Parkinson's disease occurs when some of the nerve centers in the brain lose the ability to regulate muscle movements. As a result, you may have rigid muscles, tremors, and difficulty walking and swallowing.

Parkinson's disease is one of the most common diseases affecting movement in people over age 55. It is chronic, meaning you will have it the rest of your life. It also is progressive, which means the symptoms grow worse over time. The disease may become disabling after many years. However, proper treatment should make it possible for you to lead a fulfilling, productive life.

How does it occur?

Parkinson's disease results when nerve cells in a certain part of the brain die or stop working properly. These cells stop producing an important brain chemical called dopamine. Dopamine normally transmits signals to another part of the brain that allows controlled muscle movement. Without enough dopamine, the cells in this part of the brain fire out of control. As a result, you are unable to control your movements normally.

No one knows why the nerve cells die or become impaired. Theories include:

• damage by chemical reactions in the body, such as oxidation
• toxins in the environment
• inherited tendencies
• accelerated aging.

What are the symptoms?

A major symptom of Parkinson's disease is tremors. A tremor is a rhythmic shaking over which you have no control. Tremors of the hands and sometimes the head often occur along with a constant rubbing together of thumb and forefinger.

Over time you may stop making some movements that are normally automatic, such as the natural swinging of arms that makes walking smooth. It may become harder to:

• write clearly
• speak clearly
• start to do something
• change positions
• keep your balance when you walk
• get out of a chair.

In the earliest stages of the disease, symptoms may be very slight or may not be noticed. Someone close to you might notice a slight limp, stooped posture, or a mild hand tremor.

Other symptoms may include drooling and abdominal cramps. You may have trouble swallowing. In later stages, there is often a decline in the ability to think and remember. How is it diagnosed?

Accurate diagnosis can be difficult. Your doctor will ask about your medical history and examine you. He or she will look for the physical signs of tremor, rigid muscles, and slow movements that suggest Parkinson's disease.

There are no tests that can confirm the diagnosis. However, tests are sometimes used to rule out other diseases.

How is it treated?

There is no cure yet for Parkinson's disease. However, a variety of medications can give dramatic relief from the symptoms.

In mild cases of Parkinson's disease, your doctor may not prescribe medicine to avoid the side effects it can cause. Your doctor will want to see you regularly to keep track of your symptoms and determine when you might benefit from medication.

Your doctor may prescribe medication to help restore the balance of chemicals in your brain. The main goal of treatment is to keep your movements as normal as possible with the smallest amount of medicine. It may not be possible to get rid of all your symptoms.

Your treatment may also include speech therapy and physical therapy. In severe cases not helped by medication, surgery may help prevent uncontrollable tremors.

Medication:

Several different drugs are used to treat Parkinson's disease. Your doctor will try to use the smallest effective dosage to reduce the chance of unpleasant side effects.

Levodopa is the main medicine used to treat Parkinson's disease. The brain can make dopamine from levodopa. Possible side effects of this medication are:

• abnormal movements of the face, trunk, arms, and legs
• nausea and vomiting
• short-term memory loss
• confusion.

Eating less protein may help to make levodopa work better. However, do not begin a low-protein diet without first talking to your doctor. A major risk with a low-protein diet is weight loss and malnutrition. If you have closed-angle glaucoma, you should not take levodopa.

Some of the other medications your doctor may prescribe are:

• dopaminelike drugs such as bromocriptine and pergolide
• amantadine, a drug used to treat flu
• anticholinergic drugs, such as benztropine (Cogentin), trihexyphenidyl (Artane), and orphenadrine (Norflex)
• selegiline, a drug that slows the breakdown of dopamine and may help slow down the worsening of symptoms over time, especially in the early stages of the disease.

Exercise:

A program of daily exercise will help you have better use of your muscles. Exercise can help prevent problems that occur when muscles are not used. It will increase your muscle strength and improve coordination. You will have less muscle rigidity. Physical therapy can teach you how to walk and move in a way that will reduce your risk of falling.

How long do the effects last?

As a result of treatment that relieves symptoms, many people with this disease remain in fairly good health for years. The disease progresses despite treatment, however, and can become disabling over time.

What can I do to prevent Parkinson's disease?

Doctors do not know how to prevent this disease.

How can I take care of myself?

To cope with Parkinson's disease and to relieve your symptoms:

• Be sure you and your family know how your medications work. Know what the side effects are and which side effects should prompt you to call your doctor.
• Do not take any medicines, including nonprescription products, without letting your doctor know.
• Make your house safer:
• Put up handrails along walkways.
• Use carpeting to help cushion falls.
• Be sure seats (including shower seats) have sturdy backs.
• Put handrails in the bathroom.
• Consider installing a device that raises the toilet seat.
• Use an electric shaver to avoid cuts from razors.
• Try to make it easy for you to dress yourself:
• Wear loafers or shoes that close with Velcro strips instead of shoes with laces.
• Wear clothing that is easy to get on and off.

When possible, use Velcro strips on clothing instead of zippers or buttons.

• If you have problems swallowing:
• Take as much time as you need to eat meals.
• Sit upright.
• Thick liquids are easier to swallow than thin liquids.
• Use an electric warming tray to keep food hot during the long time it may take to finish a meal.
• Weigh yourself once a week to make sure that you are not losing too much weight.
• Reduce constipation by drinking more water and eating more foods that are high in fiber. High-fiber foods include whole-grain breads and cereals, beans, fruits, and vegetables.
• If you have speech problems, work on other ways to make your needs known. Practice speech exercises your doctor or speech therapist may give you.
• Stay as active as possible. Keep involved in your work, hobbies, and other activities.
• Get support from family and friends. Keeping a positive attitude can be quite helpful.

When should I call the doctor?

Your doctor will want to see your progress and check on how well your treatment is working. Keep your follow-up appointments on the schedule your doctor recommends. Discuss any questions and concerns you have at these visits.

Call your doctor if:

• You have side effects from your medicine, such as nausea, dizziness, and mental changes.
• Your weight drops 3% to 5% in any month.
• You develop fever.
• Swallowing becomes harder.
• You become depressed. (Your doctor may be able to prescribe medicines to help.)
• You begin to have hallucinations, which can be a side effect of your medicines. (Your doctor may be able to adjust the dosages of your medicines.)

Source: www.mdconsult.com

Exams and Tests

A diagnosis of Parkinson's disease is based mostly on your medical history and a thorough neurological exam.

There are no lab tests that can diagnose Parkinson's disease. If your symptoms and the doctor's findings during the examination are not entirely typical of Parkinson's disease, certain tests may be done to help diagnose other conditions that could be contributing to your symptoms. For instance, blood tests may be done to check for abnormal thyroid hormone levels, liver damage, or other problems. A special imaging test called magnetic resonance imaging (MRI) may be used to check for signs of a stroke or brain tumor.

Another type of imaging, called positron emission tomography (PET), sometimes may detect low levels of dopamine in the brain, a key feature of Parkinson's disease. However, PET scanning is not commonly used to evaluate Parkinson's disease because it is very expensive and is not available in many hospitals.

Proper nutrition for people with Parkinson's disease

Most people with Parkinson's disease can eat the same healthy, well-balanced diet recommended for anyone. This includes plenty of fruits, vegetables, grains, cereals, legumes, poultry, fish, lean meats, and low-fat dairy products.

Protein may interfere with the absorption of levodopa and make the effects of the medication less predictable. It may be helpful to spread your protein intake evenly throughout the day or to consume most of your daily protein requirements in the evening, rather than during the daytime, so that you have a more predictable absorption of and response to levodopa during the day when you are more active.

Follow your doctor's specific recommendations on diet and medication. Eating a low-protein diet should be done only with the help of a dietitian or doctor.

Symptoms of Parkinson's disease and side effects of medications used to treat the disease can change an affected person's appetite and ability to eat. Factors that can affect nutrition include mood, dementia, chewing and swallowing problems, tremors, immobility, and inactivity. It is important to find ways to eat a nutritious diet despite these factors.

Parkinson's disease affects the movement of intestinal muscles, which contributes to constipation in many people. Many medications used to treat the disease may make constipation worse. To reduce constipation:

• Drink plenty of water.
• Eat plenty of fresh fruits, vegetables, and whole grains. Increase your fiber intake gradually to allow your system to adjust.
• Avoid repeated use of laxatives, which can create dependence over time.

Source: Healthwise Knowledgebase of www.healthwise.com/hworg

MEDICAL DETAILS

Parkinson's disease

Aminoff MJ - Neurol Clin - 01-Feb-2001; 19(1): 119-28, vi
From NIH/NLM MEDLINE

Full Source Title:
Neurologic Clinics

Author:
Michael J. Aminoff MD, DSc, FRCP

From the Department of Neurology, University of California, San Francisco, California

The syndrome of parkinsonism consists of a variable combination of tremor, rigidity, bradykinesia, and a disturbance of gait. Parkinson's disease is a chronic, progressive disorder in which parkinsonism occurs without recognizable cause or evidence of more widespread neurologic involvement. It typically begins in middle or late life and leads to increasing disability with time. It has a prevalence of 1 to 2 per 1000 of the general population and 2 per 100 among people older than 65 years. The disorder is caused by cell loss in the substantia nigra pars compacta and the locus ceruleus in the midbrain. Lewy bodies (eosinophilic intraneural inclusion granules) are widespread but occur especially in the basal ganglia, brainstem, spinal cord, and sympathetic ganglia.

Pars compacta neurons of the substantia nigra provide dopaminergic input to the striatum. These dopaminergic neurons modulate a monosynaptic GABA-ergic inhibitory output to the globus pallidus interna and pars reticulata of the substantia nigra, which project by a GABA-ergic inhibitory pathway to the ventroanterior and ventrolateral nuclei of the thalamus. Stimulation of this direct pathway disinhibits these thalamic nuclei, with a resulting increase in their excitatory output to the motor cortex. Another polysynaptic (indirect) pathway from the striatum reduces the thalamic output to the motor cortex. It involves striatal GABA-ergic inhibitory neurons that project to the globus pallidus externa which, in turn, inhibits the subthalamic nucleus. This nucleus has excitatory glutamatergic connections with the globus pallidus interna and substantia nigra pars reticulata.

Loss of dopaminergic nigral cells leads to striatal dopamine depletion. The dopamine activates excitatory D1 receptors in the direct pathway and inhibits inhibitory D2 receptors in the indirect pathway. Accordingly, dopamine depletion decreases activity of the direct pathway and increases activity of the indirect pathway, thereby reducing thalamic excitation of the motor cortex. Other neurotransmitters, such as norepinephrine, are also depleted, but with uncertain clinical consequences. The cause of Parkinson's disease is unknown. It has been attributed to exposure to environmental or endogenous toxins. Dopamine, which is readily oxidized to generate free radicals that lead to cell death, has been held to be responsible, but this is unsettled. The evidence relating Parkinson's disease to damage by free radicals is impressive.

Treatment for Parkinson's disease is divided into two categories, symptomatic therapies and preventive or protective measures. Symptomatic therapies amelionate the symptoms and signs of the disorder, but without affecting the tendency for progression to occur with time. Neuroprotective strategies, by contrast, are intended to slow the development and progression of the disorder.

Symptomatic Pharmacologic Treatment

Symptomatic treatment is generally not required unless or until the symptoms or signs of parkinsonism are beginning to affect the quality of life or are otherwise interfering with daily activities.

Nonselective muscarinic antagonists (anticholinergic drugs) are sometimes helpful, especially in relieving tremor, but side effects are common. Confusion and hallucinations are often troublesome in the elderly. Dryness of the mouth, constipation, urinary retention, and blurred vision also may occur. Narrow-angle glaucoma is sometimes aggravated. Treatment is started with a small dose of one agent that is then increased depending on response and tolerance. If this drug is not helpful, another can be substituted. The anticholinergic drugs typically have little effect on bradykinesia, which is the most disabling feature of parkinsonism.

Amantadine (100 mg twice or three times daily) is sometimes helpful, but many patients derive only transient benefit. It potentiates the release of endogenous dopamine, but its precise mode of action is unclear. All the major clinical features of the disorder may be improved. Side effects include restlessness, confusion, skin rashes, edema, and disturbances of cardiac rhythm. There is anecdotal evidence that high doses of amantadine may relieve dyskinesias caused by levodopa.

Levodopa, the metabolic precursor of dopamine, provides symptomatic benefit in most patients and is particularly helpful in relieving bradykinesia. It is generally taken in combination with an extracerebral dopa-decarboxylase inhibitor (carbidopa or benserazide) to reduce the extracerebral metabolism of levodopa and the incidence of peripheral side effects. In the United States, the combination of carbidopa and levodopa (in 1:10 and 1:4 ratios) is available commercially as Sinemet. Standard formulations are Sinemet 25/100 mg, 10/100 mg, and 25/250 mg. A common starting dose is 25/100 mg three times daily. This dose is increased gradually depending on response and tolerance to 25/250 mg three or four times daily, and is taken 30 to 60 min before meals to maximize absorption and transport across the blood-brain barrier.

Levodopa can be introduced as soon as the patient's clinical state warrants, but initial treatment with a dopamine agonist may provide similar benefit to levodopa; in consequence, levodopa should be introduced later, so that development of certain side effects of levodopa is postponed. Common initial side effects of levodopa are nausea, postural hypotension, and, occasionally, cardiac arrhythmias. Dyskinesias, akathisia, and confusion are dose-related side effects that tend to occur somewhat later. They may be present throughout the day or only at certain times. When dyskinesias relate to specific submaximal blood levels of levodopa, dose adjustment to produce higher or lower blood levels may alleviate them; when associated with peak blood levels, dose reduction is required (Table 1).

Table 1. Management of advanced parkinson's disease

Problem	Management
Inadequate response to dopaminergic therapy	Add selegiline Add COMT inhibitor
Wearing-off response to levodopa	Increase levodopa dosing frequency Try controlled-release levodopa Restrict daily protein intake; take main protein meal at night Add or increase dosing of dopamine agonist Add selegiline Add COMT inhibitor Take liquid preparation of levodopa
On-off response to levodopa	Use measures indicated for wearing-off effect Apomorphine, if available Surgical treatment
Levodopa-induced dyskinesia Peak-dose	Reduce levodopa dose and give more frequently Add or increase dosing of dopamine agonist Add amantadine Surgical treatment
At beginning and end of dose	Adjust levodopa dose Add or increase dopamine agonist
Mental side-effects of treatment	Withdraw antiparkinsonian medication in sequence selegiline anticholinergics amantadine dopamine agonists Reduce dosing of levodopa Add clozapine, quetiapine, olanzapine, risperidone

Important late complications of levodopa therapy are response fluctuations such as wearing-off effect and the on-off phenomenon (see Table 1). The pathogenesis of these fluctuations in response is uncertain but may relate to levodopa pharmacokinetics, degeneration of presynaptic dopaminergic nerve terminals, altered sensitivity of dopamine receptors, and abnormalities of nondopaminergic neurotransmitter systems. Response fluctuations can be controlled in part by taking levodopa more frequently and taking it 1 h before meals, restricting dietary protein intake (to improve transport into the blood and from the blood into the brain by avoiding competition with certain amino acids for the same carrier system), treatment with dopamine agonists, and treatment with a monoamine oxidase B or cathechol-O-methyltransferase (COMT) inhibitor. Controlled-release formulations of Sinemet (Sinemet CR 25/100 mg or 50/200 mg) may allow reduction in dosing frequency and help to maintain steady blood levels of levodopa, but are of limited utility in reducing response fluctuations. Some physicians prefer the controlled-release formulation in the belief that it provides more continuous stimulation of dopamine receptors than the pulsatile stimulation of regular Senemet, and therefore use it as soon as levodopa therapy is introduced. Surgical treatment is also helpful for patients with marked fluctuations (see further on).

Dopamine agonist drugs ameliorate symptoms by direct stimulation of dopamine receptors. Unlike levodopa, they do not require enzymatic conversion to an active metabolite. They initially were used as an adjunct to Sinemet in patients with advanced disease, and especially to smooth response fluctuations. They may be used, however, either before Sinemet or in conjunction with low-dose Sinemet therapy (25/100 mg three times daily) because any benefit is comparable to that of high-dose Sinemet but late complications (such as response fluctuations and dyskinesias) are lower than with levodopa. Dopamine agonists also may have a neuroprotective effect, although this has not been demonstrated clinically.

The older agonists, bromocriptine and pergolide, are ergot derivatives. Bromocriptine, a D2 stimulator, is started at a dose of 1.25 mg/d for 1 week and 2.5 mg/d for the next week; the daily dose is then increased by 2.5 mg every 2 weeks, depending on response and tolerance. A daily intake of between 7.5 and 30 mg taken in divided doses is common when the drug is taken with Sinemet. Pergolide, which stimulates both D1 and D2 receptors, is given in a dose of 0.05 mg daily for 2 days; the dose is then increased by 0.1 to 0.15 mg/d every 3 days for 12 days and by 0.25 mg/d every 3 days thereafter. A common maintenance dose is 1 mg three times daily. Side effects of these agonists are similar to those with levodopa, but delusions or hallucinations occur more commonly and dyskinesias are less common. Other adverse effects include headache, nasal congestion, erythromelalgia, pleural and retroperitoneal fibrosis, pulmonary infiltrates, and vasospasm. The older dopamine agonists are best avoided in patients with psychotic disorders and in those with recent myocardial infarction, severe peripheral vascular disease, or active peptic ulceration. Annual chest radiographs have been recommended for those patients on high-dose therapy with bromocriptine or pergolide to detect pleuropulmonary changes.

Pramipexole and ropinirole are newer dopamine agonists that are not ergot derivatives, so adverse effects such as erythromelalgia, vasospasm, and pleural or retroperitoneal fibrosis are unlikely. As is true for the older agents, they are effective both in patients with mild disease and in those with severe dysfunction who require adjunctive. Various new dopamine agonists and routes of administration are being evaluated (e.g., administration by subcutaneous infusion pump, sublingually, or transdermally) and may lead to a more sustained response in the future. Apomorphine (which activates D1 and D2 receptors) may be administered intravenously, subcutaneously, sublingually, or intranasally, and may reduce response fluctuations in severely affected patients. It can be useful for treating patients in a perioperative context until oral medications can be resumed.^[16] Transdermal administration of certain new agonists is currently being explored.

Selective COMT inhibitors reduce the conversion of levodopa to 3-O-methyldopa (which competes with levodopa for an active carrier mechanism) and increase the cerebral availability of levodopa, thereby enhancing the benefits of levodopa therapy. They are helpful in patients with response fluctuations to Sinemet, especially the wearing-off effect, leading to greater on-time and reduction in daily levodopa requirement. Tolcapone was the first of these inhibitors to be introduced in the United States, but acute hepatic failure has occurred in rare patients receiving it, and a transient increase in liver enzymes is not uncommon. Regular monitoring of liver function is therefore necessary when tolcapone is used, as recommended by the manufacturer. Entacapone is generally preferred when a COMT inhibitor is required, because hepatotoxicity has not been associated with its use. It nevertheless seems prudent to undertake liver function studies before and 1 to 3 months after introducing entacapone. Entacapone (200 mg) is taken with each dose of Sinemet and may thus be taken 4 to 6 times daily. The daily dose of Sinemet may have to be reduced by 20% to 30% in the first 48 h after introduction of entacapone to prevent or minimize such complications as dyskinesias, nausea, and confusion. Other adverse effects include diarrhea, abdominal pain, postural hypotension, sleep disturbances, and discolored urine.^[6] It is unknown whether any benefit accrues from the early administration of entacapone in an attempt to limit the total daily dose of Sinemet, and such a course is not recommended at this

A typical antipsychotic drugs such as clozapine, quetiapine (Seroquel), olanzapine, or risperidone are sometimes required to control psychotic symptoms that may be induced by levodopa or dopamine agonists (see Table 1). Clozapine is perhaps the most effective of these agents and also may exert an antiparkinsonian or antidyskinetic effect, but it requires weekly white blood cell counts. Dyskinetic side effects of dopaminergic therapy can sometimes be ameliorated by high doses of amantadine, which has antiglutamatergic effects.^[18]

Neuroprotective Treatment

It has been suggested that selective inhibitors of monoamine oxidase B such as selegiline (Eldepryl) may slow disease progression. In a large multicenter study, treatment with selegiline delayed the need to introduce symptomatic therapy, suggesting that disease progression had been delayed; however, selegiline itself has a mild effect on symptoms, confounding the interpretation of this study. The use of selegiline for protective purposes is thus of uncertain value. Selegiline in a standard dose (5 mg with breakfast and 5 mg with lunch) does not have the hypertensive (cheese) effect of nonselective monoamine oxidase inhibitors, but acute toxic interactions may occur with meperidine, tryclic drugs, or serotonin reuptake inhibitors; it should not be prescribed to patients receiving these medications. Selegiline is metabolized to amphetamine and methamphetamine, leading to anxiety or insomnia in some instances. An increased mortality rate was found among patients receiving selegiline in one study but not in others. Patients taking selegiline for any supposed neuroprotective effect must understand that it is not intended to relieve symptoms and that any effect on disease progression in individual cases cannot be determined. Other inhibitors of monamine oxidase B, such as rasagiline mesylate, are currently being evaluated, but preliminary reports suggest that they do indeed delay the natural history of Parkinson's disease. Some investigators prefer to use inhibitors of both monoamine oxidase A and B,^[5] but this combination is of uncertain benefit and requires special dietary precautions to avoid the so-called cheese effect.

Tocopherol (vitamin E) is an important scavenger of free radicals, but in a large study it failed to provide any protective benefit in a dose of 2000 units daily. Whether administration of larger doses and administration of vitamin C supplements are beneficial is unknown.

Accumulating evidence suggests that the dopamine agonists have a neuroprotective effect. In particular, they may serve as scavengers of free radicals and induce up-regulation of various free radical scavenging proteins, and by stimulating dopamine autoreceptors, decrease dopamine turnover, thereby reducing oxidative stress.^[8] Certain agonists have been shown to enhance the survival of cultured dopaminergic neurons, and the use of agonists in clinical practice has a levodopa-sparing effect. Glutamate agonists, especially those active on N-methyl-d-aspartate receptors, are being evaluated for a possible neuroprotective effect.

Surgical Treatment

The surgical treatment of Parkinson's disease has recently been reviewed elsewhere.^{[9] [10]} It is clear that surgery has an increasing role in the management of patients with long-standing Parkinson's disease who have developed complications of pharmacologic therapy and whose disease is inadequately controlled by such treatment. In general, however, surgical treatment is avoided in patients with atypical parkinsonism, in those who have never shown a response to dopaminergic treatment, and in those with significant cognitive decline.

Surgery on the Thalamus

It has been known for many years that thalamotomy is helpful in relieving contralateral parkinsonian tremor. The value of the procedure was hard to gauge from early studies because the placement of lesions was often inaccurate. Recent studies indicate that placement of a lesion in the ventral intermediate nucleus of the thalamus provides a lasting beneficial effect, without influencing disease progression or responsiveness to levodopa therapy. It is indicated when tremor is disabling despite medical treatment and does not help the other features of parkinsonism. For this reason, it is rarely indicated in patients with Parkinson's disease; pallidotomy is more helpful when ablative surgery is required. The morbidity rate for unilateral procedures is low, but may include hemiparesis, limb ataxia, dysarthria, dysphasia, or confusion. Complications are more common after bilateral procedures, when more than 25% of patients may experience speech disturbances (hypophonia or dysarthria) or cognitive changes.

More recently, ablative procedures on the thalamus have been replaced by high-frequency thalamic stimulation using an implanted electrode and pulse generator. The pulse generator is placed subcutaneously in the infraclavicular region and is connected subcutaneously to the implanted electrode, which has four discrete contacts. Any one of these contacts can be used for monopolar stimulation, and any two can be used for bipolar stimulation. An external programming device is used to adjust the stimulus parameters for optimal response, and the patient can turn the stimulator on or off by use of a hand-held magnet. The ventral intermediate nucleus of the thalamus is the usual target. Tremor is improved in up to 90% of patients.

Morbidity and mortality of high-frequency thalamic stimulation are low, but complications may include paresthesias, limb dystonia or ataxia, intracerebral hemorrhage, seizures, and confusion. In addition, infection or malfunction of the implanted pulse generator may occur and the lead may migrate. Side effects from stimulation are usually mild and well tolerated, and include transient paresthesias (for several seconds). The mechanism of action of high-frequency stimulation is unknown. The technique leads essentially to functional but reversible thalamotomy, with fewer complications than is produced by ablative surgery. Bilateral implantation is possible with a low morbidity. A recent study suggests that thalamic stimulation and thalamotomy are equally effective in suppressing tremor, but that the stimulation technique has fewer side effects and leads to greater improvement in function.^[21]

Surgery on the Globus Pallidus and Subthalamic Nucleus

Thalamotomy or thalamic stimulation does not alleviate the bradykinesia of parkinsonism. By contrast, pallidotomy, with placement of a lesion in the posteroventral region of the globus pallidus internus, is helpful in relieving all features of parkinsonism including bradykinesia. In patients with advanced disease and response fluctuations, clinical status during the off-period is improved significantly.^[24] Improvement during the on-phase is less marked. Dopa-induced dyskinesias are ameliorated, but disturbances of speech or gait respond less consistently. Improvement is greater in patients younger than about 55 years, compared with older patients. Even elderly patients may respond well to the procedure. Complications include hemianopic visual field disturbances, disturbances of speech or swallowing, and limb weakness. Bilateral pallidotomy has a greater morbidity than unilateral procedures and may lead to cognitive disturbances, speech impairment, and dysphagia.

Target localization can be achieved anatomically by stereotaxic computed tomography or magnetic resonance imaging and by microstimulation techniques. In addition, however, microelectrode recording is used in some centers to improve the accuracy of lesion placement.^[22] This additional recording procedure lengthens the duration of the procedure and may increase the morbidity because of the multiple needle passes that sometimes have to be made through the brain.

More recently, the utility of high-frequency stimulation of the globus pallidus internus or the subthalamic nucleus has been studied.^{[2] [7] [11] [13] [14] [22] [23]} Preliminary results from several centers suggest that these procedures can provide worthwhile antiparkinsonian benefit with lower morbidity than ablative surgery. In addition, dopa dyskinesias are reduced as a direct effect of pallidal stimulation or as a consequence of a reduction in medication requirements after stimulation of the subthalamic nucleus. At the present time, however, stimulation at these sites is still regarded as investigational, and the relative advantages of stimulation at one site rather than the other are still being evaluated. Reported complications include hemorrhage, infections, chorea, other dyskinesias, and visual hallucinations. Contraindications to the procedure include cognitive decline, concurrent infections, coexisting medical diseases that increase morbidity, an inability to cooperate for the necessary follow-up (so that the stimulator can be optimally programmed), and end-stage disease.

Other Surgical Approaches

There has been much interest in experimental surgical techniques involving the grafting or implantation of dopaminergic neurons into the neostriatum.^{[3] [4] [15] [20]} Transplanted cells include autologous adrenal medullary tissue, fetal substantia nigra tissue, and genetically engineered cells. The utility of such an approach has not yet been firmly established, and enthusiasm for it appears to have waned. The response in humans treated by this means has been variable, perhaps because only a small proportion of the grafted neurons survive.

In addition to ethical concerns about the use of human fetal tissue for transplant purposes, there also are logistical problems in supplying such tissue. The demonstration that fetal pig neural cells survived transplantation into a patient with Parkinson's disease has raised the possibility of xenografts as an alternative to human cell transplants.^[3] The role of immunosuppression and the amount of tissue required for optimal clinical benefit are unclear.

Source: www.mdconsult.com