The still under-investigated role of cognitive deficits in PML diagnosis

On Behalf Of The Italian Pml Group ,Cristina Scarpazza,Lucia Moiola,Flavia Mattioli,Ruggero Capra,Mirco Cosottini,Simonetta Gerevini,Nicola De Rossi

doi:10.1186/s40893-016-0018-7

Abstract

BackgroundDespite cognitive deficits frequently represent the first clinical manifestations of Progressive Multifocal Leukoencephalopathy (PML) in Natalizumab-treated MS patients, the importance of cognitive deficits in PML diagnosis is still under-investigated. The aim of the current study is to investigate the cognitive deficits at PML diagnosis in a group of Italian patients with PML.MethodsThirty-four PML patients were included in the study. The demographic and clinical data, the lesion load and localization, and the longitudinal clinical course was compared between patients with (n = 13) and without (n = 15) cognitive deficit upon PML suspicion (the remaining six patients were asymptomatic). Clinical presentation of cognitive symptoms was described in detail.ResultAfter symptoms detection, the time to diagnosis resulted to be shorter for patients presenting with cognitive than for patients with non cognitive onset (p = 0.03). Within patients with cognitive onset, six patients were presenting with language and/or reading difficulties (46.15%); five patients with memory difficulties (38.4%); three patients with apraxia (23.1%); two patients with disorientation (15.3%); two patients with neglect (15.3%); one patients with object agnosia (7.7%), one patient with perseveration (7.7%) and one patient with dementia (7.7%). Frontal lesions were less frequent (p = 0.03), whereas temporal lesions were slightly more frequent (p = 0.06) in patients with cognitive deficits. The longitudinal PML course seemed to be more severe in cognitive than in non cognitive patients (F = 2.73, p = 0.03), but differences disappeared (F = 1.24, p = 0.29) when balancing for the incidence of immune reconstitution syndrome and for other treatments for PML (steroids, plasma exchange (PLEX) and other therapies (Mefloquine, Mirtazapine, Maraviroc).ConclusionCognitive deficits at PML onset manifest with symptoms which are absolutely rare in MS. Their appearance in MS patients should strongly suggest PML. Clinicians should be sensitive to the importance of formal neuropsychological evaluation, with particular focus on executive function, which are not easily detected without a formal assessment.

Highlights

Despite cognitive deficits frequently represent the first clinical manifestations of Progressive Multifocal Leukoencephalopathy (PML) in Natalizumab-treated Multiple Sclerosis (MS) patients, the importance of cognitive deficits in PML diagnosis is still under-investigated
Despite widely studied in HIV patients [1], in the last decade PML has been observed in Multiple Sclerosis (MS) patients treated with Natalizumab (NTZ) [2]
The current paper describes the neuropsychological symptoms at onset and the longitudinal clinical course of a group of Italian MS patients treated with Natalizumab, who experienced PML, with the aim to better identify the possible peculiar aspects of PML related cognitive symptoms

Summary

Introduction

Despite cognitive deficits frequently represent the first clinical manifestations of Progressive Multifocal Leukoencephalopathy (PML) in Natalizumab-treated MS patients, the importance of cognitive deficits in PML diagnosis is still under-investigated. Focal neurological syndromes as well as neuropsychological deficits are described as presenting symptoms in PML [3, 6, 7], but the prevalence of specific cognitive disorders as distinctive signs of PML in differential diagnosis with other MS related cognitive impairments has not been yet clarified. Dong-Si et al [8] described 372 PML patients, who experienced during the course of PML cognitive/behavioral or speech symptoms in 75.5% of the cases. In Clifford et al [6] series, 57.1% of the patients showed cognitive, behavioral or speech symptoms at PML onset, but no specifications about the nature of cognitive deficits were provided by the authors. The importance of cognitive deficits in PML diagnosis is still underinvestigated

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