Introduction

   The incidence of cavernous angioma is reported to be between 5 to 10 % of all cerebrovascular malformations.^3)8)12) The brainstem cavernous angioma accounts for 13 to 35% of intracranial cavernous angioma, with predilection for the pons. The natural history of brainstem cavernous angioma indicates a higher morbidity and mortality than those in the other location.¹²⁾ There are different opinions about surgical intervention based on favorable outcome¹⁵⁾ or significant postoperative morbidity.¹⁰⁾ In general, surgical management of brainstem cavernous angioma has been regarded as high risk procedure recommendable for selected patients. Gamma knife radiosurgery (GKS) is a treatment modality which is accompanied with very low risk of immediate procedurerelated complication. The authors report clinical outcome of symptomatic brainstem cavernous angioma treated with GKS. 

Materials and methods 

1. Patient population 
   From December 2001 to 2007, 54 patients with intracranial cavernous angioma were treated with GKS in the authors institute. Among theses patients, twenty one patients had symptomatic cavernous angioma located in the brainstem. Mean age of the patients was 45.5 years (range 28~70). There were seven male and fourteen female patients. The location of the lesions were pons in 15 of 21 (71%) patient, midbrain in 4 (19%), and medulla oblongata in 2 (10%) (Table 1). All patients had except one solitary lesion. Most common symptom was hemiparesis in 12 of 21 (61.9%). Other clinical manifestation included sensory deficit , dizziness, diplopia, headache, dysarthria, and facial palsy (Table 2). Acute bleeding was suggested in 19 patients considering sudden onset of symptom and magnetic resonance image (MRI) finding. Two patients presented repeated episode of neurological deterioration up to four times. There was no evidence of bleeding in MRI of two patients. There were two patients who underwent incomplete surgical excision of the lesions before GKS. 

2. Gamma Knife radiosurgery 
   After application of stereotactic frame under local infiltration of anesthetics, MRI scanning was done. T2- weighted images (slice thickness of 2 mm with no gap, 512 ×512 pixel) and 3D-SPGR images after administration of double dose csontrast agent (slice thickness of 1 mm with no gap, 512× 512 pixel) were obtained. Images were transferred to planning workstation and dose planning was performed using GammaPlan version 5.34. Irradiation was performed with Leksell Gamma Knife type B or C. 
   The mean volume of the treated lesions was 1134.2 mm³ (range 130.7~3800) which was covered with median marginal dose of 15 Gy (range 13~18Gy) at 50% (range 45~80%) isodose line. 

3. Follow up 
   Mean clinical follow up period was 33 months (range 4~67 months). MRI follow up was recommended at 6 months after the GKS and once a year then. The last MRI scan was obtained at mean 18 months (range 5~51 months) from GKS and digital volumetry was done with commercial software (V-work 4.0, Cybermed^®). 

Results 

   Continuing improvement of neurological deficit was achieved in 14 of 21 (66.6%) patients. Two (9.5%) patients maintained stationary state. There were five (23.8%) patients with transient aggravation during follow-up period. The symptom got worse in four patients with swelling of the lesions and increased surrounding edema suggestive of radiation effect from 4 to 8 months after GKS. The prescribed marginal dose in these patients ranged fro 13 to 16 Gy and it was not different from that of the uncomplicated patients. Another one developed acute onset of dizziness and paresthesia and MRI finding compatible with overt bleeding at 17 months after GKS. Two patients with severe progressive symptom underwent surgical excision (one at the other hospital). They had been treated with marginal dose of 16 Gy for lesion volume of 733.9 mm³ and 15 Gy for 2300 mm³, each respectively. The other three patients including rebleeding case were managed conservatively and finally improved. Therefore 17 of 21(80.1%) patients achieved improvement of neurological deficit at the last follow up. There was no mortality. 
   Digital volumetry revealed decrease of the lesion volume in most of the cases. Mean volume of the lesions at the last MRI follow up was 724.8 mm³ (range 36.8~1322 mm³) which is 37.3% reduction from the original volume at the time of GKS (mean 1155.6 mm³, range 130.7~3800 mm³) Volume of the lesion decreased in 17 patients (81.0%). The volume of the lesion increased in four patients (19%) and two of them underwent surgical excision at 3 and 8 months after GKS each respectively. 

1. Illustrative case (Case No. 7) 
   A 56 year old male patient presented with left side weakness and dizziness. There were left side weakness and left side sensory deficit on neurological examination. In initial MRI scan, there was high signal centered lesion with surrounding low signal hemosiderin rim in his upper medulla oblongata. The lesion volume was 246.3 mm³ and it was covered with marginal dose of 14 Gy at 60% isodose line. Follow up MRI at 19 month after GKS (Fig. 1) revealed marked shrinkage of the lesion and measured lesion volume was 36.9 mm³. Symptom improved and he does not complain weakness or dizziness any more at 22 months after GKS. 

2. Illustrative case (Case No. 12) 
   A 47 year old male patient complained right side weakness, dizziness and gait disturbance nine months before visiting our hospital . There were mild right side weakness and gait disturbance on neurological examination. MRI scan showed a large cavernous angioma associated with venous angioma in the right cerebellar peduncle. The lesion volume was 733.9 mm³and prescribed marginal dose was 16 Gy at 50 % isodose line. He complained aggravation of right side weakness and gait disturbance at 9 months after GKS. Worsening of cerebellar function including ataxia, limb motor incoordination, and disequilibrium was observed. At follow up MRI scan, the lesion was swollen with increased perilesional edema (Fig. 2). It was thought to be due to radiation effect. Corticosteroid was administered for two weeks, however, symptom progressed and finally he underwent surgical excision of the lesion through supratonsillar approach. Cavernous angioma was removed completely, however, severe disequilibrium and right side limb motor incoordination developed postoperatively and took almost a year before recovery enabling independent daily activity. 

Discussion 

   The goal of radiosurgery for cavernous angioma is prevention of repeated bleeding and neurological deterioration. There is a few report about beneficial effect of radiosurgery diminishing the incidence of further hemorrhage.⁷⁾ Overall results of our patients are compatible with other reports of GKS for brainstem cavernous angiomas. Only one patient developed rebleeding after GKS. It suggests that GKS is effective for prevention of rebleeding, though it is too early to conclude decisively before knowing the natural history and incidence of hemorrhage from large population data. Also it seems to be effective in decreasing the lesion volume. Radiologic volume decrement of the lesions after GKS was achieved in 17 of 21 (80.1%) patients. However, it is not clear whether shrinkage of the volume is truly induced by radiation or absortion of hemorrhage and the issue needs further data from the natural course of the disease too. Finally most of the patients improved or at least maintained stationary neurological function. However, neurological deterioration after GKS mostly due to radiation effect was not rare (23.8% in our series) though it did not result in permanent disability in all affected patients. Considering the relatively small volume of the lesion and low prescribed marginal dose, it is certainly a higher rate of complication compared with cerebral AVM. The factors related to this high risk of radiation toxicity may be location of the lesions in critical structure, that is brainstem, and inherent biological characteristics of cavernous angioma. Whatever the true reason is, it is strongly recommended that dose prescription should be done very cautiously. According to Liscak et al.¹¹⁾ there was increased incidence of collateral edema by marginal dose exceeding 15 Gy with statistical significance. In our results, radiation-related complication developed with marginal dose as low as 13 Gy. Meanwhile we did not recognize significant difference of therapeutic effect compared with the higher marginal dose. Although optimal dose for cavernous angioma, particularly in specific locations such as brainstem has not been defined yet, threshold for adverse effect may be lower in brainstem due to its critical function and tightly organized structure. Therefore, it would be prudent to take more conservative approach in brainstem cavernous angioma than in AVM or cavernous angiomas of the other locations. 
   Concerning the selection of GKS as the primary treatment of the brainstem cavernous angioma, there are no data directly comparing the results of microsurgery and radiosurgery. The best results of surgical excision of brainstem cavernous angioma reported 12~14% of serious permanent morbidity and 8% of mortality. Only 35.7% of patients achieved improvement of their neurological condition after surgery²⁾¹³⁾ Although the characteristics of the patients and outcome measurement are different, neurological improvement in 80.1% of the patients and zero mortality in our results are favoring radiosurgery as a primary treatment in many of the patients in whom microsurgery can not be recommended strongly. However, several fundamental limitations of current knowledge should be noted before fully advocating GKS for brainstem cavernous angioma. As described above, there is no available data directly comparing efficacy and risk between each different treatment strategies (microsurgery, radiosurgery and observation without intervention). Natural course of the disease and long term outcome after GKS are not well known either. Because brainstem cavernous angioma is not a common disease, prospective data collection through multi-institutional cooperative study needs to be done to resolve the issues in the future. 

Conclusion 

   GKS is an effective treatment for the brainstem cavernous angioma. However, transient or permanent complication from radiation effect is not rare. Dose prescription needs to be cautious and rather conservative approach may be preferable to avoid potentially fatal complication in critical structures. 

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