The Spine in Patients with OI Article

Review Article The Spine in Patients With Osteogenesis Imperfecta

Abstract Maegen J. Wallace, MD Osteogenesis imperfecta is a genetic disorder of type I collagen. Richard W. Kruse, DO, MBA Although multiple genotypes and phenotypes are associated with osteogenesis imperfecta, approximately 90% of the mutations are in Suken A. Shah, MD the COL1A1 and COL1A2 genes. Osteogenesis imperfecta is characterized by bone fragility. Patients typically have multiple fractures or limb deformity; however, the spine can also be affected. Spinal manifestations include scoliosis, kyphosis, craniocervical junction abnormalities, and lumbosacral pathology. The incidence of lumbosacral spondylolysis and spondylolisthesis is higher in patients with osteogenesis imperfecta than in the general population. Use of

From the Department of Orthopedics, diphosphonates has been found to decrease the rate of progression Nemours/Alfred I. duPont Hospital for of scoliosis in patients with osteogenesis imperfecta. A lateral Children, Wilmington, DE. cervical radiograph is recommended in patients with this condition Dr. Kruse or an immediate family before age 6 years for surveillance of craniocervical junction member serves as an unpaid abnormalities, such as basilar impression. Intraoperative and consultant to DePuy Synthes and serves as a board member, owner, anesthetic considerations in patients with osteogenesis imperfecta officer, or committee member of the include challenges related to fracture risk, airway management, American Academy of Orthopaedic pulmonary function, and blood loss. Surgeons and the Pediatric Orthopaedic Society of North America. Dr. Shah or an immediate family member has received royalties from Arthrex and DePuy Synthes; steogenesis imperfecta (OI) is a aremorecommoninchildrenwith serves as a paid consultant to DePuy Ogenetic disorder of type I colla- dentinogenesis imperfecta than in Synthes and Stryker; has stock or gen, which is located mainly in bone, children without dentinogenesis stock options held in Globus Medical; has received research or institutional ligaments, dentin, and sclerae. Mul- imperfecta. Children with cranio- support from DePuy Synthes; and tiple genotypes and phenotypes are cervical junction abnormalities are serves as a board member, owner, associated with OI, and the condition not likely to have generalized officer, or committee member of the is characterized by bone fragility. hypermobility.4 AllchildrenwithOI American Academy of Orthopaedic Surgeons, the Scoliosis Research Patients typically have multiple should undergo regular physical Society, the Pediatric Orthopaedic fractures or limb deformity; how- examination of their extremities and Society of North America, and the ever, the spine can also be affected.1,2 spinetoscreenforandmonitor Setting Scoliosis Straight Foundation. Neither Dr. Wallace nor any Spinal manifestations include scoli- progression of scoliosis. immediate family member has osis, kyphosis, craniocervical junc- Seventeen genetic causes of OI have received anything of value from or has tion abnormalities, such as basilar been identified. Approximately 90% stock or stock options held in a impression, basilar invagination of the mutations are found in commercial company or institution related directly or indirectly to the and platybasia, and lumbosacral the COL1A1 and COL1A2 genes. subject of this article. pathology, such as spondylolis- COL1A1 and COL1A2 genes 3 J Am Acad Orthop Surg 2017;25: thesis. Other clinical signs of OI encode for the alpha-1 and alpha-2 100-109 include blue sclerae, early hearing chains of type I collagen.2 The DOI: 10.5435/JAAOS-D-15-00169 loss, dentinogenesis imperfecta, phenotypic expression of OI was joint hypermobility, and short stat- originally classified by Sillence et al.1 Copyright 2016 by the American 2 Academy of Orthopaedic Surgeons. ure. Scoliosis, kyphosis, and cra- Type I is nondeforming OI with blue niocervical junction abnormalities sclerae, type II is perinatally lethal OI

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Copyright ª the American Academy of Orthopaedic Surgeons. Unauthorized reproduction of this article is prohibited. Maegen J. Wallace, MD, et al with multiple intrauterine fractures, Table 1 type III can result in fractures at birth Sillence Classification of Osteogenesis Imperfecta1,2 and causes progressive deformity, and type IV OI is characterized by normal Type Severity Features Inheritance sclerae and variable long bone defor- I Mild Blue sclerae, mild bone fragility, Autosomal dominant or mities2 (Table 1). Additional types fractures after walking, new mutations have been described as knowledge of minimal deformity the genetics of OI has increased. II Lethal Blue sclerae, multiple Autosomal recessive or Diphosphonate therapy has been intrauterine fractures, severe new mutations found to have a positive effect on deformity, stillbirth or neonatal death vertebral morphology, including III Severe Normal sclerae, dentinogenesis Autosomal recessive or remodeling of deformed vertebrae in deforming imperfecta, frequent fractures, new mutations older children and preservation of deformity of long bones, short vertebral shape when started early in stature, scoliosis life.5,6 Diphosphonates are often IV Intermediate Normal sclerae, moderate bone Autosomal dominant or startedininfancyinpatientswith fragility, moderate deformity, new mutations short stature, possible type III, type IV, or severe type I dentinogenesis imperfecta OI.7,8 Kusumi et al8 reported on a group of 18 patients with OI (5 type I,7typeIII,and6typeIV)with an average age of 12 months (range, study.3 Scoliosis is rarely observed in theorized that ligamentous laxity 11 days to 23 months). They patients younger than 6 years and plays a substantial role because the showed considerable improvement can progress rapidly after it is diag- lack of stability between vertebrae in bone density via dual-energy nosed.9 Engelbert et al10 and allows scoliosis to progress. x-ray absorptiometry (DEXA) and others11 showed that children with a decreased fracture rate with no OI in whom scoliosis developed had Progression major side effects of treatment. In markedly lower DEXA Z scores one study, infants who were treated compared with those of children Untreated scoliosis is known to with diphosphonates showed no with OI in whom scoliosis did not progress in growing children with OI 13 development of scoliosis, kyphosis, or develop. Single thoracic curves are and even into adulthood. Scoliosis craniocervical junction abnormalities the most frequent type of scoliosis curve progression can be as high as ° during treatment or follow-up from curve found in patients with type I 6 per year in patients with type III ° age 3 to 6 years, although clinically OI: 97% of curves in patients with OI, 4 per year in patients with type ° relevant scoliosis generally is not type I OI who have scoliosis are IV OI, and as low as 1 per year in 7,9 12 seen before 6 years of age. single thoracic curves, whereas in patients with type I OI (Table 2). 11 Furthermore, all 11 children who patients with type III OI, 58% of Watanabe et al found that, as the were treated in the study (average curves are in the thoracic region.12 DEXA Z score worsened, the scoli- age, 4.8 years) were ambulatory. In osis progressed, suggesting that a historical cohort of children with poorer bone quality leads to more OI of similar severity who were not Etiology severe scoliosis. Ishikawa et al14 treated with diphosphonates, only The etiology of scoliosis in patients found that biconcave vertebrae, in 2of11childrencouldwalkatan with OI is controversial, with theories which the height of the midportion average age of 4.6 years, and including vertebral body fragility, of the body is ,70% of the mean of 6 other children had lost a motor vertebral body shape, ligamentous the anterior and posterior vertebral milestone previously gained during laxity, muscle weakness, limb-length body heights, were common in childhood.7 discrepancy, and pelvic obliq- patients with OI (Figure 1). The uity.11,13 Vertebral fractures are presence of six or more biconcave thought to be a leading cause of vertebrae before puberty suggested Kyphoscoliosis scoliosis because of the severe fra- that severe scoliosis would develop. gility of the vertebral growth plates Anissipour et al12 found that The prevalence of scoliosis in the and the progression that occurs with patients with type III OI who began population of patients with OI ranges continued growth.14 Benson and diphosphonate treatment before age from 39% to 80%, depending on the Newman9 and Engelbert et al10 6 years had slower curve progression

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Table 2 Prevalence of and Progression of Scoliosis in Patients With Osteogenesis Imperfecta12 No Diphosphonate Treatment Before Diphosphonate Treatment Before Age 6 Years Age 6 Years Type of Osteogenesis Prevalence of Rate of Scoliosis P Rate of Scoliosis P Imperfecta Scoliosis Progression (degrees/yr) Value Progression (degrees/yr) Value

I 39% 1 0.01 2.3 0.19 III 68% 6 ,0.01 2.3 0.01 IV 54% 4 ,0.01 3.1 0.91

° ’ Figure 1 patients with type I or IV OI did not curves reach 45 , but the patient s have a statistically significant effect age and truncal height need to be on the progression of scoliosis. taken into account to avoid thoracic insufficiency syndrome. One report Pulmonary Function indicated that children with severe OI may benefit from fusion when Widmann et al3 evaluated patients curves are 35°,16 but we prefer to with OI and found that increasing avoid fusion in young children when severity of scoliosis correlated with a possible because contemporary decrease in pulmonary function, techniques make correction of larger specifically the vital capacity, leading curves at a later stage more feasible. to restrictive lung disease. Vital Although historical methods of capacity was 78% predicted when fusion have not been found to thoracic scoliosis was ,40° and improve lung volumes, contempo- dropped to 41% predicted when rary techniques may improve results, thoracic scoliosis was .60°. The and fusion can prevent progressive authors did not find a correlation respiratory decline resulting from between pulmonary function and thoracic insufficiency syndrome.3 kyphosis or chest wall deformity. Previous methods of treatment, including noninstrumented fusion, Treatment Strategies Lateral spine radiograph Harrington rods, and Luque instru- demonstrating osteogenesis Treatment of scoliosis in patients mentation, have shown modest or no imperfecta in a 5-year-old boy. The with OI can be difficult mostly correction of curves, little improve- patient has multiple biconcave because of poor bone quality and the ment in physical function, and up to vertebrae. For T7, the anterior vertebral body height is 11 mm, the rigidity of the deformity. Brace 50% complication rates. Cristofaro 17 posterior vertebral body height is treatment has not been found to be et al performed spinal fusion in 6.9 mm, and the midportion vertebral effective and is difficult to use eight patients who had OI and sco- body height is 4.6 mm. Black lines because of the fragility of the rib liosis. Five patients underwent indicate vertebral body height measurement locations. The height cage. Chest wall deformity second- fusion with Harrington instrumen- of the midportion of the body is 51% ary to Milwaukee bracing has been tation, and three patients underwent of the mean of the anterior and reported, and progression of curves noninstrumented fusion. All eight posterior vertebral body heights. despite bracing appears to be the patients were placed in casts or norm.15 In some patients, a soft braces postoperatively, and all thoracolumbosacral orthosis can be patients attained fusion by 10.3 after the development of scoliosis used for supported sitting to assist months postoperatively. No patient than did patients who started di- with functional activities, but no had any correction of the scoliosis or phosphonate treatment after age 6 assurance should be given with re- change of ambulatory status. In years (2.3° per year versus 6° per gard to curve progression. 1982, Yong-Hing and MacEwen13 year). Diphosphonate treatment Surgical spinal fusion to halt curve published data from a survey of started after age 6 years or in progression is considered when pediatric orthopaedic and spine

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Figure 2

PA (A) and lateral (B) radiographs demonstrating severe osteogenesis imperfecta in a 16-year-old boy with an 87° thoracic curve, a 115° thoracolumbar curve, and substantial pelvic obliquity. PA (C) and lateral (D) radiographs obtained 2.5 years postoperatively demonstrate spinal fusion from T1 to the sacrum with cement-augmented pedicle screws and pelvic fixation. surgeons regarding their patients usually consisted of one Harrington long-term follow-up. Two patients with OI and scoliosis. The report rod and hooks supplemented with sustained intraoperative lamina frac- included 60 patients who were methyl methacrylate. Hanscom et al18 tures that required hook placement at treated surgically, including 39 who reported on 13 patients with OI and an adjacent level. Three patients underwent posterior fusion with scoliosis. One patient underwent had failure of instrumentation at 1 Harrington rods, 16 who underwent noninstrumented fusion, five patients to 4 years postoperatively. The noninstrumented posterior fusion, 4 underwent fusion with Harrington authors reported functional im- who underwent anterior fusion, and rods, and seven patients underwent provements,with7of20patients 1 who underwent combined anterior fusion with Luque instrumentation. upgrading their ambulation level and posterior fusion. They found an The authors reported minimal and none having a decrease in average correction of 27° (36%). correction at the time of surgery with functional level. Compared with patients who loss of correction on follow-up, one Recent evaluation of contemporary underwent noninstrumented poste- instance of pseudarthrosis, and instrumentation and correction tech- rior fusion, patients treated with overall good outcomes. niques at our institution, such as the instrumented posterior fusion had Janus et al19 evaluated 20 consec- use of pedicle screws with cement 7% better correction. The compli- utive patients with OI who under- augmentation, has shown improved cation rate was .50%; 33 of 60 went treatment for scoliosis with outcomes. Yilmaz et al20 reviewed a patients had complications, mainly preoperative halo gravity traction series of 10 patients with OI who intraoperative bleeding and implant- followed by in situ fusion, with underwent posterior spinal fusion for related problems.10 Cotrel-Dubousset instrumentation in the treatment of scoliosis. All of the In a series of spinal fusions in 18 patients and Harrington instru- patients underwent preoperative pami- patients with OI, Benson and mentation in 2 patients. All patients dronate therapy. Seven patients had Newman9 reported postoperative used body jackets for 7.5 to 18 cement-augmented pedicle screw curve progression of 16° in the months postoperatively. The authors instrumentation at the proximal and noninstrumented fusion group and found 32% improvement in the sco- distal foundations (Figure 2). These 8° in the instrumented fusion group. liosis with traction, which subsided to authors were the first to report the In that study, instrumentation 25% correction after fusion and difficulty of exposure of the thoracic

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. ° Figure 3 curves 50 in patients who are spine in patients with severe past peak height velocity or in rib deformity, especially those with patients with substantial curve thoracic lordosis, sometimes requires progression after skeletal maturity rib osteotomy and retraction. because these curves can continue All patients are monitored intra- to progress in adulthood. Curve operatively with multimodal spinal rigidity is an important factor in the cord monitoring consisting of timing of surgical treatment and is transcranial motor-evoked potentials, evaluated clinically. We will somatosensory-evoked potentials, observe curves that progress during and electromyography. growth if they remain flexible. The In our opinion, pamidronate Preoperative T2-weighted axial proximal extent of instrumentation therapy results in more robust cor- magnetic resonance image and fusion is usually T2, T3, or T4 tical bone in the spine and improves demonstrating type III osteogenesis and depends on the stable vertebra pullout strength of pedicle screw imperfecta in a 19-year-old man. in the coronal plane and the extent fixation when screws appropriately Note the severe rib deformities that made access to the posterior spinal of proximal thoracic kyphosis. The fill the pedicle. Pamidronate therapy elements challenging. Multiple rib distal extent of fusion is the verte- does not seem to affect the intra- osteotomies were required during bra that is stable on the erect operative appearance of the bone or posterior spinal fusion to gain radiograph, unless examination of the risk of bleeding. Because di- adequate access to the posterior elements for pedicle screw the sagittal plane demonstrates an phosphonates affect bone remodel- placement and Ponte osteotomies to indication for lower fusion, such as ing, continuation of pamidronate aid in correction of the deformity. thoracolumbar junctional kyphosis. therapy can theoretically affect the In addition to apical lordosis, quality of the fusion. However, no spine because of rib overgrowth and compensatory kyphosis above and evidence-based guidelines in the lit- thoracic lordosis (Figure 3). They below the apex of the thoracic and erature address the postoperative routinely performed rib and poste- thoracolumbar curves can be use of diphosphonates. On the basis rior Ponte osteotomies at the apex of problematic and needs to be ad- of personal preferences and our the thoracic curve to aid in adequate dressedintheselectionoffusion experience with the healing of long exposure and to increase flexibility of levels. Proximal instrumentation bones, we prefer to withhold pami- the curve in the coronal and sagittal andfusiontoT2,T3,orT4isfre- dronate for 4 months postoperatively planes to allow correction. Cement quently needed to control the sag- to facilitate partial resumption of augmentation of the proximal and ittal plane and prevent proximal osteoclast function to allow for distal screws was used to increase junctional kyphosis. Pelvic fixation remodeling of the fusion mass. If pullout strength of fixation in bone is sometimes indicated for the postoperative surveillance radio- and prevent pullout. The authors management of severe pelvic graphs indicate early signs of fusion reported average correction of obliquity. and the implants are stable, pami- ° 48%withnolossofcorrectionat In patients with rigid, severe (90 ) dronate therapy is resumed. Our follow-up, no neurologic deficits, curves, preoperative traction is experience with patients who have and no implant failures. They also occasionally used to avoid the need never received pamidronate therapy noted improved quality of life for three-column osteotomy and to is limited; most patients treated at our scores, pain, and sitting tolerance achieve slow correction over time. institution are on a routine infusion in these patients.20 Intraoperative traction is used schedule or are given pamidronate commonly in these patients to achieve preoperatively. ’ slow correction with release of the Authors Preferred facets and intersegmental ligaments Treatment Strategy (eg, interspinous, ligamentum Craniocervical Junction Children with OI are followed at flavum) and viscoelastic creep and to Abnormalities least annually for clinical signs of address the deformity in all three spinal deformity. For those with planes. We think that traction is a Craniocervical junction abnormali- curves .30°, more frequent follow- useful adjunct for correction because ties have been observed in 37% of up is recommended, especially it decreases the force that the patients with OI; these abnormalities during peak height velocity. Cur- instrumentation needs to exert on include basilar invagination, basilar rent indications for fusion are the spinal column. Exposure of the impression, and platybasia (seen in

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13%, 15%, and 29% of patients Basilar impression results in char- The treatment of the craniocervical with OI, respectively), as well as acteristic features of the skull. These junction abnormality depended on secondary hydrocephalus.21 Basilar features include overhang of the whether the basilar invagination invagination is the protrusion of the temporal and occipital bones, termed was successfully reduced with pre- uppermost cervical structures into the “tam-o’-shanter” or “Darth operative traction. The patients in the foramen magnum with pro- Vader” skull.24 Clinical presentation whom reduction occurred (40%) jection of the tip of the dens axis of craniocervical junction problems were treated with posterior decom- .5 mm above the Chamberlain line can range from no symptoms to pression and occipitocervical fusion (from the posterior nasal spine to brain stem compression, restriction with or without instrumentation. the posterior lip of the foramen of cerebrospinal fluid circulation The patients in whom reduction magnum) or .7mmabovethe resulting in hydrocephalus, and did not occur (60%) underwent McGregor line (from the posterior impingement of cranial nerves.25 transoral or transnasal anterior nasal spine to the most caudal por- Baseline lateral skull/cervical spine decompression, followed by poste- tion of the posterior cranial base). radiographs are recommended in all rior occipitocervical fusion. These Basilar impression is the relative patients with OI before they reach patients were treated with in situ lowering of the cranial base (occip- age 6 years. Basilar impression may occipitocervical fusion with autog- ital condyles and foramen magnum) be clearly visible on a lateral radio- enous rib strut grafting with sub- with resultant positioning of the graph with upward migration of laminar cables or contoured loop uppermost cervical vertebral struc- the cervical spine into the base of the instrumentation. Postoperatively, tures above the caudal border of the skull. In more subtle cases, the all patients used either a halo vest or skull. Platybasia is flattening of the diagnosis of basilar invagination is modified Minerva braces until solid cranial base.21,22 A study demon- made when the odontoid bone pro- union was observed. Contemporary strated skull base abnormalities in trudes above the Chamberlain, rigid occipitocervical instrumenta- all four types of OI.23 The authors McRae, and McGregor lines on the tion was not used in this series. reported that 26% of patients had at lateral radiograph24 (Figure 4, A and Although successful fusion occurred least one abnormality; specifically, B). Drawing the recommended lines at an average of 8.2 months 16% had platybasia, 6% had basi- on plain radiographs can be chal- postoperatively, progression of the lar impression, and 4% had basilar lenging because of the deformity and basilar invagination was observed in invagination. Increased clinical overlapping bony detail. If cranio- 80% of the patients. Of the 20 severity of OI was the strongest cervical abnormalities are a sub- patients with progression, 6 were predictor of skull base anomalies. stantial concern, we recommend symptomatic, including 4 with This retrospective review demon- obtaining an MRI and drawing the recurrent headache/neck pain, 1 with strated that treatment within the lines on those images (Figure 4, C). dysphagia, and 1 with myelopathy; first year of life with diphospho- these patients were treated with nates did not decrease the preva- prolonged external bracing, with lence of skull base abnormalities Treatment of Craniocervical improvement over time.26 later in life. In a different study, Junction Abnormalities In 2007, Ibrahim and Crockard27 Sillence22 found that 71% of Treatment of symptomatic craniocer- reported on their long-term experi- patients with type IV OI who also vical junction problems includes cra- ence treating 20 patients with basilar had dentinogenesis imperfecta had niocervical fusion with or without invagination and OI with ventral basilar impression, and 50% of traction (Figure 5). Sawin and decompression and dorsal occipito- patients with type IV OI and denti- Menezes26 reportedon25patients cervical fixation. The average age of nogenesis imperfecta had neurologic with basilar invagination, 18 of whom the patients was 27 years. Ten symptoms. Overall, 25% of patients hadOI.Ofthe25patients,56%were patients had type III OI, five patients with OI had basilar impression, aged 11 and 15 years, and 44% also hadtypeIVOI,andfivepatientshad and 8% of patients with OI had had symptoms of hydrocephalus. type I OI. All of the patients under- neurologic symptoms.22 Sillence22 Patients with asymptomatic basilar went anterior decompression through recommended that independent invagination were treated with an extended maxillotomy approach upright posture be delayed in all external orthotic immobilization. and elective tracheostomy. In a sec- patients with OI, especially those Symptomatic patients with hydro- ond surgical procedure 1 week later, with type IV OI, until age 18 months cephalus underwent ventriculoper- the patients underwent posterior oc- in an attempt to prevent basilar itoneal shunt placement before cipitocervical fusion from the occiput impression. treatment of basilar invagination. to C7, T1, or T2. The fixation

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Figure 4 instrumentation used in these procedures varied, with modern occipitocervical instrumentation used in more recent procedures. At hospital dis- charge, 80% of the patients showed clinical improvement or no deterio- ration of high-level function, compared with their preoperative neurologic symptoms. In three patients, clinical symptoms recurred at 2, 10, and 15 years postoperatively. At long-term follow-up, 15% of patients showed no clinical improvement, and 25% of the patients who had a recurrence of symptoms had died. The authors concluded that aggressive ventral decompression with the use of modern dorsal occipitocervical instrumentation can halt progression of basilar invagination in the long term.27

Authors’ Preferred Treatment Strategy Surgical treatment of craniocervical junction abnormalities is generally reserved for basilar invagination with clinical symptoms, which most commonly includes headaches, cranial nerve palsy, dysphagia, and symptoms of myelopathy, such as hyper- reflexia, quadriparesis, and gait abnormality. In patients with basilar invagination, hydrocephalus can be very dangerous and must be treated before any other intervention is performed. The natural history of basilar invagination can include progressive deformity and neurologic dysfunc- A, Diagram depicting the Chamberlain line, which extends from the posterior tion, creating the controversy of nasal spine to the posterior lip of the foramen magnum; the McRae line, which whether prophylactic treatment is joins the anterior and posterior margins of the foramen magnum; and the McGregor line, which extends from the posterior nasal spine to the most caudal indicated in asymptomatic patients portion of the posterior cranial base. B, Lateral radiograph of the cervical spine with basilar invagination evident on demonstrating type III osteogenesis imperfecta in a 12-year-old girl. This image imaging. We take a conservative demonstrates the difficulty of drawing the McGregor, Chamberlain, and McRae stance and prefer to monitor these lines. The McRae line was difficult to draw because the anterior and posterior aspects of the foramen magnum were difficult to visualize. C, Sagittal T2- patients for development of neuro- weighted magnetic resonance image was obtained for further evaluation of the logic symptoms, which can be subtle same patient. The McGregor, Chamberlain, and McRae lines are drawn. and can progress slowly. We cur- Hydrocephalus and syrinx are present. ADI = atlanto-dens interval, SAC = space rently do not prescribe orthotic available for spinal cord (Panel A reproduced from Willis BP, Dormans JP: Nontraumatic upper cervical spine instability in children. J Am Acad Orthop Surg braces for patients with OI who have 2006;14:233-245.) asymptomatic basilar invagination because we do not believe there is

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Figure 5 Figure 6

Lateral lumbar spine radiograph demonstrating osteogenesis imperfecta in a 20-year-old woman who reported increasing low back T2-weighted sagittal magnetic resonance image of the cervical spine pain. The patient has substantial demonstrating progressive basilar invagination in a 14-year-old boy with lumbar lordosis, elongated pedicles, osteogenesis imperfecta. The patient had headaches, neck pain, and decreased and a horizontal sacrum with sacral endurance but no overt symptoms of myelopathy. B, Postoperative lateral deformity. radiograph of the cervical spine in the same patient demonstrating occiput to C2 fusion, which was performed with intraoperative traction. patients ambulatory. Spondylolis- thesis occurred at L5/S1 in 11 of 12 convincing evidence in the literature et al30 compared the sagittal balance patients and at S1/S2 in 1 patient. that the use of a cervical brace pre- of the spine in patients with OI and a Nine patients had isthmic spondy- vents progression of basilar invagi- normal cohort. They found an lolisthesis, and three were dysplastic. nation or prevents symptomatic increase in T5-T12 kyphosis in the The grade was low in 10 patients and basilar invagination from occurring. patients with OI and equal lumbar high in 2 patients. The authors did We also do not counsel patients to lordosis compared with that of the not find that one specific type of OI delay independent upright posture control group. They found no differ- had a higher incidence of spondylo- until 18 months of age. No definitive ence in sacral slope, pelvic tilt, or listhesis than did other types, evidence in the literature has proven pelvic incidence in the patients with although seven of the nine patients that delayed sitting decreases the risk OI compared with the control group. with spondylolysis had type III OI.29 of basilar invagination, and delaying They concluded that patients with OI The clinical relevance and natural independent upright posture is nearly have increased thoracic kyphosis with history of spondylolysis and spon- impossible in most patients with OI lumbar lordosis that is unable to dylolisthesis in patients with OI are because many of these children are compensate for the kyphosis, result- not clear in the literature, and infor- motivated to sit, crawl, scoot, or ing in overall anterior sagittal balance. mation on surgical indications and stand at or near normal develop- Hatz et al29 evaluated lateral techniques is available only in sparse mental milestones. radiographs of the spine in 110 case reports. In our experience, many patients with OI to characterize patients with OI do not have normal lumbar deformities and spondylolysis/ pelvic parameters and often have Lumbosacral Pathology spondylolisthesis. They found an increased lumbar lordosis, and an 8.2% incidence of spondylolysis at increase in lumbar lordosis can even Spondylolysis and spondylolisthesis an average age of 7.5 years, with all develop at the distal end of a fusion have been found in patients with OI nine of those patients ambulatory. construct (Figures 6 and 7). The almost exclusively at the L5 level. In Spondylolisthesis occurred in 12 practitioner also needs to be aware the literature, incidence rates range patients (10.9%) at an average age of of hip flexion contractures and the from 5.3% to 10.9%.28,29 Abelin 6.4 years, with 92% of those possibility of acetabular protrusion.

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Figure 7

Lateral (A) and PA (B) radiographs of the spine demonstrating increased lumbar lordosis in a 16-year-old girl with osteogenesis imperfecta and scoliosis. Postoperative lateral (C) and PA (D) radiographs of the spine obtained 2 years after fusion demonstrate distal lordosis at the end of the fusion construct.

succinylcholine should be avoided identify asymptomatic craniocer- Anesthetic and because fasciculations can cause vical pathology. Early diphospho- Intraoperative fractures in severely affected nate treatment in patients with OI Considerations patients.24 Patients with OI can lose has been shown to be beneficial for substantial amounts of blood during the extremities and the spine by The surgeon must be aware of several spinal surgery; therefore, blood decreasing the progression of scoli- anesthetic and intraoperative con- should be available for transfusion if osis and improving bone quality. siderations in patients with OI. Frac- required. Controlled hypotension tures can occur when patients are during the spinal exposure and the transferred to the surgical table, use of tranexamic acid can decrease References positioned during the procedure, and blood loss and have been shown to transferred to the postoperative bed. Evidence-based Medicine: Levels of be effective in the surgical manage- In severely affected patients, fractures evidence are described in the table of ment of complex pediatric spinal can result from the use of blood contents. In this article, reference 7 is deformity.31 pressure cuffs and from tourniquets a level II study. References 5, 6, 8, used for insertion of intravenous 13, 16, 23, 24, and 30 are level III lines. Airway management in anes- Summary studies. References 1-4, 9-12, 14, 15, thesia is challenging because these 17-21, and 25-29 are level IV patients often have large heads, large The spine is commonly affected in studies. tongues, and short necks. They also patients with OI. Early identifica- References printed in bold type are have poor pulmonary function as a tion of scoliosis, kyphosis, and cra- those published within the past 5 result of chest wall deformities. Nor- niocervical junction abnormalities years. mal lung predictions based on age is important. By age 6 years, and size are not accurate in patients 1. Sillence DO, Senn A, Danks DM: Genetic patients should be screened with a heterogeneity in osteogenesis imperfecta. J with OI because of their stature. clinical examination, including a Med Genet 1979;16(2):101-116.

Hyperthermia and diaphoresis tend neurologic examination and a lat- 2. Van Dijk FS, Sillence DO: Osteogenesis to occur in these patients. The use of eral cervical spine radiograph to imperfecta: Clinical diagnosis,

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nomenclature and severity assessment with osteogenesis imperfecta. Spine (Phila 22. Sillence DO: Craniocervical abnormalities [published correction appears in Am J Med Pa 1976) 2007;32(17):E488-E494. in osteogenesis imperfecta: Genetic and Genet A 2015;167(5):1178]. Am J Med molecular correlation. Pediatr Radiol 1994; Genet A 2014;164(6):1470-1481. 12. Anissipour AK, Hammerberg KW, Caudill A, 24(6):427-430. et al: Behavior of scoliosis during growth 3. Widmann RF, Bitan FD, Laplaza FJ, in children with osteogenesis imperfecta. 23. Cheung MS, Arponen H, Roughley P, et al: Burke SW, DiMaio MF, Schneider R: J Bone Joint Surg Am 2014;96(3): Cranial base abnormalities in osteogenesis Spinal deformity, pulmonary compromise, 237-243. imperfecta: Phenotypic and genotypic and quality of life in osteogenesis determinants. J Bone Miner Res 2011;26 imperfecta. Spine (Phila Pa 1976) 1999;24 13. Yong-Hing K, MacEwen GD: Scoliosis (2):405-413. (16):1673-1678. associated with osteogenesis imperfecta. J Bone Joint Surg Br 1982;64(1):36-43. 24. Lubicky JP: The spine in osteogenesis 4. Engelbert RH, Gerver WJ, Breslau-Siderius LJ, imperfecta, in Weinstein SL, ed: The et al: Spinal complications in osteogenesis 14. Ishikawa S, Kumar SJ, Takahashi HE, Pediatric Spine: Principles and Practice,ed imperfecta: 47 patients 1-16 years of age. Homma M: Vertebral body shape as a 1. New York, NY, Raven Press, 1994, pp Acta Orthop Scand 1998;69(3): predictor of spinal deformity in 943-958. 283-286. osteogenesis imperfecta. J Bone Joint Surg Am 1996;78(2):212-219. 25. Khandanpour N, Connolly DJ, Raghavan A, 5. Land C, Rauch F, Munns CF, Sahebjam S, Griffiths PD, Hoggard N: Craniospinal Glorieux FH: Vertebral morphometry in 15. Benson DR, Donaldson DH, Millar EA: abnormalities and neurologic complications children and adolescents with osteogenesis The spine in osteogenesis imperfecta. J of osteogenesis imperfecta: Imaging imperfecta: Effect of intravenous Bone Joint Surg Am 1978;60(7):925-929. overview. Radiographics 2012;32(7): pamidronate treatment. Bone 2006;39(4): 2101-2112. 16. Kocher MS, Shapiro F: Osteogenesis 901-906. imperfecta. J Am Acad Orthop Surg 1998;6 26. Sawin PD, Menezes AH: Basilar 6. Semler O, Beccard R, Palmisano D, et al: (4):225-236. invagination in osteogenesis imperfecta and Reshaping of vertebrae during treatment related osteochondrodysplasias: Medical 17. Cristofaro RL, Hoek KJ, Bonnett CA, with neridronate or pamidronate in and surgical management. J Neurosurg Brown JC: Operative treatment of spine children with osteogenesis imperfecta. 1997;86(6):950-960. deformity in osteogenesis imperfecta. Clin Horm Res Paediatr 2011;76(5):321-327. Orthop Relat Res 1979;139:40-48. 27. Ibrahim AG, Crockard HA: Basilar 7. Aström E, Jorulf H, Söderhäll S: impression and osteogenesis imperfecta: A 18. Hanscom DA, Winter RB, Lutter L, Intravenous pamidronate treatment of 21-year retrospective review of outcomes in Lonstein JE, Bloom BA, Bradford DS: infants with severe osteogenesis 20 patients. J Neurosurg Spine 2007;7(6): Osteogenesis imperfecta: Radiographic imperfecta. Arch Dis Child 2007;92(4): 594-600. classification, natural history, and 332-338. treatment of spinal deformities. J Bone Joint 28. Verra WC, Pruijs HJ, Beek EJ, Castelein RM: 8. Kusumi K, Ayoob R, Bowden SA, Surg Am 1992;74(4):598-616. Prevalence of vertebral pars defects Ingraham S, Mahan JD: Beneficial effects of (spondylolysis) in a population with intravenous pamidronate treatment in 19. Janus GJ, Finidori G, Engelbert RH, osteogenesis imperfecta. Spine (Phila Pa children with osteogenesis imperfecta under Pouliquen M, Pruijs JE: Operative 1976) 2009;34(13):1399-1401. 24 months of age. J Bone Miner Metab treatment of severe scoliosis in osteogenesis 2015;33(5):560-568. imperfecta: Results of 20 patients after halo 29. Hatz D, Esposito PW, Schroeder B, Burke B, traction and posterior spondylodesis with Lutz R, Hasley BP: The incidence of 9. Benson DR, Newman DC: The spine and instrumentation. Eur Spine J 2000;9(6): spondylolysis and spondylolisthesis in surgical treatment in osteogenesis 486-491. children with osteogenesis imperfecta. J imperfecta. Clin Orthop Relat Res 1981; Pediatr Orthop 2011;31(6):655-660. 159:147-153. 20. Yilmaz G, Hwang S, Oto M, et al: Surgical treatment of scoliosis in 30. Abelin K, Vialle R, Lenoir T, Thévenin- 10. Engelbert RH, Uiterwaal CS, van der Hulst A, osteogenesis imperfecta with cement- Lemoine C, Damsin JP, Forin V: The Witjes B, Helders PJ, Pruijs HE: Scoliosis in augmented pedicle screw sagittal balance of the spine in children and children with osteogenesis imperfecta: instrumentation. J Spinal Disord Tech adolescents with osteogenesis imperfecta. Influence of severity of disease and age of 2014;27(3):174-180. Eur Spine J 2008;17(12):1697-1704. reaching motor milestones. Eur Spine J 2003;12(2):130-134. 21. Arponen H, Mäkitie O, Haukka J, et al: 31. Dhawale AA, Shah SA, Sponseller PD, et al: Prevalence and natural course of Are antifibrinolytics helpful in decreasing 11. Watanabe G, Kawaguchi S, Matsuyama T, craniocervical junction anomalies during blood loss and transfusions during spinal Yamashita T: Correlation of scoliotic growth in patients with osteogenesis fusion surgery in children with cerebral curvature with Z-score bone mineral imperfecta. J Bone Miner Res 2012;27(5): palsy scoliosis? Spine (Phila Pa 1976) density and body mass index in patients 1142-1149. 2012;37(9):E549-E555.

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