INTRADURAL OR PRIMARY SPINAL CORD TUMORS

(By Dr.Muhammad Mansoor-ul-Haq)
Patient awareness program.

Before talking about the Intradural or primary spinal cord tumors; brief discuss about CNS; central nervous system: the portion of the vertebrate nervous system consisting of the brain and spinal cord. The central nervous system (CNS) is the part of the nervous system that coordinates the activity of all parts of the bodies
Intradural or primary spinal cord tumors (neoplasms (Neoplasm is an abnormal mass of tissue as a result of neoplasia. Neoplasia (new growth in Greek) is the abnormal proliferation of cells)) are uncommon lesions (A lesion is any abnormal tissue found on or in an organism, usually damaged by disease or trauma.) and fortunately affect only a minority of the population. However, when lesions grow, they result in compression of the spinal cord, which can cause limb dysfunction, motor and sensation loss, and, possibly, lead to death. Spinal tumors are classified based on their anatomic location as related to the dura mater (lining around the spinal cord) and spinal cord (medullary) as epidural, intradural extramedullary, or intradural intramedullary. Primary spinal tumors are typically intradural in location, where extradural spinal tumors are typically due to metastatic disease.
This article focuses on the evaluation and management of intradural intramedullary spinal cord tumors. The typical histopathological types that account for 95% of these intramedullary neoplasms include astrocytomas, ependymomas, and hemangioblastomas. Spinal cord astrocytomas and ependymomas can be further classified as glial cell neoplasms.( Glia (or glial cells) and neurons (nerve cells) are the two major types of cells in the nervous system. While neurons are excitable — generating electrical impulses that transmit information throughout the central nervous system(CNS) and the peripheral nervous system (PNS) — glia are non-excitable cells that serve a wide range of essential functions in support of neurons.)

Problem
Spinal cord parenchyma consists of both gray (neurons and supporting glial cells (Nonconducting cells that serve as support cells in the nervous system and help to protect neurons)) and white matter (axonal(that part of a nerve cell through which impulses travel away from the cell body.)) and tracts that transmit impulses between the brain and body. These tracts, or circuits, control posture, movement, sensation, and autonomic system function, including bowel, bladder, and sexual function.
Neurologic dysfunction develops as the spinal cord tumors enlarge and compress adjacent healthy neural tissue, disrupting these pathways. Upon further compression, patients can lose complete motor function and sensation below the lesion. In addition to weakness and sensory loss, patients may experience pain, particularly at night. This pain is believed to be related to disturbances in venous outflow by the tumor, causing engorgement and swelling of the spinal cord.
Frequency
Intramedullary spinal cord tumors account for approximately 2% of adult and 10% of pediatric central nervous system neoplasms. In adults, 85-90% of intramedullary tumors are the glial subtypes, astrocytoma or ependymoma. Ependymomas account for approximately 60-70% of all spinal cord tumors found in adults, while, in children, 55-65% of intramedullary spinal cord tumors are astrocytomas. Hemangioblastomas account for 5% of tumors, whereas paragangliomas, oligodendrogliomas, and gangliogliomas account for the remaining lesions.
Etiology
The pathogenesis of spinal neoplasms is unknown, but most arise from normal cell types in the region of the spinal cord in which they develop. A genetic predisposition is likely, given the higher incidence in certain familial or syndromic groups (neurofibromatosis). Astrocytomas and ependymomas are more common in patients with neurofibromatosis type 2, which is associated with an abnormality on chromosome 22. In addition, spinal hemangioblastomas can develop in 30% of patients with von Hippel-Lindau syndrome, which is associated with an abnormality on chromosome 3.
Pathophysiology
The spinal cord consists of numerous nerve bundles that descend from and ascend to the brain. Electrical impulses are carried and transmitted to facilitate movement and sensation. With intramedullary spinal cord tumors, compression and stretching of these fiber tracts results in loss of the motor and sensory function. As the tumors grow, the patient's neurologic function further deteriorates.
Presentation
Patients with intramedullary glial spinal cord tumors (ie, ependymomas, astrocytomas) typically present with back pain referred from the level of the lesion, sensory changes, or worsening function. The symptoms can be of a long duration, since these lesions tend to grow slowly and typically have a benign histopathology. Patients with low-grade astrocytomas tend to experience symptoms over a mean duration of 41 months. This is in contrast to patients with malignant astrocytomas, whose symptoms persist for a mean duration of only 4-7 months before diagnosis.
Tumor-specific characteristics
• Ependymomas
o Mean age at presentation of 43 years
o Slight female predominance
o Pain localized to the spine (65%)
o Pain worse at night or upon awakening
o Dysesthetic pain (burning pain)
o Long history of symptoms
o Myxopapillary variant (mean age of presentation of 21 y; slight male predominance)
• Astrocytomas
o Equal male and female prevalence
o Pain localized to spine
o Pain worse at night or upon awakening
o Paresthesias (abnormal sensation)
• Hemangioblastomas
o Onset of symptoms by the fourth decade of life, 80% symptomatic by age 40 years
o Familial disorder (ie, von Hippel-Lindau syndrome) present in a third of patients
o Decreased posterior column sensation
o Back pain localized over lesion
Physical examination findings
• Motor weakness (late finding)
• Sensory
o Decreased touch, pain, and/or temperature sensation
o Hyperesthesias
o Decreased proprioception (inability to localize limbs in space)
o Abnormal sensation below the level of lesion
o Abnormal sensation only at level of lesion (suspended level)
• Hyperreflexia
o Hoffman sign for cervical lesions
o Clonus
o Extensor plantar response (Babinski sign)
• Spasticity
• Increased tone
• Muscle atrophy (late finding)
Indications
Intramedullary spinal cord neoplasms or tumors are typically histopathologically "benign" or slow growing. However, patients can have more aggressive neoplasms as well as morbidity due to the location of the lesion. Consequently, compared with similar intracranial neoplasms, patients may have a prolonged survival after diagnosis.
Optimal treatment options depend on the patient's clinical symptoms and neurologic finding. When and whether to treat these lesions as well as perform radiosurgery or surgical excision of lesions remains controversial. However, cures have been reported only after complete surgical resection. Therefore, patients with neurologic symptoms and confirmatory findings from imaging studies may benefit most from surgical excision, with the surgical goal of total gross resection of the lesion.
Relevant Anatomy
Arterial
Understanding the normal spinal cord vascular supply is essential to treating intramedullary spinal cord lesions; specifically because these vessels may have a variable and inconsistent distribution.
The great vessels (aorta, carotids) contribute arterial supply to the spinal cord via segmental arteries, which further branch into medullary and radicular arteries. The radicular artery provides extramedullary blood supply to the nerve root and dura; the medullary artery bifurcates into anterior and posterior divisions to form the spinal arteries. One anterior and 2 posterior spinal arteries then transverse the longitudinal axis of the spinal cord and provide the blood supply to the spinal cord. Neoplasms acquire their blood supply by leaching blood from these vessels.
Venous
The venous plexus of the spinal column, termed the Batson plexus, is unlike other venous systems in the body because the veins do not contain valves. Therefore, blood can have pathologic retrograde flow. This retrograde flow blood can back up and cause venous congestion. This can manifest as venous hypertension. Because oxygenated blood cannot pass through the spinal cord because of the congestion of outflow, patients present with progressive neurologic dysfunction.
Spinal cord
The spinal cord parenchyma consists of a central canal surrounded by an H-shaped gray matter region that contains neurons. Outer myelinated nerve tracts, termed white matter, surround the central gray matter. The central canal represents an embryologic remnant from neurulation of the neural plate and is lined with ependymal cells. Ependymomas arise from these cells and, therefore, are typically located centrally in the spinal cord parenchyma. In contrast, astrocytes support gray matter neurons and white matter axons. Neoplastic transformation of these supporting cells results in the development of astrocytomas and may occur almost anywhere within the cord.
Contraindications
Observation with serial imaging studies over a variable period is a treatment option for patients who pose a high surgical risk, who are elderly, and/or who only have minimal neurologic signs. Patients in whom pathology tissue shows a malignant neoplasm may be best treated with radiotherapy because they are expected to have an accelerated deterioration and complete surgical resection is not possible.

Intramedullary spinal cord tumors, like the one depicted in the image below, refer to a subgroup of intradural spinal tumors that arise from cells within the spinal cord, as opposed to adjacent structures such as the nerve roots or meninges. They are much less common than brain tumors and are thought to account for only 2-4% of all intrinsic tumors of the central nervous system. Their most common initial symptom is generalized back pain, which is very difficult to distinguish clinically from back pain from musculoskeletal conditions.

View of a cervical intramedullary ependymoma in situ after midline myelotomy and initial dissection (top left). The tumor was removed en bloc (right), and the postsurgical cavity in the spinal cord is shown (bottom left).

Patients are often diagnosed only after the development of neurologic signs and symptoms that may occur later in the course of the disease. Early diagnosis is important, however, because surgical removal for most tumors is curative, and surgical results are optimized when tumors are smaller. Also, neurological deficits resulting from intramedullary spinal cord tumors are seldom reversible. As such, functional outcomes after surgery are closely tied to the patient's preoperative neurologic condition.


History of the Procedure
Important events in the development of our understanding of spinal cord tumors are as follows:
• In 1887, Horsley performed the first successful removal of an intradural tumor.
• In 1907, Elsberg performed the first successful removal of an intramedullary tumor and subsequently published the seminal publication on spinal tumors. He developed a two-stage operation in which a myelotomy was performed and the dura was closed in the first stage. In the second stage, the tumor had partially extruded from the spinal cord for easier resection.
• In 1919, Dandy introduced air-contrast myelography.
• In 1940, Greenwald introduced bipolar coagulation.
• In 1964, Kurze introduced the operating microscope.
• In 1967, Greenwood published a large series detailing successfully removed tumors.
• In 1990, McCormick published a large surgical series demonstrating excellent long-term outcomes for surgery of ependymomas and established a clinical grading system.
Problem
Intramedullary spinal cord tumors are tumors that occur inside the spinal cord. They are relatively rare, compared with brain tumors, but still affect thousands of patients every year. They are generally slow growing, histologically benign tumors and are often definitely treated with surgery.
Frequency
Spinal tumors occur with an incidence of 1.1 case per 100,000 persons.
Intramedullary spinal tumors comprise approximately 2-4% of all CNS neoplasms.
The most common kinds of intramedullary tumors are ependymomas, astrocytomas, and hemangioblastomas.
In adults, ependymomas are the most common tumor type, accounting for 40-60% of all intramedullary spinal tumors, with the mean age of presentation being 35-40 years.
In children, astrocytomas are the most common tumor type, accounting for around 60% of all intramedullary spinal tumors, and the mean age of presentation is 5-10 years.
Intramedullary spinal tumors can arise anywhere in the spinal cord, from the cervicomedullary junction to the filum terminale, but they are found most frequently in the cervical cord, presumably because it contains more neural tissue than the thoracic or lumbar segments.
Etiology
The etiology of intramedullary spinal tumors remains obscure but undoubtedly varies according to histology. Most intramedullary spinal cord tumors are considered to be glial in origin because they are histologically and immunohistochemically similar to differentiated non-neuronal cell types, such as ependymal cells and astrocytes, which occur in nonpathological spinal cord tissue. The traditional thinking is that tumors occur when these differentiated cells, which normally stop propagating after spinal cord development, acquire mutations that cause them to divide again in an uncontrolled fashion.

Individuals with type I and type II neurofibromatosis (NF1 and NF2) have been recognized for some time as having an increased incidence of intramedullary spinal tumors, as well many other kinds of tumors, compared with the general population. This general predisposition to tumors has been linked to germline mutations in 2 different genes named for their associated diseases. Patients with the NF1 gene are predisposed to spinal astrocytomas, whereas patients with the NF2 gene are predisposed to spinal ependymomas. Relatively recent genetic analyses of spinal ependymomas from individuals without syndromic neurofibromatosis have shown somatic mutations in the NF2 gene in a subset of cases.

The identification of mitotically active neural stem cells and neural progenitor cells throughout the central nervous system has altered current thinking about how all intrinsic CNS tumors arise. Many lines of evidence point toward neural stem cells as the cells of origin in brain tumors. This line of inquiry is not nearly as advanced in the spinal cord, but some preliminary work has shown similarities between tumor cells from spinal ependymomas and neural stem cells from the spinal cord.

The other relatively common type of intramedullary spinal tumor is hemangioblastoma. Hemangioblastomas are thought to arise from red blood cell precursors and are not intrinsic spinal cord tumors, but they are often anatomically intramedullary because of their association with the blood vessels that penetrate and nourish the spinal cord. Hemangioblastomas occur as a result of mutations in a tumor suppressor gene called vhl, which was found to be altered in patients with the neurocutaneous disorder von Hippel-Lindau disease(VHL). Patients are predisposed to form hemangioblastomas in the brain and spinal cord, and somatic mutations in the in the vhl gene have been found in tumors from patients without syndromic VHL.
Pathophysiology
The pathophysiology of intramedullary spinal cord tumors varies according to tumor type. Ependymomas are usually indolent, encapsulated tumors that are histologically benign. Pain and neurologic deficits arise as a result of a progressive stretching and distortion of nerve fibers. Usually a clear anatomical plane is present at surgery, and a gross visual anatomic resection results in a cure. Rare anaplastic subtypes can be invasive, however, and are more likely to recur or spread through CSF spaces. Even histologically benign–appearing spinal ependymomas can metastasize in this way.

Although malignant forms do exist, most spinal astrocytomas are low grade (WHO grade II) and less aggressive than astrocytomas in the brain. Pain and neurologic defects arise from a combination of nerve fiber stretching and from invasion of cord parenchyma. Because they are infiltrative tumors, complete surgical removal without damage to functional tissue is usually not possible. Exceptions to this general rule may include some pilocytic astrocytomas of the spinal cord (WHO grade I) that are more common in children.

Hemangioblastomas are highly vascular tumors with capillaries that display an increased permeability thought to be related to a hypersensitivity to vascular endothelial growth factor (VEGF). Lesions usually become symptomatic because this capillary hyperpermeability leads to fluid collections or syringes, which are often larger than the tumor itself, causing mass effect in addition to stretching of neural pathways. These fluid spaces are not lined with tumor cells, however, and only the tumor nidus needs to be removed at surgery.
Presentation
Symptoms
The clinical features of intramedullary spinal cord tumors are variable. Symptoms are not specific to spinal cord tumors and may be present in any myelopathic process.
Because of the slow-growing nature of many of these tumors, symptoms precede diagnosis an average of 2 years. Patients with malignant or metastatic spinal cord tumors present in the range of several weeks to a few months after symptoms develop.
Pain and weakness are the most common presenting symptoms of intramedullary spinal cord tumors. Pain is often the earliest symptom, classically occurring at night when the patient is supine. The pain is typically local over the level of the tumor but may radiate.
Progressive weakness may occur in the arms (cervical tumors) or legs (cervical, thoracic, conus tumors). Impaired bowel, bladder, or sexual function often occurs early. Patients may have poor balance. Rarely, symptoms of subarachnoid hemorrhage may be present.
Intratumoral hemorrhage can cause an abrupt deterioration, a presentation most often associated with ependymomas.
Examination

Examination may reveal a combination of upper and lower motor neuron signs. Lower motor signs may be at the level of the lesion and may aid in localization. Other signs evident upon physical examination may include spine tenderness, stiffening of gait, trophic changes of extremity, sensory loss, hyperreflexia, clonus, and scoliosis ortorticollis (generally in children).
Indications
The first-line treatment for intramedullary tumors is open surgical resection. Surgery is indicated for all symptomatic lesions. Small asymptomatic lesions may be followed clinically and radiographically because the majority of intramedullary tumors are relatively benign and slow growing. However, this approach carries the risk of the development of neurological deficits that are likely not recoverable and the uncertainty that comes with undetermined diagnosis.

At surgery, aggressiveness with respect to resection depends on the histological diagnosis of a frozen section and the ability to find and maintain a surgical plane. Given the difficulty in determining many ependymomas from astrocytomas on frozen section, the presence or absence of a clear surgical plane is usually the key determining factor in defining the surgical goal. If, after analysis of all available data including imaging characteristics, frozen section, and intraoperative appearance, a diagnosis of ependymoma is perceived, a complete surgical resection should be attempted. If a diagnosis of astrocytoma is perceived, most clinicians advocate a more limited debulking of only the tissue that is clearly abnormal.

External beam radiation is generally reserved for disseminated ependymomas and infiltrative astrocytomas but remains an option whenever radiographic residual or recurrent ependymoma is found. Stereotactic radiosurgery for intramedullary tumors remains untested.
Relevant Anatomy
The spinal cord originates at the foramen magnum and extends to the conus medullaris, which terminates at the L1-L2 vertebral body junction in adults. The pia matter condenses caudally to this area, extending to the sacrum as the filum terminale. It is an ovoid structure, most narrow in the anterior-posterior direction. At every vertebral level paired ventral and dorsal nerve roots exit the lateral aspect of the cord and coalesce to form 31 pairs of spinal nerves.

In contrast to the brain, the white matter of the spinal cord surrounds the interior gray matter. The spinal cord is covered by a supporting connective tissue layer called the pia matter that acts as a trellis for the vascular supply. A vestigial extension of the ventricular system, the central canal runs the length of the spinal cord. Dilation of the central canal may be pathologic in some instances. In general, ventral portion of the spinal cord parenchyma subserves motor function, whereas the dorsal portion subserves sensation. The spinal cord contains the same cell types as the brain, but these are highly specialized to their niche in the spinal cord.

The vascular supply for the spinal cord comes from the anterior spinal artery, the paired posterior spinal arteries, and the 31 radicular arteries. The anterior and posterior spinal arteries form off branches of the vertebral arteries at the cervicomedullary junction and course inferiorly along the length of the spinal cord. The anterior spinal artery is relatively constant and runs in the middle of the ventral surface of the cord, sending deep penetrating branches into the anterior median sulcus. These branches then send arterial twigs radially to the deepest portions of the spinal cord.

The paired posterior spinal arteries are relatively inconstant, course along the posterolateral surface of the cord, medial to the dorsal root entry zones, and send short penetrating end arterioles into the dorsal cord parenchyma. Thus, the anterior spinal artery supplies the ventral two thirds of the cord, whereas the posterior spinal artery supplies the dorsal third.

The spinal arteries form the nexus of an arterial network that is replenished by the radicular arteries that enter the spinal canal through the spinal nerve root sleeves. The radicular supply to the spinal cord is highly variable, but a few vital feeding arteries are usually present. The most important of these is the artery of Adamkiewicz, which is usually found on the left side, from T9 to L2.
Contraindications
Absolute contraindications to surgical intervention include uncorrected coagulopathy and systemic infection.
Relative contraindications to surgical intervention include complete neurologic deficit over 24 hours and short life expectancy