Dataset Information

Imaging of glia activation in people with primary lateral sclerosis.

ABSTRACT:

Background

Glia activation is thought to contribute to neuronal damage in several neurodegenerative diseases based on preclinical and human post-mortem studies, but its role in primary lateral sclerosis (PLS) is unknown.

Objectives

To localize and measure glia activation in people with PLS compared to healthy controls (HC).

Methods

Ten participants with PLS and ten age-matched HCs underwent simultaneous magnetic resonance (MR) and proton emission tomography (PET). The radiotracer [¹¹C]-PBR28 was used to obtain PET-based measures of 18 kDa translocator protein (TSPO) expression, a marker of activated glial cells. MR techniques included a structural sequence to measure cortical thickness and diffusion tensor imaging (DTI) to assess white matter integrity.

Results

PET data showed increased [¹¹C]-PBR28 uptake in anatomically-relevant motor regions which co-localized with areas of regional gray matter atrophy and decreased subcortical fractional anisotropy.

Conclusions

This study supports a link between glia activation and neuronal degeneration in PLS, and suggests that these disease mechanisms can be measured in vivo in PLS. Future studies are needed to determine the longitudinal changes of these imaging measures and to clarify if MR-PET with [¹¹C]-PBR28 can be used as a biomarker for drug development in the context of clinical trials for PLS.

SUBMITTER: Paganoni S

PROVIDER: S-EPMC5681341 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Publications

Imaging of glia activation in people with primary lateral sclerosis.

Paganoni Sabrina S Alshikho Mohamad J MJ Zürcher Nicole R NR Cernasov Paul P Babu Suma S Loggia Marco L ML Chan James J Chonde Daniel B DB Garcia David Izquierdo DI Catana Ciprian C Mainero Caterina C Rosen Bruce R BR Cudkowicz Merit E ME Hooker Jacob M JM Atassi Nazem N

NeuroImage. Clinical 20171025

<h4>Background</h4>Glia activation is thought to contribute to neuronal damage in several neurodegenerative diseases based on preclinical and human <i>post</i>-<i>mortem</i> studies, but its role in primary lateral sclerosis (PLS) is unknown.<h4>Objectives</h4>To localize and measure glia activation in people with PLS compared to healthy controls (HC).<h4>Methods</h4>Ten participants with PLS and ten age-matched HCs underwent simultaneous magnetic resonance (MR) and proton emission tomography (P ...[more]

PMID: 29159046

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Project description:Magnetic resonance imaging measures have been proposed as objective markers to study upper motor neuron loss in motor neuron disorders. Cross-sectional studies have identified imaging differences between groups of healthy controls and patients with amyotrophic lateral sclerosis (ALS) or primary lateral sclerosis (PLS) that correlate with disease severity, but it is not known whether imaging measures change as disease progresses. Additionally, whether imaging measures change in a similar fashion with disease progression in PLS and ALS is unclear. To address these questions, clinical and imaging evaluations were first carried out in a prospective cross-sectional study of 23 ALS and 22 PLS patients with similar motor impairment and 19 age-matched healthy controls. Clinical evaluations consisted of a neurological examination, the ALS Functional rating scale-revised, and measures of finger tapping, gait, and timed speech. Age and ALSFRS score were not different, but PLS patients had longer duration of symptoms. Imaging measures examined were cortical thickness, regional brain volumes, and diffusion tensor imaging of the corticospinal tract and callosum. Imaging measures that differed from controls in a cross-sectional vertex-wise analysis were used as regions of interest for longitudinal analysis, which was carried out in 9 of the ALS patients (interval 1.26 ± 0.72 years) and 12 PLS patients (interval 2.08 ± 0.93 years). In the cross-sectional study both groups had areas of cortical thinning, which was more extensive in motor regions in PLS patients. At follow-up, clinical measures declined more in ALS than PLS patients. Cortical thinning and grey matter volume loss of the precentral gyri progressed over the follow-up interval. Fractional anisotropy of the corticospinal tracts remained stable, but the cross-sectional area declined in ALS patients. Changes in clinical measures correlated with changes in precentral cortical thickness and grey matter volume. The rate of cortical thinning was greater in ALS patients with shorter disease durations, suggesting that thickness decreases in a non-linear fashion. Thus, cortical thickness changes are a potential imaging marker for disease progression in individual patients, but the magnitude of change likely depends on disease duration and progression rate. Differences between PLS and ALS patients in the magnitude of thinning in cross-sectional studies are likely to reflect longer disease duration. We conclude that there is an evolution of structural imaging changes with disease progression in motor neuron disorders. Some changes, such as diffusion properties of the corticospinal tract, occur early while cortical thinning and volume loss occur later.

Project description:Primary lateral sclerosis is a sporadic disorder characterized by slowly progressive corticospinal dysfunction. Primary lateral sclerosis differs from amyotrophic lateral sclerosis by its lack of lower motor neuron signs and long survival. Few pathological studies have been carried out on patients with primary lateral sclerosis, and the relationship between primary lateral sclerosis and amyotrophic lateral sclerosis remains uncertain. To detect in vivo structural differences between the two disorders, diffusion tensor imaging of white matter tracts was carried out in 19 patients with primary lateral sclerosis, 18 patients with amyotrophic lateral sclerosis and 19 age-matched controls. Fibre tracking was used to reconstruct the intracranial portion of the corticospinal tract and three regions of the corpus callosum: the genu, splenium and callosal fibres connecting the motor cortices. Both patient groups had reduced fractional anisotropy, a measure associated with axonal organization, and increased mean diffusivity of the reconstructed corticospinal and callosal motor fibres compared with controls, without changes in the genu or splenium. Voxelwise comparison of the whole brain white matter using tract-based spatial statistics confirmed the differences between patients and controls in the diffusion properties of the corticospinal tracts and motor fibres of the callosum. This analysis further revealed differences in the regional distribution of white matter alterations between the patient groups. In patients with amyotrophic lateral sclerosis, the greatest reduction in fractional anisotropy occurred in the distal portions of the intracranial corticospinal tract, consistent with a distal axonal degeneration. In patients with primary lateral sclerosis, the greatest loss of fractional anisotropy and mean diffusivity occurred in the subcortical white matter underlying the motor cortex, with reduced volume, suggesting tissue loss. Clinical measures of upper motor neuron dysfunction correlated with reductions in fractional anisotropy in the corticospinal tract in patients with amyotrophic lateral sclerosis and increased mean diffusivity and volume loss of the corticospinal tract in patients with primary lateral sclerosis. Changes in the diffusion properties of the motor fibres of the corpus callosum were strongly correlated with changes in corticospinal fibres in patients, but not in controls. These findings indicate that degeneration is not selective for corticospinal neurons, but affects callosal neurons within the motor cortex in motor neuron disorders.

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Dataset Information

Imaging of glia activation in people with primary lateral sclerosis.

Background

Objectives

Methods

Results

Conclusions

Publications

Imaging of glia activation in people with primary lateral sclerosis.

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