Is staged bilateral thalamic radiosurgery an option for otherwise surgically ineligible patients with medically refractory bilateral tremor?

OBJECTIVE Unilateral Gamma Knife thalamotomy (GKT) is a well-established treatment for patients with medically refractory tremor who are not eligible for invasive procedures due to increased risk of compications. The purpose of this study was to evaluate whether staged bilateral GKT provides benefit with acceptable risk to patients suffering from disabling medically refractory bilateral tremor. METHODS Eleven patients underwent staged bilateral GKT during a 17-year period (1999-2016). Eight patients had essential tremor (ET), 2 had Parkinson's disease (PD)-related tremor, and 1 had multiple-sclerosis (MS)-related tremor. For the first GKT, a median maximum dose of 140 Gy was delivered to the posterior-inferior region of the nucleus ventralis intermedius (VIM) through a single isocenter with 4-mm collimators. Patients who benefitted from unilateral GKT were eligible for a contralateral GKT 1-2 years later (median 22 months). For the second GKT, a median maximum dose of 130 Gy was delivered to the opposite VIM nucleus to a single 4-mm isocenter. The Fahn-Tolosa-Marin (FTM) clinical tremor rating scale was used to score tremor, drawing, and drinking before and after each GKT. The FTM writing score was assessed only for the dominant hand before and after the first GKT. The Karnofsky Performance Status (KPS) was used to assess quality of life and activities of daily living before and after the first and second GKT. RESULTS The median time to last follow-up after the first GKT was 35 months (range 11-70 months). All patients had improvement in at least 1 FTM score after the first GKT. Three patients (27.3%) had tremor arrest and complete restoration of function (noted via FTM tremor, writing, drawing, and drinking scores equaling zero). No patient had tremor recurrence or diminished tremor relief after the first GKT. One patient experienced new temporary neurological deficit (contralateral lower-extremity hemiparesis) from the first GKT. The median time to last follow-up after the second GKT was 12 months (range 2-70 months). Nine patients had improvement in at least 1 FTM score after the second GKT. Two patients had tremor arrest and complete restoration of function. No patient experienced tremor recurrence or diminished tremor relief after the second GKT. No patient experienced new neurological or radiological adverse effect from the second GKT. Statistically significant improvements were noted in the KPS score following the first and second GKT. CONCLUSIONS Staged bilateral GKT provided effective relief for medically refractory, disabling, bilateral tremor without increased risk of neurological complications. It is an appropriate strategy for carefully selected patients with medically refractory bilateral tremor who are not eligible for deep brain stimulation.

Stereotactic radiosurgery for essential tremor: Retrospective analysis of a 19-year experience.

BACKGROUND: Essential Tremor (ET) is a common movement disorder that can be disabling. Initial treatment is in the form of medical therapies. Patients with medically refractory ET seek surgical intervention which include radiofrequency thalamotomy, deep brain stimulation, and radiosurgical thalamotomy. Radiosurgical thalamotomy is a minimally invasive surgical option which is especially valuable for elderly and high surgical risk patients. OBJECTIVE: The purpose of this study was to retrospectively analyze the outcomes of stereotactic radiosurgery for patients suffering from medically refractory essential tremor. METHODS: During a 19-year period (1996-2015), 73 patients underwent gamma knife thalamotomy for intractable essential tremor. A median central dose of 140 Gy (range, 130-150) was delivered to the nucleus ventralis intermedius through a single 4-mm isocenter. We used the Fahn-Tolosa-Marin clinical tremor rating scale to score tremor, handwriting, drawing, and ability to drink fluids. The median time to last follow-up was 28 months (range, 6-152). RESULTS: After gamma knife thalamotomy, 93.2% improved in tremor. Forty-four patients (60.3%) experienced tremor arrest or barely perceptible tremor. Eighteen patients (24.7%) noted tremor arrest and complete restoration of motor function. Tremor improvement was sustained at last follow-up in 96% of patients who experience tremor relief. Mean tremor score improved from 3.19 before to 1.27 after gamma knife thalamotomy (P < 0.0001). Mean handwriting score improved from 2.97 to 1.25 (P < 0.0001). Mean drawing score improved from 3.16 to 1.26 (P < 0.0001). Mean drinking score improved from 3.14 to 1.56 (P < 0.0001). Imaging follow-up showed three types of lesions: enhancing lesion, streaking along internal capsule on fluid-attenuated inversion recovery, and significant reactive changes. Three patients (4%) experienced temporary adverse radiation effects. CONCLUSION: Radiosurgery is a safe and valuable treatment option for medically refractory essential tremor, especially for the elderly or those with high surgical risk for DBS or radiofrequency thalamotomy. © 2017 International Parkinson and Movement Disorder Society.

Impact of dynamic changes to a bone metastases pathway in a large, integrated, National Cancer Institute-designated comprehensive cancer center network.

PURPOSE: Studies suggest equivalent pain relief from bone metastases after radiation therapy with >10-fraction regimens and shorter courses. Although American Society for Radiation Oncology evidence-based guidelines and the Choosing Wisely campaign endorse single-fraction treatments and caution against the use of extended courses, publications report single-fraction utilization rates below 5%. We evaluated the impact of our bone metastasis clinical pathway on the adoption of short-course palliative radiation in a large, integrated radiation oncology network. METHODS AND MATERIALS: We implemented a clinical pathway for the management of bone metastases in 2003 that required the entry of management decisions into an online tool that subjected off-pathway choices to peer review beginning in 2009. In 2014, the pathway was modified to encourage single-fraction treatments, and the use of >10 fractions was considered off pathway. Data were obtained from 16 integrated sites (4 academic, 12 community) from 2003 through 2014. Multivariate logistic regression was conducted to establish factors associated with treatment with a single fraction and with >10 fractions. RESULTS: In this study, 12,678 unique courses were delivered. From 2003 to 2008, the single-fraction utilization rate was 7.6%. This increased to 10.9% from 2009 to 2013 and to 15.8% in 2014. The odds ratios for single-fraction use were 1.59 (95% confidence interval [CI], 1.39-1.81) and 2.58 (95% CI, 2.11-3.15) for 2009-2013 and 2014, respectively. Academic physicians were more likely to treat with a single fraction (odds ratio, 5.00; 95% CI, 4.38-5.71). Use of >10-fraction regimens significantly decreased from 18.6% in 2003-2008 to 15.2% in 2009-2013 and 9.7% in 2014. CONCLUSIONS: Although our single-fraction utilization rate was initially in line with national rates (7.6%), the adoption rate increased to >15%. The use of >10-fraction regimens decreased significantly, predominantly among community practices. By 2014, >90% of courses were delivered with <10 fractions. This study demonstrates that provider-driven clinical pathways are able to standardize practice patterns and promote change consistent with evidence-based guidelines.

Stereotactic radiosurgery for epilepsy and functional disorders.

Stereotactic radiosurgery is used for many indications. In functional neurosurgery, it is used to modulate the function of axons, neurons, and related brain circuits. In this article, indications, current techniques, and outcomes are discussed.

Gamma Knife thalamotomy for tremor in the magnetic resonance imaging era.

OBJECT: The surgical management of disabling tremor has gained renewed vigor with the availability of deep brain stimulation. However, in the face of an aging population of patients with increasing surgical comorbidities, noninvasive approaches for tremor management are needed. The authors' purpose was to study the technique and results of stereotactic radiosurgery performed in the era of MRI targeting. METHODS: The authors evaluated outcomes in 86 patients (mean age 71 years; number of procedures 88) who underwent a unilateral Gamma Knife thalamotomy (GKT) for tremor during a 15-year period that spanned the era of MRI-based target selection (1996-2011). Symptoms were related to essential tremor in 48 patients (19 age ≥ 80 years and 3 age ≥ 90 years), Parkinson disease in 27 patients (11 age ≥ 80 years [1 patient underwent bilateral procedures]), and multiple sclerosis in 11 patients (1 patient underwent bilateral procedures). A single 4-mm isocenter was used to deliver a maximum dose of 140 Gy to the posterior-inferior region of the nucleus ventralis intermedius. The Fahn-Tolosa-Marin clinical tremor rating scale was used to grade tremor, handwriting, and ability to drink. The median follow-up was 23 months. RESULTS: The mean tremor score was 3.28 ± 0.79 before and 1.81 ± 1.15 after (p < 0.0001) GKT; the mean handwriting score was 2.78 ± 0.82 and 1.62 ± 1.04, respectively (p < 0.0001); and the mean drinking score was 3.14 ± 0.78 and 1.80 ± 1.15, respectively (p < 0.0001). After GKT, 57 patients (66%) showed improvement in all 3 scores, 11 patients (13%) in 2 scores, and 2 patients (2%) in just 1 score. In 16 patients (19%) there was a failure to improve in any score. Two patients developed a temporary contralateral hemiparesis, 1 patient noted dysphagia, and 1 sustained facial sensory loss. CONCLUSIONS: Gamma Knife thalamotomy in the MRI era was a safe and effective noninvasive surgical strategy for medically refractory tremor in the elderly or those with contraindications to deep brain stimulation or stereotactic radiofrequency (thermal) thalamotomy.

Do carbamazepine, gabapentin, or other anticonvulsants exert sufficient radioprotective effects to alter responses from trigeminal neuralgia radiosurgery?

PURPOSE: Laboratory studies have documented radioprotective effects with carbamazepine. We sought to determine whether carbamazepine or other anticonvulsant/neuroleptic drugs would show significant radioprotective effects in patients undergoing high-dose small-volume radiosurgery for trigeminal neuralgia. METHODS AND MATERIALS: We conducted a retrospective review of 200 patients undergoing Gamma Knife (Elekta Instrument AB, Stockholm, Sweden) stereotactic radiosurgery for trigeminal neuralgia between February 1995 and May 2008. We selected patients treated with a maximum dose of 80 Gy with 4-mm diameter collimators, with no previous microvascular decompression, and follow-up ≥6 months (median, 24 months; range, 6-153 months). At the time of radiosurgery, 28 patients were taking no anticonvulsants, 62 only carbamazepine, 35 only gabapentin, 21 carbamazepine plus gabapentin, 17 carbamazepine plus other anticonvulsants, and 9 gabapentin plus other anticonvulsants, and 28 were taking other anticonvulsants or combinations. RESULTS: Pain improvement developed post-radiosurgery in 187 of 200 patients (93.5%). Initial complete pain relief developed in 84 of 200 patients (42%). Post-radiosurgery trigeminal neuropathy developed in 27 of 200 patients (13.5%). We could not significantly correlate pain improvement or initial complete pain relief with use of carbamazepine, gabapentin, or use of any anticonvulsants/neuroleptic drugs or other factors in univariate or multivariate analysis. Post-radiosurgery numbness/paresthesias correlated with the use of gabapentin (1 of 36 patients with gabapentin vs. 7 of 28 without, p = 0.017). In multivariate analysis, decreasing age, purely typical pain, and use of gabapentin correlated (p = 0.008, p = 0.005, and p = 0.021) with lower risks of developing post-radiosurgery trigeminal neuropathy. New post-radiosurgery numbness/paresthesias developed in 3% (1 of 36), 5% (4 of 81), and 13% (23 of 187) of patients on gabapentin alone, with age ≤70 years, and Type 1 typical trigeminal neuralgia pain compared with 25% (7 of 28), 20% (23 of 114), and 33% (4 of 12) of patients taking no anticonvulsants, age >70 years, and partly atypical Type 2 trigeminal neuralgia, respectively. CONCLUSIONS: The use of carbamazepine or gabapentin at the time of radiosurgery does not decrease the rates of obtaining partial or complete pain relief after radiosurgery, but gabapentin may reduce the risks of developing post-radiosurgery trigeminal neuropathy.

How effective are clinical pathways with and without online peer-review? An analysis of bone metastases pathway in a large, integrated National Cancer Institute-Designated Comprehensive Cancer Center Network.

PURPOSE: Clinical pathways are an important tool used to manage the quality in health care by standardizing processes. This study evaluated the impact of the implementation of a peer-reviewed clinical pathway in a large, integrated National Cancer Institute-Designated Comprehensive Cancer Center Network. METHODS: In 2003, we implemented a clinical pathway for the management of bone metastases with palliative radiation therapy. In 2009, we required the entry of management decisions into an online tool that records pathway choices. The pathway specified 1 or 5 fractions for symptomatic bone metastases with the option of 10-14 fractions for certain clinical situations. The data were obtained from 13 integrated sites (3 central academic, 10 community locations) from 2003 through 2010. RESULTS: In this study, 7905 sites were treated with 64% of courses delivered in community practice and 36% in academic locations. Academic practices were more likely than community practices to treat with 1-5 fractions (63% vs. 23%; p < 0.0001). The number of delivered fractions decreased gradually from 2003 to 2010 for both academic and community practices (p < 0.0001); however, greater numbers of fractions were selected more often in community practices (p < 0.0001). Using multivariate logistic regression, we found that a significantly greater selection of 1-5 fractions developed after implementation online pathway monitoring (2009) with an odds ratio of 1.2 (confidence interval, 1.1-1.4) for community and 1.3 (confidence interval, 1.1-1.6) for academic practices. The mean number of fractions also decreased after online peer review from 6.3 to 6.0 for academic (p = 0.07) and 9.4 to 9.0 for community practices (p < 0.0001). CONCLUSION: This is one of the first studies to examine the efficacy of a clinical pathway for radiation oncology in an integrated cancer network. Clinical pathway implementation appears to be effective in changing patterns of care, particularly with online clinical peer review as a valuable aid to encourage adherence to evidence-based practice.

Stereotactic radiosurgery for arteriovenous malformations, Part 4: management of basal ganglia and thalamus arteriovenous malformations.

OBJECT: The authors conducted a study to define the long-term outcomes and risks of stereotactic radiosurgery (SRS) for arteriovenous malformations (AVMs) of the basal ganglia and thalamus. METHODS: Between 1987 and 2006, the authors performed Gamma Knife surgery in 996 patients with brain AVMs; 56 patients had AVMs of the basal ganglia and 77 had AVMs of the thalamus. In this series, 113 (85%) of 133 patients had a prior hemorrhage. The median target volume was 2.7 cm(3) (range 0.1-20.7 cm(3)) and the median margin dose was 20 Gy (range 15-25 Gy). RESULTS: Obliteration of the AVM eventually was documented on MR imaging in 78 patients and on angiography in 63 patients in a median follow-up period of 61 months (range 2-265 months). The actuarial rates documenting total obliteration after radiosurgery were 57%, 70%, 72%, and 72% at 3, 4, 5, and 10 years, respectively. Factors associated with a higher rate of AVM obliteration included AVMs located in the basal ganglia, a smaller target volume, a smaller maximum diameter, and a higher margin dose. Fifteen (11%) of 133 patients suffered a hemorrhage during the latency period and 7 patients died. The rate of post-SRS AVM hemorrhage was 4.5%, 6.2%, 9.0%, 11.2%, and 15.4% at 1, 2, 3, 5, and 10 years, respectively. The overall annual hemorrhage rate was 4.7%. When 5 patients with 7 hemorrhages occurring earlier than 6 months after SRS were removed from this analysis, the annual hemorrhage rate decreased to 2.7%. Larger volume AVMs had a higher risk of hemorrhage after SRS. Permanent neurological deficits due to adverse radiation effects (AREs) developed in 6 patients (4.5%), and in 1 patient a delayed cyst developed 56 months after SRS. No patient died of AREs. Factors associated with a higher risk of symptomatic AREs were larger target volume, larger maximum diameter, lower margin dose, and a higher Pollock-Flickinger score. CONCLUSIONS: Stereotactic radiosurgery is a gradually effective and relatively safe management option for deep-seated AVMs in the basal ganglia and thalamus. Although hemorrhage after obliteration did not occur in the present series, patients remain at risk during the latency interval between SRS and obliteration. The best candidates for SRS are patients with smaller volume AVMs located in the basal ganglia.

Adverse radiation effects after radiosurgery may benefit from oral vitamin E and pentoxifylline therapy: a pilot study.

BACKGROUND: Although uncommon, adverse radiation effects (ARE) are a potentially serious side effect of brain stereotactic radiosurgery (SRS). Corticosteroids are used to treat suspected ARE but side effects may be significant after long-term usage. Oral pentoxifylline (Ptx) and vitamin E therapy (VitE) are reported to benefit ARE seen in other organ systems. We treated 11 patients with suspected ARE after SRS with Ptx and VitE. METHODS: To assess the response, edema was measured using fluid-attenuated inversion recovery magnetic resonance imaging (MRI). Edema volumes were calculated by first determining the three maximum measurements in the X, Y, and Z planes of the image with the largest signal change. Volume was plotted over time for each patient that had serial MRI scans available. Two patients had 2 separate radiosurgeries and 2 patients underwent 3. Three patients received adjuvant whole-brain radiation therapy. RESULTS: The time until clinical detection of ARE after SRS varied from 3 to 18 months (median, 8 months). The change in edema volume varied from 59.6 ml in 1 patient (worse edema) to -324.2 ml (improvement). The average change in edema from pre- to post-treatment was -72.3 ml. One patient had more edema despite treatment; this patient was found to have tumor recurrence, and not an ARE. Two patients discontinued Ptx because of persistent nausea and abdominal discomfort. CONCLUSIONS: Ptx and VitE may be of benefit in the management of adverse radiation effects and should be studied further.

Gamma Knife thalamotomy for essential tremor.

OBJECTIVES: The purpose of this study was to evaluate the results following Gamma Knife thalamotomy (GKT) for medically refractory essential tremor in a series of patients in whom open surgical techniques were not desirable. METHODS: Thirty-one patients underwent GKT for disabling essential tremor after medical therapy had failed. Their mean age was 77 years. Most patients were elderly or had concomitant medical illnesses. A single 4-mm isocenter was used to target a maximum dose of 130 or 140 Gy to the nucleus ventralis intermedius. Items from the Fahn-Tolosa-Marin clinical tremor rating scale were used to grade tremor and handwriting before and after radiosurgery. RESULTS: The median follow-up was 36 months. In the group of 26 evaluable patients, the mean tremor score (+/- standard deviation) was 3.7 +/- 0.1 preoperatively and 1.7 +/- 0.3 after radiosurgery (p < 0.000015). The mean handwriting score was 2.8 +/- 0.2 before GKT and 1.7 +/- 0.2 afterward (p < 0.0002). After radiosurgery, 18 patients (69%) showed improvement in both action tremor and writing scores, 6 (23%) only in action tremor scores, and 3 (12%) in neither tremor nor writing. Permanent mild right hemiparesis and speech impairment developed in 1 patient 6 months after radiosurgery. Another patient had transient mild right hemiparesis and dysphagia. CONCLUSIONS: Gamma Knife thalamotomy is a safe and effective therapy for medically refractory essential tremor. Its use is especially valuable for patients ineligible for radiofrequency thalamotomy or deep brain stimulation. Patients must be counseled on potential complications, including the low probability of a delayed neurological deficit.