Primary lateral sclerosis: consensus diagnostic criteria

Abstract

Primary lateral sclerosis (PLS) is a neurodegenerative disorder of the adult motor system. Characterised by a slowly progressive upper motor neuron syndrome, the diagnosis is clinical, after exclusion of structural, neurodegenerative and metabolic mimics. Differentiation of PLS from upper motor neuron-predominant forms of amyotrophic lateral sclerosis remains a significant challenge in the early symptomatic phase of both disorders, with ongoing debate as to whether they form a clinical and histopathological continuum. Current diagnostic criteria for PLS may be a barrier to therapeutic development, requiring long delays between symptom onset and formal diagnosis. While new technologies sensitive to both upper and lower motor neuron involvement may ultimately resolve controversies in the diagnosis of PLS, we present updated consensus diagnostic criteria with the aim of reducing diagnostic delay, optimising therapeutic trial design and catalysing the development of disease-modifying therapy.

Figure 1

Diffusion tensor imaging and fluorodeoxyglucose (FDG) positron emission tomography (PET) findings in cases of primary lateral sclerosis (PLS). Mean diffusivity in the mid-portion of the corpus callosum is increased in cases of PLS compared with amyotrophic lateral sclerosis (row A, PLS vs ALS group findings highlighted on axial, coronal and sagittal views of the white matter tract skeleton; with kind permission of the author, see Iwata et al 37). Focal hypometabolism may be seen in the primary motor cortices in PLS (row B, FDG PET z-score images in the right sagittal, left sagittal and axial planes; with kind permission of the author, see Claassen et al 35). Neither of these techniques yet has sufficient sensitivity or specificity to be applied in isolation for the diagnosis of PLS.