Objective: to describe the rate of levodopa response, phenotypical characteristics, prognostic implications and pathological features in a large cohort of patients with pathology-confirmed Parkinson’s disease (PD), multiple system atrophy (MSA) and progressive supranuclear palsy (PSP).

Background: although levodopa response has important diagnostic and therapeutic implications in PD, MSA and PSP, there is little data from large pathology-confirmed cohorts about the phenotypical characteristics and underlying pathologies associated with a positive levodopa response.

Method: clinico-pathological cohort study with retrospective review of medical records of consecutive patients with pathology-confirmed PD, MSA and PSP treated with levodopa from the Queen Square Brain Bank (London, UK). Levodopa response was graded on a 4-point scale as per UK Parkinson’s Brain Bank criteria and considered sustained if continued benefit was noted for > 2 years. Relevant clinical and pathological variables including staging of synuclein, amyloid and tau burden were recorded.

Results: 133 patients with PD (56% male; age at onset 60.1 ± 11.8 years), 115 with MSA (56% male; 57.9 ± 10.4 years) and 191 with PSP (64% male; 67.6 ± 7.6 years) were included. A definite response (defined by a sustained > 2 years good/excellent response to levodopa) was noted in 114 patients (85.7%) with PD, 9 patients (7.8%) with MSA and 4 patients (2.1%) with PSP. 

In PD, lack of response was associated with older age, postural instability and gait difficulty subtype, early falls, early dementia, higher misdiagnosis rate and reduced survival. Severity of Lewy pathology or Alzheimer’s disease neuropathological changes did not differ by levodopa response.

Levodopa response in MSA did not show any association with clinical, prognostic or pathological variables.

PSP levodopa-responders presented more commonly PSP-parkinsonism subtype and developed falls later in the disease course. All PSP responders had Lewy body copathology at post-mortem and greater burden measured by Braak and McKeith stages directly correlated with positive levodopa response.

Conclusion: Levodopa response in PD, MSA and PSP is associated with clinical, prognostic and pathological features with important diagnostic, prognostic and pathogenic implications.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/levodopa-response-in-pathology-confirmed-parkinsons-disease-multiple-system-atrophy-and-progressive-supranuclear-palsy/