• Parkinson’s Disease symptoms are generally first treated with oral medications. The mainstay of treatment is a medication called carbidopa/levodopa. There are multiple medications clinicians may prescribe in addition to the carbidopa/levodopa to help a patient’s symptoms. These are often called adjuvant medications. 
• Some patients, despite multiple medication adjustments with a neurologist or movement disorder specialist, struggle with PD symptoms. Around this time, the conversation about device-aided therapies begins.
• PD symptoms:
  
  • Motor fluctuations, or wearing off between doses, where tremor, slowness, stiffness, and/or difficulty walking re-emerge between doses.
  • Dyskinesia, also known as Levodopa-induced dyskinesia (LID), presents as excess wiggly involuntary movements, generally occurring at the peak effect of carbidopa/levodopa.
  • Dystonia, or cramping and abnormal posture of feet or hands, are generally present during wearing off.
  • Medication refractory tremor, or tremor that persists throughout the day despite higher doses of levodopa.
    
    
• Device-aided therapies are advanced treatments beyond typical oral medications to treat PD. These use hardware, such as an electrode or a pump, to deliver treatment, such as electrical stimulation or medication, to help a patient’s symptoms. Some of these devices offer a steady release of medication throughout your day to prevent wearing off.

Subcutaneous Infusions

• Overview:
  • Patients using this therapy wear a pump on their waist or in a holster. The pump is connected to a tube with a small needle tip that the patient or caregiver inserts just under a patient’s skin, usually on the abdomen. The patient has to change the infusion site every 1-3 days. The pump slowly administers medication just under the patient’s skin throughout the day.
  • The continuous drug delivery prevents the highs and lows of medications that are experienced with intermittent oral medications. Adjusting the rate allows patients to get “on” and function well without excess dyskinesia. Patients can generally expect at least 2-3 fewer hours of “off” time during the day.
• Risks: Patients may experience pain at the insertion site, particularly when changing the needle. Pain tends to be mild and resolves quickly. Sometimes the infusion pump site may become infected. This usually can be treated with antibiotics without stopping the therapy. Some patients may develop very small painless bumps (nodules) underneath the skin in previous infusion sites which tend to resolve over time with massage.
• Invasiveness: This treatment is minimally invasive, as it just requires a small needle under the skin.
• There are three forms of subcutaneous infusion therapy… one is expected to receive FDA approval in the next month or so (as of 2/22/24). Learn more about it below.

Deep Brain Stimulation (DBS)

• DBS involves the surgical implantation of electrodes in the brain in areas important for the control of movement. Wires passing through the neck connect the electrode to a stimulator in the chest. The stimulator is a small pacemaker-like device that delivers a controlled electronic pulse to the brain. The stimulator is also called an implantable pulse generator (IPG).
• DBS involves two surgeries. One where the electrodes are placed in the brain, and a second to place the IPG. After the surgeries, a patient meets regularly with their neurologist to determine the correct amount of electrical stimulation settings to improve PD symptoms. At this time, their oral medications for PD will be adjusted and reduced as well.
• Patients who receive electrodes bilaterally have about 50% reduction in “off” severity, about 80-90% reduction in dyskinesia, PD medication reduction, and increased “on” time by up to 5-6 hours per day.
• Risks: The risks of the surgical procedure are hemorrhage, or bleeding in the brain, which is a type of stroke. This risk is 1 to 2% for each side of the brain operated on. Infection may occur in up to 5% of patients at some time after surgery, usually involving the hardware outside of the brain. The DBS device may stop working due to breaks in the wiring that connects the electrode to the pacemaker-like device in the chest or other hardware problems. This risk is less than 5% in one’s lifetime. This would require additional surgery to replace or fix the DBS hardware. Some patients have reduced clarity of speech, a decline in memory and thinking, or worsening of freezing of gait or balance after DBS. These risks vary from patient to patient.
• Invasiveness: This is an invasive therapy, requiring two surgical procedures.
• Reversibility: DBS is somewhat reversible in that the electrical stimulation can easily be turned off or adjusted. Removing the hardware from the body would require surgery and is generally only done due to hardware breaking or infection.

Focused Ultrasound (FUS)

• Focused ultrasound (FUS), is a procedure that uses sound waves to heat up and destroy part of the brain important in movement control to improve tremor, motor fluctuations, and/or dyskinesia. This is a single procedure in which the effects on PD symptoms are immediate and are not able to be adjusted afterward. There is no hardware implanted in the brain. The treatment is only approved to be performed on one side of the brain, so only improves symptoms on one side of the body. Performing the procedure on both sides of the brain is done off-label for some patients and involves greater risk.
• The effects of focused ultrasound are similar to that of DBS. Patients usually see a reduction in tremor by about 50%. This varies based on the location of the lesion. There is not enough data at present to give an estimate of “off” time reduction, though studies of this are ongoing
• Risks: Some side effects are temporary due to the procedure and these include pain, numbness, nausea, and headache.
• Long-term or permanent side effects occur when the area destroyed by FUS extends outside of the intended target. These include difficulty with walking, (4% of patients), numbness, which occurs (9% of patients), or weakness (2% of patients). Some patients have a waning of the effect of this treatment over time. There is also the risk of a poor outcome in that providers are unable to adjust the lesion after it is made, even if it does not improve a patient’s symptoms or if it causes side effects. This is a recently developed treatment and has not been used frequently, so we are still learning about the long-term effects of the surgery. There is very limited data regarding using this treatment on both sides of the brain to improve symptoms on both sides of the body.
• Invasiveness: This is a single invasive procedure requiring brain surgery.
• Reversibility: FUS is irreversible and cannot be adjusted over time.

Duopa

• Duopa therapy is a form of carbidopa/levodopa delivered in gel form (called enteral suspension) directly to where the medication is absorbed in the small intestine.
• Before Duopa may be started, a patient needs to get a minor surgery to make a small hole, called a stoma, in the stomach wall to place a tube in the intestine. This tube is connected to a pump worn in a vest, holster, or fanny pack. The pump then delivers the gel form of levodopa directly to the intestine through this tube.
• This device is effective because it is a continuous, steady delivery of drugs throughout the day as opposed to the highs and lows that occur with intermittent oral medications. This generally results in a reduction in off time by at least 2-3 hours.
• Patients, together with their neurologist, determine an appropriate continuous dose to provide most of the daily medication as well as an extra dose to be given if needed for unexpected wearing-off. At the same time, oral medications are reduced or discontinued.
• The Duopa pump is somewhat large (about 8 inches x 4 inches) and weighs about 1 lb in weight, not including the medication cassette.
• Risks:
  • Procedure-related: Patients generally experience pain after the procedure requiring pain medications for a few days. There is a small risk of air or infection in the abdominal cavity which occurs in less than 5% of procedures. The patients and providers generally let the stoma heal for a few days before starting Duopa therapy.
  • Device-related: The tube may break, become blocked, or move which would require tube replacement. The stoma may become infected which usually resolves with topical antibiotic treatment, but may require oral antibiotics, and very rarely requires IV antibiotics.
• Invasiveness: This therapy is invasive as it requires outpatient surgery to place the stoma and tube in the stomach. This surgery is somewhat less invasive than brain surgery and patients generally return home the same day as the procedure.
• Reversibility: The pump can be turned off easily and quickly. The PEG-J tube procedure can be easily reversed if necessary, by just removing the tube. The stoma heals within weeks without lasting effects.

The specific device-aided therapy chosen must be customized to a patient’s particular symptoms. Some symptoms only improve with a specific device-aided therapy. For example, troublesome tremor, despite aggressive oral treatment, generally responds only to DBS or FUS.

There may be advantages to starting with the less invasive and more easily reversible device-aided therapies. This may allow a patient to function well without exposure to more severe side effects. Patients may always try additional more invasive device-aided therapies in the future, if necessary.

• Motor fluctuations: This is when patients experience “off” time, or worsening of PD symptoms (tremor, stiffness, slowness), between doses despite taking at least 4-5 doses of levodopa daily. Levodopa should also be combined with two or three trials of additional medications when wearing off is problematic. Additional medications include MAO-B inhibitors (rasagiline, selegiline), COMT inhibitors (entacapone, tolcapone, opicapone), and dopamine agonists (pramipexole, ropinirole, rotigotine), or istradefylline. There is no hard and fast rule about how much “off” time a patient must experience for device-aided therapies to be appropriate. Generally, most patients considering device-aided treatment experience at least 2-3 hours of “off” time per day, but some may experience more or less.
• Dyskinesia: This is excess, wiggly, involuntary movements that are troublesome despite adjustment of a patient’s levodopa medications and trying amantadine or GoCovri.
• Medication refractory tremor: This is a tremor that is bothersome and interferes with a patient’s daily activities despite high doses of levodopa, at least 400-500 mg per dose, in addition to another medication such as an anticholinergic (like Artane or amantadine), clozapine, or propranolol. These patients may benefit from DBS or Focused Ultrasound. They will generally not benefit from Duopa or subcutaneous infusions more than from oral levodopa.