What is Multiple System Atrophy?

Multiple system atrophy (MSA) is an adult-onset, sporadic neurological degenerative disease with clinical manifestations of varying degrees of autonomic dysfunction, Parkinson's syndrome that is unresponsive to levodopa, and cerebellar Ataxia and pyramidal signs. Because the three systems involved in the onset are different, the clinical manifestations are different. But with the development of the disease, the pathological manifestations and clinical manifestations of all three systems will eventually appear. Epidemiological surveys abroad show that the annual incidence of MSA in people over the age of 50 is about 3 / 100,000, and there is no complete epidemiological data in China.

Jia Jianping	(Chief physician)	Department of Neurology, Xuanwu Hospital, Capital Medical University
Wang Fen	(Deputy Chief Physician)	Department of Neurology, Xuanwu Hospital, Capital Medical University

Multiple system atrophy (MSA) is an adult-onset, sporadic neurological degenerative disease with clinical manifestations of varying degrees of autonomic dysfunction, Parkinson's syndrome that is unresponsive to levodopa, and cerebellar Ataxia and pyramidal signs. Because the three systems involved in the onset are different, the clinical manifestations are different. But with the development of the disease, the pathological manifestations and clinical manifestations of all three systems will eventually appear. Epidemiological surveys abroad show that the annual incidence of MSA in people over the age of 50 is about 3 / 100,000, and there is no complete epidemiological data in China.

On May 11, 2018, the National Health Committee and other five departments jointly developed the "First Batch of Rare Diseases Catalogue", and multiple system shrinkages were included. ^[1]

Western Medicine Name

Multisystem atrophy

English name

multiple system atrophy, MSA

Affiliated Department

Internal Medicine-Neurology

The main symptoms

Urinary incontinence, frequent urination, bradykinesia, etc.

Main cause

Unclear etiology

Classification of multiple system atrophy diseases

Previous MSAs include three types, Shy-Drager syndrome (SDS), striatonigral degeneration (SND), and olivopontocerebellar atrophy (OPCA).

At present, MSA is mainly divided into two clinical subtypes. Among them, the clinical subtype with Parkinson's syndrome as the outstanding performance is called MSA-P type, and the person with cerebellar ataxia as the outstanding performance is called MSA-C type.

Causes and pathogenesis of multisystem atrophy

The cause is unclear. At present, it is believed that the pathogenesis of MSA may have two ways: one is the primary oligodendrocyte lesion hypothesis, that is, oligodendrocytes characterized by -synuclein-positive inclusion bodies first appear; Cell degeneration leads to degeneration and degeneration of myelin sheaths of neurons, activates microglia, induces oxidative stress, and leads to neuron degeneration and death. Second, the abnormal aggregation of -synuclein of neurons itself causes neuron degeneration and death. The cause of the abnormal aggregation of -synuclein has not yet been identified, and may be related to genetic susceptibility and environmental factors.

MSA patients rarely have a family history. Genome-wide single nucleotide polymorphism association analysis shows that -synuclein gene (SNCA) rs11931074, rs3857059, and rs3822086 polymorphisms increase the risk of MSA. Other candidate genes include: tau protein gene (MAPT), Parkin gene, etc. The role of environmental factors is not very clear. Studies have suggested that occupation and living habits (such as organic solvents, exposure to plastic monomers and additives, exposure to heavy metals, and agricultural work) may increase the risk of MSA, but these risk factors have not been fully confirmed. ^[2]

Multisystem atrophy pathology

The pathological hallmark of MSA is the discovery of eosinophilic inclusions in the glial cell cytoplasm. Other characteristic pathological findings include neuronal loss and glial cell proliferation. The lesions mainly involve the striatum-substantia nigra system, the olive-pontine-cerebellum system, and the medial and lateral cell columns and Onuf nucleus of the spinal cord. The core component of MSA inclusion bodies is -synuclein. Therefore, MSA is classified as synucleinopathy with Parkinson's disease and Lewy body dementia.

Clinical manifestations of multiple system atrophy

Onset in adulthood, more common in 50 to 60 years of age, the average age of onset is 54.2 years (31 to 78 years), the incidence is slightly higher in men, slowly onset, and gradually progress. The first symptoms are mostly autonomic dysfunction, Parkinson's syndrome, and cerebellar ataxia. A few patients also have muscular atrophy. Regardless of the symptom cluster of the nervous system, when the disease progresses further, neurological clusters of two or more systems will appear.

Multisystem atrophic autonomic dysfunction

Autonomic dysfunction is often the first symptom and one of the most common symptoms. Common clinical manifestations are: urinary incontinence, frequent urination, urgency, and urinary retention, male erectile dysfunction, orthostatic hypotension, dysphagia, unequal pupil size, and Horner syndrome, asthma, apnea, and dyspnea. Tracheostomy. Marks and cold hands are characteristic of autonomic nerve dysfunction. The earliest symptoms in men are erectile dysfunction, and incontinence in women.

Multiple system atrophy Parkinson syndrome

Parkinsonism is a prominent symptom of the MSA-P subtype and one of the common symptoms of other subtypes. MSA's Parkinson's syndrome is characterized by bradykinesia, muscle stiffness, and tremor. Both sides are affected at the same time, but the severity can be different. Anticholinergic drugs can alleviate some symptoms, and most of them do not respond well to L-dopa treatment. They are effective in 1/3 patients, but they do not last long and are prone to adverse reactions such as dyskinesias.

Multisystem atrophy reduces cerebral ataxia

Cerebellar ataxia is a prominent symptom of the MSA-C subtype and one of the common symptoms of other MSA subtypes. The clinical manifestations are progressive gait and ataxia of the limbs. Starting from the lower limbs, the performance of the lower limbs is prominent, and there are obvious cerebellar ataxias such as articulation disorders and nystagmus. Examination can reveal signs of severe cerebellar lesions in the lower extremities. Cerebellar signs are often obscured when combined with corticospinal tract and extrapyramidal symptoms.

Multiple system atrophy other

(1) 20% of patients have mild cognitive impairment.

(2) Common symptoms such as dysphagia and dysphonia.

(3) Sleep disorders, including sleep apnea, abnormal sleep structure, and abnormal REM sleep behavior.

(4) Other extrapyramidal symptoms: Dystonia, palatal clonics, and myoclonus are all visible. Myoclonus sensitive to hand and facial stimuli is a characteristic manifestation of MSA.

(5) Some patients had muscle atrophy, increased muscle tone, tendon reflexes, and Babinski sign, and optic nerve atrophy. A few have paralysis of the eye muscles, and paralysis of the eyeballs up or down. ^[3]

Multiple system atrophy diagnosis and differential diagnosis

Multiple system atrophy diagnosis

1. Slow onset, progressive development in adulthood, no family history.

2. The clinical manifestations are progressive autonomic dysfunction (urinary incontinence with erectile dysfunction in men, orthostatic hypotension).

3. One of the following two items: Parkinson's syndrome: bradykinesia, with rigidity, tremor, or posture reflex disorder, and poor response to levodopa; cerebellar dysfunction: gait ataxia, with cerebellar structure Sound disorders, limb ataxias, or cerebellar eye movement disorders.

4 The upright test measures blood pressure and heart rate in the supine and upright positions, and blood pressure drops 30 / 15mmHg compared with the supine position within 3 minutes of standing, and the person with no significant change in heart rate is positive (orthostatic hypotension).

5. Bladder function evaluation is helpful for early detection of neurogenic bladder dysfunction. Urodynamic experiments showed that the detrusor reflex increased excitability, urethral sphincter function decreased, and residual urine increased in the later stages of the disease. Bladder ultrasound is useful in diagnosing bladder emptying disorders.

6. Anal sphincter electromyograms often show denervation, and this test is normal to help rule out MSA.

7. 123I-m-iodobenzidine (123I-MIBG) myocardial imaging. This test can help distinguish autonomic dysfunction from sympathetic or postganglionic lesions. Myocardial uptake of 123I-MIBG was reduced in patients with Parkinson's disease, while the post-sympathetic ganglion fibers in MSA patients were relatively intact, without this change.

8. Imaging examination revealed significant atrophy of the putamen, pontine, cerebellum, and cerebellum. The fourth ventricle and pontine cerebellum and foot cistern enlarged. High field strength (above 1.5T) MRI T2 phase showed band-shaped arc-shaped high signal at the dorsal lateral margin of the putamen, cross sign at the base of the pontine and high signal at the midfoot of the cerebellum. 18F-deoxyglucose PET showed low metabolism in the striatum or brain stem. ^[4]

Differential diagnosis of multiple system atrophy

In the early stages of the disease, especially when it presents clinically with a single systemic symptom, each subtype needs to rule out its associated disease. After the symptoms have developed completely and multiple systems are involved, it is not difficult to diagnose if other diseases can be ruled out.

1. MSA-P should be distinguished from the following diseases

(1) Vascular parkinsonism (VP): Parkinson's syndrome with prominent symptoms in both lower extremities, which is characterized by gait disorder, pyramidal tract signs and pseudobulbar paralysis.

(2) Progressive supranuclear palsy: It is characterized by vertical supranuclear paralysis, especially lower vision paralysis.

(3) Corticobasal degeneration (CBD): Alien hand syndrome, apraxia, cortical sensory disturbance, asymmetric myotonia, limb dystonia, stimulation of sensitive muscles Clinical manifestations such as clonus.

(4) Lewy body dementia: Myotonia is more severe than slow movements and tremors, and early cognitive dysfunction, especially attention and alertness fluctuations, are most prominent, spontaneous hallucinations, over-sensitivity to antipsychotic drugs, extremely Prone to adverse reactions such as extrapyramidal system.

2. MSA-C should be distinguished from multiple hereditary and non-hereditary cerebellar ataxias. ^[5]

Multi-System Atrophy Treatment

There is currently no specific treatment method, mainly for symptomatic treatment of autonomic nervous disorder and Parkinson's syndrome.

Multiple system atrophy orthostatic hypotension

Non-pharmacological treatments are preferred, such as stretch socks, high-salt diets, and bedside elevations at night. Ineffective treatment can be selected with drugs: vascular alpha receptor agonist midodrine hydrochloride, can quickly increase hypertension (30-60 minutes), 2.5mg, 2 to 3 times a day, the maximum dose is 40mg / d, avoid before going to bed Taking (to prevent supine hypertension); 9- fludrocortisone: can be taken orally, 0.1 ~ 0.6mg / d, also has the effect of improving hypotension; in addition to ephedrine, non-steroidal anti-inflammatory drugs such as indole Meixin and others. However, in view of the side effects of the latter two drugs, they are not recommended for routine treatment of orthostatic hypotension in patients with MSA.

Multiple system atrophy urinary dysfunction

Trospium chloride (20mg, 2 times a day), oxybutynin (2.5-5mg, 2 to 3 times a day), tolterodine (2mg, 2 times a day) can improve early-stage detrusor muscles Spasm symptoms.

Multiple system atrophy Parkinson syndrome

Medopa is effective in a small number of patients, and dopamine receptor agonists have no significant effect. Paroxetine may help improve motor function in patients. Bilateral thalamus nucleus high frequency stimulation may be effective in a few patients with MSA-P subtype.

Multiple system atrophy other

For dystonia, botulinum toxin can be used.

Prognosis of multiple system atrophy

Most patients diagnosed with MSA have a poor prognosis. The average time from onset of symptoms to dyskinesia (pyramidal, extrapyramidal, and cerebellar dyskinesia) and autonomic nervous system dysfunction is 2 years (1 to 10 years); from onset to the need for assistance in walking, wheelchair, bedridden The average interval between death and death was 3, 5, 8 and 9 years, respectively. Studies have shown that the heavier the MSA damages the autonomic nervous system and the less damage the nigrostriatal system, the worse the patient's prognosis.

Multi-System Atrophy Disease Prevention

There are currently no effective preventive measures. People with a family history can conduct genetic counseling and necessary tests to avoid long-term exposure to organic solvents, heavy metals, pesticides, etc.

Multi-System Atrophy Care

At present, the treatment of MSA is mainly symptomatic, and there is no method to significantly delay the progress of the disease. Therefore, the care of patients with MSA is a long-term process from illness to death. Nursing mainly includes the following aspects:

Multi-System Atrophy Security Protection

Prevent suffocation. Pay attention to observe the number of breathing during sleep, whether there is increased snoring, wheezing, and the presence or absence of sleep apnea syndrome. If abnormal awakening is detected in time, sleep breathing monitoring is performed. In severe cases, trachea cannulation or incision is performed. Protection of orthostatic symptoms. Patients with MSA may experience dizziness, falls, and blurred vision. Patients need to move slowly when changing positions, and strengthen protective measures to avoid head injuries and fractures of limbs.

Cooperation and use of multiple system atrophy physiotherapy

It is the first method to prevent orthostatic hypotension, which can be used to raise the head and torso position of the patient during sleep or supine position, train the patient to adapt to blood pressure fluctuations during posture change, and wear anti-stress clothing.

Multisystem Atrophy Diet Guide

Instruct patients to eat a high-sodium, high-potassium diet, drink 2 to 2.5 L of water daily, record the amount of in and out, and adjust as appropriate according to the actual situation to maintain stable blood pressure and circulating blood volume. The diet is based on the principle of eating less and eating more foods, avoiding overeating, and inadequate blood supply to the brain due to increased gastrointestinal blood flow, aggravating dizziness and dizziness.

Nursing of multiple system atrophy drinking water cough, dysphagia

It is necessary to actively prevent aspiration from drinking water and coughing and swallowing difficulties, and provide functional exercise guidance, such as insufflation before drinking, suffocation when swallowing, eating slowly, and adjusting the diet to the tongue and feeding it in small portions Nasal feeding when severe swallowing difficulties.

Nursing of multiple system atrophic urination disorder and autonomic dysfunction

Patients with MSA may have varying degrees of dysuria, decreased libido, impotence and other autonomic dysfunction. Urinary incontinence patients should pay attention to urine collection, urine collection can use urine collectors, urine retention patients need to perform urine volume assessment, according to the condition of intermittent catheterization or permanent bladder fistula.

Multi-system atrophic mental nursing

Patients with MSA have a long course of disease and poor quality of life. They are prone to lose confidence in life and produce depression. It is necessary to strengthen psychological care, establish a good relationship between nurses and patients, strengthen the confidence and courage in treatment, and give timely encouragement to progress in treatment.

Multi-system atrophy strengthens education and prevents complications

Strengthen education on the problems that may occur in the course of the disease, and strive to prevent complications, extend the survival of patients and improve the quality of life.