On the Cutting Edge…… gamma knife radiosurgery for the treatment of trigeminal neuralgia
Morton Rosenberg, D.M.D., Vasilios Zerris, M.D., M.P.H., M.M.Sc.
Jonathan Borden, M.D.
Departments of Oral and Maxillofacial Surgery, Anesthesia and Neurosurgery
Tufts University Schools of Medicine and Dental Medicine
The revolution of sophisticated software and computer technology combined with advanced radiation physics has produced a new tool for the successful treatment of many neurologic conditions including trigeminal neuralgia. The gamma knife is not a knife; rather, it is complex machine that uses cobalt-60 as the energy and is able to focus a precise intersection of 201 beams of these gamma rays to perform radiosurgery. It has been the evolution of high resolution CT and MRI scans coupled with computer technology that allows for targets to be clearly defined. Currently there are 120 gamma knife centers around the world and 45 in North America. The Boston Gamma Knife Center at New England Medical Center is the only such facility in Massachusetts. Arteriovenous malformations, brain metastases, acoustic nerve tumors, meningiomas and other benign brain tumors as well as as functional disorders auch as intractable pain, seizures, the tremors and rigidity of Parkinson’s disease and certain psychoneuroses have all responded to gamma knife radiosurgery. Of special interest to dental profession is the use of the gamma knife in the treatment of trigeminal neuralgia.
Several options exist for the treatment of trigeminal neuralgia. Medical therapy with carbamazepine, phenytoin and more recently gabapentin has provided good first line treatment. Microvascular decompression, glycerol rhizotomy, radiofrequency rhizotomy, and nerve section have proven effective surgical options. Gamma knife radiosurgery has in recent years become the treatment of choice for people unresponsive to medical therapy. Recent advances in imaging and increased experience with its use, have underscored the importance of gamma knife as a treatment for trigeminal neuralgia
In 1951 Lars Leksell, the inventor of the Gamma knife, was the first to use radiosurgery for the treatment of functional disorders such as trigeminal neuralgia. Using a conventional stereotactic frame, he aimed the radiation beam produced by an orthovoltage x-ray tube at the trigeminal ganglion. Over the next forty years, poor imaging, poor target fixation, and the choice of the gasserion ganglion as the target brought less than satisfactory results. In 1996 a multicenter study out of the University of Pittsburgh resurfaced interest in the radiosurgical treatment of trigeminal neuralgia. In this study, the proximal trigeminal nerve near the pons rather than the ganglion in Meckel’s cave was chosen as the target, allowing direct visualization of the nerve proper. High resolution MRI permitted accurate targeting. As a result, 94 % of the patients in the study showed resolution or significant decrease of their pain.
Many authors have since reported similar results. Success rates are similar to those of other interventional procedures. Complications are limited mostly to facial numbness and occur at a frequency of less than 10%. GKS is now being used as a safe alternative to traditional surgery and as first line therapy for trigeminal neuralgia.
Planning for the procedure is performed by a multidisciplinary group. The expertise of a neuroradiologist, radiation oncologist, medical physicist, and a neurosurgeon are combined to achieve safe and effective treatment. Gamma knife surgery is a four-step procedure.
The patients are first fitted with the Leksell stereotactic head-frame. Because neurophysiological feedback is not a component of the targeting procedure high quality and accurate imaging is necessary. High resolution images of the target and the surrounding structures must be obtained. Magnetic resonance imaging is the neuro-diagnostic modality of choice. Gadolinium enhanced T1 weighted magnetic resonance imaging with magnetization-prepared rapid gradient echo, T2 weighted fast spin-echo sequences and other MRI algorithms are used. Long-Tr MR sequences can be used in adjunct to contrast the nerve against the high-signal CSF background. The trigeminal nerve is identified in coronal, axial, and sagital planes on its course from the brainstem to Meckel’s cave. For those with pacemakers, metallic foreign bodies, or other contraindications to MRI, high-resolution computerized topography with contrast cisternography can be used. The ElectaÒ Leksell gamma knife unit with cobalt-60 sources is used to irradiate the target. The trigeminal nerve is targeted at the location of an imaged vascular compression, or at the site of exit of the trigeminal nerve from the pons if no compressing vessel is identified. The effectiveness of treatment at this exit zone is probably because the proximal nerve is covered by oligodendrocyte myelin, which is more radiosensitive than the distal swan-cell myelin, or because of the concomitant irradiation of the dorsal root entry zone in the brainstem. Care is taken to protect the brainstem from radiation exposure, which is usually easily accomplished due to the precision of the gamma knife system. Target doses reported in the literature have ranged between 65-100 Gy., with a mode of 70-90 Gy. Old age and multiple sclerosis have served as criteria for lower doses. Higher doses are used for those with previous surgeries. We have found a dose of 80 Gy effective in 90% of patients, with a risk of partial numbess in the face of less than 10%, and a risk of anesthesia delorosa well under 1%. The entire procedure is performed under local anesthesia and mild sedation.
Mechanism of action
The exact mechanism of pain relief is unknown. It is thought to be a two step process. Patients report an immediate decrease in the intensity of the pain even if the attacks still occur. This is postulated to be the result of an immediate interruption of ephaptic transmission. Several weeks later there is complete cessation of the attacks. This is probably secondary to delayed demyelination injury to the nerve. Regis et al. have speculated that gamma knife irradiation has a differential effect on myelinated and unmyelinated fibers, allowing for control of pain without dysesthesia. This is not supported by the recent finding of Kodziolka et al. who performed histologic analysis on two baboons treated with gamma knife. They targeted the trigeminal nerve just anterior to the pons, and used doses in the 80-100 Gy. range. All irradiated nerves exhibited axonal degeneration with remnants of some myelinated axons. Both myelinated and unmyelinated fibers were affected. Nerve necrosis was identified with the 100 Gy. treatment. The patho-histologic changes of lower doses is not know, and further studies are needed.
Young et al reported a 74.5 % rate of complete relief, and a 95.5 % response rate. In the multicenter study published in 1996, 60 % of the patients became pain free requiring no further medical therapy, 17 % had a 50-90 % reduction in pain and 9 % had slight improvement. Of those that attained complete relief, only 10 % had relapse of their pain. Similar high response rates and long term pain relief have been found by several other authors. The effectiveness of the treatment is confounded by the type of neuralgia. Recent studies found that the highest response rate was for essential neuralgia (77 %) followed by neuralgia with multiple sclerosis (43 %), post herpetic neuralgia (38-44 %) and atypical neuralgia (33 %). Pt who have atypical symptomatology or those with prior surgical procedures, have lower initial and long term response rates. In a study of 172 patients, Brisman found that those treated with gamma knife as primary management had better outcomes than those treated as secondary management. These studies underline the possible use of the gamma knife as first line treatment. The overall response rate with gamma knife compares very favorably with that of other surgical modalities. This becomes more obvious when we consider that most patients undergoing gamma knife surgery have already failed medical and surgical treatment and present a special treatment challenge.
Side effects of gamma knife radiosurgery are limited primarily to facial paresthesias or sensory loss. In most reports the rate of such complications is less than 10 %. In the 1996 multi-institutional trial, 6 % of patients developed increased paresthesia after the procedure. Nicol et al found that higher doses (90Gy) might be associated with increased rates of paresthesia (16.7%) and dysgeusia (9.5%). The overall rate of facial paresthesia is slightly higher than MVD but substantially lower than the 60-80 % quoted for percutaneous procedures . Unlike traditional surgery though, gamma knife surgery does not carry the risk of infection, anesthesia complications, hematoma formation, CSF leak, facial weakness, hearing loss, and brain stem injury. There are rarely serious side effects, usually no hospital stay, the treatment is accomplished in one session and patients return quickly to normal activities.
In over 30 years, more than 100,000 people have received gamma knife treatment. The use of the gamma knife has clear advantages to open surgery in many cases, and its use will continue to grow.
(For more information regarding gamma knife therapy or to refer a patient for screening, please contact the Boston Gamma Knife Center at (617 636 – GAMMA) or www.bostongammaknifecenter.org)