Management of Intramedullary Spinal Cord Tumors

Published on 09/04/2015 by admin

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10 Management of Intramedullary Spinal Cord Tumors

Intramedullary spinal cord tumors (IMSCTs) are rare, a fact that is reflected by the paucity of large case series in the literature. Published accounts on the management of IMSCTs consist primarily of case reports and a handful of small case series. Current management strategies, therefore, are largely founded upon past experience, and expert opinion.¹ The earliest expert opinion on the treatment of IMSCTs dates back to 1911 with a serendipitous observation in the operating room by Elsberg, who unintentionally made a myelotomy in the posterior spinal cord while opening the dura, resulting in the extrusion of tumor tissue. Realizing his error, he closed the wound without an attempt at tumor resection. One week later, the incision was reopened and a well-defined tissue plane was noted, which permitted total tumor resection. The patient, severely quadraparetic prior to surgery, was able to ambulate without assistance and use a typewriter eight months following the procedure.² Based upon his experience, Elsberg advocated the following two stage method for resection of IMSCTs:

“If, then, after laminectomy and incision of the dura the surgeon finds that he has to deal with an intramedullary growth, he should make a short incision about 1 cm in length in the posterior median column. . . . The incision, made in the manner we have already described, should be deep enough to divide the pia and the substance of the column down to the tumor. The tumor will then begin to bulge through the incision. No matter how markedly the tumor protrudes, the surgeon must not attempt to remove the growth for fear of grave injury to the cord. The operation must be concluded for the time being, the dura left wide open, and the muscles, fascia and skin carefully closed, as if the operation was definitely ended. The actual removal of the tumor is left for a second operation.

“After about a week the wound is reopened, and the tumor, which will in all probability be found outside the cord, can be removed by dividing the few adhesions which remain. When the tumor has been removed and all bleeding controlled, the dura, muscles, fascia, and skin are closed in the usual manner.”³

During the first half of the twentieth century, other surgeons did not share Elsberg’s early success. In 1969 Schneider asserted that when an intramedullary tumor is encountered that is not obviously cystic in a patient with little or no neurological deficit, “the dura is left open with no attempt made to perform a myelotomy or procure a biopsy.”⁴ Until recently IMSCTs were treated with biopsy or subtotal removal followed by irradiation—a therapy that is usually associated with early tumor recurrence and progressive neurological impairment.⁵ The evolution of diagnostic and surgical technologies now permits a more aggressive surgical role in the management of IMSCTs.

With MRI, IMSCTs are diagnosed more frequently, and in earlier stages of their disease progression.¹ It has been shown that preoperative neurological function is the most important predictor of patient outcome following surgery for an IMSCT,^6,⁷ and in this respect early detection with MRI is extremely helpful. Improved operative technologies such as neurophysiologic monitoring, the ultrasonic aspirator, and carbon dioxide laser have also facilitated the resection of IMSCTs.⁸ These recent surgical advances, in light of poor results in tumors treated solely with radiation and chemotherapy, have led many to advocate complete surgical resection, whenever possible, as the standard of care.^1,^5,⁸^–¹⁰

Epidemiology and Presentation of Specific Intramedullary Spinal Cord Tumors

EPENDYMOMAS

Spinal ependymomas arise from the ependymal rests in the vestigial central canal, and, as a result, are centrally located within the spinal cord.¹¹ Ependymomas are the most common IMSCT in adults, comprising 40% of a large series compiled by Fischer and Brotchi.¹² In children, they are the second most common primary IMSCT (28%), second only to astrocytomas.¹³ However, there were no ependymomas in a series of IMSCTs in children under 3 years of age.¹⁴ There is an equal distribution among males and females. They occur throughout the spinal cord, but are most common in the cervical region.^12,¹⁵ Myxopapillary ependymomas are a distinct subtype occurring in the conus medullaris and cauda equina, and have a slight male predominance.¹⁶ Genetic studies have suggested a possible link between neurofibromatosis type 2 and the development of spinal ependymomas.^17,¹⁸ Families predisposed to the development of ependymal tumors have been shown to have a loss of heterozygosity on chromosome 22.¹⁹

These tumors are slow growing, with an average interval of 16 months between the onset of symptoms and diagnosis.¹⁵ Sixty-five percent of patients present with complaints of radiculopathy or regional neck pain accompanied by minimal motor or sensory deficit. Because these slowly growing tumors compress rather than invade adjacent neural tissue, they can take up a considerable volume within the spinal cord without causing significant motor deficit. Parasthesias and other sensory phenomena result from compression of the crossing spinothalamic fibers. Within the corticospinal tract, hand fibers are located medially and leg fibers are located laterally. A centrally located cervical IMSCT or associated cyst, therefore, may produce weakness and atrophy of the small hand muscles from anterior horn cell compression before lower extremity dysfunction becomes apparent. Cervical lesions rarely present with bowel or bladder dysfunction.¹⁵ Myxopapillary tumors arising from the conus, however, can compress sacral anterior horn cells and adjacent nerve roots in the cauda equina, resulting in bowel or bladder dysfunction in 20 to 25% of cases.¹⁶

ASTROCYTOMAS

Astrocytomas are a heterogeneous group of infiltrating tumors, resembling astrocytes, that occur in both the brain and spinal cord. They are categorized in an ascending grading scale based upon histopathological evidence of anaplasia. Characteristics of higher-grade lesions include vascular hyperplasia, mitotic figures, cellularity, and presence of giant cells. Necrosis is indicative of glioblastoma multiforme, the most extreme category of malignancy.

Juvenile pilocytic astrocytomas (JPA) are a unique subclass of astrocytomas. Generally speaking, low-grade astrocytomas fall into two categories: World Health Organization (WHO) grades I and II. Pilocytic astrocytomas are WHO grade I tumors, while protoplasmic, gemistiocytic, fibrillary, and mixed astrocytomas are classified as WHO grade II. Separation of pilocytic astrocytomas into their own grade reflects the fact that they have a different prognosis and clinical course. The 10-year survival rate in patients with a pilocytic spinal cord astrocytoma is 81%, while the 10-year survival rate drops to 15% in patients with diffuse fibrillary astrocytomas.²⁰

Astrocytomas are the most common pediatric IMSCT, representing 59% of the tumors in a compilation of 13 pediatric series.¹³ In adults, they are second to ependymomas in frequency, accounting for about 20% of tumors.^12,²¹ Unlike intracranial astrocytomas, spinal cord astrocytomas are usually low-grade lesions in both children and adults. High-grade lesions (WHO grades III and IV) comprise only 10% to 15% of pediatric tumors and a modestly higher proportion in adults.^22,²³ There is a slight male predominance,^12,²⁰ and the cervical area is most frequently affected, followed closely by the thoracic region. These lesions span an average of six spinal levels, but total spinal cord involvement has been described.²⁴ Genetic studies have shown a potential association between neurofibromatosis type I and the development of spinal astrocytomas.^17,^18,²⁵

In contrast to ependymomas, astrocytomas are often infiltrative lesions that occupy an eccentric location within the spinal cord. Presenting symptoms typically consist of regional back or neck pain and sensory disturbances including dysesthesias and loss of sensation, unilateral or bilateral in nature, as well as motor deficit. In the pediatric population, pain remains the most common symptom, but gait deterioration, motor regression, torticollis, and kyphoscoliosis are common presenting findings.²⁶ Symptoms resulting from low-grade lesions usually evolve over months to years.^27,²⁸ High-grade astrocytomas, however, present with a more rapid decline in motor function with progression to significant disability in only 3 to 5 months.^22,²⁸

GANGLIOGLIOMAS

Gangliogliomas are neoplasms containing both neoplastic neuronal and glial cells. They account for approximately 1.1% of all spinal neoplasms. Ten percent of intracranial gangliogliomas undergo malignant degeneration. Such malignant change is believed to be due to the glial component of the tumor. How this data regarding intracranial gangliogliomas translates to spinal cord gangliogliomas is unclear. They mainly occur in children and young adults, with both sexes affected in equal proportion.²⁹^–³¹ Symptoms include pain and weakness of the extremities, while examination findings may include myelopathy and kyphoscoliosis. Symptoms and imaging characteristics fail to distinguish these from other glial tumors.²⁹^–³¹

HEMANGIOBLASTOMAS

Hemangioblastomas consist of thin-walled blood vessels interspersed with large, pale stromal cells. They represent 3% to 11% of IMSCTs, with a slight male predominance.³² Up to one third of cases occur in association with von Hippel-Lindau (VHL) disease. VHL disease occurs in both an autosomal dominant and a sporadically inherited fashion. The autosomal dominant form results from a mutation of a tumor suppressor gene on chromosome 3p.³³

Hemangioblastomas involving the spinal cord are occasional manifestations of VHL disease,³⁴ and multiple lesions may be present, particularly in the posterior fossa. Symptom onset is typically in the fourth decade of life and the mean age at surgery is 40 years; childhood presentation is rare.³⁵ The most frequent locations are thoracic (55%) and cervical (40%). Cyst formation occurs in 87% of cases.³⁵

Hemangioblastomas differ from ependymomas and astrocytomas in that they generally are found on the dorsal or dorsolateral surface of the spinal cord. As a result, they often present with complaints of proprioceptive loss in addition to pain and sensory deficits.³⁵

LYMPHOMAS

Intramedullary spinal cord lymphoma is an unusual entity. It is most commonly seen as part of a multifocal central nervous system lymphoma, or in patients immunosuppressed from AIDS or other causes.³⁶ Pathologic studies have demonstrated that the vast majority of primary spinal cord lymphomas are of the non-Hodgkin B-cell variety.^37,³⁸ Reports of T-cell lymphomas involving the spinal cord are rare.³⁹ Presentation can range from myelopathy to paresis,^40,⁴¹ and can progress rapidly over a period of days to weeks.

LIPOMAS

Intramedullary spinal lipomas, excluding those associated with dysraphism, comprise just 1% of all IMSCT. These tumors consist of ordinary adipose tissue, and are believed to arise from rests of ectopic tissue.⁴² Lipomas are often densely adherent to surrounding neural tissue, precluding complete resection.⁴³

Most patients present in the second to fourth decade in life and there is no gender predilection.⁴⁴ Clinical presentation is that of a slowly progressive myelopathy (58%), a syringomyelic syndrome (9.5%), or a Brown-Séquard syndrome (6.5%), with the remaining 26% having atypical features.⁴² Lipomas tend to have long indolent courses, followed by a rapid decline in neurological function.^43,⁴⁴ In females, neurological deterioration may follow pregnancy and delivery.⁴⁵

CAVERNOUS ANGIOMAS

Cavernous angiomas, while not true neoplasms, can form mass lesions in the spinal cord parenchyma, and should be considered in the differential diagnosis of intramedullary spinal mass lesions. Commonly known as cavernomas, they represent 1% to 3% of IMSCTs. Cavernomas are angiographically occult vascular malformations consisting of a collection of enlarged vascular spaces surrounded by a rim of gliosis, without intervening neural tissue.⁴⁶ Both sporadic and familial forms are recognized. The familial form is inherited in an autosomal dominant fashion and is associated with multiple angiomas.^47,⁴⁸ Molecular analysis has shown that a gene mutation in CCM1, encoding the KRIT1 protein, is largely responsible for the hereditary form of cavernous angiomas.^49,⁵⁰

Cavernomas can cause progressive myelopathy due to repeated hemorrhage, resulting in reactive gliosis.^51,⁵² A large sudden hemorrhage, albeit uncommon, can lead to catastrophic neurological deterioration, and surgery is the only effective treatment.⁴⁶ Asymptomatic patients do not benefit from surgical intervention. Once a patient becomes symptomatic, however, progressive neurological deterioration from repetitive hemorrhage is the rule and surgical intervention is advisable in most cases.⁵²

METASTASES

In a large postmortem study, intramedullary spinal cord metastases were found in only 2% of 627 patients with systemic cancer.⁵³ Other accounts estimate that metastases comprise 2% to 8% of all IMSCTs.^54,⁵⁵ The incidence of intra-cerebral metastases in cancer patients, in contrast, has been estimated at 25% to 35%.⁵⁶ Because of the comparatively small volume of the spinal cord relative to the brain, metastases to the spinal cord are much less common.⁵⁷ The most common sources of intramedullary spinal cord metastases are the lung and breast. The mechanism of metastatic spread to the spinal cord is thought to be hematogenous rather than direct invasion, since metastases to the spinal cord are not always associated with disease in the adjacent tissues.^53,^58,⁵⁹ The diagnosis of spinal cord metastasis carries a grave prognosis, and 80% of patients die within three months. The presenting symptoms consist of pain and weakness. Rapid neurological deterioration is observed in almost half of all patients, progressing to cord hemisection or transection syndromes over days to weeks.⁵⁹

Diagnostic Imaging

PLAIN X-RAYS

Plain x-rays have little place in the modern diagnosis of IMSCTs and are unremarkable in the majority of cases. However, an enlarged spinal canal with scalloping of the vertebral bodies, medial pedicle erosion, and thinning of the laminae may be seen.⁶⁰ These findings are consistent with any long-standing intradural tumor that thins and remodels the surrounding bone and are not specific for IMSCTs.

Scoliosis is frequently seen in children with IMSCTs, often with the apex of the curvature to the left rather than the right. Dextroscoliosis, where the apex of the curvature is to the right, is more common in patients with idiopathic scoliosis. Although scoliosis is unusual in older adults, it may be the presenting symptom in young adults with asymptomatic onset of tumor growth during childhood. Plain x-rays are also valuable in assessing alignment as the presence of preoperative kyphosis or scoliosis may necessitate early fusion to prevent progressive deformity.⁶¹

COMPUTED TOMOGRAPHY AND CT MYELOGRAPHY

Prior to the advent of MRI, CT myelography was the primary imaging modality for the diagnosis of suspected spinal cord tumors. It can demonstrate spinal cord widening but cannot be used to confidently determine its cause. Although neoplastic lesions will enhance after the intravenous administration of iodinated contrast, plain contrast CT will not identify the type of intramedullary spinal cord tumor or distinguish between tumor-associated cysts and syringomyelia. In the past, delayed CT scanning was sometimes used to demonstrate uptake of water-soluble contrast within the center of the spinal cord, which is typical of tumor-associated cysts and syringomyelia.

SPINAL ANGIOGRAPHY

Spinal angiography may be considered when MRI suggests a hemangioblastoma (Figure 10-1). Although angiography will delineate the location of the vessels that supply and drain the hemangioblastoma, the vascular supply is generally evident at surgery and we have not found angiography to be important in the planning or execution of surgery. Cavernous angiomas are angiographically occult vascular lesions and, when suspected, angiography is not indicated.

Figure 10-1 Hemangioblastoma appearance on spinal angiography. Note the impressive tumor blush of this extremely vascular tumor.

MAGNETIC RESONANCE IMAGING (MRI)

MRI performed before and after gadolinium administration has become the imaging modality of choice in the diagnosis of IMSCT. Images are first obtained in the sagittal plane, followed by axial scans at the levels of the suspected abnormality. T2-weighted sequences define cystic structures and areas of edema in the spinal cord as regions of hyperintensity. Furthermore, cysts and regions of edema in the cord that do not contain tumor will not enhance after the administration of gadolinium, whereas most glial neoplasms and hemangioblastomas will enhance. The intravenous administration of gadolinium-DTPA with T1 and T2 imaging sequences, therefore, can help distinguish tumor from cyst or edema.

MR spectroscopy may allow for more definitive diagnosis in the future, although there are significant susceptibility artifacts because of the close proximity of tissues with different magnetic susceptibilities, such as spinal cord, CSF, bone, and muscle. Currently, this precludes evaluation by MR spectroscopy because magnetic field homogeneity is necessary for this technique.⁵⁵

Multiple Sclerosis

MS plaques are found in the white matter, are iso- to hypointense on T1-weighted images, and are hyperintense on T2-weighted images (Figure 10-6). During active demyelination, MS plaques may enhance upon administration of gadolinium. In cases of acute MS, a follow-up MRI in 4 to 6 weeks will show lessening mass effect, diminution of enhancement, and a decreased hyperintensity on T2-weighted images.