Epidemiology

IMSCTs occur with a frequency equal to that of tumors in the rest of the central nervous system (CNS) when the risk is analyzed as a function of tissue volume, but the spinal cord represents just 4% of the CNS. Currently, the incidence of CNS tumors in children in North America is 4.5 per 100,000, or 3750 per year.¹ Based on a survey of the cancer registries of 45 states for the year 2004, 5.1% of CNS tumors occur within the spinal cord or cauda equina.¹ The obvious problem with this number is the fact that tumors of the cauda equina not involving the spinal cord are lumped with the pure spinal cord tumors. Series have separated tumors of the cauda from spinal cord tumors and have come up with a ratio of 4.6 spinal cord tumors to 1 cauda tumor. This would mean that 4.2% of tumors involving the CNS are IMSCTs. Consequently, we can expect to see roughly 170 to 180 IMSCTs in the United States every year. There does not seem to be a predilection for gender, and based on a limited data set, white individuals seem to be afflicted slightly more than blacks.

A dataset developed by Constantini and colleagues in which the outcomes of 164 children operated on for IMSCTs were analyzed and subsequently updated until the primary surgeon’s (Fred J. Epstein) retirement was reviewed for this chapter.^2,3 A total of 241 children and adolescents were listed who underwent surgery for IMSCTs between 1978 and 2001 at an average age of 9.5 years. Thirty-one were infants aged 0 to 2 years, 130 were children aged 2 to 13 years, and 80 were adolescents aged 13 to 21. Discounting the second year of life, the age at diagnosis seemed fairly evenly distributed, with perhaps a tailing off in incidence in late adolescence—but this could have been confounded by the impact of the referral pattern early in the primary surgeon’s career. It is not clear why there was such a disparate number of infants who underwent surgery between the ages of 1 and 2 years. One hundred forty-one (58%) of the patients were male. Seventy-six (46%) of the children reviewed by Constantini had astrocytomas, 18 of which were malignant, and 58 (35%) children had a mixed glial-neuronal tumor, the majority of which were gangliogliomas as established by immunohistochemical staining.⁴ Nineteen (12%) were ependymomas. The remaining children had mixed gliomas⁵ or primitive neuroectodermal tumors.³ In a later review of this patient population that looked at 181 pediatric patients seen at the same practice between 1987 and 1998, 4 (2.2%) were found to have hemangioblastomas and 3 (1.7%) had cavernous malformations.^6,7

Clinical Findings

The onset of symptoms in children harboring an IMSCT is usually realized in retrospect and predates the actual diagnosis by months if not a year or more. Constantini reported an average 11.6-month delay in diagnosis and a slightly shorter delay in children younger than 3 years (5.4 months).^3,5 Frequently, an accident or other unrelated event leads the child to a physician. The ensuing examination shows an inconsistency between the initial complaint and the symptoms being exhibited, which leads to the radiographic study that makes the diagnosis. This all attests to the benign nature of the majority of these tumors and their insidious growth pattern. The history is substantially shorter in children with malignant tumors, and such a finding should warn the clinician of the aggressive nature of the tumor.

The most common complaint at initial encounter was motor regression, which occurred 65% of the time, followed by pain (48%), gait abnormality (37%), dysesthesia (32%), and progressive kyphoscoliosis (32%) in the largest reported series.³ Other series have reported the same symptoms and signs but with slightly differing incidences. Lunardi and coauthors also reported a 32% incidence of sphincter disturbance and a 48% incidence of sensory deficits.⁸ Muszynski and associates, in studying an updated version of the database developed for Constantini’s paper, found a 32% incidence of urinary retention and a 3% incidence of delay in milestones.^3,9 On examination one can expect to find signs of myelopathy in most patients.⁸

Functional status at diagnosis varies. In reviewing 45 children with IMSCTs (29 with astrocytoma and 16 with ependymoma), Innocenzi and associates divided their patients into three groups based on their Karnosky Performance Status score.¹⁰ Group 1 had scores of 80 to 100; group 2, 60 to 80; and group 3, lower than 60. Twenty-two percent were in group 1, 56% in group 2, and 22% in group 3. Constantini and colleagues used a modified McCormick scale to assess the functional status of the patients.^3,11 Fifteen of 164 (9%) were neurologically intact (grade 1), 76 (46%) were functionally independent with mild motor or sensory deficits (grade 2), 33 (20%) required an external assistive device to maintain functional independence and exhibited “moderate” deficits (grade 3), 22 (13%) had severe sensory or motor deficits, or both, rendering them functionally dependent (grade 4), and 18 (11%) had major plegia with only a flicker of movement below the level of paralysis (grade 5). Sixty of the 164 were seen at Dr. Epstein’s service with newly diagnosed disease but no previous treatment.^2,3 Of these 60, 10 (17%) were grade 1, 32 (53%) were grade 2, 10 (17%) were grade 3, 6 (10%) were grade 4, and 2 (3%) were grade 5.

Symptoms and signs can vary according to the level of the spinal cord involved with tumor. Children with IMSCT at the cervicomedullary junction can have indications of brainstem involvement such as nausea and vomiting, a history of recurrent upper respiratory tract infections, and the development of a nasal quality in their speech. When the tumor primarily involves the cervical spinal cord, the child commonly complains of neck pain with or without radiation to one or both arms. This pain can be particularly intrusive at night.¹² Loss of motor function seems to initially be limited to the upper extremities, with progression to involvement of the legs, bowel, and bladder occurring late.⁹ In younger children, the parents may report that their child has seemed to switch hand dominance, whereas parents of older children with IMSCTs note frequent tripping or falling. Sensory abnormalities trail the motor deficits and are more limited, typically being unilateral. When the sensory abnormalities are symmetrical, the diagnosis of ependymoma should be suspected.⁹

IMSCTs of the thoracic spine have a more insidious onset. The first manifestations are usually pain and progressive scoliosis. Not uncommonly, these children are simply observed for idiopathic scoliosis until such time that the degree of scoliosis or evolution of complaints mandates imaging. Younger patients frequently complain of abdominal pain, which leads to a gastroenterology referral before coming to the attention of a pediatric neurosurgeon. Examination generally shows paraspinal spasm and evidence of myelopathy. Sensory findings occur late, as do bowel and bladder dysfunction as the tumor or its cyst extends into the conus. When the epicenter of the tumor is in the conus, the early manifestations may involve the bowel and bladder and result in a history of frequent urinary tract infections and complaints of irregular, problematic bowel habits. Only late in the course will there be undeniable evidence of urinary tract dysfunction.

Hydrocephalus can be an unusual but real outcome in an individual with an IMSCT. Rifkinson-Mann and coauthors reported on 25 of 171 patients with IMSCTs operated on by Epstein in whom hydrocephalus was found to be present or develop later.¹³ This group of 171 patients included both children and adults. Eighty-eight children were operated on during this period. Two of the 25 patients reported by Rifkinson-Mann and colleagues were older than 21 years, with 1 having a malignant tumor and 1 a benign one. Consequently, there was a 26% incidence of hydrocephalus in these 88 children with IMSCT. Rifkinson-Mann and associates concluded that the incidence of hydrocephalus is much higher in children with malignant IMSCTs. They could not conclude why the hydrocephalus developed but did note that 12 of the patients (nearly half) had evidence of subarachnoid spread of their tumor, 12 (nearly half) had extension of the tumor or a cyst to the obex (inferring outlet obstruction of the fourth ventricle), and 1 had both. Interestingly, 6 of the children in this series were initially seen for treatment of intracranial hypertension and only later were found to have an IMSCT. Four of these tumors were malignant.

Diagnostic Evaluation

There is no question that magnetic resonance imaging (MRI) of the spine is the diagnostic procedure of choice when confronted with a patient with signs of myelopathy and an IMSCT is suspected. MRI provides excellent soft tissue imaging within the spinal column, and any intramedullary lesions, edema, and cysts can be visualized.^14,15 It allows one to differentiate intramedullary lesions from extramedullary lesions, define the extent of the solid portion of the lesion, and with the aid of enhancement, differentiate tumoral cysts from nontumoral, reactive cysts. By using this information one can arrive at a reasonably certain diagnosis with regard to tissue type, which in turn will direct treatment strategies. Computed tomography and plain radiography are reserved for the evaluation of associated spinal deformities/instabilities, and myelography is generally reserved for situations when MRI cannot be performed.¹⁵

At minimum, a T1-weighted sequence, with and without gadolinium enhancement, and a T2-weighted sequence should be obtained in the axial and sagittal planes.¹⁴ Anything less will compromise one’s interpretation of the imaging. A gradient echo sequence and a fluid-attenuated inversion recovery (FLAIR) sequence can add additional information about hemosiderin deposits (gradient echo) or subtle intramedullary lesions (FLAIR). A diffusion-weighted image can be used when an ischemic infarct is suspected. One expects to see a significant mass when confronting an intramedullary tumor that will stand out on at least one of the sequences. When the size is subtle or not consistent with the degree of T2 signal hyperintensity (i.e., edema), one should consider an inflammatory process such as multiple sclerosis or transverse myelitis. Scanning of the brain and delayed, repeated imaging 3 to 6 months later will clarify the situation.¹⁴

Interpretation of MRI series is simplified by the fact that there are only a limited number of pathologies that will account for an intramedullary mass lesion within the spinal cord. In children, a mass lesion within the spinal cord is probably (>90%) an astrocytoma, ganglioglioma/glial neuronal tumor, or ependymoma. A hemangioblastoma or primitive neuroectodermal tumor is a remote possibility that can be considered when an unusual image or clinical state is present.

Intramedullary astrocytomas are the most frequently encountered spinal cord tumors in children. On MRI they are seen to enlarge the cord’s diameter and on average extend over four spinal segments. Their epicenter is eccentric. On T1-weighted imaging, the majority (>80%) are hypointense with the rest being isointense (Fig. 221-1).¹⁶ Characteristically, the margins of the tumor blur into the surrounding cord parenchyma, and both tumoral cysts and reactive cysts can be present. The tumor enhances with gadolinium, as do the walls of tumoral cysts in all but the rarest of cases.¹⁷ On T2-weighted imaging they appear hyperintense, but unlike edema, this hyperintensity is inhomogeneous.¹⁴ Kulkarni and coworkers reviewed their experience with four children harboring malignant astrocytomas within the spinal cord.¹⁸ Apart from a higher incidence of subarachnoid dissemination, they found that the imaging characteristics of the tumor did not significantly differ from those expected with benign astrocytomas of the spinal cord.

FIGURE 221-1 Magnetic resonance images of low-grade intramedullary spinal cord tumor. A, Sagittal T1-weighted image of cystic astrocytoma of the conus. Note the relative homogeneity of the solid tumor and its isodense signal in comparison to the surrounding spinal cord. The solid portion of the tumor is “capped” by cysts above and below. B, Appearance of the tumor shown in A after the administration of gadolinium. Note the brightness of enhancement. This is an extreme example of enhancement. In some tumors the enhancement can be quite subtle and heterogeneous. C, Axial T1-weighted image of the same tumor after the administration of gadolinium. Note the asymmetric positioning of the tumor and its irregular border and surrounding zone of hypodensity. This irregularity with feathering attests to the infiltrative nature of the tumor, and the surrounding hypodensity may be either edema or nonenhancing tumor. D, Axial T2-weighted image of the tumor. Note the hyperintensity and lessening of the degree of hyperintensity at the margins of the tumor. This again attests to the infiltrative nature of this tumor.

The second most common tumor of the spinal cord seen in children is ganglioglioma. Like astrocytomas, these tumors tend to arise eccentrically. When discovered, their average length was twice that of astrocytomas (eight versus four segments). Patel and colleagues postulated that many such large tumors that have previously been called astrocytomas (with the use of hematoxylin and eosin staining) might well be gangliogliomas. They based this on their finding that when they reanalyzed previously diagnosed spinal cord tumors with immunohistochemical stains for glial fibrillary acidic protein, synaptophysin, and vimentin, they found many to be gangliogliomas.¹⁶ In 67 patients with IMSCTs thus analyzed, 27 were reclassified as gangliogliomas, and all tumors that were holocord tumors proved to be gangliogliomas. On T1-weighted imaging the majority have mixed-intensity signals, with only a small percentage being hypointense or isointense, as opposed to astrocytomas.¹⁶ Patchy (65%) or focal (19%) enhancement is the rule after the administration of gadolinium, and importantly, 15% show no enhancement. On T2-weighted imaging, 60% have a homogeneous hyperintensity, whereas 40% exhibit a heterogeneous signal (Fig. 221-2). Tumor cysts are more common with gangliogliomas of the spinal cord than with astrocytomas or ependymomas and occur in 46% of patients.

FIGURE 221-2 Magnetic resonance images of a ganglioglioma extending from C4 to T5. A, Sagittal T1-weighted image of the ganglioglioma. Note the length of the tumor (nine segments) and its width and heterogeneity. Also note the increased diameter of the spinal canal, which is indicative of a very chronic process. B, Sagittal T1-weighted image after the administration of gadolinium. Note the mottled appearance of enhancement and a cyst capping the tumor. C, Sagittal T2-weighted image of the same tumor. Note the extensive edema within the cord both above and below the tumor.

Unlike adults, in whom ependymoma is the most common intramedullary tumor, in children, ependymomas account for only 12% of intramedullary tumors.³ Their size at initial evaluation appears to be the same as that encountered with intramedullary astrocytomas (four vertebral levels).¹⁶ Unlike astrocytomas and gangliogliomas, ependymomas arise centrally and expand the cord symmetrically. The majority of nonmyxopapillary ependymomas are isointense or hypointense on T1-weighted imaging, as opposed to myxopapillary ependymomas, which are either isointense or hyperintense.¹⁹ T2-weighted imaging of both subtypes shows the tumor as a hyperintense signal (Fig. 221-3). Fourteen of 16 tumors in Kahan and colleagues’ series enhanced with gadolinium, with 5 showing a heterogeneous pattern, 6 a homogeneous pattern, and 3 only rim enhancement. One of their patients had minimal enhancement and one had none.¹⁹ Almost two thirds of their patients had cysts, with 8 being intratumoral, 6 rostral or caudal to the tumor, and 9 being a reactive dilation of the central canal. Twenty percent showed evidence of chronic hemorrhage. Choi and associates found that nearly 20% of their patients had some evidence of hemorrhage, with the majority showing hemosiderin susceptibility signals capping either the rostral or caudal pole.²⁰ Fine and coauthors reported a similar finding,²¹ and Nemato and coworkers found evidence of hemorrhage in 60% of their patients when they first reported this phenomenon.²²

FIGURE 221-3 Magnetic resonance images of an ependymoma within the thoracic spinal cord. A, Axial T1-weighted image after the administration of gadolinium. Note the central location of tumor and its inhomogeneous enhancement. B, Sagittal T1-weighted image of the tumor after the administration of gadolinium. Note the mottled appearance of enhancement and numerous cysts. C, Sagittal T2-weighted image of the tumor. Note the hyperintensity of the tumor and numerous cysts.

Hemangioblastomas are rare in children but do occur. Vougioukas and coauthors reported on 141 individuals with von Hippel-Lindau disease, 13 of whom were children and 5 had hemangioblastomas of the spinal cord.²³ The report mentioned that the diagnosis of von Hippel-Lindau disease is more common in children with an intramedullary hemangioblastoma than in adults with the same tumor. The distribution of these tumors reflects the volume at risk. Chu and associates found that 50% of their patients’ tumors were within the thoracic cord and 30% in the cervical cord.²⁴ Typically, these tumors extend to the pia, with most doing so dorsally.²⁴ Most are 1 cm or less in diameter, but some can be much larger. T1-weighted imaging shows the tumors to be isointense or hypointense or have mixed (isointense and hypointense) signal intensity (Fig. 221-4). On T2-weigthed imaging they are usually hyperintense with a few being either isointense or of mixed signal intensity (hyperintense and isointense). Chu and colleagues found that 14 of 15 of their patients who had lesions that were 1 cm or less in diameter had lesions that were isointense on T1-weighted and hyperintense on T2-weighted images. Medium-size lesions (11 to 20 mm in diameter) were hypointense on T1 imaging and tumors larger than 20 mm in diameter were heterogeneous on T2 imaging.²⁴ Syrinxes or cysts are common and occur in more than 50% of patients with hemangioblastomas of the spinal cord, and frequently the solid portion of the tumor appears as a nodule on the cyst wall.²⁵ Hemangioblastomas in the spinal cord enhance vividly, with the enhancement being homogeneous in smaller tumors and heterogeneous in larger ones.⁷ Many appear as brightly enhancing nodules on the wall of a cyst. Not uncommonly, flow voids are seen in tumors larger than 1.5 cm. Some can also show extensive reactive edema.²⁶ These tumors markedly enhance on angiography and show feeding arteries coming off the anterior and posterior spinal arteries and large draining veins. Because this information can be helpful in surgical planning for some tumors, angiography should be considered for a large tumor thought to possibly be a hemangioblastoma. Embolization is not indicated, however, because of the risk of interrupting the collateral circulation to the cord.⁷

FIGURE 221-4 Magnetic resonance images of a hemangioblastoma of the cervical spinal cord. A, Sagittal T1-weighted image showing a cyst extending from the midmedullary level down to C3-4. A small, isointense nodule measuring less than 1 cm in diameter extends off the dorsal wall of the cyst at C2-3. B, The same tumor after the administration of gadolinium. The nodule now vividly enhances.

Intramedullary cavernous malformations are easily diagnosed on MRI. They appear as small intra-axial lesions that are typically 1 cm or so in diameter.⁶ On T1-weighted images they appear hyperintense centrally with multiple areas of differing signal intensity consistent with multiple hemorrhages of differing ages.^27,28 Surrounding this central hyperintense area is a region of hypointensity, which results in the characteristic target sign. On T2-weighted imaging the central portion is hypointense with small areas of hyperintensity. The surrounding hypointensity is due to hemosiderin deposits and is larger than that seen on the T1 images. The lesions may be associated with a venous angioma, which will appear as an adjacent flow void. Occasionally, these lesions may show evidence of fresh hemorrhage and clot, particularly if the patient has new neurological findings.