Andrew G. Shetter

Electrical stimulation of the anterior nucleus of thalamus for treatment of refractory epilepsy.

Purpose:  We report a multicenter, double‐blind, randomized trial of bilateral stimulation of the anterior nuclei of the thalamus for localization‐related epilepsy.

Electrical Stimulation of the Anterior Nucleus of the Thalamus for the Treatment of Intractable Epilepsy

Summary:  Purpose: Animal studies and sporadic case reports in human subjects have suggested that intermittent electrical stimulation of the anterior nucleus of the thalamus reduces seizure activity. We embarked on an open‐label pilot study to determine initial safety and tolerability of bilateral stimulation of the anterior nucleus of the thalamus (ANT), to determine a range of appropriate stimulation parameters, and to begin to gather pilot efficacy data.

Spinal Epidural Hematoma Associated with Epidural Anesthesia: Complications of Systemic Heparinization in Patients Receiving Peripheral Vascular Thrombolytic Therapy

Spinal Epidural Hematoma Associated with Epidural Anesthesia: Complications of Systemic Heparinization in Patients Receiving Peripheral Vascular Thrombolytic Therapy Curtis Dickman;Steven Shedd;Robert Spetzler;Andrew Shetter;Volker Sonntag; Anesthesiology

Administration of Intraspinal Morphine Sulfate for the Treatment of Intractable Cancer Pain

A total of 24 patients with intractable cancer pain were evaluated as candidates for spinal morphine therapy. Temporary trials were carried out with bolus injections of preservative-free morphine sulfate via percutaneously inserted epidural catheters. Fourteen patients felt that pain relief was sufficient to warrant long term morphine application, and permanent drug delivery systems were implanted. These consisted of an Ommaya reservoir and an epidural spinal catheter in 6 patients and an Infusaid pump with either an epidural or subarachnoid spinal catheter in 8 patients. Pain relief with these systems was felt to be excellent in 7 patients, good in 4 patients, and fair in 3 patients. There was a statistically significant reduction in supplemental narcotic use between the pre- and postoperative periods (P less than 0.001). Median survival after operation was 3.0 months (mean, 5.0 months), with a range of 1 to 23 months. Tolerance was seen in all patients regardless of the mode of drug delivery, but it occurred more quickly with bolus injections than with continuous infusion (statistically significant difference, P less than 0.05). A persistent cerebrospinal fluid fistula developed in 1 patient; this required wound revision. No other serious complications or episodes of respiratory depression occurred. We conclude that intraspinal morphine sulfate is a beneficial treatment option for cancer patients in whom pain has become debilitating and unresponsive to oral or parenteral narcotic regimes.

Long-term pain response and quality of life in patients with typical trigeminal neuralgia treated with gamma knife stereotactic radiosurgery.

OBJECTIVEThe long-term outcome of patients treated with gamma knife radiosurgery (GKRS) for typical trigeminal neuralgia has not been fully studied. We evaluated 185 patients who underwent their first GKRS treatment between 1997 and 2003 at the Barrow Neurological Institute. METHODSFollow-up was obtained by surveys and review of medical records. Outcomes were assessed by the Barrow Neurological Institute Pain Intensity Score and Brief Pain Inventory. The most common maximum dose was 80 Gy targeted at the root entry zone. Outcomes are presented for the 136 (74%) patients for whom more than 4 years of clinical follow-up data were obtained. RESULTSTreatment failed in 33% of the cohort within 2 years, but only an additional 1% relapsed after 4 years. Actuarial analysis demonstrated that 32% of patients were pain-free off medication and 63% had at least a good outcome at 7 years. When GKRS was used as the primary treatment, 45% of the patients were pain-free at 7 years. In contrast, 10% of patients in whom previous treatment had failed were pain-free. When needed, salvage therapy with repeat GKRS, microvascular decompression, or percutaneous lesioning was successful in 70%. Posttreatment facial numbness was reported as very bothersome in 5%, most commonly in patients who underwent another invasive treatment. After GKRS, 73% reported that trigeminal neuralgia had no impact on their quality of life. CONCLUSIONGKRS is a reasonable long-term treatment option for patients with typical trigeminal neuralgia. It yields durable pain control in a majority of patients, as well as improved quality of life with limited complications and it does not significantly affect the efficacy of other surgical treatments, should they be needed.

Treatment of malignant gliomas with interstitial irradiation and hyperthermia

A Phase I study of interstitial thermoradiotherapy for high-grade supratentorial gliomas has been completed. The objective of this trial was to test the feasibility and toxicity of hyperthermia induced by ferromagnetic implants in the treatment of intracranial tumors. The patient population consisted of 16 males and 12 females, with a median age of 44 years and a median Karnofsky score of 90. Nine patients had anaplastic astrocytoma while 19 had glioblastoma multiforme. Twenty two patients were treated at the time of their initial diagnosis with a course of external beam radiotherapy (median dose 48.4 Gy) followed by an interstitial implant with Ir-192 (median dose 32.7 Gy). Six patients with recurrent tumors received only an interstitial implant (median dose 40 Gy). Median implant volume for all patients was 55.8 cc and median number of treatment catheters implanted per tumor was eighteen. A 60-minute hyperthermia treatment was given through these catheters just before and right after completion of brachytherapy. Time-averaged temperatures of all treatments were computed for sensors located within the core of (> 5 mm from edge of implant), and at the periphery of the implant (outer 5 mm). The percentage of sensors achieving an average temperature > 42 degrees C was 61% and 35%, respectively. Hyperthermia was generally well tolerated; however, there have been 11 minor toxicities, which resolved with conservative management, and one episode of massive edema resulting in the death of a patient. In addition, there were three major complications associated with the surgical implantation of the catheters. Preliminary survival analysis shows that 16 of the 28 patients have died, with a median survival of 20.6 months from diagnosis. We conclude that interstitial hyperthermia of brain tumors with ferromagnetic implants is feasible and carries significant but acceptable morbidity given the extremely poor prognosis of this patient population.

Gamma Knife Radiosurgery for Trigeminal Neuralgia

Forty-three patients with trigeminal neuralgia (TN) unresponsive to pharmacologic treatment and/or prior invasive procedures underwent stereotactic radiosurgery with the Gamma Knife (GK). Outcome was evaluated by a standardized questionnaire mailed to each patient. The mean follow-up was 9 months. Fifteen patients (35%) reported no trigeminal pain and were no longer taking medication. Three patients (7%) experienced occasional pain, but were no longer taking medication. In 15 patients (35%), pain improved and was adequately controlled by medication, often in lower dosages than preoperatively. Pain was reduced in 9 patients (21%), but their symptoms were still inadequately controlled by drug therapy, and 1 patient (2%) reported no pain relief after treatment. Three patients (7%) described new facial numbness, but in none was this bothersome. GK radiosurgery for TN appears to have minimal morbidity, although the success rate may be slightly lower than that of other operative procedures. More patients and longer follow-up are needed before drawing final conclusions regarding efficacy and complications.

Interstitial thermoradiotherapy of brain tumors: Preliminary results of a phase I clinical trial

A Phase I clinical trial has been initiated to determine the feasibility, tolerance, and toxicity of interstitial thermoradiotherapy in the treatment of high-grade supratentorial brain gliomas. Hyperthermia was delivered by means of thermally-regulating ferromagnetic implants afterloaded into stereotactically placed plastic catheters. Heat treatments were given immediately before interstitial irradiation; in addition, five patients received a second heat treatment at the completion of brachytherapy. The desired target temperature for the 60-minute hyperthermia session was between 42 degrees C and 45 degrees C. Following hyperthermia, the catheters were afterloaded with Ir-192, which delivered a variable radiation dose of 14-50 Gy depending on the clinical situation. Interstitial irradiation was supplemented with external beam radiotherapy (40-41.4 Gy) in patients with previously untreated tumors. A total of 14 patients (4 males, 10 females) have been treated to date on this protocol. Eleven of the patients had a diagnosis of glioblastoma multiforme, whereas three had anaplastic astrocytoma. The mean implant volume was 61.5 cm3 (range: 9-119 cm3); the median number of interstitial treatment catheters implanted was 19 (range: 7-33). Continuous temperature monitoring was performed by means of multisensor thermocouple probes inserted in the center as well as in the periphery of the tumor. Of the 175 monitored intratumoral points, 83 (47%) had time-averaged mean temperatures of greater than 42 degrees C, and only 12 sensors (7%) exceeded a temperature of 45 degrees C. Among the 19 heat treatments attempted, there have been four minor acute toxicities, all of which resolved with conservative medical management and one major complication resulting in the demise of a patient. These preliminary results indicate that ferromagnetic implants offer a promising new approach to treating brain tumors with hyperthermia.

Interstitial irradiation versus interstitial thermoradiotherapy for supratentorial malignant gliomas: A comparative survival analysis

PURPOSE To compare the survival of two groups of patients with supratentorial malignant gliomas who were treated on two sequential protocols with either interstitial thermoradiotherapy or with interstitial irradiation without hyperthermia. METHODS AND MATERIALS Between 1988-1992, patients with anaplastic astrocytoma or glioblastoma multiforme were treated at the University of Arizona on a Phase I/II protocol of interstitial thermoradiotherapy with ferro-magnetic seeds. The treatment protocol consisted of debulking surgery, a course of external beam radiotherapy and hyperthermia given immediately before and after brachytherapy. The survival of patients so treated was compared with that of a similar group of patients treated with interstitial brachytherapy alone at the Barrows Neurological Institute between 1982-1990. RESULTS Twenty-five patients with primary tumors treated at the time of initial presentation with thermoradiotherapy were compared with a control group of 37 patients treated with interstitial brachytherapy alone. All primary patients were followed for a minimum of 34 months post implant. Multivariate analysis based on proportional hazards models showed that hyperthermia (p = 0.027), patient age (p < or = 0.00001) and histology (anaplastic astrocytoma vs. glioblastoma multiforme, p = 0.0017) were the only factors significantly associated with survival in this data set. From the fitted model, the hazard of dying when treated with hyperthermia was .53 times (95% confidence intervals 0.29-0.94) than that of the control group. In addition, we treated a small group of patients with recurrent tumors (13 with brachytherapy alone, and eight with thermoradiotherapy) and found no survival difference (p = 0.62). CONCLUSION Within the constraints of the selection factors and the different treatment parameters used in these studies, we conclude that an interstitial thermoradiotherapy boost confers a statistically significant survival benefit to patients with primary high grade gliomas when compared to interstitial brachytherapy alone.

Scarring around cervical epidural stimulating electrode.

Scarring around the electrically stimulating electrodes has been of concern since dorsal column stimulation was introduced. This concern resurfaced in the days of cerebellar electrodes and, with the advent of epidural stimulating techniques for the control of pain and spasticity, it again arises as a potential problem. We present a patient who underwent the placement of a C-2-C-4 electrode to treat torticollis; 3 months later, a mild spastic quadriparesis developed and the stimulation became ineffective. At reexploration, dense scar surrounded the electrode and confined the cervical spinal cord. With microdissection techniques, the scar was removed from the dura mater and the dura began to pulsate freely. The quadriparesis reversed. Examination of the scar tissue microscopically showed linearly arrayed fibroblastic nuclei, and we are uncertain whether the exuberant fibroblastic response is a response to electrical stimulation, the materials used in the electrode, or some technical aspects of the operation.