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Deep brain stimulation for medically refractory epilepsy

Thomas L. Ellis and Andrew Stevens

Epilepsy is a chronic neurological disorder that affects 0.5–1% of the population. Up to one-third of patients will have incompletely controlled seizures or debilitating side effects of anticonvulsant medications. Although some of these patients may be candidates for resection, many are not. The desire to find alternative treatments for epilepsy has led to a resurgence of interest in the use of deep brain stimulation (DBS), which has been used quite successfully in movement disorders. Small pilot studies and open-label trials have yielded results that may support the use of DBS in selected patients with refractory seizures. Because of the diversity of regions involved with seizure initiation and propagation, a variety of targets for stimulation have been examined. Moreover, stimulation parameters such as amplitude, frequency, pulse duration, and continuous versus intermittent on vary from one study to the next. More studies are necessary to determine if there is an appropriate population of seizure patients for DBS, the optimal target, and the most efficacious stimulation parameters.

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Migratory neurocysticercosis mimicking a third ventricular colloid cyst

Case report

Steven D. Wray, Thomas L. Ellis, and Sabatino Bianco

✓ The authors report on a case of solitary neurocysticercosis located in the anterior third ventricle of a 21-year-old Hispanic man who presented with progressive headache, nausea, and mental decline. The appearance of the lesion on computerized tomography and magnetic resonance studies was typical of that of a colloid cyst, which was the presumptive preoperative diagnosis. A transcortical-transventricular microsurgical approach was used, and inspection of the anterior third ventricle via the ipsilateral foramen of Monro revealed no lesion. Inspection of the floor of the ipsilateral lateral ventricle revealed the intact cyst, which had migrated since the preoperative studies had been obtained. The lesion was removed intact, and histopathological examination confirmed the diagnosis of neurocysticercosis. The authors review the radiographic findings in this case and further illustrate the potential for neurocysticercosis to masquerade as other intracranial lesions.

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Glossopharyngeal neuralgia treated with gamma knife surgery: treatment outcome and failure analysis

Case report

Volker W. Stieber, J. Daniel Bourland, and Thomas L. Ellis

✓ Glossopharyngeal neuralgia (GPN) is a rare condition in which patients present with intractable deep throat pain. Similar to trigeminal neuralgia (TN), treatment with microvascular decompression (MVD) has been successful in both. Because gamma knife surgery (GKS) has also been shown to be effective in treating TN, it seemed reasonable to apply it to GPN. The authors present the first report of GKS-treated GPN in a patient who presented with severe, poorly controlled GPN and who refused MVD.

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Salvage retreatment after failure of radiosurgery in patients with arteriovenous malformations

Kelly D. Foote, William A. Friedman, Thomas L. Ellis, Frank J. Bova, John M. Buatti, and Sanford L. Meeks

Object. The goal of this study was to evaluate the outcomes of patients who underwent repeated radiosurgery to treat a residual intracranial arteriovenous malformation (AVM) after an initial radiosurgical treatment failure.

Methods. The authors reviewed the cases of 52 patients who underwent repeated radiosurgery for residual AVM at the University of Florida between December 1991 and June 1998. In each case, residual arteriovenous shunting persisted longer than 36 months after the initial treatment; the mean interval between the first and second treatment was 41 months. Each AVM nidus was measured at the time of the original treatment and again at the time of retreatment, and the dosimetric parameters of the two treatments were compared. After retreatment, patients were followed up and their outcomes were evaluated according to a standard posttreatment protocol for radiosurgery for AVMs.

The mean original lesion volume was 13.8 cm3 and the mean volume at retreatment was 4.7 cm3, for an average volume reduction of 66% after the initial treatment failure. Only two AVMs (3.8%) failed to demonstrate size reduction after the primary treatment. The median doses on initial and repeated treatment were 12.5 and 15 Gy, respectively. Five patients were lost to follow up and five refused neuroimaging follow up. One patient died of a hemorrhage shortly after retreatment. Of the remaining 41 patients, 24 had evidence of cure, 15 on angiographic studies and nine on magnetic resonance (MR) images. Seventeen had evidence of treatment failure, 10 on angiographic studies and seven on MR images. By angiographic criteria alone, the cure rate after retreatment was 60%, whereas according to angiographic and MR imaging results, the cure rate was 59%.

Conclusions. Although initial radiosurgical treatment failed to obliterate the AVM in these 52 patients, it did produce a substantial therapeutic effect (volume reduction). This size reduction commonly allowed higher doses to be delivered during radiosurgical retreatment. The results show rates of angiographically confirmed cure comparable to primary treatment and a low incidence of complications, indicating that salvage radiosurgical retreatment is a safe and effective therapy in cases of failed AVM radiosurgery.

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Rare intraparenchymal choroid plexus carcinoma resembling atypical teratoid/rhabdoid tumor diagnosed by immunostaining for INI1 protein

Case report

E. Andrew Stevens, Constance A. Stanton, Kyle Nichols, and Thomas L. Ellis

The authors present the case of a rare extraventricular, intraparenchymal choroid plexus carcinoma (CPC). This 6-year-old girl presented to the emergency department with a 1-week history of headaches, nausea, and vomiting. Imaging studies revealed an intraaxial cystic and solid mass located in the right frontal lobe with central nodular enhancement and minimally enhancing cyst walls. Gross-total resection was accomplished via craniotomy without complications. The initial pathological diagnosis was atypical teratoid/rhabdoid tumor (AT/RT); however, immunostaining for INI1 protein (using the BAF47/SNF5 antibody) showed retention of nuclear staining in the tumor cells, resulting in a change in the diagnosis to CPC. There was no evidence of recurrence at the last follow-up 2.5 years after treatment, which supports the diagnosis of CPC over AT/RT. This case emphasizes the importance of immunostaining for INI1 protein for distinguishing CPC from AT/RT in cases with atypical or indeterminate features.

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Analysis of treatment failure after radiosurgery for arteriovenous malformations

Thomas L. Ellis, William A. Friedman, Frank J. Bova, Paul S. Kubilis, and John M. Buatti

Object. The aim of this study was to evaluate the causes of treatment failure in patients with arteriovenous malformations (AVMs) who underwent radiosurgery, which is increasingly used as a treatment method for selected, surgically high-risk AVMs. Unfortunately, radiosurgical treatment fails in a small but significant percentage of patients. In the time period covered in this study, 72 patients attained angiographically confirmed cures after radiosurgery and 36 were retreated after the initial radiosurgical treatment failed.

Methods. Using a computerized image fusion technique, the initial radiosurgical dosimetry plan was superimposed on the remaining AVM nidus at the time of retreatment. Twenty-six percent of the retreated cases were found to have AVM niduses outside the original treatment isodose line, which means that targeting error was a factor. The retreated group was also statistically compared with the cured group.

Conclusions. Multivariate analysis revealed that the following factors were statistically significant predictors of treatment failure: increasing AVM size, decreasing treatment dose, and increasing Spetzler—Martin grade.

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Cholesterol granuloma of the lateral ventricle

Case report

Peter M. Grossi, Michael J. Ellis, Thomas J. Cummings, Linda L. Gray, Takanori Fukushima, and John H. Sampson

✓Cholesterol granulomas (CGs) are benign lesions resulting from an inflammatory reaction to cholesterol and hemosiderin. These masses most often arise within the temporal bone or nasal sinuses; intracerebral CGs are extremely rare. In this report the authors present an unusual case of a CG arising within the lateral ventricle.

The patient presented with transient hemiparesis and numbness. Computed tomography and magnetic resonance imaging demonstrated a cystic partially enhancing midline mass within the right lateral ventricle, expanding the ventricle and displacing the septum pellucidum. The patient underwent an interhemispheric, transcallosal resection of the lesion. Microscopic examination revealed a granulomatous inflammatory lesion containing cholesterol clefts, macrophages, and hemosiderin. Embedded within the granulomatous response were foci of tiny cystlike structures lined by nonciliated flattened cuboidal epithelium, consistent with the diagnosis of CG.

To the authors' knowledge this is the first reported case of CG presenting as an intraventricular mass. The origin of this lesion is unclear, but it may relate to prior traumatic brain injury. The authors describe the presentation, imaging findings, histopathological characteristics, and surgical treatment of this rare lesion and related pathological entities.

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Nonthermal irreversible electroporation for intracranial surgical applications

Laboratory investigation

Thomas L. Ellis, Paulo A. Garcia, John H. Rossmeisl Jr., Natalia Henao-Guerrero, John Robertson, and Rafael V. Davalos


Nonthermal irreversible electroporation (NTIRE) is a novel, minimally invasive technique to treat cancer, which is unique because of its nonthermal mechanism of tumor ablation. This paper evaluates the safety of an NTIRE procedure to lesion normal canine brain tissue.


The NTIRE procedure involved placing electrodes into a targeted area of brain in 3 dogs and delivering a series of short and intense electric pulses. The voltages of the pulses applied were varied between dogs. Another dog was used as a sham control. One additional dog was treated at an extreme voltage to determine the upper safety limits of the procedure. Ultrasonography was used at the time of the procedure to determine if the lesions could be visualized intraoperatively. The volumes of ablated tissue were then estimated on postprocedure MR imaging. Histological brain sections were then analyzed to evaluate the lesions produced.


The animals tolerated the procedure with no apparent complications except for the animal that was treated at the upper voltage limit. The lesion volume appeared to decrease with decreasing voltage of applied pulses. Histological examination revealed cell death within the treated volume with a submillimeter transition zone between necrotic and normal brain.


The authors' results reveal that NTIRE at selected voltages can be safely administered in normal canine brain and that the volume of ablated tissue correlates with the voltage of the applied pulses. This preliminary study is the first step toward using NTIRE as a brain cancer treatment.

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Safety and feasibility of the NanoKnife system for irreversible electroporation ablative treatment of canine spontaneous intracranial gliomas

John H. Rossmeisl Jr., Paulo A. Garcia, Theresa E. Pancotto, John L. Robertson, Natalia Henao-Guerrero, Robert E. Neal II, Thomas L. Ellis, and Rafael V. Davalos


Irreversible electroporation (IRE) is a novel nonthermal ablation technique that has been used for the treatment of solid cancers. However, it has not been evaluated for use in brain tumors. Here, the authors report on the safety and feasibility of using the NanoKnife IRE system for the treatment of spontaneous intracranial gliomas in dogs.


Client-owned dogs with a telencephalic glioma shown on MRI were eligible. Dog-specific treatment plans were generated by using MRI-based tissue segmentation, volumetric meshing, and finite element modeling. After biopsy confirmation of glioma, IRE treatment was delivered stereotactically with the NanoKnife system using pulse parameters and electrode configurations derived from therapeutic plans. The primary end point was an evaluation of safety over the 14 days immediately after treatment. Follow-up was continued for 12 months or until death with serial physical, neurological, laboratory, and MRI examinations.


Seven dogs with glioma were treated. The mean age of the dogs was 9.3 ± 1.6 years, and the mean pretreatment tumor volume was 1.9 ± 1.4 cm3. The median preoperative Karnofsky Performance Scale score was 70 (range 30–75). Severe posttreatment toxicity was observed in 2 of the 7 dogs; one developed fatal (Grade 5) aspiration pneumonia, and the other developed treatment-associated cerebral edema, which resulted in transient neurological deterioration. Results of posttreatment diagnostic imaging, tumor biopsies, and neurological examinations indicated that tumor ablation was achieved without significant direct neurotoxicity in 6 of the 7 dogs. The median 14-day post-IRE Karnofsky Performance Scale score of the 6 dogs that survived to discharge was 80 (range 60–90), and this score was improved over the pretreatment value in every case. Objective tumor responses were seen in 4 (80%) of 5 dogs with quantifiable target lesions. The median survival was 119 days (range 1 to > 940 days).


With the incorporation of additional therapeutic planning procedures, the NanoKnife system is a novel technology capable of controlled IRE ablation of telencephalic gliomas.

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The effect of targeted agents on outcomes in patients with brain metastases from renal cell carcinoma treated with Gamma Knife surgery

Clinical article

D. Clay Cochran, Michael D. Chan, Mebea Aklilu, James F. Lovato, Natalie K. Alphonse, J. Daniel Bourland, James J. Urbanic, Kevin P. McMullen, Edward G. Shaw, Stephen B. Tatter, and Thomas L. Ellis


Gamma Knife surgery (GKS) has been reported as an effective modality for treating brain metastases from renal cell carcinoma (RCC). The authors aimed to determine if targeted agents such as tyrosine kinase inhibitors, mammalian target of rapamycin inhibitors, and bevacizumab affect the patterns of failure of RCC after GKS.


Between 1999 and 2010, 61 patients with brain metastases from RCC were treated with GKS. A median dose of 20 Gy (range 13–24 Gy) was prescribed to the margin of each metastasis. Kaplan-Meier analysis was used to determine local control, distant failure, and overall survival rates. Cox proportional hazard regression was performed to determine the association between disease-related factors and survival.


Overall survival at 1, 2, and 3 years was 38%, 17%, and 9%, respectively. Freedom from local failure at 1, 2, and 3 years was 74%, 61%, and 40%, respectively. The distant failure rate at 1, 2, and 3 years was 51%, 79%, and 89%, respectively. Twenty-seven percent of patients died of neurological disease. The median survival for patients receiving targeted agents (n = 24) was 16.6 months compared with 7.2 months (n = 37) for those not receiving targeted therapy (p = 0.04). Freedom from local failure at 1 year was 93% versus 60% for patients receiving and those not receiving targeted agents, respectively (p = 0.01). Multivariate analysis showed that the use of targeted agents (hazard ratio 3.02, p = 0.003) was the only factor that predicted for improved survival. Two patients experienced post-GKS hemorrhage within the treated volume.


Targeted agents appear to improve local control and overall survival in patients treated with GKS for metastastic RCC.