Vascular versus neuronal defects in ALS: an fMRI and DTI study

Purpose: To study arguments pro/contra vascular and/or neuronal etiology in ALS using BOLD fMRI and DTI.

Methods: 33 ALS patients and 21 matched controls underwent fMRI and DTI examination using a 3T MRI scanner. In the first fMRI session, a motor task was performed with the right hand to assess the activation pattern in the brain when executing voluntary movements. In the second session, an alternating hyperventilation – breath-hold task was performed to assess the vascular reactivity in the brain without interference of task-induced activations.

Data were analyzed using SPM2 and activation patterns of both tasks were visualized.

DTI datasets were obtained with a standard DTI-scanning protocol. Fiber tracking analysis of the corticospinal tract (CST) was performed on DTI based color maps, providing a visualisation of left and right CST. Furthermore, FA (fractional anisotropy) and ADC (apparent diffusion coefficient) maps were generated and normalized to the MNI template. These images were entered in a voxel-based analysis.

Results: In the motor task both groups showed activation of areas typical for voluntary movement. In ALS patients, there was a recruitment of both motor and extramotor areas. There was a significant increase of %signal change of motor areas (except M1) in ALS patients.

Vascular reactivity seemed to be impaired in ALS patients in the motor cortex and frontal cortex, whereas there was no difference in the visual cortex.

Fiber tracking of CST showed significant decrease of FA and significant increase of ADC in ALS patients compared to healthy controls. When dividing the CST in motor and sensory part, the above mentioned changes were present in the motor part, whereas no significant changes of FA/MD were found in the sensory part.

In the voxel-based analysis, a distinct pattern of FA/MD changes was demonstrated, showing a significant increase of FA in ALS patients throughout the CST as well as in corpus callosum, frontal and parietal areas. A significant increase of ADC was demonstrated in the caudal part of the CST.

Conclusion: ALS patients recruit additional areas for the generation of voluntary movement when compared to healthy controls. Vascular compliance is reduced in frontal and especially motor cortex when compared to healthy controls.

The DTI-study showed that ALS patients suffer from significant white matter loss mainly in the motor part of the CST. Degeneration also occurs within the projection fibers from/to the primary motor cortex: corpus callosum, frontal and parietal areas.

Thus, there are both vascular and neuronal defects leading to the physiopathology seen in ALS.