Multimodal neuroimaging study in motor neuron diseases

Author(s)

Milena de Albuquerque

• Document type: Doctoral Thesis
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas
• Defense date: 2016-11-03

Examining board members

Marcondes Cavalcante Franca Junior; Acary Souza Bulle Oliveira; Claudia da Costa Leite; Marcio Luiz Figueredo Balthazar; Fabiano Reis

• Advisor: Marcondes Cavalcante Franca Junior

Abstract

Amyotrophic Lateral Sclerosis (ALS) is the most relevant neurodegenerative disease of the motor neuron system in adults, affecting the upper motor neurons (UMN) and lower (LMN). It manifests heterogeneously and there is no reliable marker that can predict individual standard and the rate of progression of the disease. Thus, biomarkers are needed to assess the individual prognosis, to assist in clinical trials and drug effect. Among the possible markers, there is particular interest in the Magnetic Resonance Imaging (MRI), a noninvasive technique, safe and useful. However, most studies are cross-sectional, a few involve multimodal MRI or the evaluation of the spinal cord. Thus, we proposed a study based on multimodal and longitudinal MRI to evaluate the usefulness of brain and spinal cord MRI as biomarkers in the progression of ALS. We recruited 63 patients diagnosed with ALS (El Escorial classification), evaluated by ALSFRSr scale, without clinically detectable cognitive impairment, and 64 healthy controls. To compare the pattern of degeneration found with another motor neuron disease model, 13 patients were enrolled with Hereditary Spastic Paraplegia (SPG4), with confirmatory molecular test, evaluated by SPRS scale and 23 healthy controls. MRI T1-weighted and DTI images were obtained from all subjects. The cortical thickness was analyzed by FreeSurfer software, white matter by tractography and cervical cord by SpineSeg in ALS, SPG4 and controls. Texture analysis was made of deep gray matter in 32 ALS patients and 32 controls. 27 patients with ALS were re-evaluated after 8 months. In the cross-sectional study in ALS, we observed reduced cortical thickness in the pre-central gyri bilaterally and bilateral central sulcus and middle temporal gyrus and the superior temporal sulcus in the right cerebral hemisphere and paracentral gyri and superior temporal and paracentral sulcus and precentral in the left cerebral hemisphere. There was evidence of change in bilateral thalamus and right caudate. We observed reduction in fractional anisotropy (FA) and increased radial diffusivity (RD) especially in the cortico-spinal tract and bilateral corpus callosum of patients¿ white matter. There was evidence of reduction in the spinal cord area and this was the only parameter which correlated with ALSFRSr scale. In the longitudinal study in ALS, there was no progression of damage in the cortex, only in the brainstem by FreeSurfer analysis. White matter progressed (increase in axial (AD) and mean diffusivity (MD)) in patients, more evident in the corpus callosum, but not correlated with the variation in clinical scales. In the cervical cord, there was reduction of spinal cord area that correlated with worsening ALSFSRs scale. Patients with SPG4 in cross-sectional analysis showed no cortical degeneration. There was a reduction of FA in corticospinal tracts, cingulate gyrus and splenium of the corpus callosum and reduction of the cervical spine area. There was no correlation with clinical scale. The structural brain and cervical cord MRI can detect short-term longitudinal changes in ALS. The spinal cord area is the most sensitive parameter and should be considered in future studies, including therapeutic trials in this disease (AU)

• FAPESP's process: 11/21521-3 - Study of biomarkers in amyotrophic lateral sclerosis
• Grantee: Milena de Albuquerque
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)