MRI Brainstem Shape Analysis and CSF Biomarkers in Neurodegenerative Parkinsonisms

Overview

This study investigated brainstem morphology via MRI shape analysis in Parkinson’s disease (PD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD). It correlated these imaging findings with cerebrospinal fluid (CSF) neurofilament-light chain (NfL) levels, revealing distinct local atrophy patterns and associations with clinical severity.

Background

Neurodegenerative parkinsonisms such as PD, MSA, PSP, and CBD often involve brainstem atrophy detectable by MRI. Conventional MRI markers include the 'hummingbird' sign in PSP and 'hot cross bun' sign in MSA, alongside volumetric and ratio measurements of the midbrain and pons. Shape analysis offers a novel approach to detect localized brainstem atrophy beyond global volume loss. Prior studies have not correlated brainstem shape changes with CSF biomarkers, which may provide insights into disease mechanisms and aid differential diagnosis.

Data Highlights

The study included 84 subjects with probable or clinically established diagnoses of PD, MSA, PSP, or CBD, alongside healthy controls over 55 years old. MRI was performed using 3-T scanners with high-resolution T1-weighted sequences. Brainstem structures were segmented automatically to measure midsagittal midbrain and pontine areas and calculate the pons-to-midbrain (PM) ratio. CSF NfL levels were measured by ELISA. Clinical assessments included disease duration, motor scales (UPDRS, UMSARS, PSPRS), cognition (MoCA, MMSE), and disability scales (SEADL).

Key Findings

• Distinct local brainstem shape changes were identified across neurodegenerative parkinsonisms, with midbrain atrophy prominent in PSP and pontine atrophy in MSA.
• Automated midsagittal midbrain and pontine area measurements correlated with manual assessments, validating the imaging methodology.
• The pons-to-midbrain (PM) ratio differed significantly between disease groups, supporting its utility as a differential biomarker.
• CSF neurofilament-light chain (NfL) levels were elevated in atypical parkinsonisms compared to PD and controls, correlating with brainstem atrophy severity.
• Shape analysis detected localized atrophy patterns not captured by volumetric measures alone, enhancing diagnostic discrimination.
• Clinical severity scales correlated with both MRI shape changes and CSF NfL, linking structural and biochemical markers to disease progression.

Clinical Implications

Brainstem shape analysis via MRI provides a sensitive tool to differentiate neurodegenerative parkinsonisms by detecting localized atrophy patterns. Combined with CSF NfL measurements, these biomarkers may improve diagnostic accuracy and allow monitoring of disease severity. Incorporating these assessments into clinical practice could aid early diagnosis and tailored management strategies.

Conclusion

This preliminary investigation demonstrates that MRI brainstem shape analysis, combined with CSF NfL biomarker evaluation, reveals distinct morphological and biochemical profiles across neurodegenerative parkinsonisms. These findings support further research into integrated imaging and fluid biomarkers for improved diagnosis and monitoring.

References

1. Litvan et al. 1996 -- Clinical research criteria for the diagnosis of progressive supranuclear palsy
2. Höglinger et al. 2017 -- Clinical diagnosis of progressive supranuclear palsy: The Movement Disorder Society criteria
3. Gilman et al. 2008 -- Second consensus statement on the diagnosis of multiple system atrophy
4. Marras et al. 2014 -- Diagnosis and management of Parkinson’s disease
5. Schrag et al. 2010 -- Differentiating Parkinson’s disease from atypical parkinsonian syndromes