20 18, 1 1, National Health Commission and other five departments jointly formulated the first list of rare diseases, and Parkinson's disease was included in it.
Parkinson's disease
Public site: head
Infectious: non-infectious
Scientific name of western medicine: Parkinson's disease
Department: Internal Medicine-Neurology Department
Is it covered by medical insurance? Yes.
The exact cause of Parkinson's disease is still unknown. Genetic factors, environmental factors, aging and oxidative stress may all participate in the degeneration and death of PD dopaminergic neurons.
age
The incidence and prevalence of Parkinson's disease increase with age. PD usually occurs over 60 years old, suggesting that aging is related to the onset. The data show that dopaminergic neurons in substantia nigra of normal adults will gradually decrease with age. However, the prevalence of PD in the elderly over 65 years old is not high, so aging is only one of the risk factors of PD.
hereditary factor
The role of genetic factors in the pathogenesis of Parkinson's disease has attracted more and more attention from scholars. Since the discovery of the first Parkinson's disease-causing gene α -synuclein (PARK 1) in the late 1990s, at least six genes have been associated with familial Parkinson's disease. But only 5 ~ 10% of Parkinson's disease has a family history, and most of them are sporadic cases. Genetic factors are only one of the factors of PD.
environmental factor
In 1980s, American scholar Langston and others found that some drug addicts would have typical Parkinson's disease-like symptoms soon, and levodopa preparation was effective. It was found that the synthetic heroin used by drug addicts contained a neurotoxic substance 1- methyl -4 phenyl-1, 2,3,6-tetrahydropyridine (MPTP). This substance is transformed into highly toxic 1- methyl -4- phenylpyridine ion MPP+ in the brain, which selectively enters dopaminergic neurons in substantia nigra, inhibits the activity of mitochondrial respiratory chain complex I, promotes oxidative stress, and leads to degeneration and death of dopaminergic neurons. Therefore, scholars suggest that mitochondrial dysfunction may be one of the pathogenic factors of PD. In the follow-up study, it was also confirmed that the activity of mitochondrial respiratory chain complex I in patients with primary PD decreased selectively in substantia nigra. Some herbicides and pesticides are similar in chemical structure to MPTP. With the discovery of MPTP, people realize that some chemicals similar to MPTP in the environment may be one of the pathogenic factors of PD. However, only a few drug addicts exposed to MPTP will get sick, which indicates that PD may be the result of a combination of many factors.
other
In addition to aging and genetic factors, brain trauma, smoking and drinking coffee may also increase or decrease the risk of Parkinson's disease. Smoking is negatively correlated with the occurrence of Parkinson's disease, which has reached a consistent conclusion in many studies. Caffeine has a similar protective effect. Severe brain injury may increase the risk of Parkinson's disease.
In a word, Parkinson's disease may be the result of multiple genes and environmental factors.
Principles of treatment
1, comprehensive treatment: drug therapy is the most important treatment for Parkinson's disease. Levodopa preparation is still the most effective drug. Surgical treatment is an effective supplement to drug treatment. Rehabilitation, psychotherapy and good nursing can also improve symptoms to some extent. At present, the main treatment is to improve symptoms, but it can't stop the progress of the disease.
2, medication principle: medication should be gradually increased from a small dose. Satisfactory curative effect can be achieved with a small dose, not seeking full effect. While following the general principles of drug use, individualization should be emphasized. According to the patient's condition, age, occupation and economic conditions, the best treatment scheme is adopted. Drug treatment should not only control symptoms, but also try to avoid the side effects of drugs, and try to control the clinical symptoms of patients for a long time from a long-term perspective.
medicine
1. Protective treatment: In principle, once Parkinson's disease is diagnosed, protective treatment should be given as soon as possible. At present, monoamine oxidase B (MAO-B) inhibitors are the main drugs used in clinical protective treatment. In recent years, some studies have shown that MAO-B inhibitors may delay the progress of the disease, but there is no conclusion at present.
2. Symptomatic treatment
Early treatment (Hoehn-Yahr l~II grade)
(1) When to start medication: When the illness is mild in the early stage and has no obvious influence on daily life or work, the medication can be suspended. If the disease affects the patient's daily life or work ability, or the patient requires early control of symptoms, symptomatic treatment should be started.
(2) the principle of drug selection:
Mid-term treatment (Hoehn-Yahrⅲ Ⅲ)
Patients who are treated with DR agonists, MAO-B inhibitors or amantadine/anticholinergic drugs for the first time in the early stage should be treated with compound levodopa when the symptoms cannot be well controlled by the original drugs. Patients treated with low-dose compound levodopa in the early stage should increase the dose or add DR agonist, MAO-B inhibitor, amantadine or COMT inhibitor when the symptoms in the middle stage are not well controlled.
Late treatment (Hoehn-Yahr IV-V grade)
Due to the progress of the disease itself and the occurrence of motor complications, the treatment of advanced patients is relatively complicated and difficult to deal with. Therefore, at the beginning of treatment, a reasonable treatment plan should be formulated according to the actual situation of patients, so as to delay the occurrence of sports complications as much as possible and extend the time window for effective treatment of patients.
Commonly used therapeutic drugs
1, anticholinergic drugs: mainly by inhibiting the activity of acetylcholine in the brain, the effect of dopamine is correspondingly improved. The commonly used drug in clinic is trihexyphenidyl hydrochloride. In addition, there are Kemajun, phenytoin, scopolamine and so on. Mainly suitable for patients with obvious tremor and younger age. Use with caution in elderly patients, and it is forbidden in patients with narrow-angle glaucoma and prostatic hypertrophy.
2. Amantadine: It can promote the synthesis and release of dopamine from nerve endings and prevent its reabsorption. It can slightly improve hyperactivity, 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, the degradation of dopamine is blocked, and the dopamine content is relatively increased, thus achieving the therapeutic purpose. MAO-B inhibitors can be used as monotherapy for newly diagnosed and young patients with Parkinson's disease, and can also be used as adjuvant drugs for the treatment of advanced patients with compound levodopa. It may have neuroprotective effect, so early use is recommended in principle. MAO-B inhibitors include selegiline and rasagiline. It is easy to cause insomnia when used at night, so it is recommended to take it in the morning and in the middle. Patients with gastric ulcer should use it with caution, and it is forbidden to use it with 5- hydroxytryptamine reuptake inhibitor (SSRI).
4.DR agonist: It can directly stimulate dopamine receptors and play a role. At present, non-ergot receptor agonists are commonly used in clinic. It is suitable for patients with early Parkinson's disease, and can also be combined with compound levodopa to treat patients with advanced Parkinson's disease. MAO-B inhibitor or DR agonist is the first choice for young patients in the early stage of the disease. Excitators should start with small doses and gradually increase. The incidence of symptom fluctuation and dyskinesia is low, but the incidence of postural hypotension and mental symptoms is high. Common side effects include gastrointestinal symptoms, drowsiness, hallucinations and so on. Non-ergot receptor agonists include pramipexole, ropinirole, piribedil, rotigotine and apomorphine.
5. Compound levodopa (including levodopa/benserazide and levodopa/carbidopa): levodopa is the precursor of dopamine. Peripheral levodopa can be decarboxylated into dopamine by dopa decarboxylase in the brain through the blood-brain barrier, thus playing the role of substitution therapy. Benserazide and carbidopa are peripheral decarboxylase inhibitors, which can reduce the decarboxylation of levodopa in the periphery, increase the content of levodopa in the brain and reduce its peripheral side effects.
We should start with a small dose and gradually increase the dose until we achieve satisfactory curative effect, not seeking full effect. The dose should not be increased too quickly, and the dose should not be too large. Take the medicine before meals 1h or after meals 1.5 hours. Elderly patients, younger than 65 years old, should use it as soon as possible, especially young patients with Parkinson's disease. Monoamine oxidase B inhibitor or dopamine receptor agonist should be selected first. When the above drugs can't control the symptoms well, compound levodopa should be considered. Use it with caution in patients with active digestive tract ulcer, and it is forbidden in patients with narrow-angle glaucoma and mental illness.
6. Catechol O-methyltransferase (COMT) inhibitor: By inhibiting COMT enzyme, the metabolism of levodopa in the periphery is reduced, thereby increasing the content of levodopa in the brain. COMT inhibitors include entacapone and Topca Peng. When symptoms fluctuate, COMT inhibitors can be added to patients with Parkinson's disease to reduce the "intermittent period". Entacapone needs to be taken with levodopa to be effective. The first dose of Topca Peng is taken together with compound levodopa, and then taken at intervals of 6 hours, which can be used alone. The side effects of COMT inhibitors include diarrhea, headache, hyperhidrosis, dry mouth, elevated transaminase, abdominal pain, yellow urine color and so on. Tocapone may cause liver function damage, so it is necessary to closely monitor liver function, especially in the first 3 months.
Prevention and treatment of complications
1. Diagnosis and treatment of motor complications: Patients with advanced Parkinson's disease may have motor complications, including symptom fluctuation and dyskinesia. Motor fluctuation includes wear and on-off phenomenon. The decline in curative effect means that the effective action time of each drug is shortened. The typical complaint of patients at this time is "the medicine is not as good as before." It used to be 4 hours, and now 2 hours is too strong. " At this time, you can increase the frequency of taking medicine every day or increase the dosage of each drug, or switch to sustained-release agents or add other auxiliary drugs. The phenomenon of "on-off" is characterized by sudden immobility and sudden free movement, which appear alternately in a few minutes to dozens of minutes. More common in critically ill patients, the mechanism is unknown. The patient's typical complaint at this time is "in the past, the time when the efficacy disappeared could be estimated after each medication, but now it is not working, and the efficacy is gone, which is very sudden." Even if you think the drug should still be there, it will suddenly fail. "once the' switch' phenomenon occurs, it is difficult to deal with. Micro-pump can be used for continuous infusion of levodopa methyl ester, ethyl ester or DR agonist.
Dyskinesia, also known as dyskinesia, is characterized by involuntary dance-like or dystonia-like movements of the head, face, limbs or trunk. When the blood concentration of levodopa reaches the peak, peak dose dyskinesia occurs. At this time, the patient's typical complaint is: "Every time the medicine comes up, the body is not so hard, moving fast and shaking lightly, but the body will shake involuntarily and can't control it." Is it called bipolar disorder that both the drug peak and the drug end appear? [6-7]。 At this point, the patient's typical complaint is: "Every time the drug takes effect and is about to fail, there will be involuntary shaking of the body." Painful muscle spasm in the foot or calf is called dystonia, which usually occurs before taking medicine in the morning and is also a manifestation of dyskinesia. At this time, the patient's typical complaint is: "I often feel that my feet are on the ground in the morning, I can't relax, and sometimes I feel pain." Peak shift can be treated by reducing the dose of levodopa each time or adding DR agonist or amantadine. Biphasic dyskinesia is difficult to control, so long half-life DR agonist or COMT inhibitor can be added, or levodopa methyl ester, ethyl ester or DR agonist can be continuously infused by micropump. Dystonia can increase or decrease the dosage of levodopa preparation according to whether it occurs at the end or peak of preparation.
2. Prevention of sports complications: The occurrence of sports complications is not only related to the long-term use of levodopa, but also closely related to the total drug use, onset age and course of disease. The greater the total dose, the longer the medication time, the younger the onset age and the longer the course of disease, the more likely it is to have sports complications. Age of onset and course of disease are uncontrollable factors. By optimizing the treatment scheme of levodopa, the occurrence of sports complications can be delayed as much as possible. MAO-B inhibitor or DR agonist is the first choice for new patients to delay the application of levodopa. Levodopa should start from a small dose and gradually increase; The control of symptoms can meet the needs of daily life, but it is not all effective; All these can delay the occurrence of sports complications to some extent. However, it should be emphasized that the treatment must be individualized, and levodopa preparation should not be deliberately reduced or not used in order to delay the occurrence of sports complications.
Treatment of non-motor symptoms
1. Treatment of mental disorders: Patients with Parkinson's disease may have mental symptoms in the late stage of the disease, such as hallucinations, euphoria and delusions. Moreover, anti-PD drugs can also cause mental symptoms, and the most common ones are trihexyphenidyl hydrochloride and amantadine. Therefore, when patients have mental symptoms, we should first consider gradually reducing or stopping anticholinergic drugs, amantadine, selegiline, DR agonists and compound levodopa. Antipsychotic drugs, such as clozapine and quetiapine, can be used to adjust patients who are ineffective or unable to stop taking drugs because of serious symptoms. PD patients with cognitive impairment can be added with cholinesterase inhibitors, such as huperzine A, donepezil and carbazide.
2. Treatment of autonomic nervous dysfunction: Constipation patients can increase drinking water and eat more fiber-rich foods. At the same time, you can also reduce the dose of anticholinergic drugs or take laxatives. Patients with urinary system diseases can reduce the amount of drinking water after meals, and also try peripheral anticholinergic drugs such as oxybutynin and scopolamine. Patients with postural hypotension should increase the intake of salt and water, wear elastic socks and add α -adrenergic agonist Midodrine.
3、? Sleep disorders: Patients with Parkinson's disease may have sleep disorders such as difficulty in falling asleep, dreaminess, easy awakening and early awakening. If the sleep disorder of PD is caused by the aggravation of illness at night, levodopa controlled release agent can be added before going to bed at night. If the patient has restless leg syndrome at night, which affects sleep, DR agonist can be added before going to bed. If you can't improve your sleep after adjusting anti-PD drugs, you can choose sedative sleeping pills.
Surgical therapy
There are two main surgical methods: nucleus pulposus removal and deep brain stimulation (DBS). The common targets of nucleus pulposus destruction are ventral intermediate nucleus of thalamus (Vim) and ventral posterior part of globus pallidus (PVP). Patients with tremor mainly choose the ventral intermediate nucleus of thalamus, while those with rigidity mainly choose the ventral posterior part of globus pallidus as the target. Nucleus pulposus removal has low cost and certain curative effect, so it is still used in some places. Deep brain electrical stimulation has become the first choice for surgical treatment because of its minimally invasive, safe and effective. If the curative effect of Parkinson's disease patients is obviously reduced or dyskinesia occurs, and the symptoms cannot be improved well after adjusting the drugs, surgical treatment may be considered. Surgery has a good effect on limb tremor and myotonia, but it has no obvious improvement on axial symptoms such as abnormal posture and gait and dysphagia. Surgery, like medication, can only improve symptoms, but can't cure the disease, and can't stop the progress of the disease. Medication is still needed after operation, but the dose can be reduced. Patients with secondary Parkinson's syndrome and Parkinson's superposition syndrome are ineffective in surgical treatment. Patients with early Parkinson's disease and patients with good drug treatment effect are not suitable for premature surgery.
Traditional therapy in China
Traditional Chinese medicine, acupuncture and other treatments can play a positive role in improving symptoms, but they need to go to regular medical institutions and be treated under the guidance of professional doctors.