Changes in Fatigue and Cognition in Patients with Relapsing Forms of Multiple Sclerosis Treated with Natalizumab

Wilken, Jeffrey; Kane, Robert L; Sullivan, Cynthia; Gudesblatt, Mark; Lucas, Sylvia; Fallis, Robert J.; You, Xiaojun; Foulds, Pam

doi:10.7224/1537-2073.2012-043

Cited by 44 publications

(26 citation statements)

References 37 publications

(47 reference statements)

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“…Since these symptoms are absolutely rare in MS, their appearance in MS patients treated with NTZ should be considered as a red flag and should give rise to a suspicion of PML, thus prompting a rapid MR scan. Indeed, evidences are now available regarding the positive effects of NTZ on cognitive deterioration of MS patients over long follow ups, as well as on cognitive improvement of MS patients treated with NTZ over time [15][16][17][18][19][20][21]. Furthermore, a rebound of cognitive impairment has also been described following natalizumab discontinuation [22].…”

Section: Discussionmentioning

confidence: 99%

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

Scarpazza

Rossi

Moiola

et al. 2017

Mult Scler Demyelinating Disord

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Background: 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. The aim of the current study is to investigate the cognitive deficits at PML diagnosis in a group of Italian patients with PML. Methods: Thirty-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. Result: After 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). Conclusion: Cognitive 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.

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Section: Discussionmentioning

confidence: 99%

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

Scarpazza

Rossi

Moiola

et al. 2017

Mult Scler Demyelinating Disord

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“…[15][16][17]29,30 Improvement occurred rapidly and was significant by the third month. Improvement in sleepiness, as measured by the ESS, was also observed.…”

Section: Mood and Cognitionmentioning

confidence: 93%

“…In the ENER-G (Evaluation of Natalizumab for thE Relief of MS Associated FatiGue) study, significant improvement in scores on fatigue scales was noted within 12 weeks, and this benefit persisted during the 48-week study. 15 Likewise, the TYNERGY study found that patients with MS reported significantly less fatigue after 12 months of natalizumab treatment. 16 Furthermore, the TYNERGY study found improvements in cognition, mood, and quality of life.…”

Section: Evaluationsmentioning

confidence: 98%

Naps-MS

Sater¹,

Gudesblatt²,

Kresa-Reahl³

et al. 2016

International Journal of MS Care

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Background: Patients with multiple sclerosis (MS) have higher rates of fatigue, mood disturbance, and cognitive impairments than healthy populations. Disease-modifying agents may affect sleep. Although patients taking natalizumab often show improvement in fatigue during the first year of therapy, the mechanism behind this effect is unknown. The aim of the NAPS-MS study was to investigate whether natalizumab affected objective measures of sleep as determined by polysomnography (PSG) and multiple sleep latency testing (MSLT) in patients with MS with fatigue or sleepiness initiating therapy. Additional goals were to evaluate changes in measures of fatigue, mood, and cognition and to correlate these measures with objective sleep measures. Methods: Patients underwent PSG and MSLT before their first natalizumab infusion and after their seventh. Patients completed the Modified Fatigue Impact Scale, Fatigue Severity Scale (FSS), Epworth Sleepiness Scale (ESS), and visual analogue scale for fatigue (VAS-F) at their first, fourth, and seventh natalizumab infusions. NeuroTrax cognitive tests and the Hospital Anxiety and Depression Scale (HADS) were performed at the first and seventh natalizumab infusions. Results: Changes in sleep efficiency, wakefulness after sleep onset, and multiple sleep latency from baseline to 6 months of therapy did not reach significance. The FSS, VAS-F, ESS, and HADS scores were significantly improved after 6 months of therapy; cognitive scores were not significantly improved. Conclusions: Although treatment with natalizumab was associated with improvements in fatigue, sleepiness, and mood, changes in objective measures of sleep were not significant.

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“…Another disease-modifying therapy, natalizumab, also appears to demonstrate improvements in fatigue. The ENER-G study showed benefi ts in patients with fatigue over the course of 1 year which remained stable for up to 48 weeks [ 187 ]. In the TYNERGY study, patients also had signifi cant improvements in fatigue measured over the course of 12 months, as well as in quality of life, sleepiness, depression, and cognition [ 188 ].…”

Section: Medication Therapiesmentioning

confidence: 99%