hi,
this the first comment from me as iam new member
i picked up all the information about parkinson dissease from(current medical diagnosis and treatment) to make the benefit for all pple who share in this group and found its better to pick it from the book rather than talking myself about this dissease as it will be more ordered in the book than me:
Essentials of Diagnosis

Any combination of tremor, rigidity, bradykinesia, progressive postural instability.
Seborrhea of skin quite common.
Mild intellectual deterioration may occur.
General Considerations

Parkinsonism is a relatively common disorder that occurs in all ethnic groups, with an approximately equal sex distribution. The most common variety, idiopathic Parkinson's disease (paralysis agitans), begins most often between 45 and 65 years of age.

Etiology

Parkinsonism may rarely occur on a familial basis, and the parkinsonian phenotype may result from mutations of several different genes. Postencephalitic parkinsonism is becoming increasingly rare. Exposure to certain toxins (eg, manganese dust, carbon disulfide) and severe carbon monoxide poisoning may lead to parkinsonism. Typical parkinsonism has occurred in individuals who have taken 1-methyl-4-phenyl-1,2,5,6-tetrahydr opyridine (MPTP) for recreational purposes. This compound is converted in the body to a neurotoxin that selectively destroys dopaminergic neurons in the substantia nigra. Reversible parkinsonism may develop in patients receiving neuroleptic drugs (see Psychiatry), reserpine, or metoclopramide. Only rarely is hemiparkinsonism the presenting feature of a progressive space-occupying lesion.

In idiopathic parkinsonism, dopamine depletion due to degeneration of the dopaminergic nigrostriatal system leads to an imbalance of dopamine and acetylcholine, which are neurotransmitters normally present in the corpus striatum. Treatment is directed at redressing this imbalance by blocking the effect of acetylcholine with anticholinergic drugs or by the administration of levodopa, the precursor of dopamine.

Clinical Findings

Tremor, rigidity, bradykinesia, and postural instability are the cardinal features of parkinsonism and may be present in any combination. There may also be a mild decline in intellectual function. The tremor of about four to six cycles per second is most conspicuous at rest, is enhanced by emotional stress, and is often less severe during voluntary activity. Although it may ultimately be present in all limbs, the tremor is commonly confined to one limb or to the limbs on one side for months or years before it becomes more generalized. In some patients, tremor is absent.

Rigidity (an increase in resistance to passive movement) is responsible for the characteristically flexed posture seen in many patients, but the most disabling symptoms of parkinsonism are due to bradykinesia, manifested as a slowness of voluntary movement and a reduction in automatic movements such as swinging of the arms while walking. Curiously, however, effective voluntary activity may briefly be regained during an emergency (eg, the patient is able to leap aside to avoid an oncoming motor vehicle).

Clinical diagnosis of the well-developed syndrome is usually simple. The patient has a relatively immobile face with widened palpebral fissures, infrequent blinking, and a certain fixity of facial expression. Seborrhea of the scalp and face is common. There is often mild blepharoclonus, and a tremor may be present about the mouth and lips. Repetitive tapping (about twice per second) over the bridge of the nose produces a sustained blink response (Myerson's sign). Other findings may include saliva drooling from the mouth, perhaps due to impairment of swallowing; soft and poorly modulated voice; a variable rest tremor and rigidity in some or all of the limbs; slowness of voluntary movements; impairment of fine or rapidly alternating movements; and micrographia. There is typically no muscle weakness (provided that sufficient time is allowed for power to be developed) and no alteration in the tendon reflexes or plantar responses. It is difficult for the patient to arise from a sitting position and begin walking. The gait itself is characterized by small shuffling steps and a loss of the normal automatic arm swing; there may be unsteadiness on turning, difficulty in stopping, and a tendency to fall.

Differential Diagnosis

Diagnostic problems may occur in mild cases, especially if tremor is minimal or absent. For example, mild hypokinesia or slight tremor is commonly attributed to old age. Depression, with its associated expressionless face, poorly modulated voice, and reduction in voluntary activity, can be difficult to distinguish from mild parkinsonism, especially since the two disorders may coexist; in some cases, a trial of antidepressant drug therapy is necessary. The family history, the character of the tremor, and lack of other neurologic signs should distinguish essential tremor from parkinsonism. Wilson's disease can be distinguished by its early age at onset, the presence of other abnormal movements, Kayser-Fleischer rings, and chronic hepatitis, and by increased concentrations of copper in the tissues. Huntington's disease presenting with rigidity and bradykinesia may be mistaken for parkinsonism unless the family history and accompanying dementia are recognized. In Shy-Drager syndrome, the clinical features of parkinsonism are accompanied by autonomic insufficiency (leading to postural hypotension, anhidrosis, disturbances of sphincter control, impotence, etc) and more widespread neurologic deficits (pyramidal, lower motor neuron, or cerebellar signs). In progressive supranuclear palsy, bradykinesia and rigidity are accompanied by a supranuclear disorder of eye movements, pseudobulbar palsy, and axial dystonia. Creutzfeldt-Jakob disease may be accompanied by features of parkinsonism, but dementia is usual, myoclonic jerking is common, ataxia and pyramidal signs may be conspicuous, and the electroencephalographic findings are usually characteristic. In cortical-basal ganglionic degeneration, parkinsonism is accompanied by conspicuous signs of cortical dysfunction (eg, apraxia, sensory inattention, dementia, aphasia).

Treatment

Medical Measures

Drug treatment is not required early in the course of parkinsonism, but the nature of the disorder and the availability of medical treatment for use when necessary should be discussed with the patient.

Amantadine

Patients with mild symptoms but no disability may be helped by amantadine. This drug improves all of the clinical features of parkinsonism, but its mode of action is unclear. Side effects include restlessness, confusion, depression, skin rashes, edema, nausea, constipation, anorexia, postural hypotension, and disturbances of cardiac rhythm. However, these are relatively uncommon with the usual dose (100 mg twice daily).

Anticholinergic drugs

Anticholinergics are more helpful in alleviating tremor and rigidity than bradykinesia. Treatment is started with a small dose (Table 24?6) and gradually increased until benefit occurs or side effects limit further increments. If treatment is ineffective, the drug is gradually withdrawn and another preparation then tried.

Common side effects include dryness of the mouth, nausea, constipation, palpitations, cardiac arrhythmias, urinary retention, confusion, agitation, restlessness, drowsiness, mydriasis, increased intraocular pressure, and defective accommodation.

Anticholinergic drugs are contraindicated in patients with prostatic hyperplasia, narrow-angle glaucoma, or obstructive gastrointestinal disease and are often tolerated poorly by the elderly.

Levodopa

Levodopa, which is converted in the body to dopamine, improves all of the major features of parkinsonism, including bradykinesia, but does not stop progression of the disorder. The most common early side effects of levodopa are nausea, vomiting, and hypotension, but cardiac arrhythmias may also occur. Dyskinesias, restlessness, confusion, and other behavioral changes tend to occur somewhat later and become more common with time. Levodopa-induced dyskinesias may take any conceivable form, including chorea, athetosis, dystonia, tremor, tics, and myoclonus. An even later complication is the "on-off phenomenon," in which abrupt but transient fluctuations in the severity of parkinsonism occur unpredictably but frequently during the day. The "off" period of marked bradykinesia has been shown to relate in some instances to falling plasma levels of levodopa. During the "on" phase, dyskinesias are often conspicuous but mobility is increased.

Carbidopa, which inhibits the enzyme responsible for the breakdown of levodopa to dopamine, does not cross the blood-brain barrier. When levodopa is given in combination with carbidopa, the extracerebral breakdown of levodopa is diminished. This reduces the amount of levodopa required daily for beneficial effects, and it lowers the incidence of nausea, vomiting, hypotension, and cardiac irregularities. Such a combination does not prevent the development of the "on-off phenomenon," and the incidence of other side effects (dyskinesias or psychiatric complications) may actually be increased.

Sinemet, a commercially available preparation that contains carbidopa and levodopa in a fixed ratio (1:10 or 1:4), is generally used. Treatment is started with a small dose?eg, one tablet of Sinemet 25/100 (containing 25 mg of carbidopa and 100 mg of levodopa) three times daily?and gradually increased depending on the response. Sinemet CR is a controlled-release formulation (containing 25 or 50 mg of carbidopa and 100 or 200 mg of levodopa). It is sometimes helpful in reducing fluctuations in clinical response to treatment and in reducing the frequency with which medication must be taken. The commercially available combination of levodopa with both carbidopa and entacapone (Stalevo) may also be helpful in this context and is discussed in the following section on COMT inhibitors. Response fluctuations are also reduced by keeping the daily intake of protein at the recommended minimum and taking the main protein meal as the last meal of the day.

The dyskinesias and behavioral side effects of levodopa are dose-related, but reduction in dose may eliminate any therapeutic benefit.

Levodopa therapy is contraindicated in patients with psychotic illness or narrow-angle glaucoma. It should not be given to patients taking monoamine oxidase A inhibitors or within 2 weeks of their withdrawal, because hypertensive crises may result. Levodopa should be used with care in patients with suspected malignant melanomas or with active peptic ulcers because of concerns that it may exacerbate these disorders.

Dopamine agonists

Dopamine agonists act directly on dopamine receptors, and their use in parkinsonism is associated with a lower incidence of the response fluctuations and dyskinesias that occur with long-term levodopa therapy. They were previously reserved for patients who had either become refractory to levodopa or developed the "on-off phenomenon." However, they are now best given either before the introduction of levodopa or with a low dose of Sinemet 25/100 (carbidopa 25 mg and levodopa 100 mg), one tablet three times daily when dopaminergic therapy is first introduced; the dose of Sinemet is kept constant, while the dose of the agonist is gradually increased. Two agonists, are bromocriptine and pergolide, are ergot derivatives. The initial dosage of bromocriptine is 1.25 mg twice daily; this is increased by 2.5 mg at 2-week intervals until benefit occurs or side effects limit further increments. The usual daily maintenance dose in patients with parkinsonism is between 10 and 30 mg. Pergolide is similarly started in a low dose (eg, 0.05 mg daily) and built up gradually depending on the response and tolerance.

Side effects include anorexia, nausea, vomiting, constipation, postural hypotension, digital vasospasm, cardiac arrhythmias, various dyskinesias and mental disturbances, headache, nasal congestion, erythromelalgia, and pulmonary infiltrates. There are rare reports of pericardial, pleural, or pulmonary fibrosis; pergolide has also been associated with cardiac valvopathy. Bromocriptine and pergolide have largely been replaced with other agents because of these side effects.

Pramipexole and ropinirole are two newer dopamine agonists that are not ergot derivatives. They are effective in early Parkinson's disease as well as in advanced stages of the disease. In each case, the daily dose is built up gradually. Pramipexole is started at a dosage of 0.125 mg three times daily, and the dose is doubled after 1 week and again after another week; the daily dose is then increased by 0.75 mg at weekly intervals depending on response and tolerance. Most patients require between 0.5 and 1.5 mg three times daily. Ropinirole is begun in a dosage of 0.25 mg three times daily, and the total daily dose is increased at weekly intervals by 0.75 mg until the fourth week and by 1.5 mg thereafter. Most patients require between 2 and 8 mg three times daily for benefit. Adverse effects include fatigue, somnolence, nausea, peripheral edema, dyskinesias, confusion, and postural hypotension. Less commonly, an irresistible urge to sleep may occur, sometimes in inappropriate and hazardous circumstances.

Selegiline

Selegiline is a monoamine oxidase B inhibitor that is sometimes used as adjunctive treatment for parkinsonism in patients receiving levodopa. By inhibiting the metabolic breakdown of dopamine, selegiline has been used to improve fluctuations or declining response to levodopa. In general, however, the response to treatment with it has been disappointing. The drug is taken in a standard dose of 5 mg with breakfast and 5 mg with lunch. It may increase any adverse effects of levodopa.

There are reasons to believe that selegiline may arrest the progression of Parkinson's disease. Studies have failed to establish this conclusively, but this remains an important consideration for patients who are young or have mild disease.

COMT inhibitors

Catecholamine-O-methyltransferase inhibitors reduce the metabolism of levodopa to 3-O-methyldopa and thereby alter the plasma pharmacokinetics of levodopa, leading to more sustained plasma levels and more constant dopaminergic stimulation of the brain. Two such agents, tolcapone and entacapone, are currently available and may be used as an adjunct to levodopa-carbidopa in patients with response fluctuations or an otherwise inadequate response and who either have failed with other adjunctive therapies or are not candidates for such therapies. Treatment results in reduced response fluctuations, with a greater period of responsiveness to administered levodopa. Tolcapone is given in a dosage of 100 mg or 200 mg three times daily, and entacapone is given as 200 mg with each dose of Sinemet (levodopa-carbidopa). With either preparation, the dose of Sinemet taken concurrently may have to be reduced by up to one-third to avoid side effects such as dyskinesias, confusion, hypotension, and syncope. Diarrhea is sometimes troublesome. Because rare cases of fulminant hepatic failure have followed its use, tolcapone should be avoided in patients with preexisting liver disease. Serial liver function tests should be performed at 2-week intervals for the first year and at longer intervals thereafter in patients receiving the drug?as recommended by the manufacturer. Hepatotoxicity has not been reported with entacapone, which is therefore the preferred agent, and serial liver function tests are not required.

Stalevo is the commercial preparation of levodopa combined with both carbidopa and entacapone. It is best used in patients already stabilized on equivalent doses of carbidopa/levodopa and entacapone. It is priced at or below the price of the individual ingredients (ie, carbidopa/levodopa and entacapone) and has the added convenience of requiring fewer tablets to be taken daily. It is available in three strengths: Stalevo 50 (12.5 mg of carbidopa, 50 mg of levodopa, and 200 mg of entacapone), Stalevo 100 (25 mg of carbidopa, 100 mg of levodopa, and 200 mg of entacapone), and Stalevo 150 (37.5 mg of carbidopa, 150 mg of levodopa, and 200 mg of entacapone).

Atypical antipsychotics

Confusion and psychotic symptoms, which may be iatrogenic, often respond to atypical antipsychotic agents, which have few extrapyramidal side effects and do not block the effects of dopaminergic medication. Olanzapine, quetiapine, and risperidone may be tried, but the most effective of these agents is clozapine, a dibenzodiazepine derivative. Clozapine may rarely cause marrow suppression, and weekly blood counts are therefore necessary for patients taking it. The patient is started on 6.25 mg at bedtime and the dosage increased to 25?100 mg/d as needed. In low doses, it may also improve iatrogenic dyskinesias.

General Measures

Physical therapy or speech therapy helps many patients. The quality of life can often be improved by the provision of simple aids to daily living, eg, rails or banisters placed strategically about the home, special table cutlery with large handles, nonslip rubber table mats, and devices to amplify the voice.

Surgical Measures

Thalamotomy or pallidotomy may be helpful for patients who become unresponsive to medical treatment or have intolerable side effects from antiparkinsonian agents, especially if they have no evidence of diffuse vascular disease or significant cognitive decline. Surgery should generally be confined to one side because the morbidity is considerably greater after bilateral procedures. Because of their morbidity, ablative procedures have generally been supplanted by deep brain stimulation, discussed in the following section. Surgical implantation of adrenal medullary or fetal substantia nigra tissue into the caudate nucleus has been reported to benefit some patients, but other investigators have failed to substantiate such claims or have found only modest benefits or major adverse effects. Such procedures are therefore best regarded as experimental, and further studies are required to define the role of cellular therapies.

Brain Stimulation

High-frequency thalamic stimulation is effective in suppressing the rest tremor of Parkinson's disease, and chronic bilateral stimulation of the subthalamic nuclei or globus pallidus internus may benefit all the major features of the disease. Electrical stimulation of the brain over ablative procedures has the advantage of being reversible and of causing minimal or no damage to the brain, and is therefore the preferred surgical approach to treatment. There is no evidence that the natural history of Parkinson's disease is affected.

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