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Incidence, Presentation, and Outcome of Spinal Cord Disease in Children With Systemic Cancer


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and Outcome

of Spinal



in Children

With Systemic


Donald W. Lewis, MD, Roger J. Packer, MD, Beverly Raney, MD,

Ihor W. Rak, MD, Jean Belasco, MD, and Beverly Lange, MD

From the Divisions of Neurology and Pediatrics, Children’s Hospital of Philadelphia; and Departments of Neurology and Pediatrics, University of Pennsylvania, Philadelphia

ABSTRACT. During a 40-month period, in 24 of 643 (4%) newly diagnosed patients with systemic cancer younger than 18 years of age (range: 3 months to 17 years) spinal cord disease developed. Patients with spinal cord disease included 21 children with metastatic spinal cord compres-sion, two with treatment-related transverse myelopa-thies, and one with an anterior spinal artery stroke. Spinal cord disease occurred in 13 of 102 children (12%) with sarcomas, six of 82 (7%) with neuroblastomas, and four of94 (4%) with lymphomas. Spinal cord compression occurred as the presenting sign of malignancy in six children (four with sarcomas and two with lymphomas). In the remaining 15 patients, cord compression occurred a median of 13 months after initial diagnosis, and in four patients it occurred at the time of first relapse. Symptoms

of metastatic cord compression included back pain in 17 patients (80%), weakness in 14 (67%), sphincter dysfunc-tion in 12 (57%), and sensory abnormalities in three (14%). Findings on plain radiographs of the spine were abnormal in only seven of 20 patients with cord compres-sion, and myelography was needed to differentiate compression from other causes of spinal cord disease. Treatment included high-dose corticosteroids followed by operation (seven patients) or radiotherapy (14 patients). After treatment, nine of 15 nonambulatory patients be-came ambulatory, and five of 10 incontinent patients regained sphincter control. None of the patients with nonmetastatic spinal cord disease had a satisfactory out-come. Incorrect and delayed diagnosis was frequent in children with spinal cord disease (median time from onset of symptoms to diagnosis, 2 weeks) and 12 children were paraplegic and ten had loss of sphincter control at diag-nosis. Spinal cord disease is a relatively common neuro-logic emergency in children with cancer, especially in

Received for publication Nov 15, 1985; accepted Dec 26, 1985. Presented, in part, at the Child Neurology Society, Memphis, Oct 11, 1985.

Reprint requests to (R.J.P.) Division of Neurology, Children’s Hospital of Philadelphia, 34th St & Civic Center Blvd, Phila-delphia, PA 19i04.

PEDIATRICS (ISSN 0031 4005). Copyright © i986 by the American Academy of Pediatrics.

those with sarcoma, and requires immediate investigation and intervention. Pediatrics 1986;78:438-443; spinal cord diaease, spinal cord compression, epidural cord

compres-sian, metastatic cancer, neurooncology.

Metastatic spinal cord compression is the most common cause of symptomatic spinal cord disease

in pediatric patients with oncologic diseases.’

Spinal cord compression is well-known to occur in the terminal phases of childhood cancer but may also occur as the presenting sign or early in the

course of the illness.2 Treatment-related myelopa-thies can produce acute spinal cord dysfunction that may be clinically indistinguishable from met-astatic cord compression. Delay in diagnosis of spinal cord disease may contribute significantly to morbidity.3 To better characterize the incidence, presentation, and outcome of spinal cord disease in children with systemic cancer, we reviewed our experience in 24 consecutive patients seen at the Children’s Hospital during a 4-year period.


Patients with spinal cord disease were studied during a 40-month period during 1980 to 1984 when

643 patients younger than 18 years of age were

newly diagnosed as having systemic cancer at the Children’s Hospital of Philadelphia. This includes

all patients with solid tumors and lymphoreticular malignancies but excludes all patients with primary CNS tumors.

Twenty-four patients with spinal cord disease


symp-1 Ambulatory with or without weakness of lower extremities or ataxia

2 Not ambulatory but able to lift legs

against gravity when supine

3 Paraplegic and unable to move legs

against gravity

* Adapted from Gilbert et al.7

TABLE 2. Tumor Types and Spinal Cord Disease Incidence

Type of Tumor No. of Patients With: Total No. (%) of

Patients With Spinal Cord Disease

No. of Patients Evaluated Cord



Sarcoma 12 1* 13 (12.7) 102

Rhabdomyosarcoma 6

Osteogenic sarcoma 1

Ewing’s sarcoma 3

Poorly differentiated 3

Neuroblastoma 5 1j 6 (ii) 54

Lymphoma 3 1 4 (7.5) 53

Endodermal sinus tumor 1 0 1 434

* Radiation myelopathy.

t Cord stroke.

:1:Toxoplasma transverse myelopathy. toms, management, and outcome by retrospective chart review. Because this analysis was

retrospec-tive, no predetermined criteria were used to select a specific treatment regimen. For the patients with

metastatic spinal cord compression, the decision

regarding radiation therapy v surgical decompres-sion was based upon the clinical judgement of the attending oncologist, neurologist, and neurosurgeon at the time of presentation. Patients were treated by high-dose intravenous corticosteroids, followed

by radiation therapy or by surgical decompression.

Seven of the 21 patients with cord compression had

surgical decompression and 14 had radiation


The outcome analysis was based upon the func-tional grades established by Gilbert et a17 (Table 1). Patients were divided into three groups

depend-ing upon their best motor function. Where

avail-able, we have also included sphincter function in the outcome assessment. Patients were serially evaluated while they were being treated, and the best motor function attained was used to assess outcome.


Patient Profile

In 24 of the 643 (4%) children with newly diag-nosed systemic cancer spinal cord disease devel-oped. Patients with spinal cord disease included 21 children with metastatic spinal cord compression,

TABLE 1. Function Assessment*

Grade Patient Function

two with treatment-related transverse myelopa-thies, and one with an anterior spinal artery stroke. There were 16 boys and eight girls. The patients were a median age of 8 years at diagnosis (range: 3 months to 17 years). The type of tumors associated with spinal cord disease and the incidence of spinal cord disease are listed in Table 2.

Metastatic Spinal Cord Compression

Clinical Presentation. Spinal cord compression was the most frequent cause of cord dysfunction and occurred at presentation of the illness in six children, four of whom had sarcomas (ages 2, 4, 5,

and 15 years) and two of whom had lymphomas

(both 12 years of age). In these patients, the symp-toms were present a median of 2 weeks (five days

to 4 weeks) before the diagnosis was made. In the

remaining 15 patients, spinal cord disease occurred a median of 13 months after diagnosis of systemic cancer. Spinal cord disease occurred coincident with systemic relapse in four patients (three with neuroblastoma and one with Ewing’s sarcoma) and was the first sign of relapse in two patients. Spinal

cord compression developed in four patients as a late complication of widely metastatic cancer.

Back pain was the most common symptom of spinal cord compression (Table 3) and occurred in 17 of 21 patients (80%). The pain either local or

radicular in character. The pain was located in the neck in three patients, thoracic regions in three patients, lumbosacral in seven patients, and hip or leg in an additional four children. Dysesthesias or paresthesias were present in three patients (14%). Pain was often overlooked early in the course of illness. Fourteen (67%) patients complained of weakness. Twelve patients complained of bilateral

leg weakness and two of weakness in one leg. There were no cases of upper extremity weakness or

quad-riparesis among our patients. Thirteen patients


On neurologic examination, localized spine ten-derness was the most reliable clinical finding, being present in 14 of 21 patients (67%). Twelve children

(57%) were paraplegic at the time of diagnosis. Ten

patients (48%) had complete loss of sphincter con-trol. A distinct sensory level could be found in only two patients. Ataxia of gait was recorded in two patients, although, retrospectively, it was difficult to distinguish gait ataxia from paraparesis.

The patterns of neurologic deficit that developed could be separated into three groups dependent on the spinal level of the lesion (Table 4). Based upon clinical examination, compression was located in the spinal cord in ten patients, conus medullaris in one patient, and cauda equina in ten patients.

Diagnostic Procedures: Spinal Cord Compression (Table 5). Plain spine radiographic studies were performed in 20 of 21 patients but findings were abnormal in only seven (35%). Radionucleotide bone scans showed local spine abnormality in six of 11 (54%) patients in whom they were performed. Spinal computed tomography with intrathecal me-trizamide contrast was performed in three patients and was diagnostic in all three. Magnetic resonance imaging with surface coil technique was performed in one patient and disclosed spinal cord compres-sion.

Lumbar myelography was performed in 15 of 21 patients with acute metastatic spinal cord dysfunc-tion. In 11 of these 15 patients, the metastatic disease was epidural in location: one cervical, three thoracic, two thoracolumbar, three lumbar, and two sacral. Intradural metastatic disease was present in

TABLE 3. Signs and Symptoms Compression

of Spinal Cord

Sign or Symptom % of Patients

Back pain Weakness

Sphincter dysfunction Sensory abnormality

80 67 57 14

four children, three of whom had cauda equina syndromes in the setting of systemic sarcoma and one with extensive subarachnoid spread with neu-roblastoma. Five patients did not undergo myelog-raphy and diagnosis was based on clinical findings. Four of these children were in preterminal condi-tions, and one child had a refractory thrombocyto-penia (platelet count < 9,000/id).

CSF laboratory study findings were recorded in

only four of 21 patients with metastatic epidural

spinal cord compression. Of these four patients, two had complete CSF blocks as demonstrated by mye-logram. The CSF protein values in these two pa-tients with complete block were 145 mg/dL and 252 mg/dL. Two patients had incomplete spinal block, and the CSF protein value was normal. CSF glucose concentration in all four patients was normal.

Pleo-cytosis was present in one patient with complete

block (WBC count 204il) and one with incomplete block (WBC count 31/al). CSF cytologic findings in each instance were negative for tumor cells.

Treatment. All patients with metastatic cord compression received high-dose intravenous corti-costeroid therapy (dexamethasone 1 mg/kg) im-mediately upon diagnosis. Seven of the 21 patients underwent surgical decompression, and the remain-ing 14 patients received radiation therapy. Four of the seven surgically treated patients had presented with signs of spinal cord compression without other overt signs of systemic malignancy.

Outcome. All 21 patients with metastatic rod compression were followed through the Division of

TABLE 5. Yield of Diagnostic Studies in Spinal Cord Compression

Diagnostic Study % of Patients

Myelogram 100

Bone scans 54

Plain spine radiographs 35

Spinal computed tomography (n = 3) 100

Magnetic resonance imaging (n = 1) 100

TABLE 4. Epidural Cord Compression: Clinical Localization

Sign Location

Spinal Cord Conus Medullaris Cauda Equina

Weakness Symmetric; profound Symmetric; variable Asymmetric; may be mild

Tendon reflexes Increased or absent Increased knee;

decreased ankle

Decreased; asymmetric

Babinski Extensor Extensor Plantar

Sensory Symmetric; sensory level

Symmetric; saddie Asymmetric; radicular Sphincter Spared until late Early involvement May be spared


Progression Rapid Variable, may be



Oncology at Children’s Hospital. Their outcomes are shown in Table 6. None of the six patients who presented with grade 1 functional status deterio-rated to a lower grade. Four of the six had sarcomas

and two had neuroblastomas. Four of these six had

lesions in the cauda equina and two had spinal cord

compression. Four were treated with radiation ther-apy and two had posterior decompressive laminec-tomies.

Fifteen patients presented with either grade 2 or

3 functional status and were, therefore, not

ambu-latory. Nine of these 15 (60%) were returned to ambulatory function (grade 1). Twelve patients were paraplegic (grade 3) at diagnosis of spinal cord

disease and seven of them were returned to grade 1

following treatment with radiation therapy (four patients), surgery (one patient), or surgery followed

by radiation therapy (two patients). Four of the

seven patients had sarcomas, two had lymphomas, and one had a neuroblastoma. The lesions were located in the cauda equina in five patients and the spinal cord in two patients. Three of the seven (43%) who recovered had been paraplegic for greater than 24 hours.

Five of the patients who were paraplegic (grade

3) failed to recover function, and one of them died

during therapy. Two had sarcomas, two had neu-roblastomas, and one had an endodermal sinus tumor. Three patients had spinal cord lesions and two had cauda equina syndromes. One patient had primary surgery, one had surgery because neuro-logic function deteriorated during radiation

ther-TABLE 6. Outcome*

Grade Prior to Treatment

Grade After Treatment

1 2 3

1(n=6) 2(n=3) 3(n=12)

6 2 7

0 0 0

0 1 5

* Results are numbers of patients.

apy, and three patients had radiation therapy alone.

Four of the five (80%) had been paraplegic for

greater than 24 hours.

Of the ten patients who had complete loss of sphincter control, five regained continence

follow-ing treatment. Two children were too young to

adequately assess sphincter control.

Nonmetastatic Spinal Cord Disease

The clinical presentation, etiology, diagnostic procedures, and outcome for children with nonme-tastatic spinal cord disease are shown in Table 7.


Acute spinal cord dysfunction in children with systemic malignancy is a neurologic emergency and is most commonly due to metastatic cord compres-sion.’ Although 88% of our patients had metastatic

lesions, the remaining 12% had clinically indistin-guishable syndromes but had nonmetastatic causes for their neurologic deficits. Other nonmetastatic

etiologies that must be considered included infec-tious or radiation-related transverse myelopathy, spinal cord stroke, intradural or extradural hema-toma, and extradural abscess. Obviously, treatment directed toward spinal cord compression in these patients could potentially increase neurologic com-promise.

Incidence figures regarding spinal cord involve-ment in childhood cancer have been infrequently reported. In the present study, in 4% of all patients with newly diagnosed malignancy, either metastatic

(3.6%) or nonmetastatic (0.4%) spinal cord

dys-function developed at some point in their illness.

Ch’ien et al3 found an incidence of 2.7% of

meta-static epidural compression from a population of

nearly 3,000 children followed at St Jude’s Children Research Hospital during a 17-year period. Sar-coma tumors are the most common tumors associ-ated with metastatic spinal cord disease in children

TABLE 7. Nonmetastatic Spinal Cord Disease

Pa-tient Age,


Tumor Type Etiology Diagnostic Procedure Outcome

(Grade) No.

1 17 yr, Rhabdomyosar- Radiation mye- CSF: increased pro- 3

M coma lopathy* tein; no cells

2 16 yr, Burkitts lym- Toxoplasmosist, CSF: lymphocytic 3

M phoma transverse


pleocytosis; glucose 54 mg/dl; protein 102 mg/dL Myelogram: normal

3 4 mo, Neuroblastoma Cord stroket CSF: normal 3

M Myelogram: normal

. * 4,5#{216}#{216}rads to cervical region with actinomycin radiopotentiation.


and account for 43% to 65% of all metastatic causes.3’8 Neuroblastoma, lymphomas, and

leuke-mias account for the majority of remaining

meta-static causes in childhood.’3’8 In about 10% to 12% of patients with sarcomas spinal cord disease de-velops, whereas in 7% of patients with neuroblas-toma and 3% to 4% of patients with lymphoma spinal cord disease develops.3

Spinal cord disease, either metastatic or nonme-tastatic, may occur at any point in the course of systemic malignancy. Although well-known to oc-cur in the terminal phases of widely metastatic malignancy, spinal cord compression may occur at presentation and may be the presenting complaint of systemic cancer. Twenty-five percent of our pa-tients had spinal cord compression at presentation; this included four with sarcomas and two with lymphomas. Previously, spinal cord compression has been found at presentation in 30% to 35% of patients.”3 Sarcomas, neuroblastomas, and lym-phomas seem to have an equal propensity to me-tastasize to the spinal canal early, although, within the group of sarcomas, osteogenic sarcomas tend to cause cord compression as a late complication.’3 In five patients, spinal cord disease occurred coinci-dent with relapse, and, in two of these patients, this was the first sign of relapse. Thus, in one third of our patients, cord compression occurred either at

the time cancer was diagnosed or as the first sign

of system relapse.

In our series, localized pain was the most frequent presenting symptom, occurring in 80% of patients. Previous pediatric literature reviews have indicated a lower incidence of back pain and localized spine tenderness in children with cancer and spinal cord compression. Frequency of pain between 25% to 60% have been reported.”3 Limb weakness had been found in 40% to 70% of patients.”3 Sphincter dis-turbances, usually constipation or urinary reten-tion, occurred in approximately half the patients”3 Sensory deficits have been the least useful physical finding and are frequently difficult to interpret in young children under the best of circumstances.

Myelography is the most accurate method of diagnosis and localization at this time.9 Lumbar myelography was diagnostic in all of our patients with metastatic spinal cord compression in whom the study was performed. All too often in clinical practice, obstacles to myelography occur. Patients with systemic malignancy are frequently pro-foundly thrombocytopenic as a result of their dis-ease or because of treatment-related bone marrow suppression. Coagulopathy or platelet counts of less than 20,0004d are relative contraindications to lumbar puncture.’#{176}” Alternative diagnostic studies for spinal cord disease, including plain spine films

and bone scans, were unreliable in our experience. Plain spine radiographic findings were abnormal in only 30% of patients with metastatic spinal cord compression. This is in distinction to the adult experience in which 90% of plain spine films show local bony abnormality.’2”3 In adults, the metas-tasis more often invades the epidural space from a vertebral site,5”4 whereas in children the epidural space seems to be invaded most probably by direct

spread from paraspinus sites. Likewise, bone scans

were of limited use and showed local spine

abnor-mality in only half (54%) of the patients with

metastatic spinal cord compression. Surface coil technique of magnetic resonance imaging was avail-able for our more recent patients and clearly (and noninvasively) demonstrated spinal cord compres-sion as well as the extent and source of spinal metastasis’5 As the technology and availability

in-creases, magnetic resonance imaging may become

the procedure of choice.

CSF laboratory study findings were rarely re-corded in this patient population. Because spinal cord dysfunction in the presence of systemic malig-nancy is not exclusively an extradural compressive

process, CSF studies may be of significant value in

differentiating among the other possible etiologies. Twenty-eight percent of our patients had either nonmetastatic causes for their neurologic dysfunc-tion or had intradural-subarachnoid spread of tu-mor. Both intradural tumor and transverse myelitis can produce a lymphocytic pleocytosis with high protein and low glucose concentrations, and cyto-logic studies are needed to distinguish between the two processes. Radiation myelopathy can cause an increase in CSF protein without cellular response.’6 At the time of myelography, CSF studies of cells, differential cell counts, glucose, protein, cytopath-ology, cultures, and myelin basic protein should be obtained in all children with cancer who are sus-pected of having spinal cord disease.

Based on our experience, a proposed method for evaluation of children with possible spinal cord compression is as follows. Essential to the diagnosis is a high index of suspicion when a child with systemic malignancy, particularly sarcomas, pre-sents with back pain, weakness, sphincter disturb-ances, and gait disturbance. Further supportive

evi-dence may be found with localized back tenderness, extremity weakness, and reflex changes. If findings

from the history and on physical examination

sug-gest progressive or severe dysfunction, our practice is to give a regimen of high-dose corticosteroids (dexamethasone 1 to 2 mg/kg intravenously)

fol-lowed by the immediate performance of a


orally every six hours) and arrange for a myelogram within 24 hours. In the child with only local back pain, without evidence of myelopathy on examina-tion, we will observe closely and perform bone radiographs and/or bone scan in an attempt to identify a local explanation for the pain. We gen-erally will arrange for a myelogram or spinal com-puterized tomography in these children as part of this investigation.

If an epidural mass is demonstrated by myelo-gram or computed tomography, the next decision that needs to be made regards surgical decompres-sion V radiation therapy. Recently, a third alterna-tive, that being chemotherapy alone,’7”8 has been suggested, although this remains quite controver-sial. Our retrospective analysis does not allow us to draw any conclusions concerning whether radiation or surgical decompression is more beneficial. A clear indication for surgery is the unknown pri-mary-the child who presents with neurologic dys-function without known systemic malignancy and in whom an epidural lesion is demonstrated by myelography or computed tomography. In this in-stance, surgery offers the dual benefit of decompres-sion plus identification of the tumor type. Surgery is also indicated if neurologic function deteriorates during radiation therapy.

The outcomes of children with spinal cord disease in the presence of systemic malignancy are shown in Table 6. The three patients with nonmetastatic spinal cord disease are not included in the table, and all three had unsatisfactory outcomes. Previous reviews have attempted to correlate tumor histol-ogy,6’19’2#{176}level of spinal involvement,’”5 degree of neurologic deficit at diagnosis,35 and time delay to diagnosis4’5 with variable, and often contradictory, results. Baten and Vannucci’ found that patients with spinal cord compression did less well than those with conus medullaris or cauda equina le-sions. Ch’ien et al3 found no difference in outcome between cord level lesions and lumbosacral lesions. In his review of neuroblastoma patients, Punt et a12 found a higher morbidity among children with cauda equina and conus medullaris lesions than children with spinal cord lesions. In this series, tumor histology, location of metastasis, and age did not clearly correlate with functional outcome, al-though there was a tendency for patients with sar-comas in the cauda equina to have a better outcome. It is also interesting that the two patients who were paraplegic due to lymphomas made full recoveries. In our series, the degree of disability at diagnosis was most clearly associated with functional out-come, and the degree of disability was directly re-lated to duration of symptoms and interval to di-agnosis. The cause of the delay in diagnosis was

most commonly due to misdiagnosis. Examples of disease processes for which spinal cord compression was misinterpreted included Guillian Barr#{233} syn-drome, sciatica, myopathy, plexopathy, and hip pain secondary to bony metastasis.


This work was supported, in part, by the Foerderer Fund for excellence.

We thank Lisa Gray and Linda Cella, for their secre-tarial assistance, and Peter H. Berman, MD, for review-ing this manuscript.


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3. Ch’ien LT, Kalwinsky DK, Peterson G, et al: Metastatic epidural tumors in children. Med Pediatr Oncol 1982;10:455-462

4. Tarlov IM, Herz E: Spinal cord compression studies: IV. Outlook with complete paralysis in man. AMA Arch of Neurol Psychiatry 1954;72:43-59

5. Wild WO, Porter RW: Metastatic epidural tumor of the spine. Arch Surg 1963;87:825-830

6. Smith R: An evaluation of surgical treatment for spinal cord compression due to metastatic carcinoma. J. Neurol

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8. Haft H, Ransohoff J, Carter 5: Spinal cord tumors in chil-dren. Pediatrics 1959;23:1152-1159

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10. Brem 55, Hafler DA, VanUitert RL, et al: Spinal subarach-noid hematoma: A hazard of lumbar puncture resulting in reversible paraplegia. N EngI J Med 1981;304:1020-1021 11. Edelson RN, Chernik NL, Posner JB: Spinal subdural

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15. Packer RJ, Zimmerman RA, Sutton LN, et al: Magnetic resonance imaging (MRI) of spinal cord disease of child-hood. Pediatrics 1986;78:251-256

16. Sundaresan N, Gutlerrez FA, Larsen MB: Radiation mye-lopathy in children. Ann Neurol 1978;4:47-50

17. Hayes FA, Thompson Fl, Hvizdala E, et al: Chemotherapy as an alternative to laminectomy and radiation in the man-agement of epidural tumor. J Pediatr 1981;104:221-224 18. Oviatt DL, Kirshner HS, Stein RS: Successful

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Donald W. Lewis, Roger J. Packer, Beverly Raney, Ihor W. Rak, Jean Belasco and Beverly

Systemic Cancer

Incidence, Presentation, and Outcome of Spinal Cord Disease in Children With


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Incidence, Presentation, and Outcome of Spinal Cord Disease in Children With


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