Treatment of patients with PD can be divided into three major categories: medications, physical (and mental health) therapy, and surgery. Although the pharmacologic strategies described below apply primarily to PD, they can also be tried in atypical parkinsonian conditions. MSA, PSP, and CBD, however, are typically associated with a more limited response to medications, underscoring their overall worse prognosis.
Dopamine replacement therapy is the primary medical approach to treating PD, and a variety of dopaminergic agents are available (Table 67-5). The most powerful oral drug is levodopa, the immediate precursor of dopamine. Levodopa, an amino acid precursor molecule of dopamine, can enter the brain, whereas dopamine is blocked by the blood-brain barrier. Levodopa is usually administered combined with a peripheral decarboxylase inhibitor (carbidopa or benserazide) to prevent formation of dopamine in the peripheral tissues, thereby increasing levodopa’s bioavailability and also markedly reducing gastrointestinal side effects. The brand name Sinemet is a combination of carbidopa and levodopa; the brand name Madopar is a combination of benserazide and levodopa. Such combination drugs are available in standard (ie, immediate-release) and extended-release formulations. The former allows a more rapid and predictable “on,” and the latter allows for a slightly longer plasma half-life, but with a slower and less predictable “on.” The combination of the two release formulations can be administered in an attempt to smooth out and extend plasma levels of levodopa. A version of carbidopa/levodopa that dissolves under the tongue (Parcopa) and enters the stomach via swallowing saliva is also available. This orally dissolving formulation has particular usefulness for patients who have swallowing difficulties.
TABLE 67-5DOPAMINERGIC AGENTS |Favorite Table|Download (.pdf) TABLE 67-5 DOPAMINERGIC AGENTS
Dopamine precursor: levodopa
Peripheral decarboxylase inhibitors: carbidopa, benserazide
Dopamine agonists: pramipexole, ropinirole, rotigotine, apomorphine
Catechol-O-methyltransferase inhibitors: entacapone
Dopamine releaser: amantadine
Peripheral dopamine receptor blocker: domperidone
MAO type B inhibitor: selegiline, selegiline, rasagiline
Although levodopa is the most effective drug to treat the symptoms of PD, over half of patients develop troublesome complications of disabling response fluctuations (“wearing-off”) and/or dyskinesias after 5 years of levodopa therapy.
Besides being metabolized by aromatic amino acid decarboxylase (commonly known as dopa decarboxylase), levodopa is also metabolized by catechol-O-methyltransferase (COMT) to form 3-O-methyldopa. Entacapone is a currently available COMT inhibitor. This agent extends the plasma half-life of levodopa with and also increases its peak plasma concentration, and thereby prolongs the duration of action of each dose of levodopa. Its clinical indication is to help reduce motor fluctuations, that is, increase “on” time and reduce “off” time. Because entacapone enhances levodopa’s efficacy, it can increase dyskinesias and the dosage of levodopa may need to be lowered. Entacapone is very short acting, and each 200-mg tablet is taken simultaneously with levodopa. Entacapone is also available in a combination pill with carbidopa/levodopa (Stalevo). Tolcapone (100- and 200-mg tablets) is more potent and has a longer duration of action, but it is encumbered by a greater risk of diarrhea and hepatotoxicity, the latter of which has led to its removal from the market in the United States. After levodopa, the next most powerful oral drugs in treating PD symptoms are the dopamine agonists. Several of these are available. The ergot compounds of pergolide, bromocriptine, and cabergoline have the potential to induce fibrosis (cardiac valvulopathy and retroperitoneal, pleuropulmonary, and pericardial fibrosis), so these agents are not recommended; indeed pergolide has been withdrawn from the US market. Pramipexole and ropinirole appear to be equally effective at therapeutic levels. Dopamine agonists are more likely than levodopa to cause hallucinations, confusion, and psychosis, especially in the older adults. Thus, it is safer to utilize levodopa in patients older than 70 years. On the other hand, clinical trials have shown that dopamine agonists are less likely to produce dyskinesias and the wearing-off phenomenon than levodopa. These differences are most likely due to the relatively lower potency/efficacy and longer half-life of dopamine agonists compared to levodopa. Slow-release preparations of ropinirole and pramipexole are also available. Other problems more likely to occur with dopamine agonists than levodopa are sudden sleep attacks, including falling asleep at the wheel, daytime drowsiness, ankle edema, and impulse control problems such as hypersexuality and compulsive gambling, shopping, and binge eating. The newest dopamine agonist is rotigotine which is applied via a dermal patch to the upper torso or arms. It is useful for those with swallowing difficulties and may help smooth out motor fluctuations and nocturnal akinesia, when the last prebedtime dose of levodopa does not last throughout the night. Apomorphine may be the most powerful dopamine agonist, but it needs to be injected subcutaneously (or taken sublingually or infused subcutaneously in Europe). It is used to provide faster relief to overcome a disabling “off” state.
Amantadine is adjunctive antiparkinsonian drug with several pharmacologic actions; it has mild antimuscarinic effects, but more importantly, it can activate release of dopamine from nerve terminals, block dopamine uptake into the nerve terminals, and block glutamate NMDA receptors. Its dopaminergic actions make it a useful drug to relieve symptoms in approximately two-thirds of patients, but it can induce livedo reticularis, ankle edema, visual hallucinations, and confusion. Its antiglutamatergic action is useful in reducing the severity of levodopa-induced dyskinesias, and in fact, is the only established effective antidyskinetic agent. The dose of amantadine for its anti-PD effect is usually 100 mg twice daily, but its antidyskinetic effect requires higher dosages, usually 300 to 400 mg/day. Unfortunately, the antidyskinetic effect tends to lessen over time. Older individuals often do not tolerate amantadine well because of mental adverse effects of confusion and hallucinations.
Domperidone is a peripherally active dopamine receptor blocker and is useful in preventing gastrointestinal upset from levodopa and the dopamine agonists. It is not available in the United States, but is available in other countries including Canada. Monoamine oxidase type B (MAO-B) inhibitors (selegiline, rasagiline) offer mildly effective symptomatic benefit and are without significant hypertensive diet-linked side effects seen with MAO-A inhibitors, and therefore can be used in the presence of levodopa therapy. Although there has been considerable debate about possible protective or disease-modifying benefit of MAO-B inhibitors, numerous well-powered trials have failed to convincingly demonstrate a neuroprotective benefit. The results of these trials have been interpreted variably, however, given that selegiline and rasagiline appear to have a symptomatic benefit, which has contributed to some methodological concerns regarding specific trial designs. Selegiline, but not rasagiline, is metabolized to L-amphetamine and methamphetamine. Both of these drugs can reduce the severity of motor fluctuations with levodopa.
Motor Complications of Dopaminergic Therapies
Many patients on levodopa therapy develop motor complications (Table 67-6). These motor complications, also referred to as “motor fluctuations,” usually begin as mild wearing-off, which can be defined as when an adequate dose of levodopa does not last at least 6 hours and motor symptoms of bradykinesia, rigidity, or tremor emerge or worsen. Typically, in the first couple of years of treatment, there is a long-duration response so that the timing of doses of levodopa is not important. Over time, the long-duration response becomes lost, and only a short-duration response occurs; patients then develop the wearing-off phenomenon. The “off” episodes tend to be mild at first, but over time become more frequent or severe with more severe parkinsonism. Simultaneously, the duration of the “on” response becomes shorter. Eventually, some patients develop random, sudden “offs” in which the deep state of parkinsonism develops over minutes rather than 10s of minutes, and they are less predictable in terms of synchrony with the dosing of levodopa. Many patients who develop response fluctuations also develop abnormal involuntary movements, that is, dyskinesias.
TABLE 67-6PATTERN OF DEVELOPMENT OF RESPONSE FLUCTUATIONS, DYSKINESIAS, AND OTHER COMPLICATIONS |Favorite Table|Download (.pdf) TABLE 67-6 PATTERN OF DEVELOPMENT OF RESPONSE FLUCTUATIONS, DYSKINESIAS, AND OTHER COMPLICATIONS
Dyskinesias (chorea and dystonia)
Diphasic dyskinesias (beginning and end-of-dose dyskinesias)
Sudden, unpredictable “offs” (on-offs)
Early morning “off” dystonia
“Off” dystonia during day
Drowsy from a dose of levodopa
Reverse sleep-wake cycle
Behavioral and cognitive
Treatment of “wearing-off”
The wearing-off phenomenon, when mild, may be ameliorated slightly with the addition of selegiline or rasagiline (0.5 mg once daily, and increasing to 1 mg once daily, as necessary). Both MAO-B inhibitors potentiate the action of levodopa. A higher dose of levodopa may be necessary but more frequent dosing of levodopa may be the simplest approach to manage this motor complications. Many patients can require six or more doses per day, and then, eventually, can develop dose failures owing to poor gastric emptying. These patients are often considered for duodoneal infusion of levodopa or deep brain stimulation (see Surgical Therapy later)
Continuous-release carbidopa/levodopa (Sinemet CR) can also be effective in patients with mild wearing-off in some patients or use the combination of both immediate- and extended-release formulations. Dopamine agonists, which have a longer biological half-life than levodopa, can also be used in combination with immediate-release or continuous-release versions of carbidopa/levodopa. The addition of a dopamine agonist tends to make the “off” state less severe when used in combination with carbidopa/levodopa. COMT inhibitors have been found useful for treating wearing-off. Because of the short half-life of entacapone, it is given with each dose of carbidopa/levodopa, and is about as equally effective as rasagiline in reducing the amount of daily “off” time. For those patients who have “offs” at a specific time of day, entacapone can be strategically given just with the dosage of carbidopa/levodopa that precedes this “off” period.
Behavioral or sensory “offs” can also occur as do motor “offs,” often in the absence of any motor “off,” which means a return of parkinsonism. Behavioral and sensory “offs” tend not to be easily recognized, because visibly the treating physician sees no motor changes. Behavioral/sensory “offs” can consist of pain, akathisia, depression, anxiety, dysphoria, or panic, and usually a combination of more than one of these. Sensory “offs,” like dystonic “offs” are very disabling. It is often the presence of one of these sensory and behavioral phenomena, more so than motoric parkinsonian or dystonic “offs,” that drives the patient to take more and more levodopa, leading a few patients to develop an addictive relationship with dopaminergic medications, so-called dopamine dysregulation syndrome.
Dyskinesias are involuntary movements and occur in two major forms—chorea and dystonia. Choreiform movements are irregular, nonrhythmic, unsustained dance-like movements that seem to flow from one body part to another and can appear like benign fidgeting. Dystonic movements are more sustained, twisting contractions. Many patients have a combination of choreiform and dystonic dyskinesias.
Peak-dose dyskinesias occur when the plasma concentrations of levodopa or dopamine agonists are at their peak, and the synaptic brain concentration of dopamine is too high. Reducing the individual dosage can resolve this problem of peak-dose dyskinesias. However, the patient may need to take more frequent doses at this lower amount. An alternative approach is to add amantadine, which suppresses the severity of dyskinesias, possibly because of its antiglutamatergic action. Start with a dose of 100 mg BID and increase up to 200 mg BID if necessary. Buspirone in dose up to 20 mg/day may also of benefit in treating dyskinesias in some patients.
Some patients may develop “off” dyskinesias. In the absence of so-called early morning “off” dystonia, which responds well to dopaminergic therapies, such patients are encouraged to consider deep brain stimulation (see later under Surgical Therapy). Depending on their distribution within the body and the disability associated with them, dystonic dyskinesias can also be treated with local injections of a chemodenervation agent such as botulinum toxin. This treatment can be associated with a significant improvement in quality of life but will also weaken a muscle group and thereby can impact a patient’s function, particularly if the dystonic movements are occurring in the hands.
Diphasic dyskinesias are dyskinesias that occur at the beginning and end of dose, not during the time of peak plasma and brain levels of dopaminergic medications. They tend to particularly affect the legs with a mixture of chorea and dystonia.
Dopamine medication–related nonmotor complications
In addition to motor features, a number of nonmotor problems can also occur as complications from dopaminergic therapy. Mental changes of psychosis, confusion, agitation, hallucinations, paranoid delusions, punding, impulse control disorders, and excessive sleeping are probably related to activation of dopamine receptors in anteroventral striatal regions, or nonstriatal regions, particularly the cortical and limbic structures.
Drug-induced hallucinations tend to be mild, visual in nature rather than auditory, and not frightening. Consideration should be given to reducing the total dose of dopaminergic medication to whatever degree is tolerable for the patient. A complete review of medications is indicated as well to identify any other symptomatic treatments that might be worsening encephalopathy, including benzodiazepines, anticholinergics, and opioids. Adjunctive treatment can begin with the addition of quetiapine, starting with 25 mg at bedtime. The dose should be increased steadily until the hallucinations are brought under control. If quetiapine is ineffective or if the hallucinations are frightening, clozapine, a stronger antipsychotic that will not worsen motor features of PD, should be considered. As mentioned previously, the reason clozapine is not the first drug of choice in dopaminergic-induced hallucinations is because clozapine causes agranulocytosis in approximately 1% to 2% of patients. Patients must have their blood counts monitored weekly for this potential complication, and then discontinue the drug if leukopenia develops. Both quetiapine and clozapine often cause drowsiness, so bedtime dosing is recommended.
If the psychosis is severe or if the patient is in an acute delirious state, hospitalization may be necessary, with immediate initiation of antipsychotic medications, and some reduction in anti-PD medication. These medications could even be withdrawn temporarily to overcome the psychosis, but this should be done stepwise over a 3-day period to avoid the neuroleptic malignant-like syndrome that could occur with sudden withdrawal of levodopa.
Dopamine agonist medications are associated with sleep attacks and impulse control disorders. Both of these issues can also be seen with levodopa but are much less common and less severe. Sleep attacks often manifest with a sudden wave of sleepiness that comes on with little warning and can be particularly dangerous for patients who are driving at the time. Impulse control disorders consist of behavioral changes such as compulsive gambling, shopping, and eating, and hypersexual behaviors. Not surprisingly, these changes can often have significant detrimental effects on family relationships. Both of these side effects are, to some degree, dose dependent and typically necessitate reducing the dose of the dopamine agonists or stopping them altogether. Memantine, an NMDA receptor antagonist, has shown to be of benefit in some patients with dopamine agonist–induced impulse control disorders in PD.
Nondopaminergic agents (Table 67-7) are useful to treat both motor and nonmotor symptoms of PD. Antimuscarinic drugs have been used since the 1950s to treat parkinsonian tremor, but have limited efficacy and frequently lead to cognitive impairment and hallucinations in the elderly population. For this reason antimuscarinics should be avoided in patients older than 70 years.
TABLE 67-7NONDOPAMINERGIC AGENTS |Favorite Table|Download (.pdf) TABLE 67-7 NONDOPAMINERGIC AGENTS
Parkinsonian motor symptoms:
Antimuscarinics (for tremor): trihexyphenidyl, benztropine
Antiglutamatergics (to reduce dyskinesia): amantadine
Muscle relaxants: cyclobenzaprine, diazepam, baclofen
Nonmotor symptom control:
Depression: selective and nonselective serotonin reuptake inhibitors, tricyclics, ECT
Psychosis (hallucinations, paranoia): clozapine, quetiapine
Insomnia: mirtazapine, trazodone, quetiapine, zolpidem
REM sleep behavior disorder: clonazepam, melatonin
Excessive daytime sleepiness: modafinil
Dementia: donepezil, rivastigmine
Orthostasis: fludrocortisone, midodrine, droxidopa
Restless legs: dopamine agonists, levodopa, gabapentin, opioids
Depression is common in patients with PD, and often precedes the motor symptoms of PD. Selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and other antidepressants including bupropion and tricyclic antidepressants are useful antidepressants. If insomnia is a problem for the patient, using an antidepressant that is also a soporific can be doubly advantageous: medications such as the tricyclic nortriptyline (which has fewer anticholinergic effects than amitriptyline) or an SNRI, such as low-dose mirtazapine, are good options.
Benzodiazepines including clonazepam are effective in reducing symptoms of dream enactment behavior attributable to rapid eye movement (REM) sleep behavior disorder (RBD). Nevertheless, they should be used with caution given their potential for cognitive side effects, increased risk of falls, rebound anxiety, and their addictive potential.
Psychosis induced by levodopa and the dopamine agonists can usually be controlled by quetiapine and clozapine without worsening the parkinsonism. Other antipsychotic agents—be they typical or atypical neuroleptic mediations—are more likely to worsen the parkinsonism; therefore, they should be avoided. Clozapine is more effective than quetiapine, but because clozapine treatment requires weekly blood cell counts due to risk of agranulocytosis, low-dose quetiapine should be tried first.
Insomnia in PD requires a detailed history to distinguish specific causes of impaired sleep that may require different management approaches. Common causes of insomnia in PD include restless legs, persistent tremor, nocturnal akinesia, dream enactment behavior, bladder dysfunction, and early morning motor “off” symptoms or dystonia. Both sleep-onset insomnia and sleep-maintenance insomnia occur in PD, though sleep-maintenance insomnia may be more common and troublesome. Sleep-onset insomnia is treated conventionally with low doses of hypnotics and sedating antidepressants such as low-dose mirtazapine or trazodone. In demented patients, low nighttime doses of the atypical antipsychotic quetiapine may be useful if neurobehavioral disturbances occur at night. Sleep maintenance insomnia is due often to motor dysfunction. Bradykinesia with difficulty moving in bed or adjusting bedclothes is a common cause of sleep maintenance insomnia in PD. Levodopa has a relatively short serum half-life and a common experience is loss of levodopa effect in the middle of the night with worsening bradykinesia and nocturnal arousals. Medication schedule manipulations such as instituting or increasing a bedtime dose of levodopa may be useful. Similarly, use at bedtime of extended-release levodopa preparations, adjunctive agents that lengthen the levodopa half-life, or dopamine agonists that possess relatively long half-lives may ameliorate this form of sleep-maintenance insomnia. An additional common source of sleep-maintenance insomnia in more advanced PD is bladder dysfunction, which in men with PD may coexist with prostate enlargement. Specifically, autonomic dysfunction leading to urinary frequency, urgency, and incontinence is common in more advanced PD. Conventional approaches to treating bladder dysfunction may be useful. Nocturnal use of gabapentin can also be of benefit in some patients.
RBD is common in patients with PD, DLB, and MSA and often precedes the appearance of these disorders. RBD manifests with complex, nonstereotyped dream-enactment behavior and is usually associated with vivid or frightening dream content. Normally, dreaming in REM sleep is associated with muscle paralysis to all skeletal muscles outside of the eyes and diaphragm. This normal REM-associated muscle paralysis is reduced in RBD. RBD in PD, as in other settings, does not seem to cause daytime sleepiness but can result in injuries or disrupt bed partner rest. Infrequent and mild episodes of RBD probably do not require treatment but more severe episodes can be of dangerous to the bed partner or patient. Withdrawal of antidepressants that can precipitate or exacerbate RBD may be worthwhile. Safety measures within the sleeping room may be necessary. These can include use of separate beds, placement of mattresses on the floor, efforts to sleep on the first floor, and removing dangerous objects from the bedroom. The mainstay of medical treatment is use of hour-of-bedtime clonazepam (0.5–2 mg), which appears to be effective and is tolerated well by the majority of patients. Melatonin—though less effective—may be tried first and can be combined with clonazepam. In some patients, cholinesterase inhibitors may also help RBD symptoms. Dopaminergic therapy probably has little or no effect on RBD.
Periodic leg movements of sleep (PLMS) and restless legs syndrome (RLS) are estimated to be twice as common in PD as in matched populations. Despite this association, the relationship between PD and RLS is complex. While both RLS and PLMS may contribute to insomnia in PD, one study has shown no significant worsening in daytime sleepiness seen in PD patients with RLS compared to those without. No evidence exists that RLS predisposes patients to develop PD later in life. Though dopaminergic dysfunction may play a role in both PD and RLS, imaging studies of subjects with RLS without PD have not shown convincing evidence of a nigrostriatal dopaminergic deficit. These findings suggest that RLS may not in fact be a precursor to the cardinal motor symptoms of PD and may not be a “secondary” symptom of PD, but rather a separate disease entity that can be exacerbated by PD. Assessment and management of RLS in PD involves an evaluation for iron deficiency and iron supplementation when appropriate, and use of low doses of dopaminergic agents such as long-acting dopamine agonists or L-dopa. In patients with poor or complicated responses to dopaminergic agents, gabapentin, clonazepam, or low-dose opiates may be useful.
Fatigue is an increasingly noted nonmotor symptom in PD of unclear etiology but has shown to be correlated with poor sleep and depression. Clinicians should attempt to differentiate fatigue from excessive daytime sleepiness, the latter of which is often due to poor quality of sleep at night or adverse effects associated with excess dopaminergic medications, necessitating a different approach to diagnostic work-up and management. Many patients describe fatigue as their first presenting symptom. Management should be aimed at underlying causes, such as depression. If needed, medications such as modafinil or nonprescription therapies such as liberalizing caffeine consumption can provide some benefit.
Mild cognitive symptoms can be seen in some PD patients with early disease and worsen with increasing disease duration. Early features typically include impaired attention, verbal memory, and executive dysfunction summarized as a subcortical-frontal syndrome. Dementia in PD is often associated with the development of significant visuospatial impairments, memory difficulties, and hallucinations—the latter of which may also be seen in response to dopaminergic or anticholinergic drugs. PDD and DLB patients are at a particularly high risk for developing delirium, either in association with new medications or because of underlying acute medical illnesses. Symptoms of delirium often involve profound disorientation and psychosis that can sometimes take weeks to resolve. Cholinergic deficits affecting subcortical and cortical structures are thought to play a significant role in PD cognitive impairment. Cholinesterase inhibitors, including donepezil and rivastigmine, are useful therapies for improving cognitive symptoms at all stages of PD. They are, however, limited in their efficacy due to limited central nervous system (CNS) bioavailability.
Orthostatic hypotension is common in PD and can be due to the disease itself or to dopaminergic medications, the latter of which lower blood pressure. It can also represent an early manifestation of an atypical parkinsonian condition, namely MSA. Fludrocortisone, midodrine, or droxidopa can overcome this symptom to some extent.
Constipation is common in PD. It may be further aggravated by anticholinergic medications. Besides changing dietary habits by increasing intake of more fiber and dried fruits, polypropylene glycol or lubiprostone can be effective. For those who have bloating because of suppression of peristalsis when they are “off,” keeping them “on” with levodopa can be beneficial.
Exercise and Physical Activity
An active exercise program encourages patients to have ownership over their own care, allows muscle stretching and full range of joint mobility, increases aerobic capacity, muscle strength, motor skills, and improves a patient’s mental attitude toward fighting the disease. Preclinical studies have shown that exercise slows the degeneration of dopamine neurons following local toxin, theoretically because exercise leads to an increase in brain neurotropic factors. There is also increasing evidence to suggest that sedentary behaviors, irrespective of the amount of formal exercise one performs, may have a deleterious impact on not only physical condition but also metabolic functions. These changes increase the risk for frailty among patients with PD subjects leading a decline in health. Encouraging patients to reduce the amount of time they spend seated each day is a good way to empower patients to regulate their own PD prognosis.
A regular routine of physical exercise, be it cardiovascular training or weight-based exercises, should be implemented as soon as the diagnosis is made, but is useful in all stages of disease. Stretching exercises may help to compensate for the tendency of patients to have a reduced range of motion. In moderate-to-advanced stages of PD, formal physical therapy is more valuable by keeping the joints from becoming frozen, and by providing guidance how best to remain independent in mobility, particularly with gait training and prevent injurious falls. One of the nonmotor symptoms of PD is the tendency toward apathy and conservative decision making with decreased motivation. Encouraging activity may help fight these symptoms.
DBS surgery for PD is an increasingly available treatment option associated with significant gains in quality of life for PD patients who are good surgical candidates. DBS surgery is typically indicated for PD patients with difficult-to-manage motor complications (fluctuations and/or dyskinesias) or with medication-refractory parkinsonian tremor. DBS involves placement of an impulse pulse generator (IPG) in the chest that looks much like a pacemaker. A lead from the IPG is tunneled under the skin surface to a specific region of the brain, either the STN or the GPi.
When stimulation is optimized, patients will experience an “on” state without disabling “off” features. Patients are also able to reduce their dose of dopaminergic medications, and in this way, are able to reduce dyskinesias as well. With the exception of tremor, motor features that generally do not improve with dopaminergic medications (eg, postural instability, other axial motor features, some gait freezing) also do not improve with DBS. DBS typically has little effect on the nonmotor features of PD unless they are directly related to on-off fluctuations seen with dopaminergic medications.
Patients with significant speech, gait, depression with suicidal ideation or cognitive difficulties are usually not good candidates for DBS, not only because these symptoms do not respond to stimulation, but also because in some patients, these features may become notably worse after DBS, including the risk of suicide. The selection of appropriate candidates for DBS is often best done under the guidance of an experience movement disorder neurologist. DBS is not suggested for patients with atypical parkinsonian conditions since the majority of these motor features do not respond to dopaminergic medications.