- Division of Neurosurgery, Department of Surgery, King Abdulaziz Medical City, Ministry of National Guard - Health Affairs, Riyadh, Saudi Arabia.
- College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia.
- King Abdullah International Medical Research Center, Riyadh, Saudi Arabia.
- Saudi Ministry of Health, Third Healthcare Cluster, Riyadh, Saudi Arabia.
- Department of Pathology and Laboratory Medicine, King Abdulaziz Medical City, Ministry of National Guard – Health Affairs, Riyadh, Saudi Arabia.
Ali Alkhaibary, College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia.
DOI:10.25259/SNI_135_2022Copyright: © 2022 Surgical Neurology International This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-Share Alike 4.0 License, which allows others to remix, transform, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.
How to cite this article: Bashaer Alharbi1,2,3, Hajar Alammar4, Ali Alkhaibary1,2,3, Ahoud Alharbi1,2,3, Sami Khairy1,2,3, Ali H. Alassiri2,3,5, Fahd AlSufiani3,5, Ahmed Aloraidi1,2,3, Ahmed Alkhani1,3. Primary spinal cord glioblastoma: A rare cause of paraplegia. 22-Apr-2022;13:160
How to cite this URL: Bashaer Alharbi1,2,3, Hajar Alammar4, Ali Alkhaibary1,2,3, Ahoud Alharbi1,2,3, Sami Khairy1,2,3, Ali H. Alassiri2,3,5, Fahd AlSufiani3,5, Ahmed Aloraidi1,2,3, Ahmed Alkhani1,3. Primary spinal cord glioblastoma: A rare cause of paraplegia. 22-Apr-2022;13:160. Available from: https://surgicalneurologyint.com/surgicalint-articles/11555/
Background: Primary spinal glioblastomas are extremely rare neoplasms and account for only 0.2% of glioblastoma cases. Due to the rare incidence of spinal cord glioblastoma in the literature, its natural history/ outcome remains undetermined. The present article describes the clinical presentation, radiological/pathological characteristics, and outcome of the primary spinal cord glioblastoma.
Case Description: Two young patients initially presented with paresis that rapidly progressed to paraplegia. Nondermatomal sensory deficits were also noted, mainly affecting the lower limbs. Neuroradiological imaging revealed an extensive intramedullary spinal cord lesion, with no evidence of concurrent intracranial space-occupying lesions. Thoracic laminectomy, followed by tumor debulking and/or biopsy, was performed. The histomorphology was suggestive of glioblastoma, the World Health Organization grade 4 (Isocitrate Dehydrogenase-wild type). They were discharged in stable condition and were started on chemoradiotherapy, with clinicoradiological follow-up. One patient passed away after 9 months of initial presentation. The other patient was alive at 6-month follow-up.
Conclusion: Primary spinal glioblastoma is a rare and challenging tumor. Patients commonly present with a progressive paresis, resulting in paraplegia, regardless of the surgical resection extent, and received adjuvant chemotherapy. Therefore, primary spinal cord glioblastoma should be considered in patients reporting a rapid lower limb weakness with neuroradiological evidence of extensive, exophytic intramedullary lesion of the spine. A biopsy-proven histopathological diagnosis is of indisputable importance to establish the final diagnosis and plan treatment options.
Keywords: Cervicothoracic, High-grade glioma, Intramedullary, Paresis, Weakness
Glioblastoma is a highly malignant neuroglial tumor. Intracranial glioblastomas are considered the most prevalent primary brain tumors in adults, accounting for 54% of gliomas and 16% of primary intracranial tumors with an incidence rate of 3.19/100,000 persons in the United States.[
Due to the rare incidence of spinal cord glioblastoma in the literature, its natural history/outcome remains undetermined. The present cases describe the clinical presentation, radiological/pathological characteristics, and outcome of the primary spinal cord glioblastoma.
A 37-year-old male, intellectually-challenged, presented to the emergency department with a 10-day history of progressive paresis, associated with low back pain and urinary incontinence, following a fall. Initially, the patient was able to ambulate freely with the left hip pain. However, the weakness progressed over the following days limiting his ability to ambulate independently, resulting in paraplegia. The weakness was associated with bilateral numbness and shooting, electrical-like sensation radiating from the hip to the knee. There was no history of fever, rigors, night sweats, fluctuating fatigability, or upper respiratory tract infection.
The patient was alert with a baseline intellectual disability. The muscle power was 5/5 in the upper limbs. Lower limb examination was limited due to excruciating pain. However, the muscle power in the lower limbs was 0/5. Sensation was decreased to pinprick in the lower limbs, especially on the left side, with no specific dermatomal distribution. Apart from a preserved left patellar reflex (+2), the lower limb reflexes were absent. Plantar reflexes were equivocal bilaterally.
Thoracolumbar MRI with contrast revealed an intramedullary high T2-signal lesion at T3-T7 level [
(a and b) Sagittal and axial T1-weighted MRI with contrast of the thoracic spine. (c and d) Sagittal and axial T2-weighted MRI of the thoracic spine. (e and f) Axial and coronal brain MRI with contrast. (a-d) The images demonstrate a T3–T7 intramedullary lesion with heterogenous peripheral enhancement (Arrow). The lesion measures 10.6 × 1.3 cm in craniocaudal and anterior-posterior diameters, respectively. (e and f) The brain MRI shows no evidence of intracranial space-occupying lesions.
The patient underwent upper thoracic laminectomy and tumor debulking. Intraoperatively, a biopsy was obtained from the exophytic part of the lesion and was sent for frozen section and permanent pathology. The biopsy revealed a high-grade glioma. The patient tolerated the surgery well with no complications.
Histopathological and molecular features
The histopathological sections showed a hypercellular malignant glioma [
Microscopic images of spinal cord glioblastoma. (a) Low- power micrograph showing high cellularity with palisading necrosis in the middle. (b) Intermediate-power micrograph showing both mitotic figures in green circles and microvascular proliferation (green arrows). (c) Glial differentiation is confirmed by positive nuclear staining for the antibody Olig2 (clone 211F1.1).
Outcome and follow-up
The patient continued to have persistent flaccid paraplegia with lower limb hypotonia. He was discharged in stable condition with regular clinical and radiological follow- up. Two months after discharge, the patient developed an episode of seizure. A repeat brain MRI demonstrated cerebral dissemination of the spinal tumor [
(a) Axial fluid-attenuated inversion recovery (FLAIR) MRI of the brain. (b and c) Coronal T1-weighted MRI with contrast of the brain. (a-c) There are two enhancing subependymal lesions noted in the right peritrigonal region, associated with a high signal in the FLAIR MRI (Arrow). Furthermore, there is a lesion in the inner aspect of the genu and isthmus of the corpus callosum (Arrow).
A 26-year-old female, not known to have any medical illness, was referred from another facility due to a progressive right lower limb paresis for 3 months. The weakness limited her ability to ambulate independently. Three days after the initial presentation, the patient started to complain of bilateral lower limb paresis and numbness, with a sensory level reaching the nipple, associated with urinary urge incontinence. Furthermore, the patient reported a 2-week history of neck pain radiating to the right shoulder, with no specific dermatomal distribution. There was no history of fever, rigors, night sweats, fluctuating fatigability, upper respiratory tract infection, or trauma.
The patient was alert, attentive, and oriented. The muscle power in the upper limbs was 4/5 bilaterally. Sensation in the upper limbs was intact through all dermatomes (C5-T1). Reflexes were +2 bilaterally in the upper limbs. Lower limb examination revealed a muscle power of 3/5 on the right and 4/5 on the left. The reflexes were +3 on the right and +2 on the left lower limbs. The muscle tone was increased on the right with clonus and upgoing plantar reflex. Sensation was decreased to pinprick and light touch on the left lower limb up to the level of T4 dermatome. The patient was bradykinetic, spastic, using a cane for ambulation, and leaning to her left leg more frequently.
Whole spine MRI with contrast revealed a large heterogenous intramedullary lesion of the spinal cord extending from C3 to T9, with nodular enhancement involving the exiting nerve roots [
(a-c) Sagittal T1-weighted MRI with contrast and T2-weighted MRI of the spine. (d) Axial T1-weighted MRI with contrast at the level of the cystic component. (e and f) Axial and coronal T1-weighted brain MRI with contrast. (a-d) The images demonstrate a large intramedullary heterogenous lesion extending from the level of C3–C4 until T8–T9. The lesion is causing expansion of the spinal cord, associated with a small cystic and necrotic component mainly at C7 down to T6 (Arrow) with heterogenous enhancement. Furthermore, there are areas of heterogenous enhancement of the exiting nerve roots. (e and f) The images demonstrate no intracranial space-occupying lesions or abnormal parenchymal/meningeal enhancement.
Due to the infiltrative nature of the tumor and the preserved muscle power (3-4/5) in the lower limbs, a T4–T5 laminectomy and biopsy of the intramedullary lesion were performed to establish the diagnosis. Intraoperatively, the frozen section was in favor of glioma. The patient tolerated the surgery well with no complications. Postoperatively, the patient had an unchanged neurological examination.
Histopathological and molecular features
The histomorphology was typical of glioblastoma [
Microscopic images of spinal cord glioblastoma. (a) Hematoxylin and Eosin-stained section shows low-to- moderately cellular infiltrative glioma. There is a focus of endothelial proliferation with no evidence of necrosis. The tumor cells appear round/oval and some are elongated and hyperchromatic. A few mitotic figures are observed. There are no Rosenthal fibers. (b) The tumor cells are immunopositive for GFAP and p53 (Not shown). (c) Ki-67 immunolabeling is estimated to be high (30–40%). (d) Neurofilament immunostain highlights a significant degree of infiltration
Outcome and follow-up
Three weeks after the surgery, the patient progressed to have bilateral paraplegia, associated with urinary and stool incontinence. The patient underwent radiation of the entire neuroaxis, craniospinal irradiation, followed by concomitant chemotherapy using Temozolomide. The patient is currently wheelchair-bound. She was discharged in stable condition with radiotherapy, oncology, neurosurgery, and rehabilitation follow-up. The patient was alive at 6-month follow-up. However, she travelled outside the country and was lost to follow-up.
Primary spinal cord glioblastoma can either originate as primary grade 4 astrocytoma or progress from a lower grade astrocytoma. In addition, they share similar histological features as supratentorial glioblastomas, including nuclear atypia, mitotic figures, palisading necrosis, microvascular or glomeruloid vascular proliferation, and elevated Ki-67 antigen levels.[
Primary spinal cord glioblastoma has mainly targeted younger individuals than intracranial glioblastoma, with a mean age of onset varying between 26 and 40 years among different studies with a slight male predominance.[
In the present cases, both patients initially presented with paresis that rapidly progressed to paraplegia. Furthermore, the sensory deficits mainly affected the lower limbs in a nondermatomal distribution.
Like its intracranial counterpart, primary spinal glioblastoma carries a poor prognosis and high mortality rate. The mean survival rate is estimated to be 14 months.[
It is worth mentioning that both patients in the present article had a primary spinal cord glioblastoma, that is, no evidence of space-occupying lesion in the brain. Seeding of intracranial glioblastoma to the spinal cord is present in approximately 25% of the cases; however, seeding of spinal glioblastoma intracranially is rare.[
Spinal glioblastoma was proposed to disseminate through leptomeningeal pathway.[
Due to the scarce reported cases, the optimal management remains controversial. The current treatment options include biopsy, subtotal, or gross total resection, in addition to radiotherapy, and chemotherapy.[
In the present article, the first patient underwent subtotal resection whereas the second patient underwent biopsy followed by concomitant chemoradiotherapy, using temozolomide. Considering their intricate location within the spinal cord, aiming for aggressive surgical resection might have resulted in acute neurological sequelae.
Primary spinal glioblastoma is a rare and challenging tumor. Patients commonly present with a progressive paresis, resulting in paraplegia, regardless of the surgical resection extent and received adjuvant chemotherapy. Therefore, the primary spinal cord glioblastoma should be considered in patients reporting a rapid lower limb weakness with neuroradiological evidence of extensive, exophytic intramedullary lesion of the spine. A biopsy-proven histopathological diagnosis is of indisputable importance to establish the final diagnosis and plan the treatment options. Persistent reporting and documentation of such rare cases in the literature are fundamental for the progress of the current knowledge and the contribution to the optimal treatment options.
Bashaer Alharbi: Conceptualization, Writing – Original Draft, Writing – Review and Editing. Hajar Alammar: Writing – Original Draft, Writing – Review and Editing. Ali Alkhaibary: Conceptualization, Investigation – Radiological Images, Investigations – Histopathological images, Writing – Original Draft, Writing – Review and Editing. Ahoud Alharbi: Writing – Original Draft, Writing – Review and Editing. Sami Khairy: Conceptualization, Supervision, Writing – Review and Editing. Ali H. Alassiri: Investigations – Histopathological Features, Writing – Original Draft, Writing – Review and Editing. Fahd Alsufiani: Investigations – Histopathological Features, Writing – Original Draft, Writing – Review and Editing. Ahmed Aloraidi: Conceptualization, Investigations – Surgical Management. Writing – Review and Editing. Ahmed Alkhani: Conceptualization, Investigations – Surgical Management. Writing – Review and Editing. All authors have critically reviewed and approved the final version of the manuscript.
Patient’s consent not required as patients identity is not disclosed or compromised.
There are no conflicts of interest.
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