Pediatric intramedullary spinal cord lesions: Pathological spectrum and outcome of surgery.

BACKGROUND: Pediatric intramedullary spinal cord lesions are not only rare but also different from adults in a number of aspects. We aimed to study the incidence and the frequencies of various pediatric intramedullary mass lesions, their outcome to treatment and the factors determining their outcome of treatment.
MATERIALS AND METHODS: Thirty-one consecutive children (aged 1-18 years, mean 11.1 years, male: female = 1.8:1) with pathologically proven intramedullary spinal cord lesions treated at our center were studied. Clinico-radiological, histopathological, operative, and outcome data were reviewed retrospectively. The functional status was assessed using the modified McCormick grading system.
RESULTS: Gross total tumor excision was performed in 19 patients (61.3%), subtotal in 9 patients (29%), partial excision was performed in 2 (6.5%) patient, and only biopsy was performed in 1 patient (6.5%). There was one peroperative death, 2 patients died at follow-up. Complications included wound related complications (n = 4), transient deterioration in the motor power, and respiratory complication requiring a tracheostomy. Six patients showed recurrence at a mean follow-up of 16.4 months. Developmental tumors, high-grade ependymomas, and incompletely excised grade 2 ependymomas showed a tendency to recur.
CONCLUSIONS: Children constituted nearly 1/5(th) (17.4%) of intramedullary spinal cord tumors. Astrocytomas and ependymomas taken together constituted the most common intramedullary spinal lesions in children; however, developmental tumors predominated in the first decade. Children usually presented in good functional grades preoperatively and maintained good grades after surgery. Functional outcome was dependent on the preoperative neurological status and histopathology of the lesions.

Introduction

Although tumors of the central nervous system (CNS) are the most common solid neoplasms of childhood, spinal tumors remain a relatively rare occurrence (incidence 1 per million).[12] Pediatric intramedullary spinal cord lesions (PIMSCL) account for 4–6% of all CNS tumors in this age group.[3] Studies have highlighted certain differences between the pediatric and the adult intramedullary spinal cord lesions.[245] These include a different histological spectrum of the lesions and a differential outcome to treatment. Moreover, a younger age, anesthetic considerations in very young children and deleterious effects of radiotherapy are some of the other concerns peculiar to these patients.

Keeping above differences in mind, we set out to study the incidence and the frequencies of various pediatric intramedullary mass lesions, their outcome to treatment and the factors determining their outcome to treatment. A literature review is also presented in order to discuss issues pertinent in the evaluation and management of these lesions.

Materials and Methods

Thirty-one consecutive children (aged 1–18 years, mean 11.1 years, male: female = 1.8:1) with pathologically proven intramedullary spinal cord lesions treated at our center between 2007 and 2013 were studied. PIMSCL constituted 17.4% of intramedullary tumors during this period (out of total 178 cases). The patients without a minimum of 6 months follow-up, incomplete medical records and operated previously at other centers were excluded from this study. Preoperatively, all the cases underwent magnetic resonance imaging (MRI) of the spine (with cranial screening in some selected cases). Following the surgical procedure, all patients were evaluated with MRI scans to assess the extent of tumor excision. Clinico-radiological, histopathological, operative, and outcome data were reviewed retrospectively. The functional status was assessed using the modified McCormick grading system [Table 1]. Data were managed using Statistical Package for Social Sciences software version 18.0 (Chicago, IL). In our series, the extent of resection was classified as follows:

Table 1

Modified McCormick scale

Gross total: >95% excision

Subtotal: 50–95% excision

Partial: 10–50% excision

Biopsy: <10% excision.

Results

PIMSCL constituted 17.4% of all cases (n = 178). There was a male predominance (20:11). The mean age of the children was 11.21 ± 4.78 years (range: 6 months to 18 years). 19 children (61.3%) were older than 10 years.

The pain was the most common presenting symptom (n = 16, 51.6%). Neck pain was present in 6 patients (19.3%), whereas back pain was present in 10 patients (32.2%). Motor weakness was seen in 29 (93.5%) patients. Spasticity was present in 15 patients (48.4%). Sensory symptoms were complained by 15 patients (48.4%). Bladder involvement was present in 11 patients (35.5%), whereas only 6 patients (19.4%) had complaints pertaining to bowel dysfunction. Only one patient had an accompanying respiratory compromise at presentation (3.2%). Lower cranial nerves were involved in 2 patients (6.5%) and 1 patient had involvement of fifth cranial nerve (3.2%). Posterior column involvement could be clinically documented in 13 patients (41.9%). Cerebellar symptoms were present in only 2 patients (6.5%). Table 2 summarizes the demographic and clinical features of the children analyzed in the current study. As far as modified McCormick grades at the time of presentation were concerned, 9.7% (n = 3) were in grade 1, 12 patients (38.7%) were in grade 2, 4 patients (12.9%) were in grade 3, whereas 6 patients each (19.4%) were in grade 4 and grade 5. Hence, 19 patients presented with good functional grades preoperatively.

Table 2

The summary of demographic, clinical, and radiological findings of our study

The salient imaging findings observed in our series are shown in Table 2. On MRI, tumors were located at cervical region (n = 12, 38.7%), dorsal region (n = 10, 32.2%), and at lumbar region (n = 9, 29%) in decreasing frequency. 8 out of 12 cervical tumors had cervicomedullary junction involvement. The majority of the patients had long segment involvement (more than two vertebral segment level) (n = 26, 83.8%). Of these 26 patients, the majority was constituted by astrocytomas (n = 9) followed by ependymoma (n = 6). Other tumors with multisegmental involvement were epidermoid (n = 6), dermoid (n = 2), and one case each of hemangioblastoma, neuroenteric cyst, and tuberculoma. Average segment involved in astrocytoma was 5.7, in ependymoma was 3.8, and in case of epidermoid was 4. Nine out of 10 astrocytomas and 6 out of 7 ependymomas had long segment disease. We encountered 1 patient with multifocal pilocytic astrocytoma. This patient was a 13-year-old boy and he had one lesion at C7-D1 and another lesion was located at L4-S2, between the cauda equina roots as shown in Figure 1a–c. Both lesions were operated in a single setting [Figure 1a–c].

Figure 1

This 13-year-old boy presented with two concurrent lesions at cervical (C7-D1) (a) and lumbar region (L4-S2) (b and c)

Gross total tumor excision was performed in 19 patients (61.3%), subtotal in 9 patients (29%), partial excision was performed in 2 (6.5%) patient, and the only biopsy was performed in 1 patient (6.5%). Subtotal excisions were performed in 4 cases of astrocytoma, 2 cases of tuberculoma, and one case each of long segment cervical grade 2 ependymoma, epidermoid, and cervical neuroenteric cyst, respectively. In cases of astrocytoma, a poor plane of cleavage prevented us from attempting total excision. In the patient with neuro enteric cyst spanning from the cervicomedullary junction to C7 level, the intramedullary lipoma at its caudal end was subtotally excised as it was inseparably adherent to the cord substance. In patients with tuberculoma, subtotal internal decompression was done deliberately leaving the capsule behind in order to avoid damaging the normal cord substance around the lesion. The patient with grade 2 ependymoma at D1-D5 level had a poor plane of cleavage inferiorly, which was deliberately left behind.

Both patients undergoing partial excisions had astrocytomas. Both of them had long segment lesions extending from the cervicomedullary junction to the cervicodorsal region. Intraoperative bradycardia led us to settle for partial excision in both cases.

Tumor biopsy without even decompression had to be done in one case of a long segment astrocytoma extending from the cervicomedullary junction to D6 level. This patient had poor functional grade preoperatively and his respiration was also severely compromised. During surgery, he developed cardiac arrhythmias and then arrest. Hence, surgery had to be abandoned after taking only a biopsy. This patient later expired in the Intensive Care Unit (ICU).

On histopathological analysis, the majority of our patients (n = 17, 54.8%) had gliomatous tumors. Of these 17 patients, 10 patients had astrocytoma (32.2%) and 7 patients had ependymoma (22.6%). Developmental tumors were seen in 11 patients (35.4%) and included epidermoid (n = 7, 22.6%), dermoid (n = 2, 6.5%), lipoma and neuroenteric cyst (n = 1, 3.2%) each, respectively. Other lesions encountered were hemagioblastoma (n = 1, 3.2%), tuberculoma (n = 2, 6.5%). Table 3 shows the histopathology of intramedullary lesions seen in our study.

Table 3

Histopathological diagnoses in the present series

Of great interest was that the histopathological spectrum of the lesions in the first decade of life was different from those in the second decade. In the first decade, out of 11 patients, developmental tumors accounted for majority (n = 6) (epidermoid = 3, dermoid = 1, neuroenteric cyst = 1, lipoma = 1) followed by astrocytomas (n = 3) and tuberculoma (n = 2). On the other hand, 14 out of 20 children in the second decade had gliomatous tumors (astrocytomas 7, ependymomas 7). Other tumors in the second decade were epidermoid (n = 4), hemangioblastoma (n = 1), and dermoid (n = 1). Hence, gliomatous tumors predominated in the second decade as against developmental tumors in the first.

There was one surgery related death (3.2%). This patient was a 6-year-old boy with pilocytic astrocytoma extending from C1 to D6. He had a poor preoperative functional status (modified McCormick grade 5). This patient developed cardiac arrest during surgery and died subsequently in the ICU. Other complications, apart from surgical mortality included wound related complications (n = 4), transient deterioration in the motor power, and respiratory complication requiring a tracheostomy. Wound related complications included wound infection, cerebrospinal fluid (CSF) leakage (1 patient each, 3.2%), and wound bulge in 3 patients (9.7%). Transient postoperative deterioration in the motor power was seen in 15 (48.4%) patients. Tracheostomy was required in 2 patients (6.5%). Both patients were discharged on tracheostomy and in both the cases, stoma was successfully closed later.

Postoperative radiotherapy and chemotherapy were given in 3 patients each (9.6%). Radiotherapy was given with a total dose of 5400 Gy in 30 divided fractions. Both radiotherapy and chemotherapy were given in one 16-year-old boy, a case of anaplastic ependymoma at the D4-D8 region. He received 4 cycles of procarbazine, CCNU, and vincristine (PCV) regimen. Another 15-year-old girl with anaplastic ependymoma (WHO grade 3) at D10-D11 level underwent radiotherapy and chemotherapy (4 cycles of PCV) after excision of the recurrence. Another patient with cervical glioblastoma underwent postoperative radiotherapy.

The mean follow-up was 26.5 months (range: 6-80 months). Improvement of spasticity and power was seen in 13 (44.8%) patients each. The sensory improvement was seen in 7 (46.6%) patients. Improvement in bladder function was seen in 5 (45.4%) patients while bowel symptoms improved in 2 (33.3%) patients. After treatment, the distribution based on McCormick functional grading changed as follows: 8/31 (25.8%) grade 1, 7/31 (22.6%) grade 2, 6/31 (19.4%) grade 3, 4/31 (12.9%) grade 4, and 6/31 (19.4%) grade 5. Hence, 21 out of 31 patients showed good functional recovery. Figure 2 shows the pre- and post-operative modified McCormick grades. In terms of modified McCormick grade, two out of 12 poor grade patients improved to a good grade, 1 patient died, whereas 9 patients remained in poor grade even after surgery. Those who improved were in grade 4 preoperatively. Hence, children who were in poor preoperative grade hardly improved after surgery, this particularly applied to grade 5. Histopathological analysis of the patients with poor functional outcome showed 3 cases each of low-grade astrocytomas and ependymoma, 2 cases of epidermoids, 1 case each of glioblastoma, dermoid, and tuberculoma. Hence, histopathologically, gliomatous tumors and infiltrative lesions had a tendency to present in a poor grade, and they hardly improved even after surgery.

Figure 2

Bar diagram is showing the distribution of patients as per modified McCormick grades pre- and post-operatively

We looked at the duration of symptoms prior to surgery in patients who had a poor postoperative outcome. The mean duration of symptoms was 16.8 months as compared to 16.9 months of patients belonging to good grade. Hence, the duration of preoperative symptoms did not correlate with poor outcome after surgery.

Disease progression was present in 6 patients (19.35%). These were epidermoid cyst (n = 2), anaplastic ependymoma (n = 1), grade 2 ependymoma (n = 1), dermoid (n = 1), and grade 1 astrocytoma (n = 1). 5 out of these 6 patients had total excision barring the subtotally excised grade 2 ependymoma. Mean time to progression was 16.4 months. Five out of these 6 patients underwent re-surgery. Hence, developmental tumors, high-grade ependymomas, and incompletely excised grade 2 ependymomas showed a tendency to recur.

Two patients died at follow-up. A patient with anaplastic ependymoma at D4-D8 region underwent radio-chemotherapy after subtotal surgical excision. After 4 cycles of chemotherapy regimen, the patient developed diarrhea, respiratory distress with mental obtundation, and hypotension during the treatment and succumbed to the illness. Another patient of cervical glioblastoma from the cervicomedullary junction to C6 vertebra died after 1-year of follow-up having completed his radiotherapy. The patient died from relentless disease progression.

Illustrative cases

A 16-year-old boy presented with gradually progressive spastic quadriparesis with neck pain of 8 months duration. On examination, there was the presence of wasting at right shoulder region with spasticity (grade 3) in remaining muscle groups of both upper and lower limbs. He had severe quadriparesis (power 1-2/5). There was a sensory loss in a cape-like distribution. Preoperative modified McCormick grade was 4/5. On imaging, there was a large intramedullary mass lesion extending from C1 to C6 level, the mass was ill-defined, causing and widening of the spinal cord. The lesion was hypointense on T1 and hyperintense on T2 with heterogenous contrast enhancement [Figure 3a–e].

Figure 3

T1- and T2-weighted images sagittal section (a and b) is showing the presence of an intramedullary mass lesion from C1 to C6 causing expansion of spinal cord. The mass shows patchy enhancement (c and d). Postoperative image (e) subtotal excision of tumor

At surgery (suboccipital craniectomy with C1-C6 laminectomy), the tumor was ill-defined, grayish pink in color, soft, suckable, and highly vascular. Maximal possible tumor excision was performed; however, the postoperative image showed some residual tumor that was missed during surgery [Figure 3f]. Histopathological findings were consistent with the diagnosis of glioblastoma. Although the patient required postoperative ventilatory support for 24 h, otherwise his immediate postoperative period was uneventful. He had improvement in power to 3/5. He received a postoperative adjuvant full course of radiotherapy a total dose of 5400 Gy in 30 divided fractions. He was also advised chemotherapy but because of financial constraints, chemotherapy could not be completed. The patient died after 1-year of surgery possibly from disease progression.

Discussion

The management of intramedullary spinal cord lesions has evolved over time. Due to unacceptable morbidity, these tumors were earlier treated with biopsy only or at the most, minimal decompression which was followed by adjuvant therapy.[67] In addition, these tumors were earlier excised in stages, wherein a dorsal myelotomy was done in the first stage in the hope that the tumor will self-extrude under pressure and this extruded tumor was then removed at a later stage.[78] However, recent times have seen a vast change in the way these lesions are managed. Advances in neuroimaging, microsurgical techniques as well as development of various surgical adjuncts such as LASER, cavitron ultrasonic surgical aspirator (CUSA), and intraoperative monitoring have made radical excisions of these lesions not only feasible but also reasonably safe. Furthermore, numerous studies have questioned the utility of adjuvant therapy in neoplastic spinal lesions.[791011] Hence, we have come a long way as far as the treatment of the intramedullary lesions is concerned. This particularly holds true for children.

PIMSCT are rare and account for no more than 4–6% of CNS tumors in children[31213] (the incidence of PIMSCT in our series, however, was a notch higher (17.4%). Similar higher incidence was also noted by other Indian authors.[2] This could reflect a geographical variation or a referral bias as these tumors are often referred to the higher centers for surgery.

The mean age of the children studied was 11.2 years. We encountered a higher incidence of developmental tumors as compared to the western literature. Furthermore, the spectrum of lesions differed according to the age. While developmental tumors and inflammatory lesions predominated in the first decade, astrocytomas and ependymomas accounted for a majority in the second decade. This difference in the spectrum could indicate different pathogenetic mechanisms underlying the development of these lesions at different age groups. Ependymomas have a lower incidence as compared to astrocytomas, as seen in the present study (32.2% vs. 22.6%). Ependymomas tend to increase in frequency with increasing age. A recent study by Constantini et al. failed to find even a single case of ependymoma in patients <3 years of age.[4] In our series, all the patients of ependymomas were above 12 years of age.

The pain was the most common presenting symptom and weakness was the most common sign. More than one-third of the patients presented with bladder complaints. This commensurated with the findings reported previously by others.[34714]

As far as the preoperative functional status was concerned, the majority of the children (n = 19, 62.3%) presented in good grades. This was in spite of the fact that most of them presented late for treatment (mean duration of symptom = 16.5 months). This indicates that the disease process was very slow and children tended to have a good neurological reserve. This assumes a special importance in that, although an early surgery is desirable, no matter how late the patient presents for treatment, there is always a case for surgical intervention.

In our study, 83.8% (n = 26) of the children had a long segment disease. Almost all of the astrocytomas and the ependymomas presented with a long segment involvement. The average segment involved in astrocytomas was 5.7, whereas, in ependymomas, the average segment involved was 3.8. Balériaux[15] has reported similar findings. He showed that the astrocytomas tended to be more extensive (a mean span of 5.6 vertebral bodies (minimum of 2 vertebral bodies, maximum of 19 vertebral bodies) than ependymomas (mean extent of 3–4 vertebral bodies).

Two of our patients presented with 2 concurrent lesions. In one patient, there was a long segment neuro enteric cyst with a lipoma located over the caudal end of the cyst. The second patient had multifocal pilocytic astrocytoma involving the cervical region and the conus – cauda region. This multifocality in spinal cord low-grade glioma is very rare and we have not come across any case in the literature.

Surgery remains the mainstay of treatment in intramedullary spinal cord lesions. The surgical treatment essentially aims at maximal resection of the tumor while attempting to preserve normal functions. Issues pertaining to resection of these tumors include: (1) Laminectomy versus laminoplasty. (2) Adjuncts used during the surgery and (3) extent of excision and the factors determining the same.

Laminectomy or osteoplastic laminotomy is the first step in the resection of these lesions. The major reason of preferring osteoplastic laminotomy over laminectomy is the prospect of prevention of postoperative spinal deformity in the former. Postlaminectomy spinal deformity is particularly relevant in growing skeleton such as in children.[5] Furthermore, the cervical region is more prone to have a postlaminectomy deformity as compared to the thoracic and lumbar spine.[5] The incidence of postlaminectomy spinal deformity increases with time and one-third of these patients finally required surgical intervention.[11617] Apart from its role in the prevention of spinal deformity, osteoplastic laminotomies may potentially decrease the incidence of postoperative CSF leak and operative site pain. We preferred osteoplastic laminotomy for cervical intramedullary lesions only. However, increasingly this is being carried out for all intramedullary tumors irrespective of the site of involvement.

Over the past few decades, the evolution of certain surgical adjuncts has greatly facilitated higher grades of excision in these tumors. Intraoperative use of CUSA helps in rapidly removing these tumors, particularly useful in debulking astrocytomas. It also helps in preliminary internal decompression of long segment ependymomas. Although there have been concerns that the vibration effect of CUSA could hamper the nerve conduction of the motor tracts, recent studies have proven that that these effects are practically nonconsequential beyond 1 mm of vibrating probe.[1218]

The application of laser (ND-YAG) in excision of these tumors comes during myelotomy and removal of last few bits of the tumor along the tumor cord interface. However, tissue charring and prolonged procedural time are the major limiting factors of using LASER.[1219]

Intraoperative ultrasound is another useful adjunct in the surgery of intramedullary tumors. It helps in determining the extent of the tumor, tumor cysts, and any missing tumor residue.[2021] Moreover, features such as the echogenicity, symmetricity, and location of the tumor within the cord help in determining the nature of tumors (astrocytomas vs. ependymomas).[122021] Ultrasound interpretation is however greatly dependent on the operator and may be erroneous in differentiating tumor remnants from blood and edema.

Neurophysiological monitoring is a very important adjunct during surgery. This, however, requires different anesthetics considerations, an experienced neurophysiologist and trained occupational therapy personnel. Usually, a combination of motor evoked potential and somatosensory evoked potential is used at most centers. A decrease in amplitude indicates an impending injury to the nerve fiber tracts. This requires the temporary suspension of the procedure till waves return back to normal.[19222324] Hence, neuro monitoring helps in the safe tumor resection.

The extent of tumor excision is another issue related to the management of the PIMSCL. The extent of resection is mostly dependent on the tumor morphology. In astrocytomas, it is hardly ever possible to excise every bit of tumor. This is due to the infiltrative nature of astrocytomas with consequent lack of distinct tumor-cord interface during surgery. On the other hand, tumors such as ependymomas and hemangioblastoma usually have very good planes of cleavage surrounding them, allowing them to be completely excised, more often than not. In addition, the developmental lesions (e.g., dermoid, epidermoid, neuro enteric cyst, and lipoma) and inflammatory lesions such as tuberculomas usually do not have well defined planes around them, either because of congenital or inflammatory adhesions. Hence, it is usually not possible to excise them without incurring significant neurological deficits. More ever intraoperative events such as bradycardia and hemodynamic fluctuations seen in cervicomedullary junction tumors also affect the extent of surgical excisions as seen in our study. In cases of ependymomas, complete excision is associated with zero percent recurrence, although some authors documented about 5–10% recurrence rate even after complete excision.[252627] In high-grade neoplasms (both astrocytomas and ependymomas), early recurrence is usually the rule irrespective of the grade of excision.[28]

The role of adjuvant therapy in the management of intramedullary spinal tumors has changed over time. In the early days, when biopsy and limited decompression were the rule, adjuvant radiotherapy was given to each and every patient irrespective of histopathological diagnosis.[67] Currently, however, the unequivocal indications of radiotherapy in intramedullary spinal cord tumors include high-grade lesions (astrocytomas and ependymomas) and unresectable significant residual tumor.[1329] As far as the low-grade astrocytomas are concerned, radiotherapy is not advocated after complete resection. For incompletely excised tumors, two different schools of thought exist. One school advocates adjuvant radiotherapy of total 40–45 Gy over 30 cycles. They argue that it delays the progression of the disease.[122930] Whereas the other school of thought argues that these tumors are by nature, slow growing, and do not require radiotherapy. They like to intervene either by re-surgery (if tumors are deemed resectable) or by radiotherapy when tumor shows recurrence.[710] We follow the latter policy; similar philosophy is also applied to low-grade ependymomas. Radiotherapy is not without any adverse effects. It is associated with radiation myelitis, worsening of spinal curvature, and malignant conversion of benign tumors.[1712] Radiation is, however, a must after resection of high-grade tumors. Even though it does not prolong the overall survival, the progression free survival is prolonged.[112]

The role of chemotherapy in the management of intramedullary tumors is not clear; people have tried various chemotherapy regimens in the management of high-grade spinal intramedullary neoplasms albeit with limited success.[831] In pediatric patients, chemotherapy has a role in delaying radiotherapy similar to the medulloblastomas. Chemotherapeutic agents are very toxic and at times, like in one of our patients, these complications can be lethal.[1232] Chemotherapy has a definite role in the management of intramedullary tuberculomas.[33] In 2 of our patients with tuberculoma, antitubercular therapy was given. The response rate is very high and we continue the drugs for 18–24 months.

The majority of patients showed improvement after surgery. Sensory improvement occurred in 46.6% patients followed by a motor (44.8%) and sphincteric function (45%). Twenty-one patients were in good postoperative grade indicating that children tend to tolerate surgery well and recover to reasonable postoperative functional status. As we saw, those who had poor functional outcomes, preoperative poor functional grade, and histopathology of the tumors (gliomatous tumors and inflammatory lesions) seemed to be major factors contributing to it. Duration of preoperative symptoms, however, did not appear to affect postoperative functional status.

Conclusion

Children constituted nearly 1/5th (17.4%) of intramedullary spinal cord tumors. Astrocytomas and ependymomas, taken together constituted the most common intramedullary spinal lesions in children; however, developmental tumors predominated in the first decade. Children usually presented in good functional grades preoperatively and maintained good grades after surgery. The outcome was dependent on the preoperative neurological status and histopathology of the lesions.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.