Contributions
Abstract: 172
Type: Oral
Abstract Category: Therapy - disease modifying - Risk management for disease modifying treatments
Background: Detection of JC virus (JCV) by polymerase chain reaction (PCR) in cerebrospinal fluid (CSF) is essential for the diagnosis of natalizumab-associated progressive multifocal leukoencephalopathy (NTZ-PML) according to the AAN diagnostic criteria. However, JCV PCR can be negative at the time of PML lesion detection by magnetic resonance imaging (MRI), hampering early diagnosis of NTZ-PML, in particular in patients not showing clinical symptoms suggestive of PML. The relationship between MRI findings and the presence of JCV DNA and number of JCV DNA copies in CSF measured by quantitative PCR, is not well understood.
Objective: To investigate the relationship of qualitative and quantitative JCV DNA detection in CSF with PML lesion volume, lesion dissemination and signs of inflammation on MRI.
Methods: From our cohort of local and referred NTZ-PML patients, we included patients with a brain MRI obtained within 10 days from the first CSF sample and with data available on the presence or absence of PML symptoms at PML diagnosis. Total PML lesion volumes were measured, and lesion location, lesion dissemination and findings suggestive of inflammation (contrast enhancement or perivascular T2 lesions) were scored in consensus by three raters. The association of PML lesion volume and other imaging findings with both qualitative and quantitative JCV PCR results were calculated.
Results: A total of 56 NTZ-PML patients were included. Of these, 14 showed no PML symptoms and 9 were JCV PCR negative, at NTZ-PML diagnosis. Total PML lesion volume was significantly higher in JCV PCR positive patients (median volume [IQR]: 22.9 [9.2-60.4] vs. 6.7 [4.9-14.7] ml, p=0.008). There was a significant positive correlation between PML lesion volume and the amount of JCV copies/ml in CSF (Spearman"s correlation coefficient: 0.322, p=0.031). Total PML lesion volume was significantly higher in symptomatic patients at PML diagnosis compared to asymptomatic patients (median volume [IQR]: 28.9 [10.1-60.6] vs. 9.2 [3.8-18.3] ml, p=0.005). No significant association was found between PML lesion dissemination, lesion location, signs of inflammation, or presence of PML symptoms and JCV PCR results.
Conclusion: This study shows a strong relationship between PML lesion volume and both the presence and amount of JCV DNA in CSF. In patients with low, often asymptomatic, PML lesion volumes, JCV PCR is more likely to show false negative results, with considerable implications for patient care.
Disclosure: Potential conflict of interest:
MTW, IK, MdV, BIW do not report any competing interest.
CW has received consultancy or speaking fees from Novartis, Bayer, Biogen and Teva.
BMJU has received consultancy fees from Biogen Idec, Genzyme, Merck Serono, Novartis, Roche and Teva.
FB serves as a consultant for Bayer-Schering Pharma, Sanofi-Aventis, Biogen, Teva, Novartis, Roche, Synthon BV, Genzyme and Jansen Research.
JK has received consultancy fees from Merck-Serono, Teva, Biogen, Genzyme and Novartis.
MPW has received consultancy fees from Biogen and Roche.
Abstract: 172
Type: Oral
Abstract Category: Therapy - disease modifying - Risk management for disease modifying treatments
Background: Detection of JC virus (JCV) by polymerase chain reaction (PCR) in cerebrospinal fluid (CSF) is essential for the diagnosis of natalizumab-associated progressive multifocal leukoencephalopathy (NTZ-PML) according to the AAN diagnostic criteria. However, JCV PCR can be negative at the time of PML lesion detection by magnetic resonance imaging (MRI), hampering early diagnosis of NTZ-PML, in particular in patients not showing clinical symptoms suggestive of PML. The relationship between MRI findings and the presence of JCV DNA and number of JCV DNA copies in CSF measured by quantitative PCR, is not well understood.
Objective: To investigate the relationship of qualitative and quantitative JCV DNA detection in CSF with PML lesion volume, lesion dissemination and signs of inflammation on MRI.
Methods: From our cohort of local and referred NTZ-PML patients, we included patients with a brain MRI obtained within 10 days from the first CSF sample and with data available on the presence or absence of PML symptoms at PML diagnosis. Total PML lesion volumes were measured, and lesion location, lesion dissemination and findings suggestive of inflammation (contrast enhancement or perivascular T2 lesions) were scored in consensus by three raters. The association of PML lesion volume and other imaging findings with both qualitative and quantitative JCV PCR results were calculated.
Results: A total of 56 NTZ-PML patients were included. Of these, 14 showed no PML symptoms and 9 were JCV PCR negative, at NTZ-PML diagnosis. Total PML lesion volume was significantly higher in JCV PCR positive patients (median volume [IQR]: 22.9 [9.2-60.4] vs. 6.7 [4.9-14.7] ml, p=0.008). There was a significant positive correlation between PML lesion volume and the amount of JCV copies/ml in CSF (Spearman"s correlation coefficient: 0.322, p=0.031). Total PML lesion volume was significantly higher in symptomatic patients at PML diagnosis compared to asymptomatic patients (median volume [IQR]: 28.9 [10.1-60.6] vs. 9.2 [3.8-18.3] ml, p=0.005). No significant association was found between PML lesion dissemination, lesion location, signs of inflammation, or presence of PML symptoms and JCV PCR results.
Conclusion: This study shows a strong relationship between PML lesion volume and both the presence and amount of JCV DNA in CSF. In patients with low, often asymptomatic, PML lesion volumes, JCV PCR is more likely to show false negative results, with considerable implications for patient care.
Disclosure: Potential conflict of interest:
MTW, IK, MdV, BIW do not report any competing interest.
CW has received consultancy or speaking fees from Novartis, Bayer, Biogen and Teva.
BMJU has received consultancy fees from Biogen Idec, Genzyme, Merck Serono, Novartis, Roche and Teva.
FB serves as a consultant for Bayer-Schering Pharma, Sanofi-Aventis, Biogen, Teva, Novartis, Roche, Synthon BV, Genzyme and Jansen Research.
JK has received consultancy fees from Merck-Serono, Teva, Biogen, Genzyme and Novartis.
MPW has received consultancy fees from Biogen and Roche.