Brain metabolic differences between pure bulbar and pure spinal ALS: a 2-[¹⁸F]FDG-PET study

Area of Science:

• Neuroscience
• Medical Imaging
• Neurology

Background:

• Amyotrophic Lateral Sclerosis (ALS) presents with focal cortical changes in MRI studies correlating with bulbar or spinal onset.
• Understanding the metabolic underpinnings of different ALS onset types is crucial for targeted interventions.

Purpose of the Study:

• To evaluate the capability of brain 2-[¹⁸F]FDG-PET to identify metabolic features distinguishing pure bulbar (PB) and pure spinal (PS) ALS.
• To assess the accuracy of PET-based metabolic clusters in differentiating between PB and PS patient groups.

Main Methods:

• Patients were classified as PB or PS based on ALSFRS-R scores at the time of PET imaging.
• Brain 2-[¹⁸F]FDG-PET was performed on 63 PB patients, 271 PS patients, and 40 healthy controls (HC).
• Machine learning classifiers, including Support Vector Machines (SVM), were employed for group discrimination using leave-one-out cross-validation and a separate test set.

Main Results:

• PB patients exhibited relative hypometabolism in the bilateral precentral gyrus compared to PS patients, specifically in motor cortex regions controlling bulbar function.
• Support Vector Machines (SVM) demonstrated the highest classification accuracy, with error rates of 4.19% in LOOCV and 9.09% ± 2.02% in the test set.

Conclusions:

• The findings support the concept of focal onset in ALS.
• Brain 2-[¹⁸F]FDG-PET serves as a valuable biomarker for stratifying ALS patients.
• This imaging modality can aid in the development of precision medicine-oriented clinical trials for ALS.