- Department of Neurological Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
Correspondence Address:
Douglas Kondziolka
Department of Neurological Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
DOI:10.4103/2152-7806.91604
Copyright: © 2012 Kondziolka D. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.How to cite this article: Kondziolka D, Flickinger JC, Niranjan A, Lunsford LD. Trends and importance of radiosurgery for the development of functional neurosurgery. Surg Neurol Int 14-Jan-2012;3:
How to cite this URL: Kondziolka D, Flickinger JC, Niranjan A, Lunsford LD. Trends and importance of radiosurgery for the development of functional neurosurgery. Surg Neurol Int 14-Jan-2012;3:. Available from: http://sni.wpengine.com/surgicalint_articles/trends-and-importance-of-radiosurgery-for-the-development-of-functional-neurosurgery/
Abstract
Functional neurosurgery includes surgery conducted to ablate, augment, or modulate targets that lead to improvement in neurological function or behavior. Surgical approaches for this purpose include destructive lesioning with different mechanical or biologic agents or energy sources, non-destructive electrical modulation, and cellular or chemical augmentation. Our purpose was to review the role of stereotactic radiosurgery used for functional indications and to discuss future applications and potential techniques. Imaging and neurophysiological research will enable surgeons to consider new targets and circuits that may be clinically important. Radiosurgery is one minimal access approach to those targets.
Keywords: Radiosurgery, functional neurosurgery, stereotactic
INTRODUCTION
Functional neurosurgery has been “in development” for decades. Functional surgeries were some of the most commonly performed in the 1940s (behavioral neurosurgery) and 1950s (Parkinson's disease) before their renaissance in the current era of high-resolution imaging. The history of stereotactic radiosurgery goes back almost as far as the history of functional neurosurgery when tools were being developed not only for stereotactic localization but also for lesioning. Leksell initially conceived the idea of closed-skull, single-session irradiation of a precisely defined intracranial target in 1951, only 2 years after the development of his first stereotactic frame. He applied this concept immediately to functional neurosurgery.[
In those first years, the limitations of imaging were obvious. The procedure would not be totally noninvasive since contrast encephalography was necessary to identify the target. Although the ganglionic portion of the trigeminal nerve could be indirectly located using cisternography, deep brain targets required air or positive contrast ventriculography. Direct visualization of the target for functional radiosurgery required the later development of computed imaging technology (CT). Radiosurgical techniques were used to create brain lesions without neurophysiologic guidance. This was controversial. Lack of neurophysiologic guidance retarded the use of radiosurgery for functional disorders.
What led to the current interest in the use of functional stereotactic radiosurgery? The value of radiosurgery as a “lesion generator” was based on small and large animal studies that defined the critical dose, the volume, and the temporal evolution of the radiosurgical lesion. Subsequently, functional radiosurgery was compared to microsurgical, chemical, and thermal electrode-based techniques to create a lesion. Current anatomic targets include the trigeminal nerve (for facial pain syndromes), the thalamus (for tremor or pain), the cingulate gyrus or anterior internal capsule (for pain or behavioral illness), the hypothalamus (for cancer pain and perhaps for eating disorders), and the hippocampus or other brain targets (for epilepsy).[
To treat his initial few patients with trigeminal neuralgia, Leksell coupled an orthovoltage X-ray tube to his early generation stereotactic frame.[
THE EARLY FOUNDATION
Radiosurgery was clearly ahead of its time. Functional radiosurgery was performed for a limited number of patients with intractable pain related to malignancy,[
For intractable pain related to malignancy, radiosurgery was used both for hypophysectomy as well as for medial thalamotomy. Steiner and colleagues published an autopsy study of the effects of radiosurgery used for cancer pain in 1980.[
Early animal experiments showed consistent lesion creation at doses at or above 150 Gy.[
The ablative radiosurgery lesion appears as a punched-out, circumscribed volume of complete parenchymal necrosis with cavitation. The lesion was surrounded by a 1–3 mm rim that characterizes the steep fall-off in radiation dose. In this zone, blood vessels appear thickened and hyalinized, and often protein extravasation can be identified. Magnetic resonance (MR) imaging demonstrates all of these features after radiosurgical thalamotomy – a sharply defined, contrast-enhanced rim that defines the low-signal lesion (on short TR images) surrounded by a zone of high-signal (on long TR images) brain tissue.[
Given that the above-mentioned studies were conducted, why is radiosurgery infrequently used as a functional lesion generator? Perhaps it is due to the occasional variation in the lesion volume noted clinically. Dose fall-off outside the target becomes less steep with increasing volume. The risk of perilesional reactive edema beyond the desired target volume becomes problematic.[
FUNCTIONAL RADIOSURGERY RELIES ON IMAGING
Since physiological information is excluded from the targeting component of a functional radiosurgery procedure, high-quality stereotactic neuroimaging must be performed. The imaging must be accurate since small volumes are irradiated and this accuracy must be confirmed at each institution.[
RADIOSURGICAL THALAMOTOMY
One of the oldest and most established indications for functional neurosurgery is the ventrolateral thalamotomy used to manage Parkinsonian or essential tremor. The ventralis intermedius (VIM) nucleus thalamic target has been accessed by placement of an electrode into the thalamus, physiologic recording and stimulation at the target site, and creation of a lesion or providing electrical stimulation. Radiosurgical thalamotomy by definition avoids placement of the electrode and evaluation of the physiologic response. In radiosurgery, imaging definition alone is used to determine lesion placement. Initially through the use of contrast ventriculography and later with CT imaging, and over the past two decades with stereotactic MRI, thalamotomy using the Gamma Knife has been performed at centers across the world.[
Surgeons experienced with “open” thalamic surgery began to explore the value of radiosurgery. Ohye performed radiosurgical thalamotomy contralateral to a prior radiofrequency lesion or to enlarge a previously mapped lesion.[
The mean age of 77 years in the initial Pittsburgh radiosurgery report is older than the mean age of 60 years in their DBS series.[
In a recent overview of our entire radiosurgical thalamotomy experience, 86 patients (88 procedures) underwent gamma knife thalamotomy (GKT) for disabling tremor. Tremor was due to essential tremor (n=48; 19 > age 80 and 3 > 90), Parkinson's disease (29; 11 > age 80), or multiple sclerosis.[
Thus, the ability to create a small-volume lesion using radiosurgery without placement of a burr hole and the invasive placement of an electrode remains attractive. To that end, several surgeons have evaluated the use of radiosurgery for medial thalamotomy and for pallidotomy, procedures where the usefulness of physiologic recording or stimulation initially was less clear. However, with radiosurgical pallidotomy, we have seen inconsistent lesions perhaps due to the perforating artery supply or mineralization of the pallidum. In addition, the optic tract lies only a few millimeters below the target. There are reports from several centers, but we currently do not perform this procedure.[
RADIOSURGERY FOR PAIN
The use of radiosurgery as an ablative tool to treat pain has a long history, but case series are limited. Since the case report by Leksell in 1968 and the larger series by Steiner et al. in 1980, little has been written.[
Hayashi et al. performed pituitary gland-stalk ablation by Gamma Knife radiosurgery, targeting the border between the pituitary stalk and gland with a maximum dose of 160 Gy using the 8-mm collimator to control cancer pain. They enrolled nine patients who had bone metastases and pain controlled well by morphine, Karnofsky performance score (KPS) > 40, and no previous radiation therapy.[
There is a large amount of literature on the use of stereotactic radiosurgery for trigeminal neuralgia including matched cohort comparisons to other surgical techniques and prospective trials. Over the past 20 years, radiosurgery has become an important option for patients and physicians and we think will continue to play a key management role.
RADIOSURGERY FOR BEHAVIORAL DISORDERS
There are several potential radiosurgery targets to be explored for patients with behavioral disorders. Deep brain stimulation, with the opportunity to conduct testing both on and off stimulation, is a valuable research tool to evaluate specific targets. On the other hand, radiosurgery is an excellent therapeutic tool because it is “always on” and avoids hardware placement or pulse generator failure. Nevertheless, this approach is not often performed but we think will have an expanding future role.
Of greatest current interest is the anterior internal capsule (anterior capsulotomy) in patients with medically refractory obsessive–compulsive disorder (OCD). Radiosurgery for obsessive–compulsive and anxiety neurosis has been performed for over 45 years.[
We perform radiosurgical capsulotomy only after a comprehensive psychiatric evaluation and management regimen leading to a diagnosis of severe or extreme OCD and after failure of non-surgical approaches. In Pittsburgh, we have performed Gamma Knife surgery on four patients with severe, medically intractable OCD and reported on the initial three.[
RADIOSURGERY FOR EPILEPSY
There is clinical and research interest in the use of radiosurgery for patients with focal epilepsy. Focal brain irradiation can lead to amelioration of seizures due to brain tumors, vascular malformations, and other pathologies. The history of this research tells a tale that alternates between human and animal studies. In 1985, Barcia-Salorio et al. reported on six patients with epilepsy who had low-dose radiosurgery (10 Gy). The epileptic focus was localized by means of conventional scalp electroencephalogram (EEG), subarachnoid electrodes, and depth electrodes. In 1994, they provided a long-term analysis in a series of 11 patients using a dose range of 10–20 Gy. Five patients had complete cessation of seizures and an additional five improved. Seizures began to decrease gradually after 3–12 months following radiosurgery.[
More recently, radiosurgery has been of value in patients with gelastic or generalized seizures related to hypothalamic hamartomas.[
Current issues that remain important for epilepsy radiosurgery include dose selection (necrotizing vs. non-necrotizing), localization methods for non-lesional epilepsy, the target volume necessary for irradiation, and the expected short- and long-term outcomes. It is not known what kind of tissue effect is required to stop the generation or propagation of seizures. Some groups have used low doses (i.e. 10–20 Gy) where tissue destruction would not be expected. Others have used doses as high as 100 Gy that cause target necrosis and regional brain edema.[
We think that stereotactic radiosurgery will play an increasing role in epilepsy management. There are many patients who are good surgical candidates but choose not to have surgery or are simply not referred for surgery. Radiosurgery may be an attractive option for them. Tools that enhance our ability to identify the seizure focus will increase the utility of radiosurgery.
FUNCTIONAL IMAGING AND RADIOSURGERY
Improvements in functional imaging eventually will impact radiosurgery. Functional MRI to localize cortical function prior to radiosurgery has been evaluated in pilot studies. Pre-radiosurgery localization of specific motor functions, visual and speech areas close to arteriovenous malformations and brain tumors has been used in dose planning.[
Publication of this manuscript has been made possible by an educational grant from
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