Spine Deformity Preview Issue (September 2012) 85e94 www.spine-deformity.

org

Neurobromatosis: Etiology, Commonly Encountered Spinal Deformities, Common Complications and Pitfalls of Surgical Treatment
Alvin H. Crawford, MD, FACSa,*, Marios G. Lykissas, MD, PhDa, Elizabeth K. Schorry, MDb, Sean Gaines, MDa, Viral Jain, MDa, Tiziani Greggi, MDc, David Viskochil, MDd
a

Division of Orthopaedic Surgery, Cincinnati Childrens Hospital Medical Center, 3333 Burnet Avenue, MLC 2017, Cincinnati, OH 45229, USA b Division of Human Genetics, Cincinnati Childrens Hospital Medical Center, 3333 Burnet Avenue, MLC 4006, Cincinnati, OH 45229, USA c Spine Surgery Division, Rizzoli Orthopaedic Institute, 1 Via GC Pupilli, Bolognia 40136, Italy d Shriners Hospitals for Children Salt Lake City, Fairfax Road at Virginia Street, Salt Lake City, UT 84103, USA

Abstract Neurobromatosis 1 (NF-1) is a multisystemic, autosomal dominant genetic disorder. Skeletal complications usually present early in life and can be attributed to abnormalities of bone growth, remodeling, and repair, or can be secondary to nearby soft-tissue abnormalities complicating NF-1. Skeletal complications can be categorized as generalized or focal manifestations. The incidence of spinal deformities in association with NF-1 varies from 2% to 36%, with scoliosis being the most common. Both heritable and nonheritable factors contribute to the pathogenesis of spinal deformities in NF-1 patients. Traditionally, the spinal deformities are classied into dystrophic or nondystrophic. The pathophysiology of dystrophic curves is still uncertain, but may require a nonhereditary event, such as an adjacent tumor or a second hit event in local bone cells, leading to the underlying dysplasia. Dystrophic curves may result in scoliosis, kyphosis, or frequently, kyphoscoliosis. The goal of surgical management is to arrest the progression of deformity instead of achieving complete correction. The current state-of-the-art treatment for signicant deformity is combined anterior and posterior spinal arthrodesis. Postoperative orthotic immobilization is almost always recommended in an effort to prevent pseudoarthrosis. The orthosis should be maintained until a fusion mass is obtained. Assessment of the fusion mass by computed tomography (CT) or magnetic resonance imaging (MRI) should be performed. Major complications, such as paraplegia, pseudoarthrosis, intraoperative hemorrhage, and postoperative progression of the deformity may occur. In an attempt to eliminate complications and achieve the best results, a multidisciplinary treatment strategy is needed. The intent of this article is to present the spinal deformities that are most commonly associated with NF-1, to identify the underlying biology of spinal deformities based on the most recent literature, and to address the common complications and pitfalls of their surgical management. 2012 Scoliosis Research Society.
Keywords: Neurobromatosis; Spinal deformity; Scoliosis; Kyphosis; Spinal fusion

Introduction Neurobromatosis is a multisystemic, autosomal dominant genetic disorder dened as a spectrum of multifaceted diseases involving neuroectoderm, mesoderm, and endoderm. The primary pathologic process involves activation of the Ras pathway; however, the etiology of many of the nontumor features is still unclear. The clinical features of the most common form of the disease, neurobromatosis
Author disclosures: AHC (none); MGL (none); EKS (none); SG (none); VJ (none); TG (none); DV (none). *Corresponding author. Division of Orthopaedic Surgery, Cincinnati Childrens Hospital Medical Center, 3333 Burnet Avenue, MLC 2017, Cincinnati, OH 45229, USA. Tel.: (513) 636-8932; fax: (513) 636-3928. E-mail address: Alvin.Crawford@cchmc.org (A.H. Crawford). 2212-134X/$ - see front matter 2012 Scoliosis Research Society. http://dx.doi.org/10.1016/j.jspd.2012.04.004

type 1 (NF-1), were reported in several family members by German pathologist Virchow in 1847 [1], but it was his student von Recklinghausen who, 35 years later, described the histologic features of the syndrome that often bears his name [2]. NF-1 is characterized by extreme variability of expression, with manifestations ranging from mild cutaneous lesions to severe life-threatening complications. Skeletal complications usually present early in life and can be attributed to abnormalities of bone growth, remodeling, and repair, or can be secondary to nearby soft-tissue abnormalities complicating NF-1. Skeletal complications can be categorized as generalized or focal manifestations [3]. Generalized skeletal abnormalities include osteoporosis, osteopenia, osteomalacia, shortness of stature, and

86

A.H. Crawford et al. / Spine Deformity Preview Issue (September 2012) 85e94

macrocephaly. Focal abnormalities of the skeleton are less common than generalized abnormalities, but may cause signicant morbidity. Focal manifestations include spinal deformities, dysplasia of the tibia and other long bones, sphenoid wing dysplasia, chest wall deformities (pectus excavatum), dental abnormalities, periapical cemental dysplasia, and cystic osseous lesions. The effect of generalized abnormalities in the occurrence or progression of focal skeletal manifestations remains elusive. The incidence of spinal deformities in association with NF-1 varies from 2% to 36%, with scoliosis being the most common musculoskeletal manifestation of NF-1 [4,5]. The intent of this article is to present the spinal deformities that are most commonly associated with NF-1, to identify the underlying biology of spinal deformities based on the most recent literature, and to address the common complications and pitfalls of their surgical management. Classication Neurobromatosis 1 Neurobromatosis 1 (NF-1), or peripheral neurobromatosis, is a common autosomal dominant single-gene disorder with an estimated prevalence of 1 in 3,000 [6]. It is the most common form of neurobromatosis and the one most likely to be encountered by the orthopedist. It is predicted to affect over 2 million people worldwide in all racial and ethnic groups. The NF-1 gene is large in size, in the range of 350,000 base pairs with 59 exons, and its locus was discovered on chromosome 17q11.2. The diagnosis of NF-1 is established when at least 2 of the most commonly presenting features of the disease, as dened by the 1987 Consensus Development Conference of the National Institutes of Health, are present (Table) [7]. Neurobromatosis 2 Neurobromatosis 2 (NF-2), or central neurobromatosis, has an estimated incidence of 1 in 33,000 individuals and is associated with bilateral vestibular schwannomas and
Table Diagnostic criteria for neurobromatosis 1 as dened by the 1987 Consensus Development Conference of the National Institutes of Health [7]. 1 Six or more caf e au lait macules more than 5 mm in greatest diameter in prepubertal individuals and more than 15 mm in postpubertal individuals Two or more neurobromas of any type or more than one plexiform neurobroma Freckling in the axillary or inguinal regions Two or more Lisch nodules (iris hamartomas) Optic glioma A distinctive osseous lesion, such as sphenoid dysplasia or thinning of long bone cortex, with or without pseudoarthrosis A rst degree relative (parent, sibling, or offspring) with neurobromatosis 1 by the above criteria

multiple spinal shwannomas. NF-1 and NF-2 are genetically distinct disorders with different gene loci, despite the similarity of their names. Segmental neurobromatosis Segmental neurobromatosis is characterized by features of NF-1, but involving a single body segment. Typically, only a single segment of the body (such as left upper extremity) is affected with caf e-au-lait spots and freckling, and lesions usually do not cross the body midline. Legius syndrome Legius syndrome can present with multiple caf e-au-lait spots, freckling, macrocephaly, and mild learning disabilities, but does not present with any of the benign or malignant tumors associated with NF-1. Schwannomatosis Schwannomatosis is a distinct form of neurobromatosis, which typically involves multiple schwannomas throughout the body but without the vestibular schwannomas typical of NF-2. The familial schwannomatosis is due to mutations in the INI1 gene, linked to NF-2 on chromosome 22. Spinal Deformities Etiology The cause of spinal deformity remains unknown. Several theories including metabolic bone deciency, osteomalacia, endocrine disturbance, and mesodermal dysplasia have been proposed and are, at best, inconclusive. The dystrophic changes may be attributed to intrinsic factors or may be associated with anomalies of the spinal canal secondary to abnormalities of the spinal cord dura mater (dural ectasia). Pressure erosive effects of dural ectasia and paravertebral tumors have been frequently found adjacent to and approximated to the deformities, initiating instability and subsequent deformity. Dural ectasia, a disorder unique to certain conditions, is an expansion or dilatation of the dural sac and it is thought to arise from increased hydrostatic pressure, which progressively expands the dural sac. A current alternative hypothesis is mesodermal dysplasia [8]. Scalloping was initially thought to represent the result of erosive pressure or direct inltration of the vertebra by adjacent neurobroma [9-14]. Another proposed cause is a neurobroma-derived, locally active biochemical substance or hormone that triggers dystrophic features in the adjacent vertebra [9]. The altered response of the vertebral bone in NF-1 to a paraspinal tumor has been hypothesized. Some authors suggest an interactive pathophysiological mechanism between a genetically compromised bone and a neuroectodermal derivative, such as a contiguous neurobroma or an abnormal meningeal sheath [9,11].

2 3 4 5 6 7

A.H. Crawford et al. / Spine Deformity Preview Issue (September 2012) 85e94

87

Fig. 1. (A) Eleven-year-old boy with NF-1 and severe cervical kyphosis with spinal cord compression at the level C3eC4 (A). (B) Multiple cervical paraspinal neurobromas are identied on magnetic resonance imaging scan.

A recent study of 10 monozygotic twins with NF-1 demonstrated mixed concordance and discordance for presence of scoliosis [15]. The affected twin pairs were discordant for presence of dystrophic features, degree of curvature, and need for surgery. This nding suggests that both heritable and nonheritable factors contribute to the pathogenesis of spinal deformities in patients with NF-1. Dystrophic curves most likely require a nonhereditary event, such as an adjacent tumor or dural ectasia, or a second hit event in local bone cells leading to the underlying dysplasia. Commonly encountered spinal deformities Cervical spine The dysplastic features are more commonly associated with deformities of the cervical spine compared with other regions of the spine. Most of the patients with spinal deformities are asymptomatic. When symptoms are present, neck pain is the most common presenting concern. In more severe cases, neurologic decits, including nerve root compromise and complete or incomplete spinal cord compromise, may occur. However, clinical consequences of cervical spine deformities are less marked than in other areas of the spine because the cord versus canal diameter is less critical. Anteroposterior and lateral Radiographs of the cervical spine should be obtained in all NF-1 patients who: 1) are placed in halo traction; 2) undergo surgery; 3) require endotracheal intubation; 4) present with neck tumors; 5) complain of neck pain; or 6) present with symptoms indicating intra- or extraspinal neurobromas, such as torticollis or dysphagia. If there is any suspicion of instability, computed tomography (CT) and/or exion-extension magnetic resonance imaging (MRI) are indicated. Erosive defects of the skull may be present in some patients with NF-1. Thus, plain Radiographs of the skull before application of halo or Gardner-Wells tong traction pins are

strongly recommended. A CT scan of the scull may be ordered if plain Radiographs are difcult to interpret. The most commonly encountered cervical spine deformity is kyphosis (Fig. 1). It may be associated with atlantoaxial instability. Progressive kyphosis is more common than nonprogressive kyphosis. The most common scenario is kyphosis secondary to tumor excision surgery with resection of the laminae and posterior elements without stabilization. Therefore, we recommend stabilization of the spinal column at the same time of surgical removal of tumors from the spinal canal. In cases of progressive kyphosis of the cervical spine with instability, posterior spinal fusion is recommended. If the deformity is exible, preoperative halo traction is indicated. For rigid deformities, anterior release followed by halo traction and posterior fusion is the treatment of choice. In cases of previous laminectomy, anterior release and fusion using an autologous bula followed by posterior fusion with autologous iliac bone graft and instrumentation is needed. The level of instability often requires an occipitocervical fusion. Internal xation with pedicle and lateral mass screws is preferred for posterior instrumentation. Sublaminar wire xation may be difcult secondary to dural ectasia and osseous fragility. For anterior xation, we currently use bioabsorbable plates in young children. Even with rigid plate xation, postoperative halo immobilization is recommended until a fusion mass with trabecular pattern is seen on cervical CT. Thoracolumbar spine Scoliosis. Coronal plane deformity of the thoracic and/or lumbar spine can present either with dystrophic features or in a pattern that is clinically indistinguishable from an idiopathic curve. Traditionally, the term dystrophic scoliosis is used to describe thoracic and/or lumbar curves that have, at the time of diagnosis, more than 3 dystrophic features, as identied on plain radiographs. Dystrophic

88

A.H. Crawford et al. / Spine Deformity Preview Issue (September 2012) 85e94

Fig. 2. Seven-year-old female patient with NF-1 and severe cervicothoracic scoliosis, signicant tumor burden around the thoracic spine and spinal cord compression with myelomalacia on imaging, and weakness in the lower extremities (A, B, C, D). Preoperatively, halo traction was applied. The patient underwent C6eT4 bilateral laminectomy for decompression of spinal cord followed by C4eT12 cervicothoracic posterior fusion with instrumentation and allograft (E, F, G, H).

features include rib penciling (the rib being smaller in diameter than the 2nd rib), vertebral rotation, posterior vertebral scalloping, vertebral wedging, spindling of the transverse process, anterior vertebral scalloping, widened intervertebral foramina, enlarged intervertebral foramina, and lateral vertebral scalloping. The concept of modulation refers to the ability of a spinal deformity to transform by acquiring various dystrophic features. This condition has been described only in patients with NF-1. Modulation can result either in transformation of a nondystrophic curve to dystrophic, or an addition of further dystrophic features to a curve already diagnosed as dystrophic. More recent MRI studies have questioned the theory of modulation [16]. Patients with radiographically labeled nondystrophic curves have been found to have signicant dysplastic changes on MRI. Considering the higher sensitivity of MRI in identifying dystrophic features compared with X-rays lms, we recommend characterization of the curve as dystrophic or not based on ndings from both MRI and X-ray lms.

Nondystrophic scoliosis. Nondystrophic scoliosis represents the most common spinal deformity in patients with NF-1. Clinical and radiographic ndings, treatment, and complications are similar to those described for idiopathic scoliosis [17]. Observation is indicated for patients with nondystrophic curves measuring 20 to 25 . If the patient is skeletally immature and presents with a curve between 25 and 40 , bracing or growing rod is to be considered. If the deformity exceeds 40 , it should be treated with posterior spinal fusion with instrumentation (Fig. 2). For curves exceeding 55 to 60 , the treatment is anterior disc excision and fusion with autologous bone graft of the area of curvature followed by posterior spinal fusion of all articular facets, segmental spinal instrumentation, and autogenous iliac crest bone graft [18]. Postoperative orthosis and assessment of the fusion mass by CT or MRI at 6 months after surgery are highly recommended (Fig. 3). Dystrophic Scoliosis. Although less common than nondystrophic curves, dystrophic curves represent a challenge

A.H. Crawford et al. / Spine Deformity Preview Issue (September 2012) 85e94

89

intervertebral fusion, followed by posterior fusion and stabilization with segmental instrumentation [22]. For rigid curves greater than 90 , we recommend anterior release, nasojejunal tube alimentation, and craniofemoral traction followed by posterior spinal fusion. If the curve exceeds 100 in any plane, anterior and posterior release, nasojejunal tube alimentation, and craniofemoral traction followed by posterior spinal fusion is our treatment of choice. The goal of surgical management is to arrest the progression of deformity instead of achieving complete correction [20]. We always recommend postoperative orthotic immobilization in an effort to prevent pseudoarthrosis. The orthosis should be maintained until a fusion mass is obtained. Assessment of the fusion mass by CT or MRI at 6 months after surgery is recommended. Kyphoscoliosis. Kyphoscoliosis is distinguished by a curve of 50 or more in the sagittal plane associated with any degree of coronal deformity (Fig. 4). Paraplegia is a not infrequent complication in patients with NF-1 and kyphoscoliosis. This can be explained by elongation of the spinal canal and deformation of the spinal cord after increased spinal exion, as in case of kyphosis [23]. This, in turn, will lead to excessive tension of the spinal cord parenchyma and subsequent neurologic impairment. Dural ectasia and spinal canal expansion is felt to be protective of the spinal cord in severe curves. In all NF-1 patients with paraplegia, rib protrusion into the spinal canal and intraspinal tumors should be ruled out with an MRI. Imaging evaluation of kyphoscoliosis also includes a hyperextension cross table lateral view with the patient lying over a bolster to access the exibility of the curvature. The vertebral bodies at the apex are frequently so deformed that it may be impossible to identify them on plain Radiographs. In such cases, a 3dimensional CT scan can be very helpful in surgical planning. All patients with NF-1 and associated kyphoscoliosis require both anterior and posterior fusion [22]. Even if a combined approach is performed, a bona de fusion is not always achievable, making repeat operative procedures occasionally necessary. With exible curves, these procedures can be performed during the same anesthesia, unless there is a medical contraindication. If the deformity is severe and rigid, we recommend a staged procedure to obtain better correction. Anterior release and intervertebral body fusion is followed by craniofemoral traction of 7 to 10 days, during which the patient should be observed carefully with repeated neurologic examinations. Then, posterior instrumented fusion is performed. Assessment of the fusion mass by CT at 6 months postoperatively is recommended. If pseudoarthrosis is noted, augmentation of the fusion mass is indicated. Vertebral column resection is an option in some of these cases. Lordoscoliosis. Lordoscoliosis has not been as frequently reported in patients with NF-1 as kyphoscoliosis is (Fig. 5).

Fig. 3. Postoperative coronal computed tomography of a 14-year-old male patient with dystrophic curve of the thoracic spine. A solid fusion mass is noted at 6 months after his instrumented posterior spinal fusion from T3eT12.

for the spine surgeon. They are characterized by rapid course of progression, a tendency to progress to a severe deformity, and a higher rate of pseudoarthrosis after surgery. A dystrophic curve is dened as any curvature with 3 or more dystrophic features. The classic dystrophic deformity is a short segmented and sharply angulated curve that usually involves less than 6 spinal segments in the upper thoracic spine. Apical vertebral rotation can become so severe that it rotates out of the support axis [19]. On plain radiographs, this may be interpreted as a congenital deformity. The patient may present with scoliosis, kyphosis, or frequently, with kyphoscoliosis. Almost all authors agree on an early and aggressive approach to dystrophic curves [19,20]. This discussion will not include early onset spinal deformities in children under 9 years old. Bracing has not been effective and is not recommended in any dystrophic deformity. Dystrophic curves less than 20 should be observed for progression at 6-month intervals. For patients with deformity between 20 and 40 in the coronal plane, a posterior spinal fusion from the neutral vertebra cephalad to the curve to the neutral vertebra caudal to the curve and segmental spinal instrumentation with pedicle screws, if possible, is performed [21,22]. The use of autogenous iliac crest graft is highly recommended to minimize the occurrence of pseudoarthrosis and recurrence of the deformity. Trunkal height loss is not signicant because the curve is usually short with poor growth potential in the involved vertebrae. Dystrophic curves exceeding 40 in the coronal plane or associated with kyphosis greater than 50 should be treated with anterior discectomy and

90

A.H. Crawford et al. / Spine Deformity Preview Issue (September 2012) 85e94

Fig. 4. (A, B, C) Male patient with NF-1, progressive kyphoscoliosis, and congenital heart disease. (D, E) At age 17 years, he underwent posterior spinal fusion with instrumentation from T1eL2.

However, lordosis of the thoracic spine may predispose to signicant respiratory compromise and mitral valve prolapse. Anterior release and intervertebral fusion followed by posterior instrumented fusion is considered the most reliable surgical option to achieve correction of dystrophic lordoscoliosis. Sublaminar wires, pedicle screws, or rod-multiple hook constructs can be used. Spondylolisthesis. Spondylolisthesis in patients with NF-1 is rare [14]. It is characterized by pathologic forward progression of the anterior elements of the spinal column. Spondylolisthesis in patients with NF-1 is most often

associated with pathologic elongation and thinning of the pedicles or pars interarticularis by lumbosacral foraminal neurobromas or dural ectasia with meningoceles. The vertebral bodies may also be small and dystrophic. MRI and/or CT scans are absolutely necessary for preoperative evaluation. Fusion may also be delayed because of the forward traction effect of the vertebral bodies and the slow healing and remodeling of bone for patients with NF-1. We recommend a combined anterior and posterior fusion from L4 to sacrum using intervertebral body grafting and lumbosacral instrumentation. Postoperative immobilization is indicated until the fusion is absolutely solid.

A.H. Crawford et al. / Spine Deformity Preview Issue (September 2012) 85e94

91

Fig. 5. Clinical (A, B) and radiographic (C, D, E) presentation of a 9-year-old female patient with NF-1, lordoscoliosis of the thoracic spine and signicant tracheobronchial tumor load. (F, G) She was treated with a posterior spinal fusion and instrumentation with a hybrid construct extending from T1eL1.

Complications and Pitfalls of Surgical treatment Pseudoarthrosis The incidence of pseudoarthrosis after an attempt at spinal fusion in NF-1 patients with dystrophic or nondystrophic spinal deformities is higher than in patients with idiopathic scoliosis. Crawford reported a 15% incidence of pseudoarthrosis [22]. Sirois and Drennan reported a 38% incidence of pseudoarthrosis and an average of 1.7

procedures to achieve solid fusion [24]. Parisini et al. conducted a retrospective evaluation of surgical outcomes in NF-1 patients with severe progressive scoliosis in the pediatric age group [20]. Twenty-three consecutive patients were surgically treated over 15 years. Patients were divided into 2 groups according to the surgical procedure adopted. Fusion failure was observed in 47% of patients who underwent posterior fusion alone and in 33% of patients who underwent preplanned circumferential fusion.

92

A.H. Crawford et al. / Spine Deformity Preview Issue (September 2012) 85e94

Fig. 6. Treatment algorithm in patients with neurobromatosis 1 (NF-1) and spinal deformity.

Decortication, abundant autogenous bone grafting, and segmental instrumentation are necessary to minimize the occurrence of pseudoarthrosis. Pedicle screw xation is the treatment of choice if pedicles are adequate. Hooks and/or sublaminar wires should be available. During anterior diskectomy and release, meticulous resection of all the pathologic soft tissue is of paramount importance. Any graft material that is surrounded by abnormal soft tissue tends to resorb in the midportion. Even if rigid xation has been achieved using modern instrumentation, orthotic immobilization is recommended until a fusion mass with trabecular pattern is seen in CT scan performed 6 months after surgery. Re-exploration and graft augmentation is indicated for failed fusions. Most recently, recombinant human bone morphogenetic protein-2 (rhBMP-2) has been used off label to achieve a denitive fusion. A recent report of malignant transformation of a neurobroma to sarcoma after application of rhBMP-2 has been published [25]. Although there does not appear to be a clear association, the potential for stimulation of malignant degeneration of a benign plexiform neurobroma gives one concern. Paraplegia A neurologic decit in a patient with NF-1 can be due to spinal cord compression secondary to spinal deformity, rib penetration into the spinal canal, or intraspinal tumors, including neurobromata, schwannoma or other tumors of

neuroectodermal origin. Paraplegia in young patients is usually caused by spinal deformity, whereas in older patients it is usually caused by tumors. Neurologic impairment is more common in patients with NF-1 and kyphosis. Patients with paraplegia associated with spinal curvatures and without signicant kyphosis should be assumed to have intraspinal lesions until proven otherwise. In any case, the cause should be accurately dened with an MRI of the spine. Rib protrusion Clinical presentation of intraspinal rib displacement varies with the majority of patients being asymptomatic [26]. A painful rib hump has been described as a warning sign of rib dislocation [27]. More severe cases may result in paraplegia secondary to spinal cord impingement. Rib protrusion occurs at the convex side of the apex and usually involves a single middle to lower rib. In contrast, the spinal cord in the canal usually displaces towards the concave side. When rib dislocation is present and not addressed before surgery, correcting the deformity may cause the cord to be centralized in the canal and impinged by the rib head on the convex side. Rib head dislocation into the spinal canal should be ruled out before any attempt for surgical correction of the spinal deformity because correction may result in spinal cord impingement by the unrecognized dislocated rib head.

A.H. Crawford et al. / Spine Deformity Preview Issue (September 2012) 85e94

93

Imaging with CT is indicated to accurately demonstrate bone pathology. When rib protrusion is identied before surgery, ostectomy of 2.5 to 5 cm of the protruding rib is indicated at the time of posterior fusion. Vertebral column dislocation Extensive osseous erosion secondary to dural ectasia may result in subluxation or dislocation of the spine with little radiographic or clinical warning. This diagnosis should be considered in any patient with NF-1 who complains of pain in the neck or back. Rotational dislocation of the spine in patients with NF-1 is a rare complication rst described by Duval-Beaupere and Dubousset in 1972 [28]. It usually involves the thoracic spine and results in progressive spinal deformity with or without neurologic decit. Atlantoaxial instability has been attributed to laxity of capsular and ligamentous structures. Posterior spinal fusion is recommended in patients with cervical spine instability. The level of instability often requires an occipitocervical fusion. Even when using instrumentation, a halo orthosis is recommended to stabilize the occipitocervicothoracic area until fusion takes place. The screening for instability is only carried out in patients who have undergone surgical decompression without fusion. Patients not treated with surgery are screened annually with a plain Radiograph. Intraoperative complications Bleeding during spine deformity surgery as well as postoperative hemorrhage and hematoma formation are not uncommon in patients with NF-1, especially if an anterior approach was used. Meticulous hemostasis using bipolar coagulation and hemostatic agents, ie, thrombin, hemostatic matrix (Floseal, Baxter, USA), must be carried out during surgery. The senior author recommends a putty of Gelfoam (Baxter, USA), microbrillar collagen hemostat (Avitene, Davol Inc., USA) and thrombin (human powder) to be available. Hemovac drainage is recommended in all patients with NF-1 undergoing spine surgery. Progression Progression of the deformity may be noticed after solid spinal arthrodesis. Thus, close follow-up is needed even after successful spinal fusion. In patients who are skeletally immature, anterior spinal fusion in conjunction with posterior surgery is required to prevent the occurrence of crankshaft phenomenon, which is produced by continuing unbalanced anterior vertebral growth. Pulmonary compromise Lordoscoliosis predisposes to signicant decrease in pulmonary function and mitral valve prolapse. Anterior

surgery may result in pulmonary problems, including atelectasis, pneumonia, and hemothorax. Pulmonary symptoms, including cough and dyspnea, have been associated with massive intrathoracic meningoceles. Gastrointestinal problems Ileus and nutritional problems are not infrequent when a staged anterior and posterior spine surgery is performed and while the patient is kept in craniofemoral traction. Therefore, we recommend nasojejunal tube placement and hyperalimentation for all patients who undergo staged anterior and posterior surgery. Other Additional complications after surgical treatment of spinal deformities in patients with NF-1 include dural leaks, urinary track infection, and thrombophlebitis. Conclusion Scoliosis is the most common osseous manifestation of NF-1 (Fig. 6). It is important to recognize the dystrophic curve and to distinguish it from the nondystrophic curve. Dystrophic curves may result in scoliosis, kyphosis, or frequently, kyphoscoliosis. Bracing is not effective in the management of dystrophic curves, and an aggressive approach to management is recommended. The current state-of-the-art treatment for signicant deformity is combined anterior and posterior spinal arthrodesis. Postoperative orthotic immobilization is almost always recommended in an effort to prevent pseudoarthrosis. Major complications, such as paraplegia, pseudoarthrosis, intraoperative hemorrhage, and postoperative progression of the deformity may occur. In an attempt to eliminate complications and achieve the best results, a multidisciplinary treatment strategy is needed. References
[1] Virchow R. Ueber die reform der pathologischen und therpeutischen anschaungen durch die mikrokopischen untersuchungen. Arch Pathol Anat Physiol Klin Med 1847;1:207e55. [2] Von Recklinghausen FD. Ueber die multiplen brome der haut und ihre besiehung zu den multiplen neuromen. Berlin: Hirschwald; 1882. [3] Elefteriou F, Kolanczyk M, Schindeler A, et al. Skeletal abnormalities in neurobromatosis type 1: approaches to therapeutic options. Am J Med Genet A 2009;149A:2327e38. [4] Halmai V, Dom an I, de Jonge T, et al. Surgical treatment of spinal deformities associated with neurobromatosis type 1. Report of 12 cases. J Neurosurg 2002;97(3 Suppl):310e6. [5] Akbarnia BA, Gabriel KR, Beckman E, et al. Prevalence of scoliosis in neurobromatosis. Spine (Phila Pa 1976) 1992;17(8 Suppl): S244e8. [6] Ferner RE, Huson SM, Thomas N, et al. Guidelines for the diagnosis and management of individuals with neurobromatosis 1. J Med Genet 2007;44:81e8. [7] National Institutes of Health Consensus Development Conference. Neurobromatosis. Conference Statement. Arch Neurol 1988;45:575e8.

94

A.H. Crawford et al. / Spine Deformity Preview Issue (September 2012) 85e94 [19] Winter RB, Lonstein JE, Anderson M. Neurobromatosis hyperkyphosis: a review of 33 patients with kyphosis of 80 degrees or greater. J Spinal Disord 1988;1:39e49. [20] Parisini P, Di Silvestre M, Greggi T, et al. Surgical correction of dystrophic spinal curves in neurobromatosis. A review of 56 patients. Spine (Phila Pa 1976) 1999;24:2247e53. [21] Easton DF, Ponder MA, Huson SM, et al. An analysis of variation in expression of neurobromatosis (NF) type 1 (NF1): Evidence for modifying genes. Am J Hum Genet 1993;53:305e13. [22] Crawford AH. Neurobromatosis in children. Acta Orthop Scand Suppl 1986;218:1e60. [23] Breig A. Biomechanics of the central nervous system: some basic and normal pathological phenomena concerning spine, disk and cord. Stockholm: Almquist and Wiskel; 1960. [24] Sirois 3rd JL, Drennan JC. Dystrophic spinal deformity in neurobromatosis. J Pediatr Orthop 1990;10:522e6. [25] Steib JP, Bouchaib J, Walter A, et al. Could an osteoinductor result in degeneration of a neurobroma in NF1? Eur Spine J 2010;19(Suppl 2): S220e5. [26] Ton J, Stein-Wexler R, Yen P, et al. Rib head protrusion into the central canal in type 1 neurobromatosis. Pediatr Radiol 2010;40:1902e9. [27] Gkiokas A, Hadzimichalis S, Vasiliadis E, et al. Painful rib hump: a new clinical sign for detecting intraspinal rib displacement in scoliosis due to neurobromatosis. Scoliosis 2006;1:10. [28] Zeller RD, Dubousset J. Progressive rotational dislocation in kyphoscoliotic deformities presentation and treatment. Spine (Phila Pa 1976) 2000;25:1092e7.

[8] Kissil JL, Blakeley JO, Ferner RE, et al. Whats new in neurobromatosis? Proceedings from the 2009 NF Conference: new frontiers. Am J Med Genet A 2010;152A:269e83. [9] Casselman ES, Mandell GA. Vertebral scalloping in neurobromatosis. Radiology 1979;131:89e94. [10] Laws JW, Pallis C. Spinal deformities in neurobromatosis. J Bone Joint Surg Br 1963;45:674e82. [11] Salerno NR, Edeiken J. Vertebral scalloping in neurobromatosis. Radiology 1970;97:509e10. [12] Heard G, Payne EE. Scalloping of the vertebral bodies in von Recklinghausens disease of the nervous system (neurobromatosis). J Neurol Neurosurg Psychiatr 1962;25:345e51. [13] Hunt JC, Pugh DG. Skeletal lesions in neurobromatosis. Radiology 1961;76:1e20. [14] Crawford AH, Bagamery N. Osseous manifestations of neurobromatosis in childhood. J Pediatr Orthop 1986;6:72e88. [15] Rieley MB, Stevenson DA, Viskochil DH, et al. Variable expression of neurobromatosis 1 in monozygotic twins. Am J Med Genet A 2011;155A:478e85. [16] Tsirikos AI, Ramachandran M, Lee J, et al. Assessment of vertebral scalloping in neurobromatosis type 1 with plain radiography and MRI. Clin Radiol 2004;59:1009e17. [17] Crawford AH, Schorry EK. Neurobromatosis update. J Pediatr Orthop 2006;26:413e23. [18] Crawford AH. Pitfalls of spinal deformities associated with neurobromatosis in children. Clin Orthop Relat Res 1989;245: 29e42.