entity. They represent less than 2% of all intramedullary spinal tumors, and they have been reported approximately 55 cases in the literature. They may occur in children and adults, and affect almost equally both sexes, with a slight male preponderance. Their presenting symptoms are usually spinal pain and sensory defi cits, which may be followed by motor defi cits and sphincter dysfunction, depending on the tumor’s anatomic location.
Occasionally, PSOs may present with signs of raised intracranial pressure, due to diffuse oligodendrogliomatosis, with extensive tumor cranio-spinal meningeal involvement. The imaging method of choice is MRI, which may be accompanied from plain x-rays and/or CT scan in cases of extensive tumor-associated skeletal deformities. Imaging of the entire cranio-spinal axis is necessary for ruling out any tumor CSF dissemination or distant metastases. Aggressive surgical tumor removal is required in all cases by employing microsurgical techniques and intraoperative electrophysiologi- cal monitoring. Tumor extirpation however is not possible in the vast major- ity of cases, due to the tumor’s infi ltrative character. The issue of employing post-surgical adjuvant chemotherapy and/or radiotherapy remains contro- versial. The prognosis is poor in the majority of PSO cases despite all the recent advances in their early diagnosis and their prompt management. The detailed demographic data of patients harboring PSOs, their presenting symptomatology and any tumor-associated neurological signs, their imag- ing and histopathological characteristics, as well as their management and their overall prognosis are presented in this chapter.
K. N. Fountas (*) • E. Z. Kapsalaki
Department of Neurosurgery, University Hospital of Larisa, School of Medicine , University of Thessaly , Larisa 41110 , Greece
e-mail: [email protected]
Primary Spinal Oligodendroglioma:
Diagnosis, Outcome, and Prognosis
Kostas N. Fountas and Eftychia Z. Kapsalaki
M.A. Hayat (ed.), Tumors of the Central Nervous System, Volume 6: Spinal Tumors (Part 1), Tumors of the Central Nervous System 6, DOI 10.1007/978-94-007-2866-0_8,
© Springer Science+Business Media B.V. 2012
Introduction
Primary spinal cord, intramedullary tumors rep- resent a relatively infrequent type of tumor. It has been estimated, that account for only 2–8.5% of all central nervous system tumors (CNS), and approximately for 15% of the primary intradural spinal tumors in adults (Constantini et al. 2000 ; Cooper 1989, 1996 ; Cooper and Hida 2006 ; Fischer et al. 1996 ) . Primary spinal oligodendro- gliomas (PSO) constitute an even more rare clinico-pathological entity (Alvisi et al. 1984 ; Chen 1988 ; Constantini et al . 1996 ; Cristante and Hermann 1994 ; Guidetti 1981 ; Lunardi et al . 1993 ; Miller 2000 ) . It has been estimated that PSOs represent 2% of the spinal cord tumors and only 1.5% of all CNS oligodendrogliomas (Pagni et al . 1991 ) . It has been stated that spinal cord is the CNS anatomic location with the lowest predi- lection for oligodendrogliomas (Enestrom and Grontoft 1957 ) .
The fi rst report of a spinal oligodendroglioma was made by Kernohan et al. ( 1931 ). Later on, Foerster and Gagel ( 1934 ), Rasmussen et al.
( 1940 ), and Henschen reported a total of fi ve pri- mary oligodendroglioma cases among a large clinical series of 109 intramedullary gliomas (Enestrom and Grontoft 1957 ) . Russell and Bucy ( 1949 ) reported another case and Kernohan and Sayre ( 1952 ) a few years later published three more cases of PSOs (Enestrom and Grontoft 1957 ) . There were a few case reports in the lit- erature until 1980, when Fortuna et al. ( 1980 ) in a systematic review study summated all the pre- viously reported cases. They contributed another case, raising the total number of published PSOs to 36 cases. They reported that the relative inci- dence of PSO ranged between 0.8% and 4.7%
among intramedullary and fi lum terminale tumors and PSOs represented only 1.6% of all
CNS oligodendrogliomas (Fortuna et al . 1980 ) . Guidetti et al. ( 1981 ) reported only one case of PSO among 129 patients harboring primary spi- nal gliomas. There were a few additional mini- series and several case reports published during the last three decades, raising the total number of reported PSOs to 56 cases worldwide (Alvisi et al . 1984 ; Aman et al. 2000 ; Constantini et al . 1996 ; Cristante and Hermann 1994 ; Fountas et al . 2005 ; Gilmer-Hill et al. 2000 ; Gurkanlar et al. 2006 ; Guppy et al. 2009 ; Miller 2000 ; Nam et al. 1998 ; Pagni et al. 1991 ; Ramirez et al.
2006 ; Tobias et al . 2008 ; Ushida et al. 1998 ; Wang et al. 1993 ) . Although the incidence of PSOs is quite low, their management remains challenging. In this chapter, we present their demographic characteristics, their clinical pre- sentation, their imaging characteristics, and their histopathological profi le. We also outline the general principles of their surgical management, the role of any adjuvant treatment, and their overall prognosis.
Demographic Characteristics Sex Predilection
It is widely accepted that cranial oligodendro- gliomas are more common among males (McLendon et al . 1998 ; Mork et al. 1985 ) . Previous studies regarding the sex distribution of cranial oligodendrogliomas have shown that the male:female ratio range from 3:2 to 2:1 (McLendon et al . 1998 ; Mork et al. 1985 ) . However, the existent literature shows that SPOs were almost equally distributed among males and females and there is no sex predilection.
Fortuna et al. ( 1980 ) found that SPO cases were equally distributed in both sexes in their review Keywords
Intramedullary • Outcome • Primary • Prognosis • Spinal oligodendroglioma
• Tumor
study (17 males vs. 16 females). Similarly, Fountas et al. ( 2005 ) showed in their review analysis that in 39 patients diagnosed with SPO, 53.8% were males and 46.2% females. It is apparent that although the total number of SPO cases is limited and the extraction of any statisti- cally powerful conclusions is extremely risky, the literature data demonstrate no signifi cant sex predilection.
Age Distribution
Although intramedullary spinal cord tumors appear to be more frequent in pediatric than adult patients, adult PSOs were more common than pediatric cases (Alvisi et al. 1984 ; Aman et al . 2000 ; Chen 1988 ; Constantini et al. 1996 ; Cristante and Hermann 1994 ; Enestrom and Grontoft 1957 ; Fortuna et al. 1980 ; Fountas et al.
2005 ; Gilmer-Hill et al. 2000 ; Guidetti et al.
1981 ; Gurkanlar et al . 2006 ; Guppy et al . 2009 ; Lunardi et al . 1993 ; Miller 2000 ; Nam et al. 1998 ; O’Brien et al. 1968 ; Pagni et al. 1991 ; Ramirez et al . 2006 ; Ridsdale and Moseley 1978 ; Tobias et al. 2008 ; Ushida et al. 1998 ; Wang et al. 1993 ) . Fortuna et al. ( 1980 ) reported that the age of inci- dence in their review study ranged between 6 and 52 years (mean age of incidence: 28.4 years).
They found that the peak frequency was observed in the fourth decade of life, while 31.4% of the reviewed patients were younger than 16 year old (Fortuna et al . 1980 ) . Likewise, Fountas et al.
( 2005 ) noted that in a group of 34 patients har- boring PSO with available demographic data, 56.8% of them were older than 16 years, while 43.2% were younger than 16 year old. Gilmer- Hill et al. ( 2000 ) stated that PSO is extremely uncommon among children, while Nam et al.
( 1998 ) observed in their study that the occurrence of PSO in children less than 6 year old was extremely low. Although the vast majority of the published case reports and mini-clinical series agree that SPOs are more common in adults than children, Miller ( 2000 ) found one case of spinal oligodendroglioma and three cases of mixed oligo-astrocytomas in children but no SPOs in
adults, in a large series of 294 patients with intramedullary tumors.
Clinical Presentation
The clinical presentation of PSO is similar to that of other intramedullary spinal tumors, while there are no specifi c symptoms or signs associated with PSOs. The presenting symptoms are highly vari- able, and in the majority of cases they evolve over a period of months to years (Cooper and Hida 2006 ) . Fortuna et al. ( 1980 ) reported that the presence of symptoms in their reviewed cases ranged from 1 month to 14 years (mean:
37.1 months) before establishing a diagnosis.
They postulated that the duration of symptoms was shorter among pediatric patients compared with adults (Fortuna et al . 1980 ) .
The presenting symptoms and signs depend mostly on the anatomic site of the tumor.
However, regional back pain and sensory distur- bances are the most frequent complaints, while motor and sphincter defi cits occur later on (Cooper and Hida 2006 ) . Fortuna et al. ( 1980 ) reported that spinal pain was the presenting symptom in 69.3% of their reviewed cases, while paresthesias were present in 7.7%, and motor defi cits in 23% of their cases. More infrequent presenting symptoms include sphincter distur- bances, neurogenic bladder, and/or frequent uri- nary tract infections in cases of fi lum terminale tumor location, symptoms of raised intracranial pressure in cases of high cervical PSOs, associ- ated kyphoscoliosis due to osseous changes caused by the enlarging tumors, gait disturbances, Brown-Sequard syndrome, hyperrefl exia, marked muscular atrophy, and spastic tetraparesis in cases of holocord PSOs (Cooper and Hida 2006 ; Enestrom and Grontoft. 1957 ; Fortuna et al. 1980 ; Fountas et al. 2005 ; Nam et al. 1998 ; O’Brien et al . 1968 ; Pagni et al. 1991 ; Ramirez et al . 2006 ; Ridsdale and Moseley 1978 ) . Interestingly, Fortuna et al. ( 1980 ) noted that oscillating pain (spontaneous pain alleviation and relapse), par- esthesias, and muscular twitching were also reported in rare occasions.
Imaging Characteristics Anatomic Location
In the vast majority of the reported PSO cases the tumor was localized, extending in an average of 3.5 ± 1.8 vertebral bodies (Ushida et al. 1998 ) . However, there are cases in which the tumor was extremely widespread, occupying a large propor- tion of the spinal canal and extending more than ten consecutive vertebral bodies (Fortuna et al . 1980 ; O’Brien et al. 1968 ; Pagni et al. 1991 ; Ushida et al. 1998 ) . These extensive tumors are described as holocord or widespread PSO (Fortuna et al . 1980 ; O’Brien et al. 1968 ; Pagni et al . 1991 ; Ushida et al . 1998 ) . Interestingly, all these cases occurred in young adolescents or pediatric patients, and are equally distributed among males and females (Fortuna et al . 1980 ; O’Brien et al. 1968 ; Pagni et al. 1991 ; Ushida et al. 1998 ) . Analysis of the existing data for 46 cases in which details regarding the exact ana- tomic location of the PSO are available, demon- strate that 26.1% (12/46 cases) were thoracic tumors, 26.1% (12/46 cases) were cervical, 8.7%
(4/46 cases) were located in the cervico-thoracic junction, 19.6% (9/46 cases) were lumbar, 13.0%
(6/46 cases) were thoraco-lumbar tumors, and the remaining 6.5% (3/46 cases) were widespread tumors. In the lumbar area there was a strong pre- dilection for the fi lum terminale, since 88.9%
(8/9 cases) of the lumbar PSOs originated from the fi lum. Fountas et al. ( 2005 ) and Fortuna et al.
( 1980 ) have reported similar observations regard- ing the anatomic location of PSOs in their previ- ously published review studies.
MRI Characteristics
The application of high fi eld MRI units in the routine clinical practice along with the develop- ment of advanced MR imaging protocols, have made MRI the examination of choice for the diagnostic approach of patients with spinal intramedullary tumors. Primary spinal oligoden- drogliomas usually appear as heterogenous hypo- or
iso-intense lesions on T1 weighted images (WI), and hyper-intense on T2 WI (Cooper and Hida 2006 ; McLendon et al. 1998 ; Zimmerman and Bilaniuk 1988 ) (Fig. 8.1 ). The tumor margins are usually ill-demarcated due to the infi ltrative char- acter of PSO, while in low-grade lesions the tumor periphery may be well defi ned (Cooper and Hida 2006 ; McLendon et al. 1998 ; Zimmerman and Bilaniuk 1988 ) . The vast major- ity of PSOs demonstrate mild to moderate, non- homogenous spotty enhancement after the intravenous administration of a paramagnetic substance (Cooper and Hida 2006 ; McLendon et al. 1998 ; Zimmerman and Bilaniuk 1988 ) . Focus or foci of intra-tumoral hemorrhage, which may be shown as high signal intensity methemo- globin on T1WI or areas of marked hypo-intensity on T2WI due to hemosidirin deposits, may be seen in PSOs (Cooper and Hida 2006 ; McLendon et al. 1998 ; Zimmerman and Bilaniuk 1988 ) . Cystic components or cystic necrotic areas may be occasionally seen, particularly in cases of high grade PSOs (Gilmer-Hill et al. 2000 ; McLendon et al. 1998 ) . In addition, associated syringomy- elia may be seen in PSO cases (Gilmer-Hill et al . 2000 ; McLendon et al . 1998 ) . The differen- tial diagnosis of PSOs should include other
Fig. 8.1 Pre-operative sagittal T1 weighted MRI of the Lumbar Spine after contrast administration in a case of a fi lum terminale primary spinal oligodendroglioma
intramedullary glial tumors, neurocytomas, ependymomas, gangliogliomas, and hemangio- blastomas (Cooper and Hida 2006 ; McLendon et al. 1998 ) . The role of proton MR spectroscopy, which has an important role in the differential diagnosis of intracranial lesions, is exponentially increasing. However, the exact role of this non- invasive modality and its spinal applications remains to be defi ned. The importance of obtain- ing MR imaging of the complete cranio-spinal axis preoperatively cannot be overemphasized.
The tendency of PSO dissemination through CSF pathways and the development of oligodendro- gliomatosis is well established in the literature (Fortuna et al. 1980 ; Guppy et al . 2009 ) .
CT Characteristics
Despite the wide application of MRI in the diag- nostic evaluation of patients with PSOs, CT may offer some important information regarding the presence of calcifi cations, and/or other associ- ated osseous changes such as vertebral scalloping and kyphoscoliosis (Pinto et al . 1988 ; Zimmerman and Bilaniuk 1988 ) . The presence of calcifi ca- tions in PSOs has been estimated to range between 28% and 40% (McLendon et al. 1998 ) . It has also been postulated that osseous changes are seen more frequently in cases of holocord PSOs or cases of pediatric patients, possibly due to the preserved plasticity of pediatric vertebral column (Fortuna et al . 1980 ; O’Brien et al. 1968 ; Pagni et al. 1991 ; Ushida et al . 1998 ) . The employment of CT myelography has been signifi cantly decreased due to the wide application of MRI, and is limited only to those patients, who cannot undergo a MRI study.
Other Imaging and Laboratory Study Characteristics
Plain X-rays usually cannot establish the diagno- sis of a PSO, however they may provide impor- tant information regarding the presence or not of any associated osseous deformities or any other bone abnormalities. These osseous abnormalities
may interfere with the post-resection stabilization process and the overall surgical planning. Spinal angiography is rarely employed in cases of PSOs and usually provides no further information in the diagnosis or the surgical planning of these patients. Likewise, CSF analysis is rarely employed in the preoperative evaluation of patients with PSO and has become only a diag- nostic test of historical importance. It had been demonstrated that CSF protein was elevated in the vast majority of PSOs (Fortuna et al . 1980 ; O’Brien et al. 1968 ; Ridsdale and Moseley 1978 ) . It had also been reported that the CSF protein elevation was signifi cantly higher in PSOs com- pared to any other intramedullary glioma (Fortuna et al. 1980 ) . Furthermore, CSF cytology was pathological in PSO cases, with tumor cell pres- ent, and increased lymphocyte and granulocyte counts (Fortuna et al. 1980 ) .
Surgical Management Preoperative Evaluation
In addition to the routinely employed X-rays and basic laboratory preoperative work-up, spe- cial attention needs to be paid to the patient’s pulmonary status and respiratory reserves, due to the prone surgical position and possible respiratory system compromise in cases of cer- vical, thoracic, cervico-thoracic, or widespread tumors. A detailed preoperative neurological examination including urodynamic studies when indicated, should be performed for estab- lishing a baseline neurological status for future comparisons. In cases of extensive tumors, the possibility of signifi cant operative blood loss needs to be considered preoperatively, and the surgical team should be promptly prepared for this scenario. Careful surgical planning should include not only the tumor resection process but also the necessary post-resection vertebral column stabilization. The patient and his family have to be well informed on the nature of the surgical procedure, and the possibility of post- operative neurological defi cit as well as the poor prognosis of PSO.
Surgical Procedure
The procedure is performed under electrophysi- ological monitoring for avoiding or minimizing any neuronal tissue damage and maximizing tumor removal. A baseline recording should be obtained before positioning the patient in prone position and compare it with the recordings after positioning the patient in his/her fi nal position.
A posterior approach is employed in the vast majority of PSO cases. The approach through the relatively avascular anatomic midline is of paramount importance for minimizing blood loss. Adequate dural exposure and opening for prompt tumor resection is of paramount impor- tance. In the majority of cases, laminectomies one level above and one level below the tumor poles, are required for prompt tumor identifi ca- tion and adequate resection. It is apparent that in cases of widespread PSOs multiple level lamine- ctomies are usually required for aggressive tumor resection. A midline dural opening is per- formed and the tumor is identifi ed with the usage of intraoperative ultrasound. Subsequently, the microscope is brought into the fi eld, and a midline myelotomy is performed. It has to be emphasized that frequently the identifi cation of the actual midline may be diffi cult in cases of enlarged and rotated spinal cord caused by the tumor growth (Cooper and Hida 2006 ) . In these cases, identifi cation of the exiting nerve roots may be helpful for defi ning the cord midline.
Small caliber vessels crossing the cord midline may be coagulated and safely divided. After identifying the underlying tumor, every attempt is made for developing a plane between the tumor and the adjacent normal cord. The tumor may be enucleated in a piecemeal fashion and the surrounding capsule or pseudo-capsule to be removed at the end.
Tumor extirpation is the goal in every case, however the infi ltrating nature of PSOs make their total resection extremely challenging. An aggressive tumor resection is advocated not only for cytoreductive purposes but also for inducing cell mitoses in the remaining neoplastic cell
populations, and thus making them more suscep- tible to the postoperative adjuvant therapies. The importance of applying microdissection tech- niques and utilizing Cavitron Ultrasound Surgical Aspirator and LASER cannot be overempha- sized. Despite every effort for tumor extirpation, gross total resection was possible in only 16% of the previously reported cases (Alvisi et al. 1984 ; Aman et al . 2000 ; Fortuna et al. 1980 ; Fountas et al . 2005 ; Guidetti et al. 1981 ; Nam et al. 1998 ; Pagni et al . 1991 ) . Meticulous hemostasis is per- formed after completing the tumor resection.
Ultrasound examination can identify any tumor remnants and confi rm complete tumor resection.
Particular attention needs to be paid to watertight dural closure.
Stabilization of the involved vertebral column should be performed if multi-level laminectomies were necessary for tumor removal. Performance of laminoplasties or insertion of lateral mass screws and rods for cer- vical or cervico-thoracic tumors, or insertion of pedicle screws and rods for lumbar and thoraco- lumbar cases, depends on the exact tumor loca- tion, the tumor’s size, the confi guration and the biomechanics of the patient’s vertebral column, the patient’s age, and the surgeon’s experience.
The incidence of post- laminectomy spinal deformity has been reported to be higher than 24% (Yasuoka et al. 1982 ) . Surgical stabilization should attempt not only to prevent postoperative instability but also to correct, if possible, any tumor-associated pre-existing vertebral column deformity.
Postoperative Management
Administration of low molecular weight heparin for deep venous thrombosis prophylaxis and early mobilization of the patient is important for avoiding any postoperative complications. An early postoperative MRI is important for identi- fying any residual tumor or postoperative hema- tomas and establishing a baseline for the patient’s follow up (Figs. 8.1 and 8.2 ).