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Nasser Mohammed, Yi-Chieh Hung, Thomas J. Eluvathingal Muttikkal, Roy C. Bliley, Zhiyuan Xu and Jason P. Sheehan

OBJECTIVE

The motor root of the trigeminal nerve runs close to the sensory root and receives considerable radiation during Gamma Knife radiosurgery (GKRS) for trigeminal neuralgia (TN). The object of this study was to evaluate via MRI the changes in the muscles of mastication before and after upfront GKRS in patients with idiopathic TN.

METHODS

In this single-institution retrospective cohort study, all patients with idiopathic unilateral TN treated with primary GKRS at the University of Virginia in the period from 2007 to 2017 were included provided that they had pre- and post-GKRS MRI data. The thicknesses of the temporalis, pterygoid, and masseter muscles were measured on both pre- and post-GKRS MRI in a blinded fashion. Changes in the muscles like fatty infiltration, MRI signal, or atrophy were noted.

RESULTS

Among the 68 patients eligible for inclusion in the study, 136 temporalis muscles, 136 medial pterygoid muscles, 136 lateral pterygoid muscles, and 136 masseter muscles were assessed. A subset of patients was found to have muscle atrophy even prior to GKRS. Pre-GKRS atrophy of the masseter, medial pterygoid, lateral pterygoid, and temporalis muscles was seen in 18 (26%), 16 (24%), 9 (13%), and 16 (24%) patients, respectively. Logistic regression analysis showed that distribution of pain in the V3 territory (p = 0.01, OR 5.43, 95% CI 1.46–20.12) and significant pain on chewing (p = 0.02, OR 5.32, 95% CI 1.25–22.48) were predictive of pre-GKRS atrophy. Reversal of atrophy of these muscles occurred after GKRS in a majority of the patients. The incidence of new-onset permanent post-GKRS muscle atrophy was 1.5%. The median follow-up was 39 months (range 6–108 months).

CONCLUSIONS

A subset of patients with TN with significant pain on chewing have pre-GKRS disuse atrophy of the muscles of mastication. A reversal of the atrophy occurs in a majority of the patients following GKRS. New-onset motor neuropathy post-GKRS was rare.

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Yi-Chieh Hung, Cheng-Chia Lee, Kang-Du Liu, Wen-Yuh Chung, David Hung-Chi Pan and Huai-Che Yang

Object

The authors evaluated individual anatomical variations in the trigeminal nerves of patients with medically intractable trigeminal neuralgia and clarified the relationships among the variations, radiosurgical target locations, and the clinical outcomes after high-dose Gamma Knife surgery (GKS).

Methods

From 2006 through 2011, the authors conducted a retrospective review of 106 cases of primary or secondary trigeminal neuralgia consecutively treated with GKS targeting the dorsal root entry zone (DREZ) for which a maximal dose of 90 Gy and a 20% isodose line to the brainstem were used. A questionnaire was used to evaluate patients' pre- and post-GKS clinical conditions. To evaluate individual anatomical variations among trigeminal nerves, the authors used 3 parameters: the length of the trigeminal nerve in the cistern (nerve length), the length of the target between the radiation shot and the brainstem (targeting length), and the ratio between nerve length and targeting length (targeting ratio).

Results

The median length of the trigeminal nerves in the 106 patients was 9.6 mm (range 6.04−20.74 mm), the median targeting length was 3.8 mm (range 1.81−10.84 mm), and the median targeting ratio was 38% (range 13%− 80%). No statistically significant differences in pain relief and pain recurrence were detected among patients with these various nerve characteristics. However, radiation-induced facial hypesthesia correlated with nerve length and targeting ratio (p < 0.05) but not with absolute distance from the brainstem (targeting length).

Conclusions

In trigeminal neuralgia patients who received DREZ-targeted GKS, the rate of pain relief did not differ according to anatomical nerve variations. However, the frequency of facial hypesthesia was higher among patients in whom the nerve was longer (> 11 mm) or the targeting ratio was lower (< 36%). Adjusting the target according to the targeting ratio, especially for patients with longer nerves, can reduce facial hypesthesia and enable maintenance of effective pain control.

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Po-Chuan Hsieh, Yi-Ming Wu, Alvin Yi-Chou Wang, Ching-Chang Chen, Chien-Hung Chang, Shy-Chyi Chin, Tai-Wei Erich Wu, Chieh-Tsai Wu and Shih-Tseng Lee

OBJECTIVE

Diverse treatment results are observed in patients with poor-grade aneurysmal subarachnoid hemorrhage (aSAH). Significant initial perfusion compromise is thought to predict a worse treatment outcome, but this has scant support in the literature. In this cohort study, the authors correlate the treatment outcomes with a novel poor-outcome imaging predictor representing impaired cerebral perfusion on initial CT angiography (CTA).

METHODS

The authors reviewed the treatment results of 148 patients with poor-grade aSAH treated at a single tertiary referral center between 2007 and 2016. Patients with the “venous delay” phenomenon on initial CTA were identified. The outcome assessments used the modified Rankin Scale (mRS) at the 3rd month after aSAH. Factors that may have had an impact on outcome were retrospectively analyzed.

RESULTS

Compared with previously identified outcome predictors, the venous delay phenomenon on initial CTA was found to have the strongest correlation with posttreatment outcomes on both univariable (p < 0.0001) and multivariable analysis (OR 4.480, 95% CI 1.565–12.826; p = 0.0052). Older age and a higher Hunt and Hess grade at presentation were other factors that were associated with poor outcome, defined as an mRS score of 3 to 6.

CONCLUSIONS

The venous delay phenomenon on initial CTA can serve as an imaging predictor for worse functional outcome and may aid in decision making when treating patients with poor-grade aSAH.

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Yi-Chieh Hung, Nasser Mohammed, Thomas Jose Eluvathingal Muttikkal, Kathryn N. Kearns, Chelsea Eileen Li, Aditya Narayan, David Schlesinger, Zhiyuan Xu and Jason P. Sheehan

OBJECTIVE

The benefits and risks of pre–stereotactic radiosurgery (SRS) embolization have been reported in different studies. The goal of this study was to compare the long-term outcome of arteriovenous malformations (AVMs) treated with and without pre-SRS embolization.

METHODS

A database including 1159 patients with AVMs who underwent SRS was reviewed. The embolized group was selected by including AVMs with pre-SRS embolization, maximal diameter > 30 mm, and estimated volume > 8 ml. The nonembolized group was defined as AVMs treated by SRS alone with matched de novo nidus volume. Outcomes including incidences of favorable clinical outcome (obliteration without hemorrhage, cyst formation, worsening, or new seizures), obliteration, adverse effects, and angioarchitectural complexity were evaluated.

RESULTS

The study cohort comprised 17 patients in the embolized group (median AVM volume 17.0 ml) and 35 patients in the nonembolized group (median AVM volume 13.1 ml). The rates of obliteration (embolized cohort: 33%, 44%, and 56%; nonembolized cohort: 32%, 47%, and 47% at 4, 6, and 10 years, respectively) and favorable outcome were comparable between the 2 groups. However, the embolized group had a significantly higher incidence of repeat SRS (41% vs 23%, p = 0.012) and total procedures (median number of procedures 4 vs 1, p < 0.001), even with a significantly higher margin dose delivered at the first SRS (23 Gy vs 17 Gy, p < 0.001). The median angioarchitectural complexity score was reduced from 7 to 5 after embolization. Collateral flow and neovascularization were more frequently observed in the embolized nonobliterated AVMs.

CONCLUSIONS

Both embolization plus SRS and SRS alone were effective therapies for moderately large (8–39 ml) AVMs. Even with a significantly higher prescription dose at the time of initial SRS, the embolized group still required more procedures to reach final obliteration. The presence of collateral flow and neovascularization could be risk factors for a failure to obliterate following treatment.

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Cheng-Chia Lee, Huai-Che Yang, Ching-Jen Chen, Yi-Chieh Hung, Hsiu-Mei Wu, Cheng-Ying Shiau, Wan-Yuo Guo, David Hung-Chi Pan, Wen-Yuh Chung and Kang-Du Liu

Object

Although craniopharyngiomas are benign intracranial tumors, their high recurrence rates and intimate associations with surrounding neurovascular structures make gross tumor resection challenging. Stereotactic radiosurgery has been introduced as a valuable adjuvant therapy for recurrent or residual craniopharyngiomas. However, studies with large patient populations documenting long-term survival and progression-free survival rates are rare in the literature. The current study aims to report the long-term radiosurgical results and to define the prognostic factors in a large cohort of patients with a craniopharyngioma.

Methods

A total of 137 consecutive patients who underwent 162 sessions of Gamma Knife surgery (GKS) treatments at the Taipei Veterans General Hospital between 1993 and 2012 were analyzed. The patients' median age was 30.1 years (range 1.5–84.9 years), and the median tumor volume was 5.5 ml (range 0.2–28.4 ml). There were 23 solid (16.8%), 23 cystic (16.8%), and 91 mixed solid and cystic (66.4%) craniopharyngiomas. GKS was indicated for residual or recurrent craniopharyngiomas. The median radiation dose was 12 Gy (range 9.5–16.0 Gy) at a median isodose line of 55% (range 50%–78%).

Results

At a median imaging follow-up of 45.7 months after GKS, the rates of tumor control were 72.7%, 73.9%, and 66.3% for the solid, cystic, and mixed tumors, respectively. The actuarial progression-free survival rates plotted by the Kaplan-Meier method were 70.0% and 43.8% at 5 and 10 years after radiosurgery, respectively. After repeated GKS, the actuarial progression-free survival rates were increased to 77.3% and 61.2% at 5 and 10 years, respectively. The overall survival rates were 91.5% and 83.9% at the 5- and 10-year follow-ups, respectively. Successful GKS treatment can be predicted by tumor volume (p = 0.011). Among the 137 patients who had clinical follow-up, new-onset or worsened pituitary deficiencies were detected in 11 patients (8.0%). Two patients without tumor growth had a worsened visual field, and 1 patient had a new onset of third cranial nerve palsy.

Conclusions

The current study suggests that GKS is a relatively safe modality for the treatment of recurrent or residual craniopharyngiomas, and it is associated with improved tumor control and reduced in-field recurrence rates. Acceptable rates of complications occurred.

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Nasser Mohammed, Dale Ding, Yi-Chieh Hung, Zhiyuan Xu, Cheng-Chia Lee, Hideyuki Kano, Roberto Martínez-Álvarez, Nuria Martínez-Moreno, David Mathieu, Mikulas Kosak, Christopher P. Cifarelli, Gennadiy A. Katsevman, L. Dade Lunsford, Mary Lee Vance and Jason P. Sheehan

OBJECTIVE

The role of primary stereotactic radiosurgery (SRS) in patients with medically refractory acromegaly who are not operative candidates or who refuse resection is poorly understood. The aim of this multicenter, matched cohort study was to compare the outcomes of primary versus postoperative SRS for acromegaly.

METHODS

The authors reviewed an International Radiosurgery Research Foundation database of 398 patients with acromegaly who underwent SRS and categorized them into primary or postoperative cohorts. Patients in the primary SRS cohort were matched, in a 1:2 ratio, to those in the postoperative SRS cohort, and the outcomes of the 2 matched cohorts were compared.

RESULTS

The study cohort comprised 78 patients (median follow-up 66.4 months), including 26 and 52 in the matched primary and postoperative SRS cohorts, respectively. In the primary SRS cohort, the actuarial endocrine remission rates at 2 and 5 years were 20% and 42%, respectively. The Cox proportional hazards model showed that a lower pre-SRS insulin-like growth factor–1 level was predictive of initial endocrine remission (p = 0.03), whereas a lower SRS margin dose was predictive of biochemical recurrence after initial remission (p = 0.01). There were no differences in the rates of radiological tumor control (p = 0.34), initial endocrine remission (p = 0.23), biochemical recurrence after initial remission (p = 0.33), recurrence-free survival (p = 0.32), or hypopituitarism (p = 0.67) between the 2 matched cohorts.

CONCLUSIONS

Primary SRS has a reasonable benefit-to-risk profile for patients with acromegaly in whom resection is not possible, and it has similar outcomes to endocrinologically comparable patients who undergo postoperative SRS. SRS with medical therapy in the latent period can be used as an alternative to surgery in selected patients who cannot or do not wish to undergo resection.

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Yi-Chieh Hung, Cheng-Chia Lee, Huai-che Yang, Nasser Mohammed, Kathryn N. Kearns, Shi-Bin Sun, David Mathieu, Charles J. Touchette, Ahmet F. Atik, Inga S. Grills, Bryan Squires, Dale Ding, Brian J. Williams, Mehran B. Yusuf, Shiao Y. Woo, Roman Liscak, Jaromir Hanuska, Jay C. Shiao, Douglas Kondziolka, L. Dade Lunsford, Zhiyuan Xu and Jason P. Sheehan

OBJECTIVE

Central neurocytomas (CNs) are uncommon intraventricular tumors, and their rarity renders the risk-to-benefit profile of stereotactic radiosurgery (SRS) unknown. The aim of this multicenter, retrospective cohort study was to evaluate the outcomes of SRS for CNs and identify predictive factors.

METHODS

The authors retrospectively analyzed a cohort of patients with CNs treated with SRS at 10 centers between 1994 and 2018. Tumor recurrences were classified as local or distant. Adverse radiation effects (AREs) and the need for a CSF shunt were also evaluated.

RESULTS

The study cohort comprised 60 patients (median age 30 years), 92% of whom had undergone prior resection or biopsy and 8% received their diagnosis based on imaging alone. The median tumor volume and margin dose were 5.9 cm3 and 13 Gy, respectively. After a median clinical follow-up of 61 months, post-SRS tumor recurrence occurred in 8 patients (13%). The 5- and 10-year local tumor control rates were 93% and 87%, respectively. The 5- and 10-year progression-free survival rates were 89% and 80%, respectively. AREs were observed in 4 patients (7%), but only 1 was symptomatic (2%). Two patients underwent post-SRS tumor resection (3%). Prior radiotherapy was a predictor of distant tumor recurrence (p = 0.044). Larger tumor volume was associated with pre-SRS shunt surgery (p = 0.022).

CONCLUSIONS

Treatment of appropriately selected CNs with SRS achieves good tumor control rates with a reasonable complication profile. Distant tumor recurrence and dissemination were observed in a small proportion of patients, which underscores the importance of close post-SRS surveillance of CN patients. Patients with larger CNs are more likely to require shunt surgery before SRS.

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Monica Mureb, Danielle Golub, Carolina Benjamin, Jason Gurewitz, Ben A. Strickland, Gabriel Zada, Eric Chang, Dušan Urgošík, Roman Liščák, Ronald E. Warnick, Herwin Speckter, Skyler Eastman, Anthony M. Kaufmann, Samir Patel, Caleb E. Feliciano, Carlos H. Carbini, David Mathieu, William Leduc, DCS, Sean J. Nagel, Yusuke S. Hori, Yi-Chieh Hung, Akiyoshi Ogino, Andrew Faramand, Hideyuki Kano, L. Dade Lunsford, Jason Sheehan and Douglas Kondziolka

OBJECTIVE

Trigeminal neuralgia (TN) is a chronic pain condition that is difficult to control with conservative management. Furthermore, disabling medication-related side effects are common. This study examined how stereotactic radiosurgery (SRS) affects pain outcomes and medication dependence based on the latency period between diagnosis and radiosurgery.

METHODS

The authors conducted a retrospective analysis of patients with type I TN at 12 Gamma Knife treatment centers. SRS was the primary surgical intervention in all patients. Patient demographics, disease characteristics, treatment plans, medication histories, and outcomes were reviewed.

RESULTS

Overall, 404 patients were included. The mean patient age at SRS was 70 years, and 60% of the population was female. The most common indication for SRS was pain refractory to medications (81%). The median maximum radiation dose was 80 Gy (range 50–95 Gy), and the mean follow-up duration was 32 months. The mean number of medications between baseline (pre-SRS) and the last follow-up decreased from 1.98 to 0.90 (p < 0.0001), respectively, and this significant reduction was observed across all medication categories. Patients who received SRS within 4 years of their initial diagnosis achieved significantly faster pain relief than those who underwent treatment after 4 years (median 21 vs 30 days, p = 0.041). The 90-day pain relief rate for those who received SRS ≤ 4 years after their diagnosis was 83.8% compared with 73.7% in patients who received SRS > 4 years after their diagnosis. The maximum radiation dose was the strongest predictor of a durable pain response (OR 1.091, p = 0.003). Early intervention (OR 1.785, p = 0.007) and higher maximum radiation dose (OR 1.150, p < 0.0001) were also significant predictors of being pain free (a Barrow Neurological Institute pain intensity score of I–IIIA) at the last follow-up visit. New sensory symptoms of any kind were seen in 98 patients (24.3%) after SRS. Higher maximum radiation dose trended toward predicting new sensory deficits but was nonsignificant (p = 0.075).

CONCLUSIONS

TN patients managed with SRS within 4 years of diagnosis experienced a shorter interval to pain relief with low risk. SRS also yielded significant decreases in adjunct medication utilization. Radiosurgery should be considered earlier in the course of treatment for TN.

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Yi-Chieh Hung, Cheng-Chia Lee, Huai-che Yang, Nasser Mohammed, Kathryn N. Kearns, Ahmed M. Nabeel, Khaled Abdel Karim, Reem M. Emad Eldin, Amr M. N. El-Shehaby, Wael A. Reda, Sameh R. Tawadros, Roman Liscak, Jana Jezkova, L. Dade Lunsford, Hideyuki Kano, Nathaniel D. Sisterson, Roberto Martínez Álvarez, Nuria E. Martínez Moreno, Douglas Kondziolka, John G. Golfinos, Inga Grills, Andrew Thompson, Hamid Borghei-Razavi, Tanmoy Kumar Maiti, Gene H. Barnett, James McInerney, Brad E. Zacharia, Zhiyuan Xu and Jason P. Sheehan

OBJECTIVE

The most common functioning pituitary adenoma is prolactinoma. Patients with medically refractory or residual/recurrent tumors that are not amenable to resection can be treated with stereotactic radiosurgery (SRS). The aim of this multicenter study was to evaluate the role of SRS for treating prolactinomas.

METHODS

This retrospective study included prolactinomas treated with SRS between 1997 and 2016 at ten institutions. Patients’ clinical and treatment parameters were investigated. Patients were considered to be in endocrine remission when they had a normal level of prolactin (PRL) without requiring dopamine agonist medications. Endocrine control was defined as endocrine remission or a controlled PRL level ≤ 30 ng/ml with dopamine agonist therapy. Other outcomes were evaluated including new-onset hormone deficiency, tumor recurrence, and new neurological complications.

RESULTS

The study cohort comprised 289 patients. The endocrine remission rates were 28%, 41%, and 54% at 3, 5, and 8 years after SRS, respectively. Following SRS, 25% of patients (72/289) had new hormone deficiency. Sixty-three percent of the patients (127/201) with available data attained endocrine control. Three percent of patients (9/269) had a new visual complication after SRS. Five percent of the patients (13/285) were recorded as having tumor progression. A pretreatment PRL level ≤ 270 ng/ml was a predictor of endocrine remission (p = 0.005, adjusted HR 0.487). An increasing margin dose resulted in better endocrine control after SRS (p = 0.033, adjusted OR 1.087).

CONCLUSIONS

In patients with medically refractory prolactinomas or a residual/recurrent prolactinoma, SRS affords remarkable therapeutic effects in endocrine remission, endocrine control, and tumor control. New-onset hypopituitarism is the most common adverse event.