- There is no cure for Parkinson disease (PD) and no known treatment to slow or stop the progression of the disease (Suchowersky et al., 2006).
- The treatment goal is to maintain patients' functional status and independence.
- Interventions require multidisciplinary collaboration through pharmacotherapy, rehabilitation, deep brain stimulation (DBS) surgery, patient education, and family and social support. Surgical treatment has become a mainstay of midstage PD management, but not all patients are appropriate candidates or can afford treatment.
- Adhering to the prescribed medication regimen is important. Lack of compliance may lead to increased morbidities, disease exacerbations, and more office visits and hospitalizations, resulting in higher costs. Research suggests low compliance, with more than 50% of patients missing at least one dose of their medication per week and more than 20% missing three or more doses per week (Leopold, Polansky, & Hurka, 2004).
- Refer to Table 3 in the original guideline document for dosing, purpose, action, and common side effects of the antiparkinsonian drug classifications.
- Medications to avoid. See the original guideline document for a partial listing of drugs that patients with PD should avoid.
- Medications recommended for initial treatment. A PD diagnosis is not necessarily cause to initiate drug therapy. Drug therapy is warranted when symptoms are bothersome or produce disability (Nutt & Wooten, 2005). Efficacious agents for initial therapy include levodopa, dopamine agonists, anticholinergic agents, amantadine, and selective monamine oxidase B (MAO-B) inhibitors (Table 3 in the original guideline document). Guidelines from the American Academy of Neurology (AAN) and a Movement Disorder Society evidence-based review indicate that initiating therapy with levodopa or a dopamine agonist is reasonable (Holloway et al., 2004). It is uncertain whether levodopa therapy or dopamine agonist therapy is the better choice for initial treatment ("Management of Parkinson's," 2002; Miyasaki et al., 2002).
- In elderly patients, levodopa is the usual treatment of choice compared to dopamine agonists because of its lower risk for psychiatric complications (Level 1; Abbott et al., 2001; Rascol et al., 2000).
- In younger patients, a dopamine agonist may be preferable for a longer treatment horizon and higher tolerance of side effects. In addition, agonists are less likely to provoke motor fluctuations and dyskinesias (Level 1; Rascol et al., 2000).
- If depression and anxiety are debilitating symptoms, they usually are targeted for initial therapy.
- Nausea frequently is associated with antiparkinson medications, especially levodopa or dopamine receptor agonists. Titrate these drugs slowly or reduce the dose. If nausea is associated with levodopa, additional carbidopa (Lodosyn) can be added to each dose.
- Patients taking MAO-Bs should avoid meperidine, dextromethorphan, ephedrine-like drug found in some cold remedies, amphetamines, tricyclic antidepressants, appetite suppressants, cyclobenzaprine, asthmatic drugs, barbiturates, opioids, and others. Those on rasagiline (Azilect) should avoid foods high in tyramine such as broad beans, cheeses, liver, and wine.
Nonpharmacological Treatments (Level 3; Suchowersky et al., 2006)
- Exercise and walking for flexibility, strength, and balance
- Regular exercise (neuroprotective in PD; Suchowersky et al., 2006)
- Physical therapy that incorporates massage, heat, exercise, and balance/gait retraining
- Speech therapy, which may improve speech volume (Lee Silverman Voice Treatment; El Sharkawi et al., 2002)
- Occupational therapy for assistive devices and in-home needs
- Complementary and alternative PD therapy (Ward, 2007)
- Optimal care to maximize physical and mental function and health includes a comprehensive combination of drug therapy and physical, occupational, and speech therapies, and holistic approaches, social services, and psychological counseling.
- Pharmacological therapy reduces tremor by 50% to 60% but may have dose-limiting side effects that can be troublesome for patients (Rajput, Robinson, & Rajput, 2004).
- Adverse effects including depression and male impotence should be monitored in patients on propranolol (Zesiewicz et al., 2005).
- Botulinum toxin Type A has been used to treat head, hand, and voice tremor in essential tremor (ET). Its use in the treatment of tremor of the upper extremities is limited because it commonly causes weakness. It is more useful in the treatment of head tremor because it often provides benefit without unwanted, troublesome weakness (Level 3; Zesiewicz et al., 2005). Weakness is dose-dependent and a transient side effect of botulinum toxin injections. No studies have evaluated the use of Botulinum toxin Type B for treatment of ET (Zesiewicz et al., 2005) See Table 5 in the original guideline document.
DBS for ET
- Patient selection
- Careful patient selection is the most important step in considering DBS surgery.
- Patients must have benign ET that is pharmaco-resistant. This means that despite adequate medication trials in sufficiently high doses, tremor remains disabling and/or medication side effects are intolerable. Common medications to consider before implanting patients with ET include primidone, propranolol, and one anticonvulsant such as clozapine (Clozaril) (Zesiewicz et al., 2005).
- Patients should be carefully assessed for other neurodegenerative disorders such as early PD or medication-induced tremor. There is increasing evidence that some patients with established diagnoses of benign ET may develop symptoms of PD or other atypical tremor disorders up to 10 years later (Benito-Leon & Louis, 2006).
- Surgical candidates should have normal brain scans or scans without deficits within the planned surgical region.
- DBS outcomes for ET
- Patients and family members need to be advised that improvements in ET symptoms after ventralis intermedius (VIM) stimulation demonstrate that limb or distal tremor improves more rapidly than proximal tremor (e.g., shoulder). In addition, postural tremor improves more easily than action tremor. Action tremor of the hand is the most difficult to control (e.g., when brushing teeth or drinking from a cup) (Dowsey-Limousin, 2002).
- It has been shown the thalamic VIM DBS target is highly effective for relief of controlling ET (Koller et al., 1997). Although unilateral VIM DBS has been shown to suppress contralateral limb tremor, control of head and voice tremor often requires bilateral DBS (Lyons & Pahwa, 2004). Bilateral VIM DBS is associated with stimulation-induced dysarthria from well-placed leads. Dysarthria is produced by current spreading into adjacent motor or capsular fibers. This can be minimized in some patients by programming adjustments, but sometimes this is not possible and a choice must be made to tolerate dysarthria in exchange for better tremor control. Others may choose to deactivate one implant during speaking engagements and activate both sides for fine-motor tasks. Additionally, control of proximal ataxia or cerebellar symptoms is more difficult to treat (often refractory to VIM stimulation) than distal (hand/wrist) tremor (Hamel et al., 2007). Early studies suggest implanting leads in more inferior thalamic targets (STN/zona incerta) can better control ataxia and intention tremor (Hamel et al., 2007; Herzog et al., 2007).
- Additionally, for unclear reasons, some patients with implants develop a type of ataxic gait disorder or trouble with balance after bilateral implants (Koller et al., 1997). It is unclear if this results from the spread of current/stimulation to other regions connecting with the thalamus (cerebellar fibers), or if this is related to a patient's underlying disease progression after implant (Hamel et al., 2007; Herzog et al., 2007). Tremor remains a challenging symptom to manage with DBS. In patients with a clear diagnosis of ET who have well-placed leads, however, VIM DBS has proven effective for long-term control of distal limb tremor (Koller et al., 1997).
DBS for Dystonia
- Dystonia does not generally respond to pharmacologic treatment, but has robustly responded in patients implanted with globus pallidus interna (GPi) DBS (Houeto et al., 2007; Kupsch et al., 2006; Starr et al., 2006; Vidailhet et al., 2005). Although there is a lack of large randomized DBS trials, the preliminary results from those undergoing DBS for primary dystonia diagnoses types were so compelling the Food and Drug Administration (FDA) granted approval in 2003 to treat this population under a Humanitarian Device Exemption. Recent experience shows robust DBS outcomes in patients with primary or genetic forms of dystonia and tardive dystonias; however, patients with secondary dystonias such as cerebral palsy and poststroke syndromes respond less predictably to DBS (Starr et al., 2006; Vidailhet & Pollak, 2005; Volkmann & Benecke, 2002).
- DBS outcomes for dystonia. Patient and family expectations for surgical improvement in dystonia must be based upon the type of dystonia and the knowledge that responses are variable despite correct positioning of the electrodes (Kupsch et al., 2006; Vidailhet et al., 2005). Generally, primary dystonia responds better than secondary dystonia, and the best results are achieved in patients with generalized, segmental, or hemi-dystonic dystonia (Volkmann & Benecke, 2002). Patients also must be advised that unlike in cases of PD and ET, improvement in dystonia symptoms may be delayed after surgery. Improvements often are progressive and may take up to 6 months (Bittar et al., 2005).
- When selecting dystonia candidates for DBS, look for:
- Genetically positive dystonia
- Primary idiopathic, generalized, or segmental dystonia with disability despite maximum drug and botulinum-toxin therapy
- Secondary (tardive) dystonia with stable psychiatric symptoms
- Willingness to tolerate the ambiguity of therapy response and multiple programming sessions
- Adequate social support
- Adverse effects of DBS in dystonia. The most common adverse event for patients with dystonia after DBS is dysarthria. Other common adverse outcomes include weakness on one or both sides of the body and disequilibrium. Paresthesias may occur but typically resolve with programming adjustments. Patients with dystonia are at high risk of DBS lead fracture and migration (Yianni et al., 2004) from traction of the implanted hardware.
- Limited literature supports medication adjustment after DBS for dystonia, so medication usually is not changed (Kupsch et al., 2006; Vidailhet et al., 2005). Drug classification for dystonia management is displayed in Table 6 in the original guideline document.
- If patients do not respond well to medications or botulinum toxin treatment, surgery may be considered for certain types of dystonia. Some patients use a sensory trick called "geste antagoniste" in which touching the affected or adjacent body part can reduce dystonic contractions (WE MOVE, 2006). Physical therapy aids such as head or neck braces and hand splints also can mimic the sensory trick. Exercises to improve flexibility and range of motion, strengthen underutilized muscles, and promote proper posture are recommended. Identifying activities and movements that exacerbate dystonic symptoms also is recommended.
- The benefit of DBS on levodopa-induced dyskinesia and dystonia in PD prompted similar attempts in idiopathic focal and generalized dystonia. As mentioned earlier, the GPi currently is considered the most appropriate target for dystonia. Bilateral DBS is preferred to unilateral DBS given the generalized nature of primary generalized dystonia (PGD). Although the pathophysiology of idiopathic dystonia is unknown, positron emission tomography (PET) imaging reveals dysfunction in the GPi, suggesting secondary pathologic overactivation of thalamo-cortical motor regions. Interruption of this abnormal overactive pathway may be one reason GPi DBS relieves some dystonic symptoms. Additional information about dystonia may be found at www.wemove.org and www.dystonia-foundation.org .
Surgical Management of Movement Disorders
Surgery is directed at treating motor disability when medical management is exhausted for patients with essential tremor (ET), dystonia, and PD in whom response to antiparkinsonian medications is complicated by severe motor fluctuations and dyskinesia. Careful patient selection is an important factor in evaluating patients for DBS surgery. DBS candidates and criteria may differ depending on the targeted symptom or disorder. Screening parameters for appropriate ET and dystonic surgical candidates have not been established; however, the same interdisciplinary workup conducted for PD is necessary.
Peripheral surgery is a destructive surgical procedure for treating dystonia, and it targets parts of the body other than the brain, such as selected peripheral nerves for cervical dystonias. This also is known as selective peripheral denervation. In both DBS and peripheral procedures, the goal of surgery is to interrupt the faulty communication between the brain and muscles that causes involuntary muscle movements. The purpose of surgery is to treat symptoms and improve function, but it will not cure the underlying condition.
- Appropriate candidates for PD surgery present with these traits (Pahwa et al., 2006; Voon et al., 2006).
- Idiopathic PD and continued response to levodopa
- Disabling motor symptoms despite optimized medication regimens (dyskinesias, "on-off" motor fluctuations)
- Low surgical risk
- Intact cognitive function determined by neuropsychological testing
- Adequate social support
- Depression, if any (treated)
- Exclusion criteria for DBS
- People with dementia are at greater risk for cognitive decline after surgery (Funkiewiez et al., 2004), and their condition suggests additional neuropathology (Hughes et al., 2001).
- Chronological age alone has not been established as an important predictor for DBS benefits. Younger patients with shorter disease duration may experience more improvement than older patients with longer disease durations (Level III; Pahwa et al., 2006). Older patients with borderline cognitive impairment may benefit from a staged implant in which practitioners implant one lead and wait 4 to 6 weeks before performing the second-side implant (Machado et al., 2006).
- DBS does not help the following PD symptoms (Lang, Deuschl, & Rezai, 2006):
- Symptoms that do not improve with a suprathreshold dose of levodopa
- Freezing, backwards falling/imbalance
- Flexed neck or posture
- Dementia or apathy
- Anxiety or depression
- Speech problems
- Most nonmotor symptoms
- Individualized risk-to-benefit analysis is recommended.
Involve a movement disorder specialist, neuropsychologist, primary care provider, and neurosurgeon.
Preoperative screening tests include brain imaging, a general medical physical examination (including a Unified Parkinson's Disease Rating Scale [UPDRS] motor rating in an "off" state without PD medications), blood tests, electrocardiogram (ECG), chest X ray, neuropsychological testing, and a review of contraindications to surgery, which could include a medication regimen with anticoagulants.
Include teaching and/or patient preparation by the neuroscience nurse (see Section XV, Education in the original guideline document).
Routine nursing support is needed, as the circulating and operating nurses in the surgical environment must prep scalps and position patients comfortably throughout the procedure.
- The DBS system consists of three components: the lead, the extension wire, and the neurostimulator or implantable pulse generator (IPG). The lead is a thin, insulated wire inserted through a quarter-sized burr hole that opens in the skull and is secured in the brain with a fixation device or cap (Figure 3 and Figure 4 in the original guideline document).
- The patient is awake, but may be given local anesthetic and intravenous sedation during placement of a stereotactic head frame. The surgeon may use the newer frameless system for targeting purposes. Either approach works and is facility-dependent. Brain magnetic resonance imaging (MRI) or computed tomography (CT) is obtained after the frame or frameless system is applied and surgical coordinates or measurements for the target are made using surgical software systems.
- The patient should discontinue PD medications for at least 12 hours before the procedure (this is facility-dependent) because of the need for intraoperative electrophysiological monitoring. In the medication "off" state, the patient's abnormal electrophysiology is apparent and hyperactive, and this facilitates intraoperative identification or mapping of the motor subterritory or each neuron's action potentials to identify the ideal location to place the final electrode (Gross et al., 2006).
- The patient is awake during the motor-mapping portion of the surgery to evaluate motor response or to assess side effects and efficacy during macrostimulation. In pediatric patients with dystonia, surgery often is performed under general anesthesia (Gross et al., 2006; Starr et al., 2006).
- Mapping the motor subterritory of the target identifies the best region to place the final electrode. Some surgeons use microelectrode recordings to identify the motor subterritory of the desired nucleus. Mapping involves inserting a small microelectrode that monitors the electrical activity or action potentials of each structure as it is advanced toward the target. The physiology of each nucleus is distinct, so the microelectrodes display patterns unique to each structure. The activity is displayed on an oscilloscope and allows the neurosurgeon, neurologist, or neurophysiologist to distinguish the neurons in the various regions of the brain. Brain mapping is an additional confirmatory step to ensure the selected target is accurately reached. After the motor subterritory is identified, the final lead is implanted into this location. This lead is then tested intraoperatively to assess side effects and, for some facilities, efficacy of lead location (Byrd, Marks, & Starr, 2000).
- During intraoperative test stimulation, the lead location is assessed with the patient awake so he or she can communicate symptoms and respond to the test stimulation. This is necessary to assess if usual voltages can be used without stimulating adjacent structures that can cause unacceptable side effects. The surgical team observes for adverse reactions such as tingling, eye deviation, weakness, or facial grimacing that, if they occur at too low of a threshold, may signify the need to reposition the lead away from the structure that is producing the side effect.
- Patients typically require bilateral electrodes placed for bilateral symptoms (see Figure 5 in the original guideline document) (McIntyre et al., 2004).
- It is advisable to check impedances in the operating room before incisions are closed.
- After the brain leads (Figure 6 in the original guideline document) are implanted, the patient returns 1 to 2 weeks later (a facility-dependent interval) as an outpatient for the remaining hardware implant surgery. For this aspect of the surgery, the patient is placed under general anesthesia to connect the leads to the extension cable and then to the pulse generator. The extension cable, an insulated wire that is passed under the skin of the head, neck, and shoulder, connects the lead to the neurostimulator.
- The neurostimulator is the third component and usually is implanted subcutaneously just below the clavicle, lower in the chest, or in the abdomen, similar to placement of a cardiac pacemaker. It may be done the same day as the lead implant or staged as determined by the surgeon.
- Patient symptoms may transiently improve in the first postoperative month, although DBS has not been activated (microlesion effect).
- Initial DBS programming may be done during the inpatient phase or on an outpatient basis; it is facility- and/or physician-dependent (Figure 6 in the original guideline document).
Early Postoperative Period
- Expect an average hospitalization of 1 to 3 days, and longer stays if complications arise.
- Monitor and control postoperative pain.
- Assess for surgery complications including intracranial edema (which may cause behavioral or mental status changes), bleeding, infection, seizure, and wound dehiscence. DBS has been associated with decline in cognition and psychiatric complications, although the exact mechanism of postoperative personality changes and sustained mood changes are under debate.
- Assess PD symptoms.
- If DBS programming is done on an inpatient basis, assess for side effects, which generally are mild and reversible, by readjusting DBS settings. They most often include:
- Transient paresthesias
- Speech problems
- Dizziness or lightheadedness
- Facial or limb weakness/paresthesias
- Dystonia, dyskinesia
- Motor incoordination
- Worsening of PD symptoms
- Resume the preoperative schedule of PD medications unless otherwise determined by individual patient responses.
- PD medications need to be administered on time and according to the patient's home routine schedule.
- Obtain a postoperative MRI or CT and "merge" with the preoperative MRI to confirm lead placement (Larson et al., 2008). Figure 8 in the original guideline document depicts CT lead/electrode placement.
- Provide patient and family education (see Section XV, Education, in the original guideline document).
Posthospital Discharge Period
- Monitor specific symptoms exhibited by the patient that are responsive to DBS and target them during programming sessions.
- Postoperatively, antiparkinsonian medications may be reduced after programming for patients with STN implants (Deuschl et al., 2006).
- Provide patient and family education (see Section XV, Education, in the original guideline document).
- DBS is activated 1 to 30 days postoperatively and may occur in the hospital or outpatient setting (see Section IX in the original guideline document).
- Initial DBS adjustment occurs over the course of weeks to months.
- Monitoring the response to DBS programming occurs over hours to days.
- PD medication reductions will be based on individual patient responses to DBS.
When working with patients with DBS, consider these observations and directives:
- Collaboration between the neurologist and programmer is fundamental before the physician or advanced practice nurse (APN) can adjust medications.
- Minimize programming for short-term symptom exacerbations. Patients can experience a placebo effect or benefit from visiting the clinic and programming, then return to baseline or worsen when they return to their home. Patients with advanced disease may have symptom exacerbations due to other medical problems. After a patient has an implant, it is common for practitioners to inappropriately associate new problems with the new implant.
- Ask the patient to keep a diary during the first 6 months of stimulation to record motoric problems to assess if the problematic symptoms correlate with time of day and time of medication. Have the patient try to assess if symptoms either fluctuate with medication dosing or are constant. Remind patients that stimulation-related problems are constant and medication-related problems fluctuate.
- The goal of DBS is to maximize benefit, not eliminate PD medications.
- Rescreen each contact/electrode if evaluating a patient for an initial programming session or if clinical efficacy is questioned. Check the DBS usage counter (should be 99% to 100% for patients with dystonia and PD). Check electrical impedance, especially if there has been loss of efficacy.
- Remember that each patient and his or her symptoms are different. Accurate lead location, effective programming, and good patient selection all are key factors to therapy success.
- Medtronic, Inc., offers training courses for developing programming skills and knowledge for providers working with patients with DBS.
Data Quality Classification
Class I: Randomized controlled trial without significant limitations or meta-analysis
Class II: Randomized controlled trial with important limitations (e.g., methodological flaws, inconsistent results); observational study (e.g., cohort, case control)
Class III: Qualitative study, case study, or series
Class IV: Evidence from reports of expert committees and/or expert opinion of the guideline panel, standards of care, and clinical protocols that have been identified
Levels of Recommendation
Level 1: Recommendations are supported by class I evidence.
Level 2: Recommendations are supported by class II evidence.
Level 3: Recommendations are supported by class III and class IV evidence.