Intramedullary Spinal Cord Tumors

Etiology

Although intramedullary spinal cord tumors are mostly sporadic, some are associated with clinical syndromes, such as neurofibromatosis 1 or 2 (NF-1, NF-2) and Von Hippel-Lindau disease. NF-1 is due to a mutation on chromosome 17, which encodes the tumor suppressor gene neurofibromin. About 19% of patients with NF-1 develop an intramedullary spinal cord tumor. NF-1 is largely associated with neurofibromas and intradural extramedullary-type spinal cord tumors. NF-2, caused by a mutation of the tumor suppressor protein schwannomin/merlin on chromosome 22, is reported in 2% of patients with intramedullary spinal cord tumors. Patients with NF-2 more commonly present with ependymomas and occasionally meningiomas (extramedullary). In Von Hippel-Lindau disease, hemangioblastomas are the most frequent intramedullary spinal cord tumors. Overall, astrocytomas are the most commonly encountered intramedullary spinal cord tumors.[5][6][7]

Epidemiology

Approximately 80% of intramedullary spinal cord tumors are gliomas, which can be subdivided into astrocytomas and ependymomas. Astrocytomas are more common in children with intramedullary spinal cord tumors, whereas ependymomas are more often found in adults with intramedullary spinal cord tumors. The cervical spine is the most common location (33%), followed by the thoracic region (26%) and the lumbar region (24%).[8] Children are more likely to present with a higher grade lesion compared to adults. Due to their infiltrative and expansive nature, they may present with an associated syrinx in up to 20% of cases. In adults, astrocytomas peak in the third to fifth decades, often low-grade, and are found most commonly at the thoracic level. Ependymomas are more commonly found in the lower cord, conus, and filum terminale, with a slight male predominance and peak in the third to sixth decades. Hemangioblastomas are the third most common intramedullary spinal cord tumors, comprising about 2% to 15% of all intramedullary spinal cord tumors. Metastatic intramedullary tumors are rare and most frequently develop from lung and breast tumors.[9]

Pathophysiology

Astrocytomas are characteristically infiltrative tumors with a poorly defined surgical resection plane. These tumors may progress to a malignant subtype. Ependymomas arise from ependymal cells, are soft and encapsulated, grow slowly, and are more centrally located, appearing as a focal enlargement within the spinal cord. Ependymomas span in length across 3 to 4 vertebral bodies, whereas astrocytomas can span 5 to 6 on average. A common histological subtype of ependymoma is the World Health Organization (WHO) grade 2 cellular variant with perivascular pseudorosettes. Up to one-third of ependymomas display peritumoral hemorrhage with a cap sign on magnetic resonance imaging (MRI).[10] In the filum terminale, micropapillary ependymoma, classified as a WHO grade I tumor, is the most commonly found spinal cord tumor. Hemangioblastomas are small tumors that are highly vascularized but rarely extend beyond 1 or 2 vertebral bodies. These tumors commonly exhibit cyst formation and are more prevalent in men.[11][12]

History and Physical

Although intramedullary spinal cord tumors are often asymptomatic for prolonged periods, the most common presenting symptom is pain. Pain can be diffuse or radicular and typically worsens at night when the patient is lying down.[13] If the dermatomal distribution is unusual for a disk herniation, intramedullary spinal cord tumors should be suspected. The pain can also be local, causing a stiff neck or back, and can be described as burning and bilateral. Paresthesias are the second most common complaint, followed by motor impairment. In addition to motor weakness, patients may have clumsiness, ataxia, atrophy, muscle twitches, fasciculations, and decreased deep tendon reflexes. In later stages, loss of bowel and bladder function can occur and can present as retention, incontinence, or impotence. Children can have nonspecific complaints. Gait disturbances are frequently observed signs that may be misperceived as clumsiness. Delays in motor developmental milestones may be noted. Scoliosis can be observed in 30% of patients.[13]

The McCormick scale is a standard grading system for measuring functional status in patients with intramedullary spinal cord tumors.[14]

Grade I: Patients exhibit normal neurological function with mild focal deficits that do not significantly affect limb function. Spasticity is mild or absent, reflex abnormalities are mild, and no significant gait difficulties exist.

Grade II: Sensorimotor deficits are present, affecting function. Gait difficulties range from mild to moderate, and pain affects the quality of life. Nevertheless, patients can function and ambulate independently.

Grade III: Sensorimotor deficits are more severe compared to Grade II. Patients require bracing or other assistive devices for function, and the level of functional independence varies.

Grade IV: Severe sensorimotor deficits necessitate bracing or a wheelchair for mobility. Patients typically lack functional independence and rely on external assistance for daily activities.

Evaluation

Following the assessment of symptoms and suspicion of spinal cord involvement, MRI is the preferred modality for characterizing intramedullary spinal cord tumors, aiding in treatment planning. MRI can show the tumor size, location, length, extent of surrounding edema, presence of cord-tumor interface, and associated cysts or syringomyelia. Although each of the 3 common types of intramedullary spinal cord tumors has a particular T1-, T2-, and contrast-enhanced T1-weighted imaging pattern, differentiation between them based on imaging alone remains difficult. Both ependymomas and astrocytomas span multiple vertebral segments, enhance with contrast, are hypo- or iso-intense on T1-weighted images, and are hyperintense on T2-weighted images. Ependymomas are often located centrally within the spinal cord, resulting in a symmetric expansion that spans the entire width of the cord. These tumors typically display diffuse enhancement with a distinct border. Astrocytomas tend to be positioned more eccentrically, can be non-enhancing or have an enhancing nodule or large satellite cysts, and typically do not have a well-defined border. Intratumoral hemorrhage can be observed in both types but is more common in ependymomas. Hemangioblastomas have homogeneous contrast enhancement compared to the more heterogeneous pattern found in astrocytomas or ependymomas. These tumors also have mural nodules, are associated with syringomyelia, and can have significant surrounding edema. As they are highly vascularized tumors, spinal angiography helps characterize feeder vessels and associated dilated pial veins from vascular shunting, which can help evaluate preoperative embolization.[15][6]

Treatment / Management

Surgical resection of intramedullary spinal cord tumors should be performed as soon as possible upon diagnosis due to the correlation between outcomes and the preoperative neurological condition, and observation can lead to further neurological deficits, some of which are irreversible. The primary objectives of surgical resection are to obtain tissue diagnosis, maximize safe tumor resection, and improve neurologic function. Intraoperative somatosensory and motor-evoked potential monitoring is used to detect any changes in neurological function and aid in resection. The extent of total resection greatly depends on the presence of a clear plane between the tumor and normal spinal cord tissue.

Astrocytomas are characteristically nonencapsulated and infiltrative, posing challenges for complete surgical removal. For low-grade astrocytomas, if a plane can be developed between the tumor and spinal cord, gross total resection is an option; however, for high-grade astrocytoma or low-grade astrocytoma with no definable plane of resection, biopsy plus subtotal safe resection is recommended, as aggressive resection can lead to significant neurological deficits. Postoperative targetted radiotherapy can be used for high-grade astrocytomas to address any residual tumor. Ependymomas are frequently benign with a distinct tumor-spinal cord interface, facilitating gross total resection as a viable option. The rate of recurrence is dependent on the extent of tumor resection. Due to the presence of a discrete surgical plane, gross total resection is reported in more than 90% of ependymoma cases. Similarly, hemangioblastomas are often respectable, and preoperative embolization can attenuate their rich vascular supply. Complete excision is possible in 83% to 92% of patients, with clinical improvements noted following resection.

Generally, patients with intramedullary spinal cord tumor resection have better long-term outcomes when there are fewer preoperative deficits, and recurrence depends on the extent of resection and tumor histology. Adjuvant therapies, including radiotherapy and chemotherapy, are often reserved for tumor recurrence, high-grade lesions, or when there are contraindications to complete resection. Further research into novel treatment strategies is needed to improve outcomes, especially for astrocytomas that do not have clear surgical resection planes.[16][17][18](B3)

Differential Diagnosis

The differential diagnosis of intramedullary spinal cord tumors includes:

• Benign lesions: Epidermoid cyst and lipoma
• Glial tumors: Ependymoma, myxopapillary ependymoma, astrocytoma, and ganglioglioma
• Non-glial tumors: Hemangioblastoma, metastasis, central nervous system lymphoma, multiple sclerosis, neuromyelitis optica, and meningioma

Prognosis

The prognosis for patients with intramedullary spinal cord tumors is guarded. Preoperative neurological functional status is directly correlated with postoperative outcomes. Patients with metastatic disease rarely live beyond 12 months.[19]

Complications

Complications of intramedullary spinal cord tumors include:

• Paralysis or weakness
• Sensory deficit: paresthesias, numbness, and tingling
• Urinary or bowel incontinence or both
• Complications related to chronic bed-ridden state: deep vein thrombosis, bedsores, atelectasis, and deconditioning
• Local spread of the lesion
• Death