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HOME > MSA > Article Content

Multiple System Atrophy (MSA)

by Drs. Like Wu, Xiaojuan Wang and Bo Cheng

Wu Medical Center, Beijing, China

MSA is a kind of diffusive neurodegenerative disease which usually attacks during the adult period. The clinical manifestations show the autonomic nerve disorder with different degrees, the Parkinson syndrome with poor response to levodopa, cerebellar ataxia, and pyramidal sign and so on. Because the onset successions of the affected 3 systems are different, those clinical manifestations caused are also different. With the development of the disease, the pathological and clinical manifestations of those 3 systems damaged can be occurred finally. The epidemiological survey indicates the MSA annual incidence of the over 50 year-old group is about 3/100,000.

Because of the degeneration of the diffusive substantia nigra with or without the vegetative nerve function disorder and the increase of the usually concomitant clinical and pathological recognization of the Olivopentocerebellar atrophy, the individual performance of the above every symptom are different. The published study on large samples of a few of those complicated syndromes indicated the incidence of the disease and the nature of all kinds of syndromes. 13% of the patients with idiopathic Parkinson's disease are MSA patients, shown in a survey of UK Parkinson's disease association. All the MSA patients had over 1 symptom of vegetative neural insufficiency, which includes postural hypotension, urgent urination or urinary retention, gatism, hoarseness or stridor. Half of the patients have the Babinski syndrome, 1/3 of the patients have cerebellar ataxia. The quantity of the male patients is more than that of the female patients.

The research of MSA patients found that 46% of patients have striatonigral-Parkinson syndrome as the onset symptom, the bilateral affected areas are asymmetric usually; 41% of the patients have the vegetative nerve symptom as the onset symptom; the orthostatic hypotension will appear to all of the patients at last. 5% of the patients have the cerebellar sign as the primary symptom, while the ataxia will occur among over half of the patients in the end; 29% of the patients have a slight tremor as the onset symptom. We should make clear that MSA is more serious than Parkinso's disease because 40% of the patients will live in the wheelchair or gain a serious disability, generally, within the next 5 years. Although striatonigral degeneration, olivopentocerebellar degeneration, and shy-drager syndromes will occur together regularly, every disease can appear independently. The pathological features are: the neuron consumption and the necrosis fragments accumulate inside of the gliacytes (argyrophilia colloid inclusion body). WSCMC thinks it plays a very important role in the pathogenesis that this aggregates inside the cytoplasm of the gliacytes making the onset and development of the degenerative diseases.

Classification of disease

MSA includes Shy-Drager syndrome (SDS), striatonigral degeneration (SND) and Olivopontocerebellar astrophy (OPCA), 3 types. According to the clinical manifestation, it can be classified into 2 kinds of clinical subtypes, 1 clinical subtype, Parkinson syndrome as main clinical manifestation is called MSA-P type, the other clinical subtype, cerebellar ataxia as main clinical manifestation is called MSA-C type.

The cause and Pathogenesis

The cause of the disease is not clear. The pathological symbol of MSA is that the eosinophilic inclusion body can be found in the cytoplasm of the neuroglia cell with the neuron losing and gliacyte hyperplasia.

Recently, it is thought that the pathogenesis of MSA probably has 2 ways: the first is, the pathological changes hypothesis of primary oligodendrocyte, the oligodendrocyte degeneration of a-synuclein positive inclusion body as the feature appears first, which leads to the myelinoclasis and degeneration of the neurons, activates the microglia cells, induces the oxidative stress, then causes the degeneration and death of the neurons.  The second is, a-synuclein of the neuron abnormally accumulates, which causes the degeneration and death of the neurons. The cause of a-synuclein accumulation is not clear, although it is probably related to the genetic predisposition and environmental factors.

Clinical Manifestation

Adult-onset, many patients had MSA whose ages are from fifty to sixty years old, the average age of patients at the onset of the disease is 54.2 years old. The morbidity of male is higher than female. The disease onset is slow and progresses gradually. First symptoms of MSA are the autonomic nerve dysfunction, Parkinson's syndrome and cerebellar ataxia. A few patients also have an onset with amyotrophy. 

Regardless of the start of the disease, with what kind of nervous system symptoms, when the disease progresses further, there will be two or more systematic neural symptoms group following:

1. Autonomic dysfunction

Autonomic dysfunction is often the first symptoms of MSA disease. Autonomic dysfunction is also one of the most common symptoms. Common clinical manifestations: urinary incontinence, frequent urination, urgent micturition, urinary retention, male erectile dysfunction and postural hypotension. This is accompanied with swallowing difficulty, anisocoria, Horner syndrome, asthma, apnea and breathing difficulty. If the disease is serious, it leads to tracheotomy. Speckled hands and hands that are cold to the tough are caused by autonomic nerve dysfunction, it has characteristics. The earliest symptom for males are erectile dysfunction, the earliest symptom for females is urinary incontinence.

2. Parkinson syndrome

Parkinson's is an outstanding symptom of MSA-P subtype. Parkinson's is also one of the most common symptoms of other subtypes, as well. The characteristic of MSA'S Parkinsonism is bradykinesia. This is accompanied with myotonia, a tremor involving both sides, but the degree is different. Many patients have an insufficient therapeutic response to L-dopa. This is liable to appear as dyskinesia's and other adverse reactions.

3. Cerebellar ataxia

Cerebellar ataxia is an outstanding symptom of MSA-C subtype. This is also one of the most common symptoms of other subtypes, as well. The clinical manifestation is a progressive gait disorder and limbs ataxia. This is accompanied with obvious dysarthria, nystagmus and cerebellar ataxia.

4. Others

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

(2) Common with swallowing difficulty, dysphonia and other symptoms.

(3) Sleep disorders, such as sleep apnea, and REM sleep behavior disorder and so on.

(4) Other extrapyramidal systems: dysmyotonia, palatal myoclonus and myoclonus. Stimulus of the hand and the face, the myoclonus is the characteristic performance of MSA.

(5) Some patients have muscle atrophy; later stages have hypermyotonia, tendon hyperreflexia, and optic atrophy. A few patients have ophthalmoplegia, where the eyeballs have gaze palsy up one side or down one side.

Disease prognosis

The prognosis for most patients with MSA are not good. The average time from initial symptom progress to combine dyskinesia (pyramidal system, extrapyramidal system and cerebellar sports disorder) and autonomic nerves system function disorder is 2 years. The average interval from the onset of disease to assistant walk, wheel chair, bed-ridden and failure is 3 years, 5 years, 8 years and 9 years.

The conventional treatment mainly includes symptomatic treatment and rehabilitation therapy but they are not shown to be effective. All kinds of medication therapy cannot hold back the degeneration and necrosis of the neurons and oligodendrocytes. In recent years, WSCMC found that the treatment of supplying neural stem cells, to directly increase the quantity of the neural cells in brain and repair the neural damage partly, while the neural stem cells carry normal genes, they can express normal functions and produce proteome following the proper medication controlling, those proteins with normal structures can replace the functions of abnormal proteins caused by the patients gene mutation, and decrease the quantity of accumulation inside gliacyte cytoplasm. It can partly restore neural functions; slow down the disease progress for MSA, Parkinson's disease, dementia with Lewy bodies, and a series of the degenerative diseases. But it only leads to 10% of the cells survival; the neural stem cells are injected without the proper medication guideline, while the cells location is probably difficult. Based on almost a 10-year research, WSCMC has a unique implanted stem cell location technology and adjusting technology in vivo, which can obviously increase the function level of the location and differentiation and activation of the implanted stem cells in vivo, so that leads to target the effective treatment, improve the patients' life quality and the implanted cells survival period.

Related Information:

Case Analysis for MSA

MSA Patient Stories

The Parkinson's Clinical Center
Doctor Blogs
Treatment Data
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