Multiple Sclerosis Journal - October 2017 - 1564

701316
letter2017

MSJ0010.1177/1352458517701316Multiple Sclerosis JournalR Hohlfeld, J Havla

MULTIPLE
SCLEROSIS
JOURNAL

MSJ

Letter

Patient-to-patient transmission of
natalizumab-associated PML?
Date received: 24 February 2017; accepted: 26
February 2017
We are intrigued by the recent case report of two
stepsisters who were treated with natalizumab for
multiple sclerosis (MS) and developed progressive
multifocal leukoencephalopathy (PML) 5 months
apart.1 This is reminiscent of our own report about the
co-occurrence of PML in two MS patients who were
members of a "natalizumab-infusion group".2
The two stepsisters described by Bacchetta et al.1 had
close contact before and after the first patient developed PML. After PML was diagnosed in the first
patient, her stepsister insisted that her neurologist
ordered a magnetic resonance imaging (MRI) scan to
reassure she had not PML. MRI showed a highly suggestive clinically asymptomatic lesion in her cerebellum, and PML was confirmed by CSF John Cunningham
polyomavirus-polymerase chain reaction in the cerebrospinal fluid (JCV-PCR). After natalizumab was
discontinued, she developed symptomatic immune
reconstitution inflammatory syndrome (IRIS).1
In striking parallel, after PML was diagnosed in the
first patient of our "infusion group," the second
patient stopped natalizumab because of fear of PML.
Six weeks later, she developed new brainstem symptoms caused by a PML lesion in her brainstem.2
PML was confirmed by CSF JCV-PCR. Subsequently,
the other members of the infusion group, who met
monthly to receive natalizumab infusions in the
same room at their neurologist's infusion center, also
discontinued natalizumab because they were concerned about infection.2
In our PML cases, we had the chance to compare the
mutated non-coding control regions (NCCR) of viral
DNA. We found that the JCV NCCR was unique to
each patient. This seemed to argue against the possibility of direct viral transmission between the
patients. However, as we discussed in our paper,
"there remains the remote possibility that an archetype-like strain of JCV spread by de novo infection
from one patient to the other at an earlier time point
and subsequently mutated independently in the two
patients."2 Alternatively, a shared pathogenic viral
variant might have escaped detection by PCR.
1564

In contrast to our report, no viral PCR sequences are
available from the PML-affected stepsisters.1 The
authors point out that between 2005 and 2016 there
were only three cases of natalizumab-associated PML
(including the two stepsisters) in a region of
Switzerland encompassing 1.5 million inhabitants. A
puzzling aspect of the Swiss report is that if PML
indeed spread from patient to patient, there was apparently only a short latency of a few months before the
second stepsister developed PML.1

Multiple Sclerosis Journal
2017, Vol. 23(11) 1564-1565
DOI: 10.1177/
https://doi.org/10.1177/1352458517701316
1352458517701316
https://doi.org/10.1177/1352458517701316
© The Author(s), 2017.
Reprints and permissions:
http://www.sagepub.co.uk/
journalsPermissions.nav

Viewed together, these observations1,2 renew concern
that in rare instances, transmission of natalizumabassociated PML might occur between immunocompromised patients who have close contact, as was the
case with the Swiss stepsisters and with our "natalizumab infusion group." Against this background, the
advice that "pre-disposed patients (e.g. natalizumabtreated patients, AIDS/immunosuppressed patients)
should avoid direct contact with active PML patients"1
makes a lot of sense.
Declaration of Conflicting Interests
The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: R.H. has
received grant support from Bayer, Biogen,
Genzyme-Sanofi, Merck-Serono, Novartis, and Teva
and personal fees from Actelion, Bayer, Biogen,
Genzyme-Sanofi, Medday, Merck-Serono, Novartis,
Roche, and Teva. J.H. has received consultancy fees
from Novartis, Genzyme, and Biogen. He has
received reimbursements of congress attendance and
travel costs from Novartis, Bayer, Genzyme, Biogen
and Merck. T.K. has received travel expenses and
personal compensations from Bayer Healthcare,
Teva Pharma, Merck-Serono, Novartis, GenzymeSanofi, Roche Pharma, and Biogen, as well as grant
support from Bayer-Schering AG, Novartis, and
Chugai Pharma.
Funding
The author(s) received no financial support for the
research, authorship, and/or publication of this article.

References
1.

Bacchetta F, Mathias A, Schluep M, et al. Progressive
multifocal leukoencephalopathy in two natalizumabtreated stepsisters: An intriguing coincidence. Mult
Scler 2017; 23(2): 300-303.

Havla J, Berthele A, Kumpfel T, et al. Co-occurrence
of two cases of progressive multifocal
journals.sagepub.com/home/msj

https://uk.sagepub.com/en-gb/journals-permissions https://uk.sagepub.com/en-gb/journals-permissions https://journals.sagepub.com/home/msj

Table of Contents for the Digital Edition of Multiple Sclerosis Journal - October 2017