Extensive expansion in the practice of functional neurosurgery has occurred in the last several years as neuromodulation treatments for movement disorders and pain have flourished. Deep brain stimulation for Parkinson’s disease and essential tremor is now performed in most academic centers as well as in a substantial number of community hospitals.
Recently published 5-year results for subthalamic nucleus stimulation for Parkinson’s disease demonstrate the durability of the clinical improvement with the technique, even though it did not appear to slow the progression of the disease. Patients achieve approximately 54 percent improvement with stimulation compared to their off-medication state. While some questions still remain, such as the treatment’s long-term effect on cognition, the success of DBS for Parkinson’s disease has led to the exploration of brain stimulation for several other indications, including psychiatric disease, and medically refractory epilepsy, in addition to neuropathic pain and movement disorders.
Surgery for Psychiatric Disorders
The earliest forays into brain stimulation in the 1940s and 1950s were for psychiatric disorders. Today, with increased knowledge of the neuroanatomy and neuropharmacology of psychiatric disorders, modes of treatment are cautiously being reexplored. In a recent study 15 patients with medically intractable obsessive-compulsive disorder were treated with bilateral chronic stimulation of the internal capsule. This is the same target area currently and successfully used for lesioning in patients with intractable OCD. Promising early results of the stimulation study have included significant decreases in anxiety and depression, as well as in obsessive-compulsive behavior. Results from this trial are pending, but it is hoped that the mood improvement of OCD patients treated with stimulation mirrors that noted in the OCD patients treated with lesioning. Similar trials are underway for intractable major depression.
Visser-Vandewalle and colleagues recently reported the successful treatment of three patients with Tourette’s syndrome with stimulation of the centromedian nucleus of the thalamus. Cyberonics, the manufacturer of the vagal nerve stimulator, is attempting to gain U.S. Food and Drug Administration approval to add refractory depression as an indication for the device. However, given the checkered history of surgery for psychiatric disease, these studies are proceeding under the most stringent ethical supervision.
Medically Intractable Epilepsy
Medically intractable epilepsy remains a focus of much interest for cerebral stimulation. Approximately 17,000 Americans are diagnosed with medically intractable epilepsy each year. Several devices are currently in trial for this indication. A corporately funded, long-term trial of chronic stimulation of the anterior thalamic nucleus has recently begun at 10-12 centers in North America. The anterior thalamic nucleus is part of the classic limbic circuit described by Papez. It is theorized that stimulation in this region may block incipient seizures. Human work done by Cooper in the 1970s and 1980s, as well as more recent animal and human studies by Lozano and others, have shown this to be efficacious. Other trials are focusing on stimulation of the centromedian thalamus, subthalmic nucleus, and hippocampus.
A closed-loop neurostimulation system that can sense cerebral activity and adaptively respond, rather than simply constitutively stimulate, is considered a holy grail in functional neurosurgery. Animal studies of a responsive neurostimulator recently have been completed. This device was able to sense stimulation-evoked after-discharges in sheep and stimulate in response, thus eliminating the abnormal activity. An extension of this work has been carried out in patients undergoing invasive seizure monitoring. Once sufficient data for surgical planning had been obtained in the test patients, their monitoring electrodes were attached to an external responsive stimulation unit. This computerized system proved successful at recognizing early epileptiform discharges, delivering responsive stimulation and often aborting clinical seizures. FDA approval has now been granted to a clinical trial, sponsored by Neuropace, which will test a fully implantable version of this system.
Motor Cortex Stimulation for Neuropathic Pain
Transdural stimulation of the motor cortex has proven to have significant benefits for several types of medically refractory pain. Thalamic pain syndromes and neuropathic facial pain were some of the first syndromes treated. Long-term significant improvement of greater than 50 percent in pain scores has been achieved in the majority of patients reported.
The mechanisms through which stimulation leads to pain diminution are not entirely understood. Imaging by positron emission tomography has shown increased blood flow in the ipsilateral thalamus, cingulate, orbital-frontal cortex and brainstem during motor cortex stimulation. Investigations and clinical studies suggest a functioning corticospinal tract may be necessary to achieve high levels of pain control. In one of the largest series to date, Katayama noted a 9 percent success rate in patients whose painful limb was paralyzed. This is in contrast to a 73 percent success rate in patients without weakness.
The procedure is still being refined, and a host of issues have yet to be resolved. All series to date have been retrospective in nature, and overall success rates have varied widely. Some of this variability is due to the variety of pain syndromes treated. The optimal site for stimulation is still in debate. Epidural stimulation of the motor cortex likely provides stimulation only to the crown of the precentral gyrus and not to the cortex within the central sulcus. While this is effective for thalamic pain syndromes, recent studies suggest deafferentation pain may be successfully treated using subdural electrodes to stimulate within the central sulcus. Implantation of a subdural lead may also allow better coverage of lower extremity symptoms by allowing interhemispheric electrode placement.
Cortical Stimulation for Movement Disorders
There is an ongoing trial investigating the ability of transdural cortical stimulation to facilitate motor recovery after stroke. It is theorized that stimulation of the motor cortex will encourage the development of new neural networks after the ischemic incident. Similar trials are planned for the treatment of Parkinson’s disease and essential tremor.
The practice of functional neurosurgery has changed greatly in the last several years. A substantial amount of research is being directed toward elucidating the therapeutic mechanisms of these procedures. Moreover, a new generation of hardware on the horizon features miniaturized stimulators and rechargeable batteries. Once there is understanding of how brain stimulation achieves the impressive results seen so far, the number of indications is expected to greatly increase.
Paul House, MD, is chief resident in the Neurosurgery Department at the University of Utah in Salt Lake City, and Joshua Rosenow, MD, is a neurosurgeon at Northwestern University, Chicago, Ill.
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The NS Innovations column explores neurosurgical innovations that are changing the way neurosurgeons practice. The column’s emphasis is applied science, including topics such as new instrumentation and novel applications of familiar technology, but discoveries in basic science that have the potential to impact neurosurgery and aid our patients will be considered as well. I invite you to send your ideas for this column to me at [email protected]. William T. Couldwell, MD, NS Innovations editor |