PLS is an uncommon neurodegenerative disorder of the upper motor neurons. No specific early markers of PLS are yet available and the incidence of transition to ALS is generally considered to be high. Consequently, previous diagnostic criteria have  advocated a four year wait from onset of symptoms to establish a clinical diagnosis. However, this uncertainty has prompted the exclusion of suspected PLS  patients from  studies of natural history and clinical trials. Recent criteria proposed the category ‘probable PLS’ for patients with a symptom duration of 2–4 years.

In a prospective neuroimaging study, thirty-nine patients were stratified into ‘probable’ (mean duration=3 years) or ‘definite’ PLS (duration ≥4 years, mean=10.5 years). Patients were assessed with standardised clinical instruments and underwent structural and diffusion MRI. The imaging profiles of the two PLS cohorts were contrasted with 100 healthy controls.

All patients retained a clinical diagnosis of PLS at a minimum of four years from onset with no transitions to ALS observed in either group. Patients tested negative for ALS and HSP-associated mutations. Despite a much shorter mean symptom duration in “probable PLS” group, the functional impairment, clinical upper motor neuron disease burden and motor cortical atrophy was commensurate with that of the “definite” group indicating disproportionate disease activity in the early years of PLS. Only one individual with probable PLS walked unaided. Consistent with the clinical observations, motor cortical thickness was not significantly different between the groups although corticospinal tract degeneration was more marked in the “definite” group.

These results support the introduction of the ‘probable’ PLS category, as this cohort already exhibits considerable disability and cerebral changes similar to those with long-established PLS.