the dividing septum, whether bony or fibrous [105,112]. Simple impingement of the spur on the distal crotch of the split cord during periods of increased growth (early infancy and adolescence) does not seem to be a major factor in causing symptoms. Most patients present between ages 17 months and 6 years, before significant spinal growth [55,106]. The more recent demonstration by Pang [105] that SCM type II lesions have relatively rigid attachments, however, does explain the symptomatology in patients previously identified as having no bony spur. Obviously, tethering of the spinal cord by a tight filum terminale, dermal sinus tract, lipoma, or myelomeningocele may cause symptoms [55,103,106]. There also may be regional effects on the spine involving local ischemic effects or the development of syringomyelia [106,113,114]. MRI should be used as the screening test for a SCM, revealing associated anomalies such as syringomyelia or distal tethering lesions. Syrinx cavities extending into one or both hemicords have been demonstrated in nearly 50% of the patients [105,108,114]. Distal tethering lesions, including thickened filum terminale, lipomas, and dermal sinus tracts, are present in 40% to 90% of these patients [105]. Plain-film radiography in SCMs reveals the often extensive dysraphic changes in the spinal column and is useful for defining and following any associated scoliosis. CT scanning will best show bony anomalies, and is particularly helpful in defining the origin and termination of the cleaving spur on the vertebral body and on the lamina. The spur ossifies from multiple centers, and the degree of ossification increase with time [30]. At the level of the diastematomyelia, the vertebral bodies are hypoplastic, the intervertebral disc spaces are narrowed, and the interpedicular distance is widest [30,105,106]. The most severe anomalies of adjacent vertebral bodies occur in SCM type I. The ossified septum (or spur) usually projects rostrally and ventrally, oriented somewhat obliquely, and is always at the distal end of the spinal cord cleft [30,103,105]. In SCM type II, the vertebral anomalies are less frequent and less severe and may be completely absent [105]. The fibrous septum that tethers the hemicords may not be visualized by either CT myelography or MRI but is always present [105]. Surgery As with the other forms of spinal dysraphism, the goals of surgery include the stabilization of any symptoms, prevention of further deterioration, and the possible reversal of any neurologic deficits that may be present. Surgery is indicated even in asymptomatic patients to prevent the deterioration that can be expected but whose onset cannot be predicted [55,105,107,115]. Morbidity as a direct result of surgery is infrequent [55,102,105,106]. Most patients with neurologic symptoms (80% –90%) experience stabilization or improvement in their symptoms postoperatively [55,102,109,116]. Scoliosis can be expected to stabilize in most of the patients initially, and therefore

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consideration of fusion should be delayed for many months after surgery [102,106]. Urologic dysfunction is the symptom least likely to improve but is usually stabilized.

Meningocele Defects of the dura, arachnoid, and dural pouches without neural elements are called meningoceles. Neural elements are not an intrinsic part of these lesions, although there may be a secondary herniation of nerve roots or cord through the defect [81]. The defect may arise anteriorly, laterally, or posteriorly. Anterior defects are typically in the sacral or thoracic regions. Lateral meningoceles form through the neural foramina, most frequently in the thoracic region. Posterior meningoceles are most common and are typically found in the lumbar region where they have developed through a dorsal laminar defect but remain deep to intact skin. Plain-film radiographs of the affected region show a limited region of spina bifida with the spinal canal widened at the level of the meningocele. MRI or myelography with CT scanning reveals the CSF-filled sac [30]. The sac’s communication with the spinal canal can vary in size, and in some cases the neck may be very narrow. Demonstration of the defect or the shape of the sac can be distorted by changes in intraspinal pressure, such as coughing, performing a Valsalva’s maneuver, or lying on the sac. Anterior meningoceles are most common in the sacral region, usually herniating through a focal bony defect [117]. Women are affected more commonly than men. Over time, however, the defect can enlarge through remodeling of the bony canal by the CSF pulsations. Presenting symptoms include chronic constipation, decreased anal and bladder tone (or incontinence), and sacral hyperesthesia [118]. If the pelvic sac becomes very large, significant CSF fluid shifts can occur between the sac and the spinal canal and can cause symptoms suggestive of both high and low pressure. Anterior sacral meningoceles are usually unilateral and asymmetric and on plain-film radiographs are seen as widening of the lumbosacral canal with scalloping of the sacrum and inferior sacral lamina [30]. When the sac becomes large, the remaining sacrum may become remodeled into a crescent shape [119]. On MRI, the spinal cord is usually identified in a low-lying position, with the conus near the neck of the defect. Occasionally, the cord is tethered by a lipoma or dermoid tumor, which can extend into the defect [30]. Surgical closure of these defects is usually done through a sacral laminectomy. This approach allows the identification and restoration of neural elements to the canal, the untethering of the spinal cord, and direct closure of the neck. A staged anterior abdominal approach may be necessary when the sac is huge but can be complicated by adherence of the meningocele to the rectum and bleeding from surrounding displaced epidural veins [117]. Although significant morbidity and mortality from repair were initially reported, these complications were more

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likely sequelae of prior attempts at diagnosis and treatment. Biopsy or aspiration was often performed through a contaminated route (transrectal or transvaginal) with ensuing infection [117]. Lateral meningoceles are found most often at the thoracic and lumbar levels, most frequently in patients with neurofibromatosis [120]. They protrude through one or more neural foramina. In the thoracic region they can extend into the extrapleural space of the posterolateral thoracic gutter. They are associated with scoliosis, with the meningocele on the outside of the curve and the neural elements in the canal displaced to the inside of the curve. Surgical closure of the sac is often combined with orthopedic approaches to treat the scoliosis. The repair of posterior meningoceles can be approached in a fashion similar to that of myelomeningocele repair.

Chiari II malformation In the 1890s, Chiari described four types of hindbrain anomalies associated with hydrocephalus that now bear his name [121,122]. The Chiari I malformation has no brain malformation, but the cerebellar tonsils extend below the foramen magnum. The incidence of Chiari I malformations in the general population could be as high as 15%. Tonsillar herniation of 2 to 4 mm seems to be insignificant and can be considered normal. The Chiari III malformation includes an encephalocele. The Chiari IV malformation has complete absence of the cerebellum. Cleland in 1883 gave the first anatomic description of what is now called a Chiari II malformation [121]. In 1907, Schwalbe and Gredig [123] reported on several cases with this anomaly and gratuitously attached the name of their mentor, Arnold, to the previously described malformation. The Chiari II malformation is actually an extensive constellation of anomalies affecting the entire brain, skull, and spinal cord to varying degrees, almost invariably associated with myelomeningocele [121,122,124,125]. In the Chiari II malformation, the posterior fossa is small, and the cerebellum, pons, and medulla are displaced to varying degrees into the cervical canal. Although the foramen magnum and upper cervical canal are wider than normal, there is a variable degree of compression of the brainstem. In the supratentorial compartment there may be abnormalities of the corpus callosum, and the thalamic massa intermedia is enlarged. In the upper brainstem the tectum is beaked, whereas the cervicomedullary junction is kinked and in the cervical canal. Several mechanisms of embryogenesis for the Chiari II malformation have been suggested [126 – 130]. These theories are not able to account for all the manifest abnormalities seen. A unified theory has been proposed, based on abnormal development of the ventricular system because of the open dysraphism, which could account for all the abnormalities seen in Chiari II patients [29,131]. Up to 20% of children with myelomeningocele and a Chiari II malformation develop symptoms of hindbrain compression or dysfunction [132]. The symp-

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toms may occur at any age but are the most prominent cause of morbidity and mortality in the first 2 decades [133]. The symptoms vary depending on the age at presentation, and multiple symptoms are common. Infants typically develop symptoms of brainstem dysfunction, such as difficulties with swallowing that manifest as poor or slow feeding or repeated aspirations, apnea, and stridor from vocal cord paresis. Older children are less likely to have brainstem dysfunction, but extremity weakness and recurrent aspiration predominate. The adolescent and adult patients have been described with spasticity, sensory changes, and scoliosis, but these symptoms may actually reflect the development of syringomyelia and its associated symptoms. Symptom progression is also more rapid in the infants [132,134]. Some patients do not respond to surgical decompression, and congenital absence or hypoplasia of the brainstem nuclei or ischemia induced by the hindbrain compression has been suggested as the cause for the lack of response [124,134]. Shunt dysfunction or untreated hydrocephalus can mimic all the symptoms of hindbrain compression. Therefore any hydrocephalus must be treated first, and adequate shunt function should be determined in patients with shunts for hydrocephalus. MRI is used to define the craniocervical junction and the anatomy of the Chiari malformation, with direct visualization of the extent of hindbrain displacement and compression in the cervical canal. The cerebellar displacement with compression can extend anywhere between the C1 and T1 levels. MR imaging of the entire spine may be necessary if symptoms suggest the presence of a syringomyelia. These patients may also have coexisting conditions of the craniocervical junction, such as basilar invagination, atlantoaxial instability, or segmentation anomalies, that should be evaluated with plain-film radiographs and CT. Symptomatic Chiari II malformations are treated with surgical decompression of the hindbrain in the cervical canal. Although often referred to as posterior fossa decompression, the procedure is limited to the cervical spine [132]. The outcome after surgical decompression seems to correlate directly with the severity of symptoms at presentation [134]. In particular, vocal cord paralysis or stridor is a predictor of poor outcome. Older patients with long-tract signs are the most likely to respond to decompression. Most infants stabilize or recover completely, although treatment in infants still carries a high mortality rate between 12% and 40%. The higher mortality in neonates occurs in those with severe brainstem dysfunction. This lack of response to decompression may be secondary to structural anomalies of the brainstem that are unaffected by decompression or to ischemic injury that has become irreversible by the time of operation [124,134].

Associated care issues in spinal dysraphism Many of the patients with spinal dysraphism, particularly those with myelomeningocele and lipoma of the spinal cord, have ongoing disabilities or unique pathophysiologic problems that necessitate long-term care. They are susceptible

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to delayed medical problems that may not be manifest at the time of diagnosis and initial treatment. These problems include neurologic (brainstem dysfunction and compression, hydromyelia, retethering of the spinal cord), urologic (incontinence, renal dysfunction), and orthopedic (scoliosis, limb deformities, changes in ambulation) problems. Social issues also change as the patient ages. When unrecognized or untreated, these problems can lead to significant morbidity. The neurologic problems associated with the Chiari malformation have been discussed. Urologic issues Nearly all patients with myelomeningocele and many with lipomas of the spinal cord have some degree of neurogenic bladder and bowel dysfunction that requires ongoing follow-up and treatment. The timing and methods of evaluation have been debated, but the need for appropriate care is well recognized [135]. There is some evidence that early urodynamic evaluation can identify the patients at risk for later upper urinary tract deterioration [135]. Use of clean intermittent catheterization has become routine, avoiding the need for urinary diversion procedures. Newer pharmacologic manipulations, electrical stimulation, biofeedback programs, and artificial sphincters now augment the care of these patients. Ambulation The ability to move around independently is highly valued in our society. Patients and their families are most concerned at diagnosis about the prognosis for ambulation. The most significant factor affecting ambulation is the degree of neurologic deficit. Patients with sacral lesions should be able to walk independently, whereas those with upper lumbar lesions can achieve mobility with wheelchair use. The prospects for ambulation in patients with midlumbar lesions vary, primarily depending on the specific muscle groups affected rather than on formal neurologic level [136]. Confounding the prediction of function is the effect of later neurologic injuries from Chiari compression, hydromyelia, or retethering. As many as 34% of clinically stable children show a change in mobility toward increasing use of a wheelchair, perhaps as a response to changing social goals or because of the increasing energy demands of a larger body and greater activity [136]. Latex allergy There has been an increasing recognition of latex allergy in spinal dysraphism patients. This allergy is an IgE-mediated reaction, which may be mild with urticaria or severe with bronchospasm, laryngeal edema, and systemic anaphylaxis. The prevalence of clinical allergic reactions may be as high as 20% to 30%, but in one report the serologic evidence of sensitivity was nearly 40% [137]. The operative risk of severe reaction seems low in patients without a history of

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reaction, but even patients with prior reactions can be safely treated by avoiding latex containing equipment and with premedication as necessary. A history of latex allergy should routinely be taken for all patients with spinal dysraphism, and, for those with allergy, appropriate safeguards should be maintained during their hospitalization.

Retethering and reoperation A subpopulation of myelomeningocele and lipomyelomeningocele patients has been identified with the symptoms and signs of tethered cord syndrome occurring after the original repair. The incidence of this retethering in the myelomeningocele population has been estimated at 15% to 20% [138]. This estimate is based on relatively small studies, and the true incidence is not known. The cause of the symptoms is not clearly defined but may arise through the same mechanisms that operate in occult dysraphic conditions. The tethered cord may be more susceptible to compressive injury, with the symptoms related to flattening of the cord against the thoracic kyphosis and a resultant reversible focal ischemia [57,139]. The diagnosis of retethering is primarily clinical. The patients eventually come to attention because of progressive loss of function, but the initial findings are often subtle and are best determined by careful and regular evaluations. Periodic reevaluation of neurologic and muscle function, scoliosis, and urologic function allows the early detection of any deterioration. The most common symptoms of retethering include new or progressive weakness of one or both legs, onset or progression of scoliosis, and a change in gait [58,140]. Pain in the back or legs is much more frequent in patients with lipomyelomeningocele. Urinary dysfunction, characterized by a change in the frequency of catheterization or a loss of continence, and progressive foot and hip deformities are also more common in patients with lipomyelomeningocele. A malfunctioning shunt can cause similar symptoms, and proper shunt function should be established before an untethering operation. A low-lying spinal cord should be identifiable by MRI in all patients with repaired myelomeningocele or lipoma. MRI of the tethered region should still be obtained to show the level of the conus, to define the occasional hydromyelia or tumor (dermoid, epidermoid, lipoma), or to show a previously unknown diastematomyelia. The surgical method for untethering these patients is similar to that used for lipomyelomeningoceles. Particular care must be taken to avoid incising and injuring the neural placode or conus medullaris, which may be attached dorsally to the dilated lumbar CSF space and immediately below the skin. Pathologic conditions (dermoid, lipoma, diastematomyelia) may not be visualized on preoperative MRI and are sometimes found only at operation [58,138,140]. Between 6% and 8% of untetherings are incomplete because of extensive nerve root adhesion and entrapment [140]. Depending on the dissection, patching of the dura may be necessary to effect closure.

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Operative morbidity is limited [58,140]. CSF leakage is the most frequent complication (occurring in approximately 6% of patients) but rarely requires reoperation. Immediate postoperative neurologic decline, typically a minor loss of motor function, may be seen (3%) but usually resolves. The reported results of surgery for retethering have been good, with 70% to 75% of the patients improving from the preoperative condition [58,138,140]. Pain responds best to untethering. Two thirds of the myelomeningocele patients presenting with weakness improve, and patients operated on for other symptoms also have improved motor function. Improvement in gait (less use of an ankle-foot orthosis [AFO], increased walking endurance, improved stance) occurred in 60% to 70%. There is usually much less improvement in the small group of patients presenting with urinary difficulties. The effect of untethering surgery on scoliosis is initially good, with 80% showing stabilization or improvement at 1-year follow-up [57]. When this group is subdivided by the degree of curvature at presentation, nearly all patients with a curvature less than 50° are stable or improved at 1 year, whereas most of the patients with curvature exceeding 50° require fusion. In ensuing years, however, the scoliosis progresses in as many as half of patients not fused. This delayed progression of scoliosis may represent retethering, and an argument for reoperation can be made. It is not clear if these patients should undergo repeat operations, but with the low morbidity and mortality of untethering, subsequent operations can be considered. Perhaps the ability to delay fusion until spinal maturity is reached might result in fewer patients ultimately needing fusion. Why a patient’s scoliosis should actually improve after untethering is unknown. There could be improvement of presumed reversible ischemic cord injury, or there may be improvement to asymmetric spinal musculature tone.

Long-term care One common approach to managing the long-term care of patients with spinal dysraphism patients has been the multidisciplinary clinic. Because no one physician can manage all the various problems these patients encounter, the team of physicians is present in a single setting to coordinate care. Central to the concept of the multidisciplinary clinic is the coordinator of care, whether a physician, nurse, or family member. There are a number of potential or real problems with these clinics. They may not be financially self-supporting; the usual payment and reimbursement methods have changed and may not cover all care. The rise of managed-care plans and division of responsibility for payment of care among government agencies has also led to a fragmentation of caregivers over multiple locations. In addition, the clinics are usually inefficient for the medical participants, a significant factor as resources become scarcer. This inefficiency can result in a decline in participation, sometimes to the point that the clinic can no longer function.

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A review of patients released from one multidisciplinary clinic highlights the care problems [141]. Although the individual medical services continued to be available to these patients, most patients failed to receive both regular and specialty care follow-up. The lack of follow-up was unrelated to method of payment or distance from the hospital but was related to age of the patient. These patients suffered from potentially preventable morbidity as compared with patients actively followed in a multidisciplinary clinic. In one large series of patients with retethering, those followed by such a multidisciplinary clinic presented at an average of 3 months after the onset of symptoms, whereas those referred from outside physicians had an average delay in diagnosis of 11 months [140]. Eighty-two percent of the patients who had been followed in the multidisciplinary clinic improved, compared with only 54% of the referred patients. It seems unrealistic to expect the patients and their families to assume routinely the role of care coordinator in these complicated situations, although many families are forced into this role. Such coordination is more easily done in the setting of a multidisciplinary clinic devoted to patients with spinal dysraphism. Even if there is no combined clinic, using a dedicated coordinator can alleviate many of the care issues. The success in preserving the lives and functions of these patients so that they consistently survive into young adulthood has created a major challenge in their care. The systems set up to care for most of these patients and the physicians most familiar with these pathologic problems are usually part of a pediatric practice or hospital. There are no consistent or good mechanisms for transitioning the care of these patients into the adult-care context. Many of the traditional caregivers are unable or unwilling to treat adult patients with these problems. Many of the practitioners who treat only adults are not aware of or are not sufficiently well versed in these problems. As these patients become young adults, they and their primary physicians must become familiar with the local response to this problem. In some cases, the patient continues to receive care in the pediatric setting. In other locales, an identified physician or group may handle adults. The solution to this issue is far from reliable and presents the major challenge to the continuing improvement in the care of spinal dysraphism.

Summary Defects of development of the neural tube can result in a number of seemingly different malformations. Understanding the abnormal embryology helps one understand the malformations and their surgical treatments. The clinical presentations and the follow-up of these patients require attention to various end organs besides the nervous system. For most of these conditions, long-term follow-up is necessary regardless of initial treatment. A decline in function is not a part

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of the natural history of these malformations and requires prompt evaluation and treatment.

Acknowledgment The author recognizes the contribution of Dr. Kim Rickert in preparing portions of this article.

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