Clinical Features Of Autonomic Dysfunction In Multiple System Atrophy And Correlation Analysis Of Orthostatic Hypotension And Age Of Onset

Background and Objective:Multiple system atrophy（MSA）is a kind of unclear etiology of progressiveneurological disease which is happended in degeneration of multiple system.From thefirst discovery of Olivopontocerebellar atrophy (OPCA) to Shy-Drager syndrome andnigrostriatal degeneration (SND),and then the three diseases collectively known aremerged as multiple system atrophy (MSA),it has gone through more than onehundred years.In1989,Papp and Matsuo found the inclusion bodies are presented incommon in MSA patients’glial cells,and this is known as an important marker forMSA.In1998, Gliman presented a diagnostic criteria for the diagnosis of MSA inrecent years,and revised and improved again and again.In2008,the new diagnosticcriteria for the diagnosis of MSA is presented[1].Then,we open a new chapter forstudying and understanding MSA.The diagnostic criteria for MSA shows:The necessary condition for diagnosis ofMSA is that eosinophilic inclusion bodies are found in glial cell cytoplasm by histopathology;The core component of inclusion bodies is α-synuclein. The lesionsmainly involve the substantia nigra-striatum system, olives body-pons-the middlecerebellar,cell column and Onuf’s nuclei in the middle of the spinal cord.There areother pathological changes in MSA found,like Purkinje cells dropoed out in cerebellar,thinning of granular layer, gliosis in putamen and loss of neuronal[2].The majorclinical manifestations of MSA patients is the damage of extrapyramidal system,symptoms of cerebellar system, autonomic nervous system and the cone system.SomeMSA patients present cognitive dysfunction.In the past,MSA was divided into3types:striatonigral degeneration (SND),sporadic olive pontine cerebellar atrophy (OPCA)and Shy-Drager syndrome (SDS). Currently, the MSA is divided into two kinds ofclinical subtypes:MSA-P subtype with the main symptoms of Parkinson’s disease andMSA-C subtype in the main symptoms of cerebellar ataxia.The basis pathological ofautonomic dysfunction in MSA is autonomic preganglionic lesion,affectintermediolateral cell column of spinal cord and dorsal nucleus of vagus nerve,andlesions can be involved both sympathetic and parasympathetic nervous system;theinvolvement of other cells include monoamine neurons in reticular formation ofbrainstem ventrolateral and arcuate nucleus cells.Autonomic dysfunction are presentin all subtypes, it’s pathological changes often overlap with each other in varioussubtypes. Accordingly,it is no longer typed independently.Due to histopathologicalexamination subject to various restrictions,the clinical characteristicsand performance is an important basis for the diagnosis and treatment of MSA.Previous studies also show that symptoms of autonomic dysfunction are presentedbefore or accompanied with both extrapyramidal or cerebellar involvement as themain clinical manifestations;It is not only the prerequisites of diagnosis of “probableMSA”,but also the important sign to differentiate from other movement disorders. Atpresent,the study of autonomic nervous system dysfunction in MSA is rare in thedomestic. Orthostatic hypotension is a manifestation of autonomic dysfunction.Whenpatient’s body position is changed from supine to upright, a sharp decline in bloodpressure, associated with dizziness, black mask, heart rate, and even fainting, falls.Itis more common in the elderly and neurodegenerative diseases such as Parkinson’sdisease (PD) or MSA, have a serious impact on patients’ lives. Therefore, the present study the clinical features of autonomic function disorders in MSA and therelationship between orthostatic hypotension and age of onset is important of thediagnosis, treatment and early intervention of MSA.Materials and Methods:1.68patients with probable MSA treated by new diagnostic criteria for MSAwere registered from December2010to December2013in the First AffiliatedHospital of Zhengzhou University, Department of Neurology.The MSA patients aredivided into two kinds of clinical subtypes:MSA-P subtype with the main symptomsof Parkinson’s disease and MSA-C subtype in the main symptoms of cerebellar ataxia.And the patient’s clinical data and signs are divided into four groups: Group a(dizziness or fainting, urinary and reproductive dysfunction, sleep apnea, snoring orstridor), group b (postural balance disorders, muscle rigidity, slowness of movement,expression sluggish), group c(gait ataxia, dysarthria, nystagmus, finger nose test orwith knee-shin test positive)and group d(Babinski sign was positive, tendonhyperreflexia).Symptoms characteristic of the four groups were analyzed.2.24patients with probable MSA treated by new diagnostic criteria for MSAwere registered from December2010to December2013in the First AffiliatedHospital of Zhengzhou University, Department of Neurology.MSA patients withorthostatic hypotension were divided by age distribution: Group A (40y～49y),groupB (50y～59y), group C (60y～70y).We checked the three rows by lying orthostaticblood pressure measurement.Based on provisions for the diagnosis of orthostatichypotension in the new MSA diagnostic criteria：When patients’ position from supineto upright in3min, systolic blood pressure fall by30mmHg at least or diastolic bloodpressure fall by15mmHg at least,we recorded detail mean blood pressure decreasedstatistical data and analysis the relationship between mean blood pressure decreasedand orthostatic hypotension with age of onset.3. We processed data by using SPSS13.0software,used percentage to expresscount data,and compared clinical features of multiple sets by χ2test.Each group werecounted by single factor analysis of variance test. LSD-t test was used to compare two different mean.We obtain frequency data from two categorical variables by crosscounting(contingency table)and analyze the association between two categoricalvariables by Pearson χ2independence test.P<0.05indicates significant difference.Results:1. In this study,45patients in MSA-C group, including30males (66.7%) and15females (33.3%);23patients in MSA-P group, including15males (65.2%) and8females (34.5%).Average age of onset of MSA patients was (55.3±3.5) years (40～70years).The average age of onset of MSA-C group was (55.0±3.6) years old; Theaverage age of onset of MSA-P group was (55.5±3.2) years old. The results showedthat the differences of gender between MSA-C group and MSA-P group was notstatistically significant(P>0.05). The difference of age of onset between the twosubtypes of patients with analysis of variance was not statisticallysignificant(P>0.05).2. In this study, compared clinical symptoms and signs of four groups,it is shownthat the difference of group B (postural balance disorders, muscle stiffness, tremor,goofy facial expressions) and group C (gait ataxia, dysarthria, nystagmus, finger nosetest or with knee-shin test positive) was statistically significant (P<0.05).The clinicalmanifestations, such as gait ataxia, dysarthria, nystagmus, finger nose test orknee-shin test positive,is more inclined to MSA-C subtype; The clinicalmanifestations, such as postural balance disorders, muscle rigidity, slowness ofmovement, expression sluggish, is more inclined to MSA-P subtype. The differenceof autonomic dysfunction (dizziness or fainting, urinary and reproductive dysfunction,sleep apnea, snoring or stridor) and pyramidal tract damage manifested (Babinski signwas positive, hyperreflexia) is compared between MSA-C and MSA-P was notstatistically significant (P>0.05).3. Orthostatic hypotension in MSA patients were divided by age distribution:3patients in group A(40y～49y),5patients in group B(50y～59y),4patients in groupC (60y～70y). The mean of blood pressure decreased in these five groups:(35/16)±(5/3)mmHg in group A,(43/21)±(7/5)mmHg in group B, (42/18)±(6/5)mmHg in group C. In this study,compared of different ages in these sixgroups by ANOVA, it presents that the difference of each group was not statisticallysignificant(P>0.05). Compared of different mean of blood pressure decreased inthese six groups by LSD-t test, the difference was not statistically significant (P>0.05).Correlation and regression analysis executed between orthostatic hypotension and ageof onset showed that the prevalence rate of orthostatic hypotension in MSA wascorrelated with age of onset(P <0.05). Compared with group A, group B,prevalenceof group C is higher (87.5%over33.3%,62.5%). However, the sample size is less.Alarge number of samples are needed for further research and exploration.Conclusions：1. Two MSA subtypes included common symptoms of autonomic dysfunction.Symptoms of autonomic dysfunction are the main symptoms of MSA, which is anecessary condition for the diagnosis of MSA.2. Symptoms of urinary and reproductive dysfunction and orthostatichypotension are particularly prominent in the autonomic nervous system disorder ofMSA.3. The prevalence of orthostatic hypotension may be associated with age of onsetto some extent. The prevalence of orthostatic hypotension may increase with age. Itmay be related with physical function of MSA elderly decline, whose baroreceptorsensitivity decreased, unresponsive to heart rate and compliance of arterial wallreduced.4. MSA patients’ age of onset has little impact on the degree of decline inorthostatic blood pressure. The degree of decline may be related to nervedegeneration of MSA.