Pathological response of cavernous malformations following radiosurgery

Pathological response of cavernous malformations following radiosurgery

J Neurosurg 123:938–944, 2015

Stereotactic radiosurgery (SRS) is a therapeutic option for repeatedly hemorrhagic cavernous malformations (CMs) located in areas deemed to be high risk for resection. During the latency period of 2 or more years after SRS, recurrent hemorrhage remains a persistent risk until the obliterative process has finished. The pathological response to SRS has been studied in relatively few patients. The authors of the present study aimed to gain insight into the effect of SRS on CM and to propose possible mechanisms leading to recurrent hemorrhages following SRS.

Methods During a 13-year interval between 2001 and 2013, bleeding recurred in 9 patients with CMs that had been treated using Gamma Knife surgery at the authors’ institution. Microsurgical removal was subsequently performed in 5 of these patients, who had recurrent hemorrhages between 4 months and 7 years after SRS. Specimens from 4 patients were available for analysis and used for this report.

Results Histopathological analysis demonstrated that vascular sclerosis develops as early as 4 months after SRS. In the samples from 2 to 7 years after SRS, sclerotic vessels were prominent, but there were also vessels with incomplete sclerosis as well as some foci of neovascularization.

Conclusions: Recurrent bleeding after SRS for CM could be related to incomplete sclerosis of the vessels, but neovascularization may also play a role.

Adverse radiation effect after stereotactic radiosurgery for brain metastases

Adverse radiation effect after stereotactic radiosurgery for brain metastases- incidence, time course, and risk factors

J Neurosurg 123:373–386, 2015

The authors sought to determine the incidence, time course, and risk factors for overall adverse radiation effect (ARE) and symptomatic ARE after stereotactic radiosurgery (SRS) for brain metastases.

Methods All cases of brain metastases treated from 1998 through 2009 with Gamma Knife SRS at UCSF were considered. Cases with less than 3 months of follow-up imaging, a gap of more than 8 months in imaging during the 1st year, or inadequate imaging availability were excluded. Brain scans and pathology reports were reviewed to ensure consistent scoring of dates of ARE, treatment failure, or both; in case of uncertainty, the cause of lesion worsening was scored as indeterminate. Cumulative incidence of ARE and failure were estimated with the Kaplan-Meier method with censoring at last imaging. Univariate and multivariate Cox proportional hazards analyses were performed.

Results Among 435 patients and 2200 brain metastases evaluable, the median patient survival time was 17.4 months and the median lesion imaging follow-up was 9.9 months. Calculated on the basis of 2200 evaluable lesions, the rates of treatment failure, ARE, concurrent failure and ARE, and lesion worsening with indeterminate cause were 9.2%, 5.4%, 1.4%, and 4.1%, respectively. Among 118 cases of ARE, approximately 60% were symptomatic and 85% occurred 3–18 months after SRS (median 7.2 months). For 99 ARE cases managed without surgery or bevacizumab, the probabilities of improvement observed on imaging were 40%, 57%, and 76% at 6, 12, and 18 months after onset of ARE. The most important risk factors for ARE included prior SRS to the same lesion (with 20% 1-year risk of symptomatic ARE vs 3%, 4%, and 8% for no prior treatment, prior whole brain radiotherapy [WBRT], or concurrent WBRT) and any of these volume parameters: target, prescription isodose, 12-Gy, or 10-Gy volume. Excluding lesions treated with repeat SRS, the 1-year probabilities of ARE were < 1%, 1%, 3%, 10%, and 14% for maximum diameter 0.3–0.6 cm, 0.7–1.0 cm, 1.1–1.5 cm, 1.6–2.0 cm, and 2.1–5.1 cm, respectively. The 1-year probabilities of symptomatic ARE leveled off at 13%–14% for brain metastases maximum diameter > 2.1 cm, target volume > 1.2 cm3, prescription isodose volume > 1.8 cm3, 12-Gy volume > 3.3 cm3, and 10-Gy volume > 4.3 cm3, excluding lesions treated with repeat SRS. On both univariate and multivariate analysis, capecitabine, but not other systemic therapy within 1 month of SRS, appeared to increase ARE risk. For the multivariate analysis considering only metastases with target volume > 1.0 cm3, risk factors for ARE included prior SRS, kidney primary tumor, connective tissue disorder, and capecitabine.

Conclusions Although incidence of ARE after SRS was low overall, risk increased rapidly with size and volume, leveling off at a 1-year cumulative incidence of 13%–14%. This study describes the time course of ARE and provides risk estimates by various lesion characteristics and treatment parameters to aid in decision-making and patient counseling.

A treatment paradigm for high-grade brain arteriovenous malformations: volume-staged radiosurgical downgrading followed by microsurgical resection

A treatment paradigm for high-grade brain arteriovenous malformations- volume-staged radiosurgical downgrading followed by microsurgical resection

J Neurosurg 122:419–432, 2015

The surgical treatment of many large arteriovenous malformations (AVMs) is associated with substantial risks, and many are considered inoperable. Furthermore, AVMs larger than 3 cm in diameter are not usually treated with conventional single-session radiosurgery encompassing the entire AVM volume. Volume-staged stereotactic radiosurgery (VS-SRS) is an option for large AVMs, but it has mixed results. The authors report on a series of patients with highgrade AVMs who underwent multiple VS-SRS sessions with resultant downgrading of the AVMs, followed by resection.

Methods. A cohort of patients was retrieved from a single-institution AVM patient registry consisting of prospectively collected data. VS-SRS was performed as a planned intentional treatment. Surgery was considered as salvage therapy in select patients.

Results Sixteen AVMs underwent VS-SRS followed by surgery. Four AVMs presented with rupture. The mean patient age was 25.3 years (range 13–54 years). The average initial Spetzler-Martin grade before any treatment was 4, while the average supplemented Spetzler-Martin grade (Spetzler-Martin plus Lawton-Young) was 7.1. The average AVM size in maximum dimension was 5.9 cm (range 3.3–10 cm). All AVMs were supratentorial in location and all except one were in eloquent areas of the brain, with 7 involving primary motor cortex. The mean number of VS-SRS sessions was 2.7 (range 2–5 sessions). The mean interval between first VS-SRS session and resection was 5.7 years. There were 4 hemorrhages that occurred after VS-SRS. The average Spetzler-Martin grade was reduced to 2.5 (downgrade, -1.5) and the average supplemented Spetzler-Martin grade was reduced to 5.6 (downgrade, -1.5). The maximum AVM size was reduced to an average of 3.0 cm (downsize = -2.9 cm). The mean modified Rankin Scale (mRS) scores were 1.2, 2.3, and 2.2 before VS-SRS, before surgery, and at last follow-up, respectively (mean follow-up, 6.9 years). Fifteen AVMs were cured after surgery. Ten patients had good outcomes at last follow-up (7 with mRS Score 0 or 1, and 3 with mRS Score 2). There were 2 deaths (both mRS Score 1 before treatment) and 4 patients with mRS Score 3 outcome (from mRS Scores 0, 1, and 2 [n = 2]).

Conclusions Volume-staged SRS can downgrade AVMs, transforming high-grade AVMs (initially considered inoperable) into operable AVMs with acceptable surgical risks. This treatment paradigm offers an alternative to conservative observation for young patients with unruptured AVMs and long life expectancy, where the risk of hemorrhage is substantial. Difficult AVMs were cured in 15 patients. Surgical morbidity associated with downgraded AVMs is reduced to that of postradiosurgical/preoperative supplemented Spetzler-Martin grades, not their initial AVM grades.

Vago-glossopharyngeal neuralgia

Vago-glossopharyngeal neuralgiaActa Neurochir (2015) 157:311–321

Glossopharyngeal neuralgia (GPN), or better named vago-glossopharyngeal neuralgia (VGPN), is a rare disorder amounting to 1 % of the incidence of trigeminal neuralgia (TN). Pain is paroxysmal, of the electrical shooting type, and mainly provoked by stimulation of the pharynx or deep throat, especially during swallowing. Due to its rarity, VGPN is often misdiagnosed. The front line of medical treatment is based on anticonvulsants. Surgery should be considered when the pain is refractory to medications. In most patients, the cause is neurovascular conflict on root entry zone (REZ) or midcistern portion, of the IXth and/or Xth cranial nerves. Compressive vessels can be evidenced by means of a high sensibility and a high specificity resolution MR imaging in most centers.

Present consensus is that the first option of neurosurgical treatment be microvascular decompression. In patients with precarious general conditions, stereotactic radiosurgery may be considered. Also, thermo-rhizotomy at the pars nervosa of foramen jugularis or tractotomy-nucleotomy at brainstem may be alternatives, but these methods entail a significant risk of deficits.

In this article, the authors reviewed the main literature series on neurosurgical treatments of this disease.

Gamma Knife radiosurgery for meningiomas arising from the tentorium

Gamma Knife radiosurgery for meningiomas arising from the tentorium- a 22-year experienceJ Neurooncol (2015) 121:129–134

In order to evaluate long term clinical and imaging outcomes, the authors retrospectively reviewed our 22-year experience using stereotactic radiosurgery (SRS) for tentorial meningiomas.

Thirty-nine patients with tentorial meningiomas underwent SRS using various Gamma Knife technologies between 1988 and 2010. The most common presenting symptoms were headache, dizziness or disequilibrium, and ataxia. The median tumor volume was 4.6 cm3 (range 0.5–36.6 cm3) and the median radiation dose to the tumor margin was 14 Gy (range 8.9–18 Gy). The median follow-up period was 41 months (range 6–183 months).

At the last imaging follow-up, tumor volumes decreased in 22 patients (57 %), remained stable in 13 patients (33 %), and increased in 4 patients (10 %). The progression-free survival after SRS was 97 % at 1 year, and 92 % at 5 years. At the last clinical followup, 35 patients (90 %) showed no change in symptoms, 1 patient (2 %) showed improvement of their neurologic symptom, and 3 patients (8 %) demonstrated worsening symptoms. The rate of symptom worsening after SRS was 5 % at 1 year, and 10 % at 5 years. Asymptomatic peritumoral edema after SRS occurred in 2 patients (5 %). Symptomatic adverse radiation effect developed in 2 patients (5 %).

SRS for tentorial meningiomas provided long-term effective tumor control and a low risk of radiation related complications.