OVERVIEW
多系统萎缩是一种罕见神经系统变性疾病
主要表现为肢体僵硬、口齿不清、步态不稳及尿便失禁等
病因仍不明确，可能与大脑神经胶质细胞病变有关
以对症支持治疗为主，辅以康复治疗
Definition.
Multiple system atrophy (MSA) is a rare sporadic, progressive neurodegenerative disease.
The neurologic lesions involve the extrapyramidal, pyramidal, and autonomic nervous systems.
The main manifestations are similar to Parkinson’s disease, cerebellar and autonomic dysfunction, such as slow movement, muscle rigidity, slurred speech, poor balance, impotence, constipation, and fluctuating blood pressure.
Types or classifications
According to the different main clinical symptoms are divided into Parkinson’s syndrome subtype (MSA-P) and cerebellar subtype (MSA-C)
MSA-P: manifests symptoms similar to Parkinson’s disease and is characterized by tremor, muscle tonus and bradykinesia with simultaneous bilateral involvement.
MSA-C: Prominent for cerebellar ataxia, characterized by unsteady walking, dysarthria and cerebellar nystagmus.
Incidence
It is a rare disease with a global average annual incidence of 0.6/100,000 people and a prevalence of (3.4-4.9)/100,000 people.
In Asian populations, the MSA-C subtype is 1.5 times more numerous than the MSA-P subtype.
Patients usually develop the disease after the age of 50, with slightly more men than women.
Causes
Causes
The cause of multiple system atrophy is currently unknown.
Predisposing factors
Long-term exposure to the following substances may increase the risk of the disease
Organic solvents: e.g. benzene, methanol, ether, pesticides.
Plastic products, plastic additives.
Heavy metals such as lead and mercury.
Symptoms
Main Symptoms
Autonomic dysfunction
is the first symptom in many patients and is a persistent manifestation in the majority of patients.
Cardiovascular system
直立性低血压：突然改变体位时，如从躺着、坐着改为起立时，出现头晕、眩晕、眼前发黑、肢体无力，严重时发生晕厥。
卧位高血压：血压在躺下时急剧升高。
肢体下垂时因血液淤积导致手脚颜色变深，温度冰凉。
Urinary system symptoms: urinary urgency, increased frequency of urination, dysuria, urinary incontinence, difficulty in urination.
Digestive system symptoms: constipation, fecal incontinence.
Sexual dysfunction
男性患者出现阳痿和射精不能。
女性患者出现性欲减退或闭经。
Abnormal secretion of lacrimal and sweat glands
汗液、泪液和唾液分泌减少。
皮肤少汗、无汗和对正常温度不能耐受。
Eye symptoms: unequal pupil size.
Motor dysfunction
Parkinson’s syndrome
肌肉僵硬、紧张、震颤，被动活动关节时阻力增加。
肌肉无力、运动缓慢。
姿势异常，双侧肢体表现对称。
表情呆板。
Cerebellar ataxia
运动不协调，步态不稳，容易失去平衡。
口齿不清、说话声量小，音调和节奏像念诗一样顿挫。
吞咽困难和咀嚼困难。
眼前不自主颤动，出现视力模糊或复视、双眼很难聚焦。
Other symptoms
Inability to self-control the appearance of crying or laughing-like behavior.
Sleep disorders such as insomnia, hypersomnia, nightmares.
Mental depression, dementia.
Respiratory symptoms: wheezing on inspiration, snoring is obvious, especially during sleep with multiple apneas.
Consultation
Department of Medicine
Neurology
Seek medical attention when symptoms such as fluctuations in blood pressure associated with changes in body position, unexplained urinary incontinence, abnormal sweating, and limb movement disorders occur.
Preparation
Information on how to get to the doctor: registration, preparation of documents, and frequently asked questions.
Tips for Consultation: Registration, Preparation of Documents, Frequently Asked Questions
Patients may have movement disorders and need to be accompanied to prevent accidents such as falls and injuries.
Preparation Checklist
症状清单
Pay particular attention to the time of onset of symptoms, special manifestations, etc.
Are there any symptoms such as blood pressure fluctuation, fainting, etc. related to changes in body position?
Are there any symptoms such as limb stiffness, tremor, unsteady walking, swaying from side to side, etc.?
Are there any symptoms such as urinary incontinence or constipation, inability to urinate?
(Men) Are there symptoms such as impotence and difficulty in ejaculating?
Are there any symptoms such as easy snoring while sleeping?
病史清单
Do any of your parents, siblings, or other relatives have similar symptoms?
Have you been exposed to organic solvents, plastics and additives, and heavy metals for a long time?
检查清单
Test results in the past six months, which can be brought to the doctor’s office.
Imaging tests: e.g. cranial MRI, PET-CT.
Electrophysiologic examination: electromyography, electroencephalogram, etc.
用药清单
Medication in the last 3 months, if available, bring along the box or package for medical consultation
Levodopa, midodrine hydrochloride, hydrocortisone, etc.
Sildenafil, oxybutynin, tolterodine, paroxetine, etc.
Diagnosis
Diagnosis is based on
Medical history
Insidious onset, slow progression, no similar patients in the family, age >50 years.
Clinical manifestations
Fluctuations in blood pressure associated with postural changes, poor urinary and fecal control, impotence, absence of sweating of the skin, stiffness of the limbs, tremor, unsteady walking, slurred speech, and dysphagia are present.
Have the patient lie down and measure prone blood pressure and heart rate, then stand up quickly and measure blood pressure and heart rate again. Upright hypotension was considered if blood pressure decreased ≥30/15 mmHg within 3 minutes of standing compared with the prone position, but there was no significant change in heart rate.
Thermoregulation and Sweating Test
Purpose of the test: To objectively assess the function of sweat secretion from the skin.
Significance: 80% of patients with this disease have reduced sweating, 45% have no sweating, and the severity is significantly higher than that of Parkinson’s patients.
Anal sphincter electromyography
Purpose of examination: To assess the status of autonomic function.
Significance: It can show a decrease in the contraction function of the anal sphincter, suggesting nerve damage.
Precautions: This test is painful, so try to relax and cooperate to complete the test.
Urodynamic examination
Purpose of examination: to assess the autonomic nerve function.
Significance of the test: It can find that the excitability of the reflex of the forced urethral muscle is elevated, the function of the urethral sphincter is reduced, and there is an increase in residual urine in the late stage of the disease.
Precautions: Urine holding is required before the examination.
Imaging
MRI平扫
Purpose of examination: To detect abnormal changes in the brain area and assist in diagnosis and differentiation.
Significance: Atrophy of the nucleus accumbens, middle cerebellar peduncle and pons, “cross sign” at the base of the pons, and “cleft sign” in the nucleus accumbens are typical manifestations.
Precautions
检查前需去除全身金属物品，体内有起搏器、金属植入物不能进行检查。
检查当天请勿使用发胶类产品，以避免造成假影，影响医师判读。
正电子发射计算机断层扫描（PET）
Purpose of examination: To detect abnormalities of cerebral metabolic function.
Significance: hypometabolism in cortical and subcortical areas, decreased metabolism of dopamine and 18F deoxyglucose.
Precautions
本项检查有放射性，备孕期、妊娠期妇女禁止检查，哺乳期妇女在检查结束后应禁止哺乳24小时，在此期间远离婴幼儿。
检查前需要禁食6小时以上，在此期间可以多饮水。
Diagnostic Criteria
The diagnostic certainty is categorized into probable multiple system atrophy, very probable multiple system atrophy, and confirmed multiple system atrophy.
Confirmed multiple system atrophy requires brain histopathology, which is not usually performed clinically.
Probable multiple system atrophy requires meeting strict criteria for autonomic dysfunction.
Probable multiple system atrophy requires a combination of clinical presentation, imaging, and a number of exclusions to be considered.
Differential Diagnosis
Parkinson’s disease
Similarities: Stiffness, postural abnormalities, and autonomic dysfunction may be present.
Differences: The typical tremor of Parkinson’s disease is a “pill-rubbing” resting tremor, without cerebellar dysfunction and pathological signs, and is better treated with levodopa drugs.
Idiopathic upright hypotension
Similarity: Both of them can have changes in blood pressure when the body position changes.
Difference: idiopathic upright hypotension has no other autonomic symptoms such as constipation, no sweating of the skin, and central nervous system symptoms such as stiffness of the limbs and postural abnormalities.
Lewy body dementia
Similarities: Both may present with stiffness of limbs, postural abnormalities, and cognitive impairment.
Differences: Lewy body dementia patients have earlier onset of cognitive dysfunction, hallucinations, and are very sensitive to antipsychotic drugs.
Treatment
Aim of treatment: Currently there is no specific treatment method, and symptomatic treatment is the mainstay to improve the quality of life.
Treatment principle: Drug treatment is the mainstay, supplemented by rehabilitation.
General treatment
Prevent upright hypotension.
Changes in body position should be slow, and sudden sitting up or standing up should be avoided.
Use cross legs, squatting position, compression of the abdomen, leaning forward and other positions and wear corseted tight pants and elastic stockings.
Elevating the head and trunk 15° to 20° higher than the legs in the prone position can help improve upright hypotension.
Increase water and salt intake, and for those who develop hypotension after eating, eat smaller meals and drink water or coffee before meals.
Medication
Stabilizing blood pressure treatment
Commonly used drugs: Midodrine, fludrocortisone, ergotamine, caffeine, etc.
Precautions
需密切监测血压、心率，防止血压波动过大。
需定期监测电解质、肾脏功能，需注意心脑血管疾病患者、肾功能不全者、有感染病灶、妊娠及哺乳期妇女禁服。
Improve urinary incontinence
Relieve spasm of bladder forcing muscle, improve symptoms of urinary urgency and frequency.
Commonly used drugs: oxybutynin, atropine, scopolamine, tamsulosin, etc.
Precautions
有排尿困难、尿潴留禁用者。
重症肌无力患者禁用。
可能引起视力模糊、反应变慢，用药期间需避免进行驾驶、危险作业。
需要严密监测膀胱内压、心率及血压（尤其对有心脑血管疾病患者）。
Improvement of Parkinson’s symptoms
Improve the symptoms of tremor, muscle tonus, bradykinesia, and upright hypotension.
Commonly used drugs: levodopa, pramipexole, ropinirole, etc.
Precautions
约30%的患者对左旋多巴短暂有效，平均维持3.5年。
普拉克索、罗匹尼罗的效果及耐受性通常不如左旋多巴，但部分患者对此敏感。
对于无明显不良反应的患者，不建议完全停用。
Improvement of sleep disorders
Improve insomnia, sleep talking, abnormal movements during sleep, sleep breathing disorder, etc.
Commonly used drugs: clonazepam, melatonin, triazolam and zopiclone, etc.
Precautions
可能引起困倦、嗜睡、头晕、思维不能集中、恶心、皮疹等不良反应。
需严格按照医生指导使用，避免成瘾，减药或者停药时不宜骤停。
Improvement of sexual dysfunction
Improve male erectile dysfunction.
Common drugs: Sildenafil.
Precautions
本药为按需使用，不是长期服用的药物。
加重直立性低血压，可能引起面部潮红、头痛、头昏、皮疹等不良反应。
有心脑血管疾病或正在使用硝酸甘油、硝普钠等扩血管药者慎用或禁用。
Improvement of depressive symptoms
Mental-emotional problems that occur with multiple system atrophy are associated with abnormal neurotransmitter synthesis and metabolism.
Indicated for patients with severe depression, anxiety or loss of emotional control.
Common drugs: fluoxetine, paroxetine, sertraline, etc.
Cautions: Adverse reactions such as dizziness, tremor, headache, emotional instability, drowsiness, insomnia, and euphoria may occur.
Improve constipation symptoms
Assist defecation and reduce constipation symptoms.
Commonly used drugs: Domperidone, polyethylene glycol, lactulose, etc.
Precautions
需配合增加膳食纤维、饮水量，进行腹部按摩和盆底肌肉锻炼。
用药后可出现腹痛、腹胀、腹泻等不良反应。
有严重的炎症性肠病、消化道穿孔、肠梗阻者禁止使用。
Other treatments
Improvement of urinary retention symptoms
Intermittent catheterization or suprapubic fistula can be used if the residual urine volume in the bladder is >100 ml.
For patients with ineffective drug treatment, forced urethral muscular toxin injection therapy can be used.
Improvement of respiratory symptoms
A noninvasive positive-pressure ventilation device may be used at bedtime in patients with stridor.
Tracheotomy may be performed in the presence of bilateral vocal cord adductor paralysis.
Rehabilitation
Individualized rehabilitation programs are developed according to the dysfunction that occurs at different stages.
Motor function training
Under the guidance of therapist, turn over, get up, keep sitting, stand up and walk training.
Increase the stability of the patient’s trunk and re-establish the correct posture through sensory input.
Improve balance ability by standing on both feet front and back, turning 360 degrees, standing on one foot and other actions.
Pay attention to safety and moderation of labor and leisure during training to avoid fall and over fatigue.
Respiratory training
Conduct deep breathing, blowing balloons, coughing and abdominal breathing training.
Raise the head of the bed 30°～45° to avoid vomiting and aspiration.
Sound formation and swallowing function training
Train the movement ability of facial and throat muscles to improve the clarity and fluency of pronunciation.
Improve the sensory function of the muscles of the pharynx through stimulation methods such as ice-cotton sticks and tactile sensation.
Swallowing disorder can be relieved by changing the eating posture and adjusting the nature of food.
Improve the strength of swallowing muscles through swallowing training without food and small amount of food.
Cognitive training
Adopt “one-to-one” or multi-person group training.
Memory, calculation and thinking skills can be trained by memorizing numbers, doing math and reasoning problems.
Traditional Chinese Medicine (TCM)
Medication
According to Chinese medicine theory, multi-system atrophy can be categorized into four types, and the Chinese medicine treatment is as follows:
Kidney element deficiency type: tonifying the liver and kidney, filling in the essence and marrow is the mainstay, with the addition of Di Huang Drinking Zi.
Damp-heat infiltration type: to clear away heat and eliminate dampness, and to facilitate the tendons and veins as the mainstay, with the addition and subtraction of Si-Miao-San.
Yin deficiency and internal heat type: nourishing the liver and kidney, nourishing Yin and clearing heat is the mainstay, and Tiger Diving Pill can be used with additional subtractions.
Kidney-yang deficiency: warming the yang and benefiting the kidney, glorifying the blood and nourishing the muscle is the mainstay, with the addition or subtraction of Right Angelica Pill.
Acupuncture treatment
Acupuncture and moxibustion treatment is mainly based on the combination of brain-awakening and opening up the mind acupuncture method and manna needle acupuncture treatment.
It can improve speech and swallowing, urination function, intestinal function and gait.
Prognosis
Cure
The disease progresses rapidly, with an average survival period of 6 to 10 years after onset, which seriously affects patients’ quality of life and even life safety.
The average intervals from onset to the need for assisted ambulation, wheelchair, bedridden and death are 3, 5, 8 and 9 years, respectively.
Prognostic influences
Disease factors: The degree of damage to the autonomic nervous system, age of onset, whether dysphagia and sleep breathing symptoms appear early, and whether there are underlying diseases such as diabetes mellitus all affect the prognosis of this disease.
Nursing factors: such as poor care prone to complications of decubitus ulcers, pulmonary infections, urinary tract infections, deep vein thrombosis, all of which can be life-threatening.
Hazard
This disease seriously affects the patient’s ability to move and daily living, resulting in the inability to take care of their own life, which can seriously affect their life.
Due to the decline in quality of life and reduced mobility, patients are usually accompanied by varying degrees of emotional depression.
Daily
Daily Management
Dietary management
Balanced nutrition and adequate water intake.
High sodium, high fiber diet.
Those with postprandial hypotension are advised to eat smaller meals and reduce the intake of carbohydrates such as rice, flour and bread.
Caffeinated drinks such as coffee, tea and cola help to raise blood pressure.
Patients who develop swallowing disorders may be fed via nasal feeding tube.
Life management
Patients are prone to recurrent dizziness, falls, and blurred vision. Special attention should be paid to these symptoms, and protective measures should be strengthened to prevent trauma and fracture injuries to the head and limbs due to falls.
For patients with urinary incontinence, urinary catheters or diapers can be used, and the perineum should be kept clean and dry with frequent changes.
Psychological support
Patients with this disease often have low mood, depression, anxiety.
Family members should cooperate with doctors to guide patients to correctly understand the disease, accept the disease, and establish confidence in the treatment of the disease.
Encourage patients to participate in social and family activities and do things that they can accomplish by themselves in order to enhance self-confidence.
When there is emotional instability, psychological depression, etc., timely confide in friends and relatives, can also seek help from medical personnel, if necessary, psychological counseling, so as not to affect the effectiveness of treatment due to psychological problems.
Disease monitoring
Closely observe the change of blood pressure, pay attention to measure the standing and lying blood pressure and observe the difference. Special attention should be paid to the fluctuation of blood pressure at night, and the changes of blood pressure during the medication period should be closely monitored to prevent the blood pressure from being too high or too low.
Pay attention to the patient’s respiration, urination and defecation during sleep.
Follow-up examinations
Follow up with your doctor regularly, usually every 1 to 3 months.
Tests such as MRI of the head, anal electromyography, and urodynamics may be reviewed to observe the progress of the disease and the effect of treatment.
Prevention
The cause of the disease is unknown and cannot be prevented.
The cause of multiple system atrophy is currently unknown.
Avoiding prolonged exposure to the following is likely to reduce the risk of the disease
有机溶剂：如苯、甲醇、乙醚、杀虫剂等。
塑料品、塑料添加剂。
铅、汞等重金属。
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