Stereotactic Radiosurgery For Cavernous Malformations Research Articles

SRS for Cavernous Malformations: Myths and Realities.

The optimal management of cavernous malformations (CMs) remains controversial. Over the past decade, stereotactic radiosurgery (SRS) has gained wider acceptance in the management of CMs, especially in those with deep location, eloquence, and where surgery is of high risk. Unlike arteriovenous malformations (AVMs), there is no imaging surrogate endpoint to confirm CM obliteration. Clinical response to SRS can only be gauged by a reduction in long-term CM hemorrhage rates. There is concern that the long-term benefits of SRS and the reduced rehemorrhage rate after a latency period of 2 years may only be a reflection of natural history. Of further concern is the development of adverse radiation effects (AREs), which were significant in the early experimental studies. The lessons learnt from that era have led to the progressive development of well-defined, lower marginal dose treatment protocols that have reported less toxicity (5%-7%) and consequently reduced morbidity. Currently, there is at least Class II, Level B evidence for use of SRS in solitary CMs with previous symptomatic hemorrhage in eloquent areas with high surgical risk. Recent prospective cohort studies observing untreated brainstem and thalamic CMs report significantly higher hemorrhage rates and neurological sequelae than the rates reported from contemporary pooled large natural history meta-analyses. Furthermore, this strengthens our recommendation for early proactive SRS in symptomatic deep-seated CMs due to the higher morbidity associated with observation and microsurgery. The key to successful outcomes for any surgical intervention is patient selection. We hope that our precis on contemporary SRS techniques in the management of CMs will assist this process.

Cranial Cavernous Malformations: Natural History and Treatment.

Cavernous malformations (CMs), also known as cavernous angiomas or cavernomas, are low-flow vascular malformations of the brain and spinal cord that consist of clusters of dilated sinusoidal channels lined with endothelial cells that do not exhibit intervening tight junctions. The involved blood vessels lack muscular and elastic layers, and blood at various stages of thrombosis and organization often fills the thin-walled vascular caverns. CMs are grossly distinct from adjacent brain and have a lobulated appearance sometimes likened to a mulberry, with a characteristic dark red or purple color. Hemosiderin and gliosis often surround CMs of the brain and spinal cord; no neural tissue is present inside the lesion. Except for developmental venous anomalies (DVAs) present in ≈33% of CMs,1 no abnormal vascularity is typically seen on digital subtraction angiography, leading CMs to be termed cryptic or occult vascular malformations (Figure 1). Multiple small hemorrhage events lead to a pathognomonic popcorn appearance on magnetic resonance (MR) imaging because of hemosiderin staining from blood products of various ages. Calcifications may be present on computed tomographic imaging (Figure 2). Figure 1. A 48-year-old woman presented with headaches. A , Magnetic resonance imaging of the brain with T2-weighted imaging demonstrated a 1.1-cm lesion in the cerebellar vermis with mixed signal intensity. B – D , Susceptibility-weighted imaging demonstrated hemosiderin within the lesion’s core and a developmental venous anomaly associated with the cavernous malformation (arrowheads). Figure 2. A 28-year-old woman presented with partial seizures without secondary generalization. A , Noncontrast computed tomography of the head demonstrated a 1.4-cm right posterior cingulate hyperdensity, with evidence of mild hemorrhage and calcification. Magnetic resonance imaging of the brain demonstrated the cavernous malformation to have a core of mixed signal intensity, heterogeneous enhancement, and a rim of hemosiderin consistent with a cavernous malformation, as evidenced on ( B ) susceptibility-weighted imaging, ( C ) T2-weighted …

Evaluation of linear accelerator (LINAC)-based stereotactic radiosurgery (SRS) for cerebral cavernous malformations: a 15-year single-center experience

BACKGROUND AND OBJECTIVESSurgery is the principal treatment for safely accessible hemorrhagic and symptomatic cavernous malformations. Nevertheless, the role of linear accelerator (LINAC)-based stereotactic radiosurgery (SRS) in the management of high-risk, symptomatic cavernoma lesions warrants further refinement. In this study, we evaluate the use of LINAC-based SRS for cerebral cavernous malformations (CMs) and report our 15-year single-center experience.DESIGN AND SETTINGSA retrospective study from the Department of Radiation Oncology and the Department of Neurosurgery at Gulhane Military Medical Academy and Medical Faculty, Ankara from April 1998 to June 2013.PATIENTS AND METHODSFifty-two patients (22 females and 30 males) with cerebral CM referred to our department underwent high-precision single-dose SRS using a LINAC with 6-MV photons. All patients had at least 1 bleeding episode prior to radiosurgery along with related symptoms. Median dose prescribed to the 85% to 95% isodose line encompassing the target volume was 15 Gy (range, 10–20).RESULTSOut of the total 52 patients, follow-up data were available for 47 patients (90.4%). Median age was 35 years (range, 19–63). Median follow-up time was 5.17 years (range, 0.08–9.5) after SRS. Three hemorrhages were identified in the post-SRS period. Statistically significant decrease was observed in the annual hemorrhage rate after radiosurgical treatment (pre-SRS 39% vs post-SRS 1.21, P<.0001). Overall, there were no radiosurgery-related complications resulting in mortality.CONCLUSIONLINAC-based SRS may be considered as a treatment option for high-risk, symptomatic cerebral CM of selected patients with prior bleeding from lesions located at surgically inaccessible or eloquent brain areas.

Stereotactic Radiosurgery for Cavernous Malformations: Is it Effective?

Stereotactic Radiosurgery for Cavernous Malformations: Is it Effective?

From Cavern-Dwellers to Cavernoma Science

See related article, pages 3222–3230. Since the introduction of noninvasive imaging tools roughly 30 years ago, vascular malformations of the brain have attracted increasing interest. Among them, cerebral cavernous malformations (CCM) appear to be the most frequently diagnosed entity with current prevalence estimates ranging from 100 to 500 cases per 100000 in the general population.1 They may come to clinical attention after epileptic seizures, progressive neurological syndromes, or symptomatic hemorrhage, but overall, asymptomatic lesions seem to be most frequently encountered since the introduction of highly sensitive gradient echo (T2*) weighted sequences in routine MR imaging protocols.2 Despite increasing detection rates and growing insight into underlying molecular and genetic mechanisms, many practical issues remain as yet unsolved, particularly when it comes to actual patient care and counseling: First, no standardized imaging protocols exist. Brain MRI with the aforementioned T2*-weighted images are now considered the diagnostic standard, but the absence of contrast-enhanced T1 sequences may miss an associated developmental venous anomaly and vice versa, which may for example impact on the strategy of any neurosurgical intervention (Figure 1). Figure 1. Brain MRI study of a 37-year-old woman presenting with left internuclear ophtalmoplegia, ataxia, and a dissociated sensory deficit attributable to a left posterior pontine hematoma on FLAIR-weighted images (left plane). Three-month follow-up …

Stereotactic Radiosurgery for Cavernous Malformations: Kjellberg's Experience with Proton Beam Therapy in 98 Cases at the Harvard Cyclotron

Stereotactic Radiosurgery for Cavernous Malformations: Kjellberg's Experience with Proton Beam Therapy in 98 Cases at the Harvard Cyclotron

Stereotactic Radiosurgery for Cavernous Malformations: Kjellberg's Experience with Proton Beam Therapy in 98 Cases at the Harvard Cyclotron

Stereotactic Radiosurgery for Cavernous Malformations: Kjellberg's Experience with Proton Beam Therapy in 98 Cases at the Harvard Cyclotron

Stereotactic Radiosurgery for Cavernous Malformations: Kjellberg's Experience with Proton Beam Therapy in 98 Cases at the Harvard Cyclotron

Stereotactic Radiosurgery for Cavernous Malformations: Kjellberg's Experience with Proton Beam Therapy in 98 Cases at the Harvard Cyclotron

Stereotactic Radiosurgery for Cavernous Malformations: Kjellberg's Experience with Proton Beam Therapy in 98 Cases at the Harvard Cyclotron

Stereotactic Radiosurgery for Cavernous Malformations: Kjellberg's Experience with Proton Beam Therapy in 98 Cases at the Harvard Cyclotron

Stereotactic radiosurgery for cavernous malformations: Kjellberg's experience with proton beam therapy in 98 cases at the Harvard Cyclotron.

The lack of treatment options for surgically inaccessible cavernous malformations has made radiosurgery a possible alternative to conservative management. The few previous reports of radiosurgical efficacy have been limited by small numbers, short follow-up, or lack of attention to the full spectrum of end points, including neurological disability. In an attempt to elucidate the risk-to-benefit ratio of radiosurgery for cavernous malformations, we undertook a retrospective analysis of of 95 patients with 98 lesions treated by the late Raymond N. Kjellberg. Patients were followed for an average of 5.4 years (range, 0.3-12.3 yr), and data regarding hemorrhage, seizure, neurological disability, and incidence of radiation-induced complications were gathered. The analysis revealed a drop in annual hemorrhage rates from 17.3% per lesion per year before treatment to 4.5% per lesion per year after a latency period of 2 years. Improvement in seizure control was evident. However, a 16% incidence of permanent neurological deficit and a 3% mortality rate were attributable to radiographically confirmed radiation-induced complications. Neurological disability scores, measured by the modified Rankin disability scale, indicated a significant decline in neurological functioning during the follow-up interval, a result of the combined effects of radiation-related injury, hemorrhage, and clinical progression of the lesion. We conclude that although radiosurgery does seem to reduce hemorrhage, there is potential for complications and continued lesion progression after radiosurgery. These risks and benefits must be carefully balanced against the natural history of untreated lesions if the use of radiosurgery is considered.

Stereotactic Radiosurgery for Cavernous Malformations: Kjellberg's Experience with Proton Beam Therapy in 98 Cases at the Harvard Cyclotron

Stereotactic Radiosurgery for Cavernous Malformations: Kjellberg's Experience with Proton Beam Therapy in 98 Cases at the Harvard Cyclotron

Stereotactic Radiosurgery for Cavernous Malformations: Kjellberg's Experience with Proton Beam Therapy in 98 Cases at the Harvard Cyclotron

Stereotactic Radiosurgery for Cavernous Malformations: Kjellberg's Experience with Proton Beam Therapy in 98 Cases at the Harvard Cyclotron

Reduction of hemorrhage risk after stereotactic radiosurgery for cavernous malformations.

The benefits of radiosurgery for cavernous malformations are difficult to assess because of the unclear natural history of this vascular lesion, the inability to image malformation vessels, and the lack of an imaging technique that defines "cure." The authors selected for radiosurgery 47 patients who harbored a hemorrhagic malformation in a critical intraparenchymal location remote from a pial or ependymal surface. Of these, 44 patients had experienced at least two hemorrhages before radiosurgery. The mean patient age was 39 years; six patients had previously undergone attempted surgical removal. The malformation was located in the pons/midbrain in 24 cases, the medulla in three, the thalamus in nine, the basal ganglia in three, deep in a parietal lobe in four, and deep in a temporal lobe in four. Patients had sustained initial hemorrhages from 0.5 to 12 years prior to radiosurgery (mean 4.12 years). In these patients, who were not typical of the majority of patients with cavernous malformations, there were 109 bleeds before radiosurgery in 193 prior observation-years, for 56.5% annual hemorrhage rate (including the first hemorrhage), or an annual rate of 32% subsequent to the first hemorrhage. The mean follow-up period after radiosurgery was 3.6 years (range 0.33-6.4 years). The proportion of patients with hemorrhage after radiosurgery was significantly reduced (p < 0.0001), as was the mean number of hemorrhages per patient (p = 0.00004). In the first 2 years after radiosurgery, there were seven bleeds in 80 observation-years (8.8% annual hemorrhage rate). In the 2- to 6-year interval after radiosurgery, the annual rate decreased to 1.1% (one bleed). After radiosurgery, 12 patients (26%) sustained neurological worsening that correlated with imaging changes. In eight patients these deficits were temporary; two underwent surgical resection and died. Two patients had new permanent deficits (4%). A significant reduction was observed in the hemorrhage rate after radiosurgery in patients who had deep hemorrhagic cavernous malformations, especially after a 2-year latency interval. This evidence provides further support to the belief that radiosurgery is an effective strategy for cavernous malformations, especially when located within the parenchyma of the brainstem or diencephalon.