Knowledge Review of Spinal Deformity and the Need for Fusion and Fixation following Treatment for Spinal Tumors among the Pediatric Age Group

Background: Spinal tumors are rare pathology in the pediatric population. The tumors can be classified as extradural, intradural extramedullary, or intramedullary. Any of the spinal tumors can eventually lead to spinal deformity. The progressive spinal deformity can be part of the initial presentation or evolve on long follow-up, even years after the initial intervention and treatment. Summary: Management of spinal deformity associated with spinal tumors in children is not well defined. Patients with progressive symptoms and even neurological deficits need correction for their deformity when diagnosed. Patients that do not have pain or related neurological deficits should be evaluated for the severity of their deformity and followed long-term. Special consideration is needed for young patients who need multilevel surgery or have deformity at presentation. Key Messages: When considering the need for instrumentation and fusion, the surgeon should consider the age of the patient, expected future growth of the spine, neurologic status, extent of initial deformity, and the number of vertebral levels involved by tumor. Providers should also consider how surgery may fix or prevent deformity, especially when instrumentation can affect imaging at follow-up.


Introduction
Spinal tumors are rare in the pediatric population and have diverse pathology.According to the latest Central Brain Tumor Registry of the United States (CBTRUS) in pediatric patients aged 0-19 years between 2014 and 2018, 1,330 tumors of the spinal cord and cauda equina were recorded, with an annual average incidence of 266 cases or 0.32 per 100,000 [1].Spinal tumors may be categorized as intradural intramedullary, intradural extramedullary (IDEM), or extradural.Possible histology includes primary central nervous system (CNS) tumors, metastases, embryonal tumors, meningiomas, schwannomas, neurofibromas, sarcomas, lymphoma, and others.Tumor growth and invasion of the spinal cord and surrounding structural elements can cause pain and deformity at the time of diagnosis.Surgical options include biopsy, debulking, and gross resection, with or without adjuvant treatment in the form of chemotherapy, immunotherapy, and radiation.Surgery often requires resection of structural elements that may cause or worsen spinal deformity [2,3].
Management of spinal deformity associated with spinal tumors in children is not well defined.Historically, surgeons have been averse to instrumentation and fusion after tumor resection to maintain mobility and prevent future spinal deformity.These patients also require frequent magnetic resonance imaging studies for follow-up and treatment planning.The diagnostic utility of magnetic resonance imaging is lessened by metal artifact from instrumentation.Furthermore, several extramedullary tumors such as lymphoma and sarcoma respond well to nonsurgical treatment.Even patients that require surgical debulking are often asymptomatic after surgery, regardless of obvious spinal deformity caused by the tumor.However, as length of survival has increased with advances in surgical and nonsurgical treatments, patients have begun to develop symptomatic deformities presenting with pain, poor cosmesis, or neurological deficit.This is even more significant for the pediatric patient that survives spinal tumor treatment and has potential long years to live, hence increased chance of developing future spinal deformity.The role and timing of instrumentation and fusion need to be clarified in this patient population.In this review, we stratify incidence of deformity by location of the pathology, examine current treatment strategies, and identify areas for further investigation.

Lessons from the General Population
The study of deformity in spinal oncology is relatively nascent, even more so in the pediatric population.Findings from the general population may help guide efforts in the pediatric population.
Static deformity may also contribute to spinal instability.Mechanical instability has been included as an indication for surgical stabilization in accepted guidelines such as the neurologic, oncologic, mechanical, and systemic decision framework [4].Through expert consensus, the Spinal Oncology Study Group defined spinal instability in all patients as "loss of spinal integrity as a result of a neoplastic process that is associated with movementrelated pain, symptomatic or progressive deformity, and/ or neural compromise under physiologic loads" [5].The Spinal Instability Neoplastic Score (SINS) was defined and validated and included the location of tumor within the spine, mechanical versus nonmechanical pain, lytic versus blastic or mixed bony lesions, radiographic alignment, vertebral body collapse, and posterolateral involvement of spinal elements [6].These classifications are based on adult patients.We report them here only as a reference for discussion of pediatric patients.Yet, the reader should read the recommendations along this review, understanding that most of the literature is not pediatric focused.
In the general literature, post-laminectomy cervical deformity is a well-defined phenomenon in which a new kyphotic deformity develops at a delayed interval after multilevel laminectomies [7].Complete laminectomy necessarily removes the posterior tension band, leading to anterior wedge compression because of progressive axial loading on the anterior vertebral body.Laminectomy may be required for direct decompression, which when combined with postoperative radiation, has been shown to be superior to radiation alone [8].The presence of any spinal tumor (intramedullary, IDEM, or extradural) is a known risk factor for postoperative kyphosis [7].Sciubba et al. [9] examined risk factors associated with instability that required fusion after cervical laminectomy for intradural tumor resection.In a retrospective review of all adult patients over a 10-year period at a single institution, they found 32 patients who underwent cervical laminectomy without fusion for intradural tumors of a mobile spine.IDEM pathologies included schwannoma, meningioma, neurofibroma, and metastatic lesions.Intramedullary pathologies included astrocytoma, ependymoma, hemangioblastoma, and ganglioglioma.In a mean follow-up period of 25 months (range 1-99 months), 5 patients (15.6% of all cases) underwent subsequent fusion.The average time between tumor resection and subsequent fusion was 19 months (range 1-35 months).Univariate logistic regression analysis found that each additional level of laminectomy increased risk of instability 3.1-fold.They concluded that patients likely to benefit from subsequent fusion were those that needed ≥ three levels of laminectomy and had preoperative myelopathic motor disturbance [9].
Like adult patients, pediatric patients with spinal tumors rarely present with spinal deformity.Wang et al. [10] showed that only seven of 272 (2.6%) adult and pediatric patients undergoing decompression for surgically naïve tumors had preoperative deformity.The deformity in all 7 patients deteriorated after surgery.Their study also revealed that 36 patients (13.2%) developed new deformity after surgery (mean follow-up 21.8 months, range 6-114 months).Of these, 17 (54%) were pediatric patients.Of the 43 total patients with progressive spinal deformity after surgery (seven with preoperative deformity who deteriorated and 36 with new deformity after surgery), two required further surgery.Both had originally had laminoplasty and required revision with fusion, one for kyphosis and one for lordosis and scoliosis [10].Other studies have shown rates of postoperative progressive spinal deformity ranging from 16% to 100% [11].Given the recently described concerns for deformity in general spinal oncology, special attention is warranted toward defining and refining management strategies in the pediatric population.

Pediatric Classifications
Some attempts have been made to classify tumors and guide treatment in the pediatric population.McGirt et al. developed a preoperative grading scale for intramedullary spinal cord tumors (IMSCT) that correlated with development of progressive deformity, requiring spinal fusion [11].Their scale included four factors: number of operations, preoperative Cobb angle >10°, thoracolumbar involvement, and age >13°.In a singleinstitution retrospective study of 164 patients, this scale was applied and found that a higher preoperative grade was associated with need for subsequent fusion to progressive deformity, with 41% of grade IV patients and 75% of grade 5 patients requiring spinal fusion.In their study, all preoperative deformity was scoliosis (Cobb angle >10°) and was present in 32% of all patients, while two-thirds (19 of 44) of patients with postoperative progressive deformity had a component of sagittal plane deformity and kyphosis.They also found that deformity was associated with laminectomy in 88% of patients, though subgroup analysis by location of tumor was not performed.In our review, there were no other classification systems looking specifically at defining risk factors for progressive spinal deformity in pediatric patients with spinal tumors.

Surgical Strategies
Given the burden of post-laminectomy kyphosis, efforts have been made to develop techniques that achieve the goal of decompression and tumor resection while avoiding postoperative deformity.Cervical laminoplasty, which has been utilized to decompress cervical spondylotic myelopathy while preserving motion, has become a popular tool in trying to prevent kyphosis.Hersh et al. [12] found no difference between laminoplasty and laminectomy in preventing postoperative deformity.Out of 66 consecutive pediatric patients at a single institution undergoing resection for IMSCT, 19 (29%) underwent laminectomy with mean follow-up of 25.3 months (range 9.7-58.8months), and 47 (71%) underwent laminoplasty with mean follow-up of 22.8 months (range 2.5-65.6 months) (p = 0.98).The median number of levels included in resection was four (IQR 1.5-5) in patients who underwent laminectomy and three (IQR 2-5) in patient who underwent laminoplasty (p = 0.79) Standard deviation for the number of levels involved was not reported.Fifteen (79%) of those who underwent laminectomy developed postoperative deformity, versus 39 (83%) of those who underwent laminoplasty (p = 0.81).And two (11%) of the laminectomy patients ultimately required instrumented fusion, versus eight (17%) of the laminoplasty patients (p = 0.71) [12].They concluded that the use of laminoplasty at the end of surgery did not prevent future need for spinal fusion and instrumentation.Taking their data into consideration, we can state that factors other than surgical technique influence the risk for spinal deformity.

Correcting Deformity
There exists a paucity of surgical guidelines for correcting spinal deformity associated with pediatric spinal tumorsbefore or after tumor resection.A recent review by Li et al. [13] of the MEDLINE database between 1969 and 2019 found only four articles that described approaches and surgical techniques for correction of postlaminectomy deformity after pediatric tumor resection.When their search was broadened to include all intraspinal pathology (including tethered cord, syringomyelia, and diastematomyelia), additional nine articles were found.In the absence of well-defined society or other guidelines, some of the established approaches and techniques in pediatric idiopathic and neuromuscular scoliosis may provide guidance.
Radiographic evaluation of pediatric deformity without spinal tumors commonly employs anterior-posterior and lateral standing long-cassette thoracolumbar radiographs, or full-body standing films, to evaluate coronal and sagittal curve magnitude and location.Right and left supine sidebending films may help determine curve rigidity and are Spinal Deformity and Spinal Tumors used to identify major versus minor curves in adolescent idiopathic scoliosis [14].Consensus alignment targets do not yet exist [15,16].Generally, the goals of surgery should include halting curve progression and neurologic decline rather than dramatic realignment [17].
Techniques for deformity correction in patients with spinal tumors are the same as those in other types of spinal surgery.The majority of cases will require posterior spinal fusion with pedicle screw instrumentation in the thoracic and lumbar spines [18,19].Lateral mass screw fixation may be employed in the cervical spine, with either pars or pedicle screws at C2 if needed.Osteotomies can provide angular correction and range in magnitude from partial facet joint resection (Smith-Petersen osteotomy), complete facet joint resection (Ponte osteotomy), pedicle subtraction osteotomy, pedicle subtraction osteotomy and adjacent disc resection, and one or two level vertebral column resections [20].
However, deformity correction in the setting of expansile intraspinal pathology can be catastrophic as manipulation of an already compressed or otherwise tenuous spinal cord can lead to irreversible neurologic deficit.Decompression of neural elements and resection of oncologic pathology, where possible, should precede manipulation of the spine and correction of deformity.Li et al. [13] further recommend avoiding distractive maneuvers in favor of compressive maneuvers to avoid overlengthening of the canal and stretching of the spinal cord in the setting of intraspinal masses.
The decision of whether to fuse at the time of tumor resection or in a delayed fashion is a difficult one.The merits of preserving growth potential must be balanced against the need for stabilization.Tumor resections that necessitate iatrogenic destabilization of the spinesuch as per the adult SINS criteriashould encourage simultaneous fusion.Multilevel cervical laminectomy should also prompt consideration of simultaneous fusion.
Any such correction should be performed by an experienced team at a high-volume center with the support of pediatric anesthesiology and critical care.Surgery should include intraoperative neuromonitoring with somatosensory evoked potentials and motor evoked potentials.Electromyography and D-wave monitoring may also be used at the operating surgeon's discretion [21].

Categories of Tumors
Spinal tumors may be categorized as intradural intramedullary, IDEM, and extradural.The tumor location impacts the incidence and etiology of deformity.Intra-medullary tumors, for example, may involve anterior horn cells and denervate paravertebral musculature.Weakened support of the spinal column may then lead to progressive deformity [12,22].Given that tumors of different categories preferentially affect different elements of the spine, it is useful to understand the differences in deformity associated with these tumors.Where available, we review the incidence of deformity at the time of surgery, the incidence of deformity after surgery, clinical outcomes after surgery without upfront fusion, and rates of subsequent surgery and type (fusion vs. other).

Intradural Intramedullary Tumors
Intramedullary lesions are a known risk factor for the development of spinal deformity (Fig. 1, 2).Yao et al. [23] found that in a series of 161 pediatric patients that underwent resection, in a median of 9 years (range 1-21) after surgery, progressive spinal deformity requiring fusion developed in 43 patients (27%).They found that in 79% of their cohort, GTR was achieved.In short-term follow-up, the functional status of the group that eventually needed fusion versus the one that did not was identical, but at the time for fusion surgery on long-term follow-up, the difference in their functional status was found to be significant (p = 0.006).They collected the risk factors from their cohort and found that age less than 13 years, preoperative scoliotic deformity (Cobb angle >10°), involvement of the thoracolumbar junction, and tumor-associated syrinx independently increased the odds of a postoperative progressive deformity requiring fusion.For those patients that needed further surgical resection, each subsequent resection increased the odds of a progressive deformity 1.8-fold (p < 0.05).On the other hand, emphasizing the need for early detection of spinal cord tumors, Symptoms lasting less than 1 month before surgical resection decreased the odds of spinal deformity requiring fusion ninefold (p < 0.05) [23].
Hersh et al. [12] found that 12% of pediatric patients (8 of 66) had preoperative deformity, and 82% (54 of 66) had postoperative deformity.Fifteen percent (10 of 66) required subsequent surgery, all of which were fusion procedures.Clinical outcomes or health-related quality of life scores (HRQoL) were not measured.
McGirt et al. retrospectively reviewed 58 pediatric patients in a single-institution study undergoing resection of cervical IMSCT and found that 24% (14 of 58) of patients had preoperative deformity, defined as loss of cervical lordosis or scoliosis with Cobb angle >10°.Nineteen percent (11 of 58) required subsequent fusion [24].19 percent (11 of 58) of patients developed postoperative deformity requiring fusion.Preoperative modified McCormick Scale (mMS) median was 2 (interquartile range (IQR) 2.3), which was stable postoperatively for all patients [25].
Tobias et al. [12] examined longitudinally extensive intramedullary tumors that involved at least two regions (cervical, thoracic, and lumbar) of the spine.They found 10 such pediatric patients (and three adult patients, ages 24, 36, and 45) over a 12-year period in a single institution, four of which included all three regions.Preoperative deformity was not reported.Postoperative deformity requiring fusion occurred in 5 patients (38%).Mean preoperative mMS was 2.4, which worsened in only 2 patients (15%) over mean follow-up of 3.4 years (range 1-12 years).
Ahmed et al. reviewed 55 pediatric patients over 35 years (1975-2010) with mean follow-up of 11.4 years (range 0.2-37.2years).Incidence of preoperative deformity was 20% (11 of 55), while incidence of postoperative deformity was 16% (9 of 55) [22].Univariate and multivariate analysis identified preoperative kyphoscoliosis and laminectomy/laminoplasty >4 levels as risk factors for postoperative deformity requiring fusion.MMS and 10-year survival data were similar between patients requiring and not requiring subsequent fusion.Table 1 summarizes the key publications regarding pediatric spinal intramedullary tumors in relation to spinal deformity.

IDEM Tumors
Pediatric spinal IDEM tumors are varied and may include dermoid, neurofibroma, schwannoma, meningioma, epidermoid, primitive neuroectodermal tumor, and hemangio-epithelioma. Meningiomas commonly result from cumulative radiation exposure and time elapsed thereafter and are expectedly rare in the pediatric population.As of 2017, fewer than 100 cases had been reported of pediatric spinal meningioma [28].
Neurofibroma and schwannoma are known causes of spinal deformity, especially in the setting of neurofibromatosis.Spinal deformity is the most common orthopedic manifestation of peripheral neurofibromatosis type 1 (NF-1).Scoliosis was first observed in Spinal Deformity and Spinal Tumors NF-1 by Gould in 1918, and soon after by Weiss (a dermatologist) in 1921 [29,30].The prevalence of scoliosis in NF-1 varies greatly in the literature from 2 to 69% [31].NF-1 can be divided into two subtypes which dictate the management of any deformity: dystrophic and nondystrophic.Dystrophic changes are characterized by skeletal dysplasia on radiographs and may compromise structural integrity of the spine.They include vertebral scalloping caused by dural ectasia (expansion of the thecal sac and weakening of surrounding bone and ligamentous structures), rib penciling, short curves with apical rotation, widening neural foramen and interpedicular distances, dysplastic pedicles, vertebral wedging, and paravertebral soft-tissue masses.Deformity in dystrophic NF-1 is managed aggressively as curves have increased rates of progression [32,33].Dystrophic curves less than 20°m ay be monitored without surgery.Nondystrophic curves may be managed with a brace if they were between 20 and 40°; surgery should be considered if the curve is greater than 40°.To define the natural history of NF-1, Toro et al. performed a 15-year single-center review of 438 patients referred to a neurofibromatosis center in Italy and found 43 pediatric patients with NF-1 and spinal deformity, yielding a prevalence of scoliosis in NF-1 of 9.8%.Seventeen (40%) were dystrophic and 26 were nondystrophic.Average age, sex distribution, and location of deformity were similar in both groups.A right thoracic curve was the most common.Surgery occurred more frequently in the dystrophic group than the nondystrophic group (29 vs. 14%), but the difference was not statistically significant.Their study was consistent with those of earlier studies.In 1992, Akbarnia et al. [34] reviewed all patients referred to the Neurofibromatosis Clinic at Cardinal Glennon's Children's Hospital between 1985 and 1991 and found 220 patients diagnosed with NF-1 and 23 patients with both NF-1 and spinal deformitya 10.4% prevalence rate of deformity in NF-1.Nine patients had nondystrophic curves, while 14 had dystrophic curves.The authors suggested that the true prevalence of spinal deformity in NF-1 might be closer to their observed rate and that higher prevalence rates in the literature may be the result of studies being performed in referral centers, the reputation of the surgeon, and the authors' interest in spinal deformity.More recently, Well et al. [35] in Germany reviewed 275 NF-1 patients and 262 age-and sex-matched controls and found a higher rate of scoliosis in the NF-1 group of 47% versus 5% in the control group.

Extradural Tumors
Extradural tumors may include epidural tumors, tumors involving paraspinal soft tissue, bony tumors, or multiple of these locations.Lymphoma may present in multiple locations.It is the second most common malignancy in children after leukemia [36].In children, lymphoma may involve the CNS secondarily or arise from the CNS (primary CNS lymphoma, PCNSL).When lymphoma is epidural, it may cause compression of the spinal cord manifesting as myelopathy.Dho et al. [37] presented 12 patients (out of 302 pediatric lymphoma patients) found to have spinal epidural lymphoma causing compressive myelopathy.One of these had systemic disease, and the other 11 had primary disease.Nine underwent surgery, while two underwent biopsy and one underwent radiation only.All surgical procedures involved laminotomy or laminectomy only, and none underwent laminoplasty or fusion.Mean average follow-up was 120.75 months.Preoperative incidence of deformity was not reported.However, all 9 patients (100%) went on to develop kyphotic deformity postoperatively.Data regarding how many received fusion for their deformity were not reported.In these cases, the dilemma is whether we fix the deformity even if the patient has no neurological deficits or continue the oncological treatment while following the deformity and the function closely.
Primary bone tumors of the spine are rare and can be benign (hemangioma, aneurysmal bone cyst, giant cell tumors, osteoblastoma) or malignant (chordoma, chondrosarcoma, osteosarcoma, and Ewing's sarcoma) pathologies [38].According to the American Cancer Society in 2022, approximately 3,910 new cases of bone cancer and 13,190 cases of soft-tissue sarcomas are diagnosed in the USA each year [39].Of these cases, approximately 5% involve the spine [40].When these tumors are located in the vertebral body, they will be most likely malignant which is an unusual pathology in the pediatric population.
Primary bone tumors rarely present with dominant intradural component.The main involvement usually is related to spinal cord compression or development of spinal deformity.In many cases, when the deformity is significant or the surgical debulking is needed and demanded approach that will create spinal instability, fusion and instrumentation are needed early in the treatment course because of the bony involvement.Elder et al. [41] reviewed a spine tumor database of 522 patients over 10 years at a single institution to find 5 patients with spinal osteoblastoma.Three were potentially unstable according to SINS criteria.None presented with or developed postoperative deformity, though all five were fused at the time of initial surgery.They concluded that because radical resection is needed, in many cases the surgical approach demands resection of spinal elements that affect spinal stability.In cases when the deformity does not create neurological deficit or discomfort, the surgeon should consider close follow-up rather than upfront treatment, especially in the immature spine or while the patient is still under oncological treatment.

Conclusions
Spinal tumors are rare in the pediatric population.The progressive spinal deformity either being present at initial presentation or evolved on long follow-up, demands special consideration, especially for young age patients, those with deformity at presentation, or when multilevel surgery is needed.In cases when there is spinal deformity at presentation but the patient does not show any deficit or discomfort, cautious follow-up can be practiced, especially in those cases that demand oncological treatment.

Fig. 2 .
Fig.2.17-year-old boy presented with hand writing difficulty.He was diagnosed with large intramedullary mass at C2-6, with MRI showing sagittal T2 (a) and T1 (b) large mass suggestive for ependymoma.The patient underwent biopsy followed by radiation.Histology was confirmed to be spinal cord ependymoma.6 months later since the patient was not able to be off steroids and had increased pain at night, he was transferred to our facility and had C2-6 osteoplastic laminoplasty and gross total resection (T2 (c), T1 (d)).Postoperatively the patient did very well only with mild numbness, with no other deficit.10 months after the surgical resection the patient had progressive spinal deformity (e, f).He went for posterior spinal fusion (g, h).MRI, magnetic resonance imaging.