Corticospinal Tract and Related Grey Matter Morphometric Shape Analysis in ALS Phenotypes: A Fractal Dimension Study

Venkateswaran Rajagopalan,Erik P Pioro

doi:10.3390/brainsci11030371

Abstract

A pathological hallmark of amyotrophic lateral sclerosis (ALS) is corticospinal tract (CST) degeneration resulting in upper motor neuron (UMN) dysfunction. No quantitative test is available to easily assess UMN pathways. Brain neuroimaging in ALS promises to potentially change this through identifying biomarkers of UMN dysfunction that may accelerate diagnosis and track disease progression. Fractal dimension (FD) has successfully been used to quantify brain grey matter (GM) and white matter (WM) shape complexity in various neurological disorders. Therefore, we investigated CST and whole brain GM and WM morphometric changes using FD analyses in ALS patients with different phenotypes. We hypothesized that FD would detect differences between ALS patients and neurologic controls and even between the ALS subgroups. Neuroimaging was performed in neurologic controls (n = 14), and ALS patients (n = 75). ALS patients were assigned into four groups based on their clinical or radiographic phenotypes. FD values were estimated for brain WM and GM structures. Patients with ALS and frontotemporal dementia (ALS-FTD) showed significantly higher CST FD values and lower primary motor and sensory cortex GM FD values compared to other ALS groups. No other group of ALS patients revealed significant FD value changes when compared to neurologic controls or with other ALS patient groups. These findings support a more severe disease process in ALS-FTD patients compared to other ALS patient groups. FD value measures may be a sensitive index to evaluate GM and WM (including CST) degeneration in ALS patients.

Highlights

The pathological hallmarks of amyotrophic lateral sclerosis (ALS) are combined degeneration of the corticospinal tract (CST) and anterior horn cells, progressively affecting upper motor neurons (UMNs) and lower motor neurons (LMNs), respectively to result in classic ALS (ALS-Cl)
Data from 89 subjects were assigned into one of the following groups after evaluating their clinical presentations and MR images: (a) neurologic controls whose clinical characteristics are shown in Supplementary Table S1, (b) ALS patients with classic UMN and LMN changes (ALS-Cl), (c) UMN-predominant ALS patients with CST hyperintensity seen on T2/PD-weighted images (ALS-CST+), (d) UMN-predominant ALS patients without CST hyperintensity on T2/PD-weighted images (ALS-CST−), and (e) ALS patients with frontotemporal dementia (ALS-FTD)
Fractal dimension (FD) values were significantly higher in right hemisphere primary motor cortex (PMC)-CST of ALS-FTD patients compared to ALS-CST− patients

Summary

Introduction

The pathological hallmarks of amyotrophic lateral sclerosis (ALS) are combined degeneration of the corticospinal tract (CST) and anterior horn cells, progressively affecting upper motor neurons (UMNs) and lower motor neurons (LMNs), respectively to result in classic ALS (ALS-Cl). While the aforementioned MRI sequences identify CST hyperintensity in some patients with UMN-predominant ALS (ALS-CST+), they do not in others (ALS-CST−). We previously demonstrated disruption or loss of DTT-reconstructed virtual CST fibers primarily in ALS-CST+ patients rather than in ALS-CST− patients [17] In another recent study using DTT based graph theory network analysis [18], we found severe WM degeneration primarily in frontal and temporal lobes in ALS-FTD patients. These results indicate that DTT approach may be more robust when compared to ROI- or TBSS-based analyses

Objectives

Methods

Results