Objective: To describe safety, tolerability and clinical response to continuous subcutaneous (SC) levodopa infusion in three patients with multiple system atrophy (MSA).

Background: Response to oral levodopa in MSA is typically limited or transient, and motor fluctuations may occur. Therapeutic options for motor symptoms are scarce, and device-aided therapies are not formally approved.

Continuous SC levodopa infusion provides more stable plasma levodopa levels and is widely used in advanced Parkinson’s disease. However, data regarding its use in MSA are lacking. Given the pathophysiological overlap, this therapeutic strategy may represent a potential off-label option.

Method: We conducted a retrospective descriptive case series of three patients diagnosed with clinically probable MSA according to current consensus criteria who initiated continuous SC levodopa infusion between May 2025 and February 2026.

Results: The three patients (2 females, 1 male) had MSA-P phenotype. They were aged 62-63 years, with a median disease duration of 5 years (4-6). All had previously demonstrated responsiveness to oral levodopa and experienced disabling motor fluctuations with wearing-off. Two of them also presented levodopa-induced orofacial dystonia.

Baseline levodopa equivalent daily doses (LEDD) were 457, 800 and 1050 mg/day, and UMSARS part II scores in the ON state were 27, 19 and 24, respectively.

One month after initiation of SC levodopa infusion, the first two patients reported much improvement according to the Clinical Global Impression–Improvement scale (CGI-I), which persisted at 6 month follow-up. Daily OFF time was reduced by 7 and 3 hours. Both patients used the infusion 24h, reaching LEDDs of 1141.2 and 1129.2 mg/day respectively. The patient who initiated treatment on February 2026 reported mild improvement at one month and currently continues therapy with a LEDD of 1700.4mg/day.

Dyskinesias did not worsen in any patient.

One patient experienced mild hypotension, which was controlled by adjusting the infusion dose. No other remarkable adverse events have occurred to date.

Conclusion: In this small case series, continuous SC levodopa infusion was well tolerated and effective in reducing OFF periods in selected patients with MSA-P and levodopa responsiveness with motor fluctuations. This treatment enabled an increase in LEDD without significant adverse events. Larger prospective studies are needed.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/subcutaneous-levodopa-infusion-in-multiple-system-atrophy-a-case-series/