Clinical Features Observed in General Practice Associated With the Subsequent Diagnosis of Progressive Supranuclear Palsy

Abstract

Background: Progressive supranuclear palsy (PSP) is a rare neurodegenerative disorder that is difficult for primary care physicians to recognize due to its progressive nature and similarities to other neurologic disorders. This case-control study aimed to identify clinical features observed in general practice associated with a subsequent diagnosis of PSP.Methods: We analyzed a de-identified dataset of 152 PSP cases and 3,122 matched controls from electronic medical records of general practices in Germany. We used a random forests algorithm based on machine learning techniques to identify clinical features (medical conditions and treatments received) associated with pre-diagnostic PSP without using an a priori hypothesis. We then assessed the relative effects of the features with the highest importance scores and generated multivariate models using clustered logistic regression analyses to identify a subset of clinical features associated with subsequent PSP diagnosis.Results: Using the random forests approach, we identified 21 clinical features associated with pre-diagnostic PSP (odds ratio ≥2.0 in univariate analyses). From these, we constructed a multivariate model comprising 9 clinical features with ~90% likelihood of identifying a subsequent PSP diagnosis. These features included known PSP symptoms, common misdiagnoses, and 2 novel associations, diabetes mellitus and cerebrovascular disease, which are possible modifiable risk factors for PSP.Conclusion: In this case-control study using data from electronic medical records, we identified 9 clinical features, including 2 previously unknown factors, associated with the pre-diagnostic stage of PSP. These may be used to facilitate recognition of PSP and reduce time to referral by primary care physicians.

Prediagnostic Progressive Supranuclear Palsy – Insights from the UK Biobank

“…These changes are temporally related to diagnosis with poorer performance associated with a shorter time to diagnosis. These prediagnostic features are similar to some of the prediagnostic features described in Parkinson's disease [30,31] and in recent primary and secondary care PSP cohorts [11,12]. We confirm the significantly faster progression and poorer survival in those developing PSP compared to Parkinson's disease.…”

“…Recent studies of prediagnostic PSP [11,12] have focussed on qualitative data and early clinical features, with participants' reports of their estimate of symptom onset. Symptom onset data are not available from the UKB data.…”

“…However, progress towards better definition of the prediagnostic phase has been hampered by the scarcity of PSP, the lack of a clear genetic aetiology, differences between clinical diagnosis and brain bank criteria and small, frequently underpowered retrospective case-control studies. Retrospective studies present a high risk of recall and selection bias, but by using contemporary records of symptoms reported to primary and secondary healthcare services, relevant symptoms have been identified as emerging approximately 6 years before diagnosis [11,12].…”

The Rate of Decrease in Brain Perfusion in Progressive Supranuclear Palsy and Corticobasal Syndrome May Be Impacted by Glycemic Variability—A Pilot Study

“…Several studies highlight the questionable significance of PSP and CBS differentiation, especially in advanced stages ( 4 , 6 ). The diseases share similar risk factors as hypertension and diabetes, however, the exact mechanism of their correlation has not been explored ( 7 , 8 ). In PSP, both hypertension and diabetes were identified as risk factors ( 8 ).…”

“…The diseases share similar risk factors as hypertension and diabetes, however, the exact mechanism of their correlation has not been explored ( 7 , 8 ). In PSP, both hypertension and diabetes were identified as risk factors ( 8 ). In PSP and CBS, some of the clinical manifestations are based on vascular pathogenesis ( 9 , 10 ).…”