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I. Jonathan Pomeraniec, Dale Ding, Robert M. Starke, Kenneth C. Liu, E. Kelly Mrachek, M. Beatriz Lopes and Jason P. Sheehan

OBJECTIVE

Stereotactic radiosurgery (SRS) is a commonly employed treatment modality for brain arteriovenous malformations (AVMs). However, due to the low frequency of delayed cyst formation after AVM SRS, as well as the prolonged time interval between treatment and its occurrence, the characteristics of post-SRS cyst formation are not well defined. Therefore, the aims of this retrospective cohort study are to determine the rate of cyst formation after SRS for AVMs, identify predictive factors, and evaluate the clinical sequelae of post-SRS cysts.

METHODS

The authors analyzed an SRS database for AVM patients who underwent SRS at the University of Virginia and identified those who developed post-SRS cysts. Statistical analyses were performed to determine predictors of post-SRS cyst formation and the effect of cyst formation on new or worsening seizures after SRS.

RESULTS

The study cohort comprised 1159 AVM patients treated with SRS; cyst formation occurred in 17 patients (post-SRS cyst rate of 1.5%). Compared with patients who did not develop post-SRS cysts, those with cyst formation were treated with a greater number of radiosurgical isocenters (mean 3.8 vs 2.8, p = 0.047), had a longer follow-up (mean 132 vs 71 months, p < 0.001), were more likely to develop radiological radiation-induced changes (RIC) (64.7% vs 36.1%, p = 0.021), and had a longer duration of RIC (57 vs 21 months, p < 0.001). A higher number of isocenters (p = 0.014), radiological RIC (p = 0.002), and longer follow-up (p = 0.034) were found to be independent predictors of post-SRS cyst formation in the multivariate analysis. There was a trend toward a significant association between cyst formation and new or worsening seizures in univariate analysis (p = 0.054).

CONCLUSIONS

Patients with greater nidal complexity appear to be more prone to post-SRS cyst formation. The findings of this study emphasize the importance of long-term follow-up for patients who have undergone AVM SRS, even after nidal obliteration is achieved. Post-SRS cysts may be epileptogenic, although seizure outcomes after AVM SRS are multifactorial.

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Adeel Ilyas, Ching-Jen Chen, Dale Ding, Panagiotis Mastorakos, Davis G. Taylor, I. Jonathan Pomeraniec, Cheng-Chia Lee and Jason Sheehan

OBJECTIVE

Cyst formation can occasionally occur after stereotactic radiosurgery (SRS) for brain arteriovenous malformations (AVMs). Given the limited data regarding post-SRS cyst formation in patients with AVM, the time course, natural history, and management of this delayed complication are poorly defined. The aim of this systematic review was to determine the incidence, time course, and optimal management of cyst formation after SRS for AVMs.

METHODS

A literature review was performed using PubMed to identify studies reporting cyst formation in AVM patients treated with SRS. Baseline and outcomes data, including the incidence and management of post-SRS cysts, were extracted from each study that reported follow-up duration. The mean time to cyst formation was calculated from the subset of studies that reported individual patient data.

RESULTS

Based on pooled data from 22 studies comprising the incidence analysis, the overall rate of post-SRS cyst formation was 3.0% (78/2619 patients). Among the 26 post-SRS cyst patients with available AVM obliteration data, nidal obliteration was achieved in 20 (76.9%). Of the 64 cyst patients with available symptomatology and management data, 21 (32.8%) were symptomatic; 21 cysts (32.8%) were treated with surgical intervention, whereas the remaining 43 (67.2%) were managed conservatively. Based on a subset of 19 studies reporting individual time-to-cyst-formation data from 63 patients, the mean latency period to post-SRS cyst formation was 78 months (6.5 years).

CONCLUSIONS

Cyst formation is an uncommon complication after SRS for AVMs, with a relatively long latency period. The majority of post-SRS cysts are asymptomatic and can be managed conservatively, although enlarging or symptomatic cysts may require surgical intervention. Long-term follow-up of AVM patients is crucial to the appropriate diagnosis and management of post-SRS cysts.

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Dylan Russell, Travis Peck, Dale Ding, Ching-Jen Chen, Davis G. Taylor, Robert M. Starke, Cheng-Chia Lee and Jason P. Sheehan

OBJECTIVE

Embolization of brain arteriovenous malformations (AVMs) prior to stereotactic radiosurgery (SRS) has been reported to negatively affect obliteration rates. The goal of this systematic review and meta-analysis was to compare the outcomes of AVMs treated with embolization plus SRS (E+SRS group) and those of AVMs treated with SRS alone (SRS group).

METHODS

A literature review was performed using PubMed to identify studies with 10 or more AVM patients and obliteration data for both E+SRS and SRS groups. A meta-analysis was performed to compare obliteration rates between the E+SRS and SRS groups.

RESULTS

Twelve articles comprising 1716 patients were eligible for analysis. Among the patients with radiological follow-up data, complete obliteration was achieved in 48.4% of patients (330/681) in the E+SRS group compared with 62.7% of patients (613/978) in the SRS group. A meta-analysis of the pooled data revealed that the obliteration rate was significantly lower in the E+SRS group (OR 0.51, 95% CI 0.41–0.64, p < 0.00001). Symptomatic adverse radiation effects were observed in 6.6% (27/412 patients) and 11.1% (48/433 patients) of the E+SRS and SRS groups, respectively. The annual post-SRS hemorrhage rate was 2.0%–6.5% and 0%–2.0% for the E+SRS and SRS groups, respectively. The rates of permanent morbidity were 0%–6.7% and 0%–13.5% for the E+SRS and SRS groups, respectively.

CONCLUSIONS

Arteriovenous malformation treatment with combined embolization and SRS is associated with lower obliteration rates than those with SRS treatment alone. However, this comparison does not fully account for differences in the initial AVM characteristics in the E+SRS group as compared with those in the SRS group. Further studies are warranted to address these limitations.

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Mohana Rao Patibandla, Dale Ding, Hideyuki Kano, Robert M. Starke, John Y. K. Lee, David Mathieu, Jamie Whitesell, John T. Pierce, Paul P. Huang, Douglas Kondziolka, Caleb Feliciano, Rafael Rodriguez-Mercado, Luis Almodovar, Inga S. Grills, Danilo Silva, Mahmoud Abbassy, Symeon Missios, Gene H. Barnett, L. Dade Lunsford and Jason P. Sheehan

OBJECTIVE

The role of and technique for stereotactic radiosurgery (SRS) in the management of arteriovenous malformations (AVMs) have evolved over the past four decades. The aim of this multicenter, retrospective cohort study was to compare the SRS outcomes of AVMs treated during different time periods.

METHODS

The authors selected patients with AVMs who underwent single-session SRS at 8 different centers from 1988 to 2014 with follow-up ≥ 6 months. The SRS eras were categorized as early (1988–2000) or modern (2001–2014). Statistical analyses were performed to compare the baseline characteristics and outcomes of the early versus modern SRS eras. Favorable outcome was defined as AVM obliteration, no post-SRS hemorrhage, and no permanently symptomatic radiation-induced changes (RICs).

RESULTS

The study cohort comprised 2248 patients with AVMs, including 1584 in the early and 664 in the modern SRS eras. AVMs in the early SRS era were significantly smaller (p < 0.001 for maximum diameter and volume), and they were treated with a significantly higher radiosurgical margin dose (p < 0.001). The obliteration rate was significantly higher in the early SRS era (65% vs 51%, p < 0.001), and earlier SRS treatment period was an independent predictor of obliteration in the multivariate analysis (p < 0.001). The rates of post-SRS hemorrhage and radiological, symptomatic, and permanent RICs were not significantly different between the two groups. Favorable outcome was achieved in a significantly higher proportion of patients in the early SRS era (61% vs 45%, p < 0.001), but the earlier SRS era was not statistically significant in the multivariate analysis (p = 0.470) with favorable outcome.

CONCLUSIONS

Despite considerable advances in SRS technology, refinement of AVM selection, and contemporary multimodality AVM treatment, the study failed to observe substantial improvements in SRS favorable outcomes or obliteration for patients with AVMs over time. Differences in baseline AVM characteristics and SRS treatment parameters may partially account for the significantly lower obliteration rates in the modern SRS era. However, improvements in patient selection and dose planning are necessary to optimize the utility of SRS in the contemporary management of AVMs.

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Mohana Rao Patibandla, Dale Ding, Hideyuki Kano, Zhiyuan Xu, John Y. K. Lee, David Mathieu, Jamie Whitesell, John T. Pierce, Paul P. Huang, Douglas Kondziolka, Caleb Feliciano, Rafael Rodriguez-Mercado, Luis Almodovar, Inga S. Grills, Danilo Silva, Mahmoud Abbassy, Symeon Missios, Gene H. Barnett, L. Dade Lunsford and Jason P. Sheehan

OBJECTIVE

Due to the complexity of Spetzler-Martin (SM) Grade IV–V arteriovenous malformations (AVMs), the management of these lesions remains controversial. The aims of this multicenter, retrospective cohort study were to evaluate the outcomes after single-session stereotactic radiosurgery (SRS) for SM Grade IV–V AVMs and determine predictive factors.

METHODS

The authors retrospectively pooled data from 233 patients (mean age 33 years) with SM Grade IV (94.4%) or V AVMs (5.6%) treated with single-session SRS at 8 participating centers in the International Gamma Knife Research Foundation. Pre-SRS embolization was performed in 71 AVMs (30.5%). The mean nidus volume, SRS margin dose, and follow-up duration were 9.7 cm3, 17.3 Gy, and 84.5 months, respectively. Statistical analyses were performed to identify factors associated with post-SRS outcomes.

RESULTS

At a mean follow-up interval of 84.5 months, favorable outcome was defined as AVM obliteration, no post-SRS hemorrhage, and no permanently symptomatic radiation-induced changes (RIC) and was achieved in 26.2% of patients. The actuarial obliteration rates at 3, 7, 10, and 12 years were 15%, 34%, 37%, and 42%, respectively. The annual post-SRS hemorrhage rate was 3.0%. Symptomatic and permanent RIC occurred in 10.7% and 4% of the patients, respectively. Only larger AVM diameter (p = 0.04) was found to be an independent predictor of unfavorable outcome in the multivariate logistic regression analysis. The rate of favorable outcome was significantly lower for unruptured SM Grade IV–V AVMs compared with ruptured ones (p = 0.042). Prior embolization was a negative independent predictor of AVM obliteration (p = 0.024) and radiologically evident RIC (p = 0.05) in the respective multivariate analyses.

CONCLUSIONS

In this multi-institutional study, single-session SRS had limited efficacy in the management of SM Grade IV–V AVMs. Favorable outcome was only achieved in a minority of unruptured SM Grade IV–V AVMs, which supports less frequent utilization of SRS for the management of these lesions. A volume-staged SRS approach for large AVMs represents an alternative approach for high-grade AVMs, but it requires further investigation.

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Panagiotis Mastorakos, Michael A. Hays, James P. Caruso, Ching-Jen Chen, Dale Ding, Davis G. Taylor, M. Beatriz Lopes and Mark E. Shaffrey

Optic nerve glioblastoma is a rare entity that usually presents with rapidly progressive vision loss, which eventually results in blindness and, ultimately, death. As with malignant gliomas in other anatomical locations, local recurrence is common. Isolated rapid changes in vision, atypical neuroimaging findings, and the rarity of optic nerve glioblastoma may render diagnosis challenging and, thus, delay treatment. The authors present a case of optic nerve glioblastoma that was treated with subtotal resection followed by adjuvant radiation therapy and temozolomide. One year following the initial diagnosis, the patient developed a right cerebellar lesion, which was histopathologically consistent with glioblastoma. This case represents the first report of transtentorial dissemination of an optic nerve glioblastoma. In addition, the authors reviewed the literature regarding optic nerve glioblastomas. Of the 73 previously reported cases of malignant optic nerve gliomas, 32 were histologically confirmed glioblastomas. The mean age at diagnosis was 62 years, and 56% were male; the median survival was 7 months. A malignant glioma of the optic nerve should be considered in the differential diagnosis of a patient with rapidly progressive visual loss. However, the incidence of optic nerve glioblastoma is exceedingly low.

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Robert M. Starke, Hideyuki Kano, Dale Ding, John Y. K. Lee, David Mathieu, Jamie Whitesell, John T. Pierce, Paul P. Huang, Douglas Kondziolka, Chun-Po Yen, Caleb Feliciano, Rafael Rodgriguez-Mercado, Luis Almodovar, Daniel R. Pieper, Inga S. Grills, Danilo Silva, Mahmoud Abbassy, Symeon Missios, Gene H. Barnett, L. Dade Lunsford and Jason P. Sheehan

OBJECTIVE

In this multicenter study, the authors reviewed the results following Gamma Knife radiosurgery (GKRS) of cerebral arteriovenous malformations (AVMs), determined predictors of outcome, and assessed predictive value of commonly used grading scales based upon this large cohort with long-term follow-up.

METHODS

Data from a cohort of 2236 patients undergoing GKRS for cerebral AVMs were compiled from the International Gamma Knife Research Foundation. Favorable outcome was defined as AVM obliteration and no posttreatment hemorrhage or permanent symptomatic radiation-induced complications. Patient and AVM characteristics were assessed to determine predictors of outcome, and commonly used grading scales were assessed.

RESULTS

The mean maximum AVM diameter was 2.3 cm, with a mean volume of 4.3 cm3. A mean margin dose of 20.5 Gy was delivered. Mean follow-up was 7 years (range 1–20 years). Overall obliteration was 64.7%. Post-GRKS hemorrhage occurred in 165 patients (annual risk 1.1%). Radiation-induced imaging changes occurred in 29.2%; 9.7% were symptomatic, and 2.7% had permanent deficits. Favorable outcome was achieved in 60.3% of patients. Patients with prior nidal embolization (OR 2.1, p < 0.001), prior AVM hemorrhage (OR 1.3, p = 0.007), eloquent location (OR 1.3, p = 0.029), higher volume (OR 1.01, p < 0.001), lower margin dose (OR 0.9, p < 0.001), and more isocenters (OR 1.1, p = 0.011) were more likely to have unfavorable outcomes in multivariate analysis. The Spetzler-Martin grade and radiosurgery-based AVM score predicted outcome, but the Virginia Radiosurgery AVM Scale provided the best assessment.

CONCLUSIONS

GKRS for cerebral AVMs achieves obliteration and avoids permanent complications in the majority of patients. Patient, AVM, and treatment parameters can be used to predict long-term outcomes following radiosurgery.

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Gautam U. Mehta, Michael J. Feldman, Herui Wang, Dale Ding and Prashant Chittiboina

The presence of vestibular schwannomas has long been considered an exclusion criterion for the diagnosis of schwannomatosis. Recently, 2 cases of vestibular schwannoma were reported in patients with schwannomatosis, leading to a revision of the diagnostic criteria for this genetic disorder. Overall, the relative infrequency of vestibular schwannomas in schwannomatosis is unexplained, and the genetics of this uncommon phenomenon have not been described. The authors report on a family with clinical manifestations consistent with schwannomatosis, including 4 affected members, that was identified as having an affected member harboring a unilateral cerebellopontine angle mass with extension into the internal auditory canal. Radiologically, this mass was consistent with a vestibular schwannoma and resulted in a symptomatic change in ipsilateral hearing (word recognition 86% at 52 dB) and increased latency of the wave I–V interval on auditory brainstem response testing. The patient was found to be negative for a germline mutation of NF2 and LZTR1, and her affected mother was found to harbor neither NF2 nor SMARCB1 mutations on genetic testing. Although vestibular schwannomas have been classically considered to not occur in the setting of schwannomatosis, this patient with schwannomatosis and a vestibular schwannoma further confirms that schwannomas can occur on the vestibular nerve in this syndrome. Further, this is the first such case found to be negative for a mutation on the LZTR1 gene.