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DIR Return to: TYSABRI (natalizumab)
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#Post#: 820--------------------------------------------------
(CMSC) Tysabri-related PML case w/repeated negative anti-JCV ant
ibody testing
By: agate Date: June 7, 2015, 1:39 pm
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Presented at the CMSC (Consortium of Multiple Sclerosis Centers)
conference, May 29, 2015:
[quote]1: 10,000 Is Not Zero. Lessons Learned from a
Natalizumab-Related PML Case with Repeated Negative Anti-JCV
Antibody Testing
Marie-Sarah Gagne Brosseau, MD , Neurology, University of
Washington, Seattle, WA
Gary Stobbe, MD , Neurology, University of Washington, Seattle,
WA
Deb Cramer, RN , Neurology, University of Washington, Seattle,
WA
Hillary Lipe, A.R.N.P. , Neurology, University of Washington,
Seattle, WA
Annette Wundes, MD , Neurology, University of Washington,
Seattle, WA
PDF
Background:
Progressive multifocal leukoencephalopathy (PML) is a severe
brain infection caused by the JC virus (JCV) that leads to lysis
of oligodendrocytes. Natalizumab is known to be associated with
PML. Clinical presentation varies; most common symptoms are
cognitive impairment, weakness and language deficit.
Natalizumab-related PML has a mortality rate of 22% and many
survivors have a poor functional outcome, which makes it
natalizumab’s most serious complication.
50-60% of adults have detectable serum antibodies against JCV.
Seropositivity for anti-JCV antibodies is a PML risk factor and
periodic testing is recommended. Previously, 2
natalizumab-treated multiple sclerosis PML patients were
classified as anti-JCV antibody negative, but testing dated from
8 and 9 months before diagnosis.
Objectives:
To describe a case of natalizumab-associated PML in which the
last anti-JCV antibody testing 2 weeks before onset of symptoms
was negative.
Methods:
Case presentation.
Results:
A 70-year-old woman with multiple sclerosis (MS) treated with
natalizumab for 4.5 years developed PML symptoms of right hand
weakness 2 weeks after last negative anti-JCV antibody testing.
She had never received immunosuppressants. Brain MRI showed 4
new nonenhancing lesions which were surmised due to MS. A course
of intravenous methylprednisolone for a presumed relapse was
given but her weakness worsened. Short-term repeat MRI was
suggestive of PML and CSF JCV PCR came back positive. While 4
prior quantitative anti-JCV antibody tests every 3 months had
been negative, including 2 weeks prior to onset of symptoms
(index 0.19), at time of diagnosis the result was positive
(index 2.56). Evolution and management of the present case will
be presented.
Conclusions:
Initial misdiagnosis of MS relapse may delay the diagnosis of
PML. Clinicians should be wary that a natalizumab-treated
patient with new MRI findings and/or neurological symptoms could
have PML, including those with negative anti-JCV antibody. 2
weeks is currently the shortest interval reported between last
negative anti-JCV antibody testing and onset of PML symptoms. In
negative patients, risk can be due to a false negative test
result reported as 3%, or to de novo infection. In our case, de
novo infection with seroconversion is more plausible given the
repeatedly negative testing. If PML is suspected, anti-JCV
antibodies should be repeated even if recently negative.
Moreover, short-term repeat MRI and CSF testing warrant
consideration.[/quote]
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