The still under-appreciated role of cognitive neuropsychology in the diagnosis of progressive multifocal leukoencephalopathy

Abstract

Background: Despite cognitive deficits frequently represent the first clinical manifestations of Progressive Multifocal Leukoencephalopathy (PML), an uncommon opportunistic infection occurring in patients with multiple sclerosis (MS) treated with natalizumab (NTZ), the importance of cognitive neuropsychology in PML diagnosis is still under-appreciated. The aim of the current study is to investigate the cognitive deficit at PML diagnosis in the Italian PML cohort. Methods: All the Italian patients manifesting PML up to December 2016 (n=46) were included. The clinical data, lesion load, and longitudinal clinical course were compared between patients with (n = 19) and without (n = 21) cognitive deficit upon PML suspicion (the remaining six patients were asymptomatic). Findings: Within patients with cognitive onset, 41.10% were presenting with language and/or reading difficulties; 26.31% with memory difficulties; 21.05% with apraxia; 10.5% with disorientation; 10.5% with neglect; 10.5% with agnosia, 5.26% with perseveration, 5.26% with dementia. Despite the time to diagnosis after symptoms detection was shorter for cognitive than non cognitive onset patients (p = 0.02), the number of viral copies and the percentage of patients with unilobar lesion did not differ between groups (p=0.15; p=0.3), and the longitudinal disability course was more severe in cognitive than non cognitive onset patients (F = 3.45, p = 0.017). Discussion: Cognitive deficits at PML onset manifest with symptoms which are absolutely rare in MS. Results suggested a delay in the cognitive “red flag†recognition by neurologists. Clinicians should be sensitive to the importance of formal neuropsychological evaluation as an important contribution to health psychology.