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Oral Presentations 2014 AANS Annual Scientific Meeting San Francisco, California • April 5–9, 2014

Published online June 1, 2015; DOI: 10.3171/2015.6.JNS.AANS2014abstracts

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Stereotactic radiosurgery for intracranial hemangioblastomas: a retrospective international outcome study

Hideyuki Kano, Takashi Shuto, Yoshiyasu Iwai, Jason Sheehan, Masaaki Yamamoto, Heyoung L. McBride, Mitsuya Sato, Toru Serizawa, Shoji Yomo, Akihito Moriki, Yukihiko Kohda, Byron Young, Satoshi Suzuki, Hiroyuki Kenai, Christopher Duma, Yasuhiro Kikuchi, David Mathieu, Atsuya Akabane, Osamu Nagano, Douglas Kondziolka, and L. Dade Lunsford

OBJECT

The purpose of this study was to evaluate the role of stereotactic radiosurgery (SRS) in the management of intracranial hemangioblastomas.

METHODS

Six participating centers of the North American Gamma Knife Consortium and 13 Japanese Gamma Knife centers identified 186 patients with 517 hemangioblastomas who underwent SRS. Eighty patients had 335 hemangioblastomas associated with von Hippel–Lindau disease (VHL) and 106 patients had 182 sporadic hemangioblastomas. The median target volume was 0.2 cm3 (median diameter 7 mm) in patients with VHL and 0.7 cm3 (median diameter 11 mm) in those with sporadic hemangioblastoma. The median margin dose was 18 Gy in VHL patients and 15 Gy in those with sporadic hemangioblastomas.

RESULTS

At a median of 5 years (range 0.5–18 years) after treatment, 20 patients had died of intracranial disease progression and 9 patients had died of other causes. The overall survival after SRS was 94% at 3 years, 90% at 5 years, and 74% at 10 years. Factors associated with longer survival included younger age, absence of neurological symptoms, fewer tumors, and higher Karnofsky Performance Status. Thirty-three (41%) of the 80 patients with VHL developed new tumors and 17 (16%) of the106 patients with sporadic hemangioblastoma had recurrences of residual tumor from the original tumor. The 5-year rate of developing a new tumor was 43% for VHL patients, and the 5-year rate of developing a recurrence of residual tumor from the original tumor was 24% for sporadic hemangioblastoma patients. Factors associated with a reduced risk of developing a new tumor or recurrences of residual tumor from the original tumor included younger age, fewer tumors, and sporadic rather than VHL-associated hemangioblastomas. The local tumor control rate for treated tumors was 92% at 3 years, 89% at 5 years, and 79% at 10 years. Factors associated with an improved local tumor control rate included VHL-associated hemangioblastoma, solid tumor, smaller tumor volume, and higher margin dose. Thirteen patients (7%) developed adverse radiation effects (ARE) after SRS, and one of these patients died due to ARE.

CONCLUSIONS

When either sporadic or VHL-associated tumors were observed to grow on serial imaging studies, SRS provided tumor control in 79%–92% of tumors.

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Intracranial inertial cavitation threshold and thermal ablation lesion creation using MRI-guided 220-kHz focused ultrasound surgery: preclinical investigation

Zhiyuan Xu, Carissa Carlson, John Snell, Matt Eames, Arik Hananel, M. Beatriz Lopes, Prashant Raghavan, Cheng-Chia Lee, Chun-Po Yen, David Schlesinger, Neal F. Kassell, Jean-Francois Aubry, and Jason Sheehan

OBJECT

In biological tissues, it is known that the creation of gas bubbles (cavitation) during ultrasound exposure is more likely to occur at lower rather than higher frequencies. Upon collapsing, such bubbles can induce hemorrhage. Thus, acoustic inertial cavitation secondary to a 220-kHz MRI-guided focused ultrasound (MRgFUS) surgery is a serious safety issue, and animal studies are mandatory for laying the groundwork for the use of low-frequency systems in future clinical trials. The authors investigate here the in vivo potential thresholds of MRgFUS-induced inertial cavitation and MRgFUS-induced thermal coagulation using MRI, acoustic spectroscopy, and histology.

METHODS

Ten female piglets that had undergone a craniectomy were sonicated using a 220-kHz transcranial MRgFUS system over an acoustic energy range of 5600–14,000 J. For each piglet, a long-duration sonication (40-second duration) was performed on the right thalamus, and a short sonication (20-second duration) was performed on the left thalamus. An acoustic power range of 140–300 W was used for long-duration sonications and 300–700 W for short-duration sonications. Signals collected by 2 passive cavitation detectors were stored in memory during each sonication, and any subsequent cavitation activity was integrated within the bandwidth of the detectors. Real-time 2D MR thermometry was performed during the sonications. T1-weighted, T2-weighted, gradient-recalled echo, and diffusion-weighted imaging MRI was performed after treatment to assess the lesions. The piglets were killed immediately after the last series of posttreatment MR images were obtained. Their brains were harvested, and histological examinations were then performed to further evaluate the lesions.

RESULTS

Two types of lesions were induced: thermal ablation lesions, as evidenced by an acute ischemic infarction on MRI and histology, and hemorrhagic lesions, associated with inertial cavitation. Passive cavitation signals exhibited 3 main patterns identified as follows: no cavitation, stable cavitation, and inertial cavitation. Low-power and longer sonications induced only thermal lesions, with a peak temperature threshold for lesioning of 53°C. Hemorrhagic lesions occurred only with high-power and shorter sonications. The sizes of the hemorrhages measured on macroscopic histological examinations correlated with the intensity of the cavitation activity (R2 = 0.74). The acoustic cavitation activity detected by the passive cavitation detectors exhibited a threshold of 0.09 V·Hz for the occurrence of hemorrhages.

CONCLUSIONS

This work demonstrates that 220-kHz ultrasound is capable of inducing a thermal lesion in the brain of living swines without hemorrhage. Although the same acoustic energy can induce either a hemorrhage or a thermal lesion, it seems that low-power, long-duration sonication is less likely to cause hemorrhage and may be safer. Although further study is needed to decrease the likelihood of ischemic infarction associated with the 220-kHz ultrasound, the threshold established in this work may allow for the detection and prevention of deleterious cavitations.

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The results of a third Gamma Knife procedure for recurrent trigeminal neuralgia

Zachary J. Tempel, Srinivas Chivukula, Edward A. Monaco III, Greg Bowden, Hideyuki Kano, Ajay Niranjan, Edward F. Chang, Penny K. Sneed, Anthony M. Kaufmann, Jason Sheehan, David Mathieu, and L. Dade Lunsford

OBJECT

Gamma Knife radiosurgery (GKRS) is the least invasive treatment option for medically refractory, intractable trigeminal neuralgia (TN) and is especially valuable for treating elderly, infirm patients or those on anticoagulation therapy. The authors reviewed pain outcomes and complications in TN patients who required 3 radiosurgical procedures for recurrent or persistent pain.

METHODS

A retrospective review of all patients who underwent 3 GKRS procedures for TN at 4 participating centers of the North American Gamma Knife Consortium from 1995 to 2012 was performed. The Barrow Neurological Institute (BNI) pain score was used to evaluate pain outcomes.

RESULTS

Seventeen patients were identified; 7 were male and 10 were female. The mean age at the time of last GKRS was 79.6 years (range 51.2–95.6 years). The TN was Type I in 16 patients and Type II in 1 patient. No patient suffered from multiple sclerosis. Eight patients (47.1%) reported initial complete pain relief (BNI Score I) following their third GKRS and 8 others (47.1%) experienced at least partial relief (BNI Scores II–IIIb). The average time to initial response was 2.9 months following the third GKRS. Although 3 patients (17.6%) developed new facial sensory dysfunction following primary GKRS and 2 patients (11.8%) experienced new or worsening sensory disturbance following the second GKRS, no patient sustained additional sensory disturbances after the third procedure. At a mean follow-up of 22.9 months following the third GKRS, 6 patients (35.3%) reported continued Score I complete pain relief, while 7 others (41.2%) reported pain improvement (BNI Scores II–IIIb). Four patients (23.5%) suffered recurrent TN following the third procedure at a mean interval of 19.1 months.

CONCLUSIONS

A third GKRS resulted in pain reduction with a low risk of additional complications in most patients with medically refractory and recurrent, intractable TN. In patients unsuitable for other microsurgical or percutaneous strategies, especially those receiving long-term oral anticoagulation or antiplatelet agents, GKRS repeated for a third time was a satisfactory, low risk option.

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Gamma Knife surgery for incidental cerebral arteriovenous malformations

Clinical article

Chun-Po Yen, Dale Ding, Ching-Hsiao Cheng, Robert M. Starke, Mark Shaffrey, and Jason Sheehan

Object

A relatively benign natural course of unruptured cerebral arteriovenous malformations (AVMs) has recently been recognized, and the decision to treat incidentally found AVMs has been questioned. This study aims to evaluate the long-term imaging and clinical outcomes of patients with asymptomatic, incidentally discovered AVMs treated with Gamma Knife surgery (GKS).

Methods

Thirty-one patients, each with an incidentally diagnosed AVM, underwent GKS between 1989 and 2009. The nidus volumes ranged from 0.3 to 11.1 cm3 (median 3.2 cm3). A margin dose between 15 and 26 Gy (median 20 Gy) was used to treat the AVMs. Four patients underwent repeat GKS for still-patent AVM residuals after the initial GKS procedure. Clinical follow-up ranged from 24 to 196 months, with a mean of 78 months (median 51 months) after the initial GKS.

Results

Following GKS, 19 patients (61.3%) had a total AVM obliteration on angiography. In 7 patients (22.6%), no flow voids were observed on MRI but angiographic confirmation was not available. In 5 patients (16.1%), the AVMs remained patent. A small nidus volume was significantly associated with increased AVM obliteration rate. Thirteen patients (41.9%) developed radiation-induced imaging changes: 11 were asymptomatic (35.5%), 1 had only headache (3.2%), and 1 developed seizure and neurological deficits (3.2%). Two patients each had 1 hemorrhage during the latency period (116.5 risk years), yielding an annual hemorrhage rate of 1.7% before AVM obliteration.

Conclusions

The decision to treat asymptomatic AVMs, and if so, which treatment approach to use, remain the subject of debate. GKS as a minimally invasive procedure appears to achieve a reasonable outcome with low procedure-related morbidity. In those patients with incidental AVMs, the benefits as well as the risks of radiosurgical intervention will only be fully defined with long-term follow-up.

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Letter to the Editor: Neurosurgery in obsessive-compulsive disorder

Sheng-Tzung Tsai, Hsin-Chi Tsai, Chung-Chih Kuo, Hsiang-Yi Hung, Chien-Hui Lee, and Shin-Yuan Chen

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Impact of target location on the response of trigeminal neuralgia to stereotactic radiosurgery

Clinical article

Zhiyuan Xu, David Schlesinger, Krisztina Moldovan, Colin Przybylowski, Xingwen Sun, Cheng-Chia Lee, Chun-Po Yen, and Jason Sheehan

Object

The authors evaluate the impact of target location on the rate of pain relief (PR) in patients with intractable trigeminal neuralgia (TN) undergoing stereotactic radiosurgery (SRS).

Methods

The authors conducted a retrospective review of 99 patients with idiopathic TN who were identified from a prospectively maintained database and were treated with SRS targeting the dorsal root entry zone with a maximum dose of 80 Gy. Targeting of the more proximal portion of a trigeminal nerve with the 50% isodose line overlapping the brainstem was performed in 36 patients (proximal group). In a matched group, 63 patients received SRS targeting the 20% isodose line tangential to the emergence of the brainstem (distal group). The median follow-up time was 33 months (range 6–124 months).

Results

The actuarial rate of maintenance of Barrow Neurological Institute (BNI) Pain Score I–IIIa was attained in 89% of patients at 1 year, 81% at 2 years, and 69% at 4 years, respectively, after SRS. Kaplan-Meier analysis revealed that durability of PR was only associated with the proximal location of the radiosurgical target (log-rank test, p = 0.018). Radiosurgery-induced facial numbness (BNI Score II or III) developed in 35 patients, which was significantly more frequent in the proximal group (19 patients [53%] compared with 16 [25%] in the distal group [p = 0.015]).

Conclusions

The radiosurgical target appears to affect the duration of pain relief in patients with idiopathic trigeminal neuralgia with the target closer to the brainstem affording extended pain relief. However, the proximal SRS target was also associated with an increased risk of mild to moderate facial numbness.

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The accuracy of predicting survival in individual patients with cancer

Clinical article

Douglas Kondziolka, Phillip V. Parry, L. Dade Lunsford, Hideyuki Kano, John C. Flickinger, Susan Rakfal, Yoshio Arai, Jay S. Loeffler, Stephen Rush, Jonathan P. S. Knisely, Jason Sheehan, William Friedman, Ahmad A. Tarhini, Lanie Francis, Frank Lieberman, Manmeet S. Ahluwalia, Mark E. Linskey, Michael McDermott, Paul Sperduto, and Roger Stupp

Object

Estimating survival time in cancer patients is crucial for clinicians, patients, families, and payers. To provide appropriate and cost-effective care, various data sources are used to provide rational, reliable, and reproducible estimates. The accuracy of such estimates is unknown.

Methods

The authors prospectively estimated survival in 150 consecutive cancer patients (median age 62 years) with brain metastases undergoing radiosurgery. They recorded cancer type, number of brain metastases, neurological presentation, extracranial disease status, Karnofsky Performance Scale score, Recursive Partitioning Analysis class, prior whole-brain radiotherapy, and synchronous or metachronous presentation. Finally, the authors asked 18 medical, radiation, or surgical oncologists to predict survival from the time of treatment.

Results

The actual median patient survival was 10.3 months (95% CI 6.4–14). The median physician-predicted survival was 9.7 months (neurosurgeons = 11.8 months, radiation oncologists = 11.0 months, and medical oncologist = 7.2 months). For patients who died before 10 months, both neurosurgeons and radiation oncologists generally predicted survivals that were more optimistic and medical oncologists that were less so, although no group could accurately predict survivors alive at 14 months. All physicians had individual patient survival predictions that were incorrect by as much as 12–18 months, and 14 of 18 physicians had individual predictions that were in error by more than 18 months. Of the 2700 predictions, 1226 (45%) were off by more than 6 months and 488 (18%) were off by more than 12 months.

Conclusions

Although crucial, predicting the survival of cancer patients is difficult. In this study all physicians were unable to accurately predict longer-term survivors. Despite valuable clinical data and predictive scoring techniques, brain and systemic management often led to patient survivals well beyond estimated survivals.

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Comprehensive analysis of neurobehavior associated with histomorphological alterations in a chronic constrictive nerve injury model through use of the CatWalk XT system

Laboratory investigation

Chien-Yi Chiang, Meei-Ling Sheu, Fu-Chou Cheng, Chun-Jung Chen, Hong-Lin Su, Jason Sheehan, and Hung-Chuan Pan

Object

Neuropathic pain is debilitating, and when chronic, it significantly affects the patient physically, psychologically, and socially. The neurobehavior of animals used as a model for chronic constriction injury seems analogous to the neurobehavior of humans with neuropathic pain. However, no data depicting the severity of histomorphological alterations of the nervous system associated with graded changes in neurobehavior are available. To determine the severity of histomorphological alteration related to neurobehavior, the authors created a model of chronic constrictive injury of varying intensity in rats and used the CatWalk XT system to evaluate neurobehavior.

Methods

A total of 60 Sprague-Dawley rats, weighing 250–300 g each, were randomly assigned to 1 of 5 groups that would receive sham surgery or 1, 2, 3, or 4 ligatures of 3-0 chromic gut loosely ligated around the left sciatic nerve. Neurobehavior was assessed by CatWalk XT, thermal hyperalgesia, and mechanic allodynia before injury and periodically after injury. The nerve tissue from skin to dorsal spinal cord was obtained for histomorphological analysis 1 week after injury, and brain evoked potentials were analyzed 4 weeks after injury.

Results.

Significant differences in expression of nerve growth factor existed in skin, and the differences were associated with the intensity of nerve injury. After injury, expression of cluster of differentiation 68 and tumor necrosis factor–α was increased, and expression of S100 protein in the middle of the injured nerve was decreased. Increased expression of synaptophysin in the dorsal root ganglion and dorsal spinal cord correlated with the intensity of injury. The amplitude of sensory evoked potential increased with greater severity of nerve damage. Mechanical allodynia and thermal hyperalgesia did not differ significantly among treatment groups at various time points. CatWalk XT gait analysis indicated significant differences for print areas, maximum contact maximum intensity, stand phase, swing phase, single stance, and regular index, with sham and/or intragroup comparisons.

Conclusions.

Histomorphological and electrophysiological alterations were associated with severity of nerve damage. Subtle neurobehavioral differences were detected by the CatWalk XT system but not by mechanical allodynia or thermal hyperalgesia. Thus, the CatWalk XT system should be a useful tool for monitoring changes in neuropathic pain, especially subtle alterations.

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Editorial: Arteriovenous malformations

Jason Sheehan