Parkinson's Disease

Introduction to Parkinson's disease Parkinson's disease, also known as idiopathic Parkinson's disease (PD), referred to as Parkinson disease, also known as paralysis agitation (paralysisagitans, shakingpalsy), is a common neurodegenerative disease in the elderly, is also the most middle-aged and elderly Common extrapyramidal diseases, the main lesions in the substantia nigra and striatum pathway, and decreased dopamine production. The prevalence rate of people over 65 years old is 1000/100,000. With age, men are slightly more than women. The main clinical features of the disease: resting tremor, slow movement and reduction, increased muscle tone, posture instability. basic knowledge The proportion of illness: 0.002% Susceptible population: 40 to 70 years old, the incidence increased after 60 years old. Mode of infection: non-infectious Complications: depression, sleep disorders

Causes of Parkinson's disease

Family heredity (35%):

In the long-term practice, medical scientists have found that Parkinson's disease seems to have a tendency to family aggregation. The family members of patients with Parkinson's disease have a higher incidence than their normal counterparts. The etiology of idiopathic Parkinson's disease has not been known so far. Some central nervous system degenerative diseases with Parkinson's disease symptoms are mainly characterized by degeneration of different parts of the central nervous system. There are other clinical features, so it can be called symptomatic. Parkinson's disease, such as progressive supranuclear palsy (PSP), striatum substantia nigra (SND), Shy-Drager syndrome (SDS) and oligopontocerebellar atrophy (OPCA), and some diseases or factors can be produced Similar to the clinical symptoms of PD, the disease is caused by infection, drugs (dopamine receptor blockers, etc.), poisons (MPTP, carbon monoxide, manganese, etc.), vascular (multiple cerebral infarction) and brain trauma, etc. Parkinson's syndrome (Palkinsonism).

Ageing (25%):

Parkinson mainly occurs in middle-aged and elderly people. It is rare before 40 years old, suggesting that aging is related to the disease. The study found that after 30 years old, dopaminergic neurons, tyrosine oxidase and dopa decarboxylase activity, striate The level of dopaminergic transmitters gradually decreases with age. However, only a few elderly people suffer from this disease, indicating that physiological dopaminergic neurons are not enough to cause disease. Ageing is only a trigger for the onset of this disease.

Environmental factors (5%):

Epidemiological investigations have found that there are regional differences in the prevalence of Parkinson's disease, so people suspect that there may be some toxic substances in the environment that damage the brain's neurons. Genetic susceptibility. Al53THr mutation in a common nuclear gene has been found in patients with familial Parkinson's disease in recent years, but has not been confirmed many times in the future.

It is generally believed that Parkinson's is not a single factor, and multiple factors may be involved. Genetic factors may increase the susceptibility to disease, only through interaction with environmental factors and aging, through oxidative stress, mitochondrial failure, and calcium overload. Excitatory amino acid toxicity, apoptosis, immune abnormalities and other mechanisms lead to the loss of a large number of substantia nigra dopaminergic neurons.

Pathological change

The main lesion of PD is degeneration of pigment-containing neurons, and the DA neurons of the substantia nigra pars compacta are most prominent. Under the microscope, the nerve cells are reduced, the melanocytes of the substantia nigra disappear, and the melanin particles are scattered in tissues and macrophages, with different Degree of gliosis, normal human nigral cells decrease with age, black matter cells from the original 425,000 to 200,000 at the age of 80, less than 100,000 PD patients, DA neurons can be lost when symptoms appear More than 50%, blue spot, middle nucleus, vagus nerve dorsal nucleus, globus pallidus, putamen, caudate nucleus and subthalamic nucleus can also be slightly altered.

1. The appearance of eosinophilic inclusion body in the cytoplasm of residual neurons is the important pathological feature of this disease. Lewy body is a glass-like mass composed of cytoplasmic proteins with a dense core in the center and filaments around it. Halo, a cell can sometimes be seen in a number of different sizes of Lewy bodies, seen in about 10% of residual cells, substantia nigra, globus, striatum and blue spots are also visible, alpha-synuclein and ubiquitin It is an important component of Lewy's body.

2. Neurochemical changes: DA and acetylcholine (Ach) act as two important neurotransmitters in the striatum, and their functions are mutually antagonistic. Maintaining the balance between the two plays an important role in regulating the activity of the basal ganglia. The DA transmitter pathway in the brain is mainly The substantia nigra-striate system, the DA-derived neurons of the substantia nigra pars compacta can take L-tyrosine from the bloodstream and form levodopa (L-dopa) under the action of intracellular tyrosine hydroxylase (TH). Dopamine decarboxylase (DDC) acts to form dopamine (DA), which passes through the substantia nigra-striatum bundle, DA acts on the putamen, caudate nucleus synaptic neurons, and finally decomposes into high vanillic acid (HVA).

3, due to the reduction of TH and DDC in idiopathic Parkinson's disease, the DA production is reduced (L-dopa is reduced by L-tyrosine, DA production is reduced), and monoamine oxidase B (MAO-B) inhibitor can reduce DA decomposition in neurons. Metabolism, increased DA content in the brain, catechol-oxygen-methyltransferase (COMT) inhibitors can reduce the peripheral metabolism of L-dopa and maintain the stable plasma concentration of L-dopa.

4, PD patients with substantia nigra DA can be degenerated, the degeneration of the nigrostriatal striatum DA pathway, the striatum DA content is significantly reduced (> 80%), making the Ach system function relatively hyperactive, leading to increased muscle tone, action In order to reduce the biochemical basis of other motor symptoms, the DA content in the midbrain-marginal system and the midbrain-cortex system has also been significantly reduced in recent years, which may lead to high-grade neurological activity disorder such as mental decline, behavioral emotional abnormalities, speech disorder, and DA transmitter reduction. The patient's symptom severity is consistent, the early rate of disease increases through DA (pre-synaptic compensation) and DA receptor hypersensitivity (post-synaptic compensation), clinical symptoms may not be obvious (compensatory period), with disease Progressive typical PD symptoms (decompensation), basal ganglia other transmitters or neuropeptides such as norepinephrine (NE), serotonin (5-HT), substance P (SP), enkephalin (ENK) ), somatostatin (SS) also changed.

Parkinson's disease prevention

Primary prevention (no disease prevention)

1. For those with family history of Parkinson's disease and related gene carriers, those who are exposed to toxic chemicals should be regarded as high-risk groups. They should be closely monitored for follow-up, regular physical examination, and strengthen health education and self-protection.

2. Increase the environmental protection of industrial and agricultural production, reduce the emission of harmful gases, sewage and dirt, and strengthen labor protection for hazardous workers.

3. Improve drinking water facilities in rural areas and towns, protect water resources, reduce pollution of river water, reservoir water, pond water and well water, and ensure that the broad masses of the people can drink safe and healthy drinking water.

4, the elderly with caution phenothiazines, reserpine and butyrylbenzene drugs.

5, pay attention to the prevention and treatment of senile diseases (hypertension, hyperlipemia, hyperglycemia, cerebral arteriosclerosis, etc.), enhance physical fitness, delay aging, prevent atherosclerosis, and play a positive role in the prevention of Parkinson's disease.

Secondary prevention (early detection, early diagnosis, early treatment)

1, early diagnosis, Parkinson's disease sub-clinical period, if early can carry out preclinical diagnostic techniques, such as olfactory dysfunction, PET scan, mitochondrial DNA, dopamine antibody, cerebrospinal fluid chemistry, electrophysiology, etc., will be subclinical Early detection of Parkinson's disease, treatment with neuroprotective agents (such as vitamin E, SOD, glutathione and glutathione peroxidase, neurotrophic factor, selagiline) may delay the entire clinical process.

2. In the early stage of Parkinson's disease, although the nigral and striatum nerve cells decreased, the dopamine secretion increased compensatoryly. At this time, the dopamine content in the brain was not significantly reduced, which was called compensation period, and generally did not advocate drug treatment. Physiotherapy, medical sports, Tai Chi, spa, massage, Qigong, acupuncture and other treatments can be used to maintain daily general work and life, and to delay the application of anti-shock palsy drugs, but some people advocate early application of low-dose levodopa. Reduce complications, which are treated with drugs for different people.

Tertiary prevention (delaying the development of the disease, preventing sickness and improving the quality of life)

1. Actively carry out non-drugs such as physical therapy, physical therapy, acupuncture, massage, etc., as well as comprehensive treatments such as Chinese and Western medicines or surgery to delay the development of the disease.

2, pay attention to psychological counseling and spiritual care, to ensure adequate sleep, to avoid emotional stress, to reduce the predisposing factors of increased muscle tremor.

3. Actively encourage patients to take active actions, such as eating, dressing, washing, etc. Those with language problems can work hard to practice pronunciation in the mirror, strengthen joints, muscle activity and labor training, and maintain limb movement function as much as possible. Prevent wrestling and limb malformation.

4, long-term bedridden, should strengthen life care, pay attention to cleanliness, diligently turn over the back, prevent complications such as hypostatic pneumonia and acne infection, Parkinson's disease mostly died in the lungs or other systems such as urinary system infections Pay attention to diet and nutrition, if necessary, give nasal feeding, keep the urine and urine smooth, to continuously enhance physical fitness, improve immune function and reduce mortality.

Parkinson's disease complications Complications, depression, sleep disorders

Can be associated with symptoms of autonomic dysfunction, such as sweating, sebaceous gland secretion and greasy, saliva and more sticky, fear of heat and cold, urinary dripping, dry stool, a few cases may have lower extremity edema. Most patients are also associated with high-grade neurological disorders such as dementia, depression, loss of libido, sleep disorders, anorexia, and pain in the body.

Symptoms of Parkinson's disease Common symptoms Limb involuntary tremor dysfunction sensation of limb tremor gaze stagnation cerebellar signs gait abnormal functional tremor cheeks obvious invagination joint pain depression

1, preclinical symptoms

The earliest preclinical symptoms were only reported by Fletcher (1973) and others, but the symptoms they raised have not yet received attention. These symptoms mainly include the following two aspects:

(1) Paresthesia: mainly manifested as numbness, tingling, ant feeling and burning sensation at the joints of the affected limbs, mainly in the wrist and sputum, beginning with intermittent or migratory, and the later performance is fixed. Sexual, conventional neurological examination showed no obvious objective dysfunction. Electrophysiological examination revealed the somatosensory evoked potential (SEP) of some cases, especially the latency and conduction time of the lower limbs. By the early 1990s, we had 150 patients. A retrospective survey revealed that all patients experienced sensory abnormalities of the limbs before the onset of clinical symptoms of PD, and this abnormality persisted, but it was not parallel with dyskinesia. Electrophysiological examination was mainly somatosensory, cortex. The evoked potentials have a central delay and conduction delay and an extended latency.

(2) Restless limbs and easy fatigue: In addition to subjective sensory abnormalities, about 1/2 of the patients experienced the discomfort of acid, swelling, numbness or pain that is difficult to describe in the early stage, and this discomfort is mostly tired. After the break occurs or is obvious, after knocking, it can be relieved after beating, and the performance of the like restless leg syndrome. In addition, the suffering of some patients is prone to fatigue, especially the wrist, shoulder and lower limbs of the upper limb. The ankle joint and knee joint, when tired, these parts can be found in small tremors that are difficult to find. It is effective to take general analgesics at the beginning of these symptoms, and it has no effect after several months. Efficacy.

2, clinical symptoms

There were significant individual differences in the first symptom. There were 85% of subjective sensory abnormalities reported, 85% of tremors, 19.7% of muscle stiffness or slow motion, 12.6% of dysfunctional and/or writing disorders, and 11.5% of gait disorders. Muscle pain and pain were 8.2%, mental disorders such as depression and anxiety were 4.4%, language impairment was 3.8%, general malaise or muscle weakness was 2.7%, and drooling and mask face were 1.6% each.

(1) Static tremor: often the first symptom of PD, a small number of patients, especially those over 70 years old, may not have tremor, the mechanism is caused by the regularity of the affected muscle group and antagonistic muscle group, alternating inconsistent activities, Early manifestations often occur at the distal end of the limb, starting at one side. The tremor of the upper extremity is common. Some patients start at the knee of the lower extremity. When accompanied by a rotating component, the thumb may appear, indicating the tremor of the pill. The tremor frequency is generally 4 to 8 Hz. It occurs when it is still. It stops when it is vigorously moved. It is intensified when it is nervous. It disappears during sleep. After several years, it affects the upper and lower limbs or the opposite side. In severe cases, the head, jaw, and lips can appear. The tongue, throat, and limb tremors, such as a fist or a loose fist on the side of the patient's activity, can cause tremors on the other side of the limb. This test helps to detect early mild tremors. In addition to late tremor, some patients can be combined. Action or posture tremor.

(2) muscular rigidity: myotonia is one of the main symptoms of PD, mainly due to the increased balance of active muscles and antagonist muscles. If it is always present in passive exercise, it is called lead tube. "Strength or tension", if accompanied by tremor, can feel a gear-like feeling when passively moving, it is called "gear-like rigidity or tension", muscle stiffness occurs in the affected side of the wrist, sputum, especially patients After exertion, the gentle passive wrist, the ankle joint can feel the increase of the gear-like muscle tension, due to the increase of muscle tension, can bring a series of abnormal symptoms, such as blinking, chewing, swallowing, walking, etc. .

The following clinical trials have helped to detect mild muscle rigidity: 1 to allow the patient to exercise the contralateral limbs, and the limbs of the tested limbs may be more pronounced. 2 head dropping test: The patient is in the supine position, and the head often falls slowly when the head pillow is quickly removed, rather than falling quickly. 3 Let the patient put the elbows on the table, make the forearms perpendicular to the tabletop, and relax the arms and wrist muscles as much as possible. Normally, the wrist and the forearm are about 90° flexed, and the PD patients have more or less wrists. Keeping it straight, if it is erected, it is called road sign phenomenon. In elderly patients, muscle rigidity causes joint pain, which is caused by increased muscle tension and blocked blood supply to the joint.

(3) bradykinesia: manifested in the reduction of voluntary movements, including difficulty in initial movement and slowness of movement, due to increased muscle tone, posture reflex disorder, a series of characteristic dyskinesia symptoms, such as getting up, turning over, walking and changing direction Slow, facial muscle activity is reduced, often binocular gaze, blinking reduction, masked face, finger fine movements such as button buttons, laces and other difficulties, writing more and less words, writing a small sign ( Micrographia) et al.

The movement of PD patients is slow or can not be the main cause of disability. In the past, it was thought that the movement of PD could not be caused by muscle rigidity. In fact, there is no causal relationship between the two. It has been proved that the movement of PD is reduced and cannot be a very Complex symptoms, which are mainly related to the function of the subcortical extrapyramidal drive or the action of the extrapyramidal descending motion activation device, because the symptoms of myotonia are significantly improved after surgery for patients who cannot exercise, but the frequency of exercise is not Consistency improved after taking dopa drugs.

(4) Postural gait abnormality: Postural reflex disorder is the main symptom of life difficulties for PD patients. It is second only to exercise reduction or exercise failure. The patient's limbs, trunk and neck muscles are in a particularly flexed posture. Tilt, trunk flexion, upper limb elbow flexion, wrist extension, forearm adduction, interphalangeal joint extension, thumb to palm, lower limb hip and knee joints are slightly curved, early lower limbs drag, gradually become small steps State, difficulty in starting, rushing after starting, getting faster and faster, unable to stop or turn in time, called "fatiness", the upper limb swing is reduced or disappeared while walking, due to trunk stiffness, torso and The head is accompanied by a small step of turning, which is related to the instability of the center of gravity caused by the posture balance disorder. The patient is afraid of falling, and the small obstacles are also stopped. The posture disorder is aggravated with the progress of the disease. The late self-sitting position is difficult to stand up. The mechanism of this inherent postural reflex disorder in PD patients has not been clearly explained. It is believed that this symptom is mainly related to the rupture of the globus pallidus from the thalamus to the cortex.

(5) Other symptoms:

1 repeatedly tapping the upper edge of the patient's eyebrow to induce blinking (Myerson sign), normal people do not continue to respond, may have eyelid palsy (closed eyelids mild tremor) or eyelids (eyelid involuntary closure).

2 mouth, pharyngeal, diaphragmatic dyskinesia, making speech slow, low monotonous voice, drooling, etc., severe dysphagia.

3 common sebaceous glands, sweat gland secretion caused by oily face (oily face), hyperhidrosis, gastrointestinal motility disorders caused by intractable constipation, sympathetic dysfunction leading to orthostatic hypotension, sphincter function is not tired.

4 psychiatric symptoms are more common with depression, anxiety, agitation, mild cognitive decline in some patients, visual hallucinations, usually not serious.

Parkinson's disease check

Laboratory inspection

1. Serum renin activity decreased, tyrosine content decreased, NE, 5-HT content decreased in substantia nigra and striatum, and glutamate decarboxylase (GAD) activity was reduced by 50% compared with the control group.

2. GABA decreased in CSF, and the HVA content of DA and 5-HT metabolites in CSF decreased significantly.

3, biochemical detection: radioimmunoassay detection of CSF somatostatin content decreased, urinary DA and its metabolites 3-methoxytyramine, 5-HT and adrenaline, NE also decreased.

Film degree exam

1, CT, MRI image performance

Because Parkinson's disease is a central nervous system degenerative disease, pathological changes mainly in the substantia nigra, striatum, globus pallidus, caudate nucleus and cerebral cortex, so CT imaging, in addition to universal brain atrophy In addition, sometimes basal ganglia calcification can be seen. In addition to the brain atrophy such as ventricular enlargement, MRI often has multiple high-signal spots in the basal ganglia and white matter.

2, SPECT image performance

(1) Functional imaging by dopamine receptor (DAR): Dopamine receptors are widely distributed in the dopaminergic pathway in the central nervous system, mainly in the substantia nigra, striatum system, and DAR (DL) is distributed in the striatum The cell body of cholinergic interneurons, DAR (D2) is located in the substantia nigra, striatum dopaminergic neuron cell body.

SPECT is a radionuclide, currently mainly 123I-IBZM, 131I-IBZM, a specific D2 receptor marker, after intravenous injection into the human body, through the radioactivity in the basal ganglia region and the frontal, occipital or cerebellar radioactivity Ratio, reflecting the number and function of DAR receptors, to diagnose early Parkinson's disease. If patients with early treatment with dopa preparations, up-regulation of lateral DAR (D2), long-term use of dopa preparations for patients with advanced Parkinson's disease, The basal ganglia/occipital lobes and basal ganglia/frontal ratio are reduced in the brain. SPECT functional imaging can only detect the number of DAR receptors, and can not help to determine whether it is primary Parkinson's disease, but can distinguish some secondary Parkinson's disease. It can also be used as an indicator of the pathogenesis of Parkinson's disease and drug treatment.

(2) Functional imaging by dopamine transporter (DAT): How do dopamine transporter (DAT) transport dopamine (DA) is unclear, DAT is mainly distributed in basal ganglia and thalamus, followed by frontal lobe, DAT content and Parkinson's disease The severity of this is a positive correlation, with a decrease in basal ganglia DAT, which is significant in patients with early Parkinson's disease.

SPECT uses 11C-WIN35428, 123I-CIT, after intravenous injection into the human body, the basal ganglia/cerebellar activity ratio and the ratio of thalamic/cerebellar activity are measured, reflecting the number of DAT in different regions of the central region. In patients with early Parkinson's disease, the number of DAT in the basal ganglia is significantly reduced. .

3, PET function image

Positron emission tomography (PET) diagnosis of Parkinson's disease, its working principle and method is basically similar to SPECT, currently relying mainly on cerebral glucose metabolism imaging, generally using 18F deoxyglucose (18FDG), because in the early stage of Parkinson's disease patients, The local glucose metabolism rate of the striatum is moderately reduced, and the late glucose metabolism rate is further reduced. There are many receptor imaging agents for PET. The PET neurotransmitter functional imaging agent mainly uses 18F-dopa-PET (18FD-PET). The basic principle of nuclides and SPECT, PET can be an early diagnosis of Parkinson's disease, can be used for early diagnosis of high-risk population of Parkinson's disease, is an objective indicator to determine the severity of the disease.

Diagnosis and differentiation of Parkinson's disease

diagnosis

1, diagnosis basis

(1) Middle-aged and elderly patients have a slow onset of sexual disease.

(2) There are at least two items in the four main signs (stationary tremor, myotonia, bradykinesia, posture gait disorder). The first two items have at least one of them, and the symptoms are asymmetrical.

(3) levodopa treatment is effective, levodopa test or apomorphine test positive support primary PD diagnosis.

(4) Patients with no extraocular muscle paralysis, cerebellar signs, orthostatic hypotension, cone system damage and muscle atrophy, PD clinical diagnosis and autopsy pathology confirmed the coincidence rate of 75% to 80%.

Differential diagnosis

Idiopathic PD must be differentiated from familial PD and Parkinson syndrome, and early atypical cases must be differentiated from genetic disease or degenerative disease with Parkinson syndrome.

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