The goal of deep brain stimulation (DBS) and motor cortex stimulation (MCS) is to restore function or relieve pain by stimulating neural activity through surgically implanted electrodes.
Developed in the 1980s, DBS was principally used to treat movement disorders associated with essential tremor (ET) and Parkinson's disease (PD). Today its applications include other types of movement disorders and certain nonmotor syndromes and conditions.
Successful DBS depends on careful patient selection, precise neural targeting, and extensive, individualized programming. It is generally reserved for symptoms that are unresponsive to other therapies.
For 14 years, neurologists, neurosurgeons, and members of the multidisciplinary DBS teams across Mayo Clinic's 3 sites have gained experience, conducted research, and explored new clinical applications. Overall, they agree that for certain disorders in carefully selected patients, DBS and MCS can markedly improve patient lives. The following update summarizes their findings and experience during the past several years.
The DBS teams at Mayo Clinic in Florida and Minnesota are testing the safety and efficacy of a new stimulator that delivers constant current (vs constant voltage) in patients with ET. In theory, the device will automatically sense the need for increased voltage, thus reducing the external programming burden. It can also accommodate more electrodes, thus increasing programming options.
Ryan J. Uitti, M.D., a neurologist at Mayo Clinic in Florida, points out that several years ago, bilateral electrode placement required 2 stimulators. The new device allows bilateral lead placement served by a single stimulator.
Neurosurgeon Robert E. Wharen Jr, M.D., reports that the DBS team in Florida is also exploring the use of intraoperative MRI for tremor. The procedure is conducted while the patient is asleep and eliminates the need for a stereotactic head frame.
DBS for ET continues to have positive results, and other types of tremor are being addressed. Recently, neurosurgeon Mark K. Lyons, M.D., and neurologist Virgilio H. Evidente, M.D., his colleague at Mayo Clinic in Arizona, performed the first DBS in the state for orthostatic tremor, a variant of ET that affects the lower limbs on standing and spreads up the trunk.
Six months after surgery, the patient shows 60 percent improvement in both lower limbs with bilateral thalamic DBS. Neurologist Matt Stead, M.D., Ph.D., and neurosurgeon Kendall H. Lee, M.D., Ph.D., at Mayo Clinic in Minnesota report success with bilateral thalamic placement (using 4 leads, 2 on each side) for rubral tremor, a rare tremor associated with the red nucleus, which has been difficult to control with DBS.
In the right patients, DBS continues to be effective in improving motor function and in reducing dyskinesias and symptom fluctuations related to on-off medication effects. The main indication is the patient's need for increased frequency and levels of medication.
Previously reserved for patients under the age of 70 years, DBS is now offered by Mayo physicians to treat older PD patients, some in their 90s. In a retrospective review, Drs. Lyons, Evidente, and colleagues found that positive benefit (eg, drug dose reduction) was similar with bilateral placement in the subthalamic nucleus or the globus pallidus interna (GPi). Because the GPi has evidenced fewer cognitive and neuropsychiatric adverse effects, they suggest that it may be a preferred target for PD patients at risk for these sequelae.
Drs. Uitti and Wharen and colleagues have found that, in older PD patients with asymmetric motor symptoms, unilateral subthalamic nucleus DBS may be better tolerated relative to short-term confusion, incontinence, and length of hospital stay than bilateral DBS. Drs. Lee and Stead note that in some cases, bilateral implantation of 2 leads per side is particularly effective for tremor-dominant PD.
Patients with focal and generalized dystonia represent a large percentage of the cases seen at Mayo Clinic in Minnesota. Drs. Stead and Lee report good success with DBS for early-onset primary dystonia or early-onset torsion dystonia (DYT1). Most patients with other forms of dystonia are helped, although the response may not be dramatic.
To improve outcomes, the DBS team is considering transcortical magnetic stimulation for some dystonias.
Drs. Evidente and Lyons were the first to conduct DBS on a patient with a form of progressive dystonia called lubag (its Filipino name), which occurs in 1 of every 4,000 men with maternal roots in the southern Philippines. Five years after surgery, the patient continues to do well, and now other patients with this neurodegenerative disorder are being treated with DBS. Lubag is seen in Filipinos worldwide.
Mayo Clinic has completed a study of neurostimulation for focal epilepsy. The results are not yet in, but Dr. Wharen reports that several patients whose seizures were intractable have become seizure-free. Drs. Lee and Stead provided DBS to a 3-year-old patient with Lennox-Gastaut syndrome, the youngest patient to have DBS. The seizures have been markedly reduced and are no longer impeding the patient's development.
Treatment of centrally mediated pain is experimental. The results at Mayo for trigeminal autonomic cephalgia, including cluster headaches, have been mixed. The use of preoperative positron emission tomography scans to determine if hypothalamic sites should be stimulated unilaterally or bilaterally in a given patient is under consideration. Dr. Lee says that intractable face pain in the distribution of the trigeminal nerve may respond to MCS. Dr. Wharen has used MCS in cases of unsuccessful ablation or gamma knife surgery for trigeminal neuralgia with good results.
Drs. Lee and Stead performed DBS in 2 patients with Tourette syndrome, considered both a movement and a psychiatric disorder. They are exploring DBS for other types of tics, and Mayo Clinic is in the early stages of investigating neurostimulation for depression and obsessive-compulsive disorder.
Although DBS has not been used as a primary treatment for restless legs syndrome, Drs. Evidente, Lyons, and colleagues noted that there is often a post-DBS reduction in restless legs associated with PD, a finding they confirmed in a retrospective study.
Bryan T. Klassen, M.D., a DBS fellow at Mayo, has reported a case in which severe periodic limb movements were reduced following DBS for PD. Dr. Evidente is now reviewing non-PD cases of ET and dystonia. The tentative results suggest DBS may be a promising option for restless legs syndrome.
In 2008, Drs. Lyons, Evidente, and colleagues presented the first report on improved vocal control in a patient with spasmodic dysphonia who had bilateral thalamic DBS for ET tremor of the hands. Following surgery, there was marked improvement in the patient's spasmodic dysphonia—a primary focal dystonia of the vocal muscles during speech. Dr. Lee notes that there are now a growing number of reports of DBS for spasmodic dysphonia outside the United States and that Mayo Clinic may explore this application in the future.
Understanding the mechanisms of DBS and MCS is critical to identifying new targets and making neurostimulation more effective in current applications. Dr. Evidente and colleagues are finding indirect evidence of distant effects from DBS. Their study of pre- and post-DBS activity of the Bereitschaftspotential suggests that stimulation of thalamic and subthalamic nuclei has downstream effects on motor cortex.
The Mayo-based multi-institutional DBS Consortium, directed by Dr. Lee with Charles Blaha, Ph.D., at the University of Memphis, Paul Garris, Ph.D., at Illinois State University, Pedram Mohseni, Ph.D., at Case Western Reserve University, and Kevin E. Bennet, chair of Mayo Clinic Division of Engineering, has made great strides in determining the nature of those effects.
The consortium recently developed the Wireless Instantaneous Neurotransmitter Concentration Sensing System (WINCS), a device that can monitor neuro-chemical output of targeted brain sites in real time during DBS. WINCS is providing evidence that modulation of certain central neurotransmitter systems (eg, the entire thalamocortical-basal ganglia circuit) underlies the effects of both DBS and MCS.
Continuing their work on the neurochemical basis of DBS, the investigators hope eventually to make the WINCS technology available to monitor neurotransmitter levels in humans during surgery.