Chapter 10 Radiosurgery of Cerebral Vascular Malformations
Szeifert GT, Kondziolka D, Levivier M, Lunsford LD (eds): Radiosurgery and Pathological
Fundamentals. Prog Neurol Surg. Basel, Karger, 2007, vol 20, pp 220–230
10.2.1.
Radiosurgery for Cavernous
Malformations
Douglas Kondziolkaa,b,d, John C. Flickingera,b,d,
L. Dade Lunsforda–d
Departments of aNeurological Surgery, bRadiation Oncology and cRadiology
and dThe Center for Image-Guided Neurosurgery, University of Pittsburgh,
Pittsburgh, Pa., USA
Abstract
The role of radiosurgery for cavernous malformations of the brain remains to be fully
defined. We have used Gamma Knife radiosurgery for selected patients with symptomatic,
hemorrhagic malformations in high-risk brain locations. Indications, techniques, and results
are presented.
Copyright © 2007 S. Karger AG, Basel
The management of patients with brain cavernous malformations (angiographically occult vascular malformations, cavernous angiomas, cavernomas)
remains controversial. Since the mid 1980s there has been an improved understanding of their natural history [1, 9, 15, 18, 24, 30, 33, 36], as well as documented experience with surgical resection [3, 5, 10, 31, 35, 37]. In the case of
an arteriovenous malformation (AVM), the elimination of the angiographically
identifiable anatomic shunt can be demonstrated on imaging and correlates
highly with cure. However, since a cavernous malformation cannot be defined
by angiography, complete obliteration of the malformation vessels cannot be
confirmed with imaging. Because some patients have cavernous malformations
that are not amenable to surgical resection with acceptable risk, alternative
strategies are sought. When such malformations repeatedly bleed they warrant
management. Radiosurgery is the only potential alternative to resection.
Stereotactic radiosurgery can provide a reduction in hemorrhage risk after an
initial latency interval [2, 6, 8, 12–14, 17, 19, 22, 23, 29] for patients with highrisk cavernous malformations. Our observations confirm the hypothesis that
Table 1. Locations of 112 cavernous
malformations selected for radiosurgery
Location
Malformations
Pons/midbrain
Thalamus
Medulla
Temporal lobe
Parietal lobe
Basal ganglia
Frontal lobe
Cerebellum
Occipital lobe
62
12
10
6
5
8
4
4
1
radiosurgical intervention reduces subsequent bleeding rates. The microvasculature of a cavernous malformation ultimately responds to radiosurgery in the same
way AVMs respond [20]. However, unlike with AVMs, there is little pathological
material that has been studied. Without an imaging correlate of risk elimination,
clinical follow-up remains the standard by which radiosurgery must be judged.
University of Pittsburgh Experience
High-risk cavernous malformations were managed with stereotactic radiosurgery at the University of Pittsburgh between 1987 and 2004 in a total of 112
patients. The mean age was 39 years (range 4–81 years). Almost all patients had
multiple hemorrhages (range 2–9, mean ⫽ 2.6), while some suffered a single
imaging-confirmed hemorrhage but had a subsequent stepwise decline in neurological function. A hemorrhage was defined as a symptomatic, ictal event that
consisted of new neurological symptoms or deficits and imaging confirmation
of new blood on MRI or CT. Patients were selected for radiosurgery when the
malformation caused functional deterioration due to hemorrhage. Four patients
had seizures. In general, the lesions tended to be located in critical brain regions
as demonstrated in table 1. Prior to radiosurgery, 30% of patients had surgical
interventions that included attempted malformation resection, clot evacuation,
biopsy, or shunt placement. One patient had proton beam irradiation and
Gamma Knife radiosurgery prior to care at our Center.
Radiosurgical Technique
Prior to radiosurgery, all patients underwent MRI to ensure that the lesion
was a typical cavernous malformation. Typically, MRI showed mixed signal
change within an outer hemosiderin ring of low signal intensity [25, 32] (fig. 1).
Radiosurgery for Cavernous Malformations
221
a
b
Fig. 1. a Vertebral artery angiogram showing a region of absent perfusion (arrows)
indicating the presence of a cavernous malformation. b Histological preparation showing a
cavernous malformation within the pons.
Kondziolka/Flickinger/Lunsford
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If there was any question about the diagnosis, angiography was performed to
exclude an AVM or associated venous malformation.
Radiosurgery was performed with the use of the Leksell Model G stereotactic frame (Elekta Instruments, Atlanta, Ga., USA). The frame was applied
after mild sedation and local anesthesia was administered. General anesthesia
was reserved for patients under 12 years of age. After frame application, all
patients had stereotactic imaging. CT was used for planning in all patients prior
to 1990. Patients treated from 1988 through 1992 had both CT and MRI. Since
1992, stereotactic MRI alone has been utilized, because MRI was superior to
CT in defining cavernous malformations and equally accurate. A sagittal shortrepetition time (TR) scout image acquisition was obtained, followed by axial
short- and long-TR images obtained at 3-mm image intervals. Finally, repeat
axial and coronal short-TR images with volume acquisitions (1- to 1.5-mm
slices) and contrast enhancement were obtained.
Images were transferred to the dose planning workstation of the Gamma
Knife (GammaPlan®, Elekta Instruments, Atlanta, Ga., USA). Single or multiple
isocenter (range 1–9) plans were constructed to give a conformal and selective
irradiation volume for the cavernous malformation margin (fig. 2). The mean
number of isocenters was 3.3. The target nidus was defined as the region characterized by mixed signal change within the outer hemosiderin ring, typically of low
signal intensity. Hematoma eccentric from the malformation was excluded from
dose planning. In all patients in this series, the 50% isodose or greater was used
for the target margin. The average radiosurgery dose was lower than that used for
AVMs, but dependent on the location and volume of the cavernous malformation
[12, 17]. The mean volume was 2.37 ml (range 0.12–9.5 ml), while the mean
maximum and marginal doses were 30 Gy (maximum ⫽ 40 Gy) and 16 Gy (maximum ⫽ 20 Gy), respectively. Radiosurgery was performed with a 201-source
cobalt-60 Leksell Gamma Knife, Models U, B, or C (Elekta Instruments, Atlanta,
Ga., USA). After radiosurgery, all patients received 40 mg methylprednisolone
and were discharged from the hospital within 24 h.
Follow-up
Clinical follow-up data were obtained from either the patients or their referring
physicians if they lived at a distance from Pittsburgh. Where necessary, patients
were contacted by telephone to update their outcome for the purposes of this study.
Imaging follow-up was requested at 6-month intervals for the first 2 years after
radiosurgery, and then annually. The following equation was used to determine
hemorrhage rates: rate ⫽ total hemorrhages observed/total patient-years observed.
Hemorrhage rates were compared before and after radiosurgical intervention using a paired t test. A hemorrhage was defined as a new neurological
symptom or sign associated with new blood detected on MRI.
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