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Parkinson's Disease in Wikipedia

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This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Parkinson's disease". (Source - Retrieved 2006-09-07 14:16:13 from https://en.wikipedia.org/wiki/Parkinson%27s_disease)

Introduction

Parkinson's disease (also known as Parkinson disease or PD) is a degenerative disorder of the central nervous system that affects the control of muscles, and so may affect movement, speech and posture. Parkinson's disease belongs to a group of conditions called movement disorders. It is often characterized by muscle rigidity, tremor, a slowing of physical movement (bradykinesia), and in extreme cases, a loss of physical movement (akinesia). The primary symptoms are the results of excessive muscle contraction, normally caused by the insufficient formation and action of dopamine, which is produced in the dopaminergic neurons of the brain. PD is both chronic, meaning it persists over a long period of time, and progressive.

PD is the most common cause of parkinsonism, a group of similar symptoms. PD is also called "primary parkinsonism" or "idiopathic PD" ("idiopathic" meaning of no known cause). While most forms of parkinsonism are idiopathic, there are some cases where the symptoms may result from toxicity, drugs, genetic mutation, head trauma, or other medical disorders.

History

Symptoms of Parkinson's disease have been known and treated since ancient times. However, it was not formally recognised and its symptoms documented until 1817 in An Essay on the Shaking Palsy[1] by the British physician Dr. James Parkinson. Parkinson's disease was then known as paralysis agitans. The underlying biochemical changes in the brain were identified in the $1950s$, due largely to the work of Swedish scientist Arvid Carlsson who later went on to win a Nobel prize. L-dopa entered clinical practice in 1967[1], and the first study reporting improvements in patients with Parkinson's disease resulting from treatment with L-dopa was published in 1968.[2]

Symptoms

Parkinson disease affects movement (motor symptoms). Typical other symptoms include disorders of mood, behavior, thinking, and sensation (non-motor symptoms). Individual patients' symptoms may be quite dissimilar; progression is also distinctly individual.

Motor symptoms

The cardinal symptoms are:

  • tremor: normally 4-7Hz tremor, maximal when the limb is at rest, and decreased with voluntary movement. It is typically unilateral at onset. This is the most apparent and well-known symptom. However, an estimated 30% of patients have little perceptible tremor; these are classified as akinetic-rigid.
  • rigidity: stiffness; increased muscle tone. In combination with a resting tremor, this produces a ratchety, "cogwheel" rigidity when the limb is passively moved.
  • bradykinesia/akinesia: respectively, slowness or absence of movement. Rapid, repetitive movements produce a dysrhythmic and decremental loss of amplitude.
  • postural instability: failure of postural reflexes, which leads to impaired balance and falls.

Other motor symptoms include:

  • Gait and posture disturbances:
    • Shuffling: gait is characterized by short steps, with feet barely leaving the ground, producing an audible shuffling noise. Small obstacles tend to trip the patient
    • Decreased arm swing: a form of bradykinesia
    • Turning "en bloc": rather than the usual twisting of the neck and trunk and pivoting on the toes, PD patients keep their neck and trunk rigid, requiring multiple small steps to accomplish a turn.
    • Stooped, forward-flexed posture. In severe forms, the head and upper shoulders may be bent at a right angle relative to the trunk (camptocormia).
    • Festination: a combination of stooped posture, imbalance, and short steps. It leads to a gait that gets progressively faster and faster, often ending in a fall.
    • Gait freezing: "freezing" is another word for akinesia, the inability to move. Gait freezing is characterized by inability to move the feet, especially in tight, cluttered spaces or when initiating gait.
    • Dystonia (in about 20% of cases): abnormal, sustained, painful twisting muscle contractions, usually affecting the foot and ankle in PD patients. This causes toe flexion and foot inversion, interfering with gait.
  • Speech and swallowing disturbances
    • Hypophonia: soft speech. Speech quality tends to be soft, hoarse, and monotonous.
    • Festinating speech: excessively rapid, soft, poorly-intelligible speech.
    • Drooling: most likely caused by a weak, infrequent swallow and stooped posture.
    • Non-motor causes of speech/language disturbance in both expressive and receptive language: these include decreased verbal fluency and cognitive disturbance especially related to comprehension of emotional content of speech and of facial expression[3]
    • Dysphagia: impaired ability to swallow. Can lead to aspiration, pneumonia, and ultimately death.
  • Other motor symptoms:
    • fatigue (up to 50% of cases);
    • masked facies (a mask-like face also known as hypomimia), with infrequent blinking;[4]
    • difficulty rolling in bed or rising from a seated position;
    • micrographia (small, cramped handwriting);
    • impaired fine motor dexterity and coordination;
    • impaired gross motor coordination;
    • Poverty of movement: overall loss of accessory movements, such as decreased arm swing when walking, as well as spontaneous movement.

Non-motor symptoms

Mood disturbances

  • Estimated prevalence rates of depression vary widely according to the population sampled and methodology used. Reviews of depression estimate its occurrence in anywhere from 20-80% of cases.[5] Estimates from community samples tend to find lower rates than from specialist centres. Most studies use self-report questionnaires such as the Beck Depression Inventory which may overinflate scores due to physical symptoms. Studies using diagnostic interviews by trained psychiatrists also report lower rates of depression.
  • More generally, there is an increased risk for any individual with depression to go on to develop Parkinson's disease at a later date.[6]
  • Seventy percent of individuals with Parkinson's disease diagnosed with pre-existing depression go on to develop anxiety. Ninety percent of Parkinson's disease patients with pre-existing anxiety subsequently develop depression); apathy or abulia.

Cognitive disturbances

  • slowed reaction time; both voluntary and involuntary motor responses are significantly slowed.
  • executive dysfunction, characterized by difficulties in: differential allocation of attention, impulse control, set shifting, prioritizing, evaluating the salience of ambient data, interpreting social cues, and subjective time awareness. This complex is present to some degree in most Parkinson's patients; it may progress to:
  • dementia: a later development in approximately 20-40% of all patients, typically starting with slowing of thought and progressing to difficulties with abstract thought, memory, and behavioral regulation.
  • memory loss; procedural memory is more impaired than declarative memory. Prompting elicits improved recall.
  • medication effects: some of the above cognitive disturbances are improved by dopaminergic medications, while others are actually worsened [7]

Sleep disturbances

  • Excessive daytime somnolence;
  • Initial, intermediate, and terminal insomnia;
  • Disturbances in REM sleep: disturbingly vivid dreams, and REM Sleep Disorder, characterized by acting out of dream content;

Sensation disturbances

  • impaired visual contrast sensitivity, spatial reasoning, colour discrimination, convergence insufficiency (characterized by double vision) and oculomotor control
  • dizziness and fainting; usually attributable orthostatic hypotension, a failure of the autonomous nervous system to adjust blood pressure in response to changes in body position
  • impaired proprioception (the awareness of bodily position in three-dimensional space)
  • reduction or loss of sense of smell (microsmia or anosmia),
  • pain: neuropathic, muscle, joints, and tendons, attributable to tension, dystonia, rigidity, joint stiffness, and injuries associated with attempts at accommodation

Autonomic disturbances

  • oily skin and seborrheic dermatitis
  • urinary incontinence, typically in later disease progression
  • constipation and gastric dysmotility that is severe enough to endanger comfort and even health
  • altered sexual function: characterized by profound impairment of sexual arousal, behavior, orgasm, and drive is found in mid and late Parkinson disease. Current data addresses male sexual function almost exclusively
  • weight loss, which is significant over a period of ten years - 8% of body weight lost compared with 1% in a control group.

Diagnosis

18F PET scan shows decreased dopamine activity in the \$basal ganglia\$, a pattern which aids in diagnosing Parkinson's disease.

There are currently no blood or laboratory tests that have been proven to help in diagnosing sporadic PD. Therefore the diagnosis is based on medical history and a neurological examination. The disease can be difficult to diagnose accurately. Indeed, only 75% of clinical diagnoses of PD are confirmed at autopsy[8]. Early signs and symptoms of PD may sometimes be dismissed as the effects of normal aging. The physician may need to observe the person for some time until it is apparent that the symptoms are consistently present. Usually Doctors look for shuffling of feet and lack of swing in the arms. Doctors may sometimes request brain scans or laboratory tests in order to rule out other diseases. However, CT and MRI brain scans of people with PD usually appear normal.

Descriptive epidemiology

The worldwide prevalence of Parkinson's disease is estimated to be 4 to 6 million people. There are over 1.7 million in China alone. The disease usually has a long, subtle onset, so diagnosis occurs most often after many years of subclinical disease . Prevalence estimates range from a low of 7 per 100,000 in Ethiopia to a high of 329.3 per 100,000 in Nebraska, U.S.A. (although that figure was arrived at using capture-recapture estimates), and 328.3 cases per 100,000 in the Parsi community in Bombay, India. The greatest prevalence of any country is the U.S.A., with between 100 and 250 cases per 100,000.

In countries where Parkinson's Disease is common, the average age at which symptoms begin is 55-60. Symptoms can occur at any age. In 1875, Henri Huchard (1844-1911) described the first case of juvenile Parkinson's disease, who was a 3-year-old child who had all the clinical features of Parkinson's disease. However, it is highly unusual for people under 30 to develop Parkinson's Disease.

It occurs in all parts of the world, but appears to be more common in people of European ancestry than in those of African ancestry . Those of East Asian ancestry have an intermediate risk. It is more common in rural than urban areas in developed countries, but the converse is true in poorer countries, leading Tanner to speculate about environmental causes . Men are more commonly affected than women. However, in many countries, especially Japan, women are affected far more commonly than men. There is a suggestion of increased prevalence in the California Hispanic population.[9] About 2% of the population develops the disease some time during life .

Incidence has been estimated by several groups, starting with northern California.[9] They observed age and sex corrected incidence of 13.4 per 100,000/year. They note a rapid increase in incidence with age, male rates nearly double female rates, and an elevated rate amongst Hispanics. This study was followed by a group in Spain [10] who used the two-stage survey technique pioneered in the Copiah County study to survey a cohort age 65 to 85. Within that group, incidence adjusted for age and sex was 186.8/100,000 per year, with men's rates being 2.55 times that of women. For the same age group, Van den Eeden and colleagues observed an incidence of roughly 120/100,000/year. Soon thereafter the Rotterdam sudy was published [11] using techniques similar to the Spanish group and Copiah County. They note age-specific incidence rates from 0.3 per 1000 person-years in subjects aged 55 to 65 years, to 4.4 per 1000 person-years for those aged ≥85 year, and a sex ratio of 1.55 for male incidence.

Related diseases

There are other disorders that are called Parkinson-plus diseases. These include:

Some people include dementia with Lewy bodies (DLB) as one of the 'Parkinson-plus' syndromes. Although idiopathic Parkinson's disease patients also have Lewy bodies in their brain tissue, the distribution is denser and more widespread in DLB. Even so, the relationship between Parkinson disease, Parkinson disease with dementia (PDD) and dementia with Lewy bodies (DLB) might be most accurately conceptualized as a spectrum, with a discrete area of overlap between each of the three disorders. The natural history and role of Lewy bodies is very little understood.

Patients often begin with typical Parkinson's disease symptoms which persist for some years; these Parkinson-plus diseases can only be diagnosed when other symptoms become apparent with the passage of time. These Parkinson-plus diseases usually progress more quickly than typical ideopathic Parkinson disease. The usual anti-Parkinson's medications are typically either less effective or not effective at all in controlling symptoms; patients may be exquisitely sensitive to neuroleptic medications like haloperidol. Additionally, the cholinesterase inhibiting medications have shown preliminary efficacy in treating the cognitive, psychiatric, and behavioral aspects of the disease, so correct differential diagnosis is important.

Wilson's disease (hereditary copper accumulation) may present with parkinsonistic features; young patients presenting with parkinsonism may be screened for this (rare) condition. Essential tremor is often mistaken for Parkinson's disease but usually lacks all features besides tremor.

Pathology

Dopaminergic pathways of the human brain in normal condition (left) and Parkinson's disease (right). Red Arrows indicate suppression of the target, blue arrows indicate stimulation of target structure.

The symptoms of Parkinson's disease result from the loss of dopamine-secreting (dopaminergic) cells and subsequent loss of melanin, secreted by the same cells, in the pars compacta region of the substantia nigra (literally "black substance"). These neurons project to the striatum and their loss leads to alterations in the activity of the neural circuits within the basal ganglia that regulate movement, in essence an inhibition of the direct pathway and excitation of the indirect pathway.

The direct pathway facilitates movement and the indirect pathway inhibits movement, thus the loss of these cells leads to a hypokinetic movement disorder. The lack of dopamine results in increased inhibition of the ventral lateral nucleus of the thalamus, which sends excitatory projections to the motor cortex, thus leading to hypokinesia.

There are four major dopamine pathways in the brain; the nigrostriatal pathway, referred to above, mediates movement and is the most conspicuously affected in early Parkinson's disease. The other pathways are the mesocortical, the mesolimbic, and the tuberoinfundibular. These pathways are associated with, respectively: volition and emotional responsiveness; desire, initiative, and reward; and sensory processes and maternal behavior. Disruption of dopamine along the non-striatal pathways is the likely explantion for much of the neuropsychiatric pathology associated with Parkinson's disease.

The mechanism by which the brain cells in Parkinson's are lost appears to center on an abnormal accumulation of the protein alpha-synuclein bound to ubiquitin in the damaged cells.alpha-synuclein-ubiquitin complex cannot be directed to the proteosome. This protein accumulation forms proteinaceous cytoplasmic inclusions called Lewy bodies. Excessive accumulations of iron, which are toxic to nerve cells, are also typically observed in conjunction with the protein inclusions.

The precise mechanism whereby aggregates of alpha-synuclein damage the cells is not known. The aggregates may be merely a normal reaction by the cells as part of their effort to correct a different, as-yet unknown, insult. It does appear that alpha-synuclein aggregation is enhanced by the presence of dopamine and the byproducts of dopamine production. Based on this mechanistic hypothesis, a transgenic mouse model of Parkinson's has been generated by introduction of human wild-type α-synuclein into the mouse genome under control of the platelet-derived-growth factor-β promoter. [12]

Causes of Parkinson's disease

Most people with Parkinson's disease are described as having idiopathic Parkinson's disease (having no specific cause). There are far less common causes of Parkinson's disease including genetic, toxins, head trauma, and drug induced Parkinson's disease.

Genetic

In recent years, a number of specific genetic mutations causing Parkinson's disease have been discovered, including in certain populations (Contursi). These account for a small minority of cases of Parkinson's disease. Somebody who has Parkinson's disease is more likely to have relatives that also have Parkinson's disease. However, this does not mean that the disorder has been passed on genetically.

Genetic forms that have been identified include:

external links in this section are to OMIM
  • PARK1 (OMIM #168601), caused by mutations in the SNCA gene, which codes for the protein alpha-synuclein. PARK1 causes autosomal dominant Parkinson disease. So-called PARK4 is probably caused by triplication of SNCA.[13]
  • PARK2 (OMIM *602544), caused by mutations in protein parkin. Parkin mutations may be one of the most common known genetic causes of early-onset Parkinson disease. In one study, of patients with onset of Parkinson disease prior to age 40 (10% of all PD patients), 18% had parkin mutations, with 5% homozygous mutations.[14] Patients with an autosomal recessive family history of parkinsonism are much more likely to carry parkin mutations if age at onset is less than 20 (80% vs. 28% with onset over age 40).[15]Patients with parkin mutations (PARK2) do not have Lewy bodies. Such patients develop a syndrome that closely resembles the sporadic form of PD; however, they tend to develop symptoms at a much younger age.
  • PARK3 (OMIM %602404), mapped to 2p, autosomal dominant, only described in a few kindreds.
  • PARK5, caused by mutations in the UCHL1 gene (OMIM +191342) which codes for the protein ubiquitin carboxy-terminal hydrolase L1
  • PARK6 (OMIM #605909), caused by mutations in PINK1 (OMIM *608309) which codes for the protein PTEN-induced putative kinase 1.
  • PARK7 (OMIM #606324), caused by mutations in DJ-1 (OMIM 602533)
  • PARK8 (OMIM #607060), caused by mutations in LRRK2 which codes for the protein dardarin. In vitro, mutant LRRK2 causes protein aggregation and cell death, possibly through an interaction with parkin.[16] LRRK2 mutations, of which the most common is G2019S, cause autosomal dominant Parkinson disease, with a penetrance of nearly 100% by age 80.[17] G2019S is the most common known genetic cause of Parkinson disease, found in 1-6% of U.S. and European PD patients.[18] It is especially common in Ashkenazi Jewish patients, with a prevalence of 29.7% in familial cases and 13.3% in sporadic.[19]
  • PARK12 (OMIM %300557), maps to the X chromosome

Toxins

One theory holds that the disease may result in many or even most cases from the combination of a genetically determined vulnerability to environmental toxins along with exposure to those toxins.[20] This hypothesis is consistent with the fact that Parkinson's disease is not distributed homogenously throughout the population: rather, its incidence varies geographically. It would appear that incidence varies by time as well, for although the later stages of untreated PD are distinct and readily recognizable, the disease was not remarked upon until the beginnings of the Industrial Revolution, and not long thereafter become a common observation in clinical practice. The toxins most strongly suspected at present are certain pesticides and transition-series metals such as manganese or iron, especially those that generate reactive oxygen species [2],[3] and or bind to neuromelanin, as originally suggested by G.C. Cotzias [4] [5]. MPTP is used as a model for Parkinson's as it can rapidly induce parkinsonian symptoms in human beings and other animals, of any age. MPTP was notorious for a string of Parkinson's disease cases in California in 1982 when it contaminated the illicit production of the synthetic opiate MPPP. Its toxicity likely comes from generation of reactive oxygen species[6].

Other toxin-based models employ PCBs,[21] paraquat[22] (a herbicide) in combination with maneb, a fungicide[23] rotenone[24] (an insecticide), and specific organochlorine pesticides including dieldrin[25] and lindane.[26] Numerous studies have found an increase in Parkinson disease in persons who consume rural well water; researchers theorize that water consumption is a proxy measure of pesticide exposure. In agreement with this hypothesis are studies which have found a dose-dependent an increase in PD in persons exposed to agricultural chemicals.

Almost all of the PD-causing toxins act on the mitochondrial complex I of the electron transfer chain, and sporadic PD cases have been found to have a partial loss of activity of this enzyme complex. Studies in cybrids have found that mitochondrial DNA, rather than nuclear DNA, is responsible for the dysfunction. Most recently, microheteroplasmic mutations in one of the mitochondrial complex I genes, ND5, were found to be sufficient to diagnose sporadic PD correctly in 27 out of 28 cases. While additional studies are needed, mitochondrial microheteroplasmic mutations may be the cause of the majority of PD cases.

However, the ubiquity of agricultural chemical exposures makes it difficult to gauge the true extent of the problem. In the current state of knowledge about the origins of the disease, it appears that family history of the disease and (especially) multiple episodes of head-trauma-induced unconsciousness increase individual risk more than does pesticide exposure, but research is continuing.

Head trauma

Past episodes of head trauma are reported more frequently by sufferers than by others in the population.[27] [28] [29] A methodologically strong recent study[27] found that those who have experienced a head injury are four times more likely to develop Parkinson’s disease than those who have never suffered a head injury. The risk of developing Parkinson’s increases eightfold for patients who have had head trauma requiring hospitalization, and it increases 11-fold for patients who have experienced severe head injury. The authors comment that since head trauma is a rare event, the contribution to PD incidence is slight. They express further concern that their results may be biased by recall, i.e., the PD patients because they reflect upon the causes of their illness, may remember head trauma better than the non-ill control subjects.

Drug-induced

Antipsychotics, which are used to treat schizophrenia and psychosis, can induce the symptoms of Parkinson's disease (or parkinsonism) by lowering dopaminergic activity. Due to feedback inhibition, L-dopa can eventually cause the symptoms of Parkinson's disease that it initially relieves. Dopamine receptors can also eventually contribute to Parkinson's disease symptoms by increasing the sensitivity of dopamine receptors.

Treatment

Parkinson's disease is a chronic disorder that requires broad-based management including patient and family education, support group services, general wellness maintenance, exercise, and nutrition. At present, there is no cure for PD, but medications or surgery can provide relief from the symptoms.

Levodopa

Stalevo for treatment of Parkinson's disease

The most widely used form of treatment is L-dopa in various forms. L-dopa is transfomed into dopamine in the dopaminergic neurons by L-aromatic amino acid decarboxylase (often known by its former name dopa-decarboxylase). However, only 1-5% of L-DOPA enters the dopaminergic neurons. The remaining L-DOPA is often metabolised to dopamine elsewhere, causing a wide variety of side effects. Due to feedback inhibition, L-dopa results in a reduction in the endogenous formation of L-dopa, and so eventually becomes counterproductive.

Carbidopa and benserazide are dopa decarboxylase inhibitors. They help to prevent the metabolism of L-dopa before it reaches the dopaminergic neurons and are general given as combination preparations of carbidopa/levodopa (co-careldopa BAN) co-careldopa combined L-dopa and carbidopa in fixed ratios in such branded products of Sinemetand Parcopa and benserazide/levodopa (co-beneldopa BAN) as Madopar. There are also controlled release versions of Sinemet and Madopar that spread out the effect of the L-dopa. Duodopa is a combination of levodopa and carbidopa, dispersed as a viscous gel. Using a patient-operated portable pump, the drug is continuously delivered via a tube directly into the upper small intestine, where it is rapidly absorbed.

Talcopone inhibits the COMT enzyme, thereby prolonging the effects of L-dopa, and so has been used to complement L-dopa. However, due to its side effects, such as possible liver failure is limited in its availability. A similar drug, entacapone, has similar efficacy and has not been shown to cause significant alterations of liver function. Stalevo[30] contains Levodopa, Carbidopa and Entacopone.

Mucuna pruriens, is a natural source of therapeutic quantities of L-dopa.

Dopamine agonists

The dopamine-agonists bromocriptine (Parlodel), pergolide (Permax), pramipexole (Mirapex), ropinirole (Requip), cabergoline (Cabaser), apomorphine (Apokyn), and lisuride (Revanil), are moderately effective. These have their own side effects including those listed above in addition to somnolence, hallucinations and /or insomnia. Dopamine agonists initially act by stimulating some of the dopamine receptors. However, they cause the dopamine receptors to become progressively less sensitive, thereby eventually increasing the symptoms.

Dopamine agonists can be useful for patients experiencing on-off fluctuations and dyskinesias as a result of high doses of L-dopa. Apomorphine can be administered via subcutaneous injection using a small pump which is carried by the patient. A low dose is automatically administered throughout the day, reducing the fluctuations of motor symptoms by providing a steady dose of dopaminergic stimulation. After an initial "apomorphine challenge" in hospital to test its effectiveness and brief patient and caregiver, the primary caregiver (often a spouse or partner) takes over maintenance of the pump. The injection site must be changed daily and rotated around the body to avoid the formation of nodules. Apomorphine is also available in a more acute dose as an autoinjector pen for emergency doses such as after a fall or first thing in the morning.

MAO-B inhibitors

Selegiline (Eldepryl) and rasagiline (Azilect) reduce the symptoms by inhibiting monoamine oxidase-B (MAO-B), which inhibits the breakdown of dopamine secreted by the dopaminergic neurons. By-products of selegiline include amphetamine and methamphetamine, which can cause side effects such as insomnia. Use of L-dopa in conjunction with selegiline has increased mortality rates that have not been effectively explained. Another side effect of the combination can be stomatitis. One report raised concern about increased mortality when MAO-B inhibitors were combined with L-dopa [31]; however subsequent studies have not confirmed this finding[32]. Unlike other non selective monoamine oxidase inhibitors, tyramine-containing foods do not cause a hypertensive crisis.

Surgical interventions

Illustration showing an electrode placed deep seated in the brain

Treating PD with surgery was once a common practice. But after the discovery of levodopa, surgery was restricted to only a few cases. Studies in the past few decades have led to great improvements in surgical techniques, and surgery is again being used in people with advanced PD for whom drug therapy is no longer sufficient. Deep brain stimulation is presently the most used surgical means of treatment.

Currently under investigation is gene therapy. This involves using a harmless virus to shuttle a gene into a part of the brain called the subthalamic nucleus (STN). The gene used leads to the production of an enzyme called glutamic acid decarboxylase (GAD), which catalyses the production of a neurotransmitter called GABA. GABA acts as a direct inhibitor on the overactive cells in the STN.

GDNF infusion involves, by surgical means, the infusion of GDNF (glial-derived neurotrophic factor) into the basal ganglia using implanted catheters. Via a series of biochemical reactions, GDNF stimulates the formation of L-dopa. GDNF therapy is still in development.

In the future, implantation of cells genetically engineered to produce dopamine or stem cells that transform into dopamine-producing cells may become available. Even these, however, will not constitute cures because they do not address the considerable loss of activity of the dopaminergic neurons.

Nutrients

Nutrients have been used in clinical studies and are widely used by people with Parkinson's disease in order to partially treat Parkinson's disease or slow down its deterioration. The L-dopa precursor L-tyrosine was shown to relieve an average of 70% of symptoms.[33] Ferrous iron, the essential cofactor for L-dopa biosynthesis was shown to relieve between 10% and 60% of symptoms in 110 out of 110 patients.[34] [35] Another complementary approach is Dopavite, a nutritional supplement which contains both of these substances and all the other nutrients required for dopamine formation. However, the efficacy of this nutritional supplement has not been validated in clinical trials.

More limited efficacy has been obtained with the use of THFA, NADH, and pyridoxine—coenzymes and coenzyme precursors involved in dopamine biosynthesis. Vitamin C and vitamin E in large doses are commonly used by patients in order to theoretically lessen the cell damage that occurs in Parkinson's disease. This is because the enzymes superoxide dismutase and catalase require these vitamins in order to nullify the superoxide anion, a toxin commonly produced in damaged cells. However, in the randomized controlled trial, DATATOP of patients with early PD, no beneficial effect for vitamin E compared to placebo was seen[36]

Coenzyme Q10 has more recently been used for similar reasons. MitoQ is a newly developed synthetic substance that is similar in structure and function to coenzyme Q10. However, proof of benefit has not been demonstrated yet.

Speech therapies

The most widely practiced treatment for the speech disorders associated with Parkinson's disease is Lee Silverman Voice Treatment (LSVT). LSVT focuses on increasing vocal loudness.[37]

A study found that an electronic device providing frequency-shifted auditory feedback (FAF) improved the clarity of Parkinson's patients' speech.[38]

Physical exercise

Regular physical exercise and/or therapy, including in forms such as yoga, tai chi, and dance can be beneficial to the patient for maintaining and improving mobility, flexibility, balance and a range of motion.

Qigong

There is some evidence that patients who have undergone a regimen of Qigong exercises have improved, compared with a control group. The prevalence of several non-motor symptoms decreased. However the authors say there was a methodological weakness in their study and therefore the results should be treated with caution.

Prognosis

PD is not by itself a fatal disease, but it does get worse with time. The average life expectancy of a PD patient is generally the same as for people who do not have the disease. However, in the late stages of the disease, PD may cause complications such as choking, pneumonia, and falls that can lead to death.

The progression of symptoms in PD may take 20 years or more. In some people, however, the disease progresses more quickly. There is no way to predict what course the disease will take for an individual person. One commonly used system for describing how the symptoms of PD progress is called the Hoehn and Yahr scale.

Another commonly used scale is the Unified Parkinson's Disease Rating Scale (UPDRS). This much more complicated scale has multiple ratings that measure mental functioning, behavior, and mood; activities of daily living; and motor function. Both the Hoehn and Yahr scale and the UPDRS are used to measure how individuals are faring and how much treatments are helping them. It should be noted that neither scale is specific to Parkinson's Disease; that patients with other illnesses can score in the Parkinson's range.

With appropriate treatment, most people with PD can live productive lives for many years after diagnosis.

Notable Parkinson's sufferers

Further information: Parkinson's disease sufferers

One famous sufferer of young-onset Parkinson's is Michael J. Fox, who has written a book about his experience of the disease and established The Michael J. Fox Foundation for Parkinson's Research to develop a cure for Parkinson's disease within this decade.

The film Awakenings (starring Robin Williams and Robert De Niro and based on genuine cases reported by Oliver Sacks) deals sensitively and largely accurately with a similar disease, postencephalitic parkinsonism.

Other famous sufferers include Pope John Paul II, artist Salvador Dali, evangelist Billy Graham, former US Attorney General Janet Reno, boxer Muhammad Ali, dictators Adolf Hitler, Franco and Mao Zedong, and numerous actors such as Terry Thomas, Kenneth More, Vincent Price and Michael Redgrave.

References

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Some of this article contains text from the public domain document at https://www.ninds.nih.gov/disorders/parkinsons_disease/detail_parkinsons_disease.htm

 

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