Results of three or more Gamma Knife radiosurgery procedures for recurrent trigeminal neuralgia.

OBJECTIVE: Gamma Knife radiosurgery (GKRS) is an established surgical option for the treatment of trigeminal neuralgia (TN), particularly for high-risk surgical candidates and those with recurrent pain. However, outcomes after three or more GKRS treatments have rarely been reported. Herein, the authors reviewed outcomes among patients who had undergone three or more GKRS procedures for recurrent TN. METHODS: The authors conducted a multicenter retrospective analysis of patients who had undergone at least three GKRS treatments for TN between July 1997 and April 2019 at two different institutions. Clinical characteristics, radiosurgical dosimetry and technique, pain outcomes, and complications were reviewed. Pain outcomes were scored on the Barrow Neurological Institute (BNI) scale, including time to pain relief (BNI score ≤ III) and recurrence (BNI score > III). RESULTS: A total of 30 patients were identified, including 16 women and 14 men. Median pain duration prior to the first GKRS treatment was 10 years. Three patients (10%) had multiple sclerosis. Time to pain relief was longer after the third treatment (p = 0.0003), whereas time to pain recurrence was similar across each of the successive treatments (p = 0.842). Complete or partial pain relief was achieved in 93.1% of patients after the third treatment. The maximum pain relief achieved after the third treatment was significantly better among patients with no prior percutaneous procedures (p = 0.0111) and patients with shorter durations of pain before initiation of GKRS therapy (p = 0.0449). New or progressive facial sensory dysfunction occurred in 29% of patients after the third GKRS treatment and was reported as bothersome in 14%. One patient developed facial twitching, while another experienced persistent lacrimation. No statistically significant predictors of adverse effects following the third treatment were found. Over a median of 39 months of follow-up, 77% of patients maintained complete or partial pain relief. Three patients underwent a fourth GKRS treatment, including one who ultimately received five treatments; all of them reported sustained pain relief at the extended follow-up. CONCLUSIONS: The authors describe the largest series to date of patients undergoing three or more GKRS treatments for refractory TN. A third treatment may produce outcomes similar to those of the first two treatments in terms of long-term pain relief, recurrence, and adverse effects.

Improving the Prognostic Value of Disease-Specific Graded Prognostic Assessment Model for Renal Cell Carcinoma by Incorporation of Cumulative Intracranial Tumor Volume.

BACKGROUND: We tested the prognostic value of cumulative intracranial tumor volume (CITV) in the context of a disease-specific Graded Prognostic Assessment (ds-GPA) model for renal cell carcinoma (RCC) patients with brain metastasis (BM) treated with stereotactic radiosurgery (SRS). METHODS: Patient and tumor characteristics were collected from RCC cohorts with new BM who underwent SRS. Univariable and multivariable logistic regression model was used to test the prognostic value of CITV, Karnofsky Performance Score (KPS), and the number of BM. Net reclassification index (NRI) and integrated discrimination improvement (IDI) were used to assess whether CITV improved the prognostic utility of RCC ds-GPA. RESULTS: In univariable logistic regression models, CITV, KPS, and the number of BM were independently associated with RCC patient survival. In a multivariable Cox proportional hazard model, the association between CITV and survival remained robust after controlling for KPS and the number of BM (P = 0.042). The incorporation of the CITV into the RCC ds-GPA model (consisting of KPS and number of BM) improved prognostic accuracy with NRI >0 of 0.3156 (95% confidence interval [CI], 0.0883-0.5428; P = 0.0065) and IDI of 0.0151 (95% CI, 0.0036-0.0277; P = 0.0183). These findings were validated in an independent cohort of 107 SRS-treated RCC BM patients. CONCLUSION: CITV is an important prognostic variable in SRS-treated RCC patients with BM. The prognostic value of the ds-GPA scale for RCC brain metastasis was enhanced by the incorporation of CITV.

Survival Patterns of 5750 Stereotactic Radiosurgery-Treated Patients with Brain Metastasis as a Function of the Number of Lesions.

BACKGROUND: The number of brain metastases (BMs) plays an important role in the decision between stereotactic radiosurgery (SRS) and whole-brain radiation therapy. METHODS: We analyzed the survival of 5750 SRS-treated patients with BM as a function of BM number. Survival analyses were performed with Kaplan-Meier analysis as well as univariate and multivariate Cox proportional hazards models. RESULTS: Patients with BMs were first categorized as those with 1, 2-4, and 5-10 BMs based on the scheme proposed by Yamamoto et al. (Lancet Oncology 2014). Median overall survival for patients with 1 BM was superior to those with 2-4 BMs (7.1 months vs. 6.4 months, P = 0.009), and survival of patients with 2-4 BMs did not differ from those with 5-10 BMs (6.4 months vs. 6.3 months, P = 0.170). The median survival of patients with >10 BMs was lower than those with 2-10 BMs (6.3 months vs. 5.5 months, P = 0.025). In a multivariate model that accounted for age, Karnofsky Performance Score, systemic disease status, tumor histology, and cumulative intracranial tumor volume, we observed a ∼10% increase in hazard of death when comparing patients with 1 versus 2-10 BMs (P < 0.001) or 10 versus >10 BMs (P < 0.001). When BM number was modeled as a continuous variable rather than using the classification by Yamamoto et al., we observed a step-wise 4% increase in the hazard of death for every increment of 6-7 BM (P < 0.001). CONCLUSIONS: The contribution of BM number to overall survival is modest and should be considered as one of the many variables considered in the decision between SRS and whole-brain radiation therapy.

Management patterns of patients with cerebral metastases who underwent multiple stereotactic radiosurgeries.

With escalating focus on cost containment, there is increasing scrutiny on the practice of multiple stereotactic radiosurgeries (SRSs) for patients with cerebral metastases distant to the initial tumor site. Our goal was to determine the survival patterns of patients with cerebral metastasis who underwent multiple SRSs. We retrospectively analyzed survival outcomes of 801 patients with 3683 cerebral metastases from primary breast, colorectal, lung, melanoma and renal histologies consecutively treated at the University of California, San Diego/San Diego Gamma Knife Center (UCSD/SDGKC), comparing the survival pattern of patients who underwent a single (n = 643) versus multiple SRS(s) (n = 158) for subsequent cerebral metastases. Findings were recapitulated in an independent cohort of 2472 patients, with 26,629 brain metastases treated with SRS at the Katsuta Hospital Mito GammaHouse (KHMGH). For the UCSD/SDGKC cohort, no significant difference in median survival was found for patients undergoing 1, 2, 3, or ≥4 SRS(s) (median survival of 167, 202, 129, and 127 days, respectively). Median intervals between treatments consistently ranged 140-178 days irrespective of the number of SRS(s) (interquartile range 60-300; p = 0.25). Patients who underwent >1 SRSs tend to be younger, with systemic disease control, harbor lower cumulative tumor volume but increased number of metastases, and have primary melanoma (p < 0.001, <0.001, <0.001, 0.02, and 0.009, respectively). Comparable results were found in the KHMGH cohort. Using an independent validation study design, we demonstrated comparable overall survival between judiciously selected patients who underwent a single or multiple SRS(s).

Stereotactic Radiosurgery Treatment of Trigeminal Neuralgia: Clinical Outcomes and Prognostic Factors.

BACKGROUND: Stereotactic radiosurgery (SRS) is a minimally invasive surgical option for the treatment of trigeminal neuralgia (TN). Here we review our institutional experience to identify prognostic factors associated with pain relief after SRS. METHODS: 263 patients with TN treated at the University of California, San Diego/San Diego Gamma Knife (2001-2013) were followed for more than 6 months. Univariate and multivariate Cox proportional hazard models analysis of factors associated with outcome was performed. RESULTS: Of the 263 patients, 229 (87%) presented with classical idiopathic TN, 31 (12%) presented with atypical TN, and 4 (1%) presented with secondary TN. 143 (54%) had undergone prior treatment. Most patients were treated with 85 (52%) or 90 Gy (42%). 79% of the SRS treated patients experienced a favorable response (defined as Barrow Neurological Institute Pain Scale <3 pain relief), with a median time to relief of 2.5 months. In a multivariate analysis, diagnosis of classical TN, previous percutaneous procedures, and age older than 70 years were associated with favorable responses; classical TN was associated with sustained pain relief. Dose prescription >85 Gy and prior SRS were associated with bothersome facial numbness posttreatment. For patients presenting with classical TN, diagnosis of multiple sclerosis (MS) did not decrease the likelihood of pain relief after SRS. CONCLUSIONS: Excellent TN pain relief was achieved with the delivery of 85 Gy in a single-shot, 4-mm isocenter SRS targeting the dorsal root entry zone. Patients with classical TN, with age older than 70 years, or who underwent previous percutaneous procedures were more likely to benefit from SRS. SRS is efficacious in patients with classical TN despite concurrent diagnosis of MS.

Immediate post-operative brachytherapy prior to irradiation and temozolomide for newly diagnosed glioblastoma.

To determine whether immediate post-operative brachytherapy can be safely applied to newly diagnosed glioblastomas to retard tumor progression prior to initiation of external beam radiation therapy (EBRT) and temozolomide. Between 1996 and 2011, eleven patients underwent implantation of GliaSite (n = 9) or MammoSite (n = 2) at the time of surgical resection. Brachytherapy was carried out on post-operative day 2-3, with 45-60 Gy delivered to a 1 cm margin. All patients underwent subsequent standard radiation/temozolomide treatment 4-5 weeks post-irradiation. There were no wound related complications. Toxicity was observed in two patients (2/11 or 18 %), including one post-operative seizure and one case of cerebral edema that resolved after a course of steroid treatment. Immediate post-operative and pre-irradiation/temozolomide magnetic resonance imaging assessment was available for 9 of the 11 patients. Two of these nine patients (22 %) developed new regions of contrast enhancement prior to irradiation/temozolomide. This compares favorably to historical data where 53 % of patient suffer such tumor progression. While there was a trend toward improved 6 month progression free survival in the brachytherapy/temozolomide/radiation treated patients, the overall survival of these patients were comparable to historical controls. This case series demonstrates the safety of immediate post-operative brachytherapy when applied prior to EBRT and temozolomide in the treatment of newly diagnosed glioblastomas.

Novel use of the Contura for high dose rate cranial brachytherapy.

A popular choice for treatment of recurrent gliomas was cranial brachytherapy using the GliaSite Radiation Therapy System. However, this device was taken off the market in late 2008, thus leaving a treatment void. This case study presents our experience treating a cranial lesion for the first time using a Contura multilumen, high-dose-rate (HDR) brachytherapy balloon applicator. The patient was a 47-year-old male who was diagnosed with a recurrent right frontal anaplastic oligodendroglioma. Previous radiosurgery made him a good candidate for brachytherapy. An intracavitary HDR balloon brachytherapy device (Contura) was placed in the resection cavity and treated with a single fraction of 20 Gy. The implant, treatment, and removal of the device were all completed without incident. Dosimetry of the device was excellent because the dose conformed very well to the target. V90, V100, V150, and V200 were 98.9%, 95.7%, 27.2, and 8.8 cc, respectively. This patient was treated successfully using the Contura multilumen balloon. Contura was originally designed for deployment in a postlumpectomy breast for treatment by accelerated partial breast irradiation. Being an intracavitary balloon device, its similarity to the GliaSite system makes it a viable replacement candidate. Multiple lumens in the device also make it possible to shape the dose delivered to the target, something not possible before with the GliaSite applicator.

Single-isocenter frameless intensity-modulated stereotactic radiosurgery for simultaneous treatment of multiple brain metastases: clinical experience.

PURPOSE: To describe our clinical experience using a unique single-isocenter technique for frameless intensity-modulated stereotactic radiosurgery (IM-SRS) to treat multiple brain metastases. METHODS AND MATERIALS: Twenty-six patients with a median of 5 metastases (range, 2-13) underwent optically guided frameless IM-SRS using a single, centrally located isocenter. Median prescription dose was 18 Gy (range, 14-25). Follow-up magnetic resonance imaging (MRI) and clinical examination occurred every 2-4 months. RESULTS: Median follow-up for all patients was 3.3 months (range, 0.2-21.3), with 20 of 26 patients (77%) followed up until their death. For the remaining 6 patients alive at the time of analysis, median follow-up was 14.6 months (range, 9.3-18.0). Total treatment time ranged from 9.0 to 38.9 minutes (median, 21.0). Actuarial 6- and 12-month overall survivals were 50% (95% confidence interval [C.I.], 31-70%) and 38% (95% C.I., 19-56%), respectively. Actuarial 6- and 12-month local control (LC) rates were 97% (95% C.I., 93-100%) and 83% (95% C.I., 71-96%), respectively. Tumors 1.5 cm (98% vs. 90%, p = 0.008). New intracranial metastatic disease occurring outside of the treatment volume was observed in 7 patients. Grade >or=3 toxicity occurred in 2 patients (8%). CONCLUSION: Frameless IM-SRS using a single-isocenter approach for treating multiple intracranial metastases can produce clinical outcomes that compare favorably with those of conventional SRS in a much shorter treatment time (<40 minutes). Given its faster treatment time, this technique is appealing to both patients and personnel in busy clinics.

Optically-guided frameless linac-based radiosurgery for brain metastases: clinical experience.

The purpose of this study was to describe our clinical experience using optically-guided linear accelerator (linac)-based frameless stereotactic radiosurgery (SRS) for the treatment of brain metastases. Sixty-five patients (204 lesions) were treated between 2005 and 2008 with frameless SRS using an optically-guided bite-block system. Patients had a median of 2 lesions (range, 1-13). Prescription dose ranged from 14 to 22 Gy (median, 18 Gy) and was given in a single fraction. Clinical and radiographic evaluation occurred every 2-4 months following treatment. At a median follow-up of 6.2 months, actuarial survival at 12 months was 40% [95% confidence interval (CI), 28-52). Of 135 lesions that were evaluable for local control (LC), 119 lesions (88%) did not show evidence of progression. Actuarial 12 month LC was 76% (95% CI, 66-86). Tumors 2 cm. Adverse events occurred in three patients (5%). Optically-guided linac-based frameless SRS can produce clinical outcomes that compare favorably to frame-based techniques. As this technique is convenient to use and allows for the uncomplicated delivery of hypofractionated radiotherapy, frameless SRS will likely have an increasingly important role in the management of brain metastases.

Cerebellopontine angle cyst compressing the vagus nerve: case report.

OBJECTIVE: The cerebellopontine angle (CPA) is a rare location for an arachnoid cyst. We describe a patient with a CPA arachnoid cyst who presented with hoarseness (unilateral vocal cord paralysis) and dysphagia secondary to isolated compression of the vagus nerve. This rare presentation of a CPA arachnoid cyst has not been reported previously. CLINICAL PRESENTATION: The patient described is a 50-year-old man who experienced a precipitous onset of hoarseness and dsyphagia. An otolaryngological evaluation revealed right-sided vocal cord paralysis. Brain magnetic resonance images displayed a cystic mass at the right CPA and anterior displacement of the vagus nerve. INTERVENTION: The patient underwent retrosigmoidal craniectomy with cyst fenestration, which was well tolerated. Intraoperatively, Cranial Nerve X was found splayed over the cyst and was consequently decompressed. CONCLUSION: Postoperatively, the patient's dysphagia completely resolved. However, the results of a laryngeal electromyocardiogram revealed minimal evidence of recovery in the affected vocal fold, and the patient continued to suffer from dysphonia. Although CPA arachnoid cysts are rare, they should be considered when a patient presents with an isolated cranial nerve palsy. Treatment options include cyst fenestration and cranial nerve decompression.

Idiopathic normal pressure hydrocephalus may be a "two hit" disease: benign external hydrocephalus in infancy followed by deep white matter ischemia in late adulthood.

PURPOSE: To determine if normal pressure hydrocephalus (NPH) could result from decreased resorption of cerebrospinal fluid (CSF) by the arachnoidal villi, leading to benign external hydrocephalus [BEH] in infancy, followed by deep white matter ischemia (DWMI) in late adulthood (the more hydrophilic environment increasing resistance to CSF flow through the extracellular space (ECS) of the brain). MATERIALS AND METHODS: CSF outflow via the fourth ventricle and the ECS of the brain was mathematically modeled using a parallel electrical circuit analog. The apparent diffusion coefficient (ADC) was measured as a surrogate of the amount of water in the ECS in normals, patients with symptomatic NPH, and patients with dilated ventricles without symptoms of NPH ("pre-NPH"). RESULTS: The electrical circuit model demonstrates increasing ventricular volume with increasing resistance to flow through the ECS of the brain. ADC measurements performed in the centrum semiovale are significantly higher in patients with NPH and "pre-NPH" than in age-matched controls (P<0.05), controlling for the same degree of DWMI indicating increased fluid in the ECS of the brain. CONCLUSION: The electrical circuit analog and finding of increased periventricular ADC support the theory that NPH is a "two hit" disease.

Multimodality treatment of trigeminal neuralgia: impact of radiosurgery and high resolution magnetic resonance imaging.

This study was conducted to evaluate the two main surgical modalities, microvascular decompression (MVD) and gamma-knife radiosurgery (GK), the treatment of trigeminal neuralgia (TN) and outline for an algorithm for the selection of these procedures. The authors have identified distinct differences in the two treatment groups and formulated a scale that predicts the outcome and satisfaction of patients who underwent the procedures. This series included 34 TN patients treated in 2000 and 2001 with MVD (19) and GK (15). Patients with TN associated with tumor or multiple sclerosis were excluded. Each patient's age, past medical history, clinical features of pain or pre-operative pain grade, duration of TN, medications, and prior surgical procedures were recorded. Long-term results were assessed by a structured interview by telephone. Clinical outcome was classified as excellent (complete relief without medications and numbness), good (complete relief without medications), fair (> 50% relief or with substantial numbness and weakness), or poor (< 50% relief or treatment failure). Patient self-rated satisfaction score was rated on a scale of 1 (unsatisfied) to 10 (completely satisfied). Statistical analysis was performed by paired t-tests and anova with post-hoc analysis by the Tukey-Kramer method. The median follow-up was 17 months (18 months for MVD and 16 months for GK). The average age of MVD patients was 61 years compared to 74 years for GK patients (p = 0.0005). In both groups there was a female majority (68% for MVD and 60% for GK). The latency between first symptom of TN and treatment procedure was 3.0 years for MVD and 3.9 years for GK (p > 0.05). There was no significant difference in pain grade between the two groups. The average TN complexity grade was significantly different between the two groups (3.0 for MVD and 5.8 for GK) (p < 0.001). Average response to procedure for MVD was 3.4 (good) and 2.4 (fair) for GK (p = 0.017). The satisfaction outcome for MVD was 8.7 compared to 6.4 for GK (p = 0.02). There was a significant correlation (r = -0.818, p < 0.001) between TN complexity grade and response. Additionally, a significant correlation between TN complexity grade and patient satisfaction was found (r = -0.763, p < 0.0001). The data here support the treatment algorithm employed by the senior author (JFA) of this study. The TN complexity grade accurately correlates with the patient's response and satisfaction to the surgical procedure. This complexity grade may be useful for patient counseling when choosing between treatment options.

Increased intracranial volume: a clue to the etiology of idiopathic normal-pressure hydrocephalus?

BACKGROUND AND PURPOSE: The etiology of idiopathic normal-pressure hydrocephalus (NPH) is unknown. The purpose of this study was to examine the hypothesis that NPH begins in infancy as benign external hydrocephalus due to decreased uptake of CSF by the arachnoid villi. Since this occurs before the sutures fuse, a secondary hypothesis is that the intracranial volumes of patients with NPH should be larger than those of healthy individuals. METHODS: Intracranial volumes of 51 patients with clinically suspected NPH were compared with those of age- and sex-matched control subjects. All patients underwent phase-contrast CSF velocity MR imaging. They had aqueductal CSF stroke volumes of at least 60 microL, which was 50% higher than previously published normal values. Intracranial volumes were measured and compared between groups. RESULTS: The average intracranial volume for men with NPH (n = 22) was 1682 mL compared with 1565 for male control subjects (n = 55). The NPH volume averaged 118 mL (7.5%) larger than the control volume (P = .003). The average intracranial volume for women with NPH (n = 29) was 1493 mL compared with 1405 mL for female control subjects (n = 55). The NPH volume was 88 mL (6.3%) larger than the control volume (P = .002). CONCLUSION: Patients with NPH have intracranial volumes significantly larger than normal, suggesting that the initial insult occurs before the sutures fuse at 1 year of age. The patients somehow remain asymptomatic until their later years, when a second insult must occur, leading to symptomatic NPH.

Improvement of aggressive and antisocial behavior after resection of temporal lobe tumors.

Seizures associated with temporal lobe tumors may rarely manifest as episodic aggressive behavior. We describe 2 cases involving pediatric patients who presented with histories of unusually aggressive and antisocial behavior. Magnetic resonance imaging identified right mesial temporal lobe masses in both patients. After craniotomy for tumor removal, both patients were seizure-free and had marked reductions in their aggressive behavior. Tumors in the temporal lobe may be associated with behavioral problems, including aggression and rage attacks, which can be alleviated with surgical intervention. It is important to distinguish this subgroup of pediatric patients from those with alternative diagnoses such as attention-deficit/hyperactivity disorder or oppositional defiant disorder.

Thalamic hypometabolism in a patient undergoing vagal nerve stimulation seen on F-18 FDG PET imaging.

A 31-year-old man with a vagal nerve stimulator for seizure control was noted to have decreased metabolism within the thalamus as visualized by F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET). Some investigators think the thalamus plays an important role in the regulation of seizure activity. Vagal nerve stimulation (VNS) may reduce thalamic activity, which in turn may reduce seizure activity. However, because the thalamus has diffuse connections throughout the brain, its role in seizure activity is likely complex. Observing decreased thalamic activity during VNS is just 1 small step toward understanding this role.