The Journal of Bone & Joint Surgery

The Journal of Bone & Joint Surgery, Volume 90, Issue 10

Scientific Articles | October 01, 2008

Prophylactic Bypass Grafting and Long-Term Bracing in the Management of Anterolateral Bowing of the Tibia and Neurofibromatosis-1

Onder Ofluoglu, MD¹; Richard S. Davidson, MD^b; John P. Dormans, MD^b

¹ Lütfi Kirdar Egitim ve Arastirma Hastanesi, 2. Ortopedi ve Travmatoloji Klinigi, Denizer Cad. E-5 Karayolu Cevizli, Istanbul 34890, Turkey. E-mail address: oofluoglu@gmail.com
^b Department of Orthopaedic Surgery, The Children's Hospital of Philadelphia, 34th and Civic Center Boulevard, 2nd Floor, Wood Building, Philadelphia, PA 19104-4399. E-mail address for R.S. Davidson: davidson.richard.s@gmail.com. E-mail address for J.P. Dormans: dormans@email.chop.edu

View Disclosures and Other Information

Disclosure: The authors did not receive any outside funding or grants in support of their research for or preparation of this work. Neither they nor a member of their immediate families received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, division, center, clinical practice, or other charitable or nonprofit organization with which the authors, or a member of their immediate families, are affiliated or associated.

Investigation performed at the Department of Orthopaedic Surgery, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania

The Journal of Bone and Joint Surgery, Inc.

J Bone Joint Surg Am, 2008 Oct 01;90(10):2126-2134. doi: 10.2106/JBJS.G.00272

5 Recommendations (Recommend) | 3 Comments | Saved by 3 Users Save Case

Article

Comments (2)

text A A A

Abstract

Background: Congenital anterolateral bowing of the tibia is a pre-pseudarthrosis stage of congenital pseudarthrosis of the tibia and is associated with a substantial risk of fracture and pseudarthrosis. We evaluated the results of prophylactic bypass grafting performed in combination with bracing to prevent fracture and pseudarthrosis.

Methods: This retrospective series included ten patients with pre-pseudarthrosis of the tibia treated, between 1991 and 2002, with prophylactic bypass grafting with an allograft fibula placed posteromedially in a stress-bearing fashion. The average patient age was 2.3 years at the time of diagnosis, 3.6 years at the time of surgery, and ten years at the time of final follow-up. The mean duration of follow-up was seventy-eight months. Brace protection was recommended at the time of diagnosis and was continued after the operation until maturity. Despite the bracing, a low-energy fracture developed and partially healed prior to the bypass grafting in one patient. The remaining nine patients had no fractures prior to the bypass grafting. At the time of final follow-up, the patients were examined clinically and radiographically for the presence of a fracture or pseudarthrosis and for residual deformity, including malalignment, ankle and knee joint abnormalities, and leg length discrepancy.

Results: No patient had either a fracture or a pseudarthrosis of the tibia at the time of follow-up. All grafts united to the tibia at both ends. Complications included an allograft fracture in three patients, which healed in all; allograft resorption in one patient; and pseudarthrosis of the ipsilateral host fibula in one patient. At the time of final follow-up, a mean of 9 mm (range, 0 to 37 mm) of leg length discrepancy was found. A corrective osteotomy was done for four patients (three because of ankle valgus and one because of diaphyseal deformity).

Conclusions: In this small series of ten patients with congenital anterolateral bowing of the tibia treated with bypass strut grafting and long-term bracing, there were no cases of pseudarthrosis of the tibia. Distal tibial deformity may persist throughout the growth period and require operative correction in patients treated with this procedure.

Level of Evidence: Therapeutic Level IV. See Instructions to Authors for a complete description of levels of evidence.

Figures in this Article

Introduction

Congenital anterolateral bowing of the tibia is a pre-pseudarthrosis stage of congenital pseudarthrosis of the tibia. Many cases progress to pseudarthrosis after either a spontaneous stress fracture or a corrective osteotomy^1-5. Treatment of an established pseudarthrosis often requires repeated surgical interventions. Union is difficult to achieve and can be transient, and fracture recurrence is common. In spite of radiographic signs of union, functional results may not be satisfactory because of unacceptable deformity, shortening, atrophy, and stiffness. Thus, prevention of fracture and subsequent pseudarthrosis is a worthy management goal for children with anterolateral bowing of the tibia. Treatment alternatives at the pre-pseudarthrosis stage include protection with a brace until maturity, prophylactic local bone-grafting, osteotomy with intramedullary rod fixation, and bypass grafting with use of the McFarland procedure^5-13.

Surgical treatment of anterolateral bowing of the tibia with corrective osteotomy or curettage and local bone-grafting can have an unacceptably high rate of failure. This risk is even higher if the osteotomy is done through the apex of the tibial deformity. Most cases lead to pseudarthrosis and require multiple attempts to achieve union. Crossett et al.¹ reported six cases of anterolateral bowing of the tibia associated with neurofibromatosis-1 that were treated with elective osteotomy because of progressive tibial deformity. A pseudarthrosis developed in all patients and required repeated surgical procedures to obtain osseous union. The results of secondary procedures can be disappointing, and amputation eventually may be necessary in a large number of cases^1,14.

Prophylactic bracing is employed for patients with anterolateral bowing of the tibia to delay or prevent fracture. Some cases, especially those with a normal medullary canal, can be treated successfully with bracing^9,11,12,15. However, the ability of bracing alone to prevent pseudarthrosis has not been established in the literature¹⁶. Prophylactic bypass grafting has been used to reduce the risk of fracture^5,9,7,13. However, limited information on this procedure is available in the literature, and the outcomes have been variable.

The purpose of this study was to determine whether the modified McFarland procedure, done with a standardized surgical technique for application of an allogenic fibular graft to the tibia and combined with bracing, could prevent fracture in patients with anterolateral bowing of the tibia. Several factors affecting the long-term functional outcome, including leg length discrepancy, diaphyseal deformities, ankle and knee joint malalignments, and fibular abnormalities, were analyzed.

Materials and Methods

Ten children with anterolateral bowing of the tibia and neurofibromatosis-1 who had been treated between 1991 and 2002 were identified (Table I). The patients were operated on by the senior authors (R.S.D. and J.P.D.) using prophylactic bypass grafting (the modified McFarland procedure). Patient records and radiographs were retrospectively reviewed. Institutional review board approval was obtained for this study.

View Larger

TABLE I Patient Data

	Age (yr)
Case	At Diagnosis	At Operation	At Time of Final Follow-up	Sex	Crawford Type	Fibula	Graft Type
1	<1	6	12	Male	3	Pseudarthrosis	Allograft fibula, allograft cancellous chips, autologous bone marrow
2	1	2	11.5	Male	2	Bending	Allograft fibula, allograft cancellous chips, autologous bone marrow
3	9	10	13.5	Male	1	Normal	Allograft fibula, allograft cancellous chips, autologous bone marrow
4	3	6	12	Male	2	Hypoplasia and bending	Allograft fibula, autologous bone graft
5	1	2	6	Male	2	Hypoplasia and bending	Allograft fibula, allograft cancellous chips, autologous bone marrow
6	<1	2.5	5	Male	2	Hypoplasia and bending	Allograft fibula, allograft cancellous chips
7	<1	1	12.5	Male	2	Bending	Allograft fibula, autologous bone graft
8	2	2	8	Male	2	Hypoplasia and bending	Allograft fibula, allograft cancellous chips, autologous bone marrow
9	3	3	15	Female	1	Bending	Allograft fibula, autologous bone graft
10	<1	2	5	Male	2	Hypoplasia and bending	Allograft fibula, autologous bone graft

Add to My JBJS

TABLE I Patient Data

	Age (yr)
Case	At Diagnosis	At Operation	At Time of Final Follow-up	Sex	Crawford Type	Fibula	Graft Type
1	<1	6	12	Male	3	Pseudarthrosis	Allograft fibula, allograft cancellous chips, autologous bone marrow
2	1	2	11.5	Male	2	Bending	Allograft fibula, allograft cancellous chips, autologous bone marrow
3	9	10	13.5	Male	1	Normal	Allograft fibula, allograft cancellous chips, autologous bone marrow
4	3	6	12	Male	2	Hypoplasia and bending	Allograft fibula, autologous bone graft
5	1	2	6	Male	2	Hypoplasia and bending	Allograft fibula, allograft cancellous chips, autologous bone marrow
6	<1	2.5	5	Male	2	Hypoplasia and bending	Allograft fibula, allograft cancellous chips
7	<1	1	12.5	Male	2	Bending	Allograft fibula, autologous bone graft
8	2	2	8	Male	2	Hypoplasia and bending	Allograft fibula, allograft cancellous chips, autologous bone marrow
9	3	3	15	Female	1	Bending	Allograft fibula, autologous bone graft
10	<1	2	5	Male	2	Hypoplasia and bending	Allograft fibula, autologous bone graft

The study group included nine boys and one girl with an average age of 3.6 years (range, one to ten years) at the time of the operation. Seven patients were younger than three years old, and three patients were six years old or older. The treatment of six patients was delayed for one to five years after their first visit as their parents contemplated the treatment options. A clamshell patellar tendon-bearing brace with medial and lateral rotational flares at the knee or a hinged knee-ankle-foot orthosis was ordered immediately after the diagnosis for all patients. The right tibia was involved in seven patients and the left tibia, in three. According to the classification system of Crawford and Bagamery⁶, which is based on the radiographic appearance of the dysplastic segment, type 2 was the most common (Fig. 1). One patient with type-2 anterolateral bowing sustained a nondisplaced fracture during brace protection, and this fracture had partially healed at the time of the surgery. Nine patients had no fracture at the time of the surgery. We also noted the fibular abnormalities, such as hypoplasia, bending, and pseudarthrosis, which are important features of the disease and were not taken into account in the Crawford classification. At the time of presentation, only one patient had a normal fibula. The fibula was bent in the angle of the bowed tibia in eight patients, and five of the eight patients had a hypoplastic fibula as well. One patient presented with a fibular pseudarthrosis.

View Large | Download Slide(.ppt)
Add to My JBJS

Fig. 1: The Crawford classification: 1 = a normal medullary canal, 2 = increased medullary sclerosis and an hourglass reconstruction, 3 = cystic changes, and 4 = a fracture or a frank pseudarthrosis.

Patients were evaluated to determine whether they had a fracture or pseudarthrosis at six-month intervals and, at the time of final follow-up, to determine whether they had residual deformity, including diaphyseal malalignment, ankle and knee joint abnormalities, or leg length discrepancy, and to ascertain the functional status.

Surgical Technique (Fig. 2) and Postoperative Management7

All operations were performed with use of a tourniquet. Image intensification was used to locate the proximal and distal tibial physes. The bowed tibia was rotated in the image beam to identify the oblique plane deformity of the anterolateral bow, and the leg was positioned with the oblique plane horizontal to the operating table. The skin and subcutaneous tissues were incised in the anteromedial line from the proximal to the distal physis. The periosteum was divided at the medial border from 1 cm distal to the proximal physis to 1 cm proximal to the distal physis, with use of image intensification to avoid damage to the physes. At about 2 cm from each physis, a 1-cm notch was created in the metaphysis with use of a high-speed burr and curets. A freeze-dried fibular allograft, approximately 2 cm longer than the length between the notches, was chosen. The proximal end of the fibular graft was shaped into a spike of about 6 mm in length, and this spike was impacted into the proximal tibial metaphyseal notch. Next, the distal end of the fibula was cut square, so that the distal end of the graft extended about 1 mm past the distal notch, and the distal end of the graft was pressed into the distal tibial notch under compression, loading the graft and "bypassing" the dysplastic tibia. A screw (used in one case), a wire (used in one case), or a heavy suture (used in eight cases) was then passed through previously drilled holes in the distal end of the graft and the tibial metaphysis to secure the distal end of the graft. Care was taken to place the graft along the concavity of the tibial bow. The surface of the tibia facing the graft was then lightly decorticated with a burr. Autogenous corticocancellous iliac crest bone graft was used in four patients and cancellous allograft bone chips mixed with autogenous bone marrow were used in six patients to promote incorporation of the graft and the tibia. Autogenous bone graft was preferred, but in patients under two years of age it was not possible to obtain sufficient autogenous graft to fill the space, and thus allograft was used.

View Large | Download Slide(.ppt)
Add to My JBJS

Fig. 2-A Fig. 2-B Fig. 2-C: Figs. 2-A, 2-B, and 2-C The modified McFarland bypass grafting procedure for patients with anterolateral bowing of the tibia.

Postoperatively, the leg was protected in a long leg cast with the knee bent about 30° to discourage weight-bearing until the bone graft-tibia junctions had healed (in about six to eight weeks). Even though all ten patients showed healing in this amount of time, we recommend that the cast be worn until radiographic signs of healing are seen. The leg was then protected, until the patient reached maturity, in a total contact clamshell patellar tendon-bearing orthosis that was flared at the medial and lateral aspects of the knee to control rotation or in a hinged knee-ankle-foot orthosis. After healing, all patients were allowed to remove the brace at home for sleeping and bathing. All patients were allowed to participate in regular school-recess activities and gym classes, except for track and contact sports, while they wore the brace.

Results

The mean duration of follow-up was seventy-eight months (range, thirty to 144 months). The average age was 2.3 years (range, less than one to nine years) at the time of diagnosis, 3.6 years (range, one to ten years) at the time of surgery, and ten years (range, five to fifteen years) at the time of final follow-up. The length of the allograft fibula at the time of surgery was a mean of 58% (range, 40% to 75%) of the total length of the involved tibia. All grafts united to the tibia at both the proximal and the distal end. Complete incorporation of the graft, defined as side-to-side union over the extent of the graft, occurred in eight of the ten patients (Figs. 3-A through 3-D).

View Large | Download Slide(.ppt)
Add to My JBJS

Fig. 3-A Fig. 3-B: Fig. 3-A Crawford type-2 anterolateral bowing of the tibia in a one-year-old patient. Fig. 3-B Five months after bypass grafting.

View Large | Download Slide(.ppt)
Add to My JBJS

Fig. 3-C Fig. 3-D: Fig. 3-C There was excellent incorporation of the graft at one year after the procedure. Fig. 3-D Radiographic appearance when the patient was eleven years of age. The tibia and fibula are less bowed, and the legs are of equal length.

No pseudarthrosis developed in any of the patients. In the patient who presented with the low-energy fracture of the tibia at the time of the operation, a complete tibial union occurred following the bypass grafting, without any additional intervention at the fracture site.

Residual Deformities and Shortening (Table II and Figs. 4-A and 4-B)

At the time of final follow-up, most patients had considerable residual deformity, especially in the diaphysis and the ankle. In the coronal plane, the medial proximal tibial angle was within normal limits in three patients and a slight valgus deformity (range, 93° to 104°) was found in seven. Substantial diaphyseal varus angulation (range, 18° to 80°) was found in six patients, and the remaining four patients had <5° of varus. Marked ankle valgus (>10°) was observed in four patients.

View Larger

TABLE II Residual Deformities at the Time of Final Follow-up

	Anteroposterior Angle*(deg)					Lateral†(deg)
Case	A	B	C	D	E	F
1	95	5	77	87	24	90
2	90	0	82	84	16	82
3	87	0	74	80	22	86
4	95	5	76	94	19	81
5	102	32	90	86	28	90
6	104	50	78	88	22	91
7	97	80	84	95	55	95
8	95	22	98	88	33	93
9	93	18	86	87	32	97
10	98	45	93	94	24	90
Mean	95.6	25.7	83.8	88.3	27.5	89.5

See Figure 4-A for an illustration of the angles labeled as A, B, and C.See Figure 4-B for an illustration of the angles labeled as D, E, and F.

Add to My JBJS

TABLE II Residual Deformities at the Time of Final Follow-up

	Anteroposterior Angle*(deg)					Lateral†(deg)
Case	A	B	C	D	E	F
1	95	5	77	87	24	90
2	90	0	82	84	16	82
3	87	0	74	80	22	86
4	95	5	76	94	19	81
5	102	32	90	86	28	90
6	104	50	78	88	22	91
7	97	80	84	95	55	95
8	95	22	98	88	33	93
9	93	18	86	87	32	97
10	98	45	93	94	24	90
Mean	95.6	25.7	83.8	88.3	27.5	89.5

See Figure 4-A for an illustration of the angles labeled as A, B, and C.See Figure 4-B for an illustration of the angles labeled as D, E, and F.

View Large | Download Slide(.ppt)
Add to My JBJS

Fig. 4-A Fig. 4-B: Illustrations of the anteroposterior (Fig. 4-A) and lateral (Fig. 4-B) angles shown in Table II.

In the sagittal plane, the proximal tibial angle was within normal limits in three patients and there was slight recurvatum (range, 85° to 94°) in seven patients. The mid-diaphyseal segment was in a procurvatum position (range, 18° to 55°) in all patients. The distal tibial angle was within normal limits in three patients and showed posterior tilt (range, 81° to 97°) in the others.

At the end of treatment, only two of the patients had a straight fibula. In addition, two patients had fibular pseudarthrosis: one of them presented initially with the pseudarthrosis, and in the other patient the pseudarthrosis developed during treatment. Marked ankle valgus developed in both of those patients in spite of the bracing.

At the time of final follow-up, a mean of 9 mm (range, 0 to 37 mm) of leg length discrepancy was found. Three patients had equal leg lengths and four patients had <10 mm of discrepancy. The involved side was longer in one patient.

Complications

A traumatic, low-energy, nondisplaced allograft fracture occurred at the junction between the middle and distal thirds of the allograft in three patients, two of whom fell on stairs and one of whom was a passenger in an automobile involved in a low-energy accident. Immobilization in the patellar tendon-bearing brace was the only treatment for these three allograft fractures. All three spontaneously healed, although the healing time took as long as one year.

One patient had nearly complete resorption of the allograft three years after the surgery, and the bypass procedure was repeated⁷. There was partial resorption of the allograft four years after the second graft procedure. Although the deformity progressed substantially, to 80° of varus and 50° of procurvatum, no fracture of the tibia was observed. Another patient had pseudarthrosis of the ipsilateral fibula, resulting in severe ankle valgus.

Secondary Procedures

Six of the ten patients underwent secondary procedures. Three patients with marked ankle valgus (>10°) were treated with a corrective closing wedge osteotomy. Two in whom the site was fixed with staples had healing at six months, and the other patient, who was treated with an Ilizarov fixator, had healing at seven months. Two other patients with ankle valgus were treated with plate-and-screw hemiepiphysiodesis, and they were still under observation at the time of writing.

One patient with progressive multiapical and multiplanar deformity because of recurrent graft resorption underwent a corrective osteotomy. This treatment had been deferred repeatedly over several years because of several neurofibromatosis-related illnesses, including renal hypertension. At maturity, this patient was treated with gradual correction with an external fixator and the tibia healed with a straight mechanical axis.

Final Functional Status

All ten patients treated with the bypass grafting used the patellar tendon-bearing brace until they were skeletally mature. Nine of the ten bore full weight in the brace and did not use walking aids such as crutches or canes. One patient with a progressive deformity, which reached >50°, used a cane in addition to the brace. All of the patients wore sneakers over the braces.

One patient was restricted from all running and jumping because of the severe tibial deformity. None of the other nine patients had pain during regular gym exercises until adolescence, when three had pain with activity as a result of the distal tibial deformity. All patients participated in gym class while wearing the brace.

Although specific measurements of the knee and ankle range of motion were not consistently carried out for any of the patients, a loss of motion of the knee or ankle was not reported for any patient.

Discussion

We began using the modified McFarland bypass graft procedure in combination with bracing to treat patients with anterolateral bowing of the tibia after two patients who were being treated with bracing alone had a fracture that led to pseudarthrosis. Both of these children were wearing a brace at the time of the fracture, and both were said to have been "just walking" when the fracture occurred. Since we began using the combined treatment, one fourteen-month-old child being treated with bracing sustained a fracture, while the parents were bathing the child, three days prior to a planned bypass grafting procedure. The parents reported feeling a "click," which turned out to be a fracture. The fracture developed into a pseudarthrosis in spite of cast treatment. These three patients were not part of the present study, which focused only on patients treated with the bypass grafting procedure.

When bracing is used alone to treat anterolateral bowing of the tibia, the bowed bone is not protected by the brace in many situations, such as when the child gets up at night to go to the bathroom or when the child is in a swimming pool. Our experience with bracing alone showed us that fractures leading to pseudarthrosis can occur even when a brace is being used.

To our knowledge, there have been no long-term studies of anterolateral bowing of the tibia treated with bracing alone. While our experience with bracing alone is limited, the risk of fracture and pseudarthrosis has been high. The goal of treatment in this series was to reduce the risk of pseudarthrosis of the tibia in patients being treated with bracing. It may be that the healed bypass graft could provide sufficient protection by itself, but our concern about the devastating consequences of a fracture and pseudarthrosis led us to cautiously protect the tibia with the combination of grafting and bracing. While this series of patients was too small for us to perform a controlled comparison of treatments with bracing alone, grafting alone, or the combined treatment, our series of patients who received the combined treatment can serve as a comparison group for future studies of the risk of fracture and pseudarthrosis with brace treatment alone or grafting alone.

The procedure for bypassing the involved segment was originally described by McFarland for the treatment of an established pseudarthrosis of the tibia in three patients¹⁷. His treatment concept was based on the understanding that anterolateral bowing was the main cause for persistence of pseudarthrosis and the hope that placement of a mechanical support with a strong strut autograft, harvested from the intact tibia, in the weight-bearing line might alleviate the problem. All three patients had had previous operations that had failed, and all three had successful union after the bypass grafting. McFarland subsequently reported successful healing in nine of eleven patients in whom congenital pseudarthrosis of the tibia had been treated with the procedure¹⁰.

Lloyd-Roberts and Shaw⁵ first proposed the concept of prevention of pseudarthrosis with the McFarland procedure. They reported the cases of seven patients treated with bypass grafting with use of McFarland's original technique. Three patients were operated on prior to the occurrence of a fracture or pseudarthrosis, and four had an established pseudarthrosis. At the time of follow-up, two patients had an intact tibia, at the ages of seven and nine years, the seventh patient had a very short follow-up, and four patients had a pseudarthrosis. The better results in our series as compared with those in the series reported by Lloyd-Roberts and Shaw may be related to the large number of established pseudarthroses in that series and the complete absence of pseudarthroses in our series. Both Lloyd-Roberts and Shaw⁵ and McFarland^10,17 applied the grafting technique to bowed tibiae and established pseudarthroses. The results in the patients with an established pseudarthrosis were poor, most likely because of a failure to obtain proper alignment and to adequately stabilize the pseudarthrosis. We do not see a place for such grafting in patients with an established pseudarthrosis. It is uncertain whether the patients in the series reported by Lloyd-Roberts and Shaw were treated with bracing.

Strong and Wong-Chung¹³ reported the results of prophylactic bypass grafting in nine patients with anterolateral bowing of the tibia and neurofibromatosis-1. The cases were collected from members of the Pediatric Orthopaedic Society of North America. The graft material used for the bypass varied, with the sources including the contralateral tibia, autogenous rib, and allograft fibula. The average duration of follow-up was eight years and eight months, and the average age at the time of final follow-up was eleven years and three months. Three of the nine patients had five episodes of fracture of the tibia and eventual pseudarthrosis. In six patients, the tibia did not fracture and remained intact. No information regarding residual shortening or deformity was given.

In an EPOS (European Paediatric Orthopaedic Society) multicenter review study, nineteen patients with a pre-pseudarthrosis were treated with McFarland bypass grafting⁹. The bypass grafting was used alone in sixteen patients, and it was combined with insertion of an intramedullary rod or use of external fixation in the others. The bypass grafting was the primary operation in thirteen patients, and it followed previous operations in six. At the time of final follow-up, the tibia was intact in seven patients but straight in only one. Substantial leg length discrepancies (mean, 4.5 cm; range, 1.5 to 9 cm) were reported. The bypass grafting failed in twelve patients, and subsequent operations were necessary.

In contrast to the results in previous studies, a pseudarthrosis did not develop in any of the ten patients in our study following prophylactic bypass grafting in combination with long-term bracing. There were probably a number of reasons for these results. None of the patients in our study had a pseudarthrosis at the time of the bypass grafting, and none underwent osteotomy of the bowed tibia. In all of the patients, a freeze-dried fibula was placed as a concave weight-bearing strut from the proximal tibial metaphysis to the distal tibial metaphysis, bypassing the diseased portion of the tibia. Cancellous freeze-dried bone graft was placed between the allograft and the burred tibia to improve the chances of osseous consolidation. All children wore a cast for six weeks postoperatively and then wore a brace. These steps were not consistently followed in any of the previous studies.

We observed complete incorporation of the allograft in all but two of our patients. Although the graft fractured in three patients, all three had spontaneous union while wearing the brace, indicating incorporation and vascularization of the graft.

Lehman et al.⁴ cautioned that the treatment of congenital pseudarthrosis of the tibia should not be based on obtaining bone union. They stated that "it should be based on obtaining the best and most useful leg at maturity with the least amount of permanent trauma to the patient's leg and general development, including psychological development." In their series, in which many different modalities had been used, the rate of successful healing was one in seven, with the other patients requiring bracing and amputation.

Seven of the ten patients in our series had a Crawford type-2 pattern, which has a poor prognosis. The functional results in our study are very favorable when compared with the functional results in the EPOS multicenter study on congenital pseudarthrosis of the tibia reported by Tudisco et al.¹⁵. They reported that Crawford type-2 and type-4 pseudarthroses had a worse prognosis. Of the thirteen patients with a Crawford type-2 pattern in their series, five were fully weight-bearing, four wore a brace permanently, seven wore special shoes, and one wore a brace with special shoes. Two of the thirteen patients eventually had an amputation and required a prosthesis. Of the eleven remaining patients, six had some restriction of sports activity, and five participated in no sports at all. One patient required a cane to walk.

Clinically relevant residual shortening develops in most patients with congenital pseudarthrosis of the tibia¹⁵. This is caused mainly by chronic bone resorption, surgical resections at the pseudarthrosis site during repeated attempts to obtain union, or growth disturbance of the distal tibial physis related to treatment⁵. The lengthening procedures used to address residual shortening are associated with a substantial risk of nonunion in these patients. Although one patient in our series had a 37-mm leg length discrepancy, the average leg length discrepancy was 9 mm, which demonstrates that not only can the pseudarthrosis be prevented, but additional lengthening procedures and their associated risks also can be avoided when this prophylactic bypass procedure is used.

In spite of the successful prevention of pseudarthrosis and secondary shortening, most of the patients in our series had clinically relevant residual deformities at the time of final follow-up. Variable degrees of varus were found in the diaphysis in six patients. All ten patients had a procurvatum deformity. One patient underwent surgical correction of a multilevel and multidirectional deformity with use of external fixation after maturity. In addition to anterolateral diaphyseal bowing, variable degrees of angular abnormalities of the knee and ankle joints were present in the majority of patients. Most of our patients had mild proximal tibial valgus and recurvatum. Proximal tibial deformities did not appear to progress. However, substantial valgus deformity (>10°) at the ankle joint occurred in four patients. The distal tibial valgus was present in our patients prior to the bone-grafting and did not appear to be affected by the bypass procedure. During the study period, we treated three patients with a closing wedge osteotomy (fixed by staples in two and with an Ilizarov fixator in the third). Although union was obtained primarily after all three procedures, the healing time was prolonged. It would appear logical to treat ankle valgus with plate or staple hemiepiphysiodesis to avoid problems with healing of the osteotomy site. We employed temporary hemiepiphysiodesis in another two cases, but we do not have sufficient follow-up data or experience to comment on the success of this type of procedure for correction of distal tibial valgus in these abnormal bones.

Fibular involvement is a frequent and important reported feature of congenital pseudarthrosis of the tibia that affects the final functional result. Almost two-thirds of patients with congenital pseudarthrosis of the tibia reportedly have fibular abnormalities^15,18,19. In addition, more than half of patients with fibular involvement have neurofibromatosis¹⁹. Fibular hypoplasia, bending, or pseudarthrosis was found in nine of our ten patients. After the completion of the treatment, only two of our patients had a straight and intact fibula. One patient in the series presented with a fibular pseudarthrosis, and fibular pseudarthrosis developed in another during treatment. Substantial ankle valgus developed in both patients in spite of the bracing. Thus, proactive management of ankle deformity, such as grafting of the fibula at the time of the tibial grafting and/or temporary staple or plate hemiepiphysiodesis of the medial aspect of the tibia may prove useful.

We have reported our experience with ten cases of anterolateral bowing of the tibia associated with neurofibromatosis-1 that were treated with the McFarland procedure for bypass grafting with an allogenic fibular strut in combination with long-term bracing. While this is a large series considering the rarity of the deformity, statistical analysis was not possible because of the small number of patients. We hope that the addition of grafting to long-term bracing will reduce the incidence of, and problems associated with, the complication of pseudarthrosis of the tibia. Image Not Available

Acknowledgements

Note: The authors thank Gokhan Yanik, MD, for the illustrations.

References

Crossett LS, Beaty JH, Betz RR, Warner W, Clancy M, Steel HH. Congenital pseudarthrosis of the tibia. Long-term follow-up study. Clin Orthop Relat Res.1989;245:16-8.24516 1989 [PubMed]

Dobbs MB, Rich MM, Gordon JE, Szymanski DA, Schoenecker PL. Use of an intramedullary rod for treatment of congenital pseudarthrosis of the tibia. A long-term follow-up study. J Bone Joint Surg Am.2004;86:1186-97.861186 2004

Hardinge K. Congenital anterior bowing of the tibia. The significance of the different types in relation to pseudarthrosis. Ann R Coll Surg Engl.1972;51:17-30.5117 1972

Lehman WB, Atar D, Feldman DS, Gordon JC, Grant AD. Congenital pseudoarthrosis of the tibia. J Pediatr Orthop B.2000;9:103-7.9103 2000

Lloyd-Roberts GC, Shaw NE. The prevention of pseudarthrosis in congenital kyphosis of the tibia. J Bone Joint Surg Br.1969;51:100-5.51100 1969

Crawford AH Jr, Bagamery N. Osseous manifestations of neurofibromatosis in childhood. J Pediatr Orthop.1986;6:72-88.672 1986 [CrossRef]

Dormans JP. Modified sequential McFarland bypass procedure for prepseudarthrosis of the tibia. J Orthop Tech.1995;3:176-80.3176 1995

Boyd HB. Pathology and natural history of congenital pseudarthrosis of the tibia. Clin Orthop Relat Res.1982;166:5-13.1665 1982

Grill F, Bollini G, Dungl P, Fixsen J, Hefti F, Ippolito E, Romanus B, Tudisco C, Wientroub S. Treatment approaches for congenital pseudarthrosis of tibia: results of the EPOS multicenter study. European Paediatric Orthopaedic Society (EPOS). J Pediatr Orthop B.2000;9:75-89.975 2000

McFarland B. Pseudarthrosis of the tibia in childhood. J Bone Joint Surg Br.1951;33:36-46.3336 1951

Murray HH, Lovell WW. Congenital pseudarthrosis of the tibia. A long-term follow-up study. Clin Orthop Relat Res.1982;166:14-20.16614 1982

Rathgeb JM, Ramsey PL, Cowell HR. Congenital kyphoscoliosis of the tibia. Clin Orthop Relat Res.1974;103:178-90.103178 1974 [CrossRef]

Strong ML, Wong-Chung J. Prophylactic bypass grafting of the prepseudarthrotic tibia in neurofibromatosis. J Pediatr Orthop.1991;11:757-64.11757 1991 [CrossRef]

Morrissy RT, Riseborough EJ, Hall JE. Congenital pseudarthrosis of the tibia. J Bone Joint Surg Br.1981;63:367-75.63367 1981

Tudisco C, Bollini G, Dungl P, Fixen J, Grill F, Hefti F, Romanus B, Wientroub S. Functional results at the end of skeletal growth in 30 patients affected by congenital pseudoarthrosis of the tibia. J Pediatr Orthop B.2000;9:94-102.994 2000

Wientroub S, Grill F. Congenital pseudarthrosis of the tibia: part 1. European Pediatric Orthopaedic Society multicenter study of congenital pseudoarthrosis. J Pediatr Orthop B.2000;9:1-2.91 2000

McFarland B. Birth fracture of the tibia. Br J Surg.1939;27:706-12.27706 1939 [CrossRef]

Johnston CE 2nd. Congenital pseudarthrosis of the tibia: results of technical variations in the Charnley-Williams procedure. J Bone Joint Surg Am.2002;84:1799-810.841799 2002

Keret D, Bollini G, Dungl P, Fixsen J, Grill F, Hefti F, Ippolito E, Romanus B, Tudisco C, Wientroub S. The fibula in congenital pseudoarthrosis of the tibia: the EPOS multicenter study. European Paediatric Orthopaedic Society (EPOS). J Pediatr Orthop B.2000;9:69-74.969 2000

Topics

fracture ; ankle ; fibula ; neurofibromatosis 1 ; pseudarthrosis ; tibia ; tissue transplants ; braces ; transplantation ; bypass

Username

Password

Access for Patients

Forgot Password?

Have a subscription to the print edition?

Not a Subscriber?

Buy this Article

Get online access for 30 days for $35

New to JBJS?

Subscribe to the online edition for 30 days for $75

Register for a FREE limited account to get full access to all CME activities, to comment on public articles, or to sign up for alerts.

Have a subscription to the print edition?

Current subscribers to The Journal of Bone & Joint Surgery in either the print or quarterly DVD formats receive free online access to JBJS.org.

Activate your online account now

Forgot your password?

Enter your username and email address. We'll send you a reminder to the email address on record.

Username:*

Email Address:*

Forgot your username or need assistance? Please contact customer service at subs@jbjs.org. If your access is provided
by your institution, please contact you librarian or administrator for username and password information. Institutional
administrators, to reset your institution's master username or password, please contact subs@jbjs.org

References

Accreditation Statement

These activities have been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of the American Academy of Orthopaedic Surgeons and The Journal of Bone and Joint Surgery, Inc. The American Academy of Orthopaedic Surgeons is accredited by the ACCME to provide continuing medical education for physicians.

CME Activities Associated with This Article

Submit a Comment

Please read the other comments before you post yours. Contributors must reveal any conflict of interest.
Comments are moderated and will appear on the site at the discretion of JBJS editorial staff.

* = Required Field

Comment Author(s) * (if multiple authors, separate names by comma)

Example: John Doe

Affiliation & Institution*

Comment Title*

Comment*

Cancel

Richard S Davidson, MD

Posted on November 22, 2008

Dr. Davidson and colleagures respond to Dr. El-Rosasy

ChildrenÂ’s Hospital of Philadelphia

We thanks Dr. El-Rosasy for raising certain questions regarding our paper (1).

While Dr El-Rosasy is correct that Lloyd-Roberts stated in his introduction that â€œthe results were not wholly satisfactoryâ€ a reading of the entire paper is warranted. Lloyd-Robertsâ€™s comment referred to his overall experience with this rare condition and not his reported three cases with strut grafting.[2] Lloyd-Roberts reported seven patients. In the first four, two were not treated and went on to fracture and pseudoarthrosis. The third fractured while waiting for the grafting operation. The fourth was treated only with tibial graft â€œshavingsâ€ and not a strut graft. Only three of the seven cases were treated with strut grafting and all three of these went on to heal without development of fracture or pseudoarthrosis, leading him to conclude that, â€œWe believe this operation to be justifiedâ€¦.â€. In his conclusion, Lloyd-Roberts states that â€œ1. The danger of fracture and subsequent pseudoarthrosis is emphasizedâ€¦. And 2. With the object of preventing fracture, early and urgent bone grafting is advocated.â€ [2]

Dr. El-Rosasy states in his letter that in a review of the English literature there are â€œseveral reports of patients with congenital tibial dysplasia who not only did not develop fractures, but in whom the tibia became nearly normalâ€¦.â€ However, he fails to discuss the type of deformity. While he refers to an editorial by Nicoll published in 1965 in which Dr Nicoll states that the bypass technique has not been â€œproven to be truly prophylacticâ€(3) he failed to comment on one of the main points of the editorial which is summarized by the quote, â€œone outstanding lessonâ€¦that there are at least two types with totally different patterns of behavior ranging from relatively benign at one end to exceedingly vicious at the other.â€ While there are some reports in the literature that the rare Crawford type 1 congenital tibial dysplasia (CDT) may not fracture and may even remodel, these do not constitute any long term evidence involving a large series of similar patients. This issue was discussed in our paper. [1]

Only two of the patients reported in our study were type 1; the rest were type 2. Moreover, one of our two type 1 patients developed a stress fracture and the other developed a fibular pseudoarthrosis prior to bypass grafting. We considered both of these patients as being at higher risk for fracture. It has been well reported in the literature that Crawford type 2 tibias carry a high risk of developing fractures and subsequent pseudoarthroses. We disagree with the implication that it is "an ethical issue" to try to prevent an at-risk group of patients from progressing to that risk is faulty reasoning. This is particularly true in light of the complexity of, difficulty and complications associated with the treatment of pseudoarthrosis.

Dr. El-Rosasy is not correct in stating that we â€œdescribed a technique identical to the bypass grafting described by McFarlandâ€. Not only are there many technical differences between the techniques, but McFarland applied his technique to existing pseudoarthroses while none of our patients had a pseudoarthrosis of the tibia.[4] Dr. El-Rosasy goes on to state that McFarland â€œbelieved that the cause of persistence of the pseudarthrosis must be mechanical due to angulation and the bending stresses of muscles.â€ A careful reading of McFarlandâ€™s paper, however shows that he was acutely aware of a biologic component, i.e. that a â€œdefect exists in the shaft of the tibiaâ€¦â€ [4]

Dr. El-Rosasy referrred to a paper written by Morrissy et al [5] to state that â€œthere are reports that prove that congenital pseudoarthrosis of the tibia is a biological defect.â€ To quote from Morrissyâ€™s paper â€œIt is felt that congenital pseudoarthrosis of the tibia is a biological problem and not merely a mechanical one.â€ A thorough review of the literature confirms that prevailing opinion suggests a combination of biological and mechanical factors. Importantly, neither of these issues either proves or disproves the idea that mechanical support with bypass grafting can reduce the risk of pseudoarthrosis in CDT.

Dr. El-Rosasy then states that â€œthe current best treatment depends on the type of dysplasiaâ€¦â€ but then asserts that â€œFor a dysplastic tibia without fracture, no surgery is justified and the limb should be protected in a removable braceâ€¦.â€ This assertion is made without reference to the type of â€œdysplastic tibia without fracture,â€ or reference to the many papers noting the high risk of fracture in Crawford type 2. [6,7,8]

Dr. El-Rosasy then suggests that all congenital dysplasia of the tibia without fracture can be treated by bracing alone without any reference to any study. To our knowledge, there is not one large, long- term study showing this. As noted in our study, we have seen many of our patients with congenital dysplasia of the tibia sustain a fracture and progress to pseudoarthrosis. Our patients fractured while wearing recommended bracing, while bathing out of the brace, and even while walking without the brace at home. Our paper asserts all of this. Indeed, we would welcome a study of "long-term bracing" of the different Crawford types of congenital dysplasia of the tibia associated with neurofibromatosis. However, until a large long-term study of brace treatment of the various types of congenital dysplasia of the tibia demonstrates that bracing alone is successful in preventing progression to pseudoarthrosis in these patients, Dr. El-Rosasyâ€™s statement "â€¦no surgery is justified â€¦" is itself unjustified.

Dr El-Rosasyâ€™s opinion that, â€œThe development of better fixation methodsâ€ has nothing to do with the risk of pseudoarthrosis. Dr. El- Rosasy even states in his letter that, "the limb should be protectedâ€¦until skeletal maturity when the deformity can be safely correctedâ€. In our experience and as documented in the literature, CDT can go on to fracture and pseudoarthrosis with bracing, which cannot be worn 24hours per day, seven days per week. The bypass grafting was instituted as an easy surgical procedure providing a permanent internal splint in order to avoid the more difficult and complicated treatment of pseudoarthrosis.

Once pseudoarthrosis of the tibia occurs, healing is difficult to achieve. Complications, shortening, and deformity, are common . [9,10] One recent paper reported that pseudoarthrosis was ultimately resulted with amputation in one in four of the cases. [11] While substantial limb length discrepancy is common with pseudoarthrosis, our patients who underwent the bypass grafting had a discrepancy of less than 9 mm. All of these points are addressed in our paper. It is our belief that surgical treatment is appropriate given the natural history and rate of complications associated with other forms of treatment after established pseudarthrosis.

Although our study is one of the largest of its kind for this rare dysplasia, the numbers are, as noted in our paper,too small for many conclusions that reach statistical significance. None of the patients in our study sustained a fracture, developed a pseudoarthrosis or required the extensive surgical procedure and complications from treatment of pseudoarthrosis. Our paper suggests that thr bypass grafting method can be a means of reducing fracture and pseudoarthrosis.

Finally, the last sentence of the Dr. El-Rosasyâ€™s letter states, "For a pseudoarthrotic tibia, a biological solution should be adopted including intramedullary fixation to maintain a straight leg and lessen refractures" makes reference to established pseudoarthroses. Therefore, it has no relation to the situation described in our paper, which relates to dysplastic tibias which have not gone on to pseudoarthrosis. Dr. El-Rosasyâ€™s references to his own review chapter in his letter provide insight into his opinions, and contain references to original studies and data. In the conclusion to his chapter, Dr. El-Rosasy speculates that future investigations should focus on â€œmodalities that locally stimulate osteogenesis and bone repair.â€ [12] We believe that this is precisely what the bypass grafting described in our paper appears to be doing. The graft is incorporated into the tibia, realigning the mechanical forces, strengthening the tibia and reducing the risk of fracture and pseudoarthrosis. While future treatments may permit â€œbiologic cureâ€ of the disease which causes CDT, the closest current biological and mechanical option for treatment is what was presented in our paper, that is, structural bypass grafting.

References

1.Onder Ofluoglu, Richard S. Davidson, and John P. Dormans Prophylactic Bypass Grafting and Long-Term Bracing in the Management of Anterolateral Bowing of the Tibia and Neurofibromatosis-1 J Bone Joint Surg Am 2008; 90: 2126-213.

2. Lloyd-Roberts GC, Shaw NE. The prevention of pseudarthrosis in congenital kyphosis of the tibia. J Bone Joint Surg Br. 1969 Feb 1;51(1):100-5.

3. Nicoll EA. Infantile pseudarthrosis of the tibia. J Bone Joint Surg Br. 1969 Nov;51(4):589-92.

4. McFarland B. Pseudarthrosis of the tibia in childhood. J Bone Joint Surg Br. 1951 Feb;33-B(1):36-46.

5. Morrissy RT, Riseborough EJ, Hall JE. Congenital pseudarthrosis of the tibia. J Bone Joint Surg Br. 1981;63-B(3):367-75.

6. Crawford AH Jr, Bagamery N. Osseous manifestations of neurofibromatosis in childhood. J Pediatr Orthop 1986;6:72-88.

7. Hardinge K. Congenital anterolateral bowing of the tibia. The significance of the different types in relation to pseudoarthrosis. Ann R Coll Surg Engl. 1972;51:17-30.

8. Lehman WB, Atar D, Feldman DS, Gordon JC, Grant AD. Congenital pseudoarthrosis of the tibia. J Pediatr Orthop B 2000;9:103-7.

9. Boero S, Catagni M, Donzelli O, Facchini R, Frediani PV Congenital pseudarthrosis of the tibia associated with neurofibromatosis-1: treatment with Ilizarov's device J Pediatr Orthop. 1997 Sep-Oct;17(5):675-8.

10. Paley D, Catagni M, Argnani F, Prevot J, Bell D, Armstrong P. Treatment of congenital pseudoarthrosis of the tibia using the Ilizarov technique. Clin Orthop Relat Res. 1992 Jul;(280):81-93.

11. Dobbs MB, Rich MM, Gordon JE, Szymanski DA, Schoenecker PL.Use of an intramedullary rod for treatment of congenital pseudarthrosis of the tibia. A long-term follow-up study. J Bone Joint Surg Am. 2004 Jun;86-A(6):1186-97.

12. El-Rosasy MA, Paley D, Herzenberg JE. congenital pseudarthrosis of the tibia. in Limb Lengthening and Reconstruction. Chapter 34, pages 485-495. Editors; S.R. Rozbruch and S. Ilizarov. Informa healthcare publisher, New York, London. October 25th. 2006.

Mahmoud A. El-Rosasy

Posted on October 31, 2008

Prophylactic Bypass Grafting in the Management of congenital tibial dysplasia

Department of Orthopaedic Surgery - Faculty of Medicine - University of Tanta - Tanta - Egypt

To the Editor:

I read with interest the paper by Ofluoglu et al.(1).The concept of prophylactic bypass grafting of the anterolaterally bowed tibia (congenitally dysplastic tibia) was described by Lloyd- Roberts and Shaw(2). They thought that grafting during the period before development of fracture, the "latent period", would prevent fracture. They reported its use in seven cases and described their own results as "not wholly satisfactory". A review of the English literature reveals several reports of patients with congenital tibial dysplasia who not only did not develop fractures, but in whom the tibia became nearly normal with spontaneous deformity-resolution. Thus, some tibias will not fracture even if left alone. This raises an ethical issue--is it justified to operate on an intact tibia in patients with this diagnosis only because we believe that our procedure may prevent the development of an assumed fracture?. Especially since this procedure is neither curative nor has it been proven to be truly prophylactic(3).

The authors described a technique identical to the bypass grafting described by McFarland (4). He believed that the cause of persistence of the pseudarthrosis must be mechanical due to angulation and the bending stresses of muscles. However, this theory has not been proven and there are reports that prove that congenital pseudarthrosis of the tibia (CPT) is a biological defect(5).

With the development of better fixation methods and better understanding of the pathology of CPT, the current best treatment depends on the type of dysplasia. For a dysplastic tibia without fracture, no surgery is justified and the limb should be protected in a removable brace until skeletal maturity when the deformity can be safely corrected. For a psudarthrotic tibia, a biological solution should be adopted including intramedullary fixation to maintain a straight leg and lessen refractures(6).

The author did not receive any outside funding or grants in support of his research for or preparation of this work. Neither he nor a member of his immediate family received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, division, center, clinical practice, or other charitable or nonprofit organization with which the author, or a member of his immediate family, is affiliated or associated.

References

2. Lloyd-Roberts GC, Shaw NE. The prevention of pseudarthrosis in congenital kyphosis of the tibia. J Bone Joint Surg Br. 1969 Feb 1;51(1):100-5.

3. Nicoll EA. Infantile pseudarthrosis of the tibia. J Bone Joint Surg Br. 1969 Nov;51(4):589-92.

4. McFarland B. Pseudarthrosis of the tibia in childhood. J Bone Joint Surg Br. 1951 Feb;33-B(1):36-46.

5. Morrissy RT, Riseborough EJ, Hall JE. Congenital pseudarthrosis of the tibia. J Bone Joint Surg Br. 1981;63-B(3):367-75.

6. El-Rosasy MA, Paley D, Herzenberg JE. congenital pseudarthrosis of the tibia. in Limb Lengthening and Reconstruction. Chapter 34, pages 485-495. Editors; S.R. Rozbruch and S. Ilizarov. Informa healthcare publisher, New York, London. October 25th. 2006.

Print
PDF
Email

Recipient(s) will receive an email with a link (good for 5 days) to 'Prophylactic Bypass Grafting and Long-Term Bracing in the Management of Anterolateral Bowing of the Tibia and Neurofibromatosis-1'.
Your Name:*
Example: John Doe

Email Address:* CC Me:
Enter your valid email address. Example: jdoe@example.com

Recipient's Email Address:*

Separate multiple email address with semi-colons (up to 5).

Subject:* 's The Journal of Bone & Joint Surgery: 'Prophylactic Bypass Grafting and Long-Term Bracing in the Management of Anterolateral Bowing of the Tibia and Neurofibromatosis-1'
Subject for your email.

Message:

(Optional, message will truncate at 1000 characters)

Processing your request... Please Wait...

Copyright © in the material you requested is held by The Journal of Bone & Joint Surgery, Inc. (unless otherwise noted). This email ability is provided as a courtesy, and by using it you agree that that you are requesting the material solely for personal, non-commercial use, and that it is subject to Journal of Bone & Joint Surgery, Inc.'s Terms of Use. The information provided in order to email this topic will not be used to send unsolicited email, nor will it be furnished to third parties. Please refer to The Journal of Bone & Joint Surgery Inc.'s Privacy Policy for further information.

Copyright © The Journal of Bone & Joint Surgery Inc. All rights reserved.
Share
Get Citation

Onder Ofluoglu, Richard S. Davidson, John P. Dormans; Prophylactic Bypass Grafting and Long-Term Bracing in the Management of Anterolateral Bowing of the Tibia and Neurofibromatosis-1. The Journal of Bone & Joint Surgery. 2008 Oct;90(10):2126-2134.

Download citation file:

RIS (Zotero)

EndNote

BibTex

Medlars

ProCite

RefWorks

Reference Manager

Copyright © The Journal of Bone and Joint Surgery, Inc.
Rights & Permissions
Article Alerts

Processing your request... Please Wait.
Submit a Comment