Parkinson Disease in Young Adults



Stephen T Gancher, MD, Adjunct Associate Professor, Department of Neurology, Oregon Health Sciences University

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Specialty Editor(s)

Daniel H Jacobs, MD, Associate Professor of Neurology, University of Central Florida College of Medicine

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Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine

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Nestor Galvez-Jimenez, MD, MSc, MHA, Chairman, Department of Neurology, Program Director, Movement Disorders, Department of Neurology, Division of Medicine, Cleveland Clinic Florida

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Chief Editor

Selim R Benbadis, MD, Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, University of South Florida School of Medicine, Tampa General Hospital

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Parkinson disease is a slowly progressive, degenerative neurological illness which most commonly affects middle-aged and elderly individuals. Although easily recognizable when the disease is established, mild or incipient Parkinson disease may be difficult to recognize, particularly in young individuals, and may be overlooked for several months or years.

Young-adult Parkinson disease, which is defined as symptom onset before age 40 years is unusual and juvenile parkinsonism, with onset before age 21, is extremely rare.

In young patients, dopa responsive dystonia should be seriously considered as an alternative diagnosis. Dopa-responsive dystonia usually starts as a gait disorder resulting from lower extremity dystonia, but it can also be accompanied by bradykinesia. Symptoms may exhibit substantial diurnal variation and usually respond dramatically to low doses of levodopa, with a sustained benefit and without the emergence of dyskinesia. The clinical spectrum of dopa responsive dystonia is wide, though, and distinction between Parkinson's disease and dopa responsive dystonia on a clinical basis or by age of onset is not infallible.

Patients with young-onset Parkinson disease have symptoms that are similar to those of older patients but have a higher incidence of dystonia, particularly in the lower extremities. Because dystonia as an isolated symptom of other diseases is unusual, early Parkinson disease should be suspected in middle-aged individuals with an isolated dystonia in the lower extremity.

For more information, see Medscape's Parkinson's Disease Resource Center.


Pathologically, Parkinson disease is associated with loss of dopaminergic neurons in the substantia nigra and dopamine deficiency in the striatum. This results in abnormally increased activity of the subthalamic nucleus and internal segment of the globus pallidus, which cause the motor manifestations of the disease. In Parkinson disease, other nondopaminergic neurons also are affected, resulting in a milder deficiency of the other monoamine neurotransmitters, including serotonin and norepinephrine. In concert with dopamine deficiency, depletion of these other neurotransmitters results in psychological and behavioral symptoms, including depression, asthenia, memory and concentration difficulties, and sleep disturbances. Involvement of the intermediolateral cells in the thoracic spinal cord, autonomic ganglia, and autonomic neurons in the wall of the abdominal viscera also occurs in Parkinson disease and results in dysautonomia.

Juvenile and young-onset parkinsonism may include patients with several different pathologies and is clinically heterogeneous, both in symptoms and in response to levodopa. As discussed under Causes, juvenile parkinsonism is classically an autosomal recessive inherited condition and is associated in some families with a mutation in the gene coding for the protein parkin; other recessive gene mutations have been also discovered in families with young-onset parkinsonism.[1, 2] Heterozygous mutations in the parkin gene may increase susceptibility for early-onset disease as well.[3]

In contrast to Parkinson disease and juvenile parkinsonism, dopa-responsive dystonia is not a degenerative illness, nor is it associated with loss of dopaminergic neurons. It is most commonly due to mutations in GTP cyclohydrolase I, an enzyme involved in the activation of tyrosine hydroxylase, the rate-limiting enzyme involved in dopamine synthesis.[4] This condition is described in further detail in the eMedicine article Dopamine-Responsive Dystonia.



United States

The overall prevalence of Parkinson disease is estimated at 0.2% but rises with age, affecting as many as 0.5-2% of individuals older than 70 years. The prevalence has been estimated as 25-50 cases per 100,000 population in individuals younger than 50 years, affecting as many as 100,000 patients in the United States, and approximately 5 cases per 100,000 individuals younger than 40 years.


Parkinson disease is found worldwide but is generally more prevalent in Western countries than in Asia or Africa.[5, 6]



Parkinson disease affects all races.

Race and geographical factors are associated with differences in the incidence and prevalence of Parkinson disease. In a study of members of a health maintenance organization in California, the incidence of Parkinson disease was highest in Hispanics, followed by non-Hispanic whites, Asians, and blacks.[7] It has also been observed that the prevalence of Parkinson disease in blacks living in the United States is much higher than blacks living in Nigeria, and a similar difference has been reported comparing the prevalence of Parkinson disease in urban dwelling individuals in China compared to rural inhabitants.[5]

Juvenile parkinsonism due to the parkin mutation is described as accounting for more cases of juvenile parkinsonism in Japan than in other countries. However, more recent studies in other countries have also shown a large fraction of young adults (>40 y) as having the parkin mutation.


Parkinson's disease affects both sexes but is more prevalent in males, affecting approximately 1.5-2 times as many men than women.[7]

Although the disease is similar overall in both sexes, one study found that women more often presented with tremor (67%) than men (48%).[8]




The principal manifestations of Parkinson disease are tremor, rigidity, bradykinesia, and changes in gait and posture.


Laboratory Studies

Imaging Studies

Medical Care

Surgical Care

Surgical treatment is discussed in Surgical Treatment of Parkinson Disease.



Few dietary restrictions are needed in most patients with Parkinson disease who are not experiencing significant dysphagia.

Medication Summary

A number of different medications are used in the treatment of Parkinson disease. Drugs that improve motor symptoms include dopaminergic drugs—immediate and controlled-release levodopa; catechol-O -methyltransferase (COMT) inhibitors tolcapone and entacapone; and the dopamine agonists bromocriptine, ropinirole, and pramipexole. In addition, nondopaminergic drugs, including anticholinergics, selegiline, and amantadine can help motor symptoms as well.

Patients with Parkinson disease often benefit with treatment of psychological and behavioral symptoms. For depression, any of the standard antidepressants may be used. These include tricyclic antidepressants, such as amitriptyline, nortriptyline, and doxepin, as well as the selective serotonin reuptake inhibitors (SSRIs) paroxetine (Paxil), sertraline (Zoloft), fluoxetine (Prozac), and citalopram (Celexa). Newer antidepressants unrelated to SSRIs or tricyclic antidepressants include bupropion (Wellbutrin), venlafaxine (Effexor), nefazodone (Serzone), and mirtazapine (Remeron). Concern has been expressed about the risk of serotonin syndrome with the concomitant use of selegiline and the SSRIs; however, a survey of Parkinson disease specialists reported that these drugs often are combined with negligible evidence of toxicity.

Insomnia may be especially challenging to treat. Some patients having difficulty with sleep initiation may benefit from a benzodiazepine; however, because tachyphylaxis is very common with drugs in this class, a sedating antidepressant (eg, trazodone, amitriptyline) may be a better long-term choice. Other patients awaken with symptoms of Parkinson disease such as stiffness, dystonia, or tremor; in such patients, a nocturnal dose of levodopa or a dopamine agonist may be effective.

In addition to depression and insomnia, some patients experience psychiatric reactions with levodopa or dopamine agonists. These include visual hallucinations that can evolve into a delusional state in which auditory hallucinations, paranoia, psychosis, and violent behavior can occur. These problems are sometimes so severe that the use of a dopamine agonist is precluded; however, these reactions sometimes can be eliminated or treated effectively with an antipsychotic. Of the available antipsychotics, most agents worsen the symptoms of Parkinson disease and cannot be used; however, quetiapine and clozapine are well tolerated in most patients and may be very effective at low doses.

Class Summary

These agents are used for treatment of motor fluctuations in patients treated with levodopa for long periods. Tolcapone and entacapone are inhibitors of an enzyme, COMT, which converts levodopa into an inactive metabolite, 3-O -methyldopa. Coadministration delays clearance of levodopa from plasma and prolongs the action of individual doses of levodopa. Neither drug has any effect in Parkinson disease symptoms independent of levodopa.

Entacapone (Comtan)

Clinical Context:  Selective and reversible inhibitor of COMT, used in Parkinson disease as adjunct to levodopa/carbidopa therapy.

Tolcapone (Tasmar)

Clinical Context:  Mechanism of action unknown, but possibly related to ability to inhibit COMT and alter plasma pharmacokinetics of levodopa. When given in conjunction with levodopa and an aromatic amino acid decarboxylase inhibitor, such as carbidopa, plasma levels of levodopa are more sustained than after administration of levodopa and an aromatic amino acid decarboxylase inhibitor alone. Sustained plasma levels of levodopa may result in more constant dopaminergic stimulation in brain, which may lead to greater effects on signs and symptoms of Parkinson disease as well as increased levodopa adverse effects, sometimes requiring decrease in dose of levodopa. Tolcapone enters CNS to minimal extent but has been shown to inhibit central COMT activity in animals. Should always be used as adjunct to levodopa/carbidopa therapy.

Class Summary

These agents comprise the dopaminergic agents, which stimulate dopaminergic receptors in basal ganglia; the MAO-B oxidase inhibitors, which prevent inactivation of dopamine by MAO-B and possibly the conversion of compounds into neurotoxic types; and the dopamine agonists (see separate Drug Category below).

Levodopa, carbidopa, and entacapone (Stalevo)

Clinical Context:  Stalevo is a combination of levodopa, carbidopa, and entacapone. The medication is available in 6 strengths, containing 50, 75, 100, 125, 150, or 200 mg of levodopa. All sizes contain carbidopa at 25% of the milligram dose of levodopa and 200 mg of entacapone.

Levodopa and carbidopa (Sinemet)

Clinical Context:  Available in US in combination with carbidopa, an inhibitor of dopa decarboxylase in GI mucosa. In Europe, levodopa sold in combination with benzaseride, another dopa decarboxylase inhibitor.

Used in patients with established Parkinson disease; most effective in relieving bradykinesia and rigidity; it is less consistently effective in relieving tremor and usually ineffective in relieving postural flexion, severe imbalance, freezing gait, dysarthria, and dysphagia.

In elderly patients, lower doses of levodopa should be used to initiate treatment. In patients on long-term levodopa therapy, higher doses usually are administered

Although no absolute dose limit, for patients to require more than 1.5 g/d is very unusual.

Selegiline (Eldepryl)

Clinical Context:  MAO-B oxidase inhibitor, FDA approved as adjunct to levodopa/carbidopa in patients who exhibit deterioration in response to that therapy. For patients who experience motor fluctuations on levodopa/carbidopa, addition of selegiline reduces "off" time, improves motor function, and allows levodopa dose reductions. If patient experiences increase in troublesome dyskinesia, reduce levodopa dose.

Irreversible inhibitor of MAO, acts as "suicide" substrate for enzyme such that MAO converts it to an active moiety that combines irreversibly with active site or enzyme's essential FAD cofactor. Blocks breakdown of dopamine and extends duration of action of each dose of L-dopa. Often allows L-dopa dose reduction that is needed for optimal effect.

Has greater affinity for type B than for type A active sites, thus serves as selective inhibitor of MAO type B at recommended dose. However, doses higher than 10 mg/d may significantly inhibit MAO-A sites. May inhibit dopamine reuptake. Metabolites, amphetamine and methamphetamine, may inhibit dopamine reuptake and enhance dopamine release.

Rapidly absorbed and has 73% bioavailability. Metabolized in liver to N-desmethylselegiline, L-amphetamine, and L-methamphetamine

Half-life approximately 10 h; metabolites excreted in urine.

Inhibition of MAO-B irreversible, thus loss of new protein synthesis activity, if it occurs, may last for several months.

After 2-3 d of treatment, attempt to reduce dose of levodopa/carbidopa. A 10-30% reduction is typical. Further reductions of levodopa/carbidopa may be possible during continued selegiline therapy.

Amantadine (Symmetrel)

Clinical Context:  Inhibits N -methyl-D-aspartic acid (NMDA) receptor-mediated stimulation of acetylcholine release in rat striatum. May enhance dopamine release, inhibit dopamine reuptake, stimulate postsynaptic dopamine receptors, or enhance dopamine receptor sensitivity.

Has efficacy as monotherapy and as adjunct to levodopa/carbidopa (or levodopa/benserazide in Europe) in treating Parkinson disease. Provides some benefit in tremor, rigidity, and bradykinesia.

Half-life is approximately 9-37 h and prolonged in renal insufficiency; 90% is excreted unchanged in urine

Rasagiline (Azilect)

Clinical Context:  Irreversible MAO-B inhibitor that blocks dopamine degradation. Not metabolized to amphetamine derivatives. Main metabolite, aminoindan, has some activity and has been shown to improve motor and cognitive functions in experimental models. Indicated for Parkinson disease as initial monotherapy or as adjunctive therapy with levodopa.

Class Summary

These agents may be used either as monotherapy in patients not yet taking levodopa or as adjunctive therapy in patients taking levodopa who are experiencing motor fluctuations or dyskinesias.

In patients not yet taking levodopa, dopamine agonists may relieve signs and symptoms of Parkinson disease but are somewhat less effective than levodopa; use of this class of medications is most appropriate in patients with mild disease not affecting gait or balance.

This class of medications may allow introduction of levodopa to be delayed, thus reducing the risk of developing troublesome fluctuations and dyskinesias.

In patients already taking levodopa, dopamine agonists are useful as adjunctive therapy; these medications may prolong the duration of action of individual doses of levodopa, reduce the severity of motor fluctuations such as "off" bradykinesia and dystonia, allow the doses of levodopa to be lowered, and improve dyskinesias.

All drugs in this class should be initiated at low doses and the doses increased very slowly. The first few days are usually the most troublesome, but tolerance develops rapidly to many of the peripheral adverse effects such as nausea. Because of this, all of these drugs, except bromocriptine, are available at very small initial doses.

Pergolide (Permax)

Clinical Context:  Pergolide was withdrawn from the US market March 29, 2007, because of heart valve damage resulting in cardiac valve regurgitation. It is important not to abruptly stop pergolide. Health care professionals should assess patients' need for dopamine agonist (DA) therapy and consider alternative treatment. If continued treatment with a DA is needed, another DA should be substituted for pergolide. For more information, see FDA MedWatch Product Safety Alert and Medscape Alerts: Pergolide Withdrawn From US Market.

Dopamine agonist believed to exert therapeutic effect by directly stimulating postsynaptic dopamine receptors in nigrostriatal system. Usually administered in divided doses tid. During dosage titration, dosage of concurrent levodopa/carbidopa may be decreased cautiously.

Ropinirole (Requip)

Clinical Context:  Non-ergot dopamine agonist that has high relative in vitro specificity and full intrinsic activity at D2 subfamily of dopamine receptors, binding with higher affinity to D3- than to D2- or D4-receptor subtypes.

Has moderate affinity for opioid receptors. Metabolites have negligible affinity for dopamine D1, 5-HT1, 5-HT2, benzodiazepine, GABA, and muscarinic receptors and alpha1-, alpha2-, and beta-adrenoreceptors.

Precise mechanism of action in Parkinson disease unknown. However, possibly related to stimulation of dopamine receptors in striatum.

Discontinue gradually over 7-d period. Decrease frequency of administration from tid to bid for 4 d. For remaining 3 d, decrease frequency to once daily prior to complete withdrawal.

When administered as adjunct therapy to levodopa, concurrent dose of levodopa may be decreased gradually as tolerated.

Pramipexole (Mirapex)

Clinical Context:  Nonergot dopamine agonist with specificity of D2 dopamine receptor, but also has been shown to bind to D3 and D4 receptors and may stimulate dopamine activity on nerves of striatum and substantia nigra.

Apomorphine (Apokyn)

Clinical Context:  Elicits dopamine agonist effect. Indicated to treat acute immobility episodes (hypomobility or "off-periods") in Parkinson Disease. These episodes consist of inability to rise from a chair, speak, or walk and may occur toward the end of the dose interval or may be spontaneous and unpredictable in onset. Approximately 10 percent of individuals with stage IV Parkinson Disease who do not respond to standard medications for acute immobility may respond to apomorphine.

Bromocriptine (Parlodel)

Clinical Context:  Semisynthetic, ergot alkaloid derivative; strong dopamine D2-receptor agonist; partial dopamine D1-receptor agonist; FDA approved as adjunct to levodopa/carbidopa, but less effective than other dopamine agonists.

Rarely used currently because of a concern of restrictive valvular heart disease, pleural, and retroperitoneal fibrosis common to all ergot derived drugs.

May relieve akinesia, rigidity, and tremor associated with Parkinson disease. Stimulates dopamine receptors in corpus striatum.

Approximately 28% absorbed from GI tract and metabolized in liver. Approximate elimination half-life is 50 h with 85% excreted in feces and 3-6% eliminated in urine. Initiate at low dosage; slowly increase dosage to individualize therapy. Maintain dosage during introductory period. Assess dosage titration every 2 wk. Gradually reduce dose in 2.5-mg decrements if severe adverse reactions occur.

Rotigotine (Neupro)

Clinical Context:  April 2008: A recall was issued for Neupro patch in the United States because of crystal formation in the patch resulting in decreased dopamine absorption transdermally. As of August 1, 2008, the patch is still unavailable, although the manufacturer is working to correct the defect and hopefully return it to the market. For more information see Medscape News.

Dopamine agonist stimulating D3, D2, and D1 receptors. Improvement in Parkinson-related symptoms thought to be its ability to stimulate D2 receptors within the caudate putamen in the brain. Available as transdermal patch that provides continuous delivery for 24 h (2 mg/24 h [10 cm2], 4 mg/24 h [20 cm2], or 6 mg/24 h [30 cm2]). Indicated for symptoms of early Parkinson disease.

Class Summary

These agents are used in the treatment of tremor and dystonia (painful or painless involuntary muscular contractions); they are most useful in patients with tremor. They can be administered as monotherapy or in combination with other drugs and usually are administered tid/qid; they may be effective in relieving dystonia in patients with motor fluctuations. Parenteral benztropine and diphenhydramine produce sedation, therefore, patients should not drive after receiving these medications.

Benztropine (Cogentin)

Clinical Context:  By blocking striatal cholinergic receptors, may help in balancing cholinergic and dopaminergic activity in striatum.

Available in tablets and parenteral formulation, 1 mg/mL.

Diphenhydramine (Benadryl, Benylin)

Clinical Context:  Has strong anticholinergic and sedative properties. In patient with severe tremor, IV diphenhydramine can be used as adjunct for minor surgery or to facilitate detailed examination.

Trihexyphenidyl (Artane)

Clinical Context:  Centrally acting anticholinergic that tends to diminish muscle spasms.

Procyclidine (Kemadrin)

Clinical Context:  May block excess acetylcholine at cerebral synapses.


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