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Spinal cord tumor

History

The surgery of tumors of the spinal cord dates back only to 1887, when a tumor was localized by Gowers and successfully removed by Victor Horsley.

Striking advances in our knowledge of the history and symptoms of compression of the cord have been and are still being made. The whole subject to date has been put in most clear and readable form in Elsberg's 1) book, based on one hundred cases which he personally studied and operated on. The localization of tumors of the spinal cord is easier than that of tumors of the brain, because a growth cannot attain any considerable size in the spinal canal without compressing the cord and giving definite motor, sensory and reflex signs. A careful history and repeated neurological examinations will accurately localize the great majority. Many patients have intensification of symptoms and signs after a spinal puncture, manifested by increased paralysis, or by a higher and more distinct level of sensory disturbance. The examination, therefore, should always he repeated after withdrawal of spinal fluid.

The greatest difficulty comes in attempting to differentiate very early compression from degenerative changes in the cord which simulate tumor. Dynamic and chemical studies of the spinal fluid (Queckenstedt's and Aycr's tests), are of great assistance in the detection of early partial blocks in the spinal subarachnoid spaces. A new method of diagnosis and localization was introduced in 1921 by Sicard, who showed that lipiodol introduced through a needle at the cisterna magna would be arrested at the upper margin of the tumor, where it could be demonstrated by the roentgen ray. This method unquestionably gives a perfect visual localization in the presence of a block ; but in such cases the localization can almost always be made without its use. It is irritative, and it is not absorbed in less than three years. But, more important, the lipiodol is not always arrested by a tumor. Babinski 2) and Guillain 3) have reported cases in which, after negative lipiodol tests, operations have disclosed tumors. Moreover, lipiodol sometimes shows a false arrest which has led to negative explorations. De Martel 4) has cited four such cases, operated on by him, in two of which the lipiodol localization was made by Sicard. Though the method is still subjudice, it has not lived up to the hopes which were aroused that it would, like cerebral pneumogratns in tumors of the brain, localize the few tumors of the spinal cord whose level could not be determined by other methods 5).

Classification

They can be classified according to many ways:

Age

Adult spinal cord tumor.

Pediatric spinal cord tumor.

Localization

Cervical spinal cord tumor

Thoracic spinal cord tumor

Intramedullary spinal cord tumor.

Intradural extramedullary spinal tumor.

Histology

glial neoplasms : 90 - 95% of all intramedullary tumours

Spinal cord ependymoma : 60% of all glial spinal cord tumours

Spinal cord astrocytoma : 33% of all glial spinal cord tumours

Spinal cord ganglioglioma : 1% of all glial spinal cord tumours

non-glial neoplasms

highly vascular lesions

Spinal cord hemangioblastoma

spinal paraganglioma

other rare lesions :

Intramedullary spinal cord metastasis

primary lymphoma of the spinal cord

spinal primitive neuroectodermal tumour

solitary fibrous tumour

intramedullary benign masses

spinal canal epidermoid cyst

Spinal cord lipoma

Associations

Intramedullary spinal neoplasms are more common in patients with neurofibromatosis:

ependymomas occur more often in patients with NF2

astrocytomas occur more often in patients with NF1.

Cysts

Approximately 70% of intramedullary tumours are associated with cysts.

Two types of cysts are recognised :

tumoural (or intratumoural) cysts

contained within the tumour itself

typically demonstrate peripheral enhancement

may result from necrosis, fluid secretion, or degeneration of the neoplasm

need to be resected along with the solid portion of the tumour because there is a high likelihood of neoplastic cells within the cyst wall

occurs in association with the following proportion of tumours:

spinal ganglioglioma : in 46%

spinal ependymoma : in 22%

spinal astrocytoma : in 21%

spinal haemangioblastoma : in 2 - 4%

non-tumoural (or reactive) cysts

occur rostral or caudal to the solid portion of the tumour

occur due to dilatation of the central canal

do not enhance

present in 60% of all intramedullary spinal tumours may resolve once the neoplasm is resected

Syringomyelia occurs in approximately 50% of all intramedullary tumours but is most frequently associated with spinal cord hemangioblastomas.

Clinical presentation

The clinical presentation of primary spinal cord tumors is determined in part by the location of the tumor, and in nearly all clinical instances pain is the predominant presenting symptom. Motor disturbance is the next most common symptom, followed by sensory loss.

Diagnosis

Diagnosis of a primary spinal cord tumor requires a high index of suspicion based on clinical signs and symptoms, in addition to spine-directed magnetic resonance imaging 6).

MRI is the gold standard for diagnosis and assessment of intramedullary tumors. Nevertheless, sometimes MRI may not accurately differentiate between different types of intramedullary tumors, in particular if they are associated with syringes or intra- and peritumoral cysts. This could subsequently affect surgical strategies. Intraoperative ultrasound (ioUS) has become in the last few years a very useful tool for use during neurosurgical procedures. Various ioUS modalities such as B-mode and Doppler have been applied during neurosurgical procedures. On the other hand, the use of contrast-enhanced ultrasound (CEUS) is not yet well defined and standardized in this field. We report a case of a young patient harboring a cervicothoracic intramedullary tumor, for which the preoperative neuroradiological diagnosis was in favor of a diffuse astrocytoma with nodular components whereas ioUS demonstrated 3 distinct intramedullary nodules. CEUS showed highly vascularized lesions, compatible with hemangioblastomas. These findings, particularly those obtained with CEUS, allowed better definition of the lesions for diagnosis, enhanced understanding of the physiopathological aspects, and permitted the localization of all 3 nodules, thus limiting spinal cord manipulation and allowing complete resection of the lesions, with an uneventful postoperative neurological course. This is the first report of the use of intraoperative CEUS in a case of intramedullary hemangioblastoma 7).

Differential diagnosis

Seropositive Neuromyelitis Optica imitating an Intramedullary Cervical Spinal Cord Tumor 8)

Treatment

Several uncertainties remain concerning the management of intramedullary spinal cord tumours (IMSCTs). These include the timing and extent of resection, its interrelated functional outcome, and the adequate use and timing of radiation therapy and/or chemotherapy.

Surgery

Radical resection is recommended as the first-line treatment for pediatric intramedullary spinal cord tumors (IMSCTs), but it is associated with morbidity, including risk of neurological decline and development of postoperative spinal deformity.

Nowadays, the microsurgical technique, including the use of an ultrasonic aspirator (Cavitron Ultrasonic Surgical Aspirator [CUSA]), is employed as standard. Boström et al.recommend evoked potential-guided microsurgical total resection of ependymomas and other benign lesions; partial resection or biopsy followed by adjuvant therapy should be confined to patients with high-grade astrocytomas, whereas resection or biopsy with adjuvant therapy is the best option for metastatic lesions 9).

Intraoperative monitoring

Many studies have recommended the routine use of electrophysiological monitoring, mostly somatosensory evoked potential (SSEP), although in some cases motor evoked potential (MEP) are also used; however, only a few studies have evaluated their effective impact 10) 11) 12) 13).

Intraoperative monitoring of somatosensory evoked potentials and transcranial electrical motor evoked potentials has been used previously to limit complications. Electromyography offers an opportunity for the surgeon to map the eloquent tissue associated with the tumor using intraoperative motor fiber stimulation. Similar to the use of cortical simulation in the resection of supratentorial gliomas, this technique can potentially advance the safety of intramedullary spinal cord tumor resection.

This technique led to protection of these tracts during resection of the tumor 14).

Identification of neurophysiologically viable dorsal columns (DC) and of neurophysiologically inert tissue, e.g. median raphe (MR), as a safe incision site is crucial for avoiding post-operative neurologic deficits.

The right and left DC were stimulated using a bipolar electric stimulator and the triggered somatosensory evoked potentials (SSEPs) recorded from the scalp. Phase reversal and amplitude changes of SSEPs were used to neurophysiologically identify the laterality of DC, the inert MR, as well as other safe incision sites.

The MR location was neurophysiologically confirmed in all patients in whom this structure was first visually identified as well as in those in whom it was not, with one exception. DC were identified in all patients, regardless of whether they could be visually identified. In three cases, negative mapping using this method enabled the surgeon to reliably identify additional inert tissue for incision. None of the patients had postoperative worsening of the DC function.

The technique is safe, reliable, and can be easily incorporated into routine intramedullary spinal cord tumor resection. It provides crucial information to the neurosurgeon in order to prevent post-operative neurological deficits 15).

Intraoperative vascular flow assessment using ICG-VA was easy, repeatable, and practical without any significant procedure-related risks. ICG-VA can be used for careful analysis of spinal microvascular flow or anatomical orientation, which is necessary to ensure safe and precise resection of spinal intramedullary tumors 16).

Chemotherapy

Chemotherapy is still considered experimental in the treatment of adult spinal cord tumours; a number of protocols are undergoing examination, primarily involving childhood astrocytomas 17) 18) 19).

C6 glioma cells and an intramedullary spinal cord tumor model were used to evaluate the effect of bevacizumab (Avastin) or temozolomide (TMZ).

C6 glioma cells were injected into the T5 level of the spinal cord, and TMZ and bevacizumab were administered 5 days after C6 inoculation (n = 7 for each group). Tumor size was analyzed using histology and magnetic resonance imaging at 13 days after tumor inoculation.

Histological analyses and magnetic resonance imaging findings showed that combined treatment with TMZ and bevacizumab reduced tumor mass. The tumor volume of control group was 2.8-fold higher than combined therapy (P < 0.05). Neurological outcomes demonstrated that combined therapy improved hind limb function more than TMZ-alone group or control group (P < 0.05).

This study shows that bevacizumab could be useful in combination with TMZ to increase the therapeutic benefits of TMZ for intramedullary spinal cord tumors 20).

Outcome

Tumor histology is the most important predictor of neurological outcome after surgical resection because it predicts resectability and recurrence 21).

Adult patients

Although resection did not significantly improve QOL, it is likely necessary to arrest QOL deterioration. Patients with better preoperative neurological status or ependymoma experienced QOL improvement, while postoperative complications negatively impacted long-term QOL 22).

Pediatric patients

The prognosis for pediatric IMSCTs is favorable with sustained functional improvement expected in a significant proportion of patients on long-term follow-up. Long-term survival at 10 years (75%) and 20 years (64%) is associated with aggressive resection. Gross-total resection was also associated with improved 5-year progression-free survival (86%). Hence, the treatment benefits of GTR are sustained on extended follow-up 23).

In a small cohort of children who had undergone surgery for IMSCTs with a mean follow-up of 4.2 years, quality of life scores according to the PedsQL 4.0 instrument were not different from those in a normal sample population 24).

Case series

2017

The objective of this study was to identify clinically relevant predictors of progression-free survival and functional outcomes in patients who underwent surgery for intramedullary spinal cord tumors (ISCTs). METHODS An institutional spinal tumor registry and billing records were reviewed to identify adult patients who underwent resection of ISCTs between 1993 and 2014. Extensive data were collected from patient charts and operative notes, including demographic information, extent of resection, tumor pathology, and functional and oncological outcomes. Survival analysis was used to determine important predictors of progression-free survival. Logistic regression analysis was used to evaluate the association between an “optimal” functional outcome on the Frankel or McCormick scale at 1-year follow-up and various clinical and surgical characteristics. RESULTS The consecutive case series consisted of 63 patients (50.79% female) who underwent resection of ISCTs. The mean age of patients was 41.92 ± 14.36 years (range 17.60-75.40 years). Complete microsurgical resection, defined as no evidence of tumor on initial postoperative imaging, was achieved in 34 cases (54.84%) of the 62 patients for whom this information was available. On univariate analysis, the most significant predictor of progression-free survival was tumor histology (p = 0.0027). Patients with Grade I/II astrocytomas were more likely to have tumor progression than patients with WHO Grade II ependymomas (HR 8.03, 95% CI 2.07-31.11, p = 0.0026) and myxopapillary ependymomas (HR 8.01, 95% CI 1.44-44.34, p = 0.017). Furthermore, patients who underwent radical or subtotal resection were more likely to have tumor progression than those who underwent complete resection (HR 3.46, 95% CI 1.23-9.73, p = 0.018). Multivariate analysis revealed that tumor pathology was the only significant predictor of tumor progression. On univariate analysis, the most significant predictors of an “optimal” outcome on the Frankel scale were age (OR 0.94, 95% CI 0.89-0.98, p = 0.0062), preoperative Frankel grade (OR 4.84, 95% CI 1.33-17.63, p = 0.017), McCormick scale (OR 0.22, 95% CI 0.084-0.57, p = 0.0018), and region of spinal cord (cervical vs conus: OR 0.067, 95% CI 0.012-0.38, p = 0.0023; and thoracic vs conus: OR 0.015: 95% CI 0.001-0.20, p = 0.0013). Age, tumor pathology, and region were also important predictors of 1-year McCormick scores. CONCLUSIONS Extent of tumor resection and histopathology are significant predictors of progression-free survival following resection of ISCTs. Important predictors of functional outcomes include tumor histology, region of spinal cord in which the tumor is present, age, and preoperative functional status 25).

2016

The consecutive case series consisted of 63 patients (50.79% female) who underwent resection. The mean age of patients was 41.92 ± 14.36 years (range 17.60-75.40 years). Complete microsurgical resection, defined as no evidence of tumor on initial postoperative imaging, was achieved in 34 cases (54.84%) of the 62 patients for whom this information was available. On univariate analysis, the most significant predictor of progression-free survival was tumor histology (p = 0.0027). Patients with Grade I/II astrocytomas were more likely to have tumor progression than patients with WHO Grade II ependymomas (HR 8.03, 95% CI 2.07-31.11, p = 0.0026) and spinal myxopapillary ependymomas (HR 8.01, 95% CI 1.44-44.34, p = 0.017). Furthermore, patients who underwent radical or subtotal resection were more likely to have tumor progression than those who underwent complete resection (HR 3.46, 95% CI 1.23-9.73, p = 0.018). Multivariate analysis revealed that tumor pathology was the only significant predictor of tumor progression. On univariate analysis, the most significant predictors of an “optimal” outcome on the Frankel scale were age (OR 0.94, 95% CI 0.89-0.98, p = 0.0062), preoperative Frankel grade (OR 4.84, 95% CI 1.33-17.63, p = 0.017), McCormick score (OR 0.22, 95% CI 0.084-0.57, p = 0.0018), and region of spinal cord (cervical vs conus: OR 0.067, 95% CI 0.012-0.38, p = 0.0023; and thoracic vs conus: OR 0.015: 95% CI 0.001-0.20, p = 0.0013). Age, tumor pathology, and region were also important predictors of 1-year McCormick scores. CONCLUSIONS Extent of tumor resection and histopathology are significant predictors of progression-free survival following resection of ISCTs. Important predictors of functional outcomes include tumor histology, region of spinal cord in which the tumor is present, age, and preoperative functional status 26).


Case records of 37 patients with low-grade intramedullary spinal cord tumors (IMSCTs) were identified, with a mean follow-up duration of 12.3 ± 1.4 years (range 0.5-37.2 years). Low grade astrocytomas were the most prevalent histological subtype (n = 22, 59%). Gross total resection (GTR) was achieved in 38% of patients (n = 14). Fusion surgery was required in 62% of patients with pre- or postoperative deformity (10 of 16). On presentation, functional improvement was observed in 87% and 46% of patients in McCormick scale I and II, respectively, and in 100%, 100%, and 75% in Grades III, IV, and V, respectively. Kaplan-Meier PFS rates were 63% at 5 years, 57% at 10 years, and 44% at 20 years. OS rates were 92% at 5 years, 80% at 10 years, and 65% at 20 years. On multivariate analysis, shunt placement (hazard ratio [HR] 0.33, p = 0.01) correlated with disease progression. There was a trend toward improved 5-year PFS in patients who received adjuvant chemotherapy and radiation therapy (RT; 55%) compared with those who did not (36%). Patients who underwent subtotal resection (STR) were most likely to undergo adjuvant therapy (HR 7.86, p = 0.02).

This extended follow-up duration in patients with low-grade IMSCTs beyond the first decade indicates favorable long-term OS up to 65% at 20 years. GTR improved PFS and was well tolerated with sustained functional improvement in the majority of patients. Adjuvant chemotherapy and RT improved PFS in patients who underwent STR. These results emphasize the role of resection as the primary treatment approach, with adjuvant therapy reserved for patients at risk for disease progression and those with residual tumor burden 27).

2015

A retrospective review of 102 consecutive patients with intramedullary spinal cord tumors treated at a single institution between January 1998 and March 2009.

Ependymomas were the most common tumors with 55 (53.9%), followed by 21 astrocytomas (20.6%), 12 hemangioblastomas (11.8%), and 14 miscellaneous tumors (13.7%). Gross total resection was achieved in 50 ependymomas (90.9%), 3 astrocytomas (14.3%), 11 hemangioblastomas (91.7%), and 12 miscellaneous tumors (85.7%). At a mean follow-up of 41.8 months (range, 1-132 months), they observed recurrences in 4 ependymoma cases (7.3%), 10 astrocytoma cases (47.6%), 1 miscellaneous tumor case (7.1%), and no recurrence in hemangioblastoma cases. When analyzed by tumor location, there was no difference in neurological outcomes (P = .66). At the time of their last follow-up visit, 11 patients (20%) with an ependymoma improved, 38 (69%) remained the same, and 6 (10.9%) worsened. In patients with an astrocytoma, 1 (4.8%) improved, 10 (47.6%) remained the same, and 10 (47.6%) worsened. One patient (8.3%) with a hemangioblastoma improved and 11 (91.7%) remained the same. No patient with a hemangioblastoma worsened. In the miscellaneous tumor group, 2 (14.3%) improved, 10 (71.4%) remained the same, and 2 (14.3%) worsened. Preoperative neurological status (P = .02), tumor histology (P = .005), and extent of resection (P < .0001) were all predictive of functional neurological outcomes.

Tumor histology is the most important predictor of neurological outcome after surgical resection because it predicts resectability and recurrence 28).


53 patients (23 women and 30 men; mean age 46.3 years) were included who had undergone microsurgical resection for intramedullary spinal tumors. Schebesch et al., reviewed the patient records for tumor size, edema, intratumoral hemorrhage, consistency, midline detection, resection method, extent of resection, histopathology, and recurrence. Outcome was measured by the Karnofsky Score (KPI), the McCormick score (MCS), and the Medical Research Council Neurological Performance Score (MRC-NPS).

The most frequent diagnosis was ependymoma (37.7%), lymphoma (13.2%) and astrocytoma (11.3%). The majority of tumors were located in the thoracic spine (62.2%). Gross total resection was achieved in 73.6% and most successful in patients with ependymal histology (p<0.01). Tumor recurrence - observed in 11.3% - was significantly associated with age >65 years, astrocytic histology, higher tumor grades, and higher Ki-67 labeling. At follow-up, MCS and MRC-NPS showed significantly better results than prior to resection (p<0.001), and pain and sensory deficits had improved in 67.9% and 64.2% of patients, respectively. Microsurgical resection improved the neurological status significantly. Pain and sensory deficits showed higher improvement rates than paresis and vegetative dysfunction 29).

2014

A total of 70 adult cases consisting of ependymoma (39), astrocytoma (11), carcinoma metastasis (8), haemangioblastoma (5), cavernoma (3) and others (4) were reviewed. Mean age was 46.8 years (range, 18-79 years), and mean follow-up was 4.5 years (range, 1-195 months). The proportion of localisation in descending order was thoracic (36%), cervical (33%), cervicothoracic (19%) and conus region (13%), with 45 gross total resections, 22 partial resections and three biopsies. Surgery-related morbidity with worsening postoperative symptoms occurred immediately in 13 patients (18.6%). The preoperative McCormick grade correlated significantly with the early postoperative grade and the grade at follow-up (χ2-test; p=0.001). None of the patients with preserved intraoperative evoked potentials exhibited significant postoperative deterioration. The degree of resection was correlated with progression-free survival (Duncan test; p=0.05). Most patients with malignant tumours, namely anaplastic ependymoma (3), astrocytoma (2) or metastatic lesions (5), underwent postoperative radiation therapy. Six patients (one anaplastic ependymoma, two anaplastic astrocytomas and three metastatic lesions) received postoperative chemotherapy.

IMSCTs should be operated on when symptoms are mild. They recommend evoked potential-guided microsurgical total resection of ependymomas and other benign lesions; partial resection or biopsy followed by adjuvant therapy should be confined to patients with high-grade astrocytomas, whereas resection or biopsy with adjuvant therapy is the best option for metastatic lesions 30).


A total of 55 patients (30 male and 25 female. The mean duration of follow-up (± SEM) was 11.4 ± 1.3 years (median 9.3 years, range 0.2-37.2 years). Astrocytomas were the most common tumor subtype (29 tumors [53%]). Gross-total resection (GTR) was achieved in 21 (38%) of the 55 patients. At the most recent follow-up, 30 patients (55%) showed neurological improvement, 17 (31%) showed neurological decline, and 8 (15%) remained neurologically stable. Patients presenting with McCormick scale I were more likely to show functional improvement by final follow-up (p = 0.01) than patients who presented with Grades II-V. Kaplan-Meier actuarial tumor progression-free survival rates at 5, 10, and 20 years were 61%, 54%, and 44%, respectively; the overall survival rates were 85% at 5 years, 74% at 10 years, and 64% at 20 years. On multivariate analysis, GTR (p = 0.04) and tumor histological grade (p = 0.02) were predictive of long-term survival; GTR was also associated with improved 5-year progression-free survival (p = 0.01).

The prognosis for pediatric IMSCTs is favorable with sustained functional improvement expected in a significant proportion of patients on long-term follow-up. Long-term survival at 10 years (75%) and 20 years (64%) is associated with aggressive resection. Gross-total resection was also associated with improved 5-year progression-free survival (86%). Hence, the treatment benefits of GTR are sustained on extended follow-up 31).

In a small cohort of children who had undergone surgery for IMSCTs with a mean follow-up of 4.2 years, quality of life scores according to the PedsQL 4.0 instrument were not different from those in a normal sample population 32).

2005

From December 1972 to June 2003, 202 patients underwent removal of intramedullary tumors. Lesions were located in the cervical spinal cord in 61 patients (30%), at a dorsal site in 60 (29%), at a cervicodorsal site in 51 (25%), and in the medullary cone in 30 (15%). The most frequent histological tumor types were astrocytomas (86 patients, 42%) and ependymomas (68 patients, 34%).

Of the 68 ependymomas, 55 (81%) were completely removed and 13 (19%) incompletely removed. In 66% of the patients (42 patients), the presenting signs and symptoms remained unchanged at long-term follow-up; in 25% (16 patients), they improved; and in 9% (6 patients), the clinical status worsened. Of the 27 Grade I astrocytomas, 22 (81%) were completely removed and 5 (19%) incompletely removed. Functional assessment of the 23 patients available at “late” follow-up showed that 26% (6 of 23 patients) had improved, 9% (2 of 23 patients) had worsened, and 66% (15 of 23 patients) remained unchanged from preoperative status. Conversely, of the 41 Grade II astrocytomas, only 5 (12%) were completely removed, and 10% had improved. None of the 18 Grade III to IV astrocytomas could be completely removed. In 61% (11 of 18 patients), the postoperative functional status worsened.

Determinant predictors of a good outcome after surgery for intramedullary spinal cord tumors are histological type of lesion, complete removal of the lesion, and a satisfactory neurological status before surgery 33).

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spinal_cord_tumor.txt · Last modified: 2018/11/08 08:07 by administrador