Management of Patients with Primary Intramedullary Spinal Cord Glioblastoma

doi:10.1016/j.wneu.2016.10.075

World Neurosurgery

Volume 98, February 2017, Pages 198-202

https://doi.org/10.1016/j.wneu.2016.10.075 Get rights and content

Background

Primary intramedullary spinal cord glioblastomas are very rare tumors of the spinal cord. They imply a very poor prognosis because complete surgical resection is not possible as the result of the infiltrative growth of these tumors. The aim of this study is to present our data achieved with an aggressive multimodality treatment.

Methods

We retrospectively reviewed our clinical database. All patients with histologically proven intramedullary spinal cord glioblastoma treated in our department were included in this study.

Results

Four patients with intramedullary spinal cord glioblastoma were identified between 2006 and 2015, all of whom were female. Mean age at the time of surgery was 33.5 years (range 14–50 years). Tumors were located in the cervical region in 2 patients and in the thoracic region in 2 patients. All 4 patients underwent microsurgical biopsy of the tumor. After surgery, all patients received radiation and temozolomide treatment. One patient underwent additional therapy with Bevacizumab, another patient received Rapamycin and Sunitinib, and the third patient received Chlorethyl-cyclohexyl-nitroso-urea and Etoposide as additional therapy after tumor regrowth. Tumor progression occurred in a mean time of 18.2 months (6–32 months). In this series, all patients died as the result of progression of the malignancy; median survival after diagnosis was 32.5 months.

Conclusions

The surgical outcome of intramedullary spinal cord glioblastoma still remains poor. Severe disability and amelioration of the neurologic status lead to reduced quality of life; however, an aggressive multimodal and interdisciplinary treatment for the disease may be associated with longer survival.

Introduction

Primary spinal cord (SC) tumors are rare entities, accounting for 2%–4% of all central nervous system tumors.1, 2 Among these, astrocytoma represent only 6%–8% of all intramedullary tumors, with 75%–90% of them being low-grade gliomas. Therefore, SC glioblastoma multiforme (GBM) is extremely rare, accounting for only 1.5% of all SC tumors.3, 4, 5, 6 These highly malignant lesions occur mainly in the cervicothoracic segments and have a slight tendency to occur in the first decades of life. A short clinical history before diagnosis is mainly associated with the natural history of intramedullary spinal cord glioblastoma (ISCGBM).7, 8 The overall survival (OS) of patients with ISCGBM is approximately 10–12 months, in contrast to a better prognosis of 14 months for its intracranial counterpart.⁹ ISCGBM results in death resulting from complications related to progressive SC involvement, respiratory impairment, and cerebral metastases.7, 10 Only few data exist reporting current experience about survival and progression after the introduction of temozolomide (TMZ) and novel therapeutic strategies. The aim of this paper also is to highlight the effect of new drugs on survival and tumor control.

Section snippets

Methods

The study was approved by the local ethics committee at the authors' institution. We retrospectively reviewed the medical history of all patients with intramedullary SC tumors treated at our institution during a period of 36 years. Between 2006 and 2015, 4 patients with the diagnosis of ISCGBM were identified. The medical charts were reviewed, including surgical and histologic data, treatment parameters, neurologic outcome, progression-free survival (PFS), and OS. Histologic grading of all

Results

All patients were female, and their ages ranged from 14 to 50 years at the time of surgery (mean 33.5 years). The follow-up period ranged from 10 to 46 months (mean 32.5 months). The presenting symptoms and signs were pain, hypesthesia, or paresthesia in all cases. Two patients revealed motor weakness preoperatively and only 1 patient an improvement of the neurologic status after surgery and postoperative therapy. The preoperative functional assessment, which was made in all patients, showed 1

Discussion

As a result of the extremely rare occurrence of ISCGBM the current literature is scarce. A review of the pertaining literature suggests that this entity shows a predilection in the earlier decades of life.4, 18, 19, 20 In our series, mean age was 33.5 years with one patient being younger than 18 years. Apparently, the most affected spinal areas are the cervical and thoracic region in line with the data presented here.6, 21, 22 Because complete resection of these tumors is not possible because

Conclusions

The surgical outcome of ISCGGM still remains poor. Severe disability and amelioration of the neurologic status lead to reduced quality of life; however, an aggressive multimodal and interdisciplinary treatment for the disease may be associated with longer survival.

Acknowledgments

We thank Marina Heibel for her excellent technical support.

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Cited by (25)

Primary Spinal Cord Astrocytomas: Two-Center Clinical Experience of Low- and High-Grade Lesions
2022, World Neurosurgery
Primary spinal cord astrocytomas are rare, fatal, and poorly studied.
This study included a 2-center, retrospective analysis of primary spinal cord astrocytoma patients from 1997 to 2020. Patients with drop metastases or without at least one follow-up were excluded.
Seven World Health Organization grade I, 6 grade II, 7 grade III, and 4 grade IV astrocytoma patients were included. Older patients had higher grades (median 20 years in grade I vs. 36.5 in grade IV). The median follow-up was 15 months. Thirteen patients were discharged to rehabilitation. Eight patients demonstrated radiographic progression. Adjuvant therapy was utilized more in higher grades (5 of 13 grades III vs. all 11 grades IIIIV). Six patients died (1 death in grades III vs. 5 in grades IIIIV). Ten patients had worsened symptoms at the last follow-up. The median progression-free survival in grade I, II, III, and IV tumors was 116, 36, 8, and 8.5 months, respectively. The median overall survival in grade I, II, III, and IV tumors was 142, 69, 19, and 12 months, respectively. Thrombotic complications occurred in 2 patients, one with isocitrate dehydrogenasewild type glioblastoma.
Outcomes worsen with higher grades and lead to difficult postoperative periods. Clinicians should be vigilant for thromboembolic complications. Further research is needed to understand these rare tumors.
Risk score for outcome prediction after microsurgical resection of spinal ependymoma (SOURSE score)
2021, Clinical Neurology and Neurosurgery
Microsurgical resection of spinal ependymomas is associated with a considerable risk of postoperative neurological deterioration. We aimed to develop a risk score for outcome prediction after surgery for spinal ependymoma.
All patients who underwent microsurgical resection of spinal ependymoma between 1980 and 2015 were included. Different perioperative parameters were collected for the score construction. Poor outcome was defined as the modified McCormick Scale (MMCS) >2 at 6 months after surgery.
Of 131 patients (mean age: 45.6 ± 16.7 years; 63 females), 38 cases (29%) showed poor outcome. Based on the univariate analysis, preoperative MMCS, subtotal tumor resection, proximal tumor level on the spinal cord, tumor extension, intramedullary location, and WHO grading were included in the multivariate analysis. The final risk score consisted of the following independent predictors: preoperative MMCS > 1 (1 point), proximal tumor level at Th 10 and higher (1 point), and tumor extension ≥ 3 vertebrae (1 point). The constructed score (0–3 points; Score for OUtcome after Resection of Spinal Ependymoma [SOURSE]) showed high diagnostic accuracy (area under the curve [AUC] = 0.883), which was superior to preoperative MMCS (AUC = 0.798) and Karnofsky Performance Status (AUC = 0.794). Patients scoring 0, 1, 2, and 3 points showed poor outcome in 0%, 12.9%, 54.6%, and 76.2% of the cases respectively.
The presented SOURSE score based on preoperative neurologic condition, tumor location, and tumor extension could accurately predict the postoperative outcome in patients undergoing microsurgery of spinal ependymoma. Our data should be validated in a prospective trial.
Spinal cord glioblastoma multiforme in a patient with Noonan syndrome: A clinical report
2021, Clinical Neurology and Neurosurgery
Citation Excerpt :
The development of a spinal cord glioblastoma in a patient with NS has not previously been reported to our knowledge. Primary spinal cord malignancies are a rare entity accounting for only 2–4% of all CNS tumors [4]. Of these, astrocytomas are responsible for less than 10% of spinal cord tumors, and 80% are low-grade tumors, whereas only 1.5% of spinal cord tumors are glioblastoma multiforme, a rare but devastating disease [4].
Currently, there are only 3 reported cases of central nervous system malignancies in patients with Noonan syndrome in the literature, all of which are intracranial pathologies. To our knowledge, there are no cases of spinal cord glioblastoma multiforme reported in the literature.
We describe the case of a 12-year-old girl with Noonan syndrome who presented with back pain and new onset neurological deficits and was found to have a spinal cord lesion. T10-L1 laminoplasty with safe maximal resection was done. Postoperative pathological analysis identified this lesion as a high-grade astrocytoma consistent with glioblastoma multiforme.
Spinal cord glioblastoma multiforme is a rare occurrence in the general population, particularly in a patient with an underlying diagnosis of Noonan syndrome. Patients with spinal cord tumors can present with a multitude of clinical signs and symptoms and treatment should not be delayed.
Primary spinal glioblastoma multiforme. Single center experience and literature review
2021, Interdisciplinary Neurosurgery: Advanced Techniques and Case Management
Citation Excerpt :
Indeed, according to the literature review of Konar et al [4], based on 128 patients selected from 58 published articles, median OS of 11 months was observed. Moreover, the majority of patients complained of a low quality of life; they present severe disability at the time of diagnosis, with low possibilities of neurological improvement [14]. An early diagnosis and a precocious treatment it’s mandatory to promote an improvement of OS, with preservation of quality of life.
Spinal glioblastomas represent a rare entity accounting for ca 1–3% of all intramedullary tumors; data about survival, prognostic factors and therapeutic protocols are quite poor. Even with an aggressive multimodal management the spinal glioblastoma patients’ survival remains poor, with rapid progression of the disease. This study reports our experience with the management of the primary intramedullary glioblastomas, also in regard to the current literature data.
We retrospectively analyzed the medical records of 5 patients treated at the Department for Neuro-oncology and Spine Surgery of the Clinical Center of Belgrade, Serbia, between January 2007 and December 2016 for a primary intramedullary glioblastoma. Demographic characteristics, pre-operative data and post-operative results were then compared with previous literature regarding spinal GBMs and attempt to identify potential prognostic factors.
Gross total resection was achieved in two patients, while a subtotal resection was performed in the latter 3 cases; as per protocol, all patients underwent to surgery, followed by radio and chemotherapy. There were no intraoperative complications and no patients developed a new postoperative neurological defect; the median overall survival was 6 months. Progression or recurrence of disease was noted in all patients at the 3-months follow-up, despite the adjuvant treatments.
To the date, there is a lack of consensus on specific management of spinal glioblastomas: the extent of resection can play an important role, but it appears to be not preeminent. A shorter interval between symptoms onset and treatment and a smaller extension of the tumor seem to be correlated with better outcomes and a longer overall survival. However, there is not an adjunctive viable standardized postoperative therapy yet, which results in concrete and persistent improvement of overall survival and progression free survival.
Challenges in diagnosis and management of adult spinal cord gliomas
2021, Revue Neurologique
Intramedullary spinal cord gliomas have very low incidence rates. They are associated with difficulties in diagnosis and treatment, and cause significant morbidity. Their clinical presentation and their appearance at magnetic resonance imaging are not specific. They can mimic inflammatory, infectious, vascular disorders or other neoplastic lesions. Primary treatment is surgery. Surgical resection can often be total for ependymomas, but difficult for infiltrating astrocytomas. Radiotherapy is indicated for malignant tumors, but remains controversial in some indications. Chemotherapy is reserved for recurrence, but small retrospective series are available. Genetic studies have revealed genetic alterations which could have a potential impact on treatment in the near future.
Spinal cord glioblastoma during pregnancy: Case report
2021, Neurochirurgie
Citation Excerpt :
Our patient became symptomatic at 13 weeks’ gestation, but decided with her family to wait 7 more weeks to perform the MRI and then the surgery. There are some predictive factors for overall survival of patients with spinal GBM, like age, rate of tumor removal and adjuvant radiotherapy and chemotherapy [19–24]. Disappointing prognosis with survival rates of 10–24 months were seen in patients submitted to surgery followed by CT and RT [2,5], Behmanesh et al. [24] reported a mean survival of 32.5 months which he attributed to the multimodal treatment, advocating the improvement on microsurgical technique and use of intraoperative adjuvants as neuromonitoring.

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: Conflict of interest statement: The authors declare that the article content was composed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Original ArticleManagement of Patients with Primary Intramedullary Spinal Cord Glioblastoma

Background

Methods

Results

Conclusions

Introduction

Section snippets

Methods

Results

Discussion

Conclusions

Acknowledgments

Epidemiology of primary tumours of the brain and spinal cord: a regional survey in southern England

J Neurol Neurosurg Psychiatr

Prognostic factors in intramedullary astrocytomas: a literature review

Eur Spine J

Long-term follow-up of intramedullary spinal cord tumors: a series of 202 cases

Neurosurgery

Glioblastoma multiforme of the conus medullaris

Clin Neurol Neurosurg

Intramedullary ependymomas: clinical presentation, surgical treatment strategies and prognosis

J Neurooncol

Intramedullary spinal cord tumors in patients older than 50 years of age: management and outcome analysis

J Neurosurg Spine

Spinal glioblastomas: report of seven cases and review of the literature

Neurosurgery

Spinal cord gliomas

Curr Opin Neurol

Prognostic factors and survival in primary malignant astrocytomas of the spinal cord: a population-based analysis from 1973 to 2007

Spine (Phila Pa 1976)

Malignant astrocytomas of the spinal cord

J Neurosurg

Recurrent spinal cord glioblastoma: salvage therapy with bevacizumab

J Neurooncol

Temozolomide or bevacizumab for spinal cord high-grade gliomas

J Neurooncol

Extent of surgical resection of malignant astrocytomas of the spinal cord: outcome analysis of 35 patients

Neurosurgery

Pediatric spinal glioblastoma multiforme: current treatment strategies and possible predictors of survival

Childs Nerv Syst

A retrospective observational study on the treatment outcomes of 26 patients with spinal cord astrocytoma including two cases of malignant transformation [e-pub ahead of print]

Eur Spine J

Original Article
Management of Patients with Primary Intramedullary Spinal Cord Glioblastoma