127 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_16,
© Springer Science+Business Media B.V. 2012
16
Abstract
familial neoplasia syndrome. VHL patients are predisposed to developing CNS hemangioblasto- mas (in the retina, cerebellum, brainstem, spinal cord and, infrequently in the supratentorial com- partment), as well as visceral tumors including renal cell carcinoma, pancreatic islet cell tumors and pheochromocytomas (Lonser et al . 2003a ) . Patients with VHL have a mutation of the VHL gene on chromosome 3p, which leads to tumors following loss-of-heterozygosity (Latif et al . 1993 ) . Hemangioblastomas are thought to arise from arrested embryonic hemangioblasts (Park et al . 2007 ) . Because hemangioblastomas develop throughout the lifespan of patients with VHL and have a saltatory growth pattern, treatment in VHL patients is typically reserved for symptomatic tumors.
Currently, the treatment of choice for spinal cord hemangioblastomas is surgical resection.
Although surgery for these tumors has been per- formed as early as the 1910s by Harvey Cushing and described in detail by Wyburn-Mason in the 1940s, it carries signifi cant risks (Wyburn-Mason 1943 ; Cohen-Gadol et al . 2005 ) . Hemangioblas- tomas are exquisitely vascular tumors and breach of their capsule during resection can lead to signifi cant intraoperative blood loss. Moreover, the intramedullary location of these tumors can pose signifi cant functional risk during extirpa- tion. Subsequently, defi ned resection techniques to minimize the morbidity associated with surgery for spinal cord hemangioblastomas are useful.
Here, we describe operative techniques and func- tional outcomes based on experience with the removal of over 250 spinal cord hemangioblasto- mas at the National Institutes of Health.
Surgical Technique Preoperative Management
Sporadic versus VHL cases . Because a signifi cant number of patients presenting with a spinal cord hemangioblastoma may have VHL, patients with spinal cord hemangioblastomas may need to undergo genetic and/or clinical screening for VHL (Conway et al . 2001 ) . Further, given the association of pheochromocytomas in VHL, VHL
patients being evaluated for resection of spinal cord hemangioblastomas should be screened for the presence of these catecholamine-secreting tumors, which may require either perioperative a -blockade or excision (Lonser et al . 2003a ) . Imaging . Preoperative localization of these tumors is achieved by contrast enhanced magnetic reso- nance (MR)-imaging. Hemangioblas tomas enhance intensely with the administration of gadolinium and post-contrast, T1-weighted MR-imaging is the standard preoperative imag- ing modality (Fig. 16.1a ). Peritumoral edema and tumor-associated syringomyelia is best defi ned by T2-weighted or fl uid-attenuated inversion recovery (FLAIR) MR-imaging sequences.
Large tumors and their associated vasculature can be further defi ned by preoperative arteriogra- phy. Arteriographic determination of feeding arteries associated with the tumor may aid in operative planning and resection. Selective embolization of feeding vessels can be employed to minimize tumor blood supply. Despite theo- retical benefi t of embolization, we have found that it is not necessary if careful microsurgical resection techniques are observed. Subsequently, the risks associated with both diagnostic arterio- graphy and selective embolization can be avoided in nearly all cases.
Preoperative steroids . Frequently, preoperative intravenous steroids are administered before resection of spinal cord hemangioblastomas.
Intravenous methylprednisolone can be adminis- tered before induction of anesthesia starting with a 30 mg/kg bolus over 15 min followed by a continuous infusion of 5.4 mg/kg/h for 23 h starting 45 min after completion of the bolus (Young 1990 ) .
Operative Technique
Because the majority of spinal cord hemangio- blastomas arise dorsally in the spinal cord, most of these tumors are resected using a direct posterior approach. Tumors with an anterior epicenter in relation to the spinal cord may also be approached posteriorly if the tumor mass has caused suffi - cient spinal cord rotation, (Martin et al . 1995 )
however an anterior or anterolateral approach may also be used to limit manipulation of the spi- nal cord (Pluta et al . 2003 ) . Given the frequency of dorsal tumors, a posterior approach is described below (Lonser and Oldfi eld 2005 a).
The operative fi eld is fi rst prepared and draped in a sterile fashion. An incision is made to extend rostral and caudal to the tumor by one to two spinal levels. Subperiosteal dissection is then used to separate the paraspinous muscles from the spinous processes and lamina. Laminectomies are performed to expose the dura 1–2 cm rostral and caudal to the superior and inferior poles of the tumor. To minimize the potential for spinal col- umn instability, care is taken to avoid the damag- ing the facet capsules and the medial aspect of each facet. Intraoperative ultrasound is then used to localize the echogenic hemangioblastoma and ensure adequacy of the laminectomy. Brisk blood fl ow in hemangioblastomas permits their vascu- lar supply to be easily delineated by Doppler analysis (Fig. 16.1b ).
Using the operative microscope, the dura is then sharply incised, refl ected laterally and secured with 4-0 silk sutures. The arachnoid overlying the tumor is incised and fastened to the dura with vas- cular clips. The tumor is then exposed and resected in a stepwise manner (Fig. 16.2 ). For completely intramedullary tumors, a midline or dorsal root entry zone myelotomy may be used to reach the tumor surface (Mehta et al . 2010 ) . To ensure complete resection of hemangioblas tomas in the DREZ, involved rootlets should be interrupted where they enter/exit the tumor. For tumors with a surface presentation, vessels crossing the tumor margin and feeding the tumor are coagulated and divided. The tumor capsule is exposed by circum- ferential incision at the tumor-pial margin. The dissection is carried deeper in the surrounding spinal cord using microscissors and bipolar tips, with care directed to cautery and division of vessels entering the deep surface of the tumor.
To facilitate dissection and to visualize the deep surface of the tumor (whether is has surface
Fig. 16.1 Post-contrast T1-weighted magnetic resonance imaging demonstrates the location of a symptomatic spinal cord hemangioblastoma ( left ). T2-weighted magnetic res- onance imaging demonstrates a tumor-associated syrinx cavity and surrounding edema ( middle ). Intraoperative
ultrasound, utilized before dural incision, allows for confi rmation of tumor location, with Doppler analysis demonstrating the vascular lesion ( right, top ). Heman- gioblastoma visible under operative microscope, following incision of arachnoid mater ( right, bottom )
presentation or not), the tumor is retracted by use of suction with a small cottonoid positioned between the tumor and the sucker tip. Because piecemeal dissection of the tumor can cause vigorous bleeding, every attempt is made to resect
the tumor en bloc . For larger tumors, piecemeal dissection may be necessary to limit spinal cord manipulation. In these cases, resection can be achieved by bipolar coagulation using blunt tips followed by shallow debulking of tumor and
Fig. 16.2 Illustration of the intradural steps of the micro- surgical resection of spinal cord hemangioblastomas.
Vessels crossing the margin of the tumor are coagulated with bipolar cautery ( a ) and divided ( b ) to expose the junction of the pia and the tumor margin. The pia is incised at the edge of the tumor with a diamond knife ( c ) and microscissors
( d ). After circumferential dissection of the tumor margin is complete, the caudal pole of the hemangioblastoma is refl ected with gentle suction on a cottonoid to expose the deep surface ( e, f ). The underlying vessels are then carefully cauterized with bipolar forceps ( e ) and interrupted ( f ) to complete tumor resection (From Mehta et al. 2010 )
repeating this process. If bleeding does occur from the tumor, it can be ameliorated by bipolar coagulation with large tips or by application of Gelfoam (Pfi zer, Inc.) soaked in thrombin to the site of the bleeding.
Generally, we avoid entering or draining tumor associated syringes during the course of resection because this can amplify pulsations of the spinal cord making resection more diffi cult (Lonser et al. 2005 ) . Infrequently, the syrinx cavity can be used to access the tumor if it minimizes myelo- tomy for intramedullary tumors or spinal cord retraction. Furthermore, as hemangioblastoma- associated syringes are dependent on tumor presence, the syrinx will collapse after tumor resection, regardless of drainage. Failure of syringes to collapse following resection, irre- spective of drainage has specifi cally been shown to be dependent on additional tumors (in VHL) supporting the syrinx (Mehta et al . 2010 ) .
After resection of the tumor is completed, watertight closure is achieved by closing the dura with a running suture. The paraspinous muscula- ture, fascial layers and skin are then closed in standard fashion. The wound is sterilely dressed.
Patients are maintained at bed rest overnight and encouraged to ambulate the day after resection.
Pathologic Considerations
Hemangioblastomas are classifi ed by the World Health Organization as grade I tumors and though they are categorized under other neoplasms related to the meninges , their origin and predilection for specifi c neural structures remains poorly under- stood (Louis et al . 2007 ) . Grossly the tumors are well-circumscribed, red and/or yellow nodules.
Microscopically hemangioblastomas are com- posed of a capillary network with stromal cells that are frequently lipid-rich (Burger et al . 2002 ) .
Patients with VHL often develop renal cell carcinoma (RCC) and several cases of tumor-to- tumor metastases of RCC to hemangioblastoma have been reported (Crockard et al . 1988 ; Jamjoom et al . 1992 ; Jarrell et al . 2006 ) . Routine analysis of VHL-associated hemangioblastomas often includes immunohistochemical markers
specifi c for both hemangioblastomas such as neuron-specifi c enolase, as well as markers specifi c for RCC such as epithelial membrane antigen.
Postoperative Outcome
Short-Term Outcome (Less Than 6 Months)
Immediate outcome. To determine the outcome after surgery in VHL patients undergoing resec- tion of spinal cord hemangioblastomas, analysis of functional outcome following 156 operations for 218 spinal cord VHL-associated hemangio- blastomas at the National Institutes of Health was performed. This study revealed that 61% of patients experienced new or worsened postopera- tive symptoms. However, the majority of these symptoms were mild (76%, no decrease in McCormick grade [Table 16.1 ]), not function limiting and transient (70%) (McCormick et al.
1990 ; Mehta et al . 2010 ) . New or worsened post- operative signs and symptoms typically resolved within 2 weeks to 4 months.
Outcomes after resection of sporadic spinal cord hemangioblastomas have been reported in combination with VHL-associated tumors (Guidetti and Fortuna 1967 ; Yasargil et al . 1976 ; Conway et al . 2001 ) . One study, which included
Table 16.1 McCormick clinical grading scale for neurologic function (McCormick et al. 1990 )
Grade Defi nition
I Neurologically normal; mild focal defi cit not signifi cantly affecting function of involved limb;
mild spasticity or refl ex abnormality; normal gait II Presence of sensorimotor defi cit affecting
function of involved limb; mild to moderate gait diffi culty; severe pain or dysesthetic syndrome impairing patient’s quality of life; still functions and ambulates independently
III More severe neurological defi cit; requires cane/
brace for ambulation or signifi cant bilateral upper extremity impairment; may or may not function independently
IV Severe defi cit; requires wheelchair or cane/
brace with bilateral upper extremity impairment;
usually not independent
outcomes for hemangioblastomas of any location including ten spinal cord hemangioblastomas, found no difference in resolution of symptoms for patients with VHL or patients with sporadic lesions (Conway et al . 2001 ) . Other studies that have combined sporadic and VHL-associated results, have shown that complete resection of spinal cord hemangioblastomas can result in neurological improvement ( Guidetti et al. 1967 ; Yasargil et al . 1976 ) .
6-month outcome. At 6 months post-resection, the majority of VHL patients (96%) remained at or above their preoperative functional status (Mehta et al . 2010 ) . Four percent of patients experienced persistent functional impairment following surgery (all with 1 neurological grade decline). Improvement in the preoperative chief complaint was noted in the majority of symp- tomatic patients (71%). Multivariate analysis of the relationship between preoperative variables and postoperative functional status identifi ed the presence of completely intramedullary and ventral tumors as predictors of postoperative decline.
The absolute risk of permanent functional decline with completely intramedullary tumors was 13%. For patients with ventral tumors the risk of decline was 27%, however all patients whose ventral tumors were approached anteriorly expe- rienced no change in functional status.
Complications. Complications following resec tion of spinal cord hemangioblastomas were infrequent (8%). Four percent of patients in our series experienced a CSF leak, which required either CSF diversion or surgical repair. The remaining complications including superfi cial wound infection (2%), hematoma (2%) and asep- tic meningitis (1%).
Long-Term Outcome (Greater Than 6 Months)
While long-term functional outcome has been described over the long-term (greater than 6 months) in VHL, (Mehta et al . 2010 ) no such outcome studies exist for large series of sporadic spinal cord hemangioblastomas. Though multifo- cal CNS disease and visceral malignancy may
contribute to functional status in VHL, patients who undergo resection of spinal cord hemangio- blastomas generally stay at or above their preope- rative functional grade over the long-term. By Kaplan-Meier analysis, 93%, 86%, 78% and 78%
of patients remained at their preoperative grade or higher by 2, 5, 10 and 15 years respectively (Fig. 16.3 ). Of the 15% of patients with VHL who worsened over the long-term, 6% experienced decline attributable to the effects of surgery, 6%
due to extensive VHL-associated CNS disease and 3% due to other illness.
Clinical Management
Because resection of spinal cord hemangioblas- tomas can be performed safely in most patients and is effective, surgical management of these tumors is the treatment of choice. Because sporadic spinal cord hemangioblastomas most frequently present when symptomatic, patients should be fi rst appropriately screened for VHL and these tumors should be considered for resection upon presentation. In VHL, the decision to operate is complicated by both the multiplicity and incompletely understood natural history
Fig. 16.3 Kaplan-Meier analysis demonstrates that most VHL patients with spinal cord hemangioblastomas remain stable over the long-term. The proportion of patients who remained functionally stable by their McCormick scale grade at 2, 5, 10 and 15 years follow-up was 93%, 86%, 78% and 78%, respectively. Dashed lines indicate 95%
confi dence intervals (From Mehta et al. 2010 )
of hemangioblastomas. Subsequently, it is not possible to determine which tumors will become clinically signifi cant. Given these fi ndings, spinal cord hemangioblastomas in VHL should be con- sidered for operative management if they produce neurologic symptoms.
While surgery remains the best treatment option for these tumors, surgery for every CNS heman- gioblastoma in VHL would lead to the unnecessary resection of many lesions. Ammerman and colleagues (Ammerman et al . 2006 ) evaluated the natural history of 143 hemangioblastomas in 19 patients with VHL and found that if surgery were based on radiographic tumor growth alone, patients would undergo approximately four unnecessary operations during a 10-year period.
Furthermore, the tumors were found to undergo saltatory growth patterns, with periods of quies- cence lasting on average over 2 years and 45%
of tumors requiring resection were not seen on initial imaging studies.
Stereotactic radiation therapy has also been proposed as an alternative to surgery for heman- gioblastomas. With the increasing acceptance of stereotactic radiosurgery, groups have shown success (including lack of growth) rates of treat- ment for these tumors using this modality, ranging from 70% to 100% (Patrice et al . 1996 ; Kano et al . 2008 ) . Unfortunately, length of follow-up has been limited in these studies, which often display a stuttering growth pattern. A recent long-term prospective study has shown that a large propor- tion of hemangioblastomas progress following radiosurgery, with progression-free survival at 10 and 15 years declining to 61% and 51%, respec- tively (Asthagiri et al . 2010 ) . Therefore, radiosur- gery should be reserved only for tumors that are not appropriate candidates for resection.
In conclusion, using careful resection strate- gies, surgery can be used to achieve a safe and durable result for the patient with a spinal cord hemangioblastoma. Given the unique vascularity of these tumors and their intramedullary location, it is important to resect these tumors en bloc while minimizing manipulation of neural tissue. Ventral and completely intramedullary hemangioblasto- mas carry higher risks of morbidity. Management of these tumors is further complicated when they
arise in context of the tumor suppressor gene syndrome VHL, in which patients develop mul- tiple CNS hemangioblastomas over their lifespan.
For patients with VHL, spinal cord hemangio- blastomas should be resected only when they become symptomatic.
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