What Are the Causes of Parkinson's?
Parkinson's disease (PD) is a common neurological degenerative disease. It is more common in the elderly, and the average age of onset is about 60 years. Parkinson's disease is less common in young people who develop disease under the age of 40. The prevalence of PD in people over 65 in China is about 1.7%. Most patients with Parkinson's disease are sporadic, and less than 10% have a family history. The most important pathological change of Parkinson's disease is the degeneration and death of dopamine (DA) neurons in the mesencephalic substantia nigra, which causes a significant reduction in the DA content of the striatum and causes disease. The exact cause of this pathological change is still unclear. Genetic factors, environmental factors, aging, and oxidative stress may all participate in the process of degeneration of PD dopaminergic neurons.
| Chen Biao | (Chief physician) | Department of Neurology, Xuanwu Hospital, Capital Medical University |
| Ma Jinghong | (Attending physician) | Department of Neurology, Xuanwu Hospital, Capital Medical University |
Parkinson's disease (PD) is a common neurological degenerative disease. It is more common in the elderly, and the average age of onset is about 60 years. Parkinson's disease is less common in young people who develop disease under the age of 40. The prevalence of PD in people over 65 in China is about 1.7%. Most patients with Parkinson's disease are sporadic, and less than 10% have a family history. The most important pathological change of Parkinson's disease is the degeneration and death of dopamine (DA) neurons in the mesencephalic substantia nigra, which causes a significant reduction in the DA content of the striatum and causes disease. The exact cause of this pathological change is still unclear. Genetic factors, environmental factors, aging, and oxidative stress may all participate in the process of degeneration of PD dopaminergic neurons.
On May 11, 2018, the National Health Committee and other five departments jointly developed the "First Batch of Rare Diseases List", and White Parkinson's disease was included. [1]
- Zhang Yuqing
- Chief Physician of Functional Neurosurgery, Beijing Xuanwu Hospital
- Related videos:
- What is Parkinson What are the clinical symptoms of Parkinson How is Parkinson diagnosed How is Parkinson treated
Video content provided:
- Western Medicine Name
- Parkinson's Disease
- English name
- Parkinson's disease, PD
- Affiliated Department
- Internal Medicine-Neurology
- Disease site
- head
- Contagious
- Non-contagious
- Whether to enter health insurance
- Yes
Introduction to Parkinson's disease
In 1817, the British doctor James Parkinson first described the disease in detail. Its clinical manifestations mainly include resting tremor, bradykinesia, myotonia, and posture gait disorders. At the same time, patients may be accompanied by non-exercises such as depression, constipation and sleep disorders. symptom. The diagnosis of Parkinson's disease mainly depends on history, clinical symptoms and signs. The general auxiliary examination is mostly without abnormal changes. Drug therapy is the main treatment for Parkinson's disease. Levodopa formulations remain the most effective drugs. Surgical treatment is an effective supplement to drug treatment. Rehabilitation, psychotherapy and good care can also improve symptoms to a certain extent. Although the currently applied treatments can only improve symptoms, cannot prevent the progress of the disease, and cannot cure the disease, effective treatment can significantly improve the quality of life of patients. The life expectancy of PD patients is not significantly different from the general population.
Pathogenesis of Parkinson's disease
The exact cause of Parkinson's disease is unknown. Genetic factors, environmental factors, aging, and oxidative stress may all participate in the process of degeneration and death of PD dopaminergic neurons.
Parkinson's disease aging
The incidence and prevalence of PD increase with age. PD occurs more than 60 years of age, which suggests that aging is related to disease. Data show that with age, dopaminergic neurons in the brain of normal adults gradually decrease. However, the prevalence of PD is not high among elderly people over 65 years of age. Therefore, aging is only one of the risk factors for PD.
Genetic factors of Parkinson's disease
The role of genetic factors in the pathogenesis of PD is receiving increasing attention from scholars. Since the discovery of -synuclein (PARK1), the first Parkinson's disease-causing gene in the late 1990s, at least six disease-causing genes are currently associated with familial Parkinson's disease. However, only 5 to 10% of Parkinson's disease has a family history, and most are sporadic cases. Genetic factors are only one of the factors that cause PD.
Environmental factors for Parkinson's disease
In the 1980s, American scholar Langston et al. Found that some drug users quickly develop typical Parkinson's-like symptoms and are effective for levodopa preparations. Studies have found that synthetic heroin consumed by drug users contains a 1-methyl-4phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxic substance. The substance is converted into the highly toxic 1-methyl-4phenyl-pyridine ion MPP + in the brain, and selectively enters the dopaminergic neurons of the substantia nigra, inhibits the activity of mitochondrial respiratory chain complex I, and induces oxidative stress Response, leading to the degeneration of dopaminergic neurons. Therefore, scholars have suggested that mitochondrial dysfunction may be one of the causative factors of PD. In subsequent studies, it was also confirmed that the activity of mitochondrial respiratory chain complex I in primary PD patients was selectively decreased in substantia nigra. Some herbicides and pesticides have similar chemical structures to MPTP. With the discovery of MPTP, people realized that some MPTP-like chemicals in the environment may be one of the pathogenic factors of PD. However, only a few of the many drug users exposed to MPTP develop disease, suggesting that PD may be the result of a combination of factors.
Parkinson's disease other
In addition to aging and genetic factors, brain trauma, smoking, and coffee drinking may also increase or decrease the risk of PD. There is a negative correlation between smoking and the occurrence of PD, which has been agreed in many studies. Caffeine has a similar protective effect. Severe brain trauma may increase the risk of PD.
In short, Parkinson's disease may be the result of the interaction of multiple genes and environmental factors.
Parkinson's disease pathophysiology
The prominent pathological changes of Parkinson's disease are the degeneration and death of dopamine (DA) neurons in the midbrain, significant reduction of DA content in the striatum, and the appearance of eosinophilic inclusions in the cytoplasm of residual neurons in the substantia nigra. Lewy body. When clinical symptoms appear, dopaminergic neurons in substantia nigra die at least 50% and DA content in striatum decreases by more than 80%. In addition to the dopaminergic system, the non-dopaminergic system of patients with Parkinson's disease is also significantly damaged. Such as cholinergic neurons in the basal nucleus of Meynert, noradrenergic neurons in the blue spot, serotonergic neurons in the raphe nucleus of the brainstem, and nerves in the cerebral cortex, brainstem, spinal cord, and peripheral autonomic nervous system yuan. The significant decrease in striatum dopamine is closely related to the occurrence of motor symptoms of Parkinson's disease. The significant reduction of dopamine concentrations in the midbrain-limb system and midbrain-cortex system is closely related to the decline of mental retardation and emotional disorders in patients with Parkinson's disease.
Clinical manifestations of Parkinson's disease
Parkinson's disease develops insidiously and progresses slowly. The first symptom is usually tremor or awkward movement of one limb, which affects the contralateral limb. The main clinical manifestations are resting tremor, bradykinesia, muscle rigidity and posture gait disturbance. In recent years, more and more people have noticed that non-motor symptoms such as depression, constipation, and sleep disorders are also common complaints of patients with Parkinson's disease, and their impact on the quality of life of patients even exceeds motor symptoms.
static tremor Parkinson's disease static tremor
About 70% of patients have tremor as the first symptom, mostly starting from the distal end of one side, appearing or obvious at rest, reducing or stopping when they exercise freely, exacerbating when they are nervous, and disappearing after falling asleep. Hand tremor worsens during walking. A typical manifestation is a "pill-like" tremor with a frequency of 4 to 6 Hz. Some patients may be combined with postural tremor. The typical complaint of the patient is: "One of my hands often shakes, the more I shake it, the more I shake it. When I work, I don't shake it. When I meet a person or I am excited, I shake too much. When I fall asleep, I don't shake. "
rigidity Parkinson's disease rigidity
The examiner can notice obvious resistance when moving the patient's limb, neck or torso. This increase in resistance presents the characteristics of uniformity in all directions, similar to the feeling of bending a soft lead tube, so it is called "lead tube-like rigidity" (Lead-pipe rigidity). Patients with limb tremor may experience intermittent pauses in uniform resistance, such as turning gears, which is called "cogwheel rigidity." The typical complaint of the patient is "my limb is stiff." In the early stage of the disease, sometimes myotonia is not easy to detect. At this time, the patient can actively move one limb, and the muscle tension of the affected limb will increase passively.
bradykinesia Parkinson's disease bradykinesia
Tardiness refers to slow movements, difficulty in starting, and loss of active movement. The patient's range of motion will decrease, especially when repeated exercise. Bradykinesia can manifest in a number of ways depending on the affected area. Facial expression movements are reduced, and blink reduction is called a masked face. The voice is monotonous and the words are not clear. Writing can become slower and smaller, known as "micrographia." Washing, dressing and other fine movements can be awkward and inflexible. The walking speed becomes slower and the line is often dragged, and the amplitude of arm swing will gradually decrease or even disappear. Steps become smaller. Drooling occurs due to inability to actively swallow to saliva. Difficulty turning over at night. In the early stages of the disease, patients often mistake the bradykinesia as weakness and are often misdiagnosed as cerebrovascular disease or cervical spondylosis due to weakness and weakness in one limb. Therefore, when the patient slowly develops weakness in one limb and is accompanied by increased muscle tone, he should be alert to the possibility of Parkinson's disease. The typical complaint of early patients was: "I recently found that my right hand (or left hand) was weak, not as sharp as before, and writing was not as beautiful as before. When I beat eggs, I felt that my right hand was not obedient and not as flexible as the other. The right leg (or left leg) feels heavy when walking, and seems to be a bit dragged. "
Parkinson's Disease Posture Gait Disorder
Postural reflexes often appear in the middle and late stages of the disease, and it is difficult for patients to maintain a balanced body, and a slightly uneven road may fall. The typical complaint of the patient is "I'm afraid to walk alone. Other people can trip me if they touch me or a small stone on the road. I have fallen a few times recently, so that I walk very carefully now." Reflection can be detected by a pull back test. The examiner stood behind the patient and instructed the patient to pull his shoulders when he was ready. Normal people can return to normal upright within one step back. Patients with disappeared postural reflexes often need to step back more than three steps or need support to stand upright. Patients with PD often walk faster and faster, which is difficult to reach, which is called festinating gait. The typical complaint of the patient is: "I often go faster and faster, I can't stop." Patients with advanced Parkinson's disease may appear frozen, which is manifested as a sudden inability to walk while walking, and their feet seem to stick to the ground, and they must pause It will take a few seconds before you can continue or you cannot start again. Freezing is common when starting to walk (difficult to start), turning around, approaching a target, or worrying about not being able to pass a known obstacle, such as walking through a revolving door. The typical complaint of the patient is: "I often have to pause for a few seconds before I get up, and sometimes I can't move when I walk, especially when I turn or see something in front of me blocking the road. . "
Parkinson's disease non-motor symptoms
In addition to motor symptoms such as tremor and slowness, patients with Parkinson's disease may also experience non-motor symptoms such as depression, anxiety, sleep disturbances, and cognitive impairment. Fatigue is also a common non-exercise symptom of Parkinson's disease. The typical complaints of patients are: "I feel physically tired and weak; poor sleep and often can't sleep; hard stools, once every few days; bad mood, always unhappy; poor memory and slow brain response." [2 ]
Parkinson's disease diagnosis
The diagnosis of Parkinson's disease mainly depends on history, clinical symptoms and signs. According to the characteristics of insidious onset and gradual progress, unilateral involvement then progresses to the opposite side, manifested as resting tremor and slow action, and clinical diagnosis can be made by excluding atypical Parkinson's-like symptoms. Treatment with levodopa preparations is more supportive of diagnosis. Routine blood and cerebrospinal fluid examination were normal. Head CT and MRI also showed no characteristic changes. Olfactory examinations can be found in patients with PD. Functional imaging of dopa uptake with 18F-dopa as a tracer showed reduced dopamine transmitter synthesis. Dopamine transporter (DAT) functional imaging with 125I--CIT and 99mTc-TRODAT-1 as tracers can show a decrease in the number of DATs, which can be shown in the early stages of the disease and even in the subclinical stage, which can support diagnosis. However, this inspection is relatively expensive and has not been carried out routinely.
See Table 1 for the diagnostic criteria of UK brain Parkinson's disease. The severity of Parkinson's disease can generally be assessed using H & Y (Hoehn & Yahr) classification (see Table 2).
Table 1 Clinical diagnostic criteria for Parkinson's disease in the UK
Step 1: Diagnose Parkinson's Syndrome |
Reduced movement: voluntary movement is slow at the beginning of movement, and the speed and amplitude of repetitive movements gradually decrease |
Have at least one of the following symptoms: A muscle rigidity B. Static tremor (4-6Hz) C. Upright instability (non-primary vision, vestibular function, cerebellum and proprioceptive dysfunction) Step 2: Parkinson's disease exclusion criteria Repeated stroke history, Parkinson's symptoms with stepwise progression Repeated brain injury history Exact Encephalitis History Eye movement crisis At the time of symptoms, he was being treated with neuroleptics More than 1 relative is sick Continuous remission Three years after onset, severe unilateral involvement remains Supranuclear gaze paralysis Cerebellar sign Severe autonomic involvement at an early stage Severe dementia early with memory, speech and behavioral disorders Positive pyramidal sign (Babinski sign +) CT scan shows intracranial tumors or traffic hydrocephalus Ineffective treatment with large doses of levodopa (except for malabsorption) MPTP exposure history an opioid analgesic derivative Step 3: Supporting diagnostic criteria for Parkinson's disease. A diagnosis of Parkinson's disease with three or more Unilateral onset Presence of resting tremor Progression of the disease Persistent asymmetry of symptoms, heavier on the first side Very good response to levodopa treatment (70-100%) Severe dyskinesia caused by levodopa The effect of levodopa for more than 5 years (including 5 years) More than 10 years of clinical course (including 10 years) |
Patients who meet the diagnostic criteria for Parkinson's syndrome in the first step can be clinically diagnosed as Parkinson's disease if they do not have any of the second step and meet three or more of the third step.
Table 2 H & Y classification of Parkinson's disease
0 = No signs 1.0 = Unilateral disease 1.5 = Unilateral disease and affects the muscles of the central axis 2.0 = Bilateral disease without impairing balance 2.5 = Mild bilateral disease, posture reflex is slightly worse, but can correct itself 3.0 = Bilateral disease, posture disorder, positive pull-back test 4.0 = severely disabled, but able to stand or walk on their own 5.0 = Can't get up or live in a wheelchair |
Differential diagnosis of Parkinson's disease
Parkinson's disease needs to be distinguished from other causes of Parkinson's syndrome. Parkinson's syndrome is a large category that includes primary Parkinson's disease, Parkinson's syndrome, secondary Parkinson's syndrome, and hereditary Parkinson's syndrome. Symptoms and signs of asymmetry, resting tremor, and sensitivity to levodopa treatment are more suggestive of primary Parkinson's disease.
Parkinson's disease
Parkinson's disease syndrome includes multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and cortical basal ganglia degeneration (CBD). Prominent language and gait disorders appear early in the disease, posture instability, central axis muscle tension is significantly higher than the limbs, no resting tremor, prominent autonomic dysfunction, no response to levodopa or inconsistent curative effects. Parkinson's disease syndrome is possible. Although the above clues can help determine the diagnosis of Parkinson's disease, it is more difficult to identify specific subtypes. In general, the presence of prominent orthostatic hypotension or cerebellar signs often indicates multiple system atrophy. Vertical gaze paralysis, especially difficulty in lower vision, hyperextension of the neck, and early fall often suggest progressive supranuclear palsy. Asymmetry in localized increase in muscle tone, myoclonus, disuse, and heterogeneous limb phenomenon are more suggestive of cortical basal ganglia degeneration.
Parkinson's disease secondary Parkinson's syndrome
This syndrome is caused by definite causes such as drugs, infections, poisoning, stroke, and trauma. By careful inquiry of the medical history and corresponding laboratory tests, such diseases are generally easier to distinguish from primary Parkinson's disease. Drugs are the most common cause of secondary Parkinson's syndrome. Neuroleptics (phenothiazines and butyrylbenzenes) used to treat mental illness are the most common pathogenic drugs. It should be noted that sometimes we also use these drugs to treat non-psychiatric diseases such as vomiting, such as the use of promethazine to stop vomiting. Other drugs that can cause or exacerbate Parkinson-like symptoms include reserpine, flunarizine, metoclopramide, lithium, and the like.
essential tremor, ET Parkinson's disease idiopathic tremor (ET)
The onset of the disease is insidious and progresses slowly or remissions for a long time. About 1/3 of the patients have a family history. Tremor is the only clinical symptom, mainly manifested as postural tremor and action tremor, that is, the body is prone to tremor while maintaining a certain posture or doing action. Tremors often affect both limbs, and the head is more often affected. The frequency is 6 to 12 Hz. It can be aggravated when the emotion is agitated or tense, and lightened or disappeared when still. The prominent difference between this disease and Parkinson's disease is that the onset of idiopathic tremor is mostly bilateral, without accompanying bradykinesia, no resting tremor, slow progress of the disease, more family history, and a considerable part of the patients' quality of life Hardly affected.
Parkinson's disease other
Genetic degenerative Parkinson's syndrome is often accompanied by other symptoms and signs, so it is generally not difficult to identify. Such as hepatolenticular degeneration can be associated with corneal pigmented rings and liver damage. Depression patients may experience lack of expression, retarded thinking, and reduced movement, sometimes easily misdiagnosed as Parkinson's disease, but depression is generally not accompanied by resting tremor and myotonia, symptomatic onset, obvious depression and lack of pleasure. Identification.
Parkinson's disease treatment
Parkinson's disease treatment principles
1. Comprehensive treatment: Drug treatment is the main treatment for Parkinson's disease. Levodopa formulations remain the most effective drugs. Surgical treatment is an effective supplement to drug treatment. Rehabilitation, psychotherapy and good care can also improve symptoms to a certain extent. The currently used treatments are mainly to improve symptoms, but cannot prevent the progress of the disease.
2. Medication principles: Medication should be gradually increased from a small dose. To achieve a satisfactory effect with a smaller dose, do not seek full effect. Medication should also emphasize individualization while following the general principles. According to the patient's condition, age, occupation and economic conditions and other factors, the best treatment plan is adopted. Not only should the symptoms be controlled during drug treatment, but side effects of the drug should be avoided as far as possible, and the clinical symptoms of patients should be controlled as long as possible in the long term.
Parkinson's disease medication
1. Protective treatment: In principle, once the diagnosis of Parkinson's disease is confirmed, protective treatment should be given as soon as possible. At present, the drugs used as protective treatment in clinic are mainly monoamine oxidase B (MAO-B) inhibitors. Recent studies have shown that MAO-B inhibitors may delay the progress of the disease, but there is no conclusion yet.
2. Symptomatic treatment
Early treatment (Hoehn-Yahr l ~ II)
(1) When to start medication: The disease is relatively mild in the early stage of the disease and can be suspended when there is no obvious impact on daily life or work. Symptomatic treatment should be started if the disease affects the patient's daily life or ability to work, or if the patient requires early control of symptoms.
(2) Principle of preferred drugs: <65-year-old patients without dementia can choose: non-ergotamine dopamine receptor (DR) agonist; MAO-B inhibitor; amantadine, if tremor is obvious and other anti- Anti-cholinergic drugs can be used if PD is not effective; compound levodopa + catechol-oxygen-methyltransferase (COMT) inhibitor; compound levodopa; and generally in , when the treatment effect of the program is not good. However, if you need to work to significantly improve the symptoms of exercise, or cognitive decline, you can choose the or program, or you can use a small dose of , or programs, and small doses combined program. Patients 65 years of age or with decreased intelligence: Compound levodopa is preferred, and DR agonists, MAO-B or COMT inhibitors may be added if necessary. Diphenoxine has more side effects as far as possible, especially in elderly male patients, unless there is severe tremor and the effect of other drugs is not good.
Intermediate treatment (Hoehn-Yahr grade III)
In the early stage, patients with DR agonists, MAO-B inhibitors or amantadine / anticholinergic drugs are preferred. In the middle stage, compound levodopa should be added when the original drugs cannot control the symptoms well. That is to say, patients who choose low-dose compound levodopa should increase the dose or add DR agonist, MAO-B inhibitor, amantadine or COMT inhibitor when the symptoms are not ideal in the middle stage.
Late treatment (Hoehn-Yahr IV-V)
The treatment of advanced patients is relatively complicated due to the progress of the disease itself and the emergence of motor complications, and the treatment is also difficult. Therefore, at the beginning of treatment, a reasonable treatment plan should be formulated in accordance with the actual situation of the patient, in order to delay the occurrence of sports complications as much as possible and extend the time window of effective treatment of the patient. [3]
Common medications for Parkinson's disease
1. Anticholinergic drugs: mainly by inhibiting the activity of acetylcholine in the brain, and correspondingly increasing the dopamine effect. Commonly used clinically is benzetholide hydrochloride. In addition there are Kai Majun, benztropine, scopolamine and so on. Mainly suitable for patients with obvious tremor and younger age. Elderly patients should be used with caution, narrow-angle glaucoma and patients with enlarged prostate should not be used.
2. Amantadine: It can promote the synthesis and release of dopamine in nerve endings and prevent its reabsorption. It has a mild improvement effect on less movement, stiffness and tremor, and may be effective for dyskinesia. Use with caution in patients with renal insufficiency, epilepsy, severe gastric ulcer, and liver disease.
3. Monoamine oxidase B (MAO-B) inhibitor: By irreversibly inhibiting MAO-B in the brain, blocking the degradation of dopamine, and increasing the content of dopamine to achieve the purpose of treatment. MAO-B inhibitors can be used alone to treat new and young patients with Parkinson's disease, and can also be used to assist compound levodopa in the treatment of advanced patients. It may be neuroprotective, so early use is recommended in principle. MAO-B inhibitors include selegiline and rasagiline. It is easy to cause insomnia when it is used at night, so it is recommended to take it early and middle. Patients with gastric ulcer should be used with caution, and the combination with serotonin reuptake inhibitor (SSRI) is prohibited.
4, DR agonist: can directly stimulate the dopamine receptor and play a role. At present, non-ergot DR agonists are commonly used in clinical practice. It is suitable for patients with early Parkinson's disease, and can also be combined with compound levodopa to treat patients with advanced stage. In young patients, MAO-B inhibitors or DR agonists are the first choice. Agonists should be started in small doses and gradually increased. The incidence of agonist symptom fluctuations and dyskinesia is low, but the incidence of orthostatic hypotension and psychiatric symptoms is higher. Common side effects include gastrointestinal symptoms, lethargy, hallucinations, etc. Non-ergot DR agonists include pramipexole, ropinirole, pirbedil, rotigotine, and apomorphine.
5. Compound levodopa (including levodopa / benzyrazide and levodopa / carbidopa): levodopa is a precursor of dopamine. Levodopa supplemented peripherally can pass through the blood-brain barrier and is converted into dopamine by decarboxylation of dopa decarboxylase in the brain, thus playing the role of alternative treatment. Benserazide and carbidopa are peripheral decarboxylase inhibitors, which can reduce the decarboxylation of levodopa in the periphery, increase the content of levodopa into the brain, and reduce its side effects.
It should start with a small dose and gradually increase the dose slowly until a satisfactory effect is obtained, not the full effect. Do not increase the dose too quickly, and do not increase it too much. Take the medication lh before or 1 and a half hours after a meal. Elderly patients can use it as soon as possible, younger than 65 years, especially young patients with Parkinson's disease should choose monoamine oxidase B inhibitors or dopamine receptor agonists. When the above drugs can not control the symptoms well, consider adding compound levodopa. Patients with active peptic ulcer should be used with caution, and narrow-angle glaucoma and psychiatric patients are prohibited.
6. Catechol-oxygen-methyltransferase (COMT) inhibitors: By inhibiting COMT enzymes, the metabolism of levodopa in the periphery is reduced, thereby increasing the content of levodopa in the brain. COMT inhibitors include entacapone and tocapone. In patients with Parkinson's disease, COMT inhibitors can be added to reduce the "off period" when symptoms fluctuate. Entacapone works at the same time as levodopa. The first dose of tocapone is taken with the compound levodopa, and it can be taken alone after 6 hours interval. The side effects of COMT inhibitors include diarrhea, headache, sweating, dry mouth, elevated aminotransferase, abdominal pain, yellowing of urine, etc. Tocapone may cause liver damage, and liver function must be closely monitored, especially during the first 3 months of medication.
Prevention and treatment of Parkinson's disease complications
1. Diagnosis and treatment of motor complications: Patients with intermediate and advanced Parkinson's disease may have motor complications, including fluctuations in symptoms and dyskinesias. Symptom fluctuations include wearing-off and on-off phenomena. Reduced efficacy refers to a reduction in the effective duration of each medication. The typical complaint of the patient at this time is "the drug is not working as before, the previous medication can last for 4 hours, and now the drug is overpowering for 2 hours." At this time, you can increase the number of daily medications or increase each medication. Dosage, or use extended release, or add other auxiliary drugs. The "on-off" phenomenon manifests itself as sudden inactivity and free movement, both of which alternate between minutes to tens of minutes. More common in patients with severe illness, the mechanism is unknown. The typical complaint of the patient at this time was "I can estimate the approximate time when the drug effect disappears after each dose of medication. I can estimate it now, it is not working, the effect is not there, it is sudden. Even when I think the drug effect should still be there, Will suddenly fail. " Once the "on-off" phenomenon occurs, handling is more difficult. Micropumps can be used for continuous infusion of levodopa methyl ester, ethyl ester or DR agonist.
Dyskinesia, also known as dyskinesia, is manifested as involuntary dance-like or dystonia-like movements of the head, face, limbs or trunk. The peak-dose dyskinesia occurs when the concentration of L-dopa reaches its peak. The typical complaint of the patient at this time is: "Every time the medicine is up, the body is not so hard and the movement is also It s coming, and the shaking is lighter, but the body will shake involuntarily and can't control it. Those who appear at the peak and end of the agent are called biphasic dyskinesia. At this time, the typical complaint of the patient is: "Every time the medicine starts to act and is about to fail, there will be involuntary shaking of the body." Foot or calf painful muscle spasm is called dystonia, and it usually occurs before taking the medicine in the morning. It is also a manifestation of dyskinesia. At this time, the typical complaint of the patient is: "I often come together in the morning and feel my feet touch the ground, can not relax, and sometimes feel pain." Dose peak dyskinesia can be reduced by each dose of levodopa, or by adding DR agonists or Amantadine treatment. Bipolar dyskinesia is difficult to control, and long-life DR agonists or COMT inhibitors can be added, or micropumps can be continuously infused with levodopa methyl ester, ethyl ester or DR agonist. Dystonia can be increased or decreased correspondingly to the dose of levodopa preparation according to its occurrence at the end of the dose or the peak of the dose.
2. Prevention of sports complications: The occurrence of sports complications is not only related to the long-term application of levodopa preparations, but also to the total amount of medication, the age of onset, and the course of the disease. The greater the total amount of medication, the longer the medication, the younger the age of onset, and the longer the course of disease, the more prone to motor complications. Both the age of onset and the course of disease are uncontrollable factors. Therefore, the optimization of levodopa treatment can delay the occurrence of motor complications as much as possible. New-onset patients prefer MAO-B inhibitors or DR agonists to delay the application of levodopa; levodopa should be started from a small dose and gradually increased; the symptoms can be controlled to meet the needs of daily life. These can delay the emergence of motor complications to some extent. However, it must be emphasized that treatment must be individualized, and levodopa preparations cannot be intentionally reduced or not used simply to delay the occurrence of motor complications.
Treatment of non-motor symptoms of Parkinson's disease
1. Treatment of mental disorders: Patients with Parkinson's disease may develop mental symptoms such as hallucinations, euphoria, and illusion in the later stages of the disease. Anti-PD drugs can also cause psychiatric symptoms, the most common being benzethonium hydrochloride and amantadine. Therefore, when patients develop psychiatric symptoms, first consider gradually reducing or discontinuing anticholinergic drugs, amantadine, selegiline, DR agonists, and compound levodopa. For those who are not adjusted by drugs or cannot stop anti-PD drugs due to severe symptoms, antipsychotic drugs such as clozapine and quetiapine can be added. Cholinesterase inhibitors such as huperzine A, donepezil, and carbaplatin can be added to PD patients with cognitive impairment.
2. Treatment of autonomic dysfunction: Patients with constipation can increase water intake and eat more fiber-rich foods. It can also reduce the dose of anticholinergic drugs or take laxatives. Patients with urinary disorders can reduce water intake after dinner, and can also try peripheral anticholinergic drugs such as oxybutynin and scopolamine. Patients with orthostatic hypotension should increase their salt and water intake. They can wear elastic stockings, and they can also use the alpha-adrenergic agonist Midojun.
3. Sleep Disorders: Patients with Parkinson's disease may experience sleep disturbances such as difficulty falling asleep, dreaming, awakening, and waking early. If the sleep disorder of PD is caused by the worsening of the disease at night, you can take a levodopa controlled release agent before going to bed at night. If patients have restless leg syndrome at night that affects sleep, DR agonists can be added before bedtime. If you can't improve your sleep after adjusting anti-PD drugs, sedative sleeping pills can be used. [4]
Parkinson's disease surgery
There are two main surgical methods, nucleus destruction and deep brain stimulation (DBS). The most common targets for nucleus destruction are the thalamic ventromedial nucleus (Vim) and the pallid ventral posterior part (PVP). Patients with tremor are more likely to choose the thalamic ventral nucleus, and those with stiffness are more likely to choose the back of the pale bulbum as the target. Destruction of the nucleus is low in cost and has a certain effect, so it is still used in some places. Deep brain electrical stimulation has been the first choice for surgical treatment because of its minimally invasive, safe and effective. Patients with Parkinson's disease have a significant decrease in efficacy or dyskinesias, and those who cannot be improved by medication adjustment can consider surgery. Surgery has a better effect on limb tremor and muscle rigidity, but has no significant improvement in central axis symptoms such as abnormal posture gait and dysphagia. Surgery, like medication, can only improve symptoms, not cure the disease, or prevent the disease from progressing. Drugs are still required after surgery, but the dose can be reduced. Patients with secondary Parkinson's syndrome and Parkinson's disease have no surgical treatment. In patients with early Parkinson's disease, patients with good drug treatment are not suitable for premature surgery.
Prognosis of Parkinson's disease
Parkinson's disease is a chronic progressive disease that is highly heterogeneous. Different patients have different rates of disease progression. There is currently no cure. Early patients can be well controlled by drug treatment. Although the drug still has a certain effect in the middle of the disease, the quality of life often decreases due to the occurrence of sports complications. In the late stage of the disease, the patient's response to the drug is poor, and the symptoms cannot be controlled. The patient can be stiff, unable to take care of himself, or even stay in bed for a long time, and eventually die of complications such as pneumonia.
Parkinson's disease prevention
There are currently no effective preventive measures to prevent the occurrence and progression of the disease. Dopaminergic neurons in substantia nigra die more than 50% and the DA content in the striatum decreases by more than 80% when clinical symptoms appear. Therefore, early detection of preclinical patients and effective prevention measures to prevent the degeneration of dopaminergic neurons can prevent the occurrence and progression of the disease. How to detect preclinical patients early has become one of the hot spots in the research field of Parkinson's disease. Gene mutations, as well as non-motor symptoms of PD such as rapid eye movement sleep disorder and hyposmia can occur years before motor symptoms appear. They may be early biological markers of PD. The accumulation of multiple biomarkers may increase the risk of developing PD. Protective drugs for dopaminergic neurons are currently under investigation. Epidemiological evidence suggests that drinking 3 cups of green tea a day can reduce the risk of Parkinson's disease. Vitamin E, coenzyme Q10, and fish oil may have certain protective effects on neurons.
Parkinson's disease care
There are no special dietary requirements for patients with Parkinson's disease. Patients taking levodopa preparations should be separated from meals and should be taken 1 hour before or 1 and a half hours after a meal. Patients with constipation should drink more water and eat more fiber-rich foods. Appropriate exercise can help patients recover. Recent studies have shown that Tai Chi is helpful for patients' balance function. Early patients can take care of themselves on a daily basis, and most patients need a certain amount of help in the middle. Patients in advanced stages need daily care. Nasal feeding diet can be given to patients with difficulty swallowing and coughing with drinking water. Long-term bedridden should be turned back and beat regularly to avoid bedsores and fallout pneumonia. Urinary incontinence needs urine catheterization.
