Parkinson's disease ( PD ) is a long-term degenerative disorder of the central nervous system that primarily affects the motor system. The symptoms generally come slowly from time to time. At the beginning of the disease, the most obvious is shaking, stiffness, delayed movement, and difficulty walking. Problems of thinking and behavior can also occur. Dementia becomes common in advanced stages of disease. Depression and anxiety are also common, occurring in more than a third of people with PD. Other symptoms include sensory, sleep, and emotional problems. The main motor symptoms are collectively called "Parkinsonism", or "Parkinsonian Syndrome".
The cause of Parkinson's disease is generally unknown, but it is believed to involve genetic and environmental factors. Those with affected family members are more likely to develop the disease itself. There is also an increased risk in people exposed to certain pesticides and among those who have had head injuries, while there is a reduced risk of tobacco smokers and those who drink coffee or tea. Motor symptoms of this disease is caused by the death of cells in substantia nigra, a region of the midbrain. This results in not enough dopamine in this area. The reason for this cell death is poorly understood, but it involves the buildup of proteins into Lewy's body in neurons. The diagnosis of typical cases is primarily based on symptoms, with tests such as neuroimaging being used to rule out other diseases.
There is no cure for Parkinson's disease, with medications aimed at improving symptoms. Initial treatment is usually with levodopa antiparkinson drug (L-DOPA), with dopamine agonists used once levodopa to be less effective. As the disease progresses and the neurons continue to disappear, these drugs become less effective while at the same time they produce complications characterized by accidental stretching movements. Diet and some forms of rehabilitation have shown some effectiveness in improving symptoms. Surgery to place the microelectrode for deep brain stimulation has been used to reduce motor symptoms in severe cases where the drug is ineffective. The evidence for treatment for non-movement-related PD symptoms, such as sleep disturbances and emotional problems, is less powerful.
By 2015, PD affects 6.2 million people and resulted in about 117,400 deaths globally. Parkinson's disease usually occurs in people over the age of 60, of which about one percent is affected. Men are more often exposed than women with a ratio of about 3: 2. When seen in people before the age of 50 years, it is called the young PD. The average life expectancy after diagnosis is between 7 and 14 years. The disease is named after British physician James Parkinson, who published the first detailed description in the Essay on Shaking Palsy in 1817. Public awareness campaigns include World Parkinson's Day (on James Parkinson's birthday, April 11) and use red tulips as a disease symbol. People with Parkinson's who have raised public awareness about the condition include actor Michael J. Fox, Olympic cyclists Davis Phinney, and professional final boxer Muhammad Ali.
Video Parkinson's disease
Classification
The movement difficulties found in PD are called parkinsonism and a number of different disorders feature parkinsonism. "Parkinsonism" is defined as bradykinesia (slowness in initiating voluntary movements, with progressive decreases in speed and repeated actions such as voluntary finger tapping) in combination with one of three other physical signs: muscle stiffness (tin-pipe or cogwheel), current tremors rest, and postural instability.
Parkinson's disease is the most common form of parkinsonism and is sometimes called "idiopathic parkinson", which means unidentified parkinsonism that can be identified. Causes of Parkinson's identified include toxins, infections, drug side effects, metabolic disorders, and brain lesions such as stroke. Some neurodegenerative disorders may also present with parkinsonism and are sometimes referred to as "atypical Parkinsonism" or "Parkinson plus" syndromes (a disease with parkinsonism plus some other features that differentiate them from PD). They include several atrophy, progressive supranuclear palsy systems, corticobasal degeneration, and dementia with Lewy bodies (DLB).
Scientists sometimes refer to Parkinson's disease as synucleinopathy (due to the abnormal accumulation of alpha-synuclein proteins in the brain) to differentiate it from other neurodegenerative diseases, such as Alzheimer's disease in which the brain accumulates tau proteins. There is considerable clinical and pathological overlap between tauopathies and synucleinopathies. In contrast to Parkinson's disease, Alzheimer's disease most often experiences memory loss, and cardinal signs of Parkinson's disease (slowness, tremor, stiffness, and postural instability) are not normal features of Alzheimer's.
Dementia with Lewy bodies is another synucleinopathy and has pathological similarities close to PD, especially with a subset of PD cases with dementia known as Parkinson's disease of dementia. The relationship between PD and DLB is very complex and not fully understood. They can represent sections of a continuum with different clinical and pathological traits or they may prove to be a separate disease.
Maps Parkinson's disease
Signs and symptoms
The most recognizable symptom of Parkinson's disease is the associated motion ("motor"). Non-motor symptoms, which include autonomic dysfunction, neuropsychiatric problems (mood, cognition, behavior or change of mind), and senses (especially the changing sense of smell) and difficulty sleeping, are also common. Some non-motor symptoms may be present at the time of diagnosis.
Motor
Four motor symptoms are considered cardinal in PD: tremors, movement slowness (bradykinesia), stiffness, and postural instability.
The most common presentation marks are the rough, slow tremor of the hand at rest that is lost during the voluntary movement of the affected arm and in the deeper stages of sleep. It usually only appears in one hand, eventually affecting both hands as the disease progresses. The frequency of the PD tremor is between 4 and 6 hertz (cycles per second). A tremor feature is the rolling-pill , the tendency of the index finger and the thumb to touch and perform together a circular motion. The term stems from the similarity between the movement of people with PD and early pharmaceutical techniques of making pills manually.
Bradykinesia (movement slowness) is found in every PD case, and due to impairment in motor movement initiation planning, and is associated with adversity throughout the entire process of movement, from planning to initiation to motion execution. The performance of sequential and simultaneous movements is disrupted. Bradykinesia is the most disturbing symptom of Parkinson's disease that causes difficulty with everyday tasks such as dressing, feeding, and bathing. This leads to certain difficulties in carrying out two independent motor activities at the same time and can be aggravated by emotional or concurrent illness. Paradoxically patients with Parkinson's disease can often ride bikes or climb stairs more easily than walking on the surface. While most doctors can easily see bradykinesia, formal assessment requires patients to perform repetitive movements with their fingers and toes.
Stiffness is stiffness and resistance to limb movement caused by increased muscle tone, excessive and continuous muscle contraction. In parkinsonism stiffness can be uniform ("pipe stiffness") or ratchety ("cogwheel stiffness"). The combination of tremor and tone enhancement is thought to stem from cogwheel stiffness. Stiffness may be associated with joint pain; Such pain is a frequent early manifestation of illness. In the early stages of Parkinson's disease, stiffness is often asymmetrical and tends to affect the muscles of the neck and shoulders before the facial muscles and extremities. With disease progression, stiffness usually affects the whole body and reduces the ability to move.
Postural instability is typical in the final stage of the disease, which causes balance disorders and often falls, and the second for fractures, loss of confidence, and reduced mobility. Instability is often absent in the early stages, especially in younger people, especially before the development of bilateral symptoms. Up to 40% of people diagnosed with PD may decline and about 10% may fall every week, with the number of decreases associated with the severity of PD.
Other known motor sign and symptoms include walking and posture disorders such as festination (rapid locking step and forward flexing posture while walking without folding arms swing). Freezing of the running style (short detention when the legs appear stuck on the floor, especially when turning or turning the direction), the unclear monotone voice sounds, facial expressions such as masks, and smaller and small handwriting are other common signs.
Neuropsikiatrik
Parkinson's disease can cause neuropsychiatric disorders, which can range from mild to severe. These include cognitive impairments, moods, behaviors, and thoughts.
Cognitive impairment may occur in the early stages of the disease and sometimes before the diagnosis, and an increase in the prevalence with the duration of the disease. The most common cognitive deficits in PD are executive dysfunction, which can include problems with planning, cognitive flexibility, abstract thinking, rule acquisition, impediments inappropriate behavior, initiation of appropriate actions, working memory, and attention control. Other cognitive difficulties include slow speed of cognitive processing, reminders and perceptual disorders and time estimates. However, improvements arise when withdrawals are aided by cues. Visuospatial difficulties are also part of the disease, seen eg when individuals are asked to perform face recognition tests and perceptions of line orientation drawn.
A person with PD has two to six times the risk of dementia compared with the general population. Up to 78% of people with PD have Parkinson's disease dementia. The prevalence of dementia increases with age and, to a lesser extent, the duration of the disease. Dementia is associated with decreased quality of life in people with PD and their caregivers, increased mortality, and higher probability of needing care in a nursing home.
Impulse control disorders including gambling pathologies, compulsive sexual behavior, binge eating, compulsive shopping and reckless generosity can be caused by drugs, especially dormant oral dopamine agonists. Dopamine dysregulated syndrome - with the craving of drugs that cause overusage - is a rare complication of levodopa use (Giovannoni, et al. 2000).
Changes in behavior and mood are more common in PD without cognitive impairment than in the general population, and usually present in PD with dementia. The most common mood difficulties are depression, apathy, and anxiety. Establishing a diagnosis of depression is complicated by the fact that depressed body language may be disguised as a PD including an anxious face without expression expressionless, dog appear hanging, slow motion, and monotonous speech. Up to 30% of people with PD may experience anxiety symptoms, ranging from generalized anxiety disorder to social phobia, panic disorder, and obsessive compulsive disorder. They contribute to quality of life disorders and increased severity of motor symptoms such as on/off fluctuations or frozen episodes.
Punding in which repetitive, recurrent repetitive behavior occurs over many hours is another disorder caused by anti-Parkinson's drugs.
Hallucinations or delusions occur in about 50% of people with PD during the course of the disease, and can lead to the emergence of dementia. This ranges from minor hallucinations - "sense of passage" or "sense of presence" (the perception of something/someone standing just beside or behind the person) - becomes vigorous, forming the visual hallucinations and paranoid ideology. Hearing hallucinations are rare in PD, and are rarely described as sound. It is now believed that psychosis is an integral part of the disease. A psychosis with delusions and associated delirium is a recognized complication of anti-Parkinson drug treatment and may also be caused by a urinary tract infection (as is often the case in vulnerable elderly people), but drugs and infection are not the only factors, and pathology underlying brain. or changes in neurotransmitters or their receptors (eg, acetylcholine, serotonin) are also considered to play a role in psychosis in PD.
More
In addition to neuropsychiatric and motor symptoms, PD can damage other functions.
Sleep problems are a feature of the disease and can be aggravated by drugs. Symptoms can manifest as daytime drowsiness (including sudden sleep attacks resembling narcolepsy), REM sleep disorders, or insomnia. REM behavior disorder (RBD), in which patients acted out dreams, occasionally injured themselves or their bed couples, may begin many years before motor development or cognitive features of PD or DLB.
Changes in the autonomic nervous system can cause orthostatic hypotension (low blood pressure on standing), oily skin and excessive sweating, urinary incontinence, and alteration of sexual function. Constipation and impairment of gastric dysmotility can be severe enough to cause discomfort and even harm to health. Perception changes may include olfactory disorders, impaired vision, pain, and paresthesia (tingling and numbness). All of these symptoms can occur many years before the diagnosis of the disease.
Cause
Environmental factors
Exposure to pesticides and a history of head injury are each associated with Parkinson's disease (PD), but the risks are simple. Never smoking, and never drinking caffeinated beverages, is also associated with a small increase in the risk of developing PD.
Low concentrations of uric in blood serum are associated with increased risk of PD.
Genetics
Research shows that PD is a complex interaction product of genetic and environmental factors. Approximately 15% of individuals with PD have first-degree relatives who have the disease, and 5-10% of people with PD are known to have forms of disease that occur due to mutations in one of several specific genes. Nailing one of these gene mutations may not lead to disease; vulnerability factors put individuals at increased risk, often in combination with other risk factors, which also affect the age of onset, severity and development.
Genes involved in PD development include SNCA, LRRK2, GBA, PRKN, PINK1, PARK7, VPS35, EIF4G1, DNAJC13 and CHCHD2.
SNCA gene mutations are important in PD because gene encoded proteins, alpha-synuclein, are the main components of Lewy's body that accumulate in people's brains with PD. Mutations in several genes, including SNCA, LRRK2 and GBA, have been found to be risk factors for "sporadic" (non-familial) PD. Mutations in the LRRK2 gene are the most commonly known causes of PD family and sporadic, accounting for about 5% of individuals with a family history of the disease and 3% of sporadic cases. A mutation in GBA presents the greatest genetic risk for developing Parkinson's disease.
Some Parkinson-related genes are involved in the function of lysosomes, organelles that digest cellular waste products. It has been suggested that some cases of PD can be caused by lysosomial dysfunction that reduces the ability of cells to break alpha-synuclein.
Pathophysiology
The main pathological characteristics of PD are cell death in the basal basal of the brain (affecting up to 70% of dopamine-secreting neurons in substantia nigra pars compacta at the end of life) and the presence of Lewy's body (alpha protein accumulation). synuclein) in many of the remaining neurons. The loss of these neurons is accompanied by the death of astrocyte (star-shaped glial cells) and a significant increase in the number of microglia (another type of glial cell) in the substantia nigra.
There are five major pathways in the brain that connect other areas of the brain with basal ganglia. These are known as motors, oculo-motors, associative associations, limbic and orbitofrontal, with names indicating the main projection area of ​​each circuit. All are exposed to PD, and their disorders explain many of the symptoms of the disease, because these circuits are involved in many functions, including movement, attention and learning. Scientifically, motor circuits have been examined most intensively.
Certain conceptual models of motor circuits and their changes with PD have been particularly influential since 1980, although some constraints have been shown that have caused modifications. In this model, basal ganglia usually provide a constant inhibitory effect on various motor systems, preventing them from becoming active at inappropriate times. When a decision is made to take a certain action, the inhibition is reduced to the required motor system, thus releasing it for activation. Dopamine acts to facilitate the release of this inhibition, so high levels of dopamine function tend to increase motor activity, while low levels of dopamine function, as in PD, require greater mobilization of each given motion. Thus, the net effect of dopamine depletion is to produce hypokinesia, the overall reduction in motor output. Drugs used to treat PD, in contrast, may produce excessive dopamine activity, allowing the motor system to be activated at an improper time and thus resulting in dyskinesia.
Dead brain cells
There is speculation about some of the mechanisms by which brain cells can disappear. One mechanism consists of the abnormal accumulation of the alpha-synuclein protein bound to ubiquitin in damaged cells. This insoluble protein accumulates inside the neurons that form the inclusions called the Lewy bodies. According to the Braak presentation, the classification of the disease based on pathological findings proposed by Heiko Braak, Lewy's body first appeared in the olfactory bulb, medulla oblongata and pontine tegmentum; individuals at this stage may be asymptomatic or may have early non-motor symptoms (such as loss of the sense of smell, or some sleep or automatic dysfunction). As the disease develops, Lewy's body develops in the substantia nigra, the midbrain region and the basal front brain, and finally, the neocortex. This brain site is the main site of nerve degeneration in PD; However, Lewy's body may not cause cell death and they may be protective (with abnormal proteins being sequestered or in-wall-off). Other forms of alpha-synuclein (eg, oligomers) that are not aggregated in Lewy's body and Lewy's neurites are actually the toxic forms of proteins. In people with dementia, Lewy's general presence often occurs in the cortical area. Neurofibrillary tangles and senile plaques, characteristic of Alzheimer's disease, are not common unless the person is insane.
Other cell death mechanisms include proteasomal and lysosomal system dysfunction and reduced mitochondrial activity. The accumulation of iron in the nigra substance is usually observed along with the inclusion of proteins. It may be associated with oxidative stress, protein aggregation and neuronal death, but the mechanism is not fully understood.
Diagnosis
A doctor will initially assess Parkinson's disease with a careful medical history and neurological examination. People can be given levodopa, with any improvement in motor damage helps to confirm the diagnosis of PD. Lewy's body findings in the midbrain at autopsy are usually considered final evidence that the person has PD. The clinical course of the disease over time may reveal it is not a Parkinson's disease, requiring that a clinical presentation be periodically reviewed to confirm the accuracy of the diagnosis.
Other causes that can lead to secondary parkinsonism are stroke and drugs. Parkinson's plus syndromes such as progressive supranuclear palsy and multiple system atrophy should be ruled out. Anti-Parkinson's drugs are usually less effective in controlling symptoms in Parkinson's plus syndrome. A faster rate of development, early cognitive dysfunction or postural instability, minimal tremor or symmetry at onset may indicate Parkinson's plus disease rather than PD itself. A genetic form with a dominant or recessive autosomal pattern of inheritance is sometimes referred to as familial Parkinson's disease or familial parkinsonism.
Medical organizations have established diagnostic criteria to facilitate and standardize the diagnostic process, especially in the early stages of the disease. The most widely known criteria came from the UK Queen Square Brain Bank for Neurological Disorders and the National Institute of Neurological Disorders and US Stroke. The Queen Square Brain Bank criteria require slowness of movement (bradikinesia) plus stiffness, rest tremor, or postural instability. Other possible causes of these symptoms need to be ruled out. Finally, three or more of the following supporting features are required during onset or evolution: unilateral onset, resting tremors, progression in time, asymmetry of motor symptoms, response to levodopa for at least five years, at least ten years of clinical course and dyskinesias appearance due to levodopa intake excessive.
When the diagnosis of PD was examined by autopsy, motion disorder experts were found to average to be accurate 79.6% in preliminary assessment and 83.9% accurate after they improved their diagnosis on follow-up examination. When clinical diagnoses performed primarily by nonexperts were examined by autopsies, the average accuracy was 73.8%. Overall, 80.6% of PD diagnoses were accurate, and 82.7% of diagnoses using the Brain Bank criteria were accurate.
A task force from International Parkinson and Movement Disorder Society (MDS) has proposed diagnostic criteria for Parkinson's disease as well as research criteria for diagnosis of prodromal disease, but this will require validation of more established criteria.
Imaging
Computed tomography (CT) scans people with PD usually looks normal. MRI has become more accurate in the diagnosis of disease over time, in particular through secretion of T2 * and SWI fuses that are sensitive to a minimum magnetic field strength of 3T, both of which may indicate the absence of a characteristic 'swallow tail' imaging pattern in dorsolateral substantia nigra. In meta-analysis, the absence of this pattern is 98% sensitive and 95% specific for disease. MRI diffusion has shown the potential for differentiating between PD and Parkinson plus syndrome, although its diagnostic value is still under investigation. CT and MRI are also used to exclude other diseases that may be secondary causes of parkinsonism, most commonly encephalitis and chronic ischemic deficiency, as well as less frequent entities such as basal ganglia and hydrocephalus tumors.
Dopamine related activities in basal ganglia can be directly measured by PET and SPECT scans. The discovery of dopamine activity associated with a reduction in basal ganglia may exclude drug induced parkinsonism, but basal basal ganglia dopamine-related basal activity is seen in PD and Parkinson-plus disorders so this scan is unreliable in distinguishing PD from the others. causes of neurodegenerative parkinsonism.
Prevention
Sports in middle age may reduce the risk of Parkinson's disease later in life. Caffeine also appears protective with a greater decrease in risk that occurs with a larger intake of caffeinated beverages such as coffee. People who smoke or use smokeless tobacco are less likely than nonsmokers to develop PD, and the more they use tobacco, the less likely they are to develop PD. It is not known what underlies this effect. Tobacco use can actually protect against PD, or perhaps unknown factors both increase the risk of PD and cause reluctance to tobacco or make it easier to stop using tobacco.
Antioxidants, such as vitamins C and E, have been proposed to protect against disease, but the results of the study have been contradictory and no proven positive effects. The results of fat and fatty acids have been contradictory, with various studies reporting protective effects, an increased risk or no effect effect. There are early indications that the use of anti-inflammatory drugs and calcium channel blockers may be protective. A 2010 meta-analysis found that nonsteroidal anti-inflammatory drugs (regardless of aspirin), have been associated with at least 15 percent (higher in long-term and regular users) reduction in the incidence of developing Parkinson's disease.
Management
There is no cure for Parkinson's disease, but drugs, surgery, and physical care can provide relief and are much more effective than treatments available for other neurological disorders such as Alzheimer's disease, motor neurone disease, and Parkinson's plus syndrome. The main family of drugs useful for treating motor symptoms is levodopa (always combined with dopa decarboxylase inhibitors and sometimes also with COMT inhibitors), dopamine agonists and MAO-B inhibitors. The stage of disease and age at the onset of the disease determine which group is most useful.
The three stages can be distinguished: the early stages in which individuals with PD have developed some disabilities requiring pharmacological treatment, the second stage associated with the development of complications associated with the use of levodopa, and the third stage when symptoms unrelated to dopamine deficiency or levodopa treatment may predominate.
Treatment in the first stage aims to optimally trade off between symptom control and treatment side effects. The onset of levodopa treatment may be delayed by initially using other drugs such as MAO-B inhibitors and dopamine agonists, in the hope of delaying the onset of complications due to the use of levodopa. However, levodopa is still the most effective treatment for PD motor symptoms and should not be delayed in patients whose quality of life is disrupted by these symptoms. Dyskinesia associated with levodopa is strongly correlated with duration and severity of the disease compared to duration of levodopa treatment, thus delaying this therapy may not actually allow longer time for dyskinesia than for early use.
In the second stage the goal is to reduce PD symptoms while controlling fluctuations in drug effects. A sudden withdrawal from the drug or too often has to be managed. When oral drugs are not enough to control symptoms, surgery, deep brain stimulation, day-to-day apomorphine infusion and enteral dopa pumps can be used. The third stage presents many challenging issues requiring various treatments for psychiatric symptoms, orthostatic hypotension, bladder dysfunction, etc. In the final stage of the disease, palliative care is given to improve the quality of life.
Drugs
Levodopa
The PD motor symptom is the result of a reduction in dopamine production in the basal ganglia of the brain. Dopamine does not cross the blood-brain barrier, so it can not be taken as a drug to increase the level of brain dopamine that is depleted. But the dopamine precursor, levodopa, can pass to the brain where it is readily converted to dopamine, and levodopa administration temporarily reduces PD motor symptoms. Levodopa has been the most widely used PD treatment for more than 40 years.
Only 5-10% of levodopa pass through the blood-brain barrier. Most of the rest are metabolized into dopamine elsewhere in the body, causing various side effects including nausea, vomiting and orthostatic hypotension. Carbidopa and benserazide are dopa decarboxylase inhibitors that do not penetrate the blood brain barrier and inhibit the conversion of levodopa to dopamine outside the brain, reducing side effects and increasing the availability of levodopa to enter the brain. One of these drugs is usually taken together with levodopa, often combined with levodopa in the same pill.
The use of Levodopa leads in the long run for the development of complications: unconscious movements called dyskinesias, and fluctuations in drug effectiveness. When fluctuations occur, one can cycle through the phase with a good response to the drug and reduce the symptoms of PD ("in" circumstances), and phases with poor response to drugs and significant "off" state of the PD drug. Using low doses of levodopa may reduce the risk and severity of complications caused by levodopa. A previous strategy to reduce dyskinesia and fluctuations associated with levodopa was to withdraw levodopa drugs for some time. This is now not recommended because it can cause harmful side effects such as neuroleptic malignant syndrome. Most people with PD will eventually need levodopa and will later develop the fluctuations induced by levodopa and dyskinesia.
There is a levodopa version released with the control. The older controlled levodopa preparation has poor and unreliable absorption and bioavailability and has not shown improvement in PD motor symptoms control or reduction of levodopa-related complications when compared with direct release preparation. Newer extended release levodopa preparations seem to be more effective in reducing fluctuations but in many patients' problems persist. Intravenous levodopa infusion (Duodopa) may produce marked improvement in fluctuations compared with oral levodopa when fluctuations due to inadequate absorption caused by gastroparesis. Other longer oral formulations are being investigated and other delivery methods (inhaled, transdermal) are being developed.
COMT blocker
Tolcapone inhibits the activity of COMT, an enzyme that lowers dopamine. It has been used to complement levodopa; However, its usefulness is limited by the possibility of complications such as liver damage. The same effective drug, entacapone, has not been shown to cause significant liver function changes. The permitted preparations of entacapone contain entacapone alone or in combination with carbidopa and levodopa.
dopamine agonists
Some dopamine agonists that bind to dopamine receptors in the brain have an effect similar to levodopa. It was originally used as a complementary therapy for levodopa for individuals with levodopa complications (on-off fluctuations and dyskinesias); they are now primarily used alone as the first therapy for PD motor symptoms with the aim of delaying initiation of levodopa therapy and thus delaying the onset of levodopa complications. Dopamine agonists include bromocriptine, pergolide, pramipexole, ropinirole, piribedil, cabergoline, apomorphine and lisuride.
Although dopamine agonists are less effective than levodopa in controlling PD motor symptoms, they are usually quite effective for managing these symptoms in the first years of treatment. Dyskinesias due to dopamine agonists are rare in younger people who have PD but, along with other complications, become more common with older age at onset. Thus dopamine agonists are the preferred initial treatment for younger onset PD, and levodopa is preferred for older PD onset.
Dopamine agonists produce significant side effects, although usually mild, including drowsiness, hallucinations, insomnia, nausea, and constipation. Sometimes side effects appear even at clinically effective minimal doses, which leads doctors to look for different medications. Agonists have been associated with impulse control disorders (such as compulsive sexual activity, eating, gambling and shopping) even stronger than levodopa. They tend to be more expensive than levodopa.
Apomorphine, a non-oral dopamine agonist, may be used to reduce periods and dyskinesias in PD patients. This is given by intermittent injections or continuous subcutaneous infusions. Because secondary effects such as confusion and hallucinations are common, individuals receiving apomorphine treatment should be closely monitored. Two dopamine agonists are administered through skin patches (lisuride and rotigotine) and are useful for people at an early stage and are likely to control the situation in the developed world.
MAO-B Inhibitors
MAO-B inhibitors (safinamide, selegiline and rasagiline) increase the amount of dopamine in basal ganglia by inhibiting the activity of monoamine oxidase B (MAO-B), an enzyme that breaks dopamine. Like dopamine agonists, its use may delay the onset of levodopa therapy in early disease, but MAO-B inhibitors produce more adverse and less effective effects than levodopa in controlling symptoms of PD motors. There are several studies of their effectiveness in later stages, although the results show that they are useful for reducing fluctuations between active and inactive periods. A preliminary study showed that selegiline in combination with levodopa increases the risk of death, but this then proves to be untrue.
Other drugs
Other drugs such as amantadine and anticholinergics can be useful as a treatment of motor symptoms. However, the evidence in favor of them lacks quality, so they are not the first-choice treatment. In addition to motor symptoms, PD is accompanied by various symptoms. A number of drugs have been used to treat some of these problems. Examples are the use of quetiapine for psychosis, cholinesterase inhibitors for dementia, and modafinil for daytime drowsiness.
Doxepin and rasagline can reduce physical fatigue in PD.
Surgery
Treating motor symptoms with surgery was once a common practice, but since the discovery of levodopa, the number of operations has decreased. Studies in recent decades have led to major improvements in surgical techniques, so surgery is used again in people with advanced PD who are no longer enough for drug therapy. Surgery for PD can be divided into two main groups: lesional and deep brain stimulation (DBS). Target areas for DBS or lesions include thalamus, globus pallidus or subthalamic nucleus. Deep brain stimulation is the most commonly used surgical treatment, developed in 1980 by Alim Louis Benabid and others. This involves the implantation of a medical device called a neurostimulator, which sends electrical impulses to certain parts of the brain. DBS is recommended for people who have PD with motor fluctuations and tremors that are not adequately controlled by drugs, or those who are intolerant of drugs, as long as they do not have severe neuropsychiatric problems. Other less common surgical therapy involves the formation of a deliberate lesion to suppress excessive activity of a particular subcortical area. For example, pallidotomy involves the destruction of malignant globus pallidus to control tardive.
Rehabilitation
An exercise program is recommended in people with Parkinson's disease. There is some evidence that speech or mobility problems can increase with rehabilitation, although research is still scarce and of poor quality. Regular physical exercise with or without physical therapy can be useful for maintaining and improving mobility, flexibility, strength, walking speed, and quality of life. When an exercise program is conducted under the supervision of a physiotherapist, there are more improvements in motor symptoms, mental and emotional function, daily life activities, and quality of life compared to a self-supervised exercise program at home. In terms of increasing flexibility and range of motion for people who experience stiffness, general relaxation techniques such as soft wobbles have been found to reduce excessive muscle tension. Other effective techniques for promoting relaxation include slow motion of the extremities and trunk, rhythmic initiation, diaphragmatic breathing, and meditation techniques. As for gait and overcoming challenges associated with diseases such as hypokinesia (movement slowness), dragging and decreasing arm swings; physiotherapists have various strategies to improve functional mobility and safety. An attractive area with respect to gait during the rehabilitation program focuses on, but is not limited to improving walking speed, support base, step length, stem and arm swing motion. Strategies include using pole walking and treadmill walking, verbal cues (manual, visual and auditory), exercises (marching and PNF patterns) and changing the environment (surface, input, open vs. closed). Reinforcement exercises have shown increased motor strength and function for people with underlying muscle weakness and weakness associated with inactivity with mild to moderate Parkinson's disease. However, the report showed a significant interaction between strength and timing of drugs taken. Therefore, it is recommended that people with PD should exercise 45 minutes to an hour after treatment when they are at their best. Also, due to front flexure posture, and respiratory dysfunction in advanced Parkinson's disease, deep diaphragm breathing exercises are beneficial in improving the mobility of the chest wall and vital capacity. Exercise can improve constipation. It is unclear whether exercise reduces physical fatigue in PD.
One of the most widely practiced treatments for speech disorders associated with Parkinson's disease is sound treatment of Lee Silverman (LSVT). Speech therapy and especially LSVT can improve speech. Occupational therapy (OT) aims to improve health and quality of life by helping people with diseases to participate in as many of their daily activities as possible. There have been several studies on the effectiveness of the PL and its quality is poor, although there are some indications that it can improve motor skills and quality of life during therapy.
Palliative care
Palliative care is a special medical treatment for people with serious illnesses, including Parkinson's. The purpose of this specialization is to improve the quality of life both for people with Parkinson's and families by providing relief from symptoms, pain, and stress of illness. Because Parkinson's is not a curable disease, all treatments are focused on slow declines and improving quality of life, and are therefore palliative.
Palliative care should be involved early, rather than later in the course of the disease. Palliative care specialists can help with physical symptoms, emotional factors such as loss of function and occupation, depression, fear, and existential concern.
Together by offering emotional support to patients and families, palliative care serves an important role in addressing treatment goals. People with Parkinson's may have many difficult decisions to make the disease progress such as the desire to eat tubes, non-invasive ventilators, and tracheostomies; expect or oppose cardiopulmonary resuscitation; and when to use hospital care. Members of the palliative care team can help answer questions and guide people with Parkinson's on these complex and emotional topics to help them make the best decisions based on their own values.
The muscles and nerves that control the digestive process can be affected by PD, resulting in constipation and gastroparesis (food remaining in the abdomen for longer than usual). A balanced diet, based on periodic nutritional appraisal, is recommended and should be designed to avoid weight loss or weight and minimize the consequences of gastrointestinal dysfunction. As the disease progresses, difficulty in swallowing (dysphagia) may appear. In such cases it may be helpful to use thickening agents for fluid intake and upright posture at mealtime, both steps reduce the choking risk. Gastrostomy to deliver food directly to the stomach is possible in severe cases.
Levodopa and proteins use the same transport system in the intestines and blood-brain barrier, thus competing for access. When they are taken together, this results in decreased effectiveness of the drug. Therefore, when levodopa is introduced, excessive protein consumption is recommended and a balanced Mediterranean diet is recommended. In the advanced stages, additional intake of low-protein products such as bread or pasta is recommended for similar reasons. To minimize interactions with proteins, levodopa should be taken 30 minutes before meals. At the same time, the regimen for PD limits the protein during breakfast and lunch, enabling protein intake at night.
Prognosis
PD always evolves with time. The severity assessment method known as the Unified Parkinson's disease assessment scale (UPDRS) is the most commonly used metric for clinical studies. A modified version known as MDS-UPDRS is also sometimes used. The older scale method known as the Hoehn and Yahr scale (originally published in 1967), and the same scale known as the Hoehn and Yahr Modified scales, have also been commonly used. The scale of Hoehn and Yahr defines the five basic stages of development.
Motor symptoms, if not treated, progress aggressively in the early stages of the disease and later later. Untreated, individuals are expected to lose independent ambulation after an average of eight years and lie in bed after ten years. However, it is not uncommon to find people who are not treated at this time. Drugs have improved the prognosis of motor symptoms, while at the same time it is a new source of disability, due to the undesirable effects of levodopa after years of use. In people taking levodopa, the timing of symptom progression to a high dependency stage of caregivers may be more than 15 years. However, it is difficult to predict what pathway the disease will take for a particular individual. Age is the best predictor of disease progression. The rate of motor decline is greater in those with lesser disturbance at the time of diagnosis, whereas cognitive decline is more frequent in those over 70 years of onset of symptoms.
Because current therapy improves motor symptoms, current disability is mainly associated with non-motor features of the disease. However, the relationship between disease progression and disability is not linear. The disability was initially associated with motor symptoms. As the disease progresses, disability is more associated with motor symptoms that do not respond adequately to drugs, such as swallowing/difficulty, and gait/balance problems; and also for complications caused by levodopa, which appear in 50% of individuals after 5 years of levodopa use. Finally, after ten years most people with this disease experience autonomic disorders, sleep problems, mood swings and cognitive decline. All of these symptoms, especially cognitive decline, greatly increase disability.
The life expectancy of people with PD is reduced. The mortality ratio is about twice that of unaffected persons. Cognitive decline and dementia, old age at onset, further illness and swallowing problems are risk factors for death. On the other hand, the pattern of the disease is primarily characterized by tremor as opposed to the stiffness of predicting improved survival. Deaths from aspiration pneumonia are twice as common in individuals with PD as in healthy populations.
In 2013 the PD resulted in about 103,000 deaths globally, up from 44,000 deaths in 1990. The mortality rate increased from an average of 1.5 to 1.8 per 100,000 during that time.
Epidemiology
PD is the second most common neurodegenerative disorder after Alzheimer's disease and affects about seven million people worldwide and one million people in the United States. The proportion in a population at a given time is about 0.3% in industrialized countries. PD is more common in elderly and the rate increases from 1% in those over 60 years to 4% of the population over 80 years. The mean age of onset is about 60 years, although 5-10% of cases, classified as young onset of PD, begins between the ages of 20 and 50. Men are more often affected than women with a ratio of about 3: 2. PD may be less common in African descent and Asia, although these findings are disputed. Several studies have suggested that it is more common in men than women, but others fail to detect differences between the sexes. The number of new cases per year of PD is between 8 and 18 per 100,000 person-years.
Many risk factors and protective factors have been proposed, sometimes in relation to the theory of possible disease mechanisms, however, none of which are conclusively related to PD by empirical evidence. When epidemiological studies have been conducted to examine the relationship between given factors and PD, they are often flawed and their results in some cases have been contradictory. The most frequently imitated relationship is an increased risk of PD in those exposed to pesticides, and a reduced risk to smokers.
History
Some early sources, including Egyptian papyrus, an Ayurvedic medical treatise, the Bible, and Galen's writings, illustrate symptoms resembling PD symptoms. After Galen there was no clear reference to the PD until the 17th century. In the 17th and 18th centuries, some authors wrote about the elements of the disease, including Sylvius, Gaubius, Hunter, and Chomel.
In 1817 a British physician, James Parkinson, published his essay reporting six cases of agitation paralysis. An Essay on Shaking Palsy describes the characteristics of resting tremor, abnormal posture and gait, reduced paralysis and muscle strength, and the way disease develops over time. Early neurologists who made further additions to knowledge about the disease include Trousseau, Gowers, Kinnier Wilson and Erb, and especially Jean-Martin Charcot, whose studies between 1868 and 1881 were landmarks in the understanding of disease. Among other advances, he made the distinction between stiffness, weakness and bradykinesia. He also championed the rename of the disease in honor of James Parkinson.
In 1912, Frederic Lewy described microscopic particles in the affected brain, later named "Lewy bodies". In 1919 Constantine Tretiakoff reported that the substantia nigra was the main brain structure affected, but this finding was not widely accepted until it was confirmed by further research published by Rolf Hassler in 1938. The underlying biochemical changes in the brain were identified in the 1950s, mainly due to the work of Arvid Carlsson on dopamine neurotransmitters and By Hornykiewicz on his role in PD. In 1997, alpha-synuclein was found to be a major component of Lewy's body by Spillantini, Trojanowski, Goedert and others.
Anticholinergics and surgery (lesions on the corticospinal tract or some basal ganglia structure) are the only treatment until the arrival of levodopa, which reduces its use dramatically. Levodopa was first synthesized in 1911 by Casimir Funk, but it received little attention until the mid-20th century. It entered clinical practice in 1967 and brought about a revolution in PD management. In the late 1980s the deep brain stimulation introduced by Alim Louis Benabid and his colleagues in Grenoble, France, emerged as a possible treatment.
Society and culture
Cost
PD costs for the community are high, but precise calculations are difficult due to methodological problems in research and differences between countries. The annual cost in the UK is estimated to be between 449 million to 3.3 billion pounds, while the cost per patient per year in the US may be around $ 10,000 and the total burden of about 23 billion dollars. The lion's share of direct costs come from inpatient care and nursing homes, while the part coming from medicine is much lower. High indirect costs, due to reduced productivity and caregiver burden. In addition to economic costs, PD reduces the quality of their lives with their illness and caregivers.
Advocacy
April 11, James Parkinson's birthday, has been designated as World Park Parkinson's Day. A red tulip chosen by international organizations as a symbol of disease in 2005: this tulip is a cultivar James Parkinson Tulip, registered in 1981 by a Dutch horticultural expert. The advocacy organization includes the National Parkinson Foundation, which has provided over $ 180 million in care, research, and support services since 1982, Parkinson's Disease Foundation, which has distributed over $ 115 million for research and nearly $ 50 million for educational programs and advocacy since its inception. in 1957 by William Black; American Parkinson Disease Association, founded in 1961; and the European Parkinson's Disease Association, founded in 1992.
Important case
Actor Michael J. Fox has a PD and has greatly increased public awareness of this disease. After diagnosis, Fox embraced Parkinson in a television role, sometimes acting without drugs, to better illustrate the effects of the condition. He has written two autobiographies in which his fight against illness plays a major role, and appears before the United States Congress without drugs to illustrate the effects of the disease. Michael J. Fox Foundation aims to develop a cure for Parkinson's disease. Fox received an honorary doctorate in medicine from the Karolinska Institutet for his contribution to Parkinson's disease research.
Professional cyclist and Olympic medalist Davis Phinney, who was diagnosed with Parkinson's onset at age 40, started the Davis Phinney Foundation in 2004 to support Parkinson's research, which focuses on quality of life for people with the disease.
Boxer Muhammad Ali showed signs of Parkinson's when he was 38 years old, but was not diagnosed until he was 42 years old, and has been called "the most famous Parkinson's patient in the world". Does he have PD or parkinsonism linked to boxing unsolved.
Research
There are few prospects for significant new PD care in the near future. Current active research guidelines include finding new animal models of disease and studies of the potential uses of gene therapy, stem cell transplants and neuroprotective agents.
Animal model
PD is not known to occur naturally in species other than humans, although animal models that show some features of the disease are used in the study. The emergence of parkinsonism in a group of drug addicts in the early 1980s who consumed a batch contaminated with synthetic MPPP opiates led to the discovery of MPTP chemistry as an agent that causes parkinsonism in non-human primates as well as in humans. Other poison-based models use rotenone insecticide, herbicide paraquat and fungicide maneb. Models based on toxins are most commonly used in primates. Transgenic mouse models that replicate various aspects of PD have been developed. Using neurotoxin 6-hydroxydopamine, also known as 6-OHDA, it created a model of Parkinson's disease in mice by targeting and destroying dopaminergic neurons in the nigrostriatal pathway when injected into the substantia nigra.
Gene therapy
Gene therapy usually involves the use of non-infectious viruses (ie viral vectors such as adeno-related viruses) to drain genetic material into parts of the brain. The genes used lead to the production of enzymes that help manage PD symptoms or protect the brain from further damage. In 2010 there were four clinical trials using gene therapy in PD. No adverse effects are important in this trial although the clinical efficacy of gene therapy is still unknown. One of these reported positive results in 2011, but the company filed for bankruptcy in March 2012.
Neuroprotective treatment
Investigations on the neuroprotection are at the forefront of PD research. Several molecules have been proposed as potential treatments. However, none of them has been proven with certainty to reduce degeneration. Agents currently under investigation include anti-apoptotics (omigapil, CEP-1347), antiglutamatergics, monoamine oxidase inhibitors (selegiline, rasagiline), promitochondrials (coenzyme Q10, creatine), calcium channel blockers (isradipine) and growthfactor (GDNF). Preclinical research also targets alpha-synuclein. Vaccines that provide the human immune system to destroy alpha-synuclein, PD01A (developed by the Austrian company, Affiris), have entered human clinical trials.
Nervous transplant
Since the early 1980s, fetal, pig, carotid or retinal tissue has been used in cell transplants, in which the separated cells are injected into the substantia nigra in the hope that they will merge into the brain in a way that replaces dopamine-producing cells that already lost. Although there is early evidence of dopamine cell transplantation that produces a useful mesencephalic, double-blind trials to date suggest that cell transplantation does not produce long-term benefits. A significant additional problem is the release of excess dopamine by the transplant tissue, which causes dystonia. Stem cell transplantation is a recent study target, because stem cells are easily manipulated and stem cells transplanted into the brains of rats and monkeys have been found to survive and reduce behavioral abnormalities. However, the use of fetal stem cells is still controversial. It has been proposed that effective treatments can be developed in less controversial ways by using induced pluripotent stem cells derived from adults.
More
Transcranial magnetic stimulation repeats while increasing levodopa-induced dyslynthia. Its usefulness in PD is an open research topic, Some nutrients have been proposed as possible treatments; But there is no evidence that vitamin or food additives improve symptoms. There is no evidence to prove that acupuncture and Qigong exercises, or T'ai chi, have any effect on the course of illness or symptoms. Fava beans and velvet beans are a natural source of levodopa and eaten by many people with PD; Their intake is not risk-free as life-threatening side effects have been described, such as neuroleptic malignant syndrome.
References
External links
- Parkinson's disease in Curlie (based on DMOZ)
- Parkinson's Disease: Hope Through Research (National Institute of Neurological Disorders and Stroke)
- The Parkinson's Parkinson's Association
- PDGENE - Database for genetic studies of Parkinson's disease studies
Source of the article : Wikipedia
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