Abstract
Following the exclusion of potentially reversible causes, the differential for those patients presenting with a predominant upper motor neuron syndrome includes primary lateral sclerosis (PLS), hereditary spastic paraplegia (HSP), or upper motor neuron dominant ALS (UMNdALS). Differentiation of these disorders in the early phases of disease remains challenging. While no single clinical or diagnostic tests is specific, there are several developing biomarkers and neuroimaging technologies which may help distinguish PLS from HSP and UMNdALS. Recent consensus diagnostic criteria and use of evolving technologies will allow more precise delineation of PLS from other upper motor neuron disorders and aid in the targeting of potentially disease-modifying therapeutics.
Highlights
Jean-Martin Charcot (1825–1893) and Wilhelm Erb (1840–1921) are credited with first describing a distinct clinical syndrome of upper motor neuron (UMN) tract degeneration in isolation with symptoms including spasticity, hyperreflexia, and mild weakness [1,2]
Many of the earliest described cases included cases of hereditary spastic paraplegia, amyotrophic lateral sclerosis, and underrecognized structural, infectious, or inflammatory etiologies for upper motor neuron dysfunction which have since become routinely diagnosed with the advent of advanced neuroimaging as well as genetic testing [2,3,4]
Primary lateral sclerosis is often considered on a spectrum of motor neuron disorders including those that are lower motor neuron (LMN) dominant on one end, amyotrophic lateral sclerosis (ALS) in the middle with various degrees of upper/lower motor neuron dysfunction, and the pure upper motor neuron phenotype of primary lateral sclerosis (PLS) making the opposite end of the spectrum
Summary
Jean-Martin Charcot (1825–1893) and Wilhelm Erb (1840–1921) are credited with first describing a distinct clinical syndrome of upper motor neuron (UMN) tract degeneration in isolation with symptoms including spasticity, hyperreflexia, and mild weakness [1,2]. Many of the earliest described cases included cases of hereditary spastic paraplegia, amyotrophic lateral sclerosis, and underrecognized structural, infectious, or inflammatory etiologies for upper motor neuron dysfunction which have since become routinely diagnosed with the advent of advanced neuroimaging as well as genetic testing [2,3,4]. While controversy remains as to whether there is a pathologic ‘gold standard’ to distinguish PLS from amyotrophic lateral sclerosis (ALS), especially those variants with a predominant upper motor neuron phenotype, the more benign clinical prognosis, as well as differing findings on neuroimaging and biomarker studies, continues to make this entity a clinical category of interest for further research and therapy development [2,4,6]. The goal of more permissive and accepted clinical criteria is to allow for more uniform investigations into the histopathology and biomarkers related to PLS in order to more accurately distinguish this condition from other conditions presenting with upper motor neuron dysfunction as well as allow for targeted testing of therapeutics [2,4]
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