Mail-order diagnosis

You may have noticed that I’ve been bullish on the ability of ordinary MRI scans to help diagnose PSP.  Now there’s an on-line, automated resource to allow anyone anywhere to upload MRI images and receive an answer – for free.

We’ve known for over a decade that very careful, standardized measurement of the size of various parts of the brain can track the progression of PSP over the 1-year course of treatment trial better than the PSP Rating Scale or any other “bedside” measure.  But more recently, MRI has been found to be highly useful in the differential diagnosis of PSP – that is, telling PSP from normal aging, Parkinson’s, Alzheimer’s, and other conditions. 

For an excellent, technical, open-access review of simple MRI measurements in the diagnosis of PSP, click here. The leading authors are Dr. Aldo Quattrone and his son Dr. Andrea Quattrone at Universita Magna Graecia in Catanzaro, Italy, who pioneered most of the discoveries described.

Such MRI-based measurements use only routinely obtained images like those from your local radiologist.  But actually doing the measurements requires some experience.  The Catanzaro group has created a Web portal onto which anyone can upload de-identified MRI images from a CD.  An answer returns in a few days.  The site is

The black-and-white images below show the inputs into the automated algorithm.  Sorry if these close-up brain images look like abstract expressionism.  The drawings here may help orient you.

MRI images A and B are sagittal (A is in the midline and B is a few mm to one side), images C and D are in the coronal plane and image E is in the horizontal (or axial) plane.

from: Quattrone, et al. Brain Science, 2022.

A: midbrain area (upper outline; Amb) and pons area (lower outline; Apons) (In PSP, atrophy of the midbrain is marked but atrophy of the pons is mild.)

B: middle cerebellar peduncle diameter (This atrophies only a little in PSP.)

C: superior cerebellar peduncle diameter in a slice parallel to the midline (“parasagittal” slice; This atrophies moderately in PSP.)

D: third ventricle diameter (averaging the diameters of the front, middle and back thirds) (This enlarges markedly in PSP.)

E: maximum distance between anterior horns of lateral ventricles (This atrophies moderately in PSP.)

The number derived from these measurements is called the magnetic resonance parkinsonism index (MRPI).  Its value is (Apons/Amb) x (B/C).  Values above 13.88 indicate PSP-RS with 89% sensitivity*, 95% specificity* and 94% accuracy*. This works best in separating PSP-Richardson syndrome from Parkinson’s disease. 

The MRPI 2.0 is (MRPI) x (D/E).  This works better than the original MRPI in separating PSP-Parkinson and other non-Richardson PSP variants from Parkinson’s disease.  Values above 2.70 indicate PSP with 86% sensitivity, 92% specificity and 90% accuracy.

*Sensitivity is the fraction of people with the disease who have a positive test. 

Specificity is the fraction of people without the disease who have a negative test. 

Accuracy is the fraction of people with an accurate test, whether positive or negative. 

In this case, “the disease” means PSP and “without the disease” means PD, some other disease or no disease.

The really valuable part is that this technique works well even in early, mild cases, where a diagnosis could not be made by other means.  In a few studies, such patients were followed for years until they showed more definitive signs, which were then used to validate the initial, image-based diagnoses.

This technique has not been shown effective in differentiating PSP-P from multiple system atrophy of the parkinsonian type (MSA-P), which is a common dilemma for movement disorder specialists seeing a patient with mild symptoms.  But the MRPI and MRPI 2.0 could be combined with other supplementary tests such as supine and standing blood pressure (usually abnormal in MSA-P, normal in PSP) and still-experimental tests such as blood levels of tau, phosphorylated tau and neurofilament light chain (all elevated in PSP, not in MSA) to refine its abilities.

Another important caveat:  Sometimes PSP can be mimicked by rare cases of common diseases like Alzheimer’s or dementia with Lewy bodies, or by some rare diseases like corticobasal degeneration, frontotemporal dementia with parkinsonism, or pallidopontonigral degeneration.  There haven’t yet been enough patients with those things subjected to the MRPI or MRPI 2.0 to prove those formulas able to separate those conditions from PSP.  After all, the MRI only looks for atrophy of certain brain structures, regardless of whether that atrophy is related to tau aggregation or something else.

Bottom line:  As my medical students don’t appreciate hearing, no diagnostic test short of autopsy is ever going to be definitive on its own.  Any test will have to be combined with old-fashioned history and exam and with other imaging, fluids or physiological tests.  Knowing which of those to choose for a given patient and how to interpret the results will keep humble, human neuro-diagnosticians in business for a while longer.


In my next post: another on-line tool for the diagnosis of PSP.

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