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Cavernous malformation

or angioma. (read review article here and typical MRI here)

 An abnormal collection of blood-filled channels that resemble blood vessels. These vascular channels can bleed, resulting in formation of hematomas that can cause neurologic symptoms and deficits. Cavernous malformations tend to be multiple.

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Radiosurgery for Cavernous Malformations
Epidemiologic studies indicate that these lesions are more common in persons of Hispanic descent and in woman. Some neurosurgeons recommend that family members of patients with cavernous malformations have a screening MR scan of the brain. Surgery for these lesions is indicated only if they have bleed or are likely to bleed and if the lesions are located in a surgically accessible area. Cavernous malformations in areas of "eloquent brain" or in the brainstem are usually observed (and not operated) unless they have bled at least twice.

The majority of patients with cerebral cavernous malformations present with headaches, seizures, or neurologic deficits from hemorrhage. Many of these malformations are identified in patients who undergo brain imaging for unrelated symptoms. Most patients with incidentally discovered malformations or those with minimal symptoms can be followed with periodic imaging studies unless new neurologic symptoms occur . Some malformations that have caused hemorrhage or are associated with intractable seizures are suitable for microsurgical resection. Occasional cavernous malformations are located in brain locations associated with a high risk during resection. For such patients alternative therapies are desirable. When malformations are located within the parenchyma of the brain stem or diencephalon, stereotactic radiosurgery should be considered. For patients with lobar but critically located malformations (e.g., those within motor cortex), for those that have undergone partial resection, or for those patients who refuse surgery and have progressive symptoms, radiosurgery may also be considered.

Reports of successful microsurgical extirpation of cavernous malformations were noted more frequently in the literature after 1985 . This corresponded with the introduction of magnetic resonance imaging (MRI). The use of MRI led to a significant increase in the recognition of both symptomatic and asymptomatic cavernous malformations. At this time, the natural history was poorly documented and management recommendations for patients with deeply located lesions were not consistent. In 1995, our group (Pitt) reported data from a prospectively evaluated natural history study that identified a 0.6% annual hemorrhage rate for patients who had not sustained a prior symptomatic hemorrhage and a 4.5% annual hemorrhage rate for those with one prior symptomatic hemorrhage . Also in 1995, we reported a significant reduction in the hemorrhage rate in 47 patients who had radiosurgery for high-risk cavernous malformations performed in the setting of multiple prior symptomatic bleeds . In that report, a 32% annual hemorrhage rate before radiosurgery was reduced to 8.8% in the first two years after irradiation, and then to 1.1% in the two to six year interval following radiosurgery. In this report, we review our 10 year experience in 68 patients. We also describe our current indications for radiosurgery, methods of treatment planning, and our long term results. (see online study.)

Stereotactic radiosurgery of angiographically occult vascular malformations: indications and preliminary experience.

Kondziolka D, Lunsford LD, Coffey RJ, Bissonette DJ, Flickinger JC.   Neurosurgery 1990 Dec;27(6):892-900

Department of Neurological Surgery, University of Pittsburgh, School of Medicine, Pennsylvania.

Stereotactic radiosurgery has been shown to treat successfully angiographically demonstrated arteriovenous malformations of the brain. Angiographic obliteration has represented cure and eliminated the risk of future hemorrhage. The role of radiosurgery in the treatment of angiographically occult vascular malformations (AOVMs) has been less well defined. In the initial 32 months of operation of the 201-source cobalt-60 gamma knife at the University of Pittsburgh, 24 patients meeting strict criteria for high-risk AOVMs were treated. Radiosurgery was used conservatively; each patient had sustained two or more hemorrhages and had a magnetic resonance imaging-defined AOVM located in a region of the brain where microsurgical removal was judged to pose an excessive risk. Venous angiomas were excluded by performance of high-resolution subtraction angiography in each patient. Fifteen malformations were in the medulla, pons, and/or mesencephalon, and 5 were located in the thalamus or basal ganglia. Follow-up ranged from 4 to 24 months. Nineteen patients either improved or remained clinically stable and did not hemorrhage again during the follow-up interval. One patient suffered another hemorrhage 7 months after radiosurgery. Five patients experienced temporary worsening of pre-existing neurological deficits that suggested delayed radiation injury. Magnetic resonance imaging demonstrated signal changes and edema surrounding the radiosurgical target. Dose-volume guidelines for avoiding complications were constructed. see dose nomogram)  Our initial experience indicates that stereotactic radiosurgery can be performed safely in patients with small, well-circumscribed AOVMs located in deep, critical, or relatively inaccessible cerebral locations.


Long-term results after stereotactic radiosurgery for patients with cavernous malformations.

Hasegawa T, McInerney J, Kondziolka D, Lee JY, Flickinger JC, Lunsford LD.

Department of Neurological Surgery and the Center for Image-Guided Neurosurgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.     Neurosurgery 2002 Jun;50(6):1190-7;

OBJECTIVE: Stereotactic radiosurgery has been used for patients with high-risk cavernous malformations of the brain. We performed radiosurgery for patients with symptomatic, imaging-confirmed hemorrhages for which resection was believed to be associated with high risk. This study examines the long-term hemorrhage rate after radiosurgery. METHODS: We reviewed data obtained before and after gamma knife radiosurgery on 82 patients treated between 1987 and 2000. Most patients had multiple hemorrhages from brainstem or diencephalic cavernous malformations. Follow-up data were examined to identify hemorrhages, and an overall hemorrhage rate was calculated. RESULTS: Observation before treatment averaged 4.33 years (range, 0.17-18 yr) for a total of 354 patient-years. During this period, 202 hemorrhages were observed, for an annual hemorrhage rate of 33.9%, excluding the first hemorrhage. Temporal clustering of hemorrhages was not significant. After radiosurgery, patient follow-up averaged 5 years (range, 0.42-12.08 yr), for a total of 401 patient-years. During this period, 19 hemorrhages were identified, 17 in the first 2 years posttreatment and 2 after 2 years. The annual hemorrhage rate was 12.3% per year for the first 2 years after radiosurgery, followed by 0.76% per year from Years 2 to 12. Eleven patients had new neurological symptoms without hemorrhage after radiosurgery (13.4%). The symptoms were minor in six of these patients and temporary in five. CONCLUSION: Radiosurgery confers a reduction in the risk of hemorrhage for high-risk cavernous malformations. Risk reduction, although in evidence during initial follow-up, is most pronounced after 2 years. Given the difficulty of identifying high-risk patients, treatment after one major hemorrhage should be considered in selected younger patients. Such a strategy warrants further investigation.

Treatment of symptomatic AOVMs with radiosurgery.

Kida Y, Kobayashi T, Tanaka T.

Department of Neurosurgery, Komaki City Hospital, Japan.  Acta Neurochir Suppl (Wien) 1995;63:68-72

In spite of great success in the treatment cerebral AVMs with stereotactic radiosurgery, the role of this treatment modality in angiographically occult vascular malformations (AOVMs) is not recognized. Since the installation of the Gamma-knife, we have treated 20 cases of AOVMs by radiosurgery. There were 13 males and 7 females, the age ranged from 3 to 58 years with an average age of 34.0 years. Their clinical presentations at the onset were haemorrhage in 11, convulsive seizure in 7 and progressive neurological deficits in 2. Two cases had multiple lesions. Among 20 symptomatic lesions, 14 were located supratentorially, 4 in the brain stem and 2 in the cerebellar hemispheres. Following localization with MRI and dose planning, the lesions were treated by radiosurgery and the doses ranged from 15 to 20 Gy at the margins. Follow-up studies indicate a significant control of rebleeding as well as of the convulsive seizure. Imaging studies demonstrated the shrinkage of the lesion in 3 and reduced enhancement with Gadolinium-DTPA in some others. Adverse effects, chiefly related to radiation-induced oedema, occurred in 5. But they were generally mild and well controlled by medication. Thus the preliminary results indicate a certain usefulness of radiosurgery in the treatment of symptomatic AOVMs.

Radiosurgery of intracranial cavernous malformations.

Kim DG, Choe WJ, Paek SH, Chung HT, Kim IH, Han DH.  Acta Neurochir (Wien) 2002 Sep;144(9):869-78

Department of Neurosurgery, Seoul National University College of Medicine, Clinical Research Institute, Seoul National University Hospital, Seoul, Korea.

BACKGROUND: The efficacy of radiosurgery in cases of surgically high risk symptomatic cavernous malformations (CMs) for reducing haemorrhagic risk and for seizure control has not been clearly documented and the radiation-induced complications of radiosurgery remain problematic. The authors present a retrospective clinical analysis of 22 cases of CMs treated by radiosurgery. METHODS: Twenty-two patients with symptomatic CMs were treated by linear accelerator (LINAC) radiosurgery or Gamma knife (GK) between 1995 and 1998. Medical records including radiological investigations were carefully reviewed to the last follow-up. The mean age of the patients was 34.1 years (12-56) and the male to female ratio was 12:10. Twenty patients reported at least one episode of bleeding and four had undergone microsurgery before radiosurgery. The remaining two patients presented with seizure without evidence of recent haemorrhage. In 16 cases, the CMs were deep-seated, and the others were located in the cerebral hemispheres; four were located at an eloquent area. LINAC radiosurgery using computed tomography scan was performed in 11 cases until May 1997, after which GK radiosurgery using magnetic resonance (MR) image was performed in 11 cases. The volume of the lesion ranged from 0.09 cc to 4.8 cc (mean 1.42 cc) and the mean marginal dose was 16.1 Gy (8-24). The median follow-up period after radiosurgery was 38.3 months (21-67). The rate of haemorrhage, seizure, and neurological deterioration following radiosurgery was analyzed, and the rate of haemorrhage was compared to that seen in natural course reports. FINDINGS: There was one case of haemorrhage during the follow-up period and the seizure was well controlled with anticonvulsants. In the group with prior haemorrhage, the bleeding rate of cavernous malformation after radiosurgery (1.55%/year) was lower than that of pre-radiosurgical period (35.5%/year, t=1.296, P=0.04). Six patients showed neurological deterioration following radiosurgery, however, the neurological deficits persisted in only two of the patients with LINAC. The radiosurgical modality (LINAC vs. GK) showed a possible correlation to radiation induced neurological deficits (P=0.06). On the MR images at the last follow-up, the lesion was decreased in eleven patients, increased in one, and no change was found in 10 cases. The T2 weighted MR images revealed a perilesional high signal change in nine patients. This signal change was not statistically related to lesion size (P=0.236), location (P=0.658), nor radiation dose (P=0.363), but was dependent on the treatment modality (P=0.02). New-enhancing lesion and a new cyst were each found in one case, respectively, during the follow-up. INTERPRETATION: Radiosurgery may be a good alternative option for treatment of surgically high risk CMs. However, the optimal radiosurgical technique, dose adjustment, and proper delineation of the mass are prerequisites. Radiosurgery induced complications are still problematic and post-radiosurgery MR image changes need to be further elucidated.

Radiosurgery for venous angiomas.

Lindquist C, Guo WY, Karlsson B, Steiner L.  J Neurosurg 1993 Apr;78(4):531-6

Department of Neurosurgery, Karolinska Institute, Stockholm, Sweden.

Radiosurgical treatment with the gamma knife for venous angiomas was used as an alternative to microsurgical removal in order to avoid abrupt cessation of venous drainage, which may be shared by the venous angioma and important parts of the brain. Thirteen cases of venous angioma were treated between 1977 and 1991. In two cases cavernous angiomas were also present and in one case a distant arteriovenous malformation (AVM) was also found. In two cases the angioma shared the venous drainage with an adjoining AVM; this is the first description of such pathology. For venous angiomas irradiation was prescribed to cover at least the convergence of the medullary veins. For AVM's close to a venous angioma the treatment was exclusively prescribed to the AVM nidus. After treatment, complete obliteration of the venous angioma was observed in one case, partial obliteration was observed in three cases, and five venous angiomas were unaffected by the treatment. Undue effects of radiation occurred in four cases: one focal edema and three radionecroses. Extirpation of the radionecrotic tissue 6 months after radiosurgery was necessary in one case. In the other three cases, the venous angioma was observed to be completely or partially obliterated, or unaffected by the treatment (one case each). In two cases of combined AVM and venous angioma, complete obliteration of the treatment AVM nidus was obtained. It is concluded that radiosurgery for venous angioma, although conceptually attractive, still does not fulfill the rigid criteria of minimal risk which must be set for the treatment of a lesion with a benign natural history.

Gamma knife radiosurgery of the brain stem cavernomas.

Liscak R, Vladyka V, Simonova G, Vymazal J, Novotny J Jr.   Minim Invasive Neurosurg 2000 Dec;43(4):201-7

Department of Stereotactic and Radiation Neurosurgery, Hospital Na Homolce, Prague, Czech Republic. Roman.Liscak@homolka.cz

Over 6 years (1992-1998) 26 patients with brain stem cavernomas were treated using the Leksell gamma knife in Prague. 25 patients had a follow up of 6-66, median 24 months. Annual risk of bleeding before radiosurgery was 4%. After gamma knife treatment sudden impairment of neurodeficit reported as rebleeding was observed in 4 patients at 6-51 months, median 16.5 months, after radiosurgery. This represented a 6.8% risk of rebleeding after radiosurgery, which is not significantly different from the risk before radiosurgery. MRI or CT was performed in 24 patients 6-48, median 24, months after radiosurgery. There were no signs of rebleeding in any of the patients, nor any increase of the cavernoma. A decrease of cavernoma size was observed in 8 (33%) of patients. Temporary collateral edema after radiosurgery was detected in 5 (21%) of patients 3-12, median 11, months after radiosurgery. Neurodeficit was observed in 21 of 26 patients before radiosurgery. Improvement of the neurodeficit was detected in 9 (43%) of them 6-36, median 8, months after radiosurgery. Temporary morbidity caused by collateral edema or rebleeding occurred in 7 patients (28%) and permanent morbidity remained in 2 patients (8%). 2 patients died because of rebleeding 6 and 51 months after radiosurgery and the third patient for unrelated reason. Radiosurgery of the brain stem cavernomas was indicated when there was bleeding in the history or progressive neurodeficit and microsurgery was considered too risky. Leksell gamma knife radiosurgery of cavernomas has proved its low morbidity and zero mortality. In case of an insufficient effect of radiosurgery, or if the protective effect from rebleeding comes too late, morbidity and mortality can correspond to the natural course of the disease, as it was left without any treatment.

Gamma knife radiosurgery for cavernous hemangiomas.

Zhang N, Pan L, Wang BJ, Wang EM, Dai JZ, Cai PW.   J Neurosurg 2000 Dec;93 Suppl 3:74-7

Department of Neurosurgery, Shanghai Gamma Knife Hospital and Shanghai Huashan Hospital, People's Republic of China. nanzhang@sina.com

OBJECT: The authors analyzed the outcome of 53 patients with cavernous hemangiomas who underwent gamma knife radiosurgery (GKS) and evaluated the benefit of the treatment. METHODS: From 1994 to 1995, 57 patients were treated with GKS for cavernous hemangiomas. The mean margin dose to the lesions was 20.3 Gy (range 14.5-25.2 Gy) and the prescription isodose was 50 to 80%. The mean follow-up period was 4.2 years. Four patients were lost to follow up. In 18 of 28 patients whose chief complaint was seizures, there was a decrease in seizure frequency. Five of 23 patients with hemorrhage suffered rebleeding 4 to 39 months after GKS. Seventeen patients in whom the hemangiomas were located at the frontal or parietal lobe had neurological disability and in five this was severe. Two patients underwent resection of their hemangioma after GKS. Three experienced visual problems. Follow-up imaging demonstrated shrinkage of the lesion in 19 patients. CONCLUSIONS: A higher margin dose (> 16 Gy) may be associated with a reduction in the incidence of rebleeding after GKS. Higher dosage and severe brain edema after GKS may decrease the frequency and intensity of seizures at least temporarily. Gamma knife radiosurgery may play a role in protection against hemorrhage and in reduction of the rate of seizure in selected cases with the appropriate dose.