Spinal Intramedullary Tumors

Background: Intramedullary tumors are a subgroup of spinal tumors and are associated with high morbidity and mortality. The estimated incidence of spinal tumors in general is 0.74 to 1.6 per 100 000 persons per year, with intramedullary tumors making up 10% to 30% of the total. The diagnosis is often delayed because of the insidious onset of symptoms, which are often nonspecific at first.

Methods: This review is based on pertinent publications about intramedullary tumors that were retrieved by a selective search in the PubMed database.

Results: Intramedullary tumors often cause diffuse neurologic symptoms of gradually increasing severity, progressing, in advanced cases, to a complete spinal cord transection syndrome. Magnetic resonance imaging of the spine without and with intravenous contrast is the standard diagnostic technique. The histopathological origin of most intramedullary tumors is from glial cells, but other types of intramedullary tumor exist as well. The primary treatment of all intramedullary tumors is surgical resection. 9% to 34% of patients may experience a worse neurological deficit after surgery than before, but such problems resolve completely in 25% to 41% of cases. The extent of resection is the main factor affecting the risk of tumor recurrence and progression. The extent of resection also determines the possible indication for adjuvant treatment, which is needed, in particular, for high-grade and subtotally resected tumors, and for those that display progression. The treatment of intramedullary tumors is based on case series, retrospective analyses, and case reports, as randomized trials are lacking.

Conclusion: Patients with intramedullary tumors should be cared for, as much as possible, in the setting of prospective, uniform studies of their spontaneous course and the outcomes after treatment. This will yield better evidence on the treatment of these tumors in the future.

Intramedullary tumors are a subgroup of spinal tumors that are associated with severe neurological deficits and/or an impaired quality of life. In severe cases, they can be fatal (1, 2).

Resection is the primary treatment option for all intramedullary tumors. The neurosurgical strategy requires careful evaluation. The goal of surgery is to resect as much of the tumor as possible while preserving neurological function. The extent of resection is the major determinant of the clinical outcome, with adjuvant radio- and chemotherapy playing a lesser role in this group of patients (3).

Intramedullary tumors are rare and often grow insidiously at first. They are, therefore, often not detected or misdiagnosed, with a resulting delay before appropriate treatment. The reported average time from symptom onset to diagnosis ranges from 6 to 37 months (4, 5, 6, 7, 8, 9, e1, e2, e3). It is clearly important to take measures to ensure early diagnosis and prompt treatment (2). The evidence base for the treatment of intramedullary tumors currently consists of large case series, retrospective analyses, and case reports of very rare entities. No randomized and controlled trials have been conducted to date.

In this article, we provide an overview of the pathogenesis, epidemiology, clinical manifestations, imaging diagnosis, neuropathological classification, and treatment of patients with intramedullary tumors. Neurosurgical strategies and their implications for postsurgical adjuvant treatment and for the clinical outcome are discussed. The information presented here is based on publications (2000–2024) that were retrieved by a selective search in PubMed with the keyword “intramedullary tumor” and screened for relevance. The selected articles and the references cited in them were assessed and summarized by the authors, who are specialists in neurology, neurosurgery, neuroradiology, and radiation therapy.

During the writing of the original article in German, ChatGPT-4 (OpenAI) was used to generate suggestions for improvements in wording and for reducing the length of the text. All such suggestions were implemented by the authors only after thorough consideration and appropriate adaptation to the purposes of the article.

Pathogenesis and epidemiology

Spinal tumors are rare neoplasms whose reported incidence ranges from 0.74 to 1.6 per 100 000 persons per year. They account for approximately 15% of all tumors of the central nervous system (2, 10, 11, 12, e4, e5, e6). They are classified as extradural, intradural extramedullary, or intramedullary (1).

Of the three types of spinal tumor, intramedullary tumors are the least common, accounting for 10–30% of the total (10, 13). 80% of intramedullary tumors are derived from glial cells; a wide variety of tumor entities make up the rest (2, 13). The main types of intramedullary glioma are ependymoma (60–70%) and astrocytoma (30–35%) (2, 11, 13, 14). Molecular analyses such as panel sequencing with NGS, RNA-based fusion detection, and genome-wide methylation analysis (850K/935K profiling) are now well established and, in most cases, indispensable for definitive neuropathological classification (eBox 1).

eBox 1

Association with genetic clinical syndromes and rare intramedullary tumors

Clinical manifestations and neuroradiological evaluation

Clinical manifestations

The clinical manifestations of intramedullary tumors are often nonspecific and insidiously progressive, and the diagnosis is, therefore, often delayed. Magnetic resonance imaging (MRI) of the spinal axis early on in the course of the disease is essential for the timely initiation of treatment. The most common clinical manifestations are back pain and sensory or motor deficits; disturbances of micturition and defecation arise only in later stages of the disease (e1, 1, 2, 9, 11). The type and severity of the clinical manifestations depend on the extent of spinal cord involvement by the tumor and the particular cord segments that are affected (2). The frequency of various clinical manifestations on initial presentation is shown in Table 1, as derived from two of the larger published cohorts of patients with intramedullary tumors, as well as three cohorts each of patients with intramedullary ependymomas and astrocytomas.

Table 1

The types and frequencies of symptoms at the time of presentation of intramedullary tumors (IMT), intramedullary ependymomas (IME), and intramedullary astrocytomas (IMA) (4, 7, 8, 9, 16, 25, e2)

A tumor-associated fluid-filled cavity within the spinal cord (a syrinx or syringomyelia) can also contribute to the clinical manifestations of the disease. 25-58% of patients with intramedullary tumors have a syrinx, usually at the lower cervical/upper thoracic level (e1, 2, 15). 1–8% of the affected patients have hydrocephalus and resulting symptoms and signs of intracranial hypertension, in addition to their spinal manifestations; hydrocephalus may already be present at the time of presentation (2, 16, e15) (eBox 2).

eBox 2

The pathogenesis of hydrocephalus in patients with intramedullary tumors

The McCormick score is generally used for standardized documentation of the patient’s preoperative neurological findings and the neurological outcome of surgical treatment (17) (Table 2).

Table 2

The McCormick Scale (McCormick et al. 1990) (17)

Neuroradiological diagnostic evaluation

Spinal MRI with high-resolution axial and sagittal cuts is the current standard for the diagnostic imaging of intramedullary tumors (2, 11, 13). The spinal segments to be imaged are generally chosen on the basis of the patient’s clinical presentation. Once a lesion has been demonstrated, imaging of the entire spinal axis is always indicated in order to detect further lesions or drop metastases, even more so if the initial images arouse suspicion of an ependymoma or an intramedullary metastasis (11, e11). Non-contrast T2- and T1-weighted sequences and T1-sequences after the administration of intravenous contrast medium are standard in imaging studies of intramedullary tumors. In 3-tesla MRI scanners, T1-weighted FLAIR sequences can be used as an alternative to the classic T1-weighted sequence, and the T2-weighted FLAIR that is used for cerebral imaging has no additional utility. Fat-suppressed sequences are popular for the evaluation of diseases of the spinal column but are not advantageous in the imaging of intramedullary tumors for a variety of reasons, including poorer spatial resolution and the difficulty of demarcating contrast-enhancing tumor from neighboring venous structures. Diffusion-weighted sequences are mainly used for the differential diagnosis of spinal infections, while more complex diffusion measurements for the visualization of fiber tracts have only become possible through very recent technical advances. T2* gradient measurement can provide further diagnostic information if hemorrhage or calcification is suspected (eTable 1).

eTable 1

MRI features of intramedullary tumors (e23, 2, 11)

Spinal computerized tomography (CT) or myelography are of use only for a minority of patients, e.g., those with specific types of implants (2, 11). Further diagnostic tests, such as spinal angiography, may occasionally be needed to detect or exclude rare differential diagnoses, such as a spinal dural arteriovenous fistula (e12, e13, e14).

Neuroepithelial tumors

80% of intramedullary tumors are of neuroepithelial origin. Ependymomas and astrocytomas are the most common types (2), and all others are rare (eTable 2).

eTable 2

Types of intramedullary spinal tumor, after Samartzis et al. (2)

Ependymoma

Ependymoma is the single most common type of intramedullary tumor, arising most commonly at cervical and cervicothoracic levels (18). They are more common in men than in women, with peak incidence between the ages of 30 and 60 (11, 18). The neuropathological criteria for the diagnosis of ependymoma are given in the updated CNS WHO classification of 2021. Myxopapillary ependymoma is assigned a WHO grade of 2, as the likelihood that it will recur is as high as that of an ordinary spinal ependymoma. The current SHO classification no longer makes use of the term “anaplasia”; instead, a WHO grade of 3 is now assigned on the basis of certain specified histopathological features (e17, 19).

Astrocytoma

Astrocytoma is the second most common type of intramedullary tumor in adults and the most common one in children (1). It is usually located in the cervical or thoracic segments of the spinal cord and often extends over multiple segments (2, 11). It is more common in males, with peak incidence in childhood and between the ages of 30 and 50 (11). Its WHO classification corresponds to that of cerebral astrocytoma (19). Most intramedullary astrocytomas are low-grade tumors (WHO grades 1 and 2); approximately 25% are high-grade (WHO grades 3 and 4) and bear a markedly worse prognosis (20). Low-grade tumors, and particularly pilocytic astrocytoma (WHO grade 1), are more common in childhood, while malignant transformation is more common in adults (19).

Treatment strategies

Intramedullary tumors are rare, and it is, therefore, hard to formulate uniform treatment recommendations, as there are no randomized and controlled studies on which they could be based. The current recommendations are based on retrospective case-control studies and case series, which only yield class II and III evidence. The indication for primary surgical resection is derived from clinical experience. Resection is useful for reducing tumor mass, limiting neurological dysfunction, and providing tissue for histological establishment of the diagnosis, which is indispensable for the planning of further treatment.

The European Association of Neuro-Oncology (EANO) has issued a specific guideline for intramedullary ependymoma, based on class II–III evidence. No specific guidelines are available to date for other types of intramedullary tumor (eBox 3).

eBox 3

General principles of the treatment of intramedullary tumors

The surgical and adjuvant treatment of intramedullary ependymoma

The treatment of intramedullary ependymoma is based on the EANO guideline for the diagnosis and treatment of ependymal tumors, in which the diagnosis and treatment of intramedullary ependymal tumors is separately described (21). For these tumors, too, the treatment of first choice is function-preserving microsurgical resection (class II evidence, level B recommendation) (3, 21, e22). The success rate of total resection has been shown to depend on the neurosurgeon’s expertise and the caseload of the specialized center (7, 8). The putative benefit of adjuvant radiotherapy after total resection has not been conclusively demonstrated (22). Figures from a recent systematic review imply that median progression-free survival is longer after subtotal resection and adjuvant radiotherapy than after subtotal resection alone (48 vs. 96 months); the EANO, in its guideline, therefore recommends 45 to 54 Gy of adjuvant radiotherapy after subtotal resection (21, 23). Adjuvant radiotherapy is recommended for all WHO grade 3 ependymomas regardless of the extent of resection (21) (eBox 4).

eBox 4

Chemotherapy for intramedullary ependymoma

The surgical and adjuvant treatment of intramedullary astrocytoma

Microsurgical resection is the initial treatment of choice for intramedullary astrocytoma as well (e26). As these tumors are invasive, they often cannot be totally resected; the reported rates of complete resection are 16% to 30% (16, 24). Positive factors for the success of surgery include localization in the cervical spinal cord and the identification of a plane of dissection between the tumor and the surrounding neural tissue (9, 25); negative ones are a longitudinal extent of three or more segments and infiltrative growth (20). Survival rates are a function of the histological grade, the patient’s preoperative neurological condition, and the extent of resection (6, 26, 27, 28). Low-grade intramedullary astrocytomas are associated with a 10-year survival rate of 78% (16), while the 5- and 10-year survival rates of patients with high-grade astrocytomas are 32% and 0% (6). There is still debate in the scientific literature about the relation between overall and progression-free survival and the extent of resection (5). Some studies did not reveal any significant prolongation of overall survival through the aggressive resection of high-grade astrocytomas; there is a consensus that the main surgical objective should be a safe resection or biopsy, i.e., one that does not cause any major new deficit (5, 16, 29). The individual treatment strategy for each patient must be based on a critical evaluation of these factors. The most common treatment strategy for high-grade tumors is a biopsy for histological diagnosis followed by combined radiochemotherapy, while total resection (if possible) should be considered for pilocytic astrocytomas in children. In some cases, neurological dysfunction can be alleviated with spinal cord decompression by means of tumor debulking and dural expansion (e27).

Radiotherapy is indicated for high-grade intramedullary astrocytoma, biopsied unresectable intramedullary astrocytoma, and tumor progression after an initial resection (16, e23). Some studies have shown longer overall survival after radiotherapy in patients with high-grade intramedullary astrocytoma, and longer progression-free survival in patients with low-grade intramedullary astrocytoma (16, 30, e28). In patients with low-grade tumors, postoperative radiotherapy was associated with a higher 10-year overall survival rate (80% vs. 73%), but the difference was statistically insignificant. Patients with high-grade intramedullary astrocytomas (Table 3) lived significantly longer if they had received postoperative radiation (median survival, 3 vs. 24 months) (16). Other studies did not show any prolongation of overall survival or progression-free survival by radiotherapy (31, e29). Current radiotherapeutic protocols involve fractionated radiotherapy with individual doses of 1.8 to 54 Gy for low-grade tumors, and up to 54 Gy for high-grade tumors (32) (eBox 5).

Table 3

Overview of the treatment of intramedullary ependymoma (IME) and intramedullary astrocytoma (IMA)*

eBox 5

Chemotherapy for intramedullary astrocytoma

The prognosis and quality of life after surgical resection

Many variables influence the outcome of surgery for an intramedullary tumor. Negative predictive factors include greater longitudinal extent, ventral position, greater size, cervicothoracic or thoracic location, and certain histopathological diagnoses (3, 11). Numerous factors also affect the feasibility of total resection of an intramedullary tumor. The degree of influence of certain individual factors is still debated. Some authors consider the histological diagnosis to be the main factor affecting the totality or resection, while others emphasize microsurgical aspects, such as the demarcation of a plane of dissection between the tumor and the surrounding neural tissue (3, 18).

Acute postoperative neurological deterioration is not rare; it affects 9–34 % of patients while they are still in the hospital. 25–41% of them regain their preoperative level of neurological function within 6 months (3, 4, 26). Intraoperative changes of motor evoked potentials and advanced age are further risk factors for neurological deterioration immediately after surgery (3). The clinical neurological outcome depends to a large extent on the patient’s general state of health, preoperative neurological condition, and tumor burden (33).

Aside from the histological classification, the main prognostic factors for the postoperative clinical and neurological outcome of patients with intramedullary tumors are the longitudinal extent and location of the tumor and the extent of resection (3, 7, 22). Total resection is associated with better outcomes than subtotal resection, but total resection is often not carried out when it might worsen the outcome (8). Neuropathic pain is a common postoperative symptom, arising in 13% to 60% of patients (7, 11, e32, e33). A high preoperative McCormick score generally predicts a poorer outcome (8, 11). Symptoms improve over the long term in 25% of patients, and a stable neurological condition can be expected in 66%. It is reported, however, that 9% of patients suffer a worsening of their symptoms before undergoing surgery (9).

The postoperative outcome of patients with high-grade tumors is markedly worse than that of patients with low-grade tumors. Their median survival time is comparable to that of patients with cerebral astrocytoma (34) of the corresponding WHO grade: 17–72 months for intramedullary anaplastic astrocytoma, 9–10 months for intramedullary glioblastoma (34, 35, e34).

Case illustration

Details of the case of a 53-year-old woman with a WHO grade 2 intramedullary ependymoma extending from C7 to T1 and an accompanying syrinx can be found in Table 4, the Figure, and the eFigure.

Figure

The case of a 53-year-old woman with a WHO grade 2 intramedullary ependymoma extending from C7 to T1 and an accompanying syrinx

Table 4

The case illustration in tabular form

eFigure

Artist’s depiction of surgery for an intramedullary tumor in the semi-sitting position

Conflict of interest statement
CM is the managing director of the German Society for Neuropathology and Neuroanatomy (Deutsche Gesellschaft für Neuropathologie und Neuroanatomie).

The remaining authors declare that they have no conflicts of interest.

Manuscript received on 17 September 2023, revised version accepted on 1 October 2024.

Translated from the original German by Ethan Taub, M.D.

Corresponding author
Dr. med. Belal Neyazi

Universitätsklinik für Neurochirurgie

Otto-von-Guericke-Universität Magdeburg

Leipziger Str. 44, D-39120 Magdeburg

Cite this as:
Neyazi B, Haghikia A, Mawrin C, Hattingen E, Vordermark D, Sandalcioglu IE: Spinal intramedullary tumors. Dtsch Arztebl Int 2024; 121: 840–6. DOI: 10.3238/arztebl.m2024.0213

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