Outcome of deep brain stimulation in slowly progressive multiple system atrophy: A clinico-pathological series and review of the literature
Introduction
Multiple system atrophy (MSA) is a relentlessly progressing fatal neurodegenerative disease characterized by a variable combination of poorly levodopa responsive parkinsonism, autonomic failure, cerebellar signs and pyramidal tract involvement [1]. Two clinical phenotypes exist, i.e. MSA-P with predominant parkinsonism and MSA-C with prevailing cerebellar manifestations [2]. The prognosis of MSA is generally poor with a mean survival of 6–10 years [1], [3], [4]. It is noteworthy that some patients with histologically proven MSA may present slower and more benign disease progression [5]. These patients may have prolonged levodopa responsiveness in contrast to the only initial and transient efficacy of this treatment in 20–30% of MSA patients. Dyskinesia may further extend beyond classical oro-facial dystonia and mimic generalized peak-dose dyskinesia as observed in Parkinson's disease (PD) [4], [5], [6]. A few case reports and small patient series have mostly reported a poor outcome after deep brain stimulation (DBS) in MSA patients, contrasting with the high effectiveness of this treatment in PD patients with motor complications [7], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20].
The aim of the present study is to describe the largest series of histologically proven MSA patients who underwent DBS because they were considered as having PD at the time of surgery. We also provide some considerations to better identify these patients prior to surgery.
Section snippets
Methods
Five histologically proven MSA patients who underwent DBS and experienced severe worsening of their condition after DBS surgery were identified retrospectively by the investigators of the French MSA network. These patients were followed in Lyon, Marseille, Bordeaux, Strasbourg, Aix-en-Provence and Paris.
Patient 1
This 55 year-old woman developed in 1992 levodopa-responsive left-sided akinetic-rigid and tremulous parkinsonism. No pyramidal or cerebellar signs were observed at initial examination and during follow-up. Unexplained dyspnea with slight hypoxemia occurred several years after symptom onset and was retrospectively interpreted as first manifestation of autonomic failure. Motor fluctuations and peak-dose dyskinesias appeared two years after the initiation of levodopa. Subthalamic nucleus (STN)
Discussion
This is the largest study reporting the outcome of STN-DBS in histologically proven cases of MSA. Three patients showed significant benefit within the first year after surgery, while the improvement in the two other was only mild to moderate. Irrespective of the immediate DBS outcome, all patients developed within short time after surgery additional disabling symptoms (e.g. gait ataxia, dysphagia and autonomic failure) that were resistant to levodopa and DBS stimulation parameter adjustments.
Authorship
CL, ST, WGM, DG, FT, AE, FV, CT, PD, JLH, TW, AV, NS, BL, AMDP: Substantial contributions to the conception or design of the work, or the acquisition, analysis or interpretation of data.
WGM, ST, CL: Drafting of the first version of manuscript.
AE, FV, CT, PD, JLH, TW: Critical revision and editing of earlier versions of the manuscript for important intellectual content.
CL, ST, WGM, DG, FT, AE, FV, CT, PD, JLH, TW, AV, NS, BL, AMDP: Final approval of the version published.
CL, ST, WGM, DG, FT, AE,
Competing interest
None declared regarding the present work.
Acknowledgment
No funding was obtained regarding the present study.
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- 1
These authors contributed equally.