Penn Medicine neurosurgeons and neurologists have a long history as leaders in deep brain stimulation (DBS) for movement disorders. Through robust research and high-volume expertise, the team continues to expand the understanding and use of DBS therapy.
Deep Brain Stimulation: Mechanism of Action
DBS delivers electrical stimulation to target areas of the brain involved in disease. These areas respond abnormally to signals from other brain areas or cause disruption of otherregions, leading to pathological phenomena in the brain.
While researchers have yet to pinpoint exactly how electrical stimulation restores normal brain function, Casey H. Halpern, MD, division head of Functional and Stereotactic Neurosurgery at Penn Medicine and associate professor of neurosurgery, leads preclinical and clinical research to better understand the mechanism.
“I can confidently say that DBS disrupts the abnormal circuit,” he says. “Depending on where the electrodes are placed in the brain, it’s possible that the disruption could even be an activation of an inhibitory area.”
DBS of highly active areas may quiet down activity, mimicking the effects of ablation. DBS of inhibitory areas could lead to less activity overall in a circuit. Dr. Halpern’s studies of neuronal activity patterns in response to electrical stimulation aim to improve the use of DBS in clinical practice.
Dr Halpern notes that, unlike ablation, DBS is a tunable system that can be adjusted and titrated. “It’s kind of like an implanted electrical medication.”
What Movement Disorders Does Deep Brain Stimulation Treat?
DBS can relieve motor symptoms in many patients with movement disorders, including:
- Dystonia, using DBS of the globus pallidus;
- Essential tremor, using DBS of the ventral intermediate nucleus of the thalamus;
- Parkinson’s disease (PD), using DBS of the subthalamic nucleus (STN) or globus pallidus.
“It’s really when these diseases become difficult to manage with medications that DBS can be very helpful,” says Iahn Cajigas, MD, PhD, assistant professor of neurosurgery at Penn Medicine.
“Recent studies suggest that earlier DBS in Parkinson’s may even slow down some of the disease progression. It may delay or prevent the need for high medication doses that can cause side effects.”
While DBS for dystonia is not formally approved for use by the Food and Drug Administration, it’s recognized as a beneficial therapy for this rare condition and is available to DBS patients through a Humanitarian Device Exemption through the Institutional Review Board (IRB).
“Only large, academic medical centers with an IRB can receive the Humanitarian Device Exemptions to do the surgery, and that’s something we at Penn can offer,” adds Dr. Cajigas.
Referring to a Movement Disorders Center for DBS Evaluation
Once patients have tried at least two medications, referral to a multidisciplinary movement disorders team can start the DBS evaluation and treatment process. Penn’s Movement Disorders Center is the only center in Philadelphia with a comprehensive DBS Pre-Operative Evaluation Clinic.
The pre-op clinic, led by Meredith A. Spindler, MD, associate clinical director of the Movement Disorders Center, combines the expertise of:
- Neurologists
- Neurosurgeons
- Neuropsychologists
- Psychiatrists
- Physical, occupational and speech therapists
- Radiologists
Penn neurologists refer patients who may be eligible for DBS surgery to the clinic for in-depth education, evaluation and case review during a multidisciplinary case conference. The Penn team discusses new cases as well as cases for revision.
Optimizing DBS Surgery and Programming at Penn
Finding the “sweet spot” within the target area of the brain plays a significant role in patient outcomes. MRI guidance and imaging strategies developed by Dr. Halpern’s laboratory and others at Penn help isolate and visualize the specific target area.
“We use a variety of atlases and connectivity-based approaches to look at circuits,” says Dr. Halpern. “We need to understand not just one little structure, but actually how this structure connects to the rest of the brain.”
He explains that the Penn team has been able to optimize the sweet spot over the past decade, thanks to an extremely high volume of cases. “A deep brain stimulation surgery requires about 1500 steps, and it's like a domino effect — if you miss one step, the whole surgery could be compromised,” says Dr. Halpern. “Repetition in a surgeon's experience is really important, and we do about five DBS surgeries per week.”
Programming expertise also plays a key role in a patient’s success with DBS. Dr. Spindler and the Penn neurology team see patients one month after surgery to begin programming the device. The team can also facilitate a smooth transition back to referring or local providers as needed.
The process to find optimal stimulation settings takes time, requiring several visits across about six months and regular follow-up visits to tune the device. Penn neurologists act as long-term partners to patients to find the most effective therapeutic settings, targeted at controlling patients’ most bothersome symptoms.
What Are the Latest Advances in Deep Brain Stimulation?
From function to appearance, deep brain stimulation for movement disorders has significantly evolved since its first use. Dr. Halpern and Dr. Cajigas highlight several advances in DBS care, including:
Multiple Device Options
Historically, only one DBS device existed to offer patients. Now, providers can consider several devices from three different manufacturers. Each DBS system offers unique features to choose from, such as:
- Nondirectional or directional stimulation
- Rechargeable or non-rechargeable batteries
- Recordings of brain activity (local field potentials)
- The programming and control interface
“I find that each patient will benefit from one device over another — it’s highly personalized,” says Dr. Halpern. “Figuring out which special feature can best address a patient’s specific need is an important part of the discussion.”
Advanced DBS Technology
DBS devices have become smarter, allowing for more customization during programming. The latest technology allows providers to program a patient’s device remotely, which can reduce the burden of office visits and improve access to care.
With recent advances, patients have an option to receive an internal pulse generator (IPG) that recharges using a magnetic device held over the implant site. These rechargeable IPGs can last up to 15 years, compared to the three-year battery life in a typical non-rechargeable IPG.
Smaller, Thinner and More Durable IPGs
The large, squared IPGs of the past had a higher risk of infection and wound healing complications. New slender designs allow for better healing. They also have improved cosmetic results, an important factor to many patients as they consider a permanent implant.
What’s Next in Movement Disorders DBS Research at Penn?
While DBS therapies have greatly improved, a large amount of unmet needs still exist, keeping Penn investigators forging ahead. Exciting clinical trials provide patients with opportunities to receive therapies beyond the standard of care.
“I speak with patients about research studies every time — not because they don’t fit the clinical profile, but because there might be an alternative, and I want them to know what their options are,” says Dr. Halpern.
Treating REM Sleep Disorder in PD
One ongoing trial aims to improve sleep maintenance and sleep quality in PD patients, many of whom experience REM sleep behavior disorder. Penn researchers previously found a connection between abnormal activity in the STN and sleep dysregulation. As part of the trial, participants receive DBS of the STN that modulates throughout the night based on signaling in the sleep network.
A New Target for Freezing of Gait in PD
Freezing of gait is a debilitating PD symptom that doesn’t improve with levodopa therapy or current DBS methods. In fact, freezing sometimes worsens with DBS.
A new DBS target in the midbrain — the cuneiform nucleus — may provide therapeutic benefit. After kickstarting the pilot clinical trial at the University of Miami, Dr. Cajigas is planning to launch Penn soon as the second study site in the nation.
Expanding the Use of DBS
Penn neurosurgeons are also interested in using DBS to treat other conditions, including addiction, obsessive-compulsive disorder, obesity and eating disorders. Dr. Halpern’s recent study published in Nature Medicine investigated responsive DBS of the nucleus accumbens in people with binge eating disorder and severe obesity. Responding to neuronal activity associated with cravings and loss of control, DBS was able to interfere with disordered eating behaviors and lead to weight loss. Read more about the results.
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