Orthopedic Manifestations of Neurofibromatosis Type 1 

The orthopedic manifestations and, especially, the complications after treatment of neurofibromatosis type 1 (NF1) are common and have a prominent place in the orthopedic literature. The intent of this article is to identify the complications most commonly associated with the orthopedic manifestations of neurofibromatosis and to present strategies for their management.^{[1, 2, 3]}

The orthopedic complications of neurofibromatosis, which usually appear early, include spinal deformities such as scoliosis and kyphoscoliosis, congenital bowing and pseudoarthrosis of the tibia and the forearm, overgrowth phenomenon of the extremity, and soft tissue tumors.^{[1, 4]}

Neurofibromatosis type 2 (NF2) does not appear to have any bone involvement or other orthopedic manifestations. As a result, it is not discussed in this article.

Spinal deformities have been noted to occur only in individuals with NF1. Deformities include dystrophic and nondystrophic changes. The radiologic appearance of the dystrophic changes includes the following features:

• Scalloping of the posterior vertebral margins
• Severe rotation of the apical vertebra
• Widening of the spinal canal
• Enlargement of the neural foramina
• Defective pedicles
• A paraspinal mass
• Spindling of the transverse process
• Rotation of the ribs - The ribs resemble twisted ribbons

In some cases, these changes are the result of intraspinal pathology, such as tumors,^[5] meningoceles, or dural ectasia. However, the changes may also occur in persons with entirely normal intraspinal contents. In these persons, primary bone dysplasia accounts for the dystrophic changes.^[6]

Spinal changes in individuals with NF1 are usually divided into cervical, thoracic, lumbosacral, and spinal canal pathologies.

Cervical spine changes and associated complications

Features of the cervical spine in patients with NF1 have not received enough attention in the literature. Cervical abnormalities occur much more frequently when a scoliosis or kyphoscoliosis is present in the thoracolumbar region, in which case the examiner's attention is focused on the more obvious deformity.

The manifestations of NF1 can be observed as dystrophic changes in the vertebral body, or they can be due to pathologic alignment. The most common abnormality observed is a severe cervical kyphosis, which in itself is highly suggestive of the disorder.

In a study by Yong-Hing et al, 17 patients with NF1 were found to have cervical abnormalities.^[7] Of these, 7 were asymptomatic, while the rest had either limited motion or pain in the neck. Four patients had neurologic deficits, which were probably attributed to cervical instability. Four of the 17 patients required fusion of the cervical spine. Curtis described 8 patients with paraplegia and NF1. Paraplegia in 4 of these patients was due to cervical spine instability or intraspinal pathology in the cervical spine.^[8]

Attention also should be paid to the C1-2 region. Isu described 3 patients with NF1 who had C1-2 dislocation with neurologic deficit, and all improved after decompression or fusion. No bony changes in the C1-2 relationship were observed on flexion-extension views in any of these patients. Most of the problems in the cervical spine in this study occurred after excision of the tumors, which included resection of the laminae and posterior elements. Postoperatively, the spine is unstable and tends to develop progressive kyphosis.

All patients with NF1 who undergo surgery, who require endotracheal anesthesia, who undergo halo traction, or who present with neck tumors should undergo a cervical radiographic series. If subluxation is suspected, tomograms, computed tomography (CT) scans, and/or magnetic resonance imaging (MRI) scans are appropriate. Other reasons for obtaining cervical spinal radiographs in a patient with NF1 include the evaluation of torticollis and dysphagia.

Scoliosis

Scoliosis is the most common osseous defect associated with NF1. It may vary in severity from mild and nonprogressive to severe curvatures. The cause of this spinal deformity is unknown, but some have suggested that it is secondary to endocrine disturbances, mesodermal dysplasia, and osteomalacia (a localized neurofibromatous tumor eroding and infiltrating bone).

In a general orthopedic clinic, 2% of patients with scoliosis have neurofibromatosis, whereas in a neurofibromatosis clinic, 10-20% of patients have some disorder of the spine. All preadolescent children with neurofibromatosis should be evaluated with scoliosis screening, or the bend test, to exclude a spinal deformity, which usually occurs earlier in children with neurofibromatosis.

Two primary types of scoliosis are observed in persons with neurofibromatosis. Dystrophic scoliosis is the short-segmented, sharply angulated type that includes fewer than 6 spinal segments. It has a tendency to progress to a severe deformity.^{[9, 10]} The second type of curvature, in nondystrophic scoliosis, is similar to the idiopathic curvature observed in adolescents. This form usually involves 8-10 spinal segments. The deformity is most often convex to the right; however, this is not consistent.

Meningoceles, pseudomeningoceles, dural ectasia, and dumbbell lesions are all related to the presence of neurofibroma or abnormal pressure phenomena in and around the spinal canal neuraxis. High-volume myelography or MRI should be used in the investigation of all dystrophic curves prior to treatment. Occasionally, these intraspinal elements may directly compromise the cord when instrumentation and stabilization are attempted, or they may cause erosive changes in the bone, preventing primary fusion.

The cervical spine should be evaluated with the initial scoliosis investigation. Evidence of dystrophic changes may be present on a true lateral view. Progressive cervical kyphosis is usually apparent after excision of the posterior elements. The patient presents with a neck deformity after anterior and posterior excision of a neck mass. If any suspicious area is noted on plain radiographs, right and left oblique views should be obtained to look for widening of the neuroforamina. These may represent dumbbell lesions (ie, widening of the neuroforamina caused by the exit of a neurofibroma from the spinal canal).

Kyphosis

Kyphosis observed in individuals with NF1 is distinguished by acute anteroposterior angulation. Vertebral bodies may be deformed so severely that they are confused with congenital deformities.

Spondylolisthesis

Spondylolisthesis is a rare disorder that is most often associated with a pathologic luxation of the vertebra because of erosions of the pedicles or pars from foraminal neurofibroma or dural ectasia.

Tibial bowing occurs in 1 per 140,000 live births. The bowing associated with NF1 is always anterolateral. The deformity may appear before other protean manifestations, such as café-au-lait spots. It is usually evident within the first year of life, with a fracture not uncommonly occurring by the time the child is aged 2-2.5 years. Conversely, posteromedial congenital bowing, or kyphoscoliosis tibia, is a benign condition.

Tibial bowing associated with bilateral skin dimples, ring constrictions, and foot deformities is rarely associated with NF1. The management of this anterolateral bowing deformity is most frustrating. Unlike scoliosis, treatment of congenital pseudarthrosis of the tibia does not appear to be more successful when it is initiated early.

The 2 basic types of bowing are the nondysplastic type and the dysplastic type.

Nondysplastic, or type I, bowing is defined as follows:

• Anterolateral bowing with increased bony density
• Sclerosis of the medullary canal
• Possibility of this type converting to dysplastic after osteotomy to correct the angulation

Dysplastic, or type II, bowing is defined as follows:

• Anterolateral bowing with a failure of tubulation
• Anterolateral bowing with cystic prefracture or canal enlargement from previous fracture
• Frank pseudarthrosis and atrophy with "sucked candy" narrowing of the ends of the 2 fragments

Scoliosis

Dystrophic curvatures of less than 20° should be observed for progression at 6-month intervals. For persons with curvature greater than 20-40° of angulation, a posterior spinal fusion with some form of segmental spinal instrumentation is recommended.^[11] Curves greater than 50° should be treated with anterior and posterior fusion.

Oblique radiographs are obtained every 6 months to exclude pseudarthrosis. Brace treatment has not been effective. For the very young child, early fusion causes minimal stunting of growth. Nondystrophic curvatures of less than 20° should be observed, those of 20-35° should be braced, and nondystrophic curvatures of 35° or greater should be stabilized by means of anterior and posterior fusion with segmental spinal instrumentation.

Kyphosis

Bracing is recommended for patients with kyphosis of less than 50°. In patients with curvatures greater than 50°, anterior surgery (intervertebral diskectomy, rib strut grafting, and bone chip grafting) is recommended, followed by posterior segmental instrumentation. Once a curvature exceeds 70°, indefinite bracing is required, even after spinal surgery.

Because of the association of paraplegia with kyphosis, physicians have tended to perform laminectomy. Laminectomy alone for kyphotic cord compression is absolutely contraindicated. The offending neurofibromas are usually anterior, and decompression should be performed anteriorly. The removal of the posterior element predisposes the spine to instability by removing valuable bone stock required for fusion. Spinal fusion should be performed after laminectomy.

Spondylolisthesis

Anterior and posterior stabilization is recommended for progressive deformity. Progression of spondylolistheses from grade II to grade II or the presence of pathologically elongated pedicles with or without pain are indications for surgery.

Subcutaneous plexiform neurofibromas are often overlying the incision area. When posterior spinal fusion surgery is performed, one should be aware of the very thin laminae, which are often eroded by dural ectasia surrounding the spinal cord in the thoracic region. The laminae may be inadequate to accept hooks, and pedicle screws may be necessary. Considerable bleeding may occur with dissection around subcutaneous vascular tumors. The author recommends using monopolar and bipolar electrocautery for subperiosteal exposure of the posterior elements.

Posterior subperiosteal dissection is performed by using Bovie electrocautery dissection rather than subperiosteal elevators because of the potential presence of laminar defects or the possibility of inadvertently plunging through the lamina and directly damaging the spinal cord.

Anterior spinal dissection may be complicated by venous lakes and engorgement of saccular, almost sinusoidal, vessels, which are difficult to control in and around the vertebral bodies. Extensive blood loss from the blood vessels in the cancellous bone of the vertebral bodies is distinctly possible.

Diskectomies should be performed with Bovie dissection and use of a rongeur through the annulus fibrosis instead of sharp dissections of the endplate apophysis. Sharp dissections may cause significant bleeding from the often-friable cancellous matrix of the vertebral bodies.

Bracing can be both preventive and therapeutic. Children should be fitted with polypropylene knee-ankle-foot orthoses (KAFOs) as soon as they start to stand or walk around furniture.

Pulsating electromagnetic fields may also be used in the treatment of tibial dysplasia. The source of the fields may be external, such as the clamshell device over an ankle-foot orthosis, or an internal unit implanted in the soft tissue around the area of pseudarthrosis, usually in conjunction with an autogenous bone graft. The effectiveness of this form of treatment remains highly controversial.

Obvious documented fracture is the only current direct indication for surgery in congenital tibial dysplasia. In children older than 5 years, subsequent bracing above the knee and articulated at the knee and ankle has been tremendously successful in managing angular deformities and preventing fractures. The surgical treatments include direct bone grafting, vascularized autogenous grafting, compression and distraction osteogenesis, and amputation.

Subperiosteal dissection should be performed to expose the pseudoarthrosis site in congenital tibial dysplasia. Both ends are freshened, and a decision is made regarding whether an intermedullary rod or external fixation should be used. Use of an autologous iliac crest bone graft is highly recommended, regardless of the surgical procedure. A vascularized fibular bone graft is another option.

Surgical bone grafting

Autogenous bone is placed into the excised pseudarthrosis site. An intramedullary rod is placed from the proximal tibia across the pseudarthrosis site, incorporating the graft and extending down through the ankle, across the talus, and into the calcaneus. Rod replacement is required as the patient grows, and continuous bracing is necessary. A telescoping rod may be used and affixed to the distal tibia. Another variation is to retrograde a rush rod from the calcaneus across the ankle, incorporating the grafted segment and continuing into the proximal tibial metaphysis.

Vascularized autogenous grafting

The most popular vascularized graft is the contralateral fibula, which is followed by the iliac crest. The graft is removed extraperiosteally and placed into the pseudarthrosis site. The blood vessels are then anastomosed to those normally supplying the tibia. Stabilizing the grafted segment is necessary. The distal tibia and fibula of the normal leg must be fused to prevent proximal migration of the fibular and ankle valgus.

Problems associated with vascularized grafts include progressive angular deformity, failure to achieve complete length, failure to unite with consequent further pseudarthrosis, valgus ankle instability, and disability in the donor limb.

Compression and distraction histogenesis

Compression and distraction histogenesis of bone and soft tissue using the Ilizarov method offers many theoretical advantages in the treatment of this problem. Unfortunately, the early, glowing reports of bony synostosis failed in patients in whom bracing was not continued. Efforts now are being directed toward distraction and/or compression histogenesis over an intramedullary rod. Early reports are encouraging.

Amputation

Amputation remains a viable alternative. The weight-bearing surface of the foot should be maintained á la Boyd-Syme amputation, as opposed to a transtibial amputation that predisposes the child to subsequent surgeries for bony stump overgrowth. The length from this procedure adds biomechanical stability to prosthetic wear. The new Seattle foot and/or runner's foot have made prosthetics more functional, and participation in team sports such as soccer is not prohibited after this procedure.

Surgical considerations

Regardless of the procedure used, some form of bracing is required for all of these patients until skeletal maturity is achieved. The potentially high incidence (25%) of subsequent central nervous system neoplasms should prompt consideration whether attempts at bone grafting should be continued after 3 or 4 procedures. By the time the child is aged 7 years, the benefit of further procedures, as opposed to amputation, should be scrutinized carefully.

Two disorders of bone growth are segmental hypertrophy and subperiosteal proliferative bone growth. The diffuse hypertrophy of an extremity may be related to changes in the soft tissues (eg, hemangiomatosis, lymph angiomatosis, elephantiasis, beaded plexiform neuromas). The zones of overgrowth in bone and soft tissues are usually unilateral, involving the lower extremities or the head and neck. These osseous changes characteristically cause the bone to elongate with a wavy irregularity or thickening of the cortex. A higher incidence of neoplasia is associated with segmental hypertrophy than with other lesions.

Attempts to debulk the soft tissue and to resect the bone have not necessarily resulted in significant cosmetic improvement. Early epiphyseal arrest of the involved bone or leg lengthening of the normal, short side has been fairly successful.

Spine

Bracing of progressive dystrophic curvatures is contraindicated simply because they have not been found to be effective. The authors' investigations have revealed a transition of idiopathic-type curves to dystrophic types (modulation). Posterior spinal fusion alone is now believed to be contraindicated in young patients with progressive deformities. An anterior diskectomy and intravertebral fusion followed by posterior spinal fusion is the recommended procedure. The use of segmental fixation with instrumentation, as well as postoperative bracing, is highly recommended.

Limb-length inequality

Multiple attempts should be made to control growth in the hypertrophic limbs by means of epiphyseal arrest. A shortening osteotomy of the longer side is rarely successful and strongly contraindicated. The healing of the osteotomy may be delayed and nonunion leading to pseudoarthrosis may occur. Stapling of the longer limb has resulted in marginal successes, but a shortening osteotomy is strongly contraindicated. Lengthening the opposite side when the difference is less than 7 cm may be an alternate approach, but this is considered risky.^[12]

Congenital tibial dysplasia

The elective correction of angular deformities for cosmesis is strongly contraindicated. The risk of pseudoarthrosis is too great. Consequent bracing and protection until skeletal maturity is highly recommended.^[12]