Natalizumab: JCV-Antikörper Risikofaktor für PML
Die Food and Drug Administration (FDA) weist darauf hin, dass MS-Patienten, die positiv auf JC-Virusantikörper getestet wurden, ein erhöhtes Risiko für eine progressive multifokale Leukenzephalopathie (PML) haben.
Natalizumab (Tysabri, Biogen) ist ein Immunmodulator, der bei Patienten mit Multipler Sklerose und mit Morbus Crohn eingesetzt wird. Die PML ist eine gefürchtete Nebenwirkung der Substanz. Insbesondere bei Patienten mit positivem JCV-Test und/oder weiteren Risikofaktoren für eine PMLsollten Nutzen und Risiken sehr sorgfältig abgewogen werden. Patienten die drei bekannte Risikofaktoren aufweisen, haben ein Risiko von 11/1.000 Anwender.

Diagnostisch wegweisend ist der
Nachweis von JCV-DNA im Liquor mittels
Polymerase-Ketten-Reaktion (PCR).

CMRT hilfreich.


Dimethylfumarat, Fumaderm, Tecfidera,

B-cell-mediated CNS disease secondary to alemtuzumab ::

Improvement after plasmapheresis and the B cell–depleting antibody rituximab therapy,

which the authors suggest indicate a predominantly B cell–driven pathology.

CMRT Ringenhancement hat Ähnlichkeit mit ADEM !!!


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3 Responses to “PML-Natalizumab-JCV-Fumarat-Alemtuzumab”

  1. Werner Says:

    Early Detection of PML With Natalizumab Improves Outcome

    „This study suggests that periodic monitoring [with] brain MRI while on natalizumab is important, with or without symptoms,“ Dr. Rensel concluded.

    The study was released March 10, ahead of presentation at the American Academy of Neurology (AAN) 65th Annual Meeting, to be held March 16 to 23 in San Diego, California.
    JCV John Cunningham virus

  2. Werner Says:

    Objective: To evaluate the usefulness of the punctate pattern (PP) for the diagnosis and follow-up of patients with progressive multifocal leukoencephalopathy (PML).
    Methods: A cohort of 20 consecutive patients with PML, related to natalizumab (NTZ) (n = 14) or not (n = 6), underwent 3T MRI (147 MRI examinations). MRI was available at presymptomatic (n = 9 patients), symptomatic (n = 15), immune reconstitution inflammatory syndrome (IRIS), and chronic stages (n = 20). A pathologic control group of patients without PML (n = 80), with clinically definitive multiple sclerosis or a clinically isolated syndrome suggestive of CNS demyelination, underwent the same MRI protocol. Number and appearance of punctate lesions were assessed by 3 blinded readers using T2-weighted, fluid-attenuated inversion recovery (FLAIR), and postcontrast T1-weighted images.
    Results: Interobserver agreement was good (κ = 0.79) (0.72–0.87). Of the 20 patients with PML, 18 had PP, including the 14 patients with NTZ-PML; none in the pathologic control group. Of the 9 presymptomatic patients with NTZ-PML, PP was observed in 7 (78% sensitive and 100% specific). Nonenhancing PP on T2-weighted/FLAIR images was detected in 13 patients with PML, exclusively at the presymptomatic or symptomatic stages (including 7 NTZ-PML), whereas enhancing PP occurred in 16 patients with PML, including 13 of the 14 patients with NTZ-PML at the IRIS stage.
    Conclusions: PP is a highly specific feature of PML and may be the first imaging feature at the presymptomatic stage with potential implications in patient care.
    Classification of evidence: This study provides Class II evidence that a PP on MRI accurately identifies patients with NTZ-PML.
    • Go to for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
    • Supplemental data at
    • Received June 26, 2015.
    • Accepted in final form January 7, 2016.
    • © 2016 American Academy of Neurology

  3. Werner Says:

    Two cases of what is suggested to be „the first recognised cases of severely exacerbated CNS [central nervous system] inflammation after alemtuzumab therapy in multiple sclerosis“ have been published.

    Writing in a letter in the February issue of The Lancet Neurology, a group of German and British multiple sclerosis (MS) experts describe two patients who developed severe apparent acute deterioration of their MS and several new ring-enhancing lesions on MRI a few months after their first course of alemtuzumab (Lemtrada, Genzyme) therapy.

    Both patients experienced marked improvement after plasmapheresis and the B cell–depleting antibody rituximab therapy, which the authors suggest indicate a predominantly B cell–driven pathology.

    „Alemtuzumab dependent, B-cell-mediated autoimmune diseases have been identified for several tissues other than the CNS,“ the authors, with corresponding author Ralf Gold, MD, Department of Neurology of the Ruhr-University Bochum at St Josef-Hospital, Bochum, Germany, write.

    „The exacerbated inflammation seen in our patients is consistent with the time frame in which B-cell repopulation and peripheral expansion occur following alemtuzumab treatment. Thus, it remains to be determined if the disease observed in these two patients after treatment is due to worsening of multiple sclerosis or to the development of secondary CNS-directed autoimmunity.“

    They add that a rare genetic or infectious cause was not found, as evaluated by whole genome analyses, suggesting that further cases might be identified, and that apparent relapses after alemtuzumab treatment should be promptly evaluated by MRI for the presence of ring-enhancing lesions. A specific rescue therapy comprising plasma exchange with consecutive B cell depletion can then be initiated to help prevent irreversible disability.

    The first patient described was a 41-year-old man diagnosed with MS in 2004. Despite receiving many different immunomodulatory therapies during the following decade, he had several relapses and displayed continuing MRI activity. A first course of alemtuzumab was given in July 2015, but in December 2015, the patient presented with severe dysarthria, marked cognitive symptoms, apraxia, and left-dominant tetraparesis, and MRI revealed 20 new contrast-enhancing T1 lesions, most of which were ring-enhancing.

    The patient was unresponsive to steroids, but plasmapheresis and one cycle of immunoadsorption led to marked improvement of clinical symptoms and lesion restitution by MRI. Subsequent treatment with rituximab resulted in a near absence of contrast-enhancing lesions, and by September 2016 the patient was almost free of the symptoms that prompted admission 9 months earlier.

    The second patient, a 25-year-old woman, was diagnosed with MS in 2011 and had received several different treatments since diagnosis, including interferon β-1a, natalizumab, and fingolimod. Because of continued disease activity, she received an initial course of alemtuzumab in December 2014, and she presented with tetraparesis predominantly affecting the legs in July 2015.

    Methylprednisolone improved symptoms but not completely, and in September she developed newly occurring left-sided hemiataxia and hemihypesthesia. She received more methylprednisolone and plasma exchange. The symptoms recurred in November and were treated with a higher methylprednisolone dose.

    Subsequent MRI revealed several contrast-enhancing lesions, including some with ring-enhancing characteristics. Both symptoms and MRI measures improved after treatment with rituximab.

    Dr Gold received speaker’s fees and board honoraria from Baxter, Bayer Schering, Biogen Idec, Chugai, CLB Behring, Genzyme, Merck Serono, Novartis, Talecris, TEVA, and Wyeth. His department received grant support from Bayer, Schering, Biogen Idec, Genzyme, Merck Serono, Novartis, and TEVA.

    Lancet Neurol. 2017;16:104-106. Full text

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