[Overview].
Parkinson’s disease (PD) was first described by Parkinson (1817) under the name of tremor paralysis agitans.PD is a common disease of the middle-aged and elderly characterized by degenerative loss of dopamine (DA)-ergic neurons in the substantia nigra and small Lewy bodies. neurodegenerative disease. The prevalence of the disease is between 10-405/100,000 in the world, and the prevalence is 44/100,000 in China, which is a low incidence area of Parkinson’s. The age of onset of PD is 20/100,000 for 0-39 years old, 1100/100,000 for 70-79 years old, and it is more common in 50-65 years old, and the prevalence is 1000/100,000 in people over 60 years old. The prevalence rate is 1000/100,000 in people over 60 years old and increases with age, with little difference in the distribution between the two sexes.
Etiology
The prevalence and incidence of PD increases with age, which is one of the risk factors for PD. This is one of the risk factors for PD. Among genetic factors, the family prevalence of PD patients is 7.5-94.5%, and many scholars now believe that PD is the result of the interaction between genetic susceptibility and environmental factors.
Clinical manifestations
The onset of PD is mostly seen after the age of 60, and occasionally in the 20s. The onset of the disease is insidious and develops slowly. The onset of symptoms varies from person to person. The first symptoms are tremor (60%-70%), followed by walking disorder (12%), myalgias (10%) and bradykinesia (10%). Symptoms often begin in one upper extremity and gradually spread to the ipsilateral lower extremity, contralateral upper extremity and lower extremity. The most common signs and symptoms are.
(a) tremor (trermor)
Typical is resting tremor, characterized by slow (3.5-7.0Hz), moderate amplitude or coarse tremor, present at rest, aggravated by emotional excitement, fatigue, tension, anxiety; stops when sleeping; decreases when intentional movement. Mostly started by the distal end of one upper limb, with less involvement of the lower jaw, lips, tongue and head.
(B) Rigidity
The difference between the increased muscle tone of the conus system is the increased elastic resistance to passive movements, involving both active and antagonistic muscles, and the resistance remains constant throughout the passive movements. Tonicity mainly affects the muscles of the trunk and proximal limbs and can appear early in the course of the lesion. Because the accompanying tremor causes periodic changes in muscle tone, cogwheelrigidity can be observed during passive movement of the limb.
(iii) Bradykinesia (motor retardation)
These movement disorders, either alone or in combination with myotonicity, cause multiple characteristic movement disorders and are the most important clinical manifestations that affect the patient’s ability to live and cause disability. Decreased spontaneous movements, such as lack of facial expressions and reduced transient movements, result in a “mask face”. Decreased joint movements, such as reduced or absent upper limb swing during walking. Decreased and slow voluntary movements are manifested by delayed and delayed initiation and braking of active intentional movements, as well as difficulty in initiation and slow movements. When writing, the words become smaller and smaller, showing the “writing too small sign”; shaving, washing, brushing teeth, tying shoelaces and buttons, putting on and taking off shoes, socks or pants, etc. are difficult. When walking, the gait is slow and sluggish, the pace becomes smaller and slower, and it is difficult to start, but once you step forward, you cannot stop or turn immediately, which is called “panic gait”. Salivation, monotone and low volume of speech (slow speech, even leading to speech nonsense) and swallowing difficulties are caused by muscle movement disorders of the mouth, tongue, palate and pharynx.
(iv) Loss of postural reflexes and balance disorders
Loss of postural reflexes causes the patient to lose the spontaneous ability to regulate balance during movement, so the patient often falls, and eventually the patient cannot stand alone. When sitting down from a standing position, the whole body falls and smashes into a chair, and the patient’s forward small steps and catching up with the center of gravity are in maintaining balance and avoiding falling. Abnormal postural fixation can affect the head, trunk, limbs or the whole body, resulting in an unstable position with the head tilted forward, trunk tilted forward or backward, and difficulty in staying upright and easy to fall when being pushed lightly.
(E) Other symptoms
Repeated tapping on the upper edge of the brow arch can induce frequent blinking (Myerson’s sign). In addition, depression, cognitive dysfunction, dementia, sleep abnormalities, pain, constipation, delayed urination, postural hypotension, seborrhea, hyperhidrosis, blepharospasm and, rarely, kinetic eye crisis may also be present. Late stage patients may develop visual hallucinations.
[Diagnostic points].
(A) The main basis for the diagnosis of PD
1. It is hereditary, but the cause is mostly unknown.
2. Most of them develop at the age of 40-69.
3.Most of them start from one side of resting tremor and gradually develop to bilateral, presenting three major symptoms of muscle rigidity, reduced movement and resting tremor, especially accompanied by postural reflex disorder.
4, Lipid pseudomask face, upper limb flexion with forward flexion posture, trunk forward when walking, small steps, and lack of joint movements.
5, limited to no comorbidities, no cone bundle sign, pseudobulbar palsy, nystagmus, ataxia, sensory impairment, myasthenia gravis, epilepsy, urinary incontinence, dementia, affective disorders and hallucinations and other symptoms outside of Parkinson’s syndrome.
6.The disease progresses slowly.
7. No special abnormalities in cerebrospinal fluid, blood biochemistry and electroencephalogram.
8.The application of levodopa is effective.
However, the diagnosis of PD should be noted that as long as other conditions are available, individual patients taking L-dopa is ineffective or the three major symptoms, which are not fully available or have psychiatric symptoms, should also be highly suspected of PD.
(II) Laboratory tests
Often no diagnostic value, the following tests are abnormal for reference.
1, cerebrospinal fluid DA metabolite of high vanillic acid (HVA) content is reduced.
2.Gene testing A few familial PD patients may find mutated genes.
3, imaging tests Routine CT or MRI may exclude other disorders and have differential diagnostic value.
(C) Differential diagnosis
This disease must be differentiated from idiopathic tremor and Parkinson’s syndrome of other etiologies.
Treatment plan and principles]
(I) Treatment principles
No special treatment is needed for mild symptoms. Patients should be encouraged to do more active exercises. If the disease affects the patient’s daily life and ability to work, drug therapy is required. Drug therapy should be started from small doses, slowly increasing, and try to achieve a more satisfactory effect with smaller doses; the treatment plan should be individualized, and specific drugs should be selected according to the patient’s age, symptom type, severity, occupation, etc. Publicize and educate patients that the disease cannot be cured at present, and is slowly progressive, requiring long-term cooperation and lifelong treatment.
(II) Drug treatment
l. Anticholinergic drugs have certain effect on tremor and tonicity, but are less effective on motor retardation, and are suitable for patients with prominent tremor and younger age. Commonly used drugs are: ① benzhexol (also known as Antan) 1~2mg, 3 times a day; ② benztropine (cogentin) l~2mg, 3 times a day. In addition, there are scopolamine, Biperiden (ankineton, akineton), etc., all with similar effects to Antan. The main side effects are dry mouth, blurred vision, constipation and difficulty in urination, and in severe cases, hallucinations and delusions. Glaucoma and prostatic hyperplasia patients are prohibited; because it can affect the memory function, so the elderly patients use with caution.
2, amantadine (arnantadine)
Mild improvement of hypokinesis, tonicity, tremor, dosage 100mg, twice daily. Side effects are less common, but may include restlessness, confusion, reticular cyanosis of the lower limbs, ankle edema, etc., but are less common. Use with caution in patients with renal insufficiency, epilepsy, severe gastric ulcer, liver disease, and contraindicated in nursing mothers.
3. Levodopa
Because the amount of levodopa that can cross the blood-brain barrier is limited, in order to improve the efficacy and reduce adverse effects, compound levodopa preparations should be used, including medopa (madopar). In order to improve the efficacy and reduce the adverse effects, compounded levodopa formulations should be used, including madopar and sinemet, of which madopar is available in standard, extended-release and shake-out formulations; only sinemet is available in China in controlled-release form.
The initial dose is 25mg, 2-3 times a day, and the dose is increased gradually according to the condition until the efficacy is satisfactory and no side effects occur, generally the effective dose is 125-250mg, 3 times a day, 1 hour before or 1½ hours after meal on an empty stomach. Adverse reactions are peripheral and central, the former is nausea, vomiting, hypotension, cardiac arrhythmia (occasionally); the latter has symptom fluctuation, isokinetic disorder (also known as movement disorder) and psychiatric symptoms. It is contraindicated in patients with narrow-angle glaucoma and psychiatric disorders, and should be used with caution in patients with active peptic ulcers.
Symptom fluctuations and dyskinesia are common long-term complications that occur after 5 to 7 years of drug use. Symptom fluctuations mainly include: ①wearing-off or end of dosedeterioration, which can be treated by increasing the number of daily doses, or increasing the dose per dose, or switching to extended-release agents, or adding other adjuvant drugs. ② “on-offphenomenon”: dopaminergic (DA) agonists can be tried.
The main symptoms are: ①Dose peak anisocoria: it occurs at the peak of blood concentration (NN1~2 hours), reducing the single dose of levodopa can reduce the anisocoria, and patients with advanced disease need to add DA agonists. ②Biphasic dyskinesia: It can occur at the beginning and at the end of the dose. Try to increase the dose and number of doses of compound levodopa per dose, or add DA agonist. Dystonia: often manifested as painful muscle spasms in the feet or calves, mostly occurring in the early morning before dosing, can be treated with levodopa control release or long-acting DA agonist at bedtime, or shake-type medroxyprogesterone or standard tablets before waking up; dystonia occurring at the end of the dose or at the peak of the dose can be increased or decreased accordingly.
Psychiatric symptoms can take various forms, such as vivid dreams, depression, anxiety, delusions, hallucinations, euphoria, light mania, confusion, and confusion. For severe hallucinations, mental confusion and blurred consciousness that are not effectively adjusted by drugs, the antipsychotic drugs clozapine or olanzapine can be added.
4.DA receptor agonist
It is generally advocated to be used in combination with compound levodopa, and can be applied alone in early patients with mild age of onset. They should be used in small doses and gradually increase the dose until satisfactory efficacy is achieved without side effects. The side effects are similar to compound levodopa, except that the incidence of symptom fluctuation and allodynia is low, while the incidence of postural hypotension and psychiatric symptoms is high. Commonly used DA agonists are: ① bromocriptine (bromocriptine): 0.625mg, twice daily, 0.625mg every 3-7 days, dose 7.5~15mg/d, maximum not more than 20mg/d. ② pergolide (pergolide): initial dose 0.025mg, once daily, increase every 3~5 days 0.025mg, gradually increase the dose, the general effective dose is 0.75–1.5mg daily, divided into 3 oral doses. ③Taishuoda extended-release tablets (trastalSR): initial dose of 50mg, 1, times daily, increased by 50mg every week, the general therapeutic dose is 150-250mg, divided into 37 ow orally. Other drugs are: cripar (cripar), cabergoline (cabergoline), pramipexole (pramipexole), ropinirole (ropinirole), ergot acetonide (1isuride), apomorphine (apomorphine), domestic drug-free.
5.Monoamine oxidase B (MAO-B) inhibitors
Propargyl amphetamine (deprenyl, selegiline) and compound levodopa together have a synergistic effect, and combined with high-dose vitamin E can be used as a neuroprotective agent in patients with early mild disease. The dosage is 2.5-5mg twice daily, preferably taken in the morning and noon, and should not be applied after evening to avoid causing insomnia. Side effects include dry mouth, loss of appetite, postural hypotension, etc. It should be used with caution in patients with gastric ulcer and should not be used in combination with SSRI.
6.Catechol a oxygen position a methyltransferase (COMT) inhibitors
entacapone (ketan, comtan) can be used in combination with levodopa to enhance the latter’s efficacy, but it is not effective when used alone. The effective dose is 100-200 mg in VI 3-4 times daily. Side effects include diarrhea, headache, excessive sweating, mouth in, elevated aminotransferases, abdominal pain, lighter urine color, etc. tolcapone (answer is beauty, tasmar) is not recommended due to severe cases of fatal liver toxicity.
(C) surgical treatment
Surgical treatment of Parkinson’s disease mainly includes deep brain stimulation (Deep Brain Stimulation
(DBS) and stereotactic deep brain nucleus disruption, commonly used are subthalamic nucleus
Deep Brain Stimulation (DBS) of the STN, Vim nucleus, GPi disruption or stimulation, is commonly used in patients who have failed medication, are intolerant, or are experiencing allodynia. Destructive surgery can usually only be done unilaterally in symptomatic patients at a time; for patients with symptoms bilaterally or combined with midline symptoms, DBS surgery is preferred for better results; destructive surgery is more effective in younger, unilateral tremor and myotonia dominant patients; either DBS or destructive surgery generally still requires postoperative medication, but the amount of medication used can usually be significantly reduced.
Indications and contraindications for surgery: The indications for surgery in Parkinson’s disease are generally long-term drug therapy is ineffective; the disease has progressed slowly for more than three years; the ability to work and live is significantly limited, according to Hoehn and Yahr classification of II-IV patients, and there is no contraindication to the following surgery, such as the elderly and frail, severe joint contractures, patients with significant mental disorders, severe heart, liver, kidney and brain Patients with arteriosclerosis can be treated surgically. There is no absolute age limit.
(iv) Rehabilitation treatment
Exercises for voice intonation, facial muscles, limbs and trunk, gait and postural balance can be performed.