Neuroimaging in primary lateral sclerosis

Abstract

Increased interest in the underlying pathogenesis of primary lateral sclerosis (PLS) and its relationship to amyotrophic lateral sclerosis (ALS) has corresponded to a growing number of CNS imaging studies, especially in the past decade. Both its rarity and uncertainty of definite diagnosis prior to 4 years from symptom onset have resulted in PLS being less studied than ALS. In this review, we highlight most relevant papers applying magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), and positron emission tomography (PET) to analyzing CNS changes in PLS, often in relation to ALS. In patients with PLS, mostly brain, but also spinal cord has been evaluated since significant neurodegeneration is essentially restricted to upper motor neuron (UMN) structures and related pathways. Abnormalities of cortex and subcortical white matter tracts have been identified by structural and functional MRI and MRS studies, while metabolic and cell-specific changes in PLS brain have been revealed using various PET radiotracers. Future neuroimaging studies will continue to explore the interface between the PLS-ALS continuum, identify more changes unique to PLS, apply novel MRI and MRS sequences showing greater structural and neurochemical detail, as well as expand the repertoire of PET radiotracers that reveal various cellular pathologies. Neuroimaging has the potential to play an important role in the evaluation of novel therapies for patients with PLS.

Keywords:

• Imaging
• MRI
• PET
• spectroscopy

Acknowledgements

The authors thank Dr. Sabrina Paganoni who participated in the initial stages of the preparation of this manuscript.

Declaration of interest

The authors report no conflicts of interest relevant to the present report. EPP holds the Barry Winovich (Bright Side of the Road Foundation) Chair in ALS Research, and receives support from Center for Disease Control and Prevention (R01TS000288-01-00, subaward GC10112-00-01), and Samuel J. and Connie M. Frankino Charitable Foundation. MRT is funded by the Motor Neurone Disease Association (Walker Professorship). PB is supported by the Spastic Paraplegia Foundation, Inc. (SPF), the Health Research Board (HRB EIA-2017-019), the EU Joint Programme – Neurodegenerative Disease Research (JPND) initiative, the Andrew Lydon scholarship, the Irish Institute of Clinical Neuroscience (IICN), and the Iris O’Brien Foundation; he is the patron of the Irish Motor Neuron Disease Association (IMNDA).