Intraspinal Space-Occupying Lesions in Children: Clinical Features, Neuroimaging and Surgical Outcomes of 27 Cases

Background: Pediatric intraspinal space-occupying lesions are relatively uncommon. However, these lesions can result in neurological disabilities due to misdiagnosis and delayed treatment. The main goal of the present study is to evaluate the clinical and radiological features and treatment options of pediatric intraspinal space-occupying lesions in order to improve the clinical recognition and management. Methods: Clinical data of 27 children with intraspinal space-occupying lesions who underwent surgery treatment in a tertiary-care hospital between 2010 and 2018 were retrospectively reviewed and analyzed. Results: Of these 27 patients, 14 (51.85%) were girls and 13 (48.15%) were boys. The most common age group affected was 10~14 years (62.96%, 9 girls and 8 boys in this age group). The mean age was 10.11 years old. Pain and weakness were the most common clinical symptoms. Preoperative magnetic resonance imaging (MRI) identied intramedullary (10 cases, 37.04%), intradural extramedullary (10 cases, 37.04%) and extradural (7 cases, 25.92%) lesions, respectively. The majority of the lesions were intraspinal tumors (23 cases, 85.19%). The histological diagnosis of tumors included embryonic residual tumors (6 cases, 22.22%), ependymoma (5 cases, 18.52%), primitive neuroectodermal tumors (PNET) (3 cases, 11.11%), schwannomas (2 cases, 7.4%), ganglioneuroma (1 case, 3.7%), Ewing’s sarc (1 case, 3.7%), B-cell non Hodgkin lymphoma (1 case, 3.7%), Hodgkin lymphoma (1 case, 3.7%), chondrosarcoma (1 case, 3.7%), ganglioglioma (1 case, 3.7%), and glioma (1 case, 3.7%). Conclusions: The incidence of pediatric intraspinal space-occupying lesions is low, and the clinical manifestation is lack of specicity. The prognosis for children with malignant tumors is poor and surgical resection is postoperative clinical MRI at year, once a year during follow-up. The modied was used to rate the patient’s global functional impairment during clinical examination. The score categories were: 1 = neurologically intact; 2 = mild motor or sensory decit, but functional independence; 3 = moderate decit and limitation of function; 4 = severe motor or sensory decit, dependent; and 5 = paraplegia or quadriplegia. The clinical manifestations, imaging features, tumor location, resection degree, pathological diagnosis and prognosis of Gross total resection attempted for all physiologic monitoring motor evoked laminectomy recent


Background
The intraspinal occupying-lesions comprising tumoral and non-tumoral lesions are relatively rare in children [1][2][3][4], but can lead to serious neurological impairments if left untreated. The majority of the lesions are neoplastic lesions with the incidence less than 3 per 1000,000 persons per year, accounting for only 5% of pediatric central nervous system (CNS) tumors [5]. Notably, the most frequent pediatric intraspinal tumors are residual embryonic tissue tumors and neuroepithelial tumors. In contrast, meningiomas, shwannomas and ependymomas are more common in adults [6]. When symptoms of spinal cord compression occur in patients, a series of sophisticated imaging tools such as magnetic resonance (MR) and computed tomography (CT) could assist the early detection of intraspinal tumors [7]. However, the clinical presentation of intraspinal space-occupying lesions in children is insidious and lacks speci c symptoms [1,2]. Therefore, the actual diagnosis is usually delayed by months or more, which markedly affects the prognosis for the children [6]. Due to the rareness of pediatric intraspinal space-occupying lesions, only case series with limited number of patients are reported and therapeutic guidelines are not provided for pediatric intraspinal space-occupying lesions. In this study, we collected and analyzed the clinical data of pediatric intraspinal occupying-lesions at the General Hospital of Ningxia Medical University, China between 2010 and 2018, with the purpose to improve the diagnosis and treatment of these lesions in the future.

Methods
This study was approved by the hospital's Ethics Committee and the informed consent was obtained from each child's parent or guardian prior to inclusion in this study. We reviewed the clinical data of 27 pediatric patients with intraspinal space-occupying lesions who underwent surgery or biopsy from January 2010 to February 2018 at the department of neurosurgery, the General Hospital of Ningxia Medical University, China. The inclusion criteria include: 1) The age of patients ranged from 0 to 14 years; 2) The intraspinal space-occupying lesions con rmed by operation or biopsies and diagnosed by imaging examination. Pre-and postoperative magnetic resonance imaging (MRI) and electromyography were performed for all patients. Preoperative MRI was performed after admission and postoperative MRI was performed within one week after surgery. The extent of resection was evaluated by operative records and postoperative MRI re-examination. Subsequently, clinical and MRI examinations were performed at 6 months, 1 year, and once a year during follow-up. The modi ed McCormick Scale was used to rate the patient's global functional impairment during clinical examination. The score categories were: 1 = neurologically intact; 2 = mild motor or sensory de cit, but functional independence; 3 = moderate de cit and limitation of function; 4 = severe motor or sensory de cit, dependent; and 5 = paraplegia or quadriplegia. The clinical manifestations, imaging features, tumor location, resection degree, pathological diagnosis and prognosis of the patients were analyzed. Gross total resection was attempted for all lesions whenever possible. The intraoperative physiologic monitoring and motor evoked potential measurement were used during the surgery. The surgery was performed under the standard microsurgical conditions using the conventional laminectomy in the early years and osteoplastic laminotomy in recent years.

Results
Fourteen out of the 27 patients were female (51.85%) and 13 were male (48.15%). The patients that underwent surgery were divided into three age groups, including 0-4 years group (4 patients), 5-9 years group (7 patients) and 10-14 years group (16 patients). The median age was 10.11 years old. The mean age was 10.11 years old (range 4 -14 years). The clinical data of all patients are summarized in Table 1.

Surgical treatment
The tilt angle of operating bed was adjusted according to lesions. For extramedullary tumors, the prone position was usually used; for intramedullary tumors, the lateral position was usually selected, which was more bene cial to keep the surgical eld clear. The surgical approach for all lesions was usually through a midline incision centered on the spinal lesion, based on bone surface markers. The lamina and spinous processes dorsal to the intraspinal occupying lesions were then removed. The exposure should be appropriate for adequate decompression and exposure of occupying lesions as well as maintaining the spinal stability. After the lamina was opened, the operation was performed under a microscope. For intradural tumors, a clear plane of masses between the tumor and the surrounding normal tissue was carefully dissected and resected. In the case of in ltrating tumors, it was attempted to reduce the volume as much as possible from within the lesions. Surgical resection was performed with an ultrasonic knife. If the lesions were tightly attached to the spinal cord/cauda equina nerve/ lum terminale, and the boundary was unclear, the capsule was rst incised to remove the tissue in the lesion, followed by careful separation of the nerve rootlets and spinal cord along the capsule. If necessary, the lum terminale was cut off, and the lesion was subtotally resected in blocks to preserve the nerve integrity. Before suturing the dura mater, all nerves should be combed as far as possible to avoid nerve adhesion or stretch. The spinal dura was closed with a watertight suture and the laminar and spinal process were restored. Normally no drainage tube was placed except for the in ammatory lesion.

Histopathological examination
Histopathological examination was performed in 27 cases. Intraspinal tumors were found in 23 cases (84.62%): embryonal remnants tumors in 6 cases (epidermoid cyst in 3 cases, lipoma in 2 cases, cystic teratoma in one case), ependymomas in 5 cases (myxopapillary ependymoma in 3 cases, Fig.6A (Table. 2) was performed in 27 patients. One to three weeks after surgery, the clinical symptoms and neurological function of 20 patients were improved in varying degrees. The clinical symptoms were remained unchanged in 4 patients and even deteriorated in one patient. There was no operative (in-hospital) death. The postoperative infection occurred in one case. A total of 27 cases were followed up via outpatient service and telephone. The clinical follow-up period ranged from two months to seven years. Two patients with intraspinal primitive neuroectodermal tumors (PNET) died. Two cases of myxopapillary ependymoma relapsed from L2-3 to L5-S2 and T12-L3 to S1-3 at 11 and 12 months after surgery, respectively. One patient with ependymoma experienced recurrence three years postoperatively. Malignant peripheral epithelioid schwannoma invaded into the spinal canal from posterior mediastinum in one case (Fig. 2). In one case Hodgkin lymphoma invaded from the thoracic vertebrae to the spinal canal. The lesions in 2 cases were large, involving many organs and having poor surgical outcomes, further received chemotherapy. The volume of the lesions reduced after chemotherapy.

Discussion
Intraspinal space-occupying lesions are rare in pediatric patients and lack of uniform evidence-based management strategies [5,7]. In contrast to adult intraspinal space-occupying lesions, pediatric cases have their own characteristics in clinical manifestations, histopathology, and surgical outcomes. The physiological features of child growth and development require a relatively independent system for diagnosis and treatment of diseases. The potential factors that result in misdiagnosis and missed diagnosis of pediatric intraspinal space-occupying lesions could be due to insu cient medical history and lack of comprehensive neurological examination. Therefore, the pathological, physiological, anatomical and immunological uniqueness of children should be fully taken into account when dealing with pediatric intraspinal space-occupying lesions, and a multi-disciplinary team can ensure timely diagnosis and optimal prognosis [1].
Pediatric intraspinal space-occupying lesions include a variety of tumors and non-neoplastic lesions. These tumors are originated from e.g. embryonic remnants, spinal cord and nerves, spinal dura mater and adipose tissue. In contrast to schwannomas, ependymomas and meningiomas that are most common in adults, intraspinal tumors in children are predominantly embryonic residual tissue tumors (teratomas, epidermoid cysts, dermoid cysts, enterogenous cysts, lipomas), and neuroepithelial tissue tumors [6]. A previous study has shown that the extradural and intramedullary lesions are most frequent in children as compared to adults, suggesting the location of tumors within the spinal cord, the meninges, and the spine differs between children and adults [10]. In the present study, intramedullary, intradural extramedullary and extradural lesions account for 37.04 %, 37.04% and 25.93% of all children cases, respectively.
The onset of intraspinal lesions in children is insidious, and the clinical symptoms are nonspeci c. Clinical symptoms occur only after the spinal cord and nerves are compressed by the lesion. The most frequently encountered complaint at presentation is dyskinesia, including progressive reduction of myodynamia, unstable walking, gait abnormality and hemiparesis [8]. Similarly, the most common clinical symptoms in this study are progressive reduction of myodynamia (66.67%) and unstable walking (25.92%). Another relatively common symptom is pain (nerve root pain, dull pain or radiation pain), which is usually caused by nerve root compression, but the children often have di culties to explain it verbally. Back pain caused by intradural lesions is usually exacerbated in the supine position at night and could be associated with dural swelling resulted from the venous congestion. Other symptoms include sciatica, limb numbness, muscle atrophy, and autonomic nerve dysfunction caused by spinal cord compression, the latter consists of urinary weakness, urinary retention, incontinence, and defecation di culties. These symptoms did not normally precede motor or sensory defects, and the condition was quite serious at the time of diagnosis.
Early neurological dysfunction is easily overlooked due to the relatively di cult or incomplete description of symptoms from children, particularly for infants. Some clinical manifestations such as instability of walking are important for early diagnosis. Young children could not clearly describe the nature and location of pain and in infants it could be manifested as crying for unknown reasons, sweating or scratching local skin. More attention should be paid to children with newly occurred back pain without trauma. In this study, one child with intraspinal primitive neuroectodermal tumor has suffered from aggravated abdominal pain for six months and sought medical advice at night, but it was di cult to make a de nite diagnosis before a thorough medical examination.
Moreover, autonomic dysfunction such as diurnal voiding was also easily overlooked in children with intraspinal lesions. In addition, as one-third of children with intraspinal lesions can develop scoliosis, new-onset scoliosis should also be given more attention. In particular, for scoliosis with lumbar back pain the imaging examination should be performed as early as possible [4].
A comprehensive and structured neurological examination is very important for infants who cannot accurately describe symptoms. Asymmetric nerve re ex may be an early sign of intraspinal space-occupying lesions. Tendon hyperre exia of lower extremities may indicate that lesions are located in the lower cervical spine, thoracic spine and lumbar spine, whereas hyperre exia of the higher extremities may indicate lesions in the upper cervical spine. The subtle symptoms of intraspinal space-occupying lesions can be well revealed by assessing the gait of the child, including walking postures of the toes and heels.
Because of the incompatibility of physical examination, the children are instructed to change from sitting position to standing position, and subtle changes in proximal lower limb muscle strength are observed. The tenderness on percussion over vertebral spinous process may provide a clue for the location of lesion. Digestive system and bladder dysfunctions usually occur at late stages, but sphincter tension and urodynamic examinations are still helpful. In addition, the presence of brown spots, subcutaneous nodules or Lisch's ganglia in the skin may indicate the presence of neuro bromatosis. Clustered, convoluted hair may appear on the skin near dermoid cysts, epidermoid cysts, and teratomas.
When the intraspinal space-occupying lesion is suspected, MR imaging examination should be performed as early as possible. High-resolution contrastenhanced MRI can not only display the solid components of intraspinal space-occupying lesions, secondary cysts, and edema, but also detect scoliosis, which provide adequate information for further diagnosis [4]. In addition, the heterogeneity of embryonic residual tumors such as intraspinal endothelioid cysts, epidermoid cysts or teratomas can be demonstrated by MR imaging. MRI images reveal that intramedullary ependymomas often have T1-iso-intense or slightly hypo-intense signal, T2-hyperintense signal, homogeneous enhancement, and some of the tumor poles form cavities. In contrast, the heterogeneous enhancement can be caused by cyst formation or necrosis [11]. Malignant peripheral epithelioid schwannomas are usually observed as isointense on the T1weighted MRI image and hyperintense on the T2-weighted image with well-de ned margins and strong contrast enhancement and polycystic changes are present within the lesions [12,13]. The radiographic ndings of intraspinal PNET are usually lack of speci city, and radiographic diagnosis may often indicate astrocytoma, ependeoma or schwannoma. Although imaging data is nonspeci c, the possibility of PNET should be considered in pediatric patients when MRI reveals large, well-de ned margin intraspinal space-occupying lesions [14].
The surgical resection is still the primary treatment of pediatric intraspinal space-occupying lesions. Early surgical resection and rehabilitation at early stages after surgery are bene cial to the preservation of spinal cord and recovery of neurological functions [15]. In this study, the clinical symptoms were signi cantly improved in 20 out of 25 patients with surgical resection. The challenges of surgical resection are mainly to avoid spinal cord injury and maintain spinal stability. Because children are at a special stage of growth and development, the incidence of postoperative spinal deformity is signi cantly higher than that of adults. Therefore, under the premise of adequate decompression, the destruction of bone should be minimized and the composite structure of muscle and ligament should be preserved. It has been suggested that removal of lamina, spinous process and posterior ligament complexes and reconstruction of the lamina after resection of the lesion may be bene cial to maintain spinal stability. However, some reports demonstrate this procedure has no signi cant impact [16]. Gross-total resection of spinal cord ependymoma should be performed without postoperative radiotherapy and chemotherapy, as the incomplete resection is the main cause of postoperative recurrence of ependymoma [17]. The presence or absence of intraoperative tumor planes is the most important factor in determining the extent of resection. For malignant tumors, postoperative radiotherapy and chemotherapy can improve the quality of life and prolong the survival time of children. However, due to the rareness of intraspinal tumors, there is still a large amount of research on the e cacy of radiotherapy and chemotherapy in need [18,19].

Conclusions
The intraspinal occupying-lesions are relatively rare in children. The rst symptoms or clinical manifestations of intraspinal non-neoplastic lesions in children are sometimes very similar to those with intraspinal neoplastic lesions, but the treatment and prognosis are different from those with tumor lesions. Diagnosis of these diseases depend on histopathologic ndings. Microsurgical resection of the intraspinal space-occupying lesions is the mainstay of treatment. Further studies with larger sample sizes, surgical resection combined with adjuvant radiotherapy and chemotherapy, longer follow-up periods and multicenter prospective database should yield stronger conclusions.

Declarations
Ethics approval and consent to participate This study was approved by the hospital's Ethics Committee and the informed consent was obtained from each child's parent or guardian prior to inclusion in this study.

Consent for publication
Written, informed consent was obtained from the patients for published images of this article.

Availability of data and materials
Data used to support the fndings of this study are available from the corresponding author upon request.

Competing interests
The authors declare no con ict of interest.