What Factors Affect the Prognosis of Parkinson's?

Parkinson's disease (PD), also known as tremor paralysis, is a common neurological degenerative disease in the elderly. The main lesions are in the substantia nigra and striatum. Tremor, muscle rigidity, and reduced motion are the main clinical features of the disease. Parkinson's disease is the fourth most common neurodegenerative disease in the elderly.

Basic Information

nickname: Tremor paralysis
Visiting department: Neurology
Multiple groups: Seniors
Common locations: brain

Common causes: The etiology is unknown and may be related to aging, genetic factors, environmental toxicants, infections, oxidative stress and free radical formation.
Common symptoms: Tremor, stiffness, sluggish movement, excessive salivation, depression, etc.

Causes of Parkinson's syndrome

The etiology of PD is unknown so far, and previous studies have suggested that it may be related to many factors. Some people have suggested that there are some evidences for several hypotheses, but there are many differences. Some scholars point out that it may be "multi-cause and one effect", such as the interaction between individual susceptibility and environmental factors, based on aging, and the impact of environmental toxins. In recent years, with the rapid development of science and technology, the level of research on basic theories has continued to improve, which is of great benefit to further clarify the pathogenesis of PD. The most popular are: aging, genetic factors, environmental toxicants, infection, and oxidative stress And free radical formation.

One of the most common causes of aging . The prevalence of PD changes with age. The aging process and the decrease of glutathione peroxidase and catalase in PD; monoamine oxidase increases, iron, copper, calcium accumulation with age. , Melanin aggregates. With increasing age, the incidence rate increased, the age of high incidence was 61 to 70 years old, and then decreased, and the substantia nigra and striatum dopamine neurons changed degeneratively, and the pigment particles and nerve cells were lost. normal group. Motor symptoms of PD will only occur clinically. The symptoms of this disease usually occur between 51 and 60 years of age. If age is the only cause, dopamine levels have not reached a sufficiently low level at this time. Therefore, aging is only a contributing factor to PD.

Genetic factors Through a detailed investigation of the family of PD patients, it has been widely recognized that at least part of the disease comes from genetic factors in terms of etiology.

Environmental poisons People have noticed that manganese poisoning, carbon monoxide poisoning, phenothiazine and butyrylbenzene can produce PD symptoms.

Infection with encephalitis A often occurs after PD. Some authors believe that PD is related to viral infection. Not yet confirmed.

Oxidative stress and the formation of free radicals cannot be separated from oxygen. Cell metabolism requires energy to gradually reduce molecular oxygen. The entire process occurs in the mitochondria. In addition, many other enzymes, such as tyrosine hydroxylase, monoamine oxidase NADPH-cytochrome P450 degrading enzyme and xanthine oxidase are also mediators that produce or use reactive oxygen species. Reducing oxygen plays a positive role in many normal biological processes, but excessive formation can also damage nerve cells.

In short, PD is not caused by a single factor, there may be multiple factors involved. Genetic factors can increase susceptibility to disease, but only through the combined effects of environmental factors and aging, through oxidative stress. Mitochondrial failure and other factors lead to a large number of degeneration of dopaminergic neurons in the substantia nigra and cause disease.

Clinical manifestations of Parkinson's syndrome

The age of onset of this disease is between 40 and 70 years old, and the peak of onset is more than men and women before the age of 50 to 60 years. Cases of young families have also been reported. Trauma, depression, overwork, and cold can induce the disease. Onset is hidden and slowly progressing, often with less movement, slowness or posture changes as the first symptoms. Gradual aggravation is mainly caused by the increase of resting tremor muscle tone, bradykinesia or slow movement, and autonomic nervous disorder.

Symptoms

(1) The earliest symptoms of patients with early symptoms are often difficult to detect and easy to ignore. Some call this a subclinical state. Patients lacked flexibility, less movement, gradually appeared spine, limbs are not easy to bend, as the disease progresses, the stride becomes smaller, the forward speaking voice becomes smaller, neck, back, shoulder and hip pain, fatigue, light eyelid fissure The degree becomes wider and looks like a gaze.

(2) Typical symptoms

Tremor is often the first symptom, accounting for 80% of PD. It is characterized by inactive tremor during active exercise. It usually starts from the other fingers on the distal end of one upper limb, and then gradually extends to the ipsilateral lower limb and the contralateral upper and lower limb. The mandible, lips, tongue, and head are generally the last affected tremors that are relatively coarse, with a frequency of 4-8 times / s4-8Hz, which can be temporarily controlled for consciousness but not lasting, aggravated during excitement and fatigue, and disappear during sleep.

Myotonia in patients with myotonia is due to increased tension of extrapyramidal muscles. The muscle tension of both the agonist and antagonist muscles is increased. Passive motion of the joints always maintains increased resistance. Similar to the feeling of a curved soft lead tube, it is called "lead. "Tube-like rigidity"; if some patients have tremor, you may experience intermittent pauses in uniform resistance when stretching and flexing your limbs. If the gear is rotating, it is called "gear-like rigidity". Due to increased muscle tension and imbalance, abnormal postures are often presented: the head is leaning forward, the body is adducted by the forward bending of the upper limbs, the elbows are flexed, the wrists are straight, and the metacarpophalangeal joints are flexed. Elderly patients with myotonia can cause joint pain, which is caused by an increase in muscle tone that hinders the blood supply to the joints.

Bradykinesia is a characteristic symptom of basal ganglia insufficiency in PD. Performance of various slow movements, such as dressing laces, shaving and brushing teeth are slow or difficult. Facial expressions are reduced and blink movements are reduced or even disappeared. Difficult to start, decline in ability to overcome inertia, difficulty in stopping movements, difficulty in changing exercise postures Once you start a small step, rub your feet on the ground. You can't stop calling "panic gait" immediately. When you encounter obstacles, walk or pause, and turn around in small steps along with your head and torso. Language barriers can be manifested as low pronunciation, articulation, stuttering, or repetitive language. It is called "panic language", which trembles and distorts when writing, uneven line spacing, and the smaller the writing, the smaller it is called "lower case". These characteristic dyskinesias can also be expressed as difficulty swallowing, slow chewing can be expressed as nervousness or agitation, and all motions suddenly stop, like freezing, called freezing phenomenon, which is short-lived. On the contrary, abnormal movement occurs, that is, the phenomenon of less movement is temporarily removed and normal activities are performed. In rare cases, such as emergency situations, there are also significant effective movements called contradictory movements. On-off phenomenon, the sudden movement can not and the sudden movement is free. Special signs may have repeated tapping on the upper edge of the eyebrow arch, which can induce blinking, not only the upward and simultaneous gaze of two eyes, and restricted movement, that is, the eye movement crisis is more common in the brain. Post-inflammatory and drug-induced Parkinson's syndrome.

Common autonomic dysfunction: Excessive salivary secretion causes excessive secretion of salivary sebaceous glands and increased sweating, which makes the skin, especially facial skin, oily and low blood pressure, which is prone to orthostatic hypotension, but rarely occurs in syncope. It is more common in elderly patients. Examination found that tyrosine levels were related to reduced plasma renin and low aldosterone levels. But normal blood sodium, suggestive of peripheral sympathetic defects. Patients with refractory constipation can urinate endlessly, urination, urinary incontinence, etc. The pathological basis is damage to the dorsal nucleus of the vagus nerve and sympathetic dysfunction.

Depression is common as depression, and usually mild to moderate suicide is rare. About 40% of PD patients have depression during their course, which is characterized by anorexia and sleep disorders and lack of sexual desire. Followed by dementia, the incidence of PD is 12% to 20%, and the first-degree relatives have a high risk of dementia. Other symptoms include indifferent emotions, slow thinking and slow personality changes.

2. Signs

(1) The early characteristic is a reduction in blink rate. Normally, the blink rate of healthy people is 15-20 times / minute, while PD patients can be reduced to 5-10 times / minute.

(2) Typical signs

"Striatum hand" showed flexion of the metacarpophalangeal joint, straightening of the proximal interphalangeal joint, and flexion of the distal interphalangeal joint; at the same time, foot deformity can also occur.

Myerson's disease can't restrain the blink reaction between the bridge of the nose or between the eyebrows.

Ankylosing cramps, ankylosing spasm between eyes, usually seen on the two eyes, side view and

Down vision is rare and recurrent, often with neck, mouth, and muscle spasms.

Involuntary levator muscle inhibition and orbicularis muscle inhibition for open and closed eyelid apraxia .

(3) Atypical signs The knee reflex has a large variation, which can be normal, difficult to elicit, and also active. It is limited to single PD patients. The bilateral knee reflexes are symmetrical and flexing, and the lower frontal and frontal reflexes are very high. Increase less.

Parkinson's syndrome test

Laboratory inspection

(1) Routine examinations are generally within the normal range, and some may have changes such as hyperlipidemia and abnormal electrocardiogram of diabetes.

(2) Blood cerebrospinal fluid examination can detect a decrease in dopamine levels and a decrease in the high vanillic acid concentration of its metabolite. Serotonin metabolites and -oxindole acetate were reduced; dopamine beta hydroxylase was reduced; somatostatin was significantly reduced in cerebrospinal fluid; and -aminobutyric acid levels were reduced.

(3) Molecular biology examination Biochemical detection using high performance liquid chromatography and other HPLC, can detect the reduction of HVA content in cerebrospinal fluid and urine. Gene detection uses Southern blotting and other southern-blot techniques. PCR, DNA sequence analysis, and other gene mutations may be found in a small number of familial PD patients.

2. Auxiliary inspection

(1) CTMRI of the brain generally has no characteristic findings. Elderly patients may have different degrees of brain atrophy and ventricular enlargement. Some patients have lacunar infarcts, and some have basal ganglia calcification. Recently, some scholars have shown that white matter hyperintensities can be seen in T1 weighted images of PD patients in MRI and appear in the white matter around the anterior horn of the center of the semioval and the lateral ventricle.

(2) Functional imaging detection uses PET or SPECT and specific radionuclides. For example, 6-18 fluoro-levodopa and other 6-FD other studies of dopamine metabolism can obtain information about the density and affinity of dopamine receptors, and found that the dopamine metabolic function in the brain of PD patients is significantly reduced, before the clinical symptoms appear. The striatum's absorption index was found to be less than normal. Early detection of D2 type dopamine receptor activity, early hypersensitivity, other compensatory phases, low-sensitivity, and other decompensated phases, and reduced dopamine transmitter synthesis are valuable for early diagnosis and differential diagnosis and monitoring of disease progression. But it is expensive and has not been widely used in clinical practice.

(3) Related tests: Serotonin, electrocardiogram, total phospholipids, vitamin A, cerebrospinal fluid, DNA staining.

Parkinson's syndrome diagnosis

The typical diagnosis of tremor and palsy is not difficult. According to the typical symptoms of tremor, rigidity, decreased movement, combined with rubbing-like movements, lead tube or gear-like muscle rigidity, mask face, lower case, panic gait and other signs can generally make a diagnosis.

Differential diagnosis of Parkinson's syndrome

Need to be distinguished from symptoms due to

Infection

Tremor palsy syndrome can occur after encephalitis, but its onset can occur at any age, and a clear history of encephalitis can help identify it.

2. Poisoning

More common in patients with manganese or carbon monoxide poisoning often have a history of carbon monoxide poisoning or long-term history of manganese exposure, and then gradually appear symptoms such as tremor rigidity.

3. Drug

Certain drugs, such as phenothiazines, can block dopamine's synaptic transmission and cause symptoms such as tremor and rigidity. In addition, reserpine can prevent the storage of dopamine at the end of the axon, and the metabolites of methyldopa can compete for dopamine receptors. These drugs can cause symptoms of tremor syndrome. The medication history and recovery of symptoms after discontinuation can be identified.

4. Trauma

Cerebral concussion, cerebral contusion and other injuries can cause symptoms of tremor paralysis syndrome, and the history of trauma can be identified.

5. Arteriosclerosis

Most of the clinical manifestations are caused by cerebral arteriosclerosis or multiple cerebral infarction. In addition to the symptoms of Parkinson's syndrome, there are also primary symptoms such as dementia.

Parkinson's syndrome complications

It can be complicated by stiffness, dyskinesia, infection and accidental fracture.

Parkinson's syndrome treatment

The treatment of PD can be performed from three different aspects. The first purpose of treatment is to restore the patient's function as soon as possible, delay the progression of the disease, and reduce symptoms, that is, symptomatic treatment. Drug treatment is performed before the eyes are collected. The second is protective and preventive treatment, mainly secondary and tertiary prevention, with emphasis on rehabilitation. The third is repair, which provides new nerve cells through nerve cell transplantation and produces more dopamine.

Routine treatment

(1) After many years of clinical practice, drug therapy has gradually accumulated, and constantly summarized experience, and initially formulated some principles for drug use, but some contents are still very controversial and will continue to improve with the progress of scientific research. The principle of drug treatment is to restore the balance of the two major transmitter systems of the striatum DA and ACH, but the drug cannot prevent the disease from developing and needs to be taken for life. The principle is: start with a small dose, slowly increase, maintain at the minimum dose, choose a treatment plan based on age, symptom type, severity, contraindications, price, and economic affordability, and choose a reasonable combination of timing.

2. Cell transplantation and gene therapy

In recent years, successful examples of transplantation of autologous adrenal medulla and allogeneic embryonic mesencephalic melanocytes into the striatum can correct DA transmitter deficiency and improve motor symptoms. However, 50% of patients have improved symptoms, 15% of death and disability, and limited donor sources, uncertain long-term efficacy and immune rejection. Transplantation of cells during the genetic process or direct vector-mediated gene transfection methods, and specific dopaminergic nerve growth factor are the most effective methods for the treatment of PD. The tyrosine hydroxylase gene (THCDNA) has been cloned, and THCDNA of type 1, 2 has been transfected into fibroblasts or AtT-20 cells by retrovirus, and tyrosine hydroxylation has been obtained Expression of enzyme activity. However, this method is at the stage of animal experiments, and the technology is immature, so it cannot be applied clinically.

3. Optimal plan

Because PD treatment is life-long, surgical treatment is not easy to be accepted by patients and their families at the early stage, so the choice of medicine is particularly important. At the same time, rehabilitation treatment is accompanied by the consistent treatment of medicine.

(1) Interventional treatment for early mild patients to prevent disease progression. MAO-B inhibitor + vitamin E (DATATOP program): Selegiline (oral) + vitamin E orally.

(2) The first choice for young people who have early onset without bradykinesia. Anticholinergic or amantadine:

The small dose of benhexol started to gradually increase to the dose, but not more than 4 mg / day orally.

Orthobenzamide + amantadine.

(3) Progress of the disease The above scheme is ineffective. A low-dose compound L-Dopa + DA receptor agonist can be used: levodopa / carbidopa (Sinemet) (carbidopa 10mg, levodopa 100mg) + bromocriptine (Bromocriptine) is administered orally for 3 to 4 years. Depending on the condition, it can be overdose to L-Dopa controlled release agent + DA receptor agonist to prevent side effects of movement disorders.

4. Rehabilitation

Rehabilitation as an adjunct can also play a role in improving symptoms, and its methods include the following 10 aspects.

(1) ROM training, muscle strengthening training, endurance training, balance training, gait training, facilitation technology, joint mobilization, exercise prescription, etc.

(2) Occupational Therapy

Biomechanical law;

Neurophysiological methods.

(3) Physical therapy includes high, medium and low frequency electrical stimulation for pain, biofeedback, etc.

(4) Traditional therapies such as acupuncture, massage, boxing, and qigong.

(5) Speech therapy.

(6) Rehabilitation engineering therapy.

(7) Stylistic therapy.

(8) Psychotherapy.

(9) Rehabilitation nursing.

(10) Social rehabilitation.

The goal of rehabilitation for CNS injury is to comprehensively promote physical dysfunction through physical therapy and occupational therapy to prevent dysfunction and misuse syndrome, reduce sequelae, and fully strengthen and exert residual functions. Through compensation and use of auxiliary tools, as well as the transformation of the living environment, etc., in order to achieve self-care and return to society. Rehabilitation treatment of PD patients always develops and develops along with the disease. Because each patient's condition and prognostic factors are different, the prognosis varies greatly.

Parkinson's syndrome prognosis

Parkinson's disease is a progressive degenerative disease. All drug treatments can only improve the quality of life and work of patients, but cannot prevent the disease from developing. Patients will eventually lose their viability. From the perspective of symptoms, the prognosis is better for those with tremor predominantly, while the elderly are mainly with less movement, so their prognosis is poor. The main causes of death from Parkinson's disease are complications caused by less movement in the late stage of the disease, such as bedsores and sepsis, heart failure, lung infections and urinary infections. They account for 50%, 28% of the causes of Parkinson's death, 14% and 8%. Patients with Parkinson's disease often die early in the morning because of parasympathetic nerve excitation and weakened levodopa effect in the early morning.