Objective: We aimed to characterize early clinical features of progressive supranuclear palsy (PSP) that might correlate with clinical course and neuropathologic findings.

Background: Progressive supranuclear palsy (PSP) is an atypical parkinsonian disorder that usually presents with early falls and vertical gaze palsy. The clinical syndrome is referred to as Richardson’s syndrome (RS). Other presentations include parkinsonism-predominant (PSP-P), corticobasal syndrome (PSP-CBS), frontal-behavioral syndrome (PSP-FBS), and cerebellar ataxia (PSP-C). It is unknown if early symptoms predict clinical course.

Method: Autopsy-confirmed cases of PSP without other major neurodegenerative changes in the Mayo Clinic Brain Bank were enrolled. Clinical symptoms and their timing were abstracted from medical records with a dedicated pipeline integrated with fine-tuned GPT. Neuronal loss in specific brain regions was assessed semi-quantitatively and compared to the clinical syndromes. The unbiased pipeline abstracted 167,508 excerpts with 195 neurological features from medical records of 938 PSP cases. After excluding cases evaluated with 2 or fewer of the 10 key symptoms, 392 cases were further analyzed.

Results: Overall, the median age at death was 74 years (range: 45-93) and the disease duration was 6 (range: 1‑20) years. PSP was clinically suspected in 340 (86%), corticobasal degeneration in 42 (12%), Parkinson’s disease in 15 (4%), and multiple system atrophy in 12 (3%). Some clinical syndromes presenting within the first 3 years had shorter disease durations compared to the entire cohort. These included Richardson’s syndrome (median years: 5 vs. 6, P < 0.01), parkinsonism (5 vs. 6, P < 0.01), frontal presentation (5 vs. 6, P = 0. 02), cortical signs (5 vs. 6, P = 0.02), and upper motor neuron signs (5 vs. 6, P < 0.01). Conversely, speech disorder (6 vs. 6, P = 0.70) and ataxia (5 vs. 6, P = 0.12) were not associated with short disease duration. Pathologic correlates of early cortical signs included more severe neuronal loss in the motor cortex (P < 0.01), while early ataxia correlated with more severe neuronal loss in the cerebellar dentate nucleus (P = 0.01).

Conclusion: This data-driven analysis indicates that the early syndromes in PSP predict later clinical course and association with neuronal loss in specific nuclei.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/early-syndromes-and-clinicopathologic-progression-in-progressive-supranuclear-palsy/