Introduction

Spinal hemangioblastomas are very rare and constitute 1.6–5.8% of all spinal cord tumors and 1–2.5% of all tumors of the central nervous system [4, 23]. They can present as sporadic lesions or in association with von Hippel-Lindau syndrome (vHL syndrome). Sporadic tumors constitute for majority of the cases, up to 70–80% [13]. Microsurgical excision has long been established as the standard of care for spinal hemangioblastomas [15]. Though surgical outcome of spinal hemangioblastomas has been improved as a result of advances microsurgical techniques, postoperative neurological deterioration is still common and reported in 50–80% of cases with permanent neurological deficits up to 10% [13,14,15,16,17,18]. Few studies directly compared the sporadic- and vHL-associated spinal hemangioblastomas in terms of clinical presentation, tumor characters, and neurological outcome. Management of asymptomatic tumors associated with vHL syndrome is debatable. The natural history of asymptomatic spinal tumors is not clearly understood because of the rarity of these tumors. The purpose of this study is to analyze the clinical presentation, surgical management, and long-term functional outcome of patients with sporadic- and vHL-associated spinal intramedullary hemangioblastomas.

Materials and methods

This retrospective study included 15 patients who underwent surgery for intramedullary spinal hemangioblastoma at the Department of Neurosurgery of Sri Chitra Tirunal Institute for Medical Sciences and Technology from January 2001 to June 2014. Symptoms at presentation, neurological deficits, neuroradiological features, intraoperative findings, and postoperative course were recorded prospectively. Preoperatively, all the patients underwent contrast-enhanced MRI. Spinal angiogram was done in selected patients. They also underwent screening for other manifestations of vHL syndrome including intracranial tumors, retinal angiomas, pancreatic and renal masses, and pheochromocytoma.

Clinical criteria proposed by Melmon have been used to identify patients with vHL syndrome [20]. Neurological function of the patients was graded according to the clinical scale described by McCormick [17]. Functional grade was assessed in the pre- and immediate postoperative periods, and at follow-up. Functional outcome was compared between the sporadic- and vHL-associated cases.

Results

Clinical presentation

Among 15 patients, eight (53%) of them were females, and seven were males (47%). Mean age was 33.8 years (16–55 years). Mean age of patients with vHL disease at the time of presentation was 32.5 years. Sporadic tumor was more common in female (71%); whereas, vHL tumors were more common in males (63%). Duration of illness ranged from 2 weeks to 4 years, and average duration was 10.5 months. Thirteen patients (87%) presented motor weakness in the form of hemiparesis, quadriparesis, or paraparesis at the time of presentation. Nine patients (60%) present with sensory disturbances. Pain was the presenting symptom in 4 patients (27%). Bladder disturbance was present in 3 patients (20%). Table 1 shows the clinical presentation of all the patients.

Table 1 Clinical presentation of all patients
Full size table

Fifteen patients had 23 spinal tumors. Thirteen tumors (57%) present in the thoracic spinal cord, and 9 (39%) in the cervical cord. One (4%) was present at the conus. Spinal hemangioblastomas had predilection for thoracic region in vHL subjects (6/8, 75%); whereas, only 2 lesions (28.6%) were found in thoracic spine in sporadic hemangioblastoma group (Fig 1).

Fig. 1
figure 1

MRI features of spinal hemangioblastoma. a Post contrast sagittal MRI shows dorsal tumors with syringomyelia. b Post contrast MRI shows medullary hemangioblastoma associated with pseudocyst and lower cervical tumor

Full size image

Five patients (33%) had cerebellar hemangioblastoma associated with spinal cord tumor. Seven patients (47%) had associated renal and pancreatic cysts. Two patients (13%) had retinal disease. Based on the clinical criteria for vHL disease, 8 patients (53%) were diagnosed to have vHL disease. Of the 8, one had positive family history. Syrinx was present in 10 patients (67%). Eight tumors were asymptomatic and coexisted with the symptomatic tumors. Preoperative angiogram was done in 11 patients. Preoperatively, two patients underwent embolization to reduce the blood loss during surgery. One had tumor in the conus, and the other had tumor in the dorsal cord (Fig 2).

Fig. 2
figure 2

Angiogram appearance of hemangioblastoma. a Angiogram picture shows the feeders and draining veins. b Post embolization picture shows complete obliteration of vascularity of the tumor

Full size image

McCormick functional grade was assessed before surgery, at the time of discharge, and at follow-up. Six (85.7%) cases of sporadic spinal hemangioblastomas were in grade I; whereas, 7 (87.5%) of vHL spinal hemangioblastomas were in grade II or above. Table 2 summarizes the preoperative functional grades in all patients.

Table 2 Preoperative McCormick’s grade
Full size table

Total of 15 patients underwent 19 surgeries, of which 16 for spinal hemangioblastomas and 3 for cerebellar hemangioblastomas. One patient was operated twice for cerebellar hemangioblastoma on either side, and one patient underwent surgery for right cerebellar hemangioblastoma. One patient had simultaneous resection of both cerebellar and cervical hemangioblastomas. All the patients underwent posterior spinal laminectomy and posterior midline approach for the resection of spinal tumors. Laminectomy was limited to the level of the solid portion of the tumor. All patients underwent complete microscopic resection of the tumor. None of the patients required instrumentation.

Postoperative course

Fifteen patients underwent 16 surgeries for spinal cord tumor including reoperation for a recurrent tumor. In the immediate postoperative period, three patients noticed improvement in their motor weakness. Among them, 2 had vHL syndrome, and one had sporadic tumor. Six were stable neurologically in the immediate postoperative period. Six patients (40%) experienced deterioration of preoperative neurological status in the immediate postoperative period. Three of them were sporadic tumors, and others had vHL syndrome. Three of them had tumor in the cervical cord, and three in the dorsal cord. Two patients were grade II, and the remaining four were grade I preoperatively. In 5 patients, neurological deterioration was transient and regained the preoperative functional grade at the time of discharge, and remaining one with vHL did not show any improvement.

Sensory symptoms in the remaining patients improved postoperatively. They also noticed improvement in the spasticity and motor weakness. All patients had improvement in pain symptom. Non-neurological complications were rare postoperatively. None of the patients had wound infection in the postoperative period. Only one patient had CSF leak from the wound in the postoperative period. It was managed by resuturing the wound. We had one mortality (6.7%) in the postoperative period (patient no 4). He developed massive intraventricular bleed due to malignant hypertension in the postoperative period.

Long-term follow-up

Mean follow-up was 5 years, ranging from 6 months to 11 years. Seven patients had more than 5 years of follow-up. Minimum follow-up was 6 months. During follow-up, 12 patients (80%) experienced improvement in their preoperative neurological deficit among the surviving 14 patients. Eleven patients (73%) were functionally grade I, and one was grade II. All patients with sporadic tumors (100%) noticed improvement in functional grade. Among patients with vHL syndrome, five (71%) of them noticed improvement in functional grade, and two (29%) had poor functional outcome.

Among the remaining 2 patients, one did not show improvement in functional grade. The other patient experienced deterioration in functional grade after 3 years (grade I1 to grade III) due to recurrence at the operative site though she had improvement in preoperative neurological deficit after the initial surgery. Postoperatively, she had further deterioration in her neurological deficit. Both of them had tumors in thoracic cord and were associated with vHL syndrome. These two patients had some improvement in their lower limb power following surgery, but they remained functionally dependent (McCormick grade III). Both of them had improvement in their bladder function and became free of indwelling urinary catheter.

Recurrence of the tumor was noticed at the operative site in one patient (6.7%) at 3 years of follow-up, although follow-up MRI was negative for residual lesion. She also developed another new lesion apart from the operative site and pancreatic cysts. She underwent re-exploration and excision of the recurrent tumor. Radical tumor excision was achieved, but she developed paraplegia postoperatively (preoperative functional grade II). Syrinx either resolved completely or decreased in size in the follow-up MRI in all patients who had syrinx preoperatively. None of our patient required further intervention for syrinx.

Discussion

Clinical features

Hemangioblastomas are benign and highly vascular tumors. Spinal hemangioblastoma represents 2 to 15% of primary intramedullary spinal cord tumors [24, 12]. Sporadic hemangioblastomas are always solitary. Those associated with vHL disease are often multiple and associated with tumors in other locations especially cerebellum, brainstem, and retina [26]. Majority of these tumors are intramedullary reaching the pial surface dorsally. They are often seen in association with dorsal rootlets. They can have intra- and extramedullary components. They can also be intradural extramedullary or even extradural in location.

Spinal hemangioblastomas are more common in males with male to female ratio of 1.6:1 to 5.5:1 [26]. In our series, overall incidence is slightly higher in females, but vHL-associated spinal tumors are more common in males as compared to sporadic tumor. These tumors commonly occur in the third or fourth decades, and vHL syndrome-related tumors occur in second or third decades of life. Though vHL-related spinal tumor is commonly reported in younger age as compared to sporadic tumors, symptomatic tumors can occur between 12 to 66 years of life [5]. In our series, majority of vHL cases occurred in middle age (> 35 years) as compared to sporadic tumors.

The clinical presentation depends on the location of the tumor and presence of syrinx, cyst, or edema. More than 95% of patients who are symptomatic have syrinx, edema, or cyst along with the tumor [3, 19]. Common symptoms include sensory or motor deficits, pain, dysesthesias, and bowel and urinary dysfunctions. Previous studies have reported sensory dysfunction as the most prevalent first clinical symptom [12, 14, 19]. This has been explained by the dorsal location of the tumor close to posterior column and dorsal rootlets in the spinal cord. In some series, pain was the most common symptom [9, 27]. In our series, motor weakness was the predominant symptom (86%). Apart from the direct mass effect of the tumor, presence of pseudo cyst, edema, or syrinx also contributes to the development of symptoms. This may explain the predominant motor symptoms in our series. The duration of symptoms ranges from 2 weeks to 4 years.

Contrast-enhanced MRI is the diagnostic modality of choice for spinal hemangioblastoma. Radiologically, both sporadic- and vHL-associated tumors share similar features. The most common location of hemangioblastoma in the spinal cord is cervical, thoracic, and lumbar region in the descending order of frequency in most of the studies [11, 18]. In our series, the most common site of the tumor was thoracic spinal cord (57%) followed by cervical cord (39%). Tumors associated with vHL syndrome had tendency to occur in thoracic region in our study. Kanno H et al. [13] also found that the thoracic cord was the more frequent site of tumors in vHL patients, but larger series have not shown such predilection [13, 15, 19, 21]. Incidence of syrinx and cyst component in the tumor has been reported to be between 50 and 70% [2, 6, 7, 25]. In our series, tumor-associated syrinx was seen in 66.7% of cases.

Angiography is not necessary for diagnosis and rarely required preoperatively. Preoperative embolization of feeding vessel reduces the tumor vascularity. It helps in reducing the intraoperative blood loss and thereby to achieve safe removal [11, 29]. Though preoperative embolization is not necessary for complete tumor removal, it can be considered as an adjunct to microsurgery especially in patients with large tumors and tumors in critical location like conus.

In agreement with literature, we did not find significant difference in clinical and radiological features between sporadic cases and vHL syndrome [9, 17, 30]. Though many patients with vHL syndrome in our series had significantly lower functional grade at the time of presentation as compared to sporadic cases, previous studies have not reported such a differential distribution of functional grade among vHL and sporadic cases [9, 13, 15, 17, 19, 21].

Neurological outcome

Several authors have shown good neurological outcome after surgical resection of hemangioblastoma [8, 11, 12, 14, 19, 22, 23, 27, 30]. Previous studies reported deterioration in the neurological status as high as 60% in the immediate postoperative period [12, 19]. But these are usually transient and reversible over a period of few weeks to 6 months. The incidence of permanent neurological worsening is rather low (< 10%) [13,14,15,16,17,18]. Although we had deterioration in neurological status postoperatively in 6 patients (40%), many of them were transient and showed significant improvement in the follow-up. Overall, good neurological outcome was achieved in 80% patients. All of the sporadic cases had good functional outcome. Among the patients with vHL disease, favorable long-term functional outcome was achieved in 71%.

Microsurgery for spinal hemangioblastoma has been associated with low morbidity. The long-term surgical outcome is favorable with stable or improvement in neurological status. Studies have shown favorable outcome in 68–96% following microsurgery [19, 27]. Our results are consistent with other series. In our series, patients showed improvement in preoperative functional grade by one or two grades. With timely surgery, even patients with poor functional grade noticed improvement in neurological deficit and could become functionally independent.

Neurological outcome of sporadic and vHL syndrome-related spinal tumors has also been compared in previous studies. Many studies showed surgical outcome of vHL-related spinal tumors was not different from that of sporadic tumors [30]. In contrary, Siller et al. [28] concluded vHL disease itself is a risk factor for a worse long-term prognosis. Though patients with vHL syndrome had and lower functional grade preoperatively in our study, long-term neurological outcome is equally good in both vHL and sporadic tumors. Three of the four patients with McCormick’s grade III had shown good surgical outcome. Only one patient with grade III had poor outcome. Presence of multiple tumors in spinal cord did not affect the long-term outcome. Only multiple resections of tumors at the same site in vHL syndrome may result in poor neurological outcome as in our patient who had recurrence at the previously operated site.

Several studies have tried to find out the factors which could predict the neurological outcome of spinal hemangioblastomas, but the results were not consistent in all studies [15, 19, 30]. Recently in a large study with 108 patients, Mehta and colleagues found out that tumor location and resection of completely intramedullary tumor correlated with postoperative neurological outcome using multivariate analysis [19]. Other factors like tumor volume, preoperative functional grade, presence of syrinx, and peritumoral edema did not predict the outcome.

Patients with vHL syndrome usually have multiple hemangioblastomas in the spinal cord. These can also be found in cerebellum or brainstem along with spinal tumors. All the tumors do not warrant surgical excision. The indication for surgical removal of asymptomatic tumors is still debated. Hemangioblastomas show a period of growth followed by a phase of quiescence [1]. There are no reliable threshold tumor size and threshold growth rate that could predict the evolution of symptoms or cyst [31]. In their study on 19 patients, Ammerman et al. [1] advised against the surgical resection of asymptomatic spinal cord tumor based only on radiographic progression. Such an approach could result in additional procedures which may not be required at all during follow-up. In our series, eight patients with vHL syndrome had 16 spinal cord tumors. Eight tumors remained asymptomatic and did not show radiological progression. None of them required surgical resection during follow-up.

Recurrence of hemangioblastoma is rare and usually seen in patients with vHL syndrome as in our study [10]. vHL patients should undergo screening for associated systemic tumors. Screening should include both radiological and biochemical evaluation. Urinary catecholamines should be assessed in all patients preoperatively, though pheochromocytoma associated with vHL is less likely to have symptoms or biochemical evidence of catecholamine production than sporadic cases [3]. Undiagnosed pheochromocytoma may result in grave complications in intraoperative as well as postoperative period as in our study.

Conclusion

Microsurgical resection of spinal hemangioblastomas is associated with good neurological outcome irrespective of preoperative functional grade. Radical tumor resection should be the surgical goal as most of the immediate postoperative neurological deteriorations are reversible. Age, sex, duration of illness, tumor location, volume, and preoperative functional grade do not predict the postoperative neurological improvement. There is no difference in the long-term neurological outcome between sporadic- and vHL-associated spinal hemangioblastomas. Asymptomatic spinal tumors in vHL syndrome can be safely followed without additional intervention. Appearance of symptoms should be the indication for surgical removal of asymptomatic spinal hemangioblastomas.