Nature of Parkinsonian features in multiple system atrophy

INTRODUCTION

Multiple system atrophy (MSA) is a sporadic progressive neurodegenerative disorder comprising Parkinsonian features, cerebellar features, corticospinal dysfunction, and autonomic features.^[1-4] MSA patients often come to the clinical attention due to Parkinsonian features.

However, the clinical profile of Parkinsonian features is not as clear in MSA as in some other neurodegenerative syndromes such as progressive supranuclear palsy (PSP) or Parkinson’s disease (PD). With time and validation now, there is a fair amount of clarity in Parkinsonian features to distinguish between PSP and PD. However, the literature considers some Parkinsonian features such as asymmetry, tremors, peripheral rigidity, and forward falls to be the typical features of PD,^[5-10] while it does hold some others such as symmetry, axial rigidity, backward falls, and down-gaze restriction to be the typical features of PSP.^[11-16]

In this paper, we studied Parkinsonian features in MSA to see if there is any specific pattern, which could be useful in the early diagnosis of MSA.

MATERIALS AND METHODS

In this observational study, the researchers studied patients of MSA in the Department of Neurology of the institute with an objective to study the type of Parkinsonian features in them.

RESULTS

Of all 57 cases, the mean age: 60.09 ± 10.216 years, 15 females and 42 males, 18 (31.6%) had MSA-C and 39 (68.4%) had MSA-P. The mean age at the onset of the disease was 55.95 ± 10.793 years. Table 1 depicts the demographic characteristics of the MSA-P and MSA-C patients. Figure 1 illustrates the clinical and imaging features of our MSA patients.

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Figure 1:

Percentage of MSA patients having different clinical and imaging features

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Although 86% of the MSA patients had an initial response to levodopa, 64% of them sustained this responsiveness to levodopa. Furthermore, amantadine is effective in around half of all patients. Table 1 demonstrates different clinical features found in MSA patients and in the MSA-P and MSA-C groups, and Table 2 depicts the frequency of features mimicking PSP and PD in MSA patients.

After grouping all 57 MSA (39 MSA-P and 18 MSA-C) patients on the basis of predominant extrapyramidal features, Figure 2 shows the number and percentage of those having PD-like (at least two of asymmetry, tremors, forward falls, and peripheral rigidity), PSP-like (at least two of symmetry, axial rigidity, backward falls, and gaze restriction), and a mixed presentation (P = 0.073).

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Figure 2:

Frequency and percentage of MSA, MSA-P and MSA-C patients having different types of extrapyramidal features

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Based on history, of all 57 MSA patients, 31 (54.39%) (22 MSA-P and 9 MSA-C) presented initially with pure Parkinsonian symptoms for a variable period before the appearance of any other symptom to suggest MSA (autonomic or cerebellar).

DISCUSSION

Apart from autonomic features, cerebellar features, and corticospinal dysfunction, the Parkinsonian features are an important part of MSA.^[1-4] As there is a lot of disparity in the clinical extrapyramidal features between PD and PSP, it becomes important to understand the nature of these features in MSA as well. In the present study, among the clinical features mimicking PSP, 56.1% of all MSA patients had symmetry. Quite like our study, previous studies have also shown symmetry in around 60% of MSA patients.^[19,20] Furthermore, previous researchers have shown axial rigidity to be more common in MSA.^[20] In our study also, more than half of all MSA patients had an axial rigidity, which is consistent with the previous studies. Moreover, extraocular movement disorder is an important feature in the diagnosis of PSP and helps in differentiating between MSA and PD at an early stage.^[21] However, in our study, quite a large number of patients of MSA suffered from an extraocular movement disorder in the form of downgaze restriction, upgaze restriction, abnormal saccadic eye movements, and abnormal smooth pursuit. Hence, these features may not be specific to PSP, and a large number of MSA patients may as well have these features. MSA patients may have falls.^[20,22-24] However, we do not know exactly how many patients have falls in the backward direction like PSP and how many of them fall in the forward direction like PD patients. In this study, around one-third of all patients fell in the backward direction, which is a feature resembling PSP, and the forward falls were as frequent.

Among the clinical features mimicking PD, more than one-third of all MSA patients had an asymmetry. Some studies have shown asymmetry in MSA, but the reports are few.^[25]

Tremor, however, is a known feature of MSA and may occur in as high as 80% of all MSA patients.^[26] Our study also demonstrated tremors in >70% of the MSA patients, though only one-fifth of all patients had the typical pill-rolling tremors. Furthermore, around half of all MSA patients in the present study had a predominant peripheral rigidity, which experts consider to be a very typical feature of PD.

In all, 86% of MSA patients responded initially to levodopa, and the previous studies have shown variable response to levodopa in MSA patients.^[20,27,28]

Hence, the initial presentation in some of the MSA patients was PD-like and in some others PSP-like. However, the highest proportion of them had a mixed type of presentation, and one must consider this fact while diagnosing MSA patients at an earlier stage.

Slowness of movements was the most frequent symptom in MSA patients, and peripheral rigidity was the most frequent sign. Among MSA-P patients, the most frequent symptom was slowness of movements and the most frequent sign was bradykinesia, while in MSA-C patients, the most frequent symptom was change in handwriting and the most frequent signs were peripheral rigidity, upper limb incoordination, lower limb incoordination, and truncal rigidity. In the past also, the studies reported slowness of movements and bradykinesia to be the most frequent clinical features of MSA, similar to our observation.^[29] In MSA-P patients, also the results depicting bradykinesia to be the most frequent sign are similar to the previous observations, while in MSA-C, though we expected incoordination, a very high number of individuals had rigidity as well, which was contrary to our expectations.^[29]

The only features that were significantly different in MSA-P and MSA-C groups were slowness of movements, masking of the face, and bradykinesia, which were more frequent among MSA-P patients and gait ataxia, which was more common in MSA-C patients, and these findings were consistent with the earlier knowledge.^[30] Although not the primary aim of this study, we found that cerebellar atrophy was the most frequent imaging finding in our MSA patients, the others being pontine atrophy, putaminal atrophy, and middle cerebellar peduncular atrophy. According to past research, putaminal atrophy, hyperintensive rim, cerebellar atrophy, the “hot cross bun” sign, and middle cerebellar peduncle hyperintensity are frequent in MSA. The previous researchers have found out decrease in glucose metabolism in the parietal area for PD, in the bilateral putamen for MSA-P, and in the bilateral cerebellum for MSA-C in 18F-fluorodeoxyglucose-positron emission tomography/computed tomography, and therefore, such techniques can differentiate between MSA and PD.^[31]

The limitation of this study is that this is a single-center study, and the scientific community will benefit if we get data from other regions as well in the future.

Since more than half of all MSA patients presented initially with pure Parkinsonian symptoms before the appearance of any other symptoms suggestive of MSA (cerebellar or autonomic), hence, one must keep in mind this fact and follow up all the patients, who initially present as PSP or PD for the appearance of any other symptoms or signs suggestive of MSA, as the early clinical features may be deceptive. We can generalize these results to that of the population of at least our country considering the fact that our institute caters to a number of people from all parts of India.

CONCLUSION

The extrapyramidal features of MSA patients may resemble those of PD or PSP or they may have characteristics of both. Also, one must follow all the patients with a PD-like or PSP-like presentation to look for MSA.