Mayo Clinic's neurostimulation practice was pioneered and refined in the mid-1990s by neurosurgeon Robert E. Wharen Jr., M.D., and neurologist Ryan J. Uitti, M.D., at Mayo Clinic in Florida as part of the clinical trials that led to Food and Drug Administration approval of deep brain stimulation (DBS). It has since become one of the largest neurostimulation practices in the world.
Across Mayo's three campuses, interdisciplinary teams carefully screen patients, provide treatment for common and uncommon neurologic conditions, and follow up with expert stimulator programming. They collaborate on research and practice standards. Their success rests on experience, expertise and rigorous patient selection criteria.
The directors of Mayo's neurostimulation program, which includes DBS and motor cortex stimulation, are:
Dr. Klassen joined the DBS staff at Mayo Clinic in Minnesota this year, after a neurology residency, DBS fellowship, and specialized training in movement disorders.
Dr. Lyons has conducted a review of trends and future applications of DBS in Mayo Clinic Proceedings (2011;86:662-72).
On the basis of careful analysis of outcomes reported in the medical literature and internal research, Mayo Clinic has expanded its practice to include:
Herein are a few highlights of the current DBS experience across Mayo Clinic.
DBS has largely replaced ablative surgery (stereotactic thalamotomy) for advanced cases of tremor in levodopa-responsive Parkinson's disease (PD) and medically refractory essential tremor (ET). Typically, the treatment target is either the subthalamic nucleus (STN) or the globus pallidus in PD and the thalamus in tremor disorders. In addition to improving tremor, DBS surgery for patients with PD has also been found to improve gait disturbance, rigidity and symptoms of bradykinesia and to reduce dyskinesias caused by long-term levodopa therapy.
In a recent retrospective study, Joseph Y. Matsumoto, M.D., and colleagues across Mayo Clinic used a PD rating scale to determine differences in the pattern of responses to levodopa and DBS targeting the STN (STN-DBS) in a series of 60 patients. The investigators found that the combination of levodopa and STN-DBS is superior to either DBS or levodopa therapy alone.
In the Archives of Neurology (2011;68:1033-6), Dr. Klassen and colleagues report on the efficacy of DBS in a case series of tremor associated with benign tremulous parkinsonism (BTP), a condition within the spectrum of parkinsonism. BTP may appear similar to early PD, although as the two diseases progress, their symptoms diverge. Gait is not disturbed in BTP, and tremor is usually severe and unresponsive to levodopa.
Rare types of tremor treated with DBS at Mayo include orthostatic tremor, a variant of ET that affects the lower limbs on standing and spreads up the trunk. Treated at Mayo Clinic in Arizona, a patient with orthostatic tumor showed 60 percent improvement in lower limb tremor. Drs. Lyons and Evidente have also reported successful DBS surgery for a case of primary writing tremor and a case of genetically confirmed fragile X tremor ataxia syndrome.
Restless legs syndrome (RLS) can affect up to 25 percent of adults, and its prevalence often is increased in patients with PD or ET. Mayo Clinic does not offer DBS for cases of isolated or primary RLS, but patients with PD who are undergoing DBS surgery at Mayo are given pre-surgical and post-surgical testing for RLS.
Recently, Drs. Evidente, Klassen, and Lyons reported on a patient in whom severe periodic limb movements during wakefulness were reduced following DBS for PD. The Arizona team also has reported on six patients with PD whose average RLS scores dropped by 84 percent following DBS surgery (Mov Disord. 2006;21(8):1287-9).
In a series of patients with RLS who have ET or dystonia without PD, Dr. Evidente has observed that RLS relief ranges from 25 to 100 percent with DBS (unpublished data). Periodic limb movements during sleep also were noted to improve in a patient who underwent bilateral thalamic DBS for severe ET. The Arizona team conducted a sleep study before and after DBS surgery and also studied the patient's response with and without stimulation during DBS surgery. They found that DBS markedly decreased the patient's limb movements.
Neurologists and neurosurgeons across Mayo Clinic agree that symptom improvement with DBS for dystonia is more limited than it is for tremor. Drs. Evidente and Lyons reported on the first DBS surgery for X-linked dystonia parkinsonism, or Lubag, a progressive dystonia that occurs in 1 of every 4,000 men of southern Filipino extraction. They are monitoring the results of DBS on more patients with Lubag, all of whom have had some measure of symptom relief.
Recently, Drs. Evidente and Lyons conducted DBS for a patient with dopa-responsive dystonia. As its name implies, this type of dystonia is responsive to levodopa, although some patients may not tolerate the adverse effects of or eventually may no longer benefit from levodopa therapy. Before undergoing DBS, the patient was taking levodopa every few hours, with considerable adverse effects. After DBS, the patient's need for levodopa and the adverse effects it caused were markedly diminished.
Meige syndrome is an idiopathic segmental dystonia characterized by blepharospasm and craniofacial dystonia. Although the syndrome is initially responsive to botulinum toxin injections, many patients eventually have a poor response to treatment. Reporting on one of the largest case series to date of DBS for Meige syndrome, Drs. Lyons and Evidente and colleagues found that DBS was effective (Neurosurg Focus. 2010;29:E5. DOI: 10.3171/2010.4.FOCUS1067). More recently, a patient with Meige syndrome also had marked oropharyngeal dystonia with compromised respiration and sleep that improved with DBS surgery.
Dr. Uitti notes that although DBS can be successful in treating tremor, it has little effect on the ataxia that can accompany tremor in certain conditions. In addition, limb, gait and speech ataxia can result from aggressive neurostimulation in patients with ET who undergo thalamic DBS.
In particular, ataxia can be severe in patients with Hashimoto's disease, a progressive thyroiditis. At the 2011 American Academy of Neurology meeting, the team at Mayo Clinic in Arizona presented a case of a patient with a history of hypothyroidism and ET. The patient regained control of severe bilateral hand tremor following DBS surgery, but when seen at Mayo Clinic three years later, the patient had developed cerebellar gait and limb ataxia, which did not improve upon withdrawal of neurostimulation.
The investigators speculated that the ataxia may have been due to an additive or synergistic effect between bilateral thalamic DBS and Hashimoto's disease. They suggested that before undergoing thalamic DBS surgery, patients should be screened for thyroid dysfunction and Hashimoto's disease.
Motor cortex stimulation has been used across the three sites to treat facial pain, such as anesthesia dolorosa. As Dr. Uitti points out, outcomes are best when the facial area targeted is relatively small. Pain specialists and psychiatrists participate in the evaluation of patients seeking neurostimulation for pain. Dr. Klassen and colleagues have found that in patients treated with motor cortex stimulation, subdural electrode placement may be superior to epidural placement.
Over the past two years, Drs. Uitti and Wharen have conducted DBS surgery in patients with cluster headache, a condition caused by activity in the hypothalamus. Dr. Uitti notes that the stabbing pain can be so severe that some patients contemplate suicide, so he is particularly pleased to report that most of his patients continue to be headache-free several years after DBS surgery.
Dr. Wharen explains that for these cases, pretesting helps in patient selection. Headaches can be induced through the application of histamines and the activity of the hypothalamus monitored during a pre-surgical PET procedure. During DBS surgery, the headache can again be induced to see whether electrode placement in the hypothalamus aborts the symptoms.
Mayo Clinic in Minnesota is one of the few institutions in the world to offer DBS for intractable epilepsy in children. For example, Mayo Clinic specialists operated on a 3-year-old child with Lennox-Gastaut syndrome, one of the youngest patients ever to undergo DBS. The surgery resulted in marked seizure reduction.
The symptoms of Tourette syndrome tend to improve after adolescence, and medication is effective in many cases. DBS surgery is one option for carefully selected patients with medically refractory Tourette syndrome. Drs. Lee, Stead and Klassen have conducted DBS surgery in four patients with Tourette syndrome, two of whom were adolescents who had symptoms so severe that the tics caused them physical harm. After treatment, the number of tics was markedly reduced in all four patients.
For the past three years, the DBS teams at Mayo Clinic in Florida and Mayo Clinic in Minnesota have been participating in a clinical trial to test a new stimulator device. The Florida team is the No. 1 recruiter for the study in the nation.
Mayo Clinic continues to be a leader in DBS basic science research, with Dr. Lee serving as director of Mayo's Neural Engineering Laboratory and lead investigator of a Mayo-based, National Institutes of Health-funded, multi-institutional investigation into the mechanisms of DBS. Having designed the Wireless Instantaneous Neurotransmitter Concentration Sensing System (WINCS), Dr. Lee and his colleagues are conducting real-time tests of changes in neural and neurochemical activity in DBS.