Michael L.J. Apuzzo

Computed imaging stereotaxy: experience and perspective related to 500 procedures applied to brain masses

The evolution of more sophisticated imaging techniques has initiated a renewed interest in stereotactic devices, methods, and applications. The Brown-Roberts-Wells instrument was available to us early in its prototype stage, and this report reviews the first 500 cases using the system at the University of Southern California Medical Center Hospitals. Procedures were undertaken after recognition of apparent structural alterations on imaging studies, with objectives being both diagnostic and therapeutic. Target locations were predominantly within the cerebral centrum-basal ganglia (284 cases) and diencephalic-mesencephalic regions (129 cases). Operative objectives included: histological and microbiological assay, cyst and abscess aspiration, installation of temporary or permanent drainage conduits, point source and colloid base brachytherapy, cerebroscopy and ventriculoscopy with biopsy, aspiration, and excision, and intraoperative vascular localization. Using multiple instrumentation at the target point (741 point placements), we realized procedural objectives in 95.6% of the cases. The mortality was 0.2% and the morbidity was 1%: hematoma, 2 cases; infection, 1 case; increased deficit, 1 case; intraprocedural seizure, 1 case. A specific diagnosis was not obtained in 4.4% (necrosis, 10 cases; inflammatory response, 9 cases; granuloma, 1 case; gliosis, 1 case; diagnostic error, 1 case). Individual guidelines for case selection, technique, institutional requirements, and applications of the method are discussed.(ABSTRACT TRUNCATED AT 250 WORDS)

Computed tomographic guidance stereotaxis in the management of intracranial mass lesions.

A prototype Brown-Roberts-Welles stereotactic instrument has been used as both a diagnostic and a therapeutic surgical adjunct in cases of intracranial mass lesions. Eighty-three procedures (142 point placements) required computerized guidance stereotaxy. The unit accomplished point intracranial access with an accuracy of greater than 1 mm. Pathological processes included a variety of neoplasms (56 cases), strokes (7 cases), and infections (20 cases) affecting deep regions of the cerebral hemispheres, the ventricular system, the cerebellum, and the rostral brain stem. Procedures were undertaken with the patient under local anesthesia for biopsy (300 point specimens), culture, evacuation, aspiration, endoscopic excision, and implantation of radioisotopes. The techniques and instrumentation for each of these procedures are described. Procedural objectives were satisfactorily accomplished with no mortality and an overall complication rate of 4%. Recovery of tissue specific to establish a histological diagnosis or the etiological factors related to each disease process was realized in 94% of the cases. These results were obtained with scanner utilization times averaging 15 minutes and procedurally related patient recovery periods of less than 4 hours. The value and adaptability of the instrumentation and techniques are illustrated, and potential future applications are discussed.

Transcallosal, interfornicial approaches for lesions affecting the third ventricle: surgical considerations and consequences

A group of 11 patients with a variety of lesions affecting the 3rd ventricle have been treated using a direct transcallosal interfornicial approach to the region. In 3 patients, no attendant hydrocephalus was present. In an effort to minimize potential cortical injury related to the approach, we studied the venous anatomy in the region of the coronal suture. Based on this study, appropriate flap placement and interhemispheric entry points were defined. Although no lasting, clinically apparent morbidity was observed in any of the 11 cases, we performed more sophisticated studies of the interhemispheric transfer of somesthetic and perceptual motor tasks, as well as psychometric testing related to parameters of intelligence and memory, 3 to 8 months postoperatively in 6 cases. The results and clinical material indicate that this surgical technique is a safe, feasible alternative in the management of a wide spectrum of pathological lesions within this region. A transcallosal, interfornicial approach offers excellent visualization of the entire 3rd ventricle without the dependence on hydrocephalus or an extensive extra-axial mass to enhance the exposure. With proper planning and technique, it may be accomplished with a minimum of physiological consequence.

Stereotactic biopsy in the diagnosis of brain masses: comparison of results of biopsy and resected surgical specimen.

We report the pathological accuracy of image-directed stereotactic brain biopsy in 30 patients who had mass lesions of the brain and subsequently underwent resection of the mass. The histological diagnosis at stereotactic biopsy was appropriate for direction of clinical management in 28 of 30 patients. Correlation between the stereotactic and resection diagnoses was exact in 19 of 30 cases. These included 11 of 12 nonastrocytic neoplasms and 8 of 13 astrocytic neoplasms. Correlation was imperfect in 9 of 30 cases, but not to the extent of having significant clinical impact. These included 2 cases of anaplastic astrocytoma that were upgraded to glioblastoma multiforme, 2 cases of astrocytoma that had a significant oligodendroglial component, and 5 non-neoplastic lesions that were reported on biopsy as showing nonspecific reactive changes. In 2 of 30 patients, the stereotactic biopsy was not accurate. This included one patient who had glioblastoma multiforme whose stereotactic biopsy showed only necrotic tissue. Serious diagnostic error that resulted in clinical mismanagement occurred in one patient who had a pineal germinoma that had large areas of granulomatous inflammation at which the stereotactic biopsy was directed. This study provides evidence that, with careful target placement, stereotactic biopsy can provide biopsy material that represents the entire lesion with an accuracy that is sufficient for clinical management.

Toward the Emergence of Nanoneurosurgery: Part III—Nanomedicine: Targeted Nanotherapy, Nanosurgery, and Progress Toward the Realization of Nanoneurosurgery

THE NOTION OF nanotechnology has evolved since its inception as a fantastic conceptual idea to its current position as a mainstream research initiative with broad applications among all divisions of science. In the first part of this series, we reviewed the structures and principles that comprise the main body of knowledge of nanoscience and nanotechnology. In the second part, we discussed applications of nanotechnology to the emerging field of nanomedicine, with specific attention on medical diagnostics and imaging. This article further explores the applications of nanotechnology to nanomedicine. Specific attention is given to developments in therapeutic modalities, including advanced drug delivery systems and targeted nanotherapy, which will form the basis for the treatment arm of mature nanomedicine. A variety of modalities are discussed, including polymeric nanoparticles, micelles, liposomes, dendrimers, fullerenes, hydrogels, nanoshells, and smart surfaces. Applications of nanotechnology to nanosurgery and nanoneurosurgery are presented. Femtosecond laser systems, nanoneedles, and nanotweezers are presented as technologies that are operational at the nanoscale level and have the potential to revolutionize the practice of neurosurgery in a profound and momentous way.

Vagus Nerve Stimulation Activates Central Nervous System Structures in Epileptic Patients During PET H215O Blood Flow Imaging

OBJECTIVE To determine the central areas of activation by vagal nerve stimulation (VNS) in epilepsy. VNS is a promising neurosurgical method for treating patients with partial and secondary generalized epilepsy. The anti-epileptic mechanism of action from VNS is not well understood. METHODS We performed H2(15)O PET blood flow functional imaging on three patients with epilepsy in a vagal nerve stimulation study (E04 Protocol with Cyberonics). The three patients included two that had previous epilepsy surgery but continued to have frequent seizures. Seizure onset was frontal in two patients and bitemporal in the third patient. Twelve PET scans per subject were acquired every 10 minutes with a Siemens 953/A scanner. In 6 stimulus scans, VNS was activated for 60 seconds (2 mA, 30 Hz) commensurate with isotope injection. In 6 control scans no VNS was administered. No clinical seizures were present during any scan. Three way ANOVA with linear contrasts subject, task, repetition) of coregistered images identified significant treatment effects. RESULTS The difference between PET with VNS and without revealed that left VNS activated right thalamus (P < 0.0006), right posterior temporal cortex (P < 0.0003), left putamen (P < 0.0002), and left inferior cerebellum (P < 0.0009). CONCLUSIONS VNS causes activation of several central areas including contralateral thalamus. Localization to the thalamus suggests a possible mechanism to explain the therapeutic benefit, consistent with the role of the thalamus as a generator and modulator of cerebral activity.

Gamma Knife Radiosurgery for Metastatic Melanoma: An Analysis of Survival, Outcome, and Complications

OBJECTIVE Although the mainstays for treatment of metastatic brain disease have been surgery and/or external beam radiation therapy, an increasing number of patients are being referred for stereotactic radiosurgery as the primary intervention for their intracranial pathological abnormalities. The lack of efficacy and cognitive and behavioral consequences of whole brain irradiation have prompted clinicians to select patients for alternative therapies. This study analyzes the effectiveness of Leksell gamma unit therapy for metastatic melanoma to the brain. METHODS We present our experience with 59 Leksell gamma unit treatment sessions in 45 consecutive patients who presented with metastatic melanoma to the brain. Five of these procedures were performed as salvage therapy for patients who needed second radiosurgical treatment for new lesions that were remote from the previous targets and were not included in the overall analyses. RESULTS The population included 78% male patients. The mean patient age was 53 years (age range, 24-80 yr). The mean time from diagnosis of primary melanoma to discovery of brain metastasis was 43 months (median, 27.5 mo; range, 1-180 mo). At the time of diagnosis of brain disease, 35.5% of the patients (16 of 45 patients) had neurological symptoms, 77.7% (35 of 45 patients) had known visceral metastases, and 11.1% (5 of 45 patients) had seizure disorders. Eighty-six percent of the lesions (80 of 93 lesions) were cortical, 12% (11 of 93 lesions) were cerebellar, 1% (1 of 93 lesions) were pontine, and 1% (1 of 93 lesions) were thalamic. Fifty-seven percent of the sessions (31 of 54 sessions) were performed for a single lesion, 24.1% (13 of 54 sessions) for two lesions, 9.2% (5 of 54 sessions) for three lesions, 7.4% (4 of 54 sessions) for four lesions, and 1.8% (1 of 54 sessions) for five lesions. The mean treatment volume was 5.6 cc, with a mean prescription of 21.6 Gy to the 56.0% mean isodose line. The median survival time of the patients in our population, using Kaplan-Meier curves, was 43 months from the time of diagnosis of primary melanoma (range, 3-180 mo) and 8 months (range, 1-20 mo) from the time of gamma knife treatment. Complications included seizures within 24 hours of the procedure in four patients, with transient nausea and vomiting in three patients, transient worsening of preprocedure paresis responsive to steroids in three patients, and increased confusion in one patient. All 45 patients were located for follow-up (mean follow-up duration, 1 yr). After gamma knife treatment, 78% of the patients (35 of 45 patients) experienced either improved or stable neurological symptomatology before death or at the time of the latest follow-up examination. There were 26 deaths (58%). The cause of death was determined to be neurological in only 2 of 45 patients (7.7%). Follow-up magnetic resonance images revealed a 97% local tumor control rate of gamma knife-treated lesions, with 28% radiographic disappearance (9 of 32 cases). Six patients developed new lesions remote from radiosurgical targets and underwent second procedures. CONCLUSION Although metastatic melanoma to the brain continues to have a foreboding prognosis for long-term survival, gamma knife radiosurgery seems to be a relatively safe, noninvasive, palliative therapy, halting or reversing neurological progression in 77.8% of treated patients (35 of 45 patients). The survival rate matches or exceeds those previously reported for surgery and other forms of radiotherapy. Only 7.7% of the patients in our study population who died as a result of metastatic melanoma (2 of 26 patients) died as a result of neurological disease. The routine use of therapeutic level antiseizure medication is emphasized, considering the findings of our review.

An institutional experience with cervical vagus nerve trunk stimulation for medically refractory epilepsy: rationale, technique, and outcome.

OBJECTIVE Intermittent stimulation of the left cervical vagus nerve trunk is emerging as a novel adjunct in the treatment of medically refractory seizures. We sought to evaluate theoretical and practical issues attendant to this concept. We review the anatomic and physiological background arguing for clinical application of vagus nerve stimulation, discuss salient aspects of patient selection and the nuances of surgical technique, and present our observations of and results from application of the method. METHODS Each of 18 patients with medically refractory epilepsy and at least six complex partial or secondarily generalized seizures per month underwent placement of a NeuroCybernetic Prosthesis pulse generator (Cyberonics, Webster, TX) in the chest, connected to helical platinum leads applied to the left cervical vagus nerve trunk. The patients were then randomized in a double-blinded fashion to receive either high (presumably therapeutic) or low (presumably less therapeutic) levels of vagus nerve stimulation. Reduction in seizure frequency, global assessments of quality of life, physiological measurements, and adverse events were recorded during a 3-month period. Patients in the low group were then crossed over to high-stimulation paradigms during a 15-month extension trial. RESULTS All operations were successful, uneventful, and without adverse postoperative sequelae. One patient was excluded from analysis because of inadequate seizure calendars. Of the seven patients initially assigned to high stimulation, the mean reduction in seizure frequency was 71% at 3 months and 81% at 18 months. Five (72%) of these patients had a greater than 75% reduction in seizure frequency, and one (14%) remained seizure-free after more than 1.5 years of follow-up. The mean reduction in seizure frequency among the low-stimulation group was only 6% at 3 months. No serious complications, device failures, or physiological perturbations occurred. CONCLUSION In our experience, vagus nerve stimulation has proven to be a safe, feasible, and potentially effective method of reducing seizures in select patient populations. However, the elements of strict definition for the application of the method require further study.

Stereotactic radiosurgery: Principles and comparison of treatment methods

Methods of stereotactic radiosurgery are reviewed and compared with respect to technical factors and published clinical results. Heavy-ion beams, the Leksell cobalt-60 gamma knife, and the conventional linear accelerator (linac) are compared with respect to dosimetry, radiobiology, treatment planning, cost, staffing requirements, and ease of use. Clinical results on the efficacy of treatment of arteriovenous malformations are tabulated, and other applications of radiosurgery are described. It is concluded that although there are dosimetric and radiobiological advantages to charged-particle beams that may ultimately prove critical in the application of radiosurgery to large (> 30 mm) lesions, these advantages have not yet demonstrated clinical effect. On the other hand, equally excellent clinical results are obtained for small lesions with photon beams--the gamma knife and the linac. There are only minor differences between gamma and x-ray beam dose distributions for small, spherical-shaped targets. Mechanical precision is superior for the gamma knife as compared with the linac. The superior mechanical precision is of limited importance for most clinical targets, because inaccuracy of cranial target localization based on radiological imaging is greater than the typical linac imprecision of +/- 1 mm. Treatment planning for the linac is not standardized, but existing systems are based on well-known algorithms. The linac allows flexible, ready access to individualized beam control, without intrinsic field size limitations. Thus, it is more readily possible to achieve homogeneous dose distributions for nonspherical targets with one or more dimensions greater than 25 mm, as compared with that achieved with the gamma unit.(ABSTRACT TRUNCATED AT 250 WORDS)

Longitudinal evaluation of patients with untreated prolactin-secreting pituitary adenomas

A group of 43 patients with galactorrhea, hyperprolactinemia, and radiographic evidence of pituitary adenomas were followed from 3 to 20 years. Initial polytomography and computerized tomographic (CT) scans revealed no evidence of extrasellar extension. Serum levels of prolactin (PRL) were measured at 6 month intervals, and visual fields were assessed annually. Polytomograms and CT scans were repeated every 9 to 36 months. During the period of follow-up, CT scans (but not polytomograms) indicated tumor enlargement in two patients, both of whom underwent selective transsphenoidal removal of the tumor. Polytomograms and CT scans did not show any change in the other 41 patients, and three of them have resumed normal menses, are no longer lactating, and have normal PRL levels. The initial results of this ongoing study indicate that most patients with small pituitary adenomas can be followed with annual CT scans with or without medical therapy, and that surgical treatment should be reserved for those patients with large tumors, those with visual-field loss, and those who show signs of enlargement of the tumor.