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Neuropsychological impairment in natalizumab-associated progressive multifocal leukoencephalopathy: implications for early diagnosis
  1. R Hoepner,
  2. P Klotz,
  3. S Faissner,
  4. R Schneider,
  5. M Kinner,
  6. C Prehn,
  7. R Gold,
  8. A Chan
  1. Department of Neurology, St. Josef Hospital, Ruhr-University Bochum, Bochum, Germany
  1. Correspondence to Dr R Hoepner, Department of Neurology, St Josef Hospital, Ruhr-University Bochum, Gudrunstr 56, Bochum 44879, Germany;

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Immunocompromised patients and, recently, natalizumab (NAT)-treated patients with multiple sclerosis (MS) are at risk to develop the relatively rare but potentially fatal opportunistic central nervous system infection progressive multifocal leukoencephalopathy (PML). As rapid immune reconstitution by removal of NAT appears to determine prognosis, early diagnosis is mandatory.1 Neuropsychological symptoms are common in early stages of disease,2 yet data on neuropsychological function in NAT-PML is lacking. Few studies in HIV-associated PML have demonstrated a reduction in attention/working memory, visuospatial abilities and motor speed.3 We compare the neuropsychological performance of patients with NAT-PML with patients with relapsing–remitting (RR) MS during NAT therapy and patients with RR multiple sclerosis (RRMS) with relapse; we identify specific neuropsychological abnormalities that might support early NAT-PML diagnosis.


Our monocentric retrospective analysis of data obtained during routinely performed investigations was approved by the local ethics committee (No 4566-13). Epidemiological characteristics of patients with NAT-PML (n=8, definite diagnosis4) and controls (stable NAT-treated patients, n=9; patients with RRMS with preceding relapse, n=14) are given in table 1. The time point of NAT-PML diagnosis corresponded to first detection of JC virus DNA in cerebrospinal fluid. Neuropsychological examination included Wechsler Memory Scale (digits forwards, backwards, visual reproduction I, information and general orientation), Rey Auditory Verbal Learning test, Regensburger Word Fluency Test, Shulman Clock Drawing Test and Beck Depression Inventory II. At the time point of …

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  • Contributors RH designed the study, collected and analysed the data, and drafted the manuscript. PK, SF, RS, MK, CP and RG designed the study, collected and analysed the data, and revised the manuscript. AC designed the study, collected and analysed the data, and drafted and revised the manuscript.

  • Competing interests RH received research and travel grants from BiogenIdec and travel grants from Novartis.SF received travel grants from BiogenIdec. RG declares speaker's and board honoraria from BiogenIdec, Baxter, BayerSchering, Chugai Pharmaceuticals, MerckSerono, Novartis, Roche, Sanofi-Aventis, Talecris and TEVA. He also received scientific grant support from BiogenIdec, BayerSchering, Genzyme, MerckSerono and TEVA. AC received personal compensation as a speaker or consultant for Bayer Schering, Biogen Idec, Genzyme, Merck Serono, Novartis, Sanofi-Aventis, UCB and Teva Neuroscience. AC received research support from the German Ministry for Education and Research (BMBF, German Competence Network Multiple Sclerosis (KKNMS; 01GI0914)), Biogen Idec, Genzyme and Novartis.

  • Ethics approval The ethics committee of Ruhr University Bochum (No. 4566-13).

  • Provenance and peer review Not commissioned; internally peer reviewed.