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William A. Friedman and Kelly D. Foote

Despite major advances in skull base surgery and microsurgical techniques, surgery for vestibular schwannoma (VS) carries a risk of complications. Some are inherent to general anesthesia and surgery of any type and include myocardial infarction, pneumonia, pulmonary embolism, and infection. Some are specific to neurosurgery in this area of the brain, and include hydrocephalus, cerebrospinal fluid leak, facial nerve paralysis, facial numbness, hearing loss, ataxia, dysphagia, and major stroke. Even in the hands of very experienced acoustic surgeons, these risks cannot be eliminated.

Radiosurgery provides an outpatient, noninvasive alternative for the treatment of small acoustic schwannomas. Initially radiosurgery was undertaken in “high-risk” patients, including the elderly, those with severe medical comorbidities, and those in whom tumors recurred after surgery. Additionally, a high rate of cranial nerve morbidity was reported. With improvements in dosimetry planning and dose selection, however, authors practicing at radiosurgical centers now report very low complication rates, as well as high tumor control rates.

In this report the authors specifically review the results of linear accelerator–based radiosurgery for VS and compare these outcomes with the best surgical alternatives.

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Justin D. Hilliard and Kelly D. Foote

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Francisco A. Ponce, Kelly D. Foote and Andres M. Lozano

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William A. Friedman, Gregory J. Murad, Patrick Bradshaw, Robert J. Amdur, William M. Mendenhall, Kelly D. Foote and Frank J. Bova

Object. In this paper the authors review the results of a single-center experience in the use of linear accelerator (LINAC) surgery for radiosurgical treatment of meningiomas.

Methods. A retrospective analysis of all patients treated with LINAC surgery for meningiomas between May 1989 and December 2001 was performed. All patients participated in follow-up review for a minimum of 2 years, and no patients were excluded. Two hundred ten patients were treated during the study interval.

The actuarial local control rate for benign tumors was 100% at both 1 and 2 years, and 96% at 5 years. The actuarial local control rate for atypical tumors was 100% at 1 year, 92% at 2 years, and 77% at 5 years; and that for malignant tumors was 100% at both 1 and 2 years, and only 19% at 5 years. Of the 210 patients 13 (6.2%) experienced temporary radiation-induced complications, and only five (2.3%) experienced permanent complications. In all patients with a permanent complication the histological characteristics of the meningioma were malignant.

Conclusions. Linear accelerator surgery produced high local control rates and very low rates of permanent morbidity in patients harboring benign meningiomas.

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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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Kelly D. Foote, William A. Friedman, John M. Buatti, Sanford L. Meeks, Frank J. Bova and Paul S. Kubilis

Object. The aim of this study was to identify factors associated with delayed cranial neuropathy following radiosurgery for vestibular schwannoma (VS or acoustic neuroma) and to determine how such factors may be manipulated to minimize the incidence of radiosurgical complications while maintaining high rates of tumor control.

Methods. From July 1988 to June 1998, 149 cases of VS were treated using linear accelerator radiosurgery at the University of Florida. In each of these cases, the patient's tumor and brainstem were contoured in 1-mm slices on the original radiosurgical targeting images. Resulting tumor and brainstem volumes were coupled with the original radiosurgery plans to generate dose—volume histograms. Various tumor dimensions were also measured to estimate the length of cranial nerve that would be irradiated. Patient follow-up data, including evidence of cranial neuropathy and radiographic tumor control, were obtained from a prospectively maintained, computerized database. The authors performed statistical analyses to compare the incidence of posttreatment cranial neuropathies or tumor growth between patient strata defined by risk factors of interest. One hundred thirty-nine of the 149 patients were included in the analysis of complications. The median duration of clinical follow up for this group was 36 months (range 18–94 months). The tumor control analysis included 133 patients. The median duration of radiological follow up in this group was 34 months (range 6–94 months).

The overall 2-year actuarial incidences of facial and trigeminal neuropathies were 11.8% and 9.5%, respectively. In 41 patients treated before 1994, the incidences of facial and trigeminal neuropathies were both 29%, but in the 108 patients treated since January 1994, these rates declined to 5% and 2%, respectively.

An evaluation of multiple risk factor models showed that maximum radiation dose to the brainstem, treatment era (pre-1994 compared with 1994 or later), and prior surgical resection were all simultaneously informative predictors of cranial neuropathy risk. The radiation dose prescribed to the tumor margin could be substituted for the maximum dose to the brainstem with a small loss in predictive strength. The pons—petrous tumor diameter was an additional statistically significant simultaneous predictor of trigeminal neuropathy risk, whereas the distance from the brainstem to the end of the tumor in the petrous bone was an additional marginally significant simultaneous predictor of facial neuropathy risk.

The overall radiological tumor control rate was 93% (59% tumors regressed, 34% remained stable, and 7.5% enlarged), and the 5-year actuarial tumor control rate was 87% (95% confidence interval [CI] 76–98%). Analysis revealed that a radiation dose cutpoint of 10 Gy compared with more than 10 Gy prescribed to the tumor margin yielded the greatest relative difference in tumor growth risk (relative risk 2.4, 95% CI 0.6–9.3), although this difference was not statistically significant (p = 0.207).

Conclusions. Five points must be noted. 1) Radiosurgery is a safe, effective treatment for small VSs. 2) Reduction in the radiation dose has played the most important role in reducing the complications associated with VS radiosurgery. 3) The dose to the brainstem is a more informative predictor of postradiosurgical cranial neuropathy than the length of the nerve that is irradiated. 4) Prior resection increases the risk of late cranial neuropathies after radiosurgery. 5) A prescription dose of 12.5 Gy to the tumor margin resulted in the best combination of maximum tumor control and minimum complications in this series.

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Adam P. Burdick, Hubert H. Fernandez, Michael S. Okun, Yueh-Yun Chi, Charles Jacobson and Kelly D. Foote

Object

Adverse event (AE) rates for deep brain stimulation (DBS) are variable, due to various methodologies used for identifying, collecting, and reporting AEs. This lack of a prospective, standardized AE collection method is a shortcoming in the advancement of DBS. In this paper the authors disclose the standardized and prospectively recorded AE data from their institution, correlated with clinical outcome and quality of life (QOL) measures.

Methods

All patients who underwent operations at the authors' institution for Parkinson disease (PD), essential tremor, dystonia, other tremor, and obsessive-compulsive disorder were included. Complications occurring intraoperatively or within the first 180 days following surgery were recorded, analyzed, and classified as mild, moderate, or severe, regardless of their perceived relationship to the procedure. The presence, frequency, and severity of AEs were compared with the following outcome measurements: postoperative change in the QOL scales (Medical Outcomes Study 36-Item Short-Form Survey, 39-Item PD Questionnaire); motor scales (Tremor Rating Scale, Unified Dystonia Rating Scale, Unified PD Rating Scale); and Patient Global Impression Scale (PGIS).

Results

Two hundred seventy DBS procedures were performed in 198 patients. Three hundred AEs were recorded in 146 (54.1%) of the 270 procedures, and the AEs were recorded in 119 (60.1%) of 198 patients. Of the 198 patients, the maximum severity of AEs was mild in 28 (14.1%), moderate in 35 (17.7%), and severe in 56 (28.3%). Of the 300 AEs, 102 (34.1%) of 299 were mild, 106 (35.5%) were moderate, and 91 (30.4%) were severe. The AEs were classified as probably not stimulation induced in 10 (3.4%) of 297, probably in 44 (14.9%), unclear for 89 (30%), and not applicable to stimulation in 154 (51.9%). Adverse events were also classified as probably related to surgery in 111 (37.2%) of 298, possibly related in 96 (32.2%), and probably not related to surgery in 91 (30.5%). There was no significant difference (p = 0.22) in QOL outcomes among patients who had no AEs compared with those who experienced mild, moderate, or severe AEs. There was no significant difference in QOL outcomes between patients who did not experience an AE compared with those who experienced any AE. There was no significant difference in the mean General PGIS score between patients without an AE versus those with any AE, as well as on the Symptom-Specific PGIS. Motor function outcomes did not vary between patients with or without AEs. For patients with PD with or without AEs, there was no significant difference in preoperative off-medicine Unified PD Rating Scale score and postoperative 6-month on-medication/on-stimulation change scores (p = 0.59). For patients with tremor there were no differences between those with or without AEs on the Tremor Rating Scale for motor function or activities of daily living. Patients with dystonia with and without AEs showed no differences in the Unified Dystonia Rating Scale.

Conclusions

Prospectively and systematically recording AEs may result in higher AE rates, but this does not correlate with poorer QOL, motor function, or patient-oriented outcome scores.

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Takashi Morishita, Kelly D. Foote, Samuel S. Wu, Charles E. Jacobson IV, Ramon L. Rodriguez, Ihtsham U. Haq, Mustafa S. Siddiqui, Irene A. Malaty, Christopher J. Hass and Michael S. Okun

Object

Microelectrode recording (MER) and macrostimulation (test stimulation) are used to refine the optimal deep brain stimulation (DBS) lead placement within the operative setting. It is well known that there can be a microlesion effect with microelectrode trajectories and DBS insertion. The aim of this study was to determine the impact of intraoperative MER and lead placement on tremor severity in a cohort of patients with essential tremor.

Methods

Consecutive patients with essential tremor undergoing unilateral DBS (ventral intermediate nucleus stimulation) for medication-refractory tremor were evaluated. Tremor severity was measured at 5 time points utilizing a modified Tremor Rating Scale: 1) immediately before MER; 2) immediately after MER; 3) immediately after lead implantation; 4) 6 months after DBS implantation in the off-DBS condition; and 5) 6 months after implantation in the on-DBS condition. To investigate the impact of the MER and DBS lead placement, Wilcoxon signed-rank tests were applied to test changes in tremor severity scores over the surgical course. In addition, a generalized linear mixed model including factors that potentially influenced the impact of the microlesion was also used for analysis.

Results

Nineteen patients were evaluated. Improvement was noted in the total modified Tremor Rating Scale, postural, and action tremor scores (p < 0.05) as a result of MER and DBS lead placement. The improvements observed following lead placement were similar in magnitude to what was observed in the chronically programmed clinic setting parameters at 6 months after lead implantation. Improvement in tremor severity was maintained over time even in the off-DBS condition at 6 months, which was supportive of a prolonged microlesion effect. The number of macrostimulation passes, the number of MER passes, and disease duration were not related to the change in tremor severity score over time.

Conclusions

Immediate improvement in postural and intention tremors may result from MER and DBS lead placement in patients undergoing DBS for essential tremor. This improvement could be a predictor of successful DBS lead placement at 6 months. Clinicians rating patients in the operating room should be aware of these effects and should consider using rating scales before and after lead placement to take these effects into account when evaluating outcome in and out of the operating room.

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Maryam Rahman, Muhammad M. Abd-El-Barr, Vinata Vedam-Mai, Kelly D. Foote, Gregory J. A. Murad, Michael S. Okun and Steven N. Roper

Given the tremendous success of deep brain stimulation (DBS) for the treatment of movement and neuropsychiatric disorders, clinicians have begun to open up to the possible use of electrical stimulation for the treatment of patients with uncontrolled seizures. This process has resulted in the discovery of a wide array of DBS targets, including the cerebellum, hypothalamus, hippocampus, basal ganglia, and various thalamic nuclei. Despite the ambiguity of the mechanism of action and the unknowns surrounding potentially ideal stimulation settings, several recent trials have empirically demonstrated reasonable efficacy in selected cases of medication-refractory seizures. These exciting results have fueled a number of studies aimed at firmly establishing DBS as an effective treatment for selected cases of intractable epilepsy, and many companies are aiming at Food and Drug Administration approval. We endeavor to review the studies in the context of the various DBS targets and their relevant circuitry for epilepsy. Based on the unfolding research, DBS has the potential to play an important role in treating refractory epilepsy. The challenge, as in movement disorders, is to assemble interdisciplinary teams to screen, implant, and follow patients, and to clarify patient selection. The future will undoubtedly be filled with optimization of targets and stimulation parameters and the development of best practices. With tailored therapeutic approaches, epilepsy patients have the potential to improve with DBS.

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Editorial

Unilateral or bilateral deep brain stimulation

Kim J. Burchiel