Original Article Coexistence of Multiple Rare Spinal Abnormalities in Type 1 Neurofibromatosis: a Case Report and Literature Review

Int J Clin Exp Med 2015;8(10):17289-17294 www.ijcem.com /ISSN:1940-5901/IJCEM0014389

Original Article Coexistence of multiple rare spinal abnormalities in type 1 neurofibromatosis: a case report and literature review

Chun-Ming Zhao1,2, Wen-Jie Zhang2, Ai-Bing Huang2, Qian Chen3, Yuan-Long He2, Wei Zhang2, Hui-Lin Yang1

1Department of Orthopedic Surgery, The First Affiliated Hospital of Soochow University, No. 188 Shizi St, Suzhou 215006, Jiangsu, China; 2Department of Orthopedic Surgery, Taizhou People’s Hospital, Taizhou 225300, Jiangsu, China; 3Department of Orthopaedic Surgery, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai 200032, China Received August 12, 2015; Accepted October 6, 2015; Epub October 15, 2015; Published October 30, 2015

Abstracts: Orthopaedic involvement is the most common clinical presentation of Neurofibromatosis type 1 (NF-1) patients with the spinal abnormalities more frequently affected. In the spinal deformities of NF-1 patients, despite the scoliosis is the most frequent finding, several distinctive radiographic features, such as dural ectasia, defective pedicles, and spondylolisthesis, are relatively less common. Here, we reported a 16-year-old boy diagnosed with NF-1 who presented with dural ectasia, defective pedicles, and spondylolisthesis concomitantly, described the surgical treatment and provided a literature review. The boy complained of low back and leg pain for two months. On clinical examination, the patient showed multiple café au lait spots on his back and no neurological deficit. He had a family history of neurofibromatosis as his father suffering from NF-1. Imaging results demonstrated mild scoliosis, posterior scalloping of the lumber spine, L5 spondylolisthesis on plain radiographs, and marked dural ectasia of L3-L5 on MRI. Furthermore, the CT scan showed presence of thin pedicles at L3, bilateral symmetrical pedicle clefts at L4, and pars interarticularis fractures at L5. The patient received a long level posterior fusion from L1 to S1 with pedicle screws. Iliac crest autogenous graft mixed with artificial bone were used to achieve solid arthrodesis. At nine-month follow-up, the patient was asymptomatic and able to live a normal life. Our observation demonstrated that familiarity with those distinctive features in NF-1 patients could be contributed to making an early diagnosis and optimizing treatment.

Keywords: Neurofibromatosis, dural ectasia, spondylolisthesis

Introduction The diagnosis can be made if two or more of the described criteria are present [1]. Neurofibromatosis type 1 (NF-1), or Von Recklinghausen disease, is one of the most Orthopaedic involvement is the most common common autosomal dominant disorders with a clinical presentation of NF-1 patients with the prevalence of 1 in 3000 [11]. This disorder is spinal abnormalities more frequently affected. caused by the defects of the NF-1 gene on the The incidence of spinal deformities in NF-1 long arm of chromosome 17 whose product is patients varies from 2% to 64% [1, 3, 19]. These neurofibromin. Approximately 50% of NF-1 deformities are traditionally classified into non- cases are attributable to new mutations [15, dystrophic and dystrophic types based on the 23]. radiographic evaluation [8]. The non-dystrophic type has the presentations similar to the idio- This single-gene disorder may yet multiple and pathic scoliosis, however, the dystrophic type varied clinical manifestations. The clinical has its distinctive features, including vertebral spectrum can range from mild to severe defor- scalloping, rib penciling, transverse process mities. In 1987, The Consensus Development spindling, vertebral wedging, paravertebral Conference of the National Institutes of Health soft-tissue mass, short curve with severe apical has established diagnostic criteria for NF-1. rotation, intervertebral foraminal enlargement, Multiple spinal abnormalities in NF-1

Despite scoliosis is the most frequent skeletal manifesta- tion in affected NF-1 patients with the incidence between 10% and 71% [4, 14], these distinctive radiographic features, such as dural ectasia, spondylolisthesis, and defective pedicles, are relatively less common in NF-1 patients. Familiarity with these deformities is, therefore, contributed to making an early diagnosis and optimizing treatment [22]. Here, we reported a 16- year-old boy diagnosed with NF-1 who presented with dural ectasia, defective pedicles, and spondylolisthesis Figure 1. Preoperative anterior-posterior radiograph (Left) showing mild sco- concomitantly. liosis and multiple pedicle irregularities from L2 to L5 especially at the left side. Lateral radiograph (Right) revealing marked dural ectasia with posterior vertebral scalloping from L3 to L5, associated with spondylolisthesis at the Case report lumbosacral junction. A 16-year-old boy was admit- ted to our center with low back and leg pain for two months. The patient was treated with medications in the local hospital, but his symptom did not be relieved. On examination, the patient showed multiple café au lait spots on his back and no neurological deficit. He had a family history of neurofibromatosis, and his father had NF-1.

Plain radiographs and magnetic resonance imaging (MRI) were obtained. The anterior-posterior and lateral radiographs showed mild scoliosis, posterior scalloping of the lumber spine, and L5 spondylolisthesis (Figure 1). MRI revealed marked dural ectasia with vertebral scalloping of L3-L5 (Figure 2). Axial image showed a lateral meningocele extending through the L3-L4 foramen (Figure 3).

Initially, the patient was treated conservatively with a Boston brace. One month later, he was referred to our hospital again complaining of increasingly severe back and leg pain. To pre- vent the progressive deterioration of this symp- Figure 2. Sagittal MR image of lumbar spine show- tom, a surgical stabilization was advised. ing dural ectasia with multilevel posterior scalloping, Preoperative CT scan was performed to under- and spondylolisthesis of L5 on S1. stand the anatomy of pedicle. The CT scan demonstrated the presence of thin pedicles at widened interpediculate distances and dys- L3 (Figure 4), bilateral symmetrical pedicle plastic pedicles. clefts at L4 (Figure 5), and pars interarticularis

17290 Int J Clin Exp Med 2015;8(10):17289-17294 Multiple spinal abnormalities in NF-1

Figure 6. Axial CT scan image at L5 showing bilateral Figure 3. Axial T2-W MR image of the L3 vertebra pars interarticularis fractures with dural ectasia. shows vertebral scalloping with a lateral meningocele.

Figure 4. Axial CT image at L3 showing thin pedicles (especially left).

Figure 7. Sagittal CT image showing L3-L5 vertebral scalloping and L5 Spondylolisthesis.

fractures at L5 (Figure 6). Sagittal CT image showed L3-L5 vertebral scalloping with spondylolisthesis of L5 on S1 (Figure 7).

Under general anesthesia, a long level posteri- or fusion from L1 to S1 using pedicle screws was performed. During the procedure, the pedicle screws were not possible to set at the left side of L3, L4 pedicle and the two sides of L5 pedicles. Iliac crest autogenous graft mixed Figure 5. Axial CT image at L4 showing bilateral, sym- with artificial bone was used to enhance a solid metrical pedicular cleft. arthrodesis (Figure 8).

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was ever thought to be the possible cause. However, Heard et al [12] argued that it was the result of increased dural pulsation.

The dural ectasia is associated with posterior vertebral scalloping and leads to erosion of the surrounding osse- ous structures, resulting in widening of the spinal canal, thinning of the pedicles and lamina, and ultimately destabilization of the spine. Fortunately, the neural ele- ments are always intact be- cause the spinal canal itself is widened. In spite that, surgi- Figure 8. Postoperative anterior-posterior (Left) and lateral radiographs cal stabilization should be (Right) show a long posterior fusion using the pedicle screw from L1 to S1 levels (pedicle screw on the left side of L3, L4 and two sides of L5 was not considered when radiograph- possible to set). ic examination reveals insta- bility of the spine, which may precede the occurrence of After surgery, the boy wore the Boston brace for severe progressive deformities. James [20] re- three months. At nine-month follow-up, the ported a case of a child who had neurofibroma- patient was asymptomatic and able to live a tosis, in whom the dural ectasia produced normal life. erosion of the middle column and induced a spontaneous, complete dislocation in the Discussion upper part of the thoracic spine development without neurological compromise. The patient NF-1 patients may present with varied ortho- received a internal fixation and fusion surgery paedic manifestations with the spine being to stabilize the spine. In our case, although the most commonly affected. In the literature, vari- neurological function was intact, the symptom ous spinal deformities have been depicted in could not be resolved by conservative mea- NF-1 patients. To our best knowledge, coexis- sures, thus a posterior fixation and fusion pro- tence of dural ectasia, pedicle deficiencies and cedure was performed. spondylolisthesis in one case has never been specially reported. Pedicle deficiencies

Dural ectasia Pedicle irregularities are quite rare in NF-1. A spectrum of pedicle deficiencies has been illus- Dural ectasia is defined as a circumferential trated in the literature. Mandell [16] reported dilatation of the dural sac which most frequent- three cases of neurofibromatosis, one showed ly occurs in the lumbosacral spine [2]. Dural agenesis of a pedicle, another had multiple ectasia is most commonly associated with hypoplastic pedicles, and a third presented Marfan syndrome but is also reported in bilateral hypoplastic pedicles producing a spon- patients with scoliosis, neurofibromatosis, dylolisthesis. The author explained these pedic- ankylosing spondylitis, and Ehlers-Danlos syn- ular modifications by congenital abnormalities, drome, as well as following trauma [21]. The probably due to mesodermal dysplasia and prevalence of dural ectasia in patients with suggested that hypoplasia or agenesis of a Marfan syndrome is approximately 90%, con- pedicle should be deemed as the possibility of versely, that in NF-1 patients is about 10% [9]. underlying neurofibromatosis. Eichhorn [10] The mechanism is not well understood. reported a case of neurofibromatosis treated Collagen weakness or fibroblast dysfunction with internal fixation, in whom fractures of lum-

17292 Int J Clin Exp Med 2015;8(10):17289-17294 Multiple spinal abnormalities in NF-1 bar pedicles were founded from LI to L4 with were the two possible reasons for the implant dural ectasia penetrating the body of L2. failure. Bensaid [5] presented two cases of bilateral, symmetrical pedicular clefts associated with Our patient was the fifth reported case of spon- dural ectasia in neurofibromatosis. In one case dylolisthesis with neurofibromatosis and dural the pedicular cleft was at the T12 level, while in ectasia to receive surgical stabilization. As the the other it was at L4, and was responsible for primary goal is to stabilize the spine and halt spondylolisthesis. He established two hypoth- further progression, we chose a posterior long eses to explain this unusual change and sug- level fusion and did not attempted to obtain a gested the second hypothesis to be the most complete reduction. At nine-month follow-up, probable. One was that the pedicular defect the result was satisfied. However, a long-term was a congenital abnormality; the other was follow-up should be required, as even if the that bilateral stress fractures related to thin- spine was stabilized, the dural ectasia may ning of the pedicle was caused by dural ecta- progress [7]. sia. In the described case, the presence of thin Conclusion pedicles, bilateral symmetrical pedicle cleft, and pars interarticularis fractures suggested a In summary, dural ectasia, spondylolisthesis, role of mechanical effect. Thus, we also advo- and defective pedicles are distinctive features cated the second hypothesis. in NF-1 patients. Although dural ectasia concomitant with defective pedicles or spondylolis- Spondylolisthesis thesis in NF-1 patients have been depicted in Spondylolisthesis is also a very rare finding in the literature, concurrence of these deformities NF-1 patients. It is usually secondary to in one case has not been specially described. Familiarity with these deformities is contribut- increased anteroposterior diameter of the spi- ed to making an early diagnosis and optimizing nal canal, with elongation and thinning of the treatment. pedicles. To our knowledge, only 13 cases have been reported so far and 4 cases underwent Disclosure of conflict of interest surgical treatment [6, 13, 17, 18, 21, 24, 25]. Winter and Edwards [24] reported the surgical None. treatment strategy of spondylolisthesis associated with dural ectasia in a 5-year-old boy with Address correspondence to: Dr. Hui-Lin Yang, De- neurofibromatosis. The patient had spondylo- partment of Orthopedic Surgery, The First Affiliated listhesis of L5 on S1 of 65%. They first used Hospital of Soochow University, No. 188 Shizi St, halo-femoral traction to reduce the spondylolis- Suzhou 215006, Jiangsu, China. E-mail: yanghl- thesis, and then carried out a posterolateral [email protected] fusion from L3 to S1 with Harrington rod stabilization. Wong-Chung and Gillespie treated an References 11-year-old girl with lumbosacral spondylolis- [1] Neurofibromatosis. Conference statement. Na- thesis of Grade 5 surgically by in situ postero- tional Institutes of Health Consensus De- lateral fusion and a pantaloon body cast [25]. velopment Conference. Arch Neurol 1988; 45: Toyoda et al [21] treated a case of grade 4 575-578. spondylolisthesis in a 15-year-old girl by poste- [2] Ahn NU, Sponseller PD, Ahn UM, Nallamshetty rior long level fusion with the Galveston meth- L, Rose PS, Buchowski JM, Garrett ES, Kuszyk od, and posterior lumbar interbody fusion in BS, Fishman EK, Zinreich SJ. Dural ectasia in L5/S1 and posterolateral fusion in T10-S1. In the Marfan syndrome: MR and CT findings and 2009, Modi [18] et al performed a short seg- criteria. Genet Med 2000; 2: 173-179. ment fusion with pedicle screws to treat a [3] Akbarnia BA, Gabriel KR, Beckman E, Chalk D. 15-year-old boy with neurofibromatosis, who Prevalence of scoliosis in neurofibromatosis. Spine (Phila Pa 1976) 1992; 17: S244-248. showed grade 4 spondylolisthesis concomitant [4] Akbarnia BA, Gabriel KR, Beckman E, Chalk D. with dural ectasia. Four months after surgery, Prevalence of scoliosis in neurofibromatosis. the patient had S1 screw broken and had to Spine (Phila Pa 1976) 1992; 17: 244. receive a second surgery. It was inferred that [5] Bensaid AH, Dietemann JL, Kastler B, Gangi A, short segment fixation and complete reduction Jeung MY, Wackenheim A. Neurofibromatosis

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