Advanced MRI analysis could improve early diagnosis of two rare conditions often mistaken for Parkinson’s disease, research suggests.
The study indicates that detailed assessment of brain scan patterns can distinguish between progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD), even at early stages.
Both conditions are neurodegenerative diseases that cause balance problems, falls, stiffness and difficulties with speech and movement, and are frequently misdiagnosed as Parkinson’s disease.
PSP and CBD are part of a group of disorders known as tauopathies. These are caused by abnormal build-up of tau protein in the brain, which normally helps nerve cells function.
When tau accumulates incorrectly, it damages brain regions involved in movement, balance, posture and some aspects of thinking.
The international research team developed models that estimate whether a patient has PSP or CBD by analysing patterns of brain shrinkage across different regions seen on MRI scans.
Dr Jesús García-Castro, the study’s first author, said: “These are diseases that cause balance problems, falls, stiffness, or difficulties with speech and movement.
“Many patients initially present as if they had Parkinson’s disease or are simply older adults with mobility difficulties.
“This means they are greatly underdiagnosed, and for years we have not known with enough certainty which disease each patient actually had.”
The analysis found that PSP is mainly associated with changes in deep brain structures, particularly the brainstem, alongside more selective changes in parts of the brain’s outer layer.
In CBD, the pattern showed greater involvement of cortical regions linked to motor control and sensory processing.
Dr Ignacio Illán-Gala, the study’s senior author, said: “Although they may look very similar clinically, at the brain level PSP and CBD damage the brain in different ways.
“These differences are reflected on MRI, and by combining them into a signature, we can much better determine which disease each patient has.”
The findings also suggest MRI could help track disease progression in clinical trials.
In PSP, using disease-specific MRI measures could cut the number of participants needed by about 50 per cent in a 12-month trial. In CBD, where symptoms vary more widely, the reduction could be around 80 to 85 per cent.
This matters because recruiting enough participants for trials in rare conditions such as PSP and CBD is often slow and costly.
Previous studies have also struggled because unclear diagnoses led to mixed patient groups, making it harder to identify treatment effects.
Illán-Gala said: “For a company or an academic consortium to commit to a clinical trial, it has to be feasible. If a trial requires a thousand patients, it is practically impossible.
“But if it can be conducted with a reasonable number of well-selected individuals and objective measures of progression, then there is a real chance of demonstrating whether a treatment works.”
The researchers are now extending this work with new funding, aiming to enable diagnosis at earlier stages by combining advanced imaging with blood-based biomarkers, when future treatments are more likely to be effective.
García-Castro said: “These conditions are far more common than we think, but we do not know how to detect them properly. Improving diagnosis is the first step so that these patients, who currently have no therapeutic options, can begin to have them.”
